Coronary artery disease (CAD) remains a leading cause of mortality worldwide, with substantial unmet therapeutic needs. This study aimed to identify and prioritize genetically supported therapeutic ta Show more
Coronary artery disease (CAD) remains a leading cause of mortality worldwide, with substantial unmet therapeutic needs. This study aimed to identify and prioritize genetically supported therapeutic targets for CAD using Mendelian randomization (MR). We implemented a two-sample MR framework to infer the causal effects of blood druggable cis-expression quantitative trait loci (cis-eQTLs) on CAD. To consolidate MR findings, we applied Steiger filtering, Bayesian colocalization, and multiple sensitivity analyses. Mediation and phenomewide MR analyses were employed to investigate potential mechanisms and on-target effects of prioritized druggable genes. We identified 66 causal druggable genes associated with CAD in European populations (false discovery rate < 0.001). Among these, ERP29 (odds ratio [OR] = 1.311; 95% confidence interval [CI]: 1.176-1.460), MCL1 (OR = 0.877; 95% CI: 0.840-0.915), TNXB (OR = 1.183; 95% CI: 1.102-1.269), DAGLB, FES, and TRPM4 colocalized with CAD (posterior probability for colocalization > 0.8). The associations for ERP29, MCL1, and TNXB were replicated in an East Asian cohort. Protein-protein interaction network analysis highlighted MAPK3 and TNF as prioritized druggable targets at the protein level. Mediation analysis indicated that body mass index, triglycerides, blood pressure, and atrial fibrillation partially mediate the association between MAPK3 and CAD. Phenome-wide MR analysis further suggested additional beneficial effects of targeting MAPK3 and TNF on diabetes mellitus, obesity, hypertension, unstable angina, myocardial infarction, angina pectoris, coronary atherosclerosis, ischemic heart disease, and disorders of lipoid metabolism. This druggable genome-wide MR study not only corroborated the targets of FDA-approved CAD medications (e.g., FGFR1, MAPK3, NEU1) but also uncovered several novel genes, such as ERP29, MCL1, TNXB, DAGLB, FES, and TRPM4, implicating mechanisms related to blood pressure, lipid metabolism, and additional beneficial effects on endocrine/cardiometabolic traits and circulatory system disorders. Further exploration is imperative to explore their feasibility and generalizability. We identified circulating ERP29, MCL1, TNXB, DAGLB, FES, TRPM4, MAPK3, and TNF as promising, genetically supported druggable targets for CAD treatment. Notably, MAPK3 and TNF demonstrated strong protein-level interactions and close associations with cardiometabolic disorders. 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
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a Show more
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were observed in HS tissues, with macrophages in stiff mechanical microenvironments identified as the primary lactate source. Lactate influx through MCT1 upregulated H3K23la, thereby promoting transcriptional activation of profibrotic genes HEY2 and COL11A1. Mechanistically, HEY2 activated YAP1/SMAD2 signaling, while COL11A1 stabilized MCT1 to enhance lactate transport, forming a positive loop that amplified fibrosis. Fibroblast-specific Mct1 deletion or pharmacological inhibition of Mct1 in male mice reduced collagen deposition, accelerated wound healing, and attenuated scar formation. Our findings redefine the macrophage-fibroblast crosstalk in HS and establish the MCT1-H3K23la-HEY2/COL11A1 axis, particularly its self-reinforcing loop, as a novel therapeutic target. 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
Sai Wu, Wanxia Wu, Jun Zhou+8 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The mechanisms underlying individual variability in acupuncture analgesia among patients with chronic pain remain unclear. This randomized controlled trial investigated the core mechanisms of differen Show more
