PubMed

Biochem Biophys Rep. 2026 Mar 27;46:102557. doi: 10.1016/j.bbrep.2026.102557. eCollection 2026 Jun.ABSTRACTDeciphering the polypharmacological mechanisms of chemically complex therapeutics remains a central challenge in systems biochemistry. Here, we developed an integrated computational-experimental framework to elucidate the molecular basis underlying the anti-vertigo effects of Ziyin Zhixuan Decoction (ZYZX), a multi-component formulation with documented clinical efficacy. Comprehensive chemical profiling by UPLC-Q-TOF-MS/MS identified 64 putative bioactive constituents, predominantly flavonoids, iridoids, and phenolic glycosides. These compounds were systematically mapped onto disease-relevant molecular networks through multi-database target prediction, high-confidence protein-protein interaction (PPI) analysis, and iterative topological screening, which consistently prioritized ERBB2, MAPK1, and AKT1 as central regulatory nodes. To link network-level predictions with physiological outcomes, untargeted serum metabolomics was performed in a thyroxine/reserpine-induced rat model, revealing that ZYZX treatment significantly corrected disruptions in cyclic nucleotide signaling and restored hepato-renal metabolic homeostasis. Molecular docking further supported direct interactions between representative ZYZX constituents and core signaling proteins. Importantly, these computationally inferred mechanisms were experimentally validated by quantitative RT-PCR and Western blotting, demonstrating that ZYZX modulates PI3K-AKT and MAPK signaling pathways at both transcriptional and translational levels, in parallel with improvements in vertigo-like behavioral phenotypes. Collectively, this study provides mechanistic evidence that ZYZX exerts therapeutic effects through coordinated regulation of conserved kinase-driven signaling networks and systemic metabolic pathways. More broadly, it establishes a reproducible, multi-omics-driven strategy for deconvoluting the systems-level actions of polypharmacological interventions, with applicability beyond a single therapeutic context.PMID:41958915 | PMC:PMC13059022 | DOI:10.1016/j.bbrep.2026.102557

Anal Chem. 2026 Apr 10. doi: 10.1021/acs.analchem.5c06539. Online ahead of print.ABSTRACTDisease heterogeneity leads to various clinical molecular subtypes, further limiting the development of precision medicine. Multimodal data integration shows promise for addressing this challenge, but existing methods are affected by omics noise, data imbalance, and limited interpretability. Here, we propose SMODA (Semi-Supervised Multimodal Omics Data Analysis), which is a flexible framework to integrate multimodal omics data by combining heterogeneous transfer learning and semisupervised modeling. SMODA learns shared latent representations across different modalities to reduce the cross-modal heterogeneity. Systematic benchmarking demonstrates that SMODA outperforms existing multiomics integration methods both in disease classification and subtype identification. The application of SMODA in a multimodal esophageal cancer data set still shows better classification performance. A previously unrecognized disease subtype is also identified. This subtype shows altered lipid metabolism, inflammatory responses, and distinct exposure features, which are also linked to poor clinical outcomes. SMODA provides a reliable and interpretable framework for multimodal data integration and supports clinically relevant disease stratification. The SMODA framework is available at https://github.com/zhaoxiaoqi0714/SMODA.git.PMID:41958337 | DOI:10.1021/acs.analchem.5c06539

