PubMed

Plant Cell Environ. 2026 Sep 10. doi: 10.1111/pce.70872. Online ahead of print.ABSTRACTStem architecture is a major determinant of lodging resistance, biomass accumulation, and harvest efficiency in soybean. However, the molecular features associated with contrasting stem growth habits in wild soybean remain incompletely characterised. Here, we performed an integrated transcriptomic, metabolomic, and epigenomic analysis of stem growth-habit divergence in wild soybean, comparing the wild-type accession ZYD7068 with contrasting vining and erect mutant lines derived from carbon-ion beam mutagenesis. Pairwise transcriptomic comparisons identified between 20 311 and 28 705 differentially expressed genes per contrast, with a core set of 2672 genes consistently altered across the comparisons. Functional enrichment, gene set variation analysis, and gene set enrichment analysis converged on xylem and phloem pattern formation as a prominent molecular pathway associated with growth-habit divergence. Random forest analysis identified BBR-BPC and ARF transcription factor families as major molecular discriminators, while metabolomic profiling revealed distinct metabolic profiles involving amino-acid-derived and lipid-associated metabolites. Whole-genome bisulfite sequencing revealed context-specific DNA methylation differences, including substantial variation in CHG methylation among erect mutant lines. Integrated network and in silico perturbation analyses prioritised four candidate genes associated with vascular development for future functional validation. Together, these results provide a multi-layer molecular resource for investigating stem growth-habit divergence in G. soja and establish testable candidate pathways and genes for subsequent functional studies and soybean improvement.PMID:42720448 | DOI:10.1111/pce.70872

J Ind Microbiol Biotechnol. 2026 Sep 10:kuag026. doi: 10.1093/jimb/kuag026. Online ahead of print.ABSTRACTLarge-scale untargeted bacterial metabolomics studies are often challenging to interpret, particularly for natural product discovery. Complex raw mass spectrometry data contains media components, biotransformation products, workup contaminants, and in-source fragments, making it difficult to resolve true biosynthesized bacterial products from background features. Incorporating stable isotope labels into untargeted workflows enables the selective detection of actively biosynthesized compounds, drastically reducing candidate mass spectrometry features to highlight novel or robustly expressed metabolites. Recently, our lab introduced IsoAnalyst, a parallel stable isotope labeling platform that links secondary metabolites to biosynthetic gene clusters by determining the incorporation rates of a panel of isotopically labeled building blocks. In this study we applied the IsoAnalyst protocol to a library of 114 Burkholderiales strains with the goals of profiling the specialized metabolite chemistry of this bacterial order and connecting detected natural products to their cognate BGCs based on their labeling profiles. While our strain-matching protocol, which evaluates correlations between detected metabolites and BiG-SCAPE-defined gene cluster families, did not yield confident BGC assignments, it successfully highlighted widely distributed metabolites with distinct labeling profiles. We targeted a set of these molecules for isolation, revealing two classes of compounds derived from primary biomolecule metabolism that are implicated in cellular stress responses. The first class of molecules were identified as lysophosphatidyl ethanolamine analogues while the second was characterized via NMR spectroscopy and mass spectrometry as methyl-esterified 3-hydroxybutyrate oligomers (HB6-OMe, HB7-OMe, and HB8-OMe), representing higher-degree polymer units than previously reported.PMID:42720419 | DOI:10.1093/jimb/kuag026

mSystems. 2026 Sep 10:e0072026. doi: 10.1128/msystems.00720-26. Online ahead of print.ABSTRACTDetecting metabolic dysfunction-associated steatohepatitis (MASH) before fibrosis develops remains a major challenge. We used a longitudinal streptozotocin/high-fat diet (STAM/HFD) mouse model to identify microbial and metabolic features that emerge before histological MASH onset. Integrative 16S rRNA and untargeted LC-MS/MS analyses revealed microbial and metabolite shifts weeks before disease development. Lachnospiraceae and Oscillospiraceae were enriched in non-MASH mice and were negatively correlated with fatty acids elevated under MASH conditions. Bile acid and fatty acid metabolites enriched under MASH and non-MASH states varied with collection time, showing that diurnal variation strongly shapes biomarker profiles. Analysis of a human MAFLD cohort confirmed higher abundances of Lachnospiraceae bacteria in healthy participants. Our results identify early microbial and metabolic features that are associated with subsequent histologic MASH onset and reveal how temporal factors influence biomarker detection. These time-sensitive features, together with cross-species concordance in a human MAFLD cohort, lay the groundwork for developing and validating microbiome-based diagnostics and circadian-informed interventions that target the gut-liver axis to prevent metabolic liver disease.IMPORTANCE: Metabolic dysfunction-associated steatohepatitis (MASH) often develops silently, limiting opportunities for early intervention before fibrosis occurs. In this study, we identify gut microbial taxa and stool metabolites that are associated with future histologic MASH development in a longitudinal mouse model. We show that members of the Lachnospiraceae and Oscillospiraceae families are enriched in mice that remain disease-free and that members of the Lachnospiraceae family exhibit similar patterns in a human MAFLD cohort. Importantly, we demonstrate that time of sample collection has a strong effect on metabolomic profiles, with disease-associated lipid and bile acid signals detectable only at specific sampling times. These findings highlight circadian timing as a critical variable in microbiome-based biomarker discovery and support the development of time-aware diagnostic strategies for early MASH risk assessment.PMID:42720356 | DOI:10.1128/msystems.00720-26

