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Visceral fat has weaker beige adipogenesis than subcutaneous fat with unclear mechanisms. The Wilms tumour gene (Wt1), a visceral adipocyte marker, is highly expressed in visceral adipose tissue (VAT) and visceral adipose-derived stem cells (vADSCs). In our present study, we found its protein levels in VAT decreased under high-fat diet or dexamethasone treatment, but rised in cold exposure or β3-adrenergic receptor agonist treatment, and positively correlate with uncoupling protein-1 (UCP1). Wt1 knockdown in vADSCs elevated PR domain containing 16 (PRDM16) and UCP1 mRNA but reduced their protein levels, alongside decreased ubiquitin-conjugating enzyme 9 (UBC9). Knockdown of UBC9 did not affect the mRNA levels of Wt1, PRDM16 or UCP1, but significantly reduced PRDM16 and UCP1 protein levels. Glucocorticoids including hydrocortisone, methylprednisolone and dexamethasone (Dex) dose-dependently suppress Wt1, UCP1, Alpha-enolase (ENO1) and Pyruvate kinase muscle isozyme M2 (PKM2) levels, which could be reversed by Wt1 overexpression. These findings explore the effects of Wt1 on beige remodelling of visceral adipose which might be related to the up-regulation of UBC9, and provide clues for treating abdominal obesity caused either by HFD or by glucocorticoids in a non-sympathetic-dependent manner.

Hypoxia drives pulmonary artery smooth muscle cells (PASMCs) proliferation and phenotypic remodeling, processes central to vascular adaptation. Yaks, native to high-altitude environments, provide a natural model for studying cellular responses to chronic hypoxia. In this study, hypoxic exposure enhanced yak PASMCs proliferation and induced phenotypic transformation. Transcriptome profiling revealed that hypoxia suppresses microRNA-206 (miR-206), a regulator of vascular smooth muscle homeostasis. Loss of miR-206 activated the HIF-1α/BNIP3-dependent mitophagy pathway, increased mitophagy levels, and accelerated cell-cycle progression. Restoration of miR-206 reversed these effects, confirming its inhibitory role. Mechanistically, miR-206 directly targets the HIF-1α/BNIP3 signaling axis, linking noncoding RNA regulation to mitochondrial quality control under low oxygen. These findings define a miR-206-HIF-1α/BNIP3 regulatory circuit that coordinates mitophagy and phenotypic remodeling in yak PASMCs. This mechanism highlights the contribution of miRNA-mediated mitochondrial regulation to hypoxia adaptation and offers new insight into pulmonary vascular remodeling in high-altitude mammals.

Ferroptosis has recently been implicated in seizure-induced neurodegeneration, whereas enhanced aerobic glycolysis during seizures may aggravate oxidative stress and ferroptotic damage. This study investigated whether inhibition of aerobic glycolysis suppresses ferroptosis through activation of the AMP-activated protein kinase (AMPK)-Forkhead box O3a (FoxO3a) signaling pathway in epileptic rats. A pilocarpine (PILO)-induced epilepsy model was established in male Wistar rats. Animals were treated with the aerobic glycolysis inhibitor 2-deoxy-D-glucose (2-DG), with or without the AMPK inhibitor Compound C. Behavioral evaluation, Morris water maze testing, biochemical assays, immunohistochemistry, quantitative real-time PCR, western blotting, and mitochondrial membrane potential analyses were performed. Epileptic rats exhibited significant upregulation of pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1 (PDK1), and lactate dehydrogenase A (LDHA), indicating enhanced aerobic glycolysis in the hippocampus. Treatment with 2-DG significantly reduced seizure severity and improved spatial learning and memory. Moreover, inhibition of aerobic glycolysis markedly decreased Fe²⁺ and malondialdehyde (MDA) accumulation, restored glutathione (GSH) and glutathione peroxidase 4 (Gpx4) levels, preserved mitochondrial membrane potential, and enhanced AMPK and FoxO3a activation. These protective effects were substantially reversed by Compound C administration. Inhibition of aerobic glycolysis attenuates seizure-induced ferroptosis through activation of the AMPK-FoxO3a pathway. These findings establish a mechanistic link between metabolic reprogramming and ferroptosis in epilepsy and suggest that targeting aerobic glycolysis may represent a promising therapeutic strategy for neuroprotection in epilepsy.

