👤 Jinyan Guo

Aortic aneurysm (AA) is a life-threatening vascular disease with high fatality upon rupture. While physical activity (PA) reduces cardiovascular risk, its role in AA prevention remains uncertain, particularly when assessed objectively. We analyzed 93,165 UK Biobank participants (56% women; median age 57 years) with valid 7-day wrist-worn accelerometer data. PA was categorized as light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA). Diagnosed AA was ascertained through linked hospital, death, and primary care records. Cox models estimated hazard ratios (HRs) for AA across quartiles and per-standard deviation (SD) increments, with adjustment for demographic, lifestyle, and cardiometabolic factors. Over a median 7.9-year follow-up, 499 clinically recorded AA cases occurred. Higher accelerometer-measured PA was inversely associated with AA risk. Per-SD increments in total PA, MPA, VPA, and MVPA corresponded to 17%, 22%, 19%, and 23% lower risks, respectively. Compared with the lowest quartile, the highest MVPA quartile had a 44% lower AA risk (HR = 0.56, 95% CI 0.42-0.76). Subtype analyses revealed stronger protective effects for abdominal aortic aneurysm (AAA) than thoracic aortic aneurysm (TAA), while LPA was not significantly associated. These findings demonstrate that higher levels of accelerometer-measured MVPA are robustly associated with a decreased risk of clinically detected AA in a dose-dependent manner. The associations were particularly pronounced for AAA. This study provides objective evidence supporting the potential benefits of MVPA for aortic health. Show less

Older adults in nursing homes generally face psychological adaptation problems such as depression and anxiety. This study aimed to identify social relationship profiles among nursing home residents and explore their associations with depression and anxiety. A cross-sectional study was conducted between June and October 2023 among 1108 older residents from 42 nursing homes in Fujian Province, China. Social relationships were assessed using the Social Support Rating Scale (SSRS) and the Lubben Social Network Scale-6 (LSNS-6). Depressive-anxiety symptoms were measured using the Geriatric Depression Scale-Short Form and the Self-Rating Anxiety Scale (SAS), respectively. Latent Profile Analysis (LPA) was performed to identify distinct social relationship profiles, and ANOVA/ANCOVA were used to examine differences in depression and anxiety across profiles. The LPA analysis identified six distinct social relationship profiles. The "Low social support/low social network group" (24.7%) was the most prevalent, showing significantly higher levels of depression and anxiety compared to the others. The "Moderate social support/moderate friend network group" (20.9%) demonstrated an intermediate and balanced social relationship characteristic. When compared to the "Moderate-low social support/high friend network group" (8.1%) and the "Moderate-high social support/low friend network group" (18.1%), despite these two groups scoring higher or above-average in specific dimensions of social support or friend network, they still showed higher levels of depression than the "High social support/high social network group" (15.1%) and the "High social support/super high social network group" (13.1%). Social relationship profiles among nursing home residents are heterogeneous and significantly associated with depressive-anxiety symptoms. Show less

Enzyme immobilization is critical for enhancing enzyme stability and reusability. Catalytically active inclusion bodies (CatIBs) have emerged as a promising immobilization strategy due to their straightforward production, ease of separation, and high purity. Unlike traditional cross-linked enzyme aggregates (CLEAs) that require a precipitation step, CatIBs form through carrier-free self-aggregation during expression. To overcome the limitations of conventional methods, a novel technique has been developed in this study, focusing on L-phenylserine aldolase (LPA) as the model enzyme. A hybrid tag (HLHLHL) was fused to the N-terminus of LPA to generate 3HL-LPA, which promotes the formation of active inclusion bodies. Based on structural prediction and surface properties, the active aggregation process of 3HL tags through electrostatic interactions and hydrophobic interactions was analyzed. Innovatively, we combined CatIBs and CLEAs technologies to develop novel CatIBs-CLEAs. For comparison, a control was prepared by fusing a hexahistidine tag (HHHHHH) to LPA's N-terminus (6H-LPA) to enhance soluble expression, followed by conventional CLEAs preparation. Results showed that CatIBs-CLEAs achieved an activity recovery of 69.87% after glutaraldehyde crosslinking, significantly higher than the 48.1% for conventional CLEAs. CatIBs-CLEAs also exhibited superior thermal stability across temperatures, high stability between pH 5-9, and retained over 70% activity after seven batch cycles. The integrated CatIBs-CLEAs technology combines the production advantages of CatIBs with the stability benefits of CLEAs, offering a promising strategy for designing efficient, robust industrial biocatalysts with broad application potential. Show less

