Cryogels are novel materials because the manufacturing process known as cryostructuring allows biopolymers to change their properties as a result of repeated controlled freeze-thaw cycles. Hydrogels of xanthan and karaya gums were evaluated after undergoing up to four controlled freeze-thaw cycles in indirect contact with liquid nitrogen (up to -150 °C) to form cryogels. Changes in structural, molecular, rheological, and thermal properties were evaluated and compared to those of their respective hydrogels. Samples were also analyzed by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR-ATR), Rotational Rheology (RR), Modulated Differential Scanning Calorimetry (MDSC) and zeta potential (ζ). In general, significant differences (p < 0.05) between the numbers of freeze-thaw cycles were found. Karaya cryogels were not stable to repeated cycles of cryostructuring such as the three-cycle xanthan cryogel, which has the best structural order (95.55%), molecular interactions, and thermal stability, which allows the generation of a novel material with improved thermal and structural properties that can be used as an alternative in food preservation.

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, β-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1β, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit β-amyloid (Aβ) aggregation.

In this paper, we present a comparative analysis of the solid state structures of three well-resolved hydrates of macrocyclic host molecules 1a, 1b, and 2 containing an intrannular amide-aryl substituent (lariat arm) connected to a fixed 26-membered ring in a normal (-NHCOAr, hosts 1a and 1b) or reverse manner (-CONHAr, host 2). Despite different chemical structures, these hosts crystallize as isostructural tetrahydrates in the same P-1 space group. Moreover, their crystals exhibit identical hydrogen bond motifs resulting in a stabilization of an almost identical unusual octameric water cluster built from the cyclic tetramer core and four water molecules, attached sequentially in an "up-and-down" manner. Further analysis reveals that, among the series, the structure of host 2 provides the most suitable environment for the accommodation of this type of water cluster.

1-Hexene transformations in the catalytic systems L2MCl2-XAlBui2 (L = Cp, M = Ti, Zr, Hf; L = Ind, rac-H4C2[THInd]2, M = Zr; X = H, Bu i) and [Cp2ZrH2]2-ClAlR2 activated by MMAO-12, B(C6F5)3, or (Ph3C)[B(C6F5)4] in chlorinated solvents (CH2Cl2, CHCl3, o-Cl2C6H4, ClCH2CH2Cl) were studied. The systems [Cp2ZrH2]2-MMAO-12, [Cp2ZrH2]2-ClAlBui2-MMAO-12, or Cp2ZrCl2-HAlBui2-MMAO-12 (B(C6F5)3) in CH2Cl2 showed the highest activity and selectivity towards the formation of vinylidene head-to-tail alkene dimers. The use of chloroform as a solvent provides further in situ dimer dimerization to give a tetramer yield of up to 89%. A study of the reaction of [Cp2ZrH2]2 or Cp2ZrCl2 with organoaluminum compounds and MMAO-12 by NMR spectroscopy confirmed the formation of Zr,Zr-hydride clusters as key intermediates of the alkene dimerization. The probable structure of the Zr,Zr-hydride clusters and ways of their generation in the catalytic systems were analyzed using a quantum chemical approach (DFT).

Oral contraceptives (OCs) are widely used due to their efficiency in preventing unplanned pregnancies and treating several human illnesses. Despite their medical value, the toxicity of OCs remains a public concern. Previous studies indicate the carcinogenic potential of synthetic sex hormones and their link to the development and progression of hormone-dependent malignancies such as breast cancer. However, little is known about their influence on the evolution of triple-negative breast carcinoma (TNBC), a malignancy defined by the absence of estrogen, progesterone, and HER2 receptors. This study reveals that the active ingredients of modern OCs, 17β-Ethinylestradiol, Levonorgestrel, and their combination induce differential effects in MDA-MB-231 TNBC cells. The most relevant behavioral changes occurred after the 24 h treatment with 17β-Ethinylestradiol, summarized as follows: (i) decreased cell viability (64.32% at 10 µM); (ii) cell roundness and loss of confluence; (iii) apoptotic aspect of cell nuclei (fragmentation, membrane blebbing); and (iv) inhibited cell migration, suggesting a potential anticancer effect. Conversely, Levonorgestrel was generally associated with a proliferative activity. The association of the two OCs exerted similar effects as 17β-Ethinylestradiol but was less effective. Further studies are necessary to elucidate the hormones' cytotoxic mechanism of action on TNBC cells.

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C21 terpeno-phenolic compounds specific to Cannabis. The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.

Honey consumption is attributed to potentially advantageous effects on human health due to its antioxidant capacity as well as anti-inflammatory and antimicrobial activity, which are mainly related to phenolic compound content. Phenolic compounds are secondary metabolites of plants, and their content in honey is primarily affected by the botanical and geographical origin. In this study, a high-resolution mass spectrometry (HRMS) method was applied to determine the phenolic profile of various honey matrices and investigate authenticity markers. A fruitful sample set was collected, including honey from 10 different botanical sources (n = 51) originating from Greece and Poland. Generic liquid-liquid extraction using ethyl acetate as the extractant was used to apply targeted and non-targeted workflows simultaneously. The method was fully validated according to the Eurachem guidelines, and it demonstrated high accuracy, precision, and sensitivity resulting in the detection of 11 target analytes in the samples. Suspect screening identified 16 bioactive compounds in at least one sample, with abscisic acid isomers being the most abundant in arbutus honey. Importantly, 10 markers related to honey geographical origin were revealed through non-targeted screening and the application of advanced chemometric tools. In conclusion, authenticity markers and discrimination patterns were emerged using targeted and non-targeted workflows, indicating the impact of this study on food authenticity and metabolomic fields.

Ultrafiltration polyethersulfone (PES) membranes were prepared by wet phase inversion. Commercial halloysite nanotubes (HNTs) in the quantities of 0.5 wt% vs. PES (15 wt%) were introduced into the casting solution containing the polymer and different solvents: N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), or 1-methyl-2-pyrrolidinone (NMP). The type of solvent influenced the membranes' morphology and topography, as well as permeability, separation characteristics, and antifouling and antibacterial properties. The membranes prepared using DMA exhibited the loosest cross-section structure with the thinnest skin and the roughest surface, while the densest and smoothest were the DMF-based membranes. The advanced contact angles were visibly lower in the case of the membranes prepared using DMF compared to the other solvents. The highest water permeability was observed for the DMA-based membranes, however, the most significant effect of the modification with HNTs was found for the NMP-based series. Regardless of the solvent, the introduction of HNTs resulted in an improvement of the separation properties of membranes. A noticeable enhancement of antifouling performance upon application of HNTs was found only in the case of DMF-based membranes. The study of the antibacterial properties showed that the increase in surface roughness had a positive effect on the inhibition of E. coli growth.

The aim of this study was to evaluate the involvement of nanoparticles prepared from Allium cepa L. as anti-inflammatory agents. In the present study, we identified nanoparticles from Allium cepa L. using the ultracentrifugation exosome purification method. The nanoparticles were referred to as 17,000× g and 200,000× g precipitates, and they contained quercetins, proteins, lipids, and small-sized RNA. The nanoparticles inhibited nitric oxide production from lipopolysaccharide (LPS)-stimulated RAW264 cells without cytotoxic properties. Cellular incorporation was confirmed by laser microscopic observation after PKH26 staining. The inhibition of caveolae-dependent endocytosis and macropinocytosis significantly prevented the incorporation of the nanoparticles but had no effect on the inhibition of nitric oxide in RAW264 cells. Collectively, the identified nanoparticles were capable of inhibiting the LPS response via extracellular mechanisms. Taken together, the way of consuming Allium cepa L. without collapsing the nanoparticles is expected to provide an efficient anti-inflammatory effect.

Royal jelly (RJ) is a complex, creamy secretion produced by the glands of worker bees. Due to its health-promoting properties, it is used by humans as a dietary supplement. However, RJ compounds are not fully characterized yet. Hence, in this research, we aimed to broaden the knowledge of the proteomic composition of fresh RJ. Water extracts of the samples were pre-treated using combinatorial hexapeptide ligand libraries (ProteoMinerTM kit), trypsin-digested, and analyzed by a nanoLC-MALDI-TOF/TOF MS system. To check the ProteoMinerTM performance in the MS-based protein identification, we also examined RJ extracts that were not prepared with the ProteoMinerTM kit. We identified a total of 86 proteins taxonomically classified to Apis spp. (bees). Among them, 74 proteins were detected in RJ extracts pre-treated with ProteoMinerTM kit, and only 50 proteins were found in extracts non-enriched with this technique. Ten of the identified features were hypothetical proteins whose existence has been predicted, but any experimental evidence proves their in vivo expression. Additionally, we detected four uncharacterized proteins of unknown functions. The results of this research indicate that the ProteoMinerTM strategy improves proteomic identification in complex biological samples. Broadening the knowledge of RJ composition may contribute to the development of standards and regulations, enhancing the quality of RJ, and consequently, the safety of its supplementation.

Organic materials development, especially in terms of nonlinear optical (NLO) performance, has become progressively more significant owing to their rising and promising applications in potential photonic devices. Organic moieties such as carbazole and quinoline play a vital role in charge transfer applications in optoelectronics. This study reports and characterizes the donor-acceptor-donor-π-acceptor (D-A-D-π-A) configured novel designed compounds, namely, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1. We further analyze the structure-property relationship between the quinoline-carbazole compounds for which density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed at the B3LYP/6-311G(d,p) level to obtain the optimized geometries, natural bonding orbital (NBO), NLO analysis, electronic properties, and absorption spectra of all mentioned compounds. The computed values of λmax, 364, 360, and 361 nm for Q3, Q4, and Q5 show good agreement of their experimental values: 349, 347, and 323 nm, respectively. The designed compounds (Q3D1-Q5D1) exhibited a smaller energy gap with a maximum redshift than the reference molecules (Q3-Q5), which govern their promising NLO behavior. The NBO evaluation revealed that the extended hyperconjugation stabilizes these systems and caused a promising NLO response. The dipole polarizabilities and hyperpolarizability (β) values of Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1 exceed those of the reference Q3, Q4, and Q5 molecules. These data suggest that the NLO active compounds, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1, may find their place in future hi-tech optical devices.

As film-forming agents, fillers and adsorbents, microplastics are often added to daily personal care products. Because of their chemical stability, they remain in the environment for thousands of years, endangering the safety of the environment and human health. Therefore, it is urgent to find an environmentally friendly substitute for microplastics. Using n-octyltrimethoxysilane (OTMS) and tetraethoxysilane (TEOS) as silicon sources, a novel, environmentally friendly, organic hollow mesoporous silica system is designed with a high loading capacity and excellent adsorption characteristics in this work. In our methodology, sandalwood essential oil (SEO) was successfully loaded into the nanoparticle cavities, and was involved in the formation of Pickering emulsion as well, with a content of up to 40% (w/w). The developed system was a stable carrier for the dispersion of SEO in water. This system can not only overcome the shortcomings of poor water solubility and volatility of sandalwood essential oil, but also act as a microplastic substitute with broad prospects in the cosmetics and personal care industry, laying a foundation for the preparation and applications of high loading capacity microcapsules in aqueous media.

The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.

Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated. Effort has been made throughout this comprehensive review to highlight the recent developments and milestones achieved in leukemia therapies using plant-derived compounds and the crude extracts from various medicinal plants. Furthermore, the mechanisms of action of these plants are discussed.

Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25-97%). Synthesis was performed in a "one-pot", two-step procedure, in the presence of organic base (Et3N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO-) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72-96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Ptn-GLP NCs). When Pt600-GLP NCs was added, 3,3',5,5'-tetramethylbenzidine (TMB) was rapidly catalyzed and oxidized to blue oxTMB, indicating the peroxidase-like activity of Pt600-GLP NCs. The catalytic reaction on the substrate TMB followed the Michaelis-Menton kinetics with the ping-pong mechanism. The mechanism of the colorimetric reaction was mainly due to the formation of hydroxyl radical (•OH). Furthermore, the catalytic reaction of Pt600-GLP NCs was used in the colorimetric detection of DA. The linear range for DA was 1-100 μM and the detection limit was 0.66 μM. The sensitive detection of DA using Pt-GLP NCs with peroxidase-like activity offers a simple and practical method that may have great potential applications in the biotechnology field.

Mass spectrometry imaging is a powerful tool for analyzing the different kinds of molecules in tissue sections, but some substances cannot be measured easily, due to their physicochemical properties. In such cases, chemical derivatization could be applied to introduce the charge into the molecule and facilitate its detection. Here, we study cholesterol derivatization with betaine aldehyde from tissue slices and evaluate how different sample preparation methods influence the signal from the derivatization product. In this study, we have tested different solutions for betaine aldehyde, different approaches to betaine aldehyde deposition (number of layers, deposition nozzle height), and different MALDI matrices for its analysis. As a result, we proved that the proposed approach could be used for the analysis of cholesterol in different tissues.

Despite progress achieved, there is limited available information about the antibacterial activity of constituents of essential oils (EOs) from different medicinal-aromatic plants (MAPs) against fish pathogens and the complex interactions of blended EOs thereof. The present study aimed to investigate possible synergistic antimicrobial effects of EOs from seven Greek MAPs with strong potential against Aeromonas veronii bv. sobria, a fish pathogen associated with aquaculture disease outbreaks. The main objective was to evaluate whether blending of these EOs can lead to increased antimicrobial activity against the specific microorganism. A total of 127 combinations of EOs were prepared and their effect on A. veronii bv. sobria growth was tested in vitro. We examined both the inhibitory and bactericidal activities of the individual EOs and compared them to those of the blended EOs. The vast majority of the investigated combinations exhibited significant synergistic and additive effects, while antagonistic effects were evident only in a few cases, such as the mixtures containing EOs from rosemary, lemon balm and pennyroyal. The combination of EOs from Greek oregano and wild carrot, as well as the combinations of those two with Spanish oregano or savoury were the most promising ones. Overall, Greek oregano, savoury and Spanish oregano EOs were the most effective ones when applied either in pure form or blended with other EOs.

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.

Mango is rich in polyphenols including gallotannins and gallic acid, among others. The bioavailability of mango polyphenols, especially polymeric gallotannins, is largely dependent on the intestinal microbiota, where the generation of absorbable metabolites depends on microbial enzymes. Mango polyphenols can favorably modulate bacteria associated with the production of bioactive gallotannin metabolites including Lactobacillus plantarum, resulting in intestinal health benefits. In several studies, the prebiotic effects of mango polyphenols and dietary fiber, their potential contribution to lower intestinal inflammation and promotion of intestinal integrity have been demonstrated. Additionally, polyphenols occurring in mango have some potential to interact with intestinal and less likely with hepatic enzymes or transporter systems. This review provides an overview of interactions of mango polyphenols with the intestinal microbiome, associated health benefits and underlying mechanisms.

