PubMed

J Ovarian Res. 2025 Feb 12;18(1):26. doi: 10.1186/s13048-025-01590-w.ABSTRACTOvarian cancer (OC) is the third most common malignant tumor of women and is accompanied by an alteration of systemic metabolism. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for OC diagnosis. EVs, nanosized extracellular vesicles found in the blood, have been proposed as promising biomarkers for liquid biopsies. In this study we recruited 37 OC patients, 22 benign ovarian tumor (BE) patients, and 46 clinically healthy control patients (CON). Plasma EVs were purified from blood samples and sensitive thermal separation probe-based mass spectrometry analysis using a global untargeted metabolic profiling strategy was employed to characterize the metabolite fingerprints. Uniform manifold approximation and projection (UMAP) analysis demonstrated a distinct separation of EVs among the three groups. We screened for diagnostic biomarkers from plasma EV metabolites using seven machine learning algorithms, including artificial neural network (ANN), decision tree (DT), K nearest neighbor (KNN), logistics regression (LR), Naïve Bayes (NB), random forest (RF), and support vector machine (SVM). For the OC-CON comparison, the highest AUC values were found for RF (0.91), ANN (0.90) and NB (0.90), with the F1-scores of 0.88, 0.83, and 0.76 respectively. For the OC-BE comparison, SVM (0.94), RF (0.86), and KNN (0.86) gave the highest AUCs, with F1-scores of 0.80, 0.80, and 0.91 respectively. A total of 19 and 158 metabolic features exhibited significant differences (FC = 1.5, q < 0.01) in the OC vs BE and OC vs CON comparisons, respectively. Notably, the quantities of 9-octadecenamide and 1,4-methanobenzocyclodecene were significantly elevated, while maltol showed a significant reduction in the OC group compared to the BE group. When comparing the OC group to the CON group, the concentrations of 4-amino-furazan-3-carboxylic acid 2-hydroxy-4-methoxybenzaldehyde, N-phenylethyl, and 4-morpholineethanamine were significantly elevated, while the remaining metabolites, including hydrazine and pyridine sulfonamide, were reduced, in the OC group. The metabolites showing different abundancies are associated with cancer-related mutations, immune responses, and metabolic reprogramming. We demonstrate that the RF algorithm, combined with sensitive thermal separation probe-based mass spectrometry analysis of plasma EVs, can effectively identify OC patients with good accuracy. Thus, our study has shortlisted a set of potential biomarkers in plasma EVs, and the proposed approach could serve as a routine prescreening tool for ovarian cancer.PMID:39940000 | DOI:10.1186/s13048-025-01590-w

BMC Vet Res. 2025 Feb 12;21(1):63. doi: 10.1186/s12917-024-04430-z.ABSTRACTBACKGROUND: The global rise in multidrug-resistant bacteria has significantly undermined the efficacy of traditional antibiotics. Multidrug-resistant Streptococcus suis (S. suis), a pathogen capable of infecting pigs and humans, has been identified as a critical threat, causing severe meningitis and rapid mortality. In response, researchers have increasingly focused on herbal compounds as non-traditional antimicrobial agents, which can inhibit bacterial growth while minimizing the risk of resistance development. This study investigates the mechanism through which andrographolide (AP) restores the susceptibility of S. suis to aminoglycoside antibiotics.METHODS: The intracellular ΔpH in S. suis was assessed using the 2',7' -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCCF-AM) probe to evaluate alterations in the proton motive force (PMF) following treatment with AP. Non-targeted metabolomics was employed to confirm changes in the metabolic profile of S. suis upon exposure to AP. Finally, an in vivo infection model was utilized to evaluate the therapeutic efficacy of AP in combination with antibiotics.RESULTS: Extensive in vitro experiments demonstrated that AP significantly enhances the activity of aminoglycoside antibiotics against diverse pathogens, including S. suis. Further studies revealed that bacterial death results from AP-mediated upregulation of the S. suis PMF, which enhances cellular uptake of tobramycin (TOB). Moreover, AP significantly upregulated pyruvate metabolism in S. suis, accelerated the tricarboxylic acid (TCA) cycle, and increased nicotinamide adenine dinucleotide (NADH) production. This metabolic shift further augmented the PMF. Combining AP with aminoglycoside antibiotics significantly reduced bacterial load and organ lesions in various organs in mice.CONCLUSION: AP holds promise as an adjuvant to aminoglycoside antibiotics for combating S. suis-induced infections, offering a theoretical foundation for clinical applications.PMID:39939878 | DOI:10.1186/s12917-024-04430-z