To investigate the association between quantitative retinal vascular parameters and coronary artery disease (CAD) and to evaluate the efficacy of a retinal phenotype-based diagnostic model as a non-invasive tool for early CAD screening. A retrospective cross-sectional study. A single-centre study conducted at the Cardiovascular Center of Beijing Tongren Hospital, Capital Medical University, China, between January and October 2024. 417 patients with suspected angina undergoing their first coronary angiography (CAG) were enrolled. Inclusion criteria were age >18 years and high-quality fundus photography within 24 hours pre-CAG. Major exclusions were prior coronary interventions, severe systemic/valvular heart diseases and ocular conditions impairing retinal vascular visualisation. The primary outcome was the association between quantitative retinal vascular parameters and the presence of CAD (defined as ≥50% stenosis). Secondary outcomes included the diagnostic performance area under the receiver operating characteristic curve (AUROC) of three predictive models: one based on quantitative retinal vascular parameters alone, one based on traditional risk factors and a combined model integrating both retinal and clinical variables. This study enrolled 417 patients undergoing initial CAG. Compared with non-CAD controls (n=190), patients with CAD (n=227) had higher prevalence of hypertension, dyslipidaemia and diabetes, along with elevated levels of fasting blood glucose, lipoprotein(a) (Lp(a)), triglyceride (TG) and glycated haemoglobin (HbA1c) (all p<0.05). Quantitative fundus analysis revealed that multiple retinal vascular parameters were independently associated with CAD after multivariable adjustment, including fractal dimension (FD), vessel density (VD) and specific zonal measures of vessel diameter and tortuosity (all p<0.05). Multivariable logistic regression incorporating both fundus and clinical variables identified the following independent predictors of CAD: a decrease in FD (OR=0.26, 95% CI 0.16 to 0.41, p<0.01), reduced optic disc long-to-short axis ratio (OR=0.04, 95% CI 0.004 to 0.46, p=0.01) and optic disc-to-macula distance (OR=0.91, 95% CI 0.86 to 0.97, p<0.01), male sex, dyslipidaemia and elevated levels of Lp(a), TG, low-density lipoprotein cholesterol and HbA1c (all p<0.05). The final diagnostic model achieved an AUROC of 0.802 (95% CI 0.76 to 0.845), with a sensitivity of 0.797 and a specificity of 0.679 at the optimal cut-off. Internal validation via bootstrap resampling (1000 iterations) confirmed the robustness of the identified predictors. Our findings, derived from an artificial intelligence-based fully automated quantitative retinal vascular parameters measurement method, revealed that multiple quantitative fundus parameters-including FD, VD and other morphological parameters were significantly associated with CAD risk. The CAD diagnostic model we developed demonstrates strong performance and high interpretability, making it suitable for early CAD screening and diagnosis. Show less

Given that abnormal lipid metabolism is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), this study seeks to investigate the relationship between serum lipoprotein(a) [Lp(a)] levels and the progression or regression of MASLD. A total of 12,962 participants undergoing transient elastography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University were included in the first cross-sectional study (Study 1). The longitudinal study (Study 2) included 17,661 individuals from the same center, each with at least two health check-ups involving abdominal ultrasonography. Another cross-sectional study (Study 3) included 5,927 individuals from the UK Biobank cohort who had undergone both magnetic resonance imaging proton density fat fraction (MRI-PDFF) and Lp(a) testing. Cross-sectional analysis (Study 1) revealed that elevated Lp(a) levels were inversely correlated with the severity of both hepatic steatosis and fibrosis. Longitudinal data (Study 2) further demonstrated that baseline serum Lp(a) levels were decreased in participants with the incident of MASLD, while increased in participants with the regression of MASLD during the follow-up period. A lower baseline Lp(a) level was an independent factor for new-onset MASLD and non-regression of MASLD: the fully adjusted hazard ratios (HR) were 0.895 (95%CI 0.834-0.962, Serum Lp(a) levels are inversely associated with both the progression and regression of MASLD, indicating its potential role in reflecting disease dynamics. Show less

In recent years, the global incidence of Non-Suicidal Self-Injury (NSSI) has risen, posing a significant challenge in public health. Adolescents are the main group affected. A cross-sectional study was conducted using a self-administered questionnaire to collect data from 6,311 adolescents in Hefei, China. This study employed the Compositional Isotemporal Substitution Model (CISM, a statistical method that estimates health effects of replacing time in one behavior with another while accounting for the interdependent, compositional nature of 24-h time-use data) to examine the impact of Screen Time (ST), Non-Screen-based Sedentary Time (NSST), Physical Activity, and Sleep Time on NSSI among adolescents. Compositional logistic regression analysis revealed that, relative to the remaining behavioral components, higher Light Physical Activity (LPA) ( The findings highlight those reasonably allocating adolescents' daily activities, reducing ST, can help lower the risk of NSSI among adolescents. Show less

