Despite the critical role of e-Health literacy (eHL) in modern healthcare, current research predominantly concentrates on conditions such as cancer and diabetes, as well as outpatient care settings. H Show more
Despite the critical role of e-Health literacy (eHL) in modern healthcare, current research predominantly concentrates on conditions such as cancer and diabetes, as well as outpatient care settings. However, there remains a significant gap in studies specifically addressing the eHL needs of patients with maintenance hemodialysis (MHD). This study aims to explore the latent categories of eHL among MHD patients and its impact on health-promoting lifestyle (HPL). A survey was conducted using a convenience sampling method involving 500 MHD patients from three tertiary hospitals in Baoding. Data were analyzed using latent profile analysis (LPA) and a mixed regression model. This study showed that MHD patients could be classified into low (23.17%), middle (49.78%), and high (27.05%) eHL groups, with the three-class model showing optimal fit (AIC = 2321.213, BIC = 2271.168, entropy = 0.967). MHD Patients in the high literacy group scored significantly higher in all dimensions of e-HL and overall HPL (119.58 ± 13.86) compared to those in the low literacy group (91.82 ± 11.73) (all The findings suggest a heterogeneous stratification of eHL among MHD patients, closely linked to HPL. Stratified intervention strategies should be developed for different patient groups to potentially improve their health behaviors. The study provides evidence-based support for personalized health management. Show less
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccha Show more
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752. Structural analysis revealed that BVP1 is a neutral α-mannan consisting of a backbone of 1,2,6-linked α-D-Manp, with branches composed of T-linked α-D-Manp, 1,2-linked α-D-Manp, and 1,3-linked α-D-Manp. Animal experiments showed that BVP1 significantly alleviated hepatic steatosis, liver injury and inflammation, and enhanced antioxidant activity in MAFLD mice. Single-nucleus RNA sequencing analysis revealed that BVP1 could restore HFD-induced imbalances in liver sinusoidal endothelial cells, hepatic stellate cells, macrophages and Kupffer cells by upregulating the expression of the lipid degradation gene Cps1 and downregulating the expression of the lipid synthesis gene Acsl1 in these cell subpopulations. Interestingly, BVP1 reshaped the gut microbiota and fecal metabolite profile by enriching beneficial bacteria and associated metabolites including salicylic acid, spermidine, and 4-hydroxyphenyl acetate. Fecal microbiota transplantation experiments verified that the anti-MAFLD effects are mediated by the BVP1-modified gut microbiota. Our findings highlight the potential of BVP1 as a promising therapeutic agent for MAFLD treatment. Show less
Atherosclerotic cardiovascular disease (ASCVD) is a major threat to human life and health, and dyslipidemia with elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor, and i Show more
Atherosclerotic cardiovascular disease (ASCVD) is a major threat to human life and health, and dyslipidemia with elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor, and in the optimal LDL-C scenario, apolipoprotein B (ApoB) has a more predictive value of ASCVD risk. The study is a genome-wide association study (GWAS) based on a European population. A large GWAS dataset for atherosclerotic cardiovascular diseases was targeted, including coronary heart disease (CHD), ischemic stroke (IS), large-artery atherosclerotic stroke (ISL), small-vessel stroke (ISS), and myocardial infarction (MI). Univariate two-sample mendelian randomization (MR) analyses of ApoB and the above cardiovascular diseases were performed separately, and the association was assessed mainly using the inverse variance weighted (IVW) method, with confidence intervals for the superiority ratios set at 95%. In addition, the experiment was supplemented using MR-Egger, weighted model and weighted median (WM). Based on the results of univariate two-sample mendelian randomisation analysis, it was shown that there was a causal relationship between ApoB and CHD (OR = 1.710, 95% CI 1.529-1.912, P = 0.010), ISL (OR = 1.430, 95% CI 1.231-1.661, P = 2.714E-06), ISS (OR = 1.221, 95% CI 1.062-1.405, P = 0.005) were causally related to each other and the disease prevalence ratio was positively correlated with ApoB concentration. This MR analysis demonstrated a causal relationship between ApoB and CHD, ISL, ISS, but not with the risk of developing IS and MI, which further validated the relationship between ApoB and the risk of ASCVD, and contributed to a better understanding of the genetic impact of ApoB on ASCVD, and to a certain extent, could improve the management of ApoB and reduce the prevalence of ASCVD. Show less
