PubMed

Ecotoxicol Environ Saf. 2026 Mar 3;312:119973. doi: 10.1016/j.ecoenv.2026.119973. Online ahead of print.ABSTRACTAs a widely used triazine herbicide, atrazine (ATR) has been demonstrated to exert neurotoxicity and induce metabolic disorders in organisms. Our previous studies have further revealed that maternal exposure to ATR during pregnancy and lactation can damage dopaminergic neurons in the midbrain of offspring. Current mechanistic investigations into the intergenerational neurotoxic effects of ATR and other environmental factors have mostly focused on regulatory mechanisms at the genetic material level, which present significant limitations. However, there is a lack of relevant experimental evidence to verify whether maternal ATR exposure during these special periods can induce dopaminergic neuronal damage in offspring through alternative pathways, such as altering maternal plasma metabolite levels, and the specific underlying mechanisms remain to be further explored. This study integrated multiple approaches including neurobehavioral assays, plasma metabolomics, bioinformatics, and molecular biology, systematically elucidated the mechanism by which maternal ATR exposure induces intergenerational dopaminergic neurotoxicity in offspring by remodeling the maternal plasma metabolic profile. Furthermore, by combining the analysis of single-cell transcriptomic data from Parkinson's disease patients with molecular docking and molecular dynamics simulation analyses, we revealed for the first time, from the novel perspective of the metabolite-single cell axis, the potential mechanism by which serotonin may mediate dopaminergic neuronal damage in offspring induced by maternal ATR exposure during pregnancy and lactation-specifically by regulating the AKT1/SRC pathway and intercellular crosstalk across multiple cell types. This finding provides new research strategies and directions for understanding the intergenerational neurotoxicity of environmental pollutants and their early prevention.PMID:41780476 | DOI:10.1016/j.ecoenv.2026.119973

Water Res. 2026 Mar 1;296:125672. doi: 10.1016/j.watres.2026.125672. Online ahead of print.ABSTRACTRedox oscillations within riparian ecosystems emerge as a critical threat to carbon sequestration, yet the mechanistic coupling between abiotic drivers and microbial metabolism remains elusive. Through controlled incubation experiments, we demonstrate that redox-oscillating conditions significantly reduce microbial carbon use efficiency (CUE), thus accelerating carbon loss compared to static oxic or anoxic conditions. Mechanistically, redox oscillations drove the cycling of iron (Fe) species, thereby reducing the amorphous Fe pool and liberating mineral-associated organic carbon (MAOC) composed of substantial biodegradable organic substrates (e.g., lipids and proteins). Concurrently, hydroxyl radicals (•OH) generated during Fe(II) oxidation depolymerize complex aromatic organic matter into labile forms. Integrated metagenomic and metabolomic analyses further demonstrated that redox oscillations significantly reshaped soil metabolite profiles and microbial community. In particular, microbial catabolic pathways such as pentose phosphate pathway and the tricarboxylic acid (TCA) cycle were activated to efficiently mineralize newly available substrate. Together, these results identify a coupled abiotic-biotic "prime and burn" mechanism in which Fe-driven substrate reorganization primes microbial differentiation toward enhanced respiration. This study highlights redox-oscillating zones as potential carbon leakage hotpots in the terrestrial carbon sink.PMID:41780450 | DOI:10.1016/j.watres.2026.125672

