Alzheimer's disease (AD) is frequently complicated by vascular co-morbidities. However, the specific mechanistic pathways by which vascular lesions interact with genetic susceptibility to accelerate c Show more
Alzheimer's disease (AD) is frequently complicated by vascular co-morbidities. However, the specific mechanistic pathways by which vascular lesions interact with genetic susceptibility to accelerate cognitive decline remain unclear. This study investigated whether cerebral amyloid angiopathy (CAA) and cortical microinfarcts mediate the impact of AD pathology on cognition and evaluated the modifying role of APOE genotype. We conducted a retrospective clinico-pathological study using the National Alzheimer's Coordinating Center (NACC) database. The cohort included autopsy-confirmed participants aged 50 and older. Structural Equation Modeling (SEM) was employed to quantify the pathways linking AD pathology (Thal phase) to CAA severity, microinfarcts, and cognitive performance (CDR-Sum of Boxes). We further assessed the cumulative burden of pathology by comparing "Pure AD" cases against those with a "Triple Hit" of AD, CAA, and microvascular injury. SEM analysis identified a significant statistical mediation pathway wherein parenchymal amyloid is strongly associated with CAA, which correlates with an increased risk of microinfarcts and subsequent cognitive dysfunction. We observed a significant gene-pathology interaction: APOE ε4 carriers demonstrated a steeper trajectory of cognitive decline for a given severity of CAA compared to non-carriers. Furthermore, the "Triple Hit" group exhibited significantly worse cognitive impairment than the "Pure AD" group (P < 0.001), independent of age and education. Vascular pathology is a critical mediator of cognitive failure in AD, particularly in APOE ε4 carriers. The concurrent "Triple Hit" of proteinopathy and vasculopathy is associated with a profound failure of cognitive reserve, likely reflecting a more advanced global disease state. These findings highlight the urgent need to target vascular resilience as a disease-modifying strategy in Alzheimer's disease. 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
Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated wit Show more
Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated with cognitive frailty over time. This eight-year prospective cohort study (2011-2019) recruited 605 nondemented community-dwelling older adults at baseline. Cognitive frailty, assessed biennially, was defined as physical frailty and mild cognitive impairment. Baseline plasma metabolites were evaluated using Show less
Gary Chen, Adrienne Sexton · 2026 · Patient education and counseling · Elsevier · added 2026-04-24
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinic Show more
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinical practice. Rigorous scoping review methodology was followed. Ovid Medline, Embase, PsycINFO, and CINAHL were searched with keywords and MeSH terms related to "genetic testing", "genetic counseling", "dementia", "decision making", and "patient outcomes" for peer-reviewed studies with adult participants published over the last ten years. Thirty-six articles met inclusion criteria. Narrative synthesis organized findings into temporal categories including motivations for genetic testing, experiences during the testing/counseling process, and outcomes after testing. Common motivators included reducing uncertainty, reproductive planning, life planning, and the prospect of a treatment becoming available in the future. A lack of current treatments and fear that knowledge of genetic risk would be difficult to cope with were common barriers to testing. Patient-centered communication improved satisfaction. Genetic testing was generally psychologically well tolerated, and a wide range of practical responses were reported including changes to lifestyle, diet, advanced care and financial planning, and engaging in clinical trials. This review maps the experiences and outcomes of genetic testing or counseling for people with or at potentially increased genetic risk of dementia. Genetic testing and counseling for directly causal dementia genes and APOE genotype appears well tolerated but long-term outcome data is lacking. Motivations, concerns and perceived benefits of knowing genetic results vary depending on personal, familial and cultural viewpoints. Genetic counseling can help patients and families prepare, reduce decisional regret, and adapt to results. Motivations varied, and a patient-centered approach addressing both information and psychological aspects improves satisfaction. Future longitudinal research should ascertain ways to support individuals from a wide range of demographics with understanding and adjusting to genetic risk information regarding dementia. Show less
The bioactive peptide setmelanotide is a validated MC4R agonist, yet its clinical utility is constrained by poor aqueous solubility and dose-limiting, off-target hyperpigmentation. To overcome these d Show more
