The present study aimed to investigate the combined impact of lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL) subfractions on cardiovascular outcomes in patients with acute coronary syndrome Show more
The present study aimed to investigate the combined impact of lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL) subfractions on cardiovascular outcomes in patients with acute coronary syndrome (ACS). The study enrolled 2061 ACS patients from Tianjin Chest Hospital. Participants were categorized into 4 groups based on their Lp(a) and the concentration of the sixth component particles of LDL(LDL-P6). The primary endpoint was the occurrence of major adverse cardiovascular events (MACE). The relationship between LDL-P6, Lp(a), and MACE was evaluated. Over a mean follow-up period of 5.4 years, 456 (22.1%) patients experienced MACE. Multivariate analysis identified both LDL-P6 and Lp(a) as significant independent predictors of MACE in ACS patients. Those in the highest-risk group had a substantially higher incidence of MACE compared with the lowest-risk group (HR 5.718; 95% CI 3.703-8.829; Show less
Atherosclerosis (AS) is a major underlying cause of cardiovascular diseases, with hypercholesterolemia, inflammatory responses, and macrophage polarization being established key contributors. The role Show more
Atherosclerosis (AS) is a major underlying cause of cardiovascular diseases, with hypercholesterolemia, inflammatory responses, and macrophage polarization being established key contributors. The roles of NLRP3 inflammasome activation and macrophage polarization in AS pathogenesis have garnered significant research interest. This study investigated the therapeutic potential of Schisandrol B (Sol B) against AS using an in vivo model of ApoE Show less
Speed capability is critical for early childhood development, but troubling patterns are emerging in the motor fitness of Chinese preschoolers (3-6 years). This study investigated how compositional 24 Show more
Speed capability is critical for early childhood development, but troubling patterns are emerging in the motor fitness of Chinese preschoolers (3-6 years). This study investigated how compositional 24-h movement behaviours (sleep, sedentary behaviour [SB], light physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) relate to speed capability. Via compositional data analysis and isotemporal substitution modelling, we assessed relationships between 24-h movement behaviours (sleep, SB, LPA and MVPA) and speed capability in 275 preschoolers (mean age 4.98 ± 0.76 years). Participants completed 20-m sprint tests and 7-day accelerometry. Time-reallocation effects were quantified through pairwise behavioural substitutions (5- to 30-min durations), with all models adjusted for age, sex and BMI z scores (z-BMI). Higher relative MVPA time significantly predicted faster sprint times (β = -1.302, p < 0.001), while higher LPA predicted slower times (β = 1.570, p = 0.003). Reallocating 15 min from sleep, SB or LPA to MVPA reduced sprint times by 0.176, 0.201 and 0.385 s, respectively (all p < 0.05). Conversely, reallocating MVPA to other behaviours worsened performance. The effects exhibited asymmetry: displacing time away from MVPA impaired speed capability to a greater extent than equivalent gains in MVPA time improved it. MVPA is the strongest positive predictor of speed capability in preschoolers. Optimizing 24-h movement patterns by reallocating time from LPA or SB to MVPA is associated with enhanced speed performance, supporting targeted interventions for early childhood development. 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
While the apolipoprotein E (APOE) ε4 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (TOMM40)-an adjacent gene involved in mitoch Show more
While the apolipoprotein E (APOE) ε4 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (TOMM40)-an adjacent gene involved in mitochondrial protein import-is not known. Human brain tissue, human induced pluripotent stem cell-derived neurons (iNeurons), and mice were used for study of gene expression, cholesterol metabolism, mitochondrial function, and animal cognition. Human brain transcriptomics showed reduced TOMM40 expression that correlated with cholesterol regulatory gene expression, amyloid burden, and clinical AD diagnosis. In human iNeurons, TOMM40 knockdown (KD) disrupted mitochondria-endoplasmic reticulum contact sites (MERCs), causing mitochondrial dysfunction and promoting reactive oxygen species that led to activation of liver X receptor beta (NR1H2), upregulation of APOE and low-density lipoprotein receptor (LDLR), and increased cellular cholesterol and amyloid beta (Aβ)42 independent of APOE ε4. Consistently, Tomm40 KD in mice induced increased brain cholesterol, Aβ42 content, and impaired memory. TOMM40 is a novel mediator of AD pathology through dual effects on MERCs that regulate cholesterol homeostasis and mitochondrial function. Show less