The mechanisms underlying individual variability in acupuncture analgesia among patients with chronic pain remain unclear. This randomized controlled trial investigated the core mechanisms of differential responses to acupuncture from genetic, neuroimaging, and transcriptomic perspectives in patients with chronic pain due to knee osteoarthritis (KOA). A total of 180 KOA chronic knee pain patients were randomly assigned to verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), or waiting list (WL) groups (36 each). Over 2 weeks, VA/SA received 10 sessions, SC/PB oral medication for 14 days, and WL no intervention. Baseline 3.0T MRI 3D-T1 scans and genotyping (GABRB3 rs4906902, OPRM1 rs1799971, COMT rs4680, BDNF rs6265) were performed. Efficacy was assessed via VAS and WOMAC; responders/non-responders were defined by minimally clinically important difference. Chi-square test, logistic regression, voxel-based morphometry (VBM), and Allen Human Brain Atlas-based partial least squares regression were used. No significant difference in primary outcomes was observed between VA and SA, so they were combined as the acupuncture group (AG) to enhance statistical power. Only AG had a significant association between GABRB3 rs4906902 AG/GG genotype and acupuncture response (p < 0.05); other loci showed no correlation. AG/GG carriers in AG had lower gray matter volume in caudate head, putamen, and ventral striatum, with higher GABRB3 expression in these regions. Genetic polymorphisms at GABRB3 rs4906902 could influence the analgesic effect of acupuncture treatment in patients with KOA chronic knee pain, with AG/GG genotype carriers exhibiting superior analgesic effects. This finding may be associated with pain-modulating brain regions' gray matter volume reduction and upregulation of GABRB3 gene expression. Show less
MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs) Show more
MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs). However, its role in myelin damage and cognitive dysfunction during acute cerebral ischemia is not well understood. In this study, we used the MCAO/R rat model to investigate the mechanistic involvement of miR-219. Our results show that miR-219 alleviates cognitive dysfunction induced by MCAO/R. The agonist group showed a reduced time to locate the platform in the water maze, while the antagonist group showed an increased time compared to the solvent control. Additionally, miR-219 reduced myelin damage, as demonstrated by Luxol Fast Blue (LFB) staining, which indicated substantial hippocampal demyelination repair in the agonist group, whereas the antagonist group exhibited aggravated demyelination. Electron microscopy revealed enhanced myelin sheath regeneration and increased thickness in the agonist group, while the antagonist group displayed fewer and thinner myelin sheaths. Furthermore, miR-219 regulated OPC maturation, with more CNPase-positive cells in the agonist group and fewer in the antagonist group than the solvent control. In NG2 staining, the agonist group had fewer positive cells, while the antagonist group had more. miR-219 also decreased Lingo-1 expression, leading to reduced levels of AKT, RhoA, and mTOR in the downstream signaling pathway. These findings suggest that activating the miR-219-Lingo-1 signaling pathway during ischemia-reperfusion could offer a potential therapeutic approach for improving myelin damage and alleviating cognitive dysfunction in cerebral ischemia. Show less
Rodents are widely used in immunology but do not always recapitulate human immune functions. The tree shrew (Tupaia belangeri) is phylogenetically closer to primates than rodents and may help bridge t Show more
Rodents are widely used in immunology but do not always recapitulate human immune functions. The tree shrew (Tupaia belangeri) is phylogenetically closer to primates than rodents and may help bridge this gap, yet its immune system has not been comprehensively characterised at single-cell resolution. Here, we present a single-cell transcriptomic atlas of the tree shrew immune system, profiling 39 cell types across 12 tissues. We uncover human-like tonsillar structures and two transcriptionally distinct splenic macrophage subsets: an NR1H3 Show less
Ferroptosis is an iron-dependent form of necrosis that promotes AS by accelerating endothelial dysfunction in lipid peroxidation. This study aims to investigate the role of deubiquitinase USP7 in ferr Show more
Ferroptosis is an iron-dependent form of necrosis that promotes AS by accelerating endothelial dysfunction in lipid peroxidation. This study aims to investigate the role of deubiquitinase USP7 in ferroptosis of VECs during AS. AS models were established using HFD-fed ApoE USP7, KIAA1429, and NEAT1 were upregulated in mouse AS models and ox-LDL-treated HUVECs. USP7 inhibition attenuated AS pathology and VECs ferroptosis. USP7 deubiquitinated and stabilized KIAA1429, which facilitated YTHDF1-mediated m6A modification to stabilize NEAT1. NEAT1 recruited CTCF to maintain H3K27me3 modification at the SLC7A11 promoter, repressing SLC7A11 transcription and triggering HUVECs ferroptosis. Overexpression of KIAA1429 or NEAT1 reversed protective effects of USP7 inhibition on ferroptosis. USP7 promotes VECs ferroptosis in AS via the KIAA1429/NEAT1/CTCF axis. Show less
