PubMed

Heliyon. 2025 Feb 8;11(4):e42565. doi: 10.1016/j.heliyon.2025.e42565. eCollection 2025 Feb 28.ABSTRACTMaize (Zea mays) is one of the most important cereal crops worldwide. Insect control through host plant resistance plays an important part in improving both yield and quality of maize. Spodoptera exigua is a common insect pest causing destructive damages to maize. To comprehensively understand molecular mechanism of maize defense against S. exigua, integrated transcriptomics and metabolomics analyses were conducted in the insect-resistant maize inbred line CML139 infested with S. exigua for 24 h. 9845 differentially expressed genes and 34 significantly changed metabolites were identified in infested leaves. Maize transcriptional response to S. exigua infestation involved in genes encoding enzymes in biosynthetic process (ribosome, glycerolipid, glycerophospholipid metabolism), genes in valine, leucine and isoleucine degradation, phenylpropanoid pathway and transcription factors. By metabolism analysis, accumulations of amino acids, organic acids, phenylpropanoids and benzoxazinoids (Bxs) were significantly enhanced, with the exception of salicylic acid (SA) and jasmonic acid (JA). The integrated analysis of transcriptomic and metabolic data demonstrated that both transcripts and metabolites involved in phenylpropanoid and Bxs biosynthesis were differentially modulated in S. exigua infested leaves. This study is valuable in understanding the complex mechanism of interaction between plants and insect herbivores and provide a potential strategy to maize pest control.PMID:40034323 | PMC:PMC11872508 | DOI:10.1016/j.heliyon.2025.e42565

Food Sci Nutr. 2025 Mar 2;13(3):e70027. doi: 10.1002/fsn3.70027. eCollection 2025 Mar.ABSTRACTA low-temperature condition in a root zone is a major abiotic stress that threatens cucumber (Cucumis sativus L.) growth and development, yet the molecular mechanism by which the leaf reacts to root zone chilling stress remains largely unknown. In this study, we applied three temperature treatments, including room temperature (20°C-22°C), suboptimal temperature (13°C-15°C), and low temperature (8°C-10°C), to investigate how root zone chilling affects hormone dynamics, metabolomics, and transcriptomics in the leaves of the cucumber variety "Jinyou 35", the main cultivar in northwest and southwest China. Through integrative physiological and biochemical analysis, auxin emerges as the most significant accumulated hormone, accounting for 88% in room temperature-treated leaves (RL), 99% in suboptimal temperature-treated leaves (SL), and 94% in low-temperature-treated leaves (LL). Under chilling stress, flavanones were the most abundant metabolite in cucumber leaves, constituting over 50% of total metabolites, while phenolic acids showed a marked decrease. Several differentially expressed transcription factors (DETFs), such as LOB (CsaV3_3G020650), MYB (CsaV3_3G043510), and bHLH (CsaV3_2G005070 and CsaV3_4G029740), were upregulated in SL and LL, potentially enhancing cucumber's defense against chilling injury. Additionally, terminal flower formation was observed under suboptimal and low-temperature conditions, with CsFT expression in SL and LL lower than in RL, and a significant negative correlation observed between CsFT and CsNAC6. These findings deepen our understanding of cucumber's resilience mechanisms to root zone chilling stress, shedding light on its cold tolerance strategies.PMID:40034224 | PMC:PMC11873373 | DOI:10.1002/fsn3.70027