Cancer Epidemiol Biomarkers Prev. 2026 Sep 10. doi: 10.1158/1055-9965.EPI-26-0544. Online ahead of print.ABSTRACTBACKGROUND: Ovarian cancer remains a significant health concern among U.S. women, yet its underlying etiology is not fully understood. Untargeted metabolomics enables comprehensive profiling of small molecules that may provide insight into metabolic alterations associated with ovarian cancer risk.METHODS: We conducted a case-cohort study within the Cancer Prevention Study-3, measuring pre-diagnostic plasma metabolites via untargeted metabolomics in 127 ovarian cancer cases and a randomly selected sub-cohort of 1,811 women, one of whom was later diagnosed with ovarian cancer. Median follow-up time was 2.4 years (IQR: 1.2-3.6) among ovarian cancer cases and 3.2 years (IQR: 2.5-5.2) in the sub-cohort. Metabolite associations with ovarian cancer risk were estimated using multivariable Prentice-weighted Cox models, and pathway enrichment analyses were performed. False discovery rate (FDR) correction was applied, considering FDR < 0.2 statistically significant.RESULTS: Among 868 plasma metabolites analyzed, none showed statistically significant associations with ovarian cancer risk after FDR correction. In stratified analyses by menopausal status, five metabolites remained statistically significant after FDR correction among postmenopausal women only. Pathway enrichment analyses identified several lipid-related sub-pathways enriched among metabolites associated with ovarian cancer risk (FDR-adjusted p-value < 0.2), with the strongest positive enrichment observed for primary bile acid metabolism and the strongest negative enrichment for sphingomyelins.CONCLUSIONS: In this prospective metabolomics analysis, individual pre-diagnostic plasma metabolites were not associated with ovarian cancer risk, but lipid-related pathways and possible differences by menopausal status may warrant additional investigation.IMPACT: These findings contribute to the growing untargeted metabolomics literature on ovarian cancer.PMID:42720260 | DOI:10.1158/1055-9965.EPI-26-0544

Anim Sci J. 2026 Jan-Dec;97(1):e70242. doi: 10.1111/asj.70242.ABSTRACTThis study systematically investigated age-related variations in meat quality traits, lipidomic profiles, and metabolomic profiles of breast muscle from White King pigeons, comparing 28-day-old squabs (D28) and 12-month-old adult pigeons (M12). Six biological replicates were used per group (n = 6). Physicochemical analyses and ultra-high performance liquid chromatography-tandem mass spectrometry were employed to characterize these differences. Results showed significant disparities in meat quality between the two age groups: D28 pigeons exhibited significantly higher lightness (L*), redness (a*), and yellowness (b*) values at 24-h postslaughter, along with higher water-loss rate alongside lower shear force (p < 0.05), reflecting more tender muscle texture despite weaker water retention capacity. In contrast, M12 pigeons had higher springiness but lower cohesiveness and gumminess (p < 0.05). Lipidomic analysis identified 553 lipid molecules, with 174 differential lipids categorized into six classes. D28 pigeons had significantly higher levels of glycerolipids (GLs) and fatty acyls (FAs), while M12 pigeons showed elevated saccharolipids (SLs) and prenol lipids (PRs). Metabolomic profiling detected 19,019 metabolites, among which 984 were differentially abundant (screening criteria: variable importance in projection (VIP) ≥ 1, fold change (FC) > 1.2 or FC < 0.83, FDR-adjusted p < 0.05), predominantly enriched in amino acid metabolism. Correlation analysis revealed that acylcarnitines (AcCa) and phosphatidylinositol (PI) were positively correlated with water-loss rate and L24 values (r > 0.8, p < 0.05), whereas lysophosphatidylethanolamines (LPEs), L-threonic acid, and β-glycerophosphoric acid showed positive associations with shear force and cooking loss (r > 0.8, p < 0.05). These findings reveal statistical associations between lipid/metabolite profiles and age-driven differences in pigeon breast meat quality, and identify potential candidate lipid and metabolite biomarkers correlated with pigeon meat quality phenotypes. These results identify candidate biomarkers associated with breast meat quality in male White King pigeons at two ages and offer preliminary exploratory omics data for subsequent pigeon meat research, rather than universal guidance for breeding and production.PMID:42720194 | DOI:10.1111/asj.70242

