PubMed

Food Chem X. 2025 Feb 11;26:102230. doi: 10.1016/j.fochx.2025.102230. eCollection 2025 Feb.ABSTRACTKnowledge about the quality of meat obtained from different muscles is crucial for developing high-quality camel meat for commercial use. Metabolomic and proteomic profiles of the longissimus thoracic (LT), semitendinosus (ST), and psoas major (PM) muscles of the bactrian camel, which significantly vary in aspects such as intramuscular fat (IMF) content and shear force, were comprehensively compared to evaluate the impact of these changes on meat quality. Compared with ST and PM muscles, LT muscles had higher IMF content, were more tender, and had a lower shear force. Proteomic analysis unveiled significant differences in metabolic enzymes and binding proteins among different muscles. Based on correlation analysis, 20 key proteins and metabolites closely related to meat quality were screened. Integration of proteomic and metabolomic data highlighted oxidative phosphorylation, TCA cycle, and glycolysis as key distinguishing pathways among different muscles. These results offer effective information for producing high-quality camel meat.PMID:40027112 | PMC:PMC11869849 | DOI:10.1016/j.fochx.2025.102230

Front Cell Dev Biol. 2025 Feb 14;13:1543510. doi: 10.3389/fcell.2025.1543510. eCollection 2025.ABSTRACTINTRODUCTION: Recent research indicated a strong link between the gut microbiota and osteoarthritis. However, the complex interplay between the gut microbiota, serum metabolites, and the progression of osteoarthritis in affected individuals remains largely unexplored. This study aimed to investigate the characteristics of the gut microbiota and serum metabolites in patients with osteoarthritis.METHODS: Participants with either healthy knees or osteoarthritis were enrolled and categorized into healthy control (HC) and osteoarthritis (OA) groups. Fecal and blood samples were collected for 16S rRNA gene sequencing, metabolomic analysis via liquid chromatography-mass spectrometry (LC-MS), and integrated evaluation.RESULTS: The results showed no significant variation in gut microbiota richness and diversity between the two groups. However, the abundance of Bacteroides plebeius and Faecalibacterium prausnitzii was reduced in the OA group, both of which are known for their potential as next-generation probiotics for human health. Metabolomic analysis indicated that serum metabolites, including pyrogallol and 3-hydroxybutyrate (3HB), were significantly lower in the OA group. These metabolites are known to positively impact osteoarthritis progression and other diseases and demonstrated good diagnostic performance for distinguishing osteoarthritis patients from healthy controls. Correlation analysis revealed a positive correlation between Bacteroides plebeius and Faecalibacterium prausnitzii and between pyrogallol and 3HB.DISCUSSION: This study highlighted specific gut microbiota and serum metabolite profiles in osteoarthritis patients, suggesting that the specific changes in bacteria and derived metabolites are closely tied to osteoarthritis progression. This underscores the potential of gut microbiota and serum metabolites as modifiable elements and therapeutic targets for osteoarthritis prevention.PMID:40027098 | PMC:PMC11868077 | DOI:10.3389/fcell.2025.1543510

