PubMed

Front Pharmacol. 2026 Apr 21;17:1756789. doi: 10.3389/fphar.2026.1756789. eCollection 2026.ABSTRACTOBJECTIVES: To explore the potential efficacy and identify preliminary metabolic biomarkers of the Jianpi Yishen Zhuanggu Tongluo formula (JPYSZGT) in rheumatoid arthritis (RA) complicated with sarcopenia-osteopenia (SO) using 1H-NMR-based metabolomics and in vitro experiments.METHODS: In this pilot study, forty RA-SO patients were randomly allocated into a treatment group (Group C, n = 20) receiving JPYSZGT plus conventional therapy and a control group (Group D, n = 20) receiving conventional therapy alone for 12 months. Clinical outcomes, including inflammatory markers (CRP, ESR), bone metabolism markers (CTX, PINP), insulin-like growth factor (IGF), cytokines (IL-6, TNF-α), bone mineral density (BMD), and appendicular skeletal muscle mass index (ASMI), were analyzed.RESULTS: Compared to Group D, Group C showed greater improvements in DAS28-ESR, ASMI, and BMD, and greater reductions in ESR, CRP, TNF-α, CTX, and PINP, along with a significant increase in IGF levels. Metabolomics analysis identified preliminary alterations in 14 pathways involving glucose, lipid, and amino acid metabolisms. In vitro experiments suggested that JPYSZGT may suppress macrophage activation, potentially upregulate PINK1/PARKIN, downregulate OPG/RANK pathways, and reduce TNF-α and IL-6 secretion.CONCLUSION: This exploratory study suggests that JPYSZGT may improve bone-muscle metrics in RA-SO and that its potential mechanisms could involve the modulation of the PINK1/PARKIN, OPG/RANK, and PI3K/Akt pathways. It also appears to inhibit macrophage-driven inflammation. These findings warrant further investigation in larger-scale studies.CLINICAL TRIAL REGISTRATION: identifier ChiCTR2500106729.PMID:42093870 | PMC:PMC13139347 | DOI:10.3389/fphar.2026.1756789

Int J Microbiol. 2026 May 5;2026:3823241. doi: 10.1155/ijm/3823241. eCollection 2026.ABSTRACTActinobacteria associated with medicinal plants are recognized as prolific sources of novel bioactive compounds. Kratom (Mitragyna speciosa) leaves have been reported to contain a diverse array of secondary metabolites with pharmacological activities, including antibacterial, antioxidant, and anti-inflammatory effects. In this study, 16 actinobacterial isolates were successfully obtained from the leaves of M. speciosa. Based on the 16S rRNA gene sequence analysis, the isolates were identified as members of Streptomyces and non-Streptomyces genera, including Micromonospora, Pseudonocardia, Quadrisphaera, Prauserella, and Actinomycetospora. All isolates were screened for antibacterial activity, among which Micromonospora chersina NRAIS18 demonstrated notable inhibitory effects against both Gram-positive and Gram-negative pathogens. The ethyl acetate crude extract of NRAIS18 exhibited the most potent activity against Listeria monocytogenes ATCC 7644, followed by Pseudomonas aeruginosa ATCC 27853. Metabolomic profiling using LC-MS and GC-MS revealed diverse secondary metabolites in the crude extract, including the isoflavone daidzein, harman, norharman, and soyasaponin Bb; siderophores such as ferrioxamine E and desferrioxamine E; and other volatile bioactive compounds such as fatty acids, isoquinolines, and esters. Several of these metabolites have been reported to possess antibacterial properties. These findings suggest that M. chersina NRAIS18 demonstrates significant promise as a source of antibacterial agents for pharmaceutical applications.PMID:42093748 | PMC:PMC13140871 | DOI:10.1155/ijm/3823241

Front Plant Sci. 2026 Apr 21;17:1832558. doi: 10.3389/fpls.2026.1832558. eCollection 2026.ABSTRACTSomatic embryogenesis is an artificially induced process that results in the formation of an embryo without the fusion of gametes. Despite its significant potential for plant propagation and conservation of plant genetic resources, many unknowns remain regarding the specific mechanisms and the complexity of genetic, biochemical, and cellular regulations involved. The comparative data on induction of embryogenic tissue and the maturation of somatic embryos, along with additional results, suggest that complex carbohydrate dynamics are among the key factors involved. This review summarizes recent findings focused on early stages of SE, including induction, proliferation, comparison of embryogenic cell lines with contrasting embryogenic capacity, and loss of embryogenic capacity after prolonged cultivation obtained through various methods, including metabolomics, proteomics, transcriptomics, and cytological techniques/histochemical visualization, which highlight the regulation of the energy source starch. This encompasses its synthesis and remobilization, driven by related enzymatic machinery, as crucial for determining embryogenic capacity and prognosis in embryo maturation and germination in many economically important plant species. We also outline potential future directions, critical questions to address, and anticipated advancements in the topic, including the development of new research methodologies.PMID:42093697 | PMC:PMC13139103 | DOI:10.3389/fpls.2026.1832558