J Med Virol. 2026 Sep;98(9):e71150. doi: 10.1002/jmv.71150.ABSTRACTAcute liver failure (ALF) due to hepatitis A (ALF-A) has high mortality, but admission-day markers associated with disease severity and outcome are unknown. We aimed to define gut microbiome and plasma multi-omics signatures associated with severity and 90-day outcomes in ALF-A, compared to drug-induced ALF (ALF-D) as non-viral ALF group. ALF patients (aged 26 ± 9 years; 50.7% male, 49.3% female) with IgM HAV positive (ALF-A, n = 33), ALF-D (n = 38) were recruited along with acute viral hepatitis (AVH-A, n = 27) and healthy subjects (HC, n = 20). Stool bacteria profiling was done at D0; plasma cytokines, metabolites and barrier markers were analysed at D0, 3, 5, 7. Correlations with clinical severity parameters were assessed. Associations with 90-day mortality were assessed using severity-adjusted association analyses. ALF-A patients were more severe at the time of admission than ALF-D. In ALF-A, 90-day mortality was 33% versus 18.4% with increased severity scores like KCH 21% versus 10.5%, SOFA score 7.97 ± 2.89 versus 5.87 ± 2.32, SIRS 60.6% versus 18.4%, mechanical ventilation 39% versus 21%. At D0, ALF-A was enriched for lactate/ammonia/bile salt hydrolase/histamine-producing pathobionts like Enterococcus, Ruminococcus gnavus, Flavonifractor, Thomasclavelia correlating positively with severity (|r| > 0.4, p < 0.05) showing higher baseline abundance in ALF-A non-survivors (NS). At D0 in ALF-A, histamine accumulation, reduced tryptophan, butyrate metabolism inversely correlated with severity and worsened in ALF-A_NS by D7. Pro-inflammatory cytokines, IFABP2 were elevated at Day 0 in ALF-A, correlated positively with severity, and remained increased through Day 7 in ALF-A_NS. In contrast, ALF-D_NS retained commensals, showed increased fatty acid, bile acid biosynthesis with low levels of pro-inflammatory cytokines. In ALF-A, gut and plasma integrated multi-omics features were associated with disease severity, 90-day outcomes and identified candidate biomarkers for future validation.PMID:42720154 | DOI:10.1002/jmv.71150

Crit Rev Food Sci Nutr. 2026 Sep 10:1-23. doi: 10.1080/10408398.2026.2728440. Online ahead of print.ABSTRACTCoffee and cocoa processing generates large volumes of underutilized residues such as husks, pulps, and spent grounds (80%-90% of the fruit). The improper disposal of these materials contributes to environmental and socio-economic challenges, driving interest in circular economy strategies aligned with the United Nations Sustainable Development Goals. Although previous studies have described the metabolite composition of extracts from coffee and cocoa by-products, none has comprehensively examined their metabolomic diversity, bioactive potential, and shared metabolic features. As a key contribution, this review provides the most up-to-date curated dataset of metabolites reported in both coffee and cocoa agro-industrial residues, summarizing the analytical approaches used for metabolite identification and discussing annotation challenges. Critically, this review assesses the available evidence on biological activities and identifies shared metabolic features that may support future valorization strategies.PMID:42720101 | DOI:10.1080/10408398.2026.2728440

J Sci Food Agric. 2026 Sep 10. doi: 10.1002/jsfa.71052. Online ahead of print.ABSTRACTBACKGROUND: Herbal Baijiu (HB) and traditional Baijiu (TB) contain complex chemical matrices whose metabolic fate during gastrointestinal digestion and subsequent impact on gut microbiota remain unclear. This study systematically compared HB and TB through in vitro gastrointestinal digestion to evaluate the differences in digestive profiles and microbial communities.RESULTS: Volatile metabolite profiling demonstrated that HB maintained higher stability of ester compounds, particularly ethyl pentanoate, throughout digestion, whereas TB accumulated higher levels of potentially undesirable compounds such as 2,4-di-tert-butylphenol during small intestinal digestion. Moreover, non-volatile metabolites analysis revealed clear separation between HB and TB after gastric and small intestinal digestion, while minimal differences were observed during oral digestion. HB exhibited a greater number of differential metabolites during small intestinal digestion than TB, indicating stronger digestion-induced metabolic remodeling. KEGG enrichment analysis indicated that HB was associated with lipid metabolism, bile acid biosynthesis, and one-carbon metabolism pathways, whereas TB predominantly enriched glutathione metabolism and aromatic amino acid metabolism, reflecting stronger oxidative stress responses. During fermentation, HB promoted a more beneficial and functionally diverse microbial profile, characterized by enrichment of Bifidobacterium and Lactobacillus, as well as dynamic succession of Clostridium (63.81% at 24 h) and Veillonella (54.52% at 72 h). Correlation analysis further linked HB-associated metabolites with beneficial microbial genera, whereas TB was associated with Acidaminococcus and Fusobacterium nucleatum.CONCLUSION: HB and TB exhibited distinct digestion-dependent metabolic and microbial trajectories. HB more effectively modulated digestion-derived metabolites and promoted a more favorable gut microbial profile compared with TB. © 2026 Society of Chemical Industry.PMID:42719956 | DOI:10.1002/jsfa.71052

