PubMed

Arch Biochem Biophys. 2025 Apr 17:110427. doi: 10.1016/j.abb.2025.110427. Online ahead of print.ABSTRACTSympathetic hyperactivation and metabolic reprogramming are found in heart failure. Parasympathetic activation by acetylcholine receptor agonists attenuates doxorubicin-induced heart failure by improving mitochondrial function and ameliorating apoptosis and inflammation. However, the effect of these agents on cardiac metabolic reprogramming in doxorubicin-induced heart failure has never been investigated. Male Wistar rats received either vehicle, 6 doses of 3 mg/kg/day of doxorubicin, 6 doses of 3 mg/kg/day of doxorubicin and 3 mg/kg/day of an alpha-7 nicotinic acetylcholine receptor agonist for 30 days, or 6 doses of 3 mg/kg/day of doxorubicin and 12 mg/kg/day of a muscarinic acetylcholine receptor agonist for 30 days. Then, the rats were euthanized to collect heart and serum for metabolomics study. Doxorubicin caused increased glycolysis, increased ketone body utilization, decreased fat utilization, decreased succinate oxidation, and decreased adenosine triphosphate production. Co-treatment with acetylcholine receptor agonist ameliorated an increase in glycolysis, and restored fat utilization, succinate oxidation, and adenosine triphosphate production in the heart. Metabolome alterations in serum were consistent with those in the heart. Our findings highlighted the roles of metabolomics in identifying cardiac metabolic reprogramming and emphasized the potential of acetylcholine receptor agonist in promoting a favorable pattern of cardiac metabolic reprogramming in doxorubicin-induced heart failure.PMID:40252789 | DOI:10.1016/j.abb.2025.110427

Mucosal Immunol. 2025 Apr 17:S1933-0219(25)00042-X. doi: 10.1016/j.mucimm.2025.04.004. Online ahead of print.ABSTRACTPromoting intestinal regeneration and enhancing mucosal healing have emerged as promising therapeutic alternatives for treating intestinal disorders that compromise epithelial barrier integrity and function. However, the cellular and molecular mechanisms underlying these processes remain poorly understood. This knowledge gap is partly due to the lack of reliable and cost-effective in vivo models for studying the mechanisms governing intestinal damage and regeneration. Here, we developed a controlled, inducible, and targeted intestinal epithelial cell (IEC) ablation transgenic zebrafish model that recapitulates features of intestinal damage and regeneration observed in humans. Single-cell RNAseq and live imaging revealed accumulation of macrophages in the recovering intestine, contributing to its regeneration. Furthermore, we observed overexpression of insulin-like growth factor binding protein 1a (igfbp1a) during intestinal damage. Morpholino-mediated knockdown of igfbp1a exacerbated intestinal damage and impaired subsequent regeneration. In summary, we introduced a novel zebrafish model of intestinal damage that enables in vivo high-throughput screening for identifying and validating novel modulators of mucosal healing and intestinal regeneration.PMID:40252728 | DOI:10.1016/j.mucimm.2025.04.004