Hypertrophic cardiomyopathy (HCM) arises from genetic mutations in sarcomere proteins, resulting in major structural abnormalities and limited treatment options. Patients with HCM had reduced expressi Show more
Hypertrophic cardiomyopathy (HCM) arises from genetic mutations in sarcomere proteins, resulting in major structural abnormalities and limited treatment options. Patients with HCM had reduced expression of the FGF12 (fibroblast growth factor 12), but its precise functional role remains unclear. To explore FGF12's function and interactions, we utilized clustered regularly interspaced short palindromic repeats-Cas9 technology in cardiomyocytes derived from human induced pluripotent stem cells-induced cardiomyocytes, as well as in other cell lines and mouse models (MYH7 First, we observed a decrease in FGF12 expression and a difference in its subcellular localization in patients with HCM compared with healthy volunteers. In hypertrophic mouse models, injecting adeno-associated virus 9 reduced myocardial hypertrophy. FGF12 binds to calmodulin and inhibits its phosphorylation. This interaction also suppresses the expression and phosphorylation of downstream proteins, including CaMKII, ERK1/2, CREB1, and MCU. The nuclear-localization FGF12 binds to the promoter region of CREB1. FGF12 inhibits the expression of the CREB1-MCU axis expression, leading to reductions in both mitochondrial Ca This study reveals a pathological mechanism associated with HCM linked to FGF12. FGF12, located outside the nucleus, suppresses the expression of metabolism-related genes by reducing the phosphorylation levels within the calmodulin-ERK1/2-CREB1-MCU axis. In contrast, the nuclear localization of FGF12 facilitates its binding to the promoter regions of CREB1, inhibiting CREB1 expression. This dual action maintains cardiomyocyte function and mitochondrial homeostasis. Our findings position FGF12 as a promising therapeutic target for HCM. Show less
Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In Show more
Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In this study, we investigated the therapeutic potential of clinical-grade human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) for treating refractory moderate-to-severe intrauterine adhesion (IUA). In a rabbit IUA model, sub-endometrial injection of IMRCs significantly reduced fibrosis and enhanced endometrial angiogenesis, outperforming uterine perfusion. Transcriptomic analysis revealed distinct pro-angiogenic gene expression profiles between the two delivery routes. In vitro, IMRCs co-cultured with endometrial stromal cells (ESCs) markedly enhanced angiogenic potential compared to either cell type alone. Protein array analysis of the co-culture supernatant showed elevated levels of angiogenic factors, with functional assays confirming that inhibition of ANGPTL4, a non-canonical pro-angiogenic mediator, impaired angiogenesis. In a first-in-human, single-center, phase 1 dose-escalation trial involving 18 patients with refractory IUA, high-dose sub-endometrial IMRC injection promoted angiogenesis, reduced uterine scarring, and improved pregnancy outcomes, with no safety concerns observed over 3 years of follow-up. These findings highlight the translational promise of IMRCs as a novel therapeutic strategy for endometrial regeneration in severe IUA. Show less
Indigenous chickens in tropical regions routinely survive high environmental temperatures (40-45 °C) that cause significant mortality and production loss in commercial breeds, yet the genetic mechanis Show more
Indigenous chickens in tropical regions routinely survive high environmental temperatures (40-45 °C) that cause significant mortality and production loss in commercial breeds, yet the genetic mechanisms of thermotolerance remain poorly understood. This study integrated genome-wide selective scans across 14 geographically and climatically diverse chicken breeds with multi-tissue expression data, gene expression quantitative trait locus (eQTL) analysis, transcriptome-wide association study (TWAS), and cross-species phenome-wide association study (PheWAS) to validate candidate genes. We identified 25 high-confidence genes under selection, with ATP1A1, PLCB4, RYR2 and AKT3 forming a regulatory hub coordinating cardiovascular, calcium and survival signaling. These genes converge on interconnected adrenergic, calcium, and GnRH signaling pathways, with coordinated expression across heart, hypothalamus, and liver forming an integrated thermoregulatory axis. The eQTL integration analysis using ChickenGTEx data identified 359 tissue-specific cis-eQTLs in selected regions. Additionally, TWAS analysis linked ATP1A1 to 145 gene-trait associations across 13 tissues and 14 trait categories (hepatic regulation, β = -2.13, p = 4.21 × 10⁻¹²), and cross-species PheWAS validated conserved roles in cardiovascular function (RYR2, resting heart rate p = 4.9 × 10⁻¹²), and ionic homeostasis (ATP1A1, chloride p = 1.18 × 10⁻³). In parallel, we also identified robust genomic signatures of domestication in classic candidate genes (TSHR, TBC1D1, BDNF), highlighting how initial separation from Red Jungle Fowl and subsequent adaptation to diverse climates have shaped the genetic and physiological diversity of the domesticated chicken. Collectively, our results reveal an integrated cardio-neuroendocrine calcium network driving heat adaptation, providing potential targets for breeding heat-tolerant chickens. Show less