Enhancing students' subjective well-being (SWB) is an inevitable requirement for achieving comprehensive human development. This study utilized data from 11,990 students in Beijing, Shanghai, Jiangsu, Show more
Enhancing students' subjective well-being (SWB) is an inevitable requirement for achieving comprehensive human development. This study utilized data from 11,990 students in Beijing, Shanghai, Jiangsu, and Zhejiang from the PISA 2018 survey to identify distinct SWB profiles and examine the mechanisms linking parental emotional support to these profiles. Using latent profile analysis (LPA), we identified three distinct SWB profiles: 'Low Affect-Low Cognition' (30.6 %), 'Moderate Affect-High Cognition' (45.9 %), and 'High Affect-High Cognition' (23.5 %). Path analyses, controlling for gender, age, and socioeconomic status, revealed that: (1) Parental emotional support exerted significant direct effects on membership in all three profiles. (2) Parental support influenced the 'Low Affect-Low Cognition' through the mediating role of psychological resilience alone and the serial mediation of growth mindset and psychological resilience. Parental support influenced the 'Moderate Affect-High Cognition' through the mediating role of growth mindset alone and the serial mediation of growth mindset and psychological resilience. (3) For the 'High Affect-High Cognition' profile, parental support operated through three pathways: the specific indirect effects of growth mindset and psychological resilience independently, plus their serial mediation. The findings suggest that interventions for students with low SWB should prioritize building psychological resilience, while for other groups, fostering both a growth mindset and resilience is beneficial. The research results are primarily applicable to adolescents in China's high-development level regions and caution should be exercised in generalizing them to other contexts. Show less
Parents of children with congenital heart disease (CHD) face chronic stress impairing family functioning and well-being. As a key protective factor, family resilience aids their adaptation. However, e Show more
Parents of children with congenital heart disease (CHD) face chronic stress impairing family functioning and well-being. As a key protective factor, family resilience aids their adaptation. However, existing research predominantly measures general family resilience, neglecting heterogeneous resilience patterns and subgroup profiles. Our study uses person-centered Latent Profile Analysis (LPA) to identify latent family resilience classes in Chinese culture to provide tailored support. This study adopted a cross-sectional survey design. From October 2024 to July 2025, convenience sampling was used to recruit 426 eligible parents of children with CHD from two tertiary hospitals in Yunnan Province, China. Data were collected using the General Information Questionnaire, Family Hardiness Index (FHI), Simplified Coping Style Questionnaire (SCSQ), and Social Support Rating Scale (SSRS). LPA was applied to classify the family resilience levels of these parents. Subsequently, univariate and multivariate ordinal logistic regression analyses were conducted to explore the factors associated with different latent classes of family resilience. A total of 400 valid questionnaires were collected, with an effective response rate of 93.9%. The mean total score for family resilience in parents of children with CHD was 58.13 ± 5.79, suggesting a moderate overall level of family resilience in this group. The family resilience of parents of children with CHD was classified into three latent profiles: “High family resilience responsibility-anchored type” ( Parents of children with CHD demonstrate heterogeneity in family resilience. Healthcare professionals should pay attention to the family resilience differences among parents of children with CHD and implement targeted intervention measures based on the characteristics of different subgroups, thereby enhancing parents’ family resilience and further promoting family well-being. The online version contains supplementary material available at 10.1186/s12889-025-26143-0. Show less