EClinicalMedicine. 2025 Feb 12;81:103083. doi: 10.1016/j.eclinm.2025.103083. eCollection 2025 Mar.ABSTRACTBACKGROUND: Globally, some 45 million children under five years of age are wasted (low weight-for-height). Although 2023 World Health Organisation guidelines on their care did not aim to identify optimal weight gain, they did mention 5-10 g/kg/day as a target, which is a change from prior guidelines that recommended 10-15 g/kg/day, when inpatient-only care was the norm. We aimed to inform future policy/programming on weight gain targets.METHODS: For this systematic review and meta-analysis, we searched Embase, Global Health and Medline. The final search was on 23/02/2024. Papers were included if they reported weight gain of children aged 6-59 months with severe malnutrition during inpatient (facility-based), outpatient (home-based), and hybrid treatment (initially inpatient and progressing to outpatient treatment). Summary data were extracted, and quality was assessed using a NICE Quality Appraisal Checklist. Our primary outcome was mean rate of weight gain (g/kg/day) during treatment. We conducted random-effects meta-analysis to describe pooled mean weight gain by programme type. Meta-regression investigated potential associations of weight gain with length of stay and programme outcomes. We registered the study on PROSPERO (CRD42023266472).FINDINGS: Our search yielded 3173 papers. We reviewed 321 full texts, identifying 126 eligible papers. Of these, 104 papers, including some 240,650 participants, reported weight gain as g/kg/day and were eligible for meta-analysis. Mean rate of weight gain was 8.8 g/kg/day (95% CI: 7.6, 9.9; I2 = 97.8%) across 18 inpatient programmes, 3.4 g/kg/day (95% CI: 2.0, 4.7; I2 = 99.4%) across 12 hybrid programmes, and 3.9 g/kg/day (95% CI: 3.4, 4.4; I2 = 99.7%) across 60 outpatient programmes. We found inconsistent evidence of an association between slower weight gain and higher mortality: there was weak evidence of association after adjusting for programme type (coefficient = -0.4; 95% CI: -0.7, -0.02; p = 0.04; n = 118 programmes). There was high heterogeneity between studies. Details of weight gain calculation methods varied. We found no evidence for publication bias when accounting for programme type (Egger's test p-value = 0.2).INTERPRETATION: Weight gain in outpatient programmes was markedly slower than in inpatient treatment. Clearer reporting of weight gain and a better understanding of the sequelae of faster/slower recovery is important to set future weight gain targets. Our results set an important baseline for current programmes to benchmark against.FUNDING: Medical Research Council/Global Challenges Research Fund, grant number: MR/V000802/1.PMID:40026833 | PMC:PMC11872456 | DOI:10.1016/j.eclinm.2025.103083

Int J Gen Med. 2025 Feb 25;18:1007-1022. doi: 10.2147/IJGM.S509592. eCollection 2025.ABSTRACTPURPOSE: To explore the mechanism of Zhuyang Tongbian Decoction (ZTD) in treating functional constipation (FC) by observing its effects on intestinal flora composition, the metabolic function of gut microbiota, fecal short-chain fatty acid (SCFA) levels, and serum concentrations of TLR4, NF-κB, TNF-α, and IL-6 in patients with FC.PATIENTS AND METHODS: 40 patients with FC were randomly divided into the control group and the treatment group, 20 cases in each group. And 20 healthy volunteers were recruited during the same period. The control group was administered lactulose, while the treatment group was treated with ZTD. 16s RNA sequencing technology was used to compare the changes in the structure and diversity of the intestinal flora of patients before and after treatment. Changes in the levels of SCFAs in faeces and the levels of TLR4, NF-κB, TNF-α and IL-6 in serum were analysed. Metagenomics sequencing assessed microbiota metabolic functions.RESULTS: The treatment group showed a significant increase in the relative abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, and Faecalibacterium_prausnitzii (P < 0.05), whereas Desulfobacterota and Ruminococcus were significantly reduced (P < 0.05). Notably, fecal acetic and propionic acid levels were significantly higher in the treatment group (P < 0.05). Serum biomarkers TLR4, NF-κB, TNF-α, and IL-6 decreased significantly (P < 0.05). Metagenomics sequencing showed that Carbohydrate metabolism, Metabolism of cofactors and vitamins, and C5- Branched dibasic acid metabolism were significantly increased in functional abundance (P < 0.05).CONCLUSION: ZTD notably improves intestinal flora composition and gut microbiota metabolic function, regulates SCFA levels, and reduces inflammation markers in FC patients. The strain Faecalibacterium_prausnitzii shows significant potential in regulation of intestinal inflammation and may play a crucial role in the treatment efficacy of ZTD for FC.PMID:40026814 | PMC:PMC11871934 | DOI:10.2147/IJGM.S509592