Chem Biodivers. 2026 Apr;23(4):e03562. doi: 10.1002/cbdv.202503562.ABSTRACTThis study aimed to systematically compare the inflorescence of Ocimum tenuiflorum L. (OTI) and Ocimum gratissimum L. (OGI), focusing on phytochemical composition and anti-inflammatory potentials, thereby providing the foundation for phytopharmaceutical and nutraceutical applications. The nonvolatile phytoconstituents of OTI and OGI were profiled using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/MS-QToF). Volatile constituents were analyzed using headspace gas chromatography-tandem mass spectrometry (HS-GC-MS/MS) and conventional gas chromatography-mass spectrometry (GC-MS/MS). High performance liquid chromatography was used for quantification of marker compounds including rosmarinic acid, ursolic acid, caffeic acid and 7-O-glucoronide, in OTI and OGI. The anti-inflammatory activity of both inflorescences was also evaluated by using liposaccharides (LPS) stimulated human THP-1 cell line. Comparative metabolomic analysis revealed significant interspecies variations. OGI displayed higher concentrations of most of the marker phytoconstituents, except caffeic acid, whereas OTI exhibited greater abundance of essential oils. Several metabolites including salviaflaside, suavissimoside R1, tangshenoside-1 and tricoumaroyl spermidine were also observed first time in both species. Both OTI and OGI demonstrated strong anti-inflammatory activities in THP-1 cells, though with distinct activity profile. These findings highlight the chemical diversity and biological potentials of OTI and OGI, with relevence in nature inspired drug designs.PMID:41958075 | DOI:10.1002/cbdv.202503562

Oncoimmunology. 2026 Dec 31;15(1):2657070. doi: 10.1080/2162402X.2026.2657070. Epub 2026 Apr 9.ABSTRACTAging impairs vaccine responses. Dai et al. reported that defective cDC2 migration in immunized old mice, diminishing humoral and cellular immunity. Oral yeast-derived nanoparticles restore DC migration and vaccine efficacy. These findings establish impaired DC migration as a key mechanism of age-related immune decline, introducing a noninvasive strategy to correct immunosenescence.PMID:41957938 | DOI:10.1080/2162402X.2026.2657070

Lipids Health Dis. 2026 Apr 9. doi: 10.1186/s12944-026-02944-z. Online ahead of print.ABSTRACTBACKGROUND: Obesity prevalence is increasing globally, accompanied by increases in obesity-related diseases. While obesity is usually defined by BMI, the development of obesity-related disease might be better characterized by specific adipose tissue (AT) distributions or body composition subphenotypes. Serum metabolite patterns reflecting AT distribution could provide insights into potential underlying pathophysiological pathways and the interplay between AT depots. We therefore aim to identify metabolite signatures associated with specific AT depots and body composition subphenotypes.METHODS: Targeted metabolites (Biocrates p180 kit) were measured in fasted serum for N = 390 individuals from the population-based KORA-FF4 cohort (42% women, average age 56y). AT was measured by magnetic resonance imaging. Association of n = 29 AT depots (visceral (VAT), subcutaneous (SAT), pancreas, bone marrow, skeletal muscle, heart, kidney) and five body composition subphenotypes with 146 metabolites and 40 derived indicators were investigated by linear regressions with confounder adjustment for traditional cardiovascular disease risk factors and life style parameters.RESULTS: Subphenotypes were associated with 59, and single ATs with 275 metabolites or indicators, with VAT and SAT showing most associations. Compared to subphenotype I (low overall ATs), subphenotype II (average ATs) showed positive associations with diacylglycerophospholipids with differently saturated C32 fatty acid and sphingomyelins. Subphenotype III (high muscle and bone marrow fat) was negatively associated with total lysophosphatidylcholines (lyso-PCs) and total monounsaturated lyso-PCs, while showing a positive association with total long-chain acylcarnitines (C14-C18). Subphenotype IV (high SAT, high VAT and high liver fat) exhibited positive associations with short-chain acylcarnitines, alanine and aromatic amino acids. Subphenotype V (high pancreas fat fraction) was related to arginine and the ratio of ornithine and arginine as surrogate for ornithine synthesis. Three metabolites or indicators (lysoPC C 18.2, total polyunsaturated lyso-PC, phospholipase A2 as ratio of lyso-PC/diacyl- and acylalkylglycerophospholipids) were associated with all subphenotypes. These results were supported by the associations of individual ATs with metabolites or indicators.CONCLUSIONS: ATs, including ectopic fat depots such as pancreas fat, and subphenotypes of body composition show distinct serum metabolite patterns, which can serve as a first step to characterize potential obesity-related pathophysiological pathways.PMID:41957829 | DOI:10.1186/s12944-026-02944-z

