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
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of ph Show more
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC). DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln. RNA sequencing (RNA-seq) was employed to explore the mechanism of PAGln in DIC. Subsequently, the differentially expressed genes (DEGs) were subjected to comprehensive analysis using diverse public databases, and RT-PCR was used to confirm the expression levels of the candidate genes. Finally, molecular docking techniques were used for validation. PAGln effectively prevented both in vivo and in vitro Dox-induced myocardial injury and cell apoptosis. RNA-seq results showed that 40 genes were up-regulated and 54 down-regulated in the Dox group compared to the Con group, displaying opposite changes in the Dox + PAGln group. Enrichment analysis highlighted several mechanisms by which PAGln alleviated Dox-induced cardiotoxicity, including the lipid metabolic process, calcium-mediated signaling, positive regulation of store-operated calcium channel activity, and hypertrophic cardiomyopathy. In vitro and in vivo experiments confirmed that PAGln treatment could reverse the changes in the expression levels of Klb, Ece2, Nmnat2, Casq1, Pak1, and Apob in Dox. Molecular docking results showed that these genes had good binding activity with PAGln. PAGln shows potential in alleviating Dox-induced cardiotoxicity, with Ece2 identified as key regulatory molecules related to endothelial dysfunction. Show less
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
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
While active ingredients from compound Chinese herbal medicines (CCHMs) have demonstrated potential in alleviating symptoms of polycystic ovary syndrome (PCOS), their mechanisms of action remain insuf Show more
While active ingredients from compound Chinese herbal medicines (CCHMs) have demonstrated potential in alleviating symptoms of polycystic ovary syndrome (PCOS), their mechanisms of action remain insufficiently understood. This study aimed to identify key active ingredients and gene targets in Xiaochaihu Decoction, Sijunzi Decoction, and Shensiwei that contribute to their efficacy against PCOS. Transcriptomic data of PCOS were obtained from public databases. Information on gut microbiota metabolite-related targets and active ingredients of CCHMs was retrieved from relevant databases. Key gene targets and active ingredients were identified using Graph-based Bioactive Network Analysis (GraphBAN) and toxicological assessments. Molecular docking and dynamic simulations were conducted to validate interactions. Functional enrichment and regulatory network analysis were performed. LCT, FADS1, and CYP11A1 were identified as key genes associated with α-β T cell activation, immune receptor signaling, and adaptive immune responses. LCT and FADS1 were targeted by linolenic acid, while CYP11A1 was regulated by mandenol, EIC, and linolenic acid. Three microRNAs (hsa-miR-320a-3p, hsa-miR-4487, hsa-miR-6090) co-regulated these genes. Molecular docking and dynamics simulations confirmed stable binding between key genes and active ingredients, with binding energies < -5.0 kcal/mol. The findings indicate that CCHMs exert therapeutic effects on PCOS by multi-target regulation of key genes involved in androgen synthesis, metabolic regulation, and immune-inflammatory activation. The observed strong binding affinities provide a structural basis for these interactions. This study identified three key genes and three core active ingredients in CCHMs for PCOS treatment, laying a theoretical foundation for developing multi-target therapeutics. Show less
In recent years, the global incidence of Non-Suicidal Self-Injury (NSSI) has risen, posing a significant challenge in public health. Adolescents are the main group affected. A cross-sectional study wa Show more
In recent years, the global incidence of Non-Suicidal Self-Injury (NSSI) has risen, posing a significant challenge in public health. Adolescents are the main group affected. A cross-sectional study was conducted using a self-administered questionnaire to collect data from 6,311 adolescents in Hefei, China. This study employed the Compositional Isotemporal Substitution Model (CISM, a statistical method that estimates health effects of replacing time in one behavior with another while accounting for the interdependent, compositional nature of 24-h time-use data) to examine the impact of Screen Time (ST), Non-Screen-based Sedentary Time (NSST), Physical Activity, and Sleep Time on NSSI among adolescents. Compositional logistic regression analysis revealed that, relative to the remaining behavioral components, higher Light Physical Activity (LPA) ( The findings highlight those reasonably allocating adolescents' daily activities, reducing ST, can help lower the risk of NSSI among adolescents. 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
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
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
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
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
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
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
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
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
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
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
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
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
Jianyi Li, Luyao Zhang, Jiapei Xu+7 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, s Show more
