PubMed

IEEE Trans Comput Biol Bioinform. 2026 Mar 3;PP. doi: 10.1109/TCBBIO.2026.3669919. Online ahead of print.ABSTRACTBiological age provides a more direct reflection of physiological status than chronological age, serving as a vital measure to evaluate health risks and aging interventions. While steroid metabolomics offers rich information for exploring aging mechanisms, the complex and nonlinear interactions within metabolic networks remain challenging in modeling. Here, we propose and describe METRON as a deep learning framework to predict biological ages from steroid metabolomics. Specifically, a Metabolite Interaction Perception Module (MIPM) is proposed to capture the interactions. Subsequently, a Group-Rational Kolmogorov-Arnold Network is also integrated to capture intricate dependencies and enhance the representation capability. We demonstrate that METRON achieves promising performance as compared to other machine learning and deep learning methods. Beyond performance, METRON offers interpretability by recovering the established markers such as Dehydroepiandrosterone (DHEA) and identifying 17-hydroxyprogesterone (17-OH-P4) as the key signature linked to hypothalamic-pituitary-adrenal axis dynamics. These results support the capacity of METRON not only to estimate biological age but also to uncover underappreciated metabolic drivers behind aging.PMID:41774660 | DOI:10.1109/TCBBIO.2026.3669919

mSystems. 2026 Mar 3:e0171825. doi: 10.1128/msystems.01718-25. Online ahead of print.ABSTRACTMembers of the genus Streptomyces are major producers of a wide variety of secondary metabolites that serve as bioactive compounds. Many secondary metabolites are produced in response to environmental signals such as biotic and abiotic stresses. In this study, we identified salt supplementation as one of the stimuli activating secondary metabolism in the model Streptomyces species, Streptomyces coelicolor. Comparative metabolomics revealed overproduction of several known secondary metabolites, most notably undecylprodigiosin and coelimycin P1, in addition to their biosynthetic intermediates and derivatives, as well as many unknown metabolites. Transcriptomic analysis revealed activation of diverse biological processes including cation uptake, compatible solute production, and the phosphate limitation stress response through conserved and species-specific mechanisms, presumably to overcome the increased salinity. This response leads to activation of a variety of regulatory and metabolic pathways required for production of secondary metabolites including activation of conserved metabolic pathways for energy and substrate supply and species-specific secondary metabolite biosynthetic gene clusters. Furthermore, several promoter sequences contributing to upregulation of secondary metabolism induced by salt supplementation were identified. Overall, our data show how S. coelicolor copes with the increased salinity and tailors the cellular metabolism toward secondary metabolism in a conserved and species-specific manner.IMPORTANCEPrecise control of cellular metabolism is critical to ensure directing cellular resources toward metabolic pathways required for the environment. Many Streptomyces species activate production of secondary metabolites upon exposure to environmental stimuli. This study reveals dynamic reprogramming of cellular metabolism in Streptomyces coelicolor under increased salinity, which induces production of various secondary metabolites. Notably, this model biological system redirects cellular resources toward various metabolic pathways required for proper activation of secondary metabolite biosynthesis, including precursor and energy supply and posttranslational modification of biosynthetic enzymes. Interestingly, some pathways are activated by phosphate limitation stress, presumably caused as a result of increased salinity. Certain aspects of this metabolic reprogramming are likely common in many Streptomyces species and may be controlled by rather complex regulatory pathways. Overall, this study unveils how Streptomyces species tailor the cellular metabolism toward secondary metabolism and paves the way for understanding metabolic regulation.PMID:41773877 | DOI:10.1128/msystems.01718-25