Environ Int. 2025 Apr 17;199:109461. doi: 10.1016/j.envint.2025.109461. Online ahead of print.ABSTRACTBACKGROUND: Aflatoxins are mycotoxins produced by Aspergillus fungi in crops intended for food and feed. Acute exposure to high levels of aflatoxin B1, one of the most toxic mycotoxins, can result in severe poisoning, defined as acute aflatoxicosis, which manifests as acute hepatic failure followed by death in severe cases. Currently global burden estimates of acute aflatoxicosis are lacking - in contrast to burden estimates of chronic exposure - making it difficult to implement and prioritize risk management strategies in the prevention and control of aflatoxin exposure.AIM: This systematic review assessed global evidence on the incidence and mortality of acute aflatoxicosis from 1990 to 2023. While symptomology & disease duration was also examined, it served as a secondary outcome to provide additional clinical context.SEARCH STRATEGY AND ELIGIBILITY: A structured search was conducted in PubMed, Web of Science, Embase, Scopus, INASP and grey literature. Studies were imported into Covidence for review.STUDY SELECTION AND EXTRACTION: Two independent reviewers screened and extracted titles, abstracts, and full texts. Eligible studies included all human studies.RESULTS: From 11,539 references, 9 studies were included. Heterogeneity existed in study design, region, age of the study population and aflatoxin analysis. Number of cases ranged from 1 to 317, with aflatoxin concentrations varying widely, i.e. between 10 and 51,100 µg/kg in food, 36 and 209,000 pg/mg albumin in serum, and 19 and 18,521 pg/g in tissue. Only one outbreak provided sufficient data to estimate an attack rate of 8 cases per 100,000. Mortality ranged from 16.2 to 76.5 %, affecting children under 15 and adults over 40 most severely. Common symptoms included vomiting (77-100 %), jaundice (88-100 %), and abdominal pain (8-87 %). The risk of bias was generally low.CONCLUSION: This review shows that acute aflatoxicosis remains a significant public health burden, especially among vulnerable groups in African countries, although the variability in studies and lack of standardized reporting make burden estimation difficult, highlighting the need for better warning systems and standardized reporting, despite challenges with infrastructure and resources in affected areas.PMID:40252547 | DOI:10.1016/j.envint.2025.109461

Vet Parasitol. 2025 Apr 17;337:110473. doi: 10.1016/j.vetpar.2025.110473. Online ahead of print.ABSTRACTEimeria tenella (E. tenella) is the most pathogenic avian coccidial species that targets the cecal epithelial cells of chickens. During the peak period of E. tenella oocyst shedding, the release of a large number of oocysts causes great damage to the cecal tissue. This study uses scanning electron microscopy to observe morphological changes in the host cecum during this period. Subsequently, the metabolic status and transcription level of the cecal tissue were analyzed to gain a comprehensive understanding of the interaction mechanism between E. tenella and the host. The results show substantial cecal tissue damage during the peak oocyst shedding period. The test group shows widespread epithelial cell sloughing, lamina propria exposure, widened intercellular spaces, and a scattered arrangement of absorptive epithelial cells. Combined analysis of the metabolome and transcriptome revealed that primary metabolic pathways, including amino acid metabolism, nucleic acid metabolism and lipid metabolism, were significantly altered in the process of E. tenella damage to cecal tissue. The transcription factor GLI-Kruppel family member 3 (GLI3) may be involved in regulation of primary metabolic pathways through mTORC1 signaling pathway. This study elucidates how E. tenella affects the host through physiological, metabolic and transcriptional changes in chicken cecal tissue. It provides valuable insights into the mechanisms of host immune response and the molecular dynamics of parasite-host interaction.PMID:40252508 | DOI:10.1016/j.vetpar.2025.110473

Talanta. 2025 Apr 17;293:128171. doi: 10.1016/j.talanta.2025.128171. Online ahead of print.ABSTRACTCapillary and microchip electrophoresis plays an important role in the analysis of the chemical composition of plants and nutrient soils, which finds applications in plant physiology, agrochemistry, medicine, toxicology and food science. Electrophoretic methods are used to determine minerals such as nutrients, heavy metal ions, primary and secondary metabolites, herbicides, phytohormones, peptides, proteins and extracellular vesicles. Progress is particularly evident in the following topics: i) development of mobile electrophoretic analysers for field-based monitoring of soil mineral supply, ii) direct analysis of xylem sap without sample treatment, iii) coupling of capillary and microchip electrophoresis with mass spectrometry for comprehensive metabolome and proteome characterization, iv) determination of secondary metabolites as biologically active compounds with a range of therapeutic and toxicological effects, v) monitoring of herbicides and their degradation dynamics, vi) research on plant exudates, extracellular vesicles and specific protein interactions.PMID:40252503 | DOI:10.1016/j.talanta.2025.128171

