Atherosclerotic lesions commonly develop in curved or bifurcated arteries, where blood flow exhibits characteristics of low shear stress (LSS). Subjected to LSS continually, endothelial cells (ECs) ad Show more
Atherosclerotic lesions commonly develop in curved or bifurcated arteries, where blood flow exhibits characteristics of low shear stress (LSS). Subjected to LSS continually, endothelial cells (ECs) adopt a pro-atherosclerotic phenotype. Ferroptosis is a recently identified form of controlled cell demise prompted by iron-dependent buildup of cellular reactive oxygen species (ROS), which has been associated with diverse cardiovascular diseases, particularly atherosclerosis (AS). P53 is a broadly acting tumor suppressor that can be activated by diverse stimuli and mediates multiple biological outcomes, including cell cycle arrest, DNA repair, apoptosis, and ferroptosis. However, it remains unknown whether LSS promotes the development of AS by inducing P53-dependent ferroptosis in endothelial cells. In our experiments, we induced LSS by partial ligation of the right common carotid artery in high-fat diet-fed (HFD) male ApoE Our findings demonstrated that LSS induced endothelial ferroptosis, which in turn accelerated AS development both in vivo and in vitro. This effect was partially counteracted by both the ferroptosis inhibitor Fer-1 and endothelium-specific glutathione peroxidase 4 (GPX4) overexpression in ApoE Our experiments suggested that LSS promotes atherosclerosis by inducing endothelial ferroptosis through the P53/xCT signaling pathway. Show less
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progre Show more
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progression. Although ChREBP (key metabolic regulator) protects against NP, its specific mechanisms remain unclear. NP rat model was established via spared nerve injury (SNI) surgery, and mechanical allodynia was evaluated using Von Frey tests. ChREBP expression in microglia was detected through immunofluorescence, RT-qPCR, and western blot. Functional studies involved ChREBP knockdown/overexpression to assess effects on microglial polarization, neuroinflammation, neuronal excitability, pain behaviors, and fatty acid metabolism. Mechanisms were explored via dual-luciferase reporter and chromatin immunoprecipitation assays. Mechanical pain thresholds were significantly decreased on the ipsilateral side after SNI. ChREBP was upregulated in SDH microglia after SNI and in LPS-stimulated microglia in vitro. ChREBP knockdown inhibited anti-inflammatory microglial polarization, exacerbated neuroinflammation, and aggravated pain. Conversely, ChREBP overexpression promoted the anti-inflammatory phenotype, suppressed neuroinflammation, and alleviated pain. ChREBP enhanced microglial fatty acid oxidation and energy metabolism. Mechanistically, ChREBP bound to the TFBS1 site on the PGC-1α promoter to activate its transcription. PGC-1α overexpression rescued the impairments caused by ChREBP knockdown, including reduced fatty acid oxidation, suppressed anti-inflammatory polarization, elevated inflammatory factors, and increased neuronal excitability. The protective effects of ChREBP were attenuated by the fatty acid oxidation inhibitor Etomoxir. ChREBP alleviates NP by enhancing microglial fatty acid oxidation and anti-inflammatory phenotype via PGC-1α transcriptional activation, revealing a novel metabolic-immune axis for potential NP therapy. Show less
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fue Show more
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fuels the development of an immunosuppressive tumor microenvironment, while crosstalk between immunity and angiogenesis further propels tumor immune evasion and treatment resistance. The present study aimed to establish a penpulimab-resistant model, delineate anti-PD-1 resistance traits via single-cell RNA sequencing, and unravel the precise mechanisms through which anlotinib-an anti-angiogenic agent-mitigates penpulimab resistance. These findings offer insights to guide clinical management of immune-pretreated patients. Single-cell sequencing analyses demonstrated that anlotinib reverses penpulimab resistance by reprogramming the tumor immune microenvironment, thereby boosting PD-1 blockade efficacy via modulation of immune infiltration and tumor signaling pathways. Identifying Apoe⁺ M2 macrophages, Srgn⁺ M1 macrophages, and Cxcl2⁺ T cells provides key cellular and molecular targets for developing clinically actionable immunotherapies. Taken together, this work validates the preclinical potential of anlotinib combined with immunotherapy for immunotherapy-resistant tumors. Show less