Tamoxifen (TAM) resistance limits favorable outcomes in patients with breast cancer. Bioinformatics results suggest that the miR-548as-5p/nuclear factor kappa B1 (NF-κB1) axis may regulate TAM resistance. The aim of this study was to investigate the role of the miR-548as-5p/NF-κB1 axis in TAM resistance. We successfully established a TAM-resistant MCF-7 (MCF-7/TamR) breast cancer cell line and calculated its TAM resistance index. The expression levels of miR-548as-5p and NF-κB1 in MCF-7/TamR cells were analyzed. By regulating the expression levels of miR-548as-5p and NF-κB1, the apoptosis rate and TAM resistance of MCF-7/TamR cells were analyzed in vivo and in vitro. The expression level of miR-548as-5p was considerable decreased, whereas that of NF-κB1 was markedly increased in the MCF-7/TamR cell line. The knockdown of miR-548as-5p in MCF-7/TamR cells decreased apoptosis following TAM treatment, whereas overexpression increased apoptosis. Reduced expression of miR-548as-5p increased NF-κB1 expression, thereby enhancing the resistance to TAM. Overexpression of miR-548as-5p partially restored TAM sensitivity and markedly increased apoptosis of MCF-7/TamR cells, whereas additional overexpression of NF-κB1 reversed these effects. These results were validated in vivo using a mouse model. The miR-548as-5p/NF-κB1 axis may represent a novel therapeutic target for reducing TAM resistance in breast cancer.

Environmental chemical exposure has emerged as an important modulator of cancer progression and therapeutic outcomes. Di-2-ethylhexyl phthalate (DEHP), a ubiquitous environmental plasticizer, has been widely recognized for its endocrine-disrupting effects; however, its impact on intracellular signaling reprogramming and cancer drug responsiveness remains incompletely understood. In this investigation, we aimed to elucidate the toxicological mechanisms by which DEHP alters cellular phenotypes and therapeutic sensitivity in hepatocellular carcinoma (HCC) cells. We demonstrate that DEHP exposure does not primarily promote cancer cell proliferation but instead induces epithelial-mesenchymal transition (EMT), leading to enhanced migratory and invasive capacities and reduced responsiveness to the tyrosine kinase inhibitor lenvatinib. Notably, integrative bioinformatic analyses combined with functional validation identified sperm-associated antigen 4 (SPAG4) as a key DEHP-responsive regulator mediating toxicant-induced cellular reprogramming. Mechanistic studies revealed that DEHP-induced upregulation of SPAG4 activates the MAPK/ERK signaling pathway, thereby driving EMT and attenuating lenvatinib responsiveness. Genetic silencing of SPAG4 or pharmacological inhibition of MAPK/ERK signaling effectively reversed DEHP-induced EMT and drug resistance. In conclusion, we highlight DEHP as a signaling-disrupting environmental toxicant that reprograms cancer cell states and modulates therapeutic responses through a SPAG4-dependent MAPK/ERK pathway. These findings provide mechanistic insight into how environmental chemical exposure can reshape intracellular signaling networks and influence cancer treatment outcomes, underscoring a previously underappreciated aspect of chemical toxicology.

