Snakebite envenomation through a gender intersectionality lens in low- and middle-income countries.

Snakebite envenomation continues to affect lives globally, with >1.2 million envenomations and approximately 120 000 annual mortalities. Unfortunately, low- and middle-income countries (LMICs) contribute to >80% of these global statistics.

Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines.

Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively.

Marine natural product-inspired discovery of novel BRD4 inhibitors with anti-inflammatory activity.

Bromodomain-containing protein 4 (BRD4) has been identified as a promising target in drug discovery, and the development of novel specific BRD4 bromodomain inhibitors will benefit anti-inflammatory drug discovery as well as bromodomain function role disclose. Herein, inspired by marine quinazolinone alkaloid penipanoid C, we designed and synthesized a series of quinazolin-4(3H)-ones with diverse linkers between two aromatic ring systems. Among them, compound 25 possessed good in vitro BRD4 inhibitory activities (IC = 3.

miR-468-3p suppresses osteogenic differentiation of BMSCs by targeting Runx2 and inhibits bone formation.

An improved understanding of the molecular actions underpinning bone marrow mesenchymal stem cell (BMSC) differentiation could highlight new therapeutics for osteoporosis (OP). Current evidence indicates that microRNAs (miRNAs) exert critical roles in many biological systems, including osteoblast differentiation. In this study, we examined miR-468-3p effects on osteogenic differentiation (OD).

Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance.

Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity.

Semisynthesis of Nocarterphenyl A and Its Analogues.

-Terphenyl compounds are known to possess a diverse range of biological activities, making the synthesis of novel -terphenyl derivatives a significant research objective. In this study, we report the first synthesis of nocarterphenyl A (), characterized by a thiazole-fused -terphenyl framework. Furthermore, we synthesized 18 additional analogs, including the naturally occurring compound 5-methoxy-4,7-bis(4-methoxyphenyl)benzo[]thiazol-6-ol (), employing a similar synthetic approach.

Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice.

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation.

Two New Diterpenoids Formed by Transannular Diels-Alder Cycloaddition from the Soft Coral , and Their Antibacterial and PPAR-β Agonist Activities.

Two new cembrane-derived tricyclic diterpenes belonging to the sarcophytin family, namely 4-hydroxy-chatancin () and sarcotoroid (), together with two known related ones ( and ), were isolated from the soft coral collected off Ximao Island in the South China Sea. The structures of the new compounds were elucidated by extensive spectroscopic analysis, a quantum mechanical nuclear magnetic resonance (QM-NMR) method, a time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculation, X-ray diffraction analysis, and comparison with the reported data in the literature. A plausible biosynthetic pathway of compounds - was proposed, involving undergoing a transannular Diels-Alder cycloaddition.

Knowledge, Attitude, and Practice of Providing First Aid by Commercial Motorcyclists: A Cross-Sectional Study.

Introduction: The mortality and morbidity due to road traffic crashes (RTCs) are increasing drastically world-wide. Poor prehospital care management contributes to dismal patient outcomes, especially in low- and middle-income countries (LMICs). This study aimed to assess the knowledge, attitude, and self-reported practice (KAP) of providing first aid for RTC victims by commercial motorcyclists.

Detection of decline in estimated glomerular filtration rate in patients with type 2 diabetes by cystatin C-based equations.

Background: Aging population is a significant issue in Viet Nam and across the globe. Elderly individuals are at higher risk of chronic kidney disease (CKD), especially those with diabetes. Several studies found that the estimated glomerular filtration rate (eGFR) determined using creatinine-based equations was not as accurate as that determined using cystatin C-based equations.

Seaweed Extract Protected Human Mesenchymal Stem Cells From Oxidative Stress Through NRF2 Activation.

Previous studies have shown that seaweed extracts (HMEs) possess antioxidant properties, but the molecular mechanisms accounting for this activity are not known. Thus, the present study investigated the molecular mechanisms through which HME exerted its antioxidant activity in human mesenchymal stem cells (WJ-MSCs). After the isolation of HME, its chemical composition was analyzed with gas chromatography mass spectrometry, indicating that it contained amino acids, organic acids, organic amides, sugar alcohols, saturated fatty acids, hydrogenated diterpene alcohols, and other organic compounds.

A rare cause of dyspnea: Mounier Kuhn syndrome.

Mounier-Kuhn syndrome, also known as tracheobronchomegaly, is a rare clinical and radiological condition characterized by tracheobronchial dilatation and recurrent respiratory infections. Patients may be asymptomatic or present with severe respiratory illnesses. A CT scan is sufficient to confirm the diagnosis.