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Ath Show more
Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis. Fifty C57BL/6J ApoE Atherosclerotic plaques accumulated in the aorta and aortic sinus after HFD, while statin and high-dose GP alleviated this burden. TC, TG, LDL-C, MCP-1, MCP-3 and IL-2 showed significant increase after HFD, while statin and GP decreased LDL-C, MCP-1 and MCP-3. The goblet cells, ZO-1 and Occludin decreased after HFD, while statin and GP increased them, indicating that the intestinal barrier integrity was improved. Additionally, the composition of gut microbiota was modulated by GP. Some candidate taxa were identified, such as This study suggests that GP is beneficial for alleviating atherosclerosis in HFD-induced ApoE Show less
Adolescence is a critical period for rapid emotional and cognitive development. Depression and cognitive impairment frequently co-occur in this population, yet their comorbidity patterns and symptom-l Show more
Adolescence is a critical period for rapid emotional and cognitive development. Depression and cognitive impairment frequently co-occur in this population, yet their comorbidity patterns and symptom-level interactions remain insufficiently explored. A total of 2,244 students (mean age = 16.8 ± 0.84 years; 1,218 males, 1,026 females) from a high school in Heilongjiang Province, China, were recruited. Depressive symptoms and cognitive impairment were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Perceived Deficits Questionnaire–Depression (PDQ-D). Latent profile analysis (LPA) was applied to identify subgroups, followed by network analysis to examine central symptoms (expected influence, EI), bridge symptoms (bridge expected influence, BEI), and network differences (NCT). The optimal LPA model identified three comorbidity subgroups: low, moderate, and high. NCT revealed significant differences in network structure and global strength between the low–moderate (S = 1.514, Adolescent Depression and Cognitive Impairment can be classified into low, moderate, and high comorbidity subgroups. Somatic symptoms emerged as the central symptom, while prospective memory impairment and interpersonal problems were identified as key bridge symptoms, suggesting potential intervention targets for early screening and stratified treatment. Not applicable. The online version contains supplementary material available at 10.1186/s12888-026-07946-w. 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
Although glass-based long-persistent luminescence (LPL) materials offer superior transparency and integration capability compared with conventional phosphors, their emission has been predominantly res Show more
Although glass-based long-persistent luminescence (LPL) materials offer superior transparency and integration capability compared with conventional phosphors, their emission has been predominantly restricted to the blue-green region, leaving warm-color LPL largely unexplored. In this work, Mn Show less
Dysregulation of low-density lipoprotein (LDL) cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease. Endogenous molecules targeting LDL clearanc Show more
Dysregulation of low-density lipoprotein (LDL) cholesterol is strongly correlated with the risk of metabolic dysfunction-associated steatotic liver disease. Endogenous molecules targeting LDL clearance play crucial roles in the progression of liver steatosis. Human cathelicidin LL-37 can form complexes with lipoproteins, but whether these complexes regulate lipoprotein-driven cholesterol metabolism is not clear. Here, we find that cathelicidin LL-37 binds to LDL via apolipoprotein (Apo)B-100 domains, enhancing the solubility of ApoB-100 and inhibiting the modifications and aggregation of LDL. LL-37-LDL interaction promotes LDL uptake through LDL receptor (LDLR) both in hepatocytes and macrophages. This interaction also promotes LDL cholesterol clearance by facilitating cholesterol excretion and cholesterol efflux. In Apoe Show less
This study evaluates plasma-based proteomic profiles for predicting amyloid positivity in adults with Down syndrome (DS) and examines the impact of apolipoprotein E ε4 (APOE ε4) on test performance. C Show more