Nursing interns often face maladjustment during the early stages of clinical practice, which not only directly affects their physical and mental health as well as work efficiency but also significantly inhibits their proactive feedback-seeking behavior (FSB). As an active self-regulation strategy, FSB can enhance interns' work initiative and promote role transition. However, existing research has yet to thoroughly investigate the potential heterogeneity and categorical characteristics of FSB within this population, and the role of psychological resources such as career adaptability in shaping these patterns requires further investigation. To investigate the status of FSB in early-stage nursing interns, identify latent subgroups via latent profile analysis (LPA), and analyze associated factors, thereby providing evidence for targeted clinical educational interventions. Multicenter cross-sectional research. This study employed a multistage stratified cluster sampling to survey 1,308 early-stage nursing interns from nine universities in Hubei, China, between June and September 2024. Data were collected using a demographic questionnaire, Feedback-Seeking Behavior Scale, and Career Adapt-Abilities Scale. LPA was employed to delineate FSB profiles and multivariate logistic regression analysis to examine the associated predictors. A total of 1,370 questionnaires were distributed, with 1,308 valid responses, yielding an effective response rate of 95.47%. The mean score on the feedback-seeking behavior scale was 5.06 ± 1.08. LPA identified three distinct feedback-seeking profiles: low (20.87%), moderate (38.3%), and high (40.83%). Education level, student cadre experience, internship hospital type, and career adaptability were significant predictors of profile membership ( FSB among early-stage nursing interns exhibited heterogeneity. Nursing educators and managers should implement tiered interventions: for the low and moderate feedback-seeking groups, career guidance and feedback awareness cultivation should be strengthened; for the high feedback-seeking group, peer modeling should be encouraged. This strategy can enhance proactive FSB, supports role transition and professional identity, and promotes long-term nursing workforce stability. Show less

Cardiovascular disease (CVD) is the leading cause of death among older adults, with sedentary behavior (SB) as a key modifiable risk factor. While physical activity (PA) is associated with cardiovascular health, evidence remains limited on the specific effects of replacing SB with PA of varying intensities. To systematically review evidence on the cardiovascular effects of substituting SB with PA in adults aged 65 and older using isotemporal substitution modeling (ISM). Following PRISMA guidelines, seven databases were searched up to April 2025. Risk of bias was assessed using the JBI tool, and a narrative synthesis was conducted. Eighteen observational studies (15 cross-sectional, 3 cohorts) using ISM were included. Replacing 10-60 min of SB with moderate-to-vigorous PA (MVPA) was associated with more favorable in blood pressure, triglycerides, waist circumference, inflammatory markers (CRP, IL-6, GDF-15), and insulin sensitivity (HOMA-IS, Matsuda-ISI). Light-intensity PA (LPA) showed modest associations, particularly among frail or mobility-limited individuals. A daily substitution of 30 min was identified as a feasible reference window, with ≥60 min linked to additional vascular and autonomic benefits. Replacing SB with PA, especially MVPA, was consistently associated with favorable cardiovascular profiles in older adults. Even brief substitutionsmay be beneficial, supporting intensity-stratified public health strategies and refinement of physical activity guidelines for aging populations.Because most included studies were cross-sectional, these findings should be interpreted as associations rather than definitive causal effects, and reverse causation remains a plausible concern. https://www.crd.york.ac.uk/prospero/view/CRD420251021829/1/0, PROSPERO CRD420251021829. Show less

Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to investigate the combined effect of elevated Lp(a) and DM on survival outcomes in CAD patients. This study included 65 547 CAD patients (62.6 ± 10.7 years, 27.7% female) from CIN-II and RED-CARPET cohorts. Patients were stratified into four groups by Lp(a) levels (< or ≥ 30 mg/dL) and DM status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality, examining additive and multiplicative interactions. During a median follow-up of 5.5 years, 10 686 (16.3%) patients died from all causes and 5106 (7.8%) died from cardiovascular causes. Patients with Lp(a) ≥ 30 mg/dL and DM were independently associated with cardiovascular mortality (adjusted hazard ratio [aHR]: 1.28, 95% CI: 1.20-1.35; aHR: 1.53, 95% CI: 1.44-1.62, all p < 0.001, respectively). Compared to patients with Lp(a) < 30 mg/dL without DM, the aHRs were 1.26 (95% CI: 1.16-1.36, p < 0.001), 1.51 (95% CI: 1.40-1.62, p < 0.001) and 2.00 (95% CI: 1.83-2.18, p < 0.001) for those with Lp(a) ≥ 30 mg/dL without DM, Lp(a) < 30 mg/dL with DM and Lp(a) ≥ 30 mg/dL with DM, respectively. Significant additive interaction between elevated Lp(a) and DM on cardiovascular mortality was observed, with 12% of the excess risk attributed. Similar associations were observed in all-cause mortality. In patients with CAD, elevated Lp(a) and DM act synergistically to increase the risk of cardiovascular and all-cause mortality, suggesting that both risks should be considered to integrate management. Show less

