PubMed

Front Endocrinol (Lausanne). 2026 Aug 26;17:1933396. doi: 10.3389/fendo.2026.1933396. eCollection 2026.ABSTRACTBACKGROUND: Patients presenting with both type 2 diabetes (T2D) and lung function impairment (LFI) are exposed to an amplified risk of major adverse cardiovascular events (MACE). Although the SCORE2-Diabetes algorithm is widely endorsed for clinical risk assessment, its prognostic accuracy within this specific multimorbid phenotype remains inadequately explored. This study sought to evaluate the baseline utility of SCORE2-Diabetes and to investigate whether integrating a novel, machine learning-derived metabolomic signature could optimize 10-year MACE prediction in this highly vulnerable population.METHODS: We conducted a prospective analysis of UK Biobank participants with type 2 diabetes (T2D) and no cardiovascular disease at baseline. A reference cohort of 12,130 participants with preserved lung function was used to assess the base clinical model, and the primary cohort comprised 3,706 participants with lung function impairment (LFI). We profiled 249 plasma metabolites using nuclear magnetic resonance (NMR) spectroscopy. A machine-learning framework combining least absolute shrinkage and selection operator (LASSO) Cox regression, random forest survival analysis, and extreme gradient boosting (XGBoost) was used to derive a consensus signature. Internal validation used 1,000 bootstrap resamples; the complete modeling pipeline was repeated within each resample. Incremental performance beyond SCORE2-Diabetes was assessed using Harrell's concordance index (C-index), net reclassification improvement (NRI), calibration, and decision curve analysis (DCA).RESULTS: During a median follow-up of 12 years, SCORE2-Diabetes showed lower discrimination in the LFI cohort than in the reference cohort (C-index, 0.670 vs. 0.707). Among the 3,706 participants with LFI, 845 developed major adverse cardiovascular events (MACE). Adding the 12-metabolite signature increased the C-index from 0.670 to 0.722 (absolute difference, 0.052; P < 0.001), representing a statistically significant but moderate improvement in discrimination. The five-metabolite model had a C-index of 0.708, while the two-metabolite sensitivity model yielded a C-index of 0.699 (95% CI, 0.683-0.716). Using the 2023 European Society of Cardiology SCORE2-Diabetes categories, the categorical NRI was 14.8% (95% CI, 10.8%-18.8%). Internal calibration and DCA suggested improved agreement and net benefit, but these results require external validation.CONCLUSIONS: In participants with T2D and LFI, adding a metabolomic signature to SCORE2-Diabetes produced a statistically significant but moderate improvement in risk discrimination. These internally validated findings support further evaluation in independent cohorts and prospective impact studies; they do not establish immediate clinical usefulness.PMID:42718866 | PMC:PMC13553505 | DOI:10.3389/fendo.2026.1933396

Front Plant Sci. 2026 Aug 26;17:1916983. doi: 10.3389/fpls.2026.1916983. eCollection 2026.ABSTRACTBACKGROUND: Cold stress is a major environmental constraint limiting wheat productivity worldwide. Although numerous cold-responsive pathways have been identified, the molecular basis of differential cold tolerance among genetically related wheat lines remains poorly understood. In this study, two wheat sibling lines derived from a single progeny plant of the same parental cross, Luyan951 (cold-tolerant) and Luyan955 (cold-sensitive), were employed to investigate the regulatory mechanisms of cold adaptation through integrated physiological, transcriptomic, and metabolomic analyses.RESULTS: Physiological assays revealed that Luyan951 exhibited markedly enhanced cold tolerance, with a survival rate of 52.67% following cold treatment compared with 20.67% in Luyan955. This enhanced tolerance was accompanied by 1.90-2.41-fold greater increases in antioxidant enzyme activities (SOD, CAT, and POD) and 1.84-4.50-fold greater accumulation of proline and soluble sugars relative to Luyan955, along with substantially lower MDA accumulation. Transcriptomic and metabolomic analyses identified phenylpropanoid biosynthesis and jasmonic acid (JA) signaling as key pathways associated with cold adaptation. Compared with Luyan955, cultivar Luyan951 exhibited stronger activation of these pathways under cold stress. Key genes involved in phenylpropanoid biosynthesis (CAD, and 4CL) and JA signaling (JAZ, MYC2) were significantly upregulated in Luyan951, as confirmed by qRT-PCR. Bioinformatic analyses further suggested that AP2/ERF transcription factors may act as upstream regulators of these pathways. Furthermore, subcellular localization and transcriptional activation experiments confirmed the nuclear localization and transactivation function of three AP2/ERF genes (TraesCS5D02G318400, TraesCS6A02G381000, TraesCS6D02G366100).CONCLUSIONS: Our findings indicate that the phenylpropanoid biosynthesis pathway plays a significant role in the cold tolerance of wheat, and together with the jasmonic acid signaling pathway, it forms a crucial regulatory network. This network promotes the scavenging of reactive oxygen species, maintains osmotic homeostasis, and stabilizes metabolism under low-temperature stress. Integrated analyses further suggest that this network may be coordinated by upstream ERF transcription factors. These findings provide comprehensive insights into the molecular mechanisms of wheat cold adaptation and offer valuable candidate genes and pathways for the genetic improvement of cold tolerance in wheat.PMID:42718787 | PMC:PMC13553893 | DOI:10.3389/fpls.2026.1916983

