PubMed

Cell Rep Med. 2026 Aug 13:102988. doi: 10.1016/j.xcrm.2026.102988. Online ahead of print.ABSTRACTExercise is an integral therapy for many cardiometabolic diseases, including obesity, type 2 diabetes, and hypertension. Despite its broad health benefits, the circulating factors that mediate exercise adaptations in humans remain incompletely defined, particularly across different exercise intensities. Here, we conducted a multi-cohort human exercise intervention incorporating sprint-interval exercise (SIE) and moderate-intensity exercise (MIE) to analyze intensity-dependent regulation of interorgan crosstalk. We found that exercise intensity distinctly influenced the plasma proteome and metabolome in untrained and trained participants. By integrating multi-organ gene and protein expression datasets with in vitro and in vivo tissue sampling, we mapped regulated proteins to their predicted tissues of origin and destination. Muscle fibers and adipocytes were particularly sensitive to exercise intensity and observed to undergo broad secretory and transcriptomic changes. Moreover, we leveraged a large-scale plasma-phenome database to identify intensity-dependent proteins associated with cardiometabolic health and disease, highlighting how exercise intensity differentially shapes interorgan communication and organismal health.PMID:42594877 | DOI:10.1016/j.xcrm.2026.102988

Int Immunopharmacol. 2026 Aug 13;188:117247. doi: 10.1016/j.intimp.2026.117247. Online ahead of print.ABSTRACTDuchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and persistent chronic inflammation, yet the multi-lineage cellular drivers of its pathogenesis remain incomplete. In this study, single-cell RNA sequencing (scRNA-seq) identified Atp6ap2 as a profoundly upregulated gene across multiple skeletal muscle cell types-particularly endothelial cells, fibroblasts, and myoblasts-in both mdx and severe mdx mice. Weighted gene co-expression network analysis (WGCNA) linked Atp6ap2 expression to DMD progression, while enrichment analyses revealed that its dysregulation severely impairs vascular homeostasis and extracellular matrix integrity via the PI3K-Akt, focal adhesion, and cell cycle pathways. Utilizing Connectivity Map (CMap) analysis, we identified temozolomide (TMZ) as a top pharmacological candidate capable of reversing the ATP6AP2-associated gene signature. In vivo validation demonstrated that TMZ administration significantly enhanced motor coordination, balance, and grip strength in mdx mice, while markedly preserving dystrophic muscle architecture, reducing myofiber necrosis, and alleviating interstitial fibrosis. Mechanistically, integrated transcriptomic and metabolomic profiling revealed that TMZ induced profound metabolic and signaling shifts, modulating the Notch, MAPK, and Ras pathways, as well as autophagy and glycerophospholipid metabolism. Furthermore, scRNA-seq and cell-cell communication analyses indicated that TMZ dynamically reorganized multicellular networks, decreasing aberrant fibroblast and endothelial interactions. Crucially, immunofluorescence and Western blot validations confirmed that TMZ drastically attenuated the infiltration of F4/80-positive macrophages and suppressed their pro-inflammatory M1 polarization (indicated by reduced co-localization with iNOS and ATP6AP2), while successfully reversing the dysregulation of the ATP6AP2 axis and restoring its downstream targets MAP4K2, DGKE, and EFNA1. Collectively, our findings demonstrate that TMZ mitigates dystrophic pathology by targeting the ATP6AP2 signaling axis and dampening macrophage-mediated inflammatory responses, highlighting its potential as a novel immunopharmacological therapeutic strategy for DMD.PMID:42594836 | DOI:10.1016/j.intimp.2026.117247

