This study aimed to elucidate the sedative-hypnotic effects of a stem-derived bioactive fraction from Syringa oblata Lindl. (ZDX) and to reveal its underlying mechanisms, thereby providing a theoretic Show more
This study aimed to elucidate the sedative-hypnotic effects of a stem-derived bioactive fraction from Syringa oblata Lindl. (ZDX) and to reveal its underlying mechanisms, thereby providing a theoretical and practical basis for the development of new sleep aid drugs. ZDX was prepared by optimizing the extraction and purification procedures. Using UPLC-Q-TOF-MS, the prototype compounds absorbed into the brain of insomnia mice were analyzed, and 15 bioactive compounds were identified or predicted, including Dihydrocubebin, (-)-Cubebin, Isoguamarol, and others. Its efficacy and mechanisms were investigated using network pharmacology, transcriptomics, metabolomics, and molecular docking, complemented by in vivo pharmacodynamic and molecular analyses. In an insomnia mouse model, ZDX significantly increased body weight, reduced sleep latency, and prolonged total sleep duration, while alleviating anxiety and depression-like behaviors and improving histopathological damage in the hippocampus and hypothalamus, showing significant sedative-hypnotic effects. Mechanistically, ZDX modulated key genes and proteins involved in the cAMP signaling pathway, enhanced superoxide dismutase activity, reduced malondialdehyde levels, decreased inflammatory cytokines (IL-6, IL-1β, and TNF-α), and restored neurotransmitter homeostasis in the brain. Collectively, ZDX exerts sedative-hypnotic effects, at least in part, by activating the cAMP/PKA-CREB-BDNF axis and coordinately regulating neurotransmission, oxidative stress, and inflammation. Show less
In recent years, non-traditional lipid indices have emerged as significant predictors for cardiovascular events following emergency percutaneous coronary intervention (PCI) for ST-segment elevation my Show more
In recent years, non-traditional lipid indices have emerged as significant predictors for cardiovascular events following emergency percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). However, the relationship of residual lipoprotein-cholesterol (RLP-C) and atherogenic index of plasma (AIP) with in-hospital outcomes, especially their predictive value for major adverse cardiovascular and cerebrovascular events (MACCEs) after PCI in STEMI patients, remains underexplored and warrants further investigation. This retrospective cohort study included 526 STEMI patients who underwent emergency PCI between January 2023 and August 2024. We collected baseline demographic, clinical, and laboratory data. RLP-C and AIP were calculated from lipid profiles obtained before PCI. Independent predictors of in-hospital MACCEs were identified using multivariate logistic regression, and model discrimination was evaluated using receiver operating characteristic (ROC) curve analysis. Among 526 STEMI patients receiving PCI, 92 (17.49%) developed in-hospital MACCEs. Multivariate analysis identified RLP-C (OR = 3.97, 95%CI: 1.71–9.21; RLP-C and AIP are independent predictors of in-hospital MACCEs following PCI in STEMI patients. Combined assessment of these indices improves risk stratification and may facilitate early targeted interventions to improve outcomes. The online version contains supplementary material available at 10.1186/s12872-026-05555-9. Show less
Osteoarthritis (OA) often coexists with metabolic traits (MTs), causing significant disability. Our study aims to uncover the shared genetic mechanisms between OA and MTs, revealing novel OA-MT relate Show more
Osteoarthritis (OA) often coexists with metabolic traits (MTs), causing significant disability. Our study aims to uncover the shared genetic mechanisms between OA and MTs, revealing novel OA-MT related genes, proteins and pathways. We first explored the clinical associations between OA and MTs based on UK Biobank data. Using GWAS statistics for 9 OA subtypes and 51 MTs, we identified both global and regional genetic correlations. Multi-trait GWAS helped revealed credible genes and relevant pathways through various methods. Protein-level analyses were also conducted to identify key proteins. We developed polygenic scores (PGS), machine learning models and drug repurposing strategies were explored to translate these findings into clinical applications. We identified 152 trait pairs with significant associations and 709 local regions linked to OA-MT. Key SNVs like rs13135092 (SLC39A8) and rs34811474 (ANAPC4) were associated with multiple OA-MT pairs. Lipid and glucose metabolism emerged as central pathways, with tissue-specific enrichment analyses revealing key gene clusters in hepatocytes, arteries, and brain regions. Protein-level analyses identified 205 protein subgroups. PGS integrating MTs outperformed model based solely on OA, improving AUC by 17.5%. Causal gene-based models showed strong diagnostic accuracy (average AUC = 0.875 in external cohorts). Drug prediction highlighted fenofibrate as a promising treatment among 71 candidates. This study provides new insights into the genetic links between OA and MTs. We identified genes, proteins, and pathways related to comorbidities, revealing shared mechanisms, highlighting the potential of integrating metabolic factors to improve OA prediction, diagnosis, and treatment. Show less