Bromine complexing agents (BCAs) are used to reduce the vapor pressure of bromine in the aqueous electrolytes of bromine flow batteries. BCAs bind hazardous, volatile bromine by forming a second, heavy liquid fused salt. The properties of BCAs in a strongly acidic bromine electrolyte are largely unexplored. A total of 38 different quaternary ammonium halides are investigated ex situ regarding their properties and applicability in bromine electrolytes as BCAs. The focus is on the development of safe and performant HBr/Br2/H2O electrolytes with a theoretical capacity of 180 Ah L-1 for hydrogen bromine redox flow batteries (H2/Br2-RFB). Stable liquid fused salts, moderate bromine complexation, large conductivities and large redox potentials in the aqueous phase of the electrolytes are investigated in order to determine the most applicable BCA for this kind of electrolyte. A detailed study on the properties of BCA cations in these parameters is provided for the first time, as well as for electrolyte mixtures at different states of charge of the electrolyte. 1-ethylpyridin-1-ium bromide [C2Py]Br is selected from 38 BCAs based on its properties as a BCA that should be focused on for application in electrolytes for H2/Br2-RFB in the future.

Polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), and stainless steel (SS) are commonly used in medicine and food production technologies. During contact with microorganisms on the surface of these materials, a microbial biofilm is formed. The biofilm structure is difficult to remove and promotes the development of pathogenic bacteria. For this reason, the inhibition of biofilm formation in medical and food production environments is very important. For this purpose, five naturally occurring compounds were used for antimicrobial screening tests. The two with the best antimicrobial properties were chosen to inhibit the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa. After 3 days of exposure, thymol reduced the amount of biofilm of Pseudomonas aeruginosa within the range of 70-77% and 52-75% for Staphylococcus aureus. Carvacrol inhibited the formation of biofilms by up to 74-88% for Pseudomonas aeruginosa and up to 86-100% for Staphylococcus aureus. Those phenols decreased the enzyme activity of the biofilm by up to 40-100%. After 10 days of exposure to thymol, biofilm formation was reduced by 80-100% for Pseudomonas aeruginosa and by about 79-100% for Staphylococcus aureus. Carvacrol reduced the amount of biofilm by up to 91-100% for Pseudomonas aeruginosa and up to 95-100% for Staphylococcus aureus.

A diimine ligand having two [2.2]paracyclophanyl substituents at the N atoms (L1) was prepared from the reaction of amino[2.2]paracyclophane with acenaphtenequinone. The ligand reacts with NiBr2(dme) (dme: 1,2-dimethoxyethane) to form the dibromonickel complex with (R,R) and (S,S) configuration, NiBr2(L1). The structure of the complex was confirmed by X-ray crystallography. NiBr2(L1) catalyzes oligomerization of ethylene in the presence of methylaluminoxane (MAO) co-catalyst at 10-50 °C to form a mixture of 1- and 2-butenes after 3 h. The reactions for 6 h and 8 h at 25 °C causes further increase of 2-butene formed via isomerization of 1-butene and formation of hexenes. Reaction of 1-hexene catalyzed by NiBr2(L1)-MAO produces 2-hexene via isomerization and C12 and C18 hydrocarbons via oligomerization. Consumption of 1-hexene of the reaction obeys first-order kinetics. The kinetic parameters were obtained to be ΔG‡ = 93.6 kJ mol-1, ΔH‡ = 63.0 kJ mol-1, and ΔS‡ = -112 J mol-1deg-1. NiBr2(L1) catalyzes co-dimerization of ethylene and 1-hexene to form C8 hydrocarbons with higher rate and selectivity than the tetramerization of ethylene.

Untargeted metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) can detect thousands of features in samples and produce highly complex datasets. The accurate extraction of meaningful features and the building of discriminant models are two crucial steps in the data analysis pipeline of untargeted metabolomics. In this study, pure ion chromatograms were extracted from a liquor dataset and left-sided colon cancer (LCC) dataset by K-means-clustering-based Pure Ion Chromatogram extraction method version 2.0 (KPIC2). Then, the nonlinear low-dimensional embedding by uniform manifold approximation and projection (UMAP) showed the separation of samples from different groups in reduced dimensions. The discriminant models were established by extreme gradient boosting (XGBoost) based on the features extracted by KPIC2. Results showed that features extracted by KPIC2 achieved 100% classification accuracy on the test sets of the liquor dataset and the LCC dataset, which demonstrated the rationality of the XGBoost model based on KPIC2 compared with the results of XCMS (92% and 96% for liquor and LCC datasets respectively). Finally, XGBoost can achieve better performance than the linear method and traditional nonlinear modeling methods on these datasets. UMAP and XGBoost are integrated into KPIC2 package to extend its performance in complex situations, which are not only able to effectively process nonlinear dataset but also can greatly improve the accuracy of data analysis in non-target metabolomics.

The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds.

A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.

In this work, a new ultra-performance liquid chromatograph-evaporative light-scattering detector (UPLC-ELSD) method for quantitation of glycidyl esters (GE) contents in edible oils is presented. The method features complete separation of five GE species within 20 min by a C18 column and gradient elution with a mobile phase consisting of 85% and 2.5% methanol aqueous solutions. The coefficients of regression (R2) were all ≥0.9999 for the linear-quadratic regression curves of GE species in a concentration range of 5~80 μg/mL. The intraday and interday recoveries (%) of GE species in solvent were in a range of 81.3~107.3%, and the intraday and interday coefficients of variation (CVs, %) were all ≤8.6%. The average recovery (%) of GE species spiked in extra-virgin olive oil samples ranged from 88.3~107.8% and the intermediate precision (CV, %) of ≤14% indicated acceptable accuracy and precision. The method exhibited limit of quantification (LOQ) for each GE species (0.6 μg glycidol equivalents/g oil). The method was applied to determine GE concentrations of six commercial oil samples, and total glycidol equivalents were consistent with data obtained by GC-MS method. This UPLC-ELSD method could be adopted for precursory screening and research purposes to improve food safety when MS detectors are unavailable.

The S2 state produces two basic electron paramagnetic resonance signal types due to the manganese cluster in oxygen-evolving complex, which are influenced by the solvents, and cryoprotectant added to the photosystem II samples. It is presumed that a single manganese center oxidation occurs on S1 → S2 state transition. The S2 state has readily visible multiline and g4.1 electron paramagnetic resonance signals and hence it has been the most studied of all the Kok cycle intermediates due to the ease of experimental preparation and stability. The S2 state was studied using electron paramagnetic resonance spectroscopy at X-band frequencies. The aim of this study was to determine the spin states of the g4.1 signal. The multiline signal was observed to arise from a ground state spin ½ centre while the g4.1 signal generated at ≈140 K NIR illumination was proposed to arise from a spin 52 center with rhombic distortion. The 'ground' state g4.1 signal was generated solely or by conversion from the multiline. The data analysis methods used involved numerical simulations of the experimental spectra on relevant models of the oxygen-evolving complex cluster. A strong focus in this paper was on the 'ground' state g4.1 signal, whether it is a rhombic 52 spin state signal or an axial 32 spin state signal. The data supported an X-band CW-EPR-generated g4.1 signal as originating from a near rhombic spin 5/2 of the S2 state of the PSII manganese cluster.

The 2-amino-5-(3/4-fluorostyryl)acetophenones were prepared and reacted with benzaldehyde derivatives to afford the corresponding 5-styryl-2-aminochalcone hybrids. The trans geometry of the styryl and α,β-unsaturated carbonyl arms, and the presence of NH…O intramolecular hydrogen bond were validated using 1H-NMR and X-ray data. The 2-amino-5-styrylacetophenones and their 5-styryl-2-aminochalcone derivatives were screened in vitro for their capability to inhibit α-glucosidase and/or α-amylase activities. Their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. Kinetic studies of the most active derivatives from each series against α-glucosidase and/or α-amylase activities have been performed supported by molecular docking studies to determine plausible protein-ligand interactions on a molecular level. The key aspects of the pharmacokinetics of these compounds, i.e., absorption, distribution, metabolism, and excretion have also been simulated at theoretical level. The most active compounds from each series, namely, 2a and 3e, were evaluated for cytotoxicity against the normal monkey kidney cells (Vero cells) and the adenocarcinomic human epithelial (A549) cell line to establish their safety profile at least in vitro.

In the present study, we evaluated for the first time the photoprotective effect of fish bone bioactive peptides (FBBP) preparation isolated from silver carp (Hypophthalmichthys molitrix) discarded tissue using in vitro experimental models of skin cells exposed to ultraviolet B (UVB) irradiation and stressing agents. FBBP preparation was obtained by papain treatment of minced bones and centrifugal ultrafiltration, and the molecular weight (MW) distribution was characterized by size exclusion and reversed-phase high performance liquid chromatography (RP-HPLC). In vitro assessment of the effect of FBBP pretreatment in UVB-irradiated L929 fibroblasts and HaCaT keratinocytes revealed their cytoprotective activity. Their capacity to efficiently reduce reactive oxygen species (ROS) production and lipid peroxidation varied in a dose-dependent manner, and it was greater in fibroblasts. A decrease of proinflammatory cytokines secretion, in particular of tumor necrosis factor alpha (TNF-α), was found after FBBP pretreatment of THP-1-derived inflamed macrophages. Melanin production and tyrosinase activity investigated in UVB-irradiated Mel-Juso cells were lowered in direct relation to FBBP concentrations. FBBP fractions with high radical scavenging activity were separated by ion exchange chromatography, and two collagenic sequences were identified. All these results offer new scientific data on aquaculture fish bone-derived peptides confirming their ability to control the antioxidant, anti-inflammatory and pigmentation processes developed during UV irradiation of skin cells and recommend their use as valuable natural ingredients of photoprotective cosmeceutical products.

Hydrogel adhesives are attractive for applications in intelligent soft materials and tissue engineering, but conventional hydrogels usually have poor adhesion. In this study, we designed a strategy to synthesize a novel adhesive with a thin hydrogel adhesive layer integrated on a tough substrate hydrogel. The adhesive layer with positive charges of ammonium groups on the polymer backbones strongly bonds to a wide range of nonporous materials' surfaces. The substrate layer with a dual hydrogen bond system consists of (i) weak hydrogen bonds between N,N-dimethyl acrylamide (DMAA) and acrylic acid (AAc) units and (ii) strong multiple hydrogen bonds between 2-ureido-4[1H]-pyrimidinone (UPy) units. The dual hydrogen-bond network endowed the hydrogel adhesives with unique mechanical properties, e.g., toughness, highly stretchability, and insensitivity to notches. The hydrogel adhesion to four types of materials like glass, 316L stainless steel, aluminum, Al2O3 ceramic, and two biological tissues including pig skin and pig kidney was investigated. The hydrogel bonds strongly to dry solid surfaces and wet tissue, which is promising for biomedical applications.

Dendrimers comprise a specific group of macromolecules, which combine structural properties of both single molecules and long expanded polymers. The three-dimensional form of dendrimers and the extensive possibilities for use of additional substrates for their construction creates a multivalent potential and a wide possibility for medical, diagnostic and environmental purposes. Depending on their composition and structure, dendrimers have been of interest in many fields of science, ranging from chemistry, biotechnology to biochemical applications. These compounds have found wide application from the production of catalysts for their use as antibacterial, antifungal and antiviral agents. Of particular interest are peptide dendrimers as a medium for transport of therapeutic substances: synthetic vaccines against parasites, bacteria and viruses, contrast agents used in MRI, antibodies and genetic material. This review focuses on the description of the current classes of dendrimers, the methodology for their synthesis and briefly drawbacks of their properties and their use as potential therapies against infectious diseases.

The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.

Bioassay-guided separation of young leaves extracts of Syzygium antisepticum (Blume) Merr. & L.M. Perry led to the isolation of four triterpenoids (betulinic acid, ursolic acid, jacoumaric acid, corosolic acid) and one sterol glucoside (daucosterol) from the ethyl acetate extract, and three polyphenols (gallic acid, myricitrin, and quercitrin) from the methanol (MeOH) extract. The MeOH extract of S. antisepticum and some isolated compounds, ursolic acid and gallic acid potentially exhibited acetylcholinesterase activity evaluated by Ellman's method. The MeOH extract and its isolated compounds, gallic acid, myricitrin, and quercitrin, also strongly elicited DPPH radical scavenging activity. In HEK-293 cells, the MeOH extract possessed cellular antioxidant effects by attenuating hydrogen peroxide (H2O2)-induced ROS production and increasing catalase, glutathione peroxidase-1 (GPx-1), and glutathione reductase (GRe). Furthermore, myricitrin and quercitrin also suppressed ROS production induced by H2O2 and induced GPx-1 and catalase production in HEK-293 cells. These results indicated that the young leaves of S. antisepticum are the potential sources of antioxidant and anticholinesterase agents. Consequently, S. antisepticum leaves are one of indigenous vegetables which advantage to promote the health and prevent diseases related to oxidative stress.

One of the major challenges in the computational prediction of protein-peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein-peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor-ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein-peptide complexes show that the proposed MD-based scoring approach can be used to identify protein-peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures.

Essential oils (EOs) were extracted from Eugenia patrisii, E. punicifolia, and Myrcia tomentosa, specimens A and B, using hydrodistillation. Gas chromatography coupled with mass spectrometry (GC/MS) was used to identify the volatile constituents present, and the antioxidant capacity of EOs was determined using diphenylpicryl-hydrazyl (DPPH) and trolox equivalent antioxidant capacity (TEAC) assays. For E. patrisii, germacrene D (20.03%), bicyclogermacrene (11.82%), and (E)-caryophyllene (11.04%) were identified as the major constituents of the EOs extracted from specimen A, whereas specimen B primarily comprised γ-elemene (25.89%), germacrene B (8.11%), and (E)-caryophyllene (10.76%). The EOs of E. punicifolia specimen A contained β-Elemene (25.12%), (E)-caryophyllene (13.11%), and bicyclogermacrene (9.88%), while specimen B was composed of (E)-caryophyllene (11.47%), bicyclogermacrene (5.86%), β-pinene (5.86%), and γ-muurolene (5.55%). The specimen A of M. tomentosa was characterized by γ-elemene (12.52%), germacrene D (11.45%), and (E)-caryophyllene (10.22%), while specimen B contained spathulenol (40.70%), α-zingiberene (9.58%), and γ-elemene (6.89%). Additionally, the chemical composition of the EOs was qualitatively and quantitatively affected by the collection period. Furthermore, the EOs of the studied specimens, especially specimen A of E. punicifolia, showed a greater antioxidant activity in DPPH rather than TEAC, as represented by a significantly high inhibition percentage (408.0%).

Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A "green method" has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API's physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API's solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.

Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg-1). Two days later, CA (50 mg kg-1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Anti-cancer activity of catechin nanoemulsions prepared from Oolong tea leaf waste was studied on prostate cancer cells DU-145 and DU-145-induced tumors in mice. Catechin nanoemulsions composed of lecithin, Tween-80 and water in an appropriate proportion was prepared with high stability, particle size of 11.3 nm, zeta potential of -67.2 mV and encapsulation efficiency of 83.4%. Catechin nanoemulsions were more effective than extracts in inhibiting DU-145 cell growth, with the IC50 being 13.52 and 214.6 μg/mL, respectively, after 48 h incubation. Furthermore, both catechin nanoemulsions and extracts could raise caspase-8, caspase-9 and caspase-3 activities for DU-145 cell apoptosis, arresting the cell cycle at S and G2/M phases. Compared to control, catechin nanoemulsion at 20 μg/mL and paclitaxel at 10 μg/mL were the most effective in reducing tumor volume by 41.3% and 52.5% and tumor weight by 77.5% and 90.6% in mice, respectively, through a decrease in EGF and VEGF levels in serum.

Increasing applications and markets for essential oils could bring new opportunities for cost-effective and sustainable management of unused forestry biomass; however, better knowledge of the production and application of such essential oils is necessary. The objective of this work is to contribute to greater knowledge of the essential oil production on a pilot scale from foliage biomass of wild shrubs and tree residues produced in some forestry enhancement operations and to study their antioxidant capacity (ORAC-oxygen radical absorbance capacity). Fresh biomass (twigs) of seven species (E. globulus, E. nitens, P. pinaster, P. sylvestris, R. officinalis, C. ladanifer, and J. communis) was manually collected in Spain in two different periods and was ground at 30 mm and distilled in a 30 L stainless steel still with saturated steam. The essential oil components were identified by GC-MS and quantified by GC-FID, and their antioxidant activity was determined with the ORAC method. Promising results on essential oil yield were obtained with E. globulus, E. nitens, R. officinalis, and J. communis. All essential oils studied exhibited antioxidant capacity by the ORAC assay, particularly that from C. ladanifer. Moreover, oxygenated sesquiterpenes contents, one of the minor components of oils, were significantly correlated with ORAC values.

In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer's disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspective for the development of active agents with multitarget potential. In this paper, a series of coumarin-based carbamic and amide derivatives were designed and synthesized as multipotent compounds acting on cholinergic system and eCS-related targets. Indeed, they were tested with appropriate enzymatic assays on acetyl and butyryl-cholinesterases and on fatty acid amide hydrolase (FAAH), and also evaluated as cannabinoid receptor (CB1 and CB2) ligands. Moreover, their ability to reduce the self-aggregation of beta amyloid protein (Aβ42) was assessed. Compounds 2 and 3, bearing a carbamate function, emerged as promising inhibitors of hAChE, hBuChE, FAAH and Aβ42 self-aggregation, albeit with moderate potencies, while the amide 6 also appears a promising CB1/CB2 receptors ligand. These data prove for the new compounds an encouraging multitarget profile, deserving further evaluation.

A new series of mollugin-1,2,3-triazole derivatives were synthesized using a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated mollugin with aryl azides. All the compounds were evaluated for their cytotoxicity on five human cancer cell lines (HL-60, A549, SMMC-7721, SW480, and MCF-7) using MTS assays. Among the synthesized series, most of them showed cytotoxicity and most of all, compounds 14 and 17 exhibited significant cytotoxicity of all five cancer cell lines.

The new screening method for rapid evaluation of major phenolic compounds in apples has been developed. Suitability of coupling HPLC/UHPLC separation with the diode-array detection and universal charged aerosol detection with respect to the presence of interfering substances was tested. Characteristics of both detection techniques were compared and method linearity, limits of detection and quantitation, and selectivity of them determined. Student t-test based on slopes of calibration plots was applied for the detailed comparison. The diode-array detection provided the best results regarding sensitivity and selectivity of the developed method in terms of evaluation of phenolics profiles. The response of the charged aerosol detector was negatively affected by co-eluting substances during rapid-screening analyses. Coulometric detection was used for advanced characterization of extracts in terms of antioxidant content and strength to obtain more complex information concerning sample composition. This detection also allowed evaluation of unidentified compounds with antioxidant activity. HPLC/UHPLC separation using a combination of diode-array and coulometric detectors thus represented the best approach enabling quick, yet complex characterization of bioactive compounds in apples.

BACKGROUND: Filtration of osmotic solution affects selective penetration during osmotic dehydration (OD), and after drying is finished, this can influence the chemical composition of the material, which is also modified by OD. METHODS: Osmotic dehydration was carried out in filtrated and non-filtrated concentrated chokeberry juice with the addition of mint infusion. Then, this underwent convective drying, vacuum-microwave drying and combined convective pre-drying, followed by vacuum-microwave finishing drying. Drying kinetics were presented and mathematical models were selected. The specific energy consumption for each drying method was calculated and the energy efficiency was determined. RESULTS AND DISCUSSION: The study revealed that filtration of osmotic solution did not have significant effect on drying kinetics; however, it affected selective penetration during OD. The highest specific energy consumption was obtained for the samples treated by convective drying (CD) (around 170 kJ·g-1 fresh weight (fw)) and the lowest for the samples treated by vacuum-microwave drying (VMD) (around 30 kJ·g-1 fw), which is due to the differences in the time of drying and when these methods are applied. CONCLUSIONS: Filtration of the osmotic solution can be used to obtain the desired material after drying and the VMD method is the most appropriate considering both phenolic acid content and the energy aspect of drying.

Fungi have become an invaluable source of bioactive natural products, with more than 5 million species of fungi spanning the globe. Fractionation of crude extract of Neodidymelliopsis sp., led to the isolation of a novel polyketide, (2Z)-cillifuranone (1) and five previously reported natural products, (2E)-cillifuranone (2), taiwapyrone (3), xylariolide D (4), pachybasin (5), and N-(5-hydroxypentyl)acetamide (6). It was discovered that (2Z)-cillifuranone (1) was particularly sensitive to ambient temperature and light resulting in isomerisation to (2E)-cillifuranone (2). Structure elucidation of all the natural products were conducted by NMR spectroscopic techniques. The antimicrobial activity of 2, 3, and 5 were evaluated against a variety of bacterial and fungal pathogens. A sodium [1-13C] acetate labelling study was conducted on Neodidymelliopsis sp. and confirmed that pachybasin is biosynthesised through the acetate polyketide pathway.

Mitochondria play a key role in energy metabolism within the cell. Potassium channels such as ATP-sensitive, voltage-gated or large-conductance Ca2+-regulated channels have been described in the inner mitochondrial membrane. Several hypotheses have been proposed to describe the important roles of mitochondrial potassium channels in cell survival and death pathways. In the current study, we identified two populations of mitochondrial large-conductance Ca2+-regulated potassium (mitoBKCa) channels in human bronchial epithelial (HBE) cells. The biophysical properties of the channels were characterized using the patch-clamp technique. We observed the activity of the channel with a mean conductance close to 285 pS in symmetric 150/150 mM KCl solution. Channel activity was increased upon application of the potassium channel opener NS11021 in the micromolar concentration range. The channel activity was completely inhibited by 1 µM paxilline and 300 nM iberiotoxin, selective inhibitors of the BKCa channels. Based on calcium and iberiotoxin modulation, we suggest that the C-terminus of the protein is localized to the mitochondrial matrix. Additionally, using RT-PCR, we confirmed the presence of α pore-forming (Slo1) and auxiliary β3-β4 subunits of BKCa channel in HBE cells. Western blot analysis of cellular fractions confirmed the mitochondrial localization of α pore-forming and predominately β3 subunits. Additionally, the regulation of oxygen consumption and membrane potential of human bronchial epithelial mitochondria in the presence of the potassium channel opener NS11021 and inhibitor paxilline were also studied. In summary, for the first time, the electrophysiological and functional properties of the mitoBKCa channel in a bronchial epithelial cell line were described.

As part of our studies on antiprotozoal activity of approved herbal medicinal products, we previously found that a commercial tincture from Salvia officinalis L. (common Sage, Lamiaceae) possesses high activity against Trypanosoma brucei rhodesiense (Tbr), causative agent of East African Human Trypanosomiasis. We have now investigated in detail the antitrypanosomal constituents of this preparation. A variety of fractions were tested for antitrypanosomal activity and analyzed by UHPLC/+ESI QqTOF MS. The resulting data were used to generate a partial least squares (PLS) regression model that highlighted eight particular constituents that were likely to account for the major part of the bioactivity. These compounds were then purified and identified and their activity against the pathogen tested. All identified compounds (one flavonoid and eight diterpenes) displayed significant activity against Tbr, in some cases higher than that of the total tincture. From the overall results, it can be concluded that the antitrypanosomal activity of S. officinalis L. is, for the major part, caused by abietane-type diterpenes of the rosmanol/rosmaquinone group.

The tannery industry is one of the economic sectors that contributes to the development of different countries. Globally, Europe and Asia are the main producers of this industry, although Latin America and Africa have been growing considerably in recent years. With this growth, the negative environmental impacts towards different ecosystem resources as a result of the discharges of recalcitrated pollutants, have led to different investigations to generate alternative solutions. Worldwide, different technologies have been studied to address this problem, biological and physicochemical processes have been widely studied, presenting drawbacks with some recalcitrant compounds. This review provides a context on the different existing technologies for the treatment of tannery wastewater, analyzing the physicochemical composition of this liquid waste, the impact it generates on human health and ecosystems and the advances in the different existing technologies, focusing on advanced oxidation processes and the use of microalgae. The coupling of advanced oxidation processes with biological processes, mainly microalgae, is seen as a viable biotechnological strategy, not only for the removal of pollutants, but also to obtain value-added products with potential use in the biorefining of the biomass.

The study's aim was to characterize the composition of Nigella sativa seed (NSO) and grape seed (GSO) oils, and to evaluate their cardioprotective and anti-inflammatory effect on isoproterenol (ISO)-induced ischemia in rats. Materials and Methods: NSO and GSO supplements were physicochemically characterized. Liquid chromatography-mass spectrometry (HPLC-MS), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography-mass spectrometry (GC-MS) analyses were used to determine the phytochemical composition in the oils. Total polyphenol content (TPC) and in vitro antioxidant activity were also determined. Pretreatment with 4 mL/kg/day NSO or GSO was administered to rats for 14 days. The experimental ischemia was induced by a single administration of ISO 45 mg/kg after 14 days. An electrocardiogram (ECG) was performed initially and 24 h after ISO. Biological evaluation was done at the end of experiment. Results: The HPLC-MS, GC-MS, and FTIR analyses showed that both NSO and GSO are important sources of bioactive compounds, especially catechin and phenolic acids in GSO, while NSO was enriched in flavonoids and thymol derivatives. Pretreatment with GSO and NSO significantly reduced ventricular conduction, prevented the cardiotoxic effect of ISO in ventricular myocardium, and reduced the level of proinflammatory cytokines and CK-Mb. Conclusion: Both NSO and GSO were shown to have an anti-inflammatory and cardioprotective effect in ISO-induced ischemia.

Pineapple is consumed on a large scale around the world due to its appreciated sensorial characteristics. The industry of minimally processed pineapple produces enormous quantities of by-products (30-50%) which are generally undervalued. The end-of-life of pineapple by-products (PBP) can be replaced by reuse and renewal flows in an integrated process to promote economic growth by reducing consumption of natural resources and diminishing food waste. In our study, pineapple shell (PS) and pineapple core (PC), vacuum-packed separately, were subjected to moderate hydrostatic pressure (225 MPa, 8.5 min) (MHP) as abiotic stress to increase bromelain activity and antioxidant capacity. Pressurized and raw PBP were lyophilized to produce a stable powder. The dehydrated samples were characterized by the following methodologies: chemical and physical characterization, total phenolic compounds (TPC), antioxidant capacity, bromelain activity, microbiology, and mycotoxins. Results demonstrated that PBP are naturally rich in carbohydrates (66-88%), insoluble (16-28%) and soluble (2-4%) fiber, and minerals (4-5%). MHP was demonstrated to be beneficial in improving TPC (2-4%), antioxidant activity (2-6%), and bromelain activity (6-32%) without affecting the nutritional value. Furthermore, microbial and mycotoxical analysis demonstrated that powdered PC is a safe by-product. PS application is possible but requires previous decontamination to reduce the microbiological load.

Overweight, obesity, and psychiatric disorders are serious health problems. To evidence the anxiolytic-like effects and lipid reduction in mice receiving a high-calorie diet and Bertholletia excelsa seeds in a nonpolar extract (SBHX, 30 and 300 mg/kg), animals were assessed in open-field, hole-board, and elevated plus-maze tests. SBHX (3 and 10 mg/kg) potentiated the pentobarbital-induced hypnosis. Chronic administration of SBHX for 40 days was given to mice fed with a hypercaloric diet to determine the relationship between water and food intake vs. changes in body weight. Testes, epididymal white adipose tissue (eWAT), and liver were dissected to analyze fat content, triglycerides, cholesterol, and histological effects after administering the hypercaloric diet and SBHX. Fatty acids, such as palmitoleic acid (0.14%), palmitic acid (21.42%), linoleic acid (11.02%), oleic acid (59.97%), and stearic acid (7.44%), were identified as constituents of SBHX, producing significant anxiolytic-like effects and preventing body-weight gain in mice receiving the hypercaloric diet without altering their water or food consumption. There was also a lipid-lowering effect on the testicular tissue and eWAT and a reduction of adipocyte area in eWAT. Our data evidence beneficial properties of B. excelsa seeds influencing global health concerns such as obesity and anxiety.

Due to their structural similarity with natural α-amino acids, α-aminophosphonic acid derivatives are known biologically active molecules. In view of the relevance of tetrasubstituted carbons in nature and medicine and the strong dependence of the biological activity of chiral molecules into their absolute configuration, the synthesis of α-aminophosphonates bearing tetrasubstituted carbons in an asymmetric fashion has grown in interest in the past few decades. In the following lines, the existing literatures for the synthesis of optically active tetrasubstituted α-aminophosphonates are summarized, comprising diastereoselective and enantioselective approaches.

The development of new materials based on hydroxyapatite has undergone a great evolution in recent decades due to technological advances and development of computational techniques. The focus of this review is the various attempts to improve new hydroxyapatite-based materials. First, we comment on the most used processing routes, highlighting their advantages and disadvantages. We will now focus on other routes, less common due to their specificity and/or recent development. We also include a block dedicated to the impact of computational techniques in the development of these new systems, including: QSAR, DFT, Finite Elements of Machine Learning. In the following part we focus on the most innovative applications of these materials, ranging from medicine to new disciplines such as catalysis, environment, filtration, or energy. The review concludes with an outlook for possible new research directions.