Biomed Pharmacother. 2026 Aug 13;203:119810. doi: 10.1016/j.biopha.2026.119810. Online ahead of print.ABSTRACTCKD-MBD is a metabolic disorder characterized by disrupted mineral metabolism, leading to vascular calcification, renal osteodystrophy, and high fracture risk. Sclerostin, an osteocyte-derived Wnt inhibitor, is a key regulator of both bone loss and vascular calcification. This study explored the role of phlorizin (SGLT1 and SGLT2 inhibitor) on bone loss and metabolic profile in CKD-MBD. Calvarial osteoblasts were treated with phlorizin and evaluated for ALP activity, viability, mineralization, and gene/protein expression. Molecular docking and simulation studies were performed to check phlorizin-sclerostin interactions. This was further validated by LRP-SOST interaction and TOP-FLASH luciferase reporter assays. For in vivo studies, CKD-MBD was induced in adult female SD rats via 5/6th nephrectomy. Bone samples were analysed by micro-CT, histomorphometry, and metabolite profiling, while renal function markers were measured using serum ELISA and biochemistry analyser. Phlorizin promotes primary osteoblastic cell ALP activity, mineralization, and osteogenic marker expression. It disrupts the sclerostin-LRP6 complex, promoting β-catenin nuclear localization and activating Wnt/β-catenin signaling. Phlorizin also reduced sclerostin secretion in osteocytes and reversed its inhibitory effects on primary osteoblastic cells, confirming a sclerostin-dependent mechanism. In vivo, phlorizin improved fracture healing and attenuated bone loss in 5/6th nephrectomised rats. It also improved renal function, corrected mineral imbalance, restored bone mass, and mitigated metabolic dysfunction. Phlorizin supported adaptive metabolism and sex hormone pathways, highlighting its potential as an osteo- and reno-protective agent in CKD-MBD. In conclusion, Phlorizin attenuates bone loss by disrupting the sclerostin-LRP interaction, activating Wnt/β-catenin signaling, and ameliorating metabolic alterations in CKD-MBD.PMID:42594745 | DOI:10.1016/j.biopha.2026.119810

J Physiol Sci. 2026 Aug 9;76(3):100091. doi: 10.1016/j.jphyss.2026.100091. Online ahead of print.ABSTRACTElectroacupuncture (EA) modulates neuroimmune and metabolic pathways, but acupoint-specific physiological responses remain poorly characterized. This study investigated acupoint-dependent differences in nociceptive behavior, synovial inflammation, and serum metabolomic profiles in rats with complete Freund's adjuvant (CFA)-induced knee arthritis. Animals were assigned to three groups: CFA without EA, CFA with EA at SP6, and CFA with EA at ST36. EA at ST36 significantly improved hindlimb weight-bearing (74.1% vs. 45.3% at post-injection day 8; p < 0.01), whereas EA at SP6 did not reach significance. Both acupoints comparably reduced synovial inflammation scores. Targeted GC-MS/MS serum metabolomics identified 14 significantly altered metabolites; 2-hydroxybutyric acid (2-HBA) showed the largest fold-change and was selectively normalized by EA at ST36. Intra-articular 2-HBA injection did not alter pain behavior, indicating it represents a systemic physiological consequence of inflammatory-metabolic burden rather than a nociceptive mediator. These findings demonstrate acupoint-specific modulation of redox-metabolic homeostasis by EA in inflammatory arthritis.PMID:42594733 | DOI:10.1016/j.jphyss.2026.100091

Food Chem. 2026 Aug 11;526:150768. doi: 10.1016/j.foodchem.2026.150768. Online ahead of print.ABSTRACTThis study integrated genomics and metabolomics to elucidate the role of Lactiplantibacillus plantarum LP104 as an adjunct in yogurt co-fermentation with commercial starter cultures. Comparative genomics of nine Lp. plantarum strains revealed that LP104 harbors a distinctive carbohydrate-active enzyme profile and genomic potential related to amino acid metabolism. Yogurt co-fermented with LP104 (Lb-St-LP104) showed improved physicochemical properties and microbial viability during storage. Volatile analysis indicated the co-fermentation system displayed a signature enriched in fruity-associated esters, including formic acid, pentyl ester (pentyl formate), and 1-ethylpropyl acetate. Untargeted metabolomics suggested Lb-St-LP104 was associated with higher relative lactate and peptides, reduced lactose/galactose, and marked alterations in amino acid metabolic pathways. Pathway enrichment and correlation network analyses highlighted amino acid-associated pathways as key nodes linked to aroma-related metabolites. Overall, LP104 is a promising adjunct strain for yogurt co-fermentation, improving flavor and modulating key metabolic features, providing insights for starter selection and functional yogurt development.PMID:42594648 | DOI:10.1016/j.foodchem.2026.150768