The bioactive peptide setmelanotide is a validated MC4R agonist, yet its clinical utility is constrained by poor aqueous solubility and dose-limiting, off-target hyperpigmentation. To overcome these dual liabilities, we executed a synergistic optimization strategy guided by detailed SAR investigation. This approach unveiled two critical design principles: a C-terminal "cationic imperative", where lysine uniquely conferred a > 20-fold solubility enhancement while retaining potency, and rational manipulation of the core pharmacophore, which imparted >100-fold selectivity over MC1R/MC3R. This synergy yielded the lead compound SC19, which integrates these features into a balanced profile of sub-nanomolar potency (EC₅₀ = 0.12 nM; pEC₅₀ = 9.93), exceptional selectivity, and high aqueous solubility. In a diet-induced obesity model, SC19 demonstrated robust efficacy comparable to setmelanotide in reducing weight gain and improving lipid profiles, affirming its therapeutic potential. This work not only presents a promising lead compound but also validates a synergistic optimization blueprint for concurrently enhancing the pharmacological and drug-like properties of therapeutic peptides. Show less
Atherosclerotic plaque destabilization during acute infections such as pneumonia represents a critical clinical challenge, yet the underlying molecular dynamics remain poorly characterized. This study Show more
Atherosclerotic plaque destabilization during acute infections such as pneumonia represents a critical clinical challenge, yet the underlying molecular dynamics remain poorly characterized. This study introduces a furin-responsive photoacoustic/fluorescence dual-modal probe (FRP) to investigate intraplaque furin activity in ApoE Show less
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stres Show more
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stress among Chinese female clinical nurses using latent profile analysis, compare sociodemographic differences across these subgroups, and examine their associations with premenstrual syndrome (PMS). A cross-sectional study was conducted among female nurses in tertiary hospitals in Huai'an City, Jiangsu Province, China, from November to December 2023. We recruited participants via convenience sampling, and 400 valid questionnaires were collected. Data were collected using a researcher-developed general information questionnaire, the standardized Chinese Nurses Stressor Scale (35 items), and the Premenstrual Syndrome Scale. Latent profile analysis (LPA) was performed with Mplus 8.0 to identify occupational stress subtypes. Sociodemographic predictors of these subtypes were explored using chi-square tests and multivariate logistic regression in SPSS 25.0. The association between stress subtypes and PMS symptoms was assessed using ANOVA. A Three clinical female nurse occupational stress subtypes were identified: overall low-stress (38.3%, This study identified significant heterogeneity in occupational stress among clinical female nurses, categorized into three distinct subtypes differing in stress levels and demographic characteristics. These findings highlight the importance of considering individual differences when developing interventions to address occupational stress. The study advocates for the implementation of intervention strategies targeting different types of stress in nursing education and organizational reform to better support nurses in fulfilling their responsibilities. 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
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfun Show more
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27 Show less
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its act Show more
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its active components and underlying mechanisms of action remain largely unexplored. Bauhinia brachycarpa Benth (BBB), an ethnic medicine in China, has antinociceptive effect on neuropathic pain (NP). In this study, an effective portion from BBB was screened and its antinociceptive mechanism was investigated. After the preparation of ethanolic extract from BBB (EEBb) and different soluble portion from EEBb (peEEBb, eaEEBb, nbEEBb), the total content of flavonoids and phenolic acids were measured. A partial sciatic nerve ligation (PSNL) model in vivo was applied to evaluate the antinociceptive effect and the influence on microglia function of these samples. The possible acting target of BBB was predicted by network pharmacology. And the mechanism of nbEEBb, the most effective antinociceptive portion, were studied by PSNL model in vivo and ATP-induced activation of BV2 model in vitro. nbEEBb had the strongest ability of alleviating NP as well as the obvious effect on microglia polarization. The action of nbEEBb was positively correlated to the total content of flavonoids or phenolic acids. nbEEBb inhibited the protein and gene expressions of most key components in P2X4-BDNF-TrkB signaling pathway. nbEEBb is the most effective portion from BBB on NP, and its mechanism refers to the inhibition of P2X4-BDNF-TrkB signaling pathway, which involved in neuron-microglia interaction. Show less
Glycolysis-derived lactate serves as a substrate for lysine lactylation, an epigenetic modification playing critical transcriptional regulatory roles in inflammatory diseases. Endothelial inflammation Show more