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the m Show more
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the mechanisms of disease resistance in these breeds could lay the groundwork for genetic improvements in pig immunity, potentially augmenting overall pig productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Min and Large White pigs for transcriptome sequencing. The mRNA and lncRNA in both pig breeds were analyzed, and intra-group and inter-group comparisons were also conducted. The results indicated that a greater number of immune-related pathways such as the JAK-STAT and PI3K-AKT signaling were enriched in Min pigs. Furthermore, genes involved in inflammation and antiviral responses, including IL16, IL27, USP18, and DHX58, were upregulated in post-vaccination Min pigs compared to post-vaccination Large White pigs. This heightened immune responsiveness could contribute to the observed differences in disease resistance between Min pigs and Large White pigs. Show less
Poly(A) binding protein cytoplasmic 4 (PABPC4) has been regarded as a prognostic marker in many malignancies. In this study, we evaluated PABPC4 expression at both messenger ribonucleic acid (mRNA) an Show more
Poly(A) binding protein cytoplasmic 4 (PABPC4) has been regarded as a prognostic marker in many malignancies. In this study, we evaluated PABPC4 expression at both messenger ribonucleic acid (mRNA) and protein levels. The prognostic value of PABPC4 in patients with prostate cancer (PCa) was also investigated. The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, our analysis of Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), and 65 pairs of ribonucleic acid (RNA) sequencing data from our center were employed to detect the expression of PABPC4 in PCa tissues. Tissue microarrays (TMAs) were utilized to detect the expression of the PABPC4 protein, and survival analysis as well as risk factor analysis were conducted. In the 65 pairs of sequencing data, the expression of PABPC4 in tumor tissues was significantly higher than that in paired adjacent tissues (P<0.001), and its expression also presented significant differences among different Gleason groups (P=0.041). In the CPGEA data, the expression of PABPC4 in tumor tissues was significantly higher than that in control tissues (P<0.001), and the expression of PABPC4 in M1 patients was higher than that in M0 patients, although no significant statistical difference was shown (P=0.051). In the TCGA data, the expression of PABPC4 in tumor tissues was significantly higher than that in control tissues (P<0.001). The expression of pT3/4 (pathological tumor stage 3 and pathological tumor stage 4) in high-stage tumor tissues was significantly higher than that in low-stage tumor tissues (pT2) (P=0.02), the expression of pT3/4 in GSE21034 and GSE32571 tumor tissues was significantly higher than that in control tissues (P<0.001), and the expression of pT3/4 in primary tumor tissues was higher than that in metastatic tissues in GSE6752 (P<0.001). The TCGA data revealed that patients with high PABPC4 expression had poorer overall survival (OS) than those with low PABPC4 expression (P=0.04), and the TMA data indicated that patients with high PABPC4 expression had a poor prognosis (P=0.004). Our study demonstrated that PABPC4 was overexpressed at mRNA and protein levels in PCa. We found that patients with high PABPC4 expression had a shorter biochemical recurrence (BCR)-free survival and OS, showing its value as a prognostic biomarker in patients with PCa. Show less
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; howe Show more
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation screen to identify molecular drivers of brain metastasis from an orthotopic xenograft model derived from a patient with NSCLC. We found that activating expression of the Alzheimer's disease-associated beta-secretase 1 (BACE1) led to a substantial increase in brain metastases. Furthermore, genetic and pharmacological inhibition of BACE1 blocked NSCLC brain metastasis. Mechanistically, we identified that BACE1 acts through epidermal growth factor receptor to drive this metastatic phenotype. Together, our data highlight the power of in vivo CRISPR activation screening to unveil molecular drivers and potential therapeutic targets of NSCLC brain metastasis. Show less
Bo Lin, Mengsen Li · 2025 · Frontiers in immunology · Frontiers · added 2026-04-24
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are Show more
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are loss-of-function mutations in signaling pathway regulators such as axis inhibition protein 1 (Axin1) and adenomatous polyposis coli (APC). The activation of the Wnt/β-catenin pathway synergizes with other oncogenic signal molecules such as c-Met or glypican-3, contributing to HCC development. Furthermore, Wnt/β-catenin pathway activation in the tumour microenvironment (TME) leads to cold tumour and resistance to immunotherapy. In this review, we discuss two models of Wnt/β-catenin signaling activation, role of Wnt/β-catenin signaling pathway in the development of HCC, the association between Wnt/β-catenin pathway and tumour angiogenesis, metastasis, and immune escape in the TME, and the targeting of this signaling pathway for HCC treatment. Show less
