PubMed

Clin Pharmacol Ther. 2025 Apr 1. doi: 10.1002/cpt.3657. Online ahead of print.ABSTRACTClinical inhibition and genetic variation of the Breast Cancer Resistance Protein (BCRP/ABCG2) efflux transporter can significantly influence drug exposure, highlighting the need for reliable BCRP functional biomarkers. This study aimed to identify and evaluate biomarkers predictive of BCRP function in humans. A comprehensive analysis of metabolomic genome-wide association studies (mGWAS) was conducted to discover potential BCRP biomarkers, followed by evaluation in in vitro transporter assays and a clinical drug-drug interaction (DDI) study. Across multiple mGWAS datasets, plasma concentrations of three herbicide derivatives-4-hydroxychlorothalonil (4HC), 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (BCDBA), and 3,5-dichloro-2,6-dihydroxybenzoic acid (DCDBA)-were significantly elevated (P < 5E-8) in individuals carrying reduced function ABCG2 polymorphisms. These compounds were confirmed as novel BCRP substrates via transporter uptake assays and selected for clinical evaluation alongside riboflavin, a known BCRP substrate and potential BCRP biomarker. In a DDI study with 11 healthy subjects, eltrombopag, a BCRP inhibitor, increased rosuvastatin concentrations by approximately twofold (P = 0.002). No significant changes in the plasma concentrations of organic anion transporting polypeptide 1B (OATP1B) biomarkers (CP-I and CP-III) or potential BCRP biomarkers (4HC, BCDBA, DCDBA, or riboflavin) were observed. Notably, two subjects were heterozygous carriers for the ABCG2 p.Q141K variant and exhibited significantly higher baseline concentrations of 4HC (P = 0.004) and BCDBA (P = 0.0003), consistent with reduced BCRP function. These findings suggest that 4HC and BCDBA are promising biomarkers for baseline BCRP function in specific populations, such as those harboring reduced function genetic polymorphisms, but do not appear suitable for detecting acute BCRP inhibition.PMID:40170495 | DOI:10.1002/cpt.3657

Eur J Immunol. 2025 Apr;55(4):e202451594. doi: 10.1002/eji.202451594.ABSTRACTIn recent years, we have witnessed a rapidly growing interest in the intricate communications between intestinal microorganisms and the host immune system. Research on the human microbiome is evolving from merely descriptive and correlative studies to a deeper mechanistic understanding of the bidirectional interactions between gut microbiota and the mucosal immune system. Despite numerous challenges, it has become increasingly evident that an imbalance in gut microbiota composition, known as dysbiosis, is associated with the development and progression of various metabolic, immune, cancer, and neurodegenerative disorders. A growing body of evidence highlights the importance of small molecules produced by intestinal commensal bacteria, collectively referred to as gut microbial metabolites. These metabolites serve as crucial diffusible messengers, translating the microbial language to host cells. This review aims to explore the complex and not yet fully understood molecular mechanisms through which microbiota-derived metabolites influence the activity of the immune cells and shape immune reactions in the gut and other organs. Specifically, we will discuss recent research that reveals the close relationship between microbial indole-3-propionic acid (IPA) and mucosal immunity. Furthermore, we will emphasize the beneficial effects of IPA on intestinal inflammation and discuss its potential clinical implications.PMID:40170399 | DOI:10.1002/eji.202451594

