👤 Yong Gao

Purinergic receptor P2X7 has been considered as a potential new target for detecting and treating high-risk plaque. Nanobodies are the smallest antibody fragments with high antigen binding ability and specificity, which are well-suited for radionuclide imaging. The present study aimed to develop a novel P2X7-targeted nanobody SPECT tracer and to investigate its potential for identification of atherosclerotic plaque (AP). The anti-P2X7 nanobody 1c81 was site-specifically conjugated with [ Show less

Congo Red (CR) is the histochemical staining sensor used to diagnose amyloid tissue deposition in current clinical practice. Its characteristic aryl azo linkage is generally considered to be chemically stable. Here, we discovered by serendipity that neutral borate buffer can activate the inert azo bond in CR to covalently modify amyloid proteins at ambient temperature. Such chemistry allowed us to develop a covalent amyloid sensor to image, enrich, and proteotype amyloid deposits in Alzheimer's disease (AD) tissue. We first pinpointed the boronic acid in borate buffer triggers such amyloid bioconjugation and found that ultraviolet-light-induced azo Show less

Gastric cancer (GC) is a leading cause of cancer-related deaths and has high recurrence rate. Although fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, its molecular mechanisms remain unclear. Multi-omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co-IP, WB, ChIP), explored FNDC1's function and mechanism. FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β-catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224-254) of Gβ2, disrupting Gβγ-Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β-catenin-destruction complex (GSK3 β-APC-Axin1), leading to β-catenin accumulation and Wnt pathway activation. FNDC1 drives GC malignancy by targeting the Gβ2-Dvl1 axis to activate Wnt/β-catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target. Show less

To identify plasma proteins associated with glaucoma and assess the translational potential of key proteins as both biomarkers and therapeutic targets. Genome-wide association study data were obtained from the UK Biobank Pharma Proteomics Project, FinnGen, and the Million Veteran Program. We used a four-stage analytical framework: Stage 1 applied Mendelian randomization and Bayesian colocalization to evaluate associations between 2923 plasma proteins and glaucoma; Stage 2 used summary-based Mendelian randomization to explore transcriptomic and epigenomic associations of the identified proteins with glaucoma risk; Stage 3 involved a prospective association analysis of protein levels and incident glaucoma in the UK Biobank cohort, including 40,170 glaucoma-free participants; and Stage 4 systematically evaluated the druggability of the prioritized protein targets. We identified 26 plasma proteins with putative causal associations with glaucoma, six of which were novel: COL24A1, KAZALD1, EBAG9, CSNK1D, AZI2, and AXIN1. COL24A1 (odds ratio [OR] = 0.85; 95% confidence interval [CI], 0.80-0.90; PFDR < 0.001; PP.H4 = 0.95) and EFEMP1 (OR = 0.88; 95% CI, 0.83-0.92; PFDR < 0.001; PP.H4 = 0.98) emerged as the most compelling candidates. To further elucidate the regulatory mechanisms, multiomics analyses indicated that epigenetic modifications and alternative splicing events affecting these genes were associated with elevated glaucoma risk. Notably, EFEMP1 was significantly associated with glaucoma incidence in the prospective cohort analysis (fully adjusted Cox model: hazard ratio = 1.61; 95% CI, 1.29-2.00; PFDR = 0.002), demonstrating strong predictive performance (C-index = 0.811, area under the curve = 0.806) and representing a promising therapeutic target. Our findings provide new insights into the proteomic basis of glaucoma and highlight promising opportunities for developing targeted therapies. Show less

Beta-site APP-cleaving enzyme 1 (BACE1), a critical rate-limiting enzyme that synthesizes β-amyloid peptide (Aβ), is an important marker of early pathological changes in Alzheimer's disease (AD). Early small plaques cannot be accurately detected using traditional Magnetic resonance imaging (MRI) probes. Therefore, magnetic resonance tuning (MRET) and susceptibility weighted imaging (SWI)-based smart responsive MR nanoprobes are designed to achieve the sensitive detection of BACE1 and Aβ plaques. This probe is modified with a blood-brain barrier-penetrating targeting peptide that enables its reach to the AD microenvironment. The enhancement of T1WI signals owing to the MRET effect caused by the separation of probes in response to BACE1 is used to reflect real-time BACE1 changes. When Aβ plaques are present, the remaining probes that bound around Aβ plaques underwent in situ thiol cross-linking under the action of peroxynitrite (ONOO Show less