Circulation. 2026 May 7. doi: 10.1161/CIRCULATIONAHA.126.079030. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary hypertension (PH) is a serious complication of heart failure with preserved ejection fraction (HFpEF), for which no targeted therapies are currently available. Endothelial dysfunction plays a crucial role in PH associated with HFpEF (PH-HFpEF), yet its molecular drivers remain poorly defined.METHODS: Transcriptome profiling uncovered endothelial characteristics of PH-HFpEF. Endothelial-specific GPRASP1 (GPCR [G protein-coupled receptor]-associated sorting protein 1 deletion in mice was conducted to investigate its participation in PH-HFpEF pathology. Multimodal metabolomics, isotope tracing, proteomics, and mechanistic biochemical assays were used to map downstream pathways and identify druggable mediators.RESULTS: GPRASP1 was significantly lowered in pulmonary endothelial cells of PH-HFpEF models. Endothelial Gprasp1 knockout mice exhibited major PH-HFpEF features, including pulmonary vascular remodeling, elevated pulmonary pressure, diastolic dysfunction, and abnormal glucose/lipid metabolism. GPRASP1 loss impaired tricarboxylic acid cycle activity by stabilizing ASNS (asparagine synthetase), preferentially shifting aspartate toward asparagine synthesis over oxaloacetate production. This metabolic reprogramming led to adenosine triphosphate depletion, reactive oxygen species accumulation, endothelial nitric oxide synthase uncoupling, and nitric oxide deficiency. We discovered that, beyond its classic role in GPCR sorting, GPRASP1 functioned as a noncanonical adaptor protein that scaffolded the E3 ubiquitin ligase PKN (Parkin) and ASNS, promoting PRKN-dependent K48-linked ubiquitination and proteasomal degradation of ASNS via its C-terminal domain. In parallel, under mitochondrial stress, GPRASP1 strengthened PRKN interactions with MFN1/2, enhanced their K63-linked ubiquitination, and facilitated PRKN-mediated mitophagy. Restoration of GPRASP1 expression or pharmacological inhibition of ASNS activity with olopatadine normalized aspartate utilization, improved mitochondrial bioenergetics, rescued endothelial function, and attenuated cardiopulmonary pathology in PH-HFpEF models.CONCLUSIONS: Our findings unlocked a noncanonical role of GPRASP1 in preserving pulmonary endothelial homeostasis and delineated a novel GPRASP1-PRKN-ASNS axis that connected proteostasis with endothelial metabolic integrity, highlighting aspartate metabolism as a targetable vulnerability in cardiopulmonary disease.PMID:42093650 | DOI:10.1161/CIRCULATIONAHA.126.079030

Anal Methods. 2026 May 6. doi: 10.1039/d6ay00150e. Online ahead of print.ABSTRACTExercise-induced muscle damage (EIMD) triggers a coordinated cascade of molecular responses that drive tissue repair and physiological adaptation. Recent advances in analytical chemistry have enabled multi-omics profiling to capture these complex processes across genomic, transcriptomic, proteomic, and metabolomic layers. This review critically examines the analytical strategies underlying EIMD omics research, emphasizing how modern separation and detection technologies have expanded the depth and resolution of biomolecular measurements. We outline the strengths and trade-offs of invasive and non-invasive biospecimens, highlighting how blood, urine, interstitial fluid, and sweat provide complementary insights into systemic and local muscle responses. Central to this workflow are chemometric and bioinformatic tools that enable dimensionality reduction, feature selection, and predictive modeling, transforming high-dimensional molecular data into actionable biomarkers. Case studies illustrate how metabolite panels and protein signatures can discriminate muscle damage states, reveal pathway dynamics, and support early detection of physiological stress. By linking analytical innovation with data integration, multi-omics approaches are reshaping how exercise stress, adaptation, and recovery are understood. This synthesis also acknowledges current controversies positioning multi-omics as both a powerful scientific tool and a frontier for precision exercise medicine.PMID:42093474 | DOI:10.1039/d6ay00150e

