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
The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing Show more
The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing to its lipid-regulating and anti-inflammatory effects, paeoniflorin (Pae) inhibits VSMC phenotypic transformation, making it a promising candidate for AS treatment. Mouse aortic VSMCs were treated with oxidized low-density lipoprotein (ox-LDL) and Pae, and the effects on cell phenotype were examined. An AS model was established by feeding ApoE Pae reversed weight gain and elevated TG levels in the AS model. Oil Red O staining showed that Pae inhibited VSMC-derived foam cell formation in vitro and reduced aortic sinus plaque area, aortic wall lipid deposition, and hepatic steatosis in the AS model. Immunofluorescence staining of the aortic sinus revealed that Pae mitigated α-SMA overexpression and reversed ATP-binding cassette transporter A1 (ABCA1) downregulation. Western blotting analysis revealed that Pae inhibited ERK1/2 and p65 phosphorylation, curbed MMP2 overexpression, and restored downregulated ABCA1 expression. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, and wound healing assays demonstrated that Pae inhibited ox-LDL-induced VSMC proliferation and migration. Additionally, Pae significantly inhibited the expression of the inflammatory factors IL-6 and MCP-1 both in vivo and in vitro. Pae may treat AS by inhibiting VSMC phenotypic transformation. Show less
This review comprehensively summarizes the interaction mechanisms between Megalin and several key ligands, including calcium ions, gentamicin, ApoE, ANKRA2, FVIII, TTR, STC1, RAP, and MMP-9, focusing Show more
This review comprehensively summarizes the interaction mechanisms between Megalin and several key ligands, including calcium ions, gentamicin, ApoE, ANKRA2, FVIII, TTR, STC1, RAP, and MMP-9, focusing on the specific amino acid binding sites involved. The analysis highlights the structural basis of these interactions and their clinical relevance, particularly concerning diseases such as nephrotoxicity, Alzheimer's disease, metabolic disorders, and renal pathologies. This review comprehensively summarizes the specific binding sites of Megalin with its ligands and explores the mechanisms, including protein reabsorption, blood coagulation, and neuroprotection, by integrating the results of animal studies and human clinical studies. This review proposes a theoretical framework for designing therapeutic strategies that target the binding sites of Megalin with its ligands. Gene editing technology and monoclonal antibody therapy aim to regulate Megalin receptor-ligand interactions to achieve therapeutic effects on related diseases. Show less
Alzheimer's disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) int Show more
Alzheimer's disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), and regional vulnerability was assessed with a composite vulnerability score (CVS) derived from associations between diffusion features and AD severity across clinical traits in each of the four sex-APOE groups (female or male, with or without APOE4). Brain parcellation with the Eve atlas revealed regions consistently affected across sex-APOE groups (e.g., parahippocampal and superior temporal gyri) and regions specific to individual groups (e.g., the cingulum in females with APOE4 and the middle frontal gyrus in males without APOE4). Gene co-expression network analysis of the matched blood expression data identified gene subnetworks linked to group-specific regional vulnerability, including a muscle tissue morphogenesis module regulated by NEURL1B and HIST1H2BN associated with middle frontal gyrus vulnerability. These findings demonstrate that sex and APOE genotype jointly shape region-specific WM vulnerability and its molecular signatures in AD. Understanding these interactions provides novel mechanistic insights and may inform precision approaches to drug development, biomarker discovery, and clinical trial design for AD. 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
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
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
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
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
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
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
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
The phagocytic function of macrophages is pivotal in regulating vascular inflammation and the progression of atherosclerosis (AS). Si-Miao-Yong-An Decoction (SMYAD), a traditional Chinese multi-herbal Show more
The phagocytic function of macrophages is pivotal in regulating vascular inflammation and the progression of atherosclerosis (AS). Si-Miao-Yong-An Decoction (SMYAD), a traditional Chinese multi-herbal remedy, has been used in the treatment of vascular inflammation and AS. However, its impact on the phagocytic activity of macrophages remains unexplored. ApoE SMYAD reduced lipid deposition and plaque area in ApoE This study, combining in vivo and in vitro experiments with network pharmacology, elucidates that SMYAD restores macrophage efferocytosis and mitigates vascular inflammation via the PPAR-γ/MerTK signaling pathway, offering potential therapeutic benefits for AS. 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
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
Using latent profile analysis (LPA) based on Self-Determination Theory (SDT), this study aimed to explore the profiles of health behavior motivation among Chinese patients with prediabetes and examine Show more