Osteosarcoma is the most prevalent primary malignant bone tumor in children and adolescents. However, its underlying pathogenesis and mechanisms driving metastasis remain poorly understood. Here, we i Show more
Osteosarcoma is the most prevalent primary malignant bone tumor in children and adolescents. However, its underlying pathogenesis and mechanisms driving metastasis remain poorly understood. Here, we identified a novel super-enhancer-associated long noncoding RNA (SE-lncRNA), Zinc Finger MIZ-Type Containing 1 Antisense RNA 1 (ZMIZ1-AS1), which is highly expressed in osteosarcoma and promoted tumor cell proliferation, migration, and invasion. Mechanistically, the m⁶A demethylase ALKBH5 post-transcriptionally stabilized ZMIZ1-AS1 through m⁶A demethylation. Furthermore, ZMIZ1-AS1 directly bound to the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1), facilitating the translocation of PTBP1 from the nucleus to the cytoplasm. The relocalized PTBP1 then bound to and stabilized fibroblast growth factor receptor 1 (FGFR1) mRNA. In nude mouse models, ZMIZ1-AS1 overexpression promoted tumor growth and lung metastasis. Notably, combined inhibition of ALKBH5 (using ALKBH5-IN-5) and FGFR1 (using BGJ398/infigratinib) synergistically suppressed ZMIZ1-AS1-driven oncogenesis in vivo. Our study establishes the ALKBH5/ZMIZ1-AS1/PTBP1/FGFR1 signaling axis as a key driver of osteosarcoma progression and a promising target for therapeutic intervention. Show less
Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial-mesenchymal transition (EMT) is a key driver Show more
Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial-mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM. Show less
The leopard coral grouper (Plectropomus leopardus), an increasingly important species in marine aquaculture, has garnered significant research interest due to its high market value. Despite extensive Show more
The leopard coral grouper (Plectropomus leopardus), an increasingly important species in marine aquaculture, has garnered significant research interest due to its high market value. Despite extensive research on ovarian growth and development in fish, the molecular mechanisms governing lipid droplet formation and lipid deposition in P. leopardus remain poorly understood. In this study, we conducted transcriptomic analyses of P. leopardus ovaries at three developmental stages: primary growth (PG), pre-vitellogenesis (PV), and mid-vitellogenesis (MV). A total of 534,847,090 raw reads were obtained from nine cDNA libraries, leading to the identification of 19,155 genes with 13,817 genes expressed at all stages. Differential analysis showed that 1012, 2609, and 4039 genes were up-regulated, while 168, 277, and 577 genes were down-regulated in the three comparisons, respectively. Functional enrichment analyses highlighting the critical roles of differentially expressed genes (DEGs) in lipid transport (such as fatp1, fatp4, fatp6, apoeb, lpl and fabps), fatty acid metabolism (such as elovl6, acsl1, dgat2 and gpat4) and phospholipid metabolism (such as ept1, chka and pla2g15). These findings underscore their contribution to lipid droplet formation and deposition. Furthermore, key signaling pathways, including Wnt, mTOR, PPAR and PI3K/Akt, were implicated in regulating these processes. The reliability of the RNA-seq data was confirmed through qPCR validation of 10 lipid-related genes. Based on these results, we propose a model for lipid droplet formation and lipid deposition during ovarian development in P. leopardus. This study advances our understanding of ovarian development in P. leopardus and provides a foundation for future research on marine fish reproduction, with potential applications in species conservation and aquaculture management. Show less
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined r Show more
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cell Show more
