PubMed

Hepatology. 2026 Sep 14. doi: 10.1097/HEP.0000000000001847. Online ahead of print.ABSTRACTBACKGROUND: Organelle contact sites are critical for intracellular signaling, membrane dynamics, and organelle quality control. Here we examined the role of VPS13D, a bridge-like lipid transport protein, in alcohol-induced liver injury and defined the mechanisms by which VPS13D regulates lipid metabolism at organelle contact sites.APPROACH AND RESULTS: Liver-specific Vps13d knockout (LKO) mice and matched wild-type (WT) mice were subjected to chronic-plus-binge ethanol feeding. RNA-seq and metabolomic analyses were performed to investigate changes in hepatic gene expression and metabolism. Biochemical, microscopic, and histological analyses were performed to examine organelle contacts and liver injury. Liver samples from patients with alcohol-associated hepatitis (AH) showed decreased VPS13D expression and mitochondrial-ER contact sites. Binge ethanol-fed Vps13d LKO mice developed more severe steatosis, inflammation and liver injury, with increased progenitor cells, compared with WT mice. Ethanol-fed Vps13d LKO mice exhibited decreased mitochondria-ER contact sites and peroxisome content, with increased lysosome damage and ER stress compared with WT mice. Metabolomic analysis revealed altered hepatic phospholipid homeostasis, with increased hepatic phosphatidylethanolamine (PE) and decreased phosphatidylcholine (PC) abundance, along with decreased phosphatidylethanolamine N-methyltransferase (PEMT) expression, resulting in impaired hepatic VLDL secretion in ethanol-fed Vps13d LKO mice. Adenovirus-mediated hepatic PEMT expression increased VLDL secretion and decreased steatosis and liver injury in ethanol-fed Vps13d LKO mice.CONCLUSIONS: Loss of hepatic VPS13D disrupts mitochondria-ER contact sites, decreasing hepatic PC content and VLDL secretion, promoting ethanol-induced steatosis, progenitor cell accumulation, and liver injury. ER-mitochondrial contact disruption and altered phospholipid homeostasis may be pathogenic drivers in AH.PMID:42743383 | DOI:10.1097/HEP.0000000000001847

PLoS One. 2026 Sep 15;21(9):e0357951. doi: 10.1371/journal.pone.0357951. eCollection 2026.ABSTRACTBACKGROUND: Colibacillosis, caused by pathogenic Escherichia coli, remains a significant threat to rabbit production, particularly during the critical weaning period. With the emergence of multidrug-resistant strains limiting conventional antibiotic efficacy, there is an urgent need for sustainable phytotherapeutic alternatives. This study evaluated the therapeutic efficacy of a combined aqueous leaf extract of Psidium guajava L. and Tithonia diversifolia (Hemsl.) A. Gray on systemic biological markers and organ integrity in a rabbit model of colibacillosis.METHODS: Thirty healthy rabbits were randomly grouped into six cohorts: negative control (infected-untreated), healthy control (uninfected-untreated), positive control (infected-treated with Neomycin 10 mg/kg), immunodepressed (uninfected-cyclophosphamide), and two treatment groups (infected; receiving 400 or 800 mg/kg of the combined P. guajava and T. diversifolia extract). Colibacillosis was induced via oral administration of a pathogenic E. coli isolate (1 mL/100 g body weight; 10⁹ CFU/mL). Systemic recovery was assessed through hematological, biochemical, and antioxidant profiling, alongside histological examination and multivariate Principal Component Analysis (PCA). The data were analysed using OriginLab Pro 2025 and GraphPad Prism version 8.0.1 and all multivariate analyses and visualizations were performed in the R statistical environment (v4.4.3).RESULTS: E. coli infection triggered severe haematological, biochemical, and inflammatory dysregulation, characterized by significant increases in white blood cell counts, aspartate aminotransferase, creatinine, and triglycerides, concomitant with reduced red blood cell counts, haemoglobin, and albumin. The combined extract demonstrated dose-dependent efficacy. Notably, multivariate PCA mapping revealed that the 800 mg/kg dose achieved a superior therapeutic outcome, effectively resolving clinical diarrhoea and restoring biological profiles to states comparable to those of the healthy and Neomycin-treated cohorts. Furthermore, the extract significantly mitigated systemic oxidative stress and protected organ integrity.CONCLUSION: These findings demonstrate the therapeutic efficacy and potential of the combined P. guajava and T. diversifolia extract in managing colibacillosis and associated systemic inflammation in rabbits. This study supports the traditional ethnomedicinal use of these plants and demonstrate that these combined extracts could be develop as natural alternatives to synthetic antibiotics in veterinary medicine for managing colibacillosis in rabbits.PMID:42743154 | DOI:10.1371/journal.pone.0357951