J Nanobiotechnology. 2026 Apr 9. doi: 10.1186/s12951-026-04339-9. Online ahead of print.ABSTRACTBACKGROUND: Acute kidney injury (AKI) remains a major clinical challenge due to the lack of effective interventions. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show therapeutic promise for AKI, their exact mechanisms are largely to be understood.METHODS: Human umbilical cord-derived MSC-EVs were isolated, characterized, and tested in a murine bilateral renal ischemia reperfusion injury (bIRI) model and in hypoxia/reoxygenation (H/R) treated tubular epithelial cells in vitro. Integrated transcriptomic, miRNA, and biochemical analyses were performed to elucidate the metabolic pathways and molecular mechanisms underlying the renoprotective effects of MSC-EVs.RESULTS: MSC-EVs preferentially targeted injured kidneys and significantly improved renal function, ameliorated tubular injury, and suppressed inflammation in IRI-AKI. RNA sequencing and targeted metabolomics revealed substantial dysregulation of steroid metabolism after IRI, marked by activation of the cholesterol 25-hydroxylase (CH25H)/25-hydroxycholesterol (25HC) axis. Importantly, accumulated 25HC induced lipid peroxidation and ferroptosis in tubular epithelial cells. MSC-EVs treatment reversed these pathological changes by downregulating CH25H, lowering 25HC levels, and restoring redox homeostasis. miRNA profiling further identified miR-26b-5p as a key MSC-EVs cargo that directly targets the 3'UTR of CH25H mRNA to repress its expression. Notably, inhibiting miR-26b-5p within EVs abrogated their ability to suppress CH25H/25HC-driven ferroptosis, thereby demonstrating its essential role in the metabolic and cytoprotective actions of MSC-EVs.CONCLUSIONS: Our findings unveil the CH25H/25HC axis as a key metabolic checkpoint governing tubular ferroptosis in ischemic AKI. MSC-EVs deliver miR-26b-5p to suppress this axis, thereby rectifying oxysterol metabolism and preventing ferroptosis.PMID:41957810 | DOI:10.1186/s12951-026-04339-9

J Anim Sci Biotechnol. 2026 Apr 10;17(1):63. doi: 10.1186/s40104-026-01381-3.ABSTRACTBACKGROUND: The importance of glucan additives has been widely recognized in farm animals. Yet the precise role of POLYCAN, a β-glucan derived from the black yeast Aureobasidium pullulans SM-2001, remains limited in companion animals. Therefore, this study aims to evaluate its effect on performance, nutrient digestibility, hematology, and the gut microbiome and serum metabolites in beagle dogs.METHODS: Eight healthy male beagle dogs (8 months old; 10.70 ± 1.79 kg body weight; 3.00 ± 0.15 body condition score) were enrolled in a 10-week study comprising two phases: Phase 1 (weeks 0-4) and Phase 2 (weeks 6-10), separated by a 2-week washout period. The dogs were divided into two groups and fed a control (CON), basal diet and CON diet supplemented with 1,000 mg/d of POLYCAN. Each of two diets were provided using a cross over design for eight weeks, with four beagles assigned to each treatment. During the washout period, all dogs were fed only the commercial basal diet.RESULTS: Throughout the experimental period, POLYCAN supplementation did not affect growth performance, nutrient digestibility, or fecal pH in beagles. However, serum calcium, insulin-like growth factor-1 (IGF-1), growth hormone, and immunoglobulin G (IgG) concentrations were significantly higher (P < 0.05) in the POLYCAN-supplemented group. Alpha-diversity indices of microbial richness and evenness, as well as beta-diversity based on Bray-Curtis dissimilarity and unweighted UniFrac distances, showed no significant differences between treatment group. At the phylum level, Actinobacteria and Proteobacteria were more abundant in the POLYCAN group, followed by Fusobacteria and Bacteroidota. At family level, Lachnospiraceae, Ruminococcaceae, Coriobacteriaceae, Lactobacillaceae, Peptostreptococcaceae, and Erysipelotrichaceae exhibited higher relative abundances. Furthermore, the core gut microbiota at genus level was dominated by Micrococcus and Fusobacterium. Untargeted metabolomic analysis also revealed distinct group separation, identifying key metabolites including lumichrome, D-mannitol, and 2'-deoxycytidine. Pathway enrichment analysis indicated alterations in pyrimidine, histidine, and bile acid metabolism with higher metabolite abundance observed in the POLYCAN-treated group.CONCLUSION: Overall, our findings validate that adding 1,000 mg/d POLYCAN to canines' diet could serve as a functional nutraceutical to enhance their immune and gut health without affecting growth and digestion.PMID:41957655 | DOI:10.1186/s40104-026-01381-3