Anal Methods. 2026 May 5. doi: 10.1039/d6ay00096g. Online ahead of print.ABSTRACTUnderstanding the geographical differentiation of black tea is essential for exploring the influence of territory on its chemical composition. In this study, black tea (powder) samples from key tea-producing regions, including Siliguri, Assam, and Idukki (Kerala) in India, Sylhet in Bangladesh, and Kandy in Sri Lanka, were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. The tea extracts were analysed in full MS/ddMS2 mode with heated electrospray ionization, using a non-targeted metabolomics approach. A broad range of compounds (209) including polyphenols, amino acids, organic acids and their derivatives were identified based on accurate mass measurements with mass error (±5 ppm) and retention time matching (±0.2 min). Various metabolite profiles were observed across different regional samples, with certain marker compounds identified as potential indicators of geographical origin. Principal component analysis (PCA) further confirmed clear clustering and differentiation of tea samples based on the origin, highlighting the role of regional environmental factors such as climate, soil composition, and altitude. Molecular docking and dynamics were carried out to examine the interaction of theanine and the neonatal Fc receptor (FcRn), a key regulator of IgG recycling and immune homeostasis, encoded by the FCGRT gene. Results showed that theanine forms a stable complex with the neonatal Fc receptor (FcRn) and maintained consistent hydrogen bonding, particularly with key residue Ile685, and preserved FcRn's secondary structure. Binding energy analysis (MM-PBSA) showed favourable interactions dominated by van der Waals forces, with theanine exhibiting a slightly higher binding affinity (-18.72 kcal mol-1) than RVT-1401 (-17.82 kcal mol-1), a therapeutic monoclonal antibody known to inhibit FcRn function. The findings have significant implications for the tea industry in quality control, authentication, traceability, and health benefits, which offer new insights into how territory shapes the chemical and potentially sensory attributes of black tea.PMID:42093402 | DOI:10.1039/d6ay00096g

Endocrinol Metab (Seoul). 2026 May 7. doi: 10.3803/EnM.2025.2566. Online ahead of print.ABSTRACTBACKGROUND: Diabetes mellitus (DM) with coronary artery disease (CAD), referred to as DM-CAD, is a prevalent endocrine-metabolic condition characterized by macrophage-driven inflammation and metabolic dysregulation. This study aims to investigate the role of YTH N6-methyladenosine RNA binding protein F1 (YTHDF1)-mediated N6-methyladenosine (m6A) modification in stabilizing the long non-coding RNA (lncRNA) Opa interacting protein 5 antisense RNA 1 (OIP5-AS1) and to determine its impact on macrophage metabolic dysfunction in DM-CAD.METHODS: Single-cell RNA sequencing and bulk RNA sequencing were performed using DM-CAD mouse models, with downstream analyses conducted using Seurat, CellChat, least absolute shrinkage and selection operator (LASSO) regression, and random forest algorithms. Experimental validation included RNA immunoprecipitation followed by quantitative polymerase chain reaction, actinomycin D-based RNA stability assays, and 2-deoxyglucose (2-DG) interventions in THP-1-derived macrophages, alongside metabolomic profiling and reactive oxygen species (ROS) measurements.RESULTS: Increased macrophage-endothelial cell coupling was observed in DM-CAD, with both OIP5-AS1 and YTHDF1 significantly upregulated and closely associated with glycolytic metabolic pathways. YTHDF1-mediated m6A modification stabilized OIP5-AS1, thereby promoting glycolysis, foam cell formation, ROS production, plaque development, and the upregulation of proinflammatory cytokines, collectively exacerbating atherosclerosis. Notably, treatment with 2-DG markedly reversed these pathological phenotypes.CONCLUSION: This study identifies the YTHDF1-m6A-OIP5-AS1 axis as a critical regulator of macrophage metabolic dysfunction in DM-CAD, thereby providing an epigenetic framework for understanding disease progression. Targeting this regulatory pathway may attenuate metabolic inflammation and represents a promising therapeutic strategy for endocrine-related cardiovascular complications.PMID:42093360 | DOI:10.3803/EnM.2025.2566

J Cereb Blood Flow Metab. 2026 May 6:271678X261444200. doi: 10.1177/0271678X261444200. Online ahead of print.ABSTRACTIn the last three decades, a huge amount of data and number of reports have proved that ischemic brain damage develops differently based on the time of the day at which it occurs. Differences in circadian rhythms between nocturnal rodent models and diurnal humans may explain the lost in translation crisis experienced in the stroke field. To clarify aspects related to circadian rhythm in stroke and to maximize the translatability of preclinical studies in the attempt to identify new promising therapeutic strategies in stroke, changes in biomarkers and systemic biology have been studied after stroke induction in mice. Circadian rhythms influence the metabolic response to stroke in the brain and in the peripheral blood and muscles, with greater efficacy observed during the rodent inactive phase. In the present review article, we intend to summarize the main findings recently published in the field with the attempt to underline the importance of studying the circadian timing in stroke research in order to improve the translation of brain protective strategies from animals to humans.PMID:42093232 | DOI:10.1177/0271678X261444200