This study evaluates plasma-based proteomic profiles for predicting amyloid positivity in adults with Down syndrome (DS) and examines the impact of apolipoprotein E ε4 (APOE ε4) on test performance. Cross-sectional data from 290 adults with DS were analyzed using single molecule array (SIMOA) technology to measure plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181, and total tau. Amyloid burden was quantified using Pittsburgh Compound B and (18)F-florbetapir Aβ positron emission tomography. Support vector machine analyses were conducted with biomarkers as predictors and age, sex, and APOE ε4 carrier status as covariates. Age, GFAP, and NfL contributed the most to the model performance. The proteomic profile achieved an area under the curve (AUC) of 96% in models with and without APOE ε4. These findings suggest that plasma proteomic biomarkers can effectively identify amyloid positivity in adults with DS and may support clinical triage, monitoring, and selection for clinical trials, independent of APOE ε4 status. Show less
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to c Show more
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to cancer progression remain poorly understood. Here, we identified a lung cancer-specific chimeric RNA KANSL1-ARL17A (chKANSARL) and its circular variant fusion circular RNA KANSL1-ARL17 A (F-circKA), both derived from the fusion gene KANSARL. Functional assays revealed that overexpression of either chKANSARL or F-circKA significantly enhanced lung cancer cell proliferation, migration, and invasion, while their knockdown suppressed these malignant phenotypes. In vivo experiments demonstrated that chKANSARL overexpression accelerated tumor growth in immunodeficient mice. Notably, coexpression experiments uncovered a synergistic regulatory interaction between F-circKA and chKANSARL, amplifying oncogenic effects. Mechanistically, miRNA sequencing and dual-luciferase assays revealed that F-circKA acts as a molecular sponge for miR-6860, thereby derepressing chKANSARL expression. Rescue experiments further validated this regulatory axis, wherein miR-6860 inhibition reversed the tumor-suppressive effects of F-circKA knockdown. Collectively, our study identifies and characterizes a novel F-circKA/miR-6860/chKANSARL regulatory axis, revealing how dual transcriptional outputs from the KANSARL fusion gene can synergistically drive lung cancer progression. These findings highlight a previously unrecognized layer of cooperative regulation between linear and circular fusion RNAs in oncogenesis and provide a new framework for understanding fusion gene-mediated tumorigenesis. Show less
Individuals with prediabetes or diabetes face elevated dementia risk, yet robust prediction tools and mechanistic insights remain limited. This study aimed to develop and validate a protein-based risk Show more
Individuals with prediabetes or diabetes face elevated dementia risk, yet robust prediction tools and mechanistic insights remain limited. This study aimed to develop and validate a protein-based risk score for dementia prediction in this high-risk population while elucidating underlying biological pathways and therapeutic targets. Utilising data from 10 433 UK Biobank participants with prediabetes or diabetes and proteomic profiling (2911 plasma proteins measured), we developed a dementia protein risk score in a training set ( In the training set, 23 out of 2911 proteins were selected. In the testing set, compared with the basic model (age and sex, C-index: 0.78; 95% confidence interval [CI] 0.74-0.82), the dementia protein risk score (C-index: 0.84; 95% CI 0.81-0.88) significantly improved the performance in predicting incident dementia (C-index increase: 0.06; 95% CI 0.02-0.12), while cardiovascular risk factors, ageing and dementia incidence risk factors (C-index: 0.80; 95% CI 0.76-0.83) and apolipoprotein E (APOE; age and sex included, C-index: 0.81; 95% CI 0.77-0.85) had no significant improvement. Six key proteins (glial fibrillary acidic protein [GFAP], neurofilament light polypeptide [NEFL], Brevican core protein [BCAN], protein MENT [MENT], APOE and growth/differentiation factor 15 [GDF15]) captured the most predictive power. Pathway analyses implicated extracellular matrix remodelling and cholesterol metabolism, whereas Mendelian randomisation identified causal roles for APOE, haematopoietic prostaglandin D synthase (HPGDS), BAG family molecular chaperone regulator 3 (BAG3) and GDF15. Nine proteins were prioritised as druggable targets, including HPGDS, with existing Food and Drug Administration-approved drugs. This study establishes a highly accurate protein-based risk score for dementia prediction (including 6-23 proteins) in individuals with prediabetes or diabetes, uncovering actionable biological pathways and therapeutic targets. The findings enable precision risk stratification and accelerate translational opportunities for dementia prevention in this population. Show less
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). H Show more