Plant Physiol Biochem. 2026 Aug 12;238:111623. doi: 10.1016/j.plaphy.2026.111623. Online ahead of print.ABSTRACTStreptomyces sp. HU2014 exerts a concentration-specific "inhibit-then-promote" effect on wheat at the optimal dose of 4 g kg-1 identified in previous study. Yet this suppression-enhancement switch remains mechanistically elusive. Here, HU2014 was applied to the wheat rhizosphere at 4 g kg-1 and tracked for 28 d. Shoot biomass and chlorophyll content increased by 57% and 70%, respectively, with concomitant upregulation of phenylalanine ammonia-lyase activity, whereas malondialdehyde, root activity and soluble sugars declined. Additionally, Fe, Mg, Cu and Zn concentrations increased in both leaves and roots, while Mn decreased across tissues, and P declined in leaves but rose in roots. Electron microscopy revealed thickened root cell walls, denser leaf veins, and larger relative chloroplast size with fewer starch grains in wheat tissues, collectively reinforcing membrane integrity. Non-targeted metabolomic profiling of HU2014 culture supernatant at three distinct fermentation time points (T1-T3) identified 23,420-26,020 metabolite features, among which organic acids and derivatives represented 23.6-23.8%. Notably, jasmonate and indole-3-acetic acid exhibited peak upregulation at T2 (about 33- and 5.6- fold, respectively), alongside sustained high levels of gibberellins (about 6- fold) across all three time points. Amino acid metabolic pathway analysis further revealed specific activation of glycine, serine, and threonine metabolism at T1, and significant enhancement of arginine and proline metabolism at both T2 and T3. Transcriptome profiling of wheat leaf tissues revealed that photosynthesis-antenna proteins exhibited the highest enrichment factor, followed by MAPK signaling pathway and starch and sucrose metabolism. Quantitative RT-PCR confirmed the upregulation of photosynthesis- and defense-related genes (TaPOR, TaGLU, and TaECN) and the downregulation of carbon metabolism-associated genes (TaFAR, TaHT, and TaGT). Integrated transcriptomic - physiological analysis revealed two key molecular features of HU2014 action: (i) relocation of photosynthetic antenna proteins, and (ii) reprogramming of carbon metabolism. These changes were consistent with a potential role in mediating the phenotypic transition from early rhizosphere stress to sustained photosynthetic growth. The findings provide a mechanistic framework for developing HU2014 as a precision bio-inoculant.PMID:42594628 | DOI:10.1016/j.plaphy.2026.111623

Plant Physiol Biochem. 2026 Aug 11;238:111637. doi: 10.1016/j.plaphy.2026.111637. Online ahead of print.ABSTRACTLow-temperature (LT) stress severely limits rice growth and productivity, particularly in the chilling-sensitive indica subspecies. Here, we investigated the physiological, transcriptomic, and metabolomic responses of two similar genetic backgrounds indica rice varieties but contrasting cold tolerance: Diantun502 and Diantun506. Under cold stress, Diantun502 exhibited higher survival rates, greater chlorophyll retention, and elevated accumulation of osmoprotectants, branched-chain amino acids (BCAAs), and stress-related phytohormones compared to Diantun506. Integrative multi-omics analysis revealed that amino acid metabolism, BCAA-related pathways, was prominently enriched among differentially expressed genes and metabolites. We identified OsDIAT (Os05g0244700), encoding a branched-chain amino acid aminotransferase (BCAT), as a key candidate gene. Sequence variation in Diantun506 introduced a premature stop codon and generated a truncated protein with negligible catalytic activity. In an F2 population derived from Diantun502 × Diantun506, cold-tolerance phenotypes were closely associated with OsDIAT genotypes, supporting the contribution of the Diantun506 allele to reduced LT tolerance. Overexpression of OsDIAT enhanced LT tolerance, BCAT activity, BCAA accumulation, and stress-related hormone levels, whereas knockout produced the opposite effects. Exogenous isoleucine partially restored the survival of knockout plants and promoted JA-Ile accumulation, the JA-Ile/JA ratio, and OsJAR1 expression. Collectively, these findings demonstrate that OsDIAT enhances LT tolerance by maintaining BCAA homeostasis and supporting associated JA-Ile responses, and provide a useful genetic target and molecular marker for breeding cold-tolerant indica rice.PMID:42594626 | DOI:10.1016/j.plaphy.2026.111637