The potential role of artificial sweeteners in eosinophilic esophagitis (EoE) remains poorly understood. This study aimed to investigate the molecular mechanism by which saccharin might exacerbate EoE. We integrated network toxicology with machine learning approaches to identify core pathogenic genes of EoE. The interactions between saccharin and the predicted targets were validated via molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR). Our analysis identified MAPK3, CPS1, and HS3ST1 as potential EoE-related targets of saccharin. Molecular docking demonstrated strong binding affinities between saccharin and these proteins, which was confirmed by stable binding via molecular dynamics simulations. Further SPR analysis revealed that saccharin binds directly to MAPK3. This study demonstrated that saccharin potentially aggravates EoE by directly targeting MAPK3 to activate pro-inflammatory pathways, highlighting a novel dietary risk factor and underscoring the need for a safe reevaluation for susceptible populations. Show less

RNA G-quadruplexes (rG4s), formed through guanine self-recognition into stacked tetrads, serve as critical regulators of gene expression, yet their comprehensive mapping and dynamic regulation in physiological contexts remain technically challenging. Here, we develop Ultra-low-input rG4-seq (ULI-rG4-seq), enabling precise rG4 detection enabling precise rG4 detection with ∼140 bp resolution in samples as small as 100 oocytes, and reveal notable enrichment of rG4s near crucial regulatory regions, particularly transcription start sites and end sites. This technological advance, combined with Trim-away or oocyte-specific knockout of DHX36 (also known as G4R1 or RHAU), an rG4-specific helicase, reveals acute and chronic loss of DHX36 leads to opposing effects on rG4 levels. This observation extends beyond the traditional view of helicases as unwinding enzymes and suggests sophisticated cellular mechanisms maintaining RNA structural homeostasis. Through integrated analysis of rG4 landscapes and DHX36-binding profiles, we demonstrate coordination between cytoplasmic rG4 regulation and nuclear gene expression, revealing how RNA structure dynamics orchestrate RNA stability and translation, thereby influencing transcriptional elongation, genome stability, and alternative splicing. Finally, we show that deletion of DHX36 resulted in decreased oocyte quality, premature ovarian failure and complete female infertility due to transcriptional defects and genome instability related to R-loop accumulation. These technological and conceptual advances not only deepen our understanding of RNA-based regulation but also open new therapeutic possibilities for diseases involving RNA structure. Show less

Ambient air pollution contributes to chronic obstructive pulmonary disease (COPD), but the genetic factors that may influence susceptibility remain poorly defined. We conducted a genome-wide interaction analysis to identify genetic markers that may modify the association between air pollution and COPD. We analyzed data from 16,839 Canadian Longitudinal Study of Aging participants, including spirometry, genome-wide genotype data (645,625 single-nucleotide polymorphisms [SNPs]), and air pollution exposure estimates. COPD was defined as a forced expiratory volume in 1 second to forced vital capacity ratio (FEV Show less

Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth factor 21 (FGF21) in the development and progression of chronic hepatitis B (CHB). A total of 336 participants were recruited, including 320 CHB patients and 16 healthy controls. The expression of FGF21, immune cytokines, and OS-related molecules in peripheral blood mononuclear cells (PBMCs) was detected using real-time quantitative polymerase chain reaction. The methylation level of the FGF21 gene promoter in PBMCs was detected using TaqMan probe-based quantitative methylation-specific PCR. The expression level of FGF21 in the peripheral blood of CHB patients was higher than that of HC, but the methylation level of the FGF21 promoter was lower than that of HC, especially in patients during the immune activation phase. The mRNA expression levels of CXCR3 and CCL5 in PBMCs of CHB patients during the immune activation and reactivation phases were higher than those in other clinical stages. Single-cell analysis revealed that CXCR3 and CCL5 expression in the immune tolerance and immune activation phases with high HBsAg expression was closely related to T lymphocytes (T cells) and natural killer cells (NK cells) and was highly expressed in CD4 and CD8 T cells and NK cells. In addition, the mRNA expression levels of Nrf2 and GPX4 in the reactivation phase were higher than those in other clinical stages. The mRNA expression level and methylation level of FGF21 in PBMCs of CHB patients were correlated with the viral load, immune inflammation, and OS levels during the antiviral treatment course of CHB. The methylation level of the FGF21 promoter has the potential to become a non-invasive biomarker for monitoring the progress of antiviral treatment in CHB.IMPORTANCEThis study conducted an in-depth exploration of the application of methylation detection technology, analyzing its value and driving mechanism in the oxidative stress and immune-inflammatory balance during the course of chronic hepatitis B. The study analyzed the methylation patterns of the FGF21 promoter and the expression levels of its receptor FGFR1, as well as the expression levels of chemokines CXCR3, CCL5, and oxidative stress factors GPX4 and Nrf2 in the immune tolerance period, immune clearance period, immune control period, and reactivation period of chronic hepatitis B. It clarified the association between these molecules and the FGF21/FGFR1 axis and revealed the synergistic or antagonistic mechanisms of these molecules in the oxidative stress and inflammatory vicious cycle. At the same time, this study also explored the value of FGF21 promoter methylation in disease diagnosis and prognosis, providing a theoretical basis for evaluating the antiviral treatment effect and disease progression of chronic hepatitis B. Show less

This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro , investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo . In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression. Show less

Probiotics such as The intestinal colonization ability of CIQ249 was assessed using cFDA-SE labeling and flow cytometry. Growth performance and intestinal morphology were evaluated in mice. Antimicrobial activity of CIQ249 cell-free supernatant was tested against various pathogens, and pathogen damage was visualized by scanning electron microscopy. Protective effects against CIQ249 demonstrated strong intestinal colonization and increased villus height and the villus-to-crypt ratio, contributing to improved growth performance. Its cell-free supernatant selectively inhibited enteropathogens and induced structural damage in CIQ249 enhances mucosal defense against enteropathogenic bacteria through a dual mechanism-strengthening the epithelial barrier and activating a coordinated DC-Tfh-IgA immune axis. These findings provide a multi-level mechanistic basis for its application as a microecological agent against intestinal infections. Show less

Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less

Microglia-mediated neuroinflammation, considered one of the most plausible pathogenic hypotheses underlying Alzheimer’s disease (AD), plays a pivotal role in the initiation and progression of this devastating condition. Recently, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated promising neuroprotective effects in both preclinical and clinical studies. Previously, we developed an orally-administered GLP-1RA peptide called OHP2, which is capable of crossing the blood-brain barrier for the treatment of AD. OHP2 has been shown to effectively reduce brain inflammation in AD mouse models. In this study, we discovered that OHP2 treatment induced IL-27 secretion from astrocytes and modulated microglial reprogramming from the neurotoxic M1 phenotype to the neuroprotective M2 phenotype through glycolysis/cGAS lactylation clock/mTOR pathway, thereby alleviating excessive neuroinflammation. These findings provide a rationale for further pharmacological investigations into OHP2 and suggest that IL-27 may hold significant implications for AD therapy as a metabolic regulator. [Image: see text] The online version contains supplementary material available at 10.1186/s12974-025-03683-1. Show less

To explore the latent profiles of self-stigma and their relationship with meaning in life among individuals with substance use disorders(SUDs). A total of 1001 participants were recruited from six drug rehabilitation centers in Sichuan Province between July and August 2025 and completed the self-stigma Scale for Drug Addicts (SSSDA) and the Meaning in Life Questionnaire (MLQ). Latent profile analysis (LPA) was used to identify latent profiles of self-stigma. Multinomial logistic regression was employed to analyze influencing factors, and analysis of variance (ANOVA) was used to compare differences in meaning in life across the different profiles. The self-stigma of individuals with SUDs can be categorized into four latent profiles: the "stigma-resistant profile"(10.0%), "moderate stigma-concealment profile"(46.3%), "internalized stigma profile"(19.5%), and "low internalization-adaptation profile"(24.3%). Among these, the "moderate stigma-concealment profile", "internalized stigma profile", and "low internalization-adaptation profile" represent categories with higher levels of self-stigma. Risk factors associated with these profiles include male sex, low income, a history of being left-behind children, low social support, multiple rehabilitation attempts, as well as mental illness or HIV infection. Statistically significant differences were found among the four profiles in the total score of meaning in life and its sub-dimensions-presence of meaning and search for meaning (p < 0.001). The "stigma-resistant profile" presented the highest level of MIL, whereas the "internalized stigma profile" presented the lowest level. Significant heterogeneity exists in self-stigma among individuals with substance use disorders (SUDs), and the level of self-stigma is significantly negatively correlated with MIL. Show less