Pregnant women have a high incidence of perinatal mood and anxiety disorders (PMADs). To explore the influence factor on perinatal psychology, we analysed the SCFAs, lipids, cognition, emotion, and cy Show more
Pregnant women have a high incidence of perinatal mood and anxiety disorders (PMADs). To explore the influence factor on perinatal psychology, we analysed the SCFAs, lipids, cognition, emotion, and cytokines in the late pregnant women. The mood, cognition, SCFAs of the non-pregnant group were compared to those in the late pregnancy. The differences in SCFAs, lipids, cognition, and cytokines between the high-risk and low-risk groups for affective disorders among women in the late pregnancy were analysed, and the risk factors were sought. Compared with the non-pregnant group, the pregnant group scored lower on the SDMT (P < 0.001), DST (P = 0.035), VRT (P = 0.001), and VFT (P < 0.001), and took longer on the TMTA (P = 0.004). Acetate (P = 0.001) and butyrate (P = 0.002) were higher, while propionate (P < 0.001) and isobutyrate (P = 0.001) were lower in the pregnant group than in the non-pregnant group. Among the pregnant women, CRP was higher in the high-risk group for mood disorders than in the low-risk group (P = 0.048). Meanwhile, HDL was positively associated with DST (P = 0.000), VRT (P = 0.015), and VFT (P < 0.001). Longer TMTA completion times were associated with reduced propionate (P = 0.072) and LPa (P = 0.022). Longer TMTB completion time was associated with lower life satisfaction (P = 0.037), as well as decreased cholesterol (P = 0.026). Pregnant women experience changes in cognition and SCFAs. CRP is a sensitive indicator for monitoring affective disorder. Regulation of SCFAs and lipids may be beneficial for cognition and affect. Show less
Jianlei Liu, Yaling Cui, Hongyu Wang+2 more · 2026 · Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · Blackwell Publishing · added 2026-04-24
With global population aging, the number of older adults in Chinese nursing homes is rising rapidly, and depression is the most prevalent mental health problem in this population. Most previous studie Show more
With global population aging, the number of older adults in Chinese nursing homes is rising rapidly, and depression is the most prevalent mental health problem in this population. Most previous studies assessed depression via total scale scores, ignoring individual heterogeneity of depressive symptoms. This study aimed to identify distinct depressive symptom profiles and their associated factors in this population. Data were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), with 353 valid nursing home older adults included. Depressive symptoms, anxiety and functional status were assessed using the CESD-10, GAD-7 and IADL scales. Latent profile analysis (LPA), univariate tests and multinomial logistic regression were performed, with supplementary effect size and sensitivity analyses to verify result robustness. Three distinct depressive symptom profiles were identified: low level (39%, n = 135), medium level (52%, n = 187) and high level (9%, n = 31). Town residence and anxiety were risk factors for moderate depression, while good self-rated health, regular exercise and social activity participation were protective factors. Good self-rated health protected against severe depression, while occasional television/radio viewing and anxiety were risk factors. Anxiety was the only independent correlate of high-level versus medium-level depression (OR = 1.322, p < 0.001). Supplementary analyses confirmed the robustness of core findings. The CESD-10, as a screening tool, has limited diagnostic efficacy for clinical depression, and the cross-sectional design cannot confirm causal relationships. Depressive symptoms in Chinese nursing home older adults show significant heterogeneity with three distinct latent profiles. Early screening and targeted stratified interventions should be implemented for this population to improve quality of life and promote healthy aging. Show less
While VPS13C is a recessively inherited Parkinson's disease (PD) gene, its potential dominant effects in idiopathic Rapid-eye movement (REM) sleep behavior disorder (iRBD) remain unexplored. The relat Show more
While VPS13C is a recessively inherited Parkinson's disease (PD) gene, its potential dominant effects in idiopathic Rapid-eye movement (REM) sleep behavior disorder (iRBD) remain unexplored. The relation between its monogenic form and the onset of PD suggested that subtype specificity may need to be considered. We examined the presence of likely pathogenic VPS13C variants in 150 iRBD and 180 α-synucleinopathy patients (iRBD-first and movement disorder-first). VPS13C variants were significantly enriched in iRBD patients, and ten iRBD risk variants have been identified. iRBD risk VPS13C variant carriers demonstrated more severe RBD symptoms and greater autonomic dysfunction, correlating with REM sleep EEG and autonomic network activity abnormalities. Notably, enrichment was specific to the iRBD-first α-synucleinopathy subtype, and iRBD risk VPS13C variant carriers showed accelerated progression to overt α-synucleinopathy. These results suggest that VPS13C not only contributes to iRBD susceptibility but also serves as a marker for the iRBD-first α-synucleinopathy and faster disease conversion. Show less