Front Plant Sci. 2025 Feb 14;16:1509120. doi: 10.3389/fpls.2025.1509120. eCollection 2025.ABSTRACTINTRODUCTION: Orychophragmus violaceus is a popular horticultural plant because of its bright purple flowers that are commonly found in parks and green belts. However, three flower colors (purple, light purple, and white) were observed in the wild-type O. violaceus. The molecular mechanism underlying the formation of these intriguing flower colors remains unknown.METHODS: Here, we combined metabolomics and transcriptomics to identify a pathway cascade leading to anthocyanin biosynthesis associated with flower color formation in O. violaceus.RESULTS AND DISCUSSION: A total of 152 flavonoid metabolites were identified based on metabolomic data, most of which were quercetin and kaempferol. Comparative analysis of the metabolites among the three flower samples revealed that two anthocyanins, peonidin-3-glucoside and delphinidin 3-(6''-malonyl-glucoside), are the pigments most likely responsible for the coloration of the petals of O. violaceus. Subsequent transcriptomic analysis revealed 5,918 differentially expressed genes among the three groups of flowers, 87 of which encoded 13 key enzymes in the anthocyanin biosynthetic pathway. Moreover, the high expression of two transcription factors, OvMYB and OvbHLH, in purple flowers suggests their role in the regulation of anthocyanin biosynthesis. By integrating metabolomic and transcriptomic data, OvANS, which encodes anthocyanidin synthase, was significantly upregulated in purple flowers. OvANS is the enzyme responsible for the transformation of colorless leucoanthocyanidins to colored anthocyanidins. This study provides novel insights into the molecular mechanism of flower color development in O. violaceus, laying the foundation for flower color breeding.PMID:40026389 | PMC:PMC11868260 | DOI:10.3389/fpls.2025.1509120

J Inflamm Res. 2025 Feb 25;18:2767-2780. doi: 10.2147/JIR.S503058. eCollection 2025.ABSTRACTPURPOSE: Metabolic characterization of primary angiitis of the central nervous system (PACNS) is crucial for understanding the disease pathogenesis and progression mechanisms, but it has not been reported in patients. This study aimed to explore changes in the plasma metabolome during the active and remission phases of PACNS and identify potential biomarkers.METHODS: We collected plasma samples from 35 patients with PACNS during the active and remission phases and 22 samples from patients with non-inflammatory disease as controls. Liquid and gas chromatography-mass spectrometry were used to analyze 63 plasma samples from 57 patients metabolically. Meanwhile, we cross-validated the metabolomics results with brain tissue transcriptomic data from comprehensive gene expression databases, enhancing the reliability of our conclusions.RESULTS: A total of 3,233 metabolites were identified. Enrichment analysis showed significant changes in lactate/amino acid/glycerol-pyruvic-tricarboxylic acid, glycerophospholipid/sphingolipid-membrane metabolism, lysine/tryptophan-essential amino acid metabolism, and uracil metabolism pathways during the active phase of PACNS. These findings were confirmed in both the remission phase of PACNS patients and the transcriptomic samples. Meanwhile, metabolic abnormalities in patients with PACNS were observed with benzoxazole, sesquiterpenoid, and octyl-phenolic products, and enrichment of environmental pollutants and their estrogen-like effects. Twelve metabolites, including D-Ribose, 13s-HPODE, and C16 Sphinganine, showed potential diagnostic and therapeutic evaluation value.CONCLUSION: Our study identified potential biomarkers and metabolic characteristics of PACNS using integrated metabolomics and transcriptomics approaches. These findings highlight the importance of understanding PACNS from a metabolic perspective and guide future diagnostic and therapeutic strategies.PMID:40026305 | PMC:PMC11871944 | DOI:10.2147/JIR.S503058

J Inherit Metab Dis. 2025 Mar;48(2):e70010. doi: 10.1002/jimd.70010.ABSTRACTThe human liver plays a central metabolic role; however, its physiology may become imbalanced in inborn errors of metabolism (IEM), a broad category of monogenic disorders. Liver transplantation has been increasingly used to improve patient metabolic control, especially in diseases related to amino acid metabolism, such as urea cycle disorders and organic acidurias, to provide enzyme replacement. Ex vivo liver normothermic machine perfusion (NMP) techniques have recently been developed to increase the number of transplantable grafts and improve transplantation outcomes. This study used seven NMP of explanted livers from patients with IEM undergoing transplantation as models to investigate disease-related liver metabolism and function. The perfused livers demonstrated positive viability indicators and disease-specific targeted metabolomics providing the proof-of-principle that our ex vivo model expresses the biochemical disease characteristics and responds to therapeutical intervention in a unique "physiological" milieu, offering an ideal tool to study novel treatments, in a setting closely mirroring human disease.PMID:40026238 | DOI:10.1002/jimd.70010