Biomarkers. 2026 Mar 3:1-8. doi: 10.1080/1354750X.2026.2639408. Online ahead of print.ABSTRACTBackgroundCoronary microvascular disease (CMD) is defined by impaired myocardial stress flow reactivity and is associated with worse cardiovascular outcomes. Studying CMD is complicated by the overlap of its risk factors and patient-important cardiovascular sequelae with those of epicardial atherosclerotic disease. Published studies have not yet used longitudinal data to investigate the time dependencies of dynamic processes like obesity in their effects on microvascular health.Methods and ResultsIn a mixed-sex cohort of 85 patients for whom epicardial obstruction was angiographically excluded, a multivariate model was developed to measure strengths of association between repeated-measurement metabolic data and microvascular stress flow reactivity as assessed by position emission tomography myocardial perfusion imaging (PET-MPI). Body mass index and the diagnosis of insulin-dependent diabetes mellitus were associated with CMD on clinically meaningful scales when analyzing all metabolic data collected in the year prior to stress PET-MPI (β [95%CI]: -0.019 [-0.033,-0.0051], p=0.0072; -0.33 [-0.65, -0.0026], p = 0.048). Parallel modelling using single time-point metabolomics data generated comparable results, suggesting that simplified assessments may be used as valid surrogates for repeated-measurement data in this setting.PMID:41773779 | DOI:10.1080/1354750X.2026.2639408

Anal Chem. 2026 Mar 3. doi: 10.1021/acs.analchem.5c06487. Online ahead of print.ABSTRACTThe lipid composition (lipidome) in biological samples is extremely complex, having diverse biofunctions. Quantifying lipidomes with high coverage is vital to understand such functions but challenging due to their levels spanning several orders of magnitude, limited available standards, and poor chromatographic performances for many acidic lipids such as sphingosine-1-phosphate, phosphatidylserines, and phosphatidic acids. Here, we report a reliable method for high-coverage quantitative lipidomics using ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). By using both pH and ammonium gradients in elution, all lipids, especially acidic ones, had obviously improved LC separation. By using 267 lipid standards in 49 subclasses, we also established quantitative structure-retention relationship models to predict the retention time (tR) with good accuracy (ΔtR < 0.33 min, MRE ∼3.4%) for all lipid subclasses. With UHPLC-MS/MS in multiple-reaction monitoring mode, we subsequently developed a quantitative lipidomics method using three UHPLC conditions to enable coverage of over 21,700 lipids in 190 subclasses with good sensitivity, precision, accuracy and stability. We further confirmed its applicability by quantifying 2375 lipids in seven typical biological matrices including human plasma, urine, and non-small-cell lung cancer cells together with E. coli, Arabidopsis leaves, mouse liver tissue, and feces. This offers a high-coverage quantitative method for understanding molecular phenotypes associated with lipid functions in physiology and pathophysiology.PMID:41773770 | DOI:10.1021/acs.analchem.5c06487

JMIR Res Protoc. 2026 Feb 27;15:e77571. doi: 10.2196/77571.ABSTRACTBACKGROUND: Although a high intake of plant foods is often considered healthy, some plant foods can be detrimental to health. Reliable dietary assessment is crucial to examine the relationship between diet and disease. Current dietary assessment methods rely on self-reported intake data, which are subject to bias. Objective measurement using biomarkers of food intake could mitigate this problem. However, single biomarkers of food intake have limitations as well. Combining several biomarkers of food intake into a multibiomarker panel could attenuate these limitations and allow for an accurate, objective dietary assessment.OBJECTIVE: The PLAENTI study aims to validate a multibiomarker panel for the assessment of quantity and quality of plant foods in the diet.METHODS: PLAENTI is a randomized controlled trial with 4 arms in a parallel design. Metabolically healthy adults (≥18 years old) were enrolled in the study. The study consisted of 1 week of run-in, with a standardized diet low in healthful plant foods for all participants; 2 weeks of a dietary intervention according to the assigned arm; and 1 week of washout, during which participants returned to their habitual diet. During the intervention, the participants' diet consisted of either a low, medium, or high proportion of healthful plant foods or a high proportion of unhealthful plant foods in the diet according to the assigned arm. The arm that received a high proportion of healthful plant foods served as the control. All food was provided based on energy-adjusted menu plans. During the visits, anthropometry and body composition were assessed, and blood samples were collected. Throughout the study, participants collected multiple urine samples (24-hour urine, evening and morning spot urine) and stool samples. Blood and urine samples will be analyzed by liquid chromatography-mass spectrometry to determine biomarker levels for the validation of a multibiomarker panel.RESULTS: After receiving approval from the ethics committee, recruitment began, and the first screening visit took place in November 2023. Between January and August 2024, of the 66 enrolled participants, 59 (31 female, 28 male) successfully completed the study, and their urine, blood, and stool samples are available for analysis. PLAENTI was conducted in 5 waves with a maximum of 16 participants enrolled in each wave. The mean age of the study population was 45.5 (SD 18.4) years, the mean BMI was 24.8 (SD-3.9) kg/m², and the mean total energy expenditure was 2464 (SD 440) kcal.CONCLUSIONS: PLAENTI was conducted in a highly controlled and standardized manner, yielding samples and data that will be used to examine whether the quantity and quality of plant foods in the diet can be assessed using a multibiomarker panel. Successful validation of the multibiomarker panel would enable its application for objective dietary assessment.PMID:41773674 | DOI:10.2196/77571

