PubMed

Res Pract Thromb Haemost. 2025 Jan 9;9(1):102677. doi: 10.1016/j.rpth.2025.102677. eCollection 2025 Jan.ABSTRACTBACKGROUND: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination.OBJECTIVES: Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored. Here, we examined the plasma lipidome of patients with VITT and compared it with those following ChAdOx1-S vaccination and with unprovoked venous thromboembolism (VTE) to understand the role of lipids in VITT pathophysiology.METHODS: This was a multicenter, prospective cohort study evaluating plasma lipidomics in newly diagnosed VITT samples, which were compared with both healthy controls following ChAdOx1-S vaccination and with unprovoked VTE.RESULTS: Comparison with ChAdOx1-S controls reveals a distinct lipid signature in VITT, characterized by elevations in phosphatidylserine and ceramide species, alongside reductions in several plasmalogens and acylcarnitine species. Notably, similarities between VITT lipid profiles and insulin resistance phenotypes suggest potential metabolic susceptibility. While few significant associations were found between VITT and VTE, an inverse correlation with several acylcarnitine species was demonstrated. Given the known anticoagulant role of acylcarnitine species, these findings suggest a plausible mechanistic pathway elevating the thrombotic potential of VITT above that of standard VTE.CONCLUSION: These findings underscore the important role of lipid metabolism in VITT pathophysiology and highlight the complex interplay between lipids, coagulation, and pathologic thrombosis.PMID:40041449 | PMC:PMC11879676 | DOI:10.1016/j.rpth.2025.102677

Biochem Biophys Rep. 2025 Feb 18;41:101943. doi: 10.1016/j.bbrep.2025.101943. eCollection 2025 Mar.ABSTRACTOBJECTIVE: To investigate the associations between metabolic changes and functions, including energy metabolism, immune response, and redox balance, under short-term hypobaric hypoxia exposure. Non-targeted metabolomics and bioinformatics analysis were applied to explore the adaptive mechanisms of organisms in hypobaric hypoxia.METHODS: Healthy adult male Sprague-Dawley rats were placed in environments simulating altitudes of 6500 m (HC group) and 1588 m (Control group). After 14 days, arterial serum samples were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Significant metabolites (P < 0.05, VIP >1) were identified, and KEGG enrichment analysis was conducted. Differential metabolites were globally analyzed with MetaboAnalyst 5.0.RESULTS: A total of 117 significantly altered metabolites were identified. In the HC group, 84 metabolites significantly increased, while 33 metabolites significantly decreased compared to the Control group. KEGG enrichment analysis revealed significant metabolic pathways, including the PPAR signaling pathway, bile secretion, arginine biosynthesis, alcoholism, and cholesterol metabolism (P < 0.05). Global analysis indicated that these differential metabolites were involved in various pathways, such as energy metabolism, amino acid metabolism, nucleotide metabolism, lipid metabolism, vitamin and cofactor metabolism, steroid metabolism, neurotransmitter metabolism, and heme metabolism, all of which play crucial roles in multiple biological processes.CONCLUSION: Short-term hypobaric hypoxia exposure significantly altered the metabolite profiles in the arterial serum samples of rats, revealing adaptive metabolic reprogramming in energy metabolism, redox balance, immune function, endocrine regulation, and neurological systems.PMID:40041253 | PMC:PMC11876769 | DOI:10.1016/j.bbrep.2025.101943