Plant J. 2025 Mar;121(5):e70042. doi: 10.1111/tpj.70042.ABSTRACTFritillaria unibracteata var. wabuensis is an important resource plant for the famous traditional Chinese medicine Fritillariae cirrhosae bulbus ("Chuanbeimu" in Chinese). F. cirrhosae bulbus is the dried bulbs of several species from Fritillaria genus, with isosteroidal alkaloids components assumed as the bioactive ingredients. However, the biosynthesis pathway of isosteroidal alkaloids remains elusive. Here, we adopted F. unibracteata var. wabuensis as a material to identify genes involved in the biosynthesis of isosteroidal alkaloids. We first constructed the multi-tissue metabolome and transcriptome dataset of F. unibracteata var. wabuensis. Interestingly, imperialine-3-β-d-glucoside, an isosteroidal glycoalkaloid, was found to be the major tissue-specific accumulated alkaloid. Through phylogenetic and co-expression analysis, we identified two UDP-glucosyltransferases from UGT73 family catalyzing 3-O-glucosylation of isosteroidal and steroidal alkaloids: imperialine 3-O-glucosyltransferase (FuwI3GT) can use both isosteroidal alkaloid imperialine and steroidal alkaloid solanidine as substrates, while solanidine 3-O-glucosyltransferase (FuwS3GT) can only use steroidal alkaloid solanidine as a substrate. We further approved that the W201 residue of FuwI3GT determined its substrate preference of isosteroidal alkaloids. Overall, our results identified enzymes involved in 3-O-glucosylation of isosteroidal and steroidal alkaloids in F. unibracteata var. wabuensis and paved the way to fully elucidate the isosteroidal alkaloid biosynthesis pathway in Fritillaria species.PMID:40026195 | DOI:10.1111/tpj.70042

Plant Cell Environ. 2025 Mar 2. doi: 10.1111/pce.15448. Online ahead of print.ABSTRACTEfforts to enhance protein and oil contents in soybean seeds are significant; however, a negative correlation usually exists between protein and oil levels. This observation emphasizes the need to understand the spatiotemporal dynamics and interactions in protein and oil accumulation during soybean seed development. The current study used LC-MS/MS methodology to conduct high-throughput metabolomic analyses, aiming to understand metabolite compositions and spatial distributions in soybean varieties with extreme protein and oil content phenotypes including HPHO, HPLO, LPHO and LPLO lines. Comparative investigations revealed distinct variances in the metabolic characteristics of these four lines. Key metabolites associated with oil and protein synthesis were screened out using these data and included glucose, citric acid, α-ketoglutaric acid, glycerate 3-phosphate, glyceraldehyde 3-phosphate, succinic acid, cis-aconitic acid. Pathway analyses of differentially abundant metabolites indicated significant increases in the activity of the Calvin cycle, TCA cycle, glycolysis, and shikimic acid pathways. Simultaneously, reductions were observed in pathways related to the conversion of glucose into pentose, ascorbate and aldarate. This modification supports incorporating carbon sources into amino and fatty acid synthesis pathways in protein- and oil-rich soybean seeds. These results provide a basis for future initiatives to develop soybean cultivars with enhanced protein and oil yields.PMID:40025870 | DOI:10.1111/pce.15448

