Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. Show more
Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. In this study, we designed a polysaccharide-based carrier (HF-AF) from fucoidan, featuring a dynamic supramolecular structure. A dynamic supramolecular network was established within this carrier via dynamic supramolecular interactions between hydroxypropyl-β-cyclodextrin and adamantane-methylamine. The anti-inflammatory compound tilianin, formulated into nanocrystals (Til NCs), was then encapsulated to create a shear-responsive nanosystem (HF-AF@Til NCs). The system's primary therapeutic strategy is its response to pathological hemodynamic forces: upon encountering high shear stress at a stenosis, the supramolecular network undergoes dissociation, triggering a mechanically-gated release of the encapsulated Til NCs. This shear-triggered function is complemented by the natural P-selectin affinity of the fucoidan backbone, which facilitates the anchoring of the nanocarrier at the inflamed lesion site. This sophisticated "anchor-and-release" mechanism enables superior drug accumulation precisely at plaque sites. In ApoE Show less
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
Atherosclerotic plaque destabilization during acute infections such as pneumonia represents a critical clinical challenge, yet the underlying molecular dynamics remain poorly characterized. This study Show more
Atherosclerotic plaque destabilization during acute infections such as pneumonia represents a critical clinical challenge, yet the underlying molecular dynamics remain poorly characterized. This study introduces a furin-responsive photoacoustic/fluorescence dual-modal probe (FRP) to investigate intraplaque furin activity in ApoE Show less
Timosaponin AIII (Tim-AIII), a steroidal saponin derived from Anemarrhena asphodeloides, has emerged as a promising antitumor agent, yet its precise molecular targets and mechanisms in breast cancer r Show more
Timosaponin AIII (Tim-AIII), a steroidal saponin derived from Anemarrhena asphodeloides, has emerged as a promising antitumor agent, yet its precise molecular targets and mechanisms in breast cancer remain poorly defined. Here, we identify fibroblast growth factor 2 (FGF2) as a direct binding target of Tim-AIII using a combination of network pharmacology, CETSA, and surface plasmon resonance assays. Mechanistically, Tim-AIII exhibits a dual therapeutic mode of action. First, it induces reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, activating the eIF2α-ATF4-CHOP axis and initiating apoptosis. Second, it dampens the FGF2-FGFR1-PI3K/AKT signaling cascade, thereby inhibiting epithelial-mesenchymal transition (EMT) and suppressing cell migration and invasion. RNA sequencing and enrichment analyses confirm that Tim-AIII regulates critical oncogenic pathways, including ER stress, calcium signaling, and PI3K/AKT. In vivo evaluations demonstrate that Tim-AIII significantly reduces tumor growth without detectable systemic toxicity in breast cancer-bearing mice. This study not only elucidates the molecular basis of Tim-AIII's antitumor efficacy but also positions it as a potential targeted therapeutic for breast cancer, with dual action on ERS-induced apoptosis and EMT suppression. Show less
The repair mechanisms following sciatic nerve injury involve complex signaling interactions between neurons and microglia. Recent studies have demonstrated that neurons activate microglia by releasing Show more
The repair mechanisms following sciatic nerve injury involve complex signaling interactions between neurons and microglia. Recent studies have demonstrated that neurons activate microglia by releasing chemokines, glutamate, and neurotrophic factors. In turn, microglia regulate neuronal survival and regeneration via phagocytosis, phenotypic switching, and secretion of growth factors. However, the spatiotemporal diversity of signaling pathways, metabolic regulation of the microenvironment, and barriers to clinical application remain inadequately addressed. This review provides a comprehensive analysis of morphological and functional changes in neuronal cell bodies and of the activation and regulatory mechanisms of microglia after sciatic nerve injury. It highlights the dynamic interaction network encompassing the ATP-P2X7 signaling pathway, the CX3CL1- CX3CR1 pathway, the CCL2-CCR2 chemokine axis, the BDNF-TrkB pathway, and inflammatory mediators, offering novel insights into precision therapeutic strategies targeting neuron-glial interactions. Show less
Given that abnormal lipid metabolism is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), this study seeks to investigate the relationship between serum lipoprotein(a) [L Show more