Front Cell Infect Microbiol. 2025 Feb 18;15:1511900. doi: 10.3389/fcimb.2025.1511900. eCollection 2025.ABSTRACTINTRODUCTION: Body mass index (BMI) is considered an important factor in tumor prognosis, but its role in gastric cancer (GC) remains controversial. There is a lack of studies exploring the effect of BMI on gastric cancer from the perspective of intratumoral microbiota. This study aimed to compare and analyze the differences in and functions of intratumoral microbiota among GC patients with varying BMIs, aiming to ascertain whether specific microbial features are associated with prognosis in low-BMI (LBMI) gastric cancer patients.METHODS: A retrospective analysis of the clinicopathological features and prognosis of 5567 patients with different BMIs was performed between January 2010 and December 2019. Tumor tissues from 189 GC patients were collected for 16S rRNA sequencing, 64 samples were selected for transcriptome sequencing, and 57 samples were selected for untargeted metabolomic analysis.RESULTS: Clinical cohort analysis revealed that GC patients with a low BMI presented poorer clinical and pathological characteristics than those with a non-low-BMI (NLBMI). LBMI was identified as a significant independent risk factor for adverse prognosis, potentially exerting immunosuppressive effects on postoperative adjuvant chemotherapy. 16S rRNA sequencing revealed no significant differences in the alpha and beta diversity of the intratumoral microbiota between the two groups of GC patients. However, LEfSe analysis revealed 32 differential intratumoral microbiota between the LBMI and NLBMI groups. Notably, the genus Abiotrophia was significantly enriched in the LBMI group. Further in-depth analysis indicated that the genus Abiotrophia was inversely associated with eosinophils, P2RY12, and SCN4B genes, and positively linked with LGR6 in LBMI gastric cancer patients. Metabolomic assessments revealed that LBMI was positively associated with purine metabolites, specifically guanine and inosine diphosphate (IDP).DISCUSSION: In conclusion, LBMI is an independent risk factor for poor prognosis in gastric cancer patients and may have an inhibitory effect on postoperative adjuvant chemotherapy. Intratumor flora of gastric cancer patients with different BMI levels differed, with different immune cell infiltration and metabolic characteristics. The genus Abiotrophia may promote gastric cancer development and progression by regulating eosinophils and the purine metabolism pathway, which provides a new idea for the precise treatment of gastric cancer.PMID:40041144 | PMC:PMC11876552 | DOI:10.3389/fcimb.2025.1511900

Front Plant Sci. 2025 Feb 18;16:1526733. doi: 10.3389/fpls.2025.1526733. eCollection 2025.ABSTRACTINTRODUCTION: Fruit color is a crucial quality factor strongly influencing consumer preference for citrus. The coloration of citrus fruit is primarily determined by carotenoids, which produce a range of hues. Gibberellic acid (GA) and ethylene are critical in fruit coloration during the ripening process. Nevertheless, the underlying mechanisms remain poorly understood.METHODS: The present study utilized transcriptomic and metabolomic analyses to investigate the molecular regulatory mechanisms affecting peel pigment metabolism in tangors (Citrus reticulata Blanco×Citrus sinensis L. Osbeck) following GA and ethephon (ETH) treatments.RESULTS AND DISCUSSION: Collectively, our findings indicated that GA inhibits chlorophyll degradation and the accumulation of numerous carotenoids, including five violaxanthin esters (violaxanthin palmitate, violaxanthin myristate-caprate, violaxanthin myristate-laurate, violaxanthin dilaurate, violaxanthin myristate) and two β-cryptoxanthin derivatives (β-cryptoxanthin laurate, β-cryptoxanthin myristate), while ETH promotes these processes. Furthermore, GA inhibited the downregulation of lutein, the predominant carotenoid in immature fruits. Notably, integrated transcriptomic and metabolomic analyses identified 33 transcription factors associated with pigment metabolism. Of these, two novel transcription factors, the ethylene-responsive transcription factor ABR1 and the HD-Zip transcription factor ATHB7, were uncovered through both transcriptomic analysis and weighted gene co-expression network analysis. These two transcription factors positively regulated the colouration process, as validated by transient overexpression assays in tobacco. Taken together, our findings elucidated the global carotenoid changes and transcriptional alterations in regulating citrus peel color under hormone induction, with significant implications for improving citrus production.PMID:40041021 | PMC:PMC11876184 | DOI:10.3389/fpls.2025.1526733

