Atherosclerotic plaque instability is a direct cause of cardiovascular and cerebrovascular events. In this study, a mitochondria-targeted liposome (LIP), modified with triphenylphosphonium (TPP) to en Show more
Atherosclerotic plaque instability is a direct cause of cardiovascular and cerebrovascular events. In this study, a mitochondria-targeted liposome (LIP), modified with triphenylphosphonium (TPP) to enable specific mitochondrial delivery, was innovatively constructed to encapsulate a PCSK9 inhibitor (TPP-LIP@PCSK9). The aim was to explore a novel strategy for stabilizing plaques by restoring mitochondrial function in endothelial cells. Characterization results showed that TPP-LIP@PCSK9 possesses favorable nano-characteristics, and its targeting capability was confirmed through mitochondrial co-localization experiments. In an Apoe 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
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
The global obesity epidemic necessitates therapies that enhance energy expenditure. Non-shivering thermogenesis (NST) in brown/beige adipose tissue represents a promising target, with fibroblast growt Show more
The global obesity epidemic necessitates therapies that enhance energy expenditure. Non-shivering thermogenesis (NST) in brown/beige adipose tissue represents a promising target, with fibroblast growth factor 21 (FGF21) emerging as a critical regulator linking environmental stimuli to adipose plasticity and mitochondrial function. However, the precise mechanisms of FGF21 secretion and its specific role in adipose tissue browning and subsequent NST potentiation remain incompletely elucidated. FGF21 regulates NST via distinct spatiotemporal mechanisms. Acute cold exposure triggers hepatic FGF21 secretion through a β FGF21 exhibits dual regulation: hepatic (acute lipid mobilization) and adipose-based (chronic browning); adipose-targeted FGF21 delivery is essential for therapeutic efficacy, and future studies should integrate FGF21 with UCP1-independent pathways (e.g., creatine/succinate cycles) to advance obesity treatment. 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
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-inte Show more
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) as mutually constrained components of daily time use and may inform frailty prevention and management. This scoping review maps evidence on associations between 24HMB and frailty and identifies methodological gaps to inform future research and nursing practice. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and follows Joanna Briggs Institute (JBI) guidance. We searched PubMed, Embase, CINAHL, and Web of Science. We included observational studies of adults aged ≥18 years. Exposures were objectively measured or validated self-reported sleep, SB, LPA, and MVPA, including step counts, breaks in SB, isotemporal substitution models (ISM), and compositional data analysis (CoDA). Outcomes were frailty or prefrailty assessed using validated instruments. Quality was appraised with JBI tools. Thirty-three studies showed good methodological quality. Longer SB, particularly prolonged, uninterrupted bouts, was associated with higher frailty. Greater MVPA was consistently associated with lower frailty. Light-intensity physical activity was generally beneficial but often attenuated when MVPA or total activity volume was modeled. Sleep fragmentation and poor sleep quality were associated with frailty. Isotemporal substitution models and compositional data analysis indicated that reallocating sedentary time to MVPA would yield the largest theoretical benefit, followed by reallocating to LPA. Higher daily step counts and more frequent or higher-intensity breaks in SB were associated with lower frailty. Evidence supports a 24-h integrated movement-behavior approach centered on MVPA, combined with reducing prolonged SB and improving sleep quality, for the prevention and nursing management of frailty. The study design and analytical protocol were prospectively registered on the Open Science Framework (OSF). The unique identifier is S39Y4, and the publicly accessible URL is https://doi.org/10.17605/OSF.IO/S39Y4. Show less
Metabolic reprogramming of Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-has emerged as a constitutive feature of cancer, extending far beyond their canonical roles in protein syn Show more
