Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to c Show more
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to cancer progression remain poorly understood. Here, we identified a lung cancer-specific chimeric RNA KANSL1-ARL17A (chKANSARL) and its circular variant fusion circular RNA KANSL1-ARL17 A (F-circKA), both derived from the fusion gene KANSARL. Functional assays revealed that overexpression of either chKANSARL or F-circKA significantly enhanced lung cancer cell proliferation, migration, and invasion, while their knockdown suppressed these malignant phenotypes. In vivo experiments demonstrated that chKANSARL overexpression accelerated tumor growth in immunodeficient mice. Notably, coexpression experiments uncovered a synergistic regulatory interaction between F-circKA and chKANSARL, amplifying oncogenic effects. Mechanistically, miRNA sequencing and dual-luciferase assays revealed that F-circKA acts as a molecular sponge for miR-6860, thereby derepressing chKANSARL expression. Rescue experiments further validated this regulatory axis, wherein miR-6860 inhibition reversed the tumor-suppressive effects of F-circKA knockdown. Collectively, our study identifies and characterizes a novel F-circKA/miR-6860/chKANSARL regulatory axis, revealing how dual transcriptional outputs from the KANSARL fusion gene can synergistically drive lung cancer progression. These findings highlight a previously unrecognized layer of cooperative regulation between linear and circular fusion RNAs in oncogenesis and provide a new framework for understanding fusion gene-mediated tumorigenesis. Show less
Aberrant fibroblast growth factor receptor 3 (FGFR3) activation drives bladder carcinogenesis in humans, but currently approved pan-FGFR inhibitors lack FGFR3 isoform selectivity and fail to counter c Show more
Aberrant fibroblast growth factor receptor 3 (FGFR3) activation drives bladder carcinogenesis in humans, but currently approved pan-FGFR inhibitors lack FGFR3 isoform selectivity and fail to counter clinically acquired resistance mutations (e.g., FGFR3 V555M/L). Herein, we report the structure-based drug design of 4-(1-methyl-1 Show less
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients ha Show more
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients have a relatively high risk of infection during the treatment process. Hemodialysis nurses, who are the main executors of the treatment operations and have the most contact with patients, have a close relationship with the infection risk of patients. The level of their hospital infection prevention and control literacy is closely related to the infection risk of patients. To explore the current level of knowledge, attitudes, and practices (KAP) of hospital infection prevention and control among haemodialysis nurses in the Sichuan Province, China, and identified their potential categories. This provided evidence-based recommendations for improving infection control management in hemodialysis departments. A cross-sectional study was conducted From July 15 to August 15, 2025 using a convenience sampling method to survey 470 hemodialysis nurses from 78 hospitals in Sichuan Province. Participants were licensed nurses with over 3 months of hemodialysis experience. Data were collected using the A total of 460 valid questionnaires were collected, with an effective response rate of 97.87%. The average scores for knowledge, attitudes, and practices related to hospital infection prevention and control among haemodialysis nurses were 4.67 ± 0.43, 4.59 ± 0.43, and 4.74 ± 0.34, respectively. Three latent profile models were constructed, with the two-class model identified as the optimal solution, which were defined as the "Low KAP Group" (25.9%) and "High KAP Group" (74.1%). Logistic regression analysis revealed that sex, responsibility for infection control, hospital level, annual number of infection control training sessions, organizational support, and work engagement were significant influencing factors ( The KAP level of haemodialysis nurses in hospital infection prevention and control was relatively high. Hospital managers should tailor supportive work environments on the basis of the individual characteristics and work engagement of haemodialysis nurses to improve the KAP level of nosocomial infection prevention and control among haemodialysis nurses. Show less
The clinical interpretation of Alzheimer's disease (AD) is frequently complicated by the prevalence of missense variants designated as being of uncertain significance within associated genes. Conventi Show more