Anal Bioanal Chem. 2025 Feb 12. doi: 10.1007/s00216-025-05784-5. Online ahead of print.ABSTRACTEsophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case-control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators.PMID:39939416 | DOI:10.1007/s00216-025-05784-5

Commun Biol. 2025 Feb 13;8(1):224. doi: 10.1038/s42003-025-07640-9.ABSTRACTWhite-rot fungi are efficient organisms for the mineralization of lignin and polysaccharides into CO2 and H2O. Despite their biotechnological potential, WRF metabolism remains underexplored. Building on recent findings regarding the utilization of lignin-related aromatic compounds as carbon sources by WRF, we aimed to gain further insights into these catabolic processes. For this purpose, Trametes versicolor and Gelatoporia subvermispora were incubated in varying conditions - in static and agitation modes and different antioxidant levels - during the conversion of 4-hydroxybenzoic acid (a lignin-related compound) and cellobiose. Their metabolic responses were assessed via transcriptomics, proteomics, lipidomics, metabolomics, and microscopy analyses. These analyses reveal the significant impact of cultivation conditions on sugar and aromatic catabolic pathways, as well as lipid composition of the fungal mycelia. Additionally, this study identifies biosynthetic pathways for the production of extracellular fatty acids and phenylpropanoids - both products with relevance in biotechnological applications - and provides insights into carbon fate in nature.PMID:39939400 | DOI:10.1038/s42003-025-07640-9

Sci Rep. 2025 Feb 12;15(1):5279. doi: 10.1038/s41598-025-89175-x.NO ABSTRACTPMID:39939362 | DOI:10.1038/s41598-025-89175-x

J Prev Alzheimers Dis. 2025 Feb 11:100086. doi: 10.1016/j.tjpad.2025.100086. Online ahead of print.ABSTRACTBACKGROUND: Gut microbiome-associated metabolites and white matter hyperintensities (WMH) are independently associated with cognitive impairment. However, it is unclear if gut metabolites and WMH interact to influence dementia.OBJECTIVES: To examine the association between gut microbial metabolites and cognitive outcomes and assess whether the severity of baseline WMH would impact associations between gut microbial metabolites and cognitive outcomes.DESIGN: Cross-sectional design.SETTING: Cohort of individuals who are clinically normal, mild cognitive impairment, or Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI).PARTICIPANTS: A total of 578 participants with available baseline 3.0T 2D-Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) scans and baseline gut microbial metabolite measurement were included in the analysis.MEASUREMENTS: Gut metabolite measurements and automated WMH volume estimations were obtained from FLAIR MRI and were used to assess the association and interaction with cognitive impairment.RESULTS: Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05-0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41-3.15, p < 0.001). GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10-0.32, p < 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02).CONCLUSION: An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes.PMID:39939193 | DOI:10.1016/j.tjpad.2025.100086

Int Rev Cell Mol Biol. 2025;391:1-41. doi: 10.1016/bs.ircmb.2024.08.007. Epub 2024 Sep 5.ABSTRACTCancer presents a significant challenge to global health, driving worldwide concerted efforts to advance early detection, predict therapeutic response, and identify novel targeted therapies. Liquid biopsies emerge as promising avenues for discerning cancer biomarkers, offering less invasive approaches compared to conventional methods. Utilizing increasingly robust technologies, diverse bodily fluids can unveil genetic variants, epigenetic modifications, transcriptional alterations, and metabolomic signatures associated with cancer, thereby furnishing valuable insights for clinical management. This chapter intends to review the sources of cancer-related biomarkers found in circulation, prevalent techniques utilized for their identification, and the potential implications of different biomarker types on the management of cancer. Certain biomarkers currently used in clinical practice will be addressed, as well as potential biomarkers still in the study phase, and the inherent challenges in their practical implementation.PMID:39939074 | DOI:10.1016/bs.ircmb.2024.08.007

