PURPOSE: To compare the maternal and neonatal outcomes of pregnant women who had labor induction with intravaginal misoprostol or had spontaneous labor in our clinic. Material-Method. The records of 213 pregnant women, who were followed up in Acibadem Maslak University Hospital for vaginal delivery between June 2021 and December 2021, were retrospectively evaluated. The pregnant women, who gave birth, were divided into 3 groups as follows: spontaneous labor (SL), those induced by a single dose of misoprostol (SDM), and those induced by multiple doses of misoprostol (MDM). The groups were compared in terms of delivery type, the vaginal birth rate within 12 hours, need for intervention, duration of the second stage of labor, cesarean section ratio due to fetal distress, time from the last dose to delivery, and 1st and 5th minute APGAR scores. RESULTS: Among the primiparous pregnant women, 84.7% of SL group, 65.2% of SDM group, and 37% MDM group delivered vaginally within 12 hours (p < 0.05). The time from the last misoprostol dose to delivery was also statistically significantly shorter in pregnant women, who received a single dose of misoprostol (483 vs. 720 min, respectively). When the hospitalization time was evaluated, in the SDM group, the MDM group, and the SL group, it was found to be 611, 831, and 379 min, respectively. In multiparous pregnant women, the hospitalization time was 735 min in the SDM group, 494 min in the MDM group, and 261.5 min in the SL group (p < 0.05). Other than the hospitalization time, when the aforementioned variables were studied in multiparous pregnant women, no statistically significant difference among groups was observed (p > 0.05). CONCLUSION: Intravaginal misoprostol seems to be a promising medical agent for labor induction due to its high delivery rates within 12 hours and the absence of negative fetal outcomes, its ease of storage, and affordable cost.

PURPOSE: This investigation seeks to elucidate the potential prognostic significance as well as the clinical utility of the controlling nutritional status (CONUT) score in breast cancer patients. METHODS: Breast cancer patients managed in our center between January 2010 and December 2016 were recruited for our study. They comprised 187 patients who did not undergo neoadjuvant chemotherapy and 194 who did. A receiver operating characteristic curve (ROC) was utilized in identifying the ideal cut-off CONUT value. This cut-off score was then used to reclassify patients into those with high CONUT scores (≥1) and low CONUT scores (<1). The outcomes were analyzed by statistical methods. RESULTS: Univariate and multivariate Cox regression survival analyses revealed that a CONUT score cut-off of 1 was able to significantly predict duration of disease-free survival (DFS) (p < 0.001; hazard ratio [HR]: 3.184; 95% CI: 1.786-5.677; and p < 0.001; HR: 2.465; 95% CI: 1.642-3.700) and overall survival (OS) (p < 0.001; HR: 2.326; 95% CI: 1.578-3.429; and p < 0.001; HR: 2.775; 95% CI: 1.791-4.300). The mean DFS and OS in those with lower CONUT scores were 41.59 (95% CI: 37.66-45.51 months) and 77.34 months (95% CI: 71.79-82.90 months), respectively. On the other hand, the average DFS and OS for all individuals in the raised CONUT score group were 39.18 (95% CI: 34.41-43.95 months) and 71.30 months (95% CI: 65.47-77.12 months), respectively. Moreover, Kaplan-Meier survival analysis revealed that those in the raised CONUT score cohort had remarkably worse DFS and OS survival rates compared to individuals in the low CONUT score cohort (Log-rank test, DFS: χ 2 = 12.900, p = 0.0003, and OS: χ 2 = 16.270, p < 0.0001). CONCLUSION: The survival times of breast cancer patients may be reliably predicted using the CONUT score. This score is an easy, convenient, readily accessible, and clinically significant means of prognosticating patients with breast cancer.

Computerized tomography (CT) is widely used for clinical screening and treatment planning. In this study, we aimed to reduce X-ray radiation and achieve high-quality CT imaging by using low-intensity X-rays because CT radiation is damaging to the human body. An innovative vision transformer for medical image super-resolution (SR) is applied to establish a high-definition image target. To achieve this, we proposed a method called swin transformer and attention network (STAN) that uses the swin transformer network, which employs an attention method to overcome the long-range dependency difficulties encountered in CNNs and RNNs to enhance and restore the quality of medical CT images. We adopted the peak signal-to-noise ratio for performance comparison with other mainstream SR reconstruction models used in medical CT imaging. Experimental results revealed that the proposed STAN model yields superior medical CT imaging results than the existing SR techniques based on CNNs. The proposed STAN model employs a self-attention mechanism to more effectively extract critical features and long-range information, hence enhancing the quality of medical CT image reconstruction.

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats.

Tuberculosis is a communicable mycobacterial disease of humans and animals caused by members of Mycobacterium tuberculosis complex, highly impacting the public health and economy of the country in endemic areas. Retrospective and cross-sectional study was conducted between March and August 2021. For knowledge, attitude, and practices study, five villages were randomly selected using simple random sampling. To quantify the public health burden, one-year data were collected from Jarso Health Center, and unregistered patients were identified using snowball method, and the estimation was based on disability-adjusted life years. Younger age groups (18-40 years) had shown 105.8 times more odds of knowledge towards tuberculosis than the older (>60 years). Moreover, tertiary levels of education had 9395.1 times more odds of knowledge towards tuberculosis compared to illiterates. The estimated economic burden was 7,731.25US$. Of the 51 tuberculosis patients, two died from the disease, resulting in 45.03 disability-adjusted life years. Communities of the study district were heard about tuberculosis, however, unaware of the cause and sources of the infection. Therefore, further strategic and continuous community-based health education and awareness should be given for effective control and prevention of tuberculosis in the study area.

[This retracts the article DOI: 10.1155/2014/947606.].

BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been identified as a nuclear marker of neuroendocrine tumors. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumor, its expression and clinicopathological significance in mesenchymal tumors remain unclear. METHODS: We analyzed INSM1 mRNA level in GEO database and conducted immunohistological staining to detect the expression of INSM1 on 576 mesenchymal tumors from pathology department of Tongji Hospital. RESULTS: At transcription level, INSM1 expression in AITL (angioimmunoblastic T-cell lymphoma) was higher than their adjacent normal tissues as well as Hodgkin's lymphoma. Moreover, INSM1 expression in well-differentiated liposarcoma (WDLPS) was significantly higher than normal fat (P = 0.014) and dedifferentiated liposarcoma (DDLPS) (P = 0.0248). At protein level, the positive rate of INSM1 in AITL was 18/48 (47.4%), while in DDLPS was 9/20 (45%). INSM1 expression in AITL was significantly higher than Hodgkin's lymphoma (P = 0.008). And INSM1 expression in WDLPS was significantly lower than DDLPS (P = 0.015). CONCLUSION: The combination of GEO data and immunohistochemistry data indicated that the expression level of INSM1 was higher in AITL compared with normal control, suggesting that INSM1 may be involved in pathogenesis of AITL. The abnormal expression of INSM1 was found in WDLPS, and the positive rate of INSM1 was higher in DDLPS than in WDLPS. INSM1 may be involved in the regulation of liposarcoma development. There were significant differences in the expression of INSM1 between AITL and Hodgkin's lymphoma and WDLPS and DDLPS. These findings may assist in the differential diagnosis of these tumors when common markers are difficult to identify, enriching the diagnostic index system of mesenchymal tumors.

AIM: This study was to explore the relationship of older adults' demographic information, physiological indices, and stages of frailty with their risk of falling. METHODS: In the cross-sectional study, a total of 221 older adults with the mean age 74.9 (SD = 6.8) years old were surveyed by senior fitness test. RESULTS: Results were observed in terms of participants' physical fitness, with significant differences being observed in the correlations of left-hand grip strength (t = 5.05, p < .000), right-hand grip strength (t = 6.03, p < .000), and total grip strength (t = 5.70, p < .000), time up and go test (t = -6.25, p < .000), and 30-sec chair stand test (t = 7.19, p < .000) with the risk of falling. According to the logistic regression analysis results, long-term medication (OR = 0.12, 95% CI =0.02-0.62, p < .01) and right-hand grip strength (OR = 0.86, 95% CI =0.76-0.97, p < .01) are the main predictors of older adults' risk of falling. CONCLUSIONS: Older females with low education, history of falls, weaker grip strengths; taking longer to finish the TUG test; and standing fewer times during the 30-second chair stand test were at risk of fall. In prediction, older people using long-term medication were at lower risk of falling, and the greater the hand grip strength was, the lower the fall risk was. According to the research results, nursing personnel must develop care programs and improve older adults' risk of falls.

The Ober test is an orthopedic evaluation procedure used to assess for tightness of the tensor fascia latae (TFL) and iliotibial band (ITB). Multiple versions of this test have been described using different degrees of contralateral hip joint flexion to stabilize the pelvis. The aim of this study was to analyze the hip range of motion (ROM) in the frontal plane and perceived tension produced during the Ober test using four different angles of contralateral hip flexion prepositioning. The secondary objective was to analyze the differences in the Ober test with different contralateral hip flexion angles according to limb dominance. This cross-sectional study included healthy individuals aged 18 years or older. The Ober test was performed on the right and left leg of each participant with the contralateral hip joint stabilized at 0° flexion, 45° flexion, 90° flexion, and maximal flexion. Hip range of motion in the frontal plane (abduction or adduction) was measured using a digital inclinometer. Three measurements were performed on each limb for every angle of contralateral prepositioning, using the average of the three measurements for statistical analysis. Participants were asked to report the location of any perceived tension and the intensity of tension using a Numeric Rating Scale during the test. Twenty-eight participants (17 men and 11 women) were examined. Significant differences in the Ober test hip ROM in the frontal plane (p < 0.01) were observed when comparing different angles of contralateral hip flexion prepositioning. Significant differences between tests were also present for intensity of perceived tension (p ≤ 0.001), except for the intensity of perceived tension between 0° and 45°. No statistically significant differences were observed related to limb dominance (p > 0.05) or gender (p > 0.05), except for the Ober test at 0° (p < 0.001) which was higher in men (9.61° ± 5.01°) than in women (5.05° ± 2.87°). Greater contralateral hip flexion prepositioning during the Ober test results in decreased hip adduction ROM in the tested limb and greater perceived tension in the region of tensor fascia latae-iliotibial band.

BACKGROUND: Baichanting (BCT),a traditional Chinese medicine prescription, is a combination of Acanthopanax senticosus, Paeonia lactiflora, and Uncaria three herbs, which has the effect of benefiting the kidney and calming the liver. The study was aimed at investigating the protective effect of BCT against Parkinson's disease using an integrated strategy of network pharmacology and brain metabolomics. MATERIALS AND METHODS: By integrating network pharmacology with metabolomic research, the protective effect of BCT against PD was investigated using a transgenic mouse model for α-synuclein. The metabolite level and gene level components of BCT that might be anti-PD were separated out. Indicators of behavior and pharmacodynamics were employed to gauge the effectiveness of BCT on PD in the preliminary stages. Network pharmacology, which may be the target of BCT, screened the active substances and target genes. The use of metabolomics to identify potential biomarkers of PD, and then through network pharmacology and metabolic pathways to determine their regulatory enzymes and regulatory genes, improve the pathway mechanism of the disease, has important guiding significance for the in-depth study of the pathogenesis of PD. RESULTS: 101 putative target genes were identified by the network pharmacology analysis in relation to the treatment of PD with BCT. According to the functional enrichment analysis, the proposed mechanism was primarily related to the transport of neurotransmitters, the metabolism of arachidonic acid, dopamine, and alpha-amino acids, as well as the transport of dopamine and the negative regulation of amino acid transport. 25 distinct endogenous metabolites were shown to be potential biomarkers for the BCT for treating PD based on metabolomics. These metabolites were mostly implicated in the important methionine and cysteine, tyrosine, histidine, and arginine and proline metabolic pathways. These results somewhat agreed with those of the network pharmacology analysis. CONCLUSIONS: In conclusion, this study showed that BCT could delay the occurrence and development of PD by improving the brain metabolic disorder of α-Syn mice, which revealed the mechanism of BCT through multitarget and multipathway treatment, and provided a new explanation for the mechanism of anti-PD action. Our research, on the other hand, demonstrated that the network pharmacology-integrated metabolomics approach was a potent tool for discovering the active ingredients and mechanisms underlying the pharmacological effects of traditional Chinese medicine.

This study is aimed at examining the effect of eight weeks of selected virtual-assisted games based on Montessori pedagogical principal on the motor proficiency and perceived self-control in the children with spastic hemiplegia during the coronavirus outbreak. In this quasi-experimental study, the children (6.42y ± 1.12y) with hemiplegia were randomly selected and assigned to either the experimental group or the control group. In the pretest, motor skills and self-controlling were evaluated using 36-item Lincoln-Oseretsky Motor Development Scale and Children's Perceived Self-Control Scale (CPSC) (ss, 1982), respectively. The experimental group then engaged in three 45-minute sessions of virtual game play over the course of eight weeks. 24 hours following the last practice session, the posttest was given on the same day as the pretest. After ensuring the normal distribution of collected data with Shapiro-Wilk test, the data were analyzed using Analysis of Covariance test (ANCOVA). Results showed that the experimental group compared to the control group was better in the motor proficiency and perceived self-control after performing selected virtual-assisted Montessori games can significantly improve motor proficiency and perceived self-control (P < 0.05). This pattern of data revealed that the virtual-assisted intervention based on Montessori pedagogical principles may increase motor proficiency and self-control in children with hemiplegia, particularly when confronted with the limitations imposed on by the coronavirus epidemic.