Metabolic reprogramming of Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-has emerged as a constitutive feature of cancer, extending far beyond their canonical roles in protein synthesis and energy provision. In malignancy, these essential amino acids function as pivotal signaling mediators and epigenetic modulators, thereby propelling tumor progression, facilitating immune evasion, and conferring resistance to therapeutic agents. This review delineates how cancer cells subvert branched-chain amino acid metabolism to fuel anabolic processes, activate oncogenic signaling cascades including mTOR and PI3K/AKT, and remodel the tumor microenvironment. A framework is presented to categorize the differential reliance of various cancers on key catabolic enzymes-BCAT1, BCAT2 and BCKDK-underscoring their therapeutic vulnerability. The paradoxical role of BCAAs in modulating anti-tumor immunity is examined alongside the potential of dietary modulation and the development of pharmacological inhibitors targeting this pathway. Concluding perspectives highlight the trajectory for translating these insights into precision oncology, advocating for biomarker-guided and context-specific therapeutic strategies. 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
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated Show more
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated the association between APOE ε4 and cognition in ICAS. Baseline data from a multicenter cohort were analyzed. Patients with radiologically confirmed ICAS underwent APOE genotyping, plasma biomarker assays, magnetic resonance imaging assessment of cerebral small vessel disease (CSVD) and brain atrophy, and standardized cognitive testing. Among 409 patients (mean age 60 years, 55% male), 16% carried APOE ε4. Carriers showed more frequent cognitive impairment (63% vs 48%), greater stenosis burden, and lower plasma amyloid beta (Aβ)42/40 ratios, whereas other Alzheimer's biomarkers, CSVD burden, and atrophy scores showed no difference. After adjustment, APOE ε4remained associated with cognitive impairment (odds ratio [OR] 1.86). The association was pronounced in women (OR 4.43) but absent in men. APOE ε4 is linked to cognitive impairment in ICAS, particularly in women, through mechanisms beyond Alzheimer's pathology. In patients with ICAS, cognitive impairment was more prevalent in carriers than in non-carriers. Carriers showed greater stenosis burden and lower plasma Aβ42/40 ratios. After full adjustment (stroke, CSVD, and AD biomarkers), APOE ε4 remained associated with cognitive impairment. Female carriers had substantially higher odds of cognitive impairment. Show less
Yu Song, Hang Li · 2026 · Obesity surgery · Springer · added 2026-04-24
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition, closely associated with obesity and type 2 diabetes mellitus. Despite its prevalence, there are no approved pharma Show more
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition, closely associated with obesity and type 2 diabetes mellitus. Despite its prevalence, there are no approved pharmacotherapies, making the search for effective treatments crucial. This study investigates the impact of vertical sleeve gastrectomy (VSG) on NAFLD, focusing on changes in bile acid metabolism as a potential therapeutic mechanism. We employed an ApoE-/- mouse model to simulate human NAFLD conditions. Mice were divided into two groups: one underwent VSG and the other served as a control. We monitored body weight, food intake, liver function, lipid profiles, and histological changes in hepatic tissues. Bile acid profiles were analyzed using Ultra Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (UPLC-MS/MS). Post-VSG, mice exhibited significant weight loss and reduced food intake. Biochemical analyses showed substantial improvements in liver function tests (ALT and AST), lipid profiles (cholesterol and triglycerides), and glucose regulation. Histological examination revealed marked reductions in hepatic steatosis and inflammation. Notably, VSG led to significant alterations in bile acid profiles, particularly increased primary bile acids and decreased secondary bile acids, correlating with improved liver histology and metabolic parameters. Our findings suggest that VSG, beyond its role in weight reduction, significantly improves NAFLD. The surgery alters bile acid metabolism, which may contribute to its therapeutic effects. These results highlight the potential of VSG as a metabolic surgery for NAFLD and open avenues for exploring bile acid-related therapies. Show less
The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing Show more
