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PubMed2026

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans↗

PubMed2026

A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.

OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24 hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUCτ) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.

Fusidic Acid↗

PubMed2026

Effect of a 6-month low-carbohydrate diet on the circulating fatty acid composition in patients with type 2 diabetes: a secondary analysis of an open-label randomized controlled trial.

BACKGROUND: Circulating fatty acid profiles are linked to cardiovascular disease risk and mortality. Short-term interventions suggest that low-carbohydrate diets (LCDs) promote cardioprotective shifts in circulating fatty acids in obesity. OBJECTIVES: We examined whether a 6-mo, non-calorie-restricted, LCD high in fat similarly improves circulating fatty acid composition in adults with type 2 diabetes. METHODS: In an open-label, randomized, controlled trial, 71 individuals with type 2 diabetes were randomly assigned 2:1 to an LCD [maximum of 20 E% (energy per cent) carbohydrates] or a control diet (50-60 E% carbohydrates) for 6 mo with no restriction in energy intake. The prespecified secondary outcomes were the mean difference in change between groups in serum phospholipid fatty acids in weight percentage (wt%) measured by gas chromatography and reported as 95% confidence intervals (CIs) and significance adjusted for multiple comparisons (q value). RESULTS: LCD reduced total saturated [-0.6 (CI: -0.9, -0.2)] and monounsaturated fatty acids [-0.9 (CI: -1.4, -0.3)] and increased total polyunsaturated fatty acids [1.3 (CI: 0.6, 2.0)] compared with the control diet (all q < 0.05). Importantly, LCD reduced palmitoleic acid (16:1n-7) [-0.13 (CI: -0.21, -0.06)], a marker of de novo lipogenesis, by 23% and dihomo-γ-linolenic acid (20:3n-6) [-0.38 (CI: -0.67, -0.09)] by 12%, whereas it increased arachidonic acid (20:4n-6) [1.1 (CI: 0.3, 2.0)] by 9% compared with the control diet (all q < 0.05). Moreover, the LCD improved estimated desaturase activities by lowering stearoyl-coenzyme A desaturase 1 [-0.5 (CI: -0.7, -0.2)] and Δ6 desaturase [-0.6 (CI: -0.9, -0.2)] and increasing Δ5 desaturase [1.05 (CI: 0.3, 1.79)] activities, respectively (all q < 0.01). These changes occurred despite a 2.6-fold higher intake of saturated fatty acids in the LCD group. CONCLUSIONS: A 6-mo, non-calorie-restricted LCD modified the circulating composition of fatty acids in adults with type 2 diabetes in a manner consistent with a potentially favorable cardioprotective profile. This trial was registered at www. CLINICALTRIALS: gov as NCT03068078.

Humans↗

PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans↗

PubMed2026

Evolutionary characterization and expression profiling of ACC and FASN genes in Chinese mitten crab Eriocheir sinensis.

Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) are rate-limiting enzymes in the fatty acid biosynthetic pathway, yet their evolutionary relationships, sequence features, and expression profiles remain poorly understood in crustaceans, particularly in the economically important Chinese mitten crab (Eriocheir sinensis). Here, we identified and systematically analyzed ACC and FASN genes in E. sinensis using comparative genomic analyses across 43 species. ACC was highly conserved as a single-copy gene in invertebrates, in contrast to the multiple paralogs observed in vertebrates. Similarly, FASN was generally maintained as a single-copy gene across most taxa but exhibited lineage-specific expansion in certain insect groups. Phylogenetic and structural analysis revealed strong conservation of both genes within crustaceans, supported by multiple conserved motifs and canonical functional domains. Expression profiling showed predominant expression in the hepatopancreas and midgut, suggesting their potential involvement in crustacean lipid metabolism. During the molting cycle, ACC and FASN exhibited higher expression levels during stages C and D, suggesting an increased capacity for fatty acid biosynthesis before molting. In addition, dietary lipid levels experiment revealed that ACC and FASN expression responded dynamically to dietary lipid availability, with increased expression at moderate lipid levels but reduced expression under excessive lipid supplementation, indicating a possible adaptive transcriptional response to lipid status. Collectively, this study provides insights into the evolutionary conservation and expression dynamics of ACC and FASN and improves our understanding of lipid metabolic adaptation in crustaceans.