BACKGROUND: Preventing the life of the newborn and reducing the entrenched disparity of childhood mortality across different levels is one of the crucial public health problems, especially in underdeveloped and developing countries in the world. Sustainable development goals (SDGs)-3.2 is aimed at terminating all preventable under-five child mortality and shrinking it to 25 per 1000 live births or lower than this by 2030. Several factors have been shown to be linked with childhood mortality. OBJECTIVE: This review is aimed at pointing out the significant determinants related to under-five child mortality by a systematic review of the literature. METHODS: EMBASE, PubMed, Scopus database, and Google Scholar search engine were used for the systematic search of the literature. Special keywords and Boolean operators were used to point out the relevant studies for the review. Original research articles and peer-reviewed papers published in the English language till August 10, 2022, were included in the analysis and synthesis of the results. As per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, out of 299 studies identified from different sources, only 22 articles were ascertained for this study. Eligible articles were appraised in detail, and relevant information was extracted and then integrated into the systematic review. RESULTS: Mother's education, size of child at birth, age of mother at childbirth, place of residence, birth interval, sex of child, type of birth (single or multiple), and birth order, along with other socioeconomic, maternal, child, health facility utilization, and community level variables, were observed as important covariates of under-five mortality. CONCLUSION: Women's education and easy access to quality healthcare facilities should be the apex priority to lessen childhood mortality.

BACKGROUND: Senescence is thought to be an imperative effect on the development of cancer. However, few studies pay an attention to the senescence-associated genes in pancreatic cancer (PC). The prognostic value of senescence-related genes (SRGs) and their involvement in tumor microenvironment (TME) in the PC remain obscure. The aim of this research was to investigate the prognostic role of senescence-associated genes and their affection in TME in PC. METHODS: The transcriptome and clinical information of PC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Two SRG-mediated molecular clusters were comprehensively identified. In total, data from the 285 PC patients were randomly used to develop a senescence-associated gene signature in the training set and verified in the validation set. Immune microenvironment analysis pertained to senescence-related genes was performed. RESULTS: A SRG_score including five senescence-associated genes was established to separate PC patients into two risk groups. High-risk patients had worse overall survival than low-risk patients. The result of the multivariate Cox regression analysis identified the risk score and stage as independent prognostic factors for PC patients. Receiver operating characteristic curve (ROC) analysis confirmed the credible predictive ability of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.746 at 1 year, 0.781 at 3 years, and 0.868 at 5 years in the training set and 0.653 at 1 year, 0.755 at 3 years, and 0.785 at 5 years in the validation set. Moreover, the SRG_score was associated with TME, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. CONCLUSIONS: This study found that the novel SRG_score could be an independent prognostic target for PC patients. Senescence-associated genes had a vital impact on the immune microenvironment and the treatment of PC patients.

BACKGROUND: Acute myeloid leukemia (AML) is one of the most common hematological malignancies and accounts for about 20% of childhood leukemias. Currently, immunotherapy is one of the recommended treatment schemes for recurrent AML patients to improve their survival rates. Nonetheless, low remission and high mortality rates are observed in recurrent AML and challenge the prognosis of AML patients. To address this problem, we aimed to establish and verify a reliable prognostic risk model using immune-related genes to improve the prognostic evaluation and recommendation for personalized treatment of AML. METHODS: Transcriptome data and clinical data were acquired from the TARGET database while immune genes were sourced from InnateDB and ImmPort Shared databases. The mRNA expression profile matrix of immune genes from 62 normal samples and 1408 AML cases was extracted from the transcriptome data and subjected to differential expression (DE) analysis. The entire cohort of DE immune genes was randomly divided into the test group and training group. The prognostic model associated with immune genes was constructed using the training group. The test group and entire cohort were employed for model validation. Lastly, we analyzed the potential clinical application of the model and its association with immune cell infiltration. RESULTS: In total, 751 DE immune genes were differentially regulated, including 552 upregulated and 199 downregulated. Based on these DE genes, we developed and validated a prognostic risk model composed of seven immune genes, GDF1, TPM2, IL1R1, PSMD4, IL5RA, DHCR24, and IL12RB2. This model is able to predict the 5-year survival rate more accurately compared with age, gender, and risk stratification. Further analysis showed that CD8+ T-cell contents and neutrophil infiltration decreased but macrophage infiltration increased as the risk score increased. CONCLUSIONS: A seven-immune gene model of AML was developed and validated. We propose this model as an independent prognostic variable able to estimate the 5-year survival rate. In addition, the model can also reflect the immune microenvironment of AML patients.

OBJECTIVE: The safety and efficacy of three-dimensional- (3D-) printed hydroxyapatite/polylactic acid (HA-PLA) composites in repairing cranial defects were evaluated in a rabbit experimental model. METHODS: Twelve New Zealand rabbits were selected as experimental subjects. Two holes (A and B), each with a diameter of approximately 1 cm, were made in the cranium of each rabbit. Hole A served as the experimental manipulation, and hole B served as the control manipulation. A 3D-printed HA-PLA composite was used for placement onto hole A, whereas autologous bone powder was used for placement onto hole B. Samples from the experimental holes and the control holes were collected at 30 and 90 days after surgery. The obtained materials were examined in terms of their morphologies and histopathologies and were also subjected to simultaneous hardness tests. RESULTS: Both the 3D-printed HA-PLA composite and autologous bone powder were able to repair and fill the cranial defects at 30 days and 90 days after surgery. At 30 days after surgery, the microhardness of the area repaired by the HA-PLA composite was lower than that of the area repaired by autogenous bone powder (p < 0.01), but neither of these treatments reached the hardness of normal bone at this time (p < 0.01). At 90 days after surgery, there was no statistically significant difference in the microhardness of the repaired area from the 3D-printed HA-PLA composite compared with that of the repaired area from autologous bone powder (p > 0.05), and there was no statistically significant difference in the hardness of the two repaired areas compared with that of the normal bone (p > 0.05). Hematoxylin-eosin staining showed that bone cells in the HA-PLA material in the experimental group grew and were arranged in an orderly manner. Bone trabeculae and marrow cavities were formed on the pore surface and inside of the HA-PLA scaffold, and the arrangement of bone trabeculae was regular. CONCLUSION: 3D-printed HA-PLA composites can induce bone regeneration, are biocompatible, have the same strength as autologous bone powder, are able to degrade, and are ultimately safe and effective for repairing cranial defects in rabbits. However, further research is needed to determine the feasibility of 3D-printed HA-PLA composites in human cranioplasty.

PURPOSE: The diagnosis of tuberculous meningitis (TBM) is difficult and relies on the patient's clinical presentation and initial cerebrospinal fluid testing. Treatment outcomes for some patients with early consideration of TBM meningitis are often poor. Patients and Methods. In this study, we retrospectively analyzed 24 non-TBM patients whose early changes of cerebrospinal fluid were similar to those of TBM through the second-generation cerebrospinal fluid sequencing technology. RESULTS: All patients included in this study had an acute onset, including 5 patients with a history of upper respiratory tract infection, 9 patients with fever, 6 patients with headache, 5 patients with psychiatric symptoms, 6 patients with cognitive impairment, 9 patients with signs of meningeal irritation, and 6 patients with seizures. Sixteen patients presented with altered content and level of consciousness during their admission. The leukocyte counts (median, 124.0 × 106/L) and total protein concentrations (median, 1300 mg/L) were higher than normal reference values in all patients, whereas glucose (median, 1.345 mmol/L) and chloride concentration values (average, 111.7 ± 5.2 mmol/L) were lower than normal reference values. The patients included 2 cases of Liszt's meningitis, 2 cases of Brucella infection in the CNS, 4 cases of Varicella zoster virus encephalitis, 2 cases of human herpes simplex virus type 1, 2 cases of lupus encephalopathy, 2 cases of anti-NMDAR receptor encephalitis, 2 cases of meningeal carcinomatosis, 5 cases of cryptococcal meningitis, 2 cases of CNS sarcoidosis, and a case of invasive Rhizopus oryzae infection. All patients were tested for NGS in cerebrospinal fluid. Eight patients were diagnosed with anti-NMDAR encephalitis, meningeal carcinomatosis, lupus encephalopathy, and CNS sarcoidosis. Nine patients experienced death; 15 patients had a good prognosis and left no significant sequelae. CONCLUSION: The analysis of patients with TBM-like cerebrospinal fluid changes will help improve the diagnostic accuracy of the disease and reduce misdiagnosis and underdiagnosis.

BACKGROUND: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. OBJECTIVE: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. METHODS: In this study, we examined the effectiveness of ATO and D-VC on xenograft models-AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. RESULTS: The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.

Ethyl acetate, ethanol, and acetone extracts of the medicinal plants Thymelaea hirsuta L., Urginea maritima L., and Plantago albicans L. (aerial parts) were evaluated for their phytochemical compositions, antimycotic activity against dermatophytes, and antiproliferative activity against different human cancer cell lines. Among them, the ethanolic extracts showed the highest phytochemical contents along with hyperactivities and were then selected for gas chromatography-mass spectrometry and Fourier-transform infrared spectroscopy analysis. The Fourier-transform infrared spectroscopy analysis confirmed the presence of different characteristic peak values with various functional chemical groups of the active components. However, U. maritima extracts through Fourier-transform infrared spectroscopy analysis showed distinctive peaks related to phenolic, amines, amides, aromatic, alkanes, alkyne, cyclopentanone, conjugated aldehyde, nitro, methoxy, uronic acids, aromatic esters, tertiary alcohol or ester, secondary and primary alcohols, aliphatic ether, sulfoxide, vinylidene, and halo compounds. Many bioactive main compounds with reported biological activities were detected by GC/MS (%) in the ethanolic extract of T. hirsuta, U. maritima, and P. albicans. All studied dermatophytes included a diverse set of virulence factors, including phospholipase, protease, keratinase, hemolysis, and melanoid production, all of which play vital roles in dermatophytic infection. Ethanolic extract of P. albicans inhibited the growth of Trichophyton soudanense totally and Trichophyton erinacei in addition to all Microsporum species. In contrast, the ethanolic extract of Trichophyton hirsuta at concentrations of 25 g/mL totally prevented the growth of all Trichophyton species. EtOH extract of U. maritima completely prevented the growth (100% inhibition) of all dermatophytic strains under study at the lowest concentration of 12.5 μg/mL. Scanning electron microscope analysis revealed considerable morphological modifications and structural alterations in dermatophyte species exposed to ethanolic extract of these plants. The viability of HCT-116, HepG-2, MCF-7, and HeLa cell lines was reduced after treatment with the ethanolic extracts of T. hirsuta, U. maritima, and P. albicans individually with IC50 values (10.0, 9.97, 48.5, and 56.24 μg/mL), (26.98, 25.0, 17.11, and 9.52 μg/mL), and (9.32, 7.46, 12.50, and 16.32 μg/mL), respectively. Our work revealed the significance of these traditional ethnomedical plants as potent sources for biologically active pharmaceuticals with potential applicability for the treatment of fungal and cancer diseases.

OBJECTIVE: This study explored the characteristics and associated factors of commercial sex behavior among male college students who engaged in temporary heterosexual behaviors in Zhejiang Province, China. METHODS: The participants were male college students with temporary heterosexual behaviors. We developed an online questionnaire to collect information on demographic characteristics, sexual attitudes, sexual behaviors, and HIV/AIDS interventions through stratified cluster sampling. Chi-square (χ 2) tests were performed for the different groups of participants. The occurrence of commercial sex behavior among participants was taken as the dependent variable, and logistic regression was used to analyze the factors associated with the participants' commercial sex behavior. RESULTS: This study investigated the temporary heterosexual behavior of 424 male college students. Among them were 112 students who reported commercial sex behavior (26.42%), whose average age was 20.25 ± 1.27 years, and whose household registration of Zhejiang Province accounted for 63.39%. The results of the multivariate logistic regression analysis indicated that acceptance of commercial sex behavior (Adjusted (a) OR = 3.53, 95% CI = 1.94~6.40) and feeling at risk of contracting HIV (aOR = 6.44, 95% CI = 2.98~13.94), seeking temporary sexual partners through the Internet (aOR = 2.58, 95% CI = 1.27~5.25), consistently using condoms during sex (aOR = 0.34, 95% CI = 0.16~0.70), or using condoms sometimes/frequently during sex (aOR = 0.30, 95% CI = 0.13~0.68) were independent factors associated with male college students with temporary heterosexual behavior engaging in commercial sex behavior. CONCLUSION: Open sexual attitudes, seeking temporary sexual partners through the Internet, high awareness of HIV infection risk, and low condom use are associated factors for male college students engaging in commercial sex behavior. For college students' HIV/AIDS prevention and education interventions, it is necessary to strengthen the prevention of network influence, increase peer education, increase teacher participation in education, enhance college students' risk awareness, advocate for the use of condoms, and promote HIV/AIDS prevention and treatment.

Global agriculture is frequently subjected to stresses from increased salt content, drought, heavy metals, and other factors, which limit plant growth and production, deteriorate soil health, and constitute a severe danger to global food security. Development of environmentally acceptable mitigation techniques against stresses and restrictions on the use of chemical fertilizers in agricultural fields is essential. Therefore, eco-friendly practises must be kept to prevent the detrimental impacts of stress on agricultural regions. The advanced metabolic machinery needed to handle this issue is not now existent in plants to deal against the stresses. Research has shown that the key role and mechanisms of arbuscular mycorrhiza fungi (AMF) to enhance plant nutrient uptake, immobilisation and translocation of heavy metals, and plant growth-promoting attributes may be suitable agents for plant growth under diversed stressed condition. The successful symbiosis and the functional relationship between the plant and AMF may build the protective regulatory mechansm against the key challenge in particular stress. AMF's compatibility with hyperaccumulator plants has also been supported by studies on gene regulation and theoretical arguments. In order to address this account, the present review included reducing the impacts of biotic and abiotic stress through AMF, the mechanisms of AMF to improve the host plant's capacity to endure stress, and the strategies employed by AM fungus to support plant survival in stressful conditions.

Arsenic is a known environmental carcinogenic agent. However, under certain circumstances, it may exert anticancer effects. In this systematic review, we aim to provide information on recent developments in studies on arsenic antitumor effects in breast cancer. Research included in the review refers to experimental data from in vitro studies. The data was collected using search terms "breast cancer," "arsenic," and "anticancer" (25.05.2021). Only studies in English and published in the last 10 years were included. The search identified 123 studies from the EBSCOhost, PubMed, and Scopus databases. In the selection process, thirty full-texts were evaluated as eligible for the review. The literature of the last decade provides a lot of information on mechanisms behind anticancer effects of arsenic on breast cancer. Similar to arsenic-induced carcinogenesis, these mechanisms include the activation of the redox system and the increased production of free radicals. Targets of arsenic action are systems of cell membranes, mitochondria, pathways of intracellular transmission, and the genetic apparatus of the cell. Beneficial effects of arsenic use are possible due to significant metabolic differences between cancer and healthy cells. Further efforts are needed in order to establish modes and doses of treatment with arsenic that would provide anticancer activity with minimal toxicity.

