PubMed

Circ Res. 2026 Jun 16. doi: 10.1161/CIRCRESAHA.125.328083. Online ahead of print.ABSTRACTBACKGROUND: Pathological cardiac remodeling and afterload-induced increases in energy demand together contribute to heart failure (HF). Lysosome-assisted processes, such as autophagy, coupled with alterations in mitochondrial oxidative capacity, play important roles in cardiac remodeling and HF. Furthermore, the lysosome is a hub for multiple signaling pathways governing hypertrophic growth. The TFEB (transcription factor EB) has emerged as a key regulator of lysosomal genes and mitochondrial function in multiple tissues, especially in response to external stress.METHODS: Leveraging a cardiomyocyte-specific TFEB knockout mouse (CTKO), pressure overload was induced by transverse aortic constriction (TAC) to elucidate the role of TFEB under hypertrophic stress conditions. Echocardiography was employed to assess cardiac function, and hearts were subsequently harvested for transcriptomic, proteomic, and metabolomic analyses. To glean further insight into the molecular mechanisms involved, we studied neonatal rat ventricular myocytes exposed to phenylephrine, an in vitro model of cardiomyocyte hypertrophy.RESULTS: We report that TFEB is rapidly activated and translocates to the nucleus in cardiomyocytes exposed to hypertrophic stress conditions, triggering a lysosomal gene program independent of autophagy gene changes. At baseline, contractile function measured by echocardiography appeared normal in these mice compared with their Cre-negative littermates. However, in pressure-overload stress induced by TAC, CTKO mice manifested an amplified hypertrophic response, leading rapidly to HF. Unlike WT hearts, CTKO hearts failed to increase lysosomal capacity after TAC. They manifested an increase in the steady-state levels of autophagosome-associated proteins, such as LC3II and p62, as well as accumulation of ubiquitinated proteins, suggesting a defect in protein turnover. Interestingly, CTKO mice harbored altered mitochondrial structure, reduced oxidative capacity, and reduced abundance of peroxisome PGC-1α-b (proliferator-activated receptor-1 alpha-b). Furthermore, CTKO hearts manifested reduced expression of key enzymes within metabolic pathways essential for normal myocardial metabolism, including fatty acid metabolism, carbon metabolism, and branched-chain amino acid metabolism. Surprisingly, AMPK (AMP-activated protein kinase) signaling, while normal at baseline, was significantly decreased in CTKO hearts after TAC. This reliance on TFEB for growth trigger-induced AMPK signaling was also observed in vitro in cells exposed to phenylephrine, as were the antihypertrophic effects of TFEB activation, supporting a direct role of TFEB in this process. Finally, we report that exogenous activation of AMPK in the absence of TFEB can completely rescue the exacerbated hypertrophic response both in vitro and in vivo, independent of lysosomal function. Notably, blunting of the hypertrophic response did not impact the decreased contractile function observed in TAC-treated CTKO mice, highlighting the importance of TFEB in regulating mitochondrial function in response to stress.CONCLUSIONS: Our findings demonstrate that TFEB antagonizes pathological hypertrophic cardiac remodeling through upregulation of lysosomal capacity, maintaining mitochondrial energetic function, and promoting AMPK signaling.PMID:42299666 | DOI:10.1161/CIRCRESAHA.125.328083

Kidney Res Clin Pract. 2026 Jun 11. doi: 10.23876/j.krcp.25.433. Online ahead of print.ABSTRACTBACKGROUND: Sarcopenia affects approximately 30%-40% of patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (HD), a prevalence substantially higher than that observed in community-dwelling older adults. Muscle wasting in this population is driven by chronic inflammation, amino acid losses during dialysis, and anabolic resistance, which blunt muscle protein synthesis despite nutritional intake or exercise. Leucine, a branched-chain amino acid that activates mechanistic target of rapamycin complex 1 signaling, plays a key role in muscle anabolism but is often depleted in patients undergoing HD. This pilot study evaluated the feasibility and preliminary effects of combining leucine supplementation with exercise on muscle-related outcomes in ESKD patients.METHODS: In this single-center randomized pilot trial, 24 patients undergoing maintenance HD were assigned to either exercise alone or exercise plus leucine supplementation for 12 weeks. The intervention group received 6 g/day of leucine in beverage and capsule form. The primary outcome was the change in handgrip strength. Secondary outcomes included physical performance measures (gait speed, five-times sit-to-stand, and Short Physical Performance Battery), skeletal muscle mass indices, body composition, and biochemical markers. Exploratory analyses included responder analysis and metabolomic correlation analysis in an independent cohort.RESULTS: Baseline characteristics were generally comparable between groups. The intervention group showed higher responder rates for handgrip strength and gait speed compared with the exercise-only group, while modest increases in skeletal muscle index were observed only in the intervention group. Several biochemical markers, including total protein, blood urea nitrogen, creatinine, and red blood cell count, showed directional increases in the intervention group. Independent metabolomic profiling demonstrated lower circulating leucine levels and disrupted amino acid correlations in HD patients compared with healthy controls.CONCLUSION: Adjunct leucine supplementation combined with exercise showed preliminary improvements in muscle function and selected biochemical markers in patients with ESKD undergoing HD. These findings support the potential role of leucine-based nutritional strategies in mitigating sarcopenia in this population, although larger and longer-term trials are required to confirm efficacy.PMID:42299452 | DOI:10.23876/j.krcp.25.433