J Nanobiotechnology. 2026 Apr 10. doi: 10.1186/s12951-026-04369-3. Online ahead of print.ABSTRACTBACKGROUND: Aortic dissection (AD) is a lethal condition involving vascular smooth muscle cell (VSMC) transformation and extracellular matrix degradation. While gut microbiota dysbiosis is implicated in cardiovascular diseases, its role in stress-exacerbated AD pathogenesis is unknown. This study investigates the mechanism linking chronic restraint stress (CRS) to AD progression via gut microbiota modulation.METHODS: A β-aminopropionitrile (BAPN)-induced AD mouse model combined with CRS was utilized. Aortic dilation, mortality, and VSMC phenotype shift (assessed via α-SMA/SM22α and OPN/MMP2 expression) were evaluated. Gut microbiota composition was analyzed using 16 S rRNA sequencing. Microbiota depletion was achieved via antibiotics, and fecal microbiota transplantation (FMT) from CRS-exposed mice was performed. Serum metabolomics analysis, incorporating liquid chromatography-mass spectrometry (LC-MS), has demonstrated that outer membrane vesicles (OMVs) derived from Bacteroides vulgatus (B. vulgatus) contain high levels of the key metabolite stearic acid (SA). In vitro effects of stearic acid (SA) on AngII-induced JNK phosphorylation in VSMCs were tested, with validation using the JNK agonist anisomycin. Statistical analyses included correlation tests and appropriate comparisons (e.g., t-tests, ANOVA).RESULTS: CRS significantly accelerated aortic dilation, increased mortality, and promoted a synthetic VSMC phenotype (decreased α-SMA/SM22α, increased OPN/MMP2) in BAPN-treated mice. 16 S sequencing revealed CRS reduced gut microbiota diversity, particularly depleting B. vulgatus, which correlated negatively with AD severity. Antibiotic-mediated microbiota ablation mitigated CRS-aggravated AD, while FMT from CRS mice exacerbated it. Metabolomics identified stearic acid (SA), a metabolite derived from OMVs of B. vulgatus, as negatively correlated with aortic diameter. SA supplementation inhibited VSMC synthetic transformation, reduced AD incidence, and suppressed JNK/MAPK pathway activation in vivo. Mechanistically, SA attenuated AngII-induced JNK phosphorylation in VSMCs in vitro, an effect reversed by the JNK agonist anisomycin.CONCLUSIONS: CRS exacerbates the pathogenesis of AD by disrupting the gut microbiota, particularly by reducing the abundance of B. vulgatus and the levels of SA, which is a metabolite encapsulated in the OMVs of B. vulgatus. This leads to unchecked JNK/MAPK signaling, driving detrimental VSMC transformation. Restoration of SA inhibits this pathway and mitigates AD progression. Targeting the gut microbiota-B. vulgatus-SA axis presents a novel therapeutic strategy for stress-aggravated AD.PMID:41957631 | DOI:10.1186/s12951-026-04369-3

