Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable s Show more
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable strategies for Show less
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
Alport syndrome (AS) is the most common inherited glomerular disease among patients with chronic kidney disease. With exome sequencing now widely used in clinical practice, pathogenic variants in Alpo Show more
Alport syndrome (AS) is the most common inherited glomerular disease among patients with chronic kidney disease. With exome sequencing now widely used in clinical practice, pathogenic variants in Alport-related genes (COL4A3/COL4A4/COL4A5) are increasingly identified in patients with diverse phenotypes, including proteinuria‑predominant disease and kidney failure of unknown etiology. Diagnostic complexity further increases when COL4A3/COL4A4/COL4A5 variants are co‑inherited with pathogenic variants associated with other genetic kidney disorders. We reported a 31‑year‑old male presenting with kidney failure, significant proteinuria, familial hematuria and hyperlipidemia. Whole‑exome sequencing (WES) identified two pathogenic variants: a hemizygous COL4A5 variant (c.2105G > A; p.Gly702Asp) and a heterozygous APOE Kyoto variant (c.127C > T; p.Arg43Cys). Given the potential dual diagnosis of AS and lipoprotein glomerulopathy (LPG), a kidney biopsy was performed. Histologic examination revealed uneven thickness of the glomerular basement membrane consistent with the diagnosis of AS, but no LPG-related lesions were observed, indicating incomplete penetrance of APOE Kyoto variant. Cascade family screening detected APOE Kyoto variant in the patient's father and elder sister, both of whom lacked proteinuria until follow-up period. This case highlights the complementary role of kidney biopsy alongside WES in AS with complex genetic mechanisms. It also illustrates the incomplete penetrance of APOE Kyoto, common among Chinese carriers. Show less
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson' Show more
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. In total, 120 patients with video-polysomnography confirmed isolated REM sleep behavior disorder (iRBD) and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testing, and 107 iRBD patients were prospectively followed up. Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18,878.85 pg/mL vs. 24,649.85 pg/mL, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and noncarriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease conversion (hazard ratio = 3.418, 95% CI: 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative disease. However, the BDNF Val66Met polymorphism may not be involved in the pathogenesis of iRBD as well as phenoconversion in the studied population. 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
Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neur Show more
Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neurotrophic mechanisms; however, its efficacy in aging models remains unclear. This study investigated the mechanisms underlying neuroprotective effects of chronic TB administration in senescence-accelerated mouse prone 8 (SAMP8), a model of age-related memory impairment. SAMP8 and SAMR1 mice were fed either a control diet or a diet supplemented with 0.05% TB for 50 d. Cognitive performance was evaluated by the novel object recognition (NOR) test. Neurotrophic factors (BDNF and NT-3), synaptic proteins (PSD95 and synaptophysin), and plasticity-related signaling molecules (phosphorylated CREB and TrkB) were analyzed in the prefrontal cortex and hippocampus. Inflammatory cytokines, lipid peroxides, and antioxidant enzymes were quantified. Molecular docking was used to assess TB's interaction with phosphodiesterase (PDE) enzymes. TB improved short-term memory in SAMP8, increasing discrimination index in the NOR test. This was accompanied by increased BDNF, NT-3, PSD95, and synaptophysin levels and enhanced CREB and TrkB phosphorylation. Furthermore, TB lowered the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and phosphorylated NF-κB, reduced lipid peroxidation, and increased the levels of antioxidant markers (HO-1, GSH). These effects were minimal in SAMR1. No adverse effects on body weight or blood parameters were observed. Molecular docking indicated that TB binds to PDE enzymes with weaker inhibitory activity than selective inhibitors. TB enhances short-term memory and synaptic function in aged mice via neurotrophic, antioxidant, and anti-inflammatory mechanisms, supporting its potential as a safe dietary intervention for age-related cognitive decline. 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
Primary resistance to chimeric antigen receptor (CAR) T-cell therapies has limited their widespread application. Our prior genome-wide CRISPR/Cas9 screening revealed that the loss of CD58, a crucial i Show more
