Inhibitors of NADH-O-methylquinone compound a class of antitubercular drugs.

Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level.

Talarergosteroids A-C: Three Unusual Steroid-Polyketone Conjugates with Antifungal Activity from a Derived Fungus sp.

Three previously undescribed steroid-polyketone conjugates, talarergosteroids A-C (-), together with talarergosteroid D (), which was first identified from a natural source, were isolated from a derived fungus sp. SCNU-F0041. Compounds and bear a complicated 6/6/6/5/6/6 hexacyclic ring system characterized by an oxaspiro[5.

USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination.

Background/aims: Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific proteinase 29 (USP29) plays pivotal roles in hepatic ischemia‒reperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.

The Cytochalasins and Polyketides from a Mangrove Endophytic Fungus QYF.

Twelve compounds, including four undescribed cytochalasins, xylariachalasins A-D (-), four undescribed polyketides (-), and four known cytochalasins (-), were isolated from the mangrove endophytic fungus QYF. Their structures and absolute configurations were established by extensive spectroscopic analyses (1D and 2D NMR, HRESIMS), electronic circular dichroism (ECD) calculations, C NMR calculation and DP4+ analysis, single-crystal X-ray diffraction, and the modified Mosher ester method. Compounds and are rare cytochalasin hydroperoxides.

Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

Background: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM).

Methods: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment.

Talaroacids A-D and Talaromarane A, Diterpenoids with Anti-Inflammatory Activities from Mangrove Endophytic Fungus sp. JNQQJ-4.

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A-D (-) and an isopimarane diterpenoid talaromarane A () were isolated from the mangrove endophytic fungus sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD).

Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases.

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes.

The Protective Role of Transcript-Induced in Spermiogenesis 40 in Cerebral Ischemia-Reperfusion Injury.

Prompt reperfusion after cerebral ischemia is important to maintain neuronal survival and reduce permanent disability and death. However, the resupply of blood can induce oxidative stress, inflammatory response and apoptosis, further leading to tissue damage. Here, we report the versatile biological roles of transcript-induced in spermiogenesis 40 (Tisp40) in ischemic stroke.

Isolation of two peptaibols with potent antimicrobial and cytotoxic activities from the mangrove endophytic fungus ML-P8-2.

Trichorzin PA is a family of 18-residue peptaibols with linear and flexible peptide chains. The three-dimensional structures and biological activities of trichorzin PA peptaibols are largely uncharacterised. In this work, two previously identified peptaibols, trichorzin PA VI () and II (), were isolated from ML-P8-2.

4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3.

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking.

Anti-Inflammatory Sesquiterpenes from Fruiting Bodies of .

, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (-) and one new meroterpenoid schizomycin I () together with three known analogues (-) were isolated from fruiting bodies of . Their planar structures were established by extensive spectroscopic and mass spectrometric data.

The rising death burden of atrial fibrillation and flutter in low-income regions and younger populations.

Objective: The aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade.

Methods: We retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020-2029 by developing the Bayesian age-period-cohort model.

Results: The global number of deaths from AFF increased from 117,038.

Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus sp. QQYB1.

Unlabelled: Marine microorganisms have long been recognized as potential sources for drug discovery. Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades. In this study, 12 new griseofulvin derivatives [(±)--, (+)-, (±)-, -, and -] and two new griseofulvin natural products ( and ) together with six known analogues [(-)-, -, and ] were isolated from the mangrove-derived fungus sp.

Pleosmaranes A-R, Isopimarane and 20-nor Isopimarane Diterpenoids with Anti-inflammatory Activities from the Mangrove Endophytic Fungus sp. HNQQJ-1.

Pleosmaranes A-R (-), 18 new isopimarane-type diterpenoids, together with four known analogs (-), were isolated from the mangrove endophytic fungus sp. HNQQJ-1. Their structures and absolute configurations were established by analysis of their spectroscopic data and electronic circular dichroism (ECD) calculations.

Major lipids and lipoprotein levels and risk of blood pressure elevation: a Mendelian Randomisation study.

Background: Quantitative nuclear magnetic resonance (NMR) metabolomics techniques provide detailed measurements of lipoprotein particle concentration. Metabolic dysfunction often represents a cluster of conditions, including dyslipidaemia, hypertension, and diabetes, that increase the risk of cardiovascular diseases (CVDs). However, the causal relationship between lipid profiles and blood pressure (BP) remains unclear.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/β-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.

Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus sp. QYM-13.

Six previously undescribed cytosporone derivatives (phomotones A-E (-) and phomotone F ()), two new spiro-alkanol phombistenes A-B (-), and seven known analogs (-) were isolated from the mangrove endophytic fungus sp. QYM-13. The structures of these compounds were elucidated using spectroscopic data analysis, electronic circular dichroism (ECD), and C NMR calculations.

Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.

Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity.

Mono- and Dimeric Sorbicillinoid Inhibitors Targeting IL-6 and IL-1β from the Mangrove-Derived Fungus BGRg-3.

Four new sorbicillinoids, named trichodermolide E (), trichosorbicillin J (), bisorbicillinolide B (), and demethylsorbiquinol (), together with eight known compounds (, -), were isolated from the cultures of the mangrove-derived fungus BGRg-3. The structures of the new compounds were determined by analyzing their detailed spectroscopic data, while the absolute configurations were further determined through electronic circular dichroism calculations. Snatzke's method was additionally used to determine the absolute configurations of the diol moiety in .

The Polyketides with Antimicrobial Activities from a Mangrove Endophytic Fungus ML-P8-2.

Five new polyketides, including two chromones (-), two phenyl derivatives (-), and a tandyukusin derivative (), along with five known polyketides ( and -) were isolated from mangrove endophytic fungus ML-P8-2. The planar structures of compounds were elucidated via detailed 1D, 2D NMR, and HR-ESI-MS analysis. ECD spectra, optical rotation values calculation, and alkali hydrolysis were applied in the determination of the absolute configuration of the new compounds.

Metabolites isolated from the mangrove endophytic fungus Didymella sp. CYSK-4 and their cytotoxic activities.

Two new 12- or 13- membered-ring macrocyclic alkaloids ascomylactam D and E (1 & 2), and a pair of new enantiomer (+)- and (-)- didymetone (3) were purified from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures and absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, ECD and C NMR calculations.

Cyclohexenoneterpenes A-J: Cytotoxic meroterpenoids from mangrove-associated fungus Penicillium sp. N-5.

Ten previously undescribed meroterpenoids, cyclohexenoneterpenes A-J (1-7, 18-20), together with 10 known analogues (8-17) were isolated from the mangrove-associated fungus Penicillium sp. N-5. Their structures were elucidated on the basis of extensive spectroscopic and mass spectrometric data.