The clinical interpretation of Alzheimer's disease (AD) is frequently complicated by the prevalence of missense variants designated as being of uncertain significance within associated genes. Conventional computational prediction tools often overlook disease-specific pathophysiological contexts and lack pertinence and interpretability. Therefore, the present study aimed to develop a novel, interpretable framework for predicting the pathogenicity of AD missense variants by integrating transcriptomic and proteomic data enrichment patterns with machine learning methods. A cross-sectional variant-level analysis was performed using publicly available databases. Missense variants in APOE, APP, PSEN1, PSEN2, SORL1, and TREM2 reported in AD patients were retrieved from Alzforum and compared with missense variants from individuals without neurological diseases, as cataloged in the gnomAD v2.1.1 non-neuro subset. Variants were annotated with tissue-specific expression, secondary structure, relative solvent accessibility, and other functional features using tools like AlphaFold. Enrichment of specific features was assessed with Fisher's exact tests with Bonferroni correction for multiple comparisons. Given that PSEN1 showed the strongest enrichment signals, six machine-learning algorithms were trained on PSEN1 variants to distinguish AD-associated variants from gnomAD variants, using a 10 × 5 nested cross-validation scheme. External validation was conducted using PSEN1 missense variants from ClinVar annotated as pathogenic/likely pathogenic or benign/likely benign. Model performance was compared with SIFT and PolyPhen-2, and interpretability was evaluated by feature ablation and SHapley Additive exPlanations analyses. AD-associated variants exhibited statistically significant enrichment within some transcriptomic or proteomic features, with PSEN1 contributing significantly to the enrichment observed across these features. Random forest and gradient boosting models achieved high performance in the internal training dataset and maintained high recall in the external validation dataset, outperforming SIFT and approaching the performance of PolyPhen-2. Relative solvent accessibility was the most discriminative individual feature, while regional and topological features provided complementary discriminative power. This integrative, multi-omics framework links disease-specific enrichment patterns with interpretable gene-level machine learning for AD missense variants. The results highlight the importance of expression level, structural context, etc. for PSEN1 variant pathogenicity and may help prioritize variants for functional studies. Further validation in additional genes and independent cohorts is warranted prior to any clinical application. Show less
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, and the accurate, non-invasive assessment of liver fibrosis remains an important clinical c Show more
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, and the accurate, non-invasive assessment of liver fibrosis remains an important clinical challenge. This study aimed to identify ferroptosis biomarkers associated with MASLD-related liver fibrosis progression, explore their potential biological links with MRI-derived parameters, and provide new clues for developing non-invasive diagnostic strategies for ferroptosis. A MASLD-related liver fibrosis model was established using 30 Sprague-Dawley (SD) rats. Hub differentially expressed ferroptosis-related genes (DE-FRGs) were identified through the integration of weighted gene co-expression network analysis (WGCNA), differential expression analysis, and LASSO regression. The role of ferroptosis in MASLD was evaluated using transmission electron microscopy (TEM) and measurements of glutathione (GSH) and Fe²⁺ content. T2*, R2*, and proton density fat fraction (PDFF) were obtained through magnetic resonance imaging (MRI) and were analyzed for correlations with hub DE-FRGs and Fe²⁺ levels. A total of eight hub DE-FRGs were identified: Pck2, Idh2, Nr1d1, Fads1, Sat1, Abhd12, Got1, and Srebf1. Enrichment analyses revealed that these hub DE-FRGs were predominantly implicated in carbohydrate response, amino acid biosynthesis, insulin resistance, and the AMPK signaling pathway. TEM and biochemical markers analyses demonstrated an association between MASLD-related liver fibrosis and ferroptosis. MRI‑derived parameters were significantly correlated with Fe²⁺ levels and the expression of hub DE-FRGs. This study preliminarily identified hub DE-FRGs associated with liver fibrosis in MASLD and their signaling pathways, verified indirect indicators related to ferroptosis, and proposed their potential correlation with MRI-derived parameters. 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
To investigate the causal relationship between inflammatory proteins and Alzheimer's disease (AD) and the mediating role of plasma metabolites therein. Using Mendelian mandomization (MR) methods and p Show more
To investigate the causal relationship between inflammatory proteins and Alzheimer's disease (AD) and the mediating role of plasma metabolites therein. Using Mendelian mandomization (MR) methods and publicly available genome-wide association study (GWAS) data, we selected 91 single nucleotide polymorphisms (SNPs) that were strongly linked to inflammatory proteins without reverse causality with AD as the outcome. A bidirectional two-sample MR analysis was performed. Inflammatory proteins with causal links to AD were identified via inverse variance weighted (IVW) analysis. A mediation MR analysis was then performed using 1400 plasma metabolites to assess their mediating role in this causal pathway. The preliminary bidirectional MR analysis identified 3 inflammatory proteins that had a potential positive causal association with AD without reverse causality: Axin-1, C-X-C motif chemokine ligand 11 (CXCL11), and interleukin-12β (IL-12β). Elevated levels of Axin-1 were positively causally associated with AD risk (OR=1.082, 95% This study reveals how specific inflammatory proteins influence AD risk via plasma metabolites and provides genetic evidence for inflammatory-metabolic interactions in AD to facilitate the identification of potential biomarkers and targets for early detection and intervention of AD. Show less