Diffuse liver diseases are highly prevalent conditions around the world, including pathological liver changes that occur when hepatocytes are damaged and liver function declines, often leading to a chronic condition. In the last years, Magnetic Resonance Imaging (MRI) is reaching an important role in the study of diffuse liver diseases moving from qualitative to quantitative assessment of liver parenchyma. In fact, this can allow noninvasive accurate and standardized assessment of diffuse liver diseases and can represent a concrete alternative to biopsy which represents the current reference standard. MRI approach already tested for other pathologies include diffusion-weighted imaging (DWI) and radiomics, able to quantify different aspects of diffuse liver disease. New emerging MRI quantitative methods include MR elastography (MRE) for the quantification of the hepatic stiffness in cirrhotic patients, dedicated gradient multiecho sequences for the assessment of hepatic fat storage, and iron overload. Thus, the aim of this review is to give an overview of the technical principles and clinical application of new quantitative MRI techniques for the evaluation of diffuse liver disease.

METHODS: Cells were divided into 5 groups-control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L LR + 0.6 mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. RESULTS: We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group (P < 0.01). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35); (1.00 ± 0.04 vs. 2.46 ± 0.08); (2.88 ± 0.55 vs. 8.29 ± 0.52), P < 0.01) and protein ((3338.13 ± 333.15 vs. 4963.98 ± 277.29); (1978.85 ± 124.24 vs. 2676.07 ± 100.64); (3372.00 ± 219.84 vs. 6083.20 ± 284.70), both P < 0.01) expression decreased in the LR group. The expression levels of GLUT4 mRNA ((0.75 ± 0.04 vs. 0.34 ± 0.03), P < 0.01) and protein ((3443.71 ± 191.89 vs. 2137.79 ± 118.75), P < 0.01) increased. CONCLUSION: Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.

Sarcoma, the second common type of solid tumor in children and adolescents, has a wide variety of subtypes that are often not properly diagnosed at an early stage, leading to late metastases and causing serious loss of life and property to patients and families. It exhibits a high degree of heterogeneity at the cellular, molecular, and epigenetic levels, where DNA methylation has been proposed to play a role in the diagnosis of sarcoma subtypes. Thus, this study is aimed at finding potential biomarkers at the DNA methylation level to distinguish different sarcoma subtypes. A machine learning process was designed to analyse sarcoma samples, each of which was represented by lots of methylation sites. Irrelevant sites were removed using the Boruta method, and remaining sites related to the target variables were kept for further analyses. Afterward, three feature ranking methods (LASSO, LightGBM, and MCFS) were adopted to rank these features, and six classification models were constructed by combining incremental feature selection and two classification algorithms (decision tree and random forest). Among these models, the performance of RF model was higher than that of DT model under all three ranking conditions. The specific expression of genes obtained from the annotation of highly correlated methylation site features, such as PRKAR1B, INPP5A, and GLI3, was proven to be associated with sarcoma by publications. Moreover, the quantitative rules obtained by decision tree algorithm helped us to understand the essential differences between various sarcoma types and classify sarcoma subtypes, providing a new means of clinical identification and determining new therapeutic targets.

MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into six groups: control, T2DM, metformin, high-dose BFTL (800 mg/kg), middle-dose BFTL (400 mg/kg), and low-dose BFTL (200 mg/kg). After 4 weeks of BFTL treatment, the correlations of serum indicators with protein expression in tissue were determined, and pathological changes in the liver, kidneys, and pancreas were analyzed. RESULTS: Compared with the results in the T2DM group, serum fasting blood glucose, triglyceride, total cholesterol, malondialdehyde, alanine aminotransferase, and aspartate aminotransferase levels were significantly decreased (p < 0.05), whereas superoxide dismutase and glutathione peroxidase levels were significantly increased (p < 0.05) in the high-, middle-, and low-dose BFTL groups. The treatment also improved oral glucose tolerance. In addition, the pathological changes of the liver, kidney, and pancreas were improved by BFTL treatment. Cytochrome and caspase-3 expression in pancreatic was significantly decreased (p < 0.05) by BFTL treatment, whereas the Bcl-2/Bax ratio was significantly increased (p < 0.05). Discussion and Conclusion. BFTL exerted significant hypoglycemic effect on T2DM model rats, and its mechanism involved the suppression of blood glucose levels and oxidative stress by improving the metabolism of blood lipids and antioxidant capacity, boosting β-cell function, and inhibiting β-cell apoptosis.

OBJECTIVE: This study is aimed at exploring the molecular mechanism of Shufeiya recipe in the treatment of pulmonary hypertension (PH) using network pharmacology and molecular docking analysis. METHODS: Active components and their target proteins in the recipe were screened using the TCMSP database. PH-related core proteins were screened using GeneCards, STRING database, and Cytoscape-v3.8.2. Common proteins were obtained by intersection of the target proteins of these recipe active components and pH-related core proteins. Rx64 4.0.2 software was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the common proteins to obtain pathway-enriched proteins, and then core enriched proteins were further screened. We analyzed the relationship between the active components and pathway-enriched proteins using Cytoscape-v3.8.2. AutoDock Vina was used to dock their core proteins into the components. RESULTS: Shufeiya recipe contained 67 active components. 61 common proteins of the target proteins of the active components and PH-related core proteins were obtained. The treatment involved both functional and pathway regulations. The core pathway-enriched proteins were prostaglandin G/H synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), and RAC-alpha serine/threonine-protein kinase (AKT1), and their binding energies to the corresponding components were all less than -5 kJ•mol-1. CONCLUSION: It was found that the main mechanism might be the active components acting on the core pathway-enriched proteins to regulate related signaling pathways, thereby playing roles in anticoagulation, vasodilation, anti-PASMC proliferation, promotion of PAECs apoptosis, inhibition of oxidative stress, and anti-inflammatory effects.

[This retracts the article DOI: 10.1155/2022/2056913.].

BACKGROUND: Colon cancer is the second most common malignancy causing the majority of cancer-related deaths. B7-H3 concentrations have drawn major interest as possible diagnostic biomarkers of cancer. The aim of this study was to measure the preoperative serum B7-H3 levels and to determine those that are replaced in colon cancer. METHOD: We measured preoperative serum B7-H3 concentrations of 90 patients aged 57-69 years diagnosed with colon cancer and 50 age-matched healthy individuals. B7-H3 levels were determined using the sandwich enzyme-linked immunosorbent assay (ELISA). Patients were categorized by stage based on the TNM staging system, and the serum levels of B7-H3 were compared between patients with different TNM stages. RESULT: No statistically significant difference was found between the patient and control groups in terms of age and gender. Preoperative serum B7-H3 levels were statistically significantly higher in patients with colon cancer than in the healthy group (p < 0.001). Preoperative serum B7-H3 concentration of the stage IV patients was significantly higher than those of the patients with stage I and stage II disease. In addition, higher serum B7-H3 levels were associated with lymph node status and distant metastasis in colon cancer. CONCLUSION: We showed that B7-H3 is highly expressed in colon cancer and can be used as a candidate diagnostic biomarker and a potential target in colon cancer in future.

METHODS: From April 2017 to December 2020, we retrospectively recruited 477 patients with acute ischemic stroke (within 48 hours after onset). Progressive infarction was defined as an increase of ≥1 point in motor power or ≥2 points on the total National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission and extension of the original infarction were further confirmed by diffusion-weighted imaging. Demographic characteristics, clinical information, and neuroimaging characteristics were evaluated after admission. All blood draws and initial imaging were completed within 24 hours of admission. RESULTS: PI occurred in 147 (30.8%) patients. Univariate analysis comparing the two groups revealed that hypertension, initial NIHSS score, discharge NIHSS score, modified Rankin scale score at 90 days, monocyte level, creatinine level, fasting glucose level, LMR, monocyte-to-high-density lipoprotein ratio (MHR), and lesion location were significantly different (P < 0.05). Multivariate logistic regression analysis showed that the odds ratio of PI increased as the quartile of LMR increased, with the lowest quartile as the reference value. Subgroup analyses showed that a high LMR was an independent predictor of PI only in large artery atherosclerosis (LAA) patients. The receiver operating characteristic (ROC) curve was drawn to estimate the predictive value of LMR for PI. For all cases, the area under the curve was 0.583 (95% CI 0.526-0.641), and the best predictive cutoff value was 3.506, with a sensitivity of 53.1% and a specificity of 63.9%. In patients with LAA, the area under the curve was 0.585 (95% CI 0.505-0.665), and the best predictive cutoff value was 3.944, with a sensitivity of 48.7% and a specificity of 72.8%. CONCLUSIONS: LMR was an independent predictor for progressive infarction in patients with acute ischemic stroke, especially in LAA cerebral infarction patients.

Children that are mentally and physically healthy have a higher quality of life and are better able to function in their daily lives. Therefore, this study is aimed at investigating associated factors causing functional difficulties in male and female children ages 5-17 years. This study used data from a nationally representative cross-sectional household survey named the Multiple Indicator Cluster Survey (MICS) Bangladesh 2019. A total of 58,746 children aged 5-17 were selected for the study, where 30,300 children were male, and 28,446 were female. To deal with overdispersed count data, the study used a negative binomial regression model to find the associated factors. The results show that 39.3% of the male children and 40.9% of the female children were from the age group of 10-14. Educated children had a lower risk of dysfunction. Among male children, women with a total number of children ever born of 4 or more were 1.21 times (incidence rate ratios (IRR) = 1.21) more likely to have a dysfunctional child. Children of dysfunctional mothers are more likely to be dysfunctional themselves. The incidence rate ratio for children functional difficulty among Muslim girls was 36 percent higher than non-Muslim girls in Bangladesh. When compared to the Barisal Division, female children in the Mymensingh Division had a 16% higher risk of functional problems. Based on the findings, the Bangladesh government and other development partners should initiate policies and programs to minimize the impact of functional dysfunction in children.

Acinetobacter baumannii (A. baumannii) attributes 26% of the mortality rate in hospitalized patients, and the percentage can rise to 46 in patients admitted to ICU as it is a major cause of ventilator-associated pneumonia. It has been nominated as the critical priority organism by WHO for which new therapeutic drugs are urgently required. To understand the genomic identification of different strains, antimicrobial resistance patterns, and epidemiological typing of organisms, whole-genome sequencing (WGS) analysis provides insight to explore new epitopes to develop new drugs against the organism. Therefore, the study is aimed at investigating the whole genome sequence of A. baumannii strains to report the new intensifications in its genomic profile. The genome sequences were retrieved from the NCBI database system. Pan-genome BPGA (Bacterial Pan-genome Analysis Tool) was used to analyze the core, pan, and species-specific genome analysis. The pan and core genome curves were extrapolated using the empirical power law equation f(x) = a.xb and the exponential equation f1(x) = c.e (d.x). To identify the resistant genes with resistant mutations against antibiotics, ResFinder and Galaxy Community hub bioinformatics tools were used. According to pan-genome analysis, there were 2227 core genes present in each species of the A. baumannii genome. Furthermore, the number of accessory genes ranged from 1182 to 1460, and the unique genes in the genome were 931. There were 325 exclusively absent genes in the genome of Acinetobacter baumannii. The pan-genome analysis showed that there is a 5-fold increase in the genome of A. baumannii in 5 years, and the genome is still open. There is the addition of multiple unique genes; among them, genes participating in the function of information and processing are increased.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main bacterial pathogens causing chronic infections, mainly because of its capacity to produce biofilm. Biofilm production is one of the underlying strategies for antibacterial drug resistance. Accordingly, preventing and attenuating biofilm production has become an emerging approach to controlling persistent infections. Therefore, this scoping review is aimed at surveying the published literature describing the usage of probiotics and their derivatives against biofilm-producing MRSA. METHODS: Updated literature searches were conducted across seven electronic databases including Web of Science, PubMed, Scopus, Cochrane Library, ProQuest, Embase, and Google Scholar to identify all original published articles about probiotics against MRSA. In this regard, studies were summarized and analyzed in the present review. RESULTS: In the reviewed studies, various microorganisms and compounds were used as probiotics as follows: Lactobacillus species (8 studies), Enterococcus species (4 studies), Bacillus species (2 studies), Streptomyces species (2 studies), Saccharomyces cerevisiae (1 study), Corynebacterium accolens (1 study), and Lactococcus lactis derived Nisin (3 studies). Based on our comprehensive search, 21 studies with eligibility criteria were included in the present review including 12 studies on clinical strains, 6 studies on ATCC, 2 studies simultaneously on clinical and standard strains, and finally 1 study on food sample. CONCLUSIONS: Our study showed that there was an increasing trend in the number of publications reporting probiotics against biofilm-producing MRSA. The results of this scoping review could use to guide the undertaking of the subsequent systematic reviews. In summary, probiotics with antimicrobial and antibiofilm properties can use as an embedded agent in food products or as a biopharmaceutical in the prevention and treatment of MRSA infections.

[This retracts the article DOI: 10.1155/2022/9500319.].

Vascular remodeling refers to changes in the size, contraction, distribution, and flow rate of blood vessels and even changes in vascular function. Vascular remodeling can cause cardiovascular and cerebrovascular diseases. It can also lead to other systemic diseases, such as pulmonary hypertension, pulmonary atherosclerosis, chronic obstructive pulmonary disease, stroke, and ascites of broilers. Hypoxia is one of the main causes of vascular remodeling. Prolonged hypoxia or intermittent hypoxia can lead to loss of lung ventilation, causing respiratory depression, irregular respiratory rhythms, and central respiratory failure. Animals that are unable to adapt to the highland environment are also prone to sustained constriction of the small pulmonary arteries, increased resistance to pulmonary circulation, and impaired blood circulation, leading to pulmonary hypertension and right heart failure if they live in a highland environment for long periods of time. However, limited studies have been found on the relationship between hypoxia and vascular remodeling. Therefore, this review will explore the relationship between hypoxia and vascular remodeling from the aspects of endoplasmic reticulum stress, mitochondrial dysfunction, abnormal calcium channel, disordered cellular metabolism, abnormal expression of miRNA, and other factors. This will help to understand the detailed mechanism of hypoxia-mediated smooth muscle cell proliferation and vascular remodeling for the better treatment and management of diseases due to vascular remodeling.