Food Chem. 2026 Feb 24;509:148525. doi: 10.1016/j.foodchem.2026.148525. Online ahead of print.ABSTRACTThis study revealed the formation mechanism of flavonoid aglycones in Moringa oleifera leaf (MOL) during Monascus anka fermentation via widely targeted metabolomics and data-independent acquisition-based proteomics. Bioactivity assays demonstrated that M. anka fermentation significantly enhanced MOL's bioactivity; total flavonoid and phenolic content, ABTS and DPPH radical scavenging capacities were increased by 226.8%, 45.59%, 1.28-, and 1.25-fold compared with the unfermented control, respectively. Widely targeted metabolomics identified 172 phenolic metabolites, of which flavonoids accounted for 70.9%. Notably, flavonoid aglycones (quercetin and kaempferol) were significantly accumulated during fermentation, being 5.05-, 2.65-, and 5.54-fold higher than the unfermented control. Proteomics analysis identified key carbohydrate-active enzymes associated with cell wall degradation. Importantly, β-glucosidases (GH1, GH3) and α-L-rhamnosidases (GH78) hydrolyzed flavonoid glycosidic linkages, facilitating free aglycone accumulation. Collectively, these findings indicated that M. anka-secreted enzymes exerted catalytic roles in cell wall degradation and flavonoid deglycosylation, providing a theoretical basis for targeted enhancement of MOL bioactivity.PMID:41780433 | DOI:10.1016/j.foodchem.2026.148525

J Environ Manage. 2026 Mar 3;402:129125. doi: 10.1016/j.jenvman.2026.129125. Online ahead of print.ABSTRACTPit bottom wastewater (PBW), a high-strength organic effluent from sauce-flavored Baijiu production, poses considerable environmental challenges. This study explores its valorization as a nutrient medium for biosynthesis of high-value compounds using Monascus purpureus MP-1 isolated from Daqu. Cultivation in 10% PBW-supplemented medium increased biomass by 150% and enhanced hydrolytic enzyme activities. Integrated metabolomic and transcriptomic analyses revealed that PBW supplementation suppressed Monascus pigment biosynthesis but activated the putrescine (Puu) pathway for γ-aminobutyric acid (GABA) synthesis, increasing yield by 50.38% (121.28 μg/mL). Concurrently, organic pollutants were effectively degraded via enhanced lignin catabolism and redox activities. This work establishes a sustainable waste-to-value strategy, demonstrating the potential of Monascus spp. for simultaneous resource recovery and functional metabolite production, offering dual benefits of waste reduction and value creation for the food industry.PMID:41780378 | DOI:10.1016/j.jenvman.2026.129125

Plant Physiol Biochem. 2026 Feb 7;232:111114. doi: 10.1016/j.plaphy.2026.111114. Online ahead of print.ABSTRACTUltraviolet-B (UV-B) radiation in the Qinghai-Tibet Plateau (QTP) is a crucial environmental constraint affecting plant distribution and development. E. sibiricus is an important perennial grass species used for pasture establishment and grassland restoration in the QTP, whose molecular adaptation to UV-B stress remains underexplored. Herein, phenotypic physiology, transcriptomics, and metabolomics were integrated to systematically decipher UV-B response mechanisms in E. sibiricus. Exposure to 288 kJ/m2 UV-B radiation in tolerant (SC020 2-A1, SC) and sensitive (XJ007 22-A5, XJ) E. sibiricus genotypes yielded 21,773 genes, with 5076 and 4541 genotype-specific differentially expressed genes (DEGs), respectively. Temporal profiling of the DEGs revealed 3792 and 6322 DEGs in SC, compared to 4826 and 10,890 DEGs in XJ under short- and long-term stress, respectively. Core findings demonstrated that MYB and WRKY transcription factors (TFs) mediated UV-B responses via phenylpropanoid metabolism and UVR8 signaling. In addition, 20 pivotal TFs, including EsMYB and EsbHLH, coordinated with 30 stress metabolites, such as corticosterone, to regulate the ascorbate and aldarate network, thereby activating 8 crucial pathways, including photosynthetic carbon fixation. Notably, heat shock proteins (HSP702 and HSP704) emerged as novel UV-B resistance components. These results provide molecular insights into UV-B adaptation of members of the Gramineae family and genetic resources for breeding UV-B radiation-resistant grass cultivars.PMID:41780311 | DOI:10.1016/j.plaphy.2026.111114

