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
To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health litera Show more
To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health literacy and promote LPA, thereby advancing healthy aging. This study used a convenience sampling method to select two residential neighborhoods. Subsequently, a random cluster sampling approach was employed, resulting in a total final sample of 105 community-dwelling older adults (aged 60 and above) from these neighborhoods. A three-axis accelerometer (ActiGraph wGT3X-BT) recorded the older adults' LPA, and the Electronic Health Literacy Scale assessed their e-health literacy. Multiple linear regression was used to explore the dose-response relationship between LPA and e-health literacy and sub-dimension scores. Multiple linear regression revealed that both the overall e-health literacy score and its components were positively associated with daily LPA (Tables 2 and 3). However, the empirical impact varied substantially across components. For each 1-point increase, LPA increased by 2.8 min for the overall score, 11 min for judgment ability, and 19.4 min for decision-making ability, whereas the effect of application ability was statistically significant but minimal. Notably, the effect sizes of all e-health literacy components were substantially smaller than that of educational attainment (β = 0.638-0.947), which was the strongest predictor in all models. This study provides empirical evidence that higher e-health literacy and its specific sub-dimensions are positively associated with light physical activity (LPA) among community-dwelling older adults, with educational attainment emerging as a key independent predictor. These findings suggest that public health interventions aimed at promoting LPA could be enhanced by incorporating strategies to improve e-health literacy, particularly targeting older adults with lower educational backgrounds. The development of tailored, theory-informed programs based on these insights holds promise for fostering healthy aging at the community level. Show less
Osteoporosis (OP) is a metabolic bone disease characterized by low bone mineral density (BMD), and its pathogenesis involves endoplasmic reticulum (ER) stress-related cell death. This study aimed to i Show more
Osteoporosis (OP) is a metabolic bone disease characterized by low bone mineral density (BMD), and its pathogenesis involves endoplasmic reticulum (ER) stress-related cell death. This study aimed to identify diagnostic biomarkers associated with ER stress-related cell death in OP and explore their underlying mechanisms. The training dataset (GSE56815), validation dataset (GSE56814), and single-cell RNA sequencing (scRNA-seq) dataset (GSE147287) were downloaded. Differentially expressed genes (DEGs) between OP patients and controls were identified. Candidate genes were obtained by intersecting DEGs with ER stress-related genes and programmed cell death (PCD)-related genes. Machine learning was used to screen intersection genes, and biomarkers were determined via expression level analysis. Gene set enrichment analysis (GSEA), immune cell infiltration analysis, drug prediction and molecular docking, scRNA-seq analysis, key cell screening, cell communication analysis, and pseudotime analysis were performed. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) were further conducted. A total of 28 candidate genes were obtained by intersection. CAMKK2 and DAPK3 were confirmed as biomarkers, and were consistently down-regulated in both datasets and verified by RT-qPCR. GSEA analysis revealed that biomarkers were enriched in cytokine-cytokine receptor interaction. Correlations between biomarkers and activated dendritic cells were found via immune cell infiltration analysis. Preliminary computational analyses indicated that drugs including calcitriol and danazol may potentially interact with the biomarkers in a stable manner. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were identified as potential key cells via scRNA-seq analysis. Complex interactions involving BM-MSCs, such as ANGPTL4-CDH11 mediating BM-MSC self-communication, were revealed by cell communication analysis. Dynamic expression of biomarkers during BM-MSC differentiation was shown by pseudotime analysis: CAMKK2 fluctuated with differentiation stages, while DAPK3 shifted from high to low then high expression. CAMKK2 and DAPK3 were confirmed as diagnostic biomarkers for OP, providing insights into OP diagnosis and potential therapeutic targets. Show less
The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aime Show more