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. Show less
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
Overactivation of hepatic de novo lipogenesis (DNL) contributes to fatty liver disease. Although glucose and fructose strongly promote DNL, diary-rich galactose is only weakly lipogenic. However, whet Show more
Overactivation of hepatic de novo lipogenesis (DNL) contributes to fatty liver disease. Although glucose and fructose strongly promote DNL, diary-rich galactose is only weakly lipogenic. However, whether and how it regulates hepatic DNL remains unclear. In this study, we investigated whether low-dose galactose supplementation attenuates glucose- or fructose-induced DNL activation and protects against fatty liver diseases driven by DNL overactivation, such as alcohol-associated liver disease (ALD). In this study, we used integrated hepatocyte and mouse models to assess hepatic DNL and related signaling under high-glucose or high-fructose conditions, with or without low-dose galactose. Pharmacological and genetic interventions targeting the Leloir and hexosamine biosynthetic pathways (HBP) defined underlying mechanisms. For in vivo validation, male C57BL/6 mice were fed an isocaloric control or ethanol-containing diet for 4 wk. We found that glucose engages the HBP-mTORC1-SREBP-1c axis to stimulate hepatic DNL, whereas fructose acts predominantly through carbohydrate-responsive element-binding protein (ChREBP). Low-dose galactose selectively suppressed glucose-induced hepatic fat accumulation, concomitant with the inhibition of the HBP-mTORC1-SERBP-1c pathway. These effects required an intact Leloir pathway for galactose metabolism and were not observed with fructose. In alcohol-fed mice, hepatic HBP-mTORC1-SREBP-1c signaling was markedly upregulated, contributing to steatosis and liver injury. Replacing even a small fraction of dietary glucose with galactose normalized these alterations, attenuating hepatic lipid accumulation and injury without altering systemic glucose levels. In conclusion, glucose-induced hepatic lipogenesis involves the HBP-mTORC1-SREBP-1c pathway, which is also activated during chronic alcohol exposure. Low-dose galactose, obtainable from dairy sources, attenuates this pathway, thereby limiting excessive lipogenesis and protecting against early-stage ALD. Show less
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms rema Show more
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of autophagic proteins including ATG5, BECN1 and MAP1LC3/LC3 as well as LAMP1. Accordingly, silencing of Show less
To investigate potential types of food avoidance among patients with inflammatory bowel disease (IBD) and identify the contributing factors. Food avoidance may be an important risk factor for poor phy Show more
To investigate potential types of food avoidance among patients with inflammatory bowel disease (IBD) and identify the contributing factors. Food avoidance may be an important risk factor for poor physical and mental health in patients with IBD. However, there is limited research on food avoidance within the Chinese context. Between July 2022 and December 2023, patients with IBD during appointment at the First Affiliated Hospital with Nanjing Medical University was investigated with paper questionnaires to assess food avoidance, food category avoidance, fear of disease progression, negative illness perception, IBD-related self-efficacy, and social support. Demographic and disease-related characteristics were also collected. Latent profile analysis (LPA) was used to examine food avoidance in patients with IBD, and the correlates were investigated using regression analysis. LPA showed that respondents could be classified into three groups in terms of food avoidance, namely, the mild-food avoidance adaptation group ( Patients with IBD may exhibit long-term, spontaneous food avoidance, which often presents at high levels. Furthermore, patients with IBD exhibit considerable heterogeneity in their food avoidance patterns, categorizing them into three distinct categories. Future dietary management strategies should be tailored based on the specific characteristics and predictive factors of these food avoidance patterns. Given the prevalence and heterogeneity of food avoidance in patients with IBD, nurse managers should implement stratified interventions tailored to patient characteristics. Training nurses in culturally sensitive dietary education and emotional regulation strategies may improve the management of food-related behaviors and support patients' adaptive coping with the disease. Show less