This study employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through convenience sampling, 260 breast cancer chemotherapy patients aged 18-74 years from a tertiary hospital in Henan Province were recruited between May 2024 and January 2025. Data were collected using a general demographic questionnaire, the Learned Helplessness Scale, the Brief Illness Perception Questionnaire, the Social Support Rating Scale, and the General Self-Efficacy Scale. An LPA was applied to classify learned helplessness patterns, followed by a multivariate logistic regression to determine the influencing factors. The latent profile analysis revealed three distinct profiles of learned helplessness among breast cancer patients undergoing chemotherapy: a "low helplessness-low hopelessness stable profile" (17.0%), a "moderate helplessness-moderate hopelessness fluctuating profile" (52.0%), and a "high helplessness-high hopelessness profile" (31.0%). The multivariable logistic regression revealed that age range 18-44 years, low monthly household income per capita, fatigue, and illness perception were significantly associated with the "high helplessness-high hopelessness profile" (P < 0.05). Conversely, the age range 45-59 years was significantly associated with the "moderate helplessness-moderate hopelessness fluctuating profile" (P < 0.001). Furthermore, experiencing ≤2 chemotherapy-related side effects, a higher level of perceived social support, and greater self-efficacy were significant predictors of membership in the "low helplessness-low hopelessness profile" (P < 0.05). Breast cancer chemotherapy patients were categorized into three distinct subgroups, which were influenced by age, income, fatigue, treatment side effects, illness perception, self-efficacy, and social support. Show less

TyHGB is a novel insulin resistance (IR)-related indicator, and its association with coronary heart disease (CHD) remains unclear. Additionally, studies have shown a close correlation between the diagonal earlobe crease (DELC) and CHD, yet it has not been fully applied in clinical practice to date. Therefore, this study constructed and validated a diagnostic model for CHD by combining TyHGB and DELC. A total of 1664 patients suspected of CHD who underwent coronary angiography (CAG) in the Department of Cardiology, Chengde Central Hospital from September 2021 to April 2025 were recruited for this study. Participants were categorized into a CHD group ( Age, sex, hypertension, diabetes, CR, Lp(a), TyHGB, and DELC were identified as independent risk factors for CHD through multivariate logistic regression analysis ( Both TyHGB and DELC have been identified as independent risk factors for CHD, with a linear relationship observed between TyHGB levels and CHD risk. A diagnostic model for CHD, developed by integrating TyHGB, DELC, and traditional risk factors, demonstrates strong diagnostic efficacy. The online version contains supplementary material available at 10.1186/s12944-026-02880-y. Show less

To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health literacy and promote LPA, thereby advancing healthy aging. This study used a convenience sampling method to select two residential neighborhoods. Subsequently, a random cluster sampling approach was employed, resulting in a total final sample of 105 community-dwelling older adults (aged 60 and above) from these neighborhoods. A three-axis accelerometer (ActiGraph wGT3X-BT) recorded the older adults' LPA, and the Electronic Health Literacy Scale assessed their e-health literacy. Multiple linear regression was used to explore the dose-response relationship between LPA and e-health literacy and sub-dimension scores. Multiple linear regression revealed that both the overall e-health literacy score and its components were positively associated with daily LPA (Tables 2 and 3). However, the empirical impact varied substantially across components. For each 1-point increase, LPA increased by 2.8 min for the overall score, 11 min for judgment ability, and 19.4 min for decision-making ability, whereas the effect of application ability was statistically significant but minimal. Notably, the effect sizes of all e-health literacy components were substantially smaller than that of educational attainment (β = 0.638-0.947), which was the strongest predictor in all models. This study provides empirical evidence that higher e-health literacy and its specific sub-dimensions are positively associated with light physical activity (LPA) among community-dwelling older adults, with educational attainment emerging as a key independent predictor. These findings suggest that public health interventions aimed at promoting LPA could be enhanced by incorporating strategies to improve e-health literacy, particularly targeting older adults with lower educational backgrounds. The development of tailored, theory-informed programs based on these insights holds promise for fostering healthy aging at the community level. Show less

Speed capability is critical for early childhood development, but troubling patterns are emerging in the motor fitness of Chinese preschoolers (3-6 years). This study investigated how compositional 24-h movement behaviours (sleep, sedentary behaviour [SB], light physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) relate to speed capability. Via compositional data analysis and isotemporal substitution modelling, we assessed relationships between 24-h movement behaviours (sleep, SB, LPA and MVPA) and speed capability in 275 preschoolers (mean age 4.98 ± 0.76 years). Participants completed 20-m sprint tests and 7-day accelerometry. Time-reallocation effects were quantified through pairwise behavioural substitutions (5- to 30-min durations), with all models adjusted for age, sex and BMI z scores (z-BMI). Higher relative MVPA time significantly predicted faster sprint times (β = -1.302, p < 0.001), while higher LPA predicted slower times (β = 1.570, p = 0.003). Reallocating 15 min from sleep, SB or LPA to MVPA reduced sprint times by 0.176, 0.201 and 0.385 s, respectively (all p < 0.05). Conversely, reallocating MVPA to other behaviours worsened performance. The effects exhibited asymmetry: displacing time away from MVPA impaired speed capability to a greater extent than equivalent gains in MVPA time improved it. MVPA is the strongest positive predictor of speed capability in preschoolers. Optimizing 24-h movement patterns by reallocating time from LPA or SB to MVPA is associated with enhanced speed performance, supporting targeted interventions for early childhood development. Show less