iScience. 2025 Jan 30;28(3):111915. doi: 10.1016/j.isci.2025.111915. eCollection 2025 Mar 21.ABSTRACTContamination of heavy metals (HMs) in agroecosystem presented an additional dimension of complexity along with the adverse consequences of climate change for the scientific fraternity. The increasing population and urbanization on the other hand are regarded as the main sources of urban waste (UW). Holistic utilization of UW-derived biochar (BC) has shown potential to be utilized as a source of soil supplement in the agriculture sector, fulfilling several sustainable development goals (SDGs). An attempt has been made to evaluate the techno-economical prospect, efficacy of UW-BC in remediation HMs from SDGs and circular bio-economy prospective. Current review has highlighted that biochar, when amended alone/in combination, enhances HMs remediation potential. Economic analysis of UW-BC reinforces its viability as a sustainable solution for waste management. Consequently, the application of UW-BC has the potential to contribute significantly to the achievement of multiple SDGs, warranting further research and increased investment in this field.PMID:40040805 | PMC:PMC11879596 | DOI:10.1016/j.isci.2025.111915

Plant J. 2025 Mar;121(5):e70039. doi: 10.1111/tpj.70039.ABSTRACTThe aromatic composition of lignin greatly influences the potential utility of lignocellulosic biomass. Previously, we generated transgenic rice plants with altered lignin aromatic composition and enhanced biomass utilization properties by suppressing the expression of p-COUMAROYL ESTER 3-HYDROXYLASE (C3'H). While RNAi-derived C3'H-knockdown lines displayed relatively normal growth with substantially augmented levels of p-hydroxyphenyl-type lignin units, genome-edited C3'H-knockout lines exhibited severely impaired growth phenotype, leading to arrested seedling development. In this study, we further characterized the genome-edited C3'H-knockout rice by analyzing gene expression and phenolic metabolite profiles alongside phenotypic traits and cell wall lignin structure. The seedlings of the C3'H-knockout rice displayed irregular vasculature and ectopic lignification. RNA-sequencing analysis detected widespread changes in the expression of genes associated with plant growth, hormone biosynthesis and signaling, and stress responses in the C3'H-knockout rice. Overall, our data suggested that C3'H disruption activates metabolic sensor-mediated signaling pathways, which in turn regulate phenylpropanoid metabolism. In line with this, phenolic metabolite profiling of the C3'H-knockout rice revealed not only shifts in monolignol-associated phenylpropanoids but also reductions in flavonoids and salicylic acid derivatives. Moreover, changes in the aromatic composition of the mutant lignin and phenolic metabolites indicated the presence of parallel monolignol pathways enabling rice to produce guaiacyl- and syringyl-type monolignol derivatives in the absence of C3'H activity. Our findings contribute to a deeper understanding of the mechanisms underlying the growth defects of lignin-modified mutants, with implications for optimizing the utility of grass lignocellulose.PMID:40040338 | DOI:10.1111/tpj.70039

Stem Cell Res Ther. 2025 Mar 5;16(1):115. doi: 10.1186/s13287-025-04213-9.ABSTRACTBACKGROUND: Spaceflight and microgravity environments have been shown to cause significant health impairments, including bone loss, immune dysfunction, and hematopoietic disorders. Hematopoietic stem cells (HSCs), as progenitors of the hematopoietic system, are critical for the continuous renewal and regulation of immune cells. Therefore, elucidating the regulatory mechanisms governing HSC fate and differentiation in microgravity environments is of paramount importance.METHODS: In this study, hindlimb unloading (HU) was employed in mice to simulate microgravity conditions. After 28 days of HU, cells were isolated for analysis. Flow cytometry and colony-forming assays were utilized to assess changes in HSC proliferation and differentiation. Additionally, transcriptomic and untargeted metabolomic sequencing were performed to elucidate alterations in the metabolic pathways of the bone marrow microenvironment and their molecular regulatory effects on HSCs fate.RESULTS: Our findings revealed that 28 days of HU impaired hematopoietic function, leading to multi-organ damage and hematological disorders. The simulated microgravity environment significantly increased the HSCs population in the bone marrow, particularly within the long-term and short-term subtypes, while severely compromising the differentiation capacity of hematopoietic stem/progenitor cells. Transcriptomic analysis of HSCs, combined with metabolomic profiling of bone marrow supernatants, identified 1,631 differentially expressed genes and 58 metabolites with altered abundance. Gene set enrichment analysis indicated that HU suppressed key pathways, including hematopoietic cell lineage and MAPK signaling. Furthermore, integrated analyses revealed that metabolites affected by HU, particularly hypoxanthine enriched in the purine metabolism pathway, were closely associated with hematopoietic cell lineage and MAPK signaling pathways. Molecular docking simulations and in vitro experiments confirmed that hypoxanthine interacts directly with core molecules within these pathways, influencing their expression.CONCLUSIONS: These findings demonstrate that hypoxanthine in the bone marrow supernatant acts as a signaling mediator under microgravity, influencing HSCs fate by modulating hematopoietic cell lineage and MAPK signaling pathways. This study offers novel insights into the impact of microgravity on HSC fate and gene expression, underscoring the pivotal role of bone marrow microenvironmental metabolic changes in regulating key signaling pathways that determine hematopoietic destiny.PMID:40038750 | DOI:10.1186/s13287-025-04213-9