The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing to its lipid-regulating and anti-inflammatory effects, paeoniflorin (Pae) inhibits VSMC phenotypic transformation, making it a promising candidate for AS treatment. Mouse aortic VSMCs were treated with oxidized low-density lipoprotein (ox-LDL) and Pae, and the effects on cell phenotype were examined. An AS model was established by feeding ApoE Pae reversed weight gain and elevated TG levels in the AS model. Oil Red O staining showed that Pae inhibited VSMC-derived foam cell formation in vitro and reduced aortic sinus plaque area, aortic wall lipid deposition, and hepatic steatosis in the AS model. Immunofluorescence staining of the aortic sinus revealed that Pae mitigated α-SMA overexpression and reversed ATP-binding cassette transporter A1 (ABCA1) downregulation. Western blotting analysis revealed that Pae inhibited ERK1/2 and p65 phosphorylation, curbed MMP2 overexpression, and restored downregulated ABCA1 expression. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, and wound healing assays demonstrated that Pae inhibited ox-LDL-induced VSMC proliferation and migration. Additionally, Pae significantly inhibited the expression of the inflammatory factors IL-6 and MCP-1 both in vivo and in vitro. Pae may treat AS by inhibiting VSMC phenotypic transformation. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease worldwide and is closely associated with obesity, diabetes, and other metabolic disorders. Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease worldwide and is closely associated with obesity, diabetes, and other metabolic disorders. Because MASLD progression poses serious health risks, elucidating the underlying mechanisms is essential to guide early intervention and therapeutic strategies. Proteomic analysis was used to identity high-fat diet (HFD)-induced proteins in mouse liver. Galectin-1 (GAL1) expression was assessed via immunohistochemistry in human liver tissues. Liver-specific GAL1-deficient mice were generated using adeno-associated virus. Mice were fed either a chow diet or an HFD. Functional studies were performed in cell lines using western blotting, RT-qPCR, immunofluorescence, co-immunoprecipitation, mass spectrometry, and molecular docking analysis. GAL1 expression was elevated in liver tissues from patients with MASLD and in mouse models. Liver-specific GAL1 knockdown alleviated hepatic steatosis and enhanced fatty acid oxidation (FAO). Mechanistically, GAL1 competitively bound to the BRCT domain of poly (ADP-ribose) polymerase 1 (PARP1), thereby interfering with its interaction with the WW domain -containing E3 ubiquitin protein ligase 2 (WWP2). Hepatic GAL1 knockdown promoted the PARP1 -WWP2 interaction and subsequently facilitated ubiquitin-dependent degradation of PARP1. This degradation led to increased NAD Hepatic deficiency of GAL1 alleviates hepatic steatosis by enhancing FAO through promotion of ubiquitin-dependent PARP1 degradation, thereby restoring NAD 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
Recently, macrophage senescence has been identified as an important pathological risk factor for atherosclerosis (AS). Oxymatrine (OMT) has demonstrated potential in ameliorating cellular senescence. Show more
Recently, macrophage senescence has been identified as an important pathological risk factor for atherosclerosis (AS). Oxymatrine (OMT) has demonstrated potential in ameliorating cellular senescence. This study aims to investigate the pharmacological properties and underlying mechanisms of OMT in alleviating AS progression. High-fat diet-fed ApoE Show less
Early pregnancy loss (EPL), a spontaneous death of the embryo or foetus occurring within the first trimester, is a major challenge for human reproduction with profound adverse consequences for women's Show more
Early pregnancy loss (EPL), a spontaneous death of the embryo or foetus occurring within the first trimester, is a major challenge for human reproduction with profound adverse consequences for women's health. Currently, reliable blood-based biomarkers for EPL remain limited. Therefore, there is an urgent need to discover novel biomarkers for EPL using a multi-omics-based approach to facilitate early detection and timely management. In the discovery cohort, 40 patients with EPL and 40 healthy pregnancies (HP) at 7-13 weeks of gestation were enrolled. Serum proteins and metabolites were assayed by Olink® technology and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS), respectively. Biomarkers were defined by false discovery rate (FDR) < 0.05 and fold change (FC) > 1.2. Random forest (RF) and logistic regression (LR) models incorporating selected biomarkers were employed to develop diagnostic models for EPL. In the external validation cohort, we prospectively enrolled 142 pregnancies at 7-10 gestational weeks, including 47 subjects who subsequently developed EPL and 95 pregnancies with full-term birth. Serum levels of selected biomarkers were quantified by ELISA. The combined proteomics and metabolomics screening identified 26 proteins and 21 metabolites significantly changed in the EPL group and tightly associated with EPL-related clinical phenotypes, with functional enrichment in immunoregulation and lipid oxidation processes. Moreover, integrating serum levels of angiopoietin-like 4 (ANGPTL4), programmed death-ligand 1 (PD-L1), neutrophil%, and lymphocyte% achieved an AUC of 0.944 (95% CI: 0.835-1.000) in the random