Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable s Show more
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable strategies for Show less
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroup Show more
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroups, risk factors, and symptom-level interactions underlying depression-anxiety comorbidity across adolescents and adults in multi-ethnic Southwest China. The study included a total of 41,394 adolescents (aged 9-19) and 17,345 adults (aged 18-80). Adolescents were recruited using multistage stratified cluster sampling, whereas adults were recruited by convenience sampling. All participants completed a self-designed sociodemographic questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Latent profile analysis identified subgroups, logistic regression analyzed risk/protective factors, and network analysis mapped symptom interactions and bridge nodes. This study found that three adolescent profiles emerged: high (11.66 %), moderate (31.95 %), and low/no depression-anxiety (56.39 %). Adults were classified into low/no comorbidity (90.63 %) and comorbid depression-anxiety (9.37 %). Risk factors for adolescents included female gender (OR = 2.77, 95 %CI: 2.55-3.00; OR = 1.59, 95 %CI: 1.52-1.67), higher grade levels (OR = 3.45, 95 %CI: 3.10-3.84; OR = 3.56, 95 %CI: 3.33-3.80), smoking (OR = 1.72, 95 %CI: 1.51-1.96; OR = 1.28, 95 %CI: 1.17-1.41),drinking (OR = 2.45, 95 %CI: 2.23-2.70; OR = 1.66, 95 %CI: 1.55-1.77), family instability (OR = 1.16, 95 %CI: 1.02-1.31; OR = 1.33, 95 %CI: 1.14-1.56) and "other" ethnic minority (OR = 1.15, 95 %CI: 1.04-1.26). For adults, female gender(OR = 1.68; 95 %CI: 1.44-1.97), living alone(OR = 1.37; 95 %CI: 1.14-1.65), poor self-rated health (OR = 0.13, 95 %CI: 0.11-0.15), and Dai ethnicity (OR = 0.70, 95 %CI: 0.49-0.96) predicted comorbidity. Network analysis revealed distinct bridge symptoms: adolescents in the high depression-anxiety group had five symptoms: depressed or sad mood (phq2), psychomotor agitation/retardation (phq8), nervousness or anxiety (gad1), restlessness (gad5), and irritable (gad6); however, adults with comorbidity had one symptom: afraid something will happen (gad7). This study identified three patterns of depression-anxiety comorbidity in adolescents and two in adults. Efforts should prioritize adolescents from "other" ethnic minorities, strengthening family and peer support, as well as smoking and drinking interventions for adolescents, and addressing social isolation, physical health, and catastrophizing cognition in adults may mitigate the comorbidity burden. 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 litera Show more
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
BackgroundPredicting cognitive function across dementia stages remains challenging. Plasma biomarkers and electroencephalogram (EEG) features may provide complementary information, but their combined Show more
BackgroundPredicting cognitive function across dementia stages remains challenging. Plasma biomarkers and electroencephalogram (EEG) features may provide complementary information, but their combined predictive value requires further study.ObjectiveTo evaluate the feasibility of integrating plasma biomarkers and EEG features to predict cognitive function in dementia and examine their correlations.MethodsFrom September 2023 to October 2024, 75 patients from two medical centers with mild cognitive impairment, mild dementia, or moderate dementia were enrolled. Resting-state 19-channel EEG data yielded 2737 time-frequency and connectivity features. Plasma biomarkers included tau, p-Tau181, Aβ Show less
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. Show less
Atherosclerosis is fundamentally a pathology of unresolved inflammation perpetuated by the collapse of Regulatory T cell (Treg)-mediated tolerance. Emerging evidence indicates that Treg functional int Show more
Atherosclerosis is fundamentally a pathology of unresolved inflammation perpetuated by the collapse of Regulatory T cell (Treg)-mediated tolerance. Emerging evidence indicates that Treg functional integrity is intrinsically dictated by mitochondrial fatty acid oxidation (FAO), a metabolic checkpoint often compromised under systemic metabolic stress. Current lipid-lowering therapies, such as statins, often fall short in correcting this maladaptive immunometabolic defect and may introduce collateral metabolic perturbations. This study aimed to elucidate the immunometabolic therapeutic mechanism of Dingxin Recipe III (DXR III) in ameliorating atherosclerosis. We employed an integrated systems pharmacology strategy-combining serum pharmacochemistry, multi-omics profiling, and extensive high-dimensional flow cytometry-to elucidate the therapeutic mechanism of DXR III, a traditional Chinese herbal formula in an in vivo study. ApoE DXR III treatment effectively attenuating atherosclerotic progression. Serum pharmacochemistry identified 