J Transl Med. 2025 Mar 4;23(1):260. doi: 10.1186/s12967-025-06296-7.ABSTRACTBACKGROUND: Microglia-evoked neuroinflammation contributes to neurodegenerative diseases such as multiple sclerosis (MS). Metabolic reprogramming, including changes in polyunsaturated fatty acids (PUFAs), plays a critical role in MS pathophysiology. Previous studies identified reduced plasma α-dimorphecolic acid (α-DIPA), a linoleic acid derivative, in MS patients. This study investigated the anti-inflammatory effects of α-DIPA on microglia and the underlying pathways.METHODS: Lipopolysaccharide (LPS)-induced BV-2 microglial inflammation was used as an in vitro model. α-DIPA effects were assessed via ELISA for nitric oxide (NO) release, flow cytometry was used to examine cell proliferation, activation and polarization, and transcriptomic analysis was applied to identify key signaling pathways regulated by α-DIPA.RESULTS: ELISA results showed that exogenous α-DIPA treatment significantly inhibited LPS-induced NO release from BV-2 cells in a concentration-dependent manner. Moreover, flow cytometry analysis suggested that 40 µM α-DIPA treatment significantly repressed LPS-induced BV-2 cell proliferation, activation, as well as M1 and M2 type polarization. Furthermore, transcriptome analysis revealed that exogenous α-DIPA extensively and drastically decreased the transcriptional level of numerous genes that are involved in the regulation of inflammatory responses, for instance, proinflammatory genes such as Tnf and Ccl3 related to IL-17 and TNF-α signaling. In addition, we also observed that the expression of multiple genes in NF-κB signaling were also inhibited greatly by α-DIPA, such as Nfkb2 and Nfkbia. Notably, α-DIPA robustly suppressed LPS-induced mRNA expression of abundant genes participating in the ferroptosis pathway, including Acsl4, Slc7a11, Me1, and Hmox1. Interestingly, the expressions of multiple ferroptosis-related genes were regulated specifically by α-DIPA but not LPS, such as Acsl5, Acsl6, Alox5, Cars, Dpp3, Dpp10, Slc2a5, and Slc7a1.CONCLUSION: α-DIPA inhibits microglial inflammation likely through regulating the pathways of the ferroptosis and NF-κB signaling. These results provided preliminary evidence for α-DIPA as a potential therapeutic candidate for neurodegenerative diseases like MS.PMID:40038710 | DOI:10.1186/s12967-025-06296-7