forest model and 0.954 (95% CI: 0.875-1.000) in the logistic regression model to discriminate EPL from HP. Importantly, this four-biomarker model achieved an AUC of 0.857 (95% CI: 0.747-0.968) in the random survival forest model and a C-index of 0.804 (95% CI: 0.685-0.973) in the validation cohort for EPL prediction. Our integrative omics study reveals a panel of potential circulating biomarkers for EPL, which further offer mechanistic insights into EPL pathogenesis, including impaired maternal immune tolerance and dysregulated lipid metabolism pathways. Moreover, the newly identified biomarkers exhibit promising diagnostic and predictive performance for EPL, underscoring its clinical translational value for human reproduction and maternal-foetal health. This study was supported by Research Grants Council (RGC) Germany/Hong Kong Joint Research Scheme (G-CUHK415/25), 1+1+1 CUHK-CUHK(SZ)-GDST Joint Collaboration Fund (2025A0505000077), CUHK HOPE BWCH Collaborative Medical Research Fund (CF2025002), Shenzhen Medical Research Fund (C2501040), and Shenzhen Science and Technology Program (RCYX20210609104608036). Show less
Older adults' social participation is associated with frailty, but the transition patterns and their relationship with frailty remain unclear. This longitudinal study aims to explore the latent classe Show more
Older adults' social participation is associated with frailty, but the transition patterns and their relationship with frailty remain unclear. This longitudinal study aims to explore the latent classes and transition patterns of social participation in older adults with chronic non-communicable diseases and to assess their relationship with subsequent frailty. The data set from the China Health and Retirement Longitudinal Study (CHARLS) in 2018 (T1) and 2020 (T2) was analyzed, including 4793 older adults. Latent profile analyses (LPA) and latent transition analyses (LTA) were employed to identify latent classes and the transition probabilities of social participation at T1 and T2. The ANCOVA was employed to examine the frailty index at T2 was compared across transition patterns. The LPA results supported a 4-class model labeled as inactive group, voluntary group, social interaction group, and omni-engaged group. The probability of transition from the other groups to the inactive group was significant (33.3 %, 53.8 %, 54.4 %). Age, residence, marital status, and other demographic characteristics can significantly impact transition patterns. However, after controlling for baseline frailty and other covariates, transition patterns were not significantly associated with T2 frailty levels. The short-term (two-year) effect of qualitative shifts in social participation on frailty may be limited when pre-existing health status is accounted for. Future interventions should prioritize sustained engagement and investigate the longer-term effects of both qualitative and quantitative changes in social participation. 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
After feeding carnivorous mandarin fish ( Compared to the easy-acclimation group (EA), the difficult-acclimation group (DA) exhibited significantly lower body weight and length ( The results of this s Show more
After feeding carnivorous mandarin fish ( Compared to the easy-acclimation group (EA), the difficult-acclimation group (DA) exhibited significantly lower body weight and length ( The results of this study indicate that the observed differences in growth performance post-acclimation are associated with the synergistic regulation of brain gene expression, host metabolites, and intestinal microbiota. These results elucidate key molecular mechanisms in the acclimation process of mandarin fish. The online version contains supplementary material available at 10.1186/s12864-025-12446-4. Show less
Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. Show more
Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. This study investigated whether probucol could alleviate AD-associated bone loss and Aβ42-induced osteoblast dysfunction, and further explored the underlying mechanisms. Female mice were divided into four groups (n = 5 per group): C57BL/6 wild-type (WT), WT treated with probucol (WT + PBC), APP/PS1 transgenic (AD) mice, and AD treated with probucol (AD+PBC). Bone mineral density (BMD) was assessed by micro-CT. Levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) along with bone metabolism markers including fibroblast growth factor 23 (FGF23), sclerostin, and brain-derived neurotrophic factor (BDNF) in bone and brain tissues were measured by ELISA. FOXO3a was knocked down in the bone marrow of APP/PS1 mice via stereotactic injection of lentiviral vectors. Expression of APP and FOXO3a in bone tissue was evaluated using RT-qPCR and Western blotting (WB). Mitochondrial damage in osteoblasts and