Front Nutr. 2026 Aug 26;13:1866771. doi: 10.3389/fnut.2026.1866771. eCollection 2026.ABSTRACTBACKGROUND: Epidemiological evidence on minerals in domestic water and incident metabolic dysfunction-associated steatotic liver disease (MASLD) remains limited, particularly regarding potential mediating roles of circulating metabolites. We evaluated the association between minerals and incident MASLD and characterized metabolomic biomarkers that may mediate this association.METHODS: We included 218,339 UK Biobank participants without MASLD or other liver disease at baseline. Domestic water hardness (DWH), including calcium (Ca), magnesium (Mg), and calcium carbonate (CaCO3), was obtained from water-utility outputs. MASLD was ascertained using linked health records. One hundred sixty-eight plasma biomarkers were measured using nuclear magnetic resonance profiling. We used Cox models to quantify associations between minerals and MASLD risk, while causal mediation analyses were used to evaluate mediation by these biomarkers.RESULTS: During a median follow-up of 13.7 years, 3,004 participants developed MASLD. Higher Ca in domestic water was positively associated with incident MASLD (Hazard ratio 1.087, 95% confidence interval 1.013-1.166), whereas Mg (1.042, 0.993-1.094) and CaCO3 (1.006, 0.939-1.078) showed no significant associations with MASLD. In mediation analyses, Glutamine, Lactate, and Alanine may mediated the association, with proportions mediated of 21.42, 7.53, and 5.38%, respectively.CONCLUSION: Ca in domestic water was positively associated with incident MASLD, with partial mediation by metabolites including glutamine, lactate, and alanine. These findings provide insight into the metabolic pathways of minerals-MASLD association and support prevention strategies.PMID:42718770 | PMC:PMC13553438 | DOI:10.3389/fnut.2026.1866771

Front Microbiol. 2026 Aug 26;17:1888286. doi: 10.3389/fmicb.2026.1888286. eCollection 2026.ABSTRACTThe antibiotic resistance crisis has become a major threat to global public health. Discovering natural antibacterial compounds with unique mechanisms from traditional medicinal plants is an effective strategy to overcome this challenge. Through activity-guided fractionation, three compounds were isolated from Turpinia arguta leaves, identified as piperyamine A, cynaroside, and gallic acid. Cynaroside exhibited the strongest antibacterial activity, with MIC values of 31.25 μg/mL against Staphylococcus aureus (Gram-positive) and 62.5 μg/mL against Vibrio parahaemolyticus (Gram-negative). Phenotypic experiments, including scanning electron microscopy, electrical conductivity measurements, and alkaline phosphatase (ALP) activity assays, were performed to evaluate antibacterial effects of cynaroside. The results indicated that cynaroside exerted antibacterial effects by disrupting the integrity of bacterial cell walls and cell membranes, with markedly different responses between Gram-positive and Gram-negative bacteria. Specifically, the increase in electrical conductivity was more pronounced in V. parahaemolyticus (Gram-negative), while the peak ALP activity was higher in S. aureus (Gram-positive). Integrated metabolomic and transcriptomic analyses were conducted to elucidate the differential antibacterial mechanisms. In S. aureus, cynaroside treatment was associated with suppression of pyrimidine metabolism and histidine metabolism, negatively regulating 11 metabolites with pyrC as the hub gene; in V. parahaemolyticus, it mainly inhibited glyoxylate and dicarboxylate metabolism and branched-chain amino acid degradation, negatively regulating tricarboxylic acid cycle intermediates with fdh3B as the hub gene. This study reveals the differential antibacterial mechanisms of cynaroside isolated from Turpinia arguta against Gram-positive and Gram-negative bacteria, laying a theoretical foundation for the development of species-selective natural antibacterial agents.PMID:42718745 | PMC:PMC13553902 | DOI:10.3389/fmicb.2026.1888286

