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
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Gene Show more
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Genetic risk factors strongly influence LBD susceptibility, including SNCA multiplication, particularly triplication, and the apolipoprotein E ε4 allele (APOE4), the strongest common genetic risk factor for LBD. While SNCA is predominantly expressed in neurons and APOE primarily in glial cells, how these genetic factors converge to impact neuronal vulnerability and regional pathology in the human brain remains poorly understood. Here, we applied spatial transcriptomics to postmortem temporal cortex tissue from LBD cases with SNCA triplication or different APOE genotypes, alongside age- and sex-matched controls, to map gene expression within intact cortical architecture. We identified layer 5 of the gray matter as a particularly vulnerable region, characterized by elevated SNCA expression, pronounced synaptic and metabolic dysregulation, and exacerbation of these alterations in APOE4 carriers. Reelin signaling emerged as a core Lewy body-associated pathway disrupted across cortical layers, validated in independent postmortem cohorts and human-induced pluripotent stem cell (iPSC)-derived cortical organoids. In contrast, white matter exhibited distinct molecular alterations, including disrupted myelination pathways, with APOE4 carriers showing increased myelin debris and glial responses compared with non-carriers. Cell-type deconvolution informed by single-nucleus RNA sequencing further revealed APOE4-associated impairments in neuronal vulnerability and intercellular communication. Together, these findings define spatially and cell-type-specific mechanisms through which SNCA dosage and APOE4 genotype impact LBD pathology, providing insight into regionally distinct disease processes and potential targets for genetically stratified therapeutic interventions. 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
Prior studies suggest that TikTok users vary in their engagement behaviors, including passive viewing, participatory interaction, and content creation, and exhibit varying levels of problematic-use ri Show more
Prior studies suggest that TikTok users vary in their engagement behaviors, including passive viewing, participatory interaction, and content creation, and exhibit varying levels of problematic-use risk. Yet it remains unclear which combinations of these engagement behaviors correspond to higher versus lower risk, and which psychological vulnerabilities contribute to high-risk patterns. In a two-wave study of 715 Chinese young adults, we applied latent profile analysis (LPA) to problematic TikTok use and the frequency of passive viewing, participatory, and contributory behaviors at Time 2. We then used multinomial logistic regression with the three-step method to prospectively examine how Time 1 measures of psychopathology and related affective/cognitive vulnerabilities, including depression, social anxiety, life satisfaction, emotion dysregulation, and boredom proneness, predicted TikTok profile membership. Four profiles emerged: Minimal Users (6.7%), Passive Watchers with High Problematic Use Tendencies (38.0%), Moderate Users with Mild Problematic Use Tendencies (42.4%), and Active Users with Low Problematic Use Tendencies (12.9%). Greater life satisfaction, lower social anxiety, and lower boredom proneness at baseline predicted membership in the Active rather than Passive, Moderate, or Minimal profiles. Greater emotion dysregulation predicted membership in the Passive rather than Moderate profile. These findings highlight substantial heterogeneity in TikTok use and suggest that higher baseline psychological wellbeing may increase the likelihood of more active and less problematic patterns of engagement. The current study extends prior LPA research by specifying how risk manifests in everyday use, identifying contributors to high-risk profiles, and extending empirical support for the I-PACE theoretical framework of Internet use disorders. Show less
Atherosclerotic lesions commonly develop in curved or bifurcated arteries, where blood flow exhibits characteristics of low shear stress (LSS). Subjected to LSS continually, endothelial cells (ECs) ad Show more
Atherosclerotic lesions commonly develop in curved or bifurcated arteries, where blood flow exhibits characteristics of low shear stress (LSS). Subjected to LSS continually, endothelial cells (ECs) adopt a pro-atherosclerotic phenotype. Ferroptosis is a recently identified form of controlled cell demise prompted by iron-dependent buildup of cellular reactive oxygen species (ROS), which has been associated with diverse cardiovascular diseases, particularly atherosclerosis (AS). P53 is a broadly acting tumor suppressor that can be activated by diverse stimuli and mediates multiple biological outcomes, including cell cycle arrest, DNA repair, apoptosis, and ferroptosis. However, it remains unknown whether LSS promotes the development of AS by inducing P53-dependent ferroptosis in endothelial cells. In our experiments, we induced LSS by partial ligation of the right common carotid artery in high-fat diet-fed (HFD) male ApoE Our findings demonstrated that LSS induced endothelial ferroptosis, which in turn accelerated AS development both in vivo and in vitro. This effect was partially counteracted by both the ferroptosis inhibitor Fer-1 and endothelium-specific glutathione peroxidase 4 (GPX4) overexpression in ApoE Our experiments suggested that LSS promotes atherosclerosis by inducing endothelial ferroptosis through the P53/xCT signaling pathway. 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
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
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
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
Depression has emerged as a concerning factor in colon cancer progression and treatment, yet its underlying mechanisms and therapeutic targets remain poorly defined. This study aimed to elucidate how Show more