BMC Plant Biol. 2026 May 6. doi: 10.1186/s12870-026-08772-8. Online ahead of print.ABSTRACTCadmium (Cd) contamination poses a persistent threat to plant fitness and ecosystem stability, yet the molecular basis of sex-dependent Cd tolerance in dioecious plants remains unclear. In this study, the dioecious early land plant Marchantia polymorpha was employed to investigate the transcriptomic and metabolomic responses, physiological and morphological variations, and the remedial effects of exogenous glutathione (GSH). Physiological analyses revealed pronounced sexual dimorphism: females accumulated significantly more Cd (82.97 ± 0.75 mg kg⁻1) than males (61.80 ± 0.10 mg·kg⁻1) and suffered more severe chlorosis and oxidative damage, whereas males maintained lower Cd burdens and exhibited stronger antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT). Transcriptomic analysis identified 4,547 differentially expressed genes (DEGs) in females and 4,102 in males under Cd stress, with GO and KEGG enrichment revealing that females preferentially reprogrammed photosynthesis and defense-related pathways, while males activated carbohydrate metabolism and cell wall remodeling. Metabolomic profiling further uncovered sex-divergent metabolic flux, with females accumulating naringenin chalcone (log₂FC = 3.88) and males specifically upregulating quercetin biosynthesis via F3'H. Integrated transcriptomic and metabolomic analysis highlighted three core pathways-flavonoid biosynthesis, tyrosine metabolism, and GSH metabolism-as central hubs of sex-specific Cd responses. Exogenous GSH application alleviated Cd-induced toxicity in a sex-dependent manner: males showed greater reduction in Cd accumulation (32.58%) compared to females (8.36%) and more efficient restoration of redox homeostasis, while females exhibited stronger recovery of photosynthetic pigments and flavonoid accumulation. This study provides a molecular-level perspective for understanding sex-dependent heavy metal adaptation in early land plants and offers a rationale for sex-aware phytoremediation strategies.PMID:42092781 | DOI:10.1186/s12870-026-08772-8

BMC Genomics. 2026 May 6. doi: 10.1186/s12864-026-12894-6. Online ahead of print.ABSTRACTFusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (FOC), poses a major threat to economically important crops worldwide. Figleaf gourd (Cucurbita ficifolia) has been widely adopted as a rootstock for FOC-susceptible cucumber (Cucumis sativus) due to its strong resistance, although the underlying molecular mechanisms remain elusive. In this study, we leveraged the contrasting FOC resistance between C. ficifolia and C. sativus to perform a comparative analysis aimed at elucidating the molecular basis of Fusarium wilt resistance in C. ficifolia. Compared to C. sativus, resistant C. ficifolia exhibited milder wilting, enhanced antioxidant enzyme activities, and reduced oxidative damage. Transcriptome profiling revealed 1,599 species-specific expressed genes and 3,379 orthologous genes with interspecies expression divergence. Several key defense-related pathways, such as MAPK signaling and plant-pathogen interaction, contained critical node genes that exhibited species-specific regulation, potentially contributing to the enhanced resistance of C. ficifolia. This global divergence in gene expression was associated with distinct metabolic shifts, leading to the specific activation of defense-related metabolic pathways in C. ficifolia and the subsequent accumulation of protective compounds such as brassinosteroids, phenylpropanoids, and flavonoids. These findings indicate that C. ficifolia's superior FOC resistance is not attributable to a single factor but emerges from a sophisticated orchestration of gene expression and metabolic output. This study provides novel molecular insights into Fusarium wilt resistance and offers candidate genes and metabolic targets for breeding disease-resistant cucurbit crops.PMID:42092776 | DOI:10.1186/s12864-026-12894-6

BMC Genomics. 2026 May 6. doi: 10.1186/s12864-026-12886-6. Online ahead of print.ABSTRACTBACKGROUND: Corymbia citriodora wood holds extensive application value; however, due to the cross-pollination nature of C. citriodora and the significant genetic variation among offspring, a phenomenon is observed in plantations where trees with the same parental lineage exhibit varying diameter at breast height (DBH). In this study, we hypothesized that the observed DBH variation reflects two divergent adaptation strategies under winter conditions: smaller trees may exhibit heightened cold sensitivity, activating stress responses and entering early dormancy, whereas larger trees may sustain cambial activity through coordinated regulation of cell-cycle genes and carbohydrate metabolism.RESULTS: Metabolomics showed large trees enriched in phenolic compounds like picroside I and orientin. Transcriptomics revealed their genes were enriched in cell cycle and phenylalanine/tyrosine metabolism pathways, whereas small trees were enriched in abscisic acid (ABA) pathways. Integrated analysis revealed three patterns of transcript-metabolite coordination: (i) concordant upregulation (e.g., shikimate dehydrogenase (SDH)-shikimic acid), (ii) discordant regulation suggesting post-transcriptional control (raffinose accumulation without raffinose synthase (RFS) upregulation in small trees), and (iii) pathway-level flux redirection (phenylpropanoid pathway). Systematically, during winter, small trees exhibited stress-sensitive signatures, characterized by 9-cis-epoxycarotenoid dioxygenase (NCED), pyrabactin resistance/pyrabactin resistance-like (PYR/PYL), ABA-responsive element binding factor (ABF) upregulation, accumulation of raffinose, and transcriptional shift toward lignification (cinnamyl-alcohol dehydrogenase (CAD), peroxidase upregulation). Conversely, large trees showed molecular profiles indicative of stronger adaptability, with transcriptional signatures consistent with continued cell division (E2F transcription factor 3 (E2F3), mini-chromosome maintenance (MCM2/4/5/6) upregulation), cytoskeletal organization (kinesin KIN12B), and active carbohydrate metabolism (sucrose synthase (SUS), trehalose-6-phosphate phosphatase (TPP), alpha-amylase (AMY) upregulation), accumulating cinnamate and shikimic acid.CONCLUSION: This study advances understanding of tree growth variation by demonstrating that winter conditions reveal divergent adaptation strategies linked to DBH. The key conceptual advance is the integration of stress signaling, carbon metabolism, and cell-wall regulation into a unified framework where differential dormancy timing explains within-family growth variation. Large trees maintain a permissive growth state through coordinated upregulation of cell-cycle, cytoskeletal, and biosynthetic genes, while small trees exhibit coordinated stress responses that accelerate dormancy. These findings provide species-specific targets for functional validation-including E2F3, KIN12B, and NCED-and suggest that breeding for sustained winter cambial activity could enhance biomass production in subtropical plantations.PMID:42092761 | DOI:10.1186/s12864-026-12886-6