Given that abnormal lipid metabolism is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), this study seeks to investigate the relationship between serum lipoprotein(a) [Lp(a)] levels and the progression or regression of MASLD. A total of 12,962 participants undergoing transient elastography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University were included in the first cross-sectional study (Study 1). The longitudinal study (Study 2) included 17,661 individuals from the same center, each with at least two health check-ups involving abdominal ultrasonography. Another cross-sectional study (Study 3) included 5,927 individuals from the UK Biobank cohort who had undergone both magnetic resonance imaging proton density fat fraction (MRI-PDFF) and Lp(a) testing. Cross-sectional analysis (Study 1) revealed that elevated Lp(a) levels were inversely correlated with the severity of both hepatic steatosis and fibrosis. Longitudinal data (Study 2) further demonstrated that baseline serum Lp(a) levels were decreased in participants with the incident of MASLD, while increased in participants with the regression of MASLD during the follow-up period. A lower baseline Lp(a) level was an independent factor for new-onset MASLD and non-regression of MASLD: the fully adjusted hazard ratios (HR) were 0.895 (95%CI 0.834-0.962, Serum Lp(a) levels are inversely associated with both the progression and regression of MASLD, indicating its potential role in reflecting disease dynamics. 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
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
Dementia is a growing public health concern, and although diet is a modifiable potential risk factor, the role of free sugar intake remains unclear. Excess sugar has been linked to metabolic and cardi Show more
Dementia is a growing public health concern, and although diet is a modifiable potential risk factor, the role of free sugar intake remains unclear. Excess sugar has been linked to metabolic and cardiovascular dysfunction, both associated with cognitive decline, but evidence regarding specific sugar sources is limited. This study aimed to investigate the associations between free sugar intake, its dietary sources, and the risk of all-cause dementia, Alzheimer's disease, and vascular dementia, and to assess potential modification by apolipoprotein E (APOE) ε4 status. We included 27,786 participants without dementia at baseline (mean age: 58 y; 61% females) from the Malmö Diet and Cancer Study, a population-based prospective cohort. Dietary intake was assessed using a validated diet history method. Dementia diagnoses were obtained from national registers and validated by memory clinic physicians. During a median follow-up of 25 y, 3224 participants (11.6%) were diagnosed with dementia. Free sugar intake was not significantly associated with all-cause dementia or Alzheimer's disease. However, a U-shaped association was observed for vascular dementia, with moderate intake (10%-12.5% of energy) associated with lower risk [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.52, 0.95]. Sugar-sweetened beverage intake showed no association with dementia risk. High chocolate intake was associated with lower risks of all-cause [HR for quintile 5 (Q5) compared with Q1: 0.81; 95% CI: 0.72, 0.91] and vascular dementia (HR for Q5 compared with Q1: 0.68; 95% CI: 0.50, 0.92), whereas high jam/marmalade intake was linked to a lower risk of all-cause dementia (HR: 0.86; 95% CI: 0.77, 0.97 for >10 servings per week compared with <0.5 servings per week). No significant interactions with APOE ε4 status were observed. Free sugar intake was not associated with overall dementia risk, but moderate intake may reduce the risk of vascular dementia. These findings suggest that future dietary guidelines for cognitive health should consider not only sugar quantity but also its food source. 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
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
The clinical interpretation of Alzheimer's disease (AD) is frequently complicated by the prevalence of missense variants designated as being of uncertain significance within associated genes. Conventi Show more
