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
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
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
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
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
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the Show more
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the associations between PF, RMS, and cognitive function among community-dwelling older adults in China, analyzing interactions with APOE Ɛ4 and the mediating effect of serum total bilirubin. About 1,081 Hubei Memory and Aging Cohort (HMACS) participants underwent PF (PEF, FEV1 and FVC), RMS (MIP and MEP) assessment, cognitive tests, APOE genotyping, and bilirubin measurement. Multivariate logistic regression and general linear regression were used to analyze associations. Among 1,081 participants (mean age 70.52 ± 5.55 years), 26.1% had cognitive impairment. Lower PF and RMS scores were associated with cognitive impairment. Higher comprehensive PF (c-PF) and RMS indices protected against cognitive impairment (eg, c-PF: OR = 0.482-0.609, PF (especially PEF) and RMS (especially MEP) indices are significantly associated with cognitive function and impairment in older adults, independent of APOE Ɛ4 status. These findings provide biomarkers for assessing cognitive health risk and a basis for interventions targeting PF and RMS to preserve cognitive function. Show less
This study examined the associations between 24-hour movement behaviors and health-related fitness in university students, and estimated the substitution effects using a compositional isotemporal subs Show more
This study examined the associations between 24-hour movement behaviors and health-related fitness in university students, and estimated the substitution effects using a compositional isotemporal substitution model. This study was conducted between May and June 2023, using a combination of convenience and random sampling to recruit 325 undergraduate students from Tianjin University of Science & Technology as participants, including 167 males and 158 females. Daily 24-hour activity behaviors were measured using a triaxial accelerometer(ActiGraph GT3X+), including moderate-intensity physical activity(MPA), vigorous-intensity physical activity(VPA), light-intensity physical activity(LPA), sedentary behaviors(SB), and sleep(SLP) duration. Body composition was assessed via body mass index(BMI), waist circumference, and body fat percentage. Muscular strength was measured by handgrip strength, cardiorespiratory fitness was measured by vital capacity and maximum oxygen uptake(VO₍₂ max)), and flexibility was assessed by the sit-and-reach test. Compositional data analysis was used to investigate the associations between activity behaviors and health-related physical fitness. A 15-minute isotemporal substitution model was applied to predict the effects of replacing one activity with another on outcome variables. The mean age of male participants was(19.74±1.16) years, and that of female participants was(19.51±1.29) years. Based on 24-hour compositional activity behavior analysis, college students spent an average of 16.42 minutes(1.14% of the day) in MPA, 26.57 minutes(1.85%) in VPA, 150.92 minutes(10.48%) in LPA, 645.78 minutes(46.05%) in SB, and 561.31 minutes(40.21%) in SLP. After adjusting for covariates including sex and age, isotemporal substitution models revealed that replacing an equivalent amount of sedentary time with MPA was associated with a reduction in BMI by 0.07-0.19 units, body fat percentage by 0.53-0.59 units, waist circumference by 0.16-0.27 cm, an increase in vital capacity by 119.18-152.67 mL, VO₍₂ max) by 1.76-1.88 mL/(kg·min), handgrip strength by 0.86-1.46 kg, and sit-and-reach performance by 0.19-0.38 cm. Similarly, increasing VPA led to decreases in BMI by 0.14-0.16 units, body fat percentage by 0.49-0.54 units, waist circumference by 0.12-0.23 cm, increases in vital capacity by 127.45-160.84 mL, VO₍₂ max) by 1.91-2.03 mL/(kg·min), handgrip strength by 0.98-1.56 kg, and sit-and-reach by 0.14-0.32 cm. Increasing LPA result ed in BMI increases of 0.11-0.12 units, handgrip strength increases of 0.65 kg, and sit-and-reach increases of 0.21 cm. Increasing SLP was associated with BMI reduction of 0.04 units and waist circumference reduction of 0.09 cm. MPA had the most significant effect on improving BMI, body fat percentage, and waist circumference, while VPA was more effective in enhancing cardiorespiratory fitness, muscular strength, and flexibility. SLP had a modest positive effect on BMI and waist circumference but was less impactful than MPA and VPA. SB and LPA were generally unfavorable for health-related physical fitness. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2026.01.011
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
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
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
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths Show more
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only Show less
To evaluate the apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio as a biomarker for coronary heart disease (CHD) and its clinical phenotypes, beyond traditional lipid parameters. This sing Show more
