Autophagy is integral to the rapid proliferation of esophageal squamous cell carcinoma (ESCC), and its regulation presents a promising avenue for therapeutic intervention. Recent studies have elucidat Show more
Autophagy is integral to the rapid proliferation of esophageal squamous cell carcinoma (ESCC), and its regulation presents a promising avenue for therapeutic intervention. Recent studies have elucidated the interplay between autophagy and glucose metabolism, while there is a paucity of anticancer drugs that concurrently target these 2 biological processes. In this study, we identified a natural compound, 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
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. Show less
Coronary heart disease (CHD) burden is increasing, and traditional obesity measures inadequately capture fat distribution and associated CHD risk. A body shape index (ABSI) is an emerging anthropometr Show more
Coronary heart disease (CHD) burden is increasing, and traditional obesity measures inadequately capture fat distribution and associated CHD risk. A body shape index (ABSI) is an emerging anthropometric metric of fat distribution, but evidence linking ABSI to CHD is limited, particularly in the Chinese population. This case-control study in southern China investigated the association of ABSI and related factors with CHD risk, aiming to facilitate early identification of high-risk individuals. We retrospectively studied 996 patients who underwent coronary angiography in a southern Chinese hospital. After strict screening and propensity score matching (PSM), 125 patients with CHD (>50% coronary stenosis) and 125 controls (<50% stenosis) were selected. Key CHD risk predictors were identified using feature-selection techniques (LASSO regression, recursive feature elimination, random forest importance). Univariate and multivariate logistic regression models were constructed for CHD prediction. Model performance was evaluated by receiver operating characteristic (ROC) analysis and compared to individual predictors using the DeLong test. A nomogram was developed for individualized risk estimation. Baseline characteristics were well matched between CHD and control groups after PSM. Across feature-selection methods, the most influential predictors for CHD included ABSI, prealbumin (PA), direct-to-total bilirubin ratio (DB/TB), apolipoprotein B (ApoB), globulin (GLO), apolipoprotein A-I (ApoA-I), and essential hypertension (EH). Each of these factors showed a significant univariate association with CHD ( This study identifies ABSI as a potential predictor of CHD risk among southern Chinese populations. Integrating ABSI with other candidate predictors improves the model's predictive performance. A multifactorial approach may better characterize CHD risk in this population and could inform prevention strategies. Show less
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adv Show more
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adverse factors in the periodontal microenvironment. Therefore, identifying novel therapeutic targets and elucidating the underlying molecular mechanisms to protect the proliferative and differentiation potential of PDLSCs is of significant importance. PDLSCs were exposed to electronic cigarette extract and various common oral stressors to evaluate the expression of glucagon such as peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR). PDLSCs isolated from patients with periodontitis and PDLSCs from a mouse periodontitis model were also analyzed. Functional studies were performed by GLP1R or GIPR knockdown, overexpression, and treatment with single or dual receptor agonists, followed by assessment of cell proliferation and multilineage differentiation capacities. Transcriptome (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA immunoprecipitation sequencing (RIP-seq) were applied to delineate downstream signaling pathways and RNA–protein interactions. Protein synthesis regulation was further investigated by immunoprecipitation of interferon induced protein with tetratricopeptide repeats (IFIT)-associated translation initiation factors. For in vivo validation, wild-type and GLP1R/GIPR double-knockout periodontitis mice were transplanted with CRISPR-Cas9 mCherry-labeled PDLSCs and treated with receptor agonists. Disease severity and PDLSC fate were evaluated by histology and lineage tracing. Finally, a questionnaire-based survey was conducted in 150 patients with periodontitis, including 74 individuals with long-term use (> 1 month) of GLP1R or GLP1R/GIPR dual agonists (e.g., semaglutide, liraglutide, tirzepatide), to assess their periodontal