To discover new natural resources with biological effects, the chemical investigation of antioxidant and antimicrobial activities of extract's Chaetomium globosum isolated from roots of Urginea indica. Gas chromatography-mass spectrometry (GC-MS) analysis demonstrated the presence of the major chemical constituents present in the methanol extract (1,3-oxathiolane, 1,3-cyclopentadiene, 5-(1-methylethylidene), 5,9-hexadecadienoic acid, methyl ester, decane), chloroform extract (acetic acid, diethoxy-, ethyl ester, 2,2-bis(ethylsulfonyl)propane, 3-methyl-2-(2-oxopropyl) furan), and hexane extract (3-hexanone, 4,4-dimethyl, decane,2,6-dimethyldecane, decane, 2,4,6-trimethyl, decane, 2,4,6-trimethyl, 1-butanesulfinamide, 1,1,2,2,3,3,4,4,4-nonafluoro-N-methyl, decane). The total compound identified (56.2%) in chloroform extract, (54.72%) in hexane extract, and (65%) in methanol extract. The antioxidant effects were performed using diphenylpicrylhydrazyl radical (DPPH). The results showed that the methanol extract showed significantly the highest anti-DPPH with an IC50 value of 37.61 ± 1.37 μg/mL, followed by chloroform and hexane extracts with IC50 values of 40.82 ± 3.60 and 45.20 ± 2.54 μg/mL, respectively. The antifungal activity of extracts was evaluated against pathogens fungi including Fusarium oxysporum, Rosellinia necatrix, Cladosporium xanthochromaticum, and Sclerotinia sclerotiorum. Methanolic and chloroform extracts showed maximum inhibition against all test pathogens, while hexane extract showed minimum inhibition.

BACKGROUND: Ocimum basilicum L. (OBL) is mainly used to treat neurological diseases in China. The preliminary work of this group showed that OBL improves cognitive impairment in Alzheimer's disease (AD). However, the underlying pharmacological mechanism remains unclear. METHODS: The components of OBL were compiled by literature search, and their active ingredients were screened by online database. The drug targets of OBL in the treatment of AD were predicted and analyzed using information derived from sources such as the SwissTargetPrediction tool. And through the network visual analysis function of Cytoscape software and protein-protein interaction analysis (PPI), the core targets of OBL treatment of AD are predicted. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by OBL. Moreover, AutoDock software was used to assess the potential binding affinity between the core targets and the active compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. RESULTS: A total of 35 active compounds and 188 targets of OBL were screened, of which 43 common targets were related to AD. The active compounds of 35 OBLs induced 118 GO and 78 KEGG. The results of PPI and network topology parameter analysis show that targets such as MAPK1, GSK3B, NR3C2, ESR1, and EGFR are known as the core targets for the treatment of AD by OBL and are docked with the active ingredients of OBL. Molecular docking results suggest that diterbutyl phthalate (DBP) may be the main active component of OBL for the treatment of AD. Flow cytometry analysis results showed that apoptosis decreased with increasing DBP dose. In addition, DBP significantly decreased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in the supernatant of Aβ 25-35-induced injury HT22 cell cultures, and it can be speculated that DBP has the ability to protect the stability of injured neuronal cells and improve the permeability of cell membranes, thus stabilizing the intracellular environment. Mechanistically, DBP may increase the mRNA levels of AKT, GSK-3β, etc. in AD cell models and regulate the phosphorylation of AKT/GSK-3β pathway-related. CONCLUSIONS: Conclusively, our study suggests that DBP, the main active component of OBL, has potential in the prevention or treatment of AD.

BACKGROUND: Depression is a psychiatric disorder leading to anhedonia and lack of interest and motivation. Depressive symptoms are triggered by stressful life events, and patients with major depression are at significantly increased risk of attempting suicide. The crucial concern in depression treatment with antidepressant medications is that few weeks are required to show the therapeutic effect along with moderate side effects. The use of herbal medications is a new strategy for the treatment of depression which is often based on medicinal plants.Aegle marmelos (L.) Corr. (family: Rutaceae) is reported to have several actions on the central nervous system producing beneficial effects in anxiety, Alzheimer's disease, Parkinson's disease, epilepsy, and convulsion. Thus, the current investigation designed to assess the antidepressant activity of the standardized hydroethanolic extract of Aegle marmelos (EAM) leaves in male rats exposed to the chronic unpredictable mild stress (CUMS) paradigm. METHODS: Rats were divided in 5 groups. The control group was not subjected to experimental CUMS paradigm, while 4 other groups were subjected to CUMS paradigm to induce depression-like behaviour from day 1 to day 28. Following the CUMS paradigm, 4 groups were divided as CUMS disease control, CUMS+EAM (150 mg/kg, p.o.), CUMS+EAM (300 mg/kg, p.o.), and CUMS+imipramine (15 mg/kg, p.o.), and treatment was given for seven consecutive days to the respective groups (day 29 to day 35). Behavioural parameters such as open field test, forced swim test, sucrose feeding test, and tail suspension test on day 1, day 28, and day 35 were measured, and biochemical parameters such as plasma corticosterone level, serotonergic system (5-HT, 5-HIAA, and 5-HT/5-HIAA), mitochondrial function, and proinflammatory mediators (TNF-α, IL-1β, and IL-6) were estimated in hippocampus (HIP) and prefrontal cortex (PFC) regions of the brain on day 35, after the behavioural observations. On the other hand, phytochemical profile of Aegle marmelos was done. RESULTS: On day 35, EAM (300 mg/kg) significantly reduced the immobility time during the tail suspension test from 208.66 ± 4.72 s to 108.83 ± 4.81 s and forced swim test from 200.16 ± 4.12 s to 148.5 ± 4.58 s. It also enhanced the behavioural parameters in the open field test such as ambulation from 26.5 ± 2.14 to 56.5 ± 1.80, rearing from 8.33 ± 0.71 to 19 ± 0.57, time spent in centre from 9.16 ± 0.9 to 17.16 ± 0.79 s, total distance travelled from 2.36 ± 0.12 to 4.68 ± 0.10 m, and anhedonia in the sucrose feeding test from 109.33 ± 1.08 to 135.83 ± 3.91 mL. The stimulation of the HPA axis resulting elevated corticosterone level caused by CUMS was reduced by EAM (300 mg/kg) from 80.12 ± 2.020 to 48.25 ± 2.407 μg/dL. Furthermore, EAM (300 mg/kg) increase CUMS-induced changes in serotonin (5-HT) level in HIP and PFC from 3.132 ± 0.09586 to 4.518 ± 0.1812 and 4.308 ± 0.1593 to 5.262 ± 0.1014 ng/mg protein, respectively. EAM (300 mg/kg) significantly attenuated the CUMS-induced changes in proinflammatory cytokine production and mitochondrial function in HIP and PFC. One group used to determine the acute toxicity as per OECD-23 standard protocol which resulted that 300 mg/kg EAM has no significant acute toxicity. Total phenolic content and total flavonoid content of standardized hydroalcoholic extract of AM was found 95.024 ± 2.431 and 36.820 ± 3.41, respectively, and additional identification tests showed the presence of alkaloids, tannins, saponins, cardiac glycosides, flavonoids, and terpenoids. CONCLUSION: On the basis of findings, EAM can be inferred as a potential antidepressant-like effect of this plan in preclinical research.

INTRODUCTION: To reveal the mechanisms by which luteolin, the major bioactive component of the Traditional Chinese Medicine (TCM) Polygonum cuspidatum, inhibits proliferation and promotes apoptosis in nasopharyngeal carcinoma (NPC) CNE2 cells. METHODS: Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), bioactive compounds of P. cuspidatum, potential target genes and NPC disease targets of TCMSP were screened, relationship networks were constructed using these potential targets of NPC, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The predicted compounds, targets and pathways were corroborated using in vitro experiments, such as MTT, Cytation™ 5 real-time cell monitoring, cell cycle detection, Annexin V-FITC/PI double staining, Hoechst 33342 staining, and mitochondrial membrane potential (ΔΨm) detection. RESULTS: The results showed that 10 bioactive compounds (OB ≥30% and DL ≥0.18), 157 potential target genes from P. cuspidatum, and 56 common targets related to NPC were found. These included important bioactive compounds such as luteolin, quercetin, and beta-sitosterol. Key common targets included EGFR, MYC, AKT1, CASP3, CCND1, ERBB2, and common targets were enriched for the PI3K-AKT, JAK/STAT, MAPK, and C-type lectin receptor signaling pathways. The binding energy of luteolin for six common targets was less than -5.0 kcal·mol-1. After luteolin (20 μM, and 40 μM) treatment to CNE2 cells for 36 h, cell survival rates decreased, accompanied by cell morphology changes, inhibition of the cell cycle at G2/M phase, and an induction of apoptosis. The expression of the cell proliferation related protein PCNA, the antiapoptosis protein XIAP, and the PI3K-AKT pathway diagram related proteins p-ERK1/2, ERK1/2, AKT, and PI3K, all decreased. CONCLUSION: Luteolin derived from P. cuspidatum inhibited the proliferation of NPC CNE2 cells and promoted cell apoptosis through the PI3K-AKT signal pathway.

BACKGROUND: Esophageal cancer (EC) is a common malignant tumor of the digestive system with high mortality and morbidity. Current evidence suggests that immune cells and molecules regulate the initiation and progression of EC. Accordingly, it is necessary to identify immune-related genes (IRGs) affecting the biological behaviors and microenvironmental characteristics of EC. METHODS: Bioinformatics methods, including differential expression analysis, Cox regression, and immune infiltration prediction, were conducted using R software to analyze the Gene Expression Omnibus (GEO) dataset. The Cancer Genome Atlas (TCGA) cohort was used to validate the prognostic signature. Patients were stratified into high- and low-risk groups for further analyses, including functional enrichment, immune infiltration, checkpoint relevance, clinicopathological characteristics, and therapeutic sensitivity analyses. RESULTS: A prognostic signature was established based on 21 IRGs (S100A7, S100A7A, LCN1, CR2, STAT4, GAST, ANGPTL5, TRAV39, F2RL2, PGLYRP3, KLRD1, TRIM36, PDGFA, SLPI, PCSK2, APLN, TICAM1, ITPR3, MAPK9, GATA4, and PLAU). Compared with high-risk patients, better overall survival rates and clinicopathological characteristics were found in low-risk patients. The areas under the curve of the two cohorts were 0.885 and 0.718, respectively. Higher proportions of resting CD4+ memory T lymphocytes, M2 macrophages, and resting dendritic cells and lower proportions of follicular helper T lymphocytes, plasma cells, and neutrophils were found in the high-risk tumors. Moreover, the high-risk group showed higher expression of CD44 and TNFSF4, lower expression of PDCD1 and CD40, and higher TIDE scores, suggesting they may respond poorly to immunotherapy. High-risk patients responded better to chemotherapeutic agents such as docetaxel, doxorubicin, and gemcitabine. Furthermore, IRGs associated with tumor progression, including PDGFA, ITPR3, SLPI, TICAM1, and GATA4, were identified. CONCLUSION: Our immune-related signature yielded reliable value in evaluating the prognosis, microenvironmental characteristics, and therapeutic sensitivity of EC and may help with the precise treatment of this patient population.

BACKGROUND: Phlegm-dampness constitution as one of nine constitutions in traditional Chinese medicine (TCM) has been a high risk factor for glucolipid metabolic disorders (GLMD). Based on our previous findings, Hua Tan Qu Shi recipe (HTQSR) could effectively improve metabolic indicators of GLMD by targeting on phlegm-dampness constitution. However, the proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution remain unknown. METHODS: Clinical participants from phlegm-dampness constitution with the prediabetic state (T), phlegm-dampness constitution with marginally elevated blood lipids (Z), and phlegm-dampness constitution before sickness (W) were included in this study, who orally took HTQSR for 12 weeks and, respectively, marked AT, AZ, and AW. Data-independent acquisition (DIA) and parallel reaction monitoring (PRM) were performed to identify the differential proteins; then, Venn analysis was used to investigate coexpressed and coregulated proteins. In addition, ingenuity pathway analysis (IPA) software was utilized to explore the related pathways and diseases and biofunctions. RESULTS: LXR/RXR activation, acute phase response signaling, and production of nitric oxide and reactive oxygen species in macrophages were obviously activated between the T and AT groups, as well as the Z and AZ groups. In contrast, these three pathways were inhibited between the W and AW groups. Importantly, one coexpressed and coregulated differential protein, B2MG, was validated by PRM among all groups. CONCLUSIONS: This work firstly reported the underlying proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution, indicating that intervention of phlegm-dampness constitution might be a novel strategy for the preventive treatment of GLMD.

BACKGROUND: Suicidal ideation among textile factory workers is a major public health concern worldwide and is associated with a higher risk of completed suicide. However, there are limited studies that determined the prevalence and the potential determinants of suicidal ideation in Africa, including Ethiopia. Therefore, this study is aimed at exploring the prevalence of suicidal ideation and associated factors among textile factory workers in Almeda textile factory in Adwa, Ethiopia. METHODS: An institutional-based cross-sectional study design was conducted from May 3, 2020, to June 16, 2020, at Almeda textile factory in Adwa. A total of 409 workers were identified using a systematic random sampling technique. Data were collected using a self-administered questionnaire using suicidality module of Composite International Diagnostic Interview. Data were analyzed using SPSS version 22.0, and logistic regression model was employed. Adjusted odds ratio with a 95% confidence interval was computed, and statistical significance was declared at p value < 0.05. RESULT: In this study, the prevalence of suicidal ideation was found to be 8.8% (95% CI: 6.1, 11.5). Working more than 48 hours per week (AOR = 2.88, 95% CI: 1.18, 7.04), depression (AOR = 3.90, 95% CI: 1.60, 9.50), work-related physical injury (AOR = 5.95, 95% CI: 2.37, 14.94), and interpersonal conflict (AOR = 3.54, 95% CI: 1.40, 8.90) were the significant factors associated with suicidal ideation. Conclusion and Recommendation. In this study, suicidal ideation among Almeda textile production workers was a significant problem. Factors including depression, work-related exposure to physical injury, long working hour, and interpersonal conflict can enlarge suicidal ideation.