Cytokine. 2026 Mar 3;201:157135. doi: 10.1016/j.cyto.2026.157135. Online ahead of print.ABSTRACTOBJECTIVE: Cow milk protein allergy (CMPA), a common food allergy in early childhood, involves type 2 immune cells such as group 2 innate lymphoid cells (ILC2s). Linoleic acid (LA) is a polyunsaturated fatty acid with immunomodulatory properties. Although its role in CMPA is not yet clear, previous metabolomics research by our team revealed elevated levels of linoleic acid in the intestinal ILC2s of allergic mice. In this study, the effects of linoleic acid on ILC2 activation and the mechanisms underlying this activation were explored using a mouse model of CMPA.METHODS: The linoleic acid content of intestinal ILC2s from milk protein-allergic mice was measured. Flow cytometry was used to analyse the effects of linoleic acid on the proportion of ILC2s and the release of IL-5/IL-13. The PPARα agonist WY14643 and the NF-κB signalling pathway inhibitor MLN120B were used to study immune regulation, and transcriptomic sequencing was performed to elucidate the underlying molecular mechanism.RESULTS: Compared with control mice, allergic mice presented ILC2s with increased LA levels, increased proportions of ILC2s, and increased IL-5/IL-13 release. PPARα agonists reduced the proportion of ILC2s and decreased inflammation and allergic reactions. Transcriptomic analysis revealed that LA may activate the NF-κB signalling pathway; its inhibition reduced the proportions of ILC2s and the levels of cytokines in CMPA mice.CONCLUSION: Linoleic acid may regulate ILC2s via the NF-κB signalling pathway and thereby promote IL-5/IL-13 release and exacerbate inflammation in CMPA mice. Inhibition of LA enrichment or the NF-κB signalling pathway may be potential therapies for CMPA in early childhood.PMID:41780286 | DOI:10.1016/j.cyto.2026.157135

Talanta. 2026 Feb 24;305:129584. doi: 10.1016/j.talanta.2026.129584. Online ahead of print.ABSTRACTMagnolia Officinalis Cortex (MOC), originated from the dried bark of Magnolia officinalis Rehd. et Wils., has often been used in clinical practice to treat various gastrointestinal disorders. The so called "sweating processing" endowed MOC with unique chemical qualities and specific clinical efficacy. Although previous studies have confirmed that sweating processing could change the chemical composition of MOC to affect its pharmacological effects, there is few research available so far on the dynamic chemical variations that occur during the sweating processing of MOC. In study, the method of spatial metabolomics combined with UPLC-Q-TOF-MS and MALDI-MSI was adopted to analyze the chemical components, transformation mechanisms and in situ spatial distribution during the dynamic sweating processing of MOC. The components in MOC at different sweating processing points included 36 lignans, 33 phenolic glycosides and phenolic acids, 36 alkaloids and others. Clear dynamic changes in compounds such as lignans, alkaloids, glycosidic phenols and phenylethanoid glycosides were observed, and 25 metabolic differentiators were identified to distinguish raw MOC and sweated MOC. Seven compounds including (R)-magnocurarine, syringin, (S)-magnoflorine, magnoloside B, magnoloside A, magnolol, and honokiol were quantified by HPLC. Through MALDI-MSI, the dynamic chemical changes in raw MOC and its sweating processing products were visualized. Interestingly, the syringic acid-4-O-α-L-rhamnopyranoside might be converted to magnolol or honokiol during sweating processing of MOC. In conclusion, the spatial metabolomics method based on UPLC-Q-TOF-MS, MALDI-MSI and quantitative analysis approach could effectively characterize the dynamic variations in chemical components of MOC during sweating processing. The wide application of this method would contribute to the process of monitoring and controlling MOC and others Chinese medical herb.PMID:41780248 | DOI:10.1016/j.talanta.2026.129584

