Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Synergistic and Fungicide-Reducing Effects of Biological Agents with Chemical Fungicides against Ginseng Rusty Root Rot

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):27458-27474. doi: 10.1021/acs.jafc.6c08284.ABSTRACTGinseng rusty root rot caused by Ilyonectria robusta threatens ginseng production. This study screened synergistic combinations of biocontrol agents and chemical fungicides. Combined treatments inhibited mycelial growth, yield, and conidial production and germination. Among nine combinations, five achieved over 50% control efficacy; NJF 5:1 reached 81.48% field efficacy and reduced I. robusta in roots and soil. Biocontrol strain colonization increased versus singlestrain treatments. Ginseng defense enzyme genes and soil enzyme activities were enhanced. Three-stage soil microbiomics showed improved diversity, increased beneficial Granulicella and Pseudogymnoascus, and decreased Ilyonectria pathogen, which positively correlated with disease index, while beneficial genera correlated with soil enzyme activity. Seven lipopeptide biosynthesis genes were upregulated by the combination versus single strain. Metabolomics and transcriptomics confirmed that fludioxonil promoted the accumulation of antifungal p-hydroxybenzaldehyde and 4-methylphenol in NJ13. This study presents a novel synergistic interaction model reducing chemical usage and clarifies multiple synergistic effects against ginseng rusty root rot.PMID:42715974 | DOI:10.1021/acs.jafc.6c08284

Anti-herbivore Activity of Jasmonate-Induced Theaflavins: Integrated Multi-omics Reveals Flavonoid-Mediated Defense Strategies in Tea Plants

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):27865-27878. doi: 10.1021/acs.jafc.5c13961.ABSTRACTFlavonoids are key compounds that protect plants from environmental stress and benefit human health. Understanding their metabolism can lead to advances in agriculture and human health. By integrating transcriptomics, metabolomics, proteomics, quantitative analysis and insect behavioral bioassays, this study characterized tea (Camellia sinensis L.) flavonoid profiles and decoded their dynamic reprogramming in response to herbivory and methyl jasmonate (MeJA), which induced 41 and 31 differential metabolites, respectively, dominated by methylated and oxidized flavonoids and proanthocyanidins. Critically, the two treatments activated 22 and 20 flavonoid synthase genes, respectively, sharing 15 common genes. Moreover, this study characterized theaflavins as potent, JA-inducible defenses with structure-dependent efficacy at a low dose (1.25 μg/g), and identified key peroxidases and laccases involved in their biosynthesis. These metabolic markers bridge the gap between insect resistance and quality traits in breeding programs, paving the way for developing plant-derived, eco-friendly biopesticides.PMID:42715972 | DOI:10.1021/acs.jafc.5c13961

Characterizing the Elemental Metabolome in Asparagus officinalis with Multielemental Speciation Analysis

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):28053-28059. doi: 10.1021/acs.jafc.6c10753.ABSTRACTWe report a multielemental and quantitative speciation analysis study with chromatographic inductively coupled plasma-mass spectrometry (ICP-MS/MS) detection involving four elements (sulfur, selenium, arsenic, and phosphorus) in Asparagus officinalis. The samples were locally purchased and labeled to originate from different regions in two continents. Major compounds were identified and quantified with confirmation based on chemical synthesis in pure form. Nontargeted analysis revealed significant quantitative and qualitative variation for the elemental metabolomes among samples, particularly sulfur and arsenic. Sharp contrast was observed in the diversity of the profiles between sulfur and selenium, providing insight into metabolism selectivity in Asparagus. Inorganic and methylated arsenic were both detected, but their ratios showed wide variation between samples. The present work shows the potential of multielemental speciation analysis with ICP-MS/MS as a novel dimension for food characterization based on studying heteroatom-tagged metabolome.PMID:42715969 | DOI:10.1021/acs.jafc.6c10753

Emulsified Mulberry Extract Alleviates CUMS-Induced Anxiety- and Depressive-Like Behaviors in Mice in Association with Gut Microbiota and Short-Chain Fatty Acids

