The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between th Show more
The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between the individual studies. To explore the correlation of LPA gene rs3798220 and rs10455872 polymorphisms and CHD, the current meta-analysis was performed. The random or fixed effect genetic models were used to calculate the pooled odds ratios (ORs) and their corresponding 95 % confidence intervals (CI). A significant association was found between LPA rs3798220 polymorphism and CHD under allelic (OR: 1.488), recessive (OR: 1.543), dominant (OR: 1.534), homozygous (OR: 1.544), heterozygous (OR: 1.498) and additive genetic models (OR: 1.531). There was also a significant association between LPA rs10455872 polymorphism and CHD under allelic (OR: 1.607), dominant (OR: 1.751), heterozygous (OR: 1.723) and additive genetic models (OR: 1.686). LPA rs3798220 and rs10455872 polymorphisms were significantly associated with increased CAD risk. The persons carrying C allele of LPA rs3798220 and G allele of LPA rs10455872 polymorphisms might have higher CHD risk than the T allele of rs3798220 or A allele of rs10455872 carriers. Show less
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEA Show more
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEAD) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently studied. Given the overlapping metabolic disturbances in both conditions, such as insulin resistance and lipid abnormalities, a potential relationship between Lp(a) and peripheral vascular injury in MASLD is biologically plausible. This study aimed to investigate the cross-sectional association between circulating Lp(a) concentrations and the presence of LEAD in a well-characterized MASLD population. A total of 468 MASLD patients undergoing routine health check-ups were included. Lp(a) levels were stratified into three categories: <10 mg/dL, 10–30 mg/dL, and ≥ 30 mg/dL. LEAD was diagnosed using duplex ultrasonography. Multivariable logistic regression models were used to assess the relationship between Lp(a) levels and the presence of LEAD, with adjustments for demographic variables, metabolic conditions, and lipid-related parameters. Subgroup analyses were conducted to assess potential effect modification. LEAD was diagnosed in 61.5% ( Elevated Lp(a) levels were associated with a higher prevalence of LEAD in patients with MASLD. Although the magnitude of association per unit increase was modest, higher Lp(a) concentrations were associated with greater LEAD prevalence. These findings should be interpreted cautiously and viewed as hypothesis-generating, particularly with respect to subgroup analyses. Prospective studies are needed to clarify causality and clinical relevance. The online version contains supplementary material available at 10.1186/s12872-026-05600-7. 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
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical d Show more
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and C16orf95/MAP1LC3B. Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2. We also demonstrate that these variants have significant association with Alzheimer's disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE, coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation. Show less
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human c Show more
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations. Show less
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high m Show more
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high miss rates. This study innovatively proposes using urinary hydrogen peroxide (H Show less
Improving Internet addiction among nursing students is of great significance to the future development of the nursing industry. Previous studies have proved that childhood trauma is closely related to Show more
Improving Internet addiction among nursing students is of great significance to the future development of the nursing industry. Previous studies have proved that childhood trauma is closely related to Internet addiction. However, the direct relationship between alexithymia and childhood trauma and Internet addiction has not been fully explored. The aim of this study is to identify different subgroups of nursing students based on their childhood trauma and to examine the mediating role of alexithymia between childhood trauma and Internet addiction. From April to May 2025, 3,697 nursing students were recruited as samples from Shandong, Hubei, Hunan, and Henan provinces in China by convenient sampling. This survey collected social demographic data. Including The Childhood Trauma Questionnaire - Short Form (CTQ-SF), the Toronto Alexithymia Scale (TAS-26), and the Internet addiction Scale. Potential profile analysis was used to determine the potential categories of childhood trauma characteristics of nursing students, and Pearson correlation analysis, Bayesian factor robustness analysis and mediation analysis were used to determine the potential relationships among variables. LPA identified three distinct groups based on their dominant usage: low (77.4%), medium (19.5%), and high (3.1%). In the relationship between childhood trauma and Internet addiction based on potential profile analysis, alexithymia has a significant mediating effect (SE = 0.442,95%CI = 0.095, 1.824; SE = 0.219, 95%CI = 0.093, 0.962). There is heterogeneity in childhood trauma among nursing students. Alexithymia plays an important mediating role in the relationship between childhood trauma and Internet addiction. It is suggested that nursing educators pay attention to the differences in childhood trauma among nursing students, provide corresponding psychological counseling for different students, improve them, thereby alleviating Internet addiction among nursing students and promoting their mental health. Show less