Front Vet Sci. 2026 Aug 26;13:1922191. doi: 10.3389/fvets.2026.1922191. eCollection 2026.ABSTRACTINTRODUCTION: Lactation is a critical reproductive trait that influences offspring survival and livestock productivity in equine production. Characterizing physiological transitions during the perinatal period can improve our understanding of how mares adapt to late gestation, parturition, and early lactation. However, in horses-a typical monogastric herbivore with unique digestive characteristics-the associations between gut microbiota and perinatal physiological adaptation, as well as related stage-associated microbial and metabolic features, remain largely uncharacterized.METHODS: In this study, parallel profiling of serum physiology, fecal microbiota, and fecal metabolome was performed to identify candidate stage-associated microbial and metabolic features across three perinatal stages (pre-foaling, PF; post-foaling, PoF; early lactation, EL) in 19 multiparous Mongolian mares selected from a local breeding herd with records of normal foaling and healthy weaning. We further systematically determined serum biochemical indicators, reproductive hormones and immune parameters to interpret host physiological adaptive characteristics linked to lactogenesis.RESULTS: Obvious stage-specific physiological patterns were observed: triglycerides, urea and mineral elements were present at higher serum concentrations during the pre-foaling period, which may support fetal gestation; serum glucose was higher after parturition, which may meet the energy demands of delivery and early lactation; serum IgA concentration was higher in early lactation, which may be consistent with enhanced mucosal immune activation. Of note, serum IgA does not directly reflect colostral IgA concentrations or foal passive immunity. Alpha diversity of fecal microbiota was lower during the post-foaling stage, and each perinatal stage was associated with distinct fecal microbial community structures. Microbial taxa potentially associated with carbohydrate fermentation were more abundant in the pre-foaling period; the post-foaling stage was associated with an increased relative abundance of Akkermansia, which is consistent with a possible role in intestinal barrier maintenance, along with increased PICRUSt2-predicted abundance of galactose metabolism pathways; microbial taxa potentially related to lipid metabolism and bile secretion features were predominant in early lactation.DISCUSSION: This study systematically characterized stage-specific remodeling patterns of fecal microbiota and fecal metabolome during the perinatal transition in Mongolian mares. The identified fecal microbial taxa and metabolites are described as candidate stage-associated discriminatory features rather than validated biomarkers.PMID:42718734 | PMC:PMC13553426 | DOI:10.3389/fvets.2026.1922191