Gut Microbes. 2025 Dec;17(1):2474142. doi: 10.1080/19490976.2025.2474142. Epub 2025 Mar 2.ABSTRACTObstructive sleep apnea (OSA) is characterized by intermittent hypoxia/hypercapnia (IHC), affects predominantly obese individuals, and increases atherosclerosis risk. Since we and others have implicated gut microbiota and metabolites in atherogenesis, we dissected their contributions to OSA-induced atherosclerosis. Atherosclerotic lesions were compared between conventionally-reared specific pathogen free (SPF) and germ-free (GF) Apoe-/- mice following a high fat high cholesterol diet (HFHC), with and without IHC conditions. The fecal microbiota and metabolome were profiled using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry (LC-MS/MS) respectively. Phenotypic data showed that HFHC significantly increased atherosclerosis as compared to regular chow (RC) in both aorta and pulmonary artery (PA) of SPF mice. IHC exacerbated lesions in addition to HFHC. Differential abundance analysis of gut microbiota identified an enrichment of Akkermansiaceae and a depletion of Muribaculaceae (formerly S24-7) family members in the HFHC-IHC group. LC-MS/MS showed a dysregulation of bile acid profiles with taurocholic acid, taurodeoxycholic acid, and 12-ketodeoxycholic acid enriched in the HFHC-IHC group, long-chain N-acyl amides, and phosphatidylcholines. Interestingly, GF Apoe-/- mice markedly reduced atherosclerotic formation relative to SPF Apoe-/- mice in the aorta under HFHC/IHC conditions. In contrast, microbial colonization did not show a significant impact on the atherosclerotic progression in PA. In summary, this research demonstrated that (1) IHC acts cooperatively with HFHC to induce atherosclerosis; (2) gut microbiota modulate atherogenesis, induced by HFHC/IHC, in the aorta not in PA; (3) different analytical methods suggest that a specific imbalance between Akkermansiaceae and Muribaculaceae bacterial families mediate OSA-induced atherosclerosis; and (4) derived bile acids, such as deoxycholic acid and lithocholic acid, regulate atherosclerosis in OSA. The knowledge obtained provides novel insights into the potential therapeutic approaches to prevent and treat OSA-induced atherosclerosis.PMID:40025767 | DOI:10.1080/19490976.2025.2474142

Mol Plant. 2025 Mar 1:S1674-2052(25)00090-5. doi: 10.1016/j.molp.2025.02.007. Online ahead of print.ABSTRACTEdible maize is an important food crop, providing energy and nutrients to meet human health and nutritional requirements. However, how environmental pressures and human activity have shaped the edible maize metabolome remains unclear. In this study, we collected 452 diverse edible maize accessions worldwide, comprising waxy, sweet, and field maize. A total of 3,020 non-redundant metabolites, including 802 annotated metabolites, were identified by a two-step optimized approach, which generated the most comprehensive annotated metabolites dataset in plants to date. Although specific metabolite differentiation was detected in Field-Sweet and Field-Waxy differentiations, convergent metabolite differentiation was the dominant differentiation pattern. We identified hub genes in all metabolite classes by mGWAS hotspot analysis. A total of 17 and 15 hub genes were selected as the key differentiation genes for flavonoids and lipids, respectively. Surprisingly, almost all of these genes were under diversifying selection, which indicated diversifying selection was the main genetic mechanism of convergent metabolic differentiation. Furthermore, the genetic and molecular studies reveal the roles and diversifying selection genetic mechanisms of ZmGPAT11 in convergent metabolite differentiation in lipid pathway. Based on our research, we established the first edible maize metabolome database, EMMDB (www.maizemdb.site/home/). We successfully applied EMMDB for precision improvement of nutritional and flavor traits, and an elite inbred line 6644_2 was bred with greatly improved in contents of flavonoids, lysophosphatidylcholines, lysophosphatidylethanolamines, and vitamins. These findings provide insights into the underlying genetic mechanisms of edible maize metabolite differentiation and provide a database for the breeding improvement of edible maize flavor and nutritional traits by metabolome precision design.PMID:40025737 | DOI:10.1016/j.molp.2025.02.007