Synth Syst Biotechnol. 2025 Feb 8;10(2):511-522. doi: 10.1016/j.synbio.2025.02.002. eCollection 2025 Jun.ABSTRACTCorynebacterium glutamicum is a versatile industrial microorganism for producing various amino acids. However, there have been no reports of well-defined C. glutamicum strains capable of hyperproducing l-tryptophan. This study presents a comprehensive metabolic engineering approach to establish robust C. glutamicum strains for l-tryptophan biosynthesis, including: (1) identification of potential targets by enzyme-constrained genome-scale modeling; (2) enhancement of the l-tryptophan biosynthetic pathway; (3) reconfiguration of central metabolic pathways; (4) identification of metabolic bottlenecks through comparative metabolome analysis; (5) engineering of the transport system, shikimate pathway, and precursor supply; and (6) repression of competing pathways and iterative optimization of key targets. The resulting C. glutamicum strain achieved a remarkable l-tryptophan titer of 50.5 g/L in 48h with a yield of 0.17 g/g glucose in fed-batch fermentation. This study highlights the efficacy of integrating computational modeling with systems metabolic engineering for significantly enhancing the production capabilities of industrial microorganisms.PMID:40034180 | PMC:PMC11872490 | DOI:10.1016/j.synbio.2025.02.002

Front Plant Sci. 2025 Feb 17;16:1510184. doi: 10.3389/fpls.2025.1510184. eCollection 2025.ABSTRACTPogostemon cablin (patchouli) is a well-known perennial herbaceous plant for traditional Chinese medicine, and its primary bioactive compounds are patchoulol and pogostone. The biosynthesis pathway of patchouli has been well resolved early, while the biosynthesis pathway of pogostone is still not fully resolved due to the lack of terminal enzyme directly synthesizing pogostone. Here, the present study aims to predict the terminal enzyme of pogostone biosynthesis and reconstruct its most possible complete biosynthesis, through the integrated transcriptomic and metabolomic analysis. The metabolomic and transcriptomic profiles of patchouli leaf were largely different to those of root and stem. Patchoulol analogs like patchoulene and germacrene mainly accumulated in leaf, while pogostone content was much higher in root. Based on the integrated analysis of differentially expressed genes and metabolites, we reconstructed the biosynthesis pathways of patchoulol, and predicted the most likely complete biosynthesis pathway of pogostone. Besides, we identified 29 highly-expressed genes involved in pogostone biosynthesis for the neo-octoploid genome of patchouli, and most of their expression levels were strongly correlated with pogostone content. In particular, patchouli BAHD-DCR acyltransferases (BAHD-DCRs) were phylogenetically distant from but structurally similar to the other known plant BAHD acyltransferases. Most of them possessed the conservative catalysis motif HXXXD, and the catalysis center could bind to the widely recognized substrate molecules of 4-hydroxy-6-methyl-2-pyrone and 4-methylvaleryl-CoA and product molecule of pogostone. Thus, the highly-expressed BAHD-DCRs in patchouli root were proposed to be terminal enzymes directly synthesizing pogostone. The findings here provide more supporting evidence for the medical use of patchouli whole plants, and make an important step forward fully resolving the pogostone biosynthesis pathway. The identified genes involved in pogostone biosynthesis, especially BAHD-DCRs, deserve further investigation and utilization in the synthetic production of pogostone.PMID:40034152 | PMC:PMC11872920 | DOI:10.3389/fpls.2025.1510184

iScience. 2025 Jan 14;28(2):111814. doi: 10.1016/j.isci.2025.111814. eCollection 2025 Feb 21.ABSTRACTCardiovascular diseases (CVDs) remain the primary cause of global mortality. Nutritional interventions hold promise to reduce CVD risks in an increasingly aging population. However, few nutritional interventions are proven to support heart health and act mostly on blood lipid homeostasis rather than at cardiac cell level. Here, we show that mitochondrial quality dysfunctions are common hallmarks in human cardiomyocytes upon heart aging and in chronic conditions. Preclinically, the post-biotic and mitophagy activator, urolithin A (UA), reduced both systolic and diastolic cardiac dysfunction in models of natural aging and heart failure. At a cellular level, this was associated with a recovery of mitochondrial ultrastructural defects and mitophagy. In humans, UA supplementation for 4 months in healthy older adults significantly reduced plasma ceramides clinically validated to predict CVD risks. These findings extend and translate UA's benefits to heart health, making UA a promising nutritional intervention to support cardiovascular function as we age.PMID:40034121 | PMC:PMC11875685 | DOI:10.1016/j.isci.2025.111814

