Yukang Mao, Tingting Wu, Yuer Jiang+3 more · 2026 · Obesity reviews : an official journal of the International Association for the Study of Obesity · Blackwell Publishing · added 2026-04-24
Obesity is a well-documented cardiovascular risk factor. Here, we sought to investigate whether obesity causes subclinical cardiac remodeling and heart failure (HF), and if so, to perform a systematic Show more
Obesity is a well-documented cardiovascular risk factor. Here, we sought to investigate whether obesity causes subclinical cardiac remodeling and heart failure (HF), and if so, to perform a systematic scan of the plasma protein for novel drug targets. We leveraged visceral adipose tissue (VAT), waist circumference (WC), and waist-to-hip ratio (WHR)-all adjusted for body mass index (BMI)-as indicators of obesity. Two-sample Mendelian randomization (MR) analyses were used to estimate the independent, causal effects of obesity on cardiovascular magnetic resonance (CMR)-derived cardiac traits and HF risk. Mediation analyses followed by druggability assessment were conducted to identify promising protein targets for therapeutic translation. Genetically determined VATadjBMI, WCadjBMI, and WHRadjBMI presented broad causal associations with alterations of distinct cardiac phenotypes, most of which remained significant after controlling for obesity-induced cardiometabolic risk factors, including hypertension, type 2 diabetes, and adverse lipid profiles. By contrast, WHRadjBMI is the only independent causal predictor for HF risk. Of 142 proteins with mediating effects, scavenger receptor class A member 5 (SCARA5), membrane cofactor protein (CD46), and alpha-1-antichymotrypsin (SERPINA3) may contribute to the early-stage adverse cardiovascular effect of obesity, whereas apolipoprotein C-III (APOC3), mitochondrial aldehyde dehydrogenase 2 (ALDH2), and chordin-like protein 2 (CHRDL2) may further promote the development of obesity-driven HF. Medications targeted at these candidate proteins are either approved or under evaluation in clinical trials. Our MR findings provided genetic evidence for the direct, causal associations of obesity with cardiac remodeling and HF, while also outlining druggable proteins as promising therapeutic targets. Show less
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
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variant Show more
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variants have been implicated, the cumulative impact of genetic variation within relevant biological pathways remains unexplored. We evaluated single nucleotide polymorphisms across 18 pathways previously identified as relevant to mucositis in 278 pediatric patients with acute lymphoblastic leukemia from six academic health centers across Canada. Pathway enrichment was assessed using the Joint Association of Genetic variants tool, and a predictive model was developed using XGBoost, a supervised machine learning algorithm based on gradient-boosted decision trees. Pathway enrichment identified significant associations in IL6 (P = 0.04) and WNT/β-catenin (P = 0.048) signaling pathways. The predictive model (area under the curve [AUC] = 0.76) highlighted single nucleotide polymorphisms associated with inflammation- and mucosa-related genes, including PRKCD, IL17B, MAST3, and CAPN9, with both risk and protective effects. Model performance dropped by 0.15 in AUC (from 0.76 to 0.61) after removing single nucleotide polymorphism features, underscoring their predictive value. This pathway-informed approach identifies genetic contributors to methotrexate-induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment-limiting mucositis in pediatric oncology. 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
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morronisid Show more
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morroniside (Mor), an iridoid glycoside compound in Cornus officinalis, is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used ApoE4 transgenic mice and ApoE4-transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10-month-old mice were randomly divided into the ApoE3 control group (ApoE3 + Veh), the ApoE4 model group (ApoE4 + Veh), and the ApoE4 + Mor 10, 20, and 40 mg/kg groups as in vivo models. The in vitro BV2-ApoE model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of ApoE4 transgenic mice by reducing Aβ plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1/PU.1 signaling axis, and alleviated the dysfunction of microglia both in vitro and in vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce Aβ accumulation, and improve synaptic damage in ApoE4 mice via the CX3CL1/CX3CR1/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD. Show less
Current infant formulas lack the native multilayer structure of breast milk fat globule membrane (MFGM), impacting lipid digestion. In this study, the inner layer material and concentration of the bio Show more