The international consensus classification or the World Health Organization classifications underrepresented driver alterations enriched in pediatric acute myeloid leukemia (AML). To address this, we Show more
The international consensus classification or the World Health Organization classifications underrepresented driver alterations enriched in pediatric acute myeloid leukemia (AML). To address this, we retrospectively characterized the genomic landscape of 105 pediatric patients with AML of East Asian ancestry using transcriptome and whole-exome sequencing (WES). In addition to the common recurrent fusions such as RUNX1::RUNX1T1 and CBFB::MYH11, we identified rearrangements involving KMT2A, NUP98, GLIS, as well as FLT3 and UBTF tandem duplications. The median somatic mutation rate in AML was 0.97 per megabase, as estimated by WES. Frequently mutated pathways included signaling: 68.6% (72/105), transcription: 37.1% (39/105), epigenetic regulation: 26.7% (28/105), cohesin: 7.6% (8/105), RNA binding: 3.8% (4/105), and protein modification: 5.7% (6/105). When analyzed together, high-risk genetic subtypes including GLISr, UBTF tandem duplications, PICALM::MLLT10, and HOXr were significantly associated with poorer 5 year overall survival (OS) in multivariable analysis (p-value = 0.037). Although FLT3 internal tandem duplications were significantly associated with inferior 5 year OS in univariable analysis, this effect was not significant in multivariable analysis (p-value = 0.382). Patients with RUNX1 mutations had inferior 5 year OS in multivariable analysis (p-value = 0.009). These findings suggest specific genomic alterations that may refine risk stratification and guide future therapeutic protocols in Taiwanese pediatric patients with AML. Show less
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic Show more
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Structurally composed of a low-density lipoprotein (LDL)-like particle covalently linked to apolipoprotein(a) [apo(a)], Lp(a) exhibits unique atherogenic, thrombogenic, and inflammatory properties, largely due to its role as a carrier of oxidized phospholipids (OxPL). Plasma Lp(a) concentrations are predominantly determined by the number of kringle IV type 2 (KIV-2) repeats in the LPA gene, with minimal influence from lifestyle or environmental factors. Despite substantial evidence linking elevated Lp(a) to cardiovascular risk, clinical testing remains underutilized, especially in East Asian countries. In Taiwan, although population-level Lp(a) concentrations are comparatively low, a significant subset exceeds risk thresholds, with local studies confirming its prognostic value in coronary artery disease and ischemic stroke. Barriers, including limited physician awareness, implementation barriers, and therapeutic nihilism, contribute to its under-recognition. This review highlights the molecular features of Lp(a), its pathogenesis of cardiovascular disorders, epidemiology, and current barriers and future advances in diagnostic testing, with a particular focus on implications for cardiovascular risk management in Taiwan. 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
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in Show more
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in preschool-aged children. 268 preschoolers were included in the cross-sectional study. An accelerometer was used to assess sedentary behavior (SB), light and moderate-to-vigorous physical activity (LPA and MVPA). A parental report was used to collect sleep time. Bioelectrical impedance analysis was employed to assess body composition. Compositional linear regression analysis was employed to explore how daily movement behaviors were associated with body composition. Compositional isotemporal substitution analysis was employed to estimate changes in body composition after reallocating time among behaviors. 24-h movement behaviors composition significantly predicted fat-free mass index (FFMI), soft lean mass index (SLMI), and skeletal muscle mass index (SMMI), but not fat mass index, percent body fat, and bone mineral content index. The compositional isotemporal substitution analyses consistently showed that increasing MVPA at the expenses of SB was positively associated with FFMI (+0.328 kg/m The findings highlight the importance of MVPA in improving preschoolers' body composition. Increasing MVPA at the expenses of SB may be a strategy to improve body composition in preschoolers. Show less
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
Vascular stiffness and aging are critical contributors to cardiovascular diseases. Whether betulinic acid (BA), a natural triterpenoid, alleviates vascular aging remains unclear. Mouse aortic smooth m Show more
Vascular stiffness and aging are critical contributors to cardiovascular diseases. Whether betulinic acid (BA), a natural triterpenoid, alleviates vascular aging remains unclear. Mouse aortic smooth muscle cells (MASMCs) with oleic acid (OA)-induced lipotoxic senescence were treated with BA (30 μM). Transcriptomic analysis and functional assays were conducted. Show less