ACS Nano. 2025 Mar 2. doi: 10.1021/acsnano.5c01877. Online ahead of print.ABSTRACTMechanical force initiates sterile inflammation, a process implicated in diverse physiological and pathological processes. The timely clearance of apoptotic cells by macrophages via efferocytosis is crucial for the proper resolution of sterile inflammation and for averting excessive tissue damage. Despite this, the specific role and underlying mechanisms of mechanical force on macrophage efferocytosis remain obscure. By integrating bioinformatics and metabolomics analyses, we uncovered how mechanical force disrupts the "arginine metabolism─TCA cycle─mitochondrial function" metabolic cascade, thereby impairing macrophage efferocytosis and intensifying sterile inflammation. Notably, we discovered that elevating l-arginine levels can ameliorate these crises by restoring energy metabolism. Leveraging this insight, we engineered a microneedle drug delivery system loaded with nitric-oxide driven nanomotors (MSN-LA@MNs) for targeted delivery of l-arginine. The active component, MSN-LA, exploits the heightened expression of inducible nitric oxide synthase (iNOS) in force-loaded tissues as a chemoattractant, harnessing NO generated from iNOS-catalyzed l-arginine for autonomous propulsion. In a force-induced rat orthodontic tooth movement (OTM) model, we confirmed that MSN-LA@MNs enhance macrophage efferocytosis and, under iNOS guidance, dynamically modulate sterile inflammation levels in OTM, thus facilitating the OTM process. Collectively, our findings elucidate previously unclear mechanistic links between force, macrophage efferocytosis, and sterile inflammation from a metabolic vantage point, offering a promising targeted strategy for modulating force-related biological processes such as OTM.PMID:40025734 | DOI:10.1021/acsnano.5c01877

J Agric Food Chem. 2025 Mar 2. doi: 10.1021/acs.jafc.4c12596. Online ahead of print.ABSTRACT(Poly)phenols, bioactive compounds abundant in plant-based diets, have attracted interest for their potential role in preventing chronic diseases including cardiometabolic and neurodegenerative diseases. This study investigates the global sulfatome and glucuronidated metabolome in urine samples from 100 healthy adults collected pre- and postintervention following a 3-day (poly)phenol-rich intervention consisting of flaxseeds, raspberry powder, and soy milk. Using untargeted mass spectrometric metabolomics combined with selective phase II enzymatic treatment, we detected 156 sulfated and 143 glucuronidated metabolites in urine samples. Significant changes postintervention were observed for 91 sulfates and 94 glucuronides. Receiver operating characteristic curve analysis identified a combination of six polyphenol-derived key metabolites: glucuronidated daidzein and the sulfated compounds of pyrogallol, ferulic acid, 4-methoxyphenol, enterolactone, and resorcinol, which resulted in the best combination with the highest predictive AUC of 0.97. These findings underscore the utility of these metabolites as sensitive and selective biomarkers of (poly)phenol dietary intake.PMID:40025695 | DOI:10.1021/acs.jafc.4c12596

Gut Microbes. 2025 Dec;17(1):2474148. doi: 10.1080/19490976.2025.2474148. Epub 2025 Mar 2.ABSTRACT2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.PMID:40025650 | DOI:10.1080/19490976.2025.2474148

Planta. 2025 Mar 1;261(4):71. doi: 10.1007/s00425-025-04651-y.ABSTRACTQuantitative and qualitative selenium speciation analyses of the root of white cabbage reveal the presence of elemental Se, selenate, selenomethionine and deaminated derivatives of selenohomolanthionine. White cabbage (Brassica oleracea convar. capitata var. alba) is one of the most consumed vegetable brassicas of the Brassica oleracea species whose production is compatible with the recent strip-till and no-till type farming policies. White cabbage has been in the focus of selenium research for decades as a possible source of food-derived selenium supplementation; however, the root section of the plant has hardly been targeted, being a by-product that is left in or plowed into the soil to serve as an organic fertilizer. The root of selenium-enriched white cabbage, planted on three different soil types (sand, silty sand, and silt), was analyzed for selenium speciation with the complementary use of liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and electrospray ionization high-resolution mass spectrometry (LC-ESI-HR-MS) methods after orthogonal (anion/cation exchange) chromatographic purification. Elemental selenium (Se0) was the major selenospecies in all cases, accounting for 28-43% of total selenium content. Water and proteolytic extractions could recover a median of 28% of total selenium through the quantification of selenate and selenomethionine, leaving a series of selenocompounds unassigned. Among these latter species, accounting for up to an additional 6% of total selenium, eight low-molecular-weight selenocompounds were detected; five out of the eight compounds could be tentatively identified as deaminated derivatives of selenohomolanthionine.PMID:40025298 | DOI:10.1007/s00425-025-04651-y

