PubMed

Syst Biol Reprod Med. 2026 Dec;72(1):168-184. doi: 10.1080/19396368.2026.2637454. Epub 2026 Mar 7.ABSTRACTUnexplained infertility (UI) affects ∼10% of infertile couples, yet standard diagnostic protocols fail to identify a cause. Follicular fluid (FF), which supports oocyte development, contains metabolites that may reflect underlying molecular disturbances. In this exploratory study, we investigated the FF metabolome of women with UI and compared it with controls to explore metabolic alterations associated with UI. FF was collected during oocyte retrieval from 20 women undergoing IVF (ten with UI, ten with male factor infertility), matched for age, BMI, stimulation, and fertilization protocols. Metabolomic profiling was performed using hydrophilic interaction and reversed-phase liquid chromatography coupled to Q-TOF-MS/MS, followed by metabolite identification (XCMS Online and MetaboAnalyst) and KEGG pathway analysis. Approximately 2000 features were detected. Differential metabolites were identified by OPLS-DA (VIP > 2) and validated using univariate metrics such as fold change (|log2FC| > 1), statistical significance (p < 0.05), and ROC analysis (AUC > 0.8). Twelve metabolites, including diacylglycerols, phosphatidic acids, vitamin D3 derivatives (VitD3-glucosiduronate, 1α-hydroxy-2β-(5-hydroxypentoxy)-VitD3), asparaginyl-asparagine, 3α-hydroxy-6-oxo-5β-cholan-24-oic acid, Leu-Pro-Ala-Ser-Phe, triacylglycerols, phosphatidylcholine, and lactosyl-ceramide were significantly decreased, while Ile-Lys-Val-Val was increased in women with UI. Pathway analysis highlighted disruptions in glycerophospholipid, glycerolipid, steroid, and linoleic acid metabolism. Consistent with the untargeted findings, targeted analysis demonstrated significantly reduced levels of follicular 25-hydroxyvitamin D [25(OH)D] in women with UI despite uniform oral supplementation, indicating dysregulated follicular vitamin D availability. Whilst the study was limited by sample size, the metabolome analysis was performed in triplicate for each sample, thus providing preliminary insights into the metabolic disruptions in FF from women with UI.PMID:41793761 | DOI:10.1080/19396368.2026.2637454

Clin Transl Oncol. 2026 Mar 7. doi: 10.1007/s12094-026-04288-7. Online ahead of print.ABSTRACTBACKGROUND: Liver fibrosis, a common pathological progression in chronic liver diseases, can lead to irreversible cirrhosis and hepatocellular carcinoma if untreated. Gurigumu-13, a traditional herbal formulation, has demonstrated promising protective and therapeutic effects against liver fibrosis in clinical settings. However, its underlying antifibrotic mechanisms remain unclear.METHODS: A rat model of hepatic fibrosis was induced via intraperitoneal injection of dimethylnitrosamine (DMN). Rats were treated with high, medium, or low doses of Gurigumu-13. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) were measured to evaluate liver function. Hepatic hydroxyproline (Hyp), laminin (LN), alpha-smooth muscle actin (α-SMA), and type IV collagen (Col-IV) were measured to assess liver function. Liver tissues were subjected to hematoxylin-eosin (HE), Masson, and Sirius Red staining to evaluate histopathological changes and collagen deposition. The expression of alpha-smooth muscle actin (α-SMA) and type I collagen (Col-I) in liver tissue was analyzed by immunohistochemistry (IHC) and western blot (WB). Metabolomics analysis was performed on liver samples, followed by multivariate statistical analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, network pharmacology prediction, and molecular docking to explore differential metabolites, enriched metabolic pathways, potential target genes, and key ligand-receptor interactions.RESULTS: Gurigumu-13 significantly improved liver function by reducing serum ALT, AST, and ALP levels, TBIL, Hyp, LN, α-SMA, and Col-IV and alleviating hepatic histological damage in a dose-dependent manner (H-G13 vs. DMN, p < 0.001). It also downregulated the expression of fibrosis-related markers α-SMA and Col-I (H-G13 vs. DMN, p < 0001). A total of 227 differential metabolites were identified between the DMN and H-G13 groups, showing significant alterations in lipid, amino acid, and organic acid metabolism. KEGG pathway analysis revealed enrichment in pathways such as 5 significantly enriched metabolic pathways include "L-Tyrosine", "2-Hydroxycinnamic acid", "ortho-Hydroxyphenylacetic acid", "L-3-Phenyllactic acid", "N-Acetyl-L-phenylalanine". Network pharmacology identified 144 potential target genes associated with 131 differential metabolites. Core targets included PLA2G4A, PPARG, PPARA, CYP3A4, and PTGS2. Molecular docking demonstrated that key differential metabolites, including (10E,12Z)-9-HODE, 13-OxoODE, and 2-Hydroxycinnamic acid, exhibited strong binding affinities with these core targets.CONCLUSION: This study provides the first comprehensive evidence that Gurigumu-13 possesses significant hepatoprotective and antifibrotic properties. Its antifibrotic effects are mediated through the modulation of metabolic pathways and interactions with multiple molecular targets involved in inflammation, lipid metabolism, and oxidative stress. By integrating metabolomics with network pharmacology, this work offers novel insights into the mechanisms of Gurigumu-13 and supports its potential clinical application for treating liver fibrosis.PMID:41793636 | DOI:10.1007/s12094-026-04288-7