Uncaria tomentosa (Willd.) DC is a woody climber species originating from South and Central America that has been used in the therapy of asthma, rheumatism, hypertension, and blood purification. Our previous study showed that U. tomentosa extracts altered human erythrocyte shape, which could be due to incorporation of the compounds contained in extracts into the erythrocyte membrane. The aim of the present study was to determine how the compounds contained in U. tomentosa extracts incorporate into the human erythrocyte membrane. The study has assessed the effect of aqueous and ethanolic extracts from leaves and bark of U. tomentosa on the osmotic resistance of the human erythrocyte, the viscosity of erythrocyte interior, and the fluidity of erythrocyte plasma membrane. Human erythrocytes were incubated with the studied extracts in the concentrations of 100, 250, and 500 µg/mL for 2, 5, and 24 h. All extracts tested caused a decrease in erythrocyte membrane fluidity and increased erythrocyte osmotic sensitivity. The ethanolic extracts from the bark and leaves increased viscosity of the erythrocytes. The largest changes in the studied parameters were observed in the cells incubated with bark ethanolic extract. We consider that the compounds from U. tomentosa extracts mainly build into the outer, hydrophilic monolayer of the erythrocyte membrane, thus protecting the erythrocytes against the adverse effects of oxidative stress.

Food preservatives such as NaNO2, which are widely used in human food products, undoubtedly affect, to some extent, human organs and health. For this reason, there is a need to reduce the hazards of these chemical preservatives, by replacing them with safe natural bio-preservatives, or adding them to synthetic ones, which provides synergistic and additive effects. The Citrus genus provides a rich source of such bio-preservatives, in addition to the availability of the genus and the low price of citrus fruit crops. In this study, we identify the most abundant flavonoids in citrus fruits (hesperidin) from the polar extract of mandarin peels (agro-waste) by using spectroscopic techniques, as well as limonene from the non-polar portion using GC techniques. Then, we explore the synergistic and additive effects of hesperidin from total mandarin extract with widely used NaNO2 to create a chemical preservative in food products. The results are promising and show a significant synergistic and additive activity. The combination of mandarin peel extract with NaNO2 had synergistic antibacterial activity against B. cereus, Staph. aureus, E. coli, and P. aeruginosa, while hesperidin showed a synergistic effect against B. cereus and P. aeruginosa and an additive effect against Staph. aureus and E. coli. These results refer to the ability of reducing the concentration of NaNO2 and replacing it with a safe natural bio-preservative such as hesperidin from total mandarin extract. Moreover, this led to gaining benefits from their biological and nutritive values.

N-phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted N-phenylpiperazine analogs were evaluated. Compound 6a was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound 6a was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound 6a was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease.

New nanocomposites, Fe3O4@Au-FITC, were prepared and explored to develop a fluorescent detection of Pb2+. The Fe3O4@AuNPs-FITC nanocomposites could be etched by Pb2+ in the presence of Na2S2O3, leading to fluorescence recovery of FITC quenched by Fe3O4@Au nanocomposites. With the increase of Pb2+ concentration, the fluorescence recovery of Fe3O4@AuNPs-FITC increased gradually. Under optimized conditions, a detection limit of 5.2 nmol/L of Pb2+ with a linear range of 0.02-2.0 µmol/L were obtained. The assay demonstrated negligible response to common metal ions. Recoveries of 98.2-106.4% were obtained when this fluorescent method was applied in detecting Pb2+ spiked in a lake-water sample. The above results demonstrated the high potential of ion-induced nanomaterial etching in developing robust fluorescent assays.

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

Active components from natural sources are the current focus in most pharmacological research to provide new therapeutic agents for clinical use. Essential oils from the Pinus species have been traditionally used in medicine. This study aimed to investigate the chemical profile of two Pinus species, Pinus halepensis L. and Pinus pinea Mill, from different altitudes in Libya and study the effect of environmental conditions on the biological activities of essential oils. A clevenger apparatus was used to prepare the essential oils by hydrodistillation. Analyses were done using GC/MS. Anthelmintic and antimicrobial activities were tested against the earthworm Allolobophora caliginosa, gram-positive bacteria, gram-negative bacteria, and fungi. Different chemical profiles were observed among all tested essential oils, and terpenes were the most dominant class. All studied essential oils from the Pinus species exhibited a remarkable anthelmintic activity compared to the standard piperazine citrate drug. Pinus halepensis from both altitudes showed broad-spectrum antimicrobial activity against all tested microorganisms, while Pinus pinea was effective against only Escherichia coli. From these findings, one can conclude that there are variations between studied species. The essential oil compositions are affected by environmental factors, which consequently affect the anthelmintic and antimicrobial activity.

Densazalin, a polycyclic alkaloid, was isolated from the marine sponge Haliclona densaspicula collected in Korea. The complete structure of the compound was determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, high-resolution mass spectrometry, and comparison of the calculated and measured electronic circular dichroism spectra. Densazalin possesses a unique 5,11-diazatricyclo[7.3.1.02,7]tridecan-2,4,6-triene moiety, which is connected by two linear carbon chains. This compound was derived from the biogenetic precursor bis-1,3-dialkylpyridnium. Densazalin exhibited cytotoxic activity on two human tumor cell lines (AGS and HepG2) in the Cell Counting Kit-8 (CCK-8) bioassay, with IC50 values ranging from 15.5 to 18.4 μM.

Lipid nanoparticles based on multiple emulsion (W/O/W) systems are suitable for incorporating hydrophilic active substances, including iridoid glycosides. This study involved optimization of composition of lipid nanoparticles, incorporation of active compounds (aucubin and catalpol), evaluation of stability of the resulting nanocarriers, and characterization of their lipid matrix. Based on 32 factorial design, an optimized dispersion of lipid nanoparticles (solid lipid:surfactant-4.5:1.0 wt.%) was developed, predisposed for the incorporation of iridoid glycosides by emulsification-sonication method. The encapsulation efficiency of the active substances was determined at nearly 90% (aucubin) and 77% (catalpol). Regarding the stability study, room temperature was found to be the most suitable for maintaining the expected physicochemical parameter values (particle size < 100 nm; polydispersity index < 0.3; zeta potential > |± 30 mV|). Characterization of the lipid matrix confirmed the nanometer size range of the resulting carriers (below 100 nm), as well as the presence of the lipid in the stable β' form.

The formation of a pair of extended networks sustained by halogen bonds based upon two regioisomers of a photoproduct, namely rctt-1,3-bis(4-pyridyl)-2,4-bis(phenyl)cyclobutane (ht-PP) and rctt-1,2-bis(4-pyridyl)-3,4-bis(phenyl)cyclobutane (hh-PP), that have varied topology is reported. These networks are held together via I⋯N halogen bonds between the photoproduct and the halogen-bond donor 1,4-diiodoperchlorobenzene (C6I2Cl4). The observed topology in each solid is controlled by the regiochemical position of the halogen-bond accepting 4-pyridyl group. This paper demonstrates the ability to vary the topology of molecular networks by altering the position of the halogen bond acceptor within the cyclobutane-based node.

The purpose of this paper was to characterize and investigate the antimicrobial potential of Amorpha fruticosa fruits essential oil (EO). The EO was extracted by hydrodistillation, analyzed by GC-MS, and then evaluated for its interaction with microbial and mammalian cells. The antimicrobial activity was assessed against bacterial and fungal strains, in a planktonic and adherent growth state, using qualitative and quantitative assays. The main components identified in A. fruticosa fruits EO were δ-cadinene, γ-muurolene, and α-muurolene. The Gram-positive strains proved to be more susceptible than Gram-negative bacteria and fungal strains. The EO exhibited good antibiofilm activity, inhibiting the microbial adherence to the inert (96-well plates and Foley catheter section) and cellular substrata. The flow cytometry analysis revealed as one of the possible mechanisms of antimicrobial action the alteration of cell membrane hydrophobicity. The cytotoxicity on the L929 cell line occurred at concentrations higher than 0.3 mg/mL. Taken together, our results demonstrate that A. fruticosa fruits EO contains active compounds with selective inhibitory effect on different microbial strains in planktonic and biofilm growth state, explained at least partially by the interference with microbial membranes due to their hydrophobic character.

Fracturing fluids are being increasingly used for viscosity development and proppant transport during hydraulic fracturing operations. Furthermore, the breaker is an important additive in fracturing fluid to extensively degrade the polymer mass after fracturing operations, thereby maximizing fracture conductivity and minimizing residual damaging materials. In this study, the efficacy of different enzyme breakers was examined in alkaline and medium-temperature reservoirs. The parameters considered were the effect of the breaker on shear resistance performance and sand-suspending performance of the fracturing fluid, its damage to the reservoir after gel breaking, and its gel-breaking efficiency. The experimental results verified that mannanase II is an enzyme breaker with excellent gel-breaking performance at medium temperatures and alkaline conditions. In addition, mannanase II did not adversely affect the shear resistance performance and sand-suspending performance of the fracturing fluid during hydraulic fracturing. For the same gel-breaking result, the concentration of mannanase II used was only one fifth of other enzyme breakers (e.g., mannanase I, galactosidase, and amylase). Moreover, the amount of residue and the particle size of the residues generated were also significantly lower than those of the ammonium persulfate breaker. Finally, we also examined the viscosity-reducing capability of mannanase II under a wide range of temperatures (104-158 °F) and pH values (7-8.5) to recommend its best-use concentrations under different fracturing conditions. The mannanase has potential for applications in low-permeability oilfield development and to maximize long-term productivity from unconventional oilwells.

Radiation and photodynamic therapies are used for cancer treatment by targeting DNA. However, efficiency is limited due to physico-chemical processes and the insensitivity of native nucleobases to damage. Thus, incorporation of radio- and photosensitizers into these therapies should increase both efficacy and the yield of DNA damage. To date, studies of sensitization processes have been performed on simple model systems, e.g., buffered solutions of dsDNA or sensitizers alone. To fully understand the sensitization processes and to be able to develop new efficient sensitizers in the future, well established model systems are necessary. In the cell environment, DNA tightly interacts with proteins and incorporating this interaction is necessary to fully understand the DNA sensitization process. In this work, we used dsDNA/protein complexes labeled with photo- and radiosensitizers and investigated degradation pathways using LC-MS and HPLC after X-ray or UV radiation.

The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff's bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.

We develop a fragment-based ab initio molecular dynamics (FB-AIMD) method for efficient dynamics simulation of the combustion process. In this method, the intermolecular interactions are treated by a fragment-based many-body expansion in which three- or higher body interactions are neglected, while two-body interactions are computed if the distance between the two fragments is smaller than a cutoff value. The accuracy of the method was verified by comparing FB-AIMD calculated energies and atomic forces of several different systems with those obtained by standard full system quantum calculations. The computational cost of the FB-AIMD method scales linearly with the size of the system, and the calculation is easily parallelizable. The method is applied to methane combustion as a benchmark. Detailed reaction network of methane reaction is analyzed, and important reaction species are tracked in real time. The current result of methane simulation is in excellent agreement with known experimental findings and with prior theoretical studies.

We describe a novel plastic material composed of camphene, camphor, and polypropylene that seems perfectly suited for studies on self-propelled objects on the water surface. Self-motion is one of the attributes of life, and chemically propelled objects show numerous similarities with animated motion. One of important questions is the relationship between the object shape and its motility. In our previous paper, {R. Löffler et al. PCCP, 2019, 21, 24852-24856}, we presented a novel hybrid material, obtained from the solution of camphor in camphene, that allowed making objects of various shapes. This hybrid material has wax-like mechanical properties, but it has a very high tackiness. Here, we report that a small amount of polypropylene removed this undesirable feature. We investigated the properties of camphor-camphene-polypropylene plastic by performing the statistical analysis of a pill trajectory inside a Petri dish and compared them with those of camphor-camphene wax. The plastic showed the stable character of motion for over an hour-long experiment. The surface activity of objects made of plastic did not significantly depend on the weight ratios of the compounds. Such a significant increase in usefulness came from the polypropylene, which controlled the dissipation of camphor and camphene molecules.

ABCG2 is an ABC membrane protein reverse transport pump, which removes toxic substances such as medicines out of cells. As a result, drug bioavailability is an unexpected change and negatively influences the ADMET (absorption, distribution, metabolism, excretion, and toxicity), leading to multi-drug resistance (MDR). Currently, in spite of promising studies, screening for ABCG2 inhibitors showed modest results. The aim of this study was to search for small molecules that could inhibit the ABCG2 pump. We first used the WISS MODEL automatic server to build up ABCG2 homology protein from 655 amino acids. Pharmacophore models, which were con-structed based on strong ABCG2 inhibitors (IC50 < 1 μM), consist of two hydrophobic (Hyd) groups, two hydrogen bonding acceptors (Acc2), and an aromatic or conjugated ring (Aro|PiR). Using molecular docking method, 714 substances from the DrugBank and 837 substances from the TCM with potential to inhibit the ABCG2 were obtained. These chemicals maybe favor synthesized or extracted and bioactivity testing.

Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.

In this work we report solvatochromic and luminescent properties of ethyl N-salicylideneglycinate (1), ethyl N-(5-methoxysalicylidene)glycinate (2), ethyl N-(5-bromosalicylidene)glycinate (3), and ethyl N-(5-nitrosalicylidene)glycinate (4) dyes. 1-4 correspond to a class of N-salicylidene aniline derivatives, whose photophysical properties are dictated by the intramolecular proton transfer between the OH-function and the imine N-atom, affording tautomerization between the enol-imine and keto-enamine forms. Photophysical properties of 1-4 were studied in different pure non-polar and (a)protic polar solvents as well as upon gradual addition of NEt3, NaOH, and CH3SO3H. The DFT calculations were performed to verify the structures of 1-4 as well as their electronic and optical properties.

Although natural or artificial modified pyrimidine nucleobases represent important molecules with valuable properties as constituents of DNA and RNA, no systematic analyses of the structural aspects of bromo derivatives of cytosine have appeared so far in the literature. In view of the biochemical and pharmaceutical relevance of these compounds, six different crystals containing proton-transfer derivatives of 5-bromocytosine are prepared and analyzed in the solid-state by single crystal X-ray diffraction. All six compounds are organic salts, with proton transfer occurring to the Nimino atom of the pyridine ring. Experimental results are then complemented with Hirshfeld surface analysis to quantitively evaluate the contribution of different intermolecular interactions in the crystal packing. Furthermore, theoretical calculations, based on different arrangements of molecules extracted from the crystal structure determinations, are carried out to analyze the formation mechanism of halogen bonds (XBs) in these compounds and provide insights into the nature and strength of the observed interactions. The results show that the supramolecular architectures of the six molecular salts involve extensive classical intermolecular hydrogen bonds. However, in all but one proton-transfer adducts, weak to moderate XBs are revealed by C-Br…O short contacts between the bromine atom in the fifth position, which acts as XB donor (electron acceptor). Moreover, the lone pair electrons of the oxygen atom of adjacent pyrimidine nucleobases and/or counterions or water molecules, which acts as XB acceptor (electron donor).