Animals↗

PubMed2026

Bempedoic Acid and First and Recurrent Limb Outcomes in Statin-Intolerant Patients With Peripheral Artery Disease: Insights From the CLEAR Outcomes Trial.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE). Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE in patients with PAD is unknown. METHODS: CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid [ETC1002], an ACL-Inhibiting Regimen) randomized 13 970 patients to bempedoic acid 180 mg or placebo from December 22, 2016, to August 14, 2019. The trial primary end point was MACE-4, defined as death resulting from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated MALE, including adverse events indicating worsening PAD symptoms leading to revascularization, chronic limb-threatening ischemia, and acute limb ischemia. Outcomes were assessed as time to first event and total (including recurrent) events with a negative binomial approach. RESULTS: A total of 1624 of the enrolled patients (mean±SD age, 63.9±9.9 years; 915 [56.3%] female) had PAD at baseline. In patients with PAD in the placebo group, 69 (8.3%) had MALE over a median of 40.6 months, with rate of recurrent events of 4.0%/y. Bempedoic acid reduced the risk of MALE by 36% (hazard ratio, 0.64 [95% CI, 0.44-0.93]; P=0.018). Bempedoic acid reduced total MALE by 45% (relative risk, 0.55 [95% CI, 0.35-0.85]; P=0.007). First MACE-4 or MALE was reduced overall by 13% (hazard ratio, 0.87 [95% CI, 0.80-0.95]) with consistent effects with PAD (hazard ratio, 0.82 [95% CI, 0.64-1.04]) and without PAD (hazard ratio, 0.87 [95% CI, 0.79-0.86]; Pinteraction=NS) but not statistically significant within the PAD subgroup alone. Total MACE-4 or MALE was reduced (relative risk, 0.81 [95% CI, 0.73-0.90]) overall with consistent effects in PAD (relative risk, 0.71 [95% CI, 0.54-0.95]) and without PAD (relative risk, 0.82 [95% CI, 0.73-0.92]; Pinteraction=NS). CONCLUSIONS: Patients with PAD are at high risk of MALE and MACE. Bempedoic acid reduces both MACE and MALE in patients with atherosclerotic vascular disease, with notable absolute benefits in patients with PAD. These findings support (1) the importance of lowering low-density lipoprotein cholesterol in patients with PAD to reduce overall vascular risk and (2) the benefits of bempedoic acid in this population.

Humans↗

PubMed2026

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans↗

PubMed2026

Efficacy and safety of split-dose ultra-low-volume polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate for bowel preparation: a systematic review and meta-analysis.

Colonoscopy remains the gold standard for early detection and prevention of colorectal cancer, with adequate bowel cleansing being pivotal for its success. This systematic review aims to evaluate the efficacy and safety of split-dose ultra-low-volume polyethylene glycol (PEG) with ascorbic acid (Asc) versus sodium picosulfate magnesium citrate for bowel preparation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search across Embase, PubMed, Web of Science, and Scopus from inception to July 2025. Data analysis was conducted using R version 4.2.2 (31 October 2022) and RStudio version 2022.07.2 (2009-2022, RStudio, Inc.) Our literature search yielded six eligible studies involving 3285 patients. Our findings indicate no significant differences in overall and right-sided colon adequate cleansing rates between the two regimens: risk ratio: 1.05, 95% confidence interval (CI): 0.99-1.12, P  = 0.1082; and risk ratio: 1.03, 95% CI: 0.99-1.08, P  = 0.1755, respectively. However, PEG + Asc demonstrated a significantly lower rate of vomiting compared to sodium picosulfate magnesium citrate (risk ratio: 2.58, 95% CI: 0.94-2.78, P  = 0.0008), suggesting better tolerability. Other secondary outcomes, including nausea, abdominal pain, and overall Boston Bowel Preparation Scale scores, did not show significant differences. The quality of the evidence varied across the outcomes. Our results support the comparable efficacy of both bowel preparation agents while highlighting PEG + Asc's potential advantages in tolerability. Our findings suggest that the choice between these two preparations can be tailored to the specific patient, considering their preferences or previous experiences, although some caution is advised in interpreting these findings.

Humans↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 µg vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 µg, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 µg, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans↗

PubMed2026

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p < 0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals↗

PubMed2026

Comprehensive identification of carboxylic acids by using bromine isotope-based chemical isotope labelling and structure-guided molecular network.