Environ Res. 2026 May 4:124615. doi: 10.1016/j.envres.2026.124615. Online ahead of print.ABSTRACTRiver ecosystems are facing increasing environmental pressures, and microbial communities play a key role in maintaining ecosystem stability. Although microbial research in lentic ecosystems has been relatively extensive, there is a lack of systematic comparative studies on the community structure and metabolic functions of fungi and bacteria across vertical gradients within the water-sediment continuum in flowing rivers, particularly those chronically exposed to salinity and nitrogen nutrients. This study investigated the microbial community structure, functional traits, and environmental responses across the water-sediment continuum of two Class V-polluted rivers, the Zhimai River and Xiaoqing River of the Yellow River Delta. Integrated analyses combining water quality assessment, high-throughput sequencing, and metabolomics revealed distinct microbial assembly mechanisms in the two rivers. In the Zhimai River, salinity-related factors, particularly sodium and potassium, influenced community composition, with Chytridiomycota (19.76%) and halophilic bacteria, such as Marivita (2.60%), exhibiting strong positive correlations. In contrast, nitrogenous nutrients, particularly ammonium nitrogen, played a key role as drivers in the Xiaoqing River. In this system, Absidia (23.08%), Hydrogenophaga, and Arenimonas were dominant and exhibited positive associations with nitrogen levels and perfluorooctanoic acid. These patterns indicate two response strategies, halophilic adaptation under salinity stress and nitrogen cycling under nutrient enrichment. The findings provide new insight into salinity- and nutrient-driven microbial processes in polluted river systems and offer a scientific basis for microbial remediation and ecological health assessment in the Yellow River Delta.PMID:42092675 | DOI:10.1016/j.envres.2026.124615

JHEP Rep. 2026 May 4:101884. doi: 10.1016/j.jhepr.2026.101884. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Bile acids are crucial mediators of cholesterol homeostasis, lipid digestion, and detoxification, and reliable in vitro synthesis systems are essential for liver disease research and precision medicine. Although hiPSC-derived hepatic organoids model key human liver functions, fully recapitulating bile acid biosynthesis remains challenging. Here, we generated bile acid-hepatobiliary organoids (BA-HBOs) that capture major aspects of bile acid metabolism, thereby providing a more physiologically and pathologically relevant platform for metabolic studies and drug screening.METHODS: Maturation protocols were optimized with saikosaponin A to enhance bile acid biosynthesis in BA-HBOs. Fibrotic BA-HBOs (FiBA-HBOs) were further established by TGF-β treatment. Cellular identity and functional markers were evaluated by immunofluorescence, flow cytometry, and qPCR. Organoid heterogeneity was characterized by single-cell RNA sequencing, and bile acid composition and diversity were quantified by LC-MS/MS metabolomics.RESULTS: BA-HBOs demonstrated hepatic and biliary functions, including organized lineage segregation and robust synthetic and metabolic capacities. Compared with controls, BA-HBOs showed increased bile acid synthesis, improved bile duct structure, and higher transport protein expression (n ≥ 3, p < 0.05). Targeted metabolomics identified a complex spectrum of 33 bile acid species, predominated by glycine-conjugated forms, consistent with human physiology. Single-cell RNA sequencing revealed that BA-HBOs recapitulated the transcriptional landscape of adult liver tissue, and revealed hepatocyte subpopulation restructuring associated with enhanced bile acid metabolism. Moreover, modeling fibrosis-associated dysregulation generated FiBA-HBOs, which exhibited cholestasis-like changes and disease-relevant metabolomic profiles (n ≥ 3, p < 0.05).CONCLUSION: BA-HBOs recapitulate key aspects of human liver bile acid metabolism, hepatocyte zonation, and core metabolic processes in vitro, providing a physiologically relevant platform for mechanistic studies of liver disease and screening therapeutic candidates.IMPACT AND IMPLICATIONS: Our hiPSC-derived BA-HBOs synthesize and secrete diverse bile acid species, capturing key transcriptional and metabolic profiles of the human liver. They enable modeling of liver fibrosis accompanied by disruptions in bile acid metabolism, offering a tool to dissect disease mechanisms. These robust organoids create new opportunities for basic liver research, therapeutic development, and precision medicine.PMID:42092618 | DOI:10.1016/j.jhepr.2026.101884