Shuhe Wang, Zhongguo Liu · 2026 · Frontiers in psychology · Frontiers · added 2026-04-24
This study aimed to use latent profile analysis (LPA) to identify heterogeneous configurational patterns of short video addiction and emotion dysregulation among college students, and to systematicall Show more
This study aimed to use latent profile analysis (LPA) to identify heterogeneous configurational patterns of short video addiction and emotion dysregulation among college students, and to systematically examine the predictive effects of cognitive reappraisal, emotional loneliness, and sociodemographic factors on latent profile membership. A cross-sectional survey design was employed. From April to July 2025, full-time undergraduate students were recruited from multiple universities in Shandong Province using a combination of convenience sampling and snowball sampling. Participants completed online questionnaires including the Short Video Addiction Scale, the Emotion Dysregulation Inventory (EDI), the Cognitive Reappraisal Scale, and the Emotional Loneliness Scale. A total of 1,168 valid questionnaires were obtained. LPA identified four optimal profiles: Profile 1 ("low short video addiction-low emotion dysregulation"), Profile 2 ("medium to lower short video addiction-medium to lower emotion dysregulation"), Profile 3 ("medium to upper short video addiction-medium to upper emotion dysregulation"), and Profile 4 ("high short video addiction-high emotion dysregulation"). Multivariable logistic regression analyses indicated that, with Profile 4 as the reference category, cognitive reappraisal significantly increased the likelihood of membership in lower-risk profiles, whereas emotional loneliness significantly decreased the likelihood of membership in lower-risk profiles. Among sociodemographic factors, being female and having an urban background significantly increased the likelihood of membership in Profile 1 (vs. Profile 4); being a non-only child and having no part-time work experience significantly predicted membership in Profile 3. Marked heterogeneity exists among college students in the measured dimensions of short-form video addiction and emotion dysregulation, and the two constructs exhibit highly concordant co-variation. The findings provide empirical support for developing risk-stratified and precision-oriented mental health intervention strategies. Show less
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, usi Show more
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated Show less
Fusobacterium nucleatum (F. nucleatum), a key periodontal pathogen, is increasingly detected in atherosclerotic plaques, yet its epigenetic regulatory mechanisms in atherosclerosis remain enigmatic. T Show more
Fusobacterium nucleatum (F. nucleatum), a key periodontal pathogen, is increasingly detected in atherosclerotic plaques, yet its epigenetic regulatory mechanisms in atherosclerosis remain enigmatic. This study investigates how F. nucleatum reshapes the non-coding RNA landscape to drive atherosclerosis progression. Periodontal infection with F. nucleatum significantly increased atherosclerotic lesion area (p < 0.001) and necrotic core ratio, while reducing collagen content (p < 0.05) in ApoE Show less
Tc17 cells (IL-17 The percentage of Tc17 cells, monocytes and IL-1β Higher populations of Tc17 cells, IL-1β The present results show that suppressing IL-1β expression by preventing CD80 [Figure: see t Show more
Tc17 cells (IL-17 The percentage of Tc17 cells, monocytes and IL-1β Higher populations of Tc17 cells, IL-1β The present results show that suppressing IL-1β expression by preventing CD80 [Figure: see text] The online version contains supplementary material available at 10.1186/s12964-026-02785-4. Show less
Post-traumatic stress disorder (PTSD) causes debilitating nightmares, flashbacks and anxiety stemming from a catastrophic, often life-threatening traumatic event. Originally described in soldiers expo Show more
Post-traumatic stress disorder (PTSD) causes debilitating nightmares, flashbacks and anxiety stemming from a catastrophic, often life-threatening traumatic event. Originally described in soldiers exposed to the horrors of battle, PTSD is now recognized in civilian victims of assault, natural disasters and mass casualty events. Most people experiencing trauma do not develop PTSD, so understanding neurobiological mechanisms is crucial to predicting risk and developing targeted treatments. There have been many studies seeking to find biomarkers for PTSD, and their results have converged on several brain regions, molecular pathways and neuropsychological functions. In this review, we focus on selected findings about the glucocorticoid receptor (GR), the chaperone protein FKBP51 (FK506 