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl β-lactam is described starting from Baylis-Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.

Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.

Green pepper fruit is often consumed before it is completely ripe. However, the influence of the phenological stage in which the green pepper is consumed as a potential influencing factor in its bioactive compounds content and antioxidant capacity remains unknown. In addition, no literature is available concerning the bioactive compounds changes in 'Lamuyo' green peppers along its developmental and growth cycle. For this, two different approaches have been carried out, one using twelve different phenological stages (S1 to S12), and in the other, seven different harvest dates (from 27 February to 20 April). Moreover, bioactive compounds changes during 21 days of postharvest storage at 8 °C were investigated. In this study, bioactive compounds (ascorbic acid, dehydroascorbic acid, and total phenolic content) and the total hydrophilic and lipophilic (TAA-H and TAA-L) antioxidant activity were analysed. In addition, total soluble solids, total acidity, individual sugars, and organic acids were determined. Vitamin C levels increased along the phenological stages and harvest dates due to significant increases in ascorbic and dehydroascorbic acid levels. Our results show that the total phenol content decreases as vegetables develop and subsequently increases both as ripening begins and by the last harvest date. Furthermore, TAA-H was also greater by the phenological stage S12 and the 20 April harvest date. In conclusion, the phenological stage and harvest date are key factors that significantly influence the bioactive compounds of green peppers, and those that appear by S12 and 20 April could be more beneficial to health.

The studied samples were prepared from polyethylene (PE) polymer which was coated with modified polycaprolactone (PCL) film in order to obtain bilayer films. Thin PCL film was modified with casein/aluminum oxide compound to enhance vapor permeability as well as mechanical and thermal properties of PE/PCL films. Casein/aluminum oxide modifiers were used in order to achieve some functional properties of polymer film that can be used in various applications, e.g., reduction of water vapor permeability (WVTR) and good mechanical and thermal properties. Significant improvement was observed in mechanical properties, especially in tensile strength as well as in water vapor values. Samples prepared with aluminum oxide particles indicated significantly lower values up to 60%, and samples that were prepared with casein and 5% Al2O3 showed the lowest WVTR value.

Lithium metal batteries are inspiring renewed interest in the battery community because the most advanced designs of Li-ion batteries could be on the verge of reaching their theoretical specific energy density values. Among the investigated alternative technologies for electrochemical storage, the all-solid-state Li battery concept based on the implementation of dry solid polymer electrolytes appears as a mature technology not only to power full electric vehicles but also to provide solutions for stationary storage applications. With an effective marketing started in 2011, BlueSolutions keeps developing further the so-called lithium metal polymer batteries based on this technology. The present study reports the electrochemical performance of such Li metal batteries involving indigo carmine, a cheap and renewable electroactive non-soluble organic salt, at the positive electrode. Our results demonstrate that this active material was able to reversibly insert two Li at an average potential of ≈2.4 V vs. Li+/Li with however, a relatively poor stability upon cycling. Post-mortem analyses revealed the poisoning of the Li electrode by Na upon ion exchange reaction between the Na countercations of indigo carmine and the conducting salt. The use of thinner positive electrodes led to much better capacity retention while enabling the identification of two successive one-electron plateaus.

The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

Sea buckthorn (Hippophaė rhamnoides L.) is recognized as a valuable source of vitamin C and antioxidants, frequently used as nutraceuticals and cosmeceuticals. In the present study, attempts are made to produce and characterize a novel type of marmalade using sea buckthorn berries processed at 102 °C into marmalade in two combinations, with whole cane or stevia sugar. Changes in the phytochemical profile, antioxidant activity, color, shelf-life, texture, microbiological, and sensorial characteristics were determined. The total carotenoids content in the marmalades were significantly different, with values of 0.91 ± 0.03 mg/g dry weight (DW) in the sample with whole sugar cane (Cz) and 2.69 ± 0.14 mg/g DW in the sample with Stevia sugar (Cs). Significant values of polyphenols were found, of 59.41 ± 1.13 mg GAE/g DW in Cz and 72.44 ± 2.31 mg GAE/g DW in Cs, leading to an antioxidant activity of 45.12 ± 0.001 μMol Trolox/g DW and 118.07 ± 0.01 μMol Trolox/g DW, respectively. Accelerated storage study showed a decrease in all the phytochemicals, however no significant changes were found in antioxidant activity. Values of <100 CFU/g for yeasts and molds and <5 CFU/g for Enterobacteriaceae after 21 days of storage at the room temperature of the marmalades were determined. The sensorial and color results were more than acceptable. Overall, the results highlighted the potential of using sea buckthorn as a potential rich source of bioactive compounds to be used in the sugar-based products manufacturing.

Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission at neuromuscular and autonomic ganglionic synapses in the peripheral nervous system. The postsynaptic localization of muscle ((α1)2β1γδ) and neuronal ((α3β4)2β4) nicotinic receptors at these synapses is mediated by interactions between the nAChR intracellular domains and cytoplasmic scaffolding proteins. Recent high resolution structures and functional studies provide new insights into the molecular determinants that mediate these interactions. Surprisingly, they reveal that the muscle nAChR binds 1-3 rapsyn scaffolding molecules, which dimerize and thereby form an interconnected lattice between receptors. Moreover, rapsyn binds two distinct sites on the nAChR subunit cytoplasmic loops; the MA-helix on one or more subunits and a motif specific to the β subunit. Binding at the latter site is regulated by agrin-induced phosphorylation of βY390, and increases the stoichiometry of rapsyn/AChR complexes. Similarly, the neuronal nAChR may be localized at ganglionic synapses by phosphorylation-dependent interactions with 14-3-3 adaptor proteins which bind specific motifs in each of the α3 subunit cytoplasmic loops. Thus, postsynaptic localization of nAChRs is mediated by regulated interactions with multiple scaffolding molecules, and the stoichiometry of these complexes likely helps regulate the number, density, and stability of receptors at the synapse.

New Co(II), Ni(II), and Cu(II) complexes were synthesized with the Schiff base ligand obtained by the condensation of sulfathiazole with salicylaldehyde. Their characterization was performed by elemental analysis, molar conductance, spectroscopic techniques (IR, diffuse reflectance and UV-Vis-NIR), magnetic moments, thermal analysis, and calorimetry (thermogravimetry/derivative thermogravimetry/differential scanning calorimetry), while their morphological and crystal systems were explained on the basis of powder X-ray diffraction results. The IR data indicated that the Schiff base ligand is tridentate coordinated to the metallic ion with two N atoms from azomethine group and thiazole ring and one O atom from phenolic group. The composition of the complexes was found to be of the [ML2]∙nH2O (M = Co, n = 1.5 (1); M = Ni, n = 1 (2); M = Cu, n = 4.5 (3)) type, having an octahedral geometry for the Co(II) and Ni(II) complexes and a tetragonally distorted octahedral geometry for the Cu(II) complex. The presence of lattice water molecules was confirmed by thermal analysis. XRD analysis evidenced the polycrystalline nature of the powders, with a monoclinic structure. The unit cell volume of the complexes was found to increase in the order of (2) < (1) < (3). SEM evidenced hard agglomerates with micrometric-range sizes for all the investigated samples (ligand and complexes). EDS analysis showed that the N:S and N:M atomic ratios were close to the theoretical ones (1.5 and 6.0, respectively). The geometric and electronic structures of the Schiff base ligand 4-((2-hydroxybenzylidene) amino)-N-(thiazol-2-yl) benzenesulfonamide (HL) was computationally investigated by the density functional theory (DFT) method. The predictive molecular properties of the chemical reactivity of the HL and Cu(II) complex were determined by a DFT calculation. The Schiff base and its metal complexes were tested against some bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis). The results indicated that the antibacterial activity of all metal complexes is better than that of the Schiff base.

The Artemisia genus includes a large number of species with worldwide distribution and diverse chemical composition. The secondary metabolites of Artemisia species have numerous applications in the health, cosmetics, and food sectors. Moreover, many compounds of this genus are known for their antimicrobial, insecticidal, parasiticidal, and phytotoxic properties, which recommend them as possible biological control agents against plant pests. This paper aims to evaluate the latest available information related to the pesticidal properties of Artemisia compounds and extracts and their potential use in crop protection. Another aspect discussed in this review is the use of nanotechnology as a valuable trend for obtaining pesticides. Nanoparticles, nanoemulsions, and nanocapsules represent a more efficient method of biopesticide delivery with increased stability and potency, reduced toxicity, and extended duration of action. Given the negative impact of synthetic pesticides on human health and on the environment, Artemisia-derived biopesticides and their nanoformulations emerge as promising ecofriendly alternatives to pest management.

The insecticidal activities of essential oils obtained from black pepper, eucalyptus, rosemary, and tea tree and their binary combinations were investigated against the green peach aphid, Myzus persicae (Aphididae: Hemiptera), under laboratory and glasshouse conditions. All the tested essential oils significantly reduced and controlled the green peach aphid population and caused higher mortality. In this study, black pepper and tea tree pure essential oils were found to be an effective insecticide, with 80% mortality when used through contact application. However, for combinations of essential oils from black pepper + tea tree (BT) and rosemary + tea tree (RT) tested as contact treatment, the mortality was 98.33%. The essential oil combinations exhibited synergistic and additive interactions for insecticidal activities. The combination of black pepper + tea tree, eucalyptus + tea tree (ET), and tea tree + rosemary showed enhanced activity, with synergy rates of 3.24, 2.65, and 2.74, respectively. Essential oils formulation was effective on the mortality of aphids. Fourier Transform Infrared Spectroscopy (FTIR) analysis showed that stability of a mixture of essential oils was not affected by store temperature (15, 25, and 35 °C) and the functional groups were not changed during storage. Based on our results, the essential oils can be used as a commercial insecticide against M. persicae.

Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.

For the removal of arsenic from marine products, iowaite was prepared and investigated to determine the optimal adsorption process of arsenic. Different chemical forms of arsenic (As(III), As(V)) with varying concentrations (0.15, 1.5, 5, 10, 15, and 20 mg/L) under various conditions including pH (3, 5, 7, 9, 11) and contact time (1, 2, 5, 10, 15, 30, 60, 120, 180 min) were exposed to iowaite. Adsorption isotherms and metal ions kinetic modeling onto the adsorbent were determined based on Langmuir, Freundlich, first- and second-order kinetic models. The adsorption onto iowaite varied depending on the conditions. The adsorption rates of standard solution, As(III) and As(V) exceeded 95% under proper conditions, while high complexity was noted with marine samples. As(III) and As(V) from Mactra veneriformis extraction all decreased when exposed to iowaite. The inclusion morphology and interconversion of organic arsenic limit adsorption. Iowaite can be efficiently used for inorganic arsenic removal from wastewater and different marine food products, which maybe other adsorbent or further performance of iowaite needs to be investigated for organic arsenic.

In recent decades, bicyclic nitroxyl radicals have caught chemists' attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.

For the first time, the study of the antioxidant activity, the characterization of the phytoconstituants, and the evaluation of in vitro and in vivo toxicity of A. djiboutiensis leave and latex are performed. The antioxidant activity of both latex (ADL) and the methanolic extract of leaves (ADM) is determined using 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging radical methods and ferric reducing/antioxidant power (FRAP) assay. The phytochemical study of latex is done using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and a molecular networking-based approach. The evaluation of in vivo toxicity is performed on mice by oral gavage with a suspension of ADL. Our results show that weak antioxidant activity of ADL and ADM in opposition to their high polyphenol, 83.01 mg and 46.4 mg expressed in gallic acid equivalent (GAE)/g of dry weight (DW), respectively, and flavonoid contents 13.12 mg and 4.25 mg expressed in quercetin equivalent (QE)/g dry weight (DW), respectively. Using the Global Natural Products Social Molecular Networking (GNPS) website, nine (9) anthraquinones derivatives, ten (10) chromones derivatives, two (2) flavonols/ chromones isomers are annotated in the molecular network. The treated mice do not display abnormalities in their general physical appearance and biochemistry parameters, compared to the controls. Only glucose and calcium levels are slightly higher in male treated mice compared to the vehicles.

The incidence of antibiotic resistance in pathogenic bacteria has become an alarming clinical and social problem. Therefore, the demand for alternative antimicrobial compounds has increased. In this study, a chemical profile of honey bee (Apis mellifera L.) venom (HBV) has been determined by HPLC and FTIR-ATR spectroscopy, and tested for antibacterial activity, as well as efficiency with regard to conventional antibiotics. The investigated HBV was of high quality with melittin and total protein contents of 70.10 ± 7.01%, and 84.44 ± 3.12 g/100 g, respectively. The purity of HBV was confirmed by FTIR-ATR spectral profiling, which revealed a unique pattern of absorption bands that are characteristic of its major fractions. In addition, HBV showed a broad spectrum of activity against all three tested biomasses of potentially pathogenic Gram-positive and Gram-negative bacteria with MIC values ranging between 12.5 and 200 µg/mL, and MBC between 12.5 and 400 µg/mL. When compared to conventional antibiotics, HBV (400 µg) showed up to 27.8% efficiency of tetracycline (30 µg), 52.2% erythromycin (15 µg), 21.2% ciprofloxacin (5 µg), and 34.6% of ampicillin-sulbactam (20 µg). The overall results demonstrate the therapeutic potential of the analyzed HBV.

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure-activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

Amomum Villosum Lour. (A. villosum) is a folk medicine that has been used for more than 1300 years. However, study of the polysaccharides of A. villosum is seriously neglected. The objectives of this study are to explore the structural characteristics of polysaccharides from A. villosum (AVPs) and their effects on immune cells. In this study, the acidic polysaccharides (AVPG-1 and AVPG-2) were isolated from AVPs and purified via anion exchange and gel filtration chromatography. The structural characteristics of the polysaccharides were characterized by methylation, HPSEC-MALLS-RID, HPLC, FT-IR, SEM, GC-MS and NMR techniques. AVPG-1 with a molecular weight of 514 kDa had the backbone of → 4)-α-d-Glcp-(1 → 3,4)-β-d-Glcp-(1 → 4)-α-d-Glcp-(1 →. AVPG-2 with a higher molecular weight (14800 kDa) comprised a backbone of → 4)-α-d-Glcp-(1 → 3,6)-β-d-Galp-(1 → 4)-α-d-Glcp-(1 →. RAW 264.7 cells were used to investigate the potential effect of AVPG-1 and AVPG-2 on macrophages, and lipopolysaccharide (LPS) was used as a positive control. The results from bioassays showed that AVPG-2 exhibited stronger immunomodulatory activity than AVPG-1. AVPG-2 significantly induced nitric oxide (NO) production as well as the release of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and upregulated phagocytic capacities of RAW 264.7 cells. Real-time PCR analysis revealed that AVPG-2 was able to turn the polarization of macrophages to the M1 direction. These results suggested that AVPs could be explored as potential immunomodulatory agents of the functional foods or complementary medicine.