outcomes. GLP1R and GIPR expression were markedly downregulated in PDLSCs exposed to multiple stressors and in PDLSCs isolated from periodontitis specimens. RNA-seq, ChIP-seq, and RIP-seq identified downstream pathways and RNA–protein interactions implicated in receptor-mediated regulation. Functionally, GIPR agonism promoted PDLSC proliferation via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, whereas GLP1R agonist enhanced multilineage differentiation capacity in vitro. Mechanistically, GLP1R knockdown induced robust upregulation of IFIT1/2/3, while GLP1R agonist suppressed IFIT expression. IFIT1/2/3 were shown to interact with eIF3C and to inhibit translation of differentiation-related mRNAs, linking GLP1R signaling to translational control of PDLSC fate. In vivo, transplantation experiments in both wild-type and GLP1R/GIPR double-knockout periodontitis mice demonstrated that single and dual receptor agonists significantly improved endogenous and exogenous PDLSC-mediated periodontal regeneration. Consistently, a clinical survey of 150 patients with periodontitis (74 receiving GLP1R or dual agonists) revealed significantly better periodontal staging and grading in treated individuals, with longer agonist exposure associated with greater improvement. Our findings uncover the different molecular roles of GIPR and GLP1R in self-renewal capacity and multipotency of PDLSCs, and open new avenues for developing therapeutic targets and strategies in oral tissue engineering and regenerative medicine. The online version contains supplementary material available at 10.1186/s11658-026-00867-2. Show less
Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as n Show more
Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as nutritional strategies in NDDs. We analyzed different polyphenol types across seven NDDs, 13 studies involving 849 participants were included. Prespecified outcomes comprised global cognition (Mini-Mental State Examination, MMSE), domain-specific cognition (Alzheimer's Disease Cooperative Study-Cognitive Subscale, ADCS-Cog), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), and selected biomarkers (plasma amyloid-β40 and brain-derived neurotrophic factor, BDNF). Reporting followed PRISMA 2020 guidelines, methods conformed to the Cochrane Handbook, and certainty of evidence was assessed using GRADE. Overall, polyphenol supplementation was associated with improved global cognition (pooled MD in MMSE = 2.06; 95% CI 0.62-3.49). In subgroup analyses, flavonoids were associated with a modest but significant improvement in MMSE scores, whereas stilbenes produced a significant benefit in daily functioning (ADCS-ADL) without clear gains in MMSE or ADCS-Cog and no consistent effects on NPI. Anthocyanidins, phenolic acids, and lignans did not significantly affect cognitive outcomes (MMSE or ADCS-Cog), and polyphenol subclasses did not yield robust or consistent changes in NPI or biomarker endpoints (Aβ40 and BDNF). Specific polyphenol subclasses therefore appear to confer selective cognitive and functional benefits, with stilbenes primarily supporting functional outcomes and flavonoids potentially enhancing global cognition. Show less
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive perfo Show more
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive performance. In this study, we examined the associations between plasma klotho levels and plasma biomarkers, as well as amyloid beta (Aβ) positron emission tomography (PET), tau PET, neurodegeneration, and cognition, in 354 older adults. Stratified association, interaction, and mediation analyses were conducted to elucidate apolipoprotein E (APOE) ε4-dependent relationships and potential underlying pathways. Higher plasma klotho levels were associated with lower AD-related biomarkers and cognitive decline in APOE ε4 carriers. Plasma klotho and APOE ε4 exhibited significant or marginal interactions with less abnormal changes in plasma phosphorylated tau217, glial fibrillary acidic protein, neurofilament light chain, Aβ PET, and cognition. These AD-related biomarkers mediated the protective effect of plasma klotho on cognitive function in APOE ε4 carriers. This study suggests that plasma klotho is an APOE ε4-dependent protective factor, which may attenuate AD-related pathology and improve cognitive performance. Show less
To identify plasma proteins associated with glaucoma and assess the translational potential of key proteins as both biomarkers and therapeutic targets. Genome-wide association study data were obtained Show more