the prevalence of childhood overweight and obesity has steadily increased over the past two decades, both in Spain and globally. The COVID-19 pandemic disrupted lifestyles, impacting children's diet and physical activity. we retrospectively analyzed the evolution of weight and BMI (body mass index) in 563 children aged 4 to 14 years, comparing three periods: pre-pandemic (until 2019), pandemic (2021-2022), and post-pandemic (2023-2024). before 2020, a significant weight gain trend was already present: weight Z-scores increased by +0.21 SD (standard deviations) between the ages of 4 and 6. The lockdown drastically accelerated weight gain; weight Z-scores increased by up to +0.41 SD between the ages of 4 and 6 in the immediate post-lockdown phase, nearly doubling the baseline trend. Two years later, in the late post-pandemic phase, a partial reduction in weight was observed (-0.20 SD at age 14), indicating that weight gain has not been fully reversed. The consolidation of excess weight was also found: the combined rates of overweight and obesity (BMI Z-score > +1 SD) had increased: 42.2 % at age 12 and 40.5 % at age 14. a significant weight gain was observed during the pandemic, especially in younger children, with partial persistence. The sustained increase in overweight and obesity rates highlights the urgent need for preventive strategies and monitoring of lifestyle habits in the pediatric population.

Thromboembolism is a serious complication of nephrotic syndrome and occurs disproportionately in membranous nephropathy (MN). Whether anti-phospholipase A2 receptor (PLA2R) antibodies and complement activation directly promote endothelial dysfunction and thrombosis is unclear. In a retrospective cohort of biopsy-proven MN (n=45 with thromboembolism; 1:2 time-selected controls), we quantified anti-PLA2R antibodies, C3a, and C5a and analyzed their associations with thromboembolic events. Using human umbilical vein endothelial cells (HUVECs), we tested MN plasma, purified anti-PLA2R IgG (including IgG4), and IgG fragments, and interrogated Fc and complement receptor pathways. Readouts included pro/anti-coagulant factor expression, inflammasome/pyroptosis activation, and secreted mediators. Anti-PLA2R levels were higher in patients with thromboembolism than in those without and correlated with D-dimer and fibrin degradation products. A ROC-derived threshold of 92RU/mL was associated with greater thromboembolic risk. MN plasma and anti-PLA2R IgG induced a dose- and time-dependent procoagulant phenotype in HUVECs, upregulating tissue factor (TF), ICAM-1, and PAI-1 and increasing supernatant TF and sICAM-1. The Fc fragment reproduced these effects, whereas F(ab')2 did not. Anti-PLA2R colocalized with FcγRI; FcγRI silencing abrogated procoagulant responses and reduced NLRP3, caspase-1 p20, GSDMD-N, IL-1β, and IL-18. The NLRP3 inhibitor similarly suppressed pyroptosis and procoagulant readouts. Complement anaphylatoxins C3a/C5a further increased TF/ICAM-1 via C3aR/C5aR, and antagonists reversed MN-plasma-induced effects. Anti-PLA2R antibodies promote endothelial pyroptosis and a TF-high procoagulant phenotype through FcγRI signaling in vitro.Complement signaling amplifies this response. Targeting FcγRI-inflammasome pathways may mitigate thromboembolic risk in MN.