binding protein 51), BDNF (brain-derived neurotrophic factor), fear memory reconsolidation and epigenetic regulation of gene expression in the hypothalamic-pituitary-adrenal (HPA) axis, amygdala and hippocampus. Together, these disparate aspects of brain function provide an emerging model for understanding the etiology and pathophysiology of PTSD. Avoidance of lethal threats is fundamental for survival, and this stringent evolutionary requirement has conserved many components of fear memory storage and behavioural response to danger. PTSD research can therefore rely on non-human animal model systems with better face and construct validity than most other psychiatric disorders. With this advantage, advances in PTSD biomarker identification are likely closer to clinical translation than in other mental illnesses. We attempt to highlight the most promising biomarkers that could be targeted by novel treatments and propose a map for future research work. Show less
Metabolic reprogramming of Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-has emerged as a constitutive feature of cancer, extending far beyond their canonical roles in protein syn Show more
Metabolic reprogramming of Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-has emerged as a constitutive feature of cancer, extending far beyond their canonical roles in protein synthesis and energy provision. In malignancy, these essential amino acids function as pivotal signaling mediators and epigenetic modulators, thereby propelling tumor progression, facilitating immune evasion, and conferring resistance to therapeutic agents. This review delineates how cancer cells subvert branched-chain amino acid metabolism to fuel anabolic processes, activate oncogenic signaling cascades including mTOR and PI3K/AKT, and remodel the tumor microenvironment. A framework is presented to categorize the differential reliance of various cancers on key catabolic enzymes-BCAT1, BCAT2 and BCKDK-underscoring their therapeutic vulnerability. The paradoxical role of BCAAs in modulating anti-tumor immunity is examined alongside the potential of dietary modulation and the development of pharmacological inhibitors targeting this pathway. Concluding perspectives highlight the trajectory for translating these insights into precision oncology, advocating for biomarker-guided and context-specific therapeutic strategies. Show less
Critical limb ischemia (CLI) represents a severe vascular complication of type 2 diabetes, primarily driven by impaired angiogenic capacity, and frequently results in limb amputation or mortality. Her Show more
Critical limb ischemia (CLI) represents a severe vascular complication of type 2 diabetes, primarily driven by impaired angiogenic capacity, and frequently results in limb amputation or mortality. Here, we investigated the therapeutic potential of tirzepatide in promoting perfusion recovery in diabetic hindlimb ischemia and delineated the underlying molecular mechanisms. Human umbilical vein endothelial cells (HUVECs) exposed to high glucose were employed to evaluate tirzepatide's effects on endothelial proliferation, migration, and tube formation, alongside the activation of Akt, endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, assessed by western blotting. Knockdown of GLP-1R or GIPR abrogated the pro-angiogenic effects of tirzepatide, while pharmacological inhibition of the Akt/eNOS or ERK1/2 pathways attenuated endothelial responses. In vivo, tirzepatide treatment significantly enhanced perfusion recovery and increased capillary density in the ischemic limbs of diabetic mice, corroborating its angiogenic effects. Collectively, these findings demonstrate that tirzepatide facilitates angiogenesis and accelerates ischemic limb revascularization through dual GLP-1R/GIPR activation and subsequent engagement of Akt/eNOS and ERK1/2 signaling pathways, highlighting its potential as a therapeutic strategy for diabetic CLI. Show less
The causal links between gut microbiota, inflammatory cytokines, and chronic rhinosinusitis are unclear. A Mendelian randomization study used data from the MiBioGen consortium (211 microbiota taxa, n Show more
The causal links between gut microbiota, inflammatory cytokines, and chronic rhinosinusitis are unclear. A Mendelian randomization study used data from the MiBioGen consortium (211 microbiota taxa, n = 18,340), genome-wide association studies of 91 inflammatory cytokines, and chronic rhinosinusitis data from the FinnGen consortium. Five microbiota taxa were causally linked to chronic rhinosinusitis. The genera Ruminococcaceae NK4A214 group and Victivallis were risk factors, while Lachnospiraceae NC2004 group, Ruminococcus2, and Subdoligranulum were protective. Elevated levels of axin-1, C-X-C motif chemokine 10, interleukin-18 receptor 1, interleukin-1-alpha, and vascular endothelial growth factor A increased risk, whereas C-C motif chemokine 19, CD40L receptor, and Fractalkine were protective. The Ruminococcaceae NK4A214 group id.11358 increased risk through reduced Fractalkine and elevated vascular endothelial growth factor A levels. The study supports a causal link between Ruminococcaceae NK4A214 group id.11358 and chronic rhinosinusitis, mediated by Fractalkine and vascular endothelial growth factor A levels. Show less