Eur J Immunol. 2025 Apr;55(4):e202451586. doi: 10.1002/eji.202451586.ABSTRACTIgA can form immune complexes (ICs) and activate myeloid cells via Fc alpha receptor-mediated signalling to secrete pro-inflammatory cytokines. It was previously described that of the two IgA subclasses (IgA1 and IgA2), IgA2 is more inflammatory than IgA1. However, the mechanisms underlying this differential pro-inflammatory potential remain poorly defined. Using anti-citrullinated protein IgA1 and IgA2 antibodies (ACPA) that are commonly found in rheumatoid arthritis (RA) patients and linked to chronic inflammation, we show here that, in macrophages, IgA2-ICs boost TLR-induced TNF and IL6 secretion, COX2 expression, and production of COX2-dependent lipid mediators to a higher level than IgA1-ICs. Metabolically, we found the amplification of TLR-induced cytokine production and COX2 induction by IgA2-ICs to be dependent on mitochondrial ATP synthesis, but not glycolysis. Finally, we found the potentiation of TLR-induced cytokine production by IgA-ICs to be COX2-dependent. Together this work points towards a key role for mitochondrial ATP synthesis in driving COX2 expression and subsequent IgA2-IC-dependent potentiation of TLR-induced cytokine production by macrophages. As such, our work provides new insights into the mechanisms underlying IgA2-induced inflammation in the context of RA. Thus, this may hold novel clues to be explored as therapeutic possibilities to target antibody-driven inflammation in chronic inflammatory diseases.PMID:40170376 | DOI:10.1002/eji.202451586

Sheng Wu Gong Cheng Xue Bao. 2025 Mar 25;41(3):1152-1178. doi: 10.13345/j.cjb.250065.ABSTRACTBiomanufacturing has emerged as a crucial driving force for efficient material conversion through engineered cells or cell-free systems. However, the intrinsic spatiotemporal heterogeneity, complexity, and dynamic characteristics of these processes pose significant challenges to systematic understanding, optimization, and regulation. This review summarizes essential methodologies for multi-omics data acquisition and analyses for bioprocesses and outlines modelling approaches based on multi-omics data. Furthermore, we explore practical applications of multi-omics and modelling in fine-tuning process parameters, improving fermentation control, elucidating stress response mechanisms, optimizing nutrient supplementation, and enabling real-time monitoring and adaptive adjustment. The substantial potential offered by integrating multi-omics with computational modelling for precision bioprocessing is also discussed. Finally, we identify current challenges in bioprocess optimization and propose the possible solutions, the implementation of which will significantly deepen understanding and enhance control of complex bioprocesses, ultimately driving the rapid advancement of biomanufacturing.PMID:40170317 | DOI:10.13345/j.cjb.250065

Chin Med. 2025 Apr 1;20(1):44. doi: 10.1186/s13020-025-01092-3.ABSTRACTBACKGROUND: Radiotherapy can damage hematopoietic stem cells (HSC) in bone marrow, leading to impaired hematopoietic function. Current treatments mainly target differentiated hematopoietic progenitor cells, which may accelerate their depletion. Astragaloside IV (AS-IV), derived from Astragalus membranaceus, shows potential in hematopoiesis, but its direct effects on HSC remain unclear.METHODS: The study employed both in vitro and in vivo approaches. In vitro experiments utilized K562 cells and mouse bone marrow nucleated cells (BMNCs) to evaluate AS-IV's effects on cell proliferation and mitochondrial function. In vivo studies involved a 4.0 Gy total body irradiation mouse model treated with different doses of AS-IV (50 mg/kg and 100 mg/kg). The mechanism of action was investigated through Western blot, flow cytometry, and metabolomics analyses. The AMPK/PGC1α pathway regulation was verified using AMPK inhibitors and mutant plasmid, with molecular docking confirming AS-IV's direct binding to AMPK.RESULTS: In vitro studies demonstrated that AS-IV significantly promoted the proliferation of K562 cells and BMNC while enhancing their mitochondrial membrane potential, mitochondrial mass, and ATP production. In the irradiated mouse model, AS-IV treatment led to significant improvements in peripheral blood cell counts, including white blood cells, red blood cells, and hemoglobin levels. Further investigation revealed that AS-IV increased the proportion of HSC in both bone marrow and spleen while improving their mitochondrial function. Transcriptomic sequencing and Western blot analysis identified the AMPK/PGC1α signaling pathway as the key mechanism underlying AS-IV-mediated mitochondrial enhancement. These findings were validated through pharmacological inhibition of AMPK and AMPKK45R mutation experiments.CONCLUSION: AS-IV accelerates hematopoietic reconstruction following radiation injury via activation of the AMPK/PGC1α signaling pathway, which enhances HSC mitochondrial function.PMID:40170084 | DOI:10.1186/s13020-025-01092-3