Cell Rep. 2026 Sep 15;45(9):117963. doi: 10.1016/j.celrep.2026.117963. Online ahead of print.ABSTRACTUnderstanding metabolism at the organ level is challenging, as tissue metabolite signals are transient and reflect transport, metabolism, and inter-organ communication. Here, we address this challenge by using a perifusion platform that enables time-resolved metabolite measurements in living kidney tissue under controlled input conditions. We apply this approach to native tubule and glomerulus preparations and generate >45,000 longitudinal, time-resolved metabolite measurements using targeted metabolomics. Tubules release tricarboxylic acid cycle and acetylated amino acid intermediates and show dynamic metabolic rewiring under oxidative stress. Amino acid exposure rapidly activates antioxidative and urea cycle reactions, improving resistance to oxidative damage in a sex-dependent manner. Supporting the translational relevance, metabolites released from tubules upon oxidative stress are also found in plasma from humans with acute kidney injury (secondary analyses of the original clinical trial NCT01534364). Thus, the approach developed here enables time-resolved interrogation of renal metabolic responses with defined metabolite inputs.PMID:42743055 | DOI:10.1016/j.celrep.2026.117963

Mol Cell Pediatr. 2026 Sep 15;13(1):46. doi: 10.1186/s40348-026-00258-9.ABSTRACTBACKGROUND: Perinatal factors are key modulators of neonatal metabolism and may contribute to long-term health trajectories. However, the metabolic adaptations underlying these early-life influences remain poorly characterized. In this study, we comprehensively characterized neonatal urinary metabolic profiles associated with multiple perinatal factors in full-term, healthy, breastfed infants at one month of age.METHODS: Ninety-six urine samples from full-term, healthy, breastfed infants at one month of age were analyzed using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). Exploratory multivariate analyses identified the maternal and infant factors most strongly associated with urinary metabolic variation, followed by multiblock integration to characterize the biological functions associated with the identified metabolic signatures.RESULTS: Breastfeeding type (exclusive, n = 79; mixed, n = 17) emerged as the factor most associated with urinary metabolic variability and was associated with differences in metabolites related to carbohydrate and lipid metabolism, gut microbiota, oxidative status, and vitamin handling, among others. Infant sex was also associated with metabolic differences, particularly affecting steroid metabolism, amino acid profiles, and mitochondrial-related compounds. In addition, weight gain during the first month of life was associated with variation in metabolites related to amino acid metabolism, gut-microbiota and antioxidant pathways.CONCLUSIONS: Urinary metabolomics revealed distinct metabolic signatures associated with early-life exposures. Among the factors studied, breastfeeding type (mixed vs. exclusive) was associated with the most pronounced differences in the urinary metabolome. These findings highlight the potential of urinary metabolomics for investigating early-life metabolic adaptations and provide a basis for future studies exploring the relationship between infant feeding and metabolic programming.PMID:42742783 | DOI:10.1186/s40348-026-00258-9

Arch Microbiol. 2026 Sep 15;208(12):641. doi: 10.1007/s00203-026-05177-x.ABSTRACTTotal glucosides of paeony (TGP), primarily composed of monoterpene glycosides such as paeoniflorin and albiflorin, possess diverse pharmacological activities, including anti-inflammatory and neuroprotective effects. Traditional extraction from plants is limited by long growth cycles and low active content. This study employs an integrated metabolomics and transcriptomics strategy to systematically elucidate the molecular regulatory network underlying the biosynthesis of terpenoids by the Paeonia lactiflora leaf endophytic fungus Alternaria alstroemeriae PPL7 within a root co-fermentation system. Under the optimal root powder supplementation level (1.17%, w/v), the yield of target terpenoids increased significantly. Multi-omics comparative analysis revealed a global metabolic reprogramming induced by co-fermentation: the terpenoid backbone biosynthesis pathway was significantly enriched, and key terpenoid components (e.g., paeoniflorin) were upregulated. This was accompanied by fine-tuned flux regulation of the upstream mevalonate (MVA) pathway, enhanced precursor supply at mid-stream nodes, and metabolic diversion via protein prenylation. The synergistic activation of central carbon metabolism and amino acid degradation provided the necessary energy and reducing power for efficient terpenoid synthesis. This study not only elucidates the adaptive mechanisms by which endophytic fungi remodel their metabolic networks to efficiently synthesize plant-derived terpenoids but also provides novel strain resources and a theoretical basis for the sustainable manufacturing of terpenoid natural products using synthetic biology strategies.PMID:42742735 | DOI:10.1007/s00203-026-05177-x