To identify plasma proteins associated with glaucoma and assess the translational potential of key proteins as both biomarkers and therapeutic targets. Genome-wide association study data were obtained from the UK Biobank Pharma Proteomics Project, FinnGen, and the Million Veteran Program. We used a four-stage analytical framework: Stage 1 applied Mendelian randomization and Bayesian colocalization to evaluate associations between 2923 plasma proteins and glaucoma; Stage 2 used summary-based Mendelian randomization to explore transcriptomic and epigenomic associations of the identified proteins with glaucoma risk; Stage 3 involved a prospective association analysis of protein levels and incident glaucoma in the UK Biobank cohort, including 40,170 glaucoma-free participants; and Stage 4 systematically evaluated the druggability of the prioritized protein targets. We identified 26 plasma proteins with putative causal associations with glaucoma, six of which were novel: COL24A1, KAZALD1, EBAG9, CSNK1D, AZI2, and AXIN1. COL24A1 (odds ratio [OR] = 0.85; 95% confidence interval [CI], 0.80-0.90; PFDR < 0.001; PP.H4 = 0.95) and EFEMP1 (OR = 0.88; 95% CI, 0.83-0.92; PFDR < 0.001; PP.H4 = 0.98) emerged as the most compelling candidates. To further elucidate the regulatory mechanisms, multiomics analyses indicated that epigenetic modifications and alternative splicing events affecting these genes were associated with elevated glaucoma risk. Notably, EFEMP1 was significantly associated with glaucoma incidence in the prospective cohort analysis (fully adjusted Cox model: hazard ratio = 1.61; 95% CI, 1.29-2.00; PFDR = 0.002), demonstrating strong predictive performance (C-index = 0.811, area under the curve = 0.806) and representing a promising therapeutic target. Our findings provide new insights into the proteomic basis of glaucoma and highlight promising opportunities for developing targeted therapies. Show less
Aberrant microglial activation and impaired adult hippocampal neurogenesis play critical roles in the pathogenesis of depression. Although electroacupuncture (EA) has demonstrated clinical antidepress Show more
Aberrant microglial activation and impaired adult hippocampal neurogenesis play critical roles in the pathogenesis of depression. Although electroacupuncture (EA) has demonstrated clinical antidepressant efficacy, the underlying mechanisms by which it modulates microglial activity and promotes neurogenesis remain unclear. Male C57BL/6 J mice were subjected to chronic unpredictable mild stress (CUMS) for three weeks. Following this period, the mice were divided into groups receiving either EA at the Yintang (GV29) and Baihui (GV20) acupoints, imipramine (IMI) as a positive control, or no treatment (vehicle control) for an additional 3 weeks. To evaluate depressive-like behaviors, we conducted the sucrose preference test, forced swimming test, and tail suspension test. Anxiety-like behaviors were assessed using the open field test and elevated plus maze. We employed immunofluorescence, Golgi staining, Western blotting, and real-time quantitative PCR (qRT-PCR) to elucidate the effects of EA on microglia-driven hippocampal neurogenesis and BDNF signaling. Notably, loss-of-function experiments utilizing PLX5622 for microglial ablation and ANA-12 for TrkB blockade demonstrated the necessity of both microglia and BDNF signaling for the therapeutic efficacy of EA. EA treatment significantly alleviated CUMS-induced anxiodepressive behaviors. This behavioral recovery was associated with a phenotypic shift in microglia towards a pro-neurogenic state in the hippocampus. Importantly, microglia were essential for the therapeutic effects of EA, as evidenced by their ablation with PLX5622. Furthermore, EA enhanced neurogenesis by orchestrating a multi-step augmentation of BDNF signaling, which involved PKA activation, subsequent release from MeCP2-mediated transcriptional repression, and ultimately increased maturation of BDNF. Our findings demonstrate that EA exerts antidepressant effects by promoting a pro-neurogenic transformation of microglia. Mechanistically, these microglia enhance BDNF function via the PKA/MeCP2/BDNF pathway, thereby facilitating hippocampal neurogenesis and restoring synaptic plasticity, which collectively alleviate depressive symptoms. Show less
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclero Show more
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclerotic cardiovascular diseases, their effects are limited in those with homozygous familial hypercholesterolemia. It is essential to seek new lipid-lowering targets. YAP (Yes-associated protein) may be involved in lipid metabolism in the liver; therefore, we investigated the function of hepatocyte YAP in hyperlipidemia and atherosclerosis. Hyperlipidemia models were generated in apoE knockout (apoE High-cholesterol diet-fed apoE Taken together, our findings revealed a novel role for the YAP-TEAD4-ANGPTL3 axis in lipid metabolism independent of LDLR. Inhibition of hepatocyte YAP may be an effective lipid-lowering strategy for homozygous familial hypercholesterolemia. Show less
Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF Show more
Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF patients. However, its precise mechanism in treating post-CHF cognitive dysfunction remains unclear. This study systematically investigates XJQ's effects on post-CHF cognitive dysfunction and the underlying mechanisms. The components of XJQ were identified through liquid chromatography-mass spectrometry. CHF was induced in rats via ligation of the left anterior descending coronary artery, followed by six weeks of XJQ treatment. Cardiac function was evaluated through echocardiography and hemodynamic parameters, while cognitive function was assessed using Morris water maze (MWM) and open field tests (OFT). XJQ treatment enhanced both cardiac and cognitive functions in CHF rats. Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses, inflammation, and phosphodiesterase 4 (PDE4)-dependent cyclic adenosine monophosphate (cAMP) signaling. XJQ inhibited microglial and astrocyte activation, decreased proinflammatory cytokines, and mitigated neuronal damage. Notably, XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP, protein kinase A (PKA), cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), PSD95, and synapsin I levels. Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin, kaempferol, isorhamnetin, and darutoside to PDE4. In conclusion, XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway. These findings provide valuable insight into the heart-brain axis. Show less
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on childr Show more
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on children with ASD, whereas how specific executive components relate to social functioning in adults remains less clear. This study examined whether patterns of association between EF and social responsiveness differ between children and adults with and without ASD. Data were obtained from the Autism Brain Imaging Data Exchange II (ABIDE II), including 423 participants aged 8-23 years (ASD = 184; controls = 239). EF was evaluated using the Behavior Rating Inventory of Executive Function (BRIEF/BRIEF-A), and social responsiveness was assessed with the Social Responsiveness Scale (SRS). Covariates of age, sex, and full-scale IQ (FIQ) were controlled using entropy balancing in children and multiple regression in adults. Hierarchical regression, moderated mediation analysis, and latent profile analysis (LPA) were conducted to examine the moderation, mediation, and heterogeneity effects, respectively. Across both child and adult samples, individuals with ASD exhibited significantly higher T-scores than controls on nearly all BRIEF and SRS subdomains after covariate adjustment (all adjusted p < 0.01), indicating widespread EF and social responsiveness impairments. Moderation analyses revealed no significant age group × EF interaction, indicating that the association between EF and social responsiveness was consistent across development. Mediation analysis revealed age-specific pathways, with EF broadly mediating social responsiveness in adults but showing more selective mediation in children. LPA identified four distinct subtypes, which were independent of age, sex, and FIQ. EF-social responsiveness associations were evident across development, but the functional contribution of specific executive components became more differentiated with age. Working memory showed greater relative prominence in adulthood. Latent profile analysis revealed heterogeneity in how executive difficulties align with social challenges, supporting developmentally informed assessment and clinical interpretation rather than direct treatment recommendations. Show less
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morronisid Show more
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morroniside (Mor), an iridoid glycoside compound in Cornus officinalis, is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used ApoE4 transgenic mice and ApoE4-transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10-month-old mice were randomly divided into the ApoE3 control group (ApoE3 + Veh), the ApoE4 model group (ApoE4 + Veh), and the ApoE4 + Mor 10, 20, and 40 mg/kg groups as in vivo models. The in vitro BV2-ApoE model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of ApoE4 transgenic mice by reducing Aβ plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1/PU.1 signaling axis, and alleviated the dysfunction of microglia both in vitro and in vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce Aβ accumulation, and improve synaptic damage in ApoE4 mice via the CX3CL1/CX3CR1/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD. Show less