254 prototypical absorbed constituents, including Tanshinone I (a potential Peroxisome Proliferator-Activated Receptor Gamma agonist), as bioactive candidates. Multi-omics analysis revealed that DXR III modulated the metabolic environment, coinciding with restored FAO flux. This shift was associated with a favorable metabolic niche characterized by increased FAO substrates, which correlated with the rescue of Treg differentiation and phenotypic stability. Specifically, DXR III facilitated the redistribution of Tregs from the spleen to plaque sites and significantly inhibited their trans-differentiation into Th1-like or Th17-like phenotypes. Conversely, Simvastatin treatment, despite lowering lipids, resulted in peripheral Th17 accumulation and failed to alleviate hyperglycemia. In contrast, DXR III maintained Th17 homeostasis-abolishing the pathogenic non-classical Th17 subset-and exerted dual-regulatory effects on both lipid and glucose metabolism. DXR III ameliorates atherosclerosis, a process closely associated with the modulation of the FAO metabolic checkpoint to correct the immune imbalance driving plaque progression. By rescuing the Treg differentiation, functional integrity, and phenotypic fidelity while avoiding the immunological trade-offs associated with Th1/Th17, DXR III represents a promising candidate for comprehensive cardiovascular protection. Show less
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 Show more
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 (IRF6) is a transcription factor that regulates the inflammatory response following injury. In this work, the LSS-induced AS model was induced by the partial ligation of the left carotid artery in high-fat diet-fed ApoE Show less
Changming Shao, Chunfa Cheng, Bing Chen · 2026 · Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists · SAGE Publications · added 2026-04-24
To construct a risk model for discriminating abdominal aortic aneurysm (AAA) rupture and explore its potential mechanism. Clinical data of AAA patients were obtained from the MIMIC-IV database. The mu Show more
To construct a risk model for discriminating abdominal aortic aneurysm (AAA) rupture and explore its potential mechanism. Clinical data of AAA patients were obtained from the MIMIC-IV database. The multivariable logistic analysis was performed to identify the independent risk factors associated with AAA rupture. The nomogram model was used, and its risk score was calculated. The clinical relevance of the model was assessed by receiver operating characteristic curve analysis and the Kaplan-Meier plotter. The potential mechanism was investigated by the enrichment and immune cell infiltration analyses using the GSE98278 dataset from the Gene Expression Omnibus (GEO) database. A total of 309 AAA patients were divided into rupture (n=39) and non-rupture (n=270) groups. White blood cell (WBC), hematocrit (HCT), platelets, and glucose were associated with the AAA rupture (all p<0.05). The risk score of the nomogram model (area under the curve [AUC]=0.746) was a promising index in discriminating AAA rupture. Besides, the high-risk score was related to patients' survival (1, 5 years) (HR The risk score of the nomogram model could discriminate AAA rupture, and it was also linked to the poor prognosis of AAA patients. Moreover, T cells CD4 memory activated may be related to AAA rupture by involving the immune environment.Clinical ImpactThis study identified risk factors associated with AAA rupture, constructed a risk model, and explored its underlying mechanisms. High-risk scores derived from the nomogram model were negatively associated with patient outcomes, indicating that this risk model can serve as a stratification tool to guide individualized intervention strategies. The risk model utilizing fewer indicators can be employed for initial screening, followed by application of composite scores for high-risk patients to optimize clinical decision-making and enhance the efficiency of healthcare resource allocation. Show less
Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a tempo Show more
Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a temporally controlled hydrogel microneedle system that integrates ginseng-derived exosomes (G-Exos) with biomimetic polydopamine nanoparticles (PDA@PEGs) to concurrently target the pathogenic triad of vitiligo, including oxidative stress, inflammation, and melanocyte deficiency. This system employs methacrylated hyaluronic acid (HAMA) hydrogel microneedles for rapid PDA@PEG release while utilizing glyceryl monostearate micelles to achieve matrix metalloproteinase-9 (MMP-9)-responsive G-Exo release at inflammatory foci, enabling intelligent spatiotemporal control. Functionally, G-Exos help restore redox homeostasis and suppress inflammation through bioactive constituents, thereby protecting melanocytes and enhancing keratinocyte proliferation. Moreover, PDA@PEG promotes repigmentation through the dual mechanisms of exogenous melanin deposition and endogenous melanogenesis stimulation. In murine models, this strategy achieves significant repigmentation within 3 weeks by activating follicular stem cells, upregulating melanogenic markers (Tyr/Mc1r), increasing antioxidant defense (ApoE), and suppressing inflammatory signaling (IL-17). This natural-biomimetic hybrid design leverages biocompatible materials to co-target multiple pathological axes, offering a novel self-adaptive approach for microenvironmental rehabilitation in vitiligo. Show less