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):27497-27511. doi: 10.1021/acs.jafc.6c03546.ABSTRACTMulberry, a traditional medicinal and edible plant rich in polysaccharides and flavonoids, has potential in regulating emotional behaviors. This study compared emulsified mulberry extract (EME) and aqueous mulberry extract (AME) on anxiety- and depression-like behaviors in male C57BL/6J mice exposed to chronic unpredictable mild stress (CUMS), and explored the underlying mechanisms of EME. EME alleviated anxiety- and depression-like behaviors more effectively than AME, with superior colloidal stability and dispersion. Metabolomic profiling revealed higher relative abundances of carbohydrates, eicosanoids, and flavonoids in EME. EME remodeled the gut microbiota-short-chain fatty acid (SCFA) axis, enhanced colonic barrier integrity, reduced serum lipopolysaccharide and proinflammatory cytokines, decreased stress hormone levels, elevated 5-hydroxytryptamine, and suppressed hippocampal glial activation while preserving neuronal integrity. Correlation analyses linked gut microbiota, SCFAs, hypothalamic-pituitary-adrenal axis activity, and behavioral phenotypes. These findings indicate that emulsification enhances the bioactivity of whole-component mulberry extracts, supporting their potential as natural food-based interventions for emotional disorders.PMID:42715956 | DOI:10.1021/acs.jafc.6c03546

Soluble, Insoluble, and Mixed Rice Bran Dietary Fibers Generate Distinct Host-Microbiota-Metabolome Responses in DSS-Induced Colitis

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):27657-27671. doi: 10.1021/acs.jafc.6c10465.ABSTRACTRice bran dietary fiber comprises soluble and insoluble fractions, but their differential host, microbial, and metabolic effects remain unclear. We compared RB-SDF, RB-IDF, and their mixture (RB-MIX) at two doses in DSS-induced colitis. All formulations alleviated symptoms, histological injury, barrier dysfunction, endotoxemia, and inflammation, but their relative advantages varied by end point and dose. RB-SDF showed histological protection and the greatest high-dose SCFA output, whereas RB-IDF produced distinct benefits for barrier-related and metabolic end points. RB-MIX remained effective but did not consistently match or exceed the strongest responses of the individual fractions. Microbiota profiling and untargeted metabolomics revealed formulation-dependent remodeling rather than uniform restoration. Disease-axis and factorial analyses further revealed partial shifts toward the CONTROL-associated metabolic profile and substantial contributions of fiber formulation and the formulation-by-dose interaction. These findings support the rational selection and formulation of rice bran fiber ingredients for functional foods.PMID:42715951 | DOI:10.1021/acs.jafc.6c10465

A Metabolome Atlas of Grape Biodiversity

Wed, 09/09/2026 - 12:00
J Agric Food Chem. 2026 Sep 9;74(35):28014-28025. doi: 10.1021/acs.jafc.6c04648.ABSTRACTGrapevine (Vitis spp.) is one of the world's most economically, culturally, and biologically important fruit crops, with remarkable diversity spanning thousands of V. vinifera cultivars together with rootstocks and wild relatives. Yet grapevine biodiversity has never been systematically explored at the metabolome scale, despite its importance for chemotaxonomy, breeding, and sustainable viticulture. Here, we present the Grape Metabolome (GM) Project, the first systematic liquid chromatography-mass spectrometry (LC-MS) survey of grapevine biodiversity, comprising 462 samples from 126 accessions collected across four vintages. Advanced and well-established chemometric tools resolved the major grape chemotypes together with finer cultivar-related substructure, while annotation-guided interpretation linked this organization to distinctive patterns in anthocyanins, flavonols, aroma-related compounds, and tannin-associated phenolics. This data set provides a reference framework for chemotaxonomy, breeding, authenticity, precision viticulture and enology.PMID:42715943 | DOI:10.1021/acs.jafc.6c04648

Mass spectrometry imaging in plants: Methods and applications

Wed, 09/09/2026 - 12:00
Curr Opin Plant Biol. 2026 Sep 9;94:102962. doi: 10.1016/j.pbi.2026.102962. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) has emerged as a powerful platform for spatial metabolomics, enabling direct mapping of metabolites within plant tissues. However, successful application of MSI in plants remains strongly dependent on effective sample preparation, as the unique structural features of plant tissues pose significant analytical challenges. In this review, we highlight recent advances in sample preparation strategies designed to address these limitations across diverse plant tissues. We then discuss how the methodological and technological innovations improve spatial resolution, sensitivity, specificity, and analytical throughput. Building on this technical progress, we survey the expanding biological applications of MSI in plant science, from decoding plant-environment interactions and resolving gene function to tracing the dynamics of metabolism through stable isotope labeling. By linking chemical distributions with biological processes, MSI is playing an increasingly important role in uncovering how metabolic pathways are organized and regulated within plant tissues, ultimately enabling a spatially resolved understanding of plant metabolism.PMID:42715827 | DOI:10.1016/j.pbi.2026.102962