Front Genet. 2026 Jun 1;17:1797093. doi: 10.3389/fgene.2026.1797093. eCollection 2026.ABSTRACTINTRODUCTION: Anthocyanins are important natural pigments and bioactive compounds in colored maize kernels. Although colored fresh-eating maize has attracted increasing attention because of its nutritional and functional value, the molecular basis underlying anthocyanin accumulation in maize kernels with different colors remains incompletely understood.METHODS: In this study, four fresh-eating maize cultivars with contrasting kernel colors, including white (WN 2000), yellow (HN), multicolored (CN1), and black (HTN188), were used to investigate the mechanism of anthocyanin accumulation. Total anthocyanin content was measured across developmental stages, and integrated metabolomic and transcriptomic analyses were performed to identify anthocyanin-related metabolites, differentially expressed genes, and candidate regulatory factors associated with kernel pigmentation.RESULTS: Metabolomic profiling identified 49 anthocyanin-related metabolites/features, with marked enrichment of cyanidin-, peonidin-, and pelargonidin-related compounds in the black maize cultivar HTN188. Transcriptomic analysis identified 12,557 differentially expressed genes among the four cultivars, which were mainly enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, glutathione metabolism, fructose and mannose metabolism, and glyoxylate and dicarboxylate metabolism pathways. Several anthocyanin biosynthetic genes and regulatory transcription factor candidates were upregulated in anthocyanin-rich kernels, including DFR (Zm00001d011438), MYB (Zm00001d003052), bHLH (Zm00001d015990), and NAC (Zm00001d012508). In particular, the expression of DFR (Zm00001d011438) was strongly positively correlated with total anthocyanin content. Weighted gene co-expression network analysis further identified gene modules and candidate hub regulators associated with anthocyanin accumulation.DISCUSSION: These findings provide a comparative multi-omics perspective on anthocyanin accumulation in fresh-eating maize kernels of different colors. The results suggest that the high anthocyanin accumulation in black maize is associated with the coordinated enrichment of anthocyanin-related metabolites and the upregulation of key structural genes and transcription factors. This study provides candidate genes and regulatory information for future functional studies and anthocyanin-oriented breeding in fresh-eating maize.PMID:42299342 | PMC:PMC13265062 | DOI:10.3389/fgene.2026.1797093

Small Methods. 2026 Jun 15:e70782. doi: 10.1002/smtd.70782. Online ahead of print.ABSTRACTSkin cancer is among the most prevalent malignancies worldwide, with non-melanoma types ranking among the top five and melanoma characterized by high lethality. Psoriasis, although non-malignant, imposes a substantial physical and psychological burden. Accurate and timely detection is crucial for improving clinical outcomes. Serum metabolites, as sensitive indicators of systemic physiology, represent promising noninvasive biomarkers. Here, we developed gold-modified rose-like multilayer heterojunctions (G-RMHJ) as an efficient matrix for laser desorption/ionization mass spectrometry (LDI-MS). The hierarchical multilayer architecture and heterojunction interfaces, combined with gold functionalization, synergistically enhance light absorption, interfacial energy transfer, and ionization efficiency, enabling sensitive and reproducible serum metabolite detection. In a cohort of 130 skin cancer and 23 psoriasis patients together with 218 healthy controls (HC), G-RMHJ-assisted LDI-MS yielded robust serum metabolic fingerprints, and machine learning models built on these data achieved 100% test-set accuracy for classifying patients vs. HC. Eight discriminative metabolites were identified that reliably differentiated four types of diseases from HC, with area under the curve values ranging from 0.933 to 1.000. This work demonstrates how hierarchical microstructured heterojunctions can directly translate materials-level design into enhanced bioanalytical performance, providing a generalizable and noninvasive framework for serum metabolomics-based disease classification and skin cancer subtype identification.PMID:42298887 | DOI:10.1002/smtd.70782