Arch Microbiol. 2026 Sep 15;208(12):636. doi: 10.1007/s00203-026-05200-1.ABSTRACTPlant biostimulants have emerged as transformative and sustainable tools for improving crop productivity, resource-use efficiency, and resilience under rapidly intensifying environmental stresses. Unlike conventional agrochemicals, biostimulants function by activating physiological, biochemical, and molecular processes that optimize plant performance without directly supplying nutrients or exerting pesticidal effects. This review comprehensively examines the integrated roles of plant-derived and microbial biostimulants in sustainable agriculture, with particular emphasis on microbial-mediated mechanisms underlying plant stress adaptation and rhizosphere functioning. Plant-derived biostimulants, including seaweed extracts, humic substances, protein hydrolysates, amino acids, and chitosan, enhance nutrient acquisition, root architecture, hormonal regulation, and antioxidant defense systems. More importantly, microbial biostimulants, such as plant growth-promoting rhizobacteria (PGPR), endophytic microorganisms, mycorrhizal fungi, actinomycetes, yeasts, and cyanobacteria, exert multifunctional effects through biological nitrogen fixation, mineral solubilization, phytohormone biosynthesis, volatile signaling, osmolyte accumulation, pathogen suppression, and modulation of stress-responsive genes. These beneficial microorganisms reshape rhizosphere microbial communities, improve nutrient cycling, and enhance plant tolerance to drought, salinity, heat, and heavy metal toxicity. Emerging evidence from genomics, transcriptomics, metabolomics, and microbiome-based investigations has further revealed the molecular networks and signaling pathways governing biostimulant-induced resilience and plant-microbe interactions. Despite their substantial promise, inconsistent field performance, formulation instability, regulatory limitations, and inadequate mechanistic understanding continue to restrict their large-scale adoption. This review highlights recent advances in microbial and plant-derived biostimulants while identifying critical knowledge gaps and future opportunities for precision biostimulant engineering, microbiome manipulation, and climate-resilient crop management. The integration of next generation biostimulant technologies into sustainable agricultural systems may significantly reduce dependence on agrochemicals while improving crop productivity, environmental sustainability, and global food security.PMID:42742732 | DOI:10.1007/s00203-026-05200-1

Mov Disord. 2026 Sep 15. doi: 10.1002/mds.70499. Online ahead of print.ABSTRACTBACKGROUND: Preclinical studies have suggested that DL-3-n-butylphthalide (NBP) may exhibit neuroprotective effects in neurodegenerative diseases; however, no human trial has evaluated NBP in spinocerebellar ataxia type 3 (SCA3).OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of oral NBP in patients with SCA3 over 12 months.METHODS: Patients were randomly assigned (1:1) to oral NBP (200 mg thrice daily) or placebo for 12 months. The primary outcomes were 12-month changes in the Scale for Assessment and Rating of Ataxia (SARA) and Spinocerebellar Ataxia Functional Index (SCAFI). Safety outcomes included adverse events (AEs) and serious adverse events (SAEs).RESULTS: The modified intention-to-treat (mITT) population included 116 patients (NBP, n = 56; placebo, n = 60). The primary endpoints, change in SARA and SCAFI, were significantly different between NBP and placebo groups (SARA, estimated marginal mean difference: -0.86, 95% confidence interval [CI]: -1.56 to -0.16, P = 0.02; SCAFI, estimated marginal mean difference: 0.16, 95% CI: 0.01-0.31, P = 0.03) in mITT population using a mixed-effect model, with improved clinical outcome in the NBP group. Overall, AE rates were not significantly different between groups (13 AEs [23.2%] in NBP vs. 9 AEs [15%] in placebo, P = 0.26), although drug-related AEs were numerically more frequent with NBP (12 [21.4%] vs. 6 [10.0%], P = 0.09); no SAE occurred in either group.CONCLUSIONS: Oral administration of NBP was safe and generally well tolerated. Significant differences in clinical outcomes were observed in the treatment group compared to the placebo. NBP administration showed preliminary evidence of clinical benefit in SCA3. © 2026 International Parkinson and Movement Disorder Society.PMID:42742595 | DOI:10.1002/mds.70499