Biomed Chromatogr. 2025 Apr;39(4):e70045. doi: 10.1002/bmc.70045.ABSTRACTAs a traditional Chinese medicine, velvet antler (VA) is usually processed with white wine according to the Chinese Pharmacopoeia. The practice of using aged vinegar to process VA is uncommon, which is only used in "GuiLingJi." In this study, we found significant chemical changes in vinegar processing. Network pharmacology analysis showed that 20 increased components mainly were related with fecundity through the regulation of biosynthesis of steroid hormones and the estrogen signaling pathway. Reproduction experiment using Drosophila melanogaster showed that both VA and vinegar-processed velvet antler (VPVA) could enhance the reproductive capacity and increase the steroid hormone levels in Drosophila, while VPVA was much superior to VA. In addition, metabolomics showed that energy metabolism was related with the mechanisms by which VA improves the fecundity of Drosophila. This study provides a theoretical basis for the rationale of vinegar processing of VA.PMID:40033880 | DOI:10.1002/bmc.70045

Biomed Chromatogr. 2025 Apr;39(4):e70047. doi: 10.1002/bmc.70047.ABSTRACTAlzheimer's disease (AD) is a common neurodegenerative disease for which there are no effective drugs. Kai-Xin-San (KXS), with definite curative effects, is widely used for the prevention and treatment of AD in China. But its mechanism is not yet fully understood. Based on our established rat model and previous pharmacodynamics study, Multi-omics (metabolomics, proteomics) and network analysis were integrated to explore the holistic mechanism of anti-AD effects of KXS. The key pathways were validated with western blot and ELISA methods. Morris water maze and Nissl staining showed that KXS could ameliorate cognitive deficits and pathological morphology of the hippocampus in AD rats. A total of nine metabolites were identified, which were related to pyrimidine metabolism, riboflavin metabolism, tyrosine metabolism, tryptophan metabolism, and glycerophospholipid metabolism. Proteomics results indicated that the improvement of cognitive deficits by KXS was closely related to the regulation of oxidative phosphorylation in mitochondria. Western blotting results showed that KXS significantly inhibited the expression of Mt-nd2 and Ndufb6 in AD rats. Integrated analysis indicated that the anti-AD targets of KXS were interrelated and KXS could exert its anti-AD effect by reducing oxidative stress, neurotoxicity, and inflammation.PMID:40033867 | DOI:10.1002/bmc.70047

ACS Synth Biol. 2025 Mar 3. doi: 10.1021/acssynbio.4c00728. Online ahead of print.ABSTRACTα-Bisabolene's distinctive aroma is highly prized in fragrances and cosmetics, while its antioxidant properties hold significant pharmaceutical potential. However, the production of α-bisabolene in Saccharomyces cerevisiae remains an outstanding challenge due to cell growth limitations and insufficient supply of the α-bisabolene precursor farnesyl pyrophosphate. In this work, a new S. cerevisiae platform strain capable of producing high levels of α-bisabolene was presented. Carbon flux in the α-bisabolene synthesis pathway was maximized by iterative enhancement of the mevalonate metabolic pathway. The effects of MVA pathway intermediates on cell growth were addressed through a two-stage fermentation controlled based on a temperature-sensitive regulation strategy. The fermentation medium was optimized based on metabolomics and response surface model analysis. Under the optimal fermentation process, the titer of α-bisabolene reached 18.6 g/L during fed-batch fermentation, representing the highest titer reported to date. These strategies open up new avenues for industrial-scale terpene biosynthesis.PMID:40033776 | DOI:10.1021/acssynbio.4c00728