Plant Signal Behav. 2026 Dec 31;21(1):2686334. doi: 10.1080/15592324.2026.2686334. Epub 2026 Jun 15.ABSTRACTSalvia miltiorrhiza is a valuable medicinal plant with diverse pharmacological applications and high market demand. Light quality is a critical environmental factor regulating plant growth, secondary metabolism, and interactions with rhizosphere microorganisms. However, the effects of short-term, pure monochromatic light exposure on S. miltiorrhiza remain largely unexplored. In this study, we employed integrated transcriptomic, metabolomic, and rhizosphere metagenomic analyzes to investigate the responses of S. miltiorrhiza under different monochromatic light conditions: ultraviolet (UV), blue (B), red (R), and far-red (FR), with white light (WL) as the control. GO enrichment analysis indicated that all monochromatic light treatments activated defense responses, while specific pathways related to light stimulus, wounding, and reactive oxygen species were uniquely enriched under B, R, and FR light. Metabolomic analysis showed a general decrease in metabolite abundance under monochromatic light compared to WL, with the R treatment inducing the highest number of significantly upregulated metabolites. Integrated KEGG pathway analysis of differential transcripts and metabolites highlighted the enrichment of secondary metabolic pathways, including diterpenoid, monoterpenoid, and phenylpropanoid biosynthesis. Notably, quantitative HPLC analysis confirmed that UV, R, and FR light significantly promoted the accumulation of dihydrotanshinone I and tanshinone IIA, while decreasing salvianolic acid A content. Metagenomic analysis revealed that monochromatic light, especially B light, reduced rhizosphere microbial alpha diversity and altered the abundance of specific bacterial families and species. Functional gene annotation also showed treatment-specific shifts in microbial metabolic potential and virulence factors. In conclusion, short-term monochromatic light culture, particularly R and FR, effectively modulates the transcriptome and metabolome of S. miltiorrhiza, enhancing the accumulation of key bioactive tanshinones, while simultaneously reshaping its rhizosphere microbial community. These findings offer a potential light-based strategy for improving the quality of S. miltiorrhiza.PMID:42298774 | DOI:10.1080/15592324.2026.2686334

J Sci Food Agric. 2026 Jun 15. doi: 10.1002/jsfa.70816. Online ahead of print.ABSTRACTBACKGROUND: Fermentation plays a critical role in determining the quality and aroma of cigar tobacco; however, the interactions between phyllospheric microbial succession and volatile flavor compound (VFC) formation remain insufficiently understood. This study aimed to elucidate the associations between microbial community dynamics and flavor development during tobacco fermentation using a multi-omics approach.RESULTS: Distinct stage-dependent shifts in microbial communities were observed across unfermented (F1), mid-fermentation (F2), and final-fermentation (F3) stages. Bacterial diversity showed a 'first-decrease-then-increase' trend, with Staphylococcus dominating mid-fermentation (relative abundance > 97%) and keystone genera (Methylobacterium-Methylorubrum, Aerococcus) enriching at the final stage. Fungal communities were persistently dominated by Aspergillus throughout fermentation. Volatile metabolomics identified 47 differentially abundant flavor compounds, with aldehydes (e.g. benzaldehyde, nonanal) and alcohols (e.g. 1-pentanol) significantly enriched post-fermentation. Correlation analyses revealed stronger associations between bacterial communities and VFCs compared to fungi, with Aerococcus showing significant positive correlations with key upregulated compounds (P < 0.05). Functional prediction suggested that carbohydrate, amino acid, and lipid metabolism pathways may contribute to VFC formation.CONCLUSION: This study demonstrates that microbial succession is closely associated with chemical transformation and flavor development during cigar tobacco fermentation. Bacterial taxa, particularly Aerococcus, may play important roles in shaping volatile profiles. These findings provide a theoretical basis for future microbial regulation strategies aimed at improving fermentation quality. © 2026 Society of Chemical Industry.PMID:42298740 | DOI:10.1002/jsfa.70816