Int Immunopharmacol. 2025 Apr 18;156:114665. doi: 10.1016/j.intimp.2025.114665. Online ahead of print.ABSTRACTDespite the identification of several pathogenic drivers, the molecular mechanisms underlying the development of acute myeloid leukemia (AML) remain largely unknown. Therefore, we sought to explore the key genes associated with leukemia and identified cluster of differentiation 40 (CD40) as a key mediator linked to the incidence and progression of AML. Higher levels of CD40 were detected in patients with AML compared to healthy donors. Moreover, elevated CD40 expression was associated with lower overall survival rates. Furthermore, anti-CD40 antibody significantly induced apoptosis and enhanced drug sensitivity in human AML cell lines. Conversely, ex vivo treatment of primary AML samples with a CD40 agonist significantly decreased cell apoptosis and drug sensitivity. In Kasumi-1 AML cells, CD40 knockout (KO) significantly impaired the engraftment ability of leukemia cells and reduced the leukemia burden in NSG mice compared to wild-type mice. RNA sequencing showed that differentially expressed genes were significantly enriched in the nuclear factor-kB (NF-kB) signaling pathway in CD40-KO cells, which was confirmed through Western blotting. Untargeted metabolomic analysis revealed 179 metabolites with differential expression between WT and CD40 KO cells. Subsequent analysis revealed significant changes in the main metabolic pathways, particularly the biosynthesis of unsaturated fatty acids and lipid metabolism. A targeted metabolomics study of fatty acid metabolism demonstrated that cis-5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) was markedly downregulated in CD40-KO cells compared to wild-type cells. Remarkably, EPA reversed the apoptosis and cell cycle arrest induced by CD40 deletion, simultaneously reducing the drug sensitivity of CD40-KO cells. Together, our study highlights the potential of CD40 as a target in the treatment of AML.PMID:40252467 | DOI:10.1016/j.intimp.2025.114665

Phytomedicine. 2025 Apr 12;142:156763. doi: 10.1016/j.phymed.2025.156763. Online ahead of print.ABSTRACTBACKGROUND: Ginsenosides, the primary active compounds in Panax ginseng C. A. Mey., are well known for their potent immunomodulatory effects. However, their precise mechanisms, particularly concerning the "intestinal-metabolism-immune axis", have yet to be fully elucidated.PURPOSE: This study aims to investigate how ginsenosides protect immune function through the regulation of the gut-metabolism-immune axis.STUDY DESIGN: A CTX-induced immunodeficient mouse model was established to assess the effects of ginsenosides on immune function, gut microbiota, and metabolic pathways.METHODS: The immune organ indices (spleen and thymus), levels of immune cytokines (TNF-α, IFN-γ, IL-6, IL-1β), and immunoglobulins (IgM, IgA) were assessed. Intestinal microbial diversity was analyzed using 16S rRNA sequencing, and metabolomics was employed to identify disruptions in amino acid and lipid metabolic pathways. Spearman correlation analysis and Western blotting were conducted to explore the involvement of the TLR4/MyD88/NF-κB signaling pathway.RESULTS: Ginsenosides significantly restored immune organ indices and enhanced cytokines and immunoglobulins. 16S rRNA sequencing revealed an increase in probiotic levels and a reduction in potentially harmful bacteria, thereby enhancing intestinal microbiota diversity. Metabolomics analysis showed that ginsenosides ameliorated CTX-induced metabolic disorders and stimulated the production of short-chain fatty acids (SCFAs) and bile acids. Western blot analysis confirmed the upregulation of TLR4, MyD88, and NF-κB p-p65 expression.CONCLUSION: This study systematically elucidates the mechanism by which ginsenosides enhance immune function by regulating gut microbiota, restoring metabolic balance, and activating the TLR4/MyD88/NF-κB signaling pathway. These findings provide a molecular foundation for the potential use of ginsenosides in the prevention and treatment of immune-related diseases.PMID:40252438 | DOI:10.1016/j.phymed.2025.156763