Chest. 2025 Feb;167(2):e66. doi: 10.1016/j.chest.2024.09.040.NO ABSTRACTPMID:39939067 | DOI:10.1016/j.chest.2024.09.040

Int J Biol Macromol. 2025 Feb 10:140885. doi: 10.1016/j.ijbiomac.2025.140885. Online ahead of print.ABSTRACTNeuroinflammation can lead to various neurodegenerative disorders, resulting in irreversible neurological dysfunction. Astragalus membranaceus Bunge polysaccharides (APS) present great potential in alleviating neuroinflammation; however, the specific mechanism underlying its neuroprotective effect remains unclear, leading to uncertain prospects for pharmaceutical applications. This study aims to elucidate the mechanism underlying APS-mediated inhibition of neuroinflammation in mice induced by lipopolysaccharide (LPS) through regulation of metabolic function, intestinal flora composition, and cell signaling transduction. Results indicated that APS pretreatment effectively mitigated LPS-induced brain damage. Metabolomics analysis revealed that APS pretreatment also regulated the metabolic disturbances induced by LPS through targeting five specific metabolic pathways. This regulation was supported by notable alterations in nine metabolite markers. Furthermore, APS pretreatment significantly modulated the abundance of four taxa of gut microbes (i.e., Romboutsia, Rikenella, Dubosiella, Odoribacter) closely associated with regulations in eleven metabolic and signaling pathways. Additionally, transcriptome analysis and Western blotting unveiled that APS pretreatment exerted a neuroprotective effect by modulating the MAPK/NF-κB signaling pathway. Our findings provide insights into the potential mechanisms underlying the neuroprotective effects of APS while establishing a solid foundation for future utilization of APS.PMID:39938846 | DOI:10.1016/j.ijbiomac.2025.140885

J Biol Chem. 2025 Feb 10:108283. doi: 10.1016/j.jbc.2025.108283. Online ahead of print.ABSTRACTThe success of modern metabolomics analysis depends on the separation of metabolites in complex samples using methods such as liquid chromatography and mass spectrometry. Herein, we present a protocol for resolving a broad range of polar metabolites, based on hydrophilic interaction liquid chromatography with a zwitterionic bonded phase (HILICz). In optimising this protocol, we encountered pressure fluctuations, a widespread problem that impacts metabolite analysis, restricts batch sizes, and imposes instrument downtime, ultimately incurring substantial time and financial expense. Thus, we use this opportunity as a case study to demonstrate the steps taken to overcome such pressure fluctuations, resulting in a protocol that robustly and consistently resolves polar metabolites in large batches of samples (>100 samples, equating to >40 hours of run-time). This consistency is essential to address the growing demand for repeatable in-depth metabolomics analysis of complex samples.PMID:39938797 | DOI:10.1016/j.jbc.2025.108283

J Ethnopharmacol. 2025 Feb 10:119477. doi: 10.1016/j.jep.2025.119477. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. M. Tenacissima extract is now available in China under the brand name "Xiao Ai Ping" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.PURPOSE OF THE STUDY: The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of M. tenacissima extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.MATERIALS AND METHODS: We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilised UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.RESULTS: The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.CONCLUSION: Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.PMID:39938764 | DOI:10.1016/j.jep.2025.119477

J Ethnopharmacol. 2025 Feb 10:119474. doi: 10.1016/j.jep.2025.119474. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine.AIM OF THE STUDY: The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.MATERIAL AND METHODS: The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.RESULTS: A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.CONCLUSIONS: This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Sucrose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.PMID:39938763 | DOI:10.1016/j.jep.2025.119474