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT/enhancer-binding protein beta (C/EBPβ) in hepatocyte maturation. Forced C/EBPβ expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&Tag and luciferase reporter assays confirmed C/EBPβ directly binds to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C/EBPβ and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C/EBPβ at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C/EBPβ as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications. The transcriptional activity of C/EBPβ is regulated by MAPK1 protein within the ERK/MAPK signaling pathway. MAPK1 moves from the cytoplasm into the nucleus and transfers phosphate groups to C/EBPβ. This process reverses the "self-inhibition" state of C/EBPβ and enhances its transcriptional activity on downstream target genes. 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
This study evaluated the efficacy of combining personalized acupuncture with accelerated deep transcranial magnetic stimulation (adTMS) for mild cognitive impairment (MCI). In this randomized, double- Show more
This study evaluated the efficacy of combining personalized acupuncture with accelerated deep transcranial magnetic stimulation (adTMS) for mild cognitive impairment (MCI). In this randomized, double-blind, controlled trial, 120 MCI patients were assigned to a Combined group (personalized acupuncture + active adTMS), a Single Stimulation group (active adTMS + sham acupuncture), or a Placebo group (sham TMS + sham acupuncture). The primary outcome was the change in Montreal Cognitive Assessment (MoCA) score at 12 weeks. Secondary outcomes included P300 latency, magnetic resonance spectroscopy (MRS) NAA/Cr ratio, serum brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), interleukin-6 (IL-6), and the Modified Barthel Index (MBI). The Combined group showed a significantly greater improvement in MoCA scores (3.2 ± 1.3 points) compared to the Single Stimulation (1.9 ± 1.2 points; mean difference 1.3, 95 % CI 0.4 to 2.2) and Placebo groups (1.1 ± 1.0 points; mean difference 2.1, 95 % CI 1.2 to 3.0). The Combined group also demonstrated greater reductions in P300 latency and increases in NAA/Cr ratio and serum BDNF levels than the other groups. The combination of personalized acupuncture and adTMS significantly improves cognitive function in MCI patients, supported by positive changes in electrophysiological and metabolic markers. This integrative approach represents a promising non-pharmacological strategy for MCI.Trial registration: International Traditional Medicine Clinical Trials Registry (ITMCTR2025000652). Show less
Hongbin Zhang, Li Qiao, Fan Yang+5 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Elucidating effective components and mechanisms of traditional Chinese medicine (TCM) formulas remains a critical challenge for modernization. ErShiWei RouDouKou Pills (ESWRDK), a Tibetan formula with Show more
Elucidating effective components and mechanisms of traditional Chinese medicine (TCM) formulas remains a critical challenge for modernization. ErShiWei RouDouKou Pills (ESWRDK), a Tibetan formula with cardiovascular potential, lacks systematic exploration of its anti-atherosclerotic (AS) material basis and mechanisms. A novel six-stage cascade focused strategy integrating three-dimensional filtering mode, qualitative characterization, multi-component quantification, anti-AS efficacy, multi-lipidomics and bioactive compounds evaluation was proposed, advancing TCM research by holistic and multi-layered approach. UHPLC-MS combined with mass defect-ion intensity filtering (MD-ITF), DPIs, Nl and FBMN employed for profiling. Nine characteristic components were quantitated. A 12-week high-fat diet was fed to ApoE Firstly, the MD-ITF method and structural classification was established for complicated matrix. Secondly, 426 chemical components including 74 low-abundance were characterized. Thirdly, 9 characteristic components were quantified, and content distribution were profiled. Fourthly, ESWRDK reduced lipids, inflammation, and aortic plaques in AS mice. Fifthly, a total of 38, 23 and 48 differential biomarkers were identified predominantly linked to glycerophospholipids (GP) metabolism. WB confirmed ESWRDK downregulated hepatic PLA2, upregulated p-AMPK/AMPK and PPAR-α, and suppressed SREBP-1, orchestrating and mitigating lipid dysregulation. Finally, dehydrodiisoeugenol and agarotetrol bound PLA2, formed stable 1:1 static quenchingand inhibited PLA2 activity in vitro. A novel six-stage cascade-focused strategy was successfully established to elucidate ESWRDK's anti-AS mechanisms, offering feasible paradigm for advancing modernization of TCM. Show less