J Nanobiotechnology. 2025 Apr 1;23(1):262. doi: 10.1186/s12951-025-03330-0.ABSTRACTExcessive soil cadmium (Cd) and the accumulation of pathogens pose serious threats to legume growth. However, it remains unclear whether intercropping (IFcd) and its combined treatment with silicon nanoparticles (Si-NPs) (IFcd + Si) can alleviate these challenges under Cd stress, as well as the underlying mechanisms involved. This study systematically elucidated the mechanism of faba bean-wheat intercropping and Si-NPs regulating faba bean growth under Cd stress using rhizosphere metabolomics and 16 S rRNA microbiome analysis. The results showed that IFcd and IFcd + Si treatments significantly reduced Cd accumulation by 17.3% and 56.2%, and Fusarium wilt incidence by 11.1% and 33.3%, respectively, compared with monoculture faba bean (MFcd) while promoting root and plant growth. These treatments reduced oxidative stress markers, including H2O2, MDA, and O2-, and increased the activity of defense enzymes, such as SOD, APX, and POD in plants. Furthermore, they increased NH4+-N and available potassium levels in rhizosphere soils. Interestingly, the NH4+-N content increased and was significantly positively correlated with urease (URE) activity and negatively correlated with Cd. Beneficial bacteria and functional metabolites were enriched in the rhizosphere of faba bean. Joint analysis revealed increased relative abundances of Sphingomonas, Intrasporangium, and Streptomyces, which were positively correlated with antibacterial metabolites, such as sordarin, lactucin, and 15-methylpalmate. This explains the reduced Cd accumulation and Fusarium wilt in plants. These findings provide mechanistic insights into how intercropping with Si-NPs mitigates Cd stress and controls soil-borne diseases by regulating rhizosphere metabolites, bacterial communities, and plant resistance.PMID:40170068 | DOI:10.1186/s12951-025-03330-0

Mol Psychiatry. 2025 Apr 2. doi: 10.1038/s41380-025-02977-3. Online ahead of print.ABSTRACTAltered levels of human plasma metabolites have been implicated in the etiology of bipolar disorder (BD). However, the causality between metabolites and the disease was not well described. We performed a bidirectional metabolome-wide Mendelian randomization (MR) analysis to evaluate the potential causal relationships between 871 plasma metabolites and BD. We used DrugBank and ChEMBL to evaluate whether related metabolites are potential therapeutic targets. Finally, Bayesian colocalization analysis was performed to identify shared genomic loci BD and identified metabolites. Our MR results showed that six metabolites were significantly associated with a reduced risk of BD, including arachidonate (20:4n6) (OR: 0.90, 95% CI: 0.84-0.95) and sphingomyelin (d18:2/24:1, d18:1/24:2) (OR: 0.92, 95% CI: 0.87-0.96), while five metabolites were significantly associated with an increased risk of BD, including 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (OR: 1.09, 95% CI: 1.05-1.13). However, our reverse MR analysis showed that BD was not associated with the levels of any metabolite. Additionally, the leave-one-out analysis revealed SNPs within chromosome 11 loci harboring MYRF, FADS1, and FADS2 as ones with the potential to influence partial causal effects. Druggability evaluation showed that 10 of the BD-related metabolites, such as sphingomyelin and cytidine, have been targeted by pharmacologic intervention. Colocalization analysis highlighted one colocalized region (chromosome 11q12) shared by 11 metabolites and BD and pointed to some genes as possible players, including FADS1, FADS2, FADS3, and SYT7. Our study supported a causal role of plasma metabolites in the susceptibility to BD, and the identified metabolites may provide a new avenue for the prevention and treatment of BD.PMID:40169804 | DOI:10.1038/s41380-025-02977-3