Tumor-related metabolites in the tumor microenvironment may induce immune dysfunction, leading to malignant progression and metastasis of tumors. Here, it is demonstrated that tumoral PLA2G16, a phospholipase catalyzes phospholipids to generate free fatty acid (FFA) or lysophosphatidic acid (LPA), is an important contributor to triple-negative breast cancer (TNBC) lung metastasis in an immune-dependent pattern by improving tetracosatetraenoic acid (C24:4 (n-6)) accumulation in the early metastatic niche of lung and impairing immune function of pulmonary CD8 Show less

To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in preschool-aged children. 268 preschoolers were included in the cross-sectional study. An accelerometer was used to assess sedentary behavior (SB), light and moderate-to-vigorous physical activity (LPA and MVPA). A parental report was used to collect sleep time. Bioelectrical impedance analysis was employed to assess body composition. Compositional linear regression analysis was employed to explore how daily movement behaviors were associated with body composition. Compositional isotemporal substitution analysis was employed to estimate changes in body composition after reallocating time among behaviors. 24-h movement behaviors composition significantly predicted fat-free mass index (FFMI), soft lean mass index (SLMI), and skeletal muscle mass index (SMMI), but not fat mass index, percent body fat, and bone mineral content index. The compositional isotemporal substitution analyses consistently showed that increasing MVPA at the expenses of SB was positively associated with FFMI (+0.328 kg/m The findings highlight the importance of MVPA in improving preschoolers' body composition. Increasing MVPA at the expenses of SB may be a strategy to improve body composition in preschoolers. Show less

The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable of altering the functionality of foods. This research investigated the effects of fermentation with different LAB, such as Lactobacillus acidophilus (LAC), Lactobacillus casei (LCA), Lactobacillus rhamnosus (LRH), Lactobacillus plantarum (LPL), and Lactobacillus bulgaricus (LBU), on the hypoglycemic activity and mechanism of polyphenols in highland barley. The hypoglycemic activity of the fermentation products was measured by in vitro antioxidant, enzyme activity, and glucose consumption experiments. Untargeted metabolomic analysis used UHPLC-Q Exactive HF-X/MS to reveal distinct metabolic profiles among the fermented groups. Molecular docking and western blot experiments were conducted to elucidate the mechanism underlying the hypoglycemic effect of fermentation products. Polyphenolic antioxidant activity in highland barley and its inhibitory activities against α-glucosidase and α-amylase were increased after LAC fermentation. Furthermore, the fermented extracts improved glucose consumption in HepG2 cells. The content determination and metabolomic analysis showed that fermented highland barley polyphenols were increased, and 113 differential phenolic metabolites were identified and annotated, among which 44 exhibited a significant upregulation compared with raw highland barley polyphenols. At the molecular level, the polyphenol extract upregulated PI3K and phosphorylated Akt expression in HepG2 cells. Overall, the results indicate that fermentation by LAC biotransformed highland barley polyphenols into smaller molecules with improved hypoglycemic activities, thereby enhancing their bioavailability. Show less

The primary renal complication of diabetes mellitus is diabetic kidney disease (DKD). The precise pathogenic mechanisms of DKD remain poorly elucidated. The aim of this study was to identify potential energy metabolism-related genes associated with DKD. The GSE30529 and GSE30528 datasets were retrieved from the Gene Expression Omnibus, and energy metabolism-related genes were obtained from the GeneCards database. Differentially expressed genes (DEGs) between DKD and control groups were analyzed. The biological functions and signaling pathways of these DEGs were evaluated using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The diagnostic performance of hub genes for DKD was assessed using receiver operating characteristic (ROC) curve analysis. Expression levels of five significant energy metabolism-related genes were validated through immunohistochemistry. The Nephroseq V5 tool was used to evaluate gene expression in DKD and to determine correlations between gene expression and renal function in patients with DKD. A total of 17 energy metabolism-related DEGs were identified. Five hub genes-ALB, IGF1, CD36, LPL, and UCP2-were identified. Among these, CD36 and LPL demonstrated relatively high diagnostic accuracy for DKD. The findings suggest that CD36, IGF1, LPL, and UCP2 may serve as potential biomarkers for DKD. The genes CD36, IGF1, LPL, and UCP2 represent potential energy metabolism-related biomarkers with possible applications in the diagnosis and treatment of DKD. Show less