Glycolysis-derived lactate serves as a substrate for lysine lactylation, an epigenetic modification playing critical transcriptional regulatory roles in inflammatory diseases. Endothelial inflammation, characterized by upregulated glycolysis, initiates atherosclerosis, yet the contribution of histone lactylation remains undefined. Although narciclasine exhibits anti-inflammatory and antioxidant properties, its impact on endothelial inflammation in atherosclerosis is unknown. Connectivity Map (CMap) analysis predicted narciclasine as an inhibitor of oscillatory shear stress and TNF-α-induced endothelial inflammation. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with 20 nM narciclasine significantly suppressed ox-LDL-induced expression of VCAM1, ICAM1, SELE, and CCL2, reduced reactive oxygen species (ROS) production, and inhibited monocyte adhesion and migration. In vivo, administration of narciclasine (0.02 mg/kg) attenuated carotid artery endothelial inflammation and macrophage infiltration, consequently reducing early atherogenesis in partial carotid ligation model in ApoE Show less
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform Show more
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform (MDQIP) that uses a model to objectively calculate and rank compound activities, addressing the limitations of traditional "experience-driven" evaluations, accelerates the screening and evaluation of potential AChE inhibitors from Red Gastrodia elata, offering a more efficient approach to drug discovery. Ultrafiltration-LC screening identified parishin A as having the most stable binding, with binding degree and recovery rates of 98.85% and 99.39%, respectively. Molecular docking revealed that parishins A and C were the strongest AChE inhibitors, exhibiting stable binding through hydrogen bonds, π-alkyl, and π-π interactions. Molecular dynamics simulations confirmed the stability of these compounds, with binding energies of -82.65 ± 4.24 and - 80.69 ± 4.19 kcal/mol. Enzyme kinetics showed that parishins A and C are mixed-type inhibitors, with IC 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
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and Show more
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and genotype and allele frequencies were compared between groups. Multivariate logistic regression analyzed the link between ApoE polymorphisms and CAD risk in populations at middle and high altitudes. The data revealed significant differences in These findings validated that the 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
The incidence of osteoarthritis (OA) is strongly correlated with aging. It has been shown that the accumulation of senescent cells in the synovium precedes chondrocyte senescence and cartilage degrada Show more
The incidence of osteoarthritis (OA) is strongly correlated with aging. It has been shown that the accumulation of senescent cells in the synovium precedes chondrocyte senescence and cartilage degradation, suggesting that synovial cell senescence plays a key role in OA pathogenesis. This study aimed to investigate the mechanisms underlying synovial cell senescence and its influence on intercellular communication within the joint. Using multiplex immunofluorescence, gene regulatory network reconstruction, and single-cell RNA sequencing analyses, we identified senescent cells and characterized the senescence-associated secretory phenotype in the synovium. A series of in vivo and in vitro functional experiments is conducted to elucidate the mechanisms of fibroblast senescence and its effects on macrophages and chondrocytes. We found that synovial intimal fibroblasts (SIF) display more marked premature senescence compared to other synovial cell types. A specific senescent subpopulation within SIF is identified, and we demonstrated that the transcription factors EGR1 and ATF3 regulate senescence-related pathways in these cells. Furthermore, we showed that senescent SIF promote M1 macrophage polarization and cartilage degeneration through paracrine secretion of ANGPTL4. Additionally, senescent SIF may facilitate OA progression through direct cell-cell contact with macrophages. Show less
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. Show less
This study employs latent profile analysis (LPA) to identify potential categories of nurse burnout and to analyze differences in characteristics and influencing factors across burnout categories. From Show more
This study employs latent profile analysis (LPA) to identify potential categories of nurse burnout and to analyze differences in characteristics and influencing factors across burnout categories. From June to August 2025, a mixed sampling approach combining convenience and snowball sampling was used to recruit nurses from hospitals of varying levels in Southwest China. Three tools were used for data collection: A self-designed routine information questionnaire, Maslach Burnout Inventory-General Survey (MBI-GS) and Practice Environment Scale of the Nursing Work Index (PES-NWI), LPA identifies potential categories of nurses' professional burnout and uses multivariate logistic regression analysis to explore the factors associated with these categories. This study comprised a total of 809 participants. LPA identified four distinct