Commun Med (Lond). 2026 Apr 9. doi: 10.1038/s43856-026-01566-x. Online ahead of print.ABSTRACTBACKGROUND: Short-chain fatty acids are believed to mediate microbiome-host interactions. Acetic acid is the most abundant systemic short-chain fatty acid, but knowledge about its physiological functions comes mainly from rodent experiments, with limited human research particularly in the aging population.METHODS: In this cross-sectional observational study, we examined the association between the gut microbiota and plasma acetic acid, specifically investigating the mediating effect of plasma acetic acid on the relationship between the gut microbiota and blood lipid profile, body composition, brain gray matter volume, and cognitive performance in older adults. The gut microbiome was profiled using full-length 16S rRNA gene sequencing to enable taxonomic classification.RESULTS: Here we show that specific gut microbial co-abundance group is associated with plasma acetic acid levels. Higher plasma levels of acetic acid are associated with lower plasma triglyceride levels, higher high-density lipoprotein cholesterol levels, lower body mass index, lower body fat mass, higher thalamic volume, and higher cognitive performance in certain domains. Additionally, we show that plasma acetic acid mediates the relationship between gut microbiome on these health measures.CONCLUSIONS: This study identifies gut microbial group linked to plasma acetic acid and demonstrates its potential mediating role between the gut microbiome, blood lipid profile, brain volume and cognitive function in older adults. These insights pave the way for future research and highlight the potential of acetic acid as an intervention target for metabolic and neurological diseases, contributing to strategies that promote healthy aging.PMID:41957526 | DOI:10.1038/s43856-026-01566-x

Sci Rep. 2026 Apr 9. doi: 10.1038/s41598-026-47370-4. Online ahead of print.NO ABSTRACTPMID:41957486 | DOI:10.1038/s41598-026-47370-4

Nat Commun. 2026 Apr 9. doi: 10.1038/s41467-026-71323-0. Online ahead of print.ABSTRACTMetabolic dysregulation within the epithelial immune microenvironment (EIME) drives chronic inflammatory skin diseases like psoriasis, but the immune mechanisms and downstream consequences remain unclear. Here we perform in-depth metabolomic analysis showing that nucleotide metabolism is enhanced in psoriatic patients, with elevated adenosine levels closely correlating with disease severity. Single-cell and spatial transcriptomics analyses revealed that adenosine is primarily generated from a population of CD73high fibroblasts in psoriatic skin through enhanced metabolic processes and catalytic capability. Adenosine acts as a mediator between fibroblasts and keratinocytes, causing mitochondrial dysfunction and generating oxidative stress, resulting in the release of pro-inflammatory mediators in keratinocytes via ADORA2B. Deletion of Cd73 in fibroblasts, Adora2b in keratinocytes, or the use of pharmacological inhibitors of the pathways involved, reduces epidermal inflammation in the imiquimod- and IL-23A-induced mouse skin inflammation models. Our study thus identifies the CD73high fibroblast subsets as regulators of epithelial inflammation through metabolic microenvironment interactions with keratinocytes, providing proof of principle for therapeutic strategies targeting fibroblast-keratinocyte crosstalk in inflammatory skin diseases.PMID:41957361 | DOI:10.1038/s41467-026-71323-0

Nat Commun. 2026 Apr 9. doi: 10.1038/s41467-026-71524-7. Online ahead of print.ABSTRACTMutations in GDP-mannose pyrophosphorylase B (GMPPB) cause dystroglycanopathy, a rare neuromuscular disorder characterized by α-dystroglycan hypoglycosylation, yet the pathogenic mechanisms and therapeutic options remain poorly defined. To dissect the molecular basis of dystroglycanopathy, we generate Gmppb knockout and knock-in (P32L and R287Q) mice. We show that homozygous Gmppb knockout and P32L mutant mice (both male and female) display embryonic lethality, while heterozygous Gmppb-P32L (GmppbP32L/+) mice (both male and female) develop progressive muscular dystrophy accompanied by Purkinje cell loss, peripheral demyelination, and impaired nerve conduction. Integrated biochemical, transcriptomic, metabolomic and glycoproteomic analyses reveal widespread protein hypoglycosylation, metabolic dysregulation and suppressed Wnt/β-catenin signaling, resulting in defective differentiation and regeneration of muscle stem cells. Pharmacological activation of Wnt signaling with CHIR-99021 restores myogenic capacity and improves regeneration after injury. Furthermore, AAV-mediated GMPPB gene replacement reinstates α-dystroglycan glycosylation, normalizes GDP-mannose levels, and rescues motor and electrophysiological defects. Collectively, our findings establish GmppbP32L/+ mice as a faithful model of GMPPB-associated dystroglycanopathy and demonstrate that Wnt pathway activation and AAV-based gene therapy represent promising strategies for treating glycosylation-defective muscular dystrophies.PMID:41957353 | DOI:10.1038/s41467-026-71524-7