ADAMTS2, a secreted metalloproteinase essential for collagen maturation, exhibits context-dependent roles in cancer but remains uncharacterized in prostate cancer (PCa). Its potential involvement in PCa progression and underlying mechanisms are unknown. We integrated bioinformatic analysis of TCGA-PRAD data with clinical specimen validation, in vitro functional assays (proliferation, migration, invasion), co-immunoprecipitation (Co-IP), ferroptosis sensitivity testing, pharmacological inhibition, and in vivo xenograft models to investigate ADAMTS2's expression, function, and molecular mechanisms in PCa. ADAMTS2 was significantly upregulated in PCa tissues and cell lines, correlating with aggressive clinicopathological features and poor progression-free survival. Functionally, ADAMTS2 promoted PCa cell aggressiveness in vitro and tumor growth in vivo. Mechanistically, ADAMTS2 directly interacted with and upregulated COL1A1, leading to stimulation of the FAK/PI3K/AKT pathway. This cascade, in turn, enhanced the expression of ferroptosis defense proteins (SLC7A11 and GPX4), suppressed lipid peroxidation, and conferred resistance to ferroptosis. Pharmacological inhibition of FAK reversed both the oncogenic and anti-ferroptotic effects of ADAMTS2. Our investigation considers ADAMTS2 as a novel oncogenic driver in PCa that promotes tumor progression by reinforcing a tumor-permissive extracellular matrix through upregulation of COL1A1 and by stimulating the FAK/PI3K/AKT pathway to suppress ferroptosis. These findings position ADAMTS2 as a potential predictive biomarker and a valuable therapeutic target for defeating ferroptosis resistance in PCa.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by persistent pain. The mechanisms underlying pain in SCD are poorly understood and opioids remain the primary treatment, despite their severe side effects. Here we investigated the contribution of lysophosphatidic acid (LPA), an endogenous pronociceptive lipid mediator, to chronic pain in SCD using humanized transgenic homozygous Berkeley mice that express >99% human sickle hemoglobin (HbSS mice) and control HbAA mice that express normal human hemoglobin A. Hyperalgesia in HbSS mice was associated with an increase in both plasma level of LPA and expression of LPAR1 mRNA in L1-L5 dorsal root ganglion (DRG). Blocking LPA synthesis with BI-2545 or blocking LPA1 receptor (LPA1R) function with siRNA or the LPA1R antagonist, AM966, reversed mechanical and heat hyperalgesia in HbSS mice. LPA also produced acute mechanical and heat hyperalgesia in HbAA mice, which resulted from the sensitization of C-fiber nociceptors. In HbSS mice, hyperalgesia was associated with sensitization of nociceptive DRG neurons. Nociceptors from hyperalgesic HbSS mice had lower rheobase, more positive resting membrane potential and higher frequency of action potential. Although no changes were found in the values of inward currents in nociceptors of HbSS mice compared to HbAA mice, outward-inactivating and non-inactivating currents were reduced, indicating the importance of potassium channels to sensitization in SCD. All these parameters were normalized by pretreatment of HbSS mice with LPA1R siRNA. Our results suggest that LPA signaling may be a promising target for treating pain in SCD.

Hepatocellular carcinoma (HCC) is one of the most metastatic and aggressive malignancies. Circular RNAs (circRNAs) are associated with the pathogenesis and prognosis of HCC. This study aimed to explore the role of circ_0020236 in HCC progression. Expression levels of circ_0020236, miR-1825, and IKBKB were assessed in HCC clinical samples and cell lines using quantitative real-time PCR. Bioinformatics predictions combined with dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays validated molecular interactions. Functional assays, including CCK-8, colony formation, and Transwell migration, were employed to evaluate cell proliferation and migration. The results indicated that circ_0020236 and IKBKB were significantly downregulated, whereas miR-1825 was upregulated in HCC. Ectopic expression of circ_0020236 suppressed HCC cell proliferation, migration, and tumor growth in vivo. Mechanistically, circ_0020236 functioned as a molecular sponge for miR-1825, which directly targeted IKBKB. Rescue experiments showed that miR-1825 overexpression reversed the tumor-suppressive effects of circ_0020236, while IKBKB knockdown abrogated the inhibitory phenotype induced by miR-1825 silencing. Furthermore, the RNA-binding protein ESRP2 was identified as a positive regulator of circ_0020236 biogenesis. In conclusion, our findings reveal that the ESRP2/circ_0020236/miR-1825/IKBKB axis plays a critical role in inhibiting HCC progression, positioning circ_0020236 as a promising therapeutic target for HCC intervention.