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise ant Show more
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise anti-inflammatory mechanisms and its potential to ameliorate depression-like behaviors remain incompletely understood. This study investigated the effects of COG133 in mouse models of depression induced by lipopolysaccharide (LPS), chronic social defeat stress (CSDS), and corticosterone (CORT), as well as in LPS-stimulated BV-2 microglial cells. We found that COG133 treatment significantly alleviated depression-like phenotypes and suppressed hippocampal neuroinflammation by inhibiting microglial overactivation. Using RNA sequencing (RNA-seq) and biochemical validation, we identified the MKK3/6-p38-ATF2 signaling axis as a central mechanism underlying the anti-inflammatory effects of COG133. Pharmacological modulation of p38 MAPK further confirmed that this pathway is essential for COG133-mediated behavioral and cellular recovery. Together, these findings identify COG133 as a promising peptide candidate for the treatment of depression through modulation of the p38 MAPK-mediated neuroinflammation axis. 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
C-reactive protein (CRP) is a liver-derived soluble marker of inflammation whose levels can predict the risk of atherosclerotic cardiovascular disease and therapeutic efficacy of statins. Intriguingly Show more
C-reactive protein (CRP) is a liver-derived soluble marker of inflammation whose levels can predict the risk of atherosclerotic cardiovascular disease and therapeutic efficacy of statins. Intriguingly, however, CRP is not considered as a mediator of atherosclerosis based primarily on studies examining chow diet (CD)-fed mice. The aim of this study is to investigate the role of CRP in high-fat diet (HFD)-induced atherosclerosis, which models a more prevalent scenario in the real world, and to clarify its impact on Atorvastatin treatment. Apoe-sufficient or -deficient mice with or without Crp knockout were fed with CD, HFD, or methionine- and choline-deficient diet, or subjected to carotid artery ligation or Atorvastatin treatment. Hepatic, vascular, and metabolic indexes were then analyzed. The effects of CRP on lipid droplet formation were examined by cellular assays. Knockout of Crp in Apoe-deficient mice does not affect the progression of atherosclerosis under CD feeding, but significantly reduces plaque burden under HFD feeding. The pro-atherosclerotic effects of Crp are not due to direct modulation of vascular inflammation, but appear to be the result of enhanced lipid accumulation in the liver and the ensuing aggravation of hyperlipidemia. Mechanistically, Crp enhances hepatic lipid accumulation by upregulating Cidea to promote the formation of enlarged lipid droplets in hepatocytes. We further show that the therapeutic efficacy of Atorvastatin on HFD-induced atherosclerosis in Apoe-deficient mice is largely dependent on Crp. Our findings identify a previously unrecognized role of CRP in enhancing hepatic lipid accumulation under stresses induced by dietary or genetic factors, which underlies its secondary impact on atherosclerosis and determines the therapeutic efficacy of Atorvastatin. Show less
Post-stroke depression (PSD) affects 29-52% of stroke survivors, with inflammation as a key pathophysiological mechanism. Hyperbaric oxygen therapy (HBOT) may modulate neurorestoration, but clinical e Show more
Post-stroke depression (PSD) affects 29-52% of stroke survivors, with inflammation as a key pathophysiological mechanism. Hyperbaric oxygen therapy (HBOT) may modulate neurorestoration, but clinical evidence is limited. While meta-analytic evidence suggests HBOT may benefit PSD symptoms, high-quality randomized controlled trials employing rigorous sham-control and concurrently investigating neurotrophic mechanisms remain scarce. In this randomized, double-blind, sham-controlled trial, 61 PSD patients were allocated to HBOT (n=29) or Sham-HBOT (n=32) groups, respectively. HAMD, NIHSS and MBI scores and serum Brain-Derived Neurotrophic Factor (BDNF), and beta-Nerve Growth Factor (beta-NGF), were evaluated at baseline as well as 2 and 4 weeks after HBOT intervention. The primary outcome was the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score from baseline to week 4, analyzed in the modified intention-to-treat population. The trial was registered (ChiCTR2100053522). HAMD scores decreased significantly in the HBOT group vs sham-group at weeks 2 (p=0.017) and 4 (p<0.01). Serum BDNF and beta-NGF, levels were significantly elevated in