Metabolomics. 2026 Mar 7;22(2):36. doi: 10.1007/s11306-026-02406-8.ABSTRACTINTRODUCTION: Plants are mainly influenced by abiotic stresses acting in combination rather than a single stress acting alone. In the present study leaf metabolomic profiles as well as changes in phenome and yield of four barley (Hordeum vulgare L.) genotypes of different origin under single and combined abiotic stresses were investigated.OBJECTIVES: The aim of the study was to understand the response of barley to single and combined abiotic stresses and to identify metabolic pathways associated with yield components under stress conditions.RESULTS: We found that Syrian genotype can be a donor of early resistance caused by rapid increase of amino acids (e.g. proline) under stress, constituting a valuable genetic source in barley breeding. We demonstrated that impact of combined stresses was generally based on the unique response in terms of the metabolomic alterations. However, there were also metabolites that increased their content regardless of the genotype. Methionine sulfoxide has accumulated under long-term drought, salinity and their combination; on the other hand, accumulation of other metabolites such as leucrose increased in drought, but not under its combination with salinity.CONCLUSION: Accumulation of most of analysed metabolites significantly depended on the genotype, type of stress as well as their interaction. We indicate that several of identified metabolites might serve as a stress biomarkers (e.g. aspartic acid). We observed that greater phenotypic changes are most visible under the influence of combined stresses being mostly synergistic/additive when compared to single ones as well as considerable relationship between accumulation of specific metabolites and some phenotypic traits.PMID:41793606 | DOI:10.1007/s11306-026-02406-8

Metabolomics. 2026 Mar 7;22(2):41. doi: 10.1007/s11306-026-02411-x.NO ABSTRACTPMID:41793600 | DOI:10.1007/s11306-026-02411-x

Metabolomics. 2026 Mar 7;22(2):38. doi: 10.1007/s11306-026-02413-9.ABSTRACTINTRODUCTION: LC-MS system suitability test (SST) is crucial for reliable data acquisition especially in untargeted metabolomics.OBJECTIVES: Identification of best reference materials (RMs) to improve best quality assurance (QA) and quality control (QC) practices.METHODS: Investigations were performed using a C18 reversed-phase (RP) column LC-MS approach.RESULTS: Targeted cyanotoxin analysis revealed a performance loss of the used C18 RP column although the SST confirmed a fit for purpose instrument which prompted to test several additional RMs.CONCLUSION: QA procedures for LC-MS can be improved by incorporating polar microcystins or arginine methyl ester as RMs for SST.PMID:41793599 | DOI:10.1007/s11306-026-02413-9