Omega-3 related oxylipins in pregnancy and their associations with gestational age and preterm birth: A systematic review of observational studies and randomised controlled trials

Wed, 09/09/2026 - 12:00
Prostaglandins Leukot Essent Fatty Acids. 2026 Aug 29;211:102766. doi: 10.1016/j.plefa.2026.102766. Online ahead of print.ABSTRACTBACKGROUND: Maternal omega-3 fatty acid status can influence gestational length, with low omega-3 status associated with increased preterm birth risk. However, the underlying mechanisms remain unclear. Oxylipin derivatives are plausible mediators of gestational timing and preterm birth risk. This review evaluates whether studies combining an omega-3 exposure or intervention with oxylipin profiling provide mechanistic insights into gestational length or preterm birth risk.METHODS: Randomised controlled trials (RCTs) and observational studies in pregnant women that included an omega-3 intervention or recorded omega-3 exposure, with oxylipins quantified by liquid chromatography coupled with mass spectrometry (LC-MS), were systematically reviewed.RESULTS: Two studies were identified that included an omega-3 intervention and quantification of oxylipins by LC-MS, both nested within the same parent trials. One study examined associations between oxylipins and gestational outcomes and reported that specific lipoxygenase derived oxylipins measured in early pregnancy were associated with higher risk of spontaneous preterm birth. The other study evaluated changes in oxylipin profiles in response to omega-3 supplementation but did not assess associations with gestational length or preterm birth.CONCLUSIONS: Available evidence is insufficient to clarify relationships between omega-3 status, preterm birth or gestational length. Limited findings suggest that select oxylipins may be associated with spontaneous preterm birth risk, but evidence remains hypothesis generating. Further well-designed studies using standardised LC-MS methods and broader oxylipin profiling are needed.PMID:42715778 | DOI:10.1016/j.plefa.2026.102766

Blending reshapes flavor formation beyond additive effects in mustard (Brassica juncea) tea: Insights from integrated sensomics and metabolomics

Wed, 09/09/2026 - 12:00
Food Chem. 2026 Sep 4;528:151043. doi: 10.1016/j.foodchem.2026.151043. Online ahead of print.ABSTRACTMustard leaves are rich in bioactive compounds but remain underutilized in tea products. This study evaluated mustard tea from the perspectives of processing, cultivar, and blending. Mustard teas were prepared from green and purple mustard using green and black tea processing methods selected through preliminary screening. Among the single teas, purple mustard black tea (PB) showed the highest sensory quality. However, after blending with commercial teas, the blend of purple mustard green tea and Mengding Ganlu green tea (PG-MDGL) achieved the highest overall sensory score. Volatile metabolomics revealed that the superior aroma of PG-MDGL was associated with higher levels of key aroma-active compounds, including 3-hexenal, 3-hexen-1-ol, and 1-butanol, 2-methyl-, acetate, which contribute fresh, green, sweet, and fruity notes. Correlation analysis indicated that sensory perception was governed by interactions among multiple metabolites rather than individual compounds. This study provides insights into flavor formation and supports the development of vegetable-based teas.PMID:42715731 | DOI:10.1016/j.foodchem.2026.151043

Plant-rhizosphere control of thallium mobility and detoxification in contaminated soils: Insights from multi-omics and in situ DGT