ACS Synth Biol. 2026 Mar 3. doi: 10.1021/acssynbio.5c00870. Online ahead of print.ABSTRACTDihydroxyacetone phosphate (DHAP), a key metabolic intermediate of the Embden-Meyerhof-Parnas pathway of Escherichia coli, has a considerable value as a precursor of high-added-value compounds. While eliminating the triosephosphate isomerase (tpiA) gene should theoretically channel 50% of the glycolytic flux into dead-end production of DHAP, the permanent loss of this activity triggers alternative routes that decrease (rather than increase) DHAP levels. To address this limitation and establish transient regimes of high DHAP biosynthesis, we harnessed the unusual structural tolerance of TpiA for designing a variant of the enzyme that can be rapidly degraded, thus temporarily adopting a null phenotype. This was achieved through conditional expression of the highly specific viral protease PPV-NIa, which cleaves a cognate recognition sequence strategically engineered into an exposed, permissive loop on the protein surface. Optimization of such an in vivo proteolytic device resulted in fully active TpiA variants that become nearly instantly destroyed upon induction of NIa in trans, which was itself engineered as an ON/OFF switch. Metabolomic data of an engineered E. coli strain genomically encoding the cognate genetic device showed that precise post-transcriptional targeting of TpiA leads to a substantial transitory increase of DHAP with minimal disturbance of other typical intermediates. The general value of targeting enzymes in central carbon metabolism, such as TpiA, is discussed in light of systems metabolic engineering.PMID:41773525 | DOI:10.1021/acssynbio.5c00870

Environ Sci Technol. 2026 Mar 3. doi: 10.1021/acs.est.5c14701. Online ahead of print.NO ABSTRACTPMID:41773423 | DOI:10.1021/acs.est.5c14701

ACS Appl Mater Interfaces. 2026 Mar 3. doi: 10.1021/acsami.5c21979. Online ahead of print.ABSTRACTPersistent inflammation and impaired fibrocartilage regeneration hinder the healing of the tendon-bone interface (TBI) following rotator cuff injury. To address this challenge, we propose a spatiotemporally coordinated therapeutic strategy that combines the temporal control of inflammation with targeted fibrocartilage regeneration. A multifunctional nanomedicine delivery system, designated as CMMKT, was developed using reactive oxygen species (ROS)-responsive polymers to control the release of magnesium ions (Mg2+) and kartogenin (KGN). The delivery system was coated with fibrochondrocyte cell membranes to improve spatial specificity in targeting fibrocartilage cells. CMMKT enhanced the migration and proliferation of bone marrow mesenchymal stem cells (BMSCs) in vitro under inflammatory conditions, inhibited apoptosis, restored osteogenic and chondrogenic differentiation capacities, and increased the proportion of M2 macrophages by scavenging ROS and facilitating sustained drug release. In a rat rotator cuff tear model, CMMKT-driven immunomodulation restored fibrochondrocyte-specific matrix deposition, leading to an increased collagen maturity and biomechanical strength. Transcriptomic and metabolomic analyses indicated the suppression of oxidative stress responses and the activation of anabolic pathways in fibrocartilage. Overall, this spatiotemporal coordination therapeutic concept, CMMKT, is a promising approach for TBI repair that integrates inflammatory microenvironment reprogramming with the targeted enhancement of fibrocartilage regeneration.PMID:41773418 | DOI:10.1021/acsami.5c21979