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cellular heterogeneity, molecular pathways, and clinical features of COKC are limited. In this study, we performed single-cell RNA sequencing (scRNA-seq) on three COKC samples and integrated the data with a public OKC dataset, identifying 22,509 single cells. Two COKC-specific epithelial subpopulations, Basal-C0-EXT1 and Basal-C3-HIST1H3B, were identified. These subpopulations exhibited enhanced stemness and invasive potential, respectively, suggesting their roles as key drivers of OKC carcinogenesis. Fibroblasts underwent phenotypic transitions, particularly from inflammation-associated fibroblasts (IFBs) to myofibroblasts (MFBs). Similarly, macrophage phenotypic transformation may also play a role in OKC carcinogenesis. Clinical observations of severe lesion-area pain in COKC patients suggest potential neuroinvasiveness, Supported by single-cell transcriptomic data, imaging findings, and histopathological evidence. A review of clinical data revealed that none of the COKC patients exhibited cervical lymph node metastasis. Single-cell transcriptomics suggests that this phenomenon may be associated with an active immune microenvironment in COKC, reduced epithelial-mesenchymal transition (EMT) activity, lower VEGFC expression, and upregulated MAST4 expression as a potential regulator of lymphatic metastasis. In conclusion, COKC exhibits distinct molecular, cellular, and clinical characteristics compared to OKC, featuring potent neuroinvasiveness and low lymph node metastatic potential. These findings provide important insights into the mechanisms underlying COKC development and may guide novel diagnostic and therapeutic strategies. Show less
The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) gene polymorphism (rs638405) has been widely reported to be associated with Alzheimer's disease (AD) risk. However, studies on the relati Show more
The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) gene polymorphism (rs638405) has been widely reported to be associated with Alzheimer's disease (AD) risk. However, studies on the relationship between BACE1 gene polymorphism (rs638405), brain volume, and cognition in AD patients remain scarce. To investigate the effect of genetic polymorphism in BACE1 on gray matter volume (GMV) and cognition in AD, this study recruited 111 cognitively unimpaired (CU) controls and 144 AD patients. The effect of BACE1 rs638405 polymorphism on cognition was explored in CU and AD groups. Then the interaction effect of the diagnosis and BACE1 rs638405 polymorphism on GMV was performed, following the post-hoc analysis of regions of interest (ROIs) in interaction analysis. Mediation analysis was used to elucidate the relationship among genotypes, ROIs and cognition. BACE1 rs638405 G carriers (BACE1 G+) showed significantly lower scores in global cognition and memory function than noncarriers (BACE1 G-) in AD group. Genotypes (G+/G-) and diagnosis (CU/AD) have interaction on GMV of medial temporal lobe (MTL) including the left parahippocampus and right hippocampus. Post-hoc analysis revealed that BACE1 G+ exhibited significantly lower GMV in ROIs compared to BACE1 G- in AD. Finally, mediation analysis further demonstrated that the GMV of ROIs mediated the effect of BACE1 rs638405 polymorphism on cognition in AD. Our results emphasize the BACE1 rs638405 gene polymorphisms may affect the GMV of MTL and cognition in AD, deepening the understanding of AD pathogenesis. Show less
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, c Show more
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, clinical information and mutation data of LUAD patients collected from the TCGA and GEO database, we obtained 102 endotheliocyte senescence-related genes. The "ConsensusClusterPlus" R package was employed for unsupervised cluster analysis, and the "limma" was used for the differentially expressed gene (DEG) analysis. A prognosis model was created by univariate and multivariate Cox regression analysis combined with Lasso regression utilizing the "survival" and "glmnet" packages. KM survival and receiver operator characteristic curve analyses were conducted applying the "survival" and "timeROC" packages. "MCPcounter" package was used for immune infiltration analysis. Immunotherapy response analysis was performed based on the IMvigor210 and GSE78220 cohort, and drug sensitivity was predicted by the "pRRophetic" package. Cell invasion and migration were tested by carrying out Transwell and wound healing assays. According to the results, a total of 32 genes related to endotheliocyte senescence were screened to assign patients into C1 and C2 subtypes. The C2 subtype showed a significantly worse prognosis and an overall higher somatic mutation frequency, which was associated with increased activation of cancer pathways, including Myc_targets2 and angiogenesis. Then, based on the DEGs between the two subtypes, we constructed a five-gene RiskScore model with a strong classification effectiveness for short- and long-term OS prediction. High- and low-risk groups of LUAD patients were classified by the RiskScore. High-risk patients, characterized by lower immune infiltration, had poorer outcomes in both training and validation datasets. The RiskScore was associated with the immunotherapy response in LUAD. Finally, we found that potential drugs such as Cisplatin can benefit high-risk LUAD patients. In-vitro experiments demonstrated that silencing of Angiopoietin-like 4 (ANGPTL4), Gap Junction Protein Beta 3 (GJB3), Family with sequence similarity 83-member A (FAM83A), and Anillin (ANLN) reduced the number of invasive cells and the wound healing rate, while silencing of solute carrier family 34 member 2 (SLC34A2) had the opposite effect. This study, collectively speaking, developed a prognosis model with senescence signature genes to facilitate the diagnosis and treatment of LUAD. Show less