The healthy gut microbiota communities play a complex and significant role in lipid absorption and deposition, leading to multiple health benefits. Here, we confirmed an impaired absorption and deposition function in germ-free pigs and mice, which was partially reversed after human fecal microbiota transplantation. By integrating single-cell data from adipose tissue, we identified HDAC9 as a key regulator, marked by the presence of a population of small mature adipocytes exhibiting high HDAC9 and low PPARγ expression in germ-free pigs. HDAC9 deficiency of preadipocytes drove FABP4/5-mediated lipid deposition by directly targeting PPARγ expression and acetylation modification. Finally, we verified the interaction between gut microbiota and host HDAC9/PPARγ/FABP4/5 signaling cascade might be microbial receptors (ie, Dectin1 or TLRs)-dependent rather than microbial metabolites. Altogether, our study uncovers the gut microbiota-HDAC9-PPARγ axis as a key regulator of adipocyte function and lipid deposition, offering a potential therapeutic target for lipid-related metabolic diseases.

Chemotherapy-induced ovarian damage poses a serious threat to female fertility and reproductive health, but effective and specific intervention methods remain lacking. Resveratrol liposomes was prepared using the thin-film evaporation-high-pressure homogenization method, and its particle size, PDI, zeta potential, and encapsulation efficiency were characterized. A CTX-induced ovarian injury model was established, with mice randomly divided into five groups: control group, model group, positive group, free resveratrol group, and resveratrol liposomes treatment group. Ovarian function and mechanisms were evaluated through HE staining, hormone assays, oxidative stress indicators, mitochondrial membrane potential detection, western blot, immunohistochemistry, and TUNEL staining. The study found that Res-Lipo treatment significantly improved ovarian tissue morphology, reversed the decrease in serum AMH and increase in FSH caused by CTX. Additionally, resveratrol liposomes specifically upregulated the expression of HIGD1A protein in ovarian tissue, inhibited the phosphorylation and nuclear translocation of NF-κB p65, while also elevating SOD2 protein levels. Consequently, it markedly enhanced ovarian antioxidant enzyme activity, reduced oxidative stress, improved mitochondrial membrane potential, and decreased ovarian granulosa cell apoptosis. This study confirms that resveratrol liposomes can effectively alleviate chemotherapy-induced ovarian mitochondrial oxidative stress damage and dysfunction by activating HIGD1A, inhibiting NF-κB overactivation, and upregulating SOD2 expression.

The replicative senescence during in vitro expansion severely limits the clinical application of human umbilical cord mesenchymal stem cells (hUC-MSCs). Existing senescence assessment methods still face significant limitations in terms of noninvasive and real-time quantification. In this study, using atomic force microscopy (AFM), we systematically characterized the nanomorphology and mechanical properties of naive and senescent hUC-MSCs. The results revealed that senescent cells exhibited significantly increased height, surface roughness, adhesion, and elastic modulus compared to naive cells, along with enhanced bundling and formation of F-actin stress fibers. These findings show a new "senescence-associated mechanical phenotype" unique to hUC-MSCs. Notably, the hypoxic intervention effectively reversed these senescence-related mechanical changes, demonstrating the high sensitivity of AFM in detecting senescence. To achieve precise quantitative assessment of cell senescence, we also developed a deep learning model based on a variational autoencoder (VAE), which successfully established continuous low-dimensional representations of the age-related mechanical phenotype. This work exhibited excellent predictive performance and generalization ability under different culture conditions, enabling accurate prediction and early identification of hUC-MSCs senescence.

Recent methods have been developed to map single-cell lineage statistics to population growth. Because population growth selects for exponentially rare phenotypes, these methods inherently depend on sampling large deviations from finite data, which introduces systematic errors. A comprehensive understanding of these errors in the context of finite data remains elusive. To address this gap, we study the error in growth rate estimates across different models. We show that under the usual bias-variance decomposition, the bias can be decomposed into a finite-time bias and nonlinear averaging bias. We demonstrate that finite-time bias, which dominates at short times, can be mitigated by fitting its monotonic behavior. In contrast, at longer times, nonlinear averaging bias becomes the predominant source of error, leading to a phase transition. This transition can be understood through the Random Energy Model, a mean-field model of disordered systems, where a few lineages dominate the estimator. Applying these methods to experimental data demonstrates that correcting for biases in lineage-based approaches yields consistent results for the long-term growth rate across multiple methods and enables the reverse-engineering of dynamic models. This new framework provides a quantitative understanding of growth rate estimators, clarifies the conditions under which they can be effectively applied to finite data, and introduces model-free approaches for studying the connections between physiology and cell growth.