J Dairy Sci. 2026 May 4:S0022-0302(26)01742-X. doi: 10.3168/jds.2025-28155. Online ahead of print.ABSTRACTThe objective of this study was to evaluate the effects of replacing corn silage with triticale (× Triticosecale Wittmack) silage on lactation performance, milk fatty acid profile, and rumen microbiome-metabolome interactions in dairy cows. In this study, 27 mid-lactation dairy cows were used in replicated 3 × 3 Latin squares with 3 28-d periods and 3 treatments, in which 0, 25, or 50% of the corn silage (DM basis) was replaced with triticale silage. Replacing 25% of corn silage maintained DMI and milk yield, whereas 50% replacement reduced both variables. Diets containing triticale silage lowered SCC and increased the proportion of oleic acid in milk fat. The 50% replacement further increased the proportions of linoleic acid (LA), α-linolenic acid (ALA), and milk protein concentration. In the rumen, the 50% replacement increased pH and NH3-N concentration, and triticale diets increased the proportions of ALA and several C18:1 and C18:2 biohydrogenation intermediates, resulting in a greater UFA proportion and a lower SFA: UFA ratio in rumen fluid. Metataxonomic analysis revealed higher relative abundances of Butyrivibrio_A, Ruminococcus_E, and Prevotella in triticale diets, whereas metabolomic profiling indicated enrichment of pathways related to LA, ALA, and amino acid metabolism. Correlation analysis associated Butyrivibrio_A and Ruminococcus_E with LA oxidation products and amino acid derivatives, indicating the involvement of rumen microbiome-metabolome interactions in shaping the milk UFA responses. Overall, partial replacement of corn silage with triticale silage improved the milk fatty acid profile and udder health indicators without compromising performance at 25% inclusion, indicating that winter triticale is a promising component of forage systems.PMID:42092559 | DOI:10.3168/jds.2025-28155

Chem Biol Interact. 2026 May 4:112114. doi: 10.1016/j.cbi.2026.112114. Online ahead of print.ABSTRACTBACKGROUND: Acute kidney injury (AKI) remains a major clinical challenge lacking effective pharmacological interventions. Ferroptosis has emerged as a critical mechanism contributing to renal tubular injury. While p-coumaric acid (pCA), a natural phenolic compound, has been reported to exert renoprotective effects, its regulatory role in ferroptosis, particularly under different pathological contexts of AKI, remains incompletely understood.METHODS: A folic acid (FA, 250 mg/kg)-induced AKI model was established in mice treated with pCA (10 and 50 mg/kg). Renal function, histopathology, inflammatory responses, and ferroptosis-related markers were evaluated. Integrated transcriptomic and metabolomic analyses were performed to identify global regulatory alterations. Mechanistic studies were conducted in erastin-treated HK-2 cells. NRF2 signaling involvement was further assessed using pharmacological inhibition.RESULTS: pCA treatment significantly improved renal function, attenuated tubular injury, and suppressed inflammatory responses in FA-induced AKI. Multi-omics integration revealed that pCA markedly reprogrammed metabolic and transcriptional networks associated with ferroptosis and redox homeostasis. Mechanistically, pCA restored antioxidant capacity and normalized the expression of ferroptosis-related proteins. Notably, pCA activated NRF2 signaling, leading to upregulation of downstream targets involved in ferroptosis regulation. Inhibition of NRF2 partially abolished the cytoprotective and anti-ferroptotic effects of pCA in vitro.CONCLUSION: pCA alleviates FA-induced AKI by suppressing ferroptosis through NRF2-dependent regulation of redox and metabolic homeostasis, highlighting NRF2 as a potential therapeutic target for AKI.PMID:42092523 | DOI:10.1016/j.cbi.2026.112114

