PubMed

Mol Brain. 2026 Feb 24. doi: 10.1186/s13041-026-01281-7. Online ahead of print.ABSTRACTThe Molecular and Cellular Cognition Society (MCCS) Meeting (NYU Abu Dhabi, February 17-18th, 2025) brought together leading experts in neuroscience to present breakthroughs addressing the molecular and neuronal mechanisms underlying cognition, emotion, and behavior. This review is inspired by the meeting, which emphasized emerging molecular and cellular mechanisms including epigenetic regulation of memory, dynamic engram synapse formation, synaptic epitranscriptomics, metaplasticity, and metabolomic-neuroimmune interactions. Learning and cognition have increasingly become focal points within broader advances in neuroimaging innovations, high-throughput molecular diagnostics, and computational modeling geared toward precision neurodiagnostics and personalized neurocognitive therapeutics. The meeting also scrutinized how stress, circadian rhythm disruption, and neuroinflammation converge to shape cognitive resilience and dictate dysregulated attention and learning mechanisms underlying cognitive dysfunction. Such conditions span neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Collectively, the studies highlighted how experience-dependent synaptic and circuit-level changes influence cognition, sensory integration, and motor output. Further discussions addressed the translational implications of these findings, including their potential to advance neurotechnologies such as targeted neuromodulation, pharmacogenomic interventions, and AI-based biomarker discovery. Drawing on the scientific discussions at the MCCS-NYUAD meeting, we synthesize a research roadmap for the future of precision neurocognitive medicine by integrating molecular cognition with clinical neuroscience. Future research priorities include bridging gaps in molecular biomarkers of neurocognitive aging and leveraging AI-driven neurodiagnostics and large-scale biological data analytics. Overall, the meeting laid the groundwork for a shift in neuroscience toward linking mechanistic understanding with clinical relevance to enhance cognitive health and develop targeted neurotherapeutic approaches.PMID:41772596 | DOI:10.1186/s13041-026-01281-7

BMC Genomics. 2026 Mar 2. doi: 10.1186/s12864-026-12692-0. Online ahead of print.NO ABSTRACTPMID:41772422 | DOI:10.1186/s12864-026-12692-0

Nat Methods. 2026 Mar 2. doi: 10.1038/s41592-026-03007-y. Online ahead of print.ABSTRACTDeconvolution algorithms estimate cell-type abundances from tissue-level data, enabling systematic cellular analysis of large cohorts. However, most deconvolution algorithms are specifically designed for single-omics data, thereby limiting their generalizability and scalability for various omics data from different cohorts. Here we present DECODE, a universal deconvolution framework for both cell types and cell states that can be applied to transcriptomic, proteomic and metabolomic data, and that seamlessly integrates diverse multiomics tissue datasets at the cellular level. DECODE fills the gap in metabolomics deconvolution and significantly outperformed state-of-the-art methods on different omics data across donors, disease conditions, healthy states, datasets and measurement platforms. In addition, DECODE exhibits high robustness in scenarios that are closer to real applications so it can accurately deconvolve known cell types even when the reference single-cell data are incomplete. DECODE will serve as a powerful tool for the fully extending multiomics cohort data into cellular level.PMID:41772096 | DOI:10.1038/s41592-026-03007-y

Sci Rep. 2026 Mar 2. doi: 10.1038/s41598-026-40137-x. Online ahead of print.NO ABSTRACTPMID:41771971 | DOI:10.1038/s41598-026-40137-x

Sci Rep. 2026 Mar 2. doi: 10.1038/s41598-026-41835-2. Online ahead of print.NO ABSTRACTPMID:41771968 | DOI:10.1038/s41598-026-41835-2