Clin Res Hepatol Gastroenterol. 2025 Feb 10:102546. doi: 10.1016/j.clinre.2025.102546. Online ahead of print.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth in incidence and third in mortality among all cancers. Chronic infection by hepatitis B and C viruses are the predominant risk factors for HCC, but other factors related to metabolic disorders including diabetes and obesity are also involved.METHODS: Ten male HCC patients with chronic HBV infection were included in this study. Primary HCC tissues were obtained from all study participants following liver resection. Normal tissues that were simultaneously collected served as the controls and were defined as tissue at least 5 cm from the tumor edge. Tissues were subjected to untargeted metabolomics and transcriptome analyses.RESULTS: We identified 31 and 41 differentially expressed metabolites (DEMs) in positive and negative ion modes, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 15 DEMs were enriched in ABC transporters, nine in purine metabolism, eight in central carbon metabolism in cancer, and seven in biosynthesis of amino acids. Regarding the transcriptome analysis, 1,224 significantly upregulated and 887 downregulated RNAs were found. KEGG pathway analysis revealed that the most significantly enriched pathways were metabolic pathways. Integrated analysis showed seven pathways that were highly activated in HCC tissues including PI3K/Akt, ABC transporters, caffeine metabolism, carbon metabolism, biosynthesis of amino acids, arginine biosynthesis, alanine, aspartate, and glutamate metabolism.CONCLUSION: Some DEMs could be biomarkers or therapeutic targets for HCC. Moreover, we found that MAGEB2 was significantly elevated in HCC tissues for the first time, and its association with HCC needs to be explored by functional studies.PMID:39938636 | DOI:10.1016/j.clinre.2025.102546

Biochem Biophys Res Commun. 2025 Feb 8;752:151466. doi: 10.1016/j.bbrc.2025.151466. Online ahead of print.ABSTRACTThe prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing annually, which is a global public health issue. Although clinical trials are lacking, observational studies indicate that bariatric surgery can alleviate the progression of MASH. Here, we performed sleeve gastrectomy (SG) and Sham surgery on 8-week-old mice, and then fed a AMLN diet for 24 weeks to construct a diet-inducted MASH mice model after 4-week post-surgery recovery. Applying a multi-omics approach combining metagenomics, metabolomics, and transcriptomics, we found that SG prevents the development of hepatic steatosis, inflammation, and fibrosis in MASH mice not only by significantly altering the structure of gut microbiota including s_Akkermansia muciniphila, s_Alistiples dispar, g_Helicobacter and s_uc_Oscillospiraceae, but also by modulating the levels of serum metabolites including l-arginine and taurocholic acid (TCA). These results suggest that SG and the alteration of gut microbiota and its related serum metabolites can be served as the effective therapeutic strategies for MASH.PMID:39938449 | DOI:10.1016/j.bbrc.2025.151466

Food Chem. 2025 Feb 4;474:143223. doi: 10.1016/j.foodchem.2025.143223. Online ahead of print.ABSTRACTEffective selenium supplementation strategies are essential for alleviating global selenium deficiency. This study utilized the high‑selenium-tolerant strain Lactiplantibacillus plantarum NML21 to produce selenium-enriched yogurt, successfully converting inorganic Se(IV) into organic selenium, with selenoproteins accounting for 69.52 % of the total selenium content (995.19 ± 68.60 μg/g). Selenium-enriched yogurt exhibited excellent physicochemical properties and antioxidant activity. Volatile flavor analysis identified 36 compounds, with NML21 and SeNML21 significantly enhancing ketone flavors in yogurt, particularly increasing the contents of 2-heptanone and 2,3-pentanedione. Untargeted metabolomics identified 215 non-volatile metabolites, with NML21 and SeNML21 significantly regulating key metabolic pathways, including the phosphotransferase system, ABC transporters, and amino acid biosynthesis, promoting the accumulation of beneficial metabolites. Selenium specifically influenced the biosynthesis pathways of ABC transporters, phenylalanine, tyrosine, and tryptophan. This study demonstrates that NML21 is a promising strain for producing selenium-enriched functional yogurt, offering innovative perspectives for dietary selenium supplementation and functional food development.PMID:39938303 | DOI:10.1016/j.foodchem.2025.143223