Pine nut oil (PNO) is a candidate alternative to corn oil (CO) owing to comparable unsaturated fatty-acid profiles and enrichment in pinolenic acid (Δ5-18:3) and lipid-soluble micronutrients. We syste Show more
Pine nut oil (PNO) is a candidate alternative to corn oil (CO) owing to comparable unsaturated fatty-acid profiles and enrichment in pinolenic acid (Δ5-18:3) and lipid-soluble micronutrients. We systematically compared extraction routes (solvent, supercritical CO₂, pressing), established solvent extraction as the optimal balance of yield and bioactive retention, and then characterized solvent-extracted oils from eight provenances using a weighted composite score to nominate Pinus tabuliformis for in vivo testing. In diet-induced obese mice (12-week Western diet, then 12-week intervention, n = 10 per group), replacing CO with PNO lowered body-mass gain and liver weight and improved serum lipids (triglycerides ↓ ∼ 28 %, total cholesterol ↓ ∼ 15 %, LDL-C ↓ ∼ 20 %) without affecting HDL-C or glucose; ALT and AST fell by ∼30 %, indicating hepatoprotection. Hepatic multi-omics revealed coherent remodeling toward PUFA-rich phospholipid species, activation of PPAR-centered peroxisomal/mitochondrial fatty-acid degradation and circadian pathways, and integrative correlations implicating Cyp4a10/14, Ehhadh, Slc27a2, Fgf21, Angptl4, and Plin5. Collectively, PNO reoriented hepatic lipid flux toward oxidation and membrane remodeling, supporting its development as a nutritionally advantaged culinary oil. Show less
Xiangying Xie, Juan Su, Qian Zhou+4 more · 2026 · Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver · Elsevier · added 2026-04-24
Depression and anxiety were not only common but also with serious consequence in inflammatory bowel diseases (IBD) patients. The current study endeavors to define distinct depression and anxiety profi Show more
Depression and anxiety were not only common but also with serious consequence in inflammatory bowel diseases (IBD) patients. The current study endeavors to define distinct depression and anxiety profiles of IBD patients and identify central symptoms within different profiles to facilitate targeted interventions. The research employed K-means Clustering to delineate the depression and anxiety profiles, followed by a repetition of the analysis using Latent Profile Analysis (LPA). Furthermore, network analysis was utilized to identify central symptoms within the various profiles. K‑means Clustering identified Cluster 1 (38.89%), Cluster 2 (45.33%) and Cluster 3 (15.78%), while LPA yielded the low-risk group (39.56%), the mild-risk group (44.22%) and the high-risk group (16.22%). A majority of patients in the three clusters were predominantly in a single LPA-derived patient class (96.1-99.0%). Network analysis revealed that connections within each symptom in PHQ-9 and GAD-7 were stronger than those between symptoms. Furthermore, PHQ 6 ("guilt"), PHQ2 ("sad mood")and GAD 7 ("feeling afraid") were identified as the central symptoms in Cluster 1. PHQ2 ("sad mood"), GAD 3("excessive worry") and GAD 1 ("nervousness") emerged as the central symptoms in Cluster 2. Additionally, GAD3 ("excessive worry"), GAD 4 ("trouble relaxing") and GAD 6("irritability") were identified as the central symptoms in Cluster 3. We defined three distinct depression and anxiety profiles among IBD patients and pinpointed central symptoms within each profile. These findings underscore the importance of directing research towards those central symptoms within each profile in order to develop targeted intervention strategies. Show less
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context Show more
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context, we investigated whether the circulating LL-37-ApoB-100 complex could serve as a biomarker for CAD. We performed surface plasmon resonance and protein-protein docking to demonstrate the direct LL-37-ApoB-100 interaction. We developed a specific polyclonal antibody against the complex and measured its levels in human atherosclerotic plaques and plasma, as well as in We identified that LL-37 directly interacted with multiple distinct binding sites on ApoB-100. Plasma levels of LL-37-ApoB-100 complex were significantly elevated in human patients with atherosclerosis. Consistently, levels of this complex were positively correlated with atherosclerotic plaque area in Circulating LL-37-ApoB-100 levels are strongly associated with angiographically documented CAD, highlighting LL-37-ApoB-100 as an independent predictor for CAD. Show less