J Immunol. 2026 Aug 29;215(9):vkag179. doi: 10.1093/jimmun/vkag179.ABSTRACTPsoriasis is a chronic inflammatory skin disease involving intricate neuroimmune crosstalk. However, the specific mechanisms and therapeutic targets remain elusive. In this study, a pilot clinical trial demonstrated that intravenous scopolamine, a muscarinic receptor antagonist, significantly ameliorated skin lesions in psoriasis patients. Consistently, scopolamine reduced inflammation in an imiquimod-induced mouse model. Metabolomic profiling identified acetylcholine (ACh) as a significantly upregulated neurotransmitter in psoriatic skin, and exogenous ACh exacerbated inflammatory phenotypes. To pinpoint the cellular target, single-cell RNA sequencing revealed that dendritic cells (DCs), unlike T cells or macrophages, uniquely coexpressed neurointeraction receptors and the pathogenic cytokine Il23a. Mechanistically, scopolamine competitively inhibited ACh binding to M1 muscarinic receptors (M1Rs) on DCs, suppressing interleukin (IL)-23 secretion. This therapeutic efficacy was recapitulated in mice with DC-specific M1R deletion. Crucially, the protective effect of M1R deficiency was abolished by recombinant IL-23 administration, whereas scopolamine failed to inhibit inflammation induced by direct IL-23 injection, confirming its action upstream of cytokine release. Collectively, our findings provide compelling evidence that scopolamine treats psoriasis by antagonizing elevated ACh and blocking M1 receptor-mediated IL-23 release in DCs.PMID:42742566 | DOI:10.1093/jimmun/vkag179

J Sep Sci. 2026 Sep;49(9):e70516. doi: 10.1002/jssc.70516.ABSTRACTWild-simulated ginseng (linxiashen, LXS) powder, farm-grown ginseng (yuanshen, YS) powder, and farm-grown ginseng decoction pieces (YSDP), as well as the Baoyuan decoction prepared from them (BYD-LXS, BYD-YS, and BYD-YSDP) by boiling, exhibit certain metabolic differences in their chemical composition. To elucidate the holistic molecular profile and differences, a reversed-phase UHPLC-Q-TOF-MSE metabolomics strategy with an ACQUITY HSS T3 stationary phase was applied to characterize and discover differential chemical markers. In total, 293, 663, 311, and 645 compounds (including 22, 13, 24, and 28 rare ginsenosides) were annotated in LXS/YS, BYD-LXS/BYD-YS, YS/YSDP, and BYD-YS/BYD-YSDP respectively. Based on PCA and OPLS-DA, 87, 222, 95, and 168 chemical markers (including 8, 7, 13, and 3 rare ginsenosides) were annotated in LXS/YS, BYD-LXS/BYD-YS, YS/YSDP, and BYD-YS/BYD-YSDP decoctions, respectively. Secondary metabolites such as triterpene saponins were found to be present at higher levels in LXS decoction and BYD-LXS decoction. The amount of components eluted from YSDP decoction was significantly higher than that from the decoction of YS powder. In addition, Support Vector Machine and Back Propagation Neural Network models with feature selection nested within cross-validation were constructed to classify LXS/YS, BYD-LXS/BYD-YS, YS/YSDP, and BYD-YS/BYD-YSDP decoctions, achieving 100%, 100%, 100%, and 94.44% classification accuracies, respectively. This study provides a basis for the quality assessment of ginseng and Baoyuan decoction, as well as for the development and utilization of rare ginsenosides.PMID:42742469 | DOI:10.1002/jssc.70516

J Sep Sci. 2026 Sep;49(9):e70536. doi: 10.1002/jssc.70536.ABSTRACTStemona alkaloids possess multiple stereogenic centers, giving rise to structurally diverse isomeric forms that remain challenging to differentiate by conventional mass spectrometric approaches. In this study, six tuberostemonine isomers were annotated and discriminated using LC-MS/MS in combination with molecular networking-guided spectral similarity analysis. Based on their MS/MS spectral features, these isomers were classified into two distinct groups. Gaussian fitting further revealed characteristic differences in fragmentation energy profiles and relative fragment-ion intensities, enabling refined differentiation of closely related isomeric alkaloids. The relative abundances of these isomers were subsequently compared across commercial "Bai-Bu" herbal materials. These results provide experimental evidence and an MS-based analytical strategy for the identification, discrimination, and quality evaluation of isomeric Stemona alkaloids.PMID:42742392 | DOI:10.1002/jssc.70536