Sci Rep. 2025 Mar 1;15(1):7349. doi: 10.1038/s41598-025-92216-0.ABSTRACTMetabolic disorders are an important feature of chronic lung disease. Patients diagnosed with chronic obstructive pulmonary disease (COPD) have been found to experience metabolic disorders. Nonetheless, evidence on the causal role of circulating metabolites in promoting or preventing COPD is still lacking. Conducting a methodical examination on the causal connection between blood metabolites and COPD can aid in identifying fresh objectives for the screening and prevention of COPD. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between COPD and 486 blood metabolites.We used two-sample MR techniques and genome-wide association study (GWAS) data to evaluate the correlation between COPD and 486 serum metabolites. To evaluate the causal impact of serum metabolites on the risk of COPD, we predominantly employed inverse variance weighting (IVW) methodology. The MR-Egger regression test was employed to assess multiple validity, while the presence of heterogeneity was examined using the Cochran's Q test. To ensure the reliability of the findings, a leave-one-out analysis was conducted. The Bonferroni correction is used to adjust for multiple comparisons, ensuring rigorous validation of our results.After filtering by IVW and sensitivity analysis, we identified 10 known metabolites including fructose, margarate (17:0), guanosine, 2-stearoylglycerophosphocholine, hexadecanedioate, lactate, 5-oxoproline, paraxanthine, phenyllactate (PLA) and N-acetylglycine. Of these, fructose, margarate (17:0), guanosine, 2-stearoylglycerophosphocholine and hexadecanedioate are risk metabolites, and additionally, lactate, 5-oxoproline, paraxanthine phenyllactate(PLA) and N-acetylglycine are protective metabolites. In addition, the study identified five currently unknown chemical structures. Cochran's Q-test showed no significant heterogeneity, and MR Egger's intercept analysis confirmed the absence of horizontal multidirectionality. Leave-one-out analysis also proved the reliability of the MR analysis.We identified seven COPD-related risks and eight protective human serum metabolites. By combining genomics and metabolism, it provides new insights into the underlying mechanisms of COPD, with important implications for COPD screening and prevention.PMID:40025290 | DOI:10.1038/s41598-025-92216-0

Sci Rep. 2025 Mar 1;15(1):7264. doi: 10.1038/s41598-025-91673-x.ABSTRACTChikungunya is a mosquito-borne viral disease that causes fever and severe joint pain for which there is no direct acting drug treatments. Vinyl sulfone SGC-NSP2PRO-1 (3) was identified as a potent inhibitor of the nsP2 cysteine protease (nsP2pro) that reduced viral titer against infectious isolates of Chikungunya and other alphaviruses. The covalent warhead in 3 captured the active site C478 and inactivated nsP2pro with a kinact/Ki ratio of 5950 M-1 s-1. The vinyl sulfone 3 was inactive across a panel of 23 other cysteine proteases and demonstrated remarkable proteome-wide selectivity by two chemoproteomic methods. A negative control analog SGC-NSP2PRO-1N (4) retained the isoxazole core and covalent warhead but demonstrated > 100-fold decrease in enzyme inhibition. Both 3 and 4 were stable across a wide range of pH in solution and upon prolonged storage as solids. Vinyl sulfone 3 and its negative control 4 will find utility as high-quality chemical probes to study the role of the nsP2pro in cellular studies of alphaviral replication and virulence.PMID:40025188 | DOI:10.1038/s41598-025-91673-x