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital e Show more
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital exclusion moderates the association between loneliness and depressive, and examines symptom structure and depressive subtypes. Drawing on data form the 2018 and 2020 waves of the CHARLS (N = 13,719), we employed fixed-effect and mixed-effect models to assess the effect of loneliness on depressive and the moderating role of digital exclusion. Latent profile analysis (LPA) was used to identify symptoms subtypes, while symptom network analysis assessed centrality and network stability. Loneliness significantly predicted depressive symptoms across multiple models, demonstrating robust effects. Digital exclusion was positively associated with depressive symptoms but did not exhibit a statistically significant moderating effect on the loneliness-depression relationship (p > 0.05, Δβ ≈ 0.011). LPA identified six psychologically meaningful subtypes of depression. Symptom network analysis revealed that emotional and motivational symptoms occupied central positions within the network structure, whereas loneliness, despite its strong connections, exhibited relatively low centrality. The overall network structure remained stable over two years, with the digital access group exhibiting stronger network connectivity. This study emphasizes that digital access alone is not a universal remedy for alleviating loneliness. The psychological benefits of digital technology depend on the alignment between individual motivations, usage patterns, and broader social contexts. Future research should focus on digital usage quality and contextual adaptability of interventions, promoting a shift from customization in digital mental health intervention strategies. 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
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms rema Show more
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of autophagic proteins including ATG5, BECN1 and MAP1LC3/LC3 as well as LAMP1. Accordingly, silencing of Show less
Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to Show more
Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to investigate the combined effect of elevated Lp(a) and DM on survival outcomes in CAD patients. This study included 65 547 CAD patients (62.6 ± 10.7 years, 27.7% female) from CIN-II and RED-CARPET cohorts. Patients were stratified into four groups by Lp(a) levels (< or ≥ 30 mg/dL) and DM status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality, examining additive and multiplicative interactions. During a median follow-up of 5.5 years, 10 686 (16.3%) patients died from all causes and 5106 (7.8%) died from cardiovascular causes. Patients with Lp(a) ≥ 30 mg/dL and DM were independently associated with cardiovascular mortality (adjusted hazard ratio [aHR]: 1.28, 95% CI: 1.20-1.35; aHR: 1.53, 95% CI: 1.44-1.62, all p < 0.001, respectively). Compared to patients with Lp(a) < 30 mg/dL without DM, the aHRs were 1.26 (95% CI: 1.16-1.36, p < 0.001), 1.51 (95% CI: 1.40-1.62, p < 0.001) and 2.00 (95% CI: 1.83-2.18, p < 0.001) for those with Lp(a) ≥ 30 mg/dL without DM, Lp(a) < 30 mg/dL with DM and Lp(a) ≥ 30 mg/dL with DM, respectively. Significant additive interaction between elevated Lp(a) and DM on cardiovascular mortality was observed, with 12% of the excess risk attributed. Similar associations were observed in all-cause mortality. In patients with CAD, elevated Lp(a) and DM act synergistically to increase the risk of cardiovascular and all-cause mortality, suggesting that both risks should be considered to integrate management. Show less
Visceral pain is frequently accompanied by depression, a comorbidity involving central neuroinflammation and abnormal neuronal plasticity. The P2X7 receptor (P2X7R) plays a crucial role in neuroinflam Show more
