FGFRs genetic alterations such as mutations, amplifications, and chromosomal translocations are prevalent in cancers, leading to the initiation and progression of tumors by enhancing FGFR signaling. T Show more
FGFRs genetic alterations such as mutations, amplifications, and chromosomal translocations are prevalent in cancers, leading to the initiation and progression of tumors by enhancing FGFR signaling. The substantial problems arising from the lack of decisive clinical evidence have resulted in the cessation of some inhibitor applications, and identifying effective small molecule inhibitors that selectively target FGFRs can advance the therapy of cancers driven by FGFRs abnormalities. The three-dimensional structure of the FGFR1/2/3/4 protein and the amino acid positions within the tyrosine kinase domain were downloaded from the PDB database, and small molecule data were extracted from the ZINC15 database. Then, we used molecular docking and dynamics simulations to assess compounds interacting with FGFR proteins, and screening potential small molecules targeting FGFR. Finally, we evaluated its effects by two CRC cell line HCT116 and NCI-H716. In the study, by docking with 2.8 million small molecules, we identified three promising FGFR small molecule inhibitors ranked in the top average absolute difference in free energy. By evaluating the binding stability of the docking pose of the three compounds, we found that ZINC000101867325 could form the stable binding interactions with FGFR1/2/3. And, ZINC000101867325 inhibited the activity of FGFR signaling, and resulted in cell apoptosis and decrease in cell proliferation and migration in colorectal cancer cell lines. In addition, ZINC000101867325 is also predicted to target FGFR2 mutations in colorectal cancer patients. We predicted three small molecules targeting FGFRs, and ZINC000101867325 shows superior chemical bond types and stability with FGFR1/2/3, and inhibits FGFR signaling in CRC cell lines. This study provides novel FGFRs inhibitors, which enrich treatment strategies for cancers. Show less
Alzheimer's disease (AD) is a common neurodegenerative disorder wherein reactive oxygen species (ROS) and Amyloid-β-protein (Aβ) play critical roles. Inspired by traditional Chinese charcoal drug and Show more
Alzheimer's disease (AD) is a common neurodegenerative disorder wherein reactive oxygen species (ROS) and Amyloid-β-protein (Aβ) play critical roles. Inspired by traditional Chinese charcoal drug and the anti-inflammatory properties of some carbon dots, we developed Radix Isatidis derived carbon dots (RI-CDs) via a hydrothermal method. The RI-CDs can cross the blood-brain barrier (BBB) and were thus evaluated for AD therapy. In vitro, RI-CDs scavenged ROS, inhibited Aβ 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
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
Sepsis triggered by lipopolysaccharide (LPS) is a life-threatening condition. Inspired by the specific capture mechanism of innate proteins like LBP and CD14, we develop oxidized chitosan microspheres Show more
Sepsis triggered by lipopolysaccharide (LPS) is a life-threatening condition. Inspired by the specific capture mechanism of innate proteins like LBP and CD14, we develop oxidized chitosan microspheres functionalized with hyperbranched polylysine (OCS-HBPL) as a sepsis detoxification agent. Isothermal titration calorimetry (ITC) reveals that HBPL-LPS binding is an enthalpy-driven process, distinct from the entropy-driven interaction of linear polylysine (LPL)-LPS. Validated by surface plasmon resonance (SPR), HBPL demonstrates superior affinity with a dissociation constant (K Show less
Docosahexaenoic acid (DHA), one of the most critical polyunsaturated fatty acids, is vital for the neurological growth and cognitive function of infants and children. Approximately 98% of DHA in breas Show more
Docosahexaenoic acid (DHA), one of the most critical polyunsaturated fatty acids, is vital for the neurological growth and cognitive function of infants and children. Approximately 98% of DHA in breast milk exists as triglycerides, with 60% esterified at the sn-2 position. To demonstrate the necessity of mimicking the form of DHA present in breast milk in nutritional food for young children, this study administered diets with varying sn-2 DHA contents (10%, 30%, and 50%) to four groups of mice and analyzed their behavioral performance, brain DHA concentration, expression of brain fatty acid transport proteins, histopathology, and expression of synaptic-related proteins in the hippocampus after 4 weeks. The results showed that compared with the control group, mice in the 50% sn-2 DHA group exhibited superior learning and memory capabilities in behavioral tests, with the most pronounced behavioral improvements in mice, which correlated with higher brain DHA accumulation (from 0.870 ± 0.055 mg/g brain to 1.809 ± 0.132 mg/g brain, p < 0.05), increased levels of MFSD2A (1.40-fold, p > 0.05), FABP5 (2.36-fold, p < 0.05), FATP1 (1.47-fold, p < 0.05), and ACSL6 (1.48-fold, p < 0.05), improved hippocampal neuron morphology, and enhanced the level of BDNF (1.55-fold, p < 0.05), SYN (1.45-fold, p < 0.05), and PSD-95 (1.57-fold, p < 0.05). These findings establish a foundation for developing DHA nutritional supplements. 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
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
Atherosclerosis is a chronic and progressive inflammatory disease that can lead to adverse cardiovascular and cerebrovascular events. Phenotypic switching of vascular smooth muscle cells (VSMCs) plays Show more