BMC Med. 2025 Mar 5;23(1):134. doi: 10.1186/s12916-025-03971-w.ABSTRACTBACKGROUND: Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood.METHODS: We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs.RESULTS: We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were significantly upregulated in COVID-19 convalescents. Pulmonary and molecular abnormalities persisted for 3 years in COVID-19 convalescents; impaired diffusing capacity for carbon monoxide (DLco) was the most prominent feature. We used this multi-omics profile to develop a model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) and two metabolites (arachidonoyl-EA and 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) for identification of COVID-19 convalescents with abnormal DLco.CONCLUSIONS: These data provide insights concerning molecular sequelae among COVID-19 convalescents up to 3 years after hospital discharge, clarify mechanisms driving respiratory sequelae, and support the development of a novel model to predict reduced DLco. This longitudinal multi-omics analysis may illuminate the trajectory of altered lung function in COVID-19 convalescents.PMID:40038650 | DOI:10.1186/s12916-025-03971-w

BMC Cancer. 2025 Mar 4;25(1):389. doi: 10.1186/s12885-025-13690-3.ABSTRACTBACKGROUND: Reportedly, there is an association between body metabolites and the risk of Hepatocellular Carcinoma (HCC) & Cholangiocarcinoma (CCA), possibly due to disrupted metabolic pathways leading to oxidative stress and an imbalance in cell proliferation and apoptosis, thereby increasing the risk of cancer. However, whether metabolites play a role in the onset of HCC or CCA remains inconclusive.OBJECTIVE: The aim of our study is to explore the potential causal relationship between metabolites and the risk of HCC&CCA.METHODS: Our study investigated the causal relationship between 1400 metabolites and HCC&CCA using publicly available genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with both metabolites and HCC&CCA were chosen as instrumental variables (IVs). The main approaches employed include inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (OR) used as the assessment criterion. Heterogeneity testing and sensitivity analyses were conducted to validate the results. We also conducted a reverse MR analysis to further validate the relationship between exposure and disease outcomes.RESULTS: This Mendelian Randomization (MR) study indicates a significant causal relationship between 19 metabolites and the risk of HCC&CCA. Among them, the risk factors include "Bilirubin (E, Z or Z, E) levels," "Bilirubin (Z, Z) to taurocholate ratio," "Dimethylarginine (sdma + adma) levels," "N-methyltaurine levels," "4-vinylguaiacol sulfate levels," "Cholate to adenosine 3',5'-cyclic monophosphate (cAMP) ratio," "Glycohyocholate levels," "Cholesterol levels," and "4-methylguaiacol sulfate levels." The incidence risk of HCC and CCA increases with the elevation of these metabolites. Protective factors include "Ursodeoxycholate levels," "3-hydroxybutyroylglycine levels," "Linoleoylcholine levels," "Nonanoylcarnitine (C9) levels," "Pristanate levels," "Heptenedioate (C7:1-DC) levels," "Mannonate levels," "N-acetyl-L-glutamine levels," "Sphinganine levels," and "N-lactoyl isoleucine levels." The incidence risk of HCC and CCA potentially decreases as the levels of these metabolites increase. Heterogeneity tests show that most instrumental variables do not exhibit inter-gene heterogeneity, and the possibility of pleiotropy in the analysis is very low according to the sensitivity analysis. The reverse MR analysis did not yield positive results.CONCLUSION: Our study has unveiled the intricate causal relationships between metabolites and the risk of HCC&CCA. Through our analysis, we identified nine metabolites, including "Bilirubin (E, Z or Z, E) levels," "Dimethylarginine (sdma + adma) levels," "Cholesterol levels,"ect, as risk factors for HCC&CCA. The incidence risk of HCC and CCA increases with their elevation. On the other hand, ten metabolites, such as "Ursodeoxycholate levels," "Linoleoylcholine levels," "Pristanate levels," ect, were identified as protective factors for HCC&CCA. The risk of developing HCC and CCA decreases with an increase in these metabolites. In conclusion, these findings further explore the physiological metabolic pathways underlying the pathogenesis of HCC and CCA, emphasizing future research directions. They pave the way for researchers to delve into the biological mechanisms of these diseases, facilitating early intervention and treatment strategies for these conditions.PMID:40038628 | DOI:10.1186/s12885-025-13690-3