About 20-40% of prostate cancer (PCa) develop biochemical recurrence (BCR) after surgery, and propionate metabolism may contribute to tumor progression. BCR remains a major clinical challenge in PCa, Show more
About 20-40% of prostate cancer (PCa) develop biochemical recurrence (BCR) after surgery, and propionate metabolism may contribute to tumor progression. BCR remains a major clinical challenge in PCa, as current tools based on histopathology and prostate-specific antigen (PSA) fail to capture the molecular heterogeneity driving the disease. While metabolic reprogramming is known to facilitate post-treatment adaptation, the specific role of propionate metabolism in this context remains largely unexplored. Therefore, this study aimed to systematically investigate propionate metabolism-related genes (PMRGs) to develop a novel prognostic model for the improved early prediction of recurrence. In this study, The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD), GSE70770 and 412 PMRGs were employed. Differentially expressed genes (DEGs) in PCa and control and DEGs2 in BCR and no BCR samples obtained by differential analysis were intersected with PMRGs to get candidate genes. After Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, biomarkers were identified to construct risk models. Biomarkers including In this study, PMRGs were regarded as biomarkers in PCa for risk model construction, which suggest that propionate metabolism represents a biologically relevant axis in PCa recurrence and may offer a novel framework for biomarker-driven risk assessment. Show less
Atherosclerosis (AS) serves as the pathological foundation for numerous cardiovascular and cerebrovascular diseases and is highly comorbid with depression. The mechanisms underlying this co-morbidity Show more
Atherosclerosis (AS) serves as the pathological foundation for numerous cardiovascular and cerebrovascular diseases and is highly comorbid with depression. The mechanisms underlying this co-morbidity are exceptionally complex, posing significant challenges to effective clinical treatment. Consequently, our study aims to explore the potential biomarkers and mechanisms involved in developing atherosclerosis co-depression disease. We performed differential expression analysis, protein-protein interaction analysis, Gene Ontology (GO) function enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on co-differentiated genes using AS and depression-related datasets from the GEO database. Potential biomarkers were identified through ROC curve analysis. To evaluate the effectiveness of the model, we established an animal model of AS comorbid with depressive disorder and performed a series of assessments, including the sugar-water preference test, open field test, tail suspension test, lipid profile analysis, and pathological examination of aortic sections. Additionally, RNA sequencing analysis of brain tissue, Golgi staining, and detection of synaptic function-related proteins were performed in AS comorbid depressed mice. Finally, in vitro cellular experiments were conducted to further validate the molecular targets and underlying mechanisms. We identified 968 differentially expressed genes associated with AS and 472 differentially expressed genes associated with depression, with 30 genes co-differentially expressed. Protein-protein interaction (PPI) analysis revealed that CCR5, CCR2, NPY, and OPRM1 were strongly associated with AS co-depression, while ROC analysis indicated that Shank2, MDGA2, and S100B were diagnostic markers for AS with depression. Differentially expressed genes were closely associated with the chemokine signaling pathway, neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, and taste transduction. Animal studies demonstrated that ApoE Our study identified seven candidate AS co-depression biomarkers and verified that inflammation-induced damage to synaptic plastic rows is an important mechanism of AS co-depression, providing new insights into the diagnosis and treatment of AS co-depression disorders. Show less
BackgroundAmyloid accumulation and degeneration of the cholinergic white matter pathways are key factors in early Alzheimer's disease pathogenesis and progression. However, the relationship between th Show more
BackgroundAmyloid accumulation and degeneration of the cholinergic white matter pathways are key factors in early Alzheimer's disease pathogenesis and progression. However, the relationship between them remains unclear.ObjectiveTo investigate the association between amyloid accumulation, the integrity of cholinergic white matter pathways, and cognitive performance.MethodsThis cross-sectional study recruited 109 individuals, including 37 controls with normal cognition and 72 patients with early Alzheimer's disease. All participants underwent neuropsychological testing: the Mini-Mental Status Examination (MMSE), Clinical Dementia Rating scale with sum of box (CDR-SB), and verbal fluency tests. Cholinergic white matter integrity and amyloid burden were assessed through diffusion tensor imaging study (DTI) and amyloid positron emission tomography (PET). Stepwise linear regression analyses were performed. Partial correlations between amyloid burden and cholinergic integrity were also evaluated according to apolipoprotein E4 ( Show less