Embryos produced in vitro exhibit heightened cryosensitivity due to excessive lipid accumulation. Previous studies demonstrated that cyclic guanosine monophosphate (cGMP) modulates intracellular lipid metabolism through cGMP-dependent protein kinase (PKG) signaling in various cell types. This study investigated the effects of cGMP on (i) cryosurvival in sheep embryos, (ii) embryonic quality, and (iii)lipolysis-related parameters. Specifically, we quantified lipid droplet content, free fatty acid levels, and hormone-sensitive lipase (HSL) phosphorylation status as key indicators of lipolytic activity. The results showed that cGMP pretreatment (0.5 mM) for 10 min prior to slow freezing significantly improved post-thaw embryo recovery rates and upregulated the mRNA expression of key developmental genes (POU5F1, SOX2, CDX2, and NANOG). cGMP pretreatment significantly upregulated the expression of multiple lipid catabolism genes (ACSL4, HMGCR, HMGCS1, LIPE, LPL, LIPF, and PLIN2), with LIPE (encoding HSL) exhibiting the most pronounced induction (27.10-fold increase vs. control). Following cGMP pretreatment, PKG activation triggered significant increases in the intracellular Ca Show less

Achieving long persistent luminescence (LPL) in fully organic materials with both hour-level duration and high thermal stability remains a fundamental challenge attributable to rapid exciton quenching and poor resistance to thermal disturbances. Herein, a trap engineering strategy is reported based on rigidified triphenylamine derivatives and boronic ester functionalization embedded in recycled poly(ethylene terephthalate) (PET), enabling the first fully organic polymer-based LPL system that exhibits simultaneously ultralong LPL and exceptional thermal robustness. Molecular conformation locking and optimized donor-acceptor charge transfer lead to deep trap states (≈1.03 eV), resulting in ambient LPL lifetimes exceeding 12 h. Remarkably, the luminescence is thermally enhanced by over 56 times at 500 K, rivaling high-performance inorganic phosphors. In addition, 980 nm near-infrared photo excitation further amplifies the emission, showcasing strong photo-stimulated luminescence capability. Taking advantage of PET's processability, 3D-printed luminescent structures are fabricated that retain LPL functionality and enable spatially resolved thermal sensing and real-time damage detection. This work not only introduces a sustainable and scalable platform for advanced thermal imaging and optoelectronics, but also sets a new benchmark in the design of heat-resistant organic LPL materials, bridging the gap between high-performance functionality and environmental compatibility. Show less

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendelian randomization (MR) analysis using blood cis-expression quantitative trait locus (eQTL) and HS genome-wide association study (GWAS) data. Colocalization, transcriptomic validation, single-cell RNA sequencing, and cell-cell communication analyses were integrated to explore gene function and cell-type specificity. We identified eight genes that showed significant associations with HS through MR analysis. Colocalization analysis further prioritized PSMA4 and MAST3 as the most promising druggable targets for HS. Specifically, PSMA4 (single nucleotide polymorphisms [SNPs] = 10; inverse-variance weighted [IVW] OR = 1.912, 95% CI: 1.492-2.450, Show less

Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tubules. However, the role of its active form, ChREBP-β, was previously unclear. In this study, ChREBP-β overexpression and ChREBP knockout mouse models were utilized to investigate the effects of excessive fructose intake in vivo. In addition, primary renal tubular epithelial cells from mice and human kidney-2 (HK2) cells were applied for further validation in vitro. We found that ChREBP-β leads to increased transcription to mediate endoplasmic reticulum stress and mitochondrial dysfunction, which ultimately impairs renal function. Our findings underscore the critical role of ChREBP-β in fructose-related renal disorders. Show less

Overactivation of hepatic de novo lipogenesis (DNL) contributes to fatty liver disease. Although glucose and fructose strongly promote DNL, diary-rich galactose is only weakly lipogenic. However, whether and how it regulates hepatic DNL remains unclear. In this study, we investigated whether low-dose galactose supplementation attenuates glucose- or fructose-induced DNL activation and protects against fatty liver diseases driven by DNL overactivation, such as alcohol-associated liver disease (ALD). In this study, we used integrated hepatocyte and mouse models to assess hepatic DNL and related signaling under high-glucose or high-fructose conditions, with or without low-dose galactose. Pharmacological and genetic interventions targeting the Leloir and hexosamine biosynthetic pathways (HBP) defined underlying mechanisms. For in vivo validation, male C57BL/6 mice were fed an isocaloric control or ethanol-containing diet for 4 wk. We found that glucose engages the HBP-mTORC1-SREBP-1c axis to stimulate hepatic DNL, whereas fructose acts predominantly through carbohydrate-responsive element-binding protein (ChREBP). Low-dose galactose selectively suppressed glucose-induced hepatic fat accumulation, concomitant with the inhibition of the HBP-mTORC1-SERBP-1c pathway. These effects required an intact Leloir pathway for galactose metabolism and were not observed with fructose. In alcohol-fed mice, hepatic HBP-mTORC1-SREBP-1c signaling was markedly upregulated, contributing to steatosis and liver injury. Replacing even a small fraction of dietary glucose with galactose normalized these alterations, attenuating hepatic lipid accumulation and injury without altering systemic glucose levels. In conclusion, glucose-induced hepatic lipogenesis involves the HBP-mTORC1-SREBP-1c pathway, which is also activated during chronic alcohol exposure. Low-dose galactose, obtainable from dairy sources, attenuates this pathway, thereby limiting excessive lipogenesis and protecting against early-stage ALD. Show less