J Inherit Metab Dis. 2025 Mar;48(2):e70018. doi: 10.1002/jimd.70018.ABSTRACTThe dilated cardiomyopathy with ataxia (DCMA) syndrome is a rare mitochondrial disorder caused by mutations in the poorly understood DNAJC19 gene. Cardiac involvement in DCMA ranges from mild conduction abnormalities to early severe myocardial dysfunction. Although evidence suggests that DCMA is linked to abnormalities in mitochondrial function, the molecular underpinnings of this condition are unclear, and there is no way to predict which patients will develop life-threatening disease. To address this, we developed a metabolic flux assay for assessing the metabolic function of mitochondria in fibroblasts derived from DCMA patients. Using this approach, we discovered that DCMA fibroblasts have elevated glutamine uptake, increased glutamate and ammonium secretion, and elevated lactate production. Moreover, we observed that these cellular perturbations were closely correlated with cardiac dysfunction in a blinded cohort of patient cell lines. These findings suggest that glutamine catabolism is abnormal in DCMA and may serve as a predictor of clinical progression.PMID:40033659 | DOI:10.1002/jimd.70018

Anticancer Agents Med Chem. 2025 Mar 3. doi: 10.2174/0118715206374787250227064528. Online ahead of print.ABSTRACTAnthraquinones are well known for their wide spectrum of pharmacological properties. Anthraquinone antibiotics, such as doxorubicin, daunorubicin, epirubicin, and mitoxantrone, have long been used in the clinical management of various tumors. However, their use is limited due to their toxicity effects, especially cardiomyopathy, despite their pronounced therapeutic effects. In recent years, medicinal chemists have explored the possibility of modifying the anthraquinone ring appended with structurally diverse functionality in order to develop better chemotherapeutic agents with fewer adverse effects. The fused polycyclic structure of anthraquinone offers rigidity, planarity, and aromaticity, which helps in double helix DNA intercalation, disruption of G4 DNA, and inhibition of topoisomerase-II enzyme of cancer cells, making them suitable pharmacophore for anticancer drug discovery. Incorporation of suitable functional groups such as amino, hydroxyl, and their derivatives into anthraquinone rings can improve their interactions with biological targets involved in cancer progression. These subtle structural changes produce newer anthraquinone derivatives with improved anticancer properties, increased potency, selectivity, and reduced toxicity, and can overcome multi-drug resistance. On the other hand, the molecular hybrids of the anthraquinone derivatives have been reported to act on multiple targets in cancer cells, as seen in the case of clinical candidates like alectinib, midostaurin, tucatinib, belinostat, and dacinostat. Molecular hybrid has given a new direction for anticancer drug development, which can produce bifunctional drug candidates with reduced toxicity. This review summarizes different structural modifications that have been made to the anthraquinone ring in the last decade with the aim of bringing out potent yet toxicity-free anticancer agents.PMID:40033586 | DOI:10.2174/0118715206374787250227064528

Curr Neuropharmacol. 2025 Feb 28. doi: 10.2174/011570159X379620250225075810. Online ahead of print.ABSTRACTOBJECTIVES: The objective of this study is to determine the characteristics of peripheral inflammatory profiles and their correlations with the clinical features in patients with cerebellar ataxia.METHODS: We conducted a cross-sectional study on a cohort of 140 cerebellar ataxia patients, including 74 patients with spinocerebellar ataxia (SCA), 66 patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C), and 145 healthy controls (HCs). Inflammatory profiles (PLT, MPV, NLR, PLR, MLR, SII, AISI and ESR) were measured in peripheral blood, and were compared by ANOVA and Kruskal-Wallis test. The receiver operating characteristic (ROC) curve and the area under curve (AUC) were performed to determine the sensitivity and specificity of the inflammatory markers. Spearman correlation and partial correlation analysis were performed to detect the association between inflammatory profiles and clinical scales in cerebellar ataxia.RESULTS: Inflammatory profiles from peripheral blood showed significant difference between different groups. Significant variations were observed in MPV, NLR, MLR, SII, AISI and ESR between cerebellar ataxia and HCs groups (p<0.05). NLR and ESR in both SCA and MSA-C groups were increased compared with HCs (p<0.05). The difference of MHR between SCA and MSA-C groups was observed based on HDL variation (p<0.05). The combination of ESR and PLT distinguished SCA from MSA-C (AUC=0.800). In addition, MLR was significantly corelated with clinical scales, including SARA and ICARS in SCA group as well as UMSARS and FAB in MSA-C group (r>0.3/r<-0.3).CONCLUSION: Significant variation in peripheral inflammatory profiles was firstly identified in Chinese genetic ataxias and non-genetic cerebellar ataxia cohort, which showed the potential clinical correlations between peripheral inflammatory phenotype and severity of ataxia.PMID:40033511 | DOI:10.2174/011570159X379620250225075810