Sci Rep. 2025 Apr 1;15(1):11123. doi: 10.1038/s41598-025-93181-4.ABSTRACTVector-borne diseases continue to transmit many dangerous pathogens to humans. After decades of continuous use of insecticides, many types of vectors have shown the ability to build resistance to them. This has necessitated the development of more efficient and environmentally friendly alternatives in the form of bioinsecticides. Plants contain a wide range of phytochemicals with specific targeting, rapid biodegradability, environmental sustainability and a variety of medicinal properties, making them a valuable source of biologicals. Moreover, this has led to the development of highly effective new drugs. This study aimed to identify the active ingredients in Ceratonia siliqua L., gathered from two consecutive fruiting seasons which were then divided into C. siliqua fresh (CSF), dry (CSd), and old (stored) stem (CSO) extracts Ceratonia siliqua. Metabolomics profiling was performed using UPLC/MS and multivariate data analysis. The UPLC/MS study resulted in the tentative identification of 54 secondary metabolites. These compounds included flavonoids, phenolic acids, withanolides, terpenoids, phenylpropanoids, etc. CSd showed the highest number of identified components followed by CSO and CSF. The % identification was nearly equal in the negative ion mode for the three extracts while for the positive ion mode it followed the order of CSF > CSd > CSO. After several exposure periods, the plant methanol extracts in this research showed significant insecticidal activity against mosquito larvae, Cx. pipiens, and housefly larvae M. domestica. (CSd) demonstrated the highest insecticidal activity (100 MO%) against Cx. pipiens (LC50 = 0.09 and 0.07 mg/ml) following 24- and 48-hour post-treatments at 1.0 mg/ml. The (CSF) was the most effective on M. domestica larvae (LC50 = 2.32 and 1.80 mg/ml), 24 and 48 h post-treatment with 25 mg/ml concentration. Both CSd and CSF extracts were the most effective at killing mosquito and house fly larvae, followed by the CSO extract. Therefore, C. siliqua extracts may serve as an effective bio-agent for specific vector-borne infection control.PMID:40169725 | DOI:10.1038/s41598-025-93181-4

Sci Rep. 2025 Apr 1;15(1):11126. doi: 10.1038/s41598-025-91496-w.ABSTRACTSalt stress significantly limits wheat production worldwide, jeopardizing food security and sustainable agriculture. Developing strategies to enhance wheat's resilience to salinity is critical for maintaining yield in affected regions. This study investigates the potential of chitosan-proline (Cs-Pro) and chitosan-glycine (Cs-Gly) nanoparticles in mitigating salt stress in salt-tolerant Heydari and salt-sensitive Sepahan wheat cultivars, with a special question on genotype-dependent differences. Plants were treated with nanoparticles at concentrations of 0, 200, and 400 mg L⁻¹ under salt stress levels of 0, 200, and 400 mM NaCl. The salt-tolerant Heydari cultivar exhibited superior adaptability to saline conditions, in addition reacted more positively to nanoparticle treatments. Results demonstrated significant physiological improvements, including increased relative water content (RWC), enhanced chlorophyll content and elevated proline levels, especially after 400 mg L⁻¹ Cs-Pro treatment. Oxidative stress markers, such as malondialdehyde (MDA) and hydrogen peroxide, were substantially reduced, while antioxidant enzyme activity was boosted. Certain stress-responsive genes (e.g., TaADC, TaPxPAO, TaSAMDC, TaSPDS, TaSOS1, TaNHX1) were upregulated, highlighting the importance of ionic balance and polyamine metabolism in improved stress tolerance. The application of Cs-Pro and Cs-Gly nanoparticles presents a promising approach to enhance wheat's salinity tolerance by improving physiological, biochemical, and molecular responses.PMID:40169625 | DOI:10.1038/s41598-025-91496-w

