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
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
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative i Show more
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative importance of endothelial METRNL in atherosclerosis by comparing the effects of whole-body METRNL deficiency to endothelial-specific deficiency, and to show the subcellular distribution of endothelial METRNL and its role in mitochondrial homeostasis against atherosclerosis. Our study demonstrated that a deficiency in either endothelial or global METRNL exacerbated atherosclerosis to a similar degree in both spontaneous (age-related) and high fat diet-induced atherosclerosis, suggesting that endothelial METRNL is pivotal in the progression of atherosclerosis due to METRNL deficiency. Endothelial METRNL was diffusely distributed in the cytoplasm with subcellular localization to mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus (especially enriched in mitochondria and nucleus). In both an in vivo apolipoprotein E-deficient (ApoE 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
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
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
Following spinal cord injury (SCI), neuroinflammation driven by lipid-laden macrophage foam cells is a key pathology, yet how these cells manage their lipid homeostasis is unclear. We delineate a neur Show more
Following spinal cord injury (SCI), neuroinflammation driven by lipid-laden macrophage foam cells is a key pathology, yet how these cells manage their lipid homeostasis is unclear. We delineate a neuroprotective axis in which macrophages deploy apolipoprotein E (APOE) to transfer intracellular lipids to neighboring cells, especially fibroblasts. Genetic ablation of The online version contains supplementary material available at 10.1186/s12974-026-03756-9. Show less
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological Show more
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer. Show less
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN Show more
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN injury. Placental-derived connective tissue matrix (pd-CTM) could fill this need, as it contains a plethora of cytokines with potential UVFP therapeutic benefits. This study aimed to identify and quantify the factors in a commercially available pd-CTM (CTM Flow, CTM Biomedical, Lake Worth, Florida) and to study the effects of pd-CTM on vocal fold microenvironment and glottic function in a mouse model of unilateral RLN injury. Cytokine expression (ng/mL) in pd-CTM was characterized using a cytokine array and ELISA. In a separate experiment, C57/BL6 mice were divided into three groups: uninjured negative controls (n = 12), RLN transection with ipsilateral saline thyroarytenoid (TA) injection (n = 16), and RLN transection with ipsilateral pd-CTM TA injection. Outcomes included laryngeal electromyography (L-EMG) and video laryngoscopy after 7 and 28 days, with larynges then harvested and analyzed via immunohistochemistry (IHC) and qPCR. pd-CTM characterization showed moderate-to-high levels of neurotrophic (BDNF, CNTF, GDNF, NTF-3), angiogenic (Angiogenin, VEGF-D), tissue remodeling (bFGF, IGF-1, HGF, TGF-β3), and anti-inflammatory factors (IL-10, IL-1Rα). L-EMG demonstrated increased mean normalized area under the curve ratio in pd-CTM treated mice compared to saline treated mice at the 28-day time point indicating reinnervation (p < 0.001). IHC detected innervated neuromuscular junctions 28 days after pd-CTM treatment. pd-CTM may be a novel treatment option for patients with UVFP based on the neurotrophic, angiogenic, tissue remodeling, and anti-inflammatory factors present. NA. Show less
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the w Show more
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the whole-exome sequencing data from 280 CHH probands, we identified 15 potential splice-site variants in CHD7, ANOS1 and FGFR1 by using in silico software. The functional consequences of these variants were analyzed by the minigene assay or RT-PCR analyses of RNA taken from the peripheral lymphocytes. Detailed phenotyping was performed in the CHH patients harboring deleterious variants and their available family members. 11 out of 15 potential splice-site variants were demonstrated to cause mis-splicing, resulting in loss of function through deletion, insertion or frameshift of amino acids in the proteins. Most patients with deleterious splice-site variants in CHD7, ANOS1, FGFR1 presented with gene-specific non-reproductive phenotypes, confirming the pathogenic contribution of these variants to CHH. Our study indicated that splice-site variants in CHD7, ANOS1, FGFR1 underlie the genetic basis of ~3.9% of CHH patients, warranting the inclusion of potential splice-site variants for genetic diagnosis and counseling of CHH. Show less