J Transl Med. 2025 Mar 3;23(1):256. doi: 10.1186/s12967-025-06171-5.NO ABSTRACTPMID:40033343 | DOI:10.1186/s12967-025-06171-5

BMC Plant Biol. 2025 Mar 4;25(1):279. doi: 10.1186/s12870-025-06292-5.ABSTRACTBACKGROUND: Oil palm (Elaeis guineensis), a tropical crop, is highly sensitive to temperature fluctuations, with low temperatures significantly limiting its growth, development, and geographical distribution. Understanding the adaptive mechanisms of oil palm under low-temperature stress is essential for developing cold-tolerant varieties. This study focused on analyzing the physiological and metabolomic responses of annual thin-shell oil palm seedlings to low-temperature exposure (8 °C) for different time periods: 0 h (CK), 0.5 h (CD05), 1 h (CD1), 2 h (CD2), 4 h (CD4), and 8 h (CD8).RESULTS: Physiological analysis showed a significant increase in the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and peroxidase (POD), highlighting the activation of oxidative stress defense mechanisms. Concurrently, elevated relative conductivity, indicated cell membrane damage, a common consequence of cold-induced oxidative stress. Metabolomic profiling using LC-MS/MS revealed significant changes in metabolite composition, with differential metabolites predominately enriched in key metabolic pathways such as arginine and proline metabolism, glycine, serine, and threonine metabolism, plant hormone biosynthesis, and flavonoid biosynthesis pathways. Notable metabolites such as citric acid, L-aspartic acid, L-tryptophan, and vitexin showed significant accumulation, indicating their roles in enhancing cold tolerance through improved antioxidant defenses, promoting osmoregulation, and stabilizing cellular structures. Correlation analysis further emphasized the importance of flavonoids and plant hormones in the cold stress response. In particular, vitexin, isovitexin, and apigenin 6-C-glucoside were significantly enriched, suggesting their contribution to antioxidant and stress signaling networks. Furthermore, metabolites involved in amino acid metabolism, including L-glutamic acid, sarcosine, and proline, were upregulated, supporting enhanced protein synthesis and cellular repair under stress. This metabolic reprogramming correlated with physiological improvements, as evidenced by increased relative conductivity and post cold exposure growth recovery.CONCLUSION: This study provides critical insights into the physiological and metabolic adaptations of oil palm to cold stress, emphasizing the significant role of secondary metabolites-such as flavonoids, amino acids, and plant hormones-in enhancing cold tolerance. Theses metabolites contribute to oxidative stress protection, osmotic regulation, and cell wall stabilization enabling the plant to better withstand with low temperature condition. The findings provide a strong foundation for molecular research and breeding initiatives aimed at developing cold tolerant oil palm varieties, a crop of siginificant economic value. By combining metabolomic profiling with physiological analyses, provides a holistic understanding of the adaptive mechanisms in oil palm under cold stress.This integrated approach identifies key metabolic pathways that can be targeted in breeding programs to enhance cold resilience, paving the way for improved crop performance in challenging environments.PMID:40033206 | DOI:10.1186/s12870-025-06292-5