Primary resistance to chimeric antigen receptor (CAR) T-cell therapies has limited their widespread application. Our prior genome-wide CRISPR/Cas9 screening revealed that the loss of CD58, a crucial intrinsic resistance factor in tumors, resulted in insufficient immune synapse formation and impaired CAR T-cell activation and cytotoxicity. However, the specific signaling pathway and transcriptional changes associated with CAR T-cell dysfunction have not been addressed. Here, we revealed that AP-1-mediated activation was attenuated in CAR T cells impaired by tumor CD58 loss, driving a decrease in mitochondrial biogenesis, metabolic kinetic impairment, mitochondrial membrane potential loss and ROS accumulation. Moreover, this AP-1 attenuation triggered death receptor-independent apoptosis through the intrinsic mitochondrial pathway. In seeking therapeutic strategies, we pharmacologically and genetically blocked three distinct inhibitory phosphatases positioned upstream of AP-1 signaling. Multifaceted validation has demonstrated that dual specificity phosphatase 6 (DUSP6) blockade is an effective approach to supplement AP-1 signaling while notably reducing CAR T-apoptosis and enhancing mitochondrial fitness, proliferation and long-term cytotoxicity. The transcriptomic profiles of DUSP6-ablated CAR T cells revealed markedly upregulated T-cell activation signatures and enriched metabolic pathways. Clinically, bulk and single-cell RNA-seq analyses revealed that DUSP6 was downregulated in patients who responded to T-cell-based immunotherapy, implying its relevance to patient outcomes. Our findings repositioned CD58 not merely as an immune synapse component but also a metabolic checkpoint in CAR T-cell biology, the loss of which triggers AP-1-dependent mitochondrial derangement and creates a permissive landscape for intrinsic apoptosis, which can be ameliorated by ablation of the inhibitory phosphatase DUSP6. Crucially, DUSP6 ablation represents a promising engineering target to potentiate CAR T-cell efficacy in broader applications. Show less
Chronic stress, a key contributor to neurological disorders, is mechanistically linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neuroinflammation, and hippocampal neuronal apoptosis Show more
Chronic stress, a key contributor to neurological disorders, is mechanistically linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neuroinflammation, and hippocampal neuronal apoptosis. Current therapeutic approaches remain limited in efficacy and safety. Schisandrol A, a neuroactive lignan from Show less
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. Howev Show more
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas ( Show less
Alzheimer disease (AD) is a primary neurodegenerative disorder of the brain with an unknown cause and complex pathogenesis. It is the most common form of dementia and poses a significant threat to the Show more
Alzheimer disease (AD) is a primary neurodegenerative disorder of the brain with an unknown cause and complex pathogenesis. It is the most common form of dementia and poses a significant threat to the health of the aging population worldwide. However, effective pharmacological treatments remain limited. This study employed publicly available genome-wide association study summary statistics, which included 4907 plasma proteins as exposures and AD as the outcome. To explore the causal relationship between plasma proteins and AD, 5 Mendelian randomization (MR) analyses were applied. Heterogeneity in the results was assessed using the Cochrane Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test. Sensitivity analysis was conducted using a leave-one-out approach. Plasma proteins exhibiting significant associations with AD were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to elucidate their biological functions and pathways. The protein-protein interaction network was constructed via the STRING database, and hub genes were identified based on node degree and visualized with Cytoscape. Potential drug candidates targeting these hub genes were predicted via the Drug Signatures Database. The binding affinities of the candidate drugs to the hub gene-encoded proteins were subsequently validated through molecular docking via the CB-Dock2 platform. Finally, the expression patterns of the hub genes across various cell types were explored via single-cell sequencing analysis, and an external GEO validation dataset was established for verification. MR analysis revealed that 39 plasma proteins were significantly associated with AD. Functional and pathway enrichment analyses revealed that these proteins were predominantly enriched in the nuclear factor-κB signaling pathway. Further screening identified 10 hub genes: APOE, CSF3, TNFAIP3, PHGDH, PEBP1, MICB, LGMN, TGM1, CD55, and CCL21. The Drug Signatures Database predicted 5 potential drug candidates. Molecular docking analysis demonstrated strong binding affinities between these drug candidates and the hub genes. Single-cell sequencing analysis revealed that most hub genes presented elevated expression levels in oligodendrocytes. The results of the MR analysis were consistent with those of the external validation set, underscoring the reliability of this study. Through MR analysis, this study systematically identified 10 hub genes associated with AD and predicted 5 potential drug candidates. These findings offer novel insights into the molecular mechanisms underlying AD and may contribute to improved strategies for clinical diagnosis and targeted therapy. Show less
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and Show more
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and genotype and allele frequencies were compared between groups. Multivariate logistic regression analyzed the link between ApoE polymorphisms and CAD risk in populations at middle and high altitudes. The data revealed significant differences in These findings validated that the Show less
Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss, cognitive decline, and behavioral changes. Blood-based biomarkers have recently gained significant a Show more
Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss, cognitive decline, and behavioral changes. Blood-based biomarkers have recently gained significant attention due to their accessibility and cost-effectiveness. This review highlights the latest progress in multiple key areas of bloodbased biomarkers for Alzheimer's disease. For early diagnosis, blood-based biomarkers such as amyloid-β and phosphorylated tau can identify Alzheimer's disease even before clinical symptoms emerge. Dynamic changes in blood-based biomarkers, including p-tau217 and neurofilament light chain, reflect disease progression and correlate with cognitive decline, enabling continuous monitoring of Alzheimer's disease progression. Additionally, bloodbased biomarkers such as p-tau181 and glial fibrillary acidic protein aid in differential diagnosis by distinguishing Alzheimer's disease from other dementias such as frontotemporal dementia. Blood-based biomarkers related to nerve repair have opened up new avenues for tracking nerve regeneration and therapeutic response, especially brain-derived neurotrophic factor. Furthermore, advanced detection technologies such as single-molecule array and immunoprecipitation-mass spectrometry have significantly improved the sensitivity and specificity of bloodbased biomarkers, facilitating their clinical translation. In summary, blood-based biomarkers hold strong potential to improve early diagnosis, monitor progression, differential diagnosis, and evaluate therapies in Alzheimer's disease. This review provides a comprehensive and updated evaluation of the translational potential of bloodbased biomarkers, emphasizing their practical utility in clinical settings and offering insights into future directions for large-scale application. This review emphasizes the need to prioritize the allocation of scientific resources, expedite the transition of blood-based biomarkers to clinical implementation, and ultimately achieve precise treatment of Alzheimer's disease using these biomarkers. Show less
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the ef Show more
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE Show less
American Indians have a high population risk for cerebrovascular disease, vascular brain injury (VBI), and dementia. The apolipoprotein ( We analyzed data from a population-based, longitudinal cohort Show more
American Indians have a high population risk for cerebrovascular disease, vascular brain injury (VBI), and dementia. The apolipoprotein ( We analyzed data from a population-based, longitudinal cohort of American Indians aged 64-95 years from the Strong Heart Study recruited from Northern Plains, Southern Plains, and Southwest regions. Magnetic resonance imaging markers included infarcts, lacunes, hemorrhages, and WMH. The sample size was 395 participants with a mean age of 71.3 (4.7) years and was comprised of 313 non-ε4-carriers and 82 ε4-carriers, predominantly female (70.1%). Cross-sectional analyses indicated no significant associations between Our findings echo previous work that Show less
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. Show less
Identifying high-performing advanced practice nursing roles and understanding the factors that contribute to their effectiveness are critical for advancing professional development, optimizing workfor Show more
Identifying high-performing advanced practice nursing roles and understanding the factors that contribute to their effectiveness are critical for advancing professional development, optimizing workforce deployment, and ensuring long-term sustainability in nursing. This study aimed to (1) identify distinct latent profiles of advanced practice nursing among specialist nurses in mainland China, (2) quantitatively examine the individual and contextual factors associated with high performance, as characterized by these profiles, and (3) qualitatively confirm the significant factors using explanatory semistructured interviews in the high-performance groups. A mixed-methods sequential explanatory design was used, in which quantitative data were collected first and subsequently explained through qualitative interviews. Certified specialist nurses from 16 hospitals across urban and rural areas of Shanghai were included. Latent profile analysis (LPA) was conducted using the five domains from the Advanced Practice Role Delineation tool as manifest indicators to classify nurses into distinct performance profiles. Multinomial logistic regression was used to examine potential determinants (e.g., job position) of group membership. Additionally, a backpropagation neural network (BPNN) was developed to rank the importance of contributing factors. Specialist nurses identified as high performers in the quantitative phase were purposively sampled for explanatory semistructured qualitative interviews. Three latent profiles emerged: high performance (26.1%), moderate performance (46.3%), and low performance (27.6%). Compared to APNs, staff nurses had significantly lower odds of belonging to the high-performance group ( Identifying the profiles of advanced practice nursing roles provides valuable insights for optimizing APN performance and informing targeted management and policy strategies. High-performing specialist nurses are positioned at the nexus of individual capability, interdisciplinary collaboration, and institutional support. Show less
Short-chain fatty acids (SCFAs) are key microbial metabolites that support intestinal and skeletal development, yet their coordinated effects during early life remain poorly defined. In this study, ne Show more