NPJ Sci Food. 2025 Apr 1;9(1):47. doi: 10.1038/s41538-025-00408-9.ABSTRACTArterial stiffness, a cardiovascular disease (CVD) predictor starting from youth, is under-researched in young adults. Low-intensity aerobic exercise (LAE) is generally more accessible than higher-intensity exercise and may be more sustainable for young individuals. Blueberries, renowned for vascular health benefits, may reduce arterial stiffness. This study examines the effects of LAE and blueberry juice on arterial stiffness in 48 young adults. Participants were randomized into LAE, low-, mid-, or high-volume blueberry juice (LB, MB, HB), LAE + LB, LAE + MB, LAE + HB, and control groups. Arterial stiffness was measured at baseline and at 15-, 30-, 45-, and 60 min post-intervention. Blood samples were collected pre-intervention and 30-min post-intervention for metabolomic analysis. Repeated ANOVA revealed LAE + MB significantly reduced arterial stiffness. Metabolomic analysis revealed changes in linoleic acid, sphingolipid, phenylalanine, nicotinate and nicotinamide, glycerophospholipid, and lysine degradation metabolic pathways. These findings suggest a feasible exercise-diet strategy for CVD prevention in young adults and provide metabolic insights into the mechanisms.PMID:40169604 | DOI:10.1038/s41538-025-00408-9

Transl Psychiatry. 2025 Apr 1;15(1):115. doi: 10.1038/s41398-025-03326-2.ABSTRACTGut microbiome is implicated in the onset and progression of major depressive disorder (MDD), but the dynamic alterations of depressive symptoms, gut microbiome, and fecal metabolome across different stages of stress exposure remain unclear. Here, we modified the chronic social defeat stress (CSDS) model to evaluate mice subjected to social defeat stress for 1, 4, 7, and 10 days. Behavioral tests, 16S rRNA, metagenomics, and fecal metabolomics were conducted to investigate the impact of stress exposure on behaviors, gut microbiota and fecal metabolites. We observed that depressive-like behaviors, such as anhedonia and social avoidance, worsened significantly as stress exposure increased. The microbial composition, function, and fecal metabolites exhibited distinct separations across the different social defeat stress groups. Mediation analysis identified key bacteria, such as Lachnospiraceae_UCG-001 and Bacteroidetes, and fecal metabolites like valeric acid and N-acetylaspartate. In our clinical depression cohort, we confirmed that fecal valeric acid levels, were significantly lower in depressive-like mice and MDD patients, correlating closely with stress exposure and anhedonia in mice. Further analysis of serum and brain metabolites in mice revealed sustained changes of N-acetylaspartate abundance in fecal, serum, and cortical samples following increasing stress exposure. Together, this study elucidated the characteristics of depressive-like behaviors, gut microbiome, and fecal metabolome across various social defeat stress exposure, and identified key bacteria and fecal metabolites potentially involved in modulating social defeat stress response and depressive-like behaviors, providing new insights into the pathogenesis and intervention of depression.PMID:40169555 | DOI:10.1038/s41398-025-03326-2

Cell Death Discov. 2025 Apr 1;11(1):127. doi: 10.1038/s41420-025-02406-y.ABSTRACTHepatic steatosis significantly elevates the vulnerability of the graft to ischemia-reperfusion (I/R) injury during liver transplantation (LT). We investigated the protective role of insulin-induced gene 2 (Insig2) in steatotic liver's I/R injury and underlying mechanisms. Employing mouse model with Insig2 knock-out or hepatocyte-specific overexpression and high-fat diets to induce steatosis, we subjected these mice to hepatic I/R injury. The primary hepatocytes isolated from steatotic liver were used in in vitro hypoxia/reoxygenation (H/R) experiment. Our integrated in vivo and in vitro approach uncovered that Insig2 deficiency exacerbated steatotic liver's damage following hepatic I/R injury, whereas its overexpression offers protection. Mechanically, integrative analysis of transcriptome, proteome, and metabolome found that Insig2 deficiency disturbed lipid metabolism and oxidative stress homeostasis, particularly inhibiting GPX4 expression to induce ferroptosis. Furthermore, chemical inhibition of ferroptosis reversed the deleterious effect of Insig2 deficiency; whereas the protective influence of Insig2 overexpression was negated by the target inhibition of GPX4, leading to an exacerbation of hepatic I/R damage. These insights underscored the potential of the Insig2-GPX4 axis as a therapeutic target, presenting a novel avenue for enhancing the resilience of steatotic liver grafts against I/R injury.PMID:40169542 | DOI:10.1038/s41420-025-02406-y