BMC Plant Biol. 2025 Mar 4;25(1):280. doi: 10.1186/s12870-025-06305-3.ABSTRACTIn this study, we aimed to investigate the heat tolerance mechanism in Rhododendron henanense subsp. lingbaoense (Rhl). Rhl seedlings were treated at 40℃ (RLH), 32℃ (RLM), and 24℃ (RLC), and the changes in transcriptome and metabolome were compared. Overall, 78 differentially expressed metabolites were detected, and 8450 differentially expressed genes (DEGs) were identified. KEGG analysis revealed that the DEGs in RLH vs. RLC were mainly enriched in photosynthesis, secondary metabolic biosynthesis, and flavonoid biosynthesis. Most genes encoding glutathione-S-transferase were upregulated, whereas genes related to heat shock proteins were significantly downregulated. 31 genes related to photosynthesis were significantly upregulated (P-value < 0.001). It was speculated that these DEGs are related to the response of Rhl to high temperature stress (HTS). Overall, 9 TF families might be the key regulators of Heat stress response pathways in Rhl. Mining of DEGs revealed that the expression of some genes related to heat stress function increased highly significantly, e.g., the Rhe008987 related to Glutathione-S-transferase, Rhe016769 encoding peroxidase, and Rhe001827 encoding chalcone and stilbene synthases. Metabolome and transcriptome correlation analysis revealed that three comparison groups (RLH vs. RLC, RLH vs. RLM, and RLM vs. RLC) shared 12 metabolic pathways in which the DEMs were enriched. HTS inhibited or induced expression of genes in flavonoid biosynthesis pathway and led to decreace in kaempferol content and quercetin accumulation. HT induced expression of genes in ABC pathway, which may be one of the reasons for the significant accumulation of L-isoleucine, L-leucine, and L-proline. In this study, DEGs mining found that the expression of some genes related to heat stress function increased highly significantly. And two omics correlation analysis revealed that 12 metabolic pathways were enriched in three comparison groups. These results helped in elucidating the molecular mechanisms of response of Rhl to HTS.PMID:40033196 | DOI:10.1186/s12870-025-06305-3

BMC Microbiol. 2025 Mar 4;25(1):115. doi: 10.1186/s12866-025-03810-1.ABSTRACTBACKGROUND: Dairy cow mastitis is a common and prevalent disease arose by various complicated pathogeny, which poses serious threat to the health of cows, safety of dairy product and economic benefits for pastures. Due to the high stealthiness and long incubation period, subclinical mastitis (SM) of cows causes enormous economic losses. Besides the infection by exogenous pathogenic microorganisms, previous studies demonstrated that gastrointestinal microbial dysbiosis is one of the crucial causes for occurrence and development of mastitis based on the theory of entero-mammary axis. Whereas, limited researches have been conducted on potential pathological metabolic mechanisms underlying the relationship between gut microbiota and SM in cows.RESULTS: The differences in blood parameters, gut microbiome, plasma and fecal metabolome between healthy and SM cows were compared by performing 16 S rDNA sequencing and non-targeted metabolomic analysis in the current study. The content of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and activity of catalase (CAT), total antioxidant capacity(T-AOC) were significantly decreased, while malondialdehyde (MDA) concentration was dramatically increased in serum of SM cows in comparison with healthy cows. The gut of cows with SM harbored more abundant Cyanobacteria, Proteobacteria, Succinivibrio and Lactobacillus_iners. Moreover, the abundance of Paraprevotella, Coprococcus, Succiniclasticum, Desulfovibrio and Bifidobacterium_pseudolongum were observably reduced in the gut of SM cows. Furthermore, higher abundance of pro-inflammatory metabolites were observed in feces (9(S)-HPODE, 25-hydroxycholesterol, dodecanedioic acid, etc.) and plasma (9-hydroxy-10,12-octadecadienoic acid, 13,14-dihydro PGF1α, 5,6-dehydro arachidonic acid, myristic acid, histamine, etc.) of SM cows. The abundance of certain metabolites with anti-inflammatory and antioxidant properties (mandelic acid, gamma-tocotrienol, deoxycholic acid, etc.) were notably decreased in feces or plasma of cows with SM.CONCLUSIONS: The intestinal microbial composition and metabolic profiles of healthy and SM cows were significantly distinct, that were characterized by decreased abundance of intestinal symbiotic bacteria, potential probiotics and anti-inflammatory, antioxidant compounds, along with increased abundance of potential pro-inflammatory bacteria, lipid metabolites, and the occurrence of oxidative stress in cows suffered from SM. The results of this study further enriched our understanding of the correlations between gut microbiota and metabolic profiles and SM, which provided insight into the formulation of management strategies for SM in cows.PMID:40033186 | DOI:10.1186/s12866-025-03810-1