Phytomedicine. 2025 Apr 12;142:156749. doi: 10.1016/j.phymed.2025.156749. Online ahead of print.ABSTRACTINTRODUCTION: Bile acids (BAs) are emerging as key modulators of Parkinson's disease (PD) through gut-brain interactions, yet their therapeutic potential remains underutilized. While BA imbalances contribute to PD pathogenesis, the specific subspecies regulating α-synuclein (α-syn) homeostasis and their mechanisms in enteric neurons-critical sites for PD initiation-require systematic investigation.OBJECTIVE: To investigate whether hyodeoxycholic acid (HDCA), a secondary BA with documented neuroprotective properties but unproven efficacy in synucleinopathy, modulates α-syn clearance through enteric neuronal autophagy to mitigate PD progression.METHODS: A53T transgenic mice underwent behavioral assessments for PD phenotyping. State-of-the-art UPLC/MS-based metabolomics quantified BA profiles. Pharmacological interventions using target-specific inhibitors (Gly-MCA, T0070907, VER-155,008) dissected the FXR-PPARγ-HSPA8 pathway. Multiscale analyses spanning immunofluorescence, western blotting, and LC3B autophagy flux reporter assays elucidated α-syn aggregation and autophagic dynamics in primary enteric neurons.RESULTS: HDCA decline correlated with PD severity, positioning it as a novel biomarker for gut-brain axis dysfunction in PD. HDCA supplementation not only alleviated motor/non-motor deficits but also conferred dual neuroprotection-reducing colonic α-syn oligomers and preserving nigral dopaminergic neurons. Mechanistic decoding revealed HDCA's unparalleled capacity to activate enteric neuronal autophagy via FXR-PPARγ-HSPA8 signaling, a pathway previously unrecognized in PD therapeutics.CONCLUSION: Our study reveals a novel gut-brain axis where HDCA depletion drives PD pathogenesis via FXR-PPARγ-HSPA8-mediated autophagic dysfunction in enteric neurons. PD-associated HDCA deficiency directly impairs α-syn clearance, identifying HDCA as both a gut-derived synucleinopathy biomarker and a therapeutic target.PMID:40252434 | DOI:10.1016/j.phymed.2025.156749

Phytomedicine. 2025 Apr 12;142:156756. doi: 10.1016/j.phymed.2025.156756. Online ahead of print.ABSTRACTBACKGROUND: Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.PURPOSE: This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.METHODS: The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.RESULTS: A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.CONCLUSION: TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.PMID:40252432 | DOI:10.1016/j.phymed.2025.156756

Phytomedicine. 2025 Apr 11;142:156759. doi: 10.1016/j.phymed.2025.156759. Online ahead of print.ABSTRACTBACKGROUND: Ji-Ming-San (JMS), a traditional Chinese medicine, exhibits time-dependent pharmacological effects, suggesting its potential as a circadian clock modulator. However, the precise mechanisms by which JMS regulates circadian rhythms remain unclear.PURPOSE: This study aims to elucidate how JMS influences the local circadian clock machinery, and move beyond association to mechanistic discovery.METHODS: A jet lag model of circadian disruption was used to assess the regulatory effects of JMS on circadian behavior and clock gene expression. The impact of JMS on clock genes was examined in colon epithelial cells. Non-targeted metabolomics was utilized to identify key components and potential pathways. Network pharmacology, molecular docking, Gal4 co-transfection assays, and RNA sequencing were conducted to explore potential JMS targets. Chromatin immunoprecipitation assays were performed to investigate the transcriptional regulation mechanisms.RESULTS: JMS restored circadian rhythms in locomotor activity and intestinal clock gene expression in jet-lagged mice. Under colitis conditions, JMS reduced pathological severity and inflammation in mice with circadian disruption by upregulating BMAL1 and PER2. In mice with normal circadian rhythms, the protective effect of JMS was observed during the remission phase of colitis. At the cellular level, JMS activated RORα and enhanced the transcription and expression of BMAL1 and PER2 in colonic epithelial cells. Metabolomics and RNA sequencing revealed that JMS inhibited NF-κB signaling, contributing to its anti-inflammatory action. Mechanistically, JMS enhanced RORα/HDAC3 binding to NF-κB target genes in epithelial cells, leading to reduced H3K9Ac levels and repression of Il-1β and Tnf-α, while epithelial RORα knockdown abolished the anti-inflammatory effects.CONCLUSION: This study demonstrates that JMS activates epithelial RORα to restore circadian rhythm in the colon and suppresses NF-κB signaling, ultimately promoting colitis recovery These findings underscore the role of JMS in regulating intestinal circadian rhythm and highlight its potential as a chronotherapeutic strategy for colitis.PMID:40252431 | DOI:10.1016/j.phymed.2025.156759