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
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
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
This study aims to examine the health characteristics of female sex workers (FSWs) in entertainment venues and to investigate the relationship between these characteristics and sleep quality. This stu Show more
This study aims to examine the health characteristics of female sex workers (FSWs) in entertainment venues and to investigate the relationship between these characteristics and sleep quality. This study employed a cross-sectional design and was conducted from January to April 2024 in Wuhan, China. Participants were FSWs recruited through snowball sampling from entertainment venues, including hotels, restaurants, nightclubs, karaoke bars and dance halls. Data were collected via structured questionnaires covering sociodemographic information, work experience, psychological stress, health status, sleep quality and circadian rhythms. Latent profile analysis (LPA) was employed to identify health characteristic profiles among FSWs, and multivariate logistic regression was used to examine the associations between these profiles and sleep quality. Among the 1,036 FSWs surveyed, 45.1% had poor sleep quality. LPA classified FSWs’ health characteristics into three profiles: the high overall functioning group, the lower physical–emotional functioning group and the lower psychosocial functioning group. Multivariate logistic regression analysis showed that FSWs in the lower physical–emotional functioning group had higher odds of poor sleep quality (OR = 2.184) compared with those in the high overall functioning group. FSWs in the lower psychosocial functioning group had substantially higher odds of poor sleep quality (OR = 7.755) than that in the high overall functioning group. FSWs demonstrate substantial heterogeneity in health characteristics and exhibit lower overall sleep quality compared with the general population. Psychological and physiological factors are major influencing factors for their sleep quality, suggesting the importance of prioritising mental and physical health in this population. Show less
Gary Chen, Adrienne Sexton · 2026 · Patient education and counseling · Elsevier · added 2026-04-24
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinic Show more
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinical practice. Rigorous scoping review methodology was followed. Ovid Medline, Embase, PsycINFO, and CINAHL were searched with keywords and MeSH terms related to "genetic testing", "genetic counseling", "dementia", "decision making", and "patient outcomes" for peer-reviewed studies with adult participants published over the last ten years. Thirty-six articles met inclusion criteria. Narrative synthesis organized findings into temporal categories including motivations for genetic testing, experiences during the testing/counseling process, and outcomes after testing. Common motivators included reducing uncertainty, reproductive planning, life planning, and the prospect of a treatment becoming available in the future. A lack of current treatments and fear that knowledge of genetic risk would be difficult to cope with were common barriers to testing. Patient-centered communication improved satisfaction. Genetic testing was generally psychologically well tolerated, and a wide range of practical responses were reported including changes to lifestyle, diet, advanced care and financial planning, and engaging in clinical trials. This review maps the experiences and outcomes of genetic testing or counseling for people with or at potentially increased genetic risk of dementia. Genetic testing and counseling for directly causal dementia genes and APOE genotype appears well tolerated but long-term outcome data is lacking. Motivations, concerns and perceived benefits of knowing genetic results vary depending on personal, familial and cultural viewpoints. Genetic counseling can help patients and families prepare, reduce decisional regret, and adapt to results. Motivations varied, and a patient-centered approach addressing both information and psychological aspects improves satisfaction. Future longitudinal research should ascertain ways to support individuals from a wide range of demographics with understanding and adjusting to genetic risk information regarding dementia. Show less
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
Tianpei Ma, Xin Chen, Qingwen Zhao+19 more · 2026 · The journals of gerontology. Series A, Biological sciences and medical sciences · Oxford University Press · added 2026-04-24
Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examine Show more
Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores ( β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores ( β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment. Show less
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adv Show more