Short-chain fatty acids (SCFAs) are key microbial metabolites that support intestinal and skeletal development, yet their coordinated effects during early life remain poorly defined. In this study, neonatal mice were administered SCFAs for 28 days to evaluate their impacts on growth, intestinal barrier integrity, immune modulation, bone development, and gut microbiota composition. Valerate supplementation significantly increased body weight and intestinal length. It enhanced the villus structure, crypt depth, and goblet cell number, alongside upregulation of tight junction and mucin genes, indicating improved barrier function. Valerate and propionate also promoted the expression of interleukin-4 (IL-4) and interleukin-10 (IL-10) and reduced pro-inflammatory cytokines, suggesting an immunomodulatory shift. In the skeletal system, valerate improved the microarchitecture, increased bone mineral density (BMD), and upregulated osteogenic genes runt-related transcription factor 2 (Runx2), fibroblast growth factor receptor 1 (FGFR1), and growth hormone receptor (GHR). Microbiota profiling showed enrichment of several genera ( Show less
With global climate warming increasingly threatening aquatic ecosystems, prolonged exposure to high temperatures has become a major environmental stressor for both wild and cultured fish. However, the Show more
With global climate warming increasingly threatening aquatic ecosystems, prolonged exposure to high temperatures has become a major environmental stressor for both wild and cultured fish. However, the long-term effects of chronic heat stress on blood physiology and hematopoietic processes remain poorly understood. To assess the long-term impacts of chronic heat stress on hematopoiesis in largemouth bass (Micropterus salmoides), we conducted a 180-day acclimation experiment at 34 °C. Hematological analyses showed significant reductions in red blood cell counts and hemoglobin concentrations, indicating impaired oxygen transport capacity. Blood cell morphology was altered, with erythrocytes exhibiting a lower major-to-minor axis ratio and leukocytes (lymphocytes and granulocytes) showing increased volumes. Histological and ultrastructural observations of the head kidney revealed tissue loosening, hemosiderin deposition, mitochondrial damage, and elevated apoptosis. Furthermore, transcriptomic analysis combined with GO and KEGG enrichment revealed that pathways involved in vascular development, stress response, and fatty acid metabolism were significantly activated under heat stress. Notably, key genes associated with angiogenesis, lipid metabolism, stimuli response, apoptosis and immunity, including mmp9, angptl4, abca1 and stab2, were markedly upregulated, suggesting their crucial roles in vascular remodeling and thermotolerance. Together, these results provide the first integrative cellular and molecular characterization of hematopoietic responses to prolonged high temperature in M. salmoides. The findings enhance understanding of fish physiological plasticity under environmental stress and have implications for aquaculture management and the development of heat-resilient strains. Show less
Daiyue Li, Yu Zhang, Ruonan Wang+6 more · 2026 · Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · Elsevier · added 2026-04-24
Alzheimer's disease (AD) is one of the most pressing public health challenges in an aging world. However, effective therapeutic strategies are still lacking. Imbalance in lipid homeostasis is a key dr Show more
Alzheimer's disease (AD) is one of the most pressing public health challenges in an aging world. However, effective therapeutic strategies are still lacking. Imbalance in lipid homeostasis is a key driver of AD. Given the established link between dysregulated lipid metabolism and amyloid-beta (Aβ) aggregation, we investigated whether chicoric acid (CA), a dietary polyphenol with reported lipid-modulating properties, could mitigate Aβ pathology by modulating lipid metabolism in 5xFAD transgenic mice. In the brain, we found that CA upregulated the expression of liver X receptor Beta (LXR-β) and ATP-binding cassette transporter A1 (ABCA1) in 5xFAD mice. Through this pathway, it promoted apolipoprotein E (ApoE) lipidation and enhanced the expression of Aβ-clearance proteins (IDE and LRP1). Notably, in the periphery, CA reshaped the gut microbiota in 5xFAD mice, which reduced serum neurotoxic bile acid levels and preserved the integrity of the peripheral Aβ clearance system. Together, our study first demonstrated that CA globally regulated lipid homeostasis to alleviate Aβ pathology by coordinating cerebral cholesterol efflux with peripheral bile acid metabolism. The findings facilitated exploring active compounds from traditional Chinese medicine that may reduce Aβ deposition by targeting lipid metabolism pathways. Show less
Atherosclerosis preferentially develops in regions exposed to disturbed flow, where is more susceptible to trans-endothelial retention of oxidized low-density lipoprotein (ox-LDL) and subsequent vascu Show more
Atherosclerosis preferentially develops in regions exposed to disturbed flow, where is more susceptible to trans-endothelial retention of oxidized low-density lipoprotein (ox-LDL) and subsequent vascular inflammation. While 12/15-lipoxygenase (12/15-LOX) is implicated in lipid oxidation, its role in accumulation of oxLDL in disturbed flow areas remains unknown. Human coronary artery endarterectomy specimens and cultured endothelial cells were analyzed for 12/15-LOX expression and localization under disturbed flow. Oxidized phospholipids were quantified via E06 antibody by ELISA, while ROS generation was measured using DCFH-DA. ApoE Disturbed flow upregulated 12/15-LOX expression in endothelial cells. In vitro, disturbed flow increased LDL oxidation and ROS production, both attenuated by 12/15-LOX siRNA or the specific inhibitor baicalein and ML351. Genetic deletion or pharmacological inhibition of 12/15-LOX reduced oxidized lipid deposition in disturbed flow regions. Mechanistically, 12/15-LOX increased ROS production in disturbed flow conditions in a pathway upstream of NAPDH oxidase 2. However, the 12/15-LOX-mediated LDL oxidation was independent of NOX. We identify 12/15-LOX as a hemodynamic-sensitive enzyme that is upregulated under disturbed flow to promote LDL oxidation, which proposes a promising target to mitigate atherosclerosis especially in disturbed flow areas. Show less