Atherosclerosis is a chronic and progressive inflammatory disease that can lead to adverse cardiovascular and cerebrovascular events. Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development and progression, but the upstream regulatory mechanisms remain incompletely defined. Here, we identify ubiquitin-fold modifier 1 (UFM1), a ubiquitin-like protein, as a critical regulator of VSMCs plasticity and atherogenesis. In VSMCs stimulated with oxidized low-density lipoprotein (ox-LDL), UFM1 overexpression markedly attenuated phenotypic switching, restoring contractile features and suppressing synthetic activation, accompanied by reduced proliferation and migration. In contrast, UFM1 knockdown further exacerbated these phenotypic alterations. In ApoE 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
Atherosclerosis (AS) is a major underlying cause of cardiovascular diseases, with hypercholesterolemia, inflammatory responses, and macrophage polarization being established key contributors. The role Show more
Atherosclerosis (AS) is a major underlying cause of cardiovascular diseases, with hypercholesterolemia, inflammatory responses, and macrophage polarization being established key contributors. The roles of NLRP3 inflammasome activation and macrophage polarization in AS pathogenesis have garnered significant research interest. This study investigated the therapeutic potential of Schisandrol B (Sol B) against AS using an in vivo model of ApoE 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
Ye-Qin Tao, Hui Liu, Ming-Guo Gao+5 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Based on the TCM theory of "phlegm-stasis intermingling", this study aims to investigate the mechanism of Danzha Tongmai Pills(DZTMW) in treating atherosclerosis(AS), focusing on elucidating Show more
Based on the TCM theory of "phlegm-stasis intermingling", this study aims to investigate the mechanism of Danzha Tongmai Pills(DZTMW) in treating atherosclerosis(AS), focusing on elucidating its in vivo active components, metabolic regulatory effects in serum, hepatoprotective effects, and anti-inflammatory efficacy. An AS model was established in apolipoprotein E knockout(ApoE~(-/-)) mice, which were divided into a normal group, an model group, low/medium/high-dose DZTMW groups, and an atorvastatin positive control group. The normal group was fed a standard diet, while the other groups were fed a high-fat diet to induce AS lesions. During the intervention phase, the groups were administered corresponding drugs or an equal volume of solvent by gavage. A series of tests were conducted after continuous intervention. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to identify the blood-entering components of DZTMW, and liquid chromatography-high-resolution mass spectrometry(LC-HRMS) was employed for non-targeted serum metabolomics analysis. Pearson correlation analysis was used to analyze the correlation between blood-entering components and differential metabolites. Levels of serum lipid [total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and free fatty acids(FFA)] and liver function markers [alanine aminotransferase(ALT) and aspartate aminotransferase(AST)] were measured. Liver histopathology and lipid deposition were assessed by HE and oil red O staining, and serum levels of inflammatory factors [lipoprotein-associated phospholipase A2(LP-PLA2), high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α), and interleukin-1 beta(IL-1β)] were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that 23 blood-entering components were identified from DZTMW, including three prototype compounds, 20 metabolites, and 142 differential metabolites of serum. Core blood-entering components such as hydroxyl asiatic acid M1 and neocryptotanshinone metabolite were highly/extremely correlated with differential metabolites like 5-hydroxytryptamine, lysophosphatidylcholine(P-18:1/0:0) and sphingomyelin(d18:1/15:0). DZTMW administration at various doses significantly reduced the serum levels of TC, TG, LDL-C, and FFA(P<0.01), increased the HDL-C level(P<0.01), decreased ALT and AST activities(P<0.05, P<0.01), alleviated hepatocyte steatosis and lipid droplet deposition, and down-regulated the expression of inflammatory factors in a dose-dependent manner(P<0.01). The effects of the high-dose DZTMW group were comparable to those of the atorvastatin group. In summary, DZTMW can effectively inhibit the progression of AS in ApoE~(-/-) mice. Its mechanism may involve the regulation of hepatic lipid metabolism by its in vivo active components to ameliorate the "phlegm-turbidity" pathology and reduce liver injury, and the inhibition of systemic inflammation to alleviate the "blood stasis" process. The study can provide a modern biological basis for the theory of "phlegm-stasis intermingling". 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
Anshen Bunao Syrup (ABS), a traditional Chinese medicinal formula, is widely used to treat neurological disorders such as insomnia, dizziness, and neurasthenia. However, its antidepressant effect and Show more
Anshen Bunao Syrup (ABS), a traditional Chinese medicinal formula, is widely used to treat neurological disorders such as insomnia, dizziness, and neurasthenia. However, its antidepressant effect and underlying mechanisms remain insufficiently characterized. This study aims to comprehensively evaluate the antidepressant effect of ABS in a rat model, and to elucidate the underlying mechanism. Chronic unpredictable mild stress (CUMS) induced depressive rats were used to evaluate the antidepressant effect of ABS. Histopathological alterations in the hippocampus and colonic mucosa were examined using Nissl and H&E staining. Microglial activation was evaluated by Iba-1 immunohistochemical staining. Gut microbiota composition and metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Differential gene expression and pathway regulation were investigated by transcriptomics and confirmed by Western Blot (WB). ABS significantly ameliorated depressive-like behaviors and elevated dopamine and 5-Hydroxytryptamine levels in cortical regions. Furthermore, ABS mitigated hippocampal neuronal damage, suppressed microglial overactivation and reduced oxidative stress in the cortex. 