Chem Biodivers. 2026 Sep;23(9):e71696. doi: 10.1002/cbdv.71696.ABSTRACTTripterygium Glycoside Tablets (TGTs) are primary drugs for rheumatoid arthritis (RA) but pose a risk of nephrotoxicity. Rubus chingii Hu (RCH) may enhance kidney function. This study explores a combined RA treatment by examining RCH's chemical components and using a collagen-induced arthritis (CIA) rat model to test TGTs with or without RCH. RCH boosted the therapeutic impact of TGTs in CIA rats, shown by decreased paw swelling, improved joint condition, and reduced serum TNF-α, IL-6, and IL-1β levels. The normalization of renal markers (BUN and Scr) and oxidative stress indicators (ROS, T-NOS, and T-SOD) may be associated with the Nrf2/NF-κB pathway. Metabolomics indicated that RCH may counteract nephrotoxicity by influencing the metabolism of glycine, serine, threonine, tryptophan, histidine, taurine, and sulfaurine. In summary, RCH synergizes with TGTs to treat RA by inhibiting inflammation, affecting metabolic pathways, reducing oxidative stress, and minimizing kidney toxicity, offering a new treatment strategy for RA.PMID:42742034 | DOI:10.1002/cbdv.71696

iScience. 2026 Sep 9;29(9):117426. doi: 10.1016/j.isci.2026.117426. eCollection 2026 Sep 18.ABSTRACTIdiopathic hyperaldosteronism (IHA) is a significant cause of secondary hypertension. Emerging evidence links the gut microbiota to endocrine and cardiovascular diseases. We integrated human genetics, multi-omics, and fecal microbiota transplantation (FMT) to investigate the association between IHA and gut microbiome. Two-sample Mendelian randomization identified seven bacterial taxa associated with IHA. Metagenomic analysis of 30 patients with IHA and 30 healthy control subjects revealed lower microbial diversity and depletion of protective genera identified by Mendelian randomization. Plasma metabolomics showed alterations in tryptophan metabolism and other metabolic pathways that overlapped with microbial functional changes. Tryptophan-derived metabolites correlated with the abundance of protective genera. FMT from patients with IHA increased serum aldosterone and elevated 5-hydroxy-L-tryptophan in germ-free mice. These findings support an association between gut microbiome dysbiosis, metabolic alterations, and aldosterone dysregulation, highlighting the gut microbiome as a potential target for the diagnosis and treatment of IHA.PMID:42741704 | PMC:PMC13573677 | DOI:10.1016/j.isci.2026.117426

J Cancer. 2026 Sep 3;17(9):1639-1652. doi: 10.7150/jca.140909. eCollection 2026.ABSTRACTEsophageal cancer remains one of the most lethal malignancies worldwide, largely because most tumors are detected after symptoms develop. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) differ in epidemiology, precursor lesions and molecular biology, and therefore require subtype-specific early-detection pathways. This narrative critical review used a structured PubMed/MEDLINE search and classifies evidence by intended use: population risk triage for ESCC in high-incidence regions; targeted case finding for previously undiagnosed Barrett esophagus; surveillance and progression prediction in established Barrett esophagus; diagnostic evaluation of symptomatic or referred patients; and multicancer early-detection studies as indirect contextual evidence. We evaluate nonendoscopic cell-collection devices, cfDNA methylation and fragmentomics, mutation-based circulating tumor DNA assays, circulating RNA and extracellular vesicles, autoantibodies, metabolomic and microbiome signals, and clinical risk models. Although many clinically diagnosed or case-control series report high AUROC values, such estimates often overstate performance in asymptomatic populations, where low prevalence sharply limits positive predictive value. The most credible near-term role is calibrated, risk-stratified triage that concentrates endoscopy on individuals most likely to harbor early cancer or high-grade precursors. Increased detection yield, favorable modeling and implementation feasibility are not equivalent to clinical utility; utility requires evidence that biomarker-guided care improves meaningful outcomes at acceptable cost and harm. Integrated multiomic testing remains a proposed future strategy rather than a prospectively validated esophageal-cancer screening platform.PMID:42741648 | PMC:PMC13573304 | DOI:10.7150/jca.140909