latent classes of nursing burnout: Class 1, low-burnout-high-efficacy (11.5%); Class 2, mild-burnout-unfulfilled (33.9%); Class 3, moderate-burnout-exhausted (44.6%); and Class 4, severe-burnout-dysfunctional (10.0%). Multivariate logistic regression analysis showed that age, years of work experience, hospital level, nurses' participation in hospital management, nursing quality standards, staffing and resource adequacy, and medical care cooperation are significant predictors of burnout among nurses ( Nurse burnout in southwest China is mainly moderate to severe and exhibits distinctive characteristics. It is recommended to implement personalized interventions tailored to the specific characteristics of nurses' professional burnout to alleviate the situation. Particular attention should be given to nurses with fewer than five years of experience by providing enhanced job support and psychological assistance to help them navigate critical periods of professional burnout. These measures aim to safeguard nurses' physical and mental health, improving the overall quality of nursing, and promoting the healthy development of global medical care. Show less
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet a Show more
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet addiction and psychosocial maladjustment. This study aims to explore the transition patterns of internet addiction and its associations with emotional and interpersonal problems over time. A one-year longitudinal survey was conducted among 782 middle school students in rural China. Latent Profile Analysis (LPA) was conducted to identify internet addiction profiles at two time points. Latent Profile Transition Analysis (LPTA) was then used to examine the transition patterns between profiles over time. Subsequently, statistical analyses were conducted to explore how these transitions were associated with emotional and interpersonal problems. Three profiles of internet addiction were identified: minimal-internet addiction, low-internet addiction, and high-internet addiction. Based on LPTA, most adolescents with higher internet addiction at T1 shifted to lower-severity profiles over time (high → minimal: 35.3%; low → minimal: 39.8%; high → low: 33.3%), while some with initially lower levels transitioned to more severe profiles (minimal → high: 6.9%; low → high: 12.2%; minimal → low: 25.7%). Transition into higher addiction profiles predicted increased depression, anxiety, and poorer relationships with parents, peers, and teachers. Conversely, reductions in addiction were linked to improved depressive symptoms. Changes in internet addiction have an impact on adolescent psychosocial maladjustment. Early detection and flexible interventions are essential in rural settings. Show less
Luwen Hao, Xin Chen, Bo Qin · 2026 · Frontiers in cell and developmental biology · Frontiers · added 2026-04-24
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disorder characterized by unexplained left ventricular hypertrophy and represents a leading cause of morbidity and sudden cardi Show more
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disorder characterized by unexplained left ventricular hypertrophy and represents a leading cause of morbidity and sudden cardiac death, particularly in young adults and athletes. Early studies focused on morphological features, but advances in molecular genetics have shifted emphasis toward genetic diagnosis, mechanistic insights, and family-based management. Pathogenic variants in sarcomeric genes, especially Show less
We employed a causal inference framework to estimate the counterfactual dose-response effects of light-intensity physical activity (LPA) on mortality across low, medium and high moderate- to vigorous- Show more
We employed a causal inference framework to estimate the counterfactual dose-response effects of light-intensity physical activity (LPA) on mortality across low, medium and high moderate- to vigorous-intensity physical activity (MVPA) levels, and the lower and higher thresholds of current MVPA recommendations. Eligible participants from the UK Biobank (n=71 715) were included in the current study. LPA and MVPA were measured via accelerometers, and mortality data were derived from death registry. Flexible parametric survival models were used under the counterfactual framework to estimate the marginal predicted probability of death after 10 years of follow-up. During a median follow-up period of 8.0 years, 2195 deaths occurred. A non-linear dose-response effect of LPA on all-cause mortality was evident, and the effect diminished as MVPA level increased. If all participants achieved the lower threshold of the WHO recommended 22 min/day of MVPA, the 10-year probability of death would be expected to decrease from 9.5% at 60 min/day LPA to 4.2% at 360 min/day. If all participants achieved the higher threshold of 44 min/day of MVPA, the 10-year probability of death would be expected to decrease from 6.6% at 60 min/day of LPA to 3.7% at 345 min/day. Across the MVPA values examined, the optimal dose for LPA ranged from 195 to 225 min/day. LPA may complement MVPA to reduce risk of all-cause mortality, particularly among those with low MVPA or those unable to engage in higher-intensity activities. Our study highlights the potential for integrating LPA into public health strategies and future physical activity guidelines. Show less