Xinjiang Brown cattle are an important beef breed in Northwest China. Although multigenerational selective breeding has improved their growth performance, the accompanying molecular adaptations and po Show more
Xinjiang Brown cattle are an important beef breed in Northwest China. Although multigenerational selective breeding has improved their growth performance, the accompanying molecular adaptations and potential physiological trade- ofs remain insufficiently elucidated at the systemic level. This study aimed to decipher the dynamic serum proteomic profiles shaped by both ontogeny and generational selection in Xinjiang Brown cattle, and to identify the associated key proteins and pathways. Serum samples from 18 bulls across three genera- tions (A, B, C) at 3 and 9 months of age were analyzed using Tandem Mass Tag (TMT)-based quantitative proteomics. Under stringent quality control (FDR < 1%), 583 high-confidence proteins were identified. Diferentially expressed proteins (DEPs) were screened using thresholds of |fold change| ≥ 1.2 and This study reveals that the breeding strategy for Xinjiang Brown cattle prioritizes shaping a proteomic landscape that promotes growth and metabolism, potentially at the cost of atten- uated immune-vascular reactivity. The identified panel of candidate proteins pro- vides a molecular framework for evaluating breeding outcomes and designing balanced selection strategies. Follow-up research should further investigate the functions of these candidate proteins and validate their predictive value for health and production performance in independent herds. Show less
Scavenger receptor B3/differentiation cluster 36 (SCARB3/CD36) has been established as a fatty acid transporter and genetic deficiency of CD36 in mice models shows decreased uptake of oxidized low-den Show more
Scavenger receptor B3/differentiation cluster 36 (SCARB3/CD36) has been established as a fatty acid transporter and genetic deficiency of CD36 in mice models shows decreased uptake of oxidized low-density lipoprotein (oxLDL) and reduced atherosclerosis. The present study proposes CD36 as a drug target inhibited by leonurine to alleviate inflammation and prohibit unstable atherosclerotic plaques. We showed that the anti-atherosclerotic effects of leonurine were dependent on CD36 in a mice model of arterial atherosclerosis induced by tandem stenosis surgery fed with Western diet (TS + WD) established in both wild type (WT) and Cd36 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
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
Previous studies have reported that IGF-1 single nucleotide polymorphism is associated with milk fat traits, but they are limited to trait association analysis. We previously identified a synonymous m Show more
Previous studies have reported that IGF-1 single nucleotide polymorphism is associated with milk fat traits, but they are limited to trait association analysis. We previously identified a synonymous mutation c.258 A > G (rs322131043) in IGF-1, which influenced IGF-1 expression and caused differences in metabolism. This study aims to reveal a new regulatory function of IGF-1 c.258 A > G on milk fat metabolism. Livers transcriptomics was used to identify differentially expressed genes between wild type mice (WT) and IGF-1 c.258 A > G mice (Homozygous mutation, Ho). Subsequently, lipid phenotyping, followed by metabolomics of mammary glands was conducted to verify transcriptomic findings. Finally, the potential mechanisms underlying IGF-1 c.258 A > G-induced changes in milk fat metabolism were explored though integrated transcriptomics-metabolomics analysis and Western blot validation. IGF-1 c.258 A > G changed the expression of genes related to lipid metabolism in livers of 8-week-old mice, including a 10-fold lipoprotein lipase (LPL) expression (P < 0.01) and 80-90 % downregulation of acyl-CoA thioesterase 3 (Acot3), enoyl-Coenzyme A delta isomerase 3 (Eci3), fatty acid synthase (FASN), and sterol regulatory element binding protein1 (SREBP1) expression (P < 0.01). The milk fat content of Ho dams on the second day of lactation (L2D) was decreased 50 % than that of WT dams (P < 0.05), although there was no significant difference in adipose tissue of 8-week-old WT/Ho mice. The levels of triglycerides, sphingolipids and their related fatty acyl chains (10:0, 26:0, 14:2, 20:4, 11:3, 19:0) in mammary glands of L2D Ho dams were reduced 10-50 % observed by lipid metabolomics. And combined with transcriptomics and Western blot, the data suggested that a 2.5-fold upregulation of LPL expression (P < 0.05) may contribute to the milk fat metabolism changes mediated by the IGF-1 c.258 A > G. This study revealed new function of IGF-1 c.258 A > G on milk fat metabolism, thereby informing the development of targeted genetic breeding on milk fat trait. Show less
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant t Show more
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant tumors. However, its regulatory mechanism and pathobiological roles in EC remain unclear. Rab35 expression in EC was systematically profiled via integrative analysis of clinical endometrial specimens and multi-omics databases (CPTAC and GEO). The association between clinical prognosis and Rab35 expression was examined using Kaplan-Meier analysis. Mechanistic investigations included transwell assays, western blotting, and immunofluorescence in Rab35-overexpressing and CRISPR/Cas9-mediated Rab35-knockout EC cells. A mouse xenograft tumor model was established to confirm the effects of Rab35 in vivo. The Rab35 content increased gradually from normal endometrium to atypical hyperplastic endometrium to EC. Moreover, the findings indicated that elevated Rab35 expression was significantly associated with advanced disease characteristics and poor overall survival in patients with EC. In addition, Rab35 enhanced the migratory and invasive nature of EC cells. The expression of Rab35 was inversely linked to that of the β-catenin destruction complex-related proteins Axin-1 and GSK3β, leading to the increased nuclear translocation of β-catenin in EC cells. Animal experiments further verified that Rab35 augmented EC progression by regulating the nuclear translocation of β-catenin. The study revealed that high expression of Rab35 was strongly correlated with EC progression and a poor clinical outcome. Furthermore, Rab35 promoted EC cell metastasis by accelerating the nuclear translocation of β-catenin. These findings suggest that Rab35 serves as a valuable biomarker and therapeutic target for EC. 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
To investigate the connection betweenischemic stroke (IS) patients' risk of dying after being discharged and their residual cholesterol (RC) levels uponadmission. 2021 IS patients between the ages of Show more
To investigate the connection betweenischemic stroke (IS) patients' risk of dying after being discharged and their residual cholesterol (RC) levels uponadmission. 2021 IS patients between the ages of 35 and 80were chosen as the study's subjects, and data on deathendpoints following discharge were gathered. The doseresponse association between the risk of death and the RCat admission was examined using restricted cubic spline(RCS) regression. The hazard ratio (HR) and 95% CI werecalculated via Cox regression to analyse the associationbetween the RC level at admission and the risk of deathafter discharge in patients with IS. According to the RCS model, RC levels were nonlinearly associated with deaths from IS and other causes(P<0.001). With the median RC level as the cutoff value,the subjects were divided into two groups: a low RC group(RC<0.72 mmol/L) and a high RC group (RC≥0.72mmol/L). Compared with those in the high RC group, theage and male ratio in the low RC group were significantlygreater. The fasting blood glucose (GLU), total cholesterol(TC), triglyceride (TG), low-density lipoprotein cholesterol(LDL-C), non-high-density lipoprotein cholesterol (nonHDL-C), apolipoprotein A-1 (ApoA-1), and apolipoproteinB (ApoB) levels, as well as diabetes rates, were lower (P=0.01). Cox regression analysis revealed that withoutadjusting for covariates, the high-level RC group presenteda lower risk of all-cause death than the low-level RC group(HR=0.765, 95% CI: 0.619~0.946, P=0.013) and alower risk of death from IS (HR = 0.638, 95% CI:0.435~0.936, P=0.022). After adjusting for sex, age,smoking status, drinking status, hypertension status, anddiabetes status, the high-level group still had a lower risk ofall-cause death (HR = 760, 95% CI: 0.614~0.941,P=0.012) and a lower risk of death from IS (HR=0.653,95% CI: 0.444-0.961, P=0.031). Male sex (HR=0.753,95% CI: 0.572~0.990, P=0.042). Age ≥65 years (HR=0.598, 95% CI: 0.391~0.916, P=0.018), nonsmokingstatus (HR=0.628, 95% CI: 0.408~0.967, P=0.035),nonalcoholic status (HR=0.656, 95% CI: 0.439~0.979,P=0.039), not complicated with hypertension (HR=0.321, 95% CI: 0.108~0.957, P=0.041), no diabetesmellitus (HR=0.607, 95% CI: 0.389~0.947, P=0.028).Compared with those in the high RC group, the IS patientsin the low RC group had a lower incidence of all-causedeath, IS death and other causes of death and a higher survival rate. An RC<0.72 mmol/L at admission is associated with an increased risk of all-cause death and longterm IS death after discharge. Show less
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat faci Show more
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms. A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&E staining and serum biochemical markers. QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair. 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
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
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
Hepatocellular carcinoma (HCC) exhibits diverse aetiologies and molecular heterogeneity, with a median 5-year overall survival of <70% due to high recurrence rates following curative-intent surgery. T Show more
Hepatocellular carcinoma (HCC) exhibits diverse aetiologies and molecular heterogeneity, with a median 5-year overall survival of <70% due to high recurrence rates following curative-intent surgery. This study investigated the complex tumour microenvironment (TME) in HCC and explored interactions between various cell types and their roles in disease recurrence. Using a multi-omics approach on multi-region samples of surgically resected HCC from the PLANet 1.0 cohort (NCT03267641), we performed spatial transcriptomics on 17 tissue samples from four patients and bulk RNA sequencing on 329 sectors from 90 patients. Findings were validated using immunofluorescence and multiplex immunohistochemistry. Our analysis revealed extensive intra- and intertumour gene expression heterogeneity and identified a specific subset of endothelial cells (ECs), INTS6 INTS6 The spatial co-localisation of cell types plays a significant role in the recurrence of hepatocellular carcinoma. In this study, we have pinpointed a particular group of endothelial cells, known as INTS6+ endothelial cells, which are spatially colocalised with tumour cells and enriched in microvascular invasion regions in patients experiencing recurrence. These discoveries highlight novel therapeutic targets that focus on endothelial cell interactions within the tumour microenvironment to prevent recurrence and enhance overall patient survival. Show less
This study explores the influence of congruence and incongruence in father-mother co-parenting on adolescent depression, as well as the mediating effect of self-esteem. A total of 1389 adolescents com Show more
This study explores the influence of congruence and incongruence in father-mother co-parenting on adolescent depression, as well as the mediating effect of self-esteem. A total of 1389 adolescents completed questionnaires assessing their levels of depression and self-esteem, while their fathers and mothers correspondingly reported on their own co-parenting behaviors using the Parental Co-parenting Scale in this cross-sectional study. Dates were analyzed using LPA, RSA, and mediation consecutively. The results show that: (1) We identified three distinct co-parenting profiles: positive parental co-parenting, negative parental co-parenting, and mixed parental co-parenting. (2) In cases of congruent parental co-parenting, high positive parental co-parenting was associated with lower adolescent depression, whereas high negative parental co-parenting was linked to higher depression, and the difference manifests in different forms among boys and girls. Girls showed nonlinear changes in depression while boys exhibited linear trends. (3) In cases of incongruence in parental co-parenting, mothers' co-parenting exerted a stronger influence on boys' depression, while girls were not affected by mothers' and fathers' discrepancies. (4) Self-esteem mediated the relationship between parental co-parenting (in)congruence and depression across both genders. This study provides evidence for the mechanism through which parental coparenting influences adolescent depression and offers a basis for future interventions targeting adolescent depression. Show less