J Neurol. 2025 Apr 1;272(4):304. doi: 10.1007/s00415-025-13028-w.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. Whole-genome sequencing has identified many novel ALS-associated genes, but genetics alone cannot fully explain the onset of ALS and an effective treatment is still lacking. Moreover, we need more biomarkers for accurate diagnosis and assessment of disease prognosis. Epigenetics, which includes DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs, influences gene transcription and expression by affecting chromatin accessibility and transcription factor binding without altering genetic information. These processes play a role in the onset and progression of ALS. Epigenetic targets can serve as potential biomarkers and more importantly, the reversibility of epigenetic changes supports their potential role as versatile therapeutic targets in ALS. This review summarized the alterations in different epigenetic modulations in ALS. Additionally, given the close association between aberrant metabolic profiles characterized by hypoxia and high glycolytic metabolism in ALS and epigenetic changes, we also integrate epigenetics with metabolomics. Finally, we discuss the application of therapies based on epigenetic mechanisms in ALS. Our data integration helps to identify potential diagnostic and prognostic biomarkers and support the development of new effective therapies.PMID:40169452 | DOI:10.1007/s00415-025-13028-w

New Phytol. 2025 Apr 1. doi: 10.1111/nph.70059. Online ahead of print.ABSTRACTPlant defense against herbivores is primarily regulated by the phytohormone jasmonate (JA). At the core, JA signaling is the MYC2 transcription factor (TF) that regulates the expression of an extensive array of defense-related genes. However, the regulatory mechanisms underlying MYC2-mediated herbivore resistance in rice are not fully understood. We employed brown planthopper (BPH) bioassays, transcriptional activation assays, transcriptome profiling, targeted metabolomics and cleavage under targets and tagmentation-sequencing analysis to investigate the biological function and regulatory mechanism of the JAMYB TF. JAMYB is induced by BPH infestation and is transcriptionally regulated by MYC2. Mutations of JAMYB rendered rice plants susceptible to BPH attacks under laboratory and field conditions, indicating that JAMYB positively contributes to BPH resistance. BPH-elicited biosynthesis of phenolamides and volatile compounds was reduced in jamyb mutants compared with wild-type plants. These specialized metabolites, regulated by JAMYB, function as direct and indirect defenses to deter BPH damage or attract parasitoid wasps of BPH eggs. Furthermore, we found that JAMYB directly binds to AC motifs of key phenylpropanoid pathway genes and activates their expression, likely altering the metabolic flux for phenolamide biosynthesis. This study reveals the role of the MYC2-JAMYB module in JA-mediated rice resistance to BPH.PMID:40169387 | DOI:10.1111/nph.70059

Biomol Biomed. 2025 Mar 26. doi: 10.17305/bb.2025.12164. Online ahead of print.ABSTRACTSpinal cord injury (SCI) induces profound systemic changes, including disruptions in gut microbiome composition and host metabolism. This study aimed to investigate the impact of SCI on gut microbial diversity and serum metabolites in rats, and to explore potential microbiome-metabolite interactions that may influence recovery. Male Sprague-Dawley (SD) rats were assigned to either SCI or sham-operated groups. Fecal samples were collected for whole-genome metagenomic sequencing, and serum samples were analyzed using untargeted metabolomics. Gut microbial composition and diversity were assessed using α- and β-diversity indices, while Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa. Metabolomic pathway analysis was performed to detect significant changes in serum metabolites, and Spearman's correlation was used to evaluate associations between gut microbes and metabolites. SCI significantly altered gut microbiota composition, with increased proportions of Ligilactobacillus and Staphylococcus, and decreased proportions of Lactobacillus and Limosilactobacillus. Metabolomic analysis revealed disrupted energy metabolism and elevated oxidative stress in SCI rats, as indicated by increased serum levels of pyruvate and lactic acid. Correlation analysis further identified significant associations between specific gut bacteria and key metabolites, suggesting microbiome-driven metabolic dysregulation following SCI. These findings highlight significant interactions between the gut microbiota and host metabolism after SCI and suggest that microbiome-targeted interventions may hold therapeutic potential for improving recovery by modulating metabolic function and oxidative stress responses.PMID:40169141 | DOI:10.17305/bb.2025.12164