RSC Adv. 2026 Sep 14. doi: 10.1039/d6ra05137e. Online ahead of print.ABSTRACTThe genus Salvia has received considerable attention and has been studied extensively owing to its rich polyphenolic content. In the present study, Salvia limbata essential oil (EO) and extracts from its aerial parts and roots were used to examine the chemical profile and biological activities. The chemical profiles of the EO and extracts were determined using GC-MS and UHPLC-HRMS analyses, respectively. The biological activities were assessed using six antioxidant assays, nine enzyme inhibitions, and four cell lines for cytotoxicity and antiviral properties. In the essential oils, 8,13-epoxy-15,16-dinorlabd-12-ene (16.87%) and phytol (7.84%) were the dominant compounds. UHPLC-HRMS revealed that flavonoids were the main groups in the tested extracts, as well as phenolic acids (hydroxycinnamic and hydroxybenzoic acids) and caffeic acid oligomers. Among the extracts, the ethyl acetate (EA) root extract had the highest antioxidant activity, with values of 503.32 mg TE per g, 425.44 mg TE per g, and 349.34 mg TE per g in the CUPRAC, ABTS, and FRAP assays, respectively. The aerial-part ethanol/water extract showed higher antioxidant capacity in the CUPRAC, ABTS, and DPPH assays. The EO showed strong enzyme inhibition, notably against AChE, BChE, tyrosinase, and lipase, and exhibited significantly higher inhibitory activity against CA I (IC50 = 10.93 µg mL-1) and CA II (IC50 = 27.07 µg mL-1) compared to all solvent extracts. The aerial-part hexane, ethyl acetate, and ethanolic extracts of S. limbata were moderately cytotoxic to non-cancerous and all cancer-derived cell lines, while the extract obtained from the leaves with 70% ethanol was not toxic to non-cancerous VERO cells but showed weak to moderate cytotoxicity to the other cell lines. Ethanolic and aqueous ethanolic aerial-part extracts, as well as the EO, reduced the HHV-1-induced cytopathic effect, but the titration assay indicated that the highest inhibition of virus infectivity was found for the aqueous ethanolic extract. To gain further insights into the molecular mechanisms underlying these biological activities, major identified metabolites were evaluated using network pharmacology, molecular docking, and molecular dynamics simulations. These results emphasize the significant medicinal value of S. limbata, which exhibits promising antioxidant, enzyme-inhibiting, and anticancer activities.PMID:42741613 | PMC:PMC13573238 | DOI:10.1039/d6ra05137e

Cyborg Bionic Syst. 2026 Sep 14;7:0676. doi: 10.34133/cbsystems.0676. eCollection 2026.ABSTRACTAge-related macular degeneration (AMD) is a leading cause of irreversible vision loss, yet systemic determinants of its risk remain incompletely understood. Bone mineral density (BMD), a marker of skeletal and biological aging, may reflect shared pathways linking systemic and retinal degeneration. We investigated the association between BMD and AMD using a multilayered framework integrating epidemiological analyses, Mendelian randomization (MR), proteomic and metabolomic profiling, machine learning, and an experimental low-BMD model. Across 3 cohorts, including UK Biobank, National Health and Nutrition Examination Survey, and a hospital-based Tianjin cohort, lower BMD was consistently associated with higher AMD risk, although AMD ascertainment and BMD measurement differed across cohorts. Two-sample MR analyses provided supportive genetic evidence consistent with a modest potential contribution of higher BMD to lower AMD risk, while sensitivity analyses did not indicate strong evidence of reverse causality. Machine learning models identified BMD as a recurrent predictive contributor alongside age, but its incremental clinical utility requires formal evaluation using models with and without BMD. UK Biobank proteomic and metabolomic analyses revealed overlapping molecular signatures involving extracellular matrix remodeling, lipid transport, amino acid metabolism, and inflammatory pathways. Two-step MR prioritized circulating proteins including granzyme A, collagen type II alpha 1 chain, and NEL-like protein 1 as candidate molecular intermediates rather than established mechanistic mediators. In a glucocorticoid-induced low-BMD rat model, retinal alterations relevant to degeneration, including outer retinal thinning, vascular narrowing, and delayed visual-spatial performance, were observed, but these findings should not be interpreted as direct validation of AMD pathology. Overall, these findings support an association between lower BMD and AMD risk and suggest that BMD may act as an accessible marker of systemic aging processes related to retinal vulnerability.PMID:42741500 | PMC:PMC13572803 | DOI:10.34133/cbsystems.0676