Int J Gen Med. 2026 Sep 5;19:603483. doi: 10.2147/IJGM.S603483. eCollection 2026.ABSTRACTGastric cancer remains one of the most common malignant tumors worldwide and is associated with a high disease burden. Its treatment is still challenged by multidrug resistance, an immunosuppressive tumor microenvironment, and suboptimal postoperative recovery. Traditional Chinese Medicine (TCM) has shown potential in the prevention, treatment, and rehabilitation of gastric cancer. Herein, this review aims to discuss the basic theory, clinical practice, technical progress, epidemiological research, controversies and challenges, and future prospects of TCM in gastric cancer treatment. Literature from the past five years was retrieved from PubMed and China National Knowledge Infrastructure (CNKI) using English and Chinese search terms related to gastric cancer, TCM, Chinese herbal medicine, integrated traditional Chinese and Western medicine, clinical outcomes, mechanisms, network pharmacology, metabolomics, immunotherapy, chemotherapy resistance, postoperative recovery, and translational research. Experimental studies, clinical studies, cohort studies, randomized trials, meta-analyses, guideline-related studies, and technical studies were considered only if they were relevant to the scope of this narrative review. Based on these, we discuss how TCM may exert potential anti-gastric cancer effects through the regulation of apoptotic pathways, modulation of signaling networks, and improvement of immune function. Currently, clinical studies indicate that TCM combined with chemotherapy may prolong survival in patients with advanced gastric cancer, while perioperative interventions such as transcutaneous electrical acupoint stimulation and herbal formulations may alleviate postoperative pain, promote gastrointestinal recovery, and regulate inflammatory responses. Technological advances such as network pharmacology, metabolomics, and nano-preparation technologies have been used to help clarify the molecular mechanisms of TCM and improve drug delivery efficiency. In addition, observational and real-world evidence suggest that TCM use is associated with survival-related outcomes, patient acceptance, and regional differences in clinical application patterns. Despite these findings, challenges remain, including insufficient high-quality clinical evidence, lack of standardization in syndrome differentiation and efficacy evaluation, and the need for more rigorous safety assessment. Overall, TCM may serve as a complementary component of integrated gastric cancer management, particularly in supportive care, postoperative recovery, and treatment tolerance, but its clinical value remains dependent on the quality of supporting evidence. Future studies should use standardized protocols, rigorous clinical designs, reproducible quality-control systems, and appropriate safety assessment to define its role within modern precision oncology.PMID:42719820 | PMC:PMC13557164 | DOI:10.2147/IJGM.S603483

Front Plant Sci. 2026 Aug 26;17:1842722. doi: 10.3389/fpls.2026.1842722. eCollection 2026.ABSTRACTMetabolic bioengineering has emerged as a transformative approach for reshaping plant defense by targeting intrinsic biosynthetic pathways to enhance immunity in modern agriculture. Moving beyond proof-of-concept metabolomics to broad-spectrum programmable pathway engineering addresses gaps in plant rational design and optimizes resilience in response to diverse environmental cues. This review aims to comprehensively highlight the transition of innovative approaches to phenolics, alkaloids, flavonoids, terpenoids, and benzoxazinoids, inferring adaptive reprogramming that mediates the growth-defense balance and functions as molecular sentinels in plants. Furthermore, decoding the volatile metabolome reveals a dynamic signaling interface that influences defense responses and stress-induced plant-microbe interactions, with the shikimate, jasmonate, and salicylate pathways functioning as central hubs for microbial deterrence and priming immune memory. Recent developments in multi-scalar genome-editing strategies, including CRISPR-driven combinatorial edits, enzyme orthogonalization, fluxomics, and spatially resolved multi-omics, reconfigure central and specialized metabolic fluxes toward improved defense function and regulation. Additionally, emerging tools, such as WUSCHEL2 and BABY BOOM transcriptional modules, and artificial engineering strategies integrating deep learning model-driven predictions facilitate rapid development of synthetic genetic circuits and support a predictive engineering of plants. Moreover, Mass spectrometry imaging (MSI) in spatial metabolomics enables to obtain structures and locations of unidentified endogenous metabolites within cells and tissues. Overall, this review emphasizes a diverse array of primary and secondary metabolites, spanning molecular concepts to recent advances in plant immune mechanisms. It also illustrates new frontiers in programmable metabolic engineering that accelerate the understanding of plant-microbe-metabolite cross-talks, offering strategies to improve plant resistance and advance sustainable agricultural solutions.PMID:42719693 | PMC:PMC13555926 | DOI:10.3389/fpls.2026.1842722