Current infant formulas lack the native multilayer structure of breast milk fat globule membrane (MFGM), impacting lipid digestion. In this study, the inner layer material and concentration of the biomimetic fat globule membrane were optimized by comparing particle size, Zeta-potential and interface protein load. It was found that compared with sodium caseinate (CN) and whey protein (WP), when the lactoferrin (LF) concentration was 2 %, the particle size was lower (277.85 ± 6.15 nm) and Zeta-potential value was higher (19.67 ± 1.27 mv). Using milk phospholipid (MPL) as the outer layer material, when the MPL concentration was 2 %, the emulsion had a smaller particle size (291.33 ± 1.15 nm) and a better stability (10.22 ± 0.62 %). Therefore, the biomimetic multilayer membrane was constructed by electrostatic layer-by-layer deposition of 2 % LF and 2 % MPL. Combining Fluorescence and Fourier transform infrared spectroscopy (FTIR), the interaction between LF and MPL molecules in the LF-MPL multilayer structure is primarily a spontaneous, endothermic process driven by hydrophobic forces, exhibited superior stability (except thermal stability) than LF monolayer membrane. The results of in vitro digestion showed that compared with LF, WP and WP-MPL emulsions, LF-MPL emulsions had the highest free fatty acid (FFA) release rate of 69.97 %. LF-MPL enhanced gastric stability and promoted intestinal lipolysis and improved the degree of lipid digestion. In addition, LF-MPL promoted the absorption and utilization of triglyceride (TAG) in cells and animals, and secretion and upregulated lipid absorption genes (FATP4, DGAT1, APOB, APOA4, MTTP). These findings demonstrate that biomimetic LF-MPL multilayers improve lipid digestion, absorption, and bioavailability, providing a theoretical basis for designing more breast milk-like infant formulas. Show less
Critical limb ischemia (CLI) represents a severe vascular complication of type 2 diabetes, primarily driven by impaired angiogenic capacity, and frequently results in limb amputation or mortality. Her Show more
Critical limb ischemia (CLI) represents a severe vascular complication of type 2 diabetes, primarily driven by impaired angiogenic capacity, and frequently results in limb amputation or mortality. Here, we investigated the therapeutic potential of tirzepatide in promoting perfusion recovery in diabetic hindlimb ischemia and delineated the underlying molecular mechanisms. Human umbilical vein endothelial cells (HUVECs) exposed to high glucose were employed to evaluate tirzepatide's effects on endothelial proliferation, migration, and tube formation, alongside the activation of Akt, endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, assessed by western blotting. Knockdown of GLP-1R or GIPR abrogated the pro-angiogenic effects of tirzepatide, while pharmacological inhibition of the Akt/eNOS or ERK1/2 pathways attenuated endothelial responses. In vivo, tirzepatide treatment significantly enhanced perfusion recovery and increased capillary density in the ischemic limbs of diabetic mice, corroborating its angiogenic effects. Collectively, these findings demonstrate that tirzepatide facilitates angiogenesis and accelerates ischemic limb revascularization through dual GLP-1R/GIPR activation and subsequent engagement of Akt/eNOS and ERK1/2 signaling pathways, highlighting its potential as a therapeutic strategy for diabetic CLI. 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
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
Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth fact Show more
Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth factor 21 (FGF21) in the development and progression of chronic hepatitis B (CHB). A total of 336 participants were recruited, including 320 CHB patients and 16 healthy controls. The expression of FGF21, immune cytokines, and OS-related molecules in peripheral blood mononuclear cells (PBMCs) was detected using real-time quantitative polymerase chain reaction. The methylation level of the FGF21 gene promoter in PBMCs was detected using TaqMan probe-based quantitative methylation-specific PCR. The expression level of FGF21 in the peripheral blood of CHB patients was higher than that of HC, but the methylation level of the FGF21 promoter was lower than that of HC, especially in patients during the immune activation phase. The mRNA expression levels of CXCR3 and CCL5 in PBMCs of CHB patients during the immune activation and reactivation phases were higher than those in other clinical stages. Single-cell analysis revealed that CXCR3 and CCL5 expression in the immune tolerance and immune activation phases with high HBsAg expression was closely related to T lymphocytes (T cells) and natural killer cells (NK cells) and was highly expressed in CD4 and CD8 T cells and NK cells. In addition, the mRNA expression levels of Nrf2 and GPX4 in the reactivation phase were higher than those in other clinical stages. The mRNA expression level and methylation level of FGF21 in PBMCs of CHB patients were correlated with the viral load, immune inflammation, and OS levels during the antiviral treatment course of CHB. The methylation level of the