The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aimed to identify distinct subgroups of nursing freshmen based on their bioecological attributes related to learning adaptation during the pandemic. A multicenter, cross-sectional study was conducted of 1170 first-year nursing students from six higher education institutions in China. Learning adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction, were investigated. Latent Profile Analysis (LPA) was utilized to identify distinct profiles. Descriptive statistics indicated a positive level of learning adaptation among participants, with an overall mean score of 3.51 ± 0.57. LPA revealed four distinct profiles: 'Struggling Learners' (5.47%), 'Moderate Engagers' (70.60%), 'Adaptable Strivers' (18.29%), and 'Optimal Adapters' (5.64%), which demonstrated significant differences in adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction tendencies (P < 0.05). The study's findings emphasize the heterogeneity in learning adaptation among nursing freshmen and the importance of considering bioecological attributes when developing educational interventions during crisis. Recognizing these profiles can guide the development of targeted strategies to enhance student adaptation and academic achievement. Show less
This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becom Show more
This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becomes a common issue of functional decline in the elderly. Utilizing bioinformatics analysis, this research identified 101 overlapping differentially expressed genes (DEGs) involved in both CR and endurance exercise. These genes are primarily enriched in key biological pathways related to longevity, Apelin signaling, AMPK signaling, FoxO signaling, and cGMP-PKG signaling pathways. Additionally, we identified 10 key genes (such as LPL, PPARGC1A, and IGF1), 4 transcription factors (FOXC1, POU2F2, GATA2, and STAT3), and 4 microRNAs (miR-155-5p, miR-124-3p, miR-1-3p, and miR-16-5p) interacting with these genes. Drug-gene interaction analysis identified carotuximab as a compound with potential relevance for future investigation in the context of muscle aging. These findings provide new insights into the molecular mechanisms underlying muscle functional decline in the elderly and propose potential targets and drugs for intervention development. 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
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
This study employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through c Show more
This study employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through convenience sampling, 260 breast cancer chemotherapy patients aged 18-74 years from a tertiary hospital in Henan Province were recruited between May 2024 and January 2025. Data were collected using a general demographic questionnaire, the Learned Helplessness Scale, the Brief Illness Perception Questionnaire, the Social Support Rating Scale, and the General Self-Efficacy Scale. An LPA was applied to classify learned helplessness patterns, followed by a multivariate logistic regression to determine the influencing factors. The latent profile analysis revealed three distinct profiles of learned helplessness among breast cancer patients undergoing chemotherapy: a "low helplessness-low hopelessness stable profile" (17.0%), a "moderate helplessness-moderate hopelessness fluctuating profile" (52.0%), and a "high helplessness-high hopelessness profile" (31.0%). The multivariable logistic regression revealed that age range 18-44 years, low monthly household income per capita, fatigue, and illness perception were significantly associated with the "high helplessness-high hopelessness profile" (P < 0.05). Conversely, the age range 45-59 years was significantly associated with the "moderate helplessness-moderate hopelessness fluctuating profile" (P < 0.001). Furthermore, experiencing ≤2 chemotherapy-related side effects, a higher level of perceived social support, and greater self-efficacy were significant predictors of membership in the "low helplessness-low hopelessness profile" (P < 0.05). Breast cancer chemotherapy patients were categorized into three distinct subgroups, which were influenced by age, income, fatigue, treatment side effects, illness perception, self-efficacy, and social support. Show less
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
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, w Show more