Familial chylomicronemia syndrome (FCS) is a rare Mendelian autosomal recessive disorder (MIM 238600) characterized by extreme and sustained hypertriglyceridemia due to profound reduction of lipoprote Show more
Familial chylomicronemia syndrome (FCS) is a rare Mendelian autosomal recessive disorder (MIM 238600) characterized by extreme and sustained hypertriglyceridemia due to profound reduction of lipoprotein lipase (LPL) activity. This expert opinion statement synthesizes current knowledge on the definition, pathophysiology, genetics, prevalence, diagnosis, and management of FCS. FCS typically manifests at a young age with persistent severe hypertriglyceridemia-defined as ≥10 mmol/L (≥885 mg/dL), or ≥1000 mg/dL (≥11.2 mmol/L) depending on region and whether Systeme International (SI) units are utilized-in the absence of secondary factors, resistance to conventional lipid-lowering therapies, and a high lifetime risk of acute pancreatitis. It is caused by biallelic pathogenic variants in the LPL gene encoding LPL, or 1 of 4 other related genes that encode proteins that interact with LPL. Affected individuals require a strict, lifelong very low-fat diet with <15% of energy from fat. Emerging therapies inhibiting apolipoprotein C-III show promise in reducing serum triglycerides and pancreatitis risk in patients with FCS. A multidisciplinary approach, encompassing dietary management, pharmacotherapy, and patient education, is pivotal in mitigating the significant morbidity associated with FCS. Show less
As a chronic lipid driven arterial disease, dyslipidemia is one of the most critical risk factors for atherosclerosis (AS). The gut microbiota plays an important role in regulating host lipid metaboli Show more
As a chronic lipid driven arterial disease, dyslipidemia is one of the most critical risk factors for atherosclerosis (AS). The gut microbiota plays an important role in regulating host lipid metabolism disorders. Studies have shown that the herb "Gualou-Xiebai" (GLXB) can effectively regulate the blood lipid levels of ApoE Show less
Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine implicated in fat metabolism regulation. Its genetic inactivation has been associated with improved glucose homeostasis, while elevated plasma ANG Show more
Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine implicated in fat metabolism regulation. Its genetic inactivation has been associated with improved glucose homeostasis, while elevated plasma ANGPTL4 levels are observed in diabetic and obese individuals. However, the potential link between ANGPTL4 and diabetes- or obesity-related complications remains uncertain. This study aimed to explore whether plasma ANGPTL4 level could serve as a predictor of cancer mortality, cardiovascular mortality, and all-cause mortality in a community-based cohort. A community-based cohort study was conducted, where fasting plasma ANGPTL4 concentrations were measured at baseline, and vital status was ascertained through linkage with the National Health Insurance Research Database in Taiwan. During a 10.46-year follow-up period, 29 (2.49%) of the 1163 participants died. Subjects within the highest tertile of plasma ANGPTL4 levels exhibited the lowest survival rate. In unadjusted models, plasma ANGPTL4 significantly predicted all-cause mortality, cancer mortality, and cardiovascular or cancer-related mortality. Upon adjustment for confounders including age, sex, smoking, body mass index (BMI), hypertension, diabetes mellitus (DM), and renal function, each standard deviation increase in plasma ANGPTL4 was associated with HRs of 1.35 (95% CI: 1.01-1.80, Plasma ANGPTL4 emerges as a promising biomarker capable of predicting 10-year mortality and enhancing risk prediction beyond established risk factors. Show less
Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria-related genes. This study ai Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less
Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and a Show more
Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and alopecia. Chemotherapy-induced alopecia severely impacts patients' quality of life and psychological well-being. Modified Huanjingjian (MHJJ), a traditional Chinese herbal formula, demonstrates clinical efficacy in alleviating chemotherapy-related side effects, yet its mechanisms against CTX-induced alopecia remain uncharacterized. And our main aim was to explore the efficacy and the mechanism of MHJJ in mice. UPLC-QE-Orbitrap-MS characterized MHJJ's chemical composition. A CTX-induced alopecia murine model was established. Systemic toxicity was evaluated through body weight monitoring, automated biochemical analysis (ALT/AST levels), and hematological profiling (WBC/PLT counts). Hair follicle histopathology was assessed via H&E staining. IHC and IF staining quantified proliferation markers and hair follicle stem cell (HFSC) biomarkers. Reduced representation bisulfite sequencing (RRBS) was used to map DNA methylation patterns. Wnt pathway dynamics were analyzed through qRT-PCR and IF staining. We identified 110 bioactive compounds in MHJJ. MHJJ intervention attenuated alopecia severity, restored follicular architecture, and increased follicular density compared to CTX monotherapy (p<0.05). HFSC proliferation markers (Ki67/CD34) showed significant upregulation, while apoptosis markers (Caspase-3) were suppressed. RRBS revealed MHJJ-mediated hypomethylation in differentially methylated regions, with gene body methylation constituting 60% of total methylation changes. Methylation-modulated genes predominantly localized to Wnt signaling pathways: MHJJ enhanced Wnt3/Wnt10a expression while suppressing Cer1/Axin1. Corresponding methylation reductions at promoter and gene body regions were confirmed at mRNA and protein levels. MHJJ mitigates CTX-induced alopecia through epigenetic regulation of HFSCs, specifically via DNA hypomethylation-mediated activation of Wnt3/Wnt10a and suppression of Cer1/Axin1. This mechanism promotes follicular regeneration by restoring Wnt signaling homeostasis, positioning MHJJ as a promising adjuvant for chemotherapy-induced alopecia management. Show less
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate Show more
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in Show less
Cranial neural crest cells (CNCs) play a critical role in craniofacial bone morphogenesis, engaging in intricate interactions with various molecular signals to ensure proper development, yet the molec Show more
Cranial neural crest cells (CNCs) play a critical role in craniofacial bone morphogenesis, engaging in intricate interactions with various molecular signals to ensure proper development, yet the molecular scaffolds coordinating these processes remain incompletely defined. Here, we identify neurofibromin 2 (Nf2) as a critical regulator to direct CNC-derived skull morphogenesis. Genetic ablation of Nf2 in murine CNCs causes severe craniofacial anomalies, featuring declined proliferation and increased apoptosis in osteoprogenitors, impaired type I collagen biosynthesis and trafficking, and aberrant osteogenic mineralization. Mechanistically, we uncover that Nf2 serves as a molecular linker that individually interacts with FGF receptor 1 (FGFR1) and Akt through spatially segregated phosphor-sites, and structural modeling and mutagenesis identified Ser10 and Thr230 as essential residues, with Thr230 mutation selectively ablating Akt binding while preserving FGFR1 association. Strikingly, Akt inhibition phenocopied Nf2 deficiency, reducing collagen production and Nf2 phosphorylation, whereas phospho-mimetic Nf2 (T230D) rescued CNC-derived osteogenic defects in Nf2-mutant animals. Our findings underscore the physiological significance of Nf2 as a phosphorylation-operated scaffold licensing the FGFR1/AKT axis to regulate collagen type I biogenesis and trafficking, ensuring normal CNC-derived osteogenesis and craniofacial bone development, thus exposing the Nf2/FGFR1/AKT signaling axis as a therapeutic target and promising advancements in treatment of craniofacial anomalies. Show less
Lung adenocarcinoma (LUAD) is a major cause of cancer-related morbidity and mortality globally, with challenges in prognosis and treatment due to its complex pathogenesis and heterogeneous tumor micro Show more
Lung adenocarcinoma (LUAD) is a major cause of cancer-related morbidity and mortality globally, with challenges in prognosis and treatment due to its complex pathogenesis and heterogeneous tumor microenvironment (TME). Neutrophil extracellular traps (NETs) and oxidative stress play critical roles in tumor progression: NETs promote tumor cell adhesion, migration, and immune suppression, while oxidative stress induces DNA damage and activates pro-tumor signaling pathways. Moreover, oxidative stress is an important inducer of NETs, and their crosstalk shapes the LUAD immune microenvironment. However, systematic exploration of LUAD immunotherapeutic response prediction based on NETs and oxidative stress-related genes remains lacking. The gene set related to oxidative stress was obtained from MSigDB. The gene set related to NETs was sourced from relevant literature. Transcriptomic and clinical data were integrated from The Cancer Genome Atlas (TCGA)-LUAD (training set) and GSE31210 (validation set). Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to screen gene modules and characteristic scores related to NETs and oxidative stress signatures. Differentially expressed genes (DEGs) were screened, and prognostic model was established using univariate and LASSO Cox regression. Immune infiltration was analyzed using ESTIMATE algorithm, MCP-counter and ssGSEA methods. And we developed a nomogram incorporating clinicopathological features and RiskScore model, and performed drug sensitivity analysis. Finally, the biological role of CPS1 in lung cancer cells was investigated through CCK-8, wound-healing, and Transwell experiments. 22 co-expression modules were screened, among which the brown module showed significant correlations with NETs and oxidative stress signature scores. This module was intersected with DEGs, yielding 624 overlapping genes implicated in immune-relevant pathways (like leukocyte differentiation, neutrophil activation involved in immune response). A prognostic model was established utilizing 8 key genes (ADGRE3, ARHGEF3, CD79A, CLEC7A, CPS1, EPHB2, LARGE2, and OAS3). In the TCGA database, the model demonstrated robust prognostic discrimination (area under the curve (AUC) > 0.6), with high-risk patients exhibiting shorter overall survival (OS) (p < 0.05). Its stability was validated in GSE31210 (AUC > 0.6). The RiskScore showed negative correlations with immune infiltration (like T cells, CD8 T cells, and natural killer cells) as well as immune/stromal scores. A nomogram model combining RiskScore with N staging was developed and validated, demonstrating strong predictive accuracy through calibration and decision curve analyses. High-risk patients were more sensitive to drugs like BI-2536, BMS-509744, and Pyrimethamine. Finally, in vitro tests showed that CPS1 knockdown markedly decreased the viability, migration, and invasion of lung cancer cells. The constructed prognostic model by NETs and oxidative stress-relevant genes effectively predicts LUAD prognosis, correlates with immune microenvironment characteristics, and guides drug sensitivity, providing novel insights for LUAD prognostic assessment and personalized therapy. Show less
Despite substantial progress in low-density lipoprotein cholesterol (LDL-C)-lowering strategies, residual cardiovascular risk remains. Apolipoprotein C3 (APOC3) has emerged as a novel target for lower Show more
Despite substantial progress in low-density lipoprotein cholesterol (LDL-C)-lowering strategies, residual cardiovascular risk remains. Apolipoprotein C3 (APOC3) has emerged as a novel target for lowering triglycerides. Multiple clinical trials of small-interfering RNA therapeutics targeting APOC3 are currently underway. To investigate whether genetically predicted lower APOC3 is associated with a reduction in cardiovascular risk and if the combined exposure to APOC3 and LDL-C-lowering variants is associated with a reduction in the risk of coronary heart disease (CHD). This was a population-based genetic association study with 2 × 2 factorial mendelian randomization. Included were participants of European ancestry in the UK Biobank. Data were analyzed from November 2023 to July 2024. Genetic scores were constructed to mimic the effects of APOC3, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. Plasma lipid and lipoprotein levels, CHD, and type 2 diabetes (T2D). This study included 401 548 UK Biobank participants (mean [SD] age, 56.9 [8.0] years; 216 901 female [54.0%]). Genetically predicted lower APOC3 was associated with a lower risk of CHD (odds ratio [OR], 0.96; 95% CI, 0.93-0.98) and T2D (0.97; 95% CI, 0.95-0.99). Genetically lower APOC3 and PCSK9 were associated with a similar magnitude of risk reduction in CHD per 10-mg/dL decrease in apolipoprotein B (ApoB) level (APOC3: 0.70; 95% CI, 0.59-0.83; PCSK9: 0.71; 95% CI, 0.65-0.77). Combined exposure to genetically lower APOC3 and PCSK9 was associated with an additive lower risk of CHD (APOC3: 0.96; 95% CI, 0.92-0.99; PCSK9: 0.93; 95% CI, 0.90-0.97; combined: 0.90; 95% CI, 0.86-0.93). Genetically lower HMGCR was also associated with a lower risk of CHD, and the risk was further reduced when combined with APOC3 (0.93; 95% CI, 0.90-0.97). Genetically predicted lower APOC3 was associated with a reduced risk of CHD that is comparable with that associated with lower PCSK9 per unit decrease in ApoB. Combined exposure to APOC3 and LDL-C-lowering variants was associated with an additive reduction in CHD risk. Future studies are warranted to investigate the therapeutic potential of these combined therapies, particularly among high-risk patients who cannot achieve therapeutic targets with existing lipid-lowering therapies. Show less
The early, precise, and safe management of vulnerable atherosclerotic plaques (VAPs) remains a formidable clinical challenge. Here, we present a targeted nanotherapeutic approach in which osteopontin- Show more