FGF21 promoter has the potential to become a non-invasive biomarker for monitoring the progress of antiviral treatment in CHB.IMPORTANCEThis study conducted an in-depth exploration of the application of methylation detection technology, analyzing its value and driving mechanism in the oxidative stress and immune-inflammatory balance during the course of chronic hepatitis B. The study analyzed the methylation patterns of the FGF21 promoter and the expression levels of its receptor FGFR1, as well as the expression levels of chemokines CXCR3, CCL5, and oxidative stress factors GPX4 and Nrf2 in the immune tolerance period, immune clearance period, immune control period, and reactivation period of chronic hepatitis B. It clarified the association between these molecules and the FGF21/FGFR1 axis and revealed the synergistic or antagonistic mechanisms of these molecules in the oxidative stress and inflammatory vicious cycle. At the same time, this study also explored the value of FGF21 promoter methylation in disease diagnosis and prognosis, providing a theoretical basis for evaluating the antiviral treatment effect and disease progression of chronic hepatitis B. Show less
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial Show more
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial was conducted to investigate the acute effects of a single episode of alcohol ingestion on various biomarkers in healthy individuals. A total of 45 male participants were recruited and randomized into an alcohol group (n = 40) and a control group (n = 5) at an 8:1 ratio. Volunteers in the alcohol group ingested 40% Absolut vodka within 15 min. Blood pressure, heart rate, and blood oxygen saturation were measured at 0 h, 1 h, 3 h, 5 h, 12 h, and 24 h. Venous blood samples were drawn at 0 h, 1 h, 5 h, 12 h, and 24 h after alcohol intake. Our results showed that levels of liver function markers, including α-fucosidase (AFU), albumin (ALB), and alkaline phosphatase (ALP), were significantly increased in the alcohol group compared to the control group. The 24-h area under curve (AUC) of AFU, ALB, and ALP were significantly higher in the alcohol group. The liver fibrosis maker collagen type Ⅳ (Ⅳ-C) tended to be higher at 1 h and 12 h in the alcohol group compared to the control group. Lipid levels, including triglycerides (TG), apolipoprotein A1 (APOA1), and the APOA1/APOB, were significantly elevated after alcohol ingestion, particularly at 5 h and 12 h. The 24 h-AUC of TG, APOA1, and APOA1/APOB were higher in the alcohol group than in the control group. Additionally, cardiac function indicators, including heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were significantly elevated in the alcohol group. SBP and DBP remained higher 24 h after alcohol ingestion compared to the control group. This study demonstrated that even a single episode of binge drinking could induce significant alterations of biomarkers related to liver function, cardiac function, and lipid profiles. These findings provided valuable insights into the short-term impact of alcohol on health and highlighted the importance of further research to explore the long-term implications of repeated acute alcohol exposure. Given the very small control group, these results should be interpreted as preliminary and confirmed in larger, more balanced randomized trials. The online version contains supplementary material available at 10.1038/s41598-026-40028-1. Show less
Kaempferol, a natural dietary flavonoid, has shown neuroprotective potential. However, its mechanisms of protection against age-related cognitive decline, especially those mediated
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective coho Show more
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective cohort study. Two large multi-center cohorts (UK Biobank [UKB] and Whitehall II [WHII] study) across the UK and an Eastern multi-center cohort ONE-IBD Study from China. UK Biobank discovery cohort (n=10,229) for signature derivation, internal validation cohort (n=91,306), external validation cohort Whitehall-II (n=7,893), and three additional cohorts (two Western and ONE-IBD) for validation of key metabolic drivers. Primary outcomes were UPF-related circulating metabolic signatures and their associations with CD risk; secondary outcomes included evidence supporting causal roles of candidate metabolites and genetic pathways assessed by Mendelian randomization, colocalization, and gene-environment analysis. A UPF metabolic signature of 73 metabolites was constructed and validated across cohorts (Spearman ρ: 0.20-0.25). More pronounced UPF metabolic signature was associated with increased CD risk (HR The adverse effects of UPF on CD risk may be driven by a relative deficiency of protective metabolites such as DHA, apart from additive harm to metabolic depletion. This reframes UPF-related risk and highlighting potential targets for precision nutrition in CD prevention. Show less
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
The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of Show more