The role of parenting styles during early adolescence has always been a subject of significant concern. However, previous studies have predominantly treated parenting styles as a static construct, leading to a limited understanding of their dynamic patterns. This study employed a longitudinal person-centered perspective to examine the stability of and transitions in parenting style profiles during this critical period, as well as their associations with adolescents' internalizing and externalizing problem behaviors. Data were obtained in November 2023 (T1) and November 2024 (T2) from 893 Chinese students (53.5% female; M The analysis identified three distinct parenting profiles: harsh, supportive, and low-involved. Each profile demonstrated a high degree of stability over time, although some meaningful transitions were observed. Adolescents who consistently experienced supportive parenting or transitions toward the supportive profile generally reported lower levels of internalizing and externalizing problems. Conversely, those exposed to stable harsh parenting or a shift toward the harsh profile showed higher levels of these problems. Furthermore, internalizing problems appeared to be more susceptible to changes in parenting profiles than externalizing problems. The findings underscore the potential for positive shifts in parenting styles to serve as protective factors against problem behaviors in early adolescence, offering valuable implications for prevention and intervention strategies. Show less

Capillary zone electrophoresis (CZE)-mass spectrometry (MS) has attracted tremendous attention in top-down proteomics (TDP). However, its reproducibility and long-term repeatability for TDP remain concerns, most likely due to capillary coating. Here, we present an improved procedure for making linear polyacrylamide (LPA) coating, the most widely used coating in CE-MS-based proteomics, to boost the reproducibility and long-term repeatability of CZE-MS-based TDP. We focused on the step of degassing the polymerization solution, a critical step for achieving consistent LPA coating quality. The CZE-MS system using LPA-coated capillaries prepared with the optimal degassing procedure produced excellent reproducibility and repeatability for proteoform analysis. The 210 CZE-MS runs of three protein samples (a standard protein mixture, an Show less

Accurate classification of intestinal polyps is crucial for preventing colorectal cancer but is hindered by visual similarity among subtypes and endoscopic variability. While deep learning aids in diagnosis, single-modal models face efficiency-accuracy trade-offs and ignore pathological semantics. We propose a multimodal framework that integrates endoscopic images with structured pathological descriptions to bridge this gap. We propose LPA-Tuning CLIP, which incorporates three key innovations: replacing CLIP's instance-level contrastive loss with cross-modal projection matching (CMPM) with ID loss to explicitly optimize intraclass compactness and interclass separation through label-aware image-text similarity matrices; introducing structured clinical semantic templates that encode WHO diagnostic criteria into hierarchical text prompts for consistent pathology annotations; and developing medical-aware augmentation that preserves lesion features while reducing domain shifts. The experimental results demonstrate that our proposed method achieves an accuracy of 85.8% and an F1 score of 0.862 on the internal test set, establishing a new state-of-the-art performance for intestinal polyp classification. This study proposes a multimodal polyp classification paradigm that achieves 85.8% accuracy on three-subtype classification via endoscopic image-pathology text joint representation learning, outperforming unimodal baselines by 8.7% and a multimodal baseline by 4.3%. Show less