Carboxylic acids (CAs) are important contributors to the flavor quality of sauce-flavor Chinese Baijiu, yet their comprehensive analysis remains challenging due to poor ionization efficiency, weak chromatographic retention, and limited annotation capability. Herein, we developed a workflow for the high-coverage discovery and annotation of CAs in Baijiu by coupling chemical isotope labeling-liquid chromatography-mass spectrometry with a structure-guided molecular network strategy (SGMNS). A bromine-containing derivatization reagent, 1-(3-aminopropyl)-3-bromoquinolin-1-ium bromide (APBQ), was designed and synthesized to exploit the natural isotope distribution of bromine and characteristic MS/MS fragmentation behavior. Following APBQ derivatization, the target CAs showed superior chromatographic retention and favorable analytical performance. Based on isotopic peak pairing in MS1 and diagnostic fragment validation in MS2, 372 potential CA derivatives were discovered from pooled Baijiu samples and 355 of them were validated by diagnostic fragments in MS2 spectra. To address the scarcity of derivatized spectral libraries, SGMNS was employed for annotation using a background network constructed from APBQ-labeled candidates derived from the Expanded Chinese Baijiu Compound Database. The developed method was further applied to profile Baijiu samples, revealing pronounced differences in CA composition across the seven fermentation rounds. Notably, rounds 3 to 5 exhibited the largest numbers of differential CAs. This study provided an effective analytical strategy for large-scale CA profiling, offering new insight into the chemical basis of flavor formation during multi-round fermentation of sauce-flavor Baijiu.

Isotope Labeling↗

PubMed2026

Improved comprehensive profiling of fecal bile acids through chemical derivatization combined with HPLC-MS/MS analysis.

Bile acids (BAs) facilitate the digestion and absorption of fats and influence lipid and glucose homeostasis, making them potential therapeutic targets for obesity and related metabolic disorders. The liver and intestinal microbiota modify BAs structurally, generating diverse chemical forms and isomers. Comprehensive profiling of the BA pool is critical for understanding their key biological functions and as a therapeutic approach for related diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is usually chosen as the preferred method for BA detection due to the complex chemical structures, the wide range of actual concentrations and the complexity of fecal sample matrices. However, free BAs are difficult to ionize, resulting in low detection signals and a lack of characteristic structural fragments to assist in structural identification. In this method, the labeling reagent (2-aminoethyl) trimethylammonium (AETMA) is employed to label the carboxyl group of BAs. Compared with underivatized BAs, the detection sensitivity of unconjugated BAs was enhanced by 25-180 fold, while that of conjugated BAs increased by 6-160 fold. It also generates unique fragment ions and enhances MS response, facilitating the discovery of potential BAs. Methodological parameters were validated using 38 BAs as representatives. Through methodological validation, it was verified that the precision, recovery, matrix effect and stability parameters of the method met acceptable criteria. We also identified 61 confirmed BAs and 55 additional candidate BAs in human pooled fecal samples. It has been successfully applied to fecal BA analysis in obese populations, providing valuable insights into potential therapeutic strategies for obesity.

Tandem Mass Spectrometry↗

PubMed2026

Transcriptomic insights into exogenous fatty acid-enhanced halotolerance in Zygosaccharomyces rouxii.

BACKGROUND: High salinity restricts microbial growth during brine-based food fermentation. Although exogenous unsaturated fatty acids improve the salt tolerance of Zygosaccharomyces rouxii, the associated transcriptional mechanisms remain unclear. This study investigated the transcriptomic response of Z. rouxii CGMCC 3791 to palmitoleic acid (C16:1) under high salt conditions. RESULTS: Cells were cultured in yeast extract peptone dextrose (YPD) containing 120 g L-1 NaCl, with or without 20 μg mL-1 C16:1. They were analyzed by RNA sequencing. Principal component analysis clearly separated the two treatments. Using q < 0.05 and |log2 fold change| > 1, 23 differentially expressed genes were identified - three upregulated and 20 downregulated. INO1, MLS1, POX1, MEP2, and SOD5 were among the major responsive genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that peroxisome-associated functions, lipid metabolism, oxidative stress responses, nitrogen utilization, and mitogen-activated protein kinase (MAPK) signaling were the principal C16:1-responsive processes. CONCLUSION: Exogenous C16:1 elicited a focused transcriptional adjustment rather than broad transcriptome-wide reprogramming in salt-stressed Z. rouxii. The results indicated that peroxisome-linked lipid processes and redox regulation were candidate mechanisms underlying fatty-acid-associated halotolerance and provided targets for improving the robustness of high-salt food fermentation. © 2026 Society of Chemical Industry.

Zygosaccharomyces rouxii↗

PubMed2026

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans↗

PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗

PubMed2026

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (β = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans↗