J Environ Manage. 2025 Apr 18;382:125422. doi: 10.1016/j.jenvman.2025.125422. Online ahead of print.ABSTRACTRare earth elements (REEs) are non-renewable strategic resources that are highly important for national security and development. However, the efficient and environmentally friendly mining and utilization of REEs face major challenges. Bioleaching is a clean process with the potential to replace environmentally hazardous chemical extraction methods. The present study investigated the effects of three bioleaching methods by Aspergillus niger on the extraction of ion-adsorption rare earth ore. In addition, the interaction between strain and minerals was explored by combining various characterization methods (XRD, FT-IR, Raman and SEM-EDS) and untargeted metabolomics. These findings indicated that the three-step bioleaching method was the most effective. Aspergillus niger leaches REEs through both direct action of the strain and indirect action of metabolites without destroying the mineral structure. Direct leaching (one-step and two-step methods) has been demonstrated to affect the cell morphology and structure of Aspergillus niger. Furthermore, Aspergillus niger had a certain adsorption capacity for REEs. Metabolomics analysis revealed that Aspergillus niger exhibited a regulatory response to environmental stresses during direct bioleaching, modulating tryptophan metabolism (one-step method) and the biosynthesis of secondary metabolites (two-step method). Bioleaching enables the recovery of REEs through environmentally friendly (readily biodegradable and non-toxic) metabolites produced by microbial growth, providing a green pathway for the sustainable mining of ion-adsorption rare earth ores.PMID:40252422 | DOI:10.1016/j.jenvman.2025.125422

J Plant Physiol. 2025 Apr 15;308:154492. doi: 10.1016/j.jplph.2025.154492. Online ahead of print.ABSTRACTFlowering duration is pivotal for ornamental appeal, with re-flowering being essential for prolonging the decorative period and enhancing the aesthetics of flowers. We conducted transcriptome and metabolome sequencing analyses on the primary and secondary flower buds of H. macrophylla cv 'White Angel', aiming to reveal the molecular regulatory mechanism of secondary flowering. Results showed that the key MADS-box transcription factor family genes closely related to flowering regulation such as AGL42, AGL24, and SVP demonstrated a substantial increase in expression levels within the secondary flower buds. The up-regulation of these genes may promote the transition from vegetative growth to reproductive growth by regulating the expression of downstream target genes, thus triggering secondary flowering. In addition, genes related to starch and sucrose metabolism (such as TPS and TPP) were significantly overexpressed in secondary flower buds, promoting the accumulation of energy metabolites such as Trehalose-6p, Trehalose and D-Glucose, which may create conditions for secondary flowering by providing necessary energy support. At the same time, terpenoid biosynthesis-related genes (such as KO, KAO, GA2ox and GA3ox) were highly expressed in secondary flower buds, significantly increasing the contents of GA4 and GA7, while decreasing the level of GA3. These dynamic changes of gibberellins (GAs) may regulate the expression of flowering related genes. Further promote the occurrence of secondary flowering. In summary, this study revealed the synergistic effect of genes and metabolites in the regulation of secondary flowering of Hydrangea macrophylla 'White Angel', and the MADS-box transcription factor directly promoted the transformation of reproductive growth through up-regulated expression. The accumulation of starch, sucrose and its derivatives and gibberellin metabolites may trigger the secondary flowering process of plants through energy supply and hormone signal regulation. These findings provide a new perspective for in-depth analysis of the flowering regulation mechanism of Hydrangea macrophylla, and lay a theoretical foundation for further cultivation of horticultural varieties with excellent ornamental characteristics.PMID:40252343 | DOI:10.1016/j.jplph.2025.154492