Metabolomics. 2026 Mar 7;22(2):34. doi: 10.1007/s11306-026-02409-5.ABSTRACTINTRODUCTION: Hypertriglyceridemia (HTG) is a crucial risk factor for cardiovascular disease, metabolic syndrome, and type 2 diabetes. However, its early detection remains challenging due to the dynamic fluctuations in plasma triglyceride levels and their limited utility in predicting long-term dyslipidemia.OBJECTIVES: This study aimed to elucidate the role of asymmetric dimethylguanidino valeric acid (ADGV) in HTG through integrated cohort analyses and mechanistic cellular experiments.METHODS: Circulating ADGV levels were quantified in a cross-sectional cohort from southern China (n = 588) and assessed its prospective association with incident HTG in an independent prospective cohort from northern China (n = 348, median follow-up: 1.8 years). Hepatocyte experiments were performed to examine biological plausibility and explore potential mechanisms linking ADGV to hepatic triglyceride metabolism.RESULTS: Elevated ADGV levels were significantly associated with increased risk of HTG and remained independently associated after adjustment for age, gender, BMI, eGFR, lifestyle factors, and liver function. Complementary in vitro studies in hepatocytes revealed that ADGV promoted triglyceride accumulation by stimulating de novo fatty acid synthesis, mediated through regulating the expression of key metabolic genes (ACC, CPT1α, and PGC1α).CONCLUSION: Higher circulating ADGV was independently associated with prevalent and incident hypertriglyceridemia across a cross-sectional cohort and an independent prospective cohort, and hepatocyte experiments support a contributory role of ADGV in hepatic lipogenesis.PMID:41793597 | DOI:10.1007/s11306-026-02409-5

Clin Rheumatol. 2026 Mar 7. doi: 10.1007/s10067-026-08016-y. Online ahead of print.ABSTRACTINTRODUCTION/OBJECTIVES: This study aimed to identify serum biomarkers that distinguish patients with acute calcium pyrophosphate (CPP) crystal arthritis from those with rheumatoid arthritis (RA).METHODS: This study included patients with acute CPP crystal arthritis and those with RA treated at a single centre. The screening set included 18 patients with acute CPP crystal arthritis and 12 patients with RA. Serum samples were collected from all patients. Additionally, paired samples were obtained from five patients with CPP crystal arthritis after the resolution of their arthritis. The validation set included 11 patients with CPP crystal arthritis and 13 with RA. Serum metabolites were profiled using gas chromatography-mass spectrometry (GC-MS).RESULTS: Orthogonal partial least squares discriminant analysis revealed good separation between patients with acute CPP crystal arthritis and those with RA and between the acute CPP crystal arthritis phase and the resolution phase in the same patients. A total of 101 metabolites were identified. β-Hydroxybutyrate (BHB) levels were significantly higher in patients with acute CPP crystal arthritis than in those with RA and were higher in the acute CPP crystal arthritis phase than in the resolution phase. In the validation cohort, BHB consistently distinguished acute CPP crystal arthritis from RA, with an area under the receiver operating characteristic curve of 0.748, sensitivity of 90.9%, and specificity of 69.2%.CONCLUSIONS: BHB is a potential diagnostic biomarker for distinguishing acute CPP crystal arthritis from RA. These findings highlight the potential of metabolomic analysis as a non-invasive diagnostic approach for CPP crystal deposition disease. Key Points • Serum metabolomic profiling identified distinct metabolic signatures distinguishing acute CPP crystal arthritis from rheumatoid arthritis. • β-Hydroxybutyrate was a potential differential biomarker between acute CPP crystal arthritis and RA. • Alterations in ketone body metabolism may contribute to crystal-induced inflammation.PMID:41793574 | DOI:10.1007/s10067-026-08016-y

Metabolomics. 2026 Mar 7;22(2):33. doi: 10.1007/s11306-026-02405-9.ABSTRACTINTRODUCTION: Metabolomics is an analytical profiling technique that measures and compares large numbers of metabolites in biological samples, providing insight into metabolic mechanisms. There are few studies concerning the effects of xenobiotics and their transformation products on aquatic plant metabolites, which can uptake and detoxify them using untargeted metabolomics.OBJECTIVES: This study investigates how pharmaceuticals, including diclofenac (DCF) and carbamazepine (CBZ), as well as sulfamethoxazole (SMX) and trimethoprim (TRIM), present in aquatic environments, can influence the biosynthetic pathways of Lemna minor.Based on previous research on the effects of DCF, SMX, and TRIM on Lemna pathways, specifically phenylalanine, tyrosine, and tryptophan biosynthesis, folate biosynthesis, and the phenylpropanoid pathway, including flavonoid and anthocyanin metabolism.METHODS: Lemna was incubated with DCF, CBZ, SMX, and TRIM alone and in a mixture (MIX) at 5 ppb (5 µg/L) for 5 days, at concentrations near environmental levels. The methanolic extract was analysed using a Q Exactive Focus Orbitrap to investigate changes in the aforementioned biosynthetic pathways, as reported in previous studies.RESULTS: Lemna can modulate its pathways to produce more phenolic compounds as a defence mechanism against various drugs. This modulation can be considered an indicator for each drug.CONCLUSIONS: The presence of pharmaceuticals in the aquatic environment can affect the biosynthetic pathways of Lemna. Therefore,Lemna minor can be used as a model to study the stress-response of different pharmaceuticals on plant metabolites and their pathways.PMID:41793570 | DOI:10.1007/s11306-026-02405-9