Pathological ocular neovascularization is closely linked to aberrant histone modifications, yet the underlying molecular mechanisms remain incompletely defined. This study investigates the role of the Show more
Pathological ocular neovascularization is closely linked to aberrant histone modifications, yet the underlying molecular mechanisms remain incompletely defined. This study investigates the role of the histone demethylase JMJD1C and its encoding gene Jmjd1c in driving pathological angiogenesis and evaluates its therapeutic potential in ocular proliferative vascular diseases. Jmjd1c expression was examined in mouse models of ocular neovascularization and in endothelial cells (ECs) using immunostaining, qRT-PCR, and Western blotting. The pro-angiogenic functions of JMJD1C were assessed through EdU incorporation, Transwell migration, tube-formation, and spheroid-sprouting assays in vitro, as well as retinal flat-mount isolectin-B4 staining and H&E staining in vivo. RNA sequencing, immunostaining, qPCR, Western blotting, and ChIP-qPCR were employed to dissect the molecular mechanisms by which JMJD1C regulates pathological angiogenesis. Endothelial-specific deletion of Jmjd1c markedly reduced pathological neovascularization in both oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. Loss of JMJD1C impaired endothelial cell proliferation, migration, tube formation, and sprouting angiogenesis. Mechanistically, Jmjd1c deletion suppressed Srebf2 transcription and cholesterol biosynthesis by increasing repressive H3K9me2 histone marks in endothelial cells. Pharmacological inhibition of JMJD1C similarly attenuated neovascularization in wild-type mice. JMJD1C acts as a key regulator of pathological ocular angiogenesis through histone demethylation-mediated control of endothelial cholesterol biosynthesis. These findings establish JMJD1C and the Jmjd1c-Srebf2 regulatory axis as promising therapeutic targets for ocular vascular diseases. Show less
The mammalian class III phosphatidylinositol-3-kinase complex (PtdIns3K) forms two biochemically and functionally distinct subcomplexes including the ATG14-containing complex I (PtdIns3K-C1) and the U Show more
The mammalian class III phosphatidylinositol-3-kinase complex (PtdIns3K) forms two biochemically and functionally distinct subcomplexes including the ATG14-containing complex I (PtdIns3K-C1) and the UVRAG-containing complex II (PtdIns3K-C2). Both subcomplexes adopt a V-shaped architecture with a BECN1-ATG14 or UVRAG adaptor arm and a PIK3R4/VPS15-PIK3C3/VPS34 catalytic arm. NRBF2 is a pro-autophagic modulator that specifically associates with PtdIns3K-C1 to enhance its kinase activity and promotes macroautophagy/autophagy. How NRBF2 exerts such a positive effect is not fully understood. Here we report that NRBF2 binds to PIK3R4/VPS15 with moderate affinity through a conserved site on its N-terminal MIT domain. The NRBF2-PIK3R4/VPS15 interaction is incompatible with the UVRAG-containing PtdIns3K-C2 because the C2 domain of UVRAG outcompetes NRBF2 for PIK3R4/VPS15 binding. Our crystal structure of the NRBF2 coiled-coil (CC) domain reveals a symmetric homodimer with multiple hydrophobic pairings at the CC interface, which is in distinct contrast to the asymmetric dimer observed in the yeast ortholog Atg38. Mutations in the CC domain that rendered NRBF2 monomeric led to weakened binding to PIK3R4/VPS15 and only partial rescue of autophagy deficiency in Show less
To investigate the causal relationship between inflammatory proteins and Alzheimer's disease (AD) and the mediating role of plasma metabolites therein. Using Mendelian mandomization (MR) methods and p Show more
To investigate the causal relationship between inflammatory proteins and Alzheimer's disease (AD) and the mediating role of plasma metabolites therein. Using Mendelian mandomization (MR) methods and publicly available genome-wide association study (GWAS) data, we selected 91 single nucleotide polymorphisms (SNPs) that were strongly linked to inflammatory proteins without reverse causality with AD as the outcome. A bidirectional two-sample MR analysis was performed. Inflammatory proteins with causal links to AD were identified via inverse variance weighted (IVW) analysis. A mediation MR analysis was then performed using 1400 plasma metabolites to assess their mediating role in this causal pathway. The preliminary bidirectional MR analysis identified 3 inflammatory proteins that had a potential positive causal association with AD without reverse causality: Axin-1, C-X-C motif chemokine ligand 11 (CXCL11), and interleukin-12β (IL-12β). Elevated levels of Axin-1 were positively causally associated with AD risk (OR=1.082, 95% This study reveals how specific inflammatory proteins influence AD risk via plasma metabolites and provides genetic evidence for inflammatory-metabolic interactions in AD to facilitate the identification of potential biomarkers and targets for early detection and intervention of AD. Show less
Long-term alcohol consumption drives systemic damage through metabolites such as acetaldehyde, which trigger oxidative stress, inflammation, and gut dysbiosis. This study evaluated the protective effe Show more
