Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospect Show more
Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospective UK Biobank cohort, we evaluated the bidirectional associations by time-varying Cox proportional hazards regression models and assessed shared genetic architecture using genome-wide association study summary statistics. Additionally, we employed collagen-induced arthritis (CIA) and chronic social defeat stress (CSDS) mouse models to investigate the relationship between rheumatoid arthritis (RA) and depression. Over 5,226,841 person-years of follow-up, 23,534 incident MDD cases were identified. The presence of any IMD was associated with higher MDD risk (hazard ratio [HR]: 1.95; 95% CI: 1.89-2.01). Conversely, 59,742 incident cases of IMD were documented. MDD was associated with increased IMD risk (HR: 1.47; 95% CI: 1.40-1.54). We observed significant global genetic correlations between IMDs and MDD (r Show less
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key Show more
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key genes involved in KC development and in anoikis and endoplasmic reticulum (ER) stress. KC and control datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). These were cross-referenced with anoikis and ER stress-related genes from Genecards. Functional enrichment, immune infiltration analysis, and machine learning techniques (LASSO, Random Forest) were used to identify candidate molecular signatures, which were then validated in an animal model. We identified 46 DEGs associated with anoikis and 41 DEGs related to ER stress. Functional analysis linked them to apoptosis and IL-17 signaling. Five key molecular signatures were identified: CDKN1A, MCL1, PTGS2, PTHLH, and ANGPTL4. The expression of ANGPTL4, CDKN1A, and MCL1 was consistent in the animal model. These genes are associated with inflammatory and oxidative stress responses. Twelve potential therapeutic drugs were predicted. This study identifies five candidate molecular signatures for KC related to anoikis and ER stress, offering insights into KC pathogenesis and potential targeted therapies. Show less
Chemical investigation of the soft coral Sclerophytum humesi led to the discovery of (±)-norsclerohumin A (1), a pair of enantiomeric norsesquiterpenoids possessing an unprecedented oxatricyclo[7.2.1. Show more
Chemical investigation of the soft coral Sclerophytum humesi led to the discovery of (±)-norsclerohumin A (1), a pair of enantiomeric norsesquiterpenoids possessing an unprecedented oxatricyclo[7.2.1.0 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
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
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
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
Platelets must balance hemostatic function with pathological thrombosis, particularly under metabolic stress conditions. MAPKs are central to platelet responses, but how these platelet signals differe Show more
Platelets must balance hemostatic function with pathological thrombosis, particularly under metabolic stress conditions. MAPKs are central to platelet responses, but how these platelet signals differentially regulate hemostasis remains poorly understood. To investigate the role of Traf2/Nck-interacting kinase (TNIK), we generated megakaryocyte/platelet-specific TNIK knockout mice (Tnikf/fPF4-Cre+) and evaluated platelet function, hemostasis, and thrombosis under normal and hyperlipidemic conditions using chimeric Tnikf/fPF4-Cre+Apoe-/-mice fed high-fat diets. TNIK-deficient mice exhibited prolonged bleeding times, delayed arterial thrombosis and reduced platelet activation under normal conditions, primarily due to impaired dense granule secretion. Mechanistically, TNIK interacted with c-Jun N-terminal kinase interacting protein 1 to promote mixed lineage kinase 3/mitogen-activated protein kinase kinase 4/c-Jun N-terminal kinase pathway activation during hemostatic responses. Surprisingly, under hyperlipidemic conditions, TNIK deficiency accelerated thrombosis and enhanced platelet responses to oxidized low-density lipoprotein. In this context, TNIK specifically bound to protein kinase C ε and suppressed the NADPH oxidase 2/reactive oxygen species/extracellular signal-regulated kinase 5 pathway, thereby inhibiting excessive platelet activation. We conclude that TNIK functions as a molecular switch in platelets, promoting normal hemostasis while simultaneously preventing hyperlipidemia-associated thrombosis through distinct signaling pathways. This dual regulatory mechanism provides insight into how platelets balance hemostatic function with pathological thrombosis risk and identifies TNIK as a potential therapeutic target in metabolic thrombotic disorders. 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
Calcific aortic valve disease (CAVD) is a cardiovascular disease closely associated with aging. The role of lipoprotein(a) [Lp(a)] has attracted considerable attention in recent years. However, limite Show more