Biologics. 2026 Feb 24;20:578004. doi: 10.2147/BTT.S578004. eCollection 2026.ABSTRACTBACKGROUND: Previous studies have demonstrated that numerous medicine and food homology (MFH) possess the potential to regulate purine metabolism disorders, promote uric acid excretion, and alleviate hyperuricemia symptoms. Examples include CS (Chaenomeles speciosa (Sweet) Nakai), SR (Smilax glabra Roxb.) and PL (Pueraria montana var. lobata).METHODS: Metabolomics was employed to analyze the compositional changes in medicinal and edible extracts before and after fermentation. Network pharmacology and molecular docking studies were further utilized to elucidate the interactions between these differential metabolites and the core targets of hyperuricemia. In vitro enzyme activity assays were conducted to confirm the therapeutic effects.RESULTS: A total of 283, 248, and 18 differential metabolites were identified in CS,SR and PL samples, respectively. Among these, 54 significantly upregulated differential metabolites were selected for screening. Based on these metabolites, 53 HUA-related targets were identified for CS, SR and PL. Functional enrichment analysis revealed their roles in inflammatory stress and uric acid production pathways, particularly the MAPK signaling pathway and purine metabolism regulated by XDH. Additionally, other targets in the purine metabolism pathway, such as ADA, PNP, AMPD3, and IMPDH2, were co-regulated. Enzyme activity assays indicate that fermented MFH more effectively inhibits XOD, thereby regulating the conversion of xanthine and hypoxanthine into uric acid. Molecular docking revealed two significantly upregulated compounds in CS; and five in PL; and four in SR. exhibit strong binding to XOD.CONCLUSION: These findings provide theoretical support for FMFH as a potential effective component in preventing and treating hyperuricemia. Our research demonstrates that FMFH targets multiple pathways associated with hyperuricemia, offering a promising approach for preventing this condition.PMID:41773177 | PMC:PMC12949976 | DOI:10.2147/BTT.S578004

Diabetes Obes Metab. 2026 Mar 3. doi: 10.1111/dom.70612. Online ahead of print.ABSTRACTBACKGROUND: Renal tubular injury, one of the most critical events in diabetic kidney disease (DKD), plays a pivotal role in the progression of the disease. Metabolic reprogramming of renal tubular cells emerges as a prominent pathological feature, yet its underlying molecular mechanisms remain incompletely understood.METHODS: We established a streptozotocin-induced mouse model of diabetes. Metabolomic analysis was then used to characterise DKD-specific metabolic alterations. To test the functional consequence of a metabolic intervention, DKD mice received intraperitoneal injections of oxaloacetate (OAA). Furthermore, molecular docking and cellular thermal shift assays were used to elucidate the molecular mechanisms underlying OAA's effects on renal tubular injury, which were further validated in HK-2 cells exposed to high glucose. Finally, a specific pharmacological inhibitor was applied to study the relevant signalling pathway.RESULTS: Metabolomic profiling identified a marked decrease in OAA, a key tricarboxylic acid (TCA) cycle intermediate, in injured renal tubular cells. OAA supplementation significantly attenuated tubulointerstitial injury, as evidenced by reduced tubular cell damage, fibrosis, and macrophage infiltration. Moreover, restored mitochondrial homeostasis was observed in DKD mice after OAA treatment. Mechanistically, we found that OAA inhibited prolyl hydroxylase domain 2 (PHD2), an essential regulator of hypoxia-inducible factor-1α (HIF-1α), thereby stabilising mitochondrial homeostasis. Furthermore, pharmacological inhibition of HIF-1α abolished the protective effects of OAA, confirming the involvement of the PHD2/HIF-1α axis.CONCLUSIONS: OAA ameliorates renal tubulointerstitial injury in DKD by restoring mitochondrial homeostasis through the PHD2/HIF-1α axis.PMID:41773066 | DOI:10.1111/dom.70612