This study aims to identify distinct subgroups of digital resilience among nursing students and examine the factors associated with these subgroups. Digital resilience, the ability to adapt to technol Show more
This study aims to identify distinct subgroups of digital resilience among nursing students and examine the factors associated with these subgroups. Digital resilience, the ability to adapt to technological changes and overcome challenges in higher education, is crucial for protecting students' psychological health and improving academic performance. In the context of Artificial Intelligence (AI) and digital transformation in nursing education, this resilience is essential for students to navigate virtual learning and integrate advanced technologies into their practice. A cross-sectional study. This study was conducted in eight universities in China guided by ecological systems theory and nursing students were recruited through convenience sampling. Latent profile analysis (LPA) identified subgroups and logistic regression examined related factors. A total of 331 (81.73 %) participants were included in the final analysis. The average age of participants was 20.41SD0.67 years, with 283 female (85.55 %). Latent profile analysis revealed two subgroups: the "High Digital Resilience Group" (n = 278, 83.99 %) and the "Low Digital Resilience Group" (n = 53, 16.01 %). Participants who were male (OR = 3.47, p = 0.02), had low household income (OR = 0.23, p = 0.01, low professional identity (OR = 0.86, p < 0.001) and low friend support (OR = 0.82, p < 0.001) were more likely to belong to the low digital resilience group. Educators should focus on enhancing students' professional identity and providing social support, especially for those with low digital resilience. The findings provide practical guidance for integrating AI into nursing education to enhance digital resilience. Show less
Insomnia and anxiety are highly comorbid, severely compromising quality of life. Efficacy of current pharmacological interventions for this dual condition remains limited. Zhi-Gan Formula (ZG), consis Show more
Insomnia and anxiety are highly comorbid, severely compromising quality of life. Efficacy of current pharmacological interventions for this dual condition remains limited. Zhi-Gan Formula (ZG), consisting of Zhi-Zi-Chi Decoction and Ganmai Dazao Decoction, two classic Traditional Chinese Medicine (TCM) formulae clinically widely used for insomnia or anxiety, holds promise as a therapeutic option for insomnia-anxiety comorbidity. This study aimed to assess ZG's sleep-promoting and anxiolytic efficacy, and investigate the novel mechanism through which pituitary adenylate cyclase-activating polypeptide (PACAP) in the medial prefrontal cortex (mPFC) modulates comorbid sleep and anxiety conditions. Mice received 4-chloro-DL-phenylalanine (PCPA) injections and were subsequently administered ZG or diazepam. Behaviors were assessed using the pentobarbital-induced sleep test, open-field test (OFT), and elevated plus-maze test (EPM). Key pathways were identified via network pharmacology analysis and validated using long-term potentiation (LTP) recordings and protein quantification. Viral-mediated PACAP knockdown vectors were transfected into the mPFC. PCPA administration induced insomnia and anxiety-like behaviors. ZG administered for 3 days significantly shortened sleep latency, prolonged sleep duration, and alleviated anxiety-like behaviors, whereas diazepam only partially improved anxiety-like behaviors. Network pharmacology analysis suggested ZG's engagement in neuropeptide-receptor interactions and synaptic transmission pathways. Assessments of synaptic plasticity showed that ZG improved mPFC LTP and the expression of synaptic proteins (PSD95, synapsin-1, BDNF) impaired in the model mice. Moreover, the expression of the neuropeptide PACAP and downstream eEF2 signaling for synaptic protein synthesis were all improved by ZG. Crucially, perfusion of a PACAP agonist in the mPFC brain slices from sleep-deprived mice rescued LTP deficits. Finally, mPFC PACAP knockdown abolished the therapeutic effects and the enhanced expressions of the synaptic proteins by ZG. ZG alleviated insomnia-anxiety comorbidity by restoring synaptic plasticity in the mPFC via the PACAP-eEF2-BDNF pathway, which may also shed light on the development of a novel therapeutic approach for the treatment of sleep-anxiety comorbidity. Show less