Alzheimer's disease (AD), the most prevalent form of dementia, is characterized as a slowly progressing neurodegenerative disease marked by senile plaques and neurofibrillary tangles due to the buildu Show more
Alzheimer's disease (AD), the most prevalent form of dementia, is characterized as a slowly progressing neurodegenerative disease marked by senile plaques and neurofibrillary tangles due to the buildup of amyloid-beta peptide (Aβ) and phosphorylated tau in the brain. It is reported that arctigenin (ATG) reduces the level of the enzyme 1 that cleaves β-site amyloid precursor protein and increases Aβ clearance by enhancing autophagy. Compound ARC-18 is a derivative of ATG. The main objective of this study is to investigate whether ARC-18 could improve cognitive function and disease progression by promoting autophagy in Alzheimer-like animal models. Three-month-old 5 × FAD mice were orally treated with the drug for three consecutive months. Water maze and novel object recognition were used to assess cognitive abilities of 5 × FAD mice. In the hippocampus of the mice' brain, APP processing-related proteins (sAPP Show less
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431- Show more
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431-fold signal enhancement), and specific lysosome-targeting capability. QV-S allows for not only real-time monitoring of lysosomal viscosity changes in inflammatory and foam cells but also the precise imaging of atherosclerotic plaques in the aortas of ApoE Show less
Yukang Mao, Tingting Wu, Yuer Jiang+3 more · 2026 · Obesity reviews : an official journal of the International Association for the Study of Obesity · Blackwell Publishing · added 2026-04-24
Obesity is a well-documented cardiovascular risk factor. Here, we sought to investigate whether obesity causes subclinical cardiac remodeling and heart failure (HF), and if so, to perform a systematic Show more
Obesity is a well-documented cardiovascular risk factor. Here, we sought to investigate whether obesity causes subclinical cardiac remodeling and heart failure (HF), and if so, to perform a systematic scan of the plasma protein for novel drug targets. We leveraged visceral adipose tissue (VAT), waist circumference (WC), and waist-to-hip ratio (WHR)-all adjusted for body mass index (BMI)-as indicators of obesity. Two-sample Mendelian randomization (MR) analyses were used to estimate the independent, causal effects of obesity on cardiovascular magnetic resonance (CMR)-derived cardiac traits and HF risk. Mediation analyses followed by druggability assessment were conducted to identify promising protein targets for therapeutic translation. Genetically determined VATadjBMI, WCadjBMI, and WHRadjBMI presented broad causal associations with alterations of distinct cardiac phenotypes, most of which remained significant after controlling for obesity-induced cardiometabolic risk factors, including hypertension, type 2 diabetes, and adverse lipid profiles. By contrast, WHRadjBMI is the only independent causal predictor for HF risk. Of 142 proteins with mediating effects, scavenger receptor class A member 5 (SCARA5), membrane cofactor protein (CD46), and alpha-1-antichymotrypsin (SERPINA3) may contribute to the early-stage adverse cardiovascular effect of obesity, whereas apolipoprotein C-III (APOC3), mitochondrial aldehyde dehydrogenase 2 (ALDH2), and chordin-like protein 2 (CHRDL2) may further promote the development of obesity-driven HF. Medications targeted at these candidate proteins are either approved or under evaluation in clinical trials. Our MR findings provided genetic evidence for the direct, causal associations of obesity with cardiac remodeling and HF, while also outlining druggable proteins as promising therapeutic targets. Show less
Spinal cord injury (SCI) represents significant central nervous system trauma and has consistently been a focal point of research in the domain of neural regeneration and repair. Currently, there is n Show more