J Agric Food Chem. 2025 Mar 4. doi: 10.1021/acs.jafc.4c12089. Online ahead of print.ABSTRACTCell-cultured fish fat (CCF) has the potential to enhance the flavor and texture of cell-cultured fish meat (CCM). Herein, CCF was developed through the adipogenic transdifferentiation of Larimichthys crocea muscle satellite cells (LCMSCs). A low-serum culture system and a large-scale culture system were established. A rapid transdifferentiation medium was also developed, and the mechanisms in promoting adipogenic transdifferentiation were preliminarily analyzed. The results indicated that the proliferation rate and morphology of cells were not significantly affected by serum reduction following domestication. These cells can be cultured in bioreactors, achieving a 10-fold increase in density. The combination of horse serum and oleic acid enabled adipogenic transdifferentiation within 8 days. Transcriptomic and metabolomic analyses revealed significant changes in gene expression and lipid metabolism, with enrichment of pathways related to fatty acid metabolism. Five inducers were quantified to assess the quality of CFF. This study provides a feasible method for CCF production and lays the theoretical basis for the development of CCM.PMID:40038623 | DOI:10.1021/acs.jafc.4c12089

Nat Genet. 2025 Mar 4. doi: 10.1038/s41588-025-02096-3. Online ahead of print.ABSTRACTThe biological mechanisms through which most nonprotein-coding genetic variants affect disease risk are unknown. To investigate gene-regulatory mechanisms, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA sequencing in 4,732 participants and integrated protein, metabolite and lipid data from the same individuals. We identified cis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Colocalization analyses revealed 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at disease loci with therapeutic implications, such as WARS1 in hypertension, IL7R in dermatitis and IFNAR2 in COVID-19. Our study provides an open-access resource on the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans ( https://IntervalRNA.org.uk ).PMID:40038547 | DOI:10.1038/s41588-025-02096-3

Commun Biol. 2025 Mar 4;8(1):364. doi: 10.1038/s42003-025-07795-5.ABSTRACTInvasive plants threaten global ecosystems, yet traditional analyses of functional traits cannot fully explain their dominance over co-occurring natives. Metabolomics offers insights into plant invasions, but single-technique studies often miss critical biochemical mechanisms. We employ a multimodal metabolomics approach (¹H NMR, LC MS/MS, FT-ICR-MS, and MALDI-MSI) to investigate the biochemical basis of Lehmann lovegrass (Eragrostis lehmanniana) invasion in semi-arid North America, comparing it with a co-occurring native grass, Arizona cottontop (Digitaria californica). Our analysis reveals three metabolomic traits of Lehmann lovegrass compared to Arizona cottontop: Enhanced nitrogen allocation in shoots, reduced defensive metabolites in root layers; and increased root exudate modulation under stress conditions. These traits suggest Lehmann lovegrass succeeds through adaptation to increasing aridity rather than direct competition, demonstrating adaptation to nutrient-poor environments and high phenotypic plasticity in response to increasing aridity. This integrated metabolomic approach provides new mechanistic insights into invasion ecology and plant adaptation under environmental change.PMID:40038433 | DOI:10.1038/s42003-025-07795-5

Sci Rep. 2025 Mar 4;15(1):7573. doi: 10.1038/s41598-025-90060-w.ABSTRACTEnvironmental factors play an important role in anthocyanin biosynthesis, and potassium, an essential nutrient for blueberry growth, can act as an enzyme activator. However, few reports exist on the transcriptional and anthocyanin metabolic changes in blueberries regulated by potassium. The results indicated that potassium treatment significantly increased the contents of malvidin, petunidin, and delphinidin in blueberry fruits and accelerated early color development, particularly favoring the accumulation of darker pigments such as malvidin, petunidin, and delphinidin when applied at the young fruit stage. Transcriptome analysis identified 102 glucose metabolism-related genes and 12 differential potassium transport genes potentially involved in potassium-mediated anthocyanin synthesis and accumulation, with AKT1 and KUP potassium transporters being upregulated under potassium fertilization. In the anthocyanin biosynthesis pathway, 13 genes, including UFGT, F3H, CHI, HCT, C12RT1, DFR, and F3'5'H, were closely linked to flavonoid and anthocyanin metabolite synthesis regulated by potassium. Furthermore, potassium treatment markedly enhanced the activities of key enzymes, F3H, F3'5'H, and UFGT, in the anthocyanin synthesis pathway of blueberry fruits. Overall, these findings elucidate the influence of potassium application timing on anthocyanin synthesis and provide valuable insights into the molecular mechanisms governing anthocyanin biosynthesis in blueberries.PMID:40038339 | DOI:10.1038/s41598-025-90060-w