The clinical interpretation of Alzheimer's disease (AD) is frequently complicated by the prevalence of missense variants designated as being of uncertain significance within associated genes. Conventional computational prediction tools often overlook disease-specific pathophysiological contexts and lack pertinence and interpretability. Therefore, the present study aimed to develop a novel, interpretable framework for predicting the pathogenicity of AD missense variants by integrating transcriptomic and proteomic data enrichment patterns with machine learning methods. A cross-sectional variant-level analysis was performed using publicly available databases. Missense variants in APOE, APP, PSEN1, PSEN2, SORL1, and TREM2 reported in AD patients were retrieved from Alzforum and compared with missense variants from individuals without neurological diseases, as cataloged in the gnomAD v2.1.1 non-neuro subset. Variants were annotated with tissue-specific expression, secondary structure, relative solvent accessibility, and other functional features using tools like AlphaFold. Enrichment of specific features was assessed with Fisher's exact tests with Bonferroni correction for multiple comparisons. Given that PSEN1 showed the strongest enrichment signals, six machine-learning algorithms were trained on PSEN1 variants to distinguish AD-associated variants from gnomAD variants, using a 10 × 5 nested cross-validation scheme. External validation was conducted using PSEN1 missense variants from ClinVar annotated as pathogenic/likely pathogenic or benign/likely benign. Model performance was compared with SIFT and PolyPhen-2, and interpretability was evaluated by feature ablation and SHapley Additive exPlanations analyses. AD-associated variants exhibited statistically significant enrichment within some transcriptomic or proteomic features, with PSEN1 contributing significantly to the enrichment observed across these features. Random forest and gradient boosting models achieved high performance in the internal training dataset and maintained high recall in the external validation dataset, outperforming SIFT and approaching the performance of PolyPhen-2. Relative solvent accessibility was the most discriminative individual feature, while regional and topological features provided complementary discriminative power. This integrative, multi-omics framework links disease-specific enrichment patterns with interpretable gene-level machine learning for AD missense variants. The results highlight the importance of expression level, structural context, etc. for PSEN1 variant pathogenicity and may help prioritize variants for functional studies. Further validation in additional genes and independent cohorts is warranted prior to any clinical application. 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
We examined whether the excess cardiovascular disease (CVD) risk among adults with steatotic liver disease (SLD) subtypes could be reduced or eliminated through joint control of low-density lipoprotei Show more
We examined whether the excess cardiovascular disease (CVD) risk among adults with steatotic liver disease (SLD) subtypes could be reduced or eliminated through joint control of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and high-sensitivity C-reactive protein (hs-CRP). This prospective cohort study included 291,995 participants from the UK Biobank, comprising 77,187 with metabolic dysfunction-associated steatotic liver disease (MASLD), 22,190 with metabolic dysfunction and alcohol-associated liver disease (MetALD), 5474 with alcohol-associated liver disease (ALD), and 187,144 without SLD. Cox proportional hazards models were used to assess CVD risk associated with numbers of LDL-C, Lp(a), and hs-CRP controlled within the target range. During 12 years of median follow-up, 24,251 CVD events were documented, with 19,661 coronary heart disease and 5600 stroke. Among individuals with various SLD subtypes, those with all three factors controlled had the lowest risks of CVD, with HRs (95% CIs) of 0.65 (0.58, 0.72) in MASLD, 0.61 (0.49, 0.76) in MetALD, and 0.57 (0.35, 0.93) in ALD when comparing to zero-factor control. In addition, among individuals with SLD subtypes achieving all three factors within target ranges, the HRs (95% CIs) of CVD were 0.97 (0.88, 1.07) in MASLD, 0.90 (0.75, 1.08) in MetALD, and 0.63 (0.42, 0.95) in ALD, as compared with non-SLD controls. Similar association patterns were observed for coronary heart disease and stroke. Participants with various SLD subtypes who had optimally controlled LDL-C, Lp(a), and hs-CRP showed no excess or even lower risk of CVD as compared with the general population. Not available. 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
With the widespread use of smartphones among adolescents, smartphone addiction has become a growing mental health concern. Adolescents' limited self-regulation makes them particularly vulnerable to us Show more