NPJ Parkinsons Dis. 2026 Mar 2. doi: 10.1038/s41531-026-01299-7. Online ahead of print.ABSTRACTGut ecosystem dysfunction is implicated in Parkinson's disease (PD), but integrative faecal metabolome-metagenome links are undefined. We explored these interactions in Chinese PD patients to develop diagnostic panels. Targeted faecal metabolomics (LC‒MS/MS) was performed on 132 PD and 113 healthy controls (HCs) and shotgun metagenomics was integrated for 39 PD/HC pairs. We identified 33 significantly altered faecal metabolites in PD (FDR-P < 0.05). A novel 12-metabolite panel could distinguish PD from HCs. Multi-omic integration revealed gut ecosystem dysfunction manifests via co-disruptions in microbial genes (e.g., amino acid metabolism genes) and metabolites. Critically, a combinatorial diagnostic panel integrating faecal metabolites and microbial gene markers achieved exceptional PD detection (AUC = 0.961, 95% CI = 0.923-0.998). This study deciphers metabolome-metagenome links driving gut dysfunction in PD, identifying amino acid metabolism as a core perturbed pathway. The novel diagnostic panels provide mechanistic insights and clinical tools for PD precision diagnosis.PMID:41771902 | DOI:10.1038/s41531-026-01299-7

Cell Death Dis. 2026 Mar 2. doi: 10.1038/s41419-026-08507-5. Online ahead of print.ABSTRACTAtaxia telangiectasia (AT) is a rare multisystem disorder caused by the loss of functional ATM protein, leading to immunodeficiency, cancer predisposition, neurodegeneration, diabetes, heart failure, and premature aging. Although ATM's role as a sensor of DNA double-strand breaks (DSBs) is well established, the mechanisms underlying the diverse AT phenotypes remain incompletely understood, with evidence suggesting they extend beyond DSB sensing. Here, we uncover widespread glycogen accumulation as a key feature of AT cells and tissues, driven by dysregulated glucose metabolism and impaired mitochondrial respiration assessed with a multidimensional approach including metabolomics, flux analysis, histopathology, bioenergetic measurements, and electron tomography. These metabolic defects contribute to reduced cellular viability and premature senescence observed in AT patient-derived cells. Strikingly, inactivation of FNIP2, which controls mitochondrial respiration, partially rescues these defects in AT cellular models. We show that FNIP2 interacts with the SERCA2b calcium channel, and its inactivation enhances cytoplasmic calcium availability, stimulating mitochondrial respiration and increasing glucose consumption. This metabolic reprogramming prevents glycogen accumulation and improves survival in AT primary cells. Our findings provide novel insights into AT pathophysiology and indicate the FNIP2-SERCA2b axis as a novel potential target for mitigating the systemic effects of AT and improving outcomes in this complex disease.PMID:41771847 | DOI:10.1038/s41419-026-08507-5

Chem Biodivers. 2026 Mar;23(3):e03217. doi: 10.1002/cbdv.202503217.ABSTRACTEuphorbia royleana (Euphorbiaceae) is an important succulent species and commonly known as Royle's spurge. It is used to treat inflammation, paralysis, and brain-related problems. The literature revealed that E. royleana was not well explored for phytochemical diversity and health benefits. Therefore, the current study was focused on investigating solvent-dependent chemical diversity and bioactive properties across stems, leaves, and reproductive tissue (flowers and seeds). Ethanol, 50% ethanol, and water extracts were prepared, in which the water extract of leaves showed the highest extraction efficiency (16.97%). Total phenolic content was found higher in 50% ethanol extract (112.65 ± 3.27 mg GAE/g), while flavonoid content was found higher in ethanol extract (217.31 ± 13.55 mg RE/g) of reproductive parts. Further, UPLC-PDA-based targeted polyphenol profiling showed gallic acid (23.658 ± mg/g) as the most abundant polyphenol among different parts. UHPLC-QTOF-IMS-based non-targeted metabolite profiling revealed 74 metabolites (terpenoids, flavonoid glycosides, and phenylpropanoids). Multivariate statistical analysis of identified metabolites further suggested clear organ- and solvent-specific variations. Moreover, antioxidant and tyrosinase inhibition activities were performed, and the highest activity was found in the ethanol extract of reproductive tissues. The current study provides new insights into the chemical diversity of E. royleana, highlighting its ecological significance and chemotaxonomic value within Euphorbiaceae.PMID:41771821 | DOI:10.1002/cbdv.202503217