Metabolomics. 2026 Apr 9;22(2):49. doi: 10.1007/s11306-026-02426-4.ABSTRACTBACKGROUND: Hyperlipidemia refers to the abnormal elevation in the levels of one or more plasma lipids and lipoproteins.AIMS: The purpose of this study is to examine the underlying changes in metabolic pathways associated with the lipid-lowering activity of novel carboxamide derivatives.METHODS: Hyperlipidemia was induced in male Wistar rats by the administration of Triton WR-1339. Carboxamide derivatives, N-(3-benzoylphenyl) - 5-nitrofuran- 2-carboxamide (Compound A) and N-(4-acetylphenyl) - 5-nitrofuran- 2-carboxamide (Compound B) were administered intragastrically and their activity was compared to the lipid-lowering drug fenofibrate. Metabolic analysis of plasma samples was done using proton nuclear magnetic resonance spectrometer equipped with a cryogenic probe. Moreover, expression levels of related genes were analyzed in liver, kidney and heart tissues using qPCR.RESULTS: The tested carboxamide compounds A and B significantly reduced the elevated plasma triglycerides levels by 83% and 68%, respectively. Metabolomic analysis results revealed the impact of carboxamide compounds on the levels of 22 potential biomarkers. Carboxamide compounds partially restored the dysregulated levels of the differential metabolites and reversed the metabolic disturbance induced in hyperlipidemic rats. These results were comparable to those observed in the fenofibrate group. Carboxamide compounds activity was attributed to the regulation of not only lipid metabolism but also energy metabolism, purine metabolism and amino acid metabolism. Moreover, metabolomic results were connected to the expression of related genes in different tissues. Carboxamide compounds were able to restore gene expression levels of related genes, upregulating SDHA expression in liver, SLC13A3 and SDHA in kidney, along with upregulating SLC5A3 expression and downregulating SLC25A10 in the heart.CONCLUSION: Overall, based on the lipid profile results and metabolic analysis supported by molecular analysis, both carboxamide derivatives showed promising lipid-lowering activity and displayed regulatory activity of metabolic pathways that were disturbed by hyperlipidemia induction. The efficacy of carboxamide compounds was comparable to the conventional lipid-lowering drug, fenofibrate. Compound A exhibited superior activity significantly lowering triglycerides levels and restoring many of the metabolic alterations induced in hyperlipidemia.PMID:41957326 | DOI:10.1007/s11306-026-02426-4

Curr Microbiol. 2026 Apr 9;83(6):289. doi: 10.1007/s00284-026-04886-2.ABSTRACTPhellinus pini is a large fungus with significant medicinal value. Building on the previously discovered inhibitory activity of Phellinus pini polysaccharides (PPP) against influenza viruses, this study established an influenza A mouse model through the intranasal instillation of an H1N1/PR8 virus solution. Using a combination of metabolomics and gut microbiota analysis techniques, the study further elucidated a novel mechanism by which PPP regulates influenza-induced lung damage via the "gut-lung axis". Results showed PPP reversed lung lesions, reduced the lung index and viral load in lung tissue, and exerted anti-inflammatory effects by downregulating inflammatory cytokine expression, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Additionally, 49 potential biomarkers were identified in fecal samples collected from mice infected with influenza A. After low-dose PPP administration, 16 of these biomarkers returned to normal levels. Further pathway analysis revealed that PPP primarily exerts its antiviral effects by influencing pyrimidine metabolism, steroid hormone biosynthesis, tyrosine metabolism. Gut microbiota analysis revealed that PPP improves the gut microbiota environment by significantly increasing the abundance of beneficial bacteria, such as Alistipes, which is closely related to fructose and mannose metabolism and β-lactam resistance pathways. Spearman's correlation analysis revealed that the 16 PPP-regulated biomarkers were correlated with Alistipes and pharmacological parameters. These integrated results suggest a potential mechanism by which PPP alleviates influenza-driven lung injury through the modulation of the gut microbiota-host metabolism axis. This study provides correlative evidence supporting the involvement of the gut-lung axis in PPP's protective effects, offering theoretical insights for future antiviral research.PMID:41957294 | DOI:10.1007/s00284-026-04886-2