J Exp Biol. 2026 Mar 3:jeb.251552. doi: 10.1242/jeb.251552. Online ahead of print.ABSTRACTAtmospheric oxygen, which is essential for energy metabolism, can directly influence an animal's heat tolerance by affecting oxygen transport processes, especially in those living in oxygen-poor environments such as plant tissues, underground or aquatic environments. Yet, oxygen availability and heat tolerance are rarely studied together, limiting our ability to predict their combined effects on insect performance. This study examines the larval tolerance of a large xylophagous cerambycid beetle Cacosceles newmannii to combined hypoxic and thermal stress using performance assays (duration of righting response) coupled with metabolomic and transcriptomic analyses. Metabolomic profiling showed that most metabolites were downregulated in the body but upregulated in the haemolymph as stress increased. Transcriptomic profiles clustered primarily by temperature (25 °C vs 35 °C), independent of oxygen level. Cacosceles newmannii appeared capable of modulating its performance to reduce the energy costs and physiological damage induced by hypoxia. This suggested a high baseline hypoxia tolerance rather than a rapid plastic (induced) physiological hypoxia response, probably due to the species' endophytic lifestyle. Conversely, thermal stress led to a predictable increase in metabolic activity but did not markedly affect performance, triggering adjustments to maintain cellular functions while limiting the impact of stresses expected under conditions of high temperature, such as desiccation. In short, our study highlights the distinct metabolic pathways mobilised to cope with hypoxic versus thermal stress, emphasizing the importance of integrated approaches in understanding insect responses to environmental challenges. These findings have significant implications for understanding the species' ecology, with applications for pest management and sustainable agriculture in the context of climate change.PMID:41772970 | DOI:10.1242/jeb.251552

FASEB J. 2026 Mar 15;40(5):e71611. doi: 10.1096/fj.202503916R.ABSTRACTType 2 diabetes mellitus (T2DM) is currently one of the most prominent and global chronic conditions. Cognitive decline is one of the major complications of T2DM, but its precise molecular mechanism remains unclear. Metabolomics and proteomics were combined in this study to investigate alterations in metabolites and proteins in the hippocampus of T2DM rats. KEGG Markup Language (KGML) network analysis was conducted to integrate underlying relationships among differentially expressed metabolites and proteins. 58 significantly differentially expressed metabolites and 61 differentially expressed proteins were identified between T2DM and CON rats. In proteomic analysis, GO analysis showed that DEPs involved in biological process were mainly related to neurofilament cytoskeleton organization, postsynaptic actin cytoskeleton organization and actin filament severing. KEGG pathway analysis showed the major enriched pathways were thiamine metabolism, cholesterol metabolism, pentose phosphate pathway (PPP), ABC transporters and regulation of actin cytoskeleton. In metabolomics analysis, KEGG pathway analysis showed the major enriched pathways were autophagy, lysosome, glycolysis/gluconeogenesis, PPP and ABC transporters. KGML network analysis revealed that PPP and ABC transporters were activated in the hippocampus of T2DM rats, accompanied by the up-regulation of metabolites in two pathways. Rpia was up-regulated, which is the indicator of increased PPP flux. Tap1, the unique immune-function ABC transporter, was up-regulated. Excessive PPP activation disrupts cognition-related synaptic transmission, while up-regulated immune-function ABC transporters drive aberrant synaptic remodeling and chronic neuroinflammation. These results provide a better understanding of biological mechanisms underlying T2DM-related cognitive dysfunction and may help identify potential targets for neuroprotective drugs against cognitive dysfunction in T2DM.PMID:41772872 | DOI:10.1096/fj.202503916R