Front Neurol. 2026 Aug 26;17:1888277. doi: 10.3389/fneur.2026.1888277. eCollection 2026.ABSTRACTBACKGROUND: Previous studies suggest that Yinaokang Capsules (YNKC) may offer therapeutic benefits for acute ischemic stroke (AIS) by reducing atherosclerosis, inhibiting inflammatory mediators, and exhibiting neuroprotective properties. Nonetheless, there is currently a lack of substantial clinical data that validates the overall efficacy and safety of YNKC. Furthermore, the systemic metabolic changes that underpin its neurovascular protective effects have not been thoroughly investigated in clinical contexts.METHODS: This study is a prospective, randomized, open-label, blinded-endpoint trial designed to enroll 80 patients diagnosed with AIS aged between 18 and 80 years at the Guangdong Provincial Hospital of Chinese Medicine. Eligible participants must present within 72 h of symptom onset and have a baseline National Institutes of Health Stroke Scale (NIHSS) score ranging from 4 to 22. Participants will be randomly assigned in a 1:1 ratio to either the YNKC group or the control group. Those in the YNKC group will receive four YNKC orally three times daily for a duration of 14 days. All participants will concurrently receive standard guideline-based medical treatment. The primary efficacy outcome will be the proportion of patients achieving a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 1 at day 90 following randomization. Secondary outcomes included the overall distribution of mRS scores, NIHSS score, Montreal Cognitive Assessment (MoCA) scores, Traditional Chinese Medicine (TCM) Syndrome Scores, Barthel Index (BI) score, the Stroke-Specific Quality of Life (SS-QoL) scores. The main safety outcome will be the incidence of adverse events (AEs) and serious adverse events (SAEs). Additionally, targeted blood metabolomics will be conducted to explore the underlying metabolic mechanisms of YNKC.CONCLUSION: Aims to evaluate the impact of YNKC on day 90 functional prognosis of patients with AIS, and to explore its underlying metabolic mechanisms.CLINICAL TRIAL REGISTRATION: itmctr.ccebtcm.org.cn, ITMCTR2025001037.PMID:42719659 | PMC:PMC13555605 | DOI:10.3389/fneur.2026.1888277

Reprod Med Biol. 2026 Sep 8;25(1):e70096. doi: 10.1002/rmb2.70096. eCollection 2026 Jan-Dec.ABSTRACTBACKGROUND: Semen analysis (SA), recognized by the World Health Organization (WHO) as the cornerstone of male infertility evaluation, remains indispensable in reproductive medicine. However, advances in assisted reproductive technology (ART) and artificial intelligence (AI) have highlighted the limitations of relying solely on conventional semen parameters.OBJECTIVE: To critically review the evolving clinical role of SA by integrating conventional assessment with emerging functional, molecular, and computational approaches that improve diagnostic accuracy and individualized patient care.METHODS: A narrative review of contemporary evidence was conducted, focusing on conventional semen parameters, biofunctional sperm testing, omics technologies, AI-assisted analysis, and broader clinical applications of SA.RESULTS: Conventional parameters, including sperm concentration, motility, and morphology, remain essential but inadequately reflect fertilizing capacity. Adjunctive assessments, including oxidative stress biomarkers and sperm DNA fragmentation, provide valuable insights into sperm function and reproductive potential. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, deepen mechanistic understanding, while AI enhances diagnostic precision, reproducibility, and standardization. Beyond infertility evaluation, SA also supports male contraceptive assessment, natural conception, ART, and patient counseling.CONCLUSIONS: Integrating conventional SA with functional, molecular, and AI-driven diagnostics provides a comprehensive framework for evaluating male fertility, advancing precision reproductive medicine and personalized clinical management.PMID:42719549 | PMC:PMC13555030 | DOI:10.1002/rmb2.70096

Clin Med Insights Cardiol. 2026 Sep 6;20:11795468261486227. doi: 10.1177/11795468261486227. eCollection 2026.ABSTRACTBACKGROUND: Structural remodeling and atrial fibrosis are hallmarks of atrial fibrillation (AF), yet molecular alterations associated with atrial remodeling remain incompletely characterized, particularly their spatial distribution within human atrial tissue. Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) enables spatially resolved metabolic profiling of tissue sections and may provide insight into metabolic alterations associated with atrial remodeling in AF. This study investigated whether DESI-MSI could identify distinct metabolic signatures in atrial tissue from patients with AF.METHODS: In this exploratory pilot study, atrial tissue samples from 10 patients undergoing cardiac surgery (4 with AF and 6 controls) underwent DESI-MSI analysis across an m/z range of 50-1200, followed by histologic assessment with hematoxylin-eosin staining. Metabolic profiles were analyzed using principal component analysis (PCA) and linear discriminant analysis (LDA) to explore group-specific metabolic patterns.RESULTS: Histologic evaluation demonstrated minimal fibrosis without significant differences between AF and control samples. In contrast, DESI-MSI identified distinct metabolic features associated with AF. Arachidonic acid (m/z 303.2) and phosphatidylinositol species (m/z 885.5) demonstrated spatial correspondence with myocardial architecture and contributed to metabolic separation between groups. Exploratory supervised multivariate analysis showed partial separation between AF and control spectra, while LD loading plots identified differential lipid-related ion patterns associated with AF samples.CONCLUSIONS: In this exploratory pilot cohort, DESI-MSI demonstrated preliminary metabolic differences between AF and control atrial tissues despite limited histologic remodeling. These findings should be considered hypothesis-generating and will require validation in larger, adequately matched cohorts integrating metabolic, histologic, and clinical phenotypes. Although they do not establish that metabolic remodeling precedes fibrosis, they raise the possibility that DESI-MSI may detect metabolic differences in atrial tissue exhibiting minimal histologic remodeling.PMID:42719471 | PMC:PMC13554659 | DOI:10.1177/11795468261486227