Life Sci Alliance. 2026 Mar 2;9(5):e202503555. doi: 10.26508/lsa.202503555. Print 2026 May.ABSTRACTSpinocerebellar ataxia type 8 (SCA8) is a member of a group of dominantly inherited, debilitating neurological diseases caused by CAG•CTG expansions for which there are no effective treatments. RAN translation, which was discovered in SCA8, has previously been shown to occur across CAG and CUG expansion transcripts, making treatments for SCA8 potentially relevant to a broad group of diseases, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, Huntington's disease, and myotonic dystrophy type 1. In addition, CUG and CAG expansion transcripts have been reported to cause RNA gain-of-function effects. Using SCA8 BAC transgenic mice as a model for CAG•CTG expansion diseases, we now show that metformin improves ambulatory performance using rotarod, DigiGait, and open-field testing. At the molecular level, metformin-treated mice show reduced RAN protein levels and improved splicing, without altering sense or antisense RNA levels. Metformin-treated mice also show decreased neuroinflammation, with reduced astrogliosis and fewer activated microglia. These data provide strong preclinical support for testing metformin in clinical trials for SCA8 and potentially the broader group of CAG•CTG repeat expansion disorders.PMID:41771688 | DOI:10.26508/lsa.202503555

BMJ Open. 2026 Mar 2;16(3):e100158. doi: 10.1136/bmjopen-2025-100158.ABSTRACTINTRODUCTION: Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.METHODS AND ANALYSIS: This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.ETHICS AND DISSEMINATION: This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.PMID:41771597 | DOI:10.1136/bmjopen-2025-100158

Food Chem Toxicol. 2026 Feb 28:116040. doi: 10.1016/j.fct.2026.116040. Online ahead of print.ABSTRACTDiazepam is a widely used benzodiazepine, and its presence in animal-derived food products is strictly prohibited in China. However, the occasional detection of diazepam residues in freshwater fish has raised growing concerns regarding the safety of aquatic products and potential risks to human health. This study integrated network toxicology, cytotoxicity tests, transcriptomics and metabolomics to evaluate the neurotoxic effects and underlying mechanisms associated with diazepam and its principal metabolite, nordazepam. Both compounds exhibited notable neurotoxic effects, with microglial cells (HMC3) demonstrating greater sensitivity compared to oligodendrocytes (Mo 3.13) and neurons (SH-SY5Y). Network analysis and experimental data identified STAT3, CASP3, and TSPO as core targets mediating neurotoxicity associated with withdrawal symptoms, cognitive deficits, and motor impairments. Molecular docking and dynamics simulations further confirmed stable binding to these targets. These findings suggest that current risk assessments of diazepam residues necessitate reevaluation and underscore the critical role of microglial cells in diazepam and nordazepam-induced neurotoxicity, providing valuable insights for public health and dietary exposure safety.PMID:41771474 | DOI:10.1016/j.fct.2026.116040