BACKGROUND: Excessive acetaminophen (APAP) use can lead to acute liver injury (ALI) by inducing endoplasmic reticulum stress (ERS). We previously found that pretreatment with the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand rosiglitazone (RSG) alleviated ALI in APAP-treated mice. OBJECTIVE: To examine if RSG-mediated hepatoprotection is associated with ERS suppression. METHODS: Forty-eight male CD-1 mice were randomly divided into control, RSG, APAP 4 h, APAP 24 h, RSG + APAP 4 h, and RSG + APAP 24 h groups. The RSG and RSG + APAP groups received RSG (20 mg/kg) by gavage 48, 24, and 1 h before intraperitoneal injection of 300 mg/kg APAP, while the APAP group received APAP alone and the control group received only normal saline. Animals were sacrificed immediately (RSG and control groups), 4 h (APAP 4 h and RSG + APAP 4 h), or 24 h (APAP 24 h and RSG + APAP 24 h) post-APAP injection. Liver tissues were collected for hematoxylin-eosin staining, TUNEL staining, and Western blotting for ERS-associated proteins. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured. A second cohort received APAP or RSG + APAP as described and were monitored for survival over one week. RESULTS: At 4 and 24 h following APAP injection alone, serum ALT and AST levels were significantly elevated, and central lobular necrosis of the liver was observed. Necrosis area reached 21.7% at 4 h and 32.1% at 24 h post-APAP, while apoptotic fractions reached 25.6% and 32.4%. Further, 50% of mice in the survival analysis cohort died within one week post-APAP. At 4 h post-APAP, the ERS marker glucose-regulated protein-78 (GRP78) and ERS-associated proteins pJNK, GRP78, p-eIF2α, pPERK, and pIRE were all significantly upregulated. Pretreatment with RSG significantly reduced serum ALT and AST, liver necrosis area, apoptosis rate, and expression of ERS-associated proteins compared to APAP alone, while increasing survival to 80%. CONCLUSIONS: Rosiglitazone pretreatment can alleviate APAP-induced ALI by suppressing three branches of ERS signaling.

Studies suggest that ovarian hyperstimulation syndrome (OHSS) can be treated by reducing the level of vascular endothelial growth factor (VEGF). However, due to the side effects of commercially available VEGF-reducing drugs, they can be ruled out as a suitable treatment for OHSS; therefore, researchers are looking for new medications to treat OHSS. This study is aimed at investigating the effects of cannabidiol (CBD) in an OHSS model and to evaluate its efficacy in modulating the angiogenesis pathway and VEGF gene expression. For this purpose, 32 female mice were randomly divided into four groups (eight mice per group): control group, group 2 with OHSS induction, group 3 receiving 32 nmol of dimethyl sulfoxide after OHSS induction, and group 4 receiving 30 mg/kg of CBD after OHSS induction. The animals' body weight, ovarian weight, vascular permeability (VP), and ovarian follicle count were measured, and the levels of VEGF gene and protein expression in the peritoneal fluid were assessed. Based on the results, CBD decreased the body and ovarian weights, VP, and corpus luteum number compared to the OHSS group (p < 0.05). The peritoneal VEGF gene and protein expression levels reduced in the CBD group compared to the OHSS group (p < 0.05). Also, CBD caused OHSS alleviation by suppressing VEGF expression and VP. Overall, CBD downregulated VEGF gene expression and improved VP in OHSS.

Cuproptosis, a recently found kind of programmed cell death, has been linked to tumor development, prognosis, and therapeutic response. The roles of cuproptosis-related genes (CRG) in the tumor microenvironment (TME) are, nevertheless, unknown. We evaluated alterations in CRG and assessed the related expression patterns in 1445 lung cancer (LC) samples from three separate datasets, analyzing genetic, and transcriptional domains. We discovered two separate molecular subtypes of CRG and discovered that various subtypes of CRG were connected with patient clinical features and prognosis. Furthermore, we discovered connections between distinct CRG subtypes and TME cell infiltration features. The CRG_score was then developed and validated for predicting overall survival (OS). Following that, we investigated the relationship between CRG_score and the cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity. In addition, we created a very accurate nomogram to increase the clinical usefulness of CRG_score. The potential roles of CRG in the tumor-immune-microenvironment, clinical characteristics, and prognosis in LC are demonstrated by our multiplex study. These findings expand our understanding of CRG in LC and may open up new options for assessing LC patients' prognosis and generating more effective immunotherapeutic treatments.

BACKGROUND: Scutellaria baicalensis Georgi (SBG) has significant anti-inflammatory and immune-modulating activities and is widely used in the treatment of inflammatory and autoimmune diseases. However, the mechanism of SBG in the treatment of ankylosing spondylitis (AS) remains to be elucidated. METHODS: Differentially expressed genes (DEGs) related to AS were analyzed based on two GEO gene chips. The DEGs were merged with the data derived from OMIM, GeneCards, and PharmGKB databases to ascertain AS-related targets. Active components of SBG and their targets were acquired from the TCMSP database. After overlapping the targets of AS and SBG, the action targets were acquired. Subsequently, protein-protein interaction (PPI) network and core target screening were conducted using the STRING database and Cytoscape software. Moreover, the DAVID platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of action targets. Finally, the affinity of major active components and core targets was validated with molecular docking. RESULTS: A total of 36 active components of SBG were acquired from TCMSP database. Among these, the main active components were baicalein, wogonin, and oroxylin A. The PPI network and screening showed TNF, IL-6, CXCL8, PTGS2, and VEGFA as core targets associated SBG against AS. GO and KEGG analyses indicated that SBG participated in various biological processes, via regulating IL-17, TNF, and NF-κB signaling pathways. Molecular docking results confirmed a strong binding activity between the main active components and the core targets. CONCLUSION: The therapeutic mechanism of SBG associated with AS can be characterized as a multicomponent, multitarget, and multipathway mechanism. SBG may be a promising therapeutic candidate for AS.

Opioids are a class of chemicals, naturally occurring in the opium poppy plant, and act on the brain to cause a range of impacts, notably analgesic and anti-inflammatory actions. Moreover, an overview was taken in consideration for SARS-CoV-2 incidence and complications, as well as the medicinal uses of opioids were discussed being a safe analgesic and anti-inflammatory drug in a specific dose. Also, our article focused on utilization of opioids in the medication of SARS-CoV-2. Therefore, the major objective of this study was to investigate the antiviral effect of opioids throughout an in silico study by molecular docking study to fifteen opioid compounds against SARS-CoV-2 main protease (PDB ID 6LU7, Mpro). The docking results revealed that opioid complexes potentially inhibit the Mpro active site and exhibiting binding energy (-11.0 kcal/mol), which is comparably higher than the ligand. Furthermore, ADMET prediction indicated that all the tested compounds have good oral absorption and bioavailability and can transport via biological membranes. Finally, Mpro-pholcodine complex was subjected to five MD (RMSD, RMSF, SASA, Rg, and hydrogen bonding) and two MM-PBSA, and conformational change studies, for 100 ns, confirmed the stability of pholcodine, as a representative example, inside the active site of Mpro.

OBJECTIVE: There is a high prevalence of sarcopenia in maintenance hemodialysis (MHD) patients, which is known to be associated with increased mortality. This study is aimed at analyzing the risk factors affecting muscle mass decline in MHD patients. METHODS: This retrospective study included MHD patients who underwent two body composition assessments in October 2013 and November 2017. Depending on whether there was muscle loss or not, the patients were divided into a normal muscle mass (NMM) group and a muscle mass decline (MMD) group. According to the muscle mass decline rate, patients in the MMD group were further classified into a low-rate group and a high-rate group. Biochemical variables, serum vitamin concentrations, anthropometric data, SGA, muscle mass, handgrip, and daily steps were assessed. Risk factors for muscle mass decline were screened by multivariate logistic analysis and linear regression analysis. RESULTS: Of the 72 MHD patients included in this study, 33 were male and 39 were female with a mean age of 56.80 ± 10.86 years and a mean dialysis duration of 7.50 ± 5.20 years. Age (P = .014) and serum 25(OH)D (P = .040) were found to be associated with a higher risk of muscle mass decline after adjusting for gender, dialysis vintage, albumin, and hs-CRP (P = .040). Further analysis found that dialysis vintage (β = 0.285, P = .030), 25(OH)D (β = -0.351, P = .007), and log NT-proBNP (β = 0.312, P = .020) were risk factors associated with the muscle mass decline rate in MHD patients. CONCLUSION: Age and serum 25(OH)D were associated with a higher risk of muscle mass decline, while 25(OH)D, dialysis vintage, and NT-proBNP were associated with the muscle mass decline rate in MHD patients.

Ficus benghalensis is one of the potential medicinal plants which is used locally for the treatment of various ailments such as diabetes, antiasthmatic, and wound healing. To provide a scientific background to these folklores, the current study was designed to evaluate the extract and isolated compound against various enzymes such as ureases, tyrosinase, and phosphodiesterase. The methanolic extract and carpachromene demonstrated a significant urease inhibition effect with maximum percent inhibition of 72.09 and 92.87%, respectively. Regarding the tyrosinase inhibition, the percent antagonist effect of carpachromene and the methanolic extract was 84.80 and 70.98%, respectively. The phosphodiesterase was also significantly antagonized by crude extract and carpachromene with a maximum percent inhibition of 82.98% and 89.54%, respectively. The docking study demonstrated that the carpachromene fits well into the active site of all three enzymes with significant interactions. Carpachromene might possess the potential to inhibit all three enzymes and can effectively treat different diseases associated with the hyperactivity of these enzymes. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against various diseases. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against diabetes and bronchoconstriction. Further, the current study provides scientific backup to the folklore (antidiabetic and antiasthmatic) of Ficus benghalensis.

Streptomyces species have produced a variety of bioactive secondary metabolites with intriguing antimicrobial and anticancer properties. In this study, the bioactive compound obtained from the potent strain RVE129 was purified and characterized. Its bioactivity against various pathogens and its cytotoxicity toward the human cervical cancer (HeLa) cell were also examined. The strain was previously isolated from unexplored areas of the rift valley soil of Hawassa (Ethiopia) and identified by phenotypic characteristics and complete sequencing of the 16S rRNA gene and found to be closely related to Streptomyces monomycini strain NRRL B-24309 (99.65%); accession no. (ON786620). The active fraction undergoes bioassay-guided purification using the TLC method after being extracted by ethyl acetate. Then, it was subjected to physicochemical and structural characteristics using UV-Vis, FTIR, and NMR spectroscopic methods. A minimum inhibitory concentration of the purified antibiotic was achieved by the broth microdilution method. The cytotoxicity of HeLa cells was determined using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The acquired data from spectroscopic studies was compared with that of the reported natural compounds in data bases and found to be the known antibiotic, setamycin. The antibiotic (RVE-02) showed a broad spectrum of bioactivity against both Gram-positive and Gram-negative bacteria, with MIC values that ranged from 1.97 to 125 μg/ml. The bioactivity results also demonstrated antiproliferation and morphological change in HeLa cells with an IC50 value of 24.30μg/ml of antibiotic. The antibiotic, obtained from S. monomycini RVE129, could be a potential candidate to combat pathogens including drug-resistant S. aureus. Further, the effect on HeLa cells suggests that it could be a prominent cancer chemotherapeutic agent.

BACKGROUND: To help improve the standards and quality of nursing practice, newly graduated nurses and midwives are required after passing the Nursing and Midwifery Council's Licensing Examination to undertake a one-year mandatory clinical rotation at health facilities before registration. However, there is a lack of scientific studies to explore new graduate nurses' experiences and challenges during the one-year mandatory clinical rotation programme. AIM: This study is aimed at exploring newly qualified nurses' experiences and challenges during the one-year mandatory clinical rotation in health facilities in the Volta Region of Ghana. METHODS: This qualitative exploratory study used a combination of focus group discussions (FGDs) and individual interviews. Thirty (30) newly qualified nurses were selected from two secondary and one tertiary health facilities, where newly qualified nurses are posted for a clinical rotation programmes to participate in the study. A total of two focus group discussions (FGDs) were conducted, comprising five (5) members in each group. Moreover, twenty (20) newly qualified nurses were interviewed individually, and their data were added to what was obtained from the focus group discussions. This study adopted the thematic analysis approach to analyze the data. RESULTS: The results of this study showed that newly qualified nurses experienced the following during the one-year clinical rotation programme: acquisition of more knowledge and competencies to assume professional nursing roles; lack of knowledge of the objectives of the clinical rotation programme by hospital staff; experience of frustration during the clinical rotation programme; inadequate supervision and support; accommodation and financial challenges. CONCLUSION: The study revealed important challenges experienced by new graduate nurses during the clinical rotation programme, including hospital staff's lack of knowledge regarding the objectives of the rotation programme, inadequate supervision and support, and accommodation and financial challenges. There is a need for the Nursing and Midwifery Council to develop guidelines for the one-year mandatory clinical rotation for newly graduated nurses and midwives to make the programme more effective.