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and Show more
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear. Fourteen-month-old male APP/PS1 mice received 17 weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno-associated virus. Late-life MR improved peripheral glucose/lipid profiles, reduced Aβ deposition, preserved synaptic markers, and suppressed neuroinflammation. MR-induced hepatic FGF21 and brain FGFR1-AMPKα signaling to inhibit NFκB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact. Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21-brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation. Show less
The impact of obstructive sleep apnea (OSA) on subsequent cardiovascular events in patients with acute coronary syndrome (ACS) remains debated. This study aims to investigate whether the association o Show more
The impact of obstructive sleep apnea (OSA) on subsequent cardiovascular events in patients with acute coronary syndrome (ACS) remains debated. This study aims to investigate whether the association of OSA with cardiovascular events is affected by lipoprotein (a) [Lp(a)] levels. This is a sub-analysis of prospective cohort study (OSA-ACS, NCT03362385) enrolled ACS patients. OSA defined as an apnea-hypopnea index ≥15 events/h. The effects of OSA on subsequent cardiovascular outcomes were evaluated across varying Lp(a) thresholds. Coronary plaque features by coronary computed tomography angiography were also analyzed. A total of 1137 patients were enrolled, 608 patients (53.5%) were diagnosed with OSA. At a median follow-up of 3.6 years, OSA was associated with a higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with Lp(a) level > median (HR 1.59, 95% CI 1.12-2.26, p=.009), but not in patients with Lp(a) level ≤ median (HR 1.09, 95% CI 0.80-1.49, p=.60). There were consistent increases in HRs for MACCE in the OSA group with Lp(a) levels rising, as stratified by tertiles or quartiles of Lp(a). In patients with Lp(a) level > median, OSA demonstrated a higher prevalence of ≥1 high-risk plaque (HRP) feature (51.4% vs. 33.3%, p=.03) and low-attenuation plaque (50.0% vs. 32.8, p=.04) per vessel than non-OSA. OSA was associated with a continuously increased cardiovascular risk and a higher prevalence of HRP features as Lp(a) levels rose. Lp(a) may help identify ACS patients at higher cardiovascular risk, in whom the efficacy of OSA treatment should be further investigated. Show less
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain Show more
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain, offering novel therapeutic strategies for neuropsychiatric disorders. Recent findings reveal that beyond their transient psychotropic effects, these compounds activate serotonin 5-HT Show less
C1q/TNF-related proteins (CTRPs) belong to the adipokine family. Here, we aimed to assess the relation of CTRP4 levels in serum and perivascular adipose tissue (PVAT) with coronary artery disease (CAD Show more
C1q/TNF-related proteins (CTRPs) belong to the adipokine family. Here, we aimed to assess the relation of CTRP4 levels in serum and perivascular adipose tissue (PVAT) with coronary artery disease (CAD), and investigate the effect of CTRP4 on atherosclerosis and the underlying mechanisms. CTRP4 levels were examined in serum and epicardial adipose tissue (a major PVAT) from patients with CAD. Atherosclerotic lesions were analysed in CTRP4 CTRP4 levels were lower in serum and epicardial adipose tissue of patients with CAD compared to non-CAD controls. CTRP4 knockout promoted atherosclerosis in ApoE Decreased CTRP4 levels in serum and epicardial adipose tissue are associated with CAD in patients. CTRP4 deficiency promotes the development of atherosclerosis in ApoE Show less
PurposeThis study aims to explore the latent classes of compassion fatigue among intensive care unit (ICU) nurses and identify the factors that influence their compassion fatigue.MethodsBetween Novemb Show more
