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Introduction: Scutellaria baicalensis Georgi, a traditional Chinese medicine, is widely applied to treat various diseases among people, especially in East Asia. However, the specific active compounds in S. baicalensis aqueous extracts (SBAEs) responsible for the hypoglycemic and hypolipidemic properties as well as their potential mechanisms of action remain unclear. Objectives: This work aimed to explore the potential hypoglycemic and hypolipidemic compounds from SBAE and their potential mechanisms of action. Methodology: The in vitro inhibitory tests against lipase and α‐glucosidase, and the effects of SBAE on glucose consumption and total triglyceride content in HepG2 cells were first performed to evaluate the hypoglycemic and hypolipidemic effects. Then, affinity ultrafiltration liquid chromatography–mass spectrometry (LC–MS) screening strategy with five drug targets, including α‐glucosidase, α‐amylase, protein tyrosine phosphatase 1B (PTP1B), lipase and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) was developed to screen out the potential active constituents from SBAE, and some representative active compounds were further validated. Results: SBAE displayed noteworthy hypoglycemic and hypolipidemic properties, and 4, 10, 4, 8, and 8 potential bioactive components against α‐amylase, α‐glucosidase, PTP1B, HMGCR, and lipase were initially screened out, respectively. The interaction network was thus constructed between the potential bioactive compounds screened out and their corresponding drug targets. Among them, baicalein, wogonin, and wogonoside were revealed to possess remarkable hypoglycemic and hypolipidemic effects. Conclusion: The potential hypolipidemic and hypoglycemic bioactive compounds in SBAE and their mode of action were initially explored through ligand–target interactions by combining affinity ultrafiltration LC–MS strategy with five drug targets. The potential hypolipidemic and hypoglycemic bioactive compounds in aqueous extract of Scutellaria baicalensis Georgi root and their mode of action were firstly explored through ligand–target interactions by combining affinity ultrafiltration LC‐MS strategy with five drug targets, that is, α‐amylase, α‐glucosidase, PTP1B, HMGCR, and lipase. [ABSTRACT FROM AUTHOR]

Moringa oleifera Lam. (M. oleifera) is a fast-growing and esculent plant with high nutritional and medicinal values. Traditionally, M. oleifera has been applied to treat anaemia, asthma, pain in joints, headaches, diarrhoea and so forth. Phytochemical studies have manifested that more than 300 components, including flavonoids, phenolic acids, organic acids, alkaloids, lignans, glucosinolates, carotenoids, proteins, fats, minerals, and so on, are present in different parts of M. oleifera. Simultaneously, M. oleifera has exhibited extensive notable pharmacological activities, such as antioxidant, anti-inflammatory, antimicrobial, anti-cancer, hypoglycemic, hypolipidemic, hypotensive, hepatoprotective, etc. Consequently, on the one hand, this work aims to comprehensively and holistically review the nutritional components, chemical constituents and pharmacological activities on various parts of M. oleifera, as well as its applications in functional food products and medicines. On the other hand, this work also looks forward to the new prospects and the future developments in the research of M. oleifera, and thus provides valuable insights for the follow-up and in-depth studies of this multifunctional tree. [ABSTRACT FROM AUTHOR]