Front Plant Sci. 2026 Aug 26;17:1894544. doi: 10.3389/fpls.2026.1894544. eCollection 2026.ABSTRACTINTRODUCTION: Magnoliae Flos (MF), the dried flower buds of Magnolia denudata Desr., Magnolia biondii Pamp., and Magnolia sprengeri Pamp., is a crucial East Asian medicinal herb used to treat allergic rhinitis and other ailments. However, the molecular basis for its quality differences remains unclear.METHODS: This study integrates GC-MS-based volatile metabolomics, high-throughput RNA sequencing, and RT-qPCR validation to elucidate the terpenoid metabolic differences and their regulatory mechanisms among the three MF varieties.RESULTS: The metabolomic analysis screened 55 differential terpenoids (15 key markers) that distinguish the MF varieties, with terpenoids being the primary metabolic category and the M. sprengeri vs. M. biondii group exhibiting the most differential metabolites. The transcriptomic analysis revealed TPS26 as key candidate genes involved in monoterpene synthesis, while IMPMBI2G0000034954 and IMPMBI2G0000034957 were identified as candidate genes for sesquiterpene synthesis. The expression abundances of these genes exhibited significant linear correlations with the accumulation levels of differential terpenoids, though such coordinated variation does not confirm direct causal regulation.DISCUSSION: Collectively, this work reveals the molecular basis of terpenoid diversity in MF, and provides theoretical references for germplasm discrimination, quality evaluation and genetic improvement of medicinal magnolia resources.PMID:42718721 | PMC:PMC13553886 | DOI:10.3389/fpls.2026.1894544

Wellcome Open Res. 2026 Jun 13;9:580. doi: 10.12688/wellcomeopenres.22942.2. eCollection 2024.ABSTRACTBACKGROUND: The study of non-hospitalised COVID-19 cases provides a context for improved understanding of the immune response to existing and new infections. Population-based cohorts provide a unique opportunity to do this in relation to rich longitudinal pre- and pan-pandemic data. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has subsequently followed participants for over 30 years.METHODS: A study comprising three clinic visits was implemented, in response to the COVID-19 pandemic, amongst ALSPAC participants to measure SARS-CoV-2 specific humoral and cellular responses longitudinally. Here we present data from the first clinic in December 2020 before the start of the UK vaccination campaign and examine associations with a set of exemplar pre- and pan-pandemic health factors.RESULTS: We observed humoral and cellular memory immune responses to SARS-CoV-2 infection in mild cases of COVID-19 up to 9 months post-infection. Symptomatic infection elicited a memory immune response of greater magnitude, though there was variation in response in both asymptomatic and symptomatic individuals. We examined health factors associated with severe COVID-19 and found that cardio-metabolomic, respiratory and immune-related health factors associate with a memory immune response of higher magnitude. For example, in older participants (mean age 58 years), higher BMI was associated with an immune memory response of greater magnitude, particularly with anti-S and anti-N binding antibodies.CONCLUSIONS: We set out to illustrate the use of cohort studies to deliver detailed immunological data and to provide example analyses of how life course health factors can be examined in relation to the immune response following a widespread and novel infection. We expanded this assessment to include longitudinally assessed traits, opening up the potential for the more common use of longitudinal population studies for the better understanding the aetiology of infection outcome.PMID:42718410 | PMC:PMC13550896 | DOI:10.12688/wellcomeopenres.22942.2

Circ Heart Fail. 2026 Sep 10:e014073. doi: 10.1161/CIRCHEARTFAILURE.125.014073. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is the most common type of PH and comprises 2 subtypes with distinct clinical profiles and outcomes: isolated postcapillary PH and combined pre- and postcapillary PH (Cpc-PH). Bioactive lipid derivatives may underlie these divergent subphenotypes. This study aimed to investigate the molecular heterogeneity underlying Group 2 PH subtypes and identify shared pathways between Cpc-PH and pulmonary arterial hypertension (PAH).METHODS: In a cross-sectional study, we profiled plasma bioactive lipids using liquid chromatography-mass spectrometry in 128 patients with isolated postcapillary PH (n=21), Cpc-PH (n=69), or PAH (n=38), as well as in plasma samples from animal models of severe PH.RESULTS: Of the 844 profiled metabolites, 158 differed between Cpc-PH and isolated postcapillary PH at a false discovery rate of q<0.05. Of those, 28 were higher in Cpc-PH, particularly those in the polyunsaturated fatty acid and fatty acyl esters of hydroxy fatty acid pathways. Notably, 24 of these 28 did not differ from PAH, indicating a PAH-like bioactive lipid signature. Several metabolites, including adrenic acid, linoleic acid, docosatrienoic acid, palmitoleic acid, and fatty acyl esters of hydroxy fatty acids, were associated with increased mortality. These findings were corroborated in the Su/Hx rat model of PAH, where a subset of Cpc-PH-elevated metabolites was similarly increased.CONCLUSIONS: Cpc-PH exhibits a distinct, PAH-like metabolomic signature characterized by higher polyunsaturated fatty acids and fatty acyl esters of hydroxy fatty acids and lower pro-resolvin/vasodilatory oxylipins compared with isolated postcapillary PH. These findings have implications for PH classification, may inform diagnostic strategies, and nominate lipid pathways for therapeutic targeting.PMID:42717881 | DOI:10.1161/CIRCHEARTFAILURE.125.014073