Biochim Biophys Acta Mol Cell Res. 2025 Mar 30:119948. doi: 10.1016/j.bbamcr.2025.119948. Online ahead of print.ABSTRACTThe metabolite Glucose-1,6-bisphosphate (Glc-1,6-P2) plays a vital role in human metabolism, and is a crucial activator and stabilizer for phosphomannomutase-2 (PMM2) - mutations within this protein propagate the most common congenital disorder of glycosylation (PMM2-CDG). In vivo, Glc-1,6-P2 is hydrolysed by phosphomannomutase-1 (PMM1), predominantly in the brain, under the influence of inosine monophosphate (IMP). In the present study, we employed knock-out PMM1 in Arg141His/Phe119LeuPMM2 patient-derived fibroblasts and investigated the phenotypic improvement. Increased Glc-1,6-P2 was associated with glycosylation enhancement, confirmed by glycan profiling. The prevalence of previously identified PMM2-CDG biomarkers, such as LAMP1, PTX3 and lysosomal enzymes showed empirical increases - these findings were corroborated by metabolomic and proteomic analysis. Moreover, our results support the potential of Glc-1,6-P2 modulation for PMM2-CDG, potentiating novel perspectives in drug discovery.PMID:40169095 | DOI:10.1016/j.bbamcr.2025.119948

Dev Comp Immunol. 2025 Mar 30:105365. doi: 10.1016/j.dci.2025.105365. Online ahead of print.ABSTRACTBone morphogenic proteins (BMPs) play important regulatory roles in the development of follicles in mammals. However, studies on the roles of BMPs in ovarian development in low-level aquatic animals, especially the swimming crab Portunus trituberculatus, are limited. In this study, a BMP Ⅰ-type receptor-specific activator (tacrolimus, FK506) was administered at different concentrations via in vivo injection, and the effects of FK506 on the regulation of the BMP signaling pathway during ovarian development in P. trituberculatus were examined. The tissue and cell morphology was observed, and a combined transcriptomics, proteomics and metabolomics analysis was carried out. Crabs administered FK506 exhibited elevated GSI alongside reduced HSI compared to control and blank groups. The main biological processes enriched by joint analysis included lipid metabolism, sugar metabolism, and amino acid metabolism. Fatty acid composition analysis revealed that the activator may activate the BMP signaling pathway to promote ovarian development and accelerate the transport of unsaturated fatty acids from the liver and pancreas to the ovaries. Amino acid metabolism and carbohydrate metabolism provide transporter proteins and energy for lipid metabolism. This study is highly important because it reveals the molecular mechanism by which the BMP signaling pathway regulates gonadal development in a crustacean.PMID:40169079 | DOI:10.1016/j.dci.2025.105365