BMC Genomics. 2025 Mar 3;26(1):212. doi: 10.1186/s12864-025-11380-9.ABSTRACTBACKGROUND: Tail fat is important for fat-tailed or fat-rumped sheep to survive in harsh environments. However, the molecular mechanism underlying tail fat deposition in sheep remains unclear. In this study, we comprehensively characterized the transcriptome, untargeted lipidome, and targeted metabolome profiles of the tail adipose tissues from Large-tailed Han sheep (long fat-tailed sheep) and Hu sheep (short fat-tailed sheep).RESULTS: We identified 183 differentially expressed genes (DEGs), 55 differential lipids (DLs) and 17 differential metabolites (DMs) in the adipose tissues of the tails from Large-tailed Han and Hu sheep. Among the 183 DEGs selected (Q values ≤ 0.05 and│Log2(FC)│≥ 0.5), 18 DEGs, such as UCP3, ELOVL7 and GDF10, were directly associated with lipid metabolism identified via Gene Ontology (GO) analysis. Some genes, such as PPP3R1A, ADRA1, and DSLC46A2, were reportedly associated with lipid metabolism. A fold change ≥ 1.2 or ≤ 0.83 and a P-value < 0.05 were set as the default threshold to select the DLs and DMs. Among the 55 DLs, 36 DLs were phosphatidylcholines and 9 DLs were phosphatidylethanolamines. The top six DLs with the greatest differences in content were LPE (20:4) (up), PC (42:10) (up), PC (42:8) (up), PC (16:1/16:1) (down), PC (29:0) (down), and PC (32:2) (down). DMs related to the tricarboxylic acid cycle, such as D-glucose, cis-aconitic acid and citric acid were abundant in the tail fat of Large-tailed Han sheep. The DEGs, DLs and DMs were enriched mainly in the ferroptosis, the extracellular matrix (ECM)-receptor interaction, cGMP-PKG, calcium signaling and pathways related to cardiomyopathy and the tricarboxylic acid cycle.CONCLUSION: This study obtained profiles of the transcriptome, lipidome and metabolome of the tail fat tissues of sheep with long and short fat tails. The findings suggested that ELOVL7, UCP3 and ferroptosis, ECM-receptor interaction pathways contributed to the difference in fat deposition, and phosphatidylcholines biosynthesis and tricarboxylic acid cycle may affect lipid metabolism in sheep tails. The results enhance our understanding of the differences in fat deposition in sheep tail.PMID:40033184 | DOI:10.1186/s12864-025-11380-9

Cell Mol Immunol. 2025 Mar 4. doi: 10.1038/s41423-025-01262-1. Online ahead of print.ABSTRACTAutologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical dependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and functional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired adaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells exhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO). Functional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced FAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary factor limiting T-cell proliferation in CLL. CLL T cells displayed fewer and less clustered lipid rafts, potentially explaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in lipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation. This study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel immunotherapeutic approaches to improve outcome in this challenging disease.PMID:40033083 | DOI:10.1038/s41423-025-01262-1

