A novel extracellular mannan from Bacillus velezensis ameliorates metabolic-associated fatty liver disease by modulating gut microbiota in mice model.

Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752.

Disruption of Spike Priming in Virus Entry: Tetrandrine as a Pan-Coronavirus Inhibitor.

The emergence of novel and highly transmissible coronavirus (CoVs) highlights the urgent need for broad-spectrum antiviral agents. In our pursuit of effective treatments for coronavirus, we identified tetrandrine, the traditional Chinese medicine, as a pan-coronavirus inhibitor, exhibiting efficacy against HCoV-229E, HCoV-OC43, SARS-CoV-2, and its major variants of concern (VOCs), including alpha, beta, and omicron. Mechanistic investigations revealed that tetrandrine primarily targets the viral entry stage by binding to the Spike protein, disrupting its interaction with the host protease transmembrane serine protease 2 (TMPRSS2), and promoting Spike protein degradation, ultimately blocking the membrane fusion.

Targeting HDAC8 sensitizes tyrosine kinase inhibitors in the elimination of B-cell acute lymphoblastic leukemia cells through degradation of HIF-1α.

Tyrosine kinase inhibitors (TKIs) only partially inhibit the growth of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph B-ALL) cells, and often lead to rapid relapse. Therefore, it is essential to elucidate the mechanisms of resistance and develop novel treatment strategies. Histone deacetylases (HDACs) are often dysregulated in hematological malignancies, and many HDAC inhibitors have shown potent antitumor activities.

Multifunctional Gold Nanoclusters for a Lung Tissue Distribution Study of a Novel Anti-asthma Inhaled Antibody.

Pulmonary delivery of monoclonal antibodies has revolutionized the treatment of various types of lung diseases, such as severe asthma. However, the inconsistent antibody drug concentrations in the lungs and serum highlight the importance of monitoring the actual antibody distribution change in the lungs. In this study, we developed a novel antibody-functionalized gold nanocluster with high spatiotemporal resolution for fluorescence/CT dual-modal imaging based on an antibody targeting an allergic-airway-inflammation-related free cytokine in lungs.

Domain driven mining of high activity anti-biofilm glycoside hydrolases in pathogenic bacteria.

Biofilm formation represents a critical antimicrobial resistance mechanism contributing to persistent chronic infections. Glycoside hydrolases encoded within the exopolysaccharide synthesis gene clusters of pathogenic bacteria play pivotal roles in biofilm formation and dispersal processes, making the mining of anti-biofilm glycoside hydrolases from pathogen genomes a promising therapeutic strategy. In this study, we established a systematic pipeline for screening anti-biofilm glycoside hydrolases from Klebsiella pneumoniae and Acinetobacter baumannii genomes.

Independent and combined relationships between nighttime light exposure, air pollution, PM constituents, greenness and diabetes or high blood sugar: a national prospective cohort study.

Background: Diabetes or high blood sugar (D/HBS) is a major global public health challenge, with a particularly high burden among middle-aged and older adults in China. While traditional risk factors (e.g.

Rational design, synthesis, and evaluating primary biological activities of novel HIV-1 protease inhibitors containing heteraryl acetamides as the P2 ligands.

A series of novel potent HIV-1 protease inhibitors featuring diverse hydroxyaromatic acetanilide derivatives as P2 ligands and 4-substituted phenyl sulfonamides as P2' ligands were designed, synthesized, and biologically evaluated. The majority of the target compounds demonstrated potent enzyme inhibitory activity with IC values below100 nM. Notably, compound 18h, incorporating a 2-(4-hydroxypyrimidin-5-yl) acetamide P2 ligand and a 4-methoxybenzenesulfonamide as the P2' ligand, exhibited exceptional potency with an enzyme IC of 0.

Cathepsin D promotes acute myeloid leukemia progression through stabilization of the anti-apoptotic proteins.

Cathepsin D (CTSD) is a lysosomal aspartic protease that plays vital roles in regulating the properties of solid tumors, including proliferation, apoptosis, migration, metastasis, and angiogenesis. However, the function of CTSD in haematological malignancies remains largely elusive. Here we show that CTSD is highly expressed in acute myeloid leukemia (AML) and that high CTSD expression is associated with unfavourable prognosis.

sp. nov., sp. nov., sp. nov. and sp. nov., four novel UV radiation-resistant actinobacteria isolated from Tibet Autonomous Region, China.