neuronal cells was assessed by transmission electron microscopy (TEM). In vitro study, osteoblast differentiation and mineralization deficits were evaluated using Alizarin Red staining. WB was used to measure the expression of AKT, FOXO3a, autophagy and apoptosis related proteins. Probucol attenuated bone loss and mitochondrial damage in both APP/PS1 and FOXO3a-knockdown APP/PS1 mice, and improved cognitive impairment and neuronal ultrastructure in APP/PS1 mice. Furthermore, probucol attenuated Aβ42-induced osteoblast differentiation and mineralization via the AKT/FOXO3a signaling pathway in vitro. These findings demonstrate that probucol ameliorates AD-associated bone loss and Aβ42-induced osteoblast impairments by regulating AKT/FOXO3a signaling pathway. Show less
We sought to examine the cross-sectional associations of social support and depressive symptoms with cognitive function in dementia-free rural older adults. This population-based cross-sectional study Show more
We sought to examine the cross-sectional associations of social support and depressive symptoms with cognitive function in dementia-free rural older adults. This population-based cross-sectional study included 4719 participants (age ≥ 60 years) living in rural China. Social support and depressive symptoms were measured using the Social Support Rating Scale and the 15-item Geriatric Depression Scale, respectively. Global cognition, memory, verbal fluency, attention, and executive function were assessed using a neuropsychological test battery. Mild cognitive impairment (MCI) was defined following Petersen's criteria. Data were analyzed using general linear and logistic regression models. Greater social support was associated with lower likelihood of MCI and greater z-scores of global cognition, memory, verbal fluency, and executive function (all P < 0.05). Having depressive symptoms was associated with increased likelihood of MCI and lower z-scores of global cognition, memory, verbal fluency, attention, and executive function (all P < 0.05). Greater social support was associated with higher global cognitive z-score in men, higher memory z-score in APOE ε4 non-carriers, and higher executive function z-score in participants with school education (all P < 0.01). The association of depressive symptoms with lower z-scores of global cognition and attention was stronger among people with formal schooling than those without (P < 0.01). Furthermore, depressive symptoms could significantly mediate 46.97 % of the cross-sectional association between social support and global cognition. Late-life social support and having no depressive symptoms are associated with a reduced likelihood of MCI and better cognitive function in a rural Chinese older population, with the associations varying by sex, education, and APOE genotype. Show less
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularl Show more
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis. EVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis. COPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3' untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo. This study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p-mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD. Show less
Cerebral ischemia/reperfusion injury (CI/RI) is a common complication of cerebrovascular diseases such as stroke, characterized by mitochondrial dysfunction. This study investigates the function of pr Show more
Cerebral ischemia/reperfusion injury (CI/RI) is a common complication of cerebrovascular diseases such as stroke, characterized by mitochondrial dysfunction. This study investigates the function of proliferation-associated protein 2G4 (PA2G4) released by neural stem cells (NSCs)-derived exosomes (NSC-Exo) in treating middle cerebral artery occlusion/reperfusion (MCAO/R) by regulating mitophagy. NSC-Exo were extracted and identified. Treatment of NSC-Exo alleviated neurofunctional impairments in MCAO/R-induced mice, reduced oxidative stress and inflammatory responses in hippocampal tissues, and decreased neuronal apoptosis. We analyzed the alteration of molecular mechanisms under the effect of NSC-Exo treatment using bioinformatics analysis and RNA sequencing. PA2G4 was enriched in NSC-Exo, and the absence of PA2G4 in neurons impaired the mitigating effect of NSC-Exo on hippocampal neuronal injury and inhibited mitophagy. NSC-Exo delivered PA2G4 to recruit WW domain-containing protein 2 (WWP2), thereby mediating ubiquitination and degradation of Annexin A2 (ANXA2), and overexpression of PA2G4 or WWP2 reversed the accentuating effect of ANXA2 overexpression on MCAO injury. These findings indicate that PA2G4 delivered by NSC-Exo recruits WWP2 to mediate ubiquitination of ANXA2, thereby activating mitophagy to alleviate oxidative stress in hippocampal neurons in MCAO/R. This study offers a novel target for the treatment of CI/RI. Show less