Pancreatic ductal adenocarcinoma (PDAC), as an intractable malignancy, still causes an extremely high mortality worldwide. The ubiquitin-specific protease (USP) family constitutes the major part of deubiquitinating enzymes (DUBs) which has been reported to be involved in initiation and progression of various malignancies via the function of deubiquitination. However, the biological function and clinical values of USPs in PDAC have not been comprehensively elucidated. In this study, Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) datasets, UALCAN database, and the Human Protein Atlas (HPA) online tool were used to analyze the expression level and the relationship between USP expression and clinicopathological features in PDAC. Survival module of HPA and Kaplan-Meier plotter (KMP) databases was recruited to explore the prognostic value of USPs. Tumor Immune Estimation Resource (TIMER) online tool and KMP databases were utilized to elucidate tumor immune infiltration and immune-related survival of USPs. CBioPortal online tool was used to identify the gene mutation level of USPs in PDAC. Both cBioPortal and LinkedOmics were used to confirm the potential biological functions of USPs in PDAC. Our study showed that USP10, USP14, USP18, USP32, USP33, and USP39 (termed as six-USPs) expressions were significantly elevated in tumor tissues. The high expression of the four USPs (USP10, USP14, USP18, and USP39) indicated a poor prognosis. A significant relationship was indicated between the expression of six-USPs and clinicopathological features. Also, the expression of six-USPs was related to promoter methylation level. Moreover, more than 40% genetic alterations and mutations were discovered in six-USPs. Furthermore, the six-USP expression was correlated with immune infiltration and immune-related prognosis. The functional analysis found that the six-USPs were involved in various biological processes and signaling pathways, such as nucleocytoplasmic transport, choline metabolism in cancer, cell cycle, ErbB signaling pathway, RIG-I-like receptor signaling pathway, TGF-β signaling pathway, and TNF signaling pathway. In conclusion, the results showed that six-USPs are potential prognostic biomarkers and can be recruited as possible therapeutic targets of PDAC.

In plants, light quality plays significant roles in photomorphogenesis and photosynthesis. Efficient in vitro plant propagation techniques involve tailoring of various environmental cues and culture media according to the plant species. Plant tissue culture consists of several applications in scientific research, agriculture, biotechnology, and commercial industrial purposes. Utilization of light to enhance the quality of the in vitro raised plants have been evidenced by numerous researchers in plant tissue culture. The advent of light-emitting diode- (LED-) based artificial lighting systems in plant tissue culture for micropropagation has enhanced callus induction, shoot and root organogenesis, and acclimatization of in vitro propagated plants. Plants tend to perceive the light spectra present in the photosynthetically active region (PAR) ranging from 400 to 700 nm; this includes blue and red light wavelengths. Although the influence of spectral quality is being investigated in diverse plant species, particularly, its importance in in vitro propagated horticultural crops is gaining notable interest among researchers. In recent days, the application of LEDs provides better amenability according to the plant species of interest for efficient plant regeneration. Considering the growing necessity and emerging applications of LED supplemental lights for propagation of plants in in vitro, the present review summarizes the outcomes of various research studies dealing with LEDs in plant tissue culture. Moreover, the present endeavor has provided a comprehensive overview on the effects of LEDs in the morphogenesis of plants cultured in vitro.

BACKGROUND: The most numerous cells in the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role in cancer development. Our objective was to develop a cancer-associated fibroblast breast cancer predictive model. METHODS: We acquire breast cancer (BC) scRNA-seq data from Gene Expression Omnibus (GEO), and "Seurat" was used for data processing, including quality control, filtering, principal component analysis, and t-SNE. Afterward, "singleR" software was used to annotate cells. Seurat's "FindAllMarkers" program is used to locate particular CAF markers. clusterProfiler was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The Cancer Genome Atlas (TCGA) database was utilized to provide univariate Cox regression, least absolute shrinkage operator (LASSO) analysis using bulk RNA-seq data. For model development, multivariate Cox regression studies are used. Utilizing pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms, chemosensitivity and immunotherapy response were predicted. The "rms" software was used to facilitate and simplify modeling. RESULTS: Integrating the scRNA-seq (GSE176078) dataset yielded 28 cell clusters. In addition, well-known cell types helped identify 12 cell types. We found 193 marker genes that are elevated in CAFs. In addition, a five-gene predictive model associated to CAF was created in the training set. In the training set, the validation set, and the external validation set, greater risk scores were associated with a worse prognosis. And individuals with a higher risk score were more susceptible to immunotherapy and conventional chemotherapy medicines. CONCLUSION: In conclusion, we establish a strong prognostic model comprised of 5 genes related with CAF that might serve as a potent prognostic indicator and aid clinicians in making more rational medication choices.

Metformin is commonly used as first-line treatment for T2DM (type2 diabetes mellitus). Owing to the high pharmacokinetic (PK) variability, several population pharmacokinetic (PPK) models have been developed for metformin to explore potential covariates that affect its pharmacokinetic variation. This comprehensive review summarized the published PPK studies of metformin, aimed to summarize PPK models of metformin. Most studies described metformin pharmacokinetics as a 2-compartment (2-CMT) model with 4 study describing its pharmacokinetics as 1-compartment (1-CMT). Studies on metformin PPK have shown that obesity, creatinine clearance (CLCr), gene polymorphism, degree of renal function damage, and pathological conditions all have a certain impact on the PK parameters of metformin. It is particularly important to formulate individualized dosing regimens. For future PPK studies of metformin, we believe that more attention should be paid to special populations.

BACKGROUND: The incidence and risk of both lung cancer (LC) and tuberculosis (TB) are increasing rapidly. These two diseases frequently exist together and can influence the incidence and risk of each other. The aim of the current review was to summarize the incidence and risk of LC in TB patients, and vice versa, short out research gap, and contemplate future research perspectives. Methodology. PubMed and Scopus databases, and Google Scholar search engine were searched for epidemiological studies that investigated the incidence and risk of TB and LC, published since January 2011 to April 2022, and written in English. We used the searching keyword "tuberculosis" combined with "lung cancer" and associated medical subject heading (MeSH) to retrieve eligible research articles. We retrieved information's regarding the diagnosis of TB and LC, confounders, the associations of TB and LC, and incidence and risks of each other. RESULTS: We found higher incidence rate and risks (1.64 to 6 times higher) of LC in TB patients in comparison to non-TB participants. However, the incidence rate and risks of TB in LC patients were comparatively low. Male patients were exhibited higher risks than female. The medical comorbidities, smoking habits, and age can also influence the associations and risks of LC in TB patients or vice versa. CONCLUSION: Our summarized studies might suggest that existing active TB may increase the incidence and risk of LC. However, large prospective cohort study is warranted to explore the real scenario worldwide.

OBJECTIVE: DNA damage response (DDR) is a complex system that maintains genetic integrity and the stable replication and transmission of genetic material. m6A modifies DDR-related gene expression and affects the balance of DNA damage response in tumor cells. In this study, a risk model based on m6A-modified DDR-related gene was established to evaluate its role in patients with gastric cancer. METHODS: We downloaded 639 DNA damage response genes from the Gene Set Enrichment Analysis (GSEA) database and constructed risk score models using typed differential genes. We used Kaplan-Meier curves and risk curves to verify the clinical relevance of the model, which was then validated with the univariate and multifactorial Cox analysis, ROC, C-index, and nomogram, and finally this model was used to evaluate the correlation of the risk score model with immune microenvironment, microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoints. RESULTS: In this study, 337 samples in The Cancer Genome Atlas (TCGA) database were used as training set to construct a DDR-related gene model, and GSE84437 was used as external data set for verification. We found that the prognosis and immunotherapy effect of gastric cancer patients in the low-risk group were significantly better than those in the high-risk group. CONCLUSION: We screened eight DDR-related genes (ZBTB7A, POLQ, CHEK1, NPDC1, RAMP1, AXIN2, SFRP2, and APOD) to establish a risk model, which can predict the prognosis of gastric cancer patients and guide the clinical implementation of immunotherapy.

The aim of the study was to assess the effect of external use of inert gases (helium and argon) on the state of free radical processes in vivo. The experiment was performed on 30 male Wistar stock rats (age-3 months, weight-200-220 g.), randomly distributed into 3 equal groups. The first group of animals was intact (n = 10). The animals of the second and third groups were treated with argon and helium streams, respectively. Our research has allowed us to establish that the studied inert gases have a modulating effect on the state of oxidative metabolism of rat blood, and the nature of this effect is directly determined by the type of gas. The results of this study allowed us to establish the potential antioxidant effect of the helium stream, mainly realized due to the activation of the catalytic properties of the enzymatic link of the antioxidant system of rat blood plasma. At the same time, the revealed features of shifts in oxidative metabolism during treatment with argon flow include not only stimulation of the antioxidant system but also the pronounced induction of free radical oxidation. Thus, the conducted studies made it possible to verify the specificity of the response of the oxidative metabolism of blood plasma to the use of inert gases, depending on their type.

OBJECTIVE: While simulated patients (SPs) are considered a standard tool in communication skills training, there is no evidence thus far of their comparative benefit to the more cost-effective option of student role playing. We compared the effectiveness of both approaches in developing patient-centred attitudes in students. METHODS: We retrospectively compared students who participated in the clinical communication course (CCC), based on student role playing (CCCsp-, n = 160), to students who participated in the CCC with SPs (CCCsp+, n = 146), and students with no formal CCC (CCC-, n = 122). We used validated questionnaires to assess patient centredness. We also conducted focus group interviews (FGI) to better understand the impact of CCC with sp. RESULTS: Students after the CCC with simulated patients achieved a significantly higher score in the patient-practitioner orientation scale than other groups (p < 0.001). CONCLUSIONS: There is a strong positive correlation between the implementation of simulated patients and patient-centred attitudes among students. Data from the FGI revealed that students perceived training with SP as more realistic, safe, and engaging than student role playing. Practice Implications. Our research provides evidence to justify costs and resources invested in simulated patient programs.

Introduction/Objectives. Enterococcus faecalis has been implicated in infections of treated root canals. Current irrigants and intracanal medicaments cannot eliminate E. faecalis completely from the root canal. Silver diamine fluoride (SDF) prevents caries by promoting remineralization and exerting an antibacterial effect. Studies suggest that SDF may possess antibacterial properties against E. faecalis. The purpose of this review is to systematically and critically analyze the literature, focusing on the use of SDF as an intracanal medicament or irrigant, when compared to other antibacterial agents. Data/Sources. The focused question was "Is the antibacterial effect of SDF against E. faecalis better than other intracanal medicaments and irrigants?" Using the keywords ((silver diamine fluoride) AND (Enterococcus faecalis)) AND ((sodium hypochlorite) OR (NaOCl) OR (chlorhexidine) OR (calcium hydroxide) OR (Ca(OH)2)), an electronic search was conducted on the following databases: PubMed/MEDLINE, ISI Web of Science, Scopus, EMBASE, and Google Scholar. The clinical trial registers ClinicalTrials.gov and CONTROL were also searched using the same keywords. General characteristics and outcomes were extracted, and quality of the studies was assessed using the Preferred Reporting Items for Laboratory studies in Endodontology (PRILE) guidelines. Study Selection. Six articles (five in vitro studies and one ex vivo study) were included in this systematic review. In the majority of the studies, SDF had equal or better antibacterial efficacy against E. faecalis compared to calcium hydroxide, sodium hypochlorite, and chlorhexidine. However, the majority of the studies did not fulfill several items in the PRILE criteria and had numerous sources of bias. Conclusions. Within the limitations of the systematic review and the studies reviewed, SDF may be effective against E. faecalis and therefore could be used as an intracanal medicament and/or irrigant to prevent reinfections of the root canals and improve the outcomes of endodontic treatment. However, animal and clinical studies should be carried out to determine the efficacy of SDF in endodontics. Trial Registration. The protocol for this review was registered on PROSPERO. Registration number: CRD42021224741.

Owing to the high incidence and mortality rates of colorectal cancer (CRC), novel biomarkers for CRC diagnosis are critically needed. Therefore, this study is aimed at exploring the clinical utility of serum C-X-C motif chemokine 8 (CXCL-8) for CRC diagnosis and progression compared to the routinely used biomarkers, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). This study included 227 patients with CRC, 110 patients with colorectal adenoma (CA), and 123 healthy participants, who were recruited from the Fujian Medical University Union Hospital from July 1, 2019 to October 31, 2020. Serum concentrations of CXCL-8, CEA, and CA19-9 were detected using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Clinicopathological features of patients with CRC were collected and analyzed. The diagnostic efficacy of CXCL-8, CEA, and CA19-9 for CRC was evaluated using receiver operating characteristic (ROC) curves. We found that the serum concentrations of CXCL-8, CEA, and CA19-9 were significantly higher in patients with CRC than those in patients with CA and healthy controls. The diagnostic sensitivity of CXCL-8 alone was higher than those of CEA and CA19-9 both and when combined; thus, CXCL-8 may be better at discriminating patients with CRC from healthy controls and patients with CA. Moreover, combining CXCL-8 with CEA or CA19-9 improved their respective diagnostic performances in distinguishing patients with CRC from CA patients and healthy participants. Notably, we also found that serum concentrations of CXCL-8 were positively correlated with metastases and tumor size. Therefore, our study suggests that serum CXCL-8 may serve as an improved biomarker for CRC diagnosis compared to the traditional tumor markers CEA and CA19-9. Moreover, our findings indicate the potential efficacy of serum CXCL-8 levels as a CRC prognostic biomarker.

Annona muricata have been extensively used in traditional medicine to treat multiple diseases, including cancers. This study evaluated the genotoxic potential and antigenotoxic activities of A. muricata aqueous and ethanolic leaf extracts by employing an in vivo erythrocyte rodent micronucleus assay. Different doses (187.5, 375, and 750 mg/kg) of both extracts were administered orally for 5 days alone and combined with cyclophosphamide (CP, 60 mg/kg) to BALB/c mice. Also, it was administered orally to Wistar rats for 5 days through the final stage of gestation. No genotoxic or cytotoxic effects were observed in the two adult rodent models when A. muricata was administered orally nor in newborn rats transplacentally exposed to the extracts. Moreover, A. muricata aqueous and ethanolic leaf extracts demonstrated a protective effect against CP-induced DNA damage. Due to its lack of genotoxic effect and its capacity to decrease DNA damage, A. muricata is likely to open an interest field regarding its potential safe use in clinical applications.