the HBOT group (all p<0.01). Reductions in HAMD scores correlated with increases in BDNF (r = 0.66, p < 0.05) and beta-NGF (r = 0.47, p =0.01). HAMD scores decreased significantly in the HBOT group compared to the sham-group, with the between-group difference reaching significance at week 2 (p=0.017) and week 4 (p<0.001). Exploratory subgroup analyses by stroke type (ischemic vs hemorrhagic) and age (dichotomized at the median of 65 years) were conducted and these analyses revealed no significant interaction between treatment group and either stroke subtype or age subgroup on the change in HAMD-17 scores (all p > 0.05), suggesting a consistent trend of HBOT effect across these subgroups within this limited sample. This preliminary trial suggests that a 4-week course of HBOT may alleviate depressive symptoms in PSD patients, an effect associated with increased serum BDNF and β-NGF levels. Given the limited sample size and short follow-up, its long-term efficacy and clinical positioning require validation in larger trials with extended follow-up. Show less
Significant interindividual variability in radiosensitivity poses a major challenge to conventional radiation protection and radiotherapy. Current prediction strategies relying on DNA damage or genomi Show more
Significant interindividual variability in radiosensitivity poses a major challenge to conventional radiation protection and radiotherapy. Current prediction strategies relying on DNA damage or genomic analysis have inherent limitations, underscoring the need for minimally invasive serum biomarkers. While serum apolipoproteins are crucial regulators of lipid transport, metabolism, and cellular stress response, their role as biomarkers for radiosensitivity remains largely unexplored. A 7.3 Gy ⁶⁰Co γ-ray whole-body irradiation mouse model (with training and independent validation cohorts) was established to assess individual radiosensitivity. Pre-irradiation peripheral serum samples underwent high-throughput proteomics analysis to identify differential proteins (DEPs) linked to 30-day post-irradiation survival. KEGG and GO enrichment analyses were conducted to characterize DEP-associated pathways. An XGBoost machine learning model was built using candidate biomarkers, with SHAP analysis to define their predictive contributions; Cox proportional hazards and Pearson correlation analyses were applied to evaluate survival associations. DIA-based proteomics identified 580 DEPs in the training cohort and 449 in the validation cohort. KEGG and GO enrichment analyses confirmed that these DEPs were predominantly enriched in the cholesterol metabolism and reverse cholesterol transport pathways. The predictive model based on an apolipoprotein panel (ApoA1/ApoA2/ApoA4), established using the XGBoost algorithm, exhibited exceptional performance in the training cohort (AUC = 1) and maintained robust generalizability in an independent validation cohort (AUC = 0.833). Compared with non-survivors, survivors exhibited significantly elevated serum levels of ApoA1 and ApoA2 but markedly reduced levels of ApoA4. Cox proportional hazards regression analysis established ApoA1 and ApoA2 as independent protective factors, whereas high ApoA4 expression was an adverse prognostic indicator. Notably, ApoA4 levels also demonstrated a strong negative correlation with post-irradiation survival time. The serum apolipoprotein profile (ApoA1/ApoA2/ApoA4) serves not only as a promising minimally invasive biomarker for predicting individual radiosensitivity in mice but also reveals a critical link between the cholesterol metabolic pathway and radiation response. This finding lays a theoretical foundation for translating predictive, cholesterol metabolism-related biomarkers to support radiation response assessments. Given the limitations of animal models, subsequent studies are required to validate the clinical applicability of this panel in human cohorts, with the aim of offering an effective tool for personalized radiation protection and precise radiotherapy. The online version contains supplementary material available at 10.1186/s12944-026-02868-8. Show less
As a result of individual genetic variations, some patients show no response to initial antidepressant medications. This study aims to investigate the association between specific genetic polymorphism Show more
As a result of individual genetic variations, some patients show no response to initial antidepressant medications. This study aims to investigate the association between specific genetic polymorphisms and the efficacy of antidepressant drugs and to improve the accuracy and effectiveness of treatment under the guidance of genetic testing. A retrospective screening was conducted on medical records from, Suixian People's Hospital between January 2022 and December 2024. A total 202 patients with depression carrying the CYP2C19 gene were selected after the application of exclusion criteria. They were assigned to three groups in accordance with their genetic metabolism types: the rapid metabolism group (Group A, n = 65), the intermediate metabolism group (Group B, n = 94) and the poor metabolism group (Group C, n = 43). All three groups were treated with sertraline for a six-week