J Hazard Mater. 2026 Mar 2;506:141675. doi: 10.1016/j.jhazmat.2026.141675. Online ahead of print.ABSTRACTBuprofezin (BPFN), an insecticide that inhibits arthropod chitin synthesis, is widely applied in agriculture and increasingly detected in aquatic environments. Given the evolutionary conservation of chitin biosynthesis pathways, its potential impacts on non-target crustaceans remain poorly understood. In this study, we investigated the effects of environmentally relevant BPFN concentrations on the exoskeletal properties of the whiteleg shrimp Litopenaeus vannamei. Nanoindentation revealed significant reductions in exoskeletal stiffness and hardness following BPFN exposure. Consistently, chitin and total calcium content decreased, accompanied by reduced mineral density and cuticular volume as shown by histology and micro-CT imaging. These structural impairments were closely associated with altered patterns of molt-related physiological and biochemical indicators, including changes in glycogen storage, chitinase activity, carbonic anhydrase activity, and Ca2 + dynamics, and metabolites annotated to steroid-related pathways. Integrated transcriptomic and metabolomic analyses further revealed that BPFN markedly suppressed amino sugar and nucleotide sugar metabolism, downregulating key enzymes required for chitin precursor generation. BPFN also interfered with ECM-receptor interactions and ER-associated protein processing, disrupting cuticular protein assembly, and perturbed TGF-β/BMP signaling pathways critical for calcium carbonate deposition. Correlation analyses linked these molecular disturbances with defects in chitin synthesis, matrix organization, and biomineralization. In summary, our findings demonstrate that BPFN exposure compromised the structural integrity and mechanical performance of L. vannamei exoskeleton by impairing chitin synthesis and recycling, disturbing cuticular protein processing, weakening calcium carbonate mineralization, and disrupting molt-associated physiological processes.PMID:41780231 | DOI:10.1016/j.jhazmat.2026.141675

J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Feb 26;1275:124993. doi: 10.1016/j.jchromb.2026.124993. Online ahead of print.ABSTRACTSalvia miltiorrhiza, recognized as a neuroprotective agent in traditional Chinese medicine, has been extensively utilized in the treatment of cerebrovascular diseases and ischemic stroke (IS). While current evidence substantiates the therapeutic efficacy and proposed mechanisms of Salvia miltiorrhiza in IS, there remains a paucity of comprehensive comparative studies that examine and contrast the differential therapeutic contributions and systemic mechanisms of its two primary bioactive fractions: the water-soluble salvianolic acids and the liposoluble tanshinones. This gap in research is particularly significant for understanding their overall impact on physiological circulation and their distinct pathways in mitigating IS. Therefore, this study centers on Salvia miltiorrhiza, with the objective of thoroughly investigating the potential pharmacological properties and effects of its lipophilic and hydrophilic components in the treatment of IS. By integrating network pharmacology, metabolomics, and molecular docking methodologies, the research constructs a Disease-Gene-Pathway-Components network and a Biomarkers-Reaction-Enzyme-Gene network. This comprehensive approach enables a detailed elucidation of the multi-compound synergism and mechanisms of action underlying the therapeutic efficacy of Salvia miltiorrhiza in the treatment of IS. As a result, 63 active components of Salvia miltiorrhiza were identified, which exert exerted therapeutic effects on IS by targeting proteins such as GAPDH, PPARG, EGFR, and PTGS2. Additionally, 27 biomarkers primarily involved in the metabolism of arachidonic acid, tryptophan, and unsaturated fatty acids, were identified through serum metabolomics analysis. These potential biomarkers can be modulated by the salvianolic acids and tanshinones present in Salvia miltiorrhiza. By integrating the above research strategies and findings to construct a Biomarker-Gene-Active Ingredient network, PTGS2, JAK2, SRC, KDR, MAPK1, PTPRC, and EGFR were identified as key targets for the treatment of IS with various components of Salvia miltiorrhiza. In conclusion, it is evident that the mechanism of Salvia miltiorrhiza in treating IS is closely associated with the alleviating the neuroinflammation. Salvia miltiorrhiza is anticipated to become a traditional medicine with a well-defined mechanism and mild effects for the treatment of IS, and it holds potential for widespread clinical application.PMID:41780213 | DOI:10.1016/j.jchromb.2026.124993