This study integrates the "Stress and Coping" theory with the "Ordinary Magic" model to propose a sequential "challenge appraisal -resource gain -cognitive resilience" framework. The framework aims to elucidate the psychological adaptation processes contributing to athletes' cognitive resilience in high-temperature environments. The study specifically explores the mediating role of challenge appraisal in the relationship between psychological resources and cognitive resilience, as well as the moderating effect of team support on this relationship. Data were collected from 240 professional athletes via a questionnaire-based survey, capturing multidimensional psychological and contextual variables. The analysis utilized structural equation modeling (SEM), latent profile analysis (LPA), and moderated effect testing to assess the proposed mediation, heterogeneity, and moderation pathways. Findings reveal that cognitive resilience in high-temperature environments is a dynamic process influenced by cognitive reappraisal and resource coupling. The study demonstrates that challenge appraisal mediates the relationship between psychological resources and cognitive resilience, with team support acting as a moderating factor. These results provide empirical support for targeted psychological interventions and the development of team-support systems in sports involving thermal stress. Additionally, the findings offer a theoretical advancement in sports psychology by transitioning from a static trait-oriented approach to a more dynamic "individual-context" interaction paradigm. This shift highlights the complex nature of psychological adaptation mechanisms in extreme environments. Show less

To describe the network structure and heterogeneity of symptom burden in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), and to examine factors associated with different symptom burden profiles to inform risk-stratified management after PCI. A convenience sample of 261 patients with ACS who underwent PCI at a tertiary hospital in Chongqing between November 2024 and August 2025 was recruited. Data were collected using a demographic questionnaire, the Cardiac Symptom Survey, and the Seattle Angina Questionnaire. Network analysis was conducted to identify inter-symptom associations and the structural characteristics of the symptom network. Latent profile analysis (LPA) was performed to classify symptom burden patterns, and multinomial logistic regression analysis was used to explore factors associated with profile membership. Network analysis indicated that depression was the most central symptom (strength Symptom burden in patients with ACS after PCI demonstrates substantial individual heterogeneity. Depression occupies a central position within the symptom network, and BMI is associated with moderate and high symptom burden profiles. These findings suggest that integrating symptom network characteristics and BMI status into post-PCI assessment may facilitate risk-stratified management and targeted psychological and weight-related interventions to improve recovery outcomes. Show less

To evaluate the predictive value of novel lipid parameters for coronary lesion severity in pCAD and to develop a nomogram-based prediction model. Patients newly diagnosed with pCAD at Qingdao Municipal Hospital (2021-2024) were enrolled and randomly assigned to training and validation cohorts in a 7:3 ratio. Coronary lesion severity was assessed using the Gensini score (GS), with patients stratified into mild or significant stenosis groups. Spearman correlation analysis was performed between GS and lipid parameters. Key predictors were selected using LASSO regression, and independent risk factors were identified by multivariable logistic regression to construct the nomogram model. The model's discrimination, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Lp(a), non-HDL-C, RC, FFA, and BAR were positively correlated with GS (r = 0.34, 0.34, 0.18, 0.19, 0.18; all The proposed nomogram provides an effective tool for identifying pCAD patients with severe coronary artery stenosis, demonstrating robust predictive accuracy and potential clinical utility. Show less

This study aimed to identify distinct latent profiles (categories) of health behavior protection motivation among patients with type 2 diabetes using latent profile analysis. Subsequently, we compared e-health literacy levels across these patient categories and analyzed factors influencing protection motivation. The findings are intended to provide a scientific basis for precise diabetes management. From January to March 2025, a cross-sectional survey was conducted on a convenience sample of 253 patients, and data were collected using relevant scales such as the health-related behavior protection motivation assessment. LPA was performed using Mplus 8.3 to identify motivational profiles. Binary logistic regression was applied to determine influencing factors. A total of 253 valid questionnaires were collected. Two latent profiles of health-related behavioral protection motivation were identified: the "high perceived cost-incentive-dependent group" (n = 91, 35.97%) and the "high sensitivity-high efficacy group" (n = 162, 64.03%). The total eHealth literacy score of the "high perceived cost-incentive-dependent group" was 100.35 ± 17.89, which was significantly lower than that of the "high sensitivity-high efficacy group" (110.76 ± 13.78), with a statistically significant difference (t = -5.165, P < 0.001). Logistic regression analysis revealed that patients who monitored their blood glucose more than three times per week were 2.95 times more likely to have a higher level of protective motivation compared to those who did so three times or fewer (95% CI: 1.679-5.197, P < 0.001). There is population heterogeneity in health-related behavioral protection motivation among patients with type 2 diabetes. Frequency of blood glucose monitoring per week was identified as influencing factors of motivational profile membership. Differences in eHealth literacy levels were also observed between the two groups. Targeted interventions should be provided based on population characteristics to enhance motivation, improve electronic health literacy, and behavioral compliance. Show less