Introduction: Numerous species of the Euphorbiaceae family, including Euphorbia maculata, Euphorbia humifusa, and Acalypha australis, have been used to manage bleeding disorders. However, few investigations have demonstrated their hemostatic potential, and their procoagulant compounds remain elusive. Objective: This study aimed to determine the most active procoagulant extracts from the three species' crude extract (CE) and fractions in order to screen out the active compounds and to analyze their possible mechanisms of action. Methods: An integrative approach, comprising prothrombin time and activated partial thromboplastin time evaluations and urokinase‐type plasminogen activator (uPA) inhibitory assessment, followed by bio‐affinity ultrafiltration paired with UPLC/QTOF‐MS targeting uPA and docking simulations, was used. Results: The extracts with highest procoagulant activity were the CE for both E. maculata (EMCE) and E. humifusa (EHCE) and the n‐butanol fraction (NB) for A. australis (AANB). The most promising ligands, namely, isoquercetin, orientin, rutin, and brevifolin carboxylic acid, were selected from these lead extracts. All of these compounds exhibited pronounced specific binding values to the uPA target and showed tight intercalation with the crucial side chains forming the uPA active pocket, which may explain their mode of action. The activity validation substantiated their hemostatic effectivity in inhibiting uPA as they had better inhibition constant (Ki) values than the reference drug tranexamic acid. Conclusion: Collectively, the integrative strategy applied to these three species allowed the elucidation of the mechanisms underlying their therapeutic effects on bleeding disorders, resulting in the fast detection of four potential hemostatic compounds and their mode of action. The four most promising ligands (isoquercetin, orientin, rutin, and brevifolin carboxylic acid) against uPA target were firstly selected in the active fractions extracted from E. maculata (EMCE), E. humifusa (EHCE), and A. australis (AANB), and their activity validation substantiates their hemostatic effectivity in mediating uPA as they expressed great constant inhibition (Ki) compared to the reference drug. [ABSTRACT FROM AUTHOR]

Potential resolved electrochemiluminescence (ECL) nanoluminophores are very important for precise analysis and simultaneous determination of multiple targets. Designing ideal potential resolved ECL nanoluminophores, generating multiple high efficiency ECL emissions without overlap and interference of potential and wavelength, is a challenging subject. Herein, we developed a new nanoluminophore, meso-tetra (4-carboxyphenyl) porphine (TCPP)-functionalized chitosan/Ru(bpy)32+/SiO2 (CRuSiO2) (TCPP@CRuSiO2), with cathode and anode ECL emissions by modifying TCPP on the surface of CRuSiO2 nanoluminophores. The TCPP@CRuSiO2 nanoluminophores presented a uniform sphere morphology (∼50 nm). They exhibited two ECL emissions of 695 nm and 610 nm at −1.20 V and 1.15 V, respectively, by using K2S2O8 and tripropylamine (TPrA) as coreactants. Subsequently, the relevant ECL mechanisms are proposed. In the negative potential range, sulfate radicals (SO4˙−) reacted with TCPP−, generated by the electro-reduction of S2O42− and TCPP, to form the excited state TCPP*, resulting in ECL-1. In the positive potential range, Ru(bpy)33+ and TPrA˙, obtained by electro-oxidation of Ru(bpy)32+ and TPrA, reacted with each other to produce the excited state Ru(bpy)32+*, leading to ECL-2. The synthesized TCPP@CRuSiO2 possesses not only potential and wavelength resolved ECL emissions, but also the advantages of easy synthesis, high ECL efficiency, good stability, and easy film formation on the electrode surface. This work enriches ECL nanoluminophores, which are of important application potential in precise analysis and multiplex analysis. [ABSTRACT FROM AUTHOR]

For epidemic prevention and control, molecular diagnostic techniques such as field‐effect transistor (FET) biosensors is developed for rapid screening of infectious agents, including Mycobacterium tuberculosis, SARS‐CoV‐2, rhinovirus, and others. They obtain results within a few minutes but exhibit diminished sensitivity (<75%) in unprocessed biological samples due to insufficient recognition of low‐abundance analytes. Here, an electro‐enhanced strategy is developed for the precise detection of trace‐level infectious agents by liquid‐gate graphene field‐effect transistors (LG‐GFETs). The applied gate bias preconcentrates analytes electrostatically at the sensing interface, contributing to a 10‐fold signal enhancement and a limit of detection down to 5 × 10−16 g mL−1 MPT64 protein in serum. Of 402 participants, sensitivity in tuberculosis, COVID‐19 and human rhinovirus assays reached 97.3% (181 of 186), and specificity is 98.6% (213 of 216) with a response time of <60 s. This study solves a long‐standing dilemma that response speed and result accuracy of molecular diagnostics undergo trade‐offs in unprocessed biological samples, holding unique promise in high‐quality and population‐wide screening of infectious diseases. [ABSTRACT FROM AUTHOR]