Circ Heart Fail. 2026 Sep 10:e014894. doi: 10.1161/CIRCHEARTFAILURE.126.014894. Online ahead of print.NO ABSTRACTPMID:42717879 | DOI:10.1161/CIRCHEARTFAILURE.126.014894

Circ Heart Fail. 2026 Sep 10:e014148. doi: 10.1161/CIRCHEARTFAILURE.125.014148. Online ahead of print.ABSTRACTBACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF.METHODS: We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF ≤35% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and 1H nuclear magnetic resonance-based metabolomic analysis.RESULTS: Totally 92 patients were enrolled, with a mean age of 67.3±11.3 years (37.0% female). LVEF was significantly improved from 28.9±7.6% at baseline to 36.0±11.3% at 6 months (P<0.001) and to 40.1±12.6% at 12 months (P<0.001). After CRT, 42 metabolite features were significantly decreased compared with the baseline. The ketone bodies, including 3-hydroxybutyrate (P<0.001) and acetone (P=0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT (P=0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine.CONCLUSIONS: CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.PMID:42717876 | DOI:10.1161/CIRCHEARTFAILURE.125.014148

CNS Neurosci Ther. 2026 Sep;32(9):e71048. doi: 10.1002/cns.71048.ABSTRACTBACKGROUND: Recent evidence suggests that the choroid plexus (ChP) serves as a gateway for neuroinflammation. Autoimmune encephalitis (AE) features a high inflammatory burden, yet the role of ChP in AE remains unclear. This study compared choroid plexus volume (CPV) at symptom onset between AE patients and healthy controls (HCs), and evaluated its association with prognosis.METHODS: This single-center study included 151 AE patients with definite autoantibodies. ChP volume (CPV) was segmented from baseline 3D-T1 MRI and normalized. Baseline CPV was compared between AE and age- and sex-matched HCs, and its associations with 12-month functional outcomes (mRS) and progression to autoimmune encephalitis-associated epilepsy (AEAE) were assessed. A logistic regression model based on ChP radiomic features was developed to predict AEAE. Exploratory cerebrospinal fluid (CSF) proteomics and metabolomics were performed in a small subset to generate hypotheses on underlying pathways.RESULTS: Of 151 AE patients, 141 completed 12-month follow-up; 26 (18.4%) developed AEAE. AE patients had significantly larger CPV than controls (1.235 ± 0.274 vs. 1.035 ± 0.264, p < 0.001). Larger baseline CPV was significantly associated with AEAE and mRS (p < 0.05). A two-feature radiomic model (RunEntropy and original volume) predicted AEAE with AUCs of 0.766 (training) and 0.851 (test). Exploratory proteomics in a subset suggested CPV-correlated downregulation of glutamatergic synapse pathways and upregulation of PI3K-Akt/integrin pathways.CONCLUSIONS: Baseline CPV was greater in AE patients than in HCs, and larger baseline CPV was associated with progression to AEAE and poor one-year functional outcomes. ChP imaging may aid in early risk stratification for AE patients.PMID:42717870 | DOI:10.1002/cns.71048