Spinal cord injury (SCI) represents significant central nervous system trauma and has consistently been a focal point of research in the domain of neural regeneration and repair. Currently, there is no effective treatment available. Various modalities of magnetic stimulation have emerged for recovery from spinal cord injuries; however, the underlying mechanisms remain unclear, significantly hindering the application of magnetic stimulation technologies in treating such injuries. This study aims to elucidate these relevant mechanisms by establishing a simulated closed-loop magnetic stimulation system. In this study, we established a right hemisection model at T8 in mice and administered continuous simulated closed-loop magnetic stimulation targeting the left motor cortex and right L5 nerve root over six weeks. We subsequently utilized a spinal cord dorsal hemisection model to examine regeneration of the corticospinal tract (CST). Motor-evoked potential assessments and calcium imaging techniques were employed to explore neural circuit repair. Additionally, we integrated transcriptomics, proteomics, and metabolomics approaches to investigate related mechanisms. The findings indicate that simulated closed-loop magnetic stimulation effectively restores motor function in the hind limbs, promotes the regeneration of corticospinal tracts in mice with spinal cord injuries, and facilitates the reconstruction of sensorimotor circuits and functions within the spinal cord. Simulated closed-loop magnetic stimulation significantly enhances axonal regeneration of the CST following SCI. This effect may be mediated through the activation of the AMPK-CREB-BDNF signaling pathway, which promotes neurotrophic factor secretion and subsequently induces nerve axon regeneration. This study suggests that simulated closed-loop magnetic stimulation represents a promising therapeutic approach for the treatment for impaired gait following SCI. Show less
Haojie Ni, Yiyi Xiong, Min Liu+14 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid ex Show more
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR. This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway. In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin (α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro. SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression. SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment. Show less
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable s Show more
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable strategies for 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
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. T Show more
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA + EO placebo, EO + sham EA, or EA + EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Three interventions improved the depression severity and QOL (P < 0.05), and no inter-group difference was found in the 6th week (P > 0.05). Anxiety psychic and somatic general symptoms in the EA + EO group were improved significantly than those of the other two groups (P < 0.05). After six-week treatment of EA + EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly ( Show less
This first-in-human Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of KN069, a novel dual Glucagon-like peptide-1 receptor agonist (GLP-1RA)/Glucose- Show more
This first-in-human Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of KN069, a novel dual Glucagon-like peptide-1 receptor agonist (GLP-1RA)/Glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist in Chinese men with overweight/obesity. This randomised, double-blind trial included a single ascending dose (SAD; 12-120 mg, N = 36, 3:1 active-to-placebo) and a multiple ascending dose (MAD; N = 12, dose escalation 15-60 mg) phase. Safety was assessed via adverse events (AEs) and compliance. PK was analysed using a sandwich enzyme-linked immunosorbent assay (ELISA) for Intact and Total KN069. PD included measurements of body weight, waist circumference, body mass index (BMI) and metabolic parameters. Immunogenicity was assessed by detecting anti-drug antibodies (ADA). KN069 was well tolerated, with predominantly mild-to-moderate gastrointestinal adverse events. PK showed dose-proportional exposure (12-90 mg) with a long half-life for Total KN069 (899.74-1099.01 h). In the SAD part, preliminary dose-dependent weight reductions were observed, with maximum early changes at Day 7 (90 mg: -4.71% vs. placebo: -0.41%) and sustained for up to 133 days. In the MAD part, Group B (60 mg) achieved a -2.57% mean weight reduction from baseline at Day 25, alongside a significant decrease in waist circumference (p = 0.0446). Metabolic improvements included lower fasting glucose, triglycerides, uric acid and elevated insulin/C-peptide. KN069 exhibits favourable safety, long-acting PK and preliminary dose-dependent weight reduction alongside expected pharmacologic metabolic effects, supporting further clinical development. gov Identifier: NCT06547775. Show less