J Lipid Res. 2026 May 4:101053. doi: 10.1016/j.jlr.2026.101053. Online ahead of print.ABSTRACTPeople living with HIV develop persistent neurocognitive impairment despite viral suppression through incompletely defined mechanisms. HIV-1 Tat disrupts VAPB-PTPIP51 coupling at mitochondria-associated ER membranes via PTPIP51 tyrosine phosphorylation, causing VAPB relocalization away from MAMs, a causal mechanism established in our prior work. Here, we define the downstream metabolic consequences and establish VAPB as the critical determinant of neuronal lipid pathology. Lipidomic profiling identified triglycerides as the dominant altered species, comprising polyunsaturated forms normally destined for membrane synthesis or mitochondrial oxidation, consistent with membrane catabolism rather than de novo lipogenesis. Targeted metabolomics revealed bioenergetic collapse consistent with impaired mitochondrial oxidative function. The resulting lipid imbalance, including lipid droplet accumulation, produced secondary organellar dysfunction, including Golgi dispersal and ER stress. Critically, Tat failed to induce lipid droplet accumulation in shRNA-VAPB cells, while PTPIP51 silencing had no such protective effect, establishing that VAPB relocalization is the obligate trigger. Guanosine supplementation reduced lipid droplet accumulation, suggesting a link to bioenergetic failure that warrants further investigation. In postmortem HIV-infected frontal cortex, VAPB was paradoxically elevated yet correlated with worsening dementia severity, consistent with transcriptional upregulation that cannot overcome post-translational blockade of VAPB-MAM localization. The polyunsaturated triglycerides, depleted plasmalogens, and elevated ceramides documented here closely parallel lipid signatures reported in PLWH with cerebrovascular complications, implicating Tat-driven lipid dysregulation as a candidate mechanism for the incompletely explained elevation in stroke risk in this population.PMID:42092489 | DOI:10.1016/j.jlr.2026.101053

J Ethnopharmacol. 2026 May 4:121805. doi: 10.1016/j.jep.2026.121805. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng Decoction (BTWD) is a traditional Chinese medicine formula widely used in clinical practice for treating ulcerative colitis (UC). However, its precise therapeutic mechanisms remain unclear.AIM OF THE STUDY: This study investigates the therapeutic effects of BTWD administered via colon and oral routes in a UC model induced by fecal microbiota transplantation (FMT) and dextran sodium sulfate (DSS). It further explores the distinct pharmacological mechanisms associated with each route of administration.MATERIALS AND METHODS: Male rats with UC induced by human-derived FMT and DSS were treated with BTWD via oral or colonic administration. Therapeutic outcomes were evaluated through clinical indicators and histopathology. Drug metabolites in serum and colon contents were analyzed by Ultra Performance Liquid Chromatography-Q Exactive-Orbitrap Mass Spectrometer (UPLC-QE-Orbitrap MS). Serum and fecal metabolomics identified disease-related biomarkers. Potential active substances were screened by correlating serum and fecal biomarkers with BTWD-derived components. Key active substances and targets were identified through network pharmacology and molecular docking, clarifying the pharmacological basis of each administration route. Surface plasmon resonance (SPR) and Western blot were performed to experimentally validate the binding interactions and target protein expression.RESULTS: Both administration routes of BTWD significantly alleviated UC symptoms. Compared to the model group, BTWD-treated rats exhibited reduced weight loss, lower disease activity index (DAI) scores, and recovered colon length. Serum levels of pro-inflammatory cytokines IL-6, IL-17, and IL-1β were decreased, while anti-inflammatory IL-10 was increased. Expression of Occludin and MUC2 proteins in colon tissue was significantly upregulated. In total, 82 serum and 70 colon components were identified following oral administration, while colonic administration yielded 73 serum and 78 colon components. Correlation analysis screened 36 active components associated with colonic administration and 25 with oral administration. Network pharmacology and molecular docking suggested that core components from colon administration (Anemoside B4, Betulonic acid) may act via targets such as EGFR, LCK, and MET, while oral components (Berberine, Oxyepiberberine) may target AURKA, MET, and PTGS2. SPR confirmed direct binding of anemoside B4 and berberine to EGFR with KD values of 9.47E-04 M and 2.96E-04 M, respectively. Western blot revealed route-dependent modulation of EGFR, PTGS2, LCK and AURKA expression, corroborating the predicted targeting.CONCLUSION: BTWD is effective in treating UC through both colonic and oral administration. This study provides a comprehensive "efficacy-component-metabolism-target" analysis that reveals distinct pharmacological mechanisms underlying each administration route. These findings support the traditional use of BTWD and offer a theoretical foundation for developing optimized, route-specific therapies for UC.PMID:42092473 | DOI:10.1016/j.jep.2026.121805