Redox Biol. 2026 Feb 27;92:104101. doi: 10.1016/j.redox.2026.104101. Online ahead of print.ABSTRACTEndometriosis (EM) is driven by immune dysregulation and macrophage dysfunction, yet the underlying mechanisms remain unclear. Here, metabolomic profiling revealed excessive itaconate accumulation in EM lesions, primarily due to elevated cis-aconitate decarboxylase 1 (ACOD1) expression in ectopic stromal cells (ESCs). ESC-derived itaconate was internalized by peritoneal macrophages, where it suppressed pro-inflammatory activity and phagocytosis, thereby facilitating ESC survival and dissemination. Mechanistically, itaconate exerted dual regulatory effects on macrophages: it activated NRF2 signaling to repress the transcription of pro-inflammatory genes, and it enhanced lysosomal acidification, thereby reducing lysosomal calcium release, which in turn inhibited p38-MAPK activation and further attenuated pro-inflammatory gene expression. In vivo, ACOD1 inhibition restored macrophage function and reduced lesion burden, while exogenous 4-octyl itaconate aggravated disease progression. These findings define a novel "ESC-ACOD1-itaconate-macrophage" axis that mediates immunosuppression in EM and identify ACOD1 as potential therapeutic targets.PMID:41780193 | DOI:10.1016/j.redox.2026.104101

Int J Food Microbiol. 2026 Feb 13;453:111691. doi: 10.1016/j.ijfoodmicro.2026.111691. Online ahead of print.ABSTRACTDiacetyl is a key buttery aroma compound in fermented dairy products, yet its production by Lactiplantibacillus plantarum varies widely among strains due to competition for pyruvate flux. In this study, three isolates with distinct diacetyl phenotypes were examined during yogurt co-fermentation using integrated genomics, transcriptomics, and metabolomics. Comparative genomics showed that the high-producing strain WJ108 forms an independent evolutionary branch and retains a more complete repertoire of genes related to flavor formation, carbon metabolism, redox balance, and stress response. In contrast, the low-producing strains cluster with previously reported acid-producing lineages and contain SNP mutations in several key flavor-forming genes. Community-level metatranscriptomic profiling revealed differential regulation of glycolysis, tricarboxylic-acid-associated reactions, and pyruvate metabolism across co-fermentation systems containing distinct L. plantarum strains. These transcriptional shifts were consistent with strain-dependent genomic variation and metabolite profiles, indicating that co-fermentation systems containing strain WJ108 were associated with increased routing of carbon flux toward the α-acetolactate pathway, whereas systems containing SC-4 or WJ36 favoured lactate or acetate formation and showed lower diacetyl accumulat. Overall, this work demonstrates that strain-specific diacetyl formation is associated with regulation of citrate uptake, redox homeostasis, and pyruvate flux partitioning, and identifies potential genetic markers for screening or engineering L. plantarum strains with enhanced flavor-forming capacity in dairy applications.PMID:41780150 | DOI:10.1016/j.ijfoodmicro.2026.111691

Int Immunopharmacol. 2026 Mar 3;175:116452. doi: 10.1016/j.intimp.2026.116452. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by immune dysregulation, compromised intestinal barrier integrity, and disruptions in the microbiota-metabolite axis. Current clinical management of UC remains limited, underscoring the need for novel therapeutic approaches. Cellular senescence is increasingly recognized as a significant contributor to the pathogenesis of this disease. Senescent cells promote inflammatory responses via the sustained release of pro-inflammatory mediators such as IL-6, IL-1β, and TNF-α. Conversely, persistent inflammation drives further cellular senescence, establishing a self-amplifying cycle that exacerbates disease progression. Additionally, gut microbiota dysbiosis (reduced Akkermansia abundance) and metabolic abnormalities (disrupted bile acid metabolism) may further compromise intestinal barrier integrity. Cyclosporine A (CsA), a classical immunosuppressant, has unclear mechanisms in UC, particularly regarding its potential effects on senescence and the microbiota-metabolite axis. In this investigation, using a dextran sulfate sodium (DSS)-induced UC model, we demonstrated that CsA significantly alleviated DSS-induced acute colitis in mice and senescence-associated pathological changes. Multi-omics analyses integrating network pharmacology, transcriptomics, metabolomics, and metagenomics demonstrated that CsA likely exerts its therapeutic effects through inhibition of the JAK2-STAT3/NF-κB signaling pathway. This leads to reduced release of pro-inflammatory cytokines, modulation of intestinal microbiota composition and metabolite profiles, and enhanced intestinal barrier function.These findings elucidate new mechanisms by which CsA improves DSS-induced colitis in mice through anti-senescence effects and microbiota-metabolic regulation, providing potential therapeutic targets for UC.PMID:41780079 | DOI:10.1016/j.intimp.2026.116452