Studies of surrogate decision-makers (SDMs) in the intensive care unit (ICU) often report high average levels of family decision-making self-efficacy (FDMSE). However, these findings contrast with the Show more
Studies of surrogate decision-makers (SDMs) in the intensive care unit (ICU) often report high average levels of family decision-making self-efficacy (FDMSE). However, these findings contrast with the significant decision conflict commonly observed in clinical practice. This discrepancy suggests that high aggregate FDMSE scores may mask underlying subgroups with distinct experiences. Identifying these latent profiles is essential for understanding the true experiences of ICU SDMs. This study aimed to identify distinct latent profiles of FDMSE among ICU SDMs and explore key influencing factors. A cross-sectional study was conducted among SDMs of ICU patients. Exploratory and confirmatory factor analysis (EFA/CFA) was performed to examine the factor structure of the Chinese FDMSE scale. The verified factor structure was then used for latent profile analysis (LPA). Lastly, univariate and multivariate analyses were performed to identify the main influencing factors. A total of 350 ICU SDMs were included in the analysis. The three-factor model, including treatment decision-making, comfort promotion decision-making, and facing death decision-making, provided a good fit for the Chinese FDMSE scale. Two profiles emerged: 'weak family decision-making self-efficacy', accounting for 55.9% of cases, and 'strong family decision-making self-efficacy', represented by the remaining 44.1%. The 'strong family decision-making self-efficacy' group was more likely to be observed in families where the patients held religious beliefs and were diagnosed with cancer, and where the family decision-makers held religious beliefs, had higher incomes, and had engaged in prior discussions about treatment preferences. This study verified the multi-dimensionality and heterogeneity of the FDMSE of ICU SDMs through EFA, CFA and LPA. The identification of a subgroup with low FDMSE differs from previous studies. Key modifiable factors include socio-economic resources, prior communication of the patients' preferences, and spiritual and cultural background, which serve as crucial levers for strengthening the decision-support framework in critical care settings. By identifying two distinct FDMSE profiles and key influencing factors, it offers critical care nurses a new perspective to design targeted interventions, thereby enhancing their ability to provide personalised decision support. Critical care nurses should receive structured end-of-life communication training to address the shared vulnerability of ICU SDMs in facing death decision-making self-efficacy across both profiles. Show less
Atherosclerosis (AS) is closely associated with gut microbiota that plays an important role in regulating intestinal mucosal barrier function, chronic inflammation, and immune homeostasis. Thus, targe Show more
Atherosclerosis (AS) is closely associated with gut microbiota that plays an important role in regulating intestinal mucosal barrier function, chronic inflammation, and immune homeostasis. Thus, targeting the modulation of gut microbitoa repesents a promising strategy for the control of AS. Clostridium butyricum (C. butyricum) serving as a kind of probiotics has shown a variety of biological benefits, but it's impact on atherosclerosis remains poorly understood. Sixty male ApoE C. butyricum ameliorated dyslipidemia and attenuated atherosclerotic plaque formation in ApoE C. butyricum intervention may exert anti-AS effects by reshaping gut homeostasis via the regulation of immune cells, providing a potential strategy for clinical treatment. Show less
Aortic dissection is a life-threatening cardiovascular disease whose complex cellular pathophysiology is studied using various mouse models. To systematically evaluate their fidelity, we performed cro Show more
Aortic dissection is a life-threatening cardiovascular disease whose complex cellular pathophysiology is studied using various mouse models. To systematically evaluate their fidelity, we performed cross-species single-cell RNA sequencing, integrating data from human aortic dissection with five mouse models (BAPN, Ang-II, Ang-II apoE Show less
Physical activity (PA) is known to enhance brain health; however, prior research has predominantly concentrated on the total volume of PA, often overlooking the frequency of daily PA on an hourly basi Show more