J Anim Sci Biotechnol. 2026 Jun 16;17(1):122. doi: 10.1186/s40104-026-01414-x.ABSTRACTBACKGROUND: Citrulline (Cit), an effective precursor of arginine (Arg), escapes hepatic catabolism to be almost completely absorbed into the systemic circulation, thereby being efficiently converted to Arg in the kidneys to enhance its systemic bioavailability. This study investigated the effects of dietary Cit supplementation on lactation performance in sows, as well as the underlying mechanisms related to intestinal health in their suckling piglets, using multi-omics analyses.RESULTS: Dietary Arg and Cit supplementation significantly increased average daily feed intake of lactating sows. Milk fat content and plasma nitric oxide (NO) concentration increased significantly in the Arg group and the 40%Cit group (P < 0.05), while milk threonine content increased slightly (P = 0.084). Consequently, the average daily gain of suckling piglets over the 21-day lactation period was also significantly improved. Furthermore, maternal 40%Cit supplementation improved the intestinal health of offspring by enhancing jejunal morphology and upregulating the expression of the tight junction protein occludin (P < 0.05), indicating a strengthened intestinal barrier. Mechanistically, this was achieved by activating the mTOR/S6 pathway in the piglets' jejunum. Maternal 40%Cit supplementation upregulated the expression of proteins related to mitochondrial fusion and fission (MFN2 and MFF, P < 0.05), and the protein expression of OPA1 showed an increasing trend (P = 0.097), indicating the structural and functional status of mitochondria was improved. Maternal 40%Cit supplementation also modulated the gut microbiota of piglets, increasing the abundance of beneficial bacteria (Lachnoclostridium). Metabolomic analysis of sow milk identified 58 differential metabolites. Among these metabolites, palmitic acid levels were significantly increased and positively correlated with the abundance of Lachnoclostridium in the intestine (P < 0.05).CONCLUSIONS: Dietary Cit supplementation enhanced sow lactation performance and improved intestinal barrier function in their offspring via activation of the jejunal mTOR/S6 pathway and improved mitochondrial structure and function in the piglet jejunum. These benefits were further supported by modulation of the gut microbiota and alterations in the milk fat and metabolome, ultimately promoting piglet growth.PMID:42298669 | DOI:10.1186/s40104-026-01414-x

J Transl Med. 2026 Jun 15. doi: 10.1186/s12967-026-08332-6. Online ahead of print.ABSTRACTBACKGROUND AND AIM: ALD is among the most prevalent chronic liver disorders with rising global incidence, the aim of our study is to evaluate the effect of metabolites in the progress of ALD, and build a prediction model for ALC.METHODS: A total of 161 subjects were prospectively enrolled and classified into HC, AUD, AH, ALC. Plasma samples underwent untargeted LC-MS/MS metabolomics analysis. Data were split into training, validation and test sets at a 6:2:2 ratio. Partial least squares discriminant analysis and random forest were employed for feature selection, followed by logistic regression to build metabolite-based and metabolite-plus-clinical composite models. Discrimination was evaluated by AUC, sensitivity, specificity and accuracy.RESULTS: Metabolomic profiles showed progressive separation among groups (Q² > 0.65 for all PLS-DA models). Five metabolites (Vecuronium, N-Docosahexaenoyl Cysteine, 7-Acetylintermedine, Hymenoxon, E-3174) were identified as the most influential features for distinguishing ALC from HC, yielding an AUC of 0.986 (95% CI: 0.969-0.999) in the validation set and 100% accuracy in the test set. Integration of these metabolites with AST further elevated the AUC to 0.998 with 96.70% sensitivity and 100% specificity. Similarly, a five-metabolite panel plus PT achieved perfect accuracy (AUC = 0.964) in discriminating ALC from AH.CONCLUSIONS: We delineate stage-specific metabolic fingerprints of ALD and present robust, non-invasive models for early identification of cirrhosis. Incorporating metabolomic biomarkers with routine clinical variables markedly improves diagnostic precision and offers a practical tool for risk stratification and personalized management of alcohol-related liver disease.PMID:42298593 | DOI:10.1186/s12967-026-08332-6

BMC Neurol. 2026 Jun 15. doi: 10.1186/s12883-026-05056-4. Online ahead of print.ABSTRACTBACKGROUND: Neuropsychiatric symptoms are prevalent in Parkinson's disease (PD) but remain incompletely characterized, particularly concerning sex-specific differences and the comparative performance of diagnostic tools. This study aimed to provide a comprehensive neuropsychiatric profile of a Taiwanese PD cohort, evaluate the diagnostic sensitivity of various assessment tools, and explore correlations with clinical features.MATERIALS AND METHODS: We enrolled 92 PD patients and 57 healthy controls. Participants underwent a comprehensive assessment battery, including motor scales, cognitive measures, and mood inventories. Diagnoses of dementia and depression were established using standard criteria. Diagnostic tool performance was evaluated by calculating the sensitivity and specificity, and relationships between variables were assessed using Spearman correlation.RESULTS: Dementia was identified in 34.8% and depression in 28.3% of PD patients. Female patients had lower scores on the Mini-Mental State Examination (MMSE) (25.18 vs. 28.08, p = 0.003) and Montreal Cognitive Assessment (MoCA) (21.18 vs. 25.79, p = 0.001), and higher scores on the Hamilton Depression Rating Scale (HAM-D) (6.68 vs. 5.02, p = 0.046) and Neuropsychiatric Inventory (NPI) (3.95 vs. 1.79, p = 0.018) compared with male patients. For dementia diagnosis, the clinician-rated MMSE and MoCA demonstrated sensitivities exceeding 90%, whereas the caregiver-rated Clinical Dementia Rating (CDR) had a sensitivity of only 25%. For depression, the clinician-rated HAM-D (88.5% sensitivity) outperformed the self-reported Beck's Depression Inventory II (BDI-II) (65.4% sensitivity). Most neuropsychiatric assessments were significantly correlated with age, disease duration, and motor severity.CONCLUSIONS: These findings highlight a considerable neuropsychiatric burden in PD, with a distinct female-predominant vulnerability in cognitive and affective domains. The superior performance of clinician-administered assessments emphasizes their value in improving diagnostic certainty. These results support the routine, comprehensive, and sex-specific neuropsychiatric evaluations in the clinical management of PD.PMID:42298495 | DOI:10.1186/s12883-026-05056-4