Glycolysis-derived lactate serves as a substrate for lysine lactylation, an epigenetic modification playing critical transcriptional regulatory roles in inflammatory diseases. Endothelial inflammation Show more
Glycolysis-derived lactate serves as a substrate for lysine lactylation, an epigenetic modification playing critical transcriptional regulatory roles in inflammatory diseases. Endothelial inflammation, characterized by upregulated glycolysis, initiates atherosclerosis, yet the contribution of histone lactylation remains undefined. Although narciclasine exhibits anti-inflammatory and antioxidant properties, its impact on endothelial inflammation in atherosclerosis is unknown. Connectivity Map (CMap) analysis predicted narciclasine as an inhibitor of oscillatory shear stress and TNF-α-induced endothelial inflammation. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with 20 nM narciclasine significantly suppressed ox-LDL-induced expression of VCAM1, ICAM1, SELE, and CCL2, reduced reactive oxygen species (ROS) production, and inhibited monocyte adhesion and migration. In vivo, administration of narciclasine (0.02 mg/kg) attenuated carotid artery endothelial inflammation and macrophage infiltration, consequently reducing early atherogenesis in partial carotid ligation model in ApoE Show less
Silica exposure precipitates irreversible lung injury; however, its long-term neurological sequelae—and the microglial mechanisms underlying these effects—remain poorly understood. Here, we demonstrat Show more
Silica exposure precipitates irreversible lung injury; however, its long-term neurological sequelae—and the microglial mechanisms underlying these effects—remain poorly understood. Here, we demonstrate that inhaled crystalline silica induces persistent hippocampal inflammation, anxiety- and depression-like behaviors, and neuronal loss in mice. Bulk RNA sequencing, immunophenotyping, and pharmacological depletion studies revealed that microglia are the primary source of complement C1q in silica-exposed brains. Mechanistically, silica-induced lipocalin-2 (LCN2) engages the melanocortin-4 receptor (MC4R) on microglia, activating a cAMP/PKA/NF-κB cascade that transcriptionally upregulates C1q. Pharmacological blockade of MC4R (using PF) abolished C1q overproduction, normalized brain-derived neurotrophic factor levels, and restored both synaptic integrity and behavioral performance. Our findings establish the LCN2–MC4R–C1q axis as a critical microglial pathway in silica-related neurotoxicity and identify MC4R antagonism as a promising, readily translatable intervention for occupational neuroinflammation. The online version contains supplementary material available at 10.1186/s12974-026-03695-5. Show less
This study aimed to assess the knowledge, attitudes, and practices (KAP) of patients with lower limb arteriosclerosis obliterans (ASO) toward their disease. This cross-sectional study was conducted at Show more
This study aimed to assess the knowledge, attitudes, and practices (KAP) of patients with lower limb arteriosclerosis obliterans (ASO) toward their disease. This cross-sectional study was conducted at 3 tertiary hospitals in Chengdu between August 2023 and January 2024 and included patients with lower limb ASO. Data were collected using an interviewer-administered questionnaire that captured demographic information and KAP scores. A latent profile analysis (LPA) was used to identify the KAP patterns among participants. A total of 515 nonproblematic questionnaires were collected, yielding an effective response rate of 95.72%. Among the respondents, 395 (76.85%) were male, with a disease course of 15.96 ± 17.55 months. The knowledge, attitude, and practice scores were 5.27 ± 4.69 (possible range: 0-22), 17.65 ± 2.86 (possible range: 5-25), and 107.63 ± 17.15 (possible range: 33-165), respectively. LPA identified 4 participant profiles: Profile 1 (high attitude, low practice), Profile 2 (low attitude, high practice), Profile 3 (low attitude, low practice), and Profile 4 (high attitude, high practice). Significant differences were found among profiles in residence (P = 0.028), medical insurance (P = 0.043), self-efficacy (P < 0.001), and patient activation (P < 0.001). Patients with lower limb ASO demonstrated inadequate knowledge but moderate levels of attitude and practice. Residence, medical insurance, self-efficacy, and patient activation may affect the KAP patterns of the patients. These findings suggest that tailored interventions targeting distinct patient profiles, while considering broader social determinants of health, may be critical to improving self-management and outcomes. Show less
Depression is prevalent among colorectal cancer (CRC) survivors. Although various physical activity intensities are differentially associated with depressive symptoms, the underlying mediator and mode Show more