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonst Show more
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonstrated that 5'tRF-GlyGCC is overexpressed in BC tissues and negatively associated with patients' survival. Mechanistically, 5'tRF-GlyGCC binds to lactate dehydrogenase A (LDHA), enhancing its enzymatic activity and promoting glycolysis, which drives BC cell malignancy. This binding is mediated by the phosphorylation of LDHA at tyrosine 10, and facilitated by fibroblast growth factor receptor 1 (FGFR1), through the formation of a ternary complex that amplifies oncogenic signaling. Furthermore, 5'tRF-GlyGCC/LDHA axis induces macrophage infiltration and polarization toward an M2 phenotype, mediated by the chemokine CCL7, thereby reshaping the tumor microenvironment. Additionally, it is uncovered that the biogenesis of 5'tRF-GlyGCC is regulated by ALKBH3 and ANG, which also modulate LDHA activity. In vivo, targeting 5'tRF-GlyGCC/LDHA signaling significantly suppresses tumor growth and enhances the efficacy of immunotherapy. Collectively, these findings elucidate the pivotal role of 5'tRF-GlyGCC in BC progression, highlighting its potential as therapeutic target for BC treatment. Show less
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, usi Show more
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated Show less
To explore the association between apolipoprotein E (APOE) gene polymorphisms and the risk of premature (age of onset: men ≤ 55 years old, women ≤ 65 years old) myocardial infarction (PMI). This study Show more
To explore the association between apolipoprotein E (APOE) gene polymorphisms and the risk of premature (age of onset: men ≤ 55 years old, women ≤ 65 years old) myocardial infarction (PMI). This study retrospectively collected the medical records (age, gender, hypertension, diabetes mellitus, smoking, drinking, and serum lipid) of 379 PMI patients and 628 age-matched non-AMI individuals (controls), from December 2018 to March 2024. The relationship between APOE polymorphisms and PMI was analyzed. 15(1.5%) individuals carried ɛ2/ɛ2, 147(14.6%) had ɛ2/ɛ3, 16(1.6%) presented with ɛ2/ɛ4, 670(66.5%) were ɛ3/ɛ3 carriers, 149(14.8%) had ɛ3/ɛ4, and 10 (1.0%) carried ɛ4/ɛ4. The proportion of ɛ2/ɛ3 genotype was significantly lower in the PMI group than in controls (7.7% vs. 18.8%, p < 0.001), whereas the prevalence of ɛ3/ɛ4 genotype was substantially higher in the PMI group (20.6% vs. 11.3%, p < 0.001). Logistic regression analysis identified some associated factors: smoking (odds ratio [OR]: 3.057, 95% confidence interval [CI]: 2.098-4.455, p < 0.001), hypertension (OR: 4.474, 95% CI: 3.273-6.117, p < 0.001), and dyslipidemia (OR: 1.805, 95% CI: 1.333-2.443, p < 0.001). Additionally, genetic factors were associated with PMI: the APOE ɛ3/ɛ4 genotype (vs. ɛ3/ɛ3, OR: 1.548, 95% CI: 1.038-2.309, p = 0.032) and the presence of ɛ4 allele (vs. ɛ3, OR: 1.521, 95% CI: 1.033-2.241, p = 0.034) were confirmed as independent associated factors. APOE ε3/ε4 genotype was significantly associated with PMI, suggesting that this genotype could serve as a potential genetic marker for PMI risk assessment. Show less
Harnessing the simultaneous activation of GLP-1R, GIPR, and GCGR has emerged as a highly promising therapeutic paradigm for obesity and related metabolic diseases, including nonalcoholic steatohepatit Show more
Harnessing the simultaneous activation of GLP-1R, GIPR, and GCGR has emerged as a highly promising therapeutic paradigm for obesity and related metabolic diseases, including nonalcoholic steatohepatitis (NASH). Here, we report the discovery of TPM003, a novel unimolecular GLP-1R/GIPR/GCGR triple agonist engineered by using a long-acting PEG-fatty acid (PEG-FA) stapling technology. TPM003 exhibits balanced triple receptor agonism and demonstrates an extended systemic half-life across multiple species. In obese mice, TPM003 induced robust and durable weight loss, accompanied by broad improvements in metabolic parameters, outperforming current GLP-1RA standards. Importantly, TPM003 also effectively reversed hepatic steatosis and improved markers of liver function in multiple NASH models. Furthermore, TPM003 is compatible with SNAC-based absorption enhancement, enabling oral delivery in a tablet formulation. Collectively, these findings highlight the therapeutic advantages of balanced GLP-1R/GIPR/GCGR agonism for obesity and NASH and support TPM003 as a promising preclinical candidate with translational potential. Show less