Poult Sci. 2026 Jul 27;105(11):107510. doi: 10.1016/j.psj.2026.107510. Online ahead of print.ABSTRACTThis study was conducted to systematically elucidate the molecular regulatory mechanisms underlying egg production traits in indigenous chickens. Using a self-bred White-feathered Green-shelled (WG) chicken line as the research subject, high-yield and low-yield individuals were selected based on egg numbers at 43 weeks (EN43). Hypothalamus, pituitary, and ovarian tissues were collected from these individuals for targeted metabolomics profiling and transcriptome sequencing. The results showed a significant difference in EN43 between the two groups (P < 0.05). Targeted metabolomics of ovarian tissue detected a total of 17 steroid hormones, among which pregnenolone, progesterone, and 17β-estradiol were identified as differentially expressed steroid hormones (DESHs) between the two groups. Differential expression analysis of transcriptomes identified 666, 149, and 69 differentially expressed genes (DEGs) in the hypothalamus, pituitary, and ovary, respectively. Functional enrichment analysis revealed that hypothalamic DEGs were primarily involved in transcriptional regulation, neuropeptide signaling, and neurodevelopmental processes. Pituitary DEGs were mainly enriched in synaptic plasticity, calcium ion binding, and neurotransmitter transport, while ovarian DEGs were predominantly associated with signal transduction, calcium signaling regulation, and the cGMP signaling pathway. A molecular regulatory network (MRN) was constructed based on DEGs and DESHs. Through modular analysis, four key regulatory modules were identified, involving neuroendocrine regulation, neurotransmitter transport, steroid hormone synthesis, and transcriptional/developmental regulation. Combined with comprehensive network topology scoring, 25 potential candidate genes were identified, including POMC, NPY, CRH, SLC18A2, CD36, EGF, and WNT3A. In conclusion, this study integrated multi-omics data to reveal the molecular mechanisms of the HPO axis regulating egg production traits from a multi-tissue and multi-level perspective, providing a theoretical foundation for molecular breeding in indigenous poultry.PMID:42594583 | DOI:10.1016/j.psj.2026.107510

Parkinsonism Relat Disord. 2026 Aug 11;151:108937. doi: 10.1016/j.parkreldis.2026.108937. Online ahead of print.ABSTRACTBACKGROUND: The perivascular and neurofluid-related tissue environment is implicated in neurodegeneration, but its clinical relevance in spinocerebellar ataxia type 3 (SCA3) remains unclear. We investigated alterations in diffusion tensor image analysis along the perivascular space (DTI-ALPS) across disease stages, and its longitudinal associations with clinical progression and brain atrophy.METHODS: We included 129 SCA3 (44 preclinical, 85 ataxic) at baseline, 51 with longitudinal follow-up, and 78 controls. Cross-sectional, longitudinal, and structural equation modeling (SEM) analyses examined group differences, clinical correlates, progression, associations with regional brain volumes, and relationships among age, genetic burden, DTI-ALPS index, brainstem volume, and severity.RESULTS: DTI-ALPS index was reduced in SCA3 and showed stage-dependent pattern. Ataxic SCA3 exhibited lower DTI-ALPS index than preclinical SCA3 and controls, whereas preclinical SCA3 did not differ from controls. Lower DTI-ALPS index was associated with greater clinical severity (r = -0.208, p < 0.05) and reduced volumes of the brainstem, thalamus, hippocampus, caudate, amygdala, pallidum, and putamen (p < 0.05). SEM showed that lower DTI-ALPS index was associated with greater clinical severity (β = -0.151, p < 0.05) and reduced brainstem volume (β = 0.160, p < 0.05). Longitudinally, lower baseline DTI-ALPS index was associated with faster clinical progression (β = -2.59, p < 0.01).CONCLUSION: Reduced DTI-ALPS index emerged predominantly during SCA3 symptomatic stage and was associated with greater severity, brainstem atrophy, and faster longitudinal disease progression. These findings supported DTI-ALPS index as a promising imaging marker for characterizing disease-related tissue environment changes and providing adjunctive prognostic information in SCA3.PMID:42594559 | DOI:10.1016/j.parkreldis.2026.108937

JACC Adv. 2026 Aug 13;5(9):103150. doi: 10.1016/j.jacadv.2026.103150. Online ahead of print.NO ABSTRACTPMID:42594522 | DOI:10.1016/j.jacadv.2026.103150