BMC Genomics. 2026 Jun 15. doi: 10.1186/s12864-026-13019-9. Online ahead of print.ABSTRACTBACKGROUND: During the scent secretion period, adult male muskrats (Ondatra zibethicus) produce a musk-like fragrance similar to that of the forest musk deers (Moschus berezovskii). However, the underlying mechanism of scent secretion in muskrats were not well understood. Scent glands and testicular tissues from 2-year-old muskrats during non-scenting and scenting periods were analyzed using transcriptomics and metabolomics to identify key genes, metabolites, and pathways involved in scent secretion.RESULTS: Key findings include: (1) Significant differences were observed in the tissue structure of scent glands and testes between the two phases. (2) In the scent glands, fifteen candidate genes were identified that primarily regulate the formation of major musk components through steroid biosynthesis, unsaturated fatty acid (UFA) synthesis, glyceride metabolism, cholesterol metabolism, and aldosterone-regulated sodium reabsorption pathways. (3) In the testes, seven key genes were identified that regulate muskrat sex hormone synthesis and action, thereby controlling musk secretion via steroid hormone biosynthesis, GnRH signaling, estrogen signaling, prolactin signaling, cholesterol metabolism, and aldosterone synthesis and secretion pathways. (4) Transcriptomic and metabolomic association analysis revealed that cholesterol metabolism, UFA biosynthesis, and fatty acid metabolism pathways played key roles in regulating scent secretion activity. Meanwhile, during the scent-secreting period, the testes increase the level of phosphatidylethanol through genes Itpr1, Plcb2, and Prkca, influencing the transport and biosynthesis processes of fatty acids and cholesterol in the scent glands via GnRH signaling transduction and prolactin signaling transduction pathways. In addition, the testes regulate the expression of Hsd17b3 and Cyp3a in the scent glands through genes Cyp11a and Hsd11b2 via the steroid hormone biosynthesis pathway, promoting the synthesis of sterols and steroids from cholesterol in the scent glands.CONCLUSIONS: This study discovered that the testes regulate the synthesis and transport of key components in muskrat musk within the scent glands through genes (Itpr1, Plcb2, and Prkca, Hsd11b2, and Cyp11a) via GnRH signaling transduction, prolactin signaling transduction, and steroid hormone biosynthesis pathways.PMID:42298429 | DOI:10.1186/s12864-026-13019-9

BMC Genomics. 2026 Jun 16. doi: 10.1186/s12864-026-13018-w. Online ahead of print.ABSTRACTBACKGROUND: Saline-alkaline stress, particularly sodium bicarbonate-induced alkaline stress, can cause tissue damage and oxidative stress in aquatic animals, thereby inhibiting their growth and even threatening their survival. This has become a key factor limiting the utilization of saline-alkaline water resources. This study for the first time systematically established acute and chronic time-series gradient NaHCO₃ stress treatments, and integrated histological observation, ultrastructural examination, enzyme activity determination as well as transcriptomic and metabolomic profiling to reveal the adaptive response mechanism of M. rosenbergii.RESULTS: In this study, M. rosenbergii were selected as the research object to evaluate the physiological responses under acute (96 h) and chronic (56 d) alkaline stress at NaHCO₃ concentrations of control (0.0 mmol/L), low (3.2 mmol/L, 30% LC₅₀), and high (6.4 mmol/L, 60% LC₅₀). The results indicated that during acute NaHCO₃ stress, the oxidative stress and energy metabolism-related enzyme activities fluctuated over time, reflecting adaptive response to the stress-induced damage. Chronic exposure results showed activation of a coordinated energy network-evidenced by upregulated glycolysis, accompanied by increased expression of hk2 and glut2, as well as elevated activities of HK, PFK and LDH, increased TCA intermediates (succinate, fumarate), and elevated oxidative phosphorylation metabolites, enhancing ATP production. Fatty acid metabolism exhibited a dose-dependent response: synthesis was upregulated under low stress (elevated fas, acsbgl2, and palmitic acid) likely for membrane remodeling, but suppressed under high stress. Prolonged exposure induced significant oxidative damage, evidenced by increased MDA, accumulated LysoPCs, and decreased SOD activity. Concurrently, a marked increase in autolysosomes indicated autophagy activation. Notably, these physiological disruptions were accompanied by a significant, dose-dependent decline in growth performance (FAW, WGR, SGR).CONCLUSIONS: These findings indicate that NaHCO₃ stress induces integrated physiological responses in M. rosenbergii, including enhanced energy metabolism, oxidative injury, and autophagic activation, providing a reference for the development and utilization of saline-alkaline water resources.PMID:42298383 | DOI:10.1186/s12864-026-13018-w