Environ Res. 2026 Feb 28:124148. doi: 10.1016/j.envres.2026.124148. Online ahead of print.ABSTRACTPerfluorooctanoic acid (PFOA) in soil poses a significant threat to reptile health. Given the global decline in reptile abundance and diversity, understanding reptile responses to prolonged PFOA-contaminated soil is urgently needed. In this study, Eremias argus, small lizards distributed across northern China, were exposed to PFOA (0.05 and 0.5 mg/kg) for 60 days. PFOA burden, physiological parameters, histopathological features, untargeted metabolomics, and 16S rDNA sequencing were performed to investigate the effects of soil PFOA exposure. The results revealed pronounced sex-dependent differences in PFOA accumulation and associated biological responses. Males exhibited significantly higher internal PFOA levels, whereas females showed comparatively lower burdens, which may be associated with maternal transfer of PFOA to eggs. These sex-dependent differences were accompanied by distinct pathological and metabolic alterations. Specifically, males exhibited severe intestinal barrier damage, reduced abundance of Bacteroidetes, and metabolic disturbances related to bile acid homeostasis. In contrast, females maintained relatively intact intestinal architecture and more stable Bacteroidetes populations, together with comparatively stable bile acid-related metabolic profiles, which potentially facilitating contaminant excretion. Overall, these findings provide mechanistic insights into how soil PFOA exposure may affect reptile physiology during sensitive life-history stages, thereby offering relevant information for future ecological risk assessments.PMID:41771469 | DOI:10.1016/j.envres.2026.124148

Crit Rev Oncol Hematol. 2026 Feb 28:105233. doi: 10.1016/j.critrevonc.2026.105233. Online ahead of print.ABSTRACTMaternally Expressed Gene 3 (MEG3), a long non-coding RNA (lncRNA) plays a crucial role in regulating cellular processes, including apoptosis, proliferation, and tumor suppression. MEG3 is located at the DLK1-MEG3 locus on human chromosome 14q32.3 and is implicated in multiple cancers and pathological conditions. MEG3 expression is often downregulated in various tumors due to promoter hypermethylation, leading to tumor progression and poor prognosis. Yet, it showed paradoxical expression in other malignancies. MEG3a interacts with multiple molecular pathways, including p53, NF-κB, EZH2, and miRNAs, influencing gene expression and cellular responses. Recent studies highlight its role as a competing endogenous RNA (ceRNA), modulating miRNA activity to regulate tumor-related genes. MEG3 has been identified as a potential therapeutic target in breast cancer, glioblastoma, neuroblastoma, and osteosarcoma, where its restoration inhibits tumor growth, metastasis, and drug resistance. Additionally, MEG3 contributes to epigenetic regulation, chromatin remodeling, and metabolic reprogramming in cancer cells. Its tumor-suppressive functions make it a promising biomarker for cancer diagnosis and prognosis, as well as a candidate for targeted therapies. Despite extensive research, the precise molecular mechanisms underlying MEG3 function remain incompletely understood, underscoring the need for further studies to explore its therapeutic potential in oncology and other diseases.PMID:41771457 | DOI:10.1016/j.critrevonc.2026.105233

J Allergy Clin Immunol Pract. 2026 Feb 28:S2213-2198(26)00176-5. doi: 10.1016/j.jaip.2026.02.024. Online ahead of print.ABSTRACTFood allergy affects approximately 8% of children and 11% of adults in the United States. Available treatment including oral immunotherapy and anti-IgE are not known to lead to remission. There is now increasing evidence implicating the gut microbiome as a key regulator of allergic inflammation. Distinct microbial and metabolomic alterations characterize food-allergic individuals, and gnotobiotic mouse models show that fecal microbiota from food-allergic donors transfers allergic sensitization, whereas microbiota from healthy donors protects from anaphylaxis through induction of tolerogenic Foxp3+RORγt+ regulatory T cells. Goblet cell-derived resistin-like molecule beta (RELM β) induces food allergy through modulation of the gut microbiome and depletion of indole-producing species. These findings have inspired the development of five microbial therapeutics approaches: probiotics, rationally defined bacterial consortia, fecal microbiota transplantation, metabolite-based approaches, and biologics targeting dysbiosis-associated pathways. Early-phase clinical studies support feasibility, yet long-term safety, durability, and reproducibility remain uncertain. Major challenges include inter-individual variability, ecological complexity, and regulatory standardization. Microbiome-directed therapeutics hold promise to transform food allergy management from temporary desensitization toward remission and durable immune tolerance. The application of systems biology approaches integrating metabolomics, transcriptomics, and immune phenotyping will be essential to unravel the complex host-microbial interactions that underlie the efficacy of these approaches.PMID:41771438 | DOI:10.1016/j.jaip.2026.02.024