PurposeThis study aims to explore the latent classes of compassion fatigue among intensive care unit (ICU) nurses and identify the factors that influence their compassion fatigue.MethodsBetween November 2024 and February 2025, 1029 ICU nurses were selected as study participants using convenience sampling. Data were gathered through general demographic questionnaires, the Chinese version of the Short Scale of Compassion Fatigue (CFSS), the Occupational Stress Scale, the Perceived Social Support Scale, as well as the Professional Identity Scale. A latent profile analysis (LPA) was conducted based on the three dimensions of the CFSS as observed indicators. Additionally, factors influencing outcomes were analyzed using both univariate and multivariate logistic regression methods.Ethical considerationsThis study was approved by the Institutional Review Board of the Affiliated Hospital of Qingdao University.ResultsA total of 1029 valid questionnaires were obtained, resulting in an effective response rate of 93.46%. The average score on the ICU Nurse Compassion Fatigue Scale was 60.00 ± 27.36 points. Three distinct profiles were identified: low compassion fatigue-low secondary trauma type (33.04%), moderate compassion fatigue-overall fluctuation type (48.30%), and high compassion fatigue-high burnout type (18.66%). Multivariate logistic regression analysis revealed that health status, sleep quality, highest education level, occupational stress, professional identity, and social support significantly influence the potential compassion fatigue profiles among critical care nurses ( Show less
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angio Show more
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) between January 2019 and December 2021 were enrolled. Baseline Lp(a) was measured before the operation. CIN was defined as an increase in serum creatinine of more than 25% or 44 μmol within 72 h of contrast administration. The relationship between Lp(a) and CIN risk was analyzed. A total of 928 T2DM patients were included. CIN developed in 11.1% (103/928) of patients. The Lp(a) level was significantly higher in patients with CIN than in non-CIN patients (311.12 ± 278.66 vs. 254.19 ± 274.56 mg/L, A higher serum Lp(a) level indicates an increased risk of CIN in T2DM patients undergoing CAG or PCI and can serve as an independent predictor of CIN in this population. This study's findings will aid in the clinical prevention and treatment of contrast agent-induced kidney disease. Show less
Tianpei Ma, Xin Chen, Qingwen Zhao+19 more · 2026 · The journals of gerontology. Series A, Biological sciences and medical sciences · Oxford University Press · added 2026-04-24
Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examine Show more
Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores ( β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores ( β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment. Show less
To observe the effect of moxibustion on the lipid metabolism, aortic arch and mitochondrial structure, PTEN-induced kinase 1 (PINK1)/Parkin signaling pathway, and the expressions of apoptosis-related Show more
To observe the effect of moxibustion on the lipid metabolism, aortic arch and mitochondrial structure, PTEN-induced kinase 1 (PINK1)/Parkin signaling pathway, and the expressions of apoptosis-related proteins in atherosclerotic (AS) mice, so as to explore its potential mechanisms underlying prevention and treatment of AS. Ten C57BL/6J mice were fed with normal chow and used as the control group. Thirty ApoE Compared with the control group, the contents of serum TC, TG and LDL-C, expression levels of PINK1, Parkin, Bax and Caspase3 protein, and the immunoactivity of Parkin and Cyt C were significantly increased ( Moxibustion can improve the lipid metabolism level, relieve pathological injury of the thoracic aorta, restore mitochondrial structure and function in ApoE Show less
The formation and retrieval of reward memories within the hippocampus are critical mechanisms underlying the development of substance use disorder. Nitrous oxide (N
Previous research has suggested that high levels of internet use are associated with lower levels of physical activity. However, recent studies have yielded mixed findings. First, we aim to explore th Show more
Previous research has suggested that high levels of internet use are associated with lower levels of physical activity. However, recent studies have yielded mixed findings. First, we aim to explore the prevalence of internet addiction and sedentary behavior among college students. Second, we examine the relationship between sedentary behavior and body composition. Additionally, we employ latent profile analysis (LPA) to identify subgroups of internet addiction profiles and to explore the associations between these latent profiles and sedentary behavior. This cross-sectional study examined the relationship between sedentary behavior, internet addiction, and body composition among 369 Chinese college students. Sedentary behavior was assessed via self-reported sitting time, internet addiction was measured using a standardized questionnaire, and body composition was evaluated with the InBody 120 device. LPA, an individual-centered method, was used to identify homogeneous subgroups of internet addiction. 42.3 % of students exhibited internet addiction and 72.6 % reported ≥6 h of daily sitting. LPA revealed two distinct profiles of internet addiction-"Regular" (57.2 %) and "Internet addiction" (42.8 %)-highlighting its heterogeneous nature. The findings suggest that age (p = 0.296), gender (p = 0.304), and sedentary time (p = 0.954) may not be the primary factors contributing to these profiles. Policymakers and campus health programs should tailor interventions to distinct internet addiction subgroups. Further research is needed to examine psychological, behavioral, and social contributors, as well as long-term effects. Show less