In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring The incidence of Our study revealed the heterogeneous outcomes of
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
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine lea Show more
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine learning (ML) algorithms. A total of 1608 AMI patients admitted to the First Hospital of Lanzhou University during 2023 and 2024 were retrospectively enrolled in this study. The 851 patients from 2023 were randomly divided into a training set ( LASSO regression initially identified 13 candidate features, while the random forest (RF) model demonstrated the best predictive performance in the training set. Following Boruta refinement, seven key features were retained, leading to the construction of an updated RF model. This model achieved an AUROC of 0.906, an accuracy of 0.977, a precision of 0.900, a sensitivity of 0.643, a specificity of 0.996, and a F1 score of 0.750 on the internal validation set. Temporal external validation at the same center showed an AUROC of 0.988, an accuracy of 0.967, a precision of 0.701, a sensitivity of 0.904, a specificity of 0.972, and a F1 score of 0.790. Furthermore, the model demonstrated excellent calibration, with a Brier score of 0.023 and 0.027. The SHAP analysis ranked feature importance as Killip class, D-dimer (DD), creatinine (Crea), alanine aminotransferase (ALT), apolipoprotein B/A (APOB/A), diastolic blood pressure (DBP) and lactate (Lac). We developed and validated a RF model based on seven key variables—Killip class, DD, Crea, ALT, APOB/A, DBP and Lac—that serves as a predictive tool for identifying the risk of in-hospital CS in AMI patients post-PCI. Additionally, we created an online prediction application using Streamlit, which facilitates the implementation of this model into clinical practice. 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
Central pathophysiological mechanisms underlying cognitive impairment and mood disorders are complex. Traditional Chinese Medicine (TCM)-derived bioactive compounds have significant research value in Show more
Central pathophysiological mechanisms underlying cognitive impairment and mood disorders are complex. Traditional Chinese Medicine (TCM)-derived bioactive compounds have significant research value in this field. This study aimed to synthesize current preclinical and emerging clinical evidence on the neuroprotective and psychotropic effects of key TCM constituents, with a particular focus on their roles in modulating neuroinflammatory signalling, synaptic plasticity, oxidative balance and stress-related neuroendocrine pathways. A narrative synthesis of experimental and early clinical studies was conducted, emphasizing mechanistic investigations in rodent models and exploratory human trials. Outcomes of interest included inflammatory cytokine expression, inflammasome activation, redox homeostasis, synaptic signalling pathways, neuroendocrine regulation, behavioural performance and translational pharmaceutical considerations. Multiple TCM constituents attenuate microglial activation and inflammasome signalling, suppressing interleukin-1β, interleukin-6 and tumor necrosis factor-alpha through inhibition of nuclear factor κB and NOD-like receptor pyrin domain-containing 3 pathways. These effects restore redox homeostasis, reduce synaptic loss and improve cognitive and behavioural outcomes in animal models. Concurrently, several compounds enhance synaptic resilience by upregulating brain-derived neurotrophic factor and tropomyosin receptor kinase B signalling, activating downstream mechanistic target of rapamycin complex 1 and cyclic adenosine monophosphate response element-binding protein pathways and preserving synaptic proteins. Key agents, including ginsenosides, baicalin and curcumin, have shown translational promise, with small human trials reporting improvements in depressive symptoms, cognitive function and biomarker profiles. Additionally, TCM compounds modulate HPA axis dynamics by attenuating stress-induced corticosterone elevation, restoring glucocorticoid receptor sensitivity and rebalancing monoaminergic and glutamatergic neurotransmission. However, pharmaceutical translation remains limited by challenges related to formulation, dosage standardization and poor oral bioavailability, particularly for flavonoids and saponins. TCM-derived compounds exert multifaceted neuroprotective and psychotropic effects, while successful clinical translation requires strengthened pharmaceutical characterization, standardized dosing strategies and advanced delivery systems such as nanoformulations, phytosomes and standardized granules to enhance bioavailability, reliability and regulatory acceptance. Show less