Depression is prevalent among colorectal cancer (CRC) survivors. Although various physical activity intensities are differentially associated with depressive symptoms, the underlying mediator and moderator involving interoception and mindfulness, remain unclear. This study aims to examine whether interoceptive accuracy differentially mediates the relationship between various physical activity intensities and depressive symptoms and whether mindfulness moderates these pathways. In this multicenter cross-sectional study, 395 CRC survivors completed validated questionnaires assessing depressive symptoms, physical activity participation, interoceptive accuracy, and mindfulness. Mediation and moderated mediation analyses via PROCESS version 4.1 for SPSS tested whether interoceptive accuracy mediated associations between light and moderate-to-vigorous physical activity (LPA vs. MVPA) and depressive symptoms, and whether mindfulness moderated these pathways. Both LPA and MVPA are negatively associated with depressive symptoms (p < 0.001). Interoceptive accuracy significantly mediated these associations, accounting for 49.09% of the total effect for LPA and 20.56% for MVPA. Mindfulness moderated the LPA-interoceptive accuracy (B = -0.004, p = 0.031), interoceptive accuracy-depression (B = -0.022, p = 0.004), and MVPA-depression pathways (B = -0.001, p = 0.034), suggesting differential, intensity-dependent associations. LPA showed negative associations with depressive symptoms, with interoceptive accuracy fully mediating this association. In contrast, MVPA demonstrated both direct and indirect associations with depressive symptoms, partially mediated by interoceptive accuracy. Mindfulness strengthened these relationships through complementary and synergistic moderation, highlighting the dynamic interaction between bodily awareness and physical activity in psychological recovery. Tailoring gentle, mindful movement to enhance interoception may offer a feasible, integrative rehabilitation strategy to reduce depression among CRC survivors. Show less
Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. Show more
Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. This study investigated whether probucol could alleviate AD-associated bone loss and Aβ42-induced osteoblast dysfunction, and further explored the underlying mechanisms. Female mice were divided into four groups (n = 5 per group): C57BL/6 wild-type (WT), WT treated with probucol (WT + PBC), APP/PS1 transgenic (AD) mice, and AD treated with probucol (AD+PBC). Bone mineral density (BMD) was assessed by micro-CT. Levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) along with bone metabolism markers including fibroblast growth factor 23 (FGF23), sclerostin, and brain-derived neurotrophic factor (BDNF) in bone and brain tissues were measured by ELISA. FOXO3a was knocked down in the bone marrow of APP/PS1 mice via stereotactic injection of lentiviral vectors. Expression of APP and FOXO3a in bone tissue was evaluated using RT-qPCR and Western blotting (WB). Mitochondrial damage in osteoblasts and neuronal cells was assessed by transmission electron microscopy (TEM). In vitro study, osteoblast differentiation and mineralization deficits were evaluated using Alizarin Red staining. WB was used to measure the expression of AKT, FOXO3a, autophagy and apoptosis related proteins. Probucol attenuated bone loss and mitochondrial damage in both APP/PS1 and FOXO3a-knockdown APP/PS1 mice, and improved cognitive impairment and neuronal ultrastructure in APP/PS1 mice. Furthermore, probucol attenuated Aβ42-induced osteoblast differentiation and mineralization via the AKT/FOXO3a signaling pathway in vitro. These findings demonstrate that probucol ameliorates AD-associated bone loss and Aβ42-induced osteoblast impairments by regulating AKT/FOXO3a signaling pathway. Show less
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological Show more
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer. Show less
Cerebrospinal fluid (CSF) proteomics offers insights into molecular changes in aging and Alzheimer's disease (AD). Key AD biomarkers, in particular amyloid-β (Aβ) and tau, in CSF are strongly associat Show more
Cerebrospinal fluid (CSF) proteomics offers insights into molecular changes in aging and Alzheimer's disease (AD). Key AD biomarkers, in particular amyloid-β (Aβ) and tau, in CSF are strongly associated with Show less
Diabetic refractory wounds are a severe complication of diabetes, often synchronized with diabetic peripheral neuropathy. In this study, we demonstrated a significantly downregulated expression of cal Show more