Metabolomics. 2026 Mar 7;22(2):39. doi: 10.1007/s11306-026-02416-6.ABSTRACTBACKGROUND: Phenylketonuria (PKU) is a rare metabolic disorder caused by a deficiency in the enzyme phenylalanine hydroxylase, leading to the accumulation of phenylalanine (Phe). Raised Phe levels can result in neurocognitive deficits, intellectual disabilities, and behavioral or psychiatric disorders.AIM OF REVIEW: To conduct a systematic review of human studies on metabolites identified through metabolomics in individuals with PKU, compared to healthy controls, and to provide insights into their biological significance.KEY SCIENTIFIC CONCEPTS OF REVIEW: A total of 26 human studies analyzing metabolites in urine and blood met the inclusion criteria. In total, 544 metabolites that differed between patients with PKU and healthy controls were identified through different metabolomic techniques (LC-MS, GC-MS, NMR). Differences were primarily observed in blood samples, which accounted for 95% of the total metabolites, with only 5% detected in urine samples, reflecting the limited use of this body fluid in only five studies. We found 60% of blood metabolites upregulated in patients with PKU, including Phe, Phe-related metabolites, lipids, and other amino acids, while tryptophan and kynurenine, among others, were downregulated (40%). Additionally, 35 metabolites (6% of the total) exhibited inconsistent directions of change (both up- and downregulated), including amino acids, carnitine derivatives, and lipids. These findings may be attributed to clinical factors (dietary adherence, supplementation, and treatment) and methodological differences in blood-derived matrices. Consequently, the high heterogeneity across studies, biological matrices and analytical platforms represents limitations for establishing a unique metabolomic signature. Overall, these results emphasize the metabolic complexity of PKU and highlight the potential of metabolomics to advance disease monitoring and management.PMID:41793569 | DOI:10.1007/s11306-026-02416-6

Metabolomics. 2026 Mar 7;22(2):40. doi: 10.1007/s11306-026-02417-5.NO ABSTRACTPMID:41793546 | DOI:10.1007/s11306-026-02417-5

Biodegradation. 2026 Mar 7;37(2):46. doi: 10.1007/s10532-026-10258-1.ABSTRACTPlastic pollution constitutes a critical environmental concern of this era, with synthetic polymers, i.e., polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), and polyurethane (PU), accumulating in terrestrial and aquatic ecosystems at alarming rates. One of the promising solutions to this worldwide problem is microbial plastic degradation, particularly by bacteria that can convert polymeric materials into less toxic compounds. With an emphasis on enzymatic mechanisms, critical environmental and biochemical factors influencing degradation, and the wide variety of bacteria responsible for breaking down synthetic polymers, this review focuses on the enzymatic and genetic aspects underlying bacterial plastic degradation, highlighting key enzymes such as PETase, METase, esterase, and oxidoreductase, as well as representative plastic-degrading bacteria i.e. Thermobifida, Ideonella, Bacillus, Agromyces, Pseudomonas, Schlegelella species. The significance of multi-omics tools, such as transcriptomics, proteomics, metabolomics, and genomics was demonstrated here in deepening our understanding of microbial plastic degradation without depending on pure culture. It explores the key genes and metabolic pathways that facilitate this process. Moreover, how advanced biotechnological techniques and artificial intelligence (AI) can participate in plastic biodegradation through enzyme engineering, activity-enhancing mutation design, predictive modeling, and omics data analysis was illustrated. Furthermore, this review underscores the necessity for integrative and interdisciplinary approaches to effectively harness bacterial metabolism for long-term reduction of plastic pollution. Also, it outlines future research directions and technological priorities for translating bacterial plastic degradation into practical and sustainable remediation solutions.PMID:41793537 | DOI:10.1007/s10532-026-10258-1