Drug Des Devel Ther. 2026 Sep 5;20:603123. doi: 10.2147/DDDT.S603123. eCollection 2026.ABSTRACTBACKGROUND: High-altitude hypoxia can trigger maladaptive cardiopulmonary responses, with hypoxia-induced pulmonary hypertension (HPH) representing a major clinical challenge with limited therapeutic options. Shengxian Decoction (SXT), a classical traditional Chinese medicine formula for treating "qi deficiency and sinking", has shown clinical benefits, but the molecular pathways associated with its effects remain incompletely understood.METHODS: Male Sprague-Dawley rats were exposed to simulated high altitude (5000 m; 404 mmHg, 10.8% O2) for 28 days and treated with SXT at three doses (1.8, 3.6, or 7.2 g/kg/day; n = 6/group). Integrated serum metabolomics (UHPLC-Q-TOF-MS) and lung transcriptomics (RNA-seq) were applied. Multivariate analysis, pathway enrichment, weighted gene co-expression network analysis, and cross-omics correlation were used for data integration. After randomization, allocation concealment and blinding were strictly implemented throughout all experimental procedures, with all interventions and outcome assessments performed by personnel blinded to group assignment until completion of data analysis.RESULTS: Chronic hypoxia induced HPH with elevated mPAP, RVHI, RVWI and pulmonary vascular remodeling (increased WT% and WA%), while SXT dose-dependently ameliorated these abnormalities and restored hypoxia-disrupted metabolomic and transcriptomic profiles, with the high-dose group showing the most pronounced effect. Chronic hypoxia induced pronounced metabolic and transcriptional remodeling, with model animals clearly separated from controls in principal component analysis. Most differentially expressed genes exhibited downregulated expression, indicating global transcriptional suppression. SXT treatment dose-dependently restored both metabolomic and transcriptomic profiles, with the high-dose group most closely resembling controls. These pyruvate-proximal nodes may represent potential points of convergence through which SXT-associated metabolic and transcriptional alterations are coordinated. The relationships reported here are based on cross-omics associations, and causal inference will require further functional validation.CONCLUSION: These findings suggest that SXT may ameliorate HPH partly through coordinated regulation of metabolic pathways and gene networks, particularly those related to energy metabolism, rather than fully explaining disease pathogenesis. The study provides multi-omics evidence supporting the traditional concept of "replenishing qi and elevating sunken qi" and identifies candidate metabolic biomarkers for further investigation. However, the results should be interpreted cautiously because of the relatively small sample size, the lack of functional validation experiments, and the exploratory nature of the biomarker findings. Further mechanistic and clinical studies are required to confirm these observations.PMID:42719424 | PMC:PMC13557172 | DOI:10.2147/DDDT.S603123

J Ginseng Res. 2026 Sep;50(5):101082. doi: 10.1016/j.jgr.2026.101082. Epub 2026 Jun 19.ABSTRACTBACKGROUND: Insomnia is increasingly recognized as a multifactorial disorder characterized by neuroendocrine imbalance, synaptic dysfunction, and impaired energy metabolism, particularly under conditions of chronic stress. Qiye Shen'an Tablets, formulated from total saponins of Panax notoginseng leaves (PNL), are widely used in clinical practice, however, their active constituents and underlying mechanisms remain incompletely understood. Notably, partial hydrolysis of saponins during the preparation process may modify their chemical composition, thereby potentially influencing therapeutic efficacy.METHODS: Total saponins before (TS-b) and after hydrolysis (TS-a), along with a commercial reference preparation (TS-a+b), were comparatively evaluated in a mouse model of insomnia induced by 4-chloro-DL-phenylalanine (PCPA) combined with systemic stress. Behavioral assessments, hematological analysis, neurotransmitter quantification, histological examination, and metabolomic profiling were conducted. In addition, key pathways associated with the hypothalamic-pituitary-adrenal (HPA) axis and synaptic plasticity were investigated. The neuroprotective effect of notoginsenoside Fd, a major component of TS-a, was further examined in glutamate-injured hippocampal neurons.RESULTS: Compared with TS-b and TS-a+b, TS-a exhibited a more stable composition and superior therapeutic efficacy. It significantly improved sleep-related behaviors, alleviated emotional disturbances, and partially normalized hematological parameters and neurotransmitter levels. Mechanistic analyses indicated that TS-a attenuated dysregulation of HPA axis, mitigated hippocampal glucocorticoid receptor (GR) overactivation, and enhanced the PKA-CREB-BDNF pathway, accompanied by increased expression of synaptic proteins. Metabolomic profiling further suggested the involvement of pathways related to neurotransmission and mitochondrial energy metabolism. Notoginsenoside Fd conferred neuroprotection against glutamate-induced neuronal injury, potentiallythrough modulation of GR signaling.CONCLUSION: TS-a relieves complex insomnia through coordinated regulation of stress response, synaptic function, and energy metabolism, thereby providing scientific basis for optimizing preparation processes and refining active constituents.PMID:42719352 | PMC:PMC13554450 | DOI:10.1016/j.jgr.2026.101082