Polygonatum sibiricum Red. (P. sibiricum) has been used as a traditional Chinese medicine with a wide range of pharmacology effects. However, the responsible bioactive compounds and their mechanisms of action concerning its antioxidative and anti-hyperuricemic activities remain unexplored. In this work, the antioxidant capacity of P. sibiricum was firstly evaluated with the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3ethylbenzthiazoline)-6-sulfonic acid (ABTS) and ferric-reducing antioxidant power (FRAP) assays, from which the ethyl acetate (EA) fraction exhibited the highest DPPH, ABTS radical scavenging, and ferric-reducing capacities. Meanwhile, the EA fraction displayed the highest total phenolic and flavonoid contents among the four fractions. Next, the potential ligands from the EA fraction were screened out by bio-affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC-MS) with superoxide dismutase (SOD) and xanthine oxidase (XOD). As a result, N-trans-p-coumaroyloctopamine, N-trans-feruloyloctopamine, N-trans-feruloyltyramine were identified as potential SOD ligands, while N-cis-p-coumaroyltyramine was determined as potential XOD ligand. Additionally, these four ligands effectively interact with SOD and XOD in the molecular docking analysis, with binding energies (BEs) ranging from –6.83 to –6.51 kcal/mol, and the inhibition constants (Ki) from 9.83 to 16.83 μM, which were better than the positive controls. In conclusion, our results indicated that P. sibiricum has good antioxidative and anti-hyperuricemic activities, and its corresponding active ligands targeting SOD and XOD could be explored by the UF-LC-MS method. [ABSTRACT FROM AUTHOR]

Background: Dysosma versipellis (D. versipellis) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose: This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods: Bioaffinity ultrafiltration coupled to liquid chromatography–mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis, and then further validation was conducted using in vitro inhibition assays and molecular docking. Results: A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC50 value at 0.36 ± 0.02 μM lower than indomethacin at 0.73 ± 0.07 μM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC50 value at 104.79 ± 8.26 μM comparable to quercetin 3-O-glucoside at 135.25 ± 6.54 μM. Conclusion: We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants. Graphical [ABSTRACT FROM AUTHOR]

Mass spectrometry is the enabling technology for proteomics. To fully realize the enormous potential of lab-on-a-chip in proteomics, a major advance in interfacing microfluidics with mass spectrometry is needed. Here, we report the first demonstration of monolithic integration of multinozzle electrospray emitters with a microfluidic channel via a novel silicon microfabrication process. These microfabricated monolithic multinozzle emitters ([M.sup.3] emitters) can be readily mass-produced from silicon wafers. Each emitter consists of a parallel silica nozzle array protruding out from a hollow silicon sliver with a conduit size of 100 x 10 [micro]m. The dimension and number of freestanding nozzles can be systematically and precisely controlled during the fabrication process. Once integrated with a mass spectrometer, [M.sup.3] emitters achieved sensitivity and stability in peptide and protein detection comparable to those of commercial silica-based capillary nanoelectrospray tips. These [M.sup.3] emitters may play a role as a critical component in a fully integrated silicon/silica-based micro total analysis system for proteomics.