Food Chem. 2025 Feb 6;475:143256. doi: 10.1016/j.foodchem.2025.143256. Online ahead of print.ABSTRACTHoney has been recognized for its role in disease prevention through nutritional modulation. In this study, we comprehensively assessed the physicochemical parameters, metabolic profile, antioxidant and anti-inflammatory activities of multifloral honeys produced by Apis cerana cerana in Sansha City (SS), Hainan Province. Metabolomic analysis identified SS honey had multiple bioactive compounds known for antioxidant and anti-inflammatory properties. Compared to A. cerana cerana honey from central regions of Hainan Province, SS honey showed higher levels of TFC (113.80 mg RE/100 g) and TPC (45.86 mg GAE/100 g). Furthermore, SS honey demonstrated greater antioxidant activity, as evidenced by FRAP (1503.16 μmol TE/kg), DPPH IC50 (33.59 mg/mL), and ABTS IC50 (11.03 mg/mL). SS honey significantly reduced the levels of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells, along with suppressing the mRNA expression of these inflammatory markers.PMID:39938270 | DOI:10.1016/j.foodchem.2025.143256

Plant Physiol Biochem. 2025 Jan 20;221:109462. doi: 10.1016/j.plaphy.2024.109462. Online ahead of print.ABSTRACTLignification is one of the key factors restricting the postharvest storage quality of fruit and vegetable. In this study, the potential effects of carboxymethyl chitosan (CMCS) on the phenolic compounds, metabolomic, lignin metabolites and related gene expression of okra during postharvest storage were explored. The results showed that CMCS could alleviate the accumulation of H2O2 and O2•- of postharvest okra, maintain the content of phenolic compounds and balance the antioxidant level. Metabolome data analysis showed that the biosynthesis of lignin-related metabolites in CMCS treatment group was down-regulated compared with the control group. The contents of 14 lignin metabolites in okra were further determined by LC-MS/MS, the results showed that CMCS could delay the accumulation of lignin metabolites, such as L-phenylalanine, 4-hydroxycinnamic acid, ferulic acid, coniferyl aldehyde, sinapyl alcohol, caffeyl aldehyde. The results of quantitative real-time PCR (qRT-PCR) showed that CMCS treatment could inhibit the expression of AePAL, AeC4H, AeCAD and AePOD. Collectively, CMCS can delay the lignification of postharvest okra by inhibiting the excessive accumulation of lignin metabolites in the phenylpropanoid pathway, thereby maintaining postharvest quality.PMID:39938161 | DOI:10.1016/j.plaphy.2024.109462

Plant Physiol Biochem. 2025 Feb 1;221:109588. doi: 10.1016/j.plaphy.2025.109588. Online ahead of print.ABSTRACTBoron (B) deficiency and copper (Cu) excess are common problems in citrus orchard soils. Citrus sinensis seedlings were exposed to 25 (B25) or 2.5 (B2.5) μM H3BO3 and 0.5 (Cu0.5) or 350 (Cu350) μM CuCl3 for 24 weeks. Cu350 upregulated 2210 (1012) genes and 482 (341) metabolites and downregulated 3201 (695) genes and 175 (43) metabolites in roots at B2.5 (B25). Further analysis showed that the B-mediated mitigation of Cu toxicity in roots involved the coordination of the following aspects: (a) enhancing the ability to maintain cell wall and plasma membrane stability and function; (b) lowering the impairment of Cu350 to primary and secondary metabolisms and enhancing their adaptability to Cu350; and (c) alleviating Cu350-induced oxidative stress via the coordination of reactive oxygen species (ROS) and methylglyoxal detoxification systems. Cu350 upregulated the abundances of some saccharides, amino acids and derivatives, phospholipids, secondary metabolites, and vitamins, and the expression of several ROS detoxification-related genes in roots of B2.5-treated seedlings (RB2.5), but these adaptive responses did not prevent RB2.5 from Cu-toxicity (oxidative damage). The study identified some genes, metabolites, and metabolic processes/pathways possibly involved in root Cu tolerance. Additionally, the responses of gene expression and metabolite profiling to Cu-B treatments differed between leaves and roots. Therefore, this study provided novel information for B to reduce Cu toxicity in roots and might contribute to the development of soil amendments targeting Cu excess in citrus and other crops.PMID:39938160 | DOI:10.1016/j.plaphy.2025.109588