Four Gram-stain-positive, aerobic, non-motile and non-spore-forming actinobacterial strains (CPCC 206391, CPCC 206453, CPCC 206435 and CPCC 206450) were isolated from soil samples collected from Tibet Autonomous Region, China. The 16S rRNA gene sequences of these four strains showed close relations to members of the genus of the family , with similarities of 96.1-99.

Discovery of Two New Neuroprotective Isocoumarin Dimers From the Dendrobium huoshanense-derived Streptomyces sp. AHMU XC001.

Dendrobium-derived actinomycetes represent a promising source of bioactive natural products with potential applications in pharmaceutical chemistry. In this study, a rhizosphere soil-derived actinomycete strain, Streptomyces sp. AHMU XC001, isolated from Dendrobium huoshanense, displayed moderate neuroprotective activity and was selected for further secondary metabolite isolation.

Neferine inhibits Zika virus replication by targeting viral protease.

Background: Zika virus (ZIKV) belonging to the Flaviviridae family causes critical neurological abnormalities, including congenital microcephaly and Guillain-Barré syndrome. Despite being a major public health concern, effective therapeutic interventions against ZIKV remain unavailable. NS2B-NS3 (ZIKVpro), the viral serine protease critical for polyprotein processing as well as viral replication, is a potential target for developing antiviral agents PURPOSE: This study aims to develop ZIKV inhibitors targeting the ZIKVpro from natural products.

Enhancement of carrimycin production in Streptomyces spiramyceticus 54-IA by the reporter-guided selection method with traditional mutagenesis.

Carrimycin, a new drug approved in recent years, is produced by recombinant Streptomyces spiramyceticus harboring a heterogeneous 4″-O-isovaleryltransferase gene (ist). The regulatory gene bsm42 plays a crucial role in activation of carrimycin biosynthesis, its high expression can improve the carrimycin production. The xylE-neo reporter cassette under control of the the two different lengths of bsm42 promoters, F1R and F2R, can be used to monitor the expression of bsm42 to screen carrimycin high-yield mutants treated with the composite mutagenesis of plasma and ultraviolet radiation.

Lipid Nanoparticle-Encapsulated mRNAs Encoding Tumor-Specific Toxin Proteins Selectively Target Cancer Cells and Stimulate T Cell Infiltration.

Treatment with mRNA-based therapeutics represents a potential strategy for improving outcomes of diverse diseases. Tumor-specific toxins might represent ideal candidates for mRNA-based cancer therapeutics. Here, we investigated the anti-tumor potential of lipid nanoparticle (LNP)-encapsulated mRNA encoding the tumor-specific toxin protein neutrophil elastase (ELANE or PPE).

Computational Insights into Cyst(e)inase for Cysteine and Cystine Depletion Therapies: Free Energy Calculations, Evolutionary Conservation, and Molecular Dynamics Simulations.

Cyst(e)inase, an engineered human cystathionine-γ-lyase (hCGL), effectively degrades l-Cys and CSSC, inhibiting various tumors in vivo with minimal toxicity. However, its current activity and stability limit its clinical application. To enhance its therapeutic potential, we utilized folding free energy calculations and amino acid site conservation to identify 46 potential mutants.

Independent and combined relationships between light at night, air pollutants, PM components and risk of cardiovascular-kidney-metabolic syndrome: a cohort study.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome, characterized by interconnected cardiovascular, renal, and metabolic dysfunctions, poses a growing global health burden. While both light at night (LAN) and air pollutants have independently been linked to adverse health outcomes, their synergistic and joint effects on CKM syndrome risk remain poorly understood. This study aimed to assess the independent, interactive, and joint associations of LAN, air pollutants, and PM components with CKM syndrome.

Separation of 15 impurities in semi-synthetic paclitaxel in a single run using supercritical fluid chromatography and greenness assessment by AMGS, GAPI, and AGREE tools.

The semi-synthetic approach for paclitaxel production has emerged as the predominant industrial method. However, the complex structure of paclitaxel leads to by-product formation during synthesis, and it is unstable in acidic, alkaline, and oxidative conditions. To ensure the safety, efficacy, and quality control of paclitaxel, this study successfully developed a rapid, straightforward, sensitive, and environmentally sustainable supercritical fluid chromatography (SFC) method for the quantification of 15 impurities in semi-synthetic paclitaxel raw materials.