Sci Data. 2025 Mar 4;12(1):377. doi: 10.1038/s41597-025-04652-2.ABSTRACTThe profiling of metabolites provides an immediate snapshot that depicts crucial physiological information, holding immense potential for the early diagnosis and prognosis of diseases, including diabetes. Herein, we proposed an optimized and in-depth target-based metabolome platform through an integration of six distinct conditions, including a normal phase, a pre-column chemical derivatization and four reversed phase separation methods for the quantification of a total of 1609 small molecules (32 sub-classes) in serum after normalization using isotope-labeled internal standards. After undergoing rigorous methodological validation and comprehensive comparison with untargeted strategies, we present a new dataset of metabolomic profile encompassing a cohort of 200 healthy individuals and 100 newly diagnosed Type 2 diabetes mellitus (T2DM) patients from the northern region of China. The overall differential analysis results indicated obvious metabolic disturbance of amino acid, fatty acids, lysophosphatidyl-choline and triacylglycerol in T2DM. We hereby make these technical validation results and the profiling dataset publicly available to the scientific community, showcasing its exceptional sensitivity and robustness as an invaluable tool for the comprehensive targeted metabolome analysis.PMID:40038313 | DOI:10.1038/s41597-025-04652-2

Signal Transduct Target Ther. 2025 Mar 5;10(1):79. doi: 10.1038/s41392-025-02159-1.ABSTRACTPsychological stress causes gut microbial dysbiosis and cancer progression, yet how gut microbiota determines psychological stress-induced tumor development remains unclear. Here we showed that psychological stress promotes breast tumor growth and cancer stemness, an outcome that depends on gut microbiota in germ-free and antibiotic-treated mice. Metagenomic and metabolomic analyses revealed that psychological stress markedly alters the composition and abundance of gut microbiota, especially Akkermansia muciniphila (A. muciniphila), and decreases short-chain fatty acid butyrate. Supplement of active A. muciniphila, butyrate or a butyrate-producing high fiber diet dramatically reversed the oncogenic property and anxiety-like behavior of psychological stress in a murine spontaneous tumor model or an orthotopic tumor model. Mechanistically, RNA sequencing analysis screened out that butyrate decreases LRP5 expression to block the activation of Wnt/β-catenin signaling pathway, dampening breast cancer stemness. Moreover, butyrate as a HDAC inhibitor elevated histone H3K9 acetylation level to transcriptionally activate ZFP36, which further accelerates LRP5 mRNA decay by binding adenine uridine-rich (AU-rich) elements of LRP5 transcript. Clinically, fecal A. muciniphila and serum butyrate were inversely correlated with tumoral LRP5/β-catenin expression, poor prognosis and negative mood in breast cancer patients. Altogether, our findings uncover a microbiota-dependent mechanism of psychological stress-triggered cancer stemness, and provide both clinical biomarkers and potential therapeutic avenues for cancer patients undergoing psychological stress.PMID:40038255 | DOI:10.1038/s41392-025-02159-1