Sci Transl Med. 2026 Mar 4;18(839):eadx8909. doi: 10.1126/scitranslmed.adx8909. Epub 2026 Mar 4.ABSTRACTGestational diabetes mellitus (GDM) can increase the risk for diabetes in offspring, but the mechanisms underlying the effects of intrauterine hyperglycemia (IHG) on the fetus remain unknown. Here, we show that IHG down-regulated DNA demethylases TET2/3 in fetal pancreatic islets, increased DNA methylation of γ-aminobutyric acid (GABA) synthesis gene Gad1, suppressed Gad1 expression, and elevated somatostatin (SST) protein in the pancreas in mice. Pancreas-specific double knockout (DKO) of Tet2/3 recapitulates the IHG effects, causing Gad1 hypermethylation and expression down-regulation, alongside impaired insulin secretion and glucose tolerance. Metabolomic analysis revealed that IHG and Tet2/3 DKO reduced pancreatic GABA content. Gestational dietary GABA supplementation improved metabolic defects in both IHG and Tet2/3 DKO models. scRNA-seq analysis of pancreatic islets showed that IHG or Tet2/3 DKO down-regulated the β cell signature, whereas up-regulating δ cell-related genes, particularly Sst, led to the emergence of an Ins2/Sst double-positive cell population. β cell-specific deletion of Sst rescued IHG-induced metabolic defects. In humans, GDM was associated with reduced GABA content in the umbilical arterial blood. These results uncover an epigenetically controlled pancreatic GABA-SST signaling pathway that may contribute to the GDM-induced increase in offspring diabetes risk and identify dietary GABA supplementation as a potential interventional strategy.PMID:41779871 | DOI:10.1126/scitranslmed.adx8909

Proc Natl Acad Sci U S A. 2026 Mar 10;123(10):e2518983123. doi: 10.1073/pnas.2518983123. Epub 2026 Mar 4.ABSTRACTGlucocorticoids (GCs) are potent immunosuppressive agents that compromise anticancer immune responses, yet the molecular mediators of this effect remain incompletely understood. Here, we identify the acyl-CoA-binding protein/diazepam-binding inhibitor (ACBP/DBI) as a critical effector of the GC-induced suppression of tumor immunosurveillance and immunotherapy efficacy. Using orthotopic murine models of breast cancer, non-small cell lung cancer, and cutaneous fibrosarcoma, we show that corticosterone (CORT) accelerates tumor progression and abrogates therapeutic responses to immunogenic chemotherapy and PD-1 blockade. Genetic ablation or monoclonal antibody (mAb)-mediated neutralization of ACBP/DBI prevents immunosuppression by CORT, restoring both natural and therapy-enhanced antitumor immunity in a T cell-dependent manner. Mechanistically, CORT induces Tsc22d3 expression in dendritic cells, impairs type I interferon signaling, and reduces antigen presentation capacity, which all can be reversed by ACBP/DBI neutralization. The immunosuppressive activity of GCs and the immunostimulatory function of anti-ACBP/DBI mAb converge on Tsc22d3 expression in myeloid cells, as shown by loss-of-function experiments in myeloid-specific Tsc22d3-deficient mice. These findings reveal ACBP/DBI as a central mediator of GC-induced immune evasion and suggest its neutralization as a therapeutic strategy to restore anticancer immunity during endogenous or iatrogenic GC exposure.PMID:41779791 | DOI:10.1073/pnas.2518983123