Physical activity (PA) is known to enhance brain health; however, prior research has predominantly concentrated on the total volume of PA, often overlooking the frequency of daily PA on an hourly basis. This prospective cohort study examined 69,393 middle-aged and older adults, utilizing wrist-worn accelerometer data to assess PA. A novel PA frequency score was developed, which integrated light PA (LPA) and moderate-to-vigorous PA (MVPA) across 18 hourly segments (6:00 AM-12:00 AM). Participants were categorized into Inactive, Active, and Very Active groups. After adjusting for potential confounders, it was observed that individuals in the Active and Very Active groups exhibited a reduced risk of developing brain disorders such as dementia, anxiety, depression, migraine, Parkinson's disease, and stroke over a median follow-up period of 7.41 years. Magnetic Resonance Imaging (MRI) findings demonstrated that each unit increase in the PA frequency score correlated with a 51.55 mm Show less
This paper presents the Assimilation Modified Emotional (AME) algorithm, which is an enhanced version of the traditional label propagation algorithm (LPA) designed to address key challenges in social Show more
This paper presents the Assimilation Modified Emotional (AME) algorithm, which is an enhanced version of the traditional label propagation algorithm (LPA) designed to address key challenges in social network analysis and emotional feature extraction. Traditional LPA methods, such as asynchronous label propagation and the Louvain algorithm, do not incorporate emotional representations and are often limited by local structural dependencies. The AME algorithm addresses these limitations by applying spectral algorithms, Markov chains, graph coarsening, and link prediction to simulate and optimize emotional transitions within the network. In addition, the AME algorithm enhances label representation through multi-label encoding, which allows for more accurate simulation of dynamic emotional states. Experimental results show that the AME algorithm achieves better performance than traditional LPA methods in terms of both accuracy and loss values. These findings indicate that the AME algorithm has strong potential for improving AI models used in social network analysis and emotional feature extraction. Show less
Cutaneous squamous cell carcinoma (cSCC) involves complex immune interactions. This study aimed to identify a T cell-related gene signature to characterize the immune landscape and aid in molecular di Show more
Cutaneous squamous cell carcinoma (cSCC) involves complex immune interactions. This study aimed to identify a T cell-related gene signature to characterize the immune landscape and aid in molecular diagnosis. We integrated single-cell RNA sequencing (scRNA-seq) and five bulk microarray datasets, utilizing an independent RNA-seq cohort for external validation. Feature genes were identified from the intersection of scRNA-seq-defined T cell-related genes (TRGs) and bulk differentially expressed genes using machine learning. A diagnostic nomogram was constructed, and its performance was assessed via ROC curves. In addition, immune infiltration, immunofluorescence staining, drug interactions, and clinical expression (qRT-PCR) were evaluated. Screening yielded 28 T cell-related DEGs enriched in extracellular matrix functions. machine learning selected a core signature: APOE, CYBA, and S100A2. The diagnostic model demonstrated high diagnostic performance in the studied cohorts (AUC > 0.9) across training and external validation cohorts. Clinically, qRT-PCR supported significant upregulation of CYBA and S100A2. APOE exhibited distinct immunomodulatory connectivity, correlating positively with Th17 cells and negatively with Tregs, whereas CYBA and S100A2 were associated with Treg infiltration. Immunofluorescence results revealed significantly elevated levels of S100A2 and Foxp3 in cSCC tissues compared to the control group. Pharmacogenetic analysis highlights the association of these genes, particularly the APOE gene, with drug response. This T cell-associated signature highlights the potential link between molecular diagnosis and immune characterization. Specifically, CYBA and S100A2 are identified as promising diagnostic candidate signatures, while APOE may reflect immunomodulatory heterogeneity. These findings offer insights for developing diagnostic strategies and targeted immunotherapies in cSCC. Show less
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study dem Show more
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. Show less
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile an Show more