Metabolomics. 2026 Mar 7;22(2):37. doi: 10.1007/s11306-026-02412-w.ABSTRACTBACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. Recent metabolomics studies have revealed pathogenic mechanisms and provided new perspectives for diagnosis.AIM: This study aimed to analyze plasma metabolic alterations and construct a preliminary diagnostic model for HCM based on untargeted metabolomics and machine learning (ML) algorithms, in order to explore potential pathogenic pathways and improve diagnostic accuracy during screening.METHODS: A total of 76 HCM patients and 35 normal participants were consecutively recruited from August, 2023 to December, 2023. Data were split into discovery and validation sets at a ratio of 7:3 and the feature combinations were selected using support vector machine (SVM) and random forest (RF). Stepwise multivariate linear regression analysis was performed to identify key metabolites associated with left ventricular wall thickness. Metabolic pathway analysis was performed using KEGG.RESULTS: Totally 1481 metabolites were identified with 640 differential metabolites and 240 significant differential metabolites. Multivariate statistical analysis showed that metabolism results could effectively differentiate the two cohorts (OPLS-DA positive ion mode R2Y = 0.744, Q2 = 0.456; negative ion mode R2Y = 0.611, Q2 = 0.441). SVM and RF screened the same combination of features including 7-keto-8-aminopelargonic acid (KAPA), γ-linolenoyl ethanolamid, nitrilotriacetic acid, D-quinovose and N-acetyl-l-aspartic acid (NAA), which could effectively and accurately differentiate HCM patients from normal participants (in discovery and validation sets, the SVM model AUROC was 0.996 and 0.985 with accuracies of 96.1% and 97.1%, respectively; the RF model AUROC was 1.000 with accuracies of 94.8% and 100.0%, respectively). In metabolic pathway analysis, central carbon metabolism in cancer and protein digestion and absorption were significantly upregulated in HCM patients, which were connected by alanine, aspartate and glutamate metabolism. Stepwise multivariate linear regression analysis revealed that NAA was correlated with left ventricular mass index and RV5+SV1 (P < 0.05), which may be the central target of the connecting pathway.CONCLUSION: Plasma metabolite diagnostic model including KAPA, γ-linolenoyl ethanolamid, nitrilotriacetic acid, D-quinovose and NAA can effectively and accurately screen HCM patients. Metabolomics combined with ML algorithm showed that alanine, aspartate and glutamate metabolism may be the pathogenic pathway leading to the occurrence of HCM with NAA as the central target.PMID:41793534 | DOI:10.1007/s11306-026-02412-w

Amino Acids. 2026 Mar 7. doi: 10.1007/s00726-026-03502-8. Online ahead of print.ABSTRACTHyperuricemia (HUA) is a metabolic disorder that contributes to the pathogenesis of gout arthritis (GA), chronic kidney disease (CKD), and cardiovascular disease (CVD). While current urate-lowering therapies effectively reduce serum uric acid levels, they fail to address the underlying metabolic dysregulation driving HUA progression and associated tissue damage. Emerging evidence highlights that dysregulated amino acid (AA) metabolism in bone, kidney, and vascular tissues plays a pivotal role in HUA-related complications. This review synthesizes recent advances in understanding AA metabolic pathways involved in HUA complications and elucidates the therapeutic potential of targeting tissue-specific AA metabolism. We propose precision modulation of AA metabolism as a promising strategy for both preventing and treating HUA-associated complications.PMID:41793522 | DOI:10.1007/s00726-026-03502-8