Nat Prod Res. 2026 Mar 4:1-10. doi: 10.1080/14786419.2026.2640144. Online ahead of print.ABSTRACTVegetable oils are increasingly used to formulate bioactive ingredients with pharmaceutical, nutraceutical or cosmeceutical applications. Their biological properties depend directly on their chemical profile, but so far it remains difficult to simultaneously characterise the major long chain lipidic constituents together with the minor but valuable unsaponifiable constituents specific to botanical species. Therefore accurate and comprehensive analytical strategies appear crucial. In this work, a NMR-based dereplication workflow was developed to decipher the metabolome of vegetable oils. The approach involves either a direct liquid-liquid extraction of minor oil constituents or a saponification treatment on the crude starting oil, followed by liquid-liquid fractionation, and direct NMR analysis of all fractions. Oil metabolites are then identified with the help of computer tools and a natural metabolite database. The whole process was applied to a grape seed oil sample, resulting in a rapid and unambiguous identification of 23 metabolites including fatty acid derivatives, triterpenes, sterols, and tocopherols. This NMR-based analytical workflow offers interesting perspectives for the chemical profiling of vegetable oils and oily extracts.PMID:41779431 | DOI:10.1080/14786419.2026.2640144

Appl Biochem Biotechnol. 2026 Mar 4. doi: 10.1007/s12010-026-05588-y. Online ahead of print.ABSTRACTImmunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis and a major cause of end-stage renal disease worldwide, currently lacks safe, effective therapies. Ophiocordyceps sinensis, a well-known traditional medicinal fungus and used for treating kidney-related disorders. In this study, we report for the first time the nephroprotective potential of Ophiocordyceps indica Gireesh Nadda & Aakriti Sharma 2023, a newly described entomopathogenic fungus isolated from the Indian Himalayas, against IgAN. UPLC-based metabolomic profiling of O. indica confirmed the presence of key nucleosides, including adenosine and cordycepin, exhibiting a profile comparable to O. sinensis. In vitro, O. indica extract significantly reduced oxidative stress and inflammatory markers in SV40-MES13 mesangial cells without inducing cytotoxicity. In vivo, oral administration of the extract to IgAN-induced mice improved renal function by reducing serum creatinine, urea, and urine microalbumin levels, while restoring body and kidney weights. The extract also significantly reduced pro-inflammatory cytokines (TNFα, IL6, IL18) and galactose-deficient IgA1 levels. Histological and molecular analyses revealed amelioration of glomerular hypertrophy and tubular degeneration, along with downregulation of fibrotic and kidney injury markers (TGFβ, αSMA, Nephrin, WT1, VEGF, Desmin). The nephroprotective and anti-inflammatory effects of O. indica were comparable to those of O. sinensis and dexamethasone. Our findings highlight the potent anti-inflammatory and nephroprotective properties of O. indica, supporting its potential as a novel therapeutic agent for managing IgAN.PMID:41779330 | DOI:10.1007/s12010-026-05588-y

J Chem Ecol. 2026 Mar 4;52(2):25. doi: 10.1007/s10886-026-01699-2.NO ABSTRACTPMID:41779209 | DOI:10.1007/s10886-026-01699-2

Bull Math Biol. 2026 Mar 4;88(4):52. doi: 10.1007/s11538-026-01618-2.ABSTRACTSpatial transcriptomics studies are becoming increasingly large and commonplace, necessitating simultaneous analysis of a large number of spatially resolved variables. Correspondingly, a diverse range of methodologies have been proposed to compare the spatial expression structure of genes. Here, we apply persistent homology, a method from topological data analysis, to produce a continuous quantification of spatial structure in a given gene's expression, and show how this can be used for downstream tasks such as spatially variable gene identification. We explore the unique advantages of topology for this task, deriving biologically meaningful insights into kidney disease and myocardial infarction using public spatial transcriptomics data. We also show how the non-parametric nature of homology enables our methodology to extend naturally to other spatial omics modalities, demonstrating this on a spatial metabolomics sample. Our work showcases the advantages of using a continuous quantification of spatial structure over p-value based approaches to SVG identification, the potential for developing unified methods for the analysis of different spatial omics modalities, and the utility of persistent homology in big data applications.PMID:41779089 | DOI:10.1007/s11538-026-01618-2