CNS Neurosci Ther. 2026 Sep;32(9):e71146. doi: 10.1002/cns.71146.ABSTRACTAIMS: Pyrroloquinoline quinone (PQQ) was reported to be neuroprotective after experimental traumatic brain injury (TBI), but its mechanisms remain undefined. We tested whether PQQ protects against TBI in mice and identified the associated pathways.METHODS: Male C57BL/6 mice received intraperitoneal PQQ (6.25, 12.5 or 25 mg/kg) immediately after controlled cortical impact. Mortality, modified neurological severity score (mNSS) and beam balance were followed to day 14; histopathology, immunofluorescence, western blot, ELISA and ATP assays were performed on day 3. Transcriptomics, metabolomics, network pharmacology and docking were integrated to identify candidate mechanisms.RESULTS: PQQ reduced mortality (lowest at 12.5 mg/kg) and dose-dependently improved neurological deficits, neuronal apoptosis, brain edema, pro-inflammatory cytokines, and oxidative stress; the mNSS and beam balance benefits persisted to day 14. At 12.5 mg/kg, multi-omics and network pharmacology identified arginine biosynthesis, mediated by argininosuccinate synthetase 1 (ASS1) and carbamoyl phosphate synthetase 1 (CPS1), as the top-ranked pathway suppressed by PQQ; docking predicted binding of PQQ to both enzymes, suggesting putative targets pending validation. PQQ concurrently restored PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and ATP production.CONCLUSION: PQQ attenuates secondary injury after TBI in male mice, in association with increased markers of PINK1/Parkin-mediated mitophagy initiation and suppressed ASS1/CPS1-driven arginine biosynthesis, identifying a candidate dual-axis mechanism and nominating the mitophagy-arginine axis as a target for neuroprotection in TBI.PMID:42717556 | DOI:10.1002/cns.71146

Plant Cell Environ. 2026 Sep 9. doi: 10.1111/pce.70868. Online ahead of print.ABSTRACTClimate warming can enhance the growth performance of invasive plants, potentially increasing their nitrogen (N) demand. However, whether this additional demand is supported by free-living N fixation remains unclear. Here, we used a 12-year warming experiment to determine how warming affected diazotrophic abundance, community composition, and nifH transcription in the roots and rhizosphere of the invasive plant Solidago canadensis during the growing and flowering stages. While warming increased plant biomass, it did not increase diazotrophic abundance or nifH transcription in either roots or rhizosphere soil. In the rhizosphere, warming even suppressed nifH transcription during flowering, which coincided with pronounced shifts in the rhizosphere metabolome and diazotrophic community composition, particularly among Bradyrhizobium-affiliated taxa. By contrast, these associations were weak or absent during the growing stage, indicating that plant developmental stage and concurrent seasonal variation modulate the responses of diazotrophs to climate warming. Overall, given the relatively high N availability at our study site, warming-enhanced growth of S. canadensis was unlikely to be supported by increased inputs of newly fixed N. Instead, S. canadensis may have met its increased N demand primarily through morphological and physiological adjustments that favour more efficient uptake and use of existing N pools, as indicated by higher specific root length and increased leaf N-use efficiency under warming. Future studies that directly quantify N fixation rates across gradients of N availability are warranted to validate our findings, especially in N-limited conditions where biological N fixation may contribute more substantially to plant N acquisition.PMID:42717422 | DOI:10.1111/pce.70868

BMC Plant Biol. 2026 Jul 27;26(1):1569. doi: 10.1186/s12870-026-09559-7.ABSTRACTFlavonoids play critical roles in plant adaptation to abiotic stress; however, how salt stress modulates metabolic flux distribution within flavonoid branches remains poorly understood, particularly in non-model medicinal plants. Here, we integrated targeted metabolomics, transcriptomics, and proteomics to examine flavonoid regulation in Anoectochilus roxburghii under 0, 50, 100, and 200 mmol·L- 1 NaCl. Metabolite profiling showed that salinity reshaped flavonoid composition rather than uniformly increasing flavonoid abundance. A metabolite-derived branch bias index (MI), representing the balance between reductive branch metabolites and flavonol products, increased under salt treatment, peaked at 100 mmol·L- 1 NaCl, and declined at 200 mmol·L- 1, indicating maximal branch bias under moderate stress followed by partial rebalancing under severe stress. Transcriptomic analysis showed induction of upstream phenylpropanoid and flavonoid entry genes, including PAL, 4CL, and CHS, whereas F3H was suppressed and FLS showed no induction. Furthermore, several short-chain dehydrogenase/reductase homologs (IFR-like SDR homologs) were upregulated, and the transcript-derived reductive branch index (EI) increased progressively across the salt gradient. EI was positively associated with MI, although the relationship was not strictly proportional under severe stress (200 mmol·L- 1 NaCl). Proteomic profiling further provided supportive evidence for sustained activation of upstream flavonoid biosynthesis, such as salt-induced accumulation of chalcone synthase (CHS) protein, complementing the transcriptomic and metabolomic datasets. Together, these results indicate that salt stress reorganizes flavonoid metabolism in A. roxburghii through persistent upstream activation and branch-specific regulation, favoring the reductive branch under moderate salinity.PMID:42717315 | DOI:10.1186/s12870-026-09559-7