J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Aug 11;1282:125250. doi: 10.1016/j.jchromb.2026.125250. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) has a complex and multifactorial pathogenesis, and highly effective pharmacotherapies for this condition remain limited. Qikui granules (QKG), a compound traditional Chinese medicine preparation, has shown favorable therapeutic efficacy against DKD in clinical studies. Our prior work, based on integrated network pharmacology, 16S rRNA gene sequencing, and lipidomic profiling of serum and kidney tissues, demonstrated that QKG ameliorates DKD in db/db mice by enriching Candidatus Arthromitus and modulating lipid homeostasis. As a follow-up validation of our earlier findings, the present study adopts an integrated multi-omics strategy combining fecal metabolomics, lipidomics, and 16S rRNA sequencing, coupled with a pseudo-germ-free mouse model, to further elucidate the therapeutic efficacy of QKG against DKD and the pivotal role of gut microbiota in its renoprotective effects. Firstly, fecal metabolomic and lipidomic profiling was performed to explore the pharmacological mechanisms of QKG against DKD. Subsequently, a pseudo-germ-free mouse model established via antibiotic administration was used to verify the microbiota-mediated mechanism of QKG. Metabolomic and lipidomic analysis revealed that QKG significantly reversed the upregulation of 24 special potential biomarkers (SPBs) in feces, including phosphatidylcholines (PC), phosphatidylethanolamines (PE) and unsaturated fatty acids (UFA); glycerophospholipid metabolism and arachidonic acid metabolism were identified as the most relevant pathways. The pseudo-germ-free mouse model validated the microbiota-dependent therapeutic effect of QKG on DKD from both pharmacodynamic and gut microbiota composition perspectives. Furthermore, correlation analysis showed that the 24 SPBs associated with the anti-DKD efficacy of QKG were negatively correlated with the relative abundance of Candidatus Arthromitus. Collectively, our findings suggest that QKG exerts microbiota-dependent efficacy against DKD-related metabolic disorders and inflammation, mainly by increasing the abundance of Candidatus Arthromitus and thereby reducing the levels of PC, PE, and UFA.PMID:42594502 | DOI:10.1016/j.jchromb.2026.125250

J Hazard Mater. 2026 Aug 12;516:143279. doi: 10.1016/j.jhazmat.2026.143279. Online ahead of print.ABSTRACTDi-n-butyl phthalate (DBP) pollution poses significant ecological risks, necessitating effective green remediation strategies. This study constructed a robust microbial consortium (DBP-Micro-con) and systematically elucidated its degradation mechanism using an integrated multi-omics approach. Community analysis provided that enrichment culture shifted the dominant phylum from Pseudomonadota, Acidobacteriota and Actinomycetota to Bacillota. The consortium achieved 99.07% DBP removal within 120 h, significantly outperforming isolated single strains. It exhibited remarkable environmental robustness across pH 5-10 and temperatures 20-38 °C, alongside broad-spectrum degradation capabilities against di-n-octyl phthalate (DOP) and various strobilurin fungicides. Non-targeted metabolomics identified mono-butyl phthalate (MBP) as intermediate and show metabolic profile changes, particularly in nucleotide and glycerolipid pathways. Furthermore, homology modeling and molecular docking of the key carboxylesterase CES1281, despite moderate sequence similarity, provided structural insights into the catalytic mechanism. This identified a conserved catalytic triad (Ser113-Asp166-His197) and critical hydrophobic interactions stabilizing substrate binding. Collectively, these findings advance the theoretical understanding of PAE biodegradation and offer a promising microbial resource and mechanistic framework for remediation of composite pollution.PMID:42594464 | DOI:10.1016/j.jhazmat.2026.143279