With the widespread use of smartphones among adolescents, smartphone addiction has become a growing mental health concern. Adolescents' limited self-regulation makes them particularly vulnerable to using smartphones to escape real-life stress, heightening addiction risk. However, the heterogeneity of addictive behaviors and the dynamic role of experiential avoidance have been underexplored. This 6-month longitudinal study surveyed 547 Chinese primary and secondary students using the Smartphone Addiction Scale (SAS) and the Acceptance and Action Questionnaire-II (AAQ-II). Latent profile analysis (LPA) and latent transition analysis (LTA) were applied to identify subgroups and examine transitions between these subgroups. Cross-lagged panel network analysis (CLPN) revealed key symptom interactions between experiential avoidance and addiction. The study identified two addiction subgroups: a stable "low-risk group" (84.9 percent) and a "high-risk group," 51.4 percent of whom transitioned to low risk over time. Logistic regression showed that experiential avoidance significantly predicted high-risk membership (odds ratios [OR] = 1.083-1.102) and deterioration within the low-risk group (OR = 1.036). The CLPN identified "online intimacy" (SPA-3) and "hesitation and overcautious" (EA-7) as driver nodes, with "withdrawal symptoms" (SPA-2) serving as a central node. These findings emphasize the crucial role of experiential avoidance in adolescent smartphone addiction and suggest symptom-level targets for early intervention. The results support acceptance and commitment therapy (ACT) as a promising approach for reducing smartphone addiction among youth. 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
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to Show more
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore the therapeutic potential of RTG against CRS-induced depression-like behaviors and cognitive deficits in mice and to uncover the associated molecular mechanisms. A depression-like and cognitive impairment model was established in C57BL/6 male mice using chronic restraint stress (CRS). Six-week-old C57BL/6 male mice were randomly assigned to the following groups: control (Con), model (CRS), RTG (10 mg/kg), XE-991 (2 mg/kg) or tunicamycin (Tm, 2 mg/kg). Behavioral tests were conducted to assess depression-like behaviors and cognitive function. Hippocampal neuronal morphology was examined by H&E and immunofluorescence staining, while changes in endoplasmic reticulum stress (ERS)-related signaling pathways were analyzed by Western blot. Retigabine treatment reduced hippocampal neuronal damage and the expression of ERS-related factors (GRP78, CHOP) and the pro-apoptotic factor BAX in CRS-induced mice, while it increased the levels of BDNF. These effects were antagonized by XE-991 and the ERS agonist tunicamycin (Tm). Retigabine may alleviate CRS-induced depressive-like behaviors and cognitive impairment by inhibiting ERS-mediated apoptosis, suggesting its potential as a novel therapeutic strategy for depression. 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
To investigate the association between vaginal microbiota structure in early pregnancy and gestational diabetes mellitus (GDM) and to characterize microbial signatures for early screening for GDM. The Show more
To investigate the association between vaginal microbiota structure in early pregnancy and gestational diabetes mellitus (GDM) and to characterize microbial signatures for early screening for GDM. The present study was a nested case-control study recruiting pregnant women from the Nanjing Gulou Maternal-Child Health Center, China. Vaginal swabs were collected before 20 weeks of gestation for 16S rRNA sequencing. Following 1:3 propensity score matching, 45 GDM cases and 135 controls were enrolled. The final analysis included 42 GDM cases and 121 controls. A random forest model was used to explore the genera of vaginal differential microbiota associated with GDM. Based on these findings, latent profile analysis (LPA) was conducted to explore potential types of vaginal microbiota, and logistic regression was used to analyze the association between vaginal microbiota types and GDM. The GDM group exhibited elevated alpha diversity (Chao1 index, The composition and structure of vaginal microbiota in early pregnancy are different in the two groups. The vaginal microbiota in early pregnancy, which is characterized by co-dominated by The online version contains supplementary material available at 10.1186/s12866-026-04910-2. Show less
The objective of this research was to investigate the association between non-traditional lipid parameters and optical coherence tomography (OCT)-characterized high-risk plaques in patients with acute Show more