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective coho Show more
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective cohort study. Two large multi-center cohorts (UK Biobank [UKB] and Whitehall II [WHII] study) across the UK and an Eastern multi-center cohort ONE-IBD Study from China. UK Biobank discovery cohort (n=10,229) for signature derivation, internal validation cohort (n=91,306), external validation cohort Whitehall-II (n=7,893), and three additional cohorts (two Western and ONE-IBD) for validation of key metabolic drivers. Primary outcomes were UPF-related circulating metabolic signatures and their associations with CD risk; secondary outcomes included evidence supporting causal roles of candidate metabolites and genetic pathways assessed by Mendelian randomization, colocalization, and gene-environment analysis. A UPF metabolic signature of 73 metabolites was constructed and validated across cohorts (Spearman ρ: 0.20-0.25). More pronounced UPF metabolic signature was associated with increased CD risk (HR The adverse effects of UPF on CD risk may be driven by a relative deficiency of protective metabolites such as DHA, apart from additive harm to metabolic depletion. This reframes UPF-related risk and highlighting potential targets for precision nutrition in CD prevention. Show less
Chronic pain, marked by nociceptive sensitization and maladaptive neuroplasticity, affects 30% of the global population with escalating socioeconomic burdens. Epidemiological data show a 2-3-fold incr Show more
Chronic pain, marked by nociceptive sensitization and maladaptive neuroplasticity, affects 30% of the global population with escalating socioeconomic burdens. Epidemiological data show a 2-3-fold increase in neuropsychiatric co-morbidities among individuals with chronic pain, where epigenetic dysregulation serves as a key mechanism linking ongoing pain to emotional disorders. This review systematically explores epigenetic signatures in supraspinal integration hubs, notably the limbic-paralimbic networks and prefrontal regulatory circuits. The identified epigenetic signatures encompass dysregulation of DNA methyltransferases (DNMTs), RNA modifications, histone post-translational modifications and locus-specific alterations, including aberrant methylation at the brain-derived neurotrophic factor (BDNF), opioid μ receptor and transient receptor potential ankyrin 1 (TRPA1) gene loci. Additionally, they involve dysfunction of the glucocorticoid receptor (GR)/corticotropin-releasing factor (CRF) axis via epigenetic modulation. Building on these findings, we evaluate therapeutic strategies addressing epigenetic dysregulation. While preclinical data demonstrate the efficacy of histone deacetylase (HDAC) and DNMT inhibitors, clinical translation faces significant barriers, including limited blood-brain barrier permeability. Notably, our analysis highlights the benefits of combining pharmacological interventions with non-invasive neuromodulation for enhanced co-morbidity management. Looking forward, this review proposes innovative approaches that leverage CRISPR-based chromatin editing platforms, biomimetic nanocarriers for neuron-specific delivery and closed-loop neuromodulation integrating real-time biomarker feedback, collectively establishing a precision medicine framework for pain or neuropsychiatric co-morbidities. Show less
Diabetic foot ulcers (DFU) are a major complication of diabetes, and its pathogenesis remains incompletely elucidated. Converging evidence indicates that oxidative stress and dysregulated mitochondria Show more
Diabetic foot ulcers (DFU) are a major complication of diabetes, and its pathogenesis remains incompletely elucidated. Converging evidence indicates that oxidative stress and dysregulated mitochondrial polarization participate in DFU progression, nominating these processes as therapeutically actionable targets. This study integrates bulk and single-cell transcriptomic data with machine learning to reconstruct cross-scale, cell type-resolved molecular atlases and regulatory networks. Macrophages and fibroblasts emerged as communication hubs, dominating pathway enrichment and ligand-receptor programs such as macrophage migration inhibitory factor signaling pathway (MIF), ANNEXIN signaling pathway, and COMPLEMENT signaling pathway. Peptidylprolyl isomerase F (PPIF), which encodes cyclophilin D (CypD) and apolipoprotein E (APOE) were further prioritized as