J Nutr. 2026 May 4:101575. doi: 10.1016/j.tjnut.2026.101575. Online ahead of print.ABSTRACTCarbon isotope ratio (CIR; δ13C) analysis has been proposed as a biomarker for added sugar intake from C4 sources, but its specificity is limited. CIR biomarkers measure total C4 dietary carbon, conflating added sugars with other C4 foods like corn-fed meats and whole corn products. This lack of specificity varies across populations and food systems. Moreover, metabolic redistribution of dietary carbon means that δ13C signals in tissues reflect complex mixtures of sources and processes, not sugar intake alone. Attempts to adjust for confounders rely on self-reported dietary data, undermining the objectivity CIR biomarkers aim to provide. Even under ideal conditions, CIR validity is insufficient for most nutritional research, especially when assessing causal relationships or meaningful effects. The shift in public health focus from 'added sugars' to 'free sugars', including C3-derived sources like fruit juice and honey, further limits CIR utility. While CIR has proven useful for distinguishing dietary protein sources (e.g., marine vs. terrestrial), its application to added sugars faces persistent challenges. Resources may be better directed toward improving dietary assessment tools or developing more specific metabolomic markers, acknowledging that all current methods have limitations.PMID:42092443 | DOI:10.1016/j.tjnut.2026.101575

Free Radic Biol Med. 2026 May 4:S0891-5849(26)00461-2. doi: 10.1016/j.freeradbiomed.2026.04.160. Online ahead of print.ABSTRACTDifenoconazole (DFZ), a widely used triazole fungicide, may pose a potential risk to male reproductive health, although its mechanistic basis in mammals remains incompletely understood. This study assessed DFZ-induced testicular injury through in vivo mouse models and in vitro GC-1 spermatogonia and GC-2 spermatocyte cell systems, conducting transcriptomic, metabolomic, and functional analyses concurrently. Chronic DFZ exposure was associated with dose-dependent testicular atrophy, disorganization of seminiferous tubule architecture, reduced sperm count, increased sperm malformation, and decreased serum testosterone levels, along with detectable DFZ accumulation in serum. Multi-omics profiling revealed coordinated molecular alterations in testicular tissue and germ cells, with ferroptosis-related pathways and lipid metabolic reprogramming being prominently enriched. In testicular tissue and germ cells, DFZ induced features consistent with ferroptosis, including depletion of GSH, accumulation of MDA and Fe2+, inactivation of GPX4, and mitochondrial damage. These changes were alleviated by Fer-1 and DFO, suggesting that ferroptosis contributes to DFZ-induced cytotoxicity. Moreover, GPX4 knockdown further aggravated DFZ-induced ferroptotic injury, supporting a central role for GPX4 in this process. Mechanistically, DFZ appeared to activate autophagy and NCOA4-mediated ferritinophagy, which may promote iron overload and lipid peroxidation. Wnt/β-catenin signaling activation reduced NCOA4 upregulation and ferroptotic damage, but this protective effect was nullified by NCOA4 silencing, suggesting NCOA4 operates downstream of Wnt/β-catenin signaling. These findings reveal that DFZ triggers spermatogenic ferroptosis through Wnt/β-catenin-NCOA4-mediated ferritinophagy, offering insights into triazole fungicide-induced male reproductive toxicity and highlighting potential targets for environmental infertility interventions.PMID:42092407 | DOI:10.1016/j.freeradbiomed.2026.04.160

Curr Biol. 2026 May 5:S0960-9822(26)00450-1. doi: 10.1016/j.cub.2026.04.015. Online ahead of print.ABSTRACTPlant terrestrialization necessitated overcoming a barrage of stressors.1 Embryophytes (land plants) use an integrated response network to adjust their molecular physiology in response to terrestrial stressors2-one of the important stressors is UV irradiance. The zygnematophytes are the closest streptophyte algal relatives of embryophytes,3,4,5,6 renowned for their UV resilience7,8,9 and key for inferring the UV response toolkit of the earliest embryophytes.10,11 Throughout evolution, specialized metabolism radiated, yielding chemodiverse responses to environmental challenges12,13,14,15 ranging from UV-shielding flavonoids and coumarins to the polymer lignin of tracheophytes16; homologs of the underpinning core pathway occur in streptophyte algae.17 Here, we exposed the zygnematophyte Mesotaenium to UV-B irradiation and profiled its physiological, morphological, transcriptomic, and metabolomic features. After UV-B exposure, the cells showed rapid photophysiological responses and progressively growing terminal vacuoles. Our transcriptome data capture dynamic changes in gene expression in (1) core downstream homologs of phenol metabolic enzymes, photophysiological homeostats, and DNA repair factors and (2) upstream components featuring key homologs of kinase-mediated signaling cascades, as well as light quality and abscisic acid-mediated signaling components. To scrutinize the acclimatory chassis, we created a metabolite feature database specifically for the Mesotaenium metabolome. The metabolome displayed pronounced temporal shifts, with several phenolic features that accumulate along the UV-stress-acclimation kinetics. Overall, we capture chemodiverse responses, including various phenolics such as methoxypsoralen-like derivatives and coumarins. We establish an integrated model for UV responses in the closest algal relatives of embryophytes, illuminating the toolkit that allowed the progenitors of embryophytes to move out of a protective water column.PMID:42092354 | DOI:10.1016/j.cub.2026.04.015