Diabetic refractory wounds are a severe complication of diabetes, often synchronized with diabetic peripheral neuropathy. In this study, we demonstrated a significantly downregulated expression of calcitonin gene-related peptide (CGRP) in the skin tissues of both diabetic patients and diabetic mouse models. This observation implies the crucial role of CGRP in diabetic wound healing. Based on this discovery, we engineered glucose-responsive along with sustained-release antibacterial hydrogel microspheres (BA-HPCS@CGRP) for the controlled delivery of CGRP and conducted systematic evaluation of its therapeutic efficacy. In vitro findings demonstrated that microspheres not only directly enhanced the migration and tube formation capabilities of endothelial cells impaired by high glucose but also further facilitated the restoration of endothelial cell function by promoting the secretion of angiopoietin-like protein 4 (Angptl4) by macrophages after switching to M2 phenotype by CGRP. The results from diabetic mouse models showed that BA-HPCS@CGRP accelerated diabetic wound healing by modulating macrophage polarization towards to M2 phenotype and reduced inflammation, promoted neurovascular regeneration and restored the local CGRP expression. These findings suggest that sustained releasing of low concentration of CGRP provides novel therapeutic approaches for diabetic wounds via modulating macrophage. Moreover, BA-HPCS@CGRP achieves comprehensive sequential therapy through the synergistic modulation of the "neuro-immune-vascular" axis, which might open new perspective to chronic wounds and regenerative medicine. Show less
Atherosclerosis is considered as a major contributor for cardiovascular disease with high morbidity and mortality globally. However, the cross-talk between efferocytosis and inflammation in atheroscle Show more
Atherosclerosis is considered as a major contributor for cardiovascular disease with high morbidity and mortality globally. However, the cross-talk between efferocytosis and inflammation in atherosclerosis remains elusive. ApoE (apolipoprotein E) YY1 and NEDD4L were upregulated, but MerTK was downregulated in the arteries of ApoE Our findings demonstrated that YY1 positively regulated NEDD4L to modulate MerTK-mediated efferocytosis and activate NLRP3-mediated inflammation and pyroptosis, thus exacerbating atherosclerosis. Show less
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated Show more
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated the association between APOE ε4 and cognition in ICAS. Baseline data from a multicenter cohort were analyzed. Patients with radiologically confirmed ICAS underwent APOE genotyping, plasma biomarker assays, magnetic resonance imaging assessment of cerebral small vessel disease (CSVD) and brain atrophy, and standardized cognitive testing. Among 409 patients (mean age 60 years, 55% male), 16% carried APOE ε4. Carriers showed more frequent cognitive impairment (63% vs 48%), greater stenosis burden, and lower plasma amyloid beta (Aβ)42/40 ratios, whereas other Alzheimer's biomarkers, CSVD burden, and atrophy scores showed no difference. After adjustment, APOE ε4remained associated with cognitive impairment (odds ratio [OR] 1.86). The association was pronounced in women (OR 4.43) but absent in men. APOE ε4 is linked to cognitive impairment in ICAS, particularly in women, through mechanisms beyond Alzheimer's pathology. In patients with ICAS, cognitive impairment was more prevalent in carriers than in non-carriers. Carriers showed greater stenosis burden and lower plasma Aβ42/40 ratios. After full adjustment (stroke, CSVD, and AD biomarkers), APOE ε4 remained associated with cognitive impairment. Female carriers had substantially higher odds of cognitive impairment. Show less
In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring The incidence of Our study revealed the heterogeneous outcomes of
Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohort Show more
Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohorts and a chronic unpredictable mild stress (CUMS) rat model. Targeted UPLC-MS/MS profiling was applied to a training cohort (95 MDD, 40 controls), and untargeted UPLC-HRMS profiling to an independent cohort (56 MDD, 37 controls). Candidate biomarkers were identified using univariate tests, partial least squares discriminant analysis, and three feature-selection methods (Boruta, LASSO, RFE), with predictive performance evaluated by cross-validation and external replication. Translational relevance was examined in CUMS rats through behavioral assays and lipidomic profiling of serum and brain tissues. Pathway enrichment and regression models explored metabolic context and clinical associations. In the training cohort, we found that 244 lipids were significantly altered, highlighting altered glycerophospholipid, glycerolipid, and sphingolipid metabolism. A 29-lipid panel achieved 90.4% cross-validation accuracy, while a reduced 7-lipid subset reached 94.8%. In the validation cohort, an 8-lipid panel achieved 71.2% accuracy, and a minimal 2-lipid set-LPA(18:2) and SPH(d16:1)-reached 72.1%. Cross-species analysis confirmed consistent downregulation of SPH(d16:1) in serum of both humans and rats, and of LPC(0:0/16:0) specifically in the rat prefrontal cortex. Regression analyses linked sex, age, and anxiety severity to lipid alterations. This cross-platform, cross-species study identifies reproducible lipid signatures of adolescent MDD, highlights SPH(d16:1) and LPC(0:0/16:0) as translational biomarkers, and implicates glycerophospholipid metabolism in MDD pathophysiology, providing a foundation for biomarker-guided diagnostics and therapeutics. Show less