Plant Physiol Biochem. 2025 Feb 6;221:109604. doi: 10.1016/j.plaphy.2025.109604. Online ahead of print.ABSTRACTJuglans sigillata, an endemic species in China, serves as a vital local economic resource. Aluminum (Al) stress caused by soil acidification can potentially threaten the growth of J. sigillata. This study aimed to elucidate the mechanism of the alleviation of Al stress by silicon (Si) in J. sigillata. The results showed that Si could reduce the Al accumulation of walnut and improve root growth under Al stress. Si also increased peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities and soluble sugar and proline contents, reduced malonaldehyde (MDA) and H2O2 contents and the O2- production rate, and maintained the homeostasis of cells. Transcriptome analysis revealed significant up-regulation of genes encoding plant hormones (ABA, IAA, and CTK) and photosystem II components (PsbO, PsbQ, PsbW, and PsbY). Under Al stress conditions, the application of exogenous Si notably enhanced the expression of genes associated with heavy metal transport (CAX, PAA, ABC, HMA, NRAMP, and ZIP). Comprehensive transcriptome and metabolomics analysis showed that Si regulated secondary metabolite metabolism via the phenylalanine, galactose, and tryptophan pathway, altered cell wall composition, increased energy supply, and reduced auxin synthesis in root tip transition zones to alleviate Al toxicity of J. sigillata. In summary, the application of Si significantly alleviated Al-induced damage in J. sigillata.PMID:39938159 | DOI:10.1016/j.plaphy.2025.109604

J Infect Dis. 2025 Feb 12:jiaf072. doi: 10.1093/infdis/jiaf072. Online ahead of print.ABSTRACTBACKGROUND: Accurate diagnosis of community-acquired pneumonia (CAP) can be challenging. Clinical findings are non-specific, and interpretations of chest radiographs have poor inter-rater reliability. Pilot studies demonstrate the potential for metabolomics to identify metabolite concentrations that differentiate children with CAP from those without. The objective of this study was to expand these findings in a large cohort of children with CAP compared with controls.METHODS: Urine was collected from children, 3 months to 12 years old, with emergency department visits for suspected CAP and community-based controls. Nuclear magnetic resonance spectrometry was used to identify and quantify metabolites. A random forest approach developed three models discriminating cases from community-based controls based on: 1) clinical signs and symptoms; 2) metabolites, and 3) the combination of both. The area under the receiver operating characteristic curve (AUC) was computed for each model.RESULTS: Included were 253 cases and 122 controls. The metabolite-only model had similar discriminatory ability as the combination model (AUC: 0.97 and 0.99, respectively). The discriminating metabolites in the metabolite-only model were 2-aminobutyrate, fumarate, hypoxanthine, acetone, leucine, quinolinate, valine, O-acetylcarnitine, citrate and trigonelline. In the combined model, discriminatory clinical factors included receipt of corticosteroids, fever, cough, rapid breathing, decreased oral intake, difficulty breathing, receipt of albuterol, abnormal sleepiness, vomiting and wheezing, and included five additional metabolites compared to the metabolite only model (4-hydroxybenzoate, isoleucine, carnitine, 2-hydroxyisovalerate, betaine, succinate).CONCLUSIONS: Urine metabolite concentrations can accurately discriminate healthy children from children with suspected CAP. Metabolites associated with CAP may overcome limitations of prior diagnostic approaches.PMID:39938055 | DOI:10.1093/infdis/jiaf072