Calcific aortic valve disease (CAVD) is a cardiovascular disease closely associated with aging. The role of lipoprotein(a) [Lp(a)] has attracted considerable attention in recent years. However, limited research has simultaneously explored the relationships between Lp(a), age, and CAVD. This study sought to assess the relationship linking Lp(a), time-weighted Lp(a), and CAVD. A total of 5,156 inpatients with comprehensive clinical data were recruited for this study. The associations of Lp(a) and time-weighted Lp(a) with CAVD were examined via multivariate logistic regression analysis, alongside the application of restricted cubic spline analysis. The diagnostic utility of Lp(a) and time-weighted Lp(a) for CAVD was assessed by constructing receiver operating characteristic (ROC) curves. CAVD prevalence rose with age, whereas the rate of increase diminished with advancing age. The average Lp(a) level in the young populations with CAVD was more than twice that in the No-CAVD group, particularly among those aged 55 years or younger. The prevalence of CAVD in non-elderly populations was markedly 2–4 fold greater in the higher Lp(a) group (> 30 mg/dL) than in the lower Lp(a) group (≤ 30 mg/dL). Multivariate adjusted odds ratios (ORs) for CAVD increased with advancing Lp(a) or age. Time-weighted Lp(a), which takes into account both age and Lp(a), was more strongly linked to elevated CAVD risk than Lp(a) alone. Time-weighted Lp(a) enhanced the diagnostic value of CAVD, improving both sensitivity and specificity. The risk of CAVD is strongly associated with both age and elevated Lp(a) levels. Time-weighted Lp(a), which integrates these factors, serves as a superior indicator that better captures cumulative long-term Lp(a) variation and yields stronger CAVD risk stratification. The online version contains supplementary material available at 10.1186/s12944-026-02884-8. Show less
Following spinal cord injury (SCI), neuroinflammation driven by lipid-laden macrophage foam cells is a key pathology, yet how these cells manage their lipid homeostasis is unclear. We delineate a neur Show more
Following spinal cord injury (SCI), neuroinflammation driven by lipid-laden macrophage foam cells is a key pathology, yet how these cells manage their lipid homeostasis is unclear. We delineate a neuroprotective axis in which macrophages deploy apolipoprotein E (APOE) to transfer intracellular lipids to neighboring cells, especially fibroblasts. Genetic ablation of The online version contains supplementary material available at 10.1186/s12974-026-03756-9. Show less
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive perfo Show more
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive performance. In this study, we examined the associations between plasma klotho levels and plasma biomarkers, as well as amyloid beta (Aβ) positron emission tomography (PET), tau PET, neurodegeneration, and cognition, in 354 older adults. Stratified association, interaction, and mediation analyses were conducted to elucidate apolipoprotein E (APOE) ε4-dependent relationships and potential underlying pathways. Higher plasma klotho levels were associated with lower AD-related biomarkers and cognitive decline in APOE ε4 carriers. Plasma klotho and APOE ε4 exhibited significant or marginal interactions with less abnormal changes in plasma phosphorylated tau217, glial fibrillary acidic protein, neurofilament light chain, Aβ PET, and cognition. These AD-related biomarkers mediated the protective effect of plasma klotho on cognitive function in APOE ε4 carriers. This study suggests that plasma klotho is an APOE ε4-dependent protective factor, which may attenuate AD-related pathology and improve cognitive performance. Show less
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic Show more
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic characteristics, health literacy, confidence in self-care contributions, family intimacy, and profile membership. We recruited 275 dyads of patients with COPD and their family caregivers from five tertiary hospitals between May and November 2022 using convenience sampling. Latent profile analysis (LPA) was used to identify distinct profiles of caregiver self-care contributions. Univariate analysis and multinomial logistic regression were subsequently conducted to examine associations between participant characteristics and profile membership. LPA identified four distinct profiles of caregiver self-care contributions: low-contributing, under-monitored, maintenance-prioritized, and high-contributing. Significant differences were observed across these profiles in terms of patients' symptom severity, exacerbation frequency, number of hospitalizations, caregivers' education levels, caregiving duration, health literacy, confidence in self-management contributions, and family intimacy using univariate analysis. Multinomial logistic regression analysis revealed that caregivers' education levels, caregiving duration, confidence in self-management contributions, and health literacy were significant predictors of profile membership. Caregiver self-care contributions for patients with COPD can be characterized by four distinct profiles, with caregivers' educational level, health literacy, and confidence in self-management identified as key factors associated with profile membership. Show less
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
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
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
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN Show more