Long-term alcohol consumption drives systemic damage through metabolites such as acetaldehyde, which trigger oxidative stress, inflammation, and gut dysbiosis. This study evaluated the protective effects of fermented red quinoa (FRQ) in an alcohol-exposed mouse model, with a focus on cognitive function. Male C57BL/6J mice were randomized into three groups for a 28-day study: a normal control, an alcohol-treated group gavaged with ethanol (1 mL/100 g·BW), and a group receiving the same ethanol dose co-administered with FRQ powder (human equivalent dose: 9 g/60 kg·BW). Our results demonstrated that fermentation with Lactobacillus kisonensis significantly increased the content of phenolic compounds (e.g., quercetin and veratric acid) in FRQ. FRQ intervention improved cognitive function, ameliorated synaptic structural impairment and blood-brain barrier disruption, and attenuated hepatic steatosis. The protective mechanisms involved three pathways: 1) The specific phenolic compounds in FRQ promoted alcohol metabolism by regulating ADH/ALDH activity, leading to reduced acetaldehyde levels. As a primary initiating pathway, this metabolic enhancement dominantly attenuated subsequent oxidative stress and inflammation, mitigating injury in the liver, brain, and colon. 2) It directly modulated AP-1 subunits (ΔFOSB/JUND), restored BDNF, and rebalanced the glutamate/GABA systems. 3) It regulated the gut-liver-brain axis by remodeling the gut microbiota (e.g., enriching butyrate-producing Butyricicoccus), reinforcing intestinal barrier integrity, and thereby suppressing systemic LPS translocation and inflammation. In conclusion, FRQ mitigates alcohol-induced cognitive and hepatic damage via multiple mechanisms, highlighting its promise as an integrative dietary intervention. Show less
Junjie Hu, Pei-Yang Gao, Run Di+2 more · 2026 · The Journal of neuroscience : the official journal of the Society for Neuroscience · Society for Neuroscience · added 2026-04-24
Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced co Show more
Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced cognitive dysfunction arises from a cascade of neurobiological processes, including persistent neuroinflammation, neurotransmitter dysregulation, and impaired synaptic plasticity. These mechanisms particularly affect the hippocampus and medial prefrontal cortex (mPFC)-regions essential for memory, attention, and executive function. Neuroimaging studies have documented structural atrophy and disrupted network connectivity in these brain areas in CP patients. At the molecular level, pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) impair glutamatergic and GABAergic signaling, disrupt long-term potentiation (LTP), and inhibit neurogenesis. Additionally, dysregulation of brain-derived neurotrophic factor (BDNF) signaling exacerbates synaptic vulnerability, contributing to cognitive decline. These mechanistic overlaps are particularly relevant in aging populations and in Alzheimer's disease (AD), where CP may act as a risk factor. This review integrates clinical and preclinical findings on CP-related cognitive dysfunction, outlines key molecular mechanisms, and explores emerging therapeutic strategies targeting inflammation, neurotransmitter systems, and synaptic repair. Understanding the interaction between chronic pain and cognition is critical for developing precision treatments that address both nociceptive and neurodegenerative pathways. Show less
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angio Show more
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) between January 2019 and December 2021 were enrolled. Baseline Lp(a) was measured before the operation. CIN was defined as an increase in serum creatinine of more than 25% or 44 μmol within 72 h of contrast administration. The relationship between Lp(a) and CIN risk was analyzed. A total of 928 T2DM patients were included. CIN developed in 11.1% (103/928) of patients. The Lp(a) level was significantly higher in patients with CIN than in non-CIN patients (311.12 ± 278.66 vs. 254.19 ± 274.56 mg/L, A higher serum Lp(a) level indicates an increased risk of CIN in T2DM patients undergoing CAG or PCI and can serve as an independent predictor of CIN in this population. This study's findings will aid in the clinical prevention and treatment of contrast agent-induced kidney disease. Show less
ObjectiveThis review synthesizes current evidence on the efficacy of acupuncture in managing chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients, focusing on its mechanisms, clinical Show more
ObjectiveThis review synthesizes current evidence on the efficacy of acupuncture in managing chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients, focusing on its mechanisms, clinical applications, and future research directions.MethodsThis narrative review synthesizes and critically appraises findings from randomized controlled trials (RCTs), meta-analyses, and preclinical studies, evaluating acupuncture's impact on pain relief, neurological function, and quality of life. Key databases were searched for studies published up to 2024.ResultsNineteen RCTs ( Show less