Microbiol Res. 2025 Apr 15;297:128182. doi: 10.1016/j.micres.2025.128182. Online ahead of print.ABSTRACTQinghai-Tibet Plateau (QTP) is marked by harsh environments that drive the evolution of unique nutrient metabolism mechanism in indigenous animal gut microbiotas. Yet, responses of these microbiotas to different extreme environments remain poorly understood. White-lipped deer (Przewalskium albirostris), a native endangered species in the QTP, serves as an ideal model to study how gut microbiotas adapt to season and human disturbances. Here, a multi-omics integrated analysis of 16S rRNA, metagenomics, and untargeted metabolomics was performed to investigate the composition, function, and metabolic characteristics of gut microbiota in White-lipped deer across different seasons and living environments. Our results revealed that extreme winter environment dominated the composition, function, and metabolism of gut microbiota in white-lipped deer. The white-lipped deer exhibited an enriched gut microbiota associated with producing short-chain fatty acids in winter, with core feature genera including norank_o_Rhodospirillales, Rikenellaceae_RC9_gut_group, and unclassified_c_Clostridia. However, potential pathogenic bacteria and few short-chain fatty acid producers, with core feature genera including norank_f_p-2534-18B5_gut_group, Cellulosilyticum, and Paeniclostridium, showed enrichment in captivity. Pathways associated with carbohydrate metabolism, amino acid metabolism, and immune regulation showed enrichment in winter group as an adaptation to the cold and food scarcity. Among these, Rikenellaceae_RC9_gut_group and unclassified_c_Clostridia contributed significantly to these metabolic pathways. The gut microbiota of white-lipped deer exhibited enrichment in pathways related to intestinal inflammation and enhanced immune regulation to alleviate the stress of captivity. Among these, norank_f_p-2534-18B5_gut_group contributed the most to these pathways. Butyric, valeric, and valproic acids were significantly more abundant in the winter group, while 3-hydroxybutyric and (S)-beta-aminoisobutyric acids were higher in the captive group. Furthermore, enriched metabolites and associated pathways in both groups further supported the inferences on metagenomic functions. This study confirms the key role of specific gut microbiota in adapting to high-altitude winters and anthropogenic disturbances, emphasizing its importance for environmental resilience in wild, high-altitude mammals.PMID:40252261 | DOI:10.1016/j.micres.2025.128182

J Sep Sci. 2025 Apr;48(4):e70148. doi: 10.1002/jssc.70148.ABSTRACTChromatography, a cornerstone technique in analytical chemistry, continues to evolve with the emergence of novel stationary phases. Covalent organic frameworks (COFs) have garnered significant attention due to their unique properties and versatile applications. COFs, composed of covalently linked organic building blocks, exhibit high surface area, tunable porosity, and exceptional chemical stability. These attributes make them next-generation chromatographic techniques that leverage novel materials and methodologies to achieve significant improvements in separation efficiency, selectivity, speed, and/or sensitivity compared to traditional methods. COF stationary phases demonstrate remarkable selectivity for small molecules, peptides, proteins, and nucleic acids. Their use in drug discovery, metabolomics, proteomics, and clinical diagnostics is gaining momentum. In this review, we explored their synthesis strategies, emphasizing the design principles that enable tailoring of their physicochemical properties. Further, we discuss the immobilization of COFs onto solid supports, ensuring their compatibility with existing chromatographic systems. Furthermore, we highlighted case studies where COFs outperformed traditional stationary phases, improving sensitivity and resolution. We delve into the integration of COFs as stationary phases in biomedical analysis and explore various strategies for utilizing COFs as stationary phases in chromatographic separations.PMID:40252231 | DOI:10.1002/jssc.70148