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer's disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC50 = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC50 value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.

In this study, straetlingite-based sorbents were used for NH4+ ion removal from a synthetic aqueous solution and from the wastewater of an open recirculation African catfish farming system. This study was performed using column experiments with four different filtration rates (2, 5, 10, and 15 mL/min). It was determined that breakthrough points and sorption capacity could be affected by several parameters such as flow rate and mineral composition of sorption materials. In the synthetic aqueous solution, NH4+ removal reached the highest sorption capacity, i.e., 0.341 mg/g with the S30 sorbent at a filtration rate of 10 mL/min and an initial concentration of 10 mg/L of NH4+ ions. It is important to emphasize that, in this case, the Ce/C0 ratio of 0.9 was not reached after 420 min of sorption. It was also determined that the NH4+ sorption capacity was influenced by phosphorus. In the wastewater, the NH4+ sorption capacity was almost seven times lower than that in the synthetic aqueous solution. However, it should be highlighted that the P sorption capacity reached 0.512 mg/g. According to these results, it can be concluded that straetlingite-based sorbents can be used for NH4+ ion removal from a synthetic aqueous solution, as well as for both NH4+ and P removal from industrial wastewater. In the wastewater, a significantly higher sorption capacity of the investigated sorbents was detected for P than for NH4+.

Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (Nelumbo nucifera) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group (p < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves (p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (p < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [3H]-flumazenil revealed that quercetin-3-O-glucuronide contained in the lotus leaf extract (77.27 μg/mg of extract) enhanced sleep by binding to GABAA receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-O-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.

Sophorolipids (SLs) are glycolipids that consist of a hydrophilic sophorose head group covalently linked to a hydrophobic fatty acid tail. They are produced by fermentation of non-pathogenic yeasts such as Candida Bombicola. The fermentation products predominantly consist of the diacetylated lactonic form that coexists with the open-chain acidic form. A systematic series of modified SLs were prepared by ring opening of natural lactonic SL with n-alkanols of varying chain length under alkaline conditions and lipase-selective acetylation of sophorose primary hydroxyl groups. The antimicrobial activity of modified SLs against Gram-positive human pathogens was a function of the n-alkanol length, as well as the degree of sophorose acetylation at the primary hydroxyl sites. Modified SLs were identified with promising antimicrobial activities against Gram-positive human pathogens with moderate selectivity (therapeutic index, TI = EC50/MICB. cereus = 6-33). SL-butyl ester exhibited the best antimicrobial activity (MIC = 12 μM) and selectivity (TI = 33) among all SLs tested. Kinetic studies revealed that SL-ester derivatives kill B. cereus in a time-dependent manner resulting in greater than a 3-log reduction in cell number within 1 h at 2×MIC. In contrast, lactonic SL required 3 h to achieve the same efficiency.

Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.

Soy protein isolate (SPI) powders often have poor water solubility, particularly at pH values close to neutral, which is an attribute that is an issue for its incorporation into complex nutritional systems. Therefore, the objective of this study was to improve SPI solubility while maintaining low viscosity. Thus, the intention was to examine the solubility and rheological properties of a commercial SPI powder at pH values of 2.0, 6.9, and 9.0, and determine if heat treatment at acidic or alkaline conditions might positively influence protein solubility, once re-adjusted back to pH 6.9. Adjusting the pH of SPI dispersions from pH 6.9 to 2.0 or 9.0 led to an increase in protein solubility with a concomitant increase in viscosity at 20 °C. Meanwhile, heat treatment at 90 °C significantly improved the solubility at all pH values and resulted in a decrease in viscosity in samples heated at pH 9.0. All SPI dispersions measured under low-amplitude rheological conditions showed elastic-like behaviour (i.e., G' > G″), indicating a weak "gel-like" structure at frequencies less than 10 Hz. In summary, the physical properties of SPI can be manipulated through heat treatment under acidic or alkaline conditions when the protein subunits are dissociated, before re-adjusting to pH 6.9.

Husk and pellicle as the agri-food waste in the walnut-product industry are in soaring demand because of their rich polyphenol content. This study investigated the differential compounds related to walnut polyphenol between husk and pellicle during fruit development stage. By using ultra-high performance liquid chromatography-quadrupole-orbitrap (UHPLC-Q-Orbitrap), a total of 110 bioactive components, including hydrolysable tannins, flavonoids, phenolic acids and quinones, were tentatively identified, 33 of which were different between husk and pellicle. The trend of dynamic content of 16 polyphenols was clarified during walnut development stage by high-performance liquid chromatography (HPLC). This is the first time to comprehensive identification of phenolic compounds in walnut husk and pellicle, and our results indicated that the pellicle is a rich resource of polyphenols. The dynamic trend of some polyphenols was consistent with total phenols. The comprehensive characterization of walnut polyphenol and quantification of main phenolic compounds will be beneficial for understanding the potential application value of walnut and for exploiting its metabolism pathway.

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers' phytochemicals and illustrates their potential role as drugs.

Advanced cervical cancer is primarily managed using cytotoxic therapies, despite evidence of limited efficacy and known toxicity. There is a current lack of alternative therapeutics to treat the disease more effectively. As such, there have been more research endeavors to develop targeted therapies directed at oncogenic host cellular targets over the past 4 decades, but thus far, only marginal gains in survival have been realized. The E6 oncoprotein, a protein of human papillomavirus origin that functionally inactivates various cellular antitumor proteins through protein-protein interactions (PPIs), represents an alternative target and intriguing opportunity to identify novel and potentially effective therapies to treat cervical cancer. Published research has reported a number of peptide and small-molecule modulators targeting the PPIs of E6 in various cell-based models. However, the reported compounds have rarely been well characterized in animal or human subjects. This indicates that while notable progress has been made in targeting E6, more extensive research is needed to accelerate the optimization of leads. In this review, we summarize the current knowledge and understanding of specific E6 PPI inhibition, the progress and challenges being faced, and potential approaches that can be utilized to identify novel and potent PPI inhibitors for cervical cancer treatment.

COVID-19 represents a new potentially life-threatening illness caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pathogen. In 2021, new variants of the virus with multiple key mutations have emerged, such as B.1.1.7, B.1.351, P.1 and B.1.617, and are threatening to render available vaccines or potential drugs ineffective. In this regard, we highlight 3CLpro, the main viral protease, as a valuable therapeutic target that possesses no mutations in the described pandemically relevant variants. 3CLpro could therefore provide trans-variant effectiveness that is supported by structural studies and possesses readily available biological evaluation experiments. With this in mind, we performed a high throughput virtual screening experiment using CmDock and the "In-Stock" chemical library to prepare prioritisation lists of compounds for further studies. We coupled the virtual screening experiment to a machine learning-supported classification and activity regression study to bring maximal enrichment and available structural data on known 3CLpro inhibitors to the prepared focused libraries. All virtual screening hits are classified according to 3CLpro inhibitor, viral cysteine protease or remaining chemical space based on the calculated set of 208 chemical descriptors. Last but not least, we analysed if the current set of 3CLpro inhibitors could be used in activity prediction and observed that the field of 3CLpro inhibitors is drastically under-represented compared to the chemical space of viral cysteine protease inhibitors. We postulate that this methodology of 3CLpro inhibitor library preparation and compound prioritisation far surpass the selection of compounds from available commercial "corona focused libraries".

The reaction of the redox active 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-BIAN) and iron(II) iodide in acetonitrile led to a new complex [(dpp-BIAN)FeIII2] (1). Molecular structure of 1 was determined by the single crystal X-ray diffraction analysis. The spin state of the iron cation in complex 1 at room temperature and the magnetic behavior of 1 in the temperature range of 2-300 K were studied using Mossbauer spectroscopy and magnetic susceptibility measurements, respectively. The neutral character of dpp-BIAN in 1 was confirmed by IR and UV spectroscopy. The electrochemistry of 1 was studied in solution and solid state using cyclic voltammetry. The generation of the radical anion form of the dpp-BIAN ligand upon reduction of 1 in a CH2Cl2 solution was monitored by EPR spectroscopy.

Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.

Escherichia coli colonies were grown on different supports for the removal of nitrates from water. A carbon material and different commercial metal oxides, such as SiO2, TiO2 and Al2O3, and their corresponding carbon-metal oxide composites were studied. The physicochemical properties were analyzed by different techniques and the results were correlated with their performance in the denitrification process. Developed biofilms effectively adhere to the supports and always reach the complete reduction of nitrates to gaseous products. Nevertheless, faster processes occur when the biofilm is supported on mesoporous and non-acid materials (carbon and silica).

Optically active polymers are promising multifunctional materials with great application potentials. Herein, environmentally friendly optically active polyurethanes (OPUs) were obtained by introducing rotatory binaphthol monomer to polyurethane. The influence of binaphthol monomer content on the structure, mechanical properties, infrared emissivity, and thermal insulation of OPUs was studied intensively. Structure characterization indicated that the optically active polyurethanes have been successfully synthesized. The OPU synthesized with BIMOL and BDO at the mole ratio of 1:1 presented better thermal resistance. In addition, OPUs showed enhanced tensile strength and stretchability with the increase of BINOL content to a certain extent due to its rigid structural features and high molecular weight. The optically active polyurethanes showed lower infrared emissivity values (8-14 μm) than waterborne polyurethane (WPU), and the infrared emissivity decreased from 0.850 to 0.572 as the content of the BINOL monomer increased. Moreover, OPU4 exhibited the best heat insulation and cooling ability with about a 7 °C temperature difference. The thus-synthesized optically active polyurethanes provide an effective solution for developing highly effective thermal insulation materials.

Microorganisms are highly regarded as a prominent source of natural products that have significant importance in many fields such as medicine, farming, environmental safety, and material production. Due to this, only tiny amounts of microorganisms can be cultivated under standard laboratory conditions, and the bulk of microorganisms in the ecosystems are still unidentified, which restricts our knowledge of uncultured microbial metabolism. However, they could hypothetically provide a large collection of innovative natural products. Culture-independent metagenomics study has the ability to address core questions in the potential of NP production by cloning and analysis of microbial DNA derived directly from environmental samples. Latest advancements in next generation sequencing and genetic engineering tools for genome assembly have broadened the scope of metagenomics to offer perspectives into the life of uncultured microorganisms. In this review, we cover the methods of metagenomic library construction, and heterologous expression for the exploration and development of the environmental metabolome and focus on the function-based metagenomics, sequencing-based metagenomics, and single-cell metagenomics of uncultured microorganisms.

The functionalization of the arsenic transfer reagent [Cp″2Zr(η1:1-As4)] (1) focuses on modifying its properties and enabling a broader scope of reactivity. The coordination behavior of 1 towards different Lewis-acidic transition metal complexes and main group compounds is investigated by experimental and computational studies. Depending on the steric requirements of the Lewis acids and the reaction temperature, a variety of new complexes with different coordination modes and coordination numbers could be synthesized. Depending on the Lewis acid (LA) used, a mono-substitution in [Cp″2Zr(µ,η1:1:1:1-As4)(LA)] (LA = Fe(CO)4 (4); B(C6F5)3 (7)) and [Cp″2Zr(µ,η3:1:1-As4)(Fe(CO)3)] (5) or a di-substitution [Cp″2Zr(µ3,η1:1:1:1-As4)(LA)2] (LA = W(CO)5 (2); CpMn(CO)2 (3); AlR3 (6, R = Me, Et, iBu)) are monitored. In contrast to other coordination products, 5 shows an η3 coordination in which the butterfly As4 ligand is rearranged to a cyclo-As4 ligand. The reported complexes are rationalized in terms of inverse coordination.

Ultrafast laser drilling has been proven to effectively reduce the heat-affected zone (HAZ) of carbon fiber-reinforced polymer (CFRP) composites. However, previous research mainly focused on the effects of picosecond laser parameters on CFRP drilling. Compared with a picosecond laser, a femtosecond laser can achieve higher quality CFRP drilling due to its smaller pulse width, but there are few studies on the effects of femtosecond laser parameters on CFRP drilling. Moreover, the cross-sectional taper of CFRP produced by laser drilling is very large. This paper introduces the use of the femtosecond laser to drill cylindrical holes in CFRP. The effect of laser power, rotational speed of the laser, and number of spiral passes on HAZ and ablation depth in circular laser drilling and spiral laser drilling mode was studied, respectively. It also analyzed the forming process of the drilling depth in the spiral drilling mode and studied the influence of laser energy and drilling feed depth on the holes' diameters and the taper. The experimental results show that the cylindrical hole of CFRP with a depth-to-diameter ratio of about 3:1 (taper < 0.32∘, HAZ < 10 m) was obtained by using femtosecond laser and a spiral drilling apparatus.

Dental calculus analysis can be a valuable source of archaeological knowledge, since it preserves not only microbial and host biomolecules but also dietary and environmental debris, as well as metabolic products likely originating from dietary and craft activities. Here we described GC-MS analysis of a set of historic dental calculus samples from the front teeth of the mandibles of seven individuals found in 17th- and 18th-century graves in the city of Rzeszow, located in South-eastern Poland. We have found that only saturated fatty acids, which are characteristic for fats of animal origin, were present in the tested samples. Our preliminary results indicate that the diet of modern-period inhabitants of Rzeszow was rich in animal products, such as meat and dairy products.

Safety and quality are key issues for the food industry. Consequently, there is growing demand to preserve the food chain and products against substances toxic, harmful to human health, such as contaminants, allergens, toxins, or pathogens. For this reason, it is mandatory to develop highly sensitive, reliable, rapid, and cost-effective sensing systems/devices, such as electrochemical sensors/biosensors. Generally, conventional techniques are limited by long analyses, expensive and complex procedures, and skilled personnel. Therefore, developing performant electrochemical biosensors can significantly support the screening of food chains and products. Here, we report some of the recent developments in this area and analyze the contributions produced by electrochemical biosensors in food screening and their challenges.

Natural peptides are an important class of chemical mediators, essential for most vital processes. What limits the potential of the use of peptides as drugs is their low bioavailability and enzymatic degradation in vivo. To overcome this limitation, the development of new molecules mimicking peptides is of great importance for the development of new biologically active molecules. Therefore, replacing the amide bond in a peptide with a heterocyclic bioisostere, such as the 1,2,3-triazole ring, can be considered an effective solution for the synthesis of biologically relevant peptidomimetics. These 1,2,3-triazoles may have an interesting biological activity, because they behave as rigid link units, which can mimic the electronic properties of amide bonds and show bioisosteric effects. Additionally, triazole can be used as a linker moiety to link peptides to other functional groups.