treatment cycle. The observation indicators included scores on the Hamilton Depression Scale (HAMD); onset time of drug effect; rates of response and remission; scores on the Clinical Global Impression-Improvement (CGI-I) scale; levels of the neurotransmitter factors 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA) and brain-derived neurotrophic factor (BDNF); incidence of adverse events; and scores on the Morisky Medication Adherence Scale-8 (MMAS-8). The baseline data of the three groups of patients were comparable before medication (p > 0.05). Compared with those in Groups A and B, patients in Group C showed a significantly greater reduction in HAMD scores (all p < 0.05), along with higher response rates (all p < 0.05) and remission rates (all p < 0.05). Amongst the three groups, Group C had a shorter onset time of drug effect (all p < 0.05); more significant improvement in CGI-I scores (all p < 0.05); and more prominent upregulation of neurotransmitter factors, namely, 5-HT (all p < 0.05), GABA (all p < 0.05) and BDNF (all p < 0.05). Regarding the incidence of adverse events, Group C had the highest rate, whereas Group A had the lowest (10.8% vs. 24.5% vs. 41.9%). Compared with other groups, Group B exhibited a more significant increase in MMAS-8 scores (all p < 0.05). Metabolic phenotype exerts substantial effects on the therapeutic outcome of sertraline in patients with depression carrying the CYP2C19 gene. Amongst groups, Group C showed better therapeutic efficacy but an elevated incidence of adverse events and lower medication adherence; Group A had relatively poor efficacy; and Group B demonstrated superior adherence. In clinical practice, individualised treatment can be implemented on the basis of CYP2C19 metabolic typing to improve therapeutic efficacy and reduce adverse events and medical burden. Show less
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative i Show more
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative importance of endothelial METRNL in atherosclerosis by comparing the effects of whole-body METRNL deficiency to endothelial-specific deficiency, and to show the subcellular distribution of endothelial METRNL and its role in mitochondrial homeostasis against atherosclerosis. Our study demonstrated that a deficiency in either endothelial or global METRNL exacerbated atherosclerosis to a similar degree in both spontaneous (age-related) and high fat diet-induced atherosclerosis, suggesting that endothelial METRNL is pivotal in the progression of atherosclerosis due to METRNL deficiency. Endothelial METRNL was diffusely distributed in the cytoplasm with subcellular localization to mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus (especially enriched in mitochondria and nucleus). In both an in vivo apolipoprotein E-deficient (ApoE Show less
Jingbo Lu, Runhao Xu, Tinghua Li+2 more · 2026 · Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · added 2026-04-24
To investigate changes in serum lipid profile parameters combined with tumor markers in gastric cancer (GC) patients and their value in GC screening. A total of 100 patients diagnosed with GC at Renji Show more
To investigate changes in serum lipid profile parameters combined with tumor markers in gastric cancer (GC) patients and their value in GC screening. A total of 100 patients diagnosed with GC at Renji Hospital (West) between May and September 2025 were consecutively enrolled as the GC group (54 cases in stage Ⅰ/Ⅱ and 46 cases in stage Ⅲ/Ⅳ). Additionally, 100 age- and sex-matched healthy individuals undergoing routine physical examinations were included as the healthy control (HC) group. The serum levels of nine lipid indicators (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides [TG], small and dense low-density lipoprotein cholesterol [sdLDL-C], apolipoprotein [Apo] A1, ApoB, ApoC2, and ApoC3) and five tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA] 19-9, CA50, CA242, and CA72-4) were measured using an automatic biochemical analyzer and an electrochemiluminescence instrument. Intergroup differences were analyzed using the Mann-Whitney Compared with the HC group, the GC group showed significantly lower levels of ApoA1, ApoC3, TC, HDL-C, LDL-C, and sdLDL-C ( The combined panel of ApoA1, ApoC3, HDL-C, LDL-C, TC, sdLDL-C, CEA, CA50 and age offers a potential auxiliary tool for detecting gastric cancer. Show less
Haojie Ni, Yiyi Xiong, Min Liu+14 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid ex Show more
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR. This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway. In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin (α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro. SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression. SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment. Show less
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating Show more