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic Show more
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic characteristics, health literacy, confidence in self-care contributions, family intimacy, and profile membership. We recruited 275 dyads of patients with COPD and their family caregivers from five tertiary hospitals between May and November 2022 using convenience sampling. Latent profile analysis (LPA) was used to identify distinct profiles of caregiver self-care contributions. Univariate analysis and multinomial logistic regression were subsequently conducted to examine associations between participant characteristics and profile membership. LPA identified four distinct profiles of caregiver self-care contributions: low-contributing, under-monitored, maintenance-prioritized, and high-contributing. Significant differences were observed across these profiles in terms of patients' symptom severity, exacerbation frequency, number of hospitalizations, caregivers' education levels, caregiving duration, health literacy, confidence in self-management contributions, and family intimacy using univariate analysis. Multinomial logistic regression analysis revealed that caregivers' education levels, caregiving duration, confidence in self-management contributions, and health literacy were significant predictors of profile membership. Caregiver self-care contributions for patients with COPD can be characterized by four distinct profiles, with caregivers' educational level, health literacy, and confidence in self-management identified as key factors associated with profile membership. Show less
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological Show more
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer. Show less
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impa Show more
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined. Using a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment. MCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (E Our findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy. Show less
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating Show more
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating heterogeneity of CAFs in renal cell carcinoma (RCC) could represent potential targets for reprogramming the TME. In this study, we conducted single-cell RNA sequence and flow cytometry analyses that identified a CAF subset overexpressing apolipoprotein E (ApoE), which was correlated with poor survival in patients with RCC. Mechanistically, NRF1 activation in CAFs induced formation of ApoEhigh CAFs and secretion of NRG1. ApoEhigh CAFs potentiated stemness properties in the surrounding RCC cells by secreting NRG1 and subsequently activating the HER2/NF-κB pathway. Interfering with NRG1 expression or inhibiting NF-κB signaling reduced ApoEhigh CAF-induced stemness of RCC cells. Furthermore, neutralizing NRG1 enhanced the efficacy of sunitinib in RCC models in vivo. Together, these findings highlight targeting the tumor-promoting functions of ApoEhigh CAFs as a promising approach for treating advanced RCC. NRF1 drives formation of ApoEhigh cancer-associated fibroblasts that secrete NRG1 to stimulate stemness of renal cell carcinoma, revealing a stromal-mediated mechanism that can be inhibited to improve treatment of advanced kidney cancer. Show less
Growing evidence implicates accelerated biological aging in environmentally induced psychiatric disorders, yet its role in metal-associated depression remains unclear. Using NHANES data, we evaluated Show more
Growing evidence implicates accelerated biological aging in environmentally induced psychiatric disorders, yet its role in metal-associated depression remains unclear. Using NHANES data, we evaluated associations between heavy metal mixtures and depression. Bidirectional mediation analysis was used to assess reciprocal pathways linking heavy metals, biological aging, and depression. Simultaneously, candidate genes linking heavy metal exposure to depression and biological aging were identified by mining the Comparative Toxicogenomics Database, analyzing differentially expressed genes (DEGs) from the Gene Expression Omnibus, and integrating the resulting evidence within a toxicogenomic framework to explore potential molecular mechanisms. The prevalence of depression among participants was 8.66 %. Metal mixtures significantly increased depression risk. Notably, cadmium and antimony increased the risk of depression (OR: 1.52, 95 % CI: 1.19, 1.94 and OR: 1.54, 95 % CI: 1.22, 1.93). Both metals have low thresholds (0.227 μg/L and 0.053 μg/L, respectively). Additionally, lead, cobalt, and molybdenum showed positive associations in specific models. Although population-level exposure to heavy metals declined from 1999 to 2020, concentrations remained sufficient to elevate depression risk. Our correlation analysis also identified a strong correlation between