BRCA1-deficient epithelial ovarian cancer (EOC) is reported to respond to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis); however, acquired resistance frequently emerges, limiting the long-term clinical efficacy of PARPis. The mechanisms driving acquired PARPi resistance in these patients remain poorly understood. In this study, we performed a systemic screen of epigenetic inhibitors in patient-derived organoids (PDOs) and identified enhancer of zeste homolog 2 (EZH2) as the key driver of PARPi resistance in BRCA1-deficient EOC. We found that in PARPi-resistant cells, intracellular EZH2 translocated from the nucleus to the mitochondria, where it promoted mitochondrial fusion and subsequently prevented PARPi-mediated apoptosis. Mechanistically, we determined that PARPi treatment activated YES1 to phosphorylate EZH2 at the Y728 residue, which promoted the mitochondrial translocation of EZH2 in a TOM20-dependent manner. Using mass spectrometry, we identified MYO19 as a main substrate of EZH2 in mitochondria and found that EZH2 trimethylated MYO19 at the K928 residue to trigger mitochondrial fusion. Moreover, Y728 phosphorylation also increased EZH2 protein stability by hindering TRIM4 binding, thus blocking TRIM4-mediated ubiquitination and subsequent proteasomal degradation. Notably, the efficacy of targeting YES1 or EZH2 to resensitize tumors to PARPis was validated in PDOs, xenograft models and EOC cell lines. Here, our findings reveal a YES1-EZH2-MYO19 post-translational modification cascade, whereby PARPi-induced phosphorylation of EZH2 triggered mitochondrial fusion, and targeting phosphorylated EZH2 rebalanced mitochondrial dynamics and resensitized BRCA1-deficient EOC to PARPis, suggesting a promising therapeutic strategy. Show less

Hepatic intercellular communication is the driving force for the progression of chronic Hepatitis B virus (CHB)-associated hepatopathologies, with the dynamic molecular mechanisms largely unknown. Combining scRNA-seq and spatial transcriptomic analysis, the kinetic landscape of the liver microenvironment across time and space in AAV-HBV mice, which develop from inflammation to ultimately hepatocellular carcinoma is generated. Kupffer cells (KCs), originally resided within the peri-portal area, are persistently recruited to the HBV-enriched peri-central region via increased CXCL9 produced by endothelial cells, facilitating the interaction between KCs and HBV Show less

Schizophrenia (SZ) is characterized by excitation-inhibition (E-I) imbalance as a core pathophysiological feature, but its molecular underpinnings remain elusive. Susceptibility gene Roundabout2 (Robo2), which regulates E-I balance in the central nervous system, may play a critical role in the pathogenesis of SZ by contributing to this dysregulation. We conducted a transcriptomic analysis of Robo2 in postmortem brain tissues from patients with SZ and controls using the GEO/GSE datasets. The plasma levels of Robo2 were quantified in clinical cohorts via ELISA. We assessed the correlation between plasma Robo2 levels and clinical assessments (Positive and Negative Syndrome Scale [PANSS] and MATRICS Consensus Cognitive Battery [MCCB]) or neurophysiological measures (functional near-infrared spectroscopy [fNIRS] and event-related potentials). Rats with hippocampal Robo2 knockdown underwent comprehensive behavioral, electrophysiological, and ultrastructural (Golgi staining) assessments. Proteomic sequencing with pathway enrichment analysis was conducted to identify downstream molecular mediators. Hippocampal and plasma Robo2 expression were significantly downregulated in patients with SZ. The plasma levels of Robo2 were inversely correlated with PANSS scores and positively associated with MCCB performance. Neurophysiological correlations revealed positive associations between Robo2 and dorsolateral prefrontal cortex activation (fNIRS and P300 peak amplitude). Robo2-deficient rats exhibited anxiety-like behaviors, cognitive impairments, social withdrawal, and sensory gating abnormalities, accompanied by decreased dendritic spine density and increased hippocampal field potential power. Proteomics identified disrupted GABAergic/glutamatergic synaptic pathways, with neurexin-3 (Nrxn3) downregulation emerging as a potential downstream candidate. Our findings established Robo2-Nrxn3 deficiency as a potential molecular hub linking E-I imbalance to SZ-associated behavioral and neurophysiological deficits, highlighting novel therapeutic targets for E-I modulation. Show less