Wed, 09/09/2026 - 12:00
Ecotoxicol Environ Saf. 2026 Sep 9;323:120773. doi: 10.1016/j.ecoenv.2026.120773. Online ahead of print.ABSTRACTThallium (Tl) is an extremely toxic and strongly bioaccumulative metal increasingly detected in agricultural soils, yet its behavior at the plant-rhizosphere interface remains poorly constrained. Here, we integrated in situ diffusive gradients in thin films (DGT) with multi-omics analyses (transcriptomics, metabolomics, and 16S rRNA sequencing) to elucidate how plant-rhizosphere interactions regulate Tl mobility and detoxification in Brassica rapa. In situ DGT profiling coupled with the European Community Bureau of Reference (BCR) sequential extraction identified the root-soil interface (0-3 cm) as a hotspot of labile Tl dynamics, revealing a dose-dependent shift from rhizosphere-mediated Tl mobilization under moderate exposure to immobilization under high stress. This transition was mirrored by a hormesis-driven plant response, with low Tl levels stimulating growth and uptake (bioconcentration factor, BCF = 4.2), followed by growth inhibition and restricted translocation at higher doses. Multi-omics analyses showed coordinated metabolic and transcriptional reprogramming associated with this shift, including altered central carbon metabolism, glutathione homeostasis, phenylpropanoid biosynthesis, and selective regulation of metal transporters (ZIP downregulation; ABC and MATE upregulation). Key metabolites (L-proline, sinapoyl aldehyde) and genes (e.g., TAT, PRDX6) emerged as integrative regulators linking detoxification, redox balance, and osmoprotection. Concurrently, Tl exposure induced a functional succession of the rhizosphere microbiome toward metal-resistant taxa (e.g., Nitrospira, Microvirga), closely associated with changes in root exudation patterns. Collectively, these findings advance a process-based mechanistic understanding of how rhizosphere biogeochemistry, plant molecular responses and microbial dynamics jointly control Tl mobility and detoxification, informing Tl risk assessment and plant-microbe-assisted management.PMID:42715634 | DOI:10.1016/j.ecoenv.2026.120773

Long-term ambient air pollution exposure, metabolomic signatures, and incident pulmonary hypertension: A large prospective cohort study

Wed, 09/09/2026 - 12:00
Ecotoxicol Environ Saf. 2026 Sep 8;323:120778. doi: 10.1016/j.ecoenv.2026.120778. Online ahead of print.ABSTRACTEvidence linking long-term multipollutant exposure with incident pulmonary hypertension (PH) and circulating metabolic profiles is limited. We investigated individual and joint air pollution exposures in relation to incident PH, characterized pollution-related circulating metabolic signatures, and evaluated their potential mediating roles. This prospective cohort included 444,346 participants without PH at baseline who had air pollution exposure estimates and nuclear magnetic resonance metabolomics data. PM2.5, PM10, NO2, and NOx were assessed as individual pollutants and jointly summarized using an air pollution score (APS). Exposure-related metabolic signatures were derived by elastic-net regression, and their associations with incident PH and potential mediating contributions were evaluated using Cox proportional hazards models and mediation analyses. During 13.58 years of median follow-up, 2328 participants developed PH. Higher APS was associated with increased PH risk (hazard ratio [HR] per 1-SD increment, 1.12; 95% confidence interval [CI], 1.08-1.17). Individual pollutants were also positively associated with PH, with HRs ranging from 1.06 to 1.93 per 10-μg/m3 increment. Elastic-net regression yielded 105 metabolites for the APS signature and 52-123 metabolites for pollutant-specific signatures, mainly involving lipoprotein-related measures, fatty acids, and amino acids. These signatures were also associated with incident PH (HRs per 1-SD increment, 1.12-1.24). The overall metabolic signature mediated 11.74% (95% CI, 7.91%-18.95%) of the APS-PH association, whereas pollutant-specific signatures mediated 11.38%-26.00% of the corresponding pollutant-PH associations. Both individual pollutants and the weighted APS were positively associated with incident PH, with circulating metabolic alterations potentially contributing to these associations.PMID:42715631 | DOI:10.1016/j.ecoenv.2026.120778

Maternal-fetal distribution of synthetic phenolic antioxidants and their associations with gestational diabetes mellitus: A cross-sectional analysis nested within the Chongqing PREBIC cohort