J Hazard Mater. 2026 Aug 10;516:143255. doi: 10.1016/j.jhazmat.2026.143255. Online ahead of print.ABSTRACTConcern over the nanoplastics (NPs) pollution in aquatic environment is increasing. However, the potential effects of different nitrogen sources at environmentally relevant concentrations and NPs on Microcystin-LR (MC-LR) in Microcystis aeruginosa (M. aeruginosa) are still unclear. Results demonstrate that during both acute (4 days) and long-term (10 days) exposure, MC-LR synthesis (27.86% and 59.18%) and release (21.79% and 76.68%) were significantly exacerbated by amine-modified polystyrene NPs (PS-NH2 NPs) under high concentration (5 mg-N/L) arginine treatment, compared with nitrate and leucine treatments. Mechanistically, under high concentration (5 mg-N/L) arginine treatment (1) PS-NH2 NPs exposure promoted algal nitrogen consumption efficiency, together with an increase of NPs internalization and cell membrane permeability; (2) metabolomic and transcriptomic results suggested that alterations in carbon and nitrogen metabolism, precursor availability, and membrane integrity may contribute to the increased MC-LR synthesis and release under PS-NH2 NPs exposure; and (3) stable isotope experiment verified that PS-NH2 NPs activated the precursor substances of MC-LR synthesis. The elevated temperature and light intensity further altered the effect of PS-NH2 NPs on MC-LR synthesis. These findings deepen our understanding of the interactive effect of NPs and nitrogen sources on M. aeruginosa.PMID:42594462 | DOI:10.1016/j.jhazmat.2026.143255

PLoS One. 2026 Aug 13;21(8):e0355698. doi: 10.1371/journal.pone.0355698. eCollection 2026.ABSTRACTINTRODUCTION: The gut microbiome-metabolome interplay in hemodialysis (HD) patients remains poorly characterized. Using multi-omics approaches, we compared HD patients with healthy controls (HC) to identify microbial signatures, metabolic perturbations, and their integrated correlations.METHODS: This case-control study included 192 participants (96 HD-HC pairs under identical dietary and living conditions). The gut microbiota composition was analyzed using 16S ribosomal RNA gene sequencing, and fecal metabolomes were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-HRMS). A multi-omics analysis was conducted utilizing Spearman correlation analysis, Mantel test analysis, and differential functional pathway analysis.RESULTS: We observed significant differences in gut microbiota composition between the HD and HC groups, such as Ruminococcus and Bifidobacterium. Comparative analysis revealed 497 significantly altered metabolites in the HD group versus HC, primarily associated with amino acid, vitamin, lipid, purine, and pyrimidine metabolisms. ROC analysis identified 4-pyridoxic acid, nudifloramide, imidazoleacetic acid, ascorbic acid, and tocopheronic acid as potential diagnostic biomarkers (AUC > 0.8, p < 0.01). Integrated multi-omics analysis revealed correlations between Ruminococcus and metabolites such as Docosapentoic acid (DPA), 13 - EPAHAAB (EPA), and tryptamine, with shared differential pathways in bile secretion, caffeine metabolism, gastric acid secretion, and vitamin B6 metabolism.CONCLUSION: Hemodialysis patients exhibited significant alterations in gut microbiota composition and metabolic profiles (amino acid, vitamin, and lipid metabolism) compared with healthy controls, with demonstrated microbiome-metabolome interactions and shared functional pathways. The potential diagnostic and therapeutic value of these differential features warrants further exploration and external validation.PMID:42594080 | DOI:10.1371/journal.pone.0355698

Cell Rep. 2026 Aug 12;45(8):117804. doi: 10.1016/j.celrep.2026.117804. Online ahead of print.ABSTRACTGlycosuria, whether genetically induced or triggered by SGLT2 inhibitors, activates compensatory glucose-producing pathways that limit glucose lowering in type 2 diabetes. To define these pathways, we studied renal Glut2 knockout mice, which progressively lose Slc5a2 (encoding SGLT2) expression yet maintain normoglycemia despite marked urinary glucose loss. Metabolic profiling and isotope tracing revealed coordinated adaptations in mannose and glutamine metabolism during glycosuria. Skeletal muscle reduced glucose utilization and showed increased incorporation of mannose-derived carbon into oxidative metabolism while whole-body glycolysis declined, establishing a systemic glucose-sparing state. Disruption of glutamine transport or mannose utilization caused hypoglycemia in mice treated with an SGLT2 inhibitor, consistent with reliance on these substrates to maintain glucose homeostasis during glycosuria. Multiomic profiling revealed increased expression and chromatin accessibility of mannose and glutamine transport pathways. These findings identify a kidney-coordinated metabolic program associated with maintenance of systemic glucose homeostasis during glycosuria and may inform strategies to optimize the glucose-lowering efficacy of SGLT2 inhibitors.PMID:42593967 | DOI:10.1016/j.celrep.2026.117804