Thoracic aortic dissection (TAD) is a life-threatening acute vascular condition with high morbidity and mortality. Endothelial cells (ECs) are critical for maintaining vascular homeostasis, yet the role of endothelial-to-mesenchymal transition (EndoMT), a key cell-fate process in vascular development and disease, in TAD remains poorly defined. Furthermore, the functional role of PDK4 (pyruvate dehydrogenase kinase 4) as a driver of this pathological cell-fate transition has not been elucidated. To delineate the mechanistic contribution of EndoMT to TAD, we integrated transcriptomic profiling and immunofluorescence analysis in human aortic specimens and a β-aminopropionitrile-induced murine model. Following the identification of PDK4 as a critical downstream effector of EndoMT signaling via RNA-sequencing and chromatin immunoprecipitation assays, its functional role was validated using conditional EC-specific knockout mice and adeno-associated virus-mediated endothelial gene modulation. Serum samples were collected, and ELISA was used to measure levels of endothelial injury markers for assessing EC-dysfunction. In addition, therapeutic potential was assessed using dichloroacetate, a small-molecule PDK4 inhibitor. A robust activation of the EndoMT gene program was observed in both human TAD specimens and murine aortic tissues, characterized by the loss of endothelial identity and acquisition of mesenchymal traits. Transcriptomic screening pinpointed PDK4 as a critical mediator upregulated during EndoMT. Mechanistically, we demonstrated that the transcription factor Our findings demonstrate that the pathological EndoMT program is activated in ECs by PDK4, which aggravates TAD development in β-aminopropionitrile-induced mouse models, highlighting PDK4 as a promising therapeutic target for TAD. Show less

Metabolic‒epigenetic crosstalk critically orchestrates hepatocellular carcinoma (HCC) pathogenesis. Deciphering the precise mechanism underlying epigenetic remodeling and metabolic reprogramming in HCC may lead to novel treatment paradigms, however, the key mechanisms remain elusive. RT-qPCR, western blotting and tissue microarrary Immunohistochemistry were used to detect the expression of RasGEF domain family member 1B (RASGEF1B) in HCC and normal liver tissues. Transcriptome sequencing and high-resolution untargeted metabolomics were integrated to identify the downstream regulatory mechanism through which RASGEF1B inhibited the HCC progression. Epigenetic regulation was investigated using methylation-specific PCR and luciferase reporter assays. Bioinformatic prediction and molecular docking suggested a functional interplay among RASGEF1B, ALDH7A1, and BMI1, which was experimentally confirmed through coimmunoprecipitation, GST pull-down, and immunofluorescence assays. Protein stability and ubiquitination status of ALDH7A1 were examined using cycloheximide, immunoprecipitation assay, and an in vitro reconstituted ubiquitination system. In this study, the antitumor role of RASGEF1B was confirmed in vitro and in vivo. Transcriptomic profiling revealed that RASGEF1B overexpression significantly reduced the snail family transcriptional repressor 1 (SNAI1), a master regulator of the epithelial-mesenchymal transition. Untargeted metabolomics revealed that RASGEF1B promoted SNAI1 DNA methylation through Betaine-mediated methionine metabolic reprogramming. Further analysis confirmed that RASGEF1B competitively protected the ALDH7A1 protein from BMI1-dependent ubiquitination, thereby elevating cellular Betaine levels in HCC. This study revealed that RASGEF1B inhibited SNAI1 to suppress HCC through metabolite‒epigenetic crosstalk. Our findings potentially offer a new perspective on the classical RAS signaling framework, uncovering a metabolic‒epigenetic axis as an innovative therapeutic approach for improving clinical outcomes in patients with HCC. [Image: see text] The online version contains supplementary material available at 10.1186/s12967-026-07785-z. Show less

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of EGFR-mutant non-small cell lung cancer (NSCLC); however, acquired resistance remains a major clinical challenge. While lysosomes have been implicated in drug resistance, their precise role in EGFR-TKI resistance remains unclear. In this study, we found that EGFR-TKI, including gefitinib and osimertinib, impaired WWP2-mediated proteasomal degradation of LAPTM4B. Through analysis of clinical tumor samples, genetic manipulation, and functional assays, we identify the lysosomal protein LAPTM4B as a key driver of EGFR-TKI resistance by enhancing EGFR phosphorylation and downstream signaling. Mechanistically, LAPTM4B interacts with ATP1A1 and facilitates its endocytosis, while simultaneously preventing its degradation by suppressing TRIM8-mediated K63-linked ubiquitination and proteasomal turnover. This stabilization of ATP1A1 enhances lysosomal acidification, ultimately promoting EGFR-TKI resistance. To identify potential therapeutic strategies, we conducted an unbiased high-content drug screen and identified compounds that suppress LAPTM4B expression. These compounds synergistically enhance the efficacy of EGFR-TKIs in NSCLC models Show less