The objective of this research was to investigate the association between non-traditional lipid parameters and optical coherence tomography (OCT)-characterized high-risk plaques in patients with acute myocardial infarction (AMI). This retrospective study included 249 first-episode AMI patients admitted to the First Affiliated Hospital of Lanzhou University between January 2022 and December 2024. All patients underwent OCT-guided assessment of culprit lesions before revascularization. High-risk plaques were defined by more than two of the following features: lipid arc ≥90 °, fibrous cap thickness <65 μm, or plaque rupture/thrombus. Lesions with fewer than two of these criteria were classified as non-high-risk plaques. Clinical and laboratory data were collected, and a comprehensive lipid profile was calculated, including traditional indicators [e.g., non-HDL cholesterol (non-HDL-C)] and non-traditional ratios [e.g., apolipoprotein B/A1 ratio (ApoB/A1)]. Spearman correlation was used to assess relationships between lipid parameters and high-risk plaques. After excluding collinear variables, logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed. Model discrimination and clinical value were evaluated using receiver operating characteristic (ROC) curves, the DeLong test, integrated discrimination improvement (IDI), net reclassification index (NRI), and decision curve analysis (DCA). Among 249 AMI patients, 137 (55.0%) exhibited OCT-characterized high-risk plaques. These patients were more often male (89.8%) and presented with STEMI (84.7%). They had elevated levels of myoglobin, LDL-C, non-HDL-C, ApoB, ApoB/A1, remnant lipoprotein cholesterol (RLP-C), non-HDL-C/HDL-C ratio (NHHR), and TC/HDL-C (all Both the non-traditional ApoB/A1 ratio and the traditional lipid marker non-HDL-C were independently and linearly associated with OCT-characterized high-risk plaques in AMI. Their combined assessment enhanced the identification of high-risk plaques morphology. Show less
Neuroinflammation is a key pathogenic process in multiple central nervous system (CNS) disorders. It can lead to neuronal injury and cognitive decline through excessive glial activation and aberrant e Show more
Neuroinflammation is a key pathogenic process in multiple central nervous system (CNS) disorders. It can lead to neuronal injury and cognitive decline through excessive glial activation and aberrant engagement of the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint axis. To address these pathologies, we engineered a PD-1-enriched macrophage-membrane, lactoferrin-modified, PEGylated, glycyrrhizic-acid-loaded biomimetic hybrid liposome (PMLpGL) for dual, precise modulation of the neuroinflammatory microenvironment. PMLpGL alleviates neuronal inhibitory signaling by reversibly sequestering excess PD-L1 via membrane-anchored PD-1, while its cargo GA suppresses high-mobility group box-1 (HMGB1)-driven inflammatory cascades, thereby returning inducible PD-1/PD-L1 expression and glial activation toward homeostasis. Physicochemical characterization showed a hydrodynamic diameter of 165 ± 3 nm and a zeta potential of -10.2 ± 0.2 mV. Engineered macrophage membranes displayed marked PD-1 overexpression, and ligand-depletion saturation assays demonstrated specific, saturable PD-1/PD-L1 binding. In a Transwell blood-brain barrier (BBB) model, PMLpGL achieved a 24-h permeability of 22.86 ± 0.14 %, indicating robust in-vitro BBB traversal. In vivo fluorescence imaging showed peak brain accumulation at 24 h with retention to 48 h; liquid chromatography-tandem mass spectrometry further confirmed brain targeting and persistence-at 12 h, brain GA with PMLpGL was ∼48-fold higher than free drug and remained quantifiable at 48 h. Pharmacodynamic evaluations in cells and mice demonstrated that PMLpGL suppresses glial activation and normalizes inducible checkpoint expression; reshapes the cytokine milieu by lowering IL-6, IL-1β, TNF-α, and HMGB1 while increasing IL-10, TGF-β, and brain-derived neurotrophic factor; and restores the synaptic protein synapsin-1. Correspondingly, PMLpGL significantly improved cognition in open-field, novel object recognition, and Morris water maze tests. Collectively, PMLpGL combines PD-1 decoy sequestration with GA-mediated upstream immunomodulation to attenuate neuroinflammatory cascades, protect neurons, and reverse cognitive deficits. By pairing BBB compatibility with microenvironment-precise regulation, this platform offers a promising therapeutic strategy for CNS diseases associated with cognitive decline. 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
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
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