J Am Soc Mass Spectrom. 2026 Jun 15. doi: 10.1021/jasms.5c00428. Online ahead of print.ABSTRACTReference MS/MS libraries remain incomplete due to the vast chemical diversity of metabolites, leaving many spectra from untargeted metabolomics experiments unannotated─the "dark matter" of metabolomics. Machine learning can extend metabolite annotation beyond direct library matches, but its success depends critically on how MS/MS spectra are converted into numerical representations that capture chemically meaningful features while reducing sparsity. Although numerous spectral representations exist, they have not been systematically compared. Using over 71,000 unique compounds with merged-energy MS/MS spectra, we benchmarked a broad set of spectral featurization methods, including fixed and adaptive binning, global-quantile variable-width bins, frequent-peaks representations, spectrum hashing, and learned embeddings such as Spec2Vec, MS2DeepScore, DreaMS, and SpecEmbedding. We further evaluated how vector dimensionality affects performance. A total of 105 neural network models were trained under 5-fold cross-validation to predict Mol2Vec molecular embeddings and retrieve correct structures from a 0.6-million-compound database. Retrieval was assessed at 0.1, 3, and 10 ppm mass tolerances, and a null ranking model was generated to determine expected Top-N accuracy under random candidate ordering. Adaptive binning, frequent-peaks, and DreaMS produced the most accurate embedding predictions. On the test data set, Top-1 retrieval reached 46%, 44%, and 38% for 0.1, 3, and 10 ppm, respectively, with Top-5 accuracies up to 77%. In the CASMI2022 data set, Top-1 performance remained similar at 0.1 ppm but dropped markedly at wider tolerances, reaching only 26% at 3 ppm and 23% at 10 ppm. To ensure reproducibility and broad community applicability, results were further validated on two fully open benchmark data sets, MassSpecGym and Spectraverse, with findings consistent across all three resources. These results underscore clear performance differences among featurization strategies, the strong dependence of retrieval accuracy on mass precision, and the need for evaluation metrics aligned with structure-level annotation tasks.PMID:42298320 | DOI:10.1021/jasms.5c00428

NPJ Antimicrob Resist. 2026 Jun 15. doi: 10.1038/s44259-026-00233-4. Online ahead of print.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is a significant public health threat due to both extensive antimicrobial resistance and immune evasion capabilities, necessitating alternative therapeutic strategies. Disruption of bacterial metal ion homeostasis, a process already leveraged by host nutritional immunity, represents a promising therapeutic approach. The synthetic ionophore PBT2 delivers zinc (Zn) directly into the bacterial cytosol, where it can dysregulate cellular processes and restore the efficacy of conventional antibiotics. Here, we use PBT2 and Zn (PZ) to study the cellular response to metal dysbiosis in MRSA, identifying new metal-dependent molecular vulnerabilities. Integrated transcriptomics, metabolomics and molecular analyses revealed that the antibacterial and oxacillin-resensitisation action of PZ is driven by dual metal stress: intracellular Zn accumulation and manganese (Mn) depletion. PZ disrupted central carbon metabolism at multiple key nodes, impairing glycolysis, the TCA cycle and respiration, leading to NADH and ATP depletion and compromised peptidoglycan biosynthesis. PZ also altered the metal-dependent oxidative stress response, resulting in superoxide accumulation. Collectively, this work presents the dynamic interplay between bacterial metal ion homeostasis, central metabolism, and β-lactam resistance. Uncovering how PBT2 subverts the adaptive responses of MRSA to host-imposed stresses contributes to our understanding of host-pathogen interactions and offers a foundation for developing novel antimicrobials based on metal homeostasis disruption.PMID:42298145 | DOI:10.1038/s44259-026-00233-4