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating heterogeneity of CAFs in renal cell carcinoma (RCC) could represent potential targets for reprogramming the TME. In this study, we conducted single-cell RNA sequence and flow cytometry analyses that identified a CAF subset overexpressing apolipoprotein E (ApoE), which was correlated with poor survival in patients with RCC. Mechanistically, NRF1 activation in CAFs induced formation of ApoEhigh CAFs and secretion of NRG1. ApoEhigh CAFs potentiated stemness properties in the surrounding RCC cells by secreting NRG1 and subsequently activating the HER2/NF-κB pathway. Interfering with NRG1 expression or inhibiting NF-κB signaling reduced ApoEhigh CAF-induced stemness of RCC cells. Furthermore, neutralizing NRG1 enhanced the efficacy of sunitinib in RCC models in vivo. Together, these findings highlight targeting the tumor-promoting functions of ApoEhigh CAFs as a promising approach for treating advanced RCC. NRF1 drives formation of ApoEhigh cancer-associated fibroblasts that secrete NRG1 to stimulate stemness of renal cell carcinoma, revealing a stromal-mediated mechanism that can be inhibited to improve treatment of advanced kidney cancer. Show less
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase of the TRIM superfamily, modulates critical cellular processes including ubiquitination, autophagy, and oxidative stress respons Show more
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase of the TRIM superfamily, modulates critical cellular processes including ubiquitination, autophagy, and oxidative stress response. Accumulating evidence highlights its context-dependent regulatory roles in hepatocellular carcinoma (HCC)-the most prevalent primary liver malignancy with high mortality and limited therapeutic efficacy. This review systematically summarizes the core mechanisms by which TRIM21 orchestrates HCC progression: ① Autophagy regulation: TRIM21 modulates HCC autophagy via multiple axes, including CCR4-NOT complex (TNKS1BP1/CNOT4)-mediated substrate ubiquitination, ATG14-dependent autophagosome initiation, and RETREG1-driven reticulophagy, with context-dependent effects on tumor proliferation. ② Drug resistance: TRIM21 enhances oxaliplatin sensitivity by ubiquitinating and degrading G6PD (the rate-limiting enzyme of the pentose phosphate pathway), while its role in sorafenib resistance involves dual pathways-the MST1/YAP axis and the ApoE/cholesterol/PI3K-AKT cascade. ③ Metastasis suppression: TRIM21 restricts HCC invasion and metastasis by ubiquitinating key oncoproteins, preserving epithelial integrity and inhibiting mesenchymal transition. ④ Reactive oxygen species (ROS) balance: TRIM21 regulates oxidative stress in HCC via the SQSTM1/p62-Keap1-NRF2 axis, coordinating with HIF1α to modulate antioxidant responses and tumor cell survival. Additionally, we discuss the regulatory significance of TRIM21 in HCC associated with hepatitis B virus (HBV) infection (via HBx/DNA polymerase ubiquitination) and nonalcoholic steatohepatitis (NASH) (via suppressing lipogenic enzymes to reduce steatosis-driven carcinogenesis). This review provides a theoretical basis for TRIM21 as a potential diagnostic marker and therapeutic target for HCC. Show less
Schizophrenia (SCZ) is a complex psychiatric disorder, and its pathogenic mechanisms are not yet fully understood. The identification of reliable blood biomarkers and molecular subtypes for early diag Show more
Schizophrenia (SCZ) is a complex psychiatric disorder, and its pathogenic mechanisms are not yet fully understood. The identification of reliable blood biomarkers and molecular subtypes for early diagnosis and effective therapy remains a significant challenge. To address this issue, we utilized a combination of bioinformatics and machine learning (ML) to identify potential biomarkers for SCZ. Our approach involved the integration of 12 different ML algorithms to develop a diagnostic signature based on data from several datasets, including GSE18312, GSE27383, GSE38485, GSE54913, and GSE165604. A nomogram was constructed using these datasets for potential clinical applications. In addition, clustering analysis was performed on SCZ patients using consensus clustering and non-negative matrix factorization (NMF) algorithms. We further evaluated subtype differences in biological functions and immune cells through various methods, such as gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Proteomaps, and IOBR analyses. Our results identified a diagnostic signature composed of 16 genes (APBB2, CLCN1, SYDE1, PAX5, SNAI1, DAZL, UNC93B1, PLAGL2, HS3ST1, ITPKB, PILRA, BTLA, SWAP70, AZI2, ADM, and AVPR2), which demonstrated robust performance in diagnosing SCZ across eight different datasets. A nomogram based on these genes was created, providing clinical benefits for SCZ patients. Among the identified genes, AZI2 was found to be the most critical, influencing inflammation and immunity. We also identified potential chemical compounds that could target these 16 genes. Unsupervised clustering and NMF algorithms revealed two distinct subtypes of SCZ, each associated with unique immune cell profiles, biological functions, and protein expression levels. In conclusion, this study not only developed a diagnostic signature and a novel nomogram for SCZ but also provided new insights into the subtypes of SCZ. These findings may pave the way for personalized diagnosis and treatment strategies for SCZ patients. Show less
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