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, such as Dapagliflozin (DAPA), exhibit a protective effect against cardiovascular diseases. However, the effects and mechanisms of DAPA on chronic stress-induced AS are largely unknown. The aim of this study was to determine whether DAPA confers a protective effect against chronic stress-induced AS and to elucidate its further molecular mechanisms. The combined high-fat diet-fed and chronic unpredictable mild stress in ApoE-/- mice and lipopolysaccharides- and corticosterone-induced human umbilical vein endothelial cells (HUVECs) were employed to evaluate the antiatherosclerotic effect of DAPA under chronic stress in vivo and in vitro. Histological staining, western blot analysis, siRNA transfection, reactive oxygen species (ROS) staining, and apoptosis assessment were used to investigate the potential mechanisms of DAPA against AS under chronic stress. The results indicate that DAPA significantly improved plaque size and increased plaque stability in the aorta under chronic stress and reduced inflammation and oxidative stress and inhibited apoptosis in the aorta and HUVECs. Chronic stress upregulated regulated in development and DNA damage response 1 (REDD1) expression, which exacerbated cellular inflammation, oxidative stress, and apoptosis levels, leading to endothelial dysfunction. In contrast, DAPA downregulated REDD1 expression and activated the AKT/FoxO1 pathway. In addition, p53 was a transcriptional regulator of REDD1 under chronic stress. More importantly, p53 agonists prevented DAPA from downregulating REDD1 and inhibited AKT/FoxO1 activation, thereby exacerbating chronic stress-induced endothelial dysfunction. These results suggest that DAPA effectively attenuates chronic stress-induced endothelial dysfunction and AS by downregulating REDD1 to activate the AKT/FoxO1 pathway. 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
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant t Show more
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant tumors. However, its regulatory mechanism and pathobiological roles in EC remain unclear. Rab35 expression in EC was systematically profiled via integrative analysis of clinical endometrial specimens and multi-omics databases (CPTAC and GEO). The association between clinical prognosis and Rab35 expression was examined using Kaplan-Meier analysis. Mechanistic investigations included transwell assays, western blotting, and immunofluorescence in Rab35-overexpressing and CRISPR/Cas9-mediated Rab35-knockout EC cells. A mouse xenograft tumor model was established to confirm the effects of Rab35 in vivo. The Rab35 content increased gradually from normal endometrium to atypical hyperplastic endometrium to EC. Moreover, the findings indicated that elevated Rab35 expression was significantly associated with advanced disease characteristics and poor overall survival in patients with EC. In addition, Rab35 enhanced the migratory and invasive nature of EC cells. The expression of Rab35 was inversely linked to that of the β-catenin destruction complex-related proteins Axin-1 and GSK3β, leading to the increased nuclear translocation of β-catenin in EC cells. Animal experiments further verified that Rab35 augmented EC progression by regulating the nuclear translocation of β-catenin. The study revealed that high expression of Rab35 was strongly correlated with EC progression and a poor clinical outcome. Furthermore, Rab35 promoted EC cell metastasis by accelerating the nuclear translocation of β-catenin. These findings suggest that Rab35 serves as a valuable biomarker and therapeutic target for EC. Show less
Depression is a heterogeneous psychiatric disorder with limited treatment efficacy, as 30-50% of patients exhibit inadequate responses to conventional monoaminergic antidepressants. Rhein, a bioactive Show more
Depression is a heterogeneous psychiatric disorder with limited treatment efficacy, as 30-50% of patients exhibit inadequate responses to conventional monoaminergic antidepressants. Rhein, a bioactive anthraquinone derived from Rheum palmatum, exhibits rapid and sustained antidepressant effects in both acute and chronic social defeat stress (CSDS) mouse models. Using quantitative proteomics on prefrontal cortex (PFC) samples from control, CSDS, Rhein-treated, and imipramine-treated cohorts, we identified differentially expressed proteins that revealed Rhein's multi-target regulatory profile. Functional enrichment and clustering analyses indicated that Rhein predominantly restores dysregulated pathways related to lipid metabolism, ribosomal translation, mitochondrial and endoplasmic reticulum (ER) function, and synaptic plasticity, forming a coherent mechanistic axis underlying its therapeutic effects. Comparative analysis with imipramine-treated mice further highlighted Rhein's distinct capacity to modulate organelle homeostasis and synaptic remodeling with greater breadth. Parallel reaction monitoring (PRM) and Western Blotting validated key proteins involved in mitochondrial functions (BNIP1, PISD, MRPL42, MRPS30, LRBA, IGHM), ER homeostasis (ACBD5, APOA4, RPL14), and synaptic plasticity (HDAC1, FAM3C, SSU72). These molecular findings suggest that Rhein exerts its antidepressant effects by restoring the functional integrity of mitochondria and the ER, thereby reprogramming synaptic plasticity. We inferred that this organelle-centered regulation further reinforces its potent modulation through multiple mechanisms and signaling pathways of synaptic plasticity, enabling Rhein to exert antidepressant effects through a coordinated, multi-layered mechanism. Collectively, our findings provide a systems-level mechanistic framework for Rhein's antidepressant efficacy and support its potential as a multi-pathway natural therapeutic, particularly for metabolic subtypes of depression. Show less