Immune checkpoint inhibitors (ICIs) have prolonged cancer survival but exacerbated atherosclerotic cardiovascular disease (ASCVD). This research aims to interrogate the underlying mechanism of ICIs-re Show more
Immune checkpoint inhibitors (ICIs) have prolonged cancer survival but exacerbated atherosclerotic cardiovascular disease (ASCVD). This research aims to interrogate the underlying mechanism of ICIs-related atherosclerotic progression and the potential protective effect of Red Yeast Rice (RYR) on it. A tumor-bearing atherosclerotic (TB-AS) mouse model was established by subcutaneously injecting MC38 cells in male ApoE Show less
Gene-environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-s Show more
Gene-environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-sensitive neuroplasticity. Yet, how We conducted a case-control study including 93 patients with first-episode schizophrenia (SZ) and 64 healthy controls. Childhood trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ), and symptom dimensions were evaluated with the Positive and Negative Syndrome Scale (PANSS). Three Patients with SZ exhibited significantly higher CTQ scores across all trauma subtypes compared with controls (all These findings demonstrate that Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, ac Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60-70% of all clinically diagnosed cases worldwide. The growing focus on microglia-neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia-neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia-neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia-neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions. Show less
Endothelial cell (EC) senescence is intimately linked to the development and progression of atherosclerosis. The FGFR2 (fibroblast growth factor receptor 2) signaling is crucial in regulating the phen Show more
Endothelial cell (EC) senescence is intimately linked to the development and progression of atherosclerosis. The FGFR2 (fibroblast growth factor receptor 2) signaling is crucial in regulating the phenotype of ECs. Recent studies have revealed that cell phenotype-specific alternative splicing of FGFR2 premRNA (precursor mRNA) results in the mutually exclusive inclusion of either exon IIIb or IIIc, leading to critical differences in receptor function. This study aimed to investigate the role of FGFR2 alternative splicing in EC senescence and atherosclerosis development, and to elucidate the underlying mechanisms. Clinical samples and animal models were used to assess the association between FGFR2-IIIc isoform expression and EC senescence as well as atherosclerotic plaque formation. The mechanisms underlying FGFR2-IIIc-induced EC senescence were elucidated through a combination of in vivo and in vitro investigations. In addition, genetically engineered mice with endothelial-specific overexpression or knockdown of FGFR2-IIIc were utilized to investigate the impact of FGFR2-IIIc on vascular endothelial senescence and the progression of atherosclerosis. Elevated expression of the FGFR2-IIIc isoform was detected in clinical samples and animal models of aging and atherosclerosis, where it correlated with both EC senescence and atherosclerotic plaque formation. Mechanistically, the alternative splicing-mediated switch from FGFR2-IIIb to FGFR2-IIIc established an FGF2-FGFR2-IIIc autocrine feedback loop, which drove ECs toward a senescence-associated secretory phenotype via the PKC (protein kinase C) ε/STAT3 (signal transducer and activator of transcription) pathway. Senescence-inducing stimuli promoted the binding of the splicing factor hnRNP H1 (heterogeneous nuclear ribonucleoprotein H1) to exon IIIb of the This study reveals that FGFR2 splicing mediated by hnRNP H1 promotes EC senescence and atherosclerosis via an FGF2-FGFR2-IIIc autocrine loop. These findings identify FGFR2-IIIc as a potential therapeutic target for age-related atherosclerosis. Show less