BMC Plant Biol. 2026 Aug 13;26(1):1565. doi: 10.1186/s12870-026-09745-7.ABSTRACTBACKGROUND: Pyropia yezoensis thalli exhibit pronounced cellular differentiation throughout their growth and development. In particular, basal rhizoid-like filament cells (R-region cells) differ significantly from other thallus cells in cell morphology, photosynthetic physiology and carbon metabolism. Previous studies have shown that abundant floridean starch granules accumulate in R-region cells, whereas only few floridean starch granules are present in neighbouring vegetative cells (V-region cells). However, the specific mechanism underlying floridean starch accumulation in R-region cells remains unclear.RESULTS: In this study, basal cells of the P. yezoensis thallus were first divided, according to cell morphology, structural features and functional differences, into lower R-region cells and upper V-region cells. Anthrone colorimetric quantification, iodine staining and transmission electron microscopy collectively confirmed that floridean starch content was significantly higher in basal R-region cells than in upper V-region cells. By combining physiological measurements with integrated transcriptomic and metabolomic analyses, we further provided mechanistic insights into floridean starch accumulation in R-region cells. First, compared with V-region cells, R-region cells showed a significantly lower growth rate and globally reduced energy metabolic activity, features that are consistent with reduced carbon consumption and may contribute to the net accumulation of floridean starch. Second, on this basis, R-region cells promoted the directed allocation of carbon skeletons towards starch biosynthesis through enhanced expression of UGP (UDP-glucose pyrophosphorylase) genes and increased UGPase activity, thereby increasing UDP-glucose availability for floridean starch synthesis, while downregulating the expression of genes encoding starch-degradation-related enzymes. These coordinated changes promoted starch synthesis and suppressed starch degradation, jointly contributing to the efficient accumulation of floridean starch in R-region cells.CONCLUSIONS: Based on the cellular differentiation characteristics of the P. yezoensis thallus, this study compares cells from distinct thallus regions and provides integrated physiological, biochemical, transcriptomic and metabolomic evidence that region-specific carbon metabolism is associated with floridean starch accumulation in R-region cells. These findings not only provide a theoretical basis for understanding thallus cell differentiation and carbon metabolism in P. yezoensis, but also advance our understanding of how differentiated cells in red algal thalli coordinate regional function with carbon storage.PMID:42717314 | DOI:10.1186/s12870-026-09745-7

Biol Trace Elem Res. 2026 Sep 9. doi: 10.1007/s12011-026-05280-6. Online ahead of print.ABSTRACTCadmium (Cd) is a toxic heavy metal that causes multi-organ damage, including neurotoxicity. Carvacrol (CAR), a natural phenolic compound obtained from aromatic plants, is known for its protective properties. This study investigated the effects of CAR against Cd-induced toxicity through comprehensive behavioral assessments including the Open Field Test (OFT), Elevated Plus Maze (EPM), Barnes Maze, and Rotarod test, while plasma biochemical parameters, liver and kidney histopathology, and untargeted metabolomic profiles (plasma and brain) were also evaluated. Male Wistar albino rats were randomly divided into six groups and orally administered Cd (50 mg/kg) and/or CAR (20 or 40 mg/kg body weight) for 12 days. CAR alone increased locomotor activity, altered neuroprotective related metabolic pathways and did not cause weight loss. Cd exposure significantly increased body weight loss and anxiety-like behaviors while elevating cortisol, urea, AST, ALT levels and inducing significant histopathological damage in liver and kidney tissues (p < 0.05). Integrated plasma-brain metabolomic analyses revealed that Cd exposure disrupts multiple interconnected biological systems, including the antioxidant defence system, mitochondrial energy pathways, and cell membrane integrity. Although Cd-CAR co-administration partially reversed worsening of the anxiolytic-like behavior, locomotor activity, and renal tissue integrity, it failed to fully prevent Cd-induced toxicity and further aggravated weight loss, biochemical alterations (creatinine, AST, ALT), and metabolic disturbances (p < 0.05). In conclusion, co-administration of CAR with Cd provided only limited and heterogeneous protection that was insufficient to counteract Cd-induced multisystem toxicity. This current study presents a wide assessment to the systemic use of CAR against Cd according to results of behavioral, histopathological, biochemical, and metabolomic parameters.PMID:42717167 | DOI:10.1007/s12011-026-05280-6