Dihydroartemisinin enhances remyelination by switching microglia to the reparative phenotype.

Background: Boosting myelin repair is widely recognized as one of the most powerful approaches for demyelinating therapy, essentially contributing to the recovery of neurological functions. Maintaining immune homeostasis in microglia is a prerequisite for creating a reparative environment for myelin. Dihydroartemisinin (DHA) is clinically effective in reshaping immunological status and implies potential in treating demyelinating disease.

A dual-view deep learning-driven discovery of cinnamoyl anthranilic acid derivatives against orthopoxvirus through targeting host ITGB3.

The orthopoxvirus genus, particularly the monkeypox virus (MPXV), continues to pose a significant global public health threat. Therefore, the development of novel anti-orthopoxvirus agents remains an urgent priority. Machine learning has proven to be an effective approach for identifying potential drug candidates.

Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging.

Reproductive longevity is essential for female fertility and healthy aging; however, the role of stress response, especially stress granule accumulation, in ovarian aging remains elusive and interventions are lacking. Here, we identified deleterious mutations and decreased expression of NCOA7, a stress-response protein related to granulosa cell senescence in women with physiological and pathological ovarian aging. NCOA7 deletion accelerates oxidative stress-related cellular senescence, ovarian aging and fecundity decline in mice.

Fluorescence Polarization-Based High-Throughput Screening Assay for Inhibitors Targeting Cathepsin L.

Cathepsin L (CTSL), a lysosomal cysteine protease belonging to the papain-like protease family, is primarily involved in intracellular protein degradation, antigen processing, and extracellular matrix remodeling. It plays critical roles in pathological conditions, including cancer metastasis, neurodegenerative disorders, and viral infection, due to dysregulated activity or overexpression. Thus, inhibitors targeting CTSL are under investigation for therapeutic applications.

Genome-Wide Insights into Novel Species Qhu-G9 and Its Potential for Enhancing Salt Tolerance and Growth in L. and Scop.

With the increasing severity of global climate change and soil salinization, the development of microorganisms that enhance crop salt tolerance has become a critical focus of agricultural research. In this study, we explored the potential of a novel species Qhu-G9 as a plant growth-promoting rhizobacterium (PGPR) under salt stress conditions, employing whole-genome sequencing and functional annotation. The genomic analysis revealed that Qhu-G9 harbors various genes related to plant growth promotion, including those involved in phosphate solubilization, indole-3-acetic acid (IAA) biosynthesis, antioxidant activity, and nitrogen fixation.

Emericellopsic acid, a helvolic acid derivative with a 6/5/7/5 tetracyclic skeleton from sponge-derived Emericellopsis maritima.

Emericellopsic acid (1), the first B/C ring-rearranged fusidane-type antibiotic possessing a 6/5/7/5-fused ring framework, together with seven known helvolic acid derivatives, was isolated from the sponge-associated fungus Emericellopsis maritima IMB18-123 cultivated with autoclaved Pseudomonas aeruginosa. The structure of 1 was determined by extensive spectroscopic data analysis combined with ECD calculation. Compound 1 exhibited moderate antimicrobial activities against Staphylococcus aureus and S.

Silent or low expression of and suggests potential for targeted proteomics in clinical detection of β-lactamase-related antimicrobial resistance.

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Forecasting tuberculosis epidemics using an autoregressive fractionally integrated moving average model: a 17-year time series analysis.

Background: Tuberculosis (TB) remains a significant public health challenge in Henan, China, requiring accurate forecasting to guide prevention and control efforts. While traditional models like autoregressive integrated moving average (ARIMA) are commonly used, they may not fully capture long-term dependencies in the data. This study evaluates the autoregressive fractionally integrated moving average (ARFIMA) model, which incorporates fractional differencing, to improve TB forecasting by better modelling long-range dependencies and seasonal patterns.

Design, synthesis and evaluation of new dihydropyrimidine derivatives as HBV capsid protein inhibitors.

The assembly of the capsid is a critical phase in the lifecycle of the hepatitis B virus (HBV). Capsid protein assembly inhibitors can specifically target HBV capsid formation, thereby disrupting its assembly and exerting antiviral effects. In this study, a total of 40 dihydropyrimidine derivatives across four series were synthesized by the modification of solvent-exposed region.