The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC. BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32 We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis. These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis. Show less
Substance use disorder is characterized by compulsive seeking behavior that is associated with aberrant synaptic plasticity in mature neurons. Environmental enrichment (EE) has been shown to increase Show more
Substance use disorder is characterized by compulsive seeking behavior that is associated with aberrant synaptic plasticity in mature neurons. Environmental enrichment (EE) has been shown to increase adult hippocampal neurogenesis and exert beneficial effects on addictive behaviors. However, the mechanisms of EE's effects on methamphetamine (METH)-induced synaptic plasticity in mature and newborn neurons remain unclear. We reported that EE decreased METH-induced seeking behavior with a decrease in the activity of mature granule cells and an increase in the number of newborn granule cells. Furthermore, the aberrant glutamatergic transmission in hippocampal mature and newborn granule cells was differentially regulated by EE. Moreover, EE restored the normal synaptic plasticity, accompanied by enhancement of brain derived neurotrophic factor (BDNF) expression. Importantly, the intervention of BDNF reversed the effects of EE on METH-induced reinstatement behavior and glutamatergic transmission in both mature and newborn cells. Finally, specifically knocking out the newborn neurons reversed the changes of EE in abnormal plasticity of mature neurons, as well as in seeking and cognitive behaviors. Taken together, regulating synaptic plasticity of mature and newborn neurons is involved in METH-induced seeking behavior and cognitive impairments, which highlights a critical role of adult neurogenesis in the treatment of METH addiction. 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
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
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
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
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
Although glass-based long-persistent luminescence (LPL) materials offer superior transparency and integration capability compared with conventional phosphors, their emission has been predominantly res Show more
Although glass-based long-persistent luminescence (LPL) materials offer superior transparency and integration capability compared with conventional phosphors, their emission has been predominantly restricted to the blue-green region, leaving warm-color LPL largely unexplored. In this work, Mn Show less
Controversies exist regarding the effects of calcium supplementation on lipid metabolism, and the time-specific effects and underlying mechanisms remain unclear. This study aims to elucidate the diffe Show more
Controversies exist regarding the effects of calcium supplementation on lipid metabolism, and the time-specific effects and underlying mechanisms remain unclear. This study aims to elucidate the differential impacts of calcium intervention at different times (morning/evening) on hepatic lipid metabolism and the molecular mechanisms involved. Forty female CD-1 (ICR) mice were randomly divided into four groups: Morning Control Group (MCN), Morning Calcium Intervention Group (MCI, intragastric administration of calcium carbonate at 08:00), Evening Control Group (ECN), and Evening Calcium Intervention Group (ECI, intragastric administration of calcium carbonate at 20:00). Mice were fed a normal calcium or low-calcium diet for 10 wk. Morning calcium intervention (MCI) in mice significantly increased serum and hepatic total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, and induced lipid droplet deposition and swelling in hepatocytes. Transcriptome and validation experiments showed upregulated hepatic PER1 expression in the MCI group, while PPARα and its downstream lipid metabolism genes (CPT1A, APOA5) were downregulated. In HepG2 cells, nighttime calcium incubation (NC) significantly increased intracellular TG and LDL contents, upregulated PER1 expression, and inhibited PPARα, CPT1A, and APOA5 expressions. Knocking down PER1 reversed the abnormal gene expression and lipid-elevating effects in the NC group. Collectively, our findings demonstrate that the circadian timing of calcium intake critically regulates hepatic lipid homeostasis 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
Apolipoprotein E (ApoE) serves as a critical molecular nexus between Alzheimer's disease (AD) and atherosclerosis, two age-associated inflammatory disorders that share vascular pathology, amyloid-beta Show more
Apolipoprotein E (ApoE) serves as a critical molecular nexus between Alzheimer's disease (AD) and atherosclerosis, two age-associated inflammatory disorders that share vascular pathology, amyloid-beta (Aβ) deposition, and lipid dysregulation. Atractylenolide I (AI), a promising therapeutic candidate derived from 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