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adverse factors in the periodontal microenvironment. Therefore, identifying novel therapeutic targets and elucidating the underlying molecular mechanisms to protect the proliferative and differentiation potential of PDLSCs is of significant importance. PDLSCs were exposed to electronic cigarette extract and various common oral stressors to evaluate the expression of glucagon such as peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR). PDLSCs isolated from patients with periodontitis and PDLSCs from a mouse periodontitis model were also analyzed. Functional studies were performed by GLP1R or GIPR knockdown, overexpression, and treatment with single or dual receptor agonists, followed by assessment of cell proliferation and multilineage differentiation capacities. Transcriptome (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA immunoprecipitation sequencing (RIP-seq) were applied to delineate downstream signaling pathways and RNA–protein interactions. Protein synthesis regulation was further investigated by immunoprecipitation of interferon induced protein with tetratricopeptide repeats (IFIT)-associated translation initiation factors. For in vivo validation, wild-type and GLP1R/GIPR double-knockout periodontitis mice were transplanted with CRISPR-Cas9 mCherry-labeled PDLSCs and treated with receptor agonists. Disease severity and PDLSC fate were evaluated by histology and lineage tracing. Finally, a questionnaire-based survey was conducted in 150 patients with periodontitis, including 74 individuals with long-term use (> 1 month) of GLP1R or GLP1R/GIPR dual agonists (e.g., semaglutide, liraglutide, tirzepatide), to assess their periodontal outcomes. GLP1R and GIPR expression were markedly downregulated in PDLSCs exposed to multiple stressors and in PDLSCs isolated from periodontitis specimens. RNA-seq, ChIP-seq, and RIP-seq identified downstream pathways and RNA–protein interactions implicated in receptor-mediated regulation. Functionally, GIPR agonism promoted PDLSC proliferation via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, whereas GLP1R agonist enhanced multilineage differentiation capacity in vitro. Mechanistically, GLP1R knockdown induced robust upregulation of IFIT1/2/3, while GLP1R agonist suppressed IFIT expression. IFIT1/2/3 were shown to interact with eIF3C and to inhibit translation of differentiation-related mRNAs, linking GLP1R signaling to translational control of PDLSC fate. In vivo, transplantation experiments in both wild-type and GLP1R/GIPR double-knockout periodontitis mice demonstrated that single and dual receptor agonists significantly improved endogenous and exogenous PDLSC-mediated periodontal regeneration. Consistently, a clinical survey of 150 patients with periodontitis (74 receiving GLP1R or dual agonists) revealed significantly better periodontal staging and grading in treated individuals, with longer agonist exposure associated with greater improvement. Our findings uncover the different molecular roles of GIPR and GLP1R in self-renewal capacity and multipotency of PDLSCs, and open new avenues for developing therapeutic targets and strategies in oral tissue engineering and regenerative medicine. The online version contains supplementary material available at 10.1186/s11658-026-00867-2. 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
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Ath Show more
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Atherosclerotic plaques accumulated in the aorta and aortic sinus after HFD, while statin and high-dose GP alleviated this burden. TC, TG, LDL-C, MCP-1, MCP-3 and IL-2 showed significant increase after HFD, while statin and GP decreased LDL-C, MCP-1 and MCP-3. The goblet cells, ZO-1 and Occludin decreased after HFD, while statin and GP increased them, indicating that the intestinal barrier integrity was improved. Additionally, the composition of gut microbiota was modulated by GP. Some candidate taxa were identified, such as This study suggests that GP is beneficial for alleviating atherosclerosis in HFD-induced ApoE 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
Jianyi Li, Luyao Zhang, Jiapei Xu+7 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, s Show more
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, such as Dapagliflozin (DAPA), exhibit a protective effect against cardiovascular diseases. However, the effects and mechanisms of DAPA on chronic stress-induced AS are largely unknown. The aim of this study was to determine whether DAPA confers a protective effect against chronic stress-induced AS and to elucidate its further molecular mechanisms. The combined high-fat diet-fed and chronic unpredictable mild stress in ApoE-/- mice and lipopolysaccharides- and corticosterone-induced human umbilical vein endothelial cells (HUVECs) were employed to evaluate the antiatherosclerotic effect of DAPA under chronic stress in vivo and in vitro. Histological staining, western blot analysis, siRNA transfection, reactive oxygen species (ROS) staining, and apoptosis assessment were used to investigate the potential mechanisms of DAPA against AS under chronic stress. The results indicate that DAPA significantly improved plaque size and increased plaque stability in the aorta under chronic stress and reduced inflammation and oxidative stress and inhibited apoptosis in the aorta and HUVECs. Chronic stress upregulated regulated in development and DNA damage response 1 (REDD1) expression, which exacerbated cellular inflammation, oxidative stress, and apoptosis levels, leading to endothelial dysfunction. In contrast, DAPA downregulated REDD1 expression and activated the AKT/FoxO1 pathway. In addition, p53 was a transcriptional regulator of REDD1 under chronic stress. More importantly, p53 agonists prevented DAPA from downregulating REDD1 and inhibited AKT/FoxO1 activation, thereby exacerbating chronic stress-induced endothelial dysfunction. These results suggest that DAPA effectively attenuates chronic stress-induced endothelial dysfunction and AS by downregulating REDD1 to activate the AKT/FoxO1 pathway. Show less