While the apolipoprotein E (APOE) ε4 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (TOMM40)-an adjacent gene involved in mitoch Show more
While the apolipoprotein E (APOE) ε4 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (TOMM40)-an adjacent gene involved in mitochondrial protein import-is not known. Human brain tissue, human induced pluripotent stem cell-derived neurons (iNeurons), and mice were used for study of gene expression, cholesterol metabolism, mitochondrial function, and animal cognition. Human brain transcriptomics showed reduced TOMM40 expression that correlated with cholesterol regulatory gene expression, amyloid burden, and clinical AD diagnosis. In human iNeurons, TOMM40 knockdown (KD) disrupted mitochondria-endoplasmic reticulum contact sites (MERCs), causing mitochondrial dysfunction and promoting reactive oxygen species that led to activation of liver X receptor beta (NR1H2), upregulation of APOE and low-density lipoprotein receptor (LDLR), and increased cellular cholesterol and amyloid beta (Aβ)42 independent of APOE ε4. Consistently, Tomm40 KD in mice induced increased brain cholesterol, Aβ42 content, and impaired memory. TOMM40 is a novel mediator of AD pathology through dual effects on MERCs that regulate cholesterol homeostasis and mitochondrial function. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-est Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-established risk factor for AD in women. Osthole (OST), a phytoestrogen with mild, bidirectional regulatory properties, has been proposed as a potential estrogen replacement. This study aimed to investigate the mechanisms by which OST ameliorates cognitive impairment. Cognitive deficits were induced in female Sprague-Dawley rats by bilateral ovariectomy (OVX), and OST was subsequently administered by oral gavage. Behavioral tests revealed that OST significantly improved learning and memory and reduced anxiety-like and depression-like behaviors in OVX rats. H&E staining and Nissl staining demonstrated that OST reversed neuronal damage in the hippocampus and cortex. Western blotting, ELISA, and immunofluorescence staining indicated that OST treatment restored the estrogen-cholinergic-NGF axis: E Show less
This study employed a person-centered approach to identify latent profiles of academic burnout among Chinese university students and to examine the associations between academic burnout profiles and s Show more
This study employed a person-centered approach to identify latent profiles of academic burnout among Chinese university students and to examine the associations between academic burnout profiles and smartphone addiction, sleep quality, and mindfulness. A sample of 2,948 Chinese university students was recruited to complete measures of academic burnout, smartphone addiction, sleep quality, and mindfulness. Latent profile analysis (LPA) was used to identify distinct burnout profiles, and multinomial logistic regression was used to analyze factors associated with profile membership. Three distinct profiles of academic burnout were identified: a Low Burnout profile (18.15%), a Medium Burnout profile (50.88%), and a High Burnout profile (30.97%). The profiles differed significantly on all correlates, with the high burnout group exhibiting the most severe smartphone addiction, the poorest sleep quality, and the lowest mindfulness. Regression analysis revealed that higher smartphone addiction and poorer sleep quality were significantly associated with membership in the Medium and High Burnout profiles relative to the Low Burnout profile, whereas higher mindfulness was significantly associated with lower likelihood of belonging to higher burnout profiles. Academic burnout among Chinese university students is a heterogeneous experience, with a majority falling into an at-risk or intermediate state. Smartphone addiction, poor sleep, and low mindfulness are associated with higher burnout risk. These findings highlight the need for universities to develop targeted, profile-based interventions to provide precise and effective mental health support. However, due to the cross-sectional design, causal relationships cannot be inferred. Show less
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adv Show more
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adverse factors in the periodontal microenvironment. Therefore, identifying novel therapeutic targets and elucidating the underlying molecular mechanisms to protect the proliferative and differentiation potential of PDLSCs is of significant importance. PDLSCs were exposed to electronic cigarette extract and various common oral stressors to evaluate the expression of glucagon such as peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR). PDLSCs isolated from patients with periodontitis and PDLSCs from a mouse periodontitis model were also analyzed. Functional studies were performed by GLP1R or GIPR knockdown, overexpression, and treatment with single or dual receptor agonists, followed by assessment of cell proliferation and multilineage differentiation capacities. Transcriptome (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA immunoprecipitation sequencing (RIP-seq) were applied to delineate downstream