16S rRNA sequencing analysis showed that ABS exerted antidepressant effects via modulation of the "microbiota-gut-brain" axis, particularly by altering intestinal microbiota composition, enhancing gut function, and suppressing HPA axis hyperactivity. Metabolomics revealed that ABS corrected metabolic disturbances, and alleviated inflammation-related metabolic disturbances, while transcriptomics indicated regulation of the Npas4-BDNF-PI3K/AKT signaling pathway, which was further confirmed by WB. ABS significantly ameliorated depression in a CUMS rat model, primarily through coordinated regulation of gut microbiota, metabolic homeostasis, and the Npas4-BDNF-PI3K/AKT signaling pathway, providing integrative mechanistic insights into its antidepressant effects. 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
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
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
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
Vascular calcification (VC) is prevalent in patients with chronic renal failure (CRF), and it is closely related to the morbidity and mortality of cardiovascular diseases; however, no medical treatmen Show more
Vascular calcification (VC) is prevalent in patients with chronic renal failure (CRF), and it is closely related to the morbidity and mortality of cardiovascular diseases; however, no medical treatments are available for this condition. Recent clinical studies have shown that plasma apolipoprotein C3 (ApoC3) levels are positively correlated with VC. However, whether ApoC3 is involved in VC remains unclear. Sections of calcified renal arteries from CRF patients were immunostained to measure calcium deposition and ApoC3 expression. VC was induced in ApoC3 transgenic (Tg) and knockout (KO) mice by both 5/6 nephrectomy and vitamin D ApoC3 expression levels were increased in calcified arteries from mice and patients with CRF. ApoC3 overexpression exacerbated calcium deposition in the calcified aortas from Tg mice in vivo, and in calcified aortic rings of Tg mice ex vivo and VSMCs infected by adenovirus of ApoC3 in vitro. Consistently with these findings, ApoC3 deficiency alleviated these effects. Furthermore, ApoC3 overexpression increased ferroptosis in calcified aortas and VSMCs, whereas ApoC3 deficiency suppressed ferroptosis. Further investigation revealed that ApoC3 inhibited the AMPK/NRF2 signaling pathway through toll-like receptor 2 (TLR2) in calcified VSMCs, downregulated the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), subsequently increased lipid peroxidation and promoted ferroptosis, ultimately exacerbating calcification in the VSMCs. Furthermore, we found that knockdown of ApoC3 by siRNA remarkably attenuated calcification of renal arterial rings in humans. We demonstrated that ApoC3 exacerbated VC and increased the osteogenic transdifferentiation in VSMCs by increasing ferroptosis. ApoC3 might be a potential target for VC treatment. 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
This study examined the heterogeneous nature of dual-career stress and its asymmetric associations with on adolescent athletes, aiming to: (1) identify distinct stress profiles based on academic, trai Show more
This study examined the heterogeneous nature of dual-career stress and its asymmetric associations with on adolescent athletes, aiming to: (1) identify distinct stress profiles based on academic, training, and role-conflict stressors; (2) assess whether stress associations vary across levels of athletic burnout and academic performance; and (3) test whether stress profiles moderate these relationships. A two-wave longitudinal study included 843 adolescent male football players in China. Latent Profile Analysis (LPA) categorized participants using three stressor subscales at Time 1. Quantile Regression (QR) at Time 2 (6 months later) analyzed the association between total stress and athletic burnout and academic performance across five quantiles (τ = 0.10-0.90), with stress profile as moderator, controlling for social support, time management, and demographics. LPA revealed four profiles: Balanced Moderates (37.2%), Academically Overwhelmed (28.1%), Sport-Centric Strained (22.0%), and Dual-Track Distressed (12.7%). QR showed the positive association between stress and burnout increased across quantiles (β = 0.41 at τ = 0.10 to 0.78 at τ = 0.90), with the strongest association observed among already burnt-out athletes most. For academic performance, the negative association between stress and performance was strongest at lower quantiles (β = -0.71 at τ = 0.10) and weaker at higher quantiles (β = -0.29 at τ = 0.90). Stress profiles significantly moderate these relationships: the Dual-Track Distressed profile showed the strongest association with on burnout (β = 0.89), while Academically Overwhelmed and Dual-Track Distressed profiles showed the strongest negative association with on academic performance (β = -0.79 and -0.92, respectively). Dual-career stress experiences and impacts are highly heterogeneous. Adolescents cluster into meaningful stress profiles, and stress is most strongly associated with negative outcomes among those already at extremes of burnout or poor academic performance. Findings underscore the need for personalized interventions tailored to athletes' specific stress profiles and outcome levels, supporting holistic development in dual-career contexts. 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
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
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