Depression has emerged as a concerning factor in colon cancer progression and treatment, yet its underlying mechanisms and therapeutic targets remain poorly defined. This study aimed to elucidate how depression affects colon cancer progression and chemotherapeutic response, and to explore potential molecular targets and therapeutic interventions involving the traditional Chinese medicine formula Sinisan (SNS) and its bioactive component Quercetin. A mouse model combining depression and colon cancer was established to evaluate behavioral alterations, tumor progression, and pathological features. RNA sequencing was performed to screen the differentially expressed genes. The effects of corticosterone (CORT) on proliferation, colony formation, migration, and GSTM2 expression were examined in HCT116 cells, followed by functional validation through GSTM2 overexpression and inhibition assays. Molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) were used to validate the binding of Quercetin to GSTM2. The therapeutic efficacy of SNS and Quercetin was assessed with respect to depressive symptoms, serum BDNF levels, NLRP3 inflammasome activity, and the potency of 5-fluorouracil (5-FU) chemotherapy. Mice with depression and colon cancer exhibited aggravated depressive behaviors and accelerated tumor progression. RNA-sequencing and network pharmacology analyses identified GSTM2 as a promising candidate target in colon cancer treatment, which was markedly down-regulated in the DP-CC group. CORT enhanced proliferation, colony formation, and migration of HCT116 cells while simultaneously suppressing GSTM2 expression. Conversely, GSTM2 levels negatively correlated with cell proliferation, colony formation, and chemoresistance in HCT116 cells. Treatment with SNS alleviated depressive symptoms, elevated serum BDNF, reduced NLRP3 inflammasome activity, and potentiated the efficacy of 5-FU chemotherapy. Quercetin, a bioactive component of SNS, bound to GSTM2 through hydrogen-bond and van-der-Waals interactions, up-regulated GSTM2 expression, and mitigated CORT-induced proliferation, colony formation, and chemoresistance. Our findings suggest that depression promotes colon-cancer progression by down-regulating GSTM2, whereas SNS restores GSTM2 expression and enhances chemotherapeutic response. 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
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
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
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibili Show more
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibility remain incompletely understood. Here, we employed a two-hit model combining adolescent social isolation stress (SIS) with adult chronic restraint stress (CRS) to examine how developmental stress interacts with adult stress exposure. SIS alone or CRS alone exerted minimal behavioral effects, whereas SIS followed by CRS markedly potentiated depression-like behaviors and impaired spatial and object recognition memory. Two-hit stress produced robust hippocampal neuroinflammatory responses, including increased astrocytic and microglial activation and elevated TNF-α, IL-1β, IL-6, and IL-17A levels. These inflammatory alterations were accompanied by pronounced suppression of the BDNF/TrkB/p-CREB signaling cascade, reduced synaptic protein expression, and diminished dendritic spine density and branching complexity in CA1 pyramidal neurons. Notably, light treatment (LT) administered during CRS exposure significantly reversed two-hit induced behavioral deficits, attenuated glial activation and cytokine upregulation, enhanced BDNF/TrkB and p-CREB signaling, and restored synaptic and structural plasticity. Together, these findings indicate that adolescent SIS primes the hippocampus for exaggerated neuroinflammatory and neuroplastic impairments following adult stress, thereby amplifying stress vulnerability. Furthermore, LT emerges as a safe non-pharmacological intervention capable of mitigating combined stress-induced emotional and cognitive dysfunction by targeting neuroinflammatory and neurotrophic pathways. Show less
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence sugges Show more
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence suggests that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play central and interrelated roles in its pathogenesis. In this review we examine the bidirectional functions of 5-HT and BDNF in both the reproductive and nervous systems, highlighting their importance in regulating ejaculation, emotional stability, and synaptic plasticity. A comprehensive literature search (2010-2025) was conducted across multiple databases using relevant Medical Subject Headings (MeSH) terms, including pertinent original research and review articles, to synthesize the roles and regulatory pathways of 5-HT and BDNF in PE with comorbid anxiety or depression. We summarize the shared and distinct roles of 5-HT and BDNF in maintaining physiological balance across these systems and focus on their involvement in the major pathological processes underlying PE with anxiety or depression, including neurotransmitter imbalance, neuroendocrine dysregulation, inflammation, and oxidative stress. Furthermore, we outline the related signaling pathways through which 5-HT and BDNF exert their effects and interact. We also evaluate current pharmacological and non-pharmacological interventions targeting these molecules, demonstrating their potential to improve both ejaculatory control and emotional symptoms, and critically appraise selective serotonin reuptake inhibitor (SSRI)-related risks and highlighted the need for individualized dosing and monitoring. Emerging evidence suggests that Traditional Chinese Medicine formulations can extend intravaginal ejaculatory latency and mitigate mood symptoms and may serve as stand-alone or adjunctive options to reduce reliance on selective serotonin reuptake inhibitors (SSRIs). Overall, 5-HT and BDNF are not only deeply involved in the biological mechanisms of PE with comorbid psychological disorders, but also represent promising biomarkers and therapeutic targets, and their integrative neuro-reproductive regulatory functions provide new insights into the diagnosis and treatment of this multifaceted condition. 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