Metabolomics. 2026 Mar 7;22(2):35. doi: 10.1007/s11306-026-02410-y.ABSTRACTINTRODUCTION: Grapevine trunk diseases (GTDs), such as esca, pose a major threat to viticulture worldwide and are associated with complex biochemical responses in woody tissues. Comprehensive metabolome coverage remains a challenge, as conventional methods often overlook non-polar metabolites critical to plant defense mechanisms.OBJECTIVES: This study aimed to expand metabolome and lipidome coverage of grapevine wood by integrating complementary LC-MS approaches, in order to identify metabolic signatures linked to pathogenic fungi and to a biocontrol agent.METHODS: Woody tissues of Vitis vinifera cv. Cabernet-Sauvignon were inoculated with Phaeomoniella chlamydospora, Phaeoacremonium minimum, and/or the biocontrol fungus Trichoderma atroviride (Vintec®). A biphasic extraction was coupled with three orthogonal LC-MS methods-reverse-phase (RP), hydrophilic interaction chromatography (HILIC), and lipidomics-focused RP. Data were processed through the MSCleanR workflow and integrated using the DIABLO multi-block statistical framework. Compound classification was performed with NPClassifier.RESULTS: The multiplexed strategy enabled the annotation of 1,425 unique features, representing an 83% increase compared to previous studies. Distinct metabolomic and lipidomic signatures were associated with fungal infection and biocontrol treatments. Lipidomic analysis highlighted oxidized fatty acids (oxylipins) -specifically hydroxy-eicosatetraenoic acids (13-HETE, 16(R)-HETE, and 11(R)-HETE)-as potential signaling molecules in defense responses. NPClassifier revealed diverse biosynthetic classes, including phenylpropanoids, terpenoids, and sphingolipids, underscoring the chemical heterogeneity of grapevine responses.CONCLUSION: This multiplexed LC-MS workflow provides a versatile analytical pipeline for untargeted metabolomics and lipidomics in plants. By integrating complementary methods, the study uncovered novel biomarkers of grapevine defense, particularly oxylipins, emphasizing the critical role of lipidomics in deciphering plant-pathogen interactions.PMID:41793508 | DOI:10.1007/s11306-026-02410-y

Eur J Appl Physiol. 2026 Mar 7. doi: 10.1007/s00421-026-06184-y. Online ahead of print.NO ABSTRACTPMID:41793434 | DOI:10.1007/s00421-026-06184-y

J Inherit Metab Dis. 2026 Mar;49(2):e70170. doi: 10.1002/jimd.70170.ABSTRACTChenodeoxycholic acid (CDCA) is an essential drug for patients with rare metabolic disease cerebrotendinous xanthomatosis (CTX). To ensure continuation of treatment, the Amsterdam UMC hospital pharmacy developed pharmacy compounded CDCA capsules when the authorized CDCA capsules were no longer available for Dutch patients. This study reports the safety of pharmacy compounded CDCA through pharmacovigilance monitoring and assesses its effectiveness by evaluating biochemical outcome measures, both in patients who were previously treated with authorized CDCA and subsequently switched to the compounded formulation and in new patients. Data were generated during routine patient care and collected retrospectively. Adverse events were reported by 45% of the patients; the most reported adverse events were diarrhea (16%), constipation (7%), and fatigue (7%). Biochemically, plasma cholestanol levels and urinary bile alcohol levels remained normalized before and after switching from the authorized product to pharmacy compounded capsules. It can be concluded that the pharmacy compounded CDCA capsules are well tolerated by patients with CTX and that the desired biochemical effect was maintained, supporting the use of a compounded formulation when the authorized product is unavailable.PMID:41793373 | DOI:10.1002/jimd.70170

J Agric Food Chem. 2026 Mar 7. doi: 10.1021/acs.jafc.5c13394. Online ahead of print.ABSTRACTThis study evaluated the sublethal effects of pyraclostrobin (PY) (0.750-12.0 μg/L) and its underlying toxic mechanisms following 28 days of embryonic exposure. PY at ≥3.00 μg/L caused developmental toxicity, characterized by increased larval weight, reduced body length, and hepatic and renal impairment. Different PY concentrations similarly altered glucose, pyruvate, total cholesterol, triglyceride, and free fatty acid levels and the transcription of glycolipid metabolism-related genes. Whole-larvae metabolomics further showed that PY simultaneously disrupted ABC transporters, amino acid biosynthesis, and arginine and proline metabolism pathways. Moreover, strobilurins PY, azoxystrobin, and trifloxystrobin induced Abcb4 and Abcb5 transcription during zebrafish embryo-larvae development. Molecular docking revealed that strobilurins formed hydrophobic interactions with conserved Phe793 and Phe1043 residues in zebrafish ABCB5, whereas no conserved binding interactions were observed with ABCB4, suggesting substrate specificity between strobilurins and ABCB5. This study provides potential molecular targets of PY toxicity and highlights the need to assess its chronic ecological risks.PMID:41793353 | DOI:10.1021/acs.jafc.5c13394