Wed, 09/09/2026 - 12:00
Ecotoxicol Environ Saf. 2026 Sep 8;323:120779. doi: 10.1016/j.ecoenv.2026.120779. Online ahead of print.ABSTRACTSynthetic phenolic antioxidants (SPAs) and their transformation products (TPs) are widespread environmental contaminants with endocrine-disrupting potential, yet their distribution across the maternal-fetal interface and relevance to maternal metabolic health remain unclear. Leveraging 222 paired maternal and umbilical cord plasma samples (51 cases of gestational diabetes mellitus [GDM] and 171 normoglycemic controls) from the Chongqing Preconception Reproductive Health and Birth Outcome Cohort (PREBIC), we quantified eight SPAs (AO246, DTBSBP, DtAP, AO2246, 4-tOP, BHA, 2,4-DtBP, and BHT) and five BHT-derived TPs (BHT-OH, BHT-CHO, BHT-COOH, BHT-quinol, and BHT-Q) using UPLC-MS/MS and performed targeted metabolomic profiling of 446 maternal plasma metabolites. In maternal plasma, 2,4-DtBP and BHT were the predominant compounds, whereas BHT-derived TPs, particularly BHT-Q and BHT-quinol, predominated in umbilical cord plasma. The transplacental transfer efficiency of BHT-quinol was significantly lower in GDM pregnancies. Maternal plasma concentrations of BHT-quinol and total TPs were higher in women with GDM. Each one-unit increase in ln-transformed BHT-quinol and total TP concentrations was associated with higher odds of GDM (adjusted odds ratio [OR], 1.83; 95% CI: 1.34-2.59; adjusted OR, 1.49; 95% CI: 1.08-2.11, respectively). Bayesian kernel machine regression identified BHT-quinol as the dominant contributor to the observed positive mixture-GDM association. Integrative metabolomic analyses identified 88 overlapping lipid metabolites showing consistent inverse associations with both maternal BHT-quinol concentrations and GDM status, with enrichment in pathways related to AGE-RAGE signaling in diabetic complications, sphingolipid signaling, and insulin resistance. These findings characterize the maternal-fetal distribution of BHT and its TPs among pregnant women in Southwest China and identify associations of maternal BHT-derived TPs with GDM and related metabolic alterations. Prospective studies are warranted to clarify the potential causal relationships between SPA exposure and maternal metabolic health.PMID:42715628 | DOI:10.1016/j.ecoenv.2026.120779

Mesona chinensis Benth polyphenols ameliorate type 2 diabetes mellitus in mice through coordinated regulation of gut microbiota, metabolic profiles, and host metabolic-inflammatory responses

Wed, 09/09/2026 - 12:00
Bioorg Chem. 2026 Sep 6;182:110467. doi: 10.1016/j.bioorg.2026.110467. Online ahead of print.ABSTRACTBACKGROUND: Mesona chinensis Benth polyphenols (MCP) have demonstrated potential anti-diabetic activity. However, the underlying mechanisms involved in their metabolic regulation remain incompletely understood.OBJECTIVE: This study aimed to investigate the anti-diabetic effects of MCP in HFD/STZ-induced type 2 diabetes mellitus (T2DM) mice through an integrated analysis combining network pharmacology, gut microbiota profiling, metabolomics, and molecular validation.MATERIALS AND METHODS: An HFD/STZ-induced T2DM mouse model was established to assess the effects of MCP on glucose metabolism, lipid metabolism, and tissue injury. Network pharmacology was performed to predict potential bioactive compounds, targets, and signaling pathways associated with MCP. Gut microbiota composition and metabolic profiles were analyzed to evaluate MCP-induced alterations in microbial and metabolic homeostasis. Representative proteins involved in glucose metabolism-associated signaling, inflammatory responses, and lipid metabolic regulation were further evaluated by Western blot analysis.RESULTS: MCP administration significantly improved diabetic phenotypes, as evidenced by reduced fasting blood glucose (FBG), improved oral glucose tolerance test (OGTT) responses, and decreased serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. Network pharmacology analysis identified multiple candidate pathways potentially involved in the anti-diabetic effects of MCP. Integrated omics analysis revealed that MCP reshaped gut microbiota composition and altered metabolic profiles, particularly pathways related to fatty acid metabolism, including alpha-linolenic acid and linoleic acid metabolism and fatty acid biosynthesis. Molecular validation further demonstrated that MCP modulated representative proteins associated with PI3K-Akt/GLUT4-related glucose metabolism signaling, TNF/MAPK/NF-κB-mediated inflammatory responses, and lipid metabolic regulation.CONCLUSION: These findings suggest that MCP exerts anti-diabetic effects through coordinated regulation of gut microbiota remodeling, metabolic alterations, glucose metabolism-associated signaling, inflammatory responses, and lipid metabolic homeostasis. This study provides mechanistic insights into the potential hypoglycemic effects of MCP.PMID:42715624 | DOI:10.1016/j.bioorg.2026.110467

How to live for centuries: common denominators of organisms with exceptional longevity