signaling pathways and RNA–protein interactions. Protein synthesis regulation was further investigated by immunoprecipitation of interferon induced protein with tetratricopeptide repeats (IFIT)-associated translation initiation factors. For in vivo validation, wild-type and GLP1R/GIPR double-knockout periodontitis mice were transplanted with CRISPR-Cas9 mCherry-labeled PDLSCs and treated with receptor agonists. Disease severity and PDLSC fate were evaluated by histology and lineage tracing. Finally, a questionnaire-based survey was conducted in 150 patients with periodontitis, including 74 individuals with long-term use (> 1 month) of GLP1R or GLP1R/GIPR dual agonists (e.g., semaglutide, liraglutide, tirzepatide), to assess their periodontal outcomes. GLP1R and GIPR expression were markedly downregulated in PDLSCs exposed to multiple stressors and in PDLSCs isolated from periodontitis specimens. RNA-seq, ChIP-seq, and RIP-seq identified downstream pathways and RNA–protein interactions implicated in receptor-mediated regulation. Functionally, GIPR agonism promoted PDLSC proliferation via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, whereas GLP1R agonist enhanced multilineage differentiation capacity in vitro. Mechanistically, GLP1R knockdown induced robust upregulation of IFIT1/2/3, while GLP1R agonist suppressed IFIT expression. IFIT1/2/3 were shown to interact with eIF3C and to inhibit translation of differentiation-related mRNAs, linking GLP1R signaling to translational control of PDLSC fate. In vivo, transplantation experiments in both wild-type and GLP1R/GIPR double-knockout periodontitis mice demonstrated that single and dual receptor agonists significantly improved endogenous and exogenous PDLSC-mediated periodontal regeneration. Consistently, a clinical survey of 150 patients with periodontitis (74 receiving GLP1R or dual agonists) revealed significantly better periodontal staging and grading in treated individuals, with longer agonist exposure associated with greater improvement. Our findings uncover the different molecular roles of GIPR and GLP1R in self-renewal capacity and multipotency of PDLSCs, and open new avenues for developing therapeutic targets and strategies in oral tissue engineering and regenerative medicine. The online version contains supplementary material available at 10.1186/s11658-026-00867-2. Show less
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Gene Show more
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Genetic risk factors strongly influence LBD susceptibility, including SNCA multiplication, particularly triplication, and the apolipoprotein E ε4 allele (APOE4), the strongest common genetic risk factor for LBD. While SNCA is predominantly expressed in neurons and APOE primarily in glial cells, how these genetic factors converge to impact neuronal vulnerability and regional pathology in the human brain remains poorly understood. Here, we applied spatial transcriptomics to postmortem temporal cortex tissue from LBD cases with SNCA triplication or different APOE genotypes, alongside age- and sex-matched controls, to map gene expression within intact cortical architecture. We identified layer 5 of the gray matter as a particularly vulnerable region, characterized by elevated SNCA expression, pronounced synaptic and metabolic dysregulation, and exacerbation of these alterations in APOE4 carriers. Reelin signaling emerged as a core Lewy body-associated pathway disrupted across cortical layers, validated in independent postmortem cohorts and human-induced pluripotent stem cell (iPSC)-derived cortical organoids. In contrast, white matter exhibited distinct molecular alterations, including disrupted myelination pathways, with APOE4 carriers showing increased myelin debris and glial responses compared with non-carriers. Cell-type deconvolution informed by single-nucleus RNA sequencing further revealed APOE4-associated impairments in neuronal vulnerability and intercellular communication. Together, these findings define spatially and cell-type-specific mechanisms through which SNCA dosage and APOE4 genotype impact LBD pathology, providing insight into regionally distinct disease processes and potential targets for genetically stratified therapeutic interventions. Show less
Guangming Li, Yi Jin, Xiaowei Yuan+4 more · 2026 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here Show more
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here, we applied an integrative framework combining network toxicology, Mendelian randomization (MR), multi-omics analyses, molecular docking, molecular dynamics simulations, and in vitro experiments to elucidate the mechanisms underlying DBP-associated HNSC. Lipoprotein lipase (LPL) was identified as the sole overlapping gene between DBP-related targets and HNSC-associated genes. MR analysis supported a potential causal relationship between LPL and HNSC susceptibility. Expression profiling demonstrated tissue- and cell type-specific patterns of LPL and its dysregulation in HNSC, with associations to tumor stage and prognosis. Genomic analyses revealed that LPL alterations were infrequent and mainly driven by copy number loss. LPL expression positively correlated with immune and stromal infiltration. Enrichment analyses implicated immune regulation and PI3K-AKT signaling. Molecular simulations showed stable DBP-LPL binding. Functionally, DBP promoted SCC9 proliferation and reduced LPL expression, and was associated with transcriptional changes in PI3K-AKT-mTOR-related genes, whereas LPL restoration mitigated these effects. These findings reveal a novel DBP-LPL axis in HNSC. 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