Commun Med (Lond). 2025 Mar 3;5(1):44. doi: 10.1038/s43856-025-00755-4.ABSTRACTBACKGROUND: Through a retrospective analysis of existing FDG PET-MRI images, we recently demonstrated that metformin increases the accumulation of FDG in the intestinal lumen, suggesting that metformin stimulates glucose excretion into the intestine. However, the details of this phenomenon remain unclear. We here investigate the detailed dynamics of intestinal glucose excretion, including the rate of excretion and the metabolism of excreted glucose, in both the presence and absence of metformin.METHODS: We quantified intestinal glucose excretion using newly developed FDG PET-MRI-based bioimaging in individuals with type 2 diabetes, both treated and untreated with metformin. The metabolism of excreted glucose was analyzed through mass spectrometry of fecal samples from mice intravenously injected with 13C-labeled glucose.RESULTS: Continuous FDG PET/MRI image taking reveals that FDG is initially observed in the jejunum, suggesting its involvement in FDG excretion. Metformin-treated individuals excrete a significant amount of glucose (~1.65 g h-1 per body) into the intestinal lumen. In individuals not receiving metformin, a certain amount of glucose (~0.41 g h-1per body) is also excreted into the intestinal lumen, indicating its physiological importance. Intravenous injection of 13C-labeled glucose in mice increases the content of 13C in short-chain fatty acids (SCFAs) extracted from feces, and metformin increased the incorporation of 13C into SCFAs.CONCLUSIONS: A previously unrecognized, substantial flux of glucose from the circulation to the intestinal lumen exists, which likely contributes to the symbiosis between gut microbiota and the host. This flux represents a potential target of metformin's action in humans.PMID:40033038 | DOI:10.1038/s43856-025-00755-4

Sci Rep. 2025 Mar 3;15(1):7416. doi: 10.1038/s41598-025-91798-z.ABSTRACTThe clinical application of randomly patterned skin flaps is often limited by their length-to-width ratio, which can negatively impact their viability. This study aims to investigate the effect of ginsenoside Rb1 on the survival of random skin flaps and explores the underlying mechanisms using metabonomic approaches. Sprague-Dawley rats were assigned to a control group, an ischemia-reperfusion (I/R) group, and a ginsenoside Rb1 treatment group. The serum and middle flap tissue of the rats were collected for 1H-NMR spectroscopy detection and computer pattern recognition analysis. Ten days post-surgery, the survival rate of dorsal flaps in Rb1 group (61.06 ± 3.71) % was significantly higher than in I/R group (50.46 ± 1.41)%. Analyses of 1H-NMR spectrum 24 h post-surgery demonstrated increased lipid content in the serum of I/R group. In contrast, serum samples from the Rb1 group exhibited significantly higher levels of glutamate, creatine and fumarate, while lactate, choline/phosphocholine, N-acetylglycoprotein and allantoin were decreased. The contents of ATP/ADP/AMP of glutamine, citrate, tauric acid, and fumarate in flap tissue were increased while those of lactate, acetate and acetoacetate were significantly decreased. These findings suggest that ginsenoside Rb1 may enhance the survival of random skin flaps, potentially providing protective benefits in clinical applications.PMID:40033034 | DOI:10.1038/s41598-025-91798-z

Nat Metab. 2025 Mar 3. doi: 10.1038/s42255-025-01230-z. Online ahead of print.ABSTRACTDespite the high prevalence of neurodevelopmental disorders, the influence of maternal diet during pregnancy on child neurodevelopment remains understudied. Here we show that a western dietary pattern during pregnancy is associated with child neurodevelopmental disorders. We analyse self-reported maternal dietary patterns at 24 weeks of pregnancy and clinically evaluated neurodevelopmental disorders at 10 years of age in the COPSAC2010 cohort (n = 508). We find significant associations with attention-deficit hyperactivity disorder (ADHD) and autism diagnoses. We validate the ADHD findings in three large, independent mother-child cohorts (n = 59,725, n = 656 and n = 348) through self-reported dietary modelling, maternal blood metabolomics and foetal blood metabolomics. Metabolome analyses identify 15 mediating metabolites in pregnancy that improve ADHD prediction. Longitudinal blood metabolome analyses, incorporating five time points per cohort in two independent cohorts, reveal that associations between western dietary pattern metabolite scores and neurodevelopmental outcomes are consistently significant in early-mid-pregnancy. These findings highlight the potential for targeted prenatal dietary interventions to prevent neurodevelopmental disorders and emphasise the importance of early intervention.PMID:40033007 | DOI:10.1038/s42255-025-01230-z