BACKGROUND: A plethora of inflammatory, angiogenic, and tissue remodeling factors has been reported in idiopathic epiretinal membranes (ERMs). Herein we focused on the expression of a few mediators (oxidative, inflammatory, and angiogenic/vascular factors) by means of short-term vitreal cell cultures and biomolecular analysis. METHODS: Thirty-nine (39) ERMs and vitreal samples were collected at the time of vitreoretinal surgery and biomolecular analyses were performed in clear vitreous, vitreal cell pellets, and ERMs. ROS products and iNOS were investigated in adherent vitreal cells and/or ERMs, and iNOS, VEGF, Ang-2, IFNγ, IL18, and IL22 were quantified in vitreous (ELISA/Ella, IF/WB); transcripts specific for iNOS, p65NFkB, KEAP1, NRF2, and NOX1/NOX4 were detected in ERMs (PCR). Biomolecular changes were analyzed and correlated with disease severity. RESULTS: The higher ROS production was observed in vitreal cells at stage 4, and iNOS was found in ERMs and increased in the vitreous as early as at stage 3. Both iNOS and NOX4 were upregulated at all stages, while p65NFkB was increased at stage 3. iNOS and NOX1 were positively and inversely related with p65NFkB. While NOX4 transcripts were always upregulated, NRF2 was upregulated at stage 3 and inverted at stage 4. No significant changes occurred in the release of angiogenic (VEGF, Ang-2) and proinflammatory (IL18, IL22 and IFNγ) mediators between all stages investigated. CONCLUSIONS: ROS production was strictly associated with iNOS and NOX4 overexpression and increased depending on ERM stadiation. The higher iNOS expression occurred as early as stage 3, with respect to p65NFkB and NRF2. These last mediators might have potential prognostic values in ERMs as representative of an underneath retinal damage.

The objective of this study was to verify the influence of the ACTN3 R577X polymorphism on muscle damage and the inflammatory response after an acute strength training (ST) session. Twenty-seven healthy male individuals (age: 25 ± 4.3 years) participated in the study, including 18 RR/RX and 9 XX individuals. The participants were divided into two groups (RR/RX and XX groups) and subjected to an acute ST session, which consisted of a series of leg press, leg extension machine, and seated leg curl machine. The volunteers were instructed to perform the greatest volume of work until concentric muscle failure. Each volunteer's performance was analyzed as the load and total volume of training, and the blood concentrations of C-C motif chemokine ligand 2 (CCL2), interleukin-8 (IL-8), creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, testosterone, and cortisol were measured before the ST session and 30 min and 24 h postsession. The ACTN3 R577X polymorphism effect was observed, with increased concentrations of CCL2 (p < 0.01), IL-8 (p < 0.01), and LDH (p < 0.001) in XX individuals. There was an increase in the concentration of CK in the RR/RX group compared to XX at 24 h after training (p > 0.01). The testosterone/cortisol ratio increased more markedly in the XX group (p < 0.001). Regarding performance, the RR/RX group presented higher load and total volume values in the training exercises when compared to the XX group (p < 0.05). However, the XX group presented higher values of delayed onset muscle soreness (DOMS) than the RR/RX group (p < 0.05). The influence of ACTN3 R577X polymorphism on muscle damage and the inflammatory response was observed after an acute ST session, indicating that the RR/RX genotype shows more muscle damage and a catabolic profile due to a better performance in this activity, while the XX genotype shows more DOMS.

In recent years, extensive research has been focused on the field of single cell analysis. The isolation of single cells is the first step in this type of research. However, the techniques used for direct isolation and acquisition of single adherent cells are limited. Here, we present a method of obtaining selected single adherent cells using a separation device. Compared with other single cell isolation methods, this method has the advantages of simple operation, low cost, minimal cell damage, and preservation of cell morphology. Our methodology is, therefore, suitable for the collection of selected single adherent cells.

Plant species are known to harbor large number of endophytes, which stays in plant tissues as symbionts. These endophytes secrete large array of bioactive compounds that have potency against certain diseases with no side effects. We have collected leaf samples of the Moringa oleifera plant from the Pakistan Forest Institute, Khyber Pakhtunkhwa, Pakistan for the isolation of beneficial endophytes. The strains isolated from the leaves of M. oleifera were coded with MOL and tested for antimicrobial, antifungal, germicidal, phytotoxic, insecticidal, cytotoxic, and anti-inflammatory activities. The isolates, MOL1, MOL16, MOL19, and MOL21, possessed antibacterial activity against Staphylococcus aureus, whereas MOL7 inhibited 55% of the growth of Escherichia coli. MOL3 inhibited the growth of E. coli, S. aureus, and Pseudomonas aeruginosa. The strains, MOL1 and MOL7, showed antifungal activity against Candida albicans and Saccharomyces cerevisiae, while the strains, MOL11 and MOL17, showed activity against Verticillium chlamydosporium. The isolates, MOL3, MOL7, MOL9, MOL15, MOL17, MOL18, and MOL19, inhibited the growth of Lemna minor (duckweed) at 100 μg/ml. MOL2 exhibited strong activity in the brine shrimp assay, while MOL1, MOL2, MOL5, MOL6, MOL12, MOL17, MOL19, and MOL20 showed insecticidal, and MOL3 demonstrated larvicidal and antileishmanial activity. The isolated potent endophytes were identified as Aspergillus, Penicillium, Fusarium, Tricoderma, Rhizoctonia, Mucor, Alternaria, Pestalotiopsis, Acremonium, and Cladosporium through morphological and microscopic characteristics of the colonies.

BACKGROUND: Despite good results of total knee arthroplasty (TKA) as a treatment of idiopathic osteoarthritis (OA) of the knee, significant number of patients (16-33%) complain of persistent pain of unknown origin. This phenomenon is the major cause of patient's dissatisfaction. It has been theorized that certain preoperative factors may increase the risk of persistent pain; hence, their identification should enable proper preoperative education and development of realistic expectations regarding results of TKA. This study is aimed at identifying the preoperative chronic pain predictors in patients undergoing TKA. METHODS: In this prospective cohort study, patients scheduled for TKA were examined one day prior to surgery. Demographics, comorbidities, pressure pain thresholds, pain intensity and duration, radiographic OA grade, and range of motion were recorded. Questionnaires such as Beck Depression Inventory (BDI) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were collected. Study cohort was evaluated approximately 6 months following surgery. Patients were assigned to group A if they had no pain and to group B if they complained of any pain. Collected data was analyzed by biostatistician. RESULTS: 64 patients were included in final analysis, 49 (76,6%) females and 15 (23,4%) males. Mean age was 67,6 yrs (48-84, ±7,42). Group A consisted of 21 patients (33%) while group B consisted of 43 patients (67%). There were no statistically significant differences regarding preoperative factors except for duration of preoperative pain, which was shorter in group A (36 (12-180) vs. 72 (24-180), p = 0,011). Every 12 months of preoperative pain were found to increase risk of persistent pain by 1,27 (p = 0,009). CONCLUSIONS: Preoperative duration of pain is a risk factor for chronic pain following TKA. Therefore, patients should be operated on as soon as indications arise. Should the surgical treatment of knee arthritis be postponed, intensive and individualized pain management is highly recommended.

BACKGROUND: Ubiquitination is an important regulator in physiological and pathological conditions. Ubiquitin-specific protease 2 (USP2), as a member of the USP family, exhibits oncogenic effects in multiple malignancies. However, the exact role of USP2 has not been well clarified in lung cancer pathogenesis and progression. Therefore, we aimed to further investigate the regulatory roles of USP2 in lung cancer in this study. METHODS: Firstly, immunoprecipitation-Mass Spectrometry (IP-MS), Co-immunoprecipitation (Co-IP), combined with immunofluorescent colocalization method, was conducted for USP2 protein interaction analysis in lung cancer cell lines. qRT-PCR, Western blot, and immunohistochemistry assays explored the USP2 expression pattern and USP2/ARID2- (AT-rich interactive domain 2-) specific shRNAs and overexpression vectors. Co-IP assays were designed to validate USP2-ARID2 protein interaction. Further functional studies including CHX chase assay, transwell assay, and wound healing assay were subsequently applied to evaluate the impact of USP2 modulation on lung cancer cells. RESULTS: USP2 suppression was characteristic in lung cancer cell line models and lung cancer samples. USP2 and ARID2 demonstrated protein-protein interaction and overlapping localization in cancer cell models. Functional experiments suggested USP2 inhibited lung cancer cell invasion and migration by reducing ARID2 protein degradation. Subsequent ubiquitination assays indicated ARID2 protein degradation via the ubiquitination was significantly reduced by USP2 interaction. CONCLUSIONS: Our study provided novel insight that USP2 might suppress lung cancer by reducing ARID2 protein degradation via ubiquitination.

Radiotherapy is one of the main treatment modalities in nonsmall cell lung cancer (NSCLC). However, tumor radiosensitivity is influenced by intrinsic factors like genetic variations and extrinsic factors like tumor microenvironment. Consequently, we hope to develop novel biomarkers, so as to improve the response rate of radiotherapy and overcome resistance to radiotherapy in NSCLC. We investigate the difference genes of primary NSCLC patients before and after radiotherapy in GSE162945 dataset. Gene Ontology (GO), KEGG, Reactome, and GSEA were employed to represent the essential gene and biological function. It was found that most pathway genes clustered in extracellular matrix and ECM-receptor signal pathway. Additionally, TMT-based proteomics was used to survey the differential proteins present in the supernatant of H460 cells before or after irradiation with 2 Gy of γ-rays. And then we take the intersection between the proteomics of H460 cell and ECM-receptor signal pathway proteins of GSE162945 datasets. The data revealed that fibronectin 1 (FN1) and thrombin reactive protein 1 (THBS1) were upregulated after radiation in both datasets. Subsequently, survival analyses using the GEPIA web server demonstrated that FN1 and THBS1 had significant prognostic values (Logrank test P value < 0.05) for LUAD and LUSC. Our observations from this study suggest that FN1 and THBS1 might have potential to serve as novel biomarkers for predicting NSCLC tumor response to radiotherapy.

BACKGROUND: We aimed to evaluate the prognostic value of E2F4 expression in oral squamous cell carcinoma (OSCC) and clarify its influence on immune cell infiltration and biological functions. METHODS: The Cancer Genome Atlas (TCGA) database, the STRING database, and related online tools as well as single-sample gene set enrichment analysis (ssGSEA) were used for the analyses in our study. RESULTS: The E2F4 expression was elevated in OSCC tumor tissue compared with paracancerous tissues. The high expression of E2F4 was closely related to the poorer overall survival, disease-free survival, and progression-free interval of OSCC. In addition, pathway enrichment analyses revealed that the top 49 genes most closely related to E2F4 were strongly associated with the cell cycle. E2F4-related proteins were closely related to the following KEGG pathways: cell cycle, cellular senescence, PI3K-Akt signaling pathway, Wnt signaling pathway, and notch signaling pathway. It was also demonstrated that the E2F4 expression was negatively correlated with immune purity and strongly related to immune cell infiltration in OSCC. CONCLUSIONS: E2F4 can be used as a novel biomarker for the diagnosis and prognosis of OSCC.

This study investigated the thickness of the deltoid muscle and the location of the anterior branch of the axillary nerve (AAN) and posterior circumflex humeral artery (PCHA), with the goal of maximizing the effectiveness of deltoid injections. Forty specimens from 22 adult Korean cadavers were used. A reference line was identified, connecting the anterior point of the deltoid muscle (AP) and the posterior point of the deltoid muscle (PP) on the surface. The midpoint between the AP and PP was used as the origin point (OP). The line connecting the OP and the lowest point of the deltoid tuberosity (DP) was used as the y-axis. The mean distance of the reference line from the AP to PP was 4.7 ± 0.7 cm. The vertical mean length of the deltoid muscle from the OP and DP was 16.1 ± 1.0 cm. At the 3, 5, and 7 cm sites, the thickness of the deltoid muscle was 0.62 ± 0.9, 0.73 ± 0.7, and 1.3 ± 1.1 cm, respectively. Most of the branches of the axillary nerve were concentrated in the third section (4-6 cm, 51%), while the branches of the PCHA were predominantly found in the fourth section (6-8 cm, 69%). The peripheral branches of the AAN entering the muscle were distributed between 2.2 and 9.8 cm from the acromion. The mean number of the peripheral branches of the AAN was 9.6 ± 3.4. In the deltoid muscle, the mean number of peripheral branches of the PCHA was 8.2 ± 2.8. Administering deltoid injections 5-6 cm below the OP is recommended to avoid axillary nerve injury.

OBJECTIVE: To explore the relationship between vascular overload index (VOI) and cardiovascular disease (CVD) in rural population and find effective ways to prevent cardiovascular disease in rural low-income populations. METHODS: The data for this study was obtained from a large cohort study called the Northeast China Rural Cardiovascular Health Study (NCRCHS) conducted in 2013 and followed up during 2015-2018. 10,174 subjects completed at least one follow-up visit. Cox regression equation was used to explore whether VOI and cardiovascular disease were independently related. The Kaplan-Meier curves were used to calculate the cumulative incidence of any adverse outcome, and the log-rank test and restrict mean survival analysis were used to compare group differences. Reclassification and discrimination statistics were used to determine whether VOI could strengthen the ability of the model to predict CVD events. RESULTS: The prevalence of CVD in the VOI quartiles was 1.92%, 3.96%, 5.42%, and 11.34% for Q1-Q4, respectively (P for trend <0.001). After adjusting for multiple confounders, there was a 2.466-fold increased risk of CVD when comparing the highest and lowest groups. Besides, this study found that for every standard deviation increase, the results still exist. The risk of cardiovascular disease increased by 1.358-fold in this model. The restrict mean survival analysis results show that with the increase of VOI, the restrict mean survival time (RMST) within 5 years gradually became shorter. Reclassification and discrimination statistics indicated that VOI significantly enhanced the ability to estimate CVD events within 4 years. CONCLUSION: Analyses showed that VOI was significantly associated with CVD. VOI is a simple and accurate prognostic marker of CVD risk, which has the potential ability to improve the risk stratification of CVD.