PhenoAge and chronological age (r = 0.84, P < 0.001). Mechanistically, we found that accelerated PhenoAge partially mediated the associations of several metals with depression risk, including monomethylarsonic acid (β = 0.004; 95 %CI: 0.003,0.006), cadmium (β = 0.006; 95 %CI: 0.003, 0.010), lead (β = 0.009; 95 %CI: 0.006, 0.011), cobalt (β = 0.010; 95 %CI: 0.006, 0.013), molybdenum (β = 0.009; 95 %CI: 0.006, 0.011), and antimony (β = 0.008; 95 %CI: 0.005, 0.011). Pathway analysis and DEGs implicated the contribution of neurodegeneration-multiple diseases pathway, with core molecular targets centering on BDNF, IL6, GSK3B, PTGS2, and SOD1. These findings, which imply biological aging as a potential link between metal exposure and depression, call for revised safety thresholds and pinpoint molecular targets for intervention. 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 Show more
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
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclero Show more
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclerotic cardiovascular diseases, their effects are limited in those with homozygous familial hypercholesterolemia. It is essential to seek new lipid-lowering targets. YAP (Yes-associated protein) may be involved in lipid metabolism in the liver; therefore, we investigated the function of hepatocyte YAP in hyperlipidemia and atherosclerosis. Hyperlipidemia models were generated in apoE knockout (apoE High-cholesterol diet-fed apoE Taken together, our findings revealed a novel role for the YAP-TEAD4-ANGPTL3 axis in lipid metabolism independent of LDLR. Inhibition of hepatocyte YAP may be an effective lipid-lowering strategy for homozygous familial hypercholesterolemia. Show less
Coronary artery calcification (CAC), a hallmark of coronary atherosclerosis, links closely to dysregulated lipid metabolism and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCS Show more
Coronary artery calcification (CAC), a hallmark of coronary atherosclerosis, links closely to dysregulated lipid metabolism and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors exert potent lipid-lowering and anti-inflammatory effects, holding translational potential for vascular calcification intervention. However, evidence on PCSK9 inhibition's impact on vascular calcification remains inconsistent. Here, we combined genetic causal analysis with First, we used two-sample Mendelian randomization (MR) and multivariable Mendelian randomization to identify lipid profiles genetically associated with coronary artery calcification. Subsequently, we investigated the value of the PCSK9 gene as a potential therapeutic target for CAC through drug target MR and colocalization analysis, and screened for potential inflammatory mediators via Mediation MR analyses. Following the completion of the aforementioned analyses, we verified the beneficial effect of PCSK9 inhibitors on delaying vascular calcification through animal experiments and cell experiments. MR analysis revealed that genetic proxies for apolipoprotein B (ApoB) (OR=1.64; 95%CI: 1.42-1.90; Inhibition of PCSK9 may effectively slow the progression of coronary artery calcification, with inflammatory mediators such as FGF23 playing key regulatory roles in this process. Show less
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, usi Show more
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated Show less
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no es Show more
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no established blood-based biomarkers of CR in prodromal AD. In this study, we operationalize CR as memory reserve, defined as moderation (attenuation) of the CSF pTau181-memory association. DNA methylation (DNAm) integrates genetic and environmental influences and may capture biological processes that mitigate the impact of AD pathology on memory. We aimed to identify blood DNAm loci that moderate the association between cerebrospinal fluid (CSF) phosphorylated tau (pTau181) and memory in mild cognitive impairment (MCI). We also sought to determine if a DNAm-based signature of memory reserve predicts future memory decline. We analyzed 92 amyloid positive MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with blood DNAm, CSF pTau181, and memory scores (PHC_MEM) collected at the same visit. We first regressed memory scores on covariates (age, sex, number of After removing CpGs with low variability, we identified 6 CpGs with suggestive significance for DNAm×pTau181 interaction ( Blood DNAm patterns that moderate the pTau-memory relationship capture biology underlying memory reserve involving synaptic, vascular, immune, and metabolic pathways, and can be summarized into an MRS that predicts longitudinal memory trajectories in MCI. These findings support blood DNAm as a promising, non-invasive biomarker of cognitive resilience to AD pathology. Show less
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively Show more