Job satisfaction is a critical factor influencing workplace efficiency and employee well-being. In the context of Industry 5.0 transformation, understanding the latent profiles of job satisfaction and their relationship with mental health outcomes, such as depression, anxiety, and digital-intelligence job insecurity, is critical for promoting employee well-being and organizational sustainability. This study aims to explore the latent profiles of job satisfaction among industrial workers and explore their associations with mental health outcomes. This study used cross-sectional data from 3,420 male frontline workers from a large automobile manufacturing enterprise in Jilin Province, China in April 2024. Latent profile analysis (LPA) was employed to identify distinct latent profiles of job satisfaction among industrial workers, while hierarchical linear regression analysis was used to analyze the relationship between job satisfaction and psychological health outcomes (depression, anxiety and digital-intelligence job insecurity). The score of job satisfaction among industrial workers in Jilin Province was 3.62 ± 0.90. Four profiles were identified: very low (5.97%), low-to-moderate (31.14%), moderately high (42.63%), and high job satisfaction (20.26%). Depression and anxiety showed a clear level-gradient pattern across profiles, whereas digital-intelligence job insecurity displayed a non-monotonic pattern with higher levels in the low-to-moderate and moderately high profiles. Work stress showed consistent associations with all outcomes, and job satisfaction profiles remained associated with depression and anxiety after covariate and stress adjustment; associations with digital-intelligence job insecurity were smaller but detectable. This study examined heterogeneity in job satisfaction among frontline industrial workers and its associations with mental health outcomes. Latent profile analysis identified four job satisfaction profiles. Job satisfaction profile membership remained strongly associated with depression and anxiety. Digital-intelligence job insecurity showed a non-monotonic pattern across profiles. These findings suggest that an individual-centered profile approach provides actionable differentiation of mental health symptom burden across distinct job satisfaction patterns, supporting more targeted workplace strategies. Show less

This study aimed to identify distinct in-hospital cardiac rehabilitation (CR) adherence profiles and explore their associated clinical and sociodemographic factors among patients following percutaneous coronary intervention (PCI). A cross-sectional survey was conducted among patients undergoing Phase I cardiac rehabilitation following percutaneous coronary intervention (PCI) who were hospitalized in the cardiology department between June and July 2025 (n=384). Data were collected using a general information questionnaire and a treatment adherence questionnaire (Since the study population consisted of inpatients undergoing PCI followed by phase I cardiac rehabilitation, the dimension of follow-up compliance was excluded). LPA, a person-centered method that identifies unobserved subgroups (profiles) based on response patterns, was prespecified to classify CR adherence profiles. Multinomial logistic regression was performed to examine factors associated with profile membership. Clinical indicators (number of diseased vessels, LVEF, LDL-C, and serum creatinine) were included as candidate predictors; after LASSO selection, LDL-C and number of diseased vessels were retained and entered the final multinomial logistic regression model as continuous variables (original values). Three distinct CR adherence profiles were identified: Low CR Adherence (125/384, 32.55%), Medium CR Adherence (169/384, 44.01%), and High CR Adherence (90/384, 23.44%). Profile membership was significantly associated with gender, living situation, family monthly income, residential distance, smartphone use/proficiency and LDL-C ( CR adherence among post-PCI patients was overall moderate-to-low, with substantial heterogeneity across adherence patterns. The associated sociodemographic and contextual factors may help inform profile-based, tailored support to improve CR adherence after PCI. Given the cross-sectional design, these associations are non-causal and should be validated in future multicenter longitudinal and intervention studies. Show less