J Ethnopharmacol. 2026 Feb 28:121451. doi: 10.1016/j.jep.2026.121451. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The coexistence of unhealthy diets and circadian rhythm disturbances contributes to the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), for which effective therapies are still lacking. Radix Bupleuri (BR) is a traditional Chinese medicine recognized for its hepatoprotective and lipid-modulating effects. However, the precise mechanisms by which it exerts therapeutic benefits in MASLD are not fully elucidated.AIM OF THE STUDY: This study aimed to clarify the protective effects of BR alleviates MASLD in rats and to thoroughly explore its possible action pathways and molecular mechanisms.MATERIALS AND METHODS: To establish MASLD models, rats underwent combined high-fat diet feeding and chronic circadian rhythm disruption (HFD-CRD) via a phase-delaying light-dark cycle (12 h light/12 h dark, with an 8 h delay in light onset every 48 h), followed by 6-week oral administration of BR fractions of varying polarities. Positive controls included Bicyclol and Melatonin. Physiological and biochemical assessments included body weight, liver and epididymal fat mass, locomotor activity, fasting blood glucose, oral glucose tolerance, serum lipid profile, and liver function markers. Hepatic steatosis was evaluated by H&E staining. Mechanistic insights were obtained via hepatic transcriptomics, untargeted metabolomics, targeted bile acid profiling, and qPCR validation.RESULTS: BR treatment, particularly the high polarity fraction of BR (BH), significantly reduced body weight gain, hepatic steatosis, serum ALT and AST levels, and improved glucose tolerance, lipid metabolism, and locomotor activity. Metabolomics revealed BH-mediated normalization of 25 dysregulated liver metabolites, particularly bile acid derivatives. Transcriptomics demonstrated that BH reversed HFD-CRD-induced transcriptional alterations, primarily enriching in bile secretion and insulin signaling pathways. Integrated metabolomic-transcriptomic correlation analyses demonstrated that bile acid and glucolipid related genes were closely linked with metabolic phenotypes. Targeted bile acid quantification confirmed that BH comprehensively restored the dysregulated bile acid pool, with the DCA/HCA pair emerging as the most sensitive biomarker of metabolic remodeling. Functional validation further showed that BH reversed aberrant expression of bile acid secretion and glucose metabolism genes and activated hepatic and intestinal TGR5/GLP-1 signaling, thereby improving bile acid homeostasis, glucose metabolism, and gut barrier integrity.CONCLUSIONS: BR ameliorates HFD-CRD-induced MASLD by restoring bile acid homeostasis, modulating glucolipid metabolism, and activating the TGR5/GLP-1 axis, expanding the pharmacological basis of BR for liver disorders and offering novel insights into multi-target MASLD therapeutics.PMID:41771387 | DOI:10.1016/j.jep.2026.121451