The existence of a K+ cycle in mitochondria has been predicted since the development of the chemiosmotic theory and has been shown to be crucial for several cellular phenomena, including regulation of mitochondrial volume and redox state. One of the pathways known to participate in K+ cycling is the ATP-sensitive K+ channel, MitoKATP. This channel was vastly studied for promoting protection against ischemia reperfusion when pharmacologically activated, although its molecular identity remained unknown for decades. The recent molecular characterization of MitoKATP has opened new possibilities for modulation of this channel as a mechanism to control cellular processes. Here, we discuss different strategies to control MitoKATP activity and consider how these could be used as tools to regulate metabolism and cellular events.

The dimeric dihydropyrimidine dehydrogenase (DPD), metalloenzyme, an adjunct anti-cancer drug target, contains highly specialized 4 × Fe2+4S2-4 clusters per chain. These clusters facilitate the catalysis of the rate-limiting step in the pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers a redox catabolic reaction. In the process, the bulk of the administered 5-fluorouracil (5-FU) cancer drug is inactivated, while a small proportion is activated to nucleic acid antimetabolites. The occurrence of missense mutations in DPD protein within the general population, including those of African descent, has adverse toxicity effects due to altered 5-FU metabolism. Thus, deciphering mutation effects on protein structure and function is vital, especially for precision medicine purposes. We previously proposed combining molecular dynamics (MD) and dynamic residue network (DRN) analysis to decipher the molecular mechanisms of missense mutations in other proteins. However, the presence of Fe2+4S2-4 clusters in DPD poses a challenge for such in silico studies. The existing AMBER force field parameters cannot accurately describe the Fe2+ center coordination exhibited by this enzyme. Therefore, this study aimed to derive AMBER force field parameters for DPD enzyme Fe2+ centers, using the original Seminario method and the collation features Visual Force Field Derivation Toolkit as a supportive approach. All-atom MD simulations were performed to validate the results. Both approaches generated similar force field parameters, which accurately described the human DPD protein Fe2+4S2-4 cluster architecture. This information is crucial and opens new avenues for in silico cancer pharmacogenomics and drug discovery related research on 5-FU drug efficacy and toxicity issues.

Cherries are rich in bioactive phenolic compounds and are often fermented into cherry wines. The degradation of anthocyanins during storage will cause color deterioration. The study aimed to utilize sinapic acid and grape tannins in cherry wine to maintain a high fraction in the colored forms of anthocyanins, in order to maximize the color intensity, the latter being associated with good product quality. The effects on the anthocyanin profile and on color parameters of copigments, utilizing spectral measurement combined with UPLC-MS quantitative analysis, have been evaluated in sweet cherry wines. The copigmentation effect of sinapic acid and grape tannin was accompanied by the bathochromic shift and the hyperchromic effect, which lead to an increase in color intensity (lower L*, higher a* and b*). During the aging process, sinapic and grape tannin increased the content of pyranoanthocyanins in cherry wine, especially the addition of sinapic acid makes the cherry wine generate 10-syringyl-pyranocyanidin-3-rutinoside. These results demonstrate that sinapic acid is suitable for adding before alcohol fermentation, while grape tannins can be added before aging.

Singlet fission, a multiple exciton generation process, can revolutionize existing solar cell technologies. Offering the possibility to double photocurrent, the process has become a focal point for physicists, chemists, software developers, and engineers. The following review is dedicated to the female investigators, predominantly theorists, who have contributed to the field of singlet fission. We highlight their most significant advances in the subject, from deciphering the mechanism of the process to designing coveted singlet fission materials.

Coleus amboinicus Lour., Lamiaceae, is a perennial herb that is native to Indonesia and also cultivated in Africa, Asia and Australia. The major phytochemicals responsible for its bioactivity are rosmarinic acid (RA) and its analogues, flavonoids and abietane diterpenoids. The possibility of cultivation in a colder climate would extend the use of this herb and provide new opportunities to herb growers and livestock farmers. Our study to compare feed value and phytochemical composition of C. amboinicus plants cultivated in its original region, Indonesia, and in Poland. The crude protein content was significantly higher in plants cultivated in Indonesia compared to those cultivated in Poland-21% and 13% of dry matter, respectively. The higher ADF contents were detected in C. amboinicus cultivated in Indonesia, 38-41%, in comparison to 34% in plants cultivated in Poland. The phytochemical composition was also significantly influenced by the cultivation location. Polish samples were higher in polyphenols (RA and its analogues), and also had 1.5-2-fold higher antioxidant potential, as measured by DPPH scavenging, phosphomolybdenum reduction and Fenton reaction driven lipid peroxidation. The Indonesian samples contained more diterpenoid compounds, such as dihydroxyroyleanone, and the sum of terpenoids was ca. 10 times higher than in samples from Poland (15.59-23.64 vs. 1.87 µg/g of extracts). In conclusion, C. amboinicus is suitable for cultivation in non-optimal climatic conditions but some nutritional properties and bioactivity are significantly affected.

A convergent synthetic route to a tetrasaccharide related to PI-88, which allows the incorporation of a fluorescent BODIPY-label at the reducing-end, has been developed. The strategy, which features the use of 1,2-methyl orthoesters (MeOEs) as glycosyl donors, illustrates the usefulness of suitably-designed BODIPY dyes as glycosyl labels in synthetic strategies towards fluorescently-tagged oligosaccharides.

N-Aminophthalimides and phthalazine 1,4-diones were synthesized from isobenzofuran-1,3-dione, isoindoline-1,3-dione, furo [3,4-b] pyrazine-5,7-dione, or 1H-pyrrolo [3,4-c] pyridine-1,3-dione with monohydrate hydrazine to carry out the 5-exo or 6-endo nitrogen cyclization under the different reaction conditions. Based on the control experimental results, 6-endo thermodynamic hydrohydrazination and kinetical 5-exo cyclization reactions were individually selective formation. Subsequently, Vilsmeier amidination derivatization was successfully developed to probe the structural divergence between N-aminophthalimide 2 and phthalazine 1,4-dione 3. On the other hand, the best tautomerization of N-aminophthalimide to diazinone was also determined under acetic acid mediated solution.

Diabetes mellitus (DM) is cited as a serious worldwide health problem that occupies second place in causes of annual mortality in Mexico. Among Mexican flora, nearly 300 plant species have been employed as hypoglycemic in popular use. Thus, their study entertains great relevance In this context, this work contributes a clear and timely review of the plant species utilized in Traditional Mexican Medicine and experimental biological models in which not only have the hypoglycemic properties of the extracts and the isolated compounds been considered, but also the anti-inflammatory and antioxidant properties, taking into account an integral focus based on the complex mechanisms involved in the pathogenesis and physiopathology of DM. Among the species reviewed, we highlight Psacalium decompositum (Asteraceae), due to the potent hypoglycemic, anti-inflammatory, and antioxidant activity of the sesquiterpenes identified as majority compounds isolated from the root, such as cacalol and cacalone that also possess the capacity of increasing insulin levels. In this manner, the present manuscript attempts to contribute necessary information for the future study of bioactive molecules that are useful in the treatment of DM, as well as also being a contribution to the knowledge and diffusion of Mexican Traditional Medicine.

Alzheimer's disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (Aβ) triggers the disease. Aβ accumulates at the points of contact of neurons in ordered cords and fibrils, forming the so-called senile plaques. Aβ isoforms of different lengths are found in healthy human brains regardless of age and appear to play a role in signaling pathways in the brain and to have neuroprotective properties at low concentrations. In recent years, different substances have been developed targeting Aβ production, aggregation, interaction with other molecules, and clearance, including peptide-based drugs. Aβ is a product of sequential cleavage of the membrane glycoprotein APP (amyloid precursor protein) by β- and γ-secretases. A number of familial mutations causing an early onset of the disease have been identified in the APP, especially in its transmembrane domain. The mutations are reported to influence the production, oligomerization, and conformational behavior of Aβ peptides. This review highlights the results of structural studies of the main proteins involved in Alzheimer's disease pathogenesis and the molecular mechanisms by which perspective therapeutic substances can affect Aβ production and nucleation.

The development of greener nano-constructs with noteworthy biological activity is of supreme interest, as a robust choice to minimize the extensive use of synthetic drugs. Essential oils (EOs) and their constituents offer medicinal potentialities because of their extensive biological activity, including the inhibition of fungi species. However, their application as natural antifungal agents are limited due to their volatility, low stability, and restricted administration routes. Nanotechnology is receiving particular attention to overcome the drawbacks of EOs such as volatility, degradation, and high sensitivity to environmental/external factors. For the aforementioned reasons, nanoencapsulation of bioactive compounds, for instance, EOs, facilitates protection and controlled-release attributes. Nanoliposomes are bilayer vesicles, at nanoscale, composed of phospholipids, and can encapsulate hydrophilic and hydrophobic compounds. Considering the above critiques, herein, we report the in-house fabrication and nano-size characterization of bioactive oregano essential oil (Origanum vulgare L.) (OEO) molecules loaded with small unilamellar vesicles (SUV) nanoliposomes. The study was focused on three main points: (1) multi-compositional fabrication nanoliposomes using a thin film hydration-sonication method; (2) nano-size characterization using various analytical and imaging techniques; and (3) antifungal efficacy of as-developed OEO nanoliposomes against Trichophyton rubrum (T. rubrum) by performing the mycelial growth inhibition test (MGI). The mean size of the nanoliposomes was around 77.46 ± 0.66 nm and 110.4 ± 0.98 nm, polydispersity index (PdI) of 0.413 ± 0.015, zeta potential values up to -36.94 ± 0.36 mV were obtained by dynamic light scattering (DLS). and spherical morphology was confirmed by scanning electron microscopy (SEM). The presence of OEO into nanoliposomes was displayed by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. Entrapment efficiency values of 79.55 ± 6.9% were achieved for OEO nanoliposomes. In vitro antifungal activity of nanoliposomes tested against T. rubrum strains revealed that OEO nanoliposomes exhibited the highest MGI, 81.66 ± 0.86%, at a concentration of 1.5 µL/mL compared to the rest of the formulations. In summary, this work showed that bioactive OEO molecules with loaded nanoliposomes could be used as natural antifungal agents for therapeutical purposes against T. rubrum.

Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: -17.65 kcal mol-1 (D6), -18.07 kcal mol-1 (D2), -18.13 (D5) kcal mol-1, and -10.31 kcal mol-1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (-12.84 kcal mol-1) and L-tyrosine (-9.04 kcal mol-1) in melanogenesis.

In the present work, the dielectric properties of recycled liquid crystals (LCs) (non-purified, purified, and doped with diamond nanoparticles at 0.05, 0.1, and 0.2 wt%) were investigated. The studied LC mixtures were obtained from industrial recycling of end-of-life LC displays presenting mainly nematic phases. Dielectric measurements were carried out at room temperature on a frequency range from 0.1 to 106 Hz using an impedance analyzer. The amplitude of the oscillating voltage was fixed at 1 V using cells with homogeneous and homeotropic alignments. Results show that the dielectric anisotropy of all purified samples presents positive values and decreases after the addition of diamond nanoparticles to the LC mixtures. DC conductivity values were obtained by applying the universal law of dielectric response proposed by Jonscher. In addition, conductivity of the doped LC mixtures is lower than that of the undoped and non-purified LC.

Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditionally in the treatment of trauma and neuralgia. In this study, we investigated the neuroinflammatory effect of methanol extract of L. obtusiloba stem (LOS-ME) in a scopolamine-induced amnesia model and lipopolysaccharide (LPS)-stimulated BV2 microglia cells. LOS-ME downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, inflammatory cytokines, and inhibited the phosphorylation of nuclear factor kappa-B (NF-ĸB) and extracellular signal-regulated kinase (ERK) in LPS-stimulated BV2 cells. Male C57/BL6 mice were orally administered 20 and 200 mg/kg of LOS-ME for one week, and 2 mg/kg of scopolamine was administered intraperitoneally on the 8th day. In vivo behavioral experiments (Y-maze and Morris water maze test) confirmed that LOS-ME alleviated cognitive impairments induced by scopolamine and the amount of iNOS expression decreased in the hippocampus of the mouse brain. Microglial hyper-activation was also reduced by LOS-ME pretreatment. These findings suggest that LOS-ME might have potential in the treatment for cognitive improvement by regulating neuroinflammation.

Stable, oil-in-water nanoemulsions containing astaxanthin (AsX) were produced by intense fluid shear forces resulting from pumping a coarse reagent emulsion through a self-throttling annular gap valve at 300 MPa. Compared to crude emulsions prepared by conventional homogenization, a size reduction of over two orders of magnitude was observed for AsX-encapsulated oil droplets following just one pass through the annular valve. In krill oil formulations, the mean hydrodynamic diameter of lipid particles was reduced to 60 nm after only two passes through the valve and reached a minimal size of 24 nm after eight passes. Repeated processing of samples through the valve progressively decreased lipid particle size, with an inflection in the rate of particle size reduction generally observed after 2-4 passes. Krill- and argan oil-based nanoemulsions were produced using an Ultra Shear Technology™ (UST™) approach and characterized in terms of their small particle size, low polydispersity, and stability.

We study the application of Optimal Control Theory to Ion Cyclotron Resonance. We test the validity and the efficiency of this approach for the robust excitation of an ensemble of ions with a wide range of cyclotron frequencies. Optimal analytical solutions are derived in the case without any pulse constraint. A gradient-based numerical optimization algorithm is proposed to take into account limitation in the control intensity. The efficiency of optimal pulses is investigated as a function of control time, maximum amplitude and range of excited frequencies. A comparison with adiabatic and SWIFT pulses is done. On the basis of recent results in Nuclear Magnetic Resonance, this study highlights the potential usefulness of optimal control in Ion Cyclotron Resonance.

The modification of medical devices is an area that has attracted a lot of attention in recent years; particularly, those developments which search to modify existing devices to render them antimicrobial. Most of these modifications involve at least two stages (modification of the base material with a polymer graft and immobilization of an antimicrobial agent) which are both time-consuming and complicate synthetic procedures; therefore, as an improvement, this project sought to produce antimicrobial silicone (PDMS) in a single step. Using gamma radiation as both an energy source for polymerization initiation and as a source of reducing agents in solution, PDMS was simultaneously grafted with acrylic acid and ethylene glycol dimethacrylate (AAc:EGDMA) while producing antimicrobial silver nanoparticles (AgNPs) onto the surface of the material. To obtain reproducible materials, experimental variables such as the effect of the dose, the intensity of radiation, and the concentration of the silver salt were evaluated, finding the optimal reaction conditions to obtain materials with valuable properties. The characterization of the material was performed using electronic microscopy and spectroscopic techniques such as 13C-CPMAS-SS-NMR and FTIR. Finally, these materials demonstrated good antimicrobial activity against S. aureus while retaining good cell viabilities (above 90%) for fibroblasts BALB/3T3.

Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) monitoring competitive binding between fluorescent tracers and unmodified test compounds has emerged as a robust and sensitive method to quantify ligand engagement with specific GPCRs genetically fused to NanoLuc luciferase or the luminogenic HiBiT peptide. However, development of fluorescent tracers is often challenging and remains the principal bottleneck for this approach. One way to alleviate the burden of developing a specific tracer for each receptor is using promiscuous tracers, which is made possible by the intrinsic specificity of BRET. Here, we devised an integrated tracer discovery workflow that couples machine learning-guided in silico screening for scaffolds displaying promiscuous binding to GPCRs with a blend of synthetic strategies to rapidly generate multiple tracer candidates. Subsequently, these candidates were evaluated for binding in a NanoBRET ligand-engagement screen across a library of HiBiT-tagged GPCRs. Employing this workflow, we generated several promiscuous fluorescent tracers that can effectively engage multiple GPCRs, demonstrating the efficiency of this approach. We believe that this workflow has the potential to accelerate discovery of NanoBRET fluorescent tracers for GPCRs and other target classes.

Paratuberculosis is an important disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Early detection is crucial for successful infection control, but available diagnostic tests are still dissatisfying. Methods allowing a rapid, economic, and reliable identification of animals or herds affected by MAP are urgently required. This explorative study evaluated the potential of volatile organic compounds (VOCs) to discriminate between cattle with and without MAP infections. Headspaces above fecal samples and alveolar fractions of exhaled breath of 77 cows from eight farms with defined MAP status were analyzed in addition to stable air samples. VOCs were identified by GC-MS and quantified against reference substances. To discriminate MAP-positive from MAP-negative samples, VOC feature selection and random forest classification were performed. Classification models, generated for each biological specimen, were evaluated using repeated cross-validation. The robustness of the results was tested by predicting samples of two different sampling days. For MAP classification, the different biological matrices emitted diagnostically relevant VOCs of a unique but partly overlapping pattern (fecal headspace: 19, alveolar gas: 11, stable air: 4-5). Chemically, relevant compounds belonged to hydrocarbons, ketones, alcohols, furans, and aldehydes. Comparing the different biological specimens, VOC analysis in fecal headspace proved to be most reproducible, discriminatory, and highly predictive.

Steroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter's imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which, Irosustat (STX64, 667Coumate, BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and ovarian cancer, and in treating endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess aromatase-STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of hormone-dependent cancers and possibly other non-oncological conditions.

Men with early-onset androgenetic alopecia are characterized by hormonal profiles similar to those observed in women with polycystic ovary syndrome. The purpose of this research was to investigate levels of cardiometabolic risk factors in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-treated men with early-onset androgenic alopecia. We studied two matched rosuvastatin-treated groups of men with mixed dyslipidemia: subjects with early-onset androgenic alopecia (group A) and subjects with normal hair growth (group B). Plasma lipids, glucose homeostasis markers, and levels of sex hormones, uric acid, hsCRP, homocysteine, fibrinogen, and 25-hydroxyvitamin D were measured before entering the study and six months later. Both groups differed in insulin sensitivity and levels of calculated bioavailable testosterone, dehydroepiandrosterone-sulfate, uric acid, hsCRP, fibrinogen, and 25-hydroxyvitamin D. Though observed in both study groups, treatment-induced reductions in total cholesterol, LDL cholesterol, hsCRP, and fibrinogen were more pronounced in group B than group A. Moreover, only in group A did rosuvastatin deteriorate insulin sensitivity, and only in group B did the drug affect uric acid, homocysteine, and 25-hydroxyvitamin D. The impact of rosuvastatin on cardiometabolic risk factors correlated with insulin sensitivity, calculated bioavailable testosterone, and dehydroepiandrosterone-sulfate. The obtained results suggest that men with early-onset androgenic alopecia may benefit to a lesser degree from rosuvastatin treatment than their peers.

All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer's disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood-brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood-brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.

Phosphinic and phosphonic acids are useful intermediates and biologically active compounds which may be prepared from their esters, phosphinates and phosphonates, respectively, by hydrolysis or dealkylation. The hydrolysis may take place both under acidic and basic conditions, but the C-O bond may also be cleaved by trimethylsilyl halides. The hydrolysis of P-esters is a challenging task because, in most cases, the optimized reaction conditions have not yet been explored. Despite the importance of the hydrolysis of P-esters, this field has not yet been fully surveyed. In order to fill this gap, examples of acidic and alkaline hydrolysis, as well as the dealkylation of phosphinates and phosphonates, are summarized in this review.

Wine metabolomics constitutes a powerful discipline towards wine authenticity assessment through the simultaneous exploration of multiple classes of compounds in the wine matrix. Over the last decades, wines from autochthonous Greek grape varieties have become increasingly popular among wine connoisseurs, attracting great interest for their authentication and chemical characterization. In this work, 46 red wine samples from Agiorgitiko and Xinomavro grape varieties were collected from wineries in two important winemaking regions of Greece during two consecutive vintages and analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QToF-MS). A targeted metabolomics methodology was developed, including the determination and quantification of 28 phenolic compounds from different classes (hydroxycinnamic acids, hydroxybenzoic acids, stilbenes and flavonoids). Moreover, 86 compounds were detected and tentatively identified via a robust suspect screening workflow using an in-house database of 420 wine related compounds. Supervised chemometric techniques were employed to build an accurate and robust model to discriminate between two varieties.

The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3'-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of Elavl4-/- (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3'-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders.

Cooperative supramolecular polymerization of π-conjugated compounds into one-dimensional nanostructures has received tremendous attentions in recent years. It is commonly achieved by incorporating amide linkages into the monomeric structures, which provide hydrogen bonds for intermolecular non-covalent complexation. Herein, the effect of amide linkages is elaborately studied, by comparing supramolecular polymerization behaviors of two structurally similar monomers with the same platinum(II) acetylide cores. As compared to the N-phenyl benzamide linkages, N-[(1S)-1-phenylethyl] benzamide linkages give rise to effective chirality transfer behaviors due to the closer distances between the chiral units and the platinum(II) acetylide core. They also provide stronger intermolecular hydrogen bonding strength, which consequently brings higher thermo-stability and enhanced gelation capability for the resulting supramolecular polymers. Supramolecular polymerization is further strengthened by varying the monomers from monotopic to ditopic structures. Hence, with the judicious modulation of structural parameters, the current study opens up new avenues for the rational design of supramolecular polymeric systems.

Artemisia jordanica (AJ) is one of the folkloric medicinal plants and grows in the arid condition used by Palestinian Bedouins in the Al-Naqab desert for the treatment of diabetes and gastrointestinal infections. The current investigation aimed, for the first time, to characterize the (AJ) essential oil (EO) components and evaluate EO's antioxidant, anti-obesity, antidiabetic, antimicrobial, anti-inflammatory, and cytotoxic activities. The gas chromatography-mass spectrometer (GC-MS) technique was utilized to characterize the chemical ingredients of (AJ) EO, while validated biochemical approaches were utilized to evaluate the antioxidant, anti-obesity and antidiabetic. The microbicidal efficacy of (AJ) EO was measured utilizing the broth microdilution assay. Besides, the cytotoxic activity was estimated utilizing the (MTS) procedure. Finally, the anti-inflammatory activity was measured utilizing a COX inhibitory screening test kit. The analytical investigation revealed the presence of 19 molecules in the (AJ) EO. Oxygenated terpenoids, including bornyl acetate (63.40%) and endo-borneol (17.75%) presented as major components of the (AJ) EO. The EO exhibited potent antioxidant activity compared with Trolox, while it showed a weak anti-lipase effect compared with orlistat. In addition, the tested EO displayed a potent α-amylase suppressing effect compared with the positive control acarbose. Notably, the (AJ) EO exhibited strong α-glucosidase inhibitory potential compared with the positive control acarbose. The EO had has a cytotoxic effect against all the screened tumor cells. In fact, (AJ) EO showed potent antimicrobial properties. Besides, the EO inhibited the enzymes COX-1 and COX-2, compared with the anti-inflammatory drug ketoprofen. The (AJ) EO has strong antioxidant, antibacterial, antifungal, anti-α-amylase, anti-α-glucosidase, and COX inhibitory effects which could be a favorite candidate for the treatment of various neurodegenerative diseases caused by harmful free radicals, microbial resistance, diabetes, and inflammations. Further in-depth investigations are urgently crucial to explore the importance of such medicinal plants in pharmaceutical production.

The peel color is an important external quality of melon fruit. To explore the mechanisms of melon peel color formation, we performed an integrated analysis of transcriptome and metabolome with three different fruit peel samples (grey-green 'W', dark-green 'B', and yellow 'H'). A total of 40 differentially expressed flavonoids were identified. Integrated transcriptomic and metabolomic analyses revealed that flavonoid biosynthesis was associated with the fruit peel coloration of melon. Twelve differentially expressed genes regulated flavonoids synthesis. Among them, nine (two 4CL, F3H, three F3'H, IFS, FNS, and FLS) up-regulated genes were involved in the accumulation of flavones, flavanones, flavonols, and isoflavones, and three (2 ANS and UFGT) down-regulated genes were involved in the accumulation of anthocyanins. This study laid a foundation to understand the molecular mechanisms of melon peel coloration by exploring valuable genes and metabolites.

Homogeneous olefin polymerization catalysts are activated in situ with a co-catalyst ([PhN(Me)2-H]+[B(C6F5)4]- or [Ph3C]+[B(C6F5)4]-) in bulk polymerization media. These co-catalysts are insoluble in hydrocarbon solvents, requiring excess co-catalyst (>3 eq.). Feeding the activated species as a solution in an aliphatic hydrocarbon solvent may be advantageous over the in situ activation method. In this study, highly pure and soluble ammonium tetrakis(pentafluorophenyl)borates ([Me(C18H37)2N-H]+[B(C6F5)4]- and [(C18H37)2NH2]+[B(C6F5)4]-) containing neither water nor Cl- salt impurities were prepared easily via the acid-base reaction of [PhN(Me)2-H]+[B(C6F5)4]- and the corresponding amine. Using the prepared ammonium salts, the activation reactions of commercial-process-relevant metallocene (rac-[ethylenebis(tetrahydroindenyl)]Zr(Me)2 (1-ZrMe2), [Ph2C(Cp)(3,6-tBu2Flu)]Hf(Me)2 (3-HfMe2), [Ph2C(Cp)(2,7-tBu2Flu)]Hf(Me)2 (4-HfMe2)) and half-metallocene complexes ([(η5-Me4C5)Si(Me)2(κ-NtBu)]Ti(Me)2 (5-TiMe2), [(η5-Me4C5)(C9H9(κ-N))]Ti(Me)2 (6-TiMe2), and [(η5-Me3C7H1S)(C10H11(κ-N))]Ti(Me)2 (7-TiMe2)) were monitored in C6D12 with 1H NMR spectroscopy. Stable [L-M(Me)(NMe(C18H37)2)]+[B(C6F5)4]- species were cleanly generated from 1-ZrMe2, 3-HfMe2, and 4-HfMe2, while the species types generated from 5-TiMe2, 6-TiMe2, and 7-TiMe2 were unstable for subsequent transformation to other species (presumably, [L-Ti(CH2N(C18H37)2)]+[B(C6F5)4]--type species). [L-TiCl(N(H)(C18H37)2)]+[B(C6F5)4]--type species were also prepared from 5-TiCl(Me) and 6-TiCl(Me), which were newly prepared in this study. The prepared [L-M(Me)(NMe(C18H37)2)]+[B(C6F5)4]--, [L-Ti(CH2N(C18H37)2)]+[B(C6F5)4]--, and [L-TiCl(N(H)(C18H37)2)]+[B(C6F5)4]--type species, which are soluble and stable in aliphatic hydrocarbon solvents, were highly active in ethylene/1-octene copolymerization performed in aliphatic hydrocarbon solvents.

Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Extending previous work, here we screened a panel of 245 chemically-diverse small molecules for anti-parasitic activity against Haemonchus contortus-an economically important parasitic nematode of livestock. This panel was screened in vitro against exsheathed third-stage larvae (xL3) of H. contortus using an established phenotypic assay, and the potency of select compounds to inhibit larval motility and development assessed in dose-response assays. Of the 245 compounds screened, three-designated MPK18, MPK334 and YAK308-induced non-wildtype larval phenotypes and repeatedly inhibited xL3-motility, with IC50 values of 45.2 µM, 17.1 µM and 52.7 µM, respectively; two also inhibited larval development, with IC50 values of 12.3 µM (MPK334) and 6.5 µM (YAK308), and none of the three was toxic to human liver cells (HepG2). These findings suggest that these compounds deserve further evaluation as nematocidal candidates. Future work should focus on structure-activity relationship (SAR) studies of these chemical scaffolds, and assess the in vitro and in vivo efficacies and safety of optimised compounds against adults of H. contortus.

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins.

Research on nanomaterial exposure-related health risks is still quite limited; this includes standardizing methods for measuring metals in living organisms. Thus, this study validated an atomic absorption spectrophotometry method to determine fertility and bioaccumulated iron content in Drosophila melanogaster flies after feeding them magnetite nanoparticles (Fe3O4NPs) dosed in a culture medium (100, 250, 500, and 1000 mg kg-1). Some NPs were also coated with chitosan to compare iron assimilation. Considering both accuracy and precision, results showed the method was optimal for concentrations greater than 20 mg L-1. Recovery values were considered optimum within the 95-105% range. Regarding fertility, offspring for each coated and non-coated NPs concentration decreased in relation to the control group. Flies exposed to 100 mg L-1 of coated NPs presented the lowest fertility level and highest bioaccumulation factor. Despite an association between iron bioaccumulation and NPs concentration, the 500 mg L-1 dose of coated and non-coated NPs showed similar iron concentrations to those of the control group. Thus, Drosophila flies' fertility decreased after NPs exposure, while iron bioaccumulation was related to NPs concentration and coating. We determined this method can overcome sample limitations and biological matrix-associated heterogeneity, thus allowing for bioaccumulated iron detection regardless of exposure to coated or non-coated magnetite NPs, meaning this protocol could be applicable with any type of iron NPs.

The synthesis of organometallic compounds with potential pharmacological activity has attracted the attention of many research groups, aiming to take advantage of aspects that the presence of the metal-carbon bond can bring to the design of new pharmaceutical drugs. In this context, we have gathered studies reported in the literature in which psychoactive benzodiazepine drugs were used as ligands in the preparation of organometallic and metal complexes and provide details on some of their biological effects. We also highlight that most commonly known benzodiazepine-based drugs display molecular features that allow the preparation of metallacycles via C-H activation. These organometallic compounds merit further attention regarding their potential biological effects, not only in terms of psychoactive drugs but also in the search for drug replacements, for example, for cancer treatments.

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor's ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative.

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.