J Hazard Mater. 2025 Mar 25;492:138058. doi: 10.1016/j.jhazmat.2025.138058. Online ahead of print.ABSTRACTThe wide application and low utilization rate of oxytetracycline (OTC) make it often detected in wastewater, which may cause harmful effects on microbial denitrification. Aerobic denitrification (AD) as a new microbial denitrification technology has obvious advantages. However, systematic studies on the effects of OTC on it are lacking. In this study, the effect of OTC on AD was comprehensively explored from multiple perspectives, the main results are as follows. From the perspective of bacterial performance, OTC inhibited AD bacteria growth, denitrification efficiency, and caused serious damage to cell morphological structure, results of CCK-8 confirmed that bacterial activity was significantly affected. From the perspective of electron behavior, OTC decreased electron-producing capacity of carbon metabolism, reduced activity of the electron transport system, inhibited the electron consumption of NAR and NIR to varying degrees, thus increased the risk of nitrite accumulation. From the perspective of intracellular environment, OTC broke redox balance and antioxidant mechanism, related carbon and nitrogen cycle functional genes were down-regulated, affected amino acid, organic acid and nucleotide metabolic processes. The above results provide important information for evaluating the potential risks of antibiotics on the application of AD, and provide key background and theoretical support for stabilizing the technology.PMID:40168932 | DOI:10.1016/j.jhazmat.2025.138058

Food Chem. 2025 Mar 26;481:144062. doi: 10.1016/j.foodchem.2025.144062. Online ahead of print.ABSTRACTBesides the need to adapt coffee cultivation to climate change, the growing demand for high-quality and exotic coffee has increased interest in species such as Coffea racemosa and C. zanguebariae. These species offer drought and pest resistance, fast maturation, and distinct sensory profiles. However, there is a lack of information regarding their chemical profile. Therefore, this study employed a metabolomic approach using LC-MS, ESI(±)MS, and multivariate analysis to assess the chemical profiles of these species and compare them with C. arabica and C. canephora cv. Conilon. Sixty-four compounds were identified, including chlorogenic acids, lipids, carbohydrates, amino acids, and glycosylated diterpenes. The results indicate that C. racemosa shares chemical similarities with C. arabica, particularly in their trigonelline and amino acid abundance, while C. zanguebariae is characterized by a high phospholipid content, which may influence mouthfeel. Additionally, LC-MS allows isomer separation, whereas ESI(±)MS emerged as a fast alternative for chemometric modeling.PMID:40168870 | DOI:10.1016/j.foodchem.2025.144062

Plant Physiol Biochem. 2025 Mar 27;223:109847. doi: 10.1016/j.plaphy.2025.109847. Online ahead of print.ABSTRACTSalinity and waterlogging are major abiotic stresses constraining soybean productivity, with their combined effects often surpassing individual impacts. However, the nature of these combined effects-whether additive, synergistic, or antagonistic-remains unclear. In this study, we quantitatively demonstrated that combined salinity-waterlogging stress exerts additive inhibitory effects on soybean (Glycine max L. cv. Qihuang 34) growth, surpassing individual stresses without reaching synergistic severity. Physiological analysis revealed additive inhibition, as reflected by a 38.8 % reduction in leaf area, 36.8 % decrease in dry matter accumulation, and a 63.4 % decline in net photosynthetic rate under combined stress conditions, closely aligning with theoretical additive predictions (e.g., observed vs. predicted values: 38.8 % vs. 40.8 % for leaf area; 36.8 % vs. 37.7 % for biomass). Integrated transcriptomic and metabolomic analysis identified hypoxia-induced ATP depletion as a key driver, disrupting Na+/K+ homeostasis (277.9 % increase in Na+/K+ ratio) despite upregulation of key ion transporters (SOS1: +84.3 %, NHX1a: +54.0 % and NHX1b: +68.7 %). Additive activation of flavonoid biosynthesis genes (CHI, CHR) and metabolites (prunin, chalcone 2'-O-glucoside) mitigated oxidative damage through cumulative metabolite accumulation rather than synergistic interactions. Downregulation of photosynthesis-related genes (e.g., PsbO, PsaA) and ATP synthesis collapse explained energy deficits. Crucially, cutin/suberine biosynthesis emerged as a novel adaptive signature under combined stress. This study provides mechanistic insights into additive salt-waterlogging interactions, identifying targets for stress-resilient soybean breeding.PMID:40168856 | DOI:10.1016/j.plaphy.2025.109847