Using latent profile analysis (LPA) based on Self-Determination Theory (SDT), this study aimed to explore the profiles of health behavior motivation among Chinese patients with prediabetes and examine the relationship between these profiles and self-management ability. A cross-sectional study was conducted involving 335 patients with prediabetes. The questionnaires were used to assess health behavior motivation, self-management ability, satisfaction of basic psychological needs and disease knowledge level. Latent profile analysis was performed based on five subscale scores of the health behavior motivation measure. Three distinct latent profiles were identified: a "Self-Determined" profile (C1,29.55%, n=99), a "Non Self-Determined" profile (C2, 55.82%, n=187), and a "Conflicted" profile (C3, 14.63%, n=49). Patients in the C1 profile demonstrated higher levels of autonomy and competence. Patients in the C2 profile were characterized by better disease knowledge and lower relatedness. Compared to patients in the C3 profile, patients in both the C1 and C2 profiles exhibited significantly lower self-management ability. The heterogeneity in health behavior motivation profiles must be considered in the design and clinical practice of personalized interventions for prediabetes. Profile-specific strategies serve as the foundation for enhancing patients' self-management ability and sustaining healthy behaviors. Show less
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularl Show more
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis. EVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis. COPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3' untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo. This study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p-mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD. 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
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
Age is a risk factor for aortic aneurysm (AA), and different segments of the aorta exhibit varying susceptibilities to aneurysm. The specific factors that contribute to the higher incidence of AA and Show more
Age is a risk factor for aortic aneurysm (AA), and different segments of the aorta exhibit varying susceptibilities to aneurysm. The specific factors that contribute to the higher incidence of AA and its complications with aging remain unclear. Matrix metalloproteinases (MMPs) are elevated in AA. However, the connection between aging, aortic MMP activity, and the increased prevalence of AA and its complications has not been systematically evaluated. This study leveraged MMP-targeted molecular imaging to investigate how aging affects aortic MMP expression and activity, as well as aneurysm development and survival. AA development and animal survival were monitored for 28 days after Angiotensin (Ang)-II infusion in 8-10-week-old (young) and >51-week-old (old) Old animals' survival to 28 days was significantly lower than that of young Ang-II-infused Aging is associated with increased MMP activity along the aorta and worse AA survival. MMP-targeted molecular imaging can inform the aneurysm survival prospects. Selective MMP inhibitors and tracers may help prevent and track aneurysm growth, dissection, and rupture. 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
Son Hung Tran, Siqi Zhang, Hyeon-Seong Lee+11 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Schisandrin C (SCC), a bioactive lignan compound derived from Schisandra chinensis (S. chinensis), has been demonstrated to promote intestinal health. However, the antidepressant activity of SCC and i Show more
Schisandrin C (SCC), a bioactive lignan compound derived from Schisandra chinensis (S. chinensis), has been demonstrated to promote intestinal health. However, the antidepressant activity of SCC and its impact on the gut‒brain axis have not been reported. This study aimed to investigate the antidepressant effects of SCC and elucidate its molecular mechanisms through modulation of the microbiota‒gut‒brain axis. Artificial intelligence (AI)-based target protein prediction, network pharmacology analysis, and experimental validation using intestinal cells, Caenorhabditis elegans, and mice models were conducted. Targeted metabolomics, gut microbiota analyses, and molecular biology techniques were employed for mechanistic elucidation. SCC treatment effectively suppressed depressive-like behaviors in mice subjected to chronic unpredictable mild stress (CUMS). SCC upregulated brain-derived neurotrophic factor (BDNF) expression in the brain by regulating the AKT/CREB/BDNF signaling pathway. Additionally, integrated network pharmacology, molecular docking, and metabolomics analyses revealed that SCC significantly increased brain serotonin levels by inhibiting monoamine oxidase (MAO) activity. Furthermore, SCC increased the abundance of Akkermansia and Bifidobacterium, as observed both in the synthetic microbial community in vitro and in the gut microbiota in vivo. Additionally, SCC effectively alleviated intestinal barrier dysfunction and reduced intestinal inflammation in vitro in intestinal cells, in vivo in C. elegans infected with Bacteroides fragilis, and in vivo in the CUMS-induced mice model. SCC improves depressive-like behaviors by modulating the microbiota‒gut‒brain axis. These findings underscore the potential of SCC as an effective therapeutic agent for depression. 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