Naphpyrones A-H, Antibacterial Aromatic Polyketides Isolated from the A3(2)/ ΔH3.

, a common foodborne pathogen, has a close association with agriculture and food. With the rapid emergence and widespread dissemination of antimicrobial resistance, efforts have been directed toward developing and studying new antimicrobial compounds to inhibit the growth of and other foodborne pathogens, thereby preventing contamination and ensuring food safety. Herein, we reported eight new aromatic polyketides, naphpyrones A-H (-), from the heterologous expression strain A3(2)/ ΔH3.

Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic sp. Strain.

A combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (-) from the Arctic-derived phychrophillic sp. L-016, among which - are new compounds, named nocardimicins S-W. The phenoxazole moiety in -, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues.

Marine actinomycetes-derived angucyclines and angucyclinones with biosynthesis and activity--past 10 years (2014-2023).

Actinomycete bacteria derived from marine environments are a good source of natural products with diverse biological activities such as cytotoxicity, antiviral, and antimicrobial actions. This review summarizes 191 angucyclines and angucyclinones derived from marine actinomycetes reported in the literature from 2014 to 2023 and introduced the latest developments in actinomycete-silenced biosynthetic gene cluster activation, including heterologous recombination and in situ activation. The key role of redox post-modifications in the biosynthetic process of atypical angucyclines.

Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation.

Full-thickness skin grafts often face challenges related to inefficient vascularization in clinical settings. Senescent cells, known for secreting various growth factors, have demonstrated excellent effects on angiogenesis. In this study, we induced senescence in a subset of fibroblasts in the donor dermis by co-administering trametinib and palbociclib before harvesting the skin grafts for transplantation.

Associations between dose-response of serum creatinine and type 2 diabetes mellitus risk: consistent and robust evidence from a systematic review and meta-analysis.

Background: Skeletal muscle is the key target of insulin action. Therefore, a reduction in skeletal muscle mass may trigger insulin resistance, a mechanism of diabetes. Creatinine is the only metabolite of creatine phosphate in the skeletal muscle.

Multiscale and stimuli-responsive biosensing in biomedical applications: Emerging biomaterials based on aggregation-induced emission luminogens.

Biosensors play a critical role in the diagnosis, treatment, and prognosis of diseases, with diverse applications ranging from molecular diagnostics to in vivo imaging. Conventional fluorescence-based biosensors, however, often suffer from aggregation-caused emission quenching (ACQ), limiting their effectiveness in high concentrations and complex environments. In contrast, the phenomenon of aggregation-induced emission (AIE) has emerged as a promising alternative, where luminescent materials exhibit strong emission in the aggregated state with good photostability, biocompatibility, large Stokes shift, high quantum yield, and tunable emission.

Clinicopathological Parameters and Immunohistochemical Profiles in Correlation with MRI Characteristics in Glioblastomas.

Glioblastoma is considered the most aggressive tumor of the central nervous system. The tumor microenvironment includes several components, such as endothelial cells, immune cells, and extracellular matrix components like matrix metalloproteinase-9 (MMP-9), which facilitates the proliferation of endothelial cells with pro-angiogenic roles. The MRI characteristics of glioblastomas can contribute to determining the prognosis.

Biosynthesis of Palladium Nanoparticles by Using Aqueous Bark Extract of , and for Potential Antioxidant and Antimicrobial Applications.

This study aimed to synthesize palladium nanoparticles (PdNPs) using bioactive compounds from aqueous extracts of species (, , and ) with potential biomedical applications. To optimize PdNPs biosynthesis, various parameters were explored, including the concentration of PdCl, the extract-to-PdCl ratio, and the pH of the solution. The nanoparticles were characterized using ultraviolet/visible spectroscopy (UV/Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS).

Quantification of serum daratumumab in multiple myeloma patients by LC-MS/MS, comparison with ELISA.

Daratumumab is a fully human immunoglobulin G1 monoclonal antibody employed for treating relapsed/refractory multiple myeloma and light-chain amyloidosis. Quantifying monoclonal antibodies in serum presents challenges due to interference from biological matrices. This research aimed to develop and verify an liquid chromatography tandem-mass spectrometry (LC-MS/MS) approach for quantifying serum daratumumab, employing immunoglobulin G purification without alkylation, and to assess its applicability in patients with multiple myeloma receiving intravenous daratumumab.

Metabolic characteristics of prostate cancer cells with high metastatic potential revealed by (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate inhibition.

A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145).