Biol Res Nurs. 2025 Apr 19:10998004251335639. doi: 10.1177/10998004251335639. Online ahead of print.ABSTRACTBackground: Fatigue is a frequently reported symptom in children undergoing cancer treatment. Prior research shows an inverse relationship between fatigue and physical activity. Less is known about fatigue's relationship with physical function or the underlying biological mechanisms of fatigue. This study explored associations among fatigue, physical function, and associated metabolites. Methods: Children (7-18 years) provided serum samples and self-reports of fatigue and lower extremity physical function (mobility) using Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) surveys at two timepoints during cancer therapy. PROMIS scores were categorized as high/low per established cut points (high fatigue T >47.5; high physical function T >51.5). High-resolution liquid chromatography-mass spectrometry extracted 29 metabolites hypothesized a priori to be associated with fatigue or physical function. Descriptive statistics summarized PROMIS scores, and linear mixed effect models estimated metabolite associations adjusting for age, gender and steroid use. Results: Forty children participated (female, 53%; 7-12 years, 38%; 13-18 years 62%; Hodgkins Lymphoma, 33%; Acute Lymphoblastic/Lymphocytic Leukemia, 40%; Osteosarcoma, 10%; Other, 17%). Physical function and fatigue were inversely related: T1 (r = -0.64; p < .001) and T2 (r = -0.63; p < .001). One metabolite (indole-3-latic acid) differentiated between low and high fatigue. Five metabolites differentiated significantly between low and high physical function (4-Hydroxybenzoic acid, m-Coumaric acid, myoinositol, tryptophan, and tyrosine). Conclusions:These findings substantiate prior studies showing metabolites, particularly amino acids, significantly associated with fatigue and physical function. All significant metabolites were associated with the gut microbiome. Physical function was inversely corelated with fatigue providing another potential intervention for fatigue management.PMID:40251999 | DOI:10.1177/10998004251335639

J Vasc Access. 2025 Apr 18:11297298251332047. doi: 10.1177/11297298251332047. Online ahead of print.ABSTRACTThe number of the patients treated with maintenance hemodialysis (HD) is increasing due to the increasing incidence of end stage renal disease (ESRD). Autologous arteriovenous fistula (AVF) is the preferable modality for long-term vascular access during HD. AVF stenosis is the main cause of AVF dysfunction in HD patients, but its mechanism has not been fully elucidated. Patients with ESRD often have various related complications due to intestinal microbiota disorders and their metabolites, and the intestinal axis reveals various metabolic disorders in patients with chronic kidney disease. This paper analyzes the correlation between intestinal axis abnormalities and AVF stenosis in patients with CKD through three axes: "gut-liver axis," "gut-brain axis," and "gut-spleen axis," to provide clinical significance for elucidating the mechanism of AVF stenosis and for the prevention and treatment of AVF stenosis.PMID:40251786 | DOI:10.1177/11297298251332047

BMC Genomics. 2025 Apr 18;26(1):385. doi: 10.1186/s12864-025-11497-x.ABSTRACTHypoxia often has negative effects on testis development and spermatogenesis of mammals. Plateau yaks have lived in the hypoxia environment for generations, but have ensured testicular function, which is closely related to their unique hypoxia response mechanism. Glucose metabolic reprogramming is an important way for cells to respond to stressful environments, especially the metabolite lactate, which is the energy basis for the development and differentiation of germ cells. In this study, hypoxia (5% O2) effectively promoted yak Sertoli cell proliferation and decreased autophagy and apoptosis. It was found that the cells showed good hypoxic adaptation. Metabolomics results showed that glucose metabolism was enhanced in yak Sertoli cells in response to hypoxia, and 13 glucose metabolites were increased, including the production and transport level of lactic acid (LA), which may have changed the pentose phosphate metabolic pathway of cells, these changes are conducive to support the glucose metabolism balance of cells under hypoxia. Crucially, when autophagy is activated under hypoxia, GLUT3, GLUT8, and MCT4 proteins are degraded, while GLUT1 and MCT1 are not affected, suggesting that autophagy may achieve glucose metabolic reprogramming by selectively regulating the expression of functional factors of glucose metabolism, which is conducive to energy intake and spermatogenesis in testis of yaks.PMID:40251498 | DOI:10.1186/s12864-025-11497-x