Sci Rep. 2026 Jun 15. doi: 10.1038/s41598-026-58016-w. Online ahead of print.ABSTRACTThe relationship between stress and breast cancer (BC) remains a topic of debate. We investigated the association between stress experienced within the past year and the risk of BC. Population-based incident case-control study of 600 newly diagnosed BC cases and 600 population controls (18-75 years) recruited in Isfahan, Iran between 2021 and 2023. Logistic regression model with short-term stress as main exposure was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) after adjusting for confounders. Multiplicative interaction was tested between stress and menopausal status as well as other confounders. One-year stress level was significantly associated with BC risk. Compared with women reporting low stress levels, the odds of BC were higher among those with high stress levels in both the unadjusted model (OR = 3.10, 95%Cl: 2.45-3.92) and the fully adjusted model (OR = 3.38; 95%CI (2.56, 4.47)). Based on the statistical test for multiplicative interaction, the association appeared stronger among premenopausal women (adjusted OR = 4.88, 95% CI: 3.17-7.52) than among postmenopausal women (adjusted OR = 2.34, 95% CI: 1.53-3.58), with evidence of interaction by menopausal status (p for interaction = 0.018). Despite the inherent limitations of case-control studies, including potential recall and selection biases, the findings of the current study suggest that higher levels of stress experienced within the past year may be associated with an increased risk of breast cancer, particularly among premenopausal women. Further prospective studies are warranted to clarify the nature and direction of this association.PMID:42298021 | DOI:10.1038/s41598-026-58016-w

NPJ Sci Food. 2026 Jun 15. doi: 10.1038/s41538-026-00924-2. Online ahead of print.ABSTRACTThis study aimed to identify dietary patterns and metabolomic signatures associated with metabolic syndrome (MetS) and develop machine learning models integrating both dietary and metabolomic data for risk assessment. In this cross-sectional study of 2810 adults, four dietary patterns derived using principal component analysis were associated with MetS. Serum metabolomic profiling was conducted in 400 participants using liquid chromatography-tandem mass spectrometry. Metabolic signatures of the meat and traditional Chinese patterns remained positively associated with MetS, whereas the rice and tuber pattern metabolic signature remained inversely associated. Metabolomic analysis revealed 71 differential metabolites associated with MetS, including elevated monoacylglycerols and decreased metabolites such as 4-Hydroxyisoleucine. A metabolomic risk score based on key metabolites showed a strong association with MetS (OR = 23.55, 95% CI: 11.77-47.12). Integrating dietary patterns with MetS-specific biomarkers significantly improved risk assessment models (AUC: 0.759-0.820) compared to using dietary patterns and pattern-associated metabolites (AUC: 0.640-0.709), with the Support Vector Machine (SVM) model performing optimally (AUC: 0.820). Specific dietary patterns and their associated metabolomic signatures are significantly associated with MetS. Integrating dietary and metabolomic data markedly improves the SVM model's risk assessment accuracy for MetS risk, offering a robust approach for precision prevention in high-risk populations.PMID:42297822 | DOI:10.1038/s41538-026-00924-2

NPJ Biofilms Microbiomes. 2026 Jun 15. doi: 10.1038/s41522-026-01016-5. Online ahead of print.ABSTRACTThe pervasive accumulation of microplastics (MPs) in ecosystems and human bodies has prompted growing concern regarding their biological effects. However, whether intermittent fasting (IF) modulates MP-induced gut injury remains unclear. We established a murine model of chronic oral exposure to 1 μm polystyrene MPs combined with a daily 8-h feeding window. Multi-omics analyses, including 16S rRNA sequencing, untargeted metabolomics, and immune profiling, were performed. In a murine model of chronic oral exposure to 1 μm polystyrene microplastics, IF aggravated colonic inflammation and oxidative stress. 16S rRNA sequencing showed that IF further altered the microplastic-associated gut microbiota, notably reducing Rikenella abundance. Untargeted metabolomics revealed disrupted purine metabolism, including decreased hypoxanthine levels, which positively correlated with Rikenella. Combined MP and IF exposure was associated with an increased Th17/Treg ratio. Supplementation with Rikenella or hypoxanthine partially attenuated inflammatory changes. These findings unveil a previously unappreciated risk of IF under conditions of environmental microplastic exposure, and highlight the necessity of integrating environmental toxicants into evaluations of dietary interventions.PMID:42297818 | DOI:10.1038/s41522-026-01016-5