To evaluate the apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio as a biomarker for coronary heart disease (CHD) and its clinical phenotypes, beyond traditional lipid parameters. This single-center, case-control study analyzed 7,277 patients undergoing coronary angiography. Multivariable logistic regression assessed the independent association of the ApoB/ApoA-I ratio with CHD, acute myocardial infarction (AMI), multivessel disease (MVD), and percutaneous coronary intervention (PCI). Predictive performance was evaluated via ROC curve analysis, with prespecified subgroup analyses. The ApoB/ApoA-I ratio was the strongest independent lipid predictor of CHD (adjusted OR 4.49, 95% CI 1.98-10.19). It significantly predicted severe clinical phenotypes: AMI (OR 1.94, 95% CI 1.44-2.62), MVD (OR 1.67, 95% CI 1.24-2.26), and PCI requirement (OR 1.95, 95% CI 1.43-2.66). The ratio showed significant discriminatory power for all endpoints (AUCs 0.569-0.608). Subgroup analyses revealed markedly stronger associations in males, older adults (≥60 years), and hypertensive patients, but substantially attenuated predictive value in diabetic patients. The ApoB/ApoA-I ratio is a superior biomarker for CHD risk stratification, particularly for identifying severe disease manifestations and guiding revascularization decisions in specific patient subgroups. Its integration into clinical practice could enable more precise cardiovascular risk management. Show less
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have recently emerged as critical mediators in Show more
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have recently emerged as critical mediators in cardiovascular pathophysiology; however, their specific contributions to CHD pathogenesis remain largely unexplored. This study aimed to identify and validate MAM-related biomarkers in CHD through integrated analysis of transcriptomic sequencing data and Mendelian randomization, and to elucidate their underlying mechanisms. We analyzed two gene expression microarray datasets (GSE113079 and GSE42148) and one genome-wide association study (GWAS) dataset (ukb-d-I9_CHD) to identify differentially expressed genes (DEGs) associated with CHD. MAM-related DEGs were filtered using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis, Mendelian randomization, and machine learning algorithms were employed to identify biomarkers with direct causal relationships to CHD. A diagnostic model was constructed to evaluate the clinical utility of the identified biomarkers. Additionally, we validated the two hub genes in peripheral blood samples from CHD patients and normal controls, as well as in aortic tissue samples from a low-density lipoprotein receptor-deficient (LDLR-/-) atherosclerosis mouse model. We identified 4174 DEGs, from which 3326 MAM-related DEGs (DE-MRGs) were further filtered. Mendelian randomization analysis coupled with machine learning identified two biomarkers, DHX36 and GPR68, demonstrating direct causal relationships with CHD. These biomarkers exhibited excellent diagnostic performance with areas under the receiver operating characteristic (ROC) curve exceeding 0.9. A molecular interaction network was constructed to reveal the biological pathways and molecular mechanisms involving these biomarkers. Furthermore, validation using peripheral blood from CHD patients and aortic tissues from the Ldlr-/- atherosclerosis mouse model corroborated these findings. This study provides evidence supporting a mechanistic link between MAM dysfunction and CHD pathogenesis, identifying candidate biomarkers that have the potential to serve as diagnostic tools and therapeutic targets for CHD. While the validated biomarkers offer valuable insights into the molecular pathways underlying disease development, additional studies are needed to confirm their clinical relevance and therapeutic potential in larger, independent cohorts. 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
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
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
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
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
Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF Show more
Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF patients. However, its precise mechanism in treating post-CHF cognitive dysfunction remains unclear. This study systematically investigates XJQ's effects on post-CHF cognitive dysfunction and the underlying mechanisms. The components of XJQ were identified through liquid chromatography-mass spectrometry. CHF was induced in rats via ligation of the left anterior descending coronary artery, followed by six weeks of XJQ treatment. Cardiac function was evaluated through echocardiography and hemodynamic parameters, while cognitive function was assessed using Morris water maze (MWM) and open field tests (OFT). XJQ treatment enhanced both cardiac and cognitive functions in CHF rats. Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses, inflammation, and phosphodiesterase 4 (PDE4)-dependent cyclic adenosine monophosphate (cAMP) signaling. XJQ inhibited microglial and astrocyte activation, decreased proinflammatory cytokines, and mitigated neuronal damage. Notably, XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP, protein kinase A (PKA), cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), PSD95, and synapsin I levels. Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin, kaempferol, isorhamnetin, and darutoside to PDE4. In conclusion, XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway. These findings provide valuable insight into the heart-brain axis. 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
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
Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein (ANGPTL) family, is a physiological inhibitor of lipoprotein lipase (LPL), and plays a critical role in lipoprotein and Show more
Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein (ANGPTL) family, is a physiological inhibitor of lipoprotein lipase (LPL), and plays a critical role in lipoprotein and triglyceride metabolism in response to nutritional cues. ANGPTL8 is implicated in a wide range of systemic and cellular processes and is closely associated with metabolic and cardiovascular diseases (CVD). Circulating ANGPTL8 is primarily secreted by the liver, with adipose tissue as a secondary source. Its expression is regulated by multiple transcription factors and microRNAs, and is responsive to fasting/refeeding states, hormonal signals, and stress conditions. In lipid metabolism, ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4 to modulate LPL activity under fasting and feeding conditions. In glucose metabolism, ANGPTL8 plays a complex role. While some studies suggest it may improve glucose tolerance and insulin resistance, others indicate it could exacerbate glucose metabolism disorders and diabetes, or have no effect. Cardiovascular diseases are intricately linked to metabolic disorders and diseases. Increasing evidence also links ANGPTL8 to various cardiovascular pathologies, including atherosclerosis, hypertension, cardiomyopathy, cardiac hypertrophy, aortic aneurysm, and dissection. Given the strong interplay between metabolic dysregulation and CVDs, elucidating the role of ANGPTL8 in these processes is of significant interest. This review provides a balanced assessment of ANGPTL8's roles in key pathophysiological processes, highlighting its established functions in metabolism alongside its emerging involvement in CVDs. Understanding the diverse functions of ANGPTL8 in various tissues and metabolic states will lead to new opportunities for therapeutic intervention in cardiometabolic disorders. Show less
The Climate Change Anxiety Scale (CCAS) is an emerging psychometric instrument designed to assess climate change anxiety (CCA). This study aimed to preliminarily identify reference cutoff scores and c Show more
The Climate Change Anxiety Scale (CCAS) is an emerging psychometric instrument designed to assess climate change anxiety (CCA). This study aimed to preliminarily identify reference cutoff scores and core items of the CCAS in a Chinese adult population. We conducted an online cross-sectional survey in China between May and June 2024, recruiting 653 Chinese adults (mean age = 32.62 ± 7.40 years; 53.8% female) via Wenjuanxing. CCA was assessed using the CCAS. External variables included generalized anxiety (Chinese GAD-7), self-rated sleep quality (single-item, past week), and self-reported experience of meteorological disasters (yes/no). Latent profile analysis (LPA) and receiver operating characteristic (ROC) analyses were used to derive reference cutoff scores, and network analysis was applied to identify core items. LPA supported a two-profile solution and yielded an overall reference cutoff score of 27.5, above which participants were categorized as having elevated CCA risk. Participants classified as high risk reported higher generalized anxiety, poorer sleep quality, and a higher likelihood of meteorological disaster experience. Sex-stratified analyses indicated different optimal cutoffs: 28.5 for males (sensitivity = 1.000; specificity = 0.982) and 26.5 for females (sensitivity = 0.986; specificity = 0.986). Network analysis further suggested that the item Show less
To elucidate the molecular basis of intramuscular fat (IMF) variation in yellow-feathered broilers, we selected 10 high-IMF (HF) and 10 low-IMF (LF) breast muscle samples from a total of 214 samples, Show more
To elucidate the molecular basis of intramuscular fat (IMF) variation in yellow-feathered broilers, we selected 10 high-IMF (HF) and 10 low-IMF (LF) breast muscle samples from a total of 214 samples, after z-score filtering for LC-MS lipidomics and RNA-seq analyses. Lipidomics identified 94 differentially expressed lipids (DELs; 83 upregulated, 11 downregulated in HF), predominantly triglycerides (TGs, 20.2%), phosphatidylethanolamines (PEs, 15.3%), phosphatidylcholines (PCs, 12.1%), and sphingomyelins (SMs, 8.4%). LION/web enrichment indicated an unsaturated lipid-rich phenotype, characterized by fatty acids containing ≥ 2 double bonds and membrane structural components. RNA-seq revealed 423 differentially expressed genes (DEGs; 312 upregulated, 111 downregulated in HF), enriched in plasma membrane, cell periphery, retinol metabolism, and steroid hormone biosynthesis pathways. RT-qPCR validation of nine lipid metabolism-related DEGs confirmed the RNA-seq trends. Cross-omics Pearson correlation between these DEGs and the top 20 DELs identified PLIN1, SCD, and APOB as central regulatory hubs strongly associated with multiple polyunsaturated TGs and PCs. Functional overlap across omics layers suggests coordinated membrane remodeling and unsaturated lipid deposition in HF breast muscle, providing a data-driven framework for future mechanistic validation and breeding strategies. Show less
Type 2 diabetes mellitus (T2DM) requires multi-target therapeutic approaches addressing both insulin resistance and insulin secretion deficits. Although natural compounds are promising multi-target ca Show more
Type 2 diabetes mellitus (T2DM) requires multi-target therapeutic approaches addressing both insulin resistance and insulin secretion deficits. Although natural compounds are promising multi-target candidates, systematic identification of their polypharmacological profiles remains challenging. The objective of this study was to establish a computational framework for identifying natural compounds with multi-target therapeutic potential against T2DM through integrated structure-activity analysis and experimental validation. We developed an SELFormer deep learning model to predict natural compound activities against six T2DM-related proteins including glucagon-like peptide-1 receptor (GLP1R), kinesin family member-11 (KIF11) for insulin secretion and insulin receptor (INSR), peroxisome proliferator-activated receptor-gamma (PPARG), fibroblast growth factor receptor-1 (FGFR1) and insulin-like growth factor-1 receptor (IGF1R) for insulin resistance. Uniform Manifold Approximation and Projection (UMAP) for dimension reduction clustering characterized chemical space distributions and molecular docking validated multi-target binding. Selected compounds were experimentally validated using 3T3-L1 adipocytes and mouse insulinoma (MIN6) pancreatic β-cells. The SELFormer model achieved 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
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