Appl Environ Microbiol. 2026 Mar 4:e0259325. doi: 10.1128/aem.02593-25. Online ahead of print.ABSTRACTMarine biofilms are known as a reservoir of bacterial specialized metabolites, but the majority of these metabolites remain unexplored because most biofilm-associated bacteria have not yet been cultivated or genomically characterized. In a recent study, we isolated and cultivated 713 bacterial strains from marine biofilms and generated their nearly complete genomes. Here, we conduct a systematic analysis of biosynthetic gene clusters (BGCs) contained in these bacterial genomes. A total of 3,146 BGCs are predicted and organized into 2,176 mostly new gene cluster families (GCFs), in comparison with the GCFs in the Minimum Information about a Biosynthetic Gene cluster database, and those from genomes of global seawater bacteria. In particular, certain less-studied microorganisms, such as members of the Roseobacteriaceae family, possess a number of novel BGCs. Moreover, through bacterial antagonistic tests, 50 of the 713 strains inhibit the growth of at least one tested pathogenic bacterial strain. Furthermore, metabolomics followed by molecular networking reveals previously uncharacterized antimicrobial activities associated with known secondary metabolites, represented by the polycyclic tetramate macrolactam alteramide A.IMPORTANCE: Marine microorganisms are important sources of natural products, yet quite a few studies have systematically explored the production of active molecules by marine biofilm-associated bacteria. In the present study, we analyzed nearly complete genomes of 713 strains isolated from marine biofilms to assess their biosynthetic potential. We further conducted experiments to discover compounds with a strong inhibitory effect against pathogenic bacterial strains. This work has laid the groundwork for further prospecting marine biofilm-associated bacterial strains for antibacterial agents.PMID:41778798 | DOI:10.1128/aem.02593-25

Gut Microbes. 2026 Dec 31;18(1):2638004. doi: 10.1080/19490976.2026.2638004. Epub 2026 Mar 4.ABSTRACTTuberculosis (TB) remains a leading infectious killer, with growing evidence that the human microbiome-particularly in the gut and lungs-shapes susceptibility, progression, and treatment outcomes. Over the past decade, studies have reported that TB-associated dysbiosis, which is more common in the gut than in the lung, is often marked by the loss of short-chain fatty acid-producing taxa and the expansion of opportunistic microbes. However, findings are frequently confounded by diet, antibiotic exposure, comorbidities, geography, and methodological variability. Most research has relied on compositional profiling, offering limited insight into functional mechanisms. This narrative review synthesizes recent evidence, emphasizing the need to integrate multiomics approaches-metagenomics, metatranscriptomics, and metabolomics-and experimental validation to uncover causal links between microbiome alterations and TB pathogenesis or therapy response. We discuss potential clinical applications, including microbiome-based diagnostics (such as stool-based microbial or metabolite signatures for TB risk stratification), prognostic indicators (such as gut microbiome recovery predicting immune normalization during therapy), and adjunctive interventions (including microbiome-derived products to reduce drug-induced liver injury or fecal microbiota transplantation, which has been shown to be safe in people with HIV on stable ART) to mitigate drug toxicity or enhance immune recovery. Key priorities include methodological standardization, confounder control, mechanistic studies, and the inclusion of high-burden settings. By moving beyond descriptive surveys toward functional, translational research, integrating insights from different microbiome methods into TB prevention, diagnosis, and treatment could redefine the clinical research agenda and open new avenues for precision medicine in this global disease.PMID:41778780 | DOI:10.1080/19490976.2026.2638004