Sci Rep. 2025 Mar 3;15(1):7381. doi: 10.1038/s41598-025-91324-1.ABSTRACTWe proposed that cerebrospinal fluid would provide objective evidence for disrupted brain metabolism in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS). The concept of postexertional malaise (PEM) with disabling symptom exacerbation after limited exertion that does not respond to rest is a diagnostic criterion for ME/CFS. We proposed that submaximal exercise provocation would cause additional metabolic perturbations. The metabolomic and lipidomic constituents of cerebrospinal fluid from separate nonexercise and postexercise cohorts of ME/CFS and sedentary control subjects were contrasted using targeted mass spectrometry (Biocrates) and frequentist multivariate general linear regression analysis with diagnosis, exercise, gender, age and body mass index as independent variables. ME/CFS diagnosis was associated with elevated serine but reduced 5-methyltetrahydrofolate (5MTHF). One carbon pathways were disrupted. Methylation of glycine led to elevated sarcosine but further methylation to dimethylglycine and choline was decreased. Creatine and purine intermediates were elevated. Transaconitate from the tricarboxylic acid cycle was elevated in ME/CFS along with essential aromatic amino acids, lysine, purine, pyrimidine and microbiome metabolites. Serine is a precursor of phospholipids and sphingomyelins that were also elevated in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. The findings differ from prior hypometabolic findings in ME/CFS plasma. The novel findings generate new hypotheses regarding serine-folate-glycine one carbon and serine-phospholipid metabolism, elevation of end products of catabolic pathways, shifts in folate, thiamine and other vitamins with exercise, and changes in sphingomyelins that may indicate myelin and white matter dysfunction in ME/CFS.PMID:40025157 | DOI:10.1038/s41598-025-91324-1

Nat Commun. 2025 Mar 1;16(1):2095. doi: 10.1038/s41467-025-57302-x.ABSTRACTThe apicoplast, a relic plastid organelle derived from secondary endosymbiosis, is crucial for many medically relevant Apicomplexa. While it no longer performs photosynthesis, the organelle retains several essential metabolic pathways. In this study, we examine the four primary metabolic pathways in the Toxoplasma gondii apicoplast, along with an accessory pathway, and identify conditions that can bypass these. Contrary to the prevailing view that the apicoplast is indispensable for T. gondii, we demonstrate that bypassing all pathways renders the apicoplast non-essential. We further show that T. gondii lacking an apicoplast (T. gondii-Apico) can be maintained indefinitely in culture, establishing a unique model to study the functions of this organelle. Through comprehensive metabolomic, transcriptomic, and proteomic analyses of T. gondii-Apico we uncover significant adaptation mechanisms following loss of the organelle and identify numerous putative apicoplast proteins revealed by their decreased abundance in T. gondii-Apico. Moreover, T. gondii-Apico parasites exhibit reduced sensitivity to apicoplast targeting compounds, providing a valuable tool for discovering new drugs acting on the organelle. The capability to culture T. gondii without its plastid offers new avenues for exploring apicoplast biology and developing novel therapeutic strategies against apicomplexan parasites.PMID:40025025 | DOI:10.1038/s41467-025-57302-x

Nat Commun. 2025 Mar 1;16(1):2089. doi: 10.1038/s41467-025-57253-3.ABSTRACTPrenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on the Wuhan Healthy Baby Cohort, China (N = 1088), eleven metals were measured in maternal urine during early pregnancy (13.1 ± 1.1 weeks) and metabolomics profiling was conducted in cord blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development in 2-year-old children to obtain the mental development index (MDI) and psychomotor development index (PDI). After false discovery rate correction, higher maternal urinary levels of manganese, nickel, aluminum, rubidium, gallium, and the summary score of metals were only significantly associated with lower MDI scores. The weighted quantile sum index of the metal mixture showed a significant inverse association with MDI and PDI scores, with aluminum contributing the most to the associations. Histidine, beta-alanine, purine, and pyrimidine metabolism significantly mediated the above associations, suggesting that disturbances in amino acids, neurotransmitter and neuroendocrine metabolism may be important mediators in contributing to impaired neurodevelopment of children.PMID:40025012 | DOI:10.1038/s41467-025-57253-3