J Ginseng Res. 2026 Sep;50(5):101081. doi: 10.1016/j.jgr.2026.101081. Epub 2026 Jul 1.ABSTRACTBACKGROUND: Protopanaxatriol (PPT), a key aglycone of ginsenosides, exhibits significant anti-inflammatory potential but suffers from poor oral bioavailability. After oral administration, PPT is transformed by gastric acid, gut microbiota, and liver enzymes into metabolites with enhanced bioactivity.METHODS: We employed an integrated metabolomics strategy combining LC-HRMS, in silico prediction, and molecular networking to systematically characterize PPT metabolism in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Metabolites were identified across serum, urine, and feces samples.RESULTS: A total of 20 metabolites were identified, including the novel 25-hydroxy-PPT (25OH-PPT), discovered for the first time. Mechanistic in vitro assays demonstrated that 25OH-PPT was exclusively generated under simulated gastric conditions via an acid-catalyzed, non-enzymatic hydroxylation pathway. Functional evaluation showed that 25OH-PPT exhibited significantly stronger anti-inflammatory activity than PPT (IC50 = 1.52 μM vs. 40.34 μM in RAW 264.7 cells).CONCLUSIONS: These findings uncover a new metabolic activation pathway of PPT, providing mechanistic insights into its pharmacological effects and offering new perspectives for designing PPT-based therapeutics.PMID:42719344 | PMC:PMC13554427 | DOI:10.1016/j.jgr.2026.101081

Front Microbiol. 2026 Aug 26;17:1920057. doi: 10.3389/fmicb.2026.1920057. eCollection 2026.ABSTRACTL-glufosinate-ammonium (L-GLA), a widely used herbicide, exerts detrimental non-target effects on crops, soil microorganisms, and ecosystems. However, its impacts on soil microbial communities and metabolic functions remain poorly understood. In this study, we applied L-GLA at two concentrations-600 g a.i. hm-2 (low, L) and 3,000 g a.i. hm-2 (high, H)-to yellow-brown soil and investigated its effects on microbial community composition, carbon cycle-related metabolic functions, and soil metabolites using integrated metagenomics and soil environmental pseudotargeted metabolomics at 30 and 60 days post-application. The degradation rate of L-GLA was concentration-dependent, with half-lives of 18.8 days (L) and 29.7 days (H). Both doses significantly reduced soil organic matter (SOM) and available potassium (AK) content, and markedly altered microbial community richness, structure, and composition. L-GLA exposure also disrupted the complexity of soil microbial co-occurrence networks and the activities of carbon-cycle-related enzymes. Metabolomic analysis further revealed significant (p < 0.05) and dose-dependent alterations in the soil metabolite profile. Correlation analysis indicated strong associations between characteristic microbial taxa and differential metabolites. Our findings provided critical insights into how L-GLA influences the soil microecological environment and contributed to a deeper understanding of soil microbial ecology in the context of modern agricultural practices.PMID:42719130 | PMC:PMC13553860 | DOI:10.3389/fmicb.2026.1920057

Front Med (Lausanne). 2026 Aug 26;13:1907194. doi: 10.3389/fmed.2026.1907194. eCollection 2026.ABSTRACTINTRODUCTION: Kawasaki disease (KD) is one of the most common rheumatic diseases in children and manifests with multisystem clinical features. Using untargeted metabolomics, our study investigated alterations in small-molecule metabolites in plasma of children with acute KD. Our study aimed to identify differential metabolic pathways and potential biomarkers.METHODS: Plasma samples were collected from 30 children diagnosed with KD and 30 age-matched healthy controls (HC) at Jinhua Maternal and Child Health Hospital between January 2025 and December 2025. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to analyse plasma samples. Enriched pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and differential metabolic pathways were determined using MetaboAnalyst 5.0. Differential metabolites were screened using the nonparametric Mann-Whitney U-test and receiver operating characteristic curve area (AUC). The conservative average AUC from nested cross-validation was reported as the primary performance metric. Pearson correlation analysis was conducted to evaluate correlations between metabolites and clinical parameters.RESULTS: In total, 261 differential metabolites were identified between the KD and HC groups, including 87 lipids and lipid-like molecules, 69 organic heterocyclic compounds, 38 benzenoids, 34 organic acids, 14 phenylpropanoids, and 19 other compounds. Pathway analysis of these differential metabolites revealed 30 putatively enriched metabolic pathways for exploratory analysis. Of these pathways, primary bile acid biosynthesis, arginine biosynthesis, histidine metabolism, and phenylalanine-tyrosine-tryptophan biosynthesis were nominally associated with KD. Six metabolites with exploratory discriminatory performance (AUC > 0.8) were further identified: L-tyrosine, L-tryptophan, glutamine, histidine, histamine, and taurocholic acid. A combined model incorporating these metabolites achieved an apparent AUC of 0.984 in the full dataset; nested cross-validation yielded a more conservative AUC of 0.889 (95% CI 0.798-0.968), indicating promising exploratory discriminatory performance.CONCLUSION: Untargeted metabolomics enables identification of metabolically perturbed pathways during the acute phase of KD. L-tyrosine, L-tryptophan, glutamine, histidine, histamine, and taurocholic acid may serve as candidate biomarkers for acute phase of KD.PMID:42719062 | PMC:PMC13553804 | DOI:10.3389/fmed.2026.1907194