Visceral pain is frequently accompanied by depression, a comorbidity involving central neuroinflammation and abnormal neuronal plasticity. The P2X7 receptor (P2X7R) plays a crucial role in neuroinflammation and pyroptosis, while Jujuboside A (JuA), a major saponin extracted from Ziziphus jujuba seeds, has been reported to exert significant antidepressant and analgesic effects. In this study, we systematically evaluated the regulatory effects of JuA on the P2X7R-brain-derived neurotrophic factor (BDNF) pathway and on pyroptosis and apoptosis using a rat model of colorectal distension (CRD) and primary neuron/astrocyte cultures. JuA markedly alleviated visceral hypersensitivity and depressive-like behaviors in CRD rats and reduced P2X7R expression in both the spinal cord (SC) and hippocampus (HPC). Further investigations in vitro revealed that JuA inhibited excessive P2X7R activation in SC astrocytes, thereby decreasing the expression of NLRP3, Caspase-1, GSDMD, IL-1β and TNF-α, indicating suppression of pyroptosis. Similarly, JuA exerted an anti-pyroptotic effect in HPC astrocytes and inhibited neuronal apoptosis by reducing Caspase-3 and Bax levels while increasing Bcl2 expression, leading to upregulation of HPC BDNF. Collectively, JuA targets P2X7R and suppresses downstream pyroptotic and apoptotic signaling in vitro, which may contribute to its neuroprotective effects. These findings provide experimental evidence supporting the potential of JuA as a therapeutic agent for comorbid visceral pain and depression. Show less
This study examined heterogeneous patterns of trauma-related adaptation among Chinese adolescents during the post-COVID-19 recovery phase, focusing on the co-occurrence of posttraumatic distress (PTD) Show more
This study examined heterogeneous patterns of trauma-related adaptation among Chinese adolescents during the post-COVID-19 recovery phase, focusing on the co-occurrence of posttraumatic distress (PTD) and posttraumatic growth (PTG). We also investigated how modifiable psychosocial protective and vulnerability factors were associated with membership in different adaptation profiles. A large-scale cross-sectional survey was administered to 5, 044 students (aged 9-17 years; 46.6% male) from 15 primary and secondary schools in Wuhan, China. Validated instruments assessed posttraumatic stress symptoms (PCL-C), posttraumatic growth (PTGI), depressive symptoms (CES-D), and anxiety (SAS). Protective and vulnerability factors included resilience (CD-RISC), perceived social support (SSRS), physical activity (PARS-3), school belonging (PSSM), adaptive coping (SCSQ), and trait anxiety (TAI). Latent profile analysis (LPA) was used to identify adaptation profiles, and multinomial logistic regression examined how modifiable psychosocial factors were associated with profile membership. LPA revealed four empirically derived profiles: a High Distress/High Growth-Moderate PTSD profile (76.9%), a Low Distress-High Growth profile (4.8%), a Low Growth-Moderate Distress profile (3.9%), and a High Distress/High Growth-High PTSD profile (14.4%). The vast majority of adolescents showed some degree of both PTD and PTG, consistent with dual-process perspectives. In multinomial models, higher resilience, social support, school belonging, adaptive coping, and physical activity were associated with greater likelihood of belonging to the Low Distress-High Growth profile rather than more distressed profiles, whereas higher trait anxiety was associated with increased odds of membership in profiles characterized by greater distress. In this large school-based sample of Chinese adolescents, distress and growth frequently co-occurred and clustered into distinct adaptation profiles that differed systematically in psychosocial resources. Resilience, social connectedness, school belonging, and physical activity emerged as promising targets for trauma-informed, school-based support, whereas trait anxiety appeared to mark heightened vulnerability. Given the cross-sectional and single-region design, these findings should be interpreted as exploratory, and longitudinal and cross-cultural studies are needed to clarify temporal and contextual influences on adolescent trauma adaptation. Show less
The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that ha Show more
The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that has been increasingly investigated for its potential to support cognitive function in older adults. Clinical evidence suggests that RT may be associated with benefits in certain cognitive domains, including memory, executive function, processing speed, and visuospatial ability. However, findings across studies remain heterogeneous, with several trials reporting neutral outcomes. Most intervention studies involve structured RT programs conducted at moderate to high intensity and performed multiple times per week. However, optimal training parameters have not yet been clearly established due to variability in study design and the absence of formal dose-response analyses. Emerging evidence suggests that the cognitive effects of RT may be mediated, at least in part, through muscle-brain axis signaling involving exercise-induced myokines. Factors such as irisin, brain-derived neurotrophic factor, interleukin-6, interleukin-15, and insulin-like growth factor-1 have been implicated in processes related to neuroplasticity, neuroinflammatory regulation, and neurovascular function, primarily based on preclinical and translational research. This review synthesizes current evidence on RT-related molecular mechanisms and clinical findings to provide an integrative perspective on the potential role of resistance training in mitigating age-related cognitive decline. Show less