Metabolic syndrome (MetS) is a recognized risk factor for prostate cancer (PCa), yet the precise biological mechanisms driving this association remain poorly understood. Unraveling these molecular pat Show more
Metabolic syndrome (MetS) is a recognized risk factor for prostate cancer (PCa), yet the precise biological mechanisms driving this association remain poorly understood. Unraveling these molecular pathways is essential for developing targeted interventions to improve patient outcomes. In this study, we analyzed NHANES (2005-2014) data to examine associations between MetS and PCa outcomes, finding that MetS was significantly associated with higher PCa risk (OR = 1.52), all-cause mortality (HR = 1.53), and cancer-specific mortality (HR = 2.17). Through integrated multi-omics, weighted gene co-expression network analysis, and machine learning, we identified the orphan receptor GPRC5B as a critical hub gene downregulated in both conditions. Single-cell transcriptomic analysis further confirmed that GPRC5B is predominantly expressed in endothelial cells. Mechanistically, GPRC5B loss was found to hyperactivate p38 MAPK signaling through a specific dual mechanism: increasing phosphorylation of upstream MKK3/6 kinases while concurrently suppressing the negative feedback phosphatase DUSP1. This synergistic dysregulation drove enhanced endothelial proliferation, migration, and tube formation in vitro. In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression. Show less
Hyposalivation affects cognitive function. However, its impact on hippocampus-dependent memory remains unclear. Saliva contains brain-derived neurotrophic factor (BDNF), which is also synthesized in t Show more
Hyposalivation affects cognitive function. However, its impact on hippocampus-dependent memory remains unclear. Saliva contains brain-derived neurotrophic factor (BDNF), which is also synthesized in the hippocampus and can pass through the blood-brain barrier (BBB) to influence hippocampal plasticity. Therefore, we hypothesized that hyposalivation reduces peripheral BDNF availability, leading to decreased hippocampal BDNF levels and cognitive impairment. In this study, this relationship was investigated using an in vivo model of sialadenectomy-induced hyposalivation. A total of 24 8-week-old male ddY mice were divided into control and extraction (EXT) groups. The EXT group underwent submandibular and sublingual salivary gland extractions, whereas the control group underwent a sham operation. Saliva was collected at baseline (0 weeks) and at 2- and 3-weeks postoperatively. Cognitive function was assessed using the Y-maze, fear conditioning (FC), novel object recognition (NOR), and object location tests (OLT). Anxiety-like behavior was evaluated using the open field test (OFT) and elevated plus-maze (EPM) tests. Hippocampi were collected at 3 weeks post-operation for BDNF quantification using enzyme-linked immunosorbent assay, and its concentration in subregions of the hippocampus was determined by semi-quantitative analysis. Hyposalivation significantly impaired spatial working memory in the Y-maze test and contextual fear memory in the FC, both of which are hippocampus-dependent. NOR showed only a transient deficit at 24 h during the 2-week period (no significant difference in 3-week post-operation), whereas long-term spatial memory measured by the OLT exhibited a persistent 24-h impairment at both 2 and 3 weeks, indicating reduced long-term spatial memory rather than accelerated decay. No significant differences were observed in anxiety-like behavior. Although sialoadenectomy significantly reduced salivary secretion and total salivary BDNF output, the concentration of BDNF in saliva in both groups remained unchanged at 2- and 3-weeks post-operation. However, hippocampal BDNF levels were significantly lower in the EXT group than in the control group. These findings suggest that hyposalivation may selectively impair hippocampus-related spatial memory without affecting recognition memory or anxiety-related behaviors. Show less
Atherosclerosis is a lipid-driven chronic inflammatory process, in which the functional status of macrophages significantly influences its initiation, progression, and eventual outcomes. Tartrate-Resi Show more
Atherosclerosis is a lipid-driven chronic inflammatory process, in which the functional status of macrophages significantly influences its initiation, progression, and eventual outcomes. Tartrate-Resistant Acid Phosphatase 5 (ACP5) has been shown to be highly expressed in various cancers and serves as a serum biomarker for extensive bone metastasis and poor prognosis. However, its role and underlying mechanisms in atherosclerosis remain largely unknown. In this study, we found that high-fat diet-fed Apoe Show less