Signal Transduct Target Ther. 2026 Jun 15;11(1):233. doi: 10.1038/s41392-026-02724-2.ABSTRACTType 1 diabetes (T1D) exhibits age-related heterogeneity in clinical progression and immune pathology, yet the underlying molecular mechanisms remain poorly understood. Here, we integrate microbiome, metabolome, lipidome, and transcriptome profiling from 108 newly diagnosed pediatric patients with T1D, along with 56 healthy controls, to investigate age-related endotypes. Patients were stratified into early-onset (E-T1D, <7 years), intermediate-onset (I-T1D, 7-12 years), and late-onset (L-T1D, ≥13 years) groups. Multi-omics analyses revealed distinct molecular signatures among T1D subgroups. The most enriched microbial signatures were the genus Acetatifactor in E-T1D, the phylum Firmicutes A in I-T1D, and the family Bacteroidaceae in L-T1D (Linear Discriminant Analysis scores = 3.49, 5.56, and 5.78, respectively). For metabolites, pipecolic acid increased most in E-T1D, testosterone in I-T1D, while N-acetylhomocitrulline was most enriched in L-T1D. Lipidomic profiling revealed subgroup-specific alterations, with increased levels of LPA(16:1) in E-T1D, TG(16:0/18:2/18:3) in I-T1D, and TG(18:0/18:1/18:1) in L-T1D. The proportion of peripheral B cells to total lymphocytes was the highest in E-T1D (median = 11.64%) and associated with upregulated immune-related pathways, lowest in L-T1D (median = 5.99%) and linked to metabolic processes, while I-T1D (median = 8.47%) exhibited intermediate features of both groups. Integration of multi-omics interaction networks and experimental validation revealed that the microbial species Dialister invisus may promote peripheral B cell proliferation via docosapentaenoic acid, potentially contributing to early-onset T1D. Together, these findings provide a molecular framework for understanding age-related T1D endotypes and suggest potential targets for precision intervention. Workflow and key findings of the study.A multi-omics integration strategy was applied to newly diagnosed pediatric type 1 diabetes (T1D) patients stratified by age at diagnosis: early-onset (E-T1D), intermediate-onset (I-T1D), and late-onset (L-T1D), to delineate age-related T1D endotypes. Comprehensive profiling included gut microbiome, serum metabolome, lipidome, and peripheral immune transcriptome analyses. An integrated multi-omics interaction network revealed 665 direct microbiota-gene connections and 2,608 microbiota-metabolite/lipid-gene triadic interactions, highlighting a D. invisus-docosapentaenoic acid (DPA)-STMN1 axis mediating B-cell activation in early-onset T1D.PMID:42297781 | DOI:10.1038/s41392-026-02724-2

Mov Disord. 2026 Jun 15. doi: 10.1002/mds.70404. Online ahead of print.ABSTRACTBACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease with highly variable progression and poor prognosis. This study aimed to characterize survival patterns, identify prognostic factors, and develop an interpretable machine learning model for individualized survival prediction in MSA.METHODS: In this multicenter longitudinal cohort study, 391 MSA patients were analyzed. Prognostic factors were identified using Kaplan-Meier and Cox regression analyses. Six survival models were trained with five-fold cross-validation, with Shapley Additive Explanations (SHAP) being used for feature selection and interpretability.RESULTS: During a median follow-up of 4.9 years, 149 deaths occurred, with a median survival of 6.9 years. The random survival forest model achieved the best performance (C-index 0.769; mean time-dependent area under the curve [AUC] 0.815) with 11 predictors. An interactive web-based platform and a risk score were developed for clinical application.CONCLUSION: This interpretable machine learning model accurately predicted individualized survival in MSA and identified key prognostic factors. © 2026 International Parkinson and Movement Disorder Society.PMID:42297723 | DOI:10.1002/mds.70404

J Biosci Bioeng. 2026 Jun 15:S1389-1723(26)00217-3. doi: 10.1016/j.jbiosc.2026.05.008. Online ahead of print.ABSTRACTLignin is a complex aromatic polymer and a major component of lignocellulosic biomass, whose sustainable utilization is critical for the development of a low-carbon society. The white-rot fungus Phanerochaete sordida YK-624 exhibits high lignin-degrading activity. However, the pathways underlying the metabolism of lignin-derived aromatic compounds by this fungus remain unclear. Here, we combined genomic, transcriptomic, and metabolomic analyses to elucidate the catabolism of lignin-derived aromatic compounds in P. sordida YK-624. Multi-omics data suggest that this strain primarily metabolizes lignin-derived aromatic compounds using 1,2,4-trihydroxybenzene (THB) as a central intermediate, subsequently converting it first into 3-hydroxy-cis,cis-muconic acid (HMA) and then into 3-hydroxyhex-2-enedioic acid. The genes Psthbd and Pshmar 1 or 2, encoding putative THB dioxygenase and HMA reductase in P. sordida YK-624, were heterologously expressed in Escherichia coli. Functional assays confirmed that recombinant PsTHBD catalyzes the dioxygenation of THB and catechol, whereas PsHMAR2 exhibits HMA reductase activity. In contrast, PsHMAR1 showed no detectable activity, suggesting differences in cofactor binding or catalytic function. Our results demonstrate the involvement of PsTHBD and PsHMAR2 in THB degradation and identify for the first time an HMA reductase gene in white-rot fungi. This study advances our understanding of the catabolism of lignin-derived aromatic compounds and highlights the potential of P. sordida YK-624 as a platform for lignin valorization in biotechnological applications.PMID:42297715 | DOI:10.1016/j.jbiosc.2026.05.008

J Ethnopharmacol. 2026 Jun 15:122002. doi: 10.1016/j.jep.2026.122002. Online ahead of print.NO ABSTRACTPMID:42297648 | DOI:10.1016/j.jep.2026.122002