Wed, 09/09/2026 - 12:00
Aging (Albany NY). 2026 Sep 8;18(1):1147-1162. doi: 10.18632/aging.206419. Epub 2026 Sep 8.ABSTRACTOrganisms vary in their lifespan. Understanding this variation may help us live healthier and longer. Here, we focus on species living twice as long as humans, or more. Out of the 101 multicellular species with a maximum lifespan of 250+ years, 11 are animals and 90 are plants. We surveyed the genetic, transcriptional, proteomic, metabolomic, regeneration-, stress-, and cancer-related components of intraspecific and interspecific lifespan variation, across these species. We examined whether the mechanisms regulating intraspecific lifespan variation across these species are the same or different from mechanisms regulating interspecific lifespan variation. We identified several similarities: both types of variation include mechanisms related to DNA maintenance, stemness, and stress management. Such mechanisms are also typical of early developmental stages and germ cells. Nonetheless, caution should be exercised when attempting to draw robust conclusions based on available data, given the lack of in-depth molecular studies on the healthspan and lifespan across thousands of individuals and species, the methodological variation across published studies, and our partial understanding of the interplay between physiology and the environment across species.PMID:42715610 | DOI:10.18632/aging.206419

Evolutionary constraints and regulatory plasticity shape host specialization in the <em>Magnaporthe oryzae</em> species complex

Wed, 09/09/2026 - 12:00
Virulence. 2026 Dec;17(1):2728454. doi: 10.1080/21505594.2026.2728454. Epub 2026 Sep 9.ABSTRACTRice blast caused by Magnaporthe oryzae threatens global rice production, and wheat blast emergence highlights the pathogen's capacity for host shifts. Although numerous studies have described M. oryzae genome organization and infection mechanisms, critical questions remain regarding the evolutionary drivers of stable host specialization. Importantly, the blast pathogen comprises a species complex of genetically differentiated, host-adapted lineages rather than single homogeneous species. To address this knowledge gap, we integrate evidence from evolutionary genomics, transcriptomics, and metabolomics to develop the "Constrained Plasticity" framework. We argue that host adaptation arises from three interacting layers: genomic scaffolding (including epigenetic and noncoding RNA regulation), regulatory networks (enabling transcriptional plasticity), and metabolic compatibility (determining physiological success). This systems-level perspective explains the long-term stability of host-adapted lineages and the rare breakdowns resulting in host shifts, such as wheat blast. This framework generates testable predictions for pathogen emergence and provides a roadmap for developing lineage-aware resistance strategies.PMID:42715011 | DOI:10.1080/21505594.2026.2728454

Perilla seed oil reshapes the rumen microbiome and increases fermentation end-products in vitro

Wed, 09/09/2026 - 12:00
J Appl Microbiol. 2026 Sep 9:lxag233. doi: 10.1093/jambio/lxag233. Online ahead of print.ABSTRACTAIMS: The effect of Perilla frutescens seed oil (PSO) on an in vitro rumen microbial ecosystem was evaluated by integrating fermentation measurements, microbiome profiling, metagenomics, and untargeted metabolomics.METHODS AND RESULTS: Rumen inoculum was incubated for 24 h with a control TMR substrate (CK), TMR supplemented with 23.7 mg of Perilla seeds per bottle (PS), or TMR supplemented with 8.5 μL of Perilla seed oil per bottle (PSO), with the PS and PSO treatments providing equivalent amounts of seed oil. Fermentation kinetics and volatile fatty acids were measured, and microbial and metabolic responses were characterized using 16S rRNA gene sequencing, metagenomics, KEGG and CAZy annotation, untargeted metabolomics and MetOrigin2 source tracing. PSO increased maximum gas production and total volatile fatty acid concentrations while maintaining pH within the physiological range. Community diversity was unchanged, but PSO altered microbial composition, including increases in Firmicutes, Verrucomicrobia, Vagococcus, Clostridium and Lactobacillus and decreases in Shigella sonnei and Methanosarcina sp. Ant1. PSO also altered microbial functional profiles and increased several lipid- and vitamin-associated metabolites, including linoleic acid, 13-HODE, 9-oxoODE, pantothenic acid and thiamine, while reducing lactate.CONCLUSIONS: PSO changed rumen microbial community structure and functional potential in parallel with increased fermentation end-products and extensive metabolic shifts. These in vitro findings identify microbial and metabolic responses that warrant validation in vivo.PMID:42714846 | DOI:10.1093/jambio/lxag233

Unveiling novel transcriptomic prognostic biomarkers for specific breast cancer subtypes and treatment regimens