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, we identify a regulatory axis wherein the transcription factor ZBED6 activates the expression of the autophagy-initiating kinase PIK3C3 via the repression of IGF2, thereby driving pro-tumorigenic autophagy. Spatial analysis confirms the co-localization of ZBED6 and PIK3C3 in tumor tissues. Using genes associated with this axis, we develop a six-gene prognostic signature that stratifies patients with distinct survival outcomes and differential responses to immunotherapy and targeted therapy. Functional assays show that ZBED6 promotes ccRCC cell proliferation, migration, and invasion. This work elucidates a pathway governing autophagy in ccRCC and provides a framework for prognostic assessment and precision therapy. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive amyloid-β (Aβ) accumulation, neuroinflammation, and oxidative stress. Exosomes derived from human umbili Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive amyloid-β (Aβ) accumulation, neuroinflammation, and oxidative stress. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSC@Exo) represent promising nanoscale carriers for targeted drug delivery. In this study, Baicalein (Bac), a potent antioxidant and anti-inflammatory flavonoid, was encapsulated into hUC-MSC-derived exosomes (Exo@Bac) to enhance its therapeutic efficacy. The neuroprotective potential of Exo@Bac was evaluated in a rat model of Aβ1-42-induced AD. Rats received intraperitoneal injections of Bac, hUC-MSC@Exo, or Exo@Bac, and cognitive performance was assessed using the passive avoidance test and Morris water maze. Exo@Bac treatment significantly improved memory deficits and elevated brain-derived neurotrophic factor (BDNF) expression compared to controls. Histopathological analyses revealed reduced neuronal damage and apoptosis, alongside decreased Aβ1-42 deposition in Exo@Bac-treated rats. Furthermore, Exo@Bac enhanced antioxidant defense (increased SOD), attenuated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and lowered lipid peroxidation (MDA). Mechanistically, Exo@Bac promoted AMPK phosphorylation while suppressing NF-κB p65 signaling, indicating modulation of both oxidative stress and neuroinflammatory pathways. These findings demonstrate that Exo@Bac acts as a nanotherapeutic agent capable of mitigating AD pathology, highlighting its potential as a novel strategy for Alzheimer's disease therapy. 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
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a Show more
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a natural flavonoid, exhibits anti-inflammatory and neuroprotective properties, yet its potential therapeutic effects on UC and associated anxiety, as well as the underlying mechanisms, remain largely unexplored. A murine model of DSS-induced colitis was established and treated with HYP. Disease activity was assessed through body weight, colon length, and histopathology. Anxiety-like behaviors were evaluated using open field and elevated plus maze tests. Neuroinflammation was examined through immunohistochemistry of BDNF expression and microglial activation. Gut microbiota composition was profiled by metagenomic sequencing, and metabolomic profiling was conducted using the Q300 Kit. Network pharmacology and molecular docking were employed to predict signaling pathways, which were further validated by Western blotting. Additionally, antibiotic depletion experiments were conducted to determine microbiota dependency. HYP administration significantly ameliorated DSS-induced colitis, as evidenced by attenuated weight loss, restored colon length, and improved histopathology. It suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restored intestinal barrier integrity by upregulating Mucin-2 and ZO-1. Furthermore, HYP also alleviated anxiety-like behaviors and mitigated neuroinflammation by increasing BDNF levels and suppressing microglial activation. HYP treatment also restored gut microbial homeostasis, enriching beneficial bacteria such as Our findings demonstrate that HYP effectively alleviates DSS-induced colitis and comorbid anxiety-like behaviors. Its efficacy is dependent on the gut microbiota and is associated with the restoration of microbial homeostasis, enhancement of arginine metabolism, and modulation of the MAPK/PI3K-Akt/NF-κB signaling pathways. HYP represents a promising microbiota-targeting therapeutic candidate for UC and its neuropsychiatric comorbidities. Show less
Chao Chen, Fang Lv · 2026 · British journal of hospital medicine (London, England : 2005) · added 2026-04-24
Lipoprotein(a) [Lp(a)] is recognized as a cardiovascular risk indicator; however, its connection to peripheral arterial disease (PAD) in individuals with type 2 diabetes mellitus (T2DM) is not well es Show more
Lipoprotein(a) [Lp(a)] is recognized as a cardiovascular risk indicator; however, its connection to peripheral arterial disease (PAD) in individuals with type 2 diabetes mellitus (T2DM) is not well established. This research seeks to explore how Lp(a) concentrations relate to the occurrence of PAD in T2DM patients. A retrospective analysis was conducted on 590 patients diagnosed with T2DM who were admitted to Hefei First People's Hospital from January 2022 to August 2024. Participants were grouped into tertiles according to their Lp(a) levels. The diagnosis of PAD was made using the ankle-brachial index (ABI), with an ABI <0.9 considered indicative of PAD. The association between Lp(a) concentrations and PAD was examined using multivariate logistic regression models, subgroup analyses, receiver operating characteristic (ROC) curves, and restricted cubic spline (RCS) plotting. Compared to lower Lp(a) levels, the group with higher Lp(a) levels exhibited a higher prevalence of PAD ( A significant correlation was observed between elevated Lp(a) levels and an increased risk of PAD in patients with T2DM. Show less
Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor Show more
Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor (GABAAR) signaling contributes to ICH-induced neurotoxicity, presenting a promising therapeutic target. To assess the neurorestorative effects of the GABAAR α1-selective partial positive allosteric modulator (PAM) CL218872 and the α5-selective negative allosteric modulator (NAM) MRK-016 on synaptic plasticity and neural repair following ICH. An ICH mouse model was constructed using collagenase IV, and ICH mice were administered the GABAAR modulators CL218872 or MRK-016. Differences in inflammation and neurological deficit score were compared between different groups of mice. Morphologic and functional changes in mouse neuronal cells were next determined by Nissl and Golgi-Cox staining. Synaptic structural changes in ICH mice were visualized by transmission electron microscopy, and changes in synaptic plasticity-related molecules were quantified to assess the effects of GABAAR modulators on synapses in ICH mice. Treatment with CL218872 resulted in a reduction in hemorrhage and improved neurobehavioral outcomes in ICH mice. Additionally, CL218872 mitigated inflammation by downregulating phospho-p65, IL-6 and TNF-α expression. Histological analysis revealed an increase in neuronal density, preservation of cell morphology, and enhanced synaptic connectivity following CL218872 treatment. Furthermore, synaptic structure was restored, and there was an upregulation of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density protein 95 (PSD-95), and synaptophysin in ICH mice. However, treatment with MRK-016 yielded the opposite result. The GABAAR α1-selective PAM CL218872 exerts neuroprotective and neurorestorative effects in ICH, suggesting its therapeutic potential for ICH management. 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
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroup Show more
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroups, risk factors, and symptom-level interactions underlying depression-anxiety comorbidity across adolescents and adults in multi-ethnic Southwest China. The study included a total of 41,394 adolescents (aged 9-19) and 17,345 adults (aged 18-80). Adolescents were recruited using multistage stratified cluster sampling, whereas adults were recruited by convenience sampling. All participants completed a self-designed sociodemographic questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Latent profile analysis identified subgroups, logistic regression analyzed risk/protective factors, and network analysis mapped symptom interactions and bridge nodes. This study found that three adolescent profiles emerged: high (11.66 %), moderate (31.95 %), and low/no depression-anxiety (56.39 %). Adults were classified into low/no comorbidity (90.63 %) and comorbid depression-anxiety (9.37 %). Risk factors for adolescents included female gender (OR = 2.77, 95 %CI: 2.55-3.00; OR = 1.59, 95 %CI: 1.52-1.67), higher grade levels (OR = 3.45, 95 %CI: 3.10-3.84; OR = 3.56, 95 %CI: 3.33-3.80), smoking (OR = 1.72, 95 %CI: 1.51-1.96; OR = 1.28, 95 %CI: 1.17-1.41),drinking (OR = 2.45, 95 %CI: 2.23-2.70; OR = 1.66, 95 %CI: 1.55-1.77), family instability (OR = 1.16, 95 %CI: 1.02-1.31; OR = 1.33, 95 %CI: 1.14-1.56) and "other" ethnic minority (OR = 1.15, 95 %CI: 1.04-1.26). For adults, female gender(OR = 1.68; 95 %CI: 1.44-1.97), living alone(OR = 1.37; 95 %CI: 1.14-1.65), poor self-rated health (OR = 0.13, 95 %CI: 0.11-0.15), and Dai ethnicity (OR = 0.70, 95 %CI: 0.49-0.96) predicted comorbidity. Network analysis revealed distinct bridge symptoms: adolescents in the high depression-anxiety group had five symptoms: depressed or sad mood (phq2), psychomotor agitation/retardation (phq8), nervousness or anxiety (gad1), restlessness (gad5), and irritable (gad6); however, adults with comorbidity had one symptom: afraid something will happen (gad7). This study identified three patterns of depression-anxiety comorbidity in adolescents and two in adults. Efforts should prioritize adolescents from "other" ethnic minorities, strengthening family and peer support, as well as smoking and drinking interventions for adolescents, and addressing social isolation, physical health, and catastrophizing cognition in adults may mitigate the comorbidity burden. Show less
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the w Show more