Clin Rheumatol. 2026 Apr 10. doi: 10.1007/s10067-026-08060-8. Online ahead of print.NO ABSTRACTPMID:41957291 | DOI:10.1007/s10067-026-08060-8

Sci Rep. 2026 Apr 9. doi: 10.1038/s41598-026-47892-x. Online ahead of print.ABSTRACTAmong the various natural products found in Hydrangea species, the bioactive dihydroisocoumarin, phyllodulcin (PD) stands out as a non-caloric, high-intensity sweetener, which is up to 800 times sweeter than sucrose. Additionally, PD possesses medicinal properties and plays plant-specific roles in pathogen resistance and abiotic stress tolerance. However, the biosynthetic pathway of PD in Hydrangea has remained unexplored. To identify intermediates and candidate genes involved in the biosynthesis of PD, we first conducted a screening approach, in which 14 out of 182 different Hydrangea accessions were selected for their contrasting foliar concentrations of PD and closely related hydrangenol (HD). Analysis of phenylpropanoid pathway (PPP) metabolites showed that accessions of H. macrophylla with high PD levels displayed distinct metabolite profiles compared to those with low PD concentrations. Specifically, caffeic acid, ferulic acid, and their derivatives, such as scopolin, scopoletin, esculetin, and fraxetin, were predominant in accessions with low PD concentrations. Conversely, the metabolite levels of phenylalanine, umbelliferone, p-coumaric acid, naringenin, resveratrol, and thunbergiol C (Thn C) were higher in accessions producing more PD. Transcriptome analysis revealed differentially expressed genes involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and stilbene biosynthesis pathways that are crucial for PD biosynthesis. Moreover, the identification of cyclase and ketoreductase genes, which were upregulated in accessions with high PD, provided further evidence for the biosynthetic pathway leading to PD. Based on metabolite profiling and gene expression data, we propose a hypothetical biosynthetic pathway for PD.PMID:41957113 | DOI:10.1038/s41598-026-47892-x

Nat Commun. 2026 Apr 9. doi: 10.1038/s41467-026-71644-0. Online ahead of print.ABSTRACTPolymerization-based wastewater treatment offers reduced oxidant demand and product recovery, yet practical application is hindered by catalyst fouling and unselective reactions due to single-site competition. Here, we report a readily synthesized and scalable ZnO/CuO catalyst featuring dual functional sites that decouple pollutant and oxidant activation. Zn sites preferentially adsorb/activate organics, whereas Cu sites predominantly activate the oxidant. This site differentiation programs two pathway regimes governed by pollutant electronic structure: electron-transfer-mediated polymerization for electron-rich substrates and radical-induced mineralization for electron-deficient substrates. Importantly, radicals generated during mineralization depolymerize the accumulated foulant layer in situ, effecting autonomous catalyst regeneration with a 2.5-fold performance recovery and reduced external regeneration demand. Process performance is validated in a 200 L self-circulating reactor, maintaining 98% removal efficiency for both pollutant classes over ten cycles. Toxicological profiling across multiple biological models, supported by metabolomics, confirmed effective detoxification of multi-pollutant wastewater, including restoration of normal metabolic function in zebrafish (e.g., lipid and glutathione metabolism). This study establishes a dual-site cooperative catalysis framework that leverages intrinsic wastewater chemistry for self-regeneration, showcasing a complete trajectory from atomic-scale design to reactor-scale implementation.PMID:41957009 | DOI:10.1038/s41467-026-71644-0