New Phytol. 2026 Mar 7. doi: 10.1111/nph.71058. Online ahead of print.ABSTRACTTrade-offs between induced plant defenses and competitive growth are regarded as being universal. This seems particularly true for often-studied early succession annuals, where exposure to competition often suppresses defense expression. However, whether such trade-offs are universal across plant life histories remains unclear, especially considering recent work demonstrating that the trade-off can be artificially uncoupled. We test the hypothesis that Solidago altissima, a perennial herbaceous plant, naturally uncouples this trade-off by adjusting its investment in chemical defenses when exposed to competitive cues, allowing for persistence in high-competition environments despite herbivore pressure. Using a factorial glasshouse experiment, we manipulated competition cues (far-red light and conspecific neighbors) and insect herbivory to assess impacts on growth, resistance, and secondary metabolite production. S. altissima maintained or even enhanced herbivore-induced resistance in the presence of competition cues. Bioassays revealed reduced herbivore performance on previously damaged plants, particularly when they were exposed to neighbors. Metabolomic profiling showed herbivory-induced production of several secondary metabolite classes. Most notably, we found competition-enhanced production of hydroxycinnamic acids, dominated by 3-O-(E)-feruloylquinic acid, associated with resistance. Our findings challenge the generality of the growth-defense trade-off and highlight the importance of ecological context and life-history strategy in shaping plastic responses.PMID:41793111 | DOI:10.1111/nph.71058

Mol Omics. 2026 Mar 7:aaiag011. doi: 10.1093/molecular-omics/aaiag011. Online ahead of print.ABSTRACTMalaria remains a major public health challenge due to drug and insecticide resistance, underscoring the need for novel therapies with distinct mechanisms of action. In this study, silver nanoparticles were green-synthesized using the brown marine algae Padina tetrastromatica (Ag-PT) and evaluated through integrated in vitro, in vivo, metabolomics, network pharmacology, and in silico approaches. Ag-PT showed potent antiplasmodial activity, with significantly lower IC₅₀ values and superior parasite suppression compared to chemically synthesized silver nanoparticles (Ag-NP). Untargeted metabolomics revealed that Ag-PT treatment specifically restored malaria-induced disruptions in fatty acid, arginine, and arachidonic acid metabolism. This included elevating precursors of specialised pro-resolving mediators (SPMs) such as DHA, 14-HDHA, and 18-HEPE, and replenishing L-arginine to improve nitric oxide synthesis and vascular function. Integration with network pharmacology identified COX-2 (PTGS2) as a key hub gene. Molecular docking and dynamics confirmed strong binding of the Ag-PT phytochemical eriodictyol to COX-2, suggesting inhibition that shifts arachidonic acid metabolism toward anti-inflammatory SPM production. Collectively, these findings reveal that Ag-PT offers a multifaceted therapeutic strategy by simultaneously targeting the parasite while modulating host inflammatory and metabolic pathways. This integrated therapeutic strategy highlights the potential of eco-friendly, plant-based nanomedicines as a next-generation intervention for malaria management.PMID:41792924 | DOI:10.1093/molecular-omics/aaiag011

J Transl Med. 2026 Mar 6. doi: 10.1186/s12967-026-07951-3. Online ahead of print.ABSTRACTBACKGROUND: Nearly 80% of patients with High grade serous ovarian cancer (HGSOC) will experience recurrence within 5 years, but little is known about the mechanisms that drive this process.METHODS: In this study we used whole genome sequencing to assess SNV and SV burdens. These were in turn used to estimate clonal dynamics, genomic scarring, and establish mutational patterns.RESULTS: Mutational burdens and clonal compositions are established early and are maintained throughout recurrence. Using both next generation and ultra long read sequencing to analyze single nucleotide and structural variants (SVs) we discovered that although tumors from the same patient remained relatively stable, homologous recombination repair proficient (HRP) and homologous recombination repair deficient (HRD) tumors presented with distinct clonal profiles. SV signature analysis revealed three distinct classes: tumors defined by DNA losses, DNA gains, and copy number neutral changes. Each class displayed structural variation affecting distinct regions of the genome. Ultra long read sequencing validated most of the SVs identified in short read sequencing and identified additional SVs. A novel candidate driver gene involved in DNA repair, MDC1, was significantly mutated in patients with HRP tumors.CONCLUSIONS: The phenotype of high grade serous ovarian tumors, as defined by mutation and clonality profiles, is established early in disease development and remain largely unchanged through chemotherapy and recurrence. This, when considered with the significant inter-patient heterogeneity identified in HGSOC, demonstrates the need for personalized therapies based on tumor profiling. Loss of MDC1 increases invasive properties in cell lines and may drive HRD in a subset of patients.PMID:41792798 | DOI:10.1186/s12967-026-07951-3