Anim Nutr. 2026 Aug 4;27:167-179. doi: 10.1016/j.aninu.2026.03.011. eCollection 2026 Dec.ABSTRACTHyperuricemia (HUA) and gout in goslings are increasingly recognized in intensive production systems, yet liver involvement in HUA remains poorly understood. This study examines how a high-protein diet influences gosling HUA through liver transcriptional and metabolic alterations. In Exp. Ⅰ, a total of 80 one-d-old male goslings (93.13 ± 0.96 g) were randomly assigned to four dietary treatments containing 18% (control group), 21% (P21 group), 24% (P24 group), and 27% (P27 group) crude protein (CP), with four replicates of five birds per treatment, for an 18-d experimental period to establish a HUA model. Goslings fed the 24% CP diet exhibited joint swelling, sparse plumage, and white feces, accompanied by reduced average daily gain (ADG; P = 0.011) and average daily feed intake (ADFI; P < 0.001). Serum uric acid (P = 0.005), xanthine oxidase (XOD; P = 0.009), xanthine dehydrogenase (XDH; P = 0.018), aspartate aminotransferase (AST; P < 0.001), urea (P < 0.001), interleukin-1β (IL-1β; P = 0.010), and tumor necrosis factor-α (TNF-α; P < 0.001) levels were significantly elevated in the P24 group, consistent with HUA-associated metabolic and inflammatory alterations. In Exp. Ⅱ, a total of 40 one-d-old goslings (93.88 + 0.92 g) were randomly assigned to two groups (n = 20 per group) and fed an 18% CP basal diet (CON group) or a 24% CP diet (HUA group) for 18 d. The HUA group showed increased liver index (P = 0.001), hydropic and partial lipid degeneration, hepatocyte swelling, and marked mitochondrial swelling observed by transmission electron microscopy (TEM). Integrated transcriptomics and metabolomics of the liver revealed that decreased levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 8(S)-hydroxyeicosatetraenoic acid [8(S)-HETE] were associated with suppression of the peroxisome proliferator-activated receptor α/γ (PPARα/γ) signaling pathway. Meanwhile, the upregulation of ACSL6 and ACSBG2 was linked to a 2.61-fold increase in adenosine monophosphate (AMP) accumulation. Elevated AMPD3 and NT5C1B expression enhanced AMP-to-inosine conversion (1.69-fold), and coordinated up-regulation of NT5C1B, PNP, and XDH further accelerated UA formation in purine metabolism, collectively contributing to HUA and associated inflammatory responses. Although graded increases in dietary CP induced proportional shifts in digestible amino acid concentrations, these results reveal a strong correlation between high-protein diets and HUA, as well as subsequent liver and renal injuries in goslings.PMID:42741484 | PMC:PMC13572764 | DOI:10.1016/j.aninu.2026.03.011

ISME Commun. 2026 Aug 19;6(1):ycag238. doi: 10.1093/ismeco/ycag238. eCollection 2026 Jan.ABSTRACTIron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is a chemically underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals, and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language code to determine siderophore production by Microbulbifer spp. in mono- and mixed cultures. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing an unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.PMID:42741352 | PMC:PMC13573596 | DOI:10.1093/ismeco/ycag238

Front Plant Sci. 2026 Aug 31;17:1907085. doi: 10.3389/fpls.2026.1907085. eCollection 2026.ABSTRACTPaeonia lactiflora Pall. (Chinese peony), a perennial plant indigenous to northeastern China, exhibits extensive flower-color variation, but the metabolite-gene relationships underlying anthocyanin accumulation remain incompletely understood. We integrated metabolomic and transcriptomic of petals from three cultivars with pink (cv. 'Exclusive Memory', PF), pale pink (cv. 'Salad', PPF), and white (cv. 'Duchess', WF) flowers. Metabolomic profiling detected 689 metabolites, including 169 flavonoids and six anthocyanins. Pairwise comparisons identified 153, 199, and 137 differentially accumulated metabolites in PF vs. PPF, PF vs. WF, and PPF vs. WF, respectively, with 27 metabolites shared among the three comparisons. The total anthocyanin signal in PF petals was 3.25-fold that in PPF petals and 60.37-fold that in WF petals. By contrast, the abundance of the individual compound cyanidin-3,5-O-diglucoside (cyanin) was 76.85-fold higher in PF than in WF and 23.10-fold higher in PPF than in WF, these values therefore describe compound-specific rather than total-anthocyanin differences. RNA-seq identified 6,777, 8,030, and 6,794 differentially expressed genes in the three pairwise comparisons, including 779 shared genes. Correlation analysis prioritized 21 flavonoid-pathway structural genes and 53 candidate transcription factors associated with anthocyanin abundance. Weighted gene co-expression network analysis identified a turquoise module positively associated with anthocyanins and a DFR-centered subnetwork containing 24 candidate transcription factors, including MYB and bHLH genes. qRT-PCR of 12 selected genes reproduced the RNA-seq expression trends. These results elucidate the metabolic basis of peony petal coloration and identify candidate regulatory networks and key genes potentially involved in anthocyanin biosynthesis, providing a foundation for future functional validation.PMID:42741340 | PMC:PMC13572631 | DOI:10.3389/fpls.2026.1907085