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
We aimed to identify key molecules that can moderately enhance the compensatory capacity of beta cells during obesity. Single-cell RNA-seq was used to profile the RNA expression of islet cells from di Show more
We aimed to identify key molecules that can moderately enhance the compensatory capacity of beta cells during obesity. Single-cell RNA-seq was used to profile the RNA expression of islet cells from diet-induced obese mice and pregnant mice. The gene and protein expression levels of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) were verified by quantitative PCR and immunofluorescence, respectively. The roles of ENPP2 were investigated using gain-of-function and loss-of-function approaches in Min6 beta cells, global Enpp2-knockout mice and beta cell Enpp2-overexpressing transgenic (Enpp2-Tg) mice. Using single-cell RNA-seq, we demonstrated that proliferation is the primary and common mechanism for compensating for beta cell numbers during both mouse obesity and pregnancy, with proliferation being more pronounced in pregnancy than in obesity. Additionally, many differentially expressed genes were co-regulated in both conditions. Among these, the pro-proliferative phosphodiesterase ENPP2 showed the highest increase in beta cells of pregnant mice and a moderate increase in beta cells of obese mice. Overexpression or knockdown of ENPP2 in Min6 beta cells revealed that ENPP2 promoted beta cell proliferation, inhibited apoptosis and enhanced high-glucose-stimulated insulin secretion. These effects of ENPP2 were further validated in vivo using Enpp2-Tg mice. In Enpp2-knockout mice fed a high-fat diet, the deficiency of ENPP2 resulted in insufficient compensation of beta cells during obesity. The pro-proliferative role of ENPP2 in beta cells was mediated through the lysophosphatidic acid (LPA)-Akt/mammalian target of rapamycin (mTOR) signalling pathway via LPA receptor 2. However, the expression of ENPP2 was reduced in the mouse model of diabetes and in human participants with type 2 diabetes compared with non-diabetic control groups. Furthermore, ENPP2 was co-upregulated by a synergy of oestradiol and progesterone. ENPP2 may serve as a key regulator in beta cell compensation during obesity, and modulating its levels in beta cells could be a potential therapeutic target for mitigating beta cell deterioration in diabetes. Show less
Lumbrokinase belongs to a group of fibrinolytic enzymes, particularly tissue plasminogen activator (tPA), which can facilitate the proteolytic maturation of brain-derived neurotrophic factor (BDNF). D Show more
Lumbrokinase belongs to a group of fibrinolytic enzymes, particularly tissue plasminogen activator (tPA), which can facilitate the proteolytic maturation of brain-derived neurotrophic factor (BDNF). Drugs administered via oral or intravenous routes are often metabolized in the liver or kidneys, and these delivery methods for brain-targeted therapies must overcome the natural barriers of the central nervous system (CNS). Intranasal drug delivery via the nose-to-brain route has emerged as a promising approach to bypass these barriers, enhance drug penetration into the brain, and minimize exposure to peripheral organs. In this study, we demonstrate that intranasally administered lumbrokinase successfully reached the brain. Behaviorally, lumbrokinase significantly improved chronic social defeat stress (CSDS)-induced social avoidance and cognitive impairments. At the molecular level, CSDS increased hippocampal precursor BDNF (proBDNF) expression and reduced mature BDNF (mBDNF) compared with control mice. Importantly, lumbrokinase treatment promoted the expression of tPA and plasmin, thereby restoring the proBDNF/mBDNF balance in the hippocampus and reversing stress-induced maladaptive behaviors. Additionally, lumbrokinase increased TrkB, PSD95, and enhanced phosphorylation of PI3K, AKT, and mTOR in the hippocampus, indicating improved synaptic signaling and plasticity. In conclusion, this study demonstrates that intranasal delivery enables lumbrokinase to reach the brain effectively, providing robust therapeutic benefits against CSDS-induced behavioral and cognitive deficits. Enhancing plasmin-mediated BDNF maturation through non-invasive intranasal enzyme delivery may represent a promising approach for treating stress-related mood disorders. Show less
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 Show more
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 (IRF6) is a transcription factor that regulates the inflammatory response following injury. In this work, the LSS-induced AS model was induced by the partial ligation of the left carotid artery in high-fat diet-fed ApoE Show less