The early, precise, and safe management of vulnerable atherosclerotic plaques (VAPs) remains a formidable clinical challenge. Here, we present a targeted nanotherapeutic approach in which osteopontin-targeted nanoparticles encapsulate luteolin (NPs-Lut) for the precise delivery and treatment of VAPs. This engineered system enables site-specific accumulation and sustained release of luteolin at plaque sites. We innovatively constructed an osteopontin-targeted drug delivery system designed for vulnerable atherosclerotic plaques, in which luteolin and atorvastatin were successfully encapsulated. The system demonstrated sustained-release capability in vitro, and its biosafety and histocompatibility were comprehensively evaluated both in vitro and in vivo. Moreover, therapeutic efficacy was further assessed in ApoE In vivo evaluation in ApoE This work provides a robust and translationally promising nanoplatform for the precision treatment of VAPs, offering a novel strategy for safe and effective intervention in atherosclerotic cardiovascular disease. Show less
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive Show more
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive of its therapeutic potential against T2DM. In this study, we evaluated the protective effects of KA against apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (LDL) (AC3RL)-induced β-cell apoptosis and its underlying mechanism of action. ApoE Show less
In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian random Show more
In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the potential causal connection between blood lipids and COPD. A genome-wide association study (GWAS) on COPD was conducted, encompassing a total of 112,583 European participants from the MRC-IEU. Additionally, extensive UK Biobank data pertaining to blood lipid profiles within European cohorts included measurements for low-density lipoprotein cholesterol (LDL-C) with 440,546 individuals, high-density lipoprotein cholesterol (HDL-C) with 403,943 individuals, triglycerides (TG) with 441,016 individuals, total cholesterol (TC) with 187,365 individuals, apolipoprotein A-I (apoA-I) with 393,193 individuals, and apolipoprotein B (apoB) with 439,214 individuals. Then, MR analyses were performed for lipids and COPD, respectively. The primary analytical technique employed was the inverse-variance weighted (IVW) approach, which included a 95% confidence interval (CI) to calculate the odds ratio (OR). Additionally, a sensitivity analysis was conducted to assess the dependability of the MR analysis outcomes. MR analysis was primarily based on IVW, unveiled a causal link between COPD and LDL-C (OR=0.994, 95% CI (0.989, 0.999), P=0.019), TG (OR=1.005, 95% CI (1.002, 1.009), P=0.006), and apoA-I (OR=0.995, 95% CI (0.992, 0.999), P=0.008), in addition, no causal link was found with HDL-C, TC, apoB. Sensitivity analysis demonstrated the robustness of these causal relationships. However, through multivariate MR(MVMR) and multiple testing correction, LDL-C and TG had no causal effect on the outcome. ApoA-I remained a protective factor for the risk of COPD (OR=0.994, 95% CI (0.990-0.999), P=0.008). Through MR analysis, this study offers evidence of a causal link between apoA-I with COPD. This further substantiates the potential role of lipid metabolism in COPD, and has significant clinical implications for the prevention and management of COPD. Show less
Coronary heart disease (CHD) and type 2 diabetes (T2D) represent a significant global comorbidity burden, with shared yet incompletely understood molecular mechanisms. This study aimed to identify sha Show more
Coronary heart disease (CHD) and type 2 diabetes (T2D) represent a significant global comorbidity burden, with shared yet incompletely understood molecular mechanisms. This study aimed to identify shared diagnostic biomarkers and elucidate core pathways linking CHD and T2D pathogenesis. Integrated bioinformatics of CHD/T2D transcriptomes identified shared differentially expressed genes (DEGs) and co-expression modules via Weighted Gene Co-expression Network Analysis (WGCNA). Receiver operating characteristic (ROC) analysis selected CPD, GGCT, SUZ12, and ZMYM2 as top diagnostic biomarkers. These predictions were validated using C57BL/6 and ApoE Bioinformatics revealed 328 shared DEGs, with CPD, GGCT, SUZ12, and ZMYM2 showing high diagnostic efficacy. T2D mice exhibited persistent hyperglycemia. Aortic histopathology confirmed disease-specific changes: atherosclerotic plaques in CHD and vascular basement membrane thickening in T2D. Critically, all four biomarkers showed concurrent upregulation in diseased vessels at both protein (immunofluorescence, Western blot) and mRNA (RT-qPCR) levels. This study establishes CPD, GGCT, SUZ12, and ZMYM2 as shared CHD/T2D diagnostic biomarkers. Their validated co-upregulation highlights their dual-disease diagnostic and therapeutic potential. Show less