Front Microbiol. 2026 Aug 26;17:1909946. doi: 10.3389/fmicb.2026.1909946. eCollection 2026.ABSTRACTINTRODUCTION: Dietary supplementation with probiotics has emerged as a promising strategy to enhance the health and productivity of farmed fish. However, the systemic metabolic effects of probiotics on the liver of marine aquaculture species, particularly the underlying molecular mechanisms, remain insufficiently explored. This study employed histopathological examination, biochemical assays, and non-targeted liver metabolomics to systematically evaluate the effects of dietary Bacillus coagulans on hepatic morphology, oxidative status, and metabolic profiles, and to elucidate the potential metabolic regulatory mechanisms underlying its protective action in fourfinger threadfin (Eleutheronema tetradactylum).METHODS: Juvenile E. tetradactylum were fed either a control diet or a diet supplemented with 1 × 10⁸ CFU/g B. coagulans. At the end of the eight-week feeding trial, liver samples were collected to evaluated the effects of dietary B. coagulans on the hepatic morphology, oxidative status, and metabolic profiles.RESULTS: B. coagulans supplementation improved hepatic tissue architecture, characterized by a more orderly cellular arrangement and reduced fibrosis. ALT activity was elevated in the B. coagulans group, indicating enhanced amino acid metabolism rather than hepatocellular injury. Activities of AKP, LZM, CAT, and SOD remained at healthy baseline levels with no significant intergroup differences, while MDA showed a non-significant downward trend. Metabolomics revealed 43 altered hepatic metabolites, with pathway enrichment indicating upregulated amino acid turnover, enhanced lipid metabolism (including cholesterol clearance), accelerated tricarboxylic acid cycle (increased isocitric acid), and elevated xanthine, a potent endogenous antioxidant.CONCLUSION: Collectively, these findings demonstrated that B. coagulans supplementation safely optimizes hepatic metabolic flux and structural integrity, highlighting its potential as a highly effective functional additive to promote metabolic homeostasis in the aquaculture of E. tetradactylum.PMID:42718986 | PMC:PMC13553840 | DOI:10.3389/fmicb.2026.1909946

Cancer Commun (Lond). 2026 Sep 9;46:0046. doi: 10.34133/cancomm.0046. eCollection 2026.ABSTRACTBackground: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits high metastatic potential, linked not only to intrinsic cancer cell traits but also to critical crosstalk with the tumor microenvironment. However, the coevolutionary mechanisms between cancer cells and multiple stromal subpopulations in driving distant metastasis remain poorly understood. Therefore, this study aimed to explore the microenvironmental regulatory mechanisms of breast tumor-initiating cells and their roles in HER2-positive breast cancer metastasis. Methods: Integrated multi-omics analyses (spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics) were used to identify novel cell subpopulations and their interactions. High-throughput sequencing of exosomal microRNAs (miRNAs) and single-nucleus RNA from the same tissue was performed to explore the molecular mechanisms underlying cell crosstalk. In vitro experiments were conducted to verify the interaction between stromal cells and prominin 1 (PROM1)+ SMAD family member 5 (SMAD5)+ cells. In vivo murine breast cancer models were established to confirm the role of stromal subpopulations in pulmonary metastasis, and parabiosis assays were carried out to compare key cell subpopulations between tumor-bearing mice and normal mice. Clinical samples were analyzed to correlate key cell subpopulations with clinicopathological features and prognosis. Results: A breast tumor-initiating subpopulation, PROM1+ SMAD5+ cells, and its interactions with stromal cells, specifically adiponectin (ADIPOQ)+ notch receptor 4 (NOTCH4)+ adipocytes and decorin (DCN)+ transmembrane 4 L six family member 1 (TM4SF1)+ fibroblasts, were identified by integrated multi-omics analyses. Mechanistically, these 2 stromal subpopulations delivered functional miRNAs and mediated coatomer protein complex subunit alpha (COPA)-dependent epidermal growth factor receptor (EGFR) activation in PROM1+SMAD5+ cells, thereby triggering the EGFR-SMAD5-cytochrome P450 family 3 subfamily A member 4 (CYP3A4) axis to induce partial epithelial-mesenchymal transition (pEMT) and metastasis. Additionally, stroma-secreted exosomal miR-671-3p down-regulated Claudin1 in PROM1+SMAD5+ cells, promoting their evolution into PROM1+SMAD5+Claudin1- subpopulations with enhanced stemness and metastatic potential. In vivo experiments confirmed that the 2 stromal subpopulations markedly promoted pulmonary metastasis, and the 3 identified subpopulations preferentially accumulated in the primary tumors, lymph nodes, and pulmonary metastatic lesions of tumor-bearing mice. Clinically, these 3 subpopulations form a "trinity niche", whose aggregation associated with HER2 positivity, high malignancy, and lymph node/pulmonary metastasis, and predicted poor prognosis. Conclusion: This study clarified the microenvironmental regulation of breast tumor-initiating cells and provided new insights into precision therapy.PMID:42718887 | PMC:PMC13554431 | DOI:10.34133/cancomm.0046