ISME Commun. 2026 Aug 24;6(1):ycag242. doi: 10.1093/ismeco/ycag242. eCollection 2026 Jan.ABSTRACTWater droplets entrapped in crude oil have recently been recognized as unexpected but metabolically active microbial habitats in shale oil reservoirs. However, the key environmental drivers that shape the community composition and metabolic profiles of these droplet microorganisms remain poorly understood. Here, we investigated three shale oil samples from Jiangsu oilfield, all of which contained abundant water droplets (>105 droplets/ml oil) of ancient formation water origin. Integrated microscopy, metagenomics, and metabolomics revealed that the physicochemical properties of the enclosing oil, primarily API gravity and viscosity, are associated with droplet size and may influence the droplet microbiomes. These factors appear to jointly drive a fundamental metabolic dichotomy, where in light oil with low-salinity water, communities are enriched with hydrocarbon degraders together with molecular signatures of active petroleum hydrocarbon metabolism. In more viscous, light-to-medium oil with high-salinity water, however, communities shift towards necromass recycling and strong genetic adaptations to osmotic stress. Our findings demonstrate that microbial life in water droplets enclosed in shale oil is widely found in the shale oil reservoirs examined, and selected by carbon quality and environmental pressure. This study provides a mechanistic framework for understanding microbial ecology and biogeochemical processes in shale oil reservoirs and offers insights for microbial enhanced oil recovery in heavy oil reservoirs.PMID:42741332 | PMC:PMC13573599 | DOI:10.1093/ismeco/ycag242

Front Neurol. 2026 Aug 31;17:1887127. doi: 10.3389/fneur.2026.1887127. eCollection 2026.ABSTRACTBACKGROUND: Complex metabolic disorders are a key characteristic of Alzheimer's disease (AD). Although studies have shown that combining repetitive transcranial magnetic stimulation (rTMS) with cognitive training (CT) can alleviate AD symptoms, the specific pathophysiological processes involved remain poorly understood. Our goal is to analyze metabolomic changes associated with bilateral cerebellar rTMS plus CT in AD treatment, to identify potential biomarkers of disease progression and therapeutic outcomes, and to validate these findings against a systematic review of existing literature.METHODS: We enrolled 12 individuals with early AD and 12 healthy controls (HC). The AD group received 2 weeks of bilateral cerebellar rTMS combined with CT. We performed ultra-high-performance liquid chromatography-tandem mass spectrometry analysis on serum samples obtained from AD patients (before and after intervention) and HC. The PubMed database was used to conduct a systematic review of AD metabolomics literature, from which differential metabolites were identified and analyzed using pathway enrichment analysis.RESULTS: A total of 510 metabolites were differentially expressed in response to treatment, with 202 consistent with improved clinical status. Fourteen pathways were enriched, including those involved in valine, leucine, and isoleucine biosynthesis, as well as glycine, serine, and threonine metabolism, which are linked to the pathology and treatment of AD. Metabolites such as lysophosphatidylcholine (22:6) and citric acid, increased after treatment and shifted toward healthy control levels, whereas γ-guanidinobutyric acid, proline, decreased after treatment. Systematic review analysis suggested Phenylalanine as a potential biomarker for AD screening at the mild cognitive impairment stage.CONCLUSION: This study's integrative analysis offers preliminary insights into treatment-associated metabolic alterations in AD and identifies candidate metabolites for further investigation as markers of disease status and treatment response.TRIAL REGISTRATION: ChiCTR2200061754.PMID:42741217 | PMC:PMC13572263 | DOI:10.3389/fneur.2026.1887127