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated. PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN. Show less
Ting Fang, Xinyu Yang, Xiaoqing Deng+5 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
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 tu Show more
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
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonst Show more
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonstrated that 5'tRF-GlyGCC is overexpressed in BC tissues and negatively associated with patients' survival. Mechanistically, 5'tRF-GlyGCC binds to lactate dehydrogenase A (LDHA), enhancing its enzymatic activity and promoting glycolysis, which drives BC cell malignancy. This binding is mediated by the phosphorylation of LDHA at tyrosine 10, and facilitated by fibroblast growth factor receptor 1 (FGFR1), through the formation of a ternary complex that amplifies oncogenic signaling. Furthermore, 5'tRF-GlyGCC/LDHA axis induces macrophage infiltration and polarization toward an M2 phenotype, mediated by the chemokine CCL7, thereby reshaping the tumor microenvironment. Additionally, it is uncovered that the biogenesis of 5'tRF-GlyGCC is regulated by ALKBH3 and ANG, which also modulate LDHA activity. In vivo, targeting 5'tRF-GlyGCC/LDHA signaling significantly suppresses tumor growth and enhances the efficacy of immunotherapy. Collectively, these findings elucidate the pivotal role of 5'tRF-GlyGCC in BC progression, highlighting its potential as therapeutic target for BC treatment. Show less
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN Show more
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN injury. Placental-derived connective tissue matrix (pd-CTM) could fill this need, as it contains a plethora of cytokines with potential UVFP therapeutic benefits. This study aimed to identify and quantify the factors in a commercially available pd-CTM (CTM Flow, CTM Biomedical, Lake Worth, Florida) and to study the effects of pd-CTM on vocal fold microenvironment and glottic function in a mouse model of unilateral RLN injury. Cytokine expression (ng/mL) in pd-CTM was characterized using a cytokine array and ELISA. In a separate experiment, C57/BL6 mice were divided into three groups: uninjured negative controls (n = 12), RLN transection with ipsilateral saline thyroarytenoid (TA) injection (n = 16), and RLN transection with ipsilateral pd-CTM TA injection. Outcomes included laryngeal electromyography (L-EMG) and video laryngoscopy after 7 and 28 days, with larynges then harvested and analyzed via immunohistochemistry (IHC) and qPCR. pd-CTM characterization showed moderate-to-high levels of neurotrophic (BDNF, CNTF, GDNF, NTF-3), angiogenic (Angiogenin, VEGF-D), tissue remodeling (bFGF, IGF-1, HGF, TGF-β3), and anti-inflammatory factors (IL-10, IL-1Rα). L-EMG demonstrated increased mean normalized area under the curve ratio in pd-CTM treated mice compared to saline treated mice at the 28-day time point indicating reinnervation (p < 0.001). IHC detected innervated neuromuscular junctions 28 days after pd-CTM treatment. pd-CTM may be a novel treatment option for patients with UVFP based on the neurotrophic, angiogenic, tissue remodeling, and anti-inflammatory factors present. NA. Show less
Anti-inflammatory colchicine therapy has emerged as a new era for atherosclerotic cardiovascular diseases. However, the therapeutic benefit of colchicine has not been clearly defined. Herein, we prese Show more
Anti-inflammatory colchicine therapy has emerged as a new era for atherosclerotic cardiovascular diseases. However, the therapeutic benefit of colchicine has not been clearly defined. Herein, we present a double coordination-driven approach to fabricate a stable metal-organic nano-assembly of colchicine (COL-TA-Zn) by uniting the tropolone ring of colchicine (COL), phenolic groups of tannic acid (TA), and Zn Show less
Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the U Show more
Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly linked to mortality. Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the GABBR1 and ECM1 genes, and brain structure. Distinct organ-specific pathogenic pathways were identified, with the brain and artery clocks linking synaptic loss, vascular dysfunction and glial activation to cognitive decline and dementia. The brain aging clock further stratified Alzheimer's disease risk across APOE haplotypes, and a super-youthful brain appears to confer resilience to APOE4. Together, proteomic organ aging clocks provide a biologically interpretable framework for tracking aging and disease risk across diverse populations. Show less
Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thorou Show more
Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like Lactobacillus and Bifidobacterium. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/β-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy. Show less