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile analysis (LPA) classifies individuals into distinct subgroups via continuous FoP indicators, boosting classification accuracy by accounting for variable uncertainty. Given FoP's heterogeneity, investigating FoP profiles and their influencing factors in stroke patients is clinically significant for personalized psychological care and improved patient quality of life. A total of 366 stroke patients were selected as study subjects through convenience sampling, and a cross-sectional survey was conducted. FoP was assessed using the Fear of Progression Questionnaire-Short Form (FoP-Q-SF, 2 dimensions, 12 items). Independent variables included demographic characteristics, clinical indicators, the Recurrence Risk Perception Scale for Stroke patients (RRPSS), and the Medical Coping Modes Questionnaire (MCMQ). LPA was performed on the FoP-Q-SF items to identify subgroups. The R3STEP method was used to analyze influencing factors of subgroup membership, and the BCH method was applied to compare differences in distal outcomes across subgroups. Statistical significance was set at The study sample had a mean age of 63.93 ± 10.58 years, with 70.5% males and 65.0% first-ever stroke patients. Two latent profiles were identified: Low-FoP Adaptive Type (C1, 48.6%) and High-FoP Sustained Type (C2, 51.4%). The R3STEP showed that age 18-59 years (OR = 0.476, 95%CI = 0.245-0.924, This study revealed significant heterogeneity in FoP among stroke patients. Age, hypertension comorbidity, excessive recurrence risk perception, MCMQ-confrontation, and MCMQ-avoidance were associated with high FoP. Healthcare providers should prioritize identifying high-risk individuals and develop tailored interventions to reduce FoP and improve rehabilitation outcomes. Show less
A health-promoting lifestyle involves increasing health awareness and actively adopting healthier habits. For women with osteopenia, becoming more aware of osteoporosis prevention and taking positive Show more
A health-promoting lifestyle involves increasing health awareness and actively adopting healthier habits. For women with osteopenia, becoming more aware of osteoporosis prevention and taking positive preventive actions can effectively improve health outcomes. This study employed latent profile analysis (LPA) to assess the potential categories of healthy lifestyle promotion for women at high risk of primary osteoporosis. It aimed to identify high-risk subgroups, analyze differences and influencing factors among these groups, and offer evidence-based guidance for clinical nursing practice. From December 2024 to July 2025, women were recruited using convenience sampling from endocrine outpatient departments and physical examination centers at two Grade A tertiary hospitals in Guiyang City. Data collection followed the planned time frame, and only eligible samples were included. Latent profile analysis was performed with Mplus 8.3, and univariate and multiple logistic regression analyses were conducted using SPSS 27.0. A total of 340 valid questionnaires were analyzed. Participants were categorized into three latent profiles: the low self-management-ineffective health behaviors group (28.8 %), the moderate self-management-average health behaviors group (45.3 %), and the high self-management-favorable health behaviors group (25.9 %). These findings highlight disparities in the adoption of healthy lifestyles among women at high risk of primary osteoporosis. In clinical practice, nurses help patients with low health management recognize and overcome cognitive biases, use healthcare resources appropriately, and understand the importance of bone health. For patients with moderate health management, the can suggest exercise in addition to calcium supplementation. For those with high self-management, nurses can support their social networks to help maintain healthy behaviors over time. Show less
Conventional nanocarriers are readily cleared by macrophages in the liver, with only a minimal fraction reaching hepatocytes. This limitation has been effectively overcome in clinically approved lipid Show more
Conventional nanocarriers are readily cleared by macrophages in the liver, with only a minimal fraction reaching hepatocytes. This limitation has been effectively overcome in clinically approved lipid nanoparticles (LNPs) through the incorporation of ionizable lipids. Inspired by this property, we explored whether incorporating ionizable lipids into the lipid bilayer membrane of mesoporous silica nanoparticles (silicasomes) could similarly enhance their hepatic cellular uptake. We developed ionizable silicasomes (I-silicasomes) and systematically compared them with ionizable liposomes (I-liposomes), as well as their conventional counterparts (C-silicasomes and C-liposomes). Surprisingly, I-silicasomes did not enhance hepatocyte uptake Show less
Conversion of cholesterol into bile acids is a central pathway for cholesterol disposal, which was mainly controlled by cholesterol 7alpha-hydroxylase (Cyp7a1). In present study, we aimed to investiga Show more