To examine associations between the 24-h composition of movement behaviors (sedentary behavior [SB], light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], and sleep) and physical and mental health in older adults using compositional data analysis. Data came from 4,150 adults aged ≥ 60 in the 2015 China Health and Nutrition Survey. Multiple‑balance isometric log‑ratio regression and compositional isotemporal substitution models were used to assess relative associations and the effect of time reallocation. The 24‑hour geometric mean composition was 43.1% sleep, 30.6% SB, 21.8% LPA, and 4.5% MVPA. LPA was positively associated with physical (β = 0.062, Replacing sedentary time or sleep with LPA, even in small amounts, is associated with better physical and mental health in older adults, supporting integrated 24‑hour activity guidelines that emphasize light‑intensity movement. Show less

Cancer patients face a markedly elevated risk of thromboembolism (TE), including both venous thromboembolism (VTE) and arterial thromboembolism (ATE), which contribute substantially to morbidity and mortality in this population. This study examined sex disparities in associations between sleep, sedentary behavior (SB), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and TE risk, in cancer patients using data from the UK Biobank. A longitudinal cohort analysis of 6,765 cancer patients (2,774 men and 3,991 women) from the accelerometry subsample was conducted using Cox proportional hazards and isotemporal substitution models stratified by sex. The incidence of VTE was 3.0% in men versus 2.2% in women, while ATE incidence was 5.0% versus 2.2%, respectively. Compared with high LPA, medium and low durations were associated with 2.75- and 2.88-fold higher VTE risk only in men. Reallocating 1 h per day from sleep or SB to LPA reduced VTE risk by 24% and 19% in men. Low MVPA was associated with 3.35- and 1.59-fold higher ATE risk in women and men, respectively. Reallocating 1 h per day from sleep, SB, or LPA to MVPA reduced ATE risk by 71%, 70%, and 66%, respectively, only in women. LPA was associated with a lower risk of VTE only in male cancer patients, whereas MVPA was linked to a lower risk of ATE in female patients, indicating sex-specific associations between movement behaviors and TE risk. Show less

This is a cross-sectional study designed to identify the latent profiles of psychological resilience in elderly patients with fracture and examine the relationship between resilience categories and fear of falling (FOF), thereby informing individualized rehabilitation strategies. A convenience sample was drawn from elderly patients admitted to the Department of Traumatology and Orthopedics at a tertiary general hospital in Beijing between September 2024 and July 2025 due to fall-related fractures. A total of 213 older adults aged 60 and above with fall-related fractures were included. Psychological resilience was assessed using the Connor-Davidson Resilience Scale (CD-RISC), and FOF was measured with the Falls Efficacy Scale-International (FES-I). Latent Profile Analysis (LPA) was used to identify resilience profiles. Logistic and linear regression analyses, adjusting for age, sex, comorbidities, pain level, functional status, and time since fracture/surgery, were performed to explore the relationship between resilience subtypes (entered as a continuous CD-RISC score), demographic and clinical factors, and FOF levels. The age of elderly patients with fall-related fractures was 60–98 (75.28 ± 8.73) years old, and the median age was 74 years old. Three latent resilience profiles were identified: low (33.5%), moderate (22.7%), and high (43.8%) resilience groups. Patients in the high-resilience group exhibited significantly lower FOF scores than those in the other two groups ( Psychological resilience is independently associated with fear of falling among elderly fracture patients, with a clear gradient across resilience profiles. Enhancing resilience, particularly in low-resilience individuals, may be a potential target for intervention, though causal inference is limited by the cross-sectional design and single-center, convenience sampling strategy. Integrating resilience assessment into clinical evaluation could support more holistic rehabilitation planning. ChiCTR2400089221, September 4, 2024. Show less

Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohorts and a chronic unpredictable mild stress (CUMS) rat model. Targeted UPLC-MS/MS profiling was applied to a training cohort (95 MDD, 40 controls), and untargeted UPLC-HRMS profiling to an independent cohort (56 MDD, 37 controls). Candidate biomarkers were identified using univariate tests, partial least squares discriminant analysis, and three feature-selection methods (Boruta, LASSO, RFE), with predictive performance evaluated by cross-validation and external replication. Translational relevance was examined in CUMS rats through behavioral assays and lipidomic profiling of serum and brain tissues. Pathway enrichment and regression models explored metabolic context and clinical associations. In the training cohort, we found that 244 lipids were significantly altered, highlighting altered glycerophospholipid, glycerolipid, and sphingolipid metabolism. A 29-lipid panel achieved 90.4% cross-validation accuracy, while a reduced 7-lipid subset reached 94.8%. In the validation cohort, an 8-lipid panel achieved 71.2% accuracy, and a minimal 2-lipid set-LPA(18:2) and SPH(d16:1)-reached 72.1%. Cross-species analysis confirmed consistent downregulation of SPH(d16:1) in serum of both humans and rats, and of LPC(0:0/16:0) specifically in the rat prefrontal cortex. Regression analyses linked sex, age, and anxiety severity to lipid alterations. This cross-platform, cross-species study identifies reproducible lipid signatures of adolescent MDD, highlights SPH(d16:1) and LPC(0:0/16:0) as translational biomarkers, and implicates glycerophospholipid metabolism in MDD pathophysiology, providing a foundation for biomarker-guided diagnostics and therapeutics. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) that drives a significant residual risk through proatherogenic, proinflammatory, and prothrombotic pathways. However, current mainstay lipid-lowering therapies such as statins have limited efficacy in reducing Lp(a) levels, highlighting a critical therapeutic gap. This review aims to synthesize evidence on the role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in targeting Lp(a). We systematically searched PubMed and Embase for clinical trials and mechanistic studies (2010-2025), using the PRISMA and AMSTAR-2 frameworks to ensure methodological rigor and demonstrated that PCSK9 inhibitors (eg, alirocumab, evolocumab, and tafolecimab) not only reduced low-density lipoprotein (LDL-C) by 55%-60% but also lowered Lp(a) by 20%-30%. The efficacy of these agents varies ethnically, with tafolecimab showing superior performance in East Asian populations, which is partly attributable to the higher prevalence of the PCSK9 R46L loss-of-function allele. Mechanistically, PCSK9 inhibitors lowered Lp(a) levels through 2 pathways: suppression of hepatic synthesis and enhanced plasma clearance. This evidence supports the 2023 ESC guidelines, which issued a Class IIa recommendation for PCSK9 inhibitor use in patients with ASCVD and elevated Lp(a) levels. Given the evolving landscape, further research is warranted to confirm the role of these therapies in precision medicine paradigms for managing Lp(a)-associated risks. Show less

Calcific aortic valve disease (CAVD) is a cardiovascular disease closely associated with aging. The role of lipoprotein(a) [Lp(a)] has attracted considerable attention in recent years. However, limited research has simultaneously explored the relationships between Lp(a), age, and CAVD. This study sought to assess the relationship linking Lp(a), time-weighted Lp(a), and CAVD. A total of 5,156 inpatients with comprehensive clinical data were recruited for this study. The associations of Lp(a) and time-weighted Lp(a) with CAVD were examined via multivariate logistic regression analysis, alongside the application of restricted cubic spline analysis. The diagnostic utility of Lp(a) and time-weighted Lp(a) for CAVD was assessed by constructing receiver operating characteristic (ROC) curves. CAVD prevalence rose with age, whereas the rate of increase diminished with advancing age. The average Lp(a) level in the young populations with CAVD was more than twice that in the No-CAVD group, particularly among those aged 55 years or younger. The prevalence of CAVD in non-elderly populations was markedly 2–4 fold greater in the higher Lp(a) group (> 30 mg/dL) than in the lower Lp(a) group (≤ 30 mg/dL). Multivariate adjusted odds ratios ‌(ORs) for CAVD increased with advancing Lp(a) or age. Time-weighted Lp(a), which takes into account both age and Lp(a), was more strongly linked to elevated CAVD risk than Lp(a) alone. Time-weighted Lp(a) enhanced the diagnostic value of CAVD, improving both sensitivity and specificity. The risk of CAVD is strongly associated with both age and elevated Lp(a) levels. Time-weighted Lp(a), which integrates these factors, serves as a superior indicator that better captures cumulative long-term Lp(a) variation and yields stronger CAVD risk stratification. The online version contains supplementary material available at 10.1186/s12944-026-02884-8. Show less