Geroscience. 2025 Mar 4. doi: 10.1007/s11357-025-01571-3. Online ahead of print.ABSTRACTA significant challenge in multi-omic geroscience research is the collection of high quality, fit-for-purpose biospecimens from a diverse and well-characterized study population with sufficient sample size to detect age-related changes in physiological biomarkers. The Dog Aging Project designed the precision cohort to study the mechanisms underlying age-related change in the metabolome, microbiome, and epigenome in companion dogs, an emerging model system for translational geroscience research. One thousand dog-owner pairs were recruited into cohort strata based on life stage, sex, size, and geography. We designed and built a novel implementation of the REDCap electronic data capture system to manage study participants, logistics, and biospecimen and survey data collection in a secure online platform. In collaboration with primary care veterinarians, we collected and processed blood, urine, fecal, and hair samples from 976 dogs. The resulting data include complete blood count, chemistry profile, immunophenotyping by flow cytometry, metabolite quantification, fecal microbiome characterization, epigenomic profile, urinalysis, and associated metadata characterizing sample conditions at collection and during lab processing. The project, which has already begun collecting second- and third-year samples from precision cohort dogs, demonstrates that scientifically useful biospecimens can be collected from a geographically dispersed population through collaboration with private veterinary clinics and downstream labs. The data collection infrastructure developed for the precision cohort can be leveraged for future studies. Most important, the Dog Aging Project is an open data project. We encourage researchers around the world to apply for data access and utilize this rich, constantly growing dataset in their own work.PMID:40038157 | DOI:10.1007/s11357-025-01571-3

J Ethnopharmacol. 2025 Mar 3:119523. doi: 10.1016/j.jep.2025.119523. Online ahead of print.NO ABSTRACTPMID:40038003 | DOI:10.1016/j.jep.2025.119523

Semin Arthritis Rheum. 2025 Feb 23:152696. doi: 10.1016/j.semarthrit.2025.152696. Online ahead of print.ABSTRACTTo enhance our understanding of the pathogenesis of diseases, including rheumatic diseases, and to improve disease control, it is essential to attain a thorough understanding of the human immune system, alongside mouse immunology. Historically, the investigation of the human immune system has posed significant challenges due to methodological limitations. Nonetheless, recent advancements in genomic studies of multifactorial diseases have elucidated that numerous risk-associated genetic variants affecting quantitative differences in cell-specific gene expression. In light of these findings, we are currently examining individual genetic variations in both healthy individuals and patients, as well as categorizing cells into distinct subsets in order to construct a comprehensive dataset concerning the human immune system. This is accomplished by combining data on gene expression, factors influencing the expression mechanisms, protein expression, metabolomics, and environmental variables pertinent to immune functionality-such as gut microbiota. These datasets will facilitate the comprehensive characterization of the human immune system. Using these datasets and through the integrative analyses of data related to risk genetic variations and gene expression profiles of each disease and individual, we anticipate uncovering novel insights into the human immune system, the heterogeneity of diseases, immune function mechanisms, and their regulatory strategies that may not be achievable through murine models.PMID:40037996 | DOI:10.1016/j.semarthrit.2025.152696

Carbohydr Polym. 2025 May 1;355:123367. doi: 10.1016/j.carbpol.2025.123367. Epub 2025 Feb 10.ABSTRACTPectins have demonstrated significant prebiotic potential in modulating gut microbiota and enhancing microbial metabolic functions. Nevertheless, the exact relationship between pectin structure and related properties on gut microbiota regulation is yet to be fully elucidated. To explore this, the interactions between four purified pectins with specific structural characteristics and gut microbiota were examined and compared through in vitro fecal fermentation, followed by full-length 16S rRNA gene sequencing, metabolomics, and bioinformatic analysis. The result shows that the pectins selectively modulated the composition of gut microbiota while being degraded into different levels of SCFAs. Moreover, the metabolite profiles in the pectin groups were also qualitatively and quantitatively different, suggesting that the structural variations in pectins further impacted the metabolic functionality of gut microbiota. The bioinformatic analysis revealed that various structural parameters of pectins, including the α-(1 → 4)-linked galacturonic acid composed linear chain in smooth region, arabinose residue determined hair region contribution, conjugated protein content, and molecular weight, are crucial factors in controlling their interaction with gut microbiota, the bacterial cross-feeding, and finally the microbial metabolic outcomes. This research advances our current understanding of the connection between pectin structure and its regulatory properties on gut microbiota at the level of purified pectin molecules.PMID:40037737 | DOI:10.1016/j.carbpol.2025.123367