Conversion of cholesterol into bile acids is a central pathway for cholesterol disposal, which was mainly controlled by cholesterol 7alpha-hydroxylase (Cyp7a1). In present study, we aimed to investigate the effect and the potential underlying mechanism of microRNA-96 (miR-96) on atherosclerosis development. The anti-atherosclerosis effects of a miR-96 inhibitor (miR-96i) were evaluated using ApoE KO mice fed a high-fat diet, which was treated with miR-96i for 8 weeks. The regulatory mechanism was revealed and validated by RNA-seq transcriptomics, quantitative PCR and western blotting analyses in hepatic cells. The authors identified that miR-96i significantly decreased serum cholesterol and bile acid levels and attenuated arterial plaque in mice. We further revealed that miR-96 regulated Cyp7a1 via a FOXO1-involved indirect pathway, in which miR-96 directly modulated FOXO1 in a posttranscriptional manner. A coordinated regulatory effect of miR-96 and miR-185 on FOXO1 was also observed. The full spectrum of mechanisms underlying the antiatherosclerotic activity beside miR-96-FOXO1-CYP7A1 axis remains to be elucidated. This study provides convincing evidence for the pivotal role of miR-96 in FOXO1 modulation and CYP7A1-involved cholesterol-bile acid metabolism, suggesting that miR-96 is a novel therapeutic target for the discovery and development of drugs against ACVD. Show less
RNA G-quadruplexes (rG4s), formed through guanine self-recognition into stacked tetrads, serve as critical regulators of gene expression, yet their comprehensive mapping and dynamic regulation in phys Show more
RNA G-quadruplexes (rG4s), formed through guanine self-recognition into stacked tetrads, serve as critical regulators of gene expression, yet their comprehensive mapping and dynamic regulation in physiological contexts remain technically challenging. Here, we develop Ultra-low-input rG4-seq (ULI-rG4-seq), enabling precise rG4 detection enabling precise rG4 detection with ∼140 bp resolution in samples as small as 100 oocytes, and reveal notable enrichment of rG4s near crucial regulatory regions, particularly transcription start sites and end sites. This technological advance, combined with Trim-away or oocyte-specific knockout of DHX36 (also known as G4R1 or RHAU), an rG4-specific helicase, reveals acute and chronic loss of DHX36 leads to opposing effects on rG4 levels. This observation extends beyond the traditional view of helicases as unwinding enzymes and suggests sophisticated cellular mechanisms maintaining RNA structural homeostasis. Through integrated analysis of rG4 landscapes and DHX36-binding profiles, we demonstrate coordination between cytoplasmic rG4 regulation and nuclear gene expression, revealing how RNA structure dynamics orchestrate RNA stability and translation, thereby influencing transcriptional elongation, genome stability, and alternative splicing. Finally, we show that deletion of DHX36 resulted in decreased oocyte quality, premature ovarian failure and complete female infertility due to transcriptional defects and genome instability related to R-loop accumulation. These technological and conceptual advances not only deepen our understanding of RNA-based regulation but also open new therapeutic possibilities for diseases involving RNA structure. Show less
Women show higher levels of Alzheimer's disease (AD) pathology than men, but the implications for cognitive decline remain unclear. Determining the extent to which tau burden differentially accelerate Show more
Women show higher levels of Alzheimer's disease (AD) pathology than men, but the implications for cognitive decline remain unclear. Determining the extent to which tau burden differentially accelerates cognitive decline in men and women will provide critical insights into sex-specific pathways of disease progression. We leveraged tau positron emission tomography (PET), amyloid beta (Aβ) PET, apolipoprotein E (APOE) ε4 genotyping, and longitudinal cognitive data over approximately 8.6 (standard deviation [SD] = 3.8) years from 1007 cognitively unimpaired adults across three cohorts. Cognitive trajectories were modeled with linear mixed-effects regression including sex × tau × time interactions, and results were synthesized using random-effects meta-analysis. Higher tau burden in medial and lateral temporal regions was associated with faster cognitive decline in women than in men. High tau burden carries a disproportionately greater cognitive cost for women, underscoring the need for sex-specific approaches to early detection and therapeutic intervention in AD. A meta-analysis across three independent cohorts shows that female cognitive advantage at low tau shifts to vulnerability at higher tau. Sex differences in tau-related cognitive decline were consistent after accounting for amyloid burden. Sex-specific rates of cognitive decline should be considered in clinical trial design. Show less