putative drivers within macrophages and fibroblasts, and a five-gene classifier was derived with robust performance (internal/external AUC = 0.833/0.933). Within DFU lesions, under the control of non-coding RNA circuitry, SOX5 may shape the inflammatory microenvironment, APOE may participate in lipid-metabolic remodeling, and PPIF (CypD) likely links reactive oxygen species (ROS) accumulation to a p53-dependent mitochondrial death pathway (necroptosis/apoptosis). Orthogonal validation showed significantly increased CypD in diabetic foot ulcer skin (DFUS) and diabetic foot ulcer tendon (DFUT) relative to diabetic foot skin (DFS) and DFT (Diabetic foot tendon), with up-regulated p53 and Cytc and down-regulated ApoE in DFUS; in primary foot-skin fibroblasts, a high-glucose plus tert-butyl hydroperoxide (HG+TBHP) model reproduced elevated ROS, loss of mitochondrial Δψm (mitochondrial membrane potential), growth restriction, and apoptosis, supporting a ROS-CypD/mPTP (mitochondrial permeability transition pore)-Δψm depolarization-p53/Cytc apoptosis axis. The delineated PPIF-centered regulatory network includes upstream transcription factors CEBPB/REL/SPI1 and a downstream ceRNA axis comprising miR-128-3p/miR-23a-3p-long non-coding RNA OIP5-AS1. Additionally, the significant role of polarization-specific reprogramming in regulating macrophage function highlights therapeutic strategies focused on metabolic reprogramming and inhibition of the PPIF/mPTP pathway. Collectively, a cell type-resolved molecular map of DFU is provided, healing-relevant cell populations and regulatory circuits are prioritized, and a translational, testable intervention framework is proposed. Show less
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. Show less
Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, Show more
Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, forming foam cells, and driving inflammation. The ubiquitin-proteasome system regulates immune and inflammatory responses in atherosclerosis. This study investigated the protective role of TRIM31 (tripartite motif-containing 31), an E3 ubiquitin ligase, in macrophage lipid metabolism and inflammation through selective regulation of LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). Transcriptomic profiling, macrophage-specific TRIM31 was selectively upregulated in macrophages under oxidized low-density lipoprotein stimulation and in atherosclerosis plaques. Trim31 deficiency exacerbated plaque burden, foam cell formation, and inflammatory signaling (n=8 per group). Single-cell analysis revealed enrichment of lipid transport and inflammatory pathways in Trim31-deficient plaques. LOX-1 was identified as a key TRIM31 substrate. TRIM31 promoted K48-linked ubiquitination of LOX-1 at lysine 12, facilitating its degradation. The atheroprotective effects of Trim31 were abolished in TRIM31, an inducible, macrophage-enriched protective factor in atherosclerosis, restricts foam cell formation and inflammation by targeting LOX-1 for proteasomal degradation. These findings position TRIM31 as a promising therapeutic target for macrophage-driven atherogenesis. Show less
The APOE4 is a well-established and significant genetic risk factor associated with the accumulation of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau) in the pathogenesis of Alzheimer's di Show more
The APOE4 is a well-established and significant genetic risk factor associated with the accumulation of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau) in the pathogenesis of Alzheimer's disease (AD). Our previous research has implicated circular RNA FoxO3 (circ-FoxO3) in the clearance of aggregated proteins in ischemic stroke. However, the role of circ-FoxO3 in the accumulation of abnormal proteins during AD development remains unclear. In this study, we demonstrate that circ-FoxO3 mitigates APOE4-driven neurotoxic protein aggregation by enhancing FoxO3-mediated autophagy. Specifically, transgenic mice expressing human APOE4 exhibited elevated levels of p-tau and Aβ, and these pathological alterations were significantly ameliorated by circ-FoxO3. Mechanistically, we found that circ-FoxO3 upregulates its host gene FoxO3, leading to activation of autophagy and subsequent clearance of neurotoxic protein aggregates. The findings highlight a critical role for circ-FoxO3 in counteracting APOE4-induced brain damage and suggest its potential as a therapeutic target for mitigating APOE4-related neuropathology. Show less