Free Radic Biol Med. 2026 Feb 28:S0891-5849(26)00176-0. doi: 10.1016/j.freeradbiomed.2026.02.072. Online ahead of print.ABSTRACTLung transplantation serves as a life-saving therapeutic intervention for patients with end-stage pulmonary diseases, with the lung ischemia-reperfusion injury (LIRI) as the major challenge. Correcting lipid metabolic dysregulation in alveolar epithelial cells by targeting key causative molecules is a promising therapeutic strategy for LIRI. Quantitative proteomics and metabolomics revealed that dysregulated fatty acid metabolism dominates the LIRI metabolic network. Transcriptome analysis of human LIRI samples indicated disorder of fatty acid oxidation and mitochondrial homeostasis disruption. Within this pathway, hydroxyacyl-CoA dehydrogenase (HADH), a key mitochondrial β-oxidation enzyme, was identified as a potential biomarker (AUC = 0.79). In Sprague-Dawley (SD) rats exposed to 60-min ischemia and 2-h reperfusion (I/R), the pulmonary expression of HADH decreased by about 50%. HADH overexpression mediated by adenoviruses conferred multi-faceted pulmonary protection both in vivo and in vitro: in I/R-subjected SD rats, it alleviated mitochondrial impairment, boosted ATP production, diminished ROS levels, and limited alveolar apoptosis; these effects were corroborated in RLE-6TN AT2 cells exposed to 2-h hypoxia/4-h reoxygenation (H/R). Building on evidence that lysine succinylation modulates mitochondrial enzyme activity, we further identified 7 succinylated lysine residues within the catalytic domain of HADH-rather than its dimerization domain-highlighting its potential functional significance. Specifically, 3-oxoacid CoA-transferase 1 (OXCT1) increased HADH succinylation at lysine 81 (K81), stabilizing HADH by blocking its degradation via chaperone-mediated autophagy (CMA). The activated OXCT1-HADH axis reduced non-esterified fatty acid accumulation. OXCT1-succinylated K81 disrupted binding between HADH and heat shock protein A8 (HSPA8), a CMA recognition factor. HADH has a canonical HSPA8-binding CMA motif; mutating its key glutamine (Q132) or silencing HSPA8 inhibited CMA-mediated HADH degradation. Virtual screening shows that small-molecule drugs binding to HSPA8's active pocket (near its interaction region with HADH K81) have potential in treating post-lung transplantation dysfunction. Our findings elucidate the succinylation-dependent regulatory mechanism of HADH and provide a potential therapeutic strategy for LIRI.PMID:41771361 | DOI:10.1016/j.freeradbiomed.2026.02.072

Biochem Biophys Res Commun. 2026 Feb 21;810:153512. doi: 10.1016/j.bbrc.2026.153512. Online ahead of print.ABSTRACTAIMS: Given the high prevalence of periodontitis and potential for undetected primary hyperparathyroidism (pHPT) to exacerbate periodontal damage, managing pHPT in advanced periodontitis (stages III/IV) is critical. The causal link between pHPT and periodontitis remains unclear. This study aims to investigate the causal effect and mechanisms between hyperparathyroidism and periodontitis.METHODS: A two-sample Mendelian randomization study used genome-wide association studies (GWAS) summary data to explore the causal link between hyperparathyroidism and periodontitis, employing single nucleotide polymorphisms (SNPs) as instrumental variables and methods like MR-Egger regression and Weighted median for robust results. PTH levels were detected on samples from both healthy and periodontitis-affected gingival tissues and gingival crevicular fluids. We assessed the impact of PTH on periodontal inflammation through treating gingival fibroblasts with PTH and detecting endoplasmic reticulum stress-related markers. Transcriptomics and metabolomics analyses were integrated to explore genetic pathways related to PTH.RESULTS: Hyperparathyroidism increased the risk of periodontitis, but analyses of periodontitis on hyperparathyroidism showed no reverse causality. PTH levels increased in gingival tissues and gingival crevicular fluid. Multi-omics analysis revealed significant gene and metabolite enrichment in calcium signaling and parathyroid hormone pathways. Since calcium ions are mainly from the endoplasmic reticulum, we focused on endoplasmic reticulum stress and found its effect on lessening PTH-induced periodontal inflammation.CONCLUSIONS: This study suggests that periodontitis may serve as a warning sign for pHPT, highlighting the importance of screening for hyperparathyroidism in periodontitis patients. The principal molecules involved in the endoplasmic reticulum stress pathway present promising therapeutic targets for improving periodontal health in patients with hyperparathyroidism.PMID:41771208 | DOI:10.1016/j.bbrc.2026.153512

