BACKGROUND: The demand for point-of-care testing (POCT) devices has rapidly grown since they offer immediate test results with ease of use, makingthem suitable for home self-testing patients and caretakers. However, the POCT development has faced the challenges of increased cost and limited resources. Therefore, the paper substrate as a low-cost material has been employed to develop a cost-effective POCT device, known as "Microfluidic paper-based analytical devices (μPADs)". This device is gaining attention as a promising tool for medicinal diagnostic applications owing to its unique features of simple fabrication, low cost, enabling manipulation flow (capillarydriven flow), the ability to store reagents, and accommodating multistep assay requirements. OBJECTIVE: This review comprehensively examines the fabrication methods and device designs (2D/3D configuration) and their advantages and disadvantages, focusing on updated μPADs applications for motif identification. METHODS: The evolution of paper-based devices, starting from the traditional devices of dipstick and lateral flow assay (LFA) with μPADs, has been described. Patterned structure fabrication of each technique has been compared among the equipment used, benefits, and drawbacks. Microfluidic device designs, including 2D and 3D configurations, have been introduced as well as their modifications. Various designs of μPADs have been integrated with many powerful detection methods such as colorimetry, electrochemistry, fluorescence, chemiluminescence, electrochemiluminescence, and SER-based sensors for medicinal diagnosis applications. CONCLUSION: The μPADs potential to deal with commercialization in terms of the state-of-the-art of μPADs in medicinal diagnosis has been discussed. A great prototype, which is currently in a reallife application breakthrough, has been updated.

Scutellaria baicalensis Georgi, known as "Huangqin" in its dried root form, is a herb widely used in traditional Chinese medicine for "clearing away heat, removing dampness, purging fire and detoxification". Baicalin, baicalein, wogonin, and wogonoside are the main flavonoid compounds found in Scutellaria baicalensis. This review summarizes the latest and most comprehensive information regarding the absorption, distribution, metabolism and excretion of the Scutellaria baicalensis components in vivo. We examined the main advantages of nanodrug delivery systems and collected detailed information on nanosystem delivery of the Scutellaria baicalensis components, including nanosuspensions and various lipid-based nanosystems. Lipid-based systems including liposomes, solid lipid nanoparticles, nanoemulsions and self-microemulsifying drug delivery systems are introduced in detail. In addition, we make recommendations for related and future research directions. Future research should further examine the absorption mechanisms and metabolic pathways of nanoformulations of the components of Scutellaria baicalensis in vivo, and accurately track the in vivo behavior of these drug delivery systems to discover the specific reasons for the enhanced bioavailability of nanoformulations of the Scutellaria baicalensis components. The development of targeted oral administration of intact nanoparticles of Scutellaria baicalensis components is an exciting prospect.

Extracellular vesicles (EVs) are lipid bilayer-delimited particles secreted by cells and are regarded as a promising class of nanocarriers for biomedical applications such as disease diagnosis, drug delivery, and immunomodulation, as they carry biomarkers from the parental cells and can also transport diverse cargo molecules between cells. Surface functionalization of EVs can help obtain detectable signals for their quantification and also add various properties for EV-based delivery. Aptamers are specific oligonucleotides selected as artificial antibodies that could serve as 'cruise missiles' to target EVs for diagnosis or as navigators to bring EVs to lesions for treatment. DNA logic devices or nanostructures based on aptamers are intelligent designs to endow EVs with additional features, such as multi-target disease diagnosis in one pot and promoting retention of EVs in complex disease microenvironments. Oligonucleotides or DNA nanostructures composed of natural nucleic acids can be easily degraded by nuclease in the biological sample which limits their applications. Thus, the oligonucleotides composed of artificial nucleic acids which are synthesized against degradation would be a potential strategy to improve their stability in vitro or in vivo. Herein, we review the methods for surface functionalization of EVs by nucleic acids and highlight their applications in quantification and targeted delivery towards disease diagnosis and therapy.

Malaria, caused by parasites of the Plasmodium species, is still a fatal and dangerous disease in mainly tropical and subtropical regions. The widespread resistance of P. falciparum to antimalarial drugs forces the search for new molecules with activity against this parasite. One of the most promising approaches has been the identification of effective inhibitors of P-type cation-transporter ATPase 4 (PfATP4) in P. falciparum. PfATP4 is a Na+ efflux pump that maintains a low cytosolic Na+ in the parasite. The current review presents PfATP4 function in the context of the pharmacological influence of its inhibitors. In addition, compounds with inhibitory activities belonging to spiroindolones, dihydroisoquinolones, aminopyrazoles, pyrazoleamides, and 4-cyano-3-methylisoquinolines, are also reviewed. Particular emphasis is placed on the results of preclinical and clinical studies in which their effectiveness was tested. PfATP4-associated antimalarials rapidly cleared parasites both in mouse models as well as in preliminary human trials. These findings highlight a fundamental biochemical mechanism sensitive to pharmacological intervention that can form a medicinal chemistry approach for antimalarial drug design to create new molecules with potent PfATP4 inhibitory activity.