Recently, macrophage senescence has been identified as an important pathological risk factor for atherosclerosis (AS). Oxymatrine (OMT) has demonstrated potential in ameliorating cellular senescence. Show more
Recently, macrophage senescence has been identified as an important pathological risk factor for atherosclerosis (AS). Oxymatrine (OMT) has demonstrated potential in ameliorating cellular senescence. This study aims to investigate the pharmacological properties and underlying mechanisms of OMT in alleviating AS progression. High-fat diet-fed ApoE Show less
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
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
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on childr Show more
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on children with ASD, whereas how specific executive components relate to social functioning in adults remains less clear. This study examined whether patterns of association between EF and social responsiveness differ between children and adults with and without ASD. Data were obtained from the Autism Brain Imaging Data Exchange II (ABIDE II), including 423 participants aged 8-23 years (ASD = 184; controls = 239). EF was evaluated using the Behavior Rating Inventory of Executive Function (BRIEF/BRIEF-A), and social responsiveness was assessed with the Social Responsiveness Scale (SRS). Covariates of age, sex, and full-scale IQ (FIQ) were controlled using entropy balancing in children and multiple regression in adults. Hierarchical regression, moderated mediation analysis, and latent profile analysis (LPA) were conducted to examine the moderation, mediation, and heterogeneity effects, respectively. Across both child and adult samples, individuals with ASD exhibited significantly higher T-scores than controls on nearly all BRIEF and SRS subdomains after covariate adjustment (all adjusted p < 0.01), indicating widespread EF and social responsiveness impairments. Moderation analyses revealed no significant age group × EF interaction, indicating that the association between EF and social responsiveness was consistent across development. Mediation analysis revealed age-specific pathways, with EF broadly mediating social responsiveness in adults but showing more selective mediation in children. LPA identified four distinct subtypes, which were independent of age, sex, and FIQ. EF-social responsiveness associations were evident across development, but the functional contribution of specific executive components became more differentiated with age. Working memory showed greater relative prominence in adulthood. Latent profile analysis revealed heterogeneity in how executive difficulties align with social challenges, supporting developmentally informed assessment and clinical interpretation rather than direct treatment recommendations. 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
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of ph Show more
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC). DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln. RNA sequencing (RNA-seq) was employed to explore the mechanism of PAGln in DIC. Subsequently, the differentially expressed genes (DEGs) were subjected to comprehensive analysis using diverse public databases, and RT-PCR was used to confirm the expression levels of the candidate genes. Finally, molecular docking techniques were used for validation. PAGln effectively prevented both in vivo and in vitro Dox-induced myocardial injury and cell apoptosis. RNA-seq results showed that 40 genes were up-regulated and 54 down-regulated in the Dox group compared to the Con group, displaying opposite changes in the Dox + PAGln group. Enrichment analysis highlighted several mechanisms by which PAGln alleviated Dox-induced cardiotoxicity, including the lipid metabolic process, calcium-mediated signaling, positive regulation of store-operated calcium channel activity, and hypertrophic cardiomyopathy. In vitro and in vivo experiments confirmed that PAGln treatment could reverse the changes in the expression levels of Klb, Ece2, Nmnat2, Casq1, Pak1, and Apob in Dox. Molecular docking results showed that these genes had good binding activity with PAGln. PAGln shows potential in alleviating Dox-induced cardiotoxicity, with Ece2 identified as key regulatory molecules related to endothelial dysfunction. Show less
Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involveme Show more
Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis. Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess the role of Dapk2 in vivo, EC-specific DAPK2 expression was elevated in OSS-exposed regions of human and murine arteries. Mechanistically, Krüppel-like factor 2 (KLF2) suppressed DAPK2-driven phosphorylation of PKM2 at threonine 45 orchestrates endothelial inflammatory responses to disturbed flow, identifying a novel mechanistic axis and potential therapeutic target in atherosclerosis. Show less