Cancer Discov. 2026 Mar 3. doi: 10.1158/2159-8290.CD-25-1449. Online ahead of print.ABSTRACTEsophageal squamous cell carcinoma (ESCC) exhibits heterogeneous responses to chemoimmunotherapy, with only a minority achieving durable benefit, necessitating dynamic precision monitoring. Through longitudinal plasma metabolomics of 541 serial samples from 252 ESCORT-1st trial patients receiving chemoimmunotherapy plus three independent cohorts of 288 samples, we established an integrated risk assessment framework spanning the entire therapeutic continuum: (1) a baseline predictor for initial responders based on metabolite signatures; (2) an on-treatment predictor in prognosticating long-term responders among initial ones based on treatment-induced metabolic shift patterns; (3) a real-time model based on dual alteration of sphingolipid and glycerophospholipid dynamically stratifying progression risk. Meanwhile, two dietary metabolites, garlic-derived S-allyl-L-cysteine and cruciferous vegetable-derived indole-3-carbinol, were confirmed to improve outcomes by promoting NK cells infiltration and reversing CD8+ T cells exhaustion. In conclusion, we provide the first metabolomic roadmap for precision chemoimmunotherapy in ESCC, unifying baseline prediction, longitudinal surveillance, and dietary modulation into clinically actionable paradigm.PMID:41771153 | DOI:10.1158/2159-8290.CD-25-1449

J Agric Food Chem. 2026 Mar 2. doi: 10.1021/acs.jafc.5c15440. Online ahead of print.ABSTRACTPolyhydroxyalkanoates (PHA) are promising biodegradable alternatives to petroleum-based plastics, but high production costs limit their deployment. In this study, we evaluated a cosubstrate strategy combining vanillic acid (VA), representative of lignin-derived aromatics, with palm oil (PO) recovered from oil palm fruit residues to enhance PHA synthesis in Pseudomonas putida. Cofeeding 4 g/L VA and 4 g/L PO increased PHA titer to 1.13 g/L, a 52.7% improvement over VA alone, and yielded a new monomer, 3-hydroxyhexanoate (3HHx). Integrated transcriptome and metabolomic analyses revealed that cosubstrate metabolism attenuated TCA flux, enhanced β-oxidation and hydroxyacyl precursor pools, and altered NAD(P)H turnover and membrane lipids. These shifts were correlated with expanded monomer diversity. This study demonstrates that cofeeding lignin-derived aromatics with agricultural oils provides a synergistic route to improve PHA yield and diversify monomer composition, linking biomass valorization with circular, low-carbon material production.PMID:41770876 | DOI:10.1021/acs.jafc.5c15440

PLoS One. 2026 Mar 2;21(3):e0343024. doi: 10.1371/journal.pone.0343024. eCollection 2026.ABSTRACTUV-B radiation, worsened by ozone layer depletion, threatens plant health. The alpine plant Rhododendron chrysanthum has evolved mechanisms to counteract UV-B damage. This study examined the response of R. chrysanthum seedlings to UV-B radiation in an artificial climate chamber, focusing on the molecular mechanisms through metabolomics and transcriptomics. We identified 2 distinct amino acids, 35 differentially expressed genes (DEGs), and 2 families of transcription factors (TFs), which involved in amino acids metabolic pathways, including the biosynthesis of phenylalanine, tyrosine, and tryptophan, as well as phenylpropanoid biosynthesis and phenylalanine metabolism. Under UV-B stress, bHLH TFs significantly correlated with the expression of aroD, aroE, TAT, TRP3, trpD, DDC/TDC, PAAS, HCT, CCR, and COMT, thereby accumulating L-phenylalanine and L-tyrosine levels. WRKY TFs significantly correlated with the expression of all these enzymes except COMT, thus accumulating the levels of L-phenylalanine and L-tyrosine. These two families of TFs exhibit both synergistic and antagonistic regulatory roles in amino acid metabolic pathways. The findings presented are significant not only for understanding the UV-B resistance of R. chrysanthum but also for serving as a reference for the study of other plant species. This research will contribute to the theoretical foundation necessary for the cultivation of plant varieties with enhanced UV-B stress tolerance.PMID:41770831 | DOI:10.1371/journal.pone.0343024