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
Older adults typically have higher sedentary behaviour (SB) and lower physical activity (PA) than younger adults. Studies on replacing SB with PA in relation to all-cause mortality in racially diverse Show more
Older adults typically have higher sedentary behaviour (SB) and lower physical activity (PA) than younger adults. Studies on replacing SB with PA in relation to all-cause mortality in racially diverse older adults remain limited. This study included 122 966 older adults from the China Kadoorie Biobank (CKB) and 207 212 older adults from the UK Biobank (UKB). SB and PA were assessed using baseline questionnaires, with PA classified as light (LPA), moderate (MPA) or vigorous (VPA) based on metabolic equivalents. Cox proportional hazards models and isotemporal substitution models were used to examine the associations between replacing SB with different PA intensities and all-cause mortality. Longer SB (per 30 min/day increase) was associated with a higher risk of all-cause mortality in both cohorts (CKB: HR 1.013, 95% CI 1.010 to 1.017; UKB: HR 1.012, 95% CI 1.009 to 1.015). PA of any intensity was associated with a reduced risk of all-cause mortality. In the CKB, replacing 30 min/day of SB with an equivalent duration of PA showed comparable protective associations (LPA: HR 0.963, 95% CI 0.958 to 0.968; MPA: HR 0.967, 95% CI 0.961 to 0.972; VPA: HR 0.965, 95% CI 0.960 to 0.971). In the UKB, replacing 30 min/day of SB with VPA was associated with the largest reduction in mortality risk (HR: 0.950, 95% CI 0.931 to 0.970). Replacing SB with PA of any intensity was associated with reduced all-cause mortality risk in older adults, with variations across populations. These findings highlight the need for population-specific PA recommendations to promote healthy ageing. Show less
Jianyi Li, Luyao Zhang, Jiapei Xu+7 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, s Show more
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, such as Dapagliflozin (DAPA), exhibit a protective effect against cardiovascular diseases. However, the effects and mechanisms of DAPA on chronic stress-induced AS are largely unknown. The aim of this study was to determine whether DAPA confers a protective effect against chronic stress-induced AS and to elucidate its further molecular mechanisms. The combined high-fat diet-fed and chronic unpredictable mild stress in ApoE-/- mice and lipopolysaccharides- and corticosterone-induced human umbilical vein endothelial cells (HUVECs) were employed to evaluate the antiatherosclerotic effect of DAPA under chronic stress in vivo and in vitro. Histological staining, western blot analysis, siRNA transfection, reactive oxygen species (ROS) staining, and apoptosis assessment were used to investigate the potential mechanisms of DAPA against AS under chronic stress. The results indicate that DAPA significantly improved plaque size and increased plaque stability in the aorta under chronic stress and reduced inflammation and oxidative stress and inhibited apoptosis in the aorta and HUVECs. Chronic stress upregulated regulated in development and DNA damage response 1 (REDD1) expression, which exacerbated cellular inflammation, oxidative stress, and apoptosis levels, leading to endothelial dysfunction. In contrast, DAPA downregulated REDD1 expression and activated the AKT/FoxO1 pathway. In addition, p53 was a transcriptional regulator of REDD1 under chronic stress. More importantly, p53 agonists prevented DAPA from downregulating REDD1 and inhibited AKT/FoxO1 activation, thereby exacerbating chronic stress-induced endothelial dysfunction. These results suggest that DAPA effectively attenuates chronic stress-induced endothelial dysfunction and AS by downregulating REDD1 to activate the AKT/FoxO1 pathway. Show less
Ribonuclease P (RNase P) is an essential metallonuclease found in all three domains of life. However, the structural basis for the ancient RNase P RNA component acting alone as a ribozyme and catalyti Show more
Ribonuclease P (RNase P) is an essential metallonuclease found in all three domains of life. However, the structural basis for the ancient RNase P RNA component acting alone as a ribozyme and catalytic metal-ion chemistry remains unknown. We report a series of cryo-EM structures, at resolutions of 2.8-3.5 Å, of the Geobacillus stearothermophilus RNase P aporibozyme (apoE) in various states of the catalytic cycle. The formation of both the tetraloop/tetraloop-receptor interaction and the interdigitated double T-loop motif in the substrate-specificity domain facilitates substrate binding. The apoE uses two metal ions for catalysis, suggesting a catalytic mechanism and evolutionary importance of the RNase P ribozyme to function without its protein component. Together, our data portray the regulatory RNA-RNA interfaces, dynamic structures, and cation traffic that confer function to a trans-acting ribozyme. Show less
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative i Show more
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative importance of endothelial METRNL in atherosclerosis by comparing the effects of whole-body METRNL deficiency to endothelial-specific deficiency, and to show the subcellular distribution of endothelial METRNL and its role in mitochondrial homeostasis against atherosclerosis. Our study demonstrated that a deficiency in either endothelial or global METRNL exacerbated atherosclerosis to a similar degree in both spontaneous (age-related) and high fat diet-induced atherosclerosis, suggesting that endothelial METRNL is pivotal in the progression of atherosclerosis due to METRNL deficiency. Endothelial METRNL was diffusely distributed in the cytoplasm with subcellular localization to mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus (especially enriched in mitochondria and nucleus). In both an in vivo apolipoprotein E-deficient (ApoE 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