Discov Oncol. 2025 Apr 18;16(1):565. doi: 10.1007/s12672-025-02338-0.ABSTRACTMetabolic reprogramming, a pivotal hallmark of cancer, plays a crucial role in both the initiation and progression of colorectal cancer (CRC). Despite the vast unknowns surrounding the identity and biological activities of most natural metabolites in diseases, our study, utilizing native metabolomics results through GC-MS/MS, identified a small molecule, 4,4-Dimethyl-2-cyclohexen-1-one, named HEX-1 in the serum of CRC patients. We have further explored and assessed its biological activities. HEX-1 suppressed the proliferation of cancer cells and tumorigenesis via the inactivation and sensitization of PIN1. Notably, HEX-1 exhibits similar functional effects as all-trans retinoic acid (atRA) but stands out by not inducing the degradation of PIN1 mRNA or protein expression, unlike biological compounds associated with atRA. HEX-1 demonstrated the ability to induce G1/S arrest in vitro and ameliorate the progression of inflammatory CRC in mice by remodeling the gut microbiota. As volatile organic compounds (VOCs), HEX-1 could be detected feasibly. Its unique ability to penetrate whole cell populations positions it as a promising approach for cancer therapy and as an enhancer for chemotherapy and immunotherapy. The findings suggest that HEX-1 holds the potential as a valuable addition to the armamentarium against CRC.PMID:40251462 | DOI:10.1007/s12672-025-02338-0

Nat Microbiol. 2025 Apr 18. doi: 10.1038/s41564-025-01985-x. Online ahead of print.ABSTRACTMetabolic remodelling underpins macrophage effector functions in response to various stimuli, but the mechanisms involved are unclear. Here we report that viral-infection-induced inflammatory stimulation causes a rewiring of the urea cycle and the tricarboxylic acid cycle metabolism in macrophages to form a cyclic pathway called the aspartate-argininosuccinate (AAS) shunt. Using RNA sequencing, unbiased metabolomics and stable isotope tracing, we found that fumarate generated from the AAS shunt is driven by argininosuccinate synthase (ASS1) in the cytosol and potentiates inflammatory effects. Genetic ablation of ASS1 reduces intracellular fumarate levels and interferon-β production, and mitochondrial respiration is also suppressed. Notably, viral challenge or fumarate esters enhance interferon-β production via direct succination of the mitochondrial antiviral signalling protein and activation of the retinoic acid-inducible gene-I-like receptor signalling. In addition to the vesicular stomatitis virus, the Sendai virus and influenza A virus can also exert these effects. In addition, patients with Ebola virus disease have increased ASS1 expression and ASS1-deficient mice show suppressed macrophage interferon responses to vesicular stomatitis virus infection. These findings reveal that fumarate can be produced from the viral inflammation-induced AAS shunt and is essential for antiviral innate immunity.PMID:40251448 | DOI:10.1038/s41564-025-01985-x

Sci Rep. 2025 Apr 18;15(1):13401. doi: 10.1038/s41598-025-98347-8.ABSTRACTRight ventricular failure as a severe consequence of pulmonary arterial hypertension (PAH) is an independent risk factor for poor prognosis, although the pathogenesis of right ventricular remodeling (RVR) remains unclear. Exploring the shared molecular pathways and key molecules in the right ventricle in monocrotaline (MCT) and pulmonary artery banding (PAB) rat models may reveal critical RVR mechanisms. Untargeted proteome and metabolome analysis were performed on the right ventricular myocardium of two RVR models (MCT-induced PAH rats and PAB-operated rats) to identify the altered proteins and metabolites, followed by validation using parallel reaction monitoring analysis and quantitative real-time polymerase chain reaction (qPCR). The multi-omics profiles of MCT and PAB rat models were compared to explore the key dysregulated molecules and pathways in RVR. Our proteomics study identified 25 shared RVR-altered differentially expressed proteins. Multiple common biological pathways were identified between PAB and MCT rat models, encompassing myocardial remodeling and energy metabolism alternation, etc. Various molecules and pathways related to vesicle transport and autophagy were identified, including nidogen-1, the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) signaling pathway, and the microautophagy pathway (all previously unreported in RVR). Glycerophospholipid metabolism was the sole statistically significant common metabolic pathway enriched by metabolomics. Underreported biological processes, including vesicle transport and autophagy, may contribute to the pathophysiology of PAH-induced RVR.PMID:40251385 | DOI:10.1038/s41598-025-98347-8