High seed vigor is an important trait for successful seed germination and seedling establishment in rice. However, the underlying regulatory mechanism remains unclear. In this study, we identified the stress associated protein gene OsSAP3 as a key regulator of seed vigor. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that OsSAP3 is highly expressed during seed development and germination, with its expression further induced by abscisic acid (ABA) during germination. Knockout of OsSAP3 resulted in reduced reserve mobilization capacity during rice seed germination, elevated expression levels of ABA signaling transduction genes, and enhanced sensitivity to ABA, ultimately leading to decreased seed vigor. Meanwhile, Ossap3 seeds narrowed the appropriate germination temperature range, which is due to their lower endogenous hydrogen peroxide (H2O2) levels. Exogenous H2O2 treatment could restore the seed vigor of Ossap3 by accelerating ABA degradation, suppressing ABA signaling, and enhancing starch mobilization via α-amylase-mediated hydrolysis to increase soluble metabolites. These regulatory mechanisms mediated by OsSAP3 are crucial for enhancing rice seed vigor and broadening temperature adaptability during seed germination, providing critical insights into the molecular mechanisms underlying seed vigor regulation.

Parkinson's disease is a progressive neurodegenerative disorder marked by dopaminergic neuron loss in the substantia nigra, pathological α-synuclein aggregation, and persistent neuroinflammation. Current therapies mainly offer symptomatic relief but do not halt or reverse disease progression, largely because of the restrictive blood-brain barrier. Exosomes, naturally occurring nanoscale vesicles, possess key attributes such as biocompatibility, low immunogenicity, and the capacity to cross the blood-brain barrier. In Parkinson's disease, exosomes have a dual role: they propagate α-syn pathology and amplify inflammatory signaling, accelerating disease progression; conversely, they can be engineered as carriers of neurotrophic factors, microRNAs, or small-molecule drugs, conferring neuroprotective and anti-inflammatory benefits. This review examines current strategies for exosome engineering, with emphasis on surface modification and optimized cargo loading. However, clinical translation remains hindered by suboptimal delivery efficiency, limited brain accumulation, potential immunogenicity, exosome heterogeneity, and regulatory barriers. Future research should prioritize high-affinity targeting ligands, multimodal delivery platforms, deeper insights into blood-brain barrier translocation, and integration with regenerative medicine approaches. These advancements are essential for standardized large-scale production and personalized therapies, ultimately advancing precision medicine in Parkinson's disease.

Impaired immune clearance of senescent fibroblasts is a putative driver of pulmonary fibrosis. Exhausted natural killer (NK) cells have been implicated in this process, yet the underlying immune evasion mechanisms remain poorly understood. Using single-cell RNA sequencing (scRNA-seq) and spectral flow cytometry, we identified natural killer group 2 member A (NKG2A) as the predominant inhibitory checkpoint receptor expressed on NK cells in fibrotic lung diseases. Mechanistic in vitro coculture studies showed that NK cell suppression was mediated by senescent fibroblasts expressing human leukocyte antigen-E (HLA-E), the high-affinity ligand for NKG2A. scRNA-seq analysis of lungs from patients with idiopathic pulmonary fibrosis (IPF) further identified selective HLA-E expression in senescent HAS1+ fibroblast subsets. Further, spatial transcriptomics and multiplex immunofluorescence of patient lungs demonstrated that HLA-E+ fibroblasts were positioned at the periphery of fibroblast foci adjacent to NKG2A+ NK cells, establishing an immune-privileged niche. In contrast, extracellular matrix-producing myofibroblasts at the core of fibrotic foci lacked HLA-E and exhibited minimal NK engagement. In vivo, therapeutic blockade of NKG2A restored NK cell function, promoted clearance of senescent fibroblasts, and promoted fibrosis resolution in the bleomycin-induced mouse model. Monalizumab, a clinical-grade NKG2A inhibitor, reactivated patient-derived NK cells and enhanced lysis of human senescent fibroblasts in vitro. Together, these findings uncover a spatially restricted immune checkpoint axis that allows senescent fibroblasts to evade immune NK surveillance. Targeting the HLA-E/NKG2A axis represents a promising therapeutic strategy to restore NK cell-mediated immune clearance of senescent fibroblasts and reverse pulmonary fibrosis.