Wed, 09/09/2026 - 12:00
Pharmacol Rep. 2026 Sep 9. doi: 10.1007/s43440-026-00895-x. Online ahead of print.ABSTRACTBACKGROUND: Breast cancer (BRCA) is the most common cancer in women worldwide, yet current gene expression panels offer limited insight into treatment responses across different subtypes and therapies. This study aimed to identify reliable biomarkers for predicting treatment outcomes in specific BRCA subtypes and treatment regimens.METHODS: This study analyzed transcriptomic data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs) in patient groups treated with different combinations of hormone therapy (H), chemotherapy (C), radiotherapy (R), and targeted therapy (T). Non-negative matrix factorization clustering was performed to stratify patients into clusters representing different BRCA subtypes. Functional enrichment analysis was performed, and survival assessments were conducted using the METABRIC dataset.RESULTS: A total of 1,148 DEGs were identified across treatment regimens, with 75 common DEGs shared across multiple regimens. Among these, 12 candidate biomarkers were associated with luminal subtypes treated with H, including LRP1B, of which high expression predicted cancer recurrence. In triple-negative breast cancer (TNBC) treated with C, 76 candidate biomarkers were identified, including TTYH1 for recurrence and ANXA8L1 and MPZ for non-recurrence. Functional analyses identified intermediate filament organization and keratinization as pathways associated with specific candidate biomarkers of TNBC following C. Survival analysis using METABRIC strengthened the prognostic ability of LRP1B and TTYH1 to predict worse survival and ANXA8L1 and MPZ to predict prolonged survival, with four additional prognostic biomarkers.CONCLUSION: This study identified gene expression prognostic biomarkers for luminal and TNBC subtypes, thereby supporting personalized therapies. Further experimental validation is required to confirm these findings for clinical application.CLINICAL TRIAL REGISTRY: No.PMID:42714781 | DOI:10.1007/s43440-026-00895-x

Gut Microbiota and Aldosterone Regulate Natriuretic Peptide B Expression to Drive Mitophagy and Metabolic Reprogramming in Sepsis-Like Model of Myocardial Injury

Wed, 09/09/2026 - 12:00
J Am Heart Assoc. 2026 Sep 9:e046120. doi: 10.1161/JAHA.125.046120. Online ahead of print.ABSTRACTBACKGROUND: Myocardial injury is a major contributor to mortality in sepsis, yet the mechanisms underlying gut-heart communication in sepsis-induced myocardial injury remain insufficiently defined. Natriuretic peptide B (NPPB) is a cardiac stress-responsive gene, but its involvement in mitochondrial homeostasis and metabolic regulation is unclear. This study investigated how gut microbiota and aldosterone influence myocardial mitophagy and metabolic reprogramming through NPPB in sepsis-induced myocardial injury.METHODS: A sepsis-like myocardial injury model was induced in mice by intraperitoneal lipopolysaccharide (LPS). Fecal microbiota transplantation from septic mice into pseudo-germ-free recipients assessed microbial contributions. Metagenomic, metabolomic, and transcriptomic analyses identified disrupted metabolites and cardiac gene signatures. Heart-specific NPPB-knockout mice were used to determine its in vivo role. Mitochondrial function and metabolic alterations were evaluated by energy metabolism assays. In vitro, aldosterone-treated AC16 cardiomyocytes were used to examine NPPB-mediated mitophagy and metabolic changes. Molecular docking, dynamics simulation, and machine-learning screening identified Lestaurtinib, whose therapeutic effects were validated pharmacologically.RESULTS: Sepsis caused pronounced microbial dysbiosis and elevated aldosterone levels. Multi-omics analysis identified NPPB as a central regulator of mitophagy and metabolic remodeling. NPPB deficiency mitigated mitochondrial impairment and metabolic disturbances in vivo. Aldosterone upregulated NPPB in cardiomyocytes, promoting mitophagy and metabolic reprogramming. Lestaurtinib, identified as a candidate targeting the aldosterone-NPPB axis, improved cardiac structure and function while partially restoring microbial and metabolic homeostasis.CONCLUSIONS: This study uncovers a novel gut microbiota-aldosterone-NPPB axis driving LPS-induced myocardial injury through dysregulated mitophagy and metabolism and highlights Lestaurtinib as a potential therapeutic strategy for sepsis-induced myocardial injury.PMID:42714425 | DOI:10.1161/JAHA.125.046120

Real-time volatilomics reveals microbiota and pathogen fingerprints in the honey bee