The subchronic cardiotoxicity of 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), an unregulated disinfection byproduct with high environmental detection rates, remains poorly characterized. Using integrated Show more
The subchronic cardiotoxicity of 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), an unregulated disinfection byproduct with high environmental detection rates, remains poorly characterized. Using integrated multi-omics (transcriptomics, proteomics, phosphoproteomics) and histopathological analyses in zebrafish, this study systematically elucidated its dose-dependent (low-dose, 10 nM; medium-dose, 100 nM; high-dose, 1000 nM) cardiotoxicity, from adaptive remodeling to failure, over a 35-day exposure period. A reduction in atrioventricular inflow ranging from 81.4 % to 93.9 %, along with lipid droplet accumulation and Z-disc rupture, indicate a dose-dependent cardiac crisis induced by 2,6-DCBQ. Multi-omics analyses, revealed that the kinase cascade involving braf (Myhpc2_T1545), camk2a (Mybpc3_S291), and mark3b (Ttn.1_S28131) arranged dose-dependent cytoskeletal remodeling. High-dose exposure initiated an inflammation-cytoskeleton vicious cycle, wherein chemokine-driven collagen degradation exacerbated Z-disc rupture, while lipotoxic lipid droplets recruit inflammatory infiltrates, collectively escalating irreversible cardiac decompensation. These findings demonstrate that subchronic exposure to 2,6-DCBQ initiates cardiac remodeling, escalating cardiovascular susceptibility in exposed populations. Show less
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term tre Show more
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term treatments of the existing drugs suffered safety concerns. Show less
Increasing evidence indicates that modulating pyroptosis in endothelial cells (ECs) can alleviate atherosclerosis (AS) progression; however, despite reports that nucleolin (NCL) regulates vascular smo Show more
Increasing evidence indicates that modulating pyroptosis in endothelial cells (ECs) can alleviate atherosclerosis (AS) progression; however, despite reports that nucleolin (NCL) regulates vascular smooth muscle cell proliferation in AS, the potential mechanism by which cell surface NCL mediates pyroptosis in ECs during AS remains poorly understood. AS was induced in ApoE AS model mice developed severe aortic lesions accompanied by pronounced EC pyroptosis and inflammation, together with elevated NCL expression in ECs of the aortic root. Both inhibition of NLRP3 and NCL knockdown alleviated atherosclerotic lesion severity in ApoE This study demonstrates that, in AS, NCL exacerbates EC pyroptosis and promotes disease progression by facilitating nuclear transport of RASSF2. This study defines the mechanistic roles of NCL in AS, thereby identifying a new molecular pathway and suggesting potential therapeutic targets. Show less
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the Show more
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the interaction between the gut microbiota and the central nervous system (CNS). The gut-brain axis (GBA), as a bidirectional communication pathway, plays an increasingly recognized role in regulating cognitive functions. Ganoderma lucidum polysaccharides (GLP), a traditional medicinal and edible substance, can regulate gut microbiota homeostasis and short-chain fatty acid (SCFAs) levels through the GBA. GLP reduces the Firmicutes/Bacteroidetes ratio, significantly increases the abundance of Lactobacillus, and further suppresses oxidative stress and inflammatory responses by controlling microglial overactivation and neuroinflammation, thereby enhancing the expression of synapse-associated proteins and brain-derived neurotrophic factor (BDNF). Consequently, GLP shows potential for improving cognitive dysfunction. This review systematically summarizes the bioactivities of GLP, explores the neurodegenerative mechanisms of aging, and proposes the possibility that GLP mitigates aging-induced inflammation and improves cognitive function via modulation of the gut microbiota. Show less