The antibacterial strategy that utilizes ultraviolet-A (UVA)-irradiated natural photosensitizers is promising, being particularly effective against multidrug-resistant pathogens with high bactericidal efficiency and minimal resistance-inducing risk. Rutin is a natural flavonoid with wide availability, low cytotoxicity, and diverse pharmacological activities, making it a promising photosensitizer; however, its UVA-induced photodynamic antibacterial properties remain underexplored. The aim of this study is to systematically evaluate the antibacterial efficacy and mechanism of UVA-Rutin against foodborne Escherichia coli O157:H7. In the study, Fourier transform infrared spectroscopy and Raman spectroscopy were used to characterize structural alterations in rutin post-UVA irradiation, focusing on functional groups relevant to photodynamic activity. Antibacterial efficacy was assessed via standardized assays including minimum inhibitory concentration (MIC) determination, while biocompatibility was evaluated using MTT cytotoxicity assays. To confirm the antibacterial effects, physiological/structural perturbations of bacteria were measured, including cell membrane integrity, DNA damage, motility, biofilm formation, and extracellular polysaccharide (EPS) production, as well as the generation of intracellular reactive oxygen species (ROS) measured using fluorescent probes. Reverse transcription quantitative polymerase chain reaction was used to analyze key virulence- and quorum sensing-related genes (luxS, phoP, qseB, qseC). Results showed that UVA-induced structural changes enhanced the photosensitizing activity of rutin. UVA-Rutin exhibited significant antibacterial activity (low MIC) and good biocompatibility, triggering the generation of massive intracellular ROS, disrupting cell membranes, inducing DNA damage, impairing motility, inhibiting biofilm/EPS production, and downregulating target genes. Collectively, UVA-Rutin exerts potent antibacterial effects via ROS-mediated structural/functional disruption and virulence gene regulation, highlighting its potential as a novel food industry antibacterial agent.

Prevention remains a key strategy to address the growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD), highlighting the importance of exploring modifiable risk factors. Accumulating evidence suggests a close link between physical frailty and MASLD. However, how frailty interacts with metabolic syndrome to affect MASLD and the causality and direction of the association remain largely unknown. Leveraging data from 405,224 UK Biobank participants with a 13.65-year follow-up, we found that physical frailty was associated with an increased risk of clinically diagnosed MASLD and exacerbated the adverse effect of metabolic syndrome on MASLD incidence, implying that frail people may be more vulnerable to this disease because of metabolic syndrome. Mendelian randomization provided evidence for a potential causal effect of physical frailty on MASLD but not the reverse direction. Moreover, the metabolome-wide association analysis revealed widespread associations of plasma metabolites with both frailty and MASLD, suggesting a shared metabolomic foundation between them. Some metabolites, including fatty acids and triglyceride-rich lipoprotein biomarkers, partially explained the frailty-MASLD relationship, indicating a potential metabolomic mechanism. If confirmed in further studies, frailty screening may help identify high-risk individuals and inform early prevention for MASLD, especially for those with metabolic syndrome.