Wed, 09/09/2026 - 12:00
mBio. 2026 Sep 9:e0141926. doi: 10.1128/mbio.01419-26. Online ahead of print.ABSTRACTUnderstanding the complex relationship between gut microbiota and their hosts often relies on invasive sampling techniques. Honey bees provide a tractable model for host-microbe studies. Here, we establish single-bee volatilomics using secondary electrospray ionization-high-resolution mass spectrometry (SESI-HRMS) to examine volatile organic compounds released to the air around an individual live honey bee. Specifically, we focused on the primary gut microbiota metabolites present in gnotobiotic bees. Our findings reveal distinct volatilome profiles in honey bees that depend on their gut bacterial colonization state. We cross-validated our findings using an established metabolomics technique, liquid chromatography-high-resolution mass spectrometry (LC-HRMS), to compare and contrast the metabolites detectable with each method. Finally, we assessed the ability of SESI-HRMS to detect colonization with the bee pathogen Serratia marcescens. By comparing the volatile signature of this bacterium grown in liquid culture with that of infected honey bee headspace, we identified overlapping compounds, including butane-2,3-diol, that were elevated in infected bees relative to uninfected controls. Non-invasive SESI-HRMS volatilomics, paired with LC-HRMS, therefore, have the potential to identify biomarkers of bee microbiome composition and infection at the level of individual insects. These biomarkers represent practical targets for the development of simple, field-ready diagnostic tools for monitoring pollinator health.IMPORTANCE: Honey bees are vital to various ecosystems and human agriculture as globally present pollinators. Current declines in bee populations threaten crop productivity and biodiversity and are driven by many factors, including habitat loss, pesticides, and pathogenic infections. The findings presented in this work demonstrate how the analysis of volatile species can precisely detect products of metabolic activity coming from the honey bee and its associated gut microbial community. We were able to demonstrate how high-resolution mass spectrometry can be used to study the host-microbiota relationship on the level of an individual insect. This technique, combined with volatilomics, allowed us to outline a volatile signature of infection in honey bees, which could become a target for in-field beehive disease monitoring.PMID:42714137 | DOI:10.1128/mbio.01419-26

Mitochondrial Respiratory Metabolism in Salt-Stressed Barley (Hordeum vulgare): TCA Cycle Activation With Limited GABA Shunt Engagement

Wed, 09/09/2026 - 12:00
Plant Cell Environ. 2026 Sep 9. doi: 10.1111/pce.70863. Online ahead of print.ABSTRACTPlants maintain energy balance under salinity stress through increased respiration and energy use, processes also associated with reactive oxygen species generation. Although respiration imposes a high energy cost, mitochondrial respiration and the tricarboxylic acid (TCA) cycle activity are vital for ATP production and for providing electron donors that drive ion exclusion and ROS detoxification. This study examined the molecular basis of salinity-induced respiratory responses in barley using physiological, biochemical, metabolomic and proteomic analyses. Salt exposure resulted in sodium accumulation, decreased photosynthesis and biomass, and increased respiration. Metabolite profiling indicated activation of the TCA cycle, while proteomics showed increased abundance of all targeted TCA enzymes, including phosphoenolpyruvate carboxylase isoforms and succinate dehydrogenase. Enhanced pyruvate oxidation and accumulation of downstream metabolites are consistent with a central role for the classical TCA cycle in barley's salinity response. Conversely, reduced levels of 2-oxoglutarate and succinate, together with non-detection of key GABA shunt enzymes (SSADH, GDH), are consistent with limited GABA shunt contribution under the conditions examined, although we cannot exclude dynamic GABA cycling that does not result in net accumulation. The absence of detectable arginine and ornithine, unlike their salt-induced increase in wheat, further suggests that the GABA shunt may contribute less to barley's salinity response under these conditions. Overall, the combined metabolomic and proteomic evidence supports an interpretation that barley preferentially relies on enhanced mitochondrial respiration and the canonical TCA cycle under these experimental conditions, with a lesser contribution from GABA shunt metabolism than in wheat. As neither metabolite pool sizes nor protein abundances measure pathway flux directly, this is presented as an interpretation of the combined datasets rather than a demonstration of the relative fluxes through the two pathways. These results point to a species-specific divergence in respiratory and osmotic adjustment strategies under salinity and invite future investigation into how key compatible solutes such as glycine betaine, an alternative osmolyte with a known relationship to GABA metabolism, contribute to barley's salinity tolerance.PMID:42713811 | DOI:10.1111/pce.70863

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