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN injury. Placental-derived connective tissue matrix (pd-CTM) could fill this need, as it contains a plethora of cytokines with potential UVFP therapeutic benefits. This study aimed to identify and quantify the factors in a commercially available pd-CTM (CTM Flow, CTM Biomedical, Lake Worth, Florida) and to study the effects of pd-CTM on vocal fold microenvironment and glottic function in a mouse model of unilateral RLN injury. Cytokine expression (ng/mL) in pd-CTM was characterized using a cytokine array and ELISA. In a separate experiment, C57/BL6 mice were divided into three groups: uninjured negative controls (n = 12), RLN transection with ipsilateral saline thyroarytenoid (TA) injection (n = 16), and RLN transection with ipsilateral pd-CTM TA injection. Outcomes included laryngeal electromyography (L-EMG) and video laryngoscopy after 7 and 28 days, with larynges then harvested and analyzed via immunohistochemistry (IHC) and qPCR. pd-CTM characterization showed moderate-to-high levels of neurotrophic (BDNF, CNTF, GDNF, NTF-3), angiogenic (Angiogenin, VEGF-D), tissue remodeling (bFGF, IGF-1, HGF, TGF-β3), and anti-inflammatory factors (IL-10, IL-1Rα). L-EMG demonstrated increased mean normalized area under the curve ratio in pd-CTM treated mice compared to saline treated mice at the 28-day time point indicating reinnervation (p < 0.001). IHC detected innervated neuromuscular junctions 28 days after pd-CTM treatment. pd-CTM may be a novel treatment option for patients with UVFP based on the neurotrophic, angiogenic, tissue remodeling, and anti-inflammatory factors present. NA. Show less
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
Coronary heart disease (CHD) is driven by endothelial dysfunction and chronic vascular inflammation. hsa-miR-2110 (miR-2110) has been associated with adverse cardiovascular outcomes, but its mechanist Show more
Coronary heart disease (CHD) is driven by endothelial dysfunction and chronic vascular inflammation. hsa-miR-2110 (miR-2110) has been associated with adverse cardiovascular outcomes, but its mechanistic role in CHD remains unclear. In this study, miR-2110 expression was quantified in peripheral blood from CHD patients and healthy controls. Functional effects were assessed in EA.hy926 endothelial cells following lentiviral overexpression of miR-2110. The target gene 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
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
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to Show more
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore the therapeutic potential of RTG against CRS-induced depression-like behaviors and cognitive deficits in mice and to uncover the associated molecular mechanisms. A depression-like and cognitive impairment model was established in C57BL/6 male mice using chronic restraint stress (CRS). Six-week-old C57BL/6 male mice were randomly assigned to the following groups: control (Con), model (CRS), RTG (10 mg/kg), XE-991 (2 mg/kg) or tunicamycin (Tm, 2 mg/kg). Behavioral tests were conducted to assess depression-like behaviors and cognitive function. Hippocampal neuronal morphology was examined by H&E and immunofluorescence staining, while changes in endoplasmic reticulum stress (ERS)-related signaling pathways were analyzed by Western blot. Retigabine treatment reduced hippocampal neuronal damage and the expression of ERS-related factors (GRP78, CHOP) and the pro-apoptotic factor BAX in CRS-induced mice, while it increased the levels of BDNF. These effects were antagonized by XE-991 and the ERS agonist tunicamycin (Tm). Retigabine may alleviate CRS-induced depressive-like behaviors and cognitive impairment by inhibiting ERS-mediated apoptosis, suggesting its potential as a novel therapeutic strategy for depression. Show less
This study aims to identify the latent profiles of sense of coherence (SOC) in patients with advanced cancer and explore its influencing factors encompassing sociodemographic and clinical characterist Show more
This study aims to identify the latent profiles of sense of coherence (SOC) in patients with advanced cancer and explore its influencing factors encompassing sociodemographic and clinical characteristics, and generalized resistance resources (GRRs). A cross-sectional study of 262 patients with advanced cancer was conducted by convenience sampling in Guangzhou, China, from September 2023 to July 2024. Data were collected including sociodemographic and clinical characteristics, SOC-13, Revised Life Orientation Test (LOT-R), Rosenberg Self-Esteem Scale (RSES), Inner Peace State Scale (IPSS), Gratitude Questionnaire-6 (GQ-6), and Social Support Rating Scale (SSRS). Statistical analysis was performed using latent profile analysis (LPA) and multivariate logistic regression analysis. Three latent profiles of SOC were identified: low SOC and low comprehensibility group (29.01%), moderate SOC and high meaningfulness group (40.08%), and high SOC and high manageability group (30.91%). This study found that SOC was impacted by self-perceived severity of the disease and GRRs including optimism, self-esteem, and inner peace ( SOC in patients with advanced cancer exhibited different characteristics. Enhancing positive disease perception and GRRs including optimism, self-esteem, and inner peace may be effective strategies for improving their SOC. Healthcare professionals can formulate strategies such as tailored health education, symptom management, and positive psychological interventions to enhance SOC in patients with advanced cancer. 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
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