Adv Sci (Weinh). 2026 Aug 13:e77123. doi: 10.1002/advs.77123. Online ahead of print.ABSTRACTOrgan transplantation provides a life-saving intervention for patients with end-stage lung disease; however, access to this treatment remains limited by the shortage of donor organs. Ex vivo lung perfusion (EVLP) is a platform that enables surgeons to assess extended-criteria for donor lungs prior to transplantation and has safely expanded the donor pool. Yet current EVLP biochemical assessments rely on intermittent manual sampling and fail to capture dynamic metabolic changes. Here we present MetaboSense, a first-of-its-kind microfluidic platform for continuous, real-time, multiplexed monitoring of glucose and lactate-key metabolites that report on donor lung metabolism-during EVLP. The system integrates a bead-based, quantum dot-mediated aptamer assay with modular microfluidics for in-line biomarker measurement. MetaboSense achieves limits of detection of 0.74 mM (glucose) and 1.19 mM (lactate) with analytical precision (R2 > 0.97). Clinical validation across eleven EVLP cases demonstrates strong correlation with gold-standard arterial blood gas measurements. In-line deployment within an EVLP circuit during perfusion of porcine lungs confirms MetaboSense's ability to track metabolite fluctuations with 60-s temporal resolution. This platform eliminates labor-intensive sampling and provides unprecedented granularity in lung metabolomics during EVLP, representing an important step toward real-time EVLP analytics and improved organ selection and transplant outcomes.PMID:42593849 | DOI:10.1002/advs.77123

J Cardiovasc Transl Res. 2026 Aug 13;19(1):106. doi: 10.1007/s12265-026-10834-z.ABSTRACTPatients with heart failure (HF) demonstrate dysregulation in bilirubin metabolism. The specific characteristics of intestinal bilirubin metabolism in HF remain unclear. This study involved metagenomic sequencing and metabolomic profiling of fecal samples from 45 children with HF and 32 healthy children. Serum total bilirubin levels were 11.3umol/L, 19.4umol/L and 5.0umol/L in HF New York Heart Association (NYHA) I-II, NYHA III-IV and control group (p < 0.001 ), and the median gut microbiome health index (GMHI) were - 0.78, -1.53 and 0.09 in each (p < 0.001). The abundance of 2 bacteria species containing bilirubin reductase, Ruminococcus gnavus (p = 0.028) and Clostridium sp.M62/1 (p = 0.002) significantly decreased in NYHA III-IV group. The gut downstream bilirubin products, urobilinogen and stercobilin were decreased in the HF group; while the upstream bilirubin products, unconjugated and conjugated bilirubin increased. Dysbiosis of the gut microbiome and the decrease of bilirubin reductase containing bacteria in pediatric HF patients related to a reduction in gut bilirubin metabolism.PMID:42593705 | DOI:10.1007/s12265-026-10834-z

Fish Physiol Biochem. 2026 Aug 13;52(4):152. doi: 10.1007/s10695-026-01775-0.ABSTRACTSalinity fluctuations are key environmental drivers that shape physiological homeostasis in euryhaline teleosts by altering osmotic balance and energy allocation. In this study, marine medaka (Oryzias melastigma) was used to elucidate skeletal muscle adaptation to chronic low-salinity stress by integrating histology, transmission electron microscopy (TEM), antioxidant indices, transcriptomics, and metabolomics. Offspring (F₁) derived from low-salinity-acclimated parents were reared at a salinity of 2.5‰ and sampled at 4 months, with fish from 25‰ seawater serving as controls. Low salinity significantly reduced the mean cross-sectional area of myofibers while increasing fiber density. TEM revealed a marked widening of the I-band without changes in sarcomere length, suggesting an altered actin-myosin overlap that may help maintain contractile performance under osmotic stress. Biochemical assays showed unchanged catalase activity but significantly elevated total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, indicating enhanced lipid peroxidation accompanied by compensatory activation of the antioxidant defense network. Transcriptome profiling identified 1266 differentially expressed genes (985 downregulated, 281 upregulated), enriched in cytoskeletal and contractile remodeling (desmosomes, myofibrils, myosin filaments) as well as signaling pathways including Wnt/β-catenin and mTOR. Metabolomic analysis detected 112 differential metabolites, including increased POVPC and 3-hydroxycoumarin and decreased uric acid. These metabolites were mainly associated with mTOR signaling, amino acid metabolism, efferocytosis, and the sulfur relay system. Collectively, the results indicate that chronic low salinity shifts skeletal muscle from growth-oriented processes toward structural maintenance, redox regulation, metabolic reallocation, and cellular repair. These findings provide a multi-omics framework for understanding muscle plasticity under hypo-osmotic stress and offer candidate targets for optimizing brackish and freshwater aquaculture practices.PMID:42593696 | DOI:10.1007/s10695-026-01775-0