Millions of people around the world have bone-tissue defects. Autologous and allogeneic bone grafting are frequent therapeutic techniques; however, none has produced the best therapeutic results. This has inspired researchers to investigate novel bone-regeneration technologies. In recent years, the development of bone tissue engineering (BTE) scaffolds has been at the forefront of this discipline. Due to their limitless supply and lack of disease transmission, engineered bone tissue has been advanced for the repair and reconstruction of bone deformities. Bone tissue is a highly vascularized, dynamic tissue that constantly remodels during an individual's lifetime. Bone tissue engineering is aimed at stimulating the creation of new, functional bone by combining biomaterials, cells, and factor treatment synergistically. This article provides a review of wollastonite's biomaterial application in bone tissue engineering. This work includes an explanation of wollastonite minerals including mining, raw materials for the synthesis of artificial wollastonite with various methods, its biocompatibility, and biomedical applications. Future perspectives are also addressed, along with topics like bone tissue engineering, the qualities optimal bone scaffolds must have, and the way a scaffold is designed can have a big impact on how the body reacts.

Azakheli is relatively smaller riverine breed with a very peculiar characteristics kept under unique traditional husbandry practices in comparison with rest of the Pakistani buffalo breeds; however, milk production is comparable. The present study was conducted to evaluate the genetic diversity of Azakheli breed. A total of sixty-six blood samples were collected for the amplification of mtDNA D-loop region and MC1R gene sequencing analysis. Median-joining network analysis of 191 mtDNA D-loop sequences of Azakheli and eight Indian riverine buffalo breeds clustered into three clades. Ancient Azakheli Region 1 clade was the oldest with the highest mutation steps and was present close to the root of UPGMA phylogenetic tree. There was 5 mutated lines distance between Pakistan buffalo and Indian riverine buffaloes. The populations of neighboring countries did not share any haplotypes with Azakheli buffalo of Pakistan. Possibly, residing for so long in the cold atmosphere and high elevation regions caused the mutation in mtDNA D-loop, though these conditions did not affect the overall performance of Azakheli as milch buffalo breed of Pakistan. MC1R analyses showed high mutations in Azakheli of Albino phenotype and all the black phenotype individuals of Azakheli buffalo share haplotypes with dominant Chinese and Indian black phenotypes buffaloes in MC1R median-joining network, indicating the reason of black coat color is due to MC1R gene. The haplotype diversity and nucleotide diversity was (H. 0.923, Pi: 0.00895) in Azakheli. Current results illustrated Asian ancestry for Azakheli buffalo, and mtDNA and MC1R analyses provided further evidence. Additional genetic analyses and archeological studies may provide further insight into the domestication period and history of Azakheli buffalo breed. The further studies are required on different coat colors with different genes on Azakheli buffalo to understand the phenotype variation.

INTRODUCTION: Menopause is an inevitable part of women's lives. Physical activity as nonhormonal therapy can decrease the symptoms of menopause. This study is aimed at investigating the effect of educational intervention based on the transtheoretical model (TTM) on physical activity and menopausal symptoms of female clients of the health center in Pasargad City, Iran. METHODS: This quasi-experimental study was performed on 140 females admitted to health center of Pasargad City, Fars Province, Iran (intervention = 70 and control = 70). The data collection tool consisted of demographic data, menopause rating scale, international physical activities questionnaire, and TTM questionnaire (stages of change, processes of change, decision-making balance, and self-efficacy) that were completed before and two months after intervention. For intervention group, the educational program was implemented during 5 sessions of 50-55 min. Data were analyzed by SPSS 25 and by using Chi-square test, independent t-test, and paired t-test. RESULTS: After intervention, the mean scores of physical symptoms are sleep problems, muscle problems and discomfort, psychological symptoms, depression, irritability, and anxiety of intervention group decreased significantly post intervention (p < 0.001). Analysis showed that psychological symptoms, mental fatigue, somatic, and urogenital symptoms, and vaginal dryness increased 2 months after the intervention. Also, the mean score of cons, pros, decision balance, self-efficacy, consciousness raising, dramatic relief, environmental reevaluation, and self-reevaluation have significant changed in intervention group (p < 0.05). In addition, the top percent of progress can be seen in contemplation (31. 5%). CONCLUSION: This study showed the effectiveness of educational intervention based on TTM to reduce menopausal symptoms and promote physical activity in postmenopausal women.

In recent studies, stem cell-based therapy is a potential new approach in the treatment of stroke. The mechanism of human umbilical cord mesenchymal stem cell (hUMSC) transplantation as one of the new approaches in the treatment of ischemic stroke is still unclear. The aim of this study was to determine the traits of immune responses during stroke progression after treatment with human umbilical cord blood MSCs by bioinformatics, to predict potential prognostic biomarkers that could lead to sex differences, and to reveal potential therapeutic targets. The microarray dataset GSE78731 (mRNA profile) of middle cerebral artery occlusion (MCAO) rats was obtained from the Gene Expression Omnibus (GEO) database. First, two potentially expressed genes (DEGs) were screened using the Bioconductor R package. Ultimately, 30 specific DEGs were obtained (22 upregulated and 353 downregulated). Next, bioinformatic analysis was performed on these specific DEGs. We performed a comparison for the differentially expressed genes screened from between the hUMSC and MCAO groups. Gene Ontology enrichment and pathway enrichment analyses were then performed for annotation and visualization. Gene Ontology (GO) functional annotation analysis shows that DEGs are mainly enriched in leukocyte migration, neutrophil activation, neutrophil degranulation, the external side of plasma membrane, cytokine receptor binding, and carbohydrate binding. KEGG pathway enrichment analysis showed that the first 5 enrichment pathways were cytokine-cytokine receptor interaction, chemokine signal pathway, viral protein interaction with cytokine and cytokine receptor, cell adhesion molecules (CAMs), and phagosome. The top 10 key genes of the constructed PPI network were screened, including Cybb, Ccl2, Cd68, Ptprc, C5ar1, Il-1b, Tlr2, Itgb2, Itgax, and Cd44. In summary, hUMSC is likely to be a promising means of treating IS by immunomodulation.

INTRODUCTION: The aim of this study was to compare selected spatiotemporal parameters and changes in the range of motion in the joints of lower and upper limbs during normal gait and during Nordic walking performed with classical and mechatronic poles of females and males. METHODS: The study involved 19 physical education students (11 males and 8 females). The MyoMotion research motion analysis system was used to collect gait kinematic variables. The subject task was to cover a 100 m distance in a straight line with three types of gait: gait without poles, gait with classical poles, and gait with mechatronic poles at preferred velocity. Parameters were measured both on the right (RT) and on the left side (LT) of the body. The data was analyzed using two-way repeated measures ANOVA with the between-subject factor "sex." Friedman's test was used when necessary. RESULTS: The most significant differences in spatiotemporal parameters between males and females were revealed in gait with the classical and mechatronic pole (stance phase LT and RT, load response LT and RT, single support LT and RT, preswing LT and RT, swing phase LT and RT, double stance LT and RT, and step length LT), the least in gait without a pole (stance phase RT, load response LT, single support LT, preswing RT, and swing phase RT); whereas, the most significant differences in kinematic parameters were revealed in gait without poles (shoulder rotation RT, wrist radial-ulnar LT, hip flexion-extension LT and RT, knee flexion-extension LT and RT, ankle inversion-eversion LT, and ankle abduction-adduction LT and RT), the least in gait with mechatronic poles (knee flexion-extension LT and RT, ankle dorsiflexion-plantarflexion LT, ankle inversion-eversion LT, and ankle abduction-adduction LT and RT). CONCLUSION: Statistical analysis revealed many differences in spatiotemporal and kinematic parameters in normal gait, as well as in gait with the classical and mechatronic poles, which allows the conclusion that the gait of females and males should be analyzed separately.

Deemed one of the most problematic neurodegenerative diseases in the elderly population, Parkinson's disease remains incurable to date. Ongoing diagnostic studies, however, have revealed that a large number of small molecule drugs that trigger the BMP2-Smad signaling pathway with an osteogenic nature may be effective in Parkinson's disease treatment. Although BMP2 and Smad1, 3, and 5 biomolecules promote neurite outgrowth and neuroprotection in dopaminergic cells as well, small molecules are quicker at crossing the BBB and reaching the damaged dopaminergic neurons located in the substantia nigra due to a molecular weight less than 500 Da. It is worth noting that osteogenic small molecules that inhibit Smurf1 phosphorylation do not offer therapeutic opportunities for Parkinson's disease; whereas, osteogenic small molecules that trigger Smad1, 3, and 5 phosphorylation may have strong therapeutic implications in Parkinson's disease by increasing the survival rate of dopaminergic cells and neuritogenesis. Notably, from a different perspective, it might be said that osteogenic small molecules can possibly put forth therapeutic options for Parkinson's disease by improving neuritogenesis and cell survival.

Mitochondrial dysfunction and increased oxidative stress cause damage to cells which can lead to the aging process and age-related diseases. Antioxidants such as resveratrol and high-intensity exercise can benefit oxidative damage prevention. This study is aimed at evaluating the effects of swimming high-intensity interval training and resveratrol on mitochondrial metabolism key proteins, SIRT5, SOD1, and PDH-E1α, and the level of NAD+ as a cofactor in the deacetylation process in aged rat hippocampus. Forty-five male Wistar rats, aged 20 months, were randomly divided into five groups: control (C), Swimming High-Intensity Interval Training (HIIT) (S-HIIT), Swimming HIIT with resveratrol supplementation (S-HIIT-R), resveratrol supplementation (R), and solvent of resveratrol supplementation (SR). S-HIIT and resveratrol groups performed the exercise and received resveratrol (10 mg/kg/day, gavage) for six weeks. Western blot analysis was performed to determine the protein level in the hippocampus. The amount of SIRT5 and SOD1 proteins in the hippocampus increased. S-HIIT with resveratrol or resveratrol alone increased the PDH-E1α level significantly. The amount of NAD+ was analyzed by assay kit that was reduced in S-HIIT, S-HIIT-R, and SR groups compared to controls. The results showed that resveratrol and S-HIIT attenuated the age-related brain changes by increasing the expression of SOD1 and SIRT5 and reducing the level of NAD+ in the hippocampus. Considering these findings, S-HIIT and resveratrol supplementation could be proposed as strategies to attenuate age-related brain changes. Resveratrol alone and exercise through the regulation of crucial proteins and cofactors can influence mitochondrial metabolism and oxidative stress in the hippocampus of aged rats.

Gaming addiction has gradually developed among medical students and has been a contentious topic for nearly a decade. This study is aimed at estimating the prevalence of gaming addiction among medical students at King Saud University and examining the relationship between perceived stress levels and gaming addiction. We conducted a cross-sectional study among 370 students from 2019 to 2020 using a self-reporting questionnaire consisting of two validated test scales: the Gaming Disorder Test and the Perceived Stress Scale. The questionnaire was sent to all students through an email. Descriptive analyses and t-test statistical tests were used in this study. The prevalence rate of gaming addiction was found to be 4.6%, while the prevalence of perceived stress was confirmed at 95.9%. Students with excellent GPAs and high family income were associated (p < 0.001). Younger groups, females, and students with high family incomes showed higher levels of perceived stress than others. According to Pearson's correlation, gaming addiction was not significantly correlated with stress among medical students (p > 0.05). According to chi-square test also, no significant association was found between gaming disorder and perceived stress (χ 2 = 4.412; p = 0.353). In conclusion, gaming addiction among medical students has scored low prevalence, indicating gaming is not a factor contributing to stress among this group. The high level of perceived stress among medical students should draw attention to the provision of regular psychological care.

OBJECTIVE: The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non-GDM groups, respectively. Study Design. To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case-cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non-GDM group were analyzed, respectively. RESULTS: The proportion of GDM in the sPTB (19.51%) was higher than the controls (7.47%, P = 0.018). The vaginal microbiota of pregnant women with sPTB exhibited higher alpha diversity metrics (observed features, P = 0.001; Faith's phylogenetic diversity, P = 0.013) and different beta diversity metrics (unweighted UniFrac, P = 0.006; Jaccard's distance, P = 0.004), compared with controls. The presence of Lactobacillus paragasseri/gasseri (aOR: 3.12, 95% CI: 1.24-7.84), Streptococcus (aOR: 3.58, 95% CI: 1.68-7.65), or Proteobacteria (aOR: 3.39, 95% CI: 1.55-7.39) was associated with an increased risk of sPTB in the non-GDM group (P < 0.05). However, the relative abundance of novel L. mulieris (a new species of the L. delbrueckii group) was associated with a decreased risk of sPTB (false discovery rate, 0.10) in all pregnant women. CONCLUSION: GDM may modify the association of vaginal taxa with sPTB, suggesting that maternal GDM should be considered when using vaginal taxa to identify pregnant women at high risk of sPTB.

INTRODUCTION: Esophagus squamous cell carcinoma (ESCC) has a poor prognosis, a high rate of metastasis, and rapid clinical progression. One hypothesis is that therapeutic failure is due to the presence of cancer stem cells (CSC). Previous studies showed the anticancer effect of cerium oxide nanoparticles (CNP) in different cancer cells. In this study, we aim to evaluate the effect of cerium oxide nanoparticles on cell antioxidants, toxicity, as well as cell oxidant level in esophageal cancer (YM1) and cancer stem cell-like (CSC-LC) cell lines. METHOD: YM1 and CSC-LC spheres were treated with CNP at different concentrations. The cell viability was assessed by using the MTT test. Antioxidant levels (SOD (superoxide dismutase, CAT (catalase), thiol, and TAC (total antioxidant capacity)), antioxidant genes expression (SOD and CAT), ROS (reactive oxygen species), and MDA (malondialdehyde) levels were assessed in both cell lines. RESULTS: CSC-LC had significantly elevated SOX4 and OCT4 pluripotent genes. The ROS and MDA levels were significantly reduced in both YM1 and CSC-LC spheres after treatment with CNP. Also, the antioxidant levels and expressions were elevated significantly in both cell lines after CNP treatment. CONCLUSION: These results suggest the potential anticancer effect of CNP by elevating antioxidant levels and expressions, and reducing oxidant levels.