Nat Microbiol. 2026 Sep 9. doi: 10.1038/s41564-026-02503-3. Online ahead of print.NO ABSTRACTPMID:42716994 | DOI:10.1038/s41564-026-02503-3

NPJ Sci Food. 2026 Sep 3;10(1):276. doi: 10.1038/s41538-026-01125-7.ABSTRACTOdor detection threshold (ODT) quantifies the perceptual potency of volatile compounds and is a key parameter in flavor chemistry. It is widely used to identify key food odorants, calculate odor activity values, and evaluate the contribution of volatiles to overall aroma perception. However, reliable ODT data remain sparse and inconsistent, and are unavailable for many volatiles detected in metabolomics analyses, complicating the identification of key food odorants and the quantitative interpretation of aroma contributions. Here we developed a machine learning framework to predict aqueous ODTs using a curated dataset of 1003 compounds, achieving a test-set R² of 0.83. External validation with 177 independently measured compounds supported the model's predictive utility, with 87.0% of predictions falling within a 10-fold deviation and 97.7% within a 100-fold deviation. Structural analysis suggested that aliphatic acids and nitrogen-containing compounds exhibit relatively high ODTs, whereas acyclic sulfur compounds, methoxypyrazines, haloanisoles, and exocyclic esters display low ODTs. Model-guided screening prioritized candidate high-potency odorants, and human sensory evaluation of 12 representative compounds provided preliminary prospective support for the prioritization workflow. These results provide a computational framework for prioritizing potent food odorants and offer data-driven insights into molecular features associated with odor potency in food aroma chemistry.PMID:42716919 | DOI:10.1038/s41538-026-01125-7

NPJ Sci Food. 2026 Sep 2;10(1):277. doi: 10.1038/s41538-026-01072-3.ABSTRACTNutritional interventions may complement established approaches for managing atopic dermatitis (AD). Here, we evaluated Saussurea involucrata cell culture (SIC), a sustainable functional-food material, in a DNCB-induced mouse model of AD-like inflammation. Chemical profiling established the phytochemical composition of SIC, and both topical and oral interventions improved macroscopic and histopathological outcomes. Under the tested conditions, the oral groups showed more consistent changes in systemic indices, providing the basis for subsequent mechanistic analyses. Integrated transcriptomic and metabolomic analyses, targeted lipid-mediator profiling, and qRT-PCR identified coordinated changes in the arachidonic acid (AA) metabolic network. Exploratory docking and molecular dynamics provided descriptive computational support for target-dependent retention or reorientation of selected ligand-protein configurations, while tissue-level immunohistochemistry supported corresponding changes in selected AA pathway-associated, type 2 inflammatory, and epidermal-junction proteins. Together, these findings associate oral SIC supplementation with attenuation of AD-like inflammation and AA metabolic remodeling.PMID:42716935 | DOI:10.1038/s41538-026-01072-3

J Formos Med Assoc. 2026 Sep 9:S0929-6646(26)00879-X. doi: 10.1016/j.jfma.2026.09.012. Online ahead of print.NO ABSTRACTPMID:42716894 | DOI:10.1016/j.jfma.2026.09.012