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the whole-exome sequencing data from 280 CHH probands, we identified 15 potential splice-site variants in CHD7, ANOS1 and FGFR1 by using in silico software. The functional consequences of these variants were analyzed by the minigene assay or RT-PCR analyses of RNA taken from the peripheral lymphocytes. Detailed phenotyping was performed in the CHH patients harboring deleterious variants and their available family members. 11 out of 15 potential splice-site variants were demonstrated to cause mis-splicing, resulting in loss of function through deletion, insertion or frameshift of amino acids in the proteins. Most patients with deleterious splice-site variants in CHD7, ANOS1, FGFR1 presented with gene-specific non-reproductive phenotypes, confirming the pathogenic contribution of these variants to CHH. Our study indicated that splice-site variants in CHD7, ANOS1, FGFR1 underlie the genetic basis of ~3.9% of CHH patients, warranting the inclusion of potential splice-site variants for genetic diagnosis and counseling of CHH. Show less
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HF Show more
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HFD, n = 30). After 8 weeks of HFD feeding, 24 obese rats were further randomised into three subgroups: HFD (H, n = 8), HFD + moderate-intensity training (HMT, n = 8), and HFD + HIIT (HHT, n = 8). The HMT and HHT groups underwent 8 week training interventions (six sessions/week). The HMT protocol included a 10 min warm-up (treadmill speed: 10 m/min), a 40 min moderate-intensity aerobic phase (60%-70% of maximum speed), and a 10 min recovery (10 m/min). The HHT protocol featured 10 min warm-up and recovery phases (10 m/min), with 40 min of alternating treadmill training: 3 min at 50% maximum speed followed by 3 min at 90% maximum speed. No significant differences in body weight were observed between the HHT and HMT groups. HHT rats displayed significantly lower plasma triglyceride levels than H and HMT rats. Compared with HMT, HHT reduced adipose mass and adipocyte size and increased mitochondrial succinate dehydrogenase and cytochrome c oxidase (COX) activities in adipose tissue. However, HHT rats displayed lower COX activity in visceral white adipose tissue than HMT rats. Training upregulated browning-related genes and uncoupling protein 1 (UCP1) in adipose tissue, with stronger effects in HHT than in HMT. Plasma and adipose tissue IL-27 levels, as well as p38 MAPK-PGC-1α signalling pathway activation, were significantly elevated in both training groups, with greater increases in HHT. HIIT promotes adipose tissue browning by activating the IL-27 signalling pathway and ameliorates obesity-associated metabolic disorders more effectively than MAIT, supporting its potential as a therapeutic strategy for obesity. 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
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
Serous endometrial cancer (SEC) is an aggressive subtype of endometrial cancer (EC) with poor prognosis and limited treatment options. Here, we developed a clinically relevant, immunocompetent serous- Show more
Serous endometrial cancer (SEC) is an aggressive subtype of endometrial cancer (EC) with poor prognosis and limited treatment options. Here, we developed a clinically relevant, immunocompetent serous-like mouse model incorporating oncogenic Show less
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. Show less
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). H Show more
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT/enhancer-binding protein beta (C/EBPβ) in hepatocyte maturation. Forced C/EBPβ expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&Tag and luciferase reporter assays confirmed C/EBPβ directly binds to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C/EBPβ and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C/EBPβ at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C/EBPβ as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications. The transcriptional activity of C/EBPβ is regulated by MAPK1 protein within the ERK/MAPK signaling pathway. MAPK1 moves from the cytoplasm into the nucleus and transfers phosphate groups to C/EBPβ. This process reverses the "self-inhibition" state of C/EBPβ and enhances its transcriptional activity on downstream target genes. 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
Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is Show more
Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is very important. This study analyzes the impact of a nursing intervention of case management combined with cognitive-behavioral therapy on anxiety and depression and quality of life in postoperative NSCLC patients. A single-center, non-randomized controlled study in which 80 NSCLC patients from the Hospital were enrolled from May 2023 to January 2024, and were categorized into case management (CM) and cognitive-behavioral therapy (CBT) groups depending on treatment modalities, with case management care in both groups, and cognitive-behavioral therapy care added to the CM combined with CBT (CC) group. The Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), self-perception burden scale (SPBS), life qualities (QLQ-C30), neurotransmitter levels, and clinical effectiveness were primarily assessed in both groups post-treatment. Secondary outcomes included pain level (VAS score), nursing satisfaction, adverse events, and complications. After treatment, the indicators of both groups were significantly different from those of the pre-treatment. Post-treatment, the CC group demonstrated significantly lower scores than the CM group in HAMA (10.18 ± 2.10 vs. 16.04 ± 3.89), HAMD (11.94 ± 2.91 vs. 16.81 ± 3.19), and SPBS (25.52 ± 3.17 vs. 33.50 ± 5.61) (all P < 0.05). Conversely, the CC group showed significantly higher QLQ-C30 scores and levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). The nursing intervention of case management combined with cognitive behavioral therapy has a good improvement effect on the anxiety and depression status of NSCLC patients. It can improve the quality of life, which is worth promoting and using in the clinic. Show less
Dietary protocatechuic acid (PCA) inhibits atherosclerosis development in male ApoE-/- mice. However, its anti-atherosclerotic property in genetically unmodified (wild-type) male or female mice remain Show more
Dietary protocatechuic acid (PCA) inhibits atherosclerosis development in male ApoE-/- mice. However, its anti-atherosclerotic property in genetically unmodified (wild-type) male or female mice remains unknown.Five-week-old C57BL/6J mice (half males and females) were divided into negative (fed a chow diet), positive (fed an atherogenic diet), or 5, 25, 50, 100, or 200 mg/kg BW/d of PCA (fed an atherogenic diet) groups. Oral gavage with PCA between 25-100 mg/kg BW/d for 25 weeks significantly attenuated atherogenic diet-induced plaque formation in a dose-dependent manner, whereas the anti-atherosclerotic efficiency of 200 mg/kg BW/d of PCA was comparable with that of 50 mg/kg BW/d. PCA did not affect serum lipids (total triglyceride, total cholesterol, HDL cholesterol), pro-inflammatory cytokines (tumor necrosis factor alpha, IL-1b, IL-6), oxidized LDL, and total antioxidant capacity, and acetylcholine or sodium nitroprusside-induced aortic relaxation. Instead, PCA (≥25 mg/kg BW/d) reduced macrophage accumulation and content of tumor necrosis factor alpha, superoxide, and 4-hydroxynonenal within plaques, and inhibited monocyte adhesion to aortic endothelium in both male and female mice.PCA inhibits early atherosclerosis formation in both male and female C57BL/6J mice with a "U-shaped" dose-response relationship, possibly by reducing inflammation burden and oxidative stress within atherosclerotic plaques. Show less
Ting Li, Ke Chen · 2026 · Journal of affective disorders · Elsevier · added 2026-04-24
Internalizing and externalizing behavior problems co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few studies have explored this heterogeneity and its de Show more
Internalizing and externalizing behavior problems co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few studies have explored this heterogeneity and its developmental mechanisms from a person-centered perspective. The primary aim of this study is to employ Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA)-person-centered statistical approaches-to explore this underlying heterogeneity, uncover its dynamic developmental trajectories, and further examine the key factors that influence class membership and transitions. A sample of 2232 Chinese college students from three universities in Chongqing was assessed at two time points spaced ten months apart. Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA) were conducted on measures of internalizing and externalizing problems. LPA revealed three distinct profiles for both internalizing problems ("Low-Risk/Well-Adapted", "Moderate-Risk/Affective-Distress", "High-Risk/Comorbid") and externalizing problems ("Well-Adapted", "Adaptation Difficulties", "Maladaptive") at T1, with similar structures at T2. LTA indicated high stability for the low- and high-risk internalizing profiles, but significant fluidity in the middle, with nearly half of the moderate-risk group transitioning to the high-risk profile. For externalizing problems, there was a pronounced shift toward the "Maladaptive" profile over time. Negative parental rearing and PWU were significant risk factors for adverse transitions, while positive parenting, self-transcendence values, and objective social support served as protective factors. Co-occurring internalizing and externalizing problems among Chinese college students are heterogeneous and dynamic. The moderate-risk group represents a critical target for early intervention. Modifiable ecological factors across family, individual, and technological domains significantly predict longitudinal trajectories, informing targeted prevention strategies. Show less