Curr Microbiol. 2026 Aug 13;83(10):511. doi: 10.1007/s00284-026-05111-w.ABSTRACTWith the aim to harness synergistic potential of multiple beneficial microbes, we developed consortia (BC6) bioformulations that comprise six bacterial strains in multiple delivery forms (both powder and liquid). The bioefficacy of the consortia was assessed in terms of plant growth, fruit quality, productivity, stress response and metabolite profile in tomato fruits. The novel liquid bioformulation demonstrated superior shelf-life stability beyond 12 months. Bacillus sp. IIVRBT-12, a prominent member of consortia exhibited plant growth-promoting (PGP) traits including phosphate (13.84 mg P-released/100 mg tricalcium phosphate) and zinc (47.24 mg ZnCO3 L- 1) solubilization. Bacillus sp. IIVRBB-3 showed high indole acetic acid (IAA) production (59.14 µg ml- 1) and ACC deaminase (872.42 nmol α-ketobutyrate mg-1h- 1) activity. Three-stage concomitant application (seed priming, root dip, and soil treatment) significantly improved plant growth with BC6-L treated plants showing enhanced height (89.95 cm) and root development (36.95 cm) compared to BC6-P, although both performed significantly against the control plants. The treatments improved flowering time and increased flowers per cluster (5.25 in BC6-L compared to 3.5 in BC6-P treated plants). Treatments enhanced fruit yield from 3.1 kg in BC6-P to 3.72 in BC6-L per plant. The consortia also significantly improved activity of defense enzymes and enhanced biochemical parameters (carotenoids, flavonoids, and ascorbic acid) of fruit nutritional quality. LC-MS/MS based putative metabolomic characterization of metabolites uniquely identified scopoletin, deoxyribose-5-phosphate, 2'-deoxycytidine-5'-diphosphate (sodium salt), adenosine monophosphate, 2'-deoxyuridine-5'-monophosphate (disodium salt) and cytidine-5'-monophosphate monohydrate in BC6 liquid inoculated plants. These findings demonstrated potential of BC6 consortia as an effective plant growth promoter offering enhanced crop productivity, improved nutritional quality, and increased stress resilience.PMID:42593534 | DOI:10.1007/s00284-026-05111-w

J Inherit Metab Dis. 2026 Sep;49(5):e70233. doi: 10.1002/jimd.70233.ABSTRACTPhosphomannomutase deficiency (PMM2-CDG), the most common congenital disorder of glycosylation (CDG), is characterized by multisystem involvement and a lack of disease-modifying therapies. While previous transcriptomic studies have uncovered disrupted cellular pathways, the functional consequences of these alterations remain poorly understood. To further investigate PMM2-CDG pathophysiology, we integrated proteomic and metabolomic profiling of patient-derived fibroblasts with previously published transcriptomic data. Proteomic analysis was performed using Tandem Mass Tag-based mass spectrometry, while metabolomics was conducted via Nuclear Magnetic Resonance spectroscopy. Multi-omics integration was performed using principal component analysis-based dimensionality reduction, incorporating clinical metadata as supplementary variables. Proteomic analysis identified 43 significantly altered proteins, with enrichment in the retinoic acid synthesis pathway, wound healing, and cytoskeletal organization. Metabolomic profiling revealed altered amino acid levels and elevated concentrations of UDP-GlcNAc, consistent with perturbation of the hexosamine biosynthesis pathway, and increased levels of myo-inositol. Notably, myo-inositol levels showed a strong association with disease severity in the integrated analysis. RT-qPCR confirmed the upregulation of GFPT2. This integrative multi-omics study identifies consistent alterations in the retinoic acid synthesis pathway and hexosamine biosynthesis in PMM2-CDG patient-derived fibroblasts and reveals an association between intracellular myo-inositol levels and disease severity. These findings provide new insights into PMM2-CDG-associated molecular alterations and illustrate the value of multi-omics integration for hypothesis generation in rare diseases.PMID:42593233 | DOI:10.1002/jimd.70233