J Anim Sci Biotechnol. 2026 Mar 3;17(1):36. doi: 10.1186/s40104-025-01349-9.ABSTRACTBACKGROUND: Yeast enzyme hydrolysis slurry (YS) has the potential to optimize feed utilization efficiency and improve the health of farmed animals, as it contains abundant bioactive components like small-molecule peptides and amino acids. However, its function and application effects in juvenile largemouth bass (Micropterus salmoides) are unclear.METHODS: Three hundred and twenty largemouth bass (8.20 ± 0.05 g) were randomly divided into four groups (4 replicates of 20 fish). Four isonitrogenous (52%) and isolipidic (10%) diets were formulated: FM group (positive control), SBM group (soybean meal replaced 30% of fish meal protein, negative control), and the SBM group supplemented with 1% YS (SBM + 1% YS) and 2% YS (SBM + 2% YS), respectively. After a 56-day feeding period, the fish were assessed for growth, intestinal health, and metabolic regulation-related indices.RESULTS: Our study found that weight gain rate (P = 0.032) and specific growth rate (P = 0.030) in the SBM + 1% YS and SBM + 2% YS groups were significantly higher than those in the SBM group. Relative to the SBM group, YS-supplemented groups exhibited marked elevations in intestinal folds, goblet cell numbers, serum acid and alkaline phosphatase activities, catalase and superoxide dismutase activities, as well as the activities of key digestive enzymes (lipase, α-amylase, pepsin, chymotrypsin), accompanied by downregulated mRNA expression of anorexigenic genes cholecystokinin and leptin. Meanwhile, these groups showed significantly lower serum D-lactate, diamine oxidase, lipopolysaccharide levels and malondialdehyde content. The abundance of beneficial genus Cetobacterium increased while the abundance of pathogenic genus Edwardsiella (P = 0.0265) significantly reduced in SBM + 1% YS and SBM comparison groups. Metabolomics analysis revealed that protein digestion and absorption (P = 0.0041), and amino acid metabolism pathways (P = 0.0052) were significantly enriched in the comparison between SBM + 1%YS and SBM groups. Correlation analysis further indicated that differential metabolites such as arginine and methionine exhibite a strong negative association with Edwardsiella.CONCLUSION: Yeast enzyme hydrolysis slurry in soybean meal-based diets with partial fishmeal replacement enhanced the antioxidant capacity, reduced intestinal permeability, altered the abundances of intestinal microbiota and associated core metabolites. These positive changes collectively contributed to improved growth performance in largemouth bass.PMID:41772723 | DOI:10.1186/s40104-025-01349-9

Trials. 2026 Mar 3. doi: 10.1186/s13063-026-09573-y. Online ahead of print.ABSTRACTBACKGROUND: Gastrointestinal toxicity during FOLFOX chemotherapy for colorectal cancer (CRC) is frequent and can impair oral intake, quality of life, and planned chemotherapy delivery. Safe and scalable dietary strategies are needed as adjuncts to standard supportive care. This trial will evaluate whether a structured plant-based dietary strategy reduces chemotherapy-induced gastrointestinal toxicity (CIGT) and improves related biological and patient-centered outcomes.METHODS: This multicentre, stratified, three-arm, parallel-group, assessor-blinded, superiority randomised controlled trial will enrol 114 adults (18-65 years) with pathologically confirmed CRC receiving (or scheduled to receive) FOLFOX chemotherapy at two hospitals in Chengdu, China. Participants will be randomised (1:1:1), stratified by study site and sex, to (1) a structured plant-based dietary strategy, (2) conventional dietary guidance, or (3) conventional dietary guidance plus an oncology complete nutritional formula, for 6 weeks. Assessments will be performed at baseline and at prespecified time points through week 6. Primary outcomes are (i) the participant-level incidence of any prespecified CTCAE gastrointestinal toxicity of grade ≥ 2 during follow-up, (ii) serum inflammatory biomarkers, and (iii) stool-based profiling. Secondary outcomes include dietary intake and diet quality, body composition by bioelectrical impedance analysis, routine clinical laboratory indices, fatigue, anxiety/depression, physical activity, and adverse events. Primary analyses will follow the intention-to-treat principle.DISCUSSION: This trial will provide evidence on the efficacy and safety of a plant-based dietary strategy to mitigate CIGT during FOLFOX chemotherapy. Integrated clinical, biomarker, and stool multi-omics measures may also support exploration of biological correlates of symptom burden and treatment tolerance.TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2500095215; registered 03 January 2025. https://www.chictr.org.cn/showproj.html?proj=254099.PMID:41772652 | DOI:10.1186/s13063-026-09573-y

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