Parasitic infections impose a significant burden on public health worldwide. European pharmacopoeia records and ethnopharmacological studies indicate that Hagenia abyssinica (Bruce) J.F. Gmel. has traditionally been used to treat a variety of parasitic infections, while the potential antiparasitic compounds remain ambiguous. Acetylcholinesterase (AChE), lactate dehydrogenases (LDH), and glutathione reductase (GR) are the key target enzymes in the survival of parasites. The aim of our work was to screen antiparasitic compounds targeting AChE, LDH, and GR from H. abyssinica. Ultrafiltration-liquid chromatography–mass spectrometry (UF-LC–MS) combined with molecular docking was used in this study. Therein, the alamarBlue® and Ellman's methods were employed to reveal the antitrypanosomal effect and AChE inhibitory activity. Meanwhile, the UF-LC–MS was carried out to screen the potential active compounds from H. abyssinica. Subsequently, molecular docking was performed to evaluate the binding mechanisms of these active compounds with AChE, LDH, and GR. Finally, the AChE inhibitory activity of potential inhibitors was detected in vitro. H. abyssinica exhibited significant antitrypanosomal and AChE inhibitory activity. Corilagin, brevifolin carboxylic acid, brevifolin, quercetin, and methyl ellagic acid were recognized as potential AChE inhibitors by UF-LC–MS, while methyl brevifolin carboxylate was identified as AChE, LDH, and GR multi-target inhibitor, with binding degree ranged from 20.96% to 49.81%. Molecular docking showed that these potential inhibitors had a strong affinity with AChE, LDH, and GR, with binding energies ranging from −6.98 to −9.67 kcal/mol. These findings were further supported by the observation that corilagin, quercetin, brevifolin carboxylic acid, and methyl brevifolin carboxylate displayed significant AChE inhibitory activity compared with the positive control (gossypol, 0.42 ± 0.04 mM), with IC 50 values of 0.15 ± 0.05, 0.56 ± 0.03, 0.99 ± 0.01, and 1.02 ± 0.03 mM, respectively. This study confirms the antiparasitic potential of H. abyssinica , supporting the traditional use of H. abyssinica in local ethnopharmacology to treat parasites. At the same time, corilagin, brevifolin carboxylic acid, brevifolin, quercetin, methyl ellagic acid, and methyl brevifolin carboxylate exert their anti-parasitic effects by inhibiting AChE, LDH, and GR, and they are expected to be natural lead compounds for the treatment of parasitic diseases. [Display omitted] • Hagenia abyssinica exhibited good antiparasitic activity against T. b. brucei. • Explore AChE, LDH and GR inhibitors from H. abyssinica with an integrated strategy. • Six compounds revealed as potential AChE inhibitors. • Methyl brevifolin carboxylate was AChE, LDH, and GR multi-target inhibitor. • Mechanisms of enzyme-inhibitor interactions explored by molecular docking. [ABSTRACT FROM AUTHOR]

Salvia officinalis is one of the most important medicinal and aromatic plants in terms of nutritional and medicinal value because it contains a variety of vital active ingredients. Terpenoid compounds, particularly monoterpenes (C10) and sesquiterpenes, are the most important and abundant among these active substances (C15). Terpenes play a variety of roles and have beneficial biological properties in plants. With these considerations, the current study sought to clone theNAD+-dependent farnesol dehydrogenase (SoFLDH, EC: 1.1.1.354) gene from S. officinalis. Functional analysis revealed that, SoFLDH has an open reading frame of 2,580 base pairs that encodes 860 amino acids.SoFLDH has two conserved domains and four types of highly conserved motifs: YxxxK, RXR, RR (X8) W, TGxxGhaG. However, SoFLDH was cloned from Salvia officinalis leaves and functionally overexpressed in Arabidopsis thaliana to investigate its role in sesquiterpenoid synthases. In comparison to the transgenic plants, the wild-type plants showed a slight delay in growth and flowering formation. To this end, a gas chromatography-mass spectrometry analysis revealed that SoFLDH transgenic plants were responsible for numerous forms of terpene synthesis, particularly sesquiterpene. These results provide a base for further investigation on SoFLDH gene role and elucidating the regulatory mechanisms for sesquiterpene synthesis in S. offcinalis. And our study paves the way for the future metabolic engineering of the biosynthesis of useful terpene compounds in S. offcinalis. [ABSTRACT FROM AUTHOR]