Chin Med J (Engl). 2026 Apr 9. doi: 10.1097/CM9.0000000000003990. Online ahead of print.ABSTRACTImmunoglobulin G4-related disease (IgG4-RD) is a chronic disease characterized by inflammation and fibrosis within multiple organs. The fundamental immunopathogenic mechanisms of IgG4-RD remain largely unidentified. Advancements in multiple omics technologies have enabled researchers to characterize the cellular heterogeneity of IgG4-RD. The pursuit of understanding the immune dysfunction in IgG4-RD is principally guided by genomic, transcriptomic, and proteomic investigations, encompassing three crucial aspects of the traditional central dogma. Besides, genetic and epigenetic mechanisms, along with alterations in posttranslational modifications (PTMs) and small molecules identified through metabolomics and microbiomics studies, interact to uncover the functional basis of abnormal cellular activities. Here, we systematically review the application of multiple omics technologies to uncover the fundamental mechanisms driving IgG4-RD, organized around the traditional central dogma of molecular biology and its remodeling. We also propose an integrated pathophysiological model of multi-layered immune dysregulation, illustrating a self-sustaining loop of immune activation and tissue remodeling in IgG4-RD. It is believed that adopting a combination of diverse technological advancements to examine a series of cellular processes holds promise for the development of personalized approaches to managing IgG4-RD patients.PMID:41956965 | DOI:10.1097/CM9.0000000000003990

Injury. 2026 Apr 3:113245. doi: 10.1016/j.injury.2026.113245. Online ahead of print.ABSTRACTThis letter critically appraises the recent multi-omics study by Gou et al. proposing early biomarkers for venous thromboembolism after severe trauma, highlighting concerns regarding residual confounding, physiological instability at sampling, and limited external validity. While innovative and hypothesis-generating, the findings require prospective validation with rigorous adjustment for injury severity and resuscitation factors before clinical translation.PMID:41956843 | DOI:10.1016/j.injury.2026.113245

Gut. 2026 Apr 9:gutjnl-2025-336025. doi: 10.1136/gutjnl-2025-336025. Online ahead of print.ABSTRACTBACKGROUND: Certain gut bacteria are associated with improved responses to immunotherapy.OBJECTIVE: We aim to identify bacteria that inhibit colorectal cancer (CRC) progression and enhance immunotherapy efficacy.DESIGN: The abundance of bacteria in CRC patients was evaluated in our in-house cohorts and validated in published datasets. The effect of candidate bacterium with anti-PD-1 therapy was determined in two syngeneic mouse models of MC38 (microsatellite instability-high) and CT26 (microsatellite stable, MSS), transgenic Apc min/+ mice and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC tumourigenesis model. Immune landscape changes were identified by multicolour flow cytometry and immunohistochemistry staining. Metabolomic profiling was performed on stool, serum and tumour tissues.RESULTS: Bifidobacterium catenulatum was significantly depleted in stool samples of 110 CRC patients compared with 112 healthy controls, which was further validated in 3 published metagenomic datasets comprising 198 CRC patients and 176 normal subjects. Oral administration of B. catenulatum inhibited tumour growths in multiple CRC models including MC38 and CT26 syngeneic models, Apcmin/+ mice and AOM/DSS-induced CRC. Notably, B. catenulatum synergised with anti-PD-1 therapy through enhancing intratumoural CD8+ T cell infiltration in MSS CRC models of Apcmin/+ mice and CT26 allografts. B. catenulatum-derived acetate was identified as the functional metabolite. Mechanistically, acetate directly bound to MCT-4 in CD8+ T cells and activated mitogen-activated protein kinase signalling. Pharmacological and genetic MCT4 ablation abolished acetate-mediated CD8+ T cell activation in vitro.CONCLUSION: B. catenulatum suppresses colorectal tumourigenesis through generating acetate, which also improves anti-PD-1 efficacy through activating CD8+ T cells in MSS CRC. B. catenulatum is a potential adjuvant to improve immunotherapy against CRC.PMID:41956809 | DOI:10.1136/gutjnl-2025-336025