EDTA抗原修复液(50×)

Background Hepatocellular carcinoma (HCC) ranks among the most aggressive malignancies worldwide, with poor outcomes attributed to delayed diagnosis and therapeutic limitations. Emerging evidence suggests that de novo lipogenesis (DNL) plays a crucial role in HCC progression and its interaction with the immune microenvironment. Methods We systematically analyzed DNL-related gene expression profiles from TCGA, GEO, ICGC-LIRI datasets, and our Xiangya HCC cohort ( n  = 106) to construct a prognostic risk model. Through LASSO-Cox regression analysis, we identified six signature genes (G6PD, LCAT, SERPINE1, SOAT2, CYP2C9, and UGT1A10) that effectively stratified patients into distinct risk groups. We evaluated clinical characteristics, immune cell infiltration patterns, and differential therapeutic responses between high-risk and low-risk groups. Comprehensive validation included immunohistochemical analysis and Western blotting to assess expression levels of key model genes, along with multiplex immunofluorescence staining and single-cell RNA sequencing(scRNA-seq) to characterize immune microenvironmental differences between risk groups. Results We successfully established a robust six-gene prognostic signature (G6PD, LCAT, SERPINE1, SOAT2, CYP2C9, and UGT1A10) based on de novo lipogenesis pathways, which demonstrated excellent predictive performance (AUC: 0.78–0.82). The model revealed significant differences in immune infiltration patterns between risk groups, with the high-risk group exhibiting immunosuppressive characteristics characterized by increased Treg cell infiltration, while the low-risk group showed greater NK cell retention. Integrated scRNA-seq and our cohort validation further demonstrated that high-risk scores were associated with poorer response to immunotherapy but greater sensitivity to targeted therapies. These findings suggest that de novo lipogenesis-mediated immune evasion contributes to therapy resistance and worse prognosis in high-risk HCC patients, whereas low-risk HCC patients maintain an immunologically active microenvironment more amenable to immunotherapy. Conclusions This study provided a novel prognostic model for HCC, incorporating 6 representative DNLs. The model demonstrated the potential for predicting HCC prognosis and highlighted the involvement of immune cell infiltration and the association between risk scores and clinical therapy. Validation of model genes further supported the association between de novo lipogenesis and HCC development.

Background:Chronic heart failure (CHF) is a serious cardiovascular condition. Vascular peroxidase 1 (VPO1) is associated with various cardiovascular diseases, yet its role in CHF remains unclear. This research aims to explore the involvement of VPO1 in CHF.Methods:CHF was induced in rats using adriamycin, and the expression levels of VPO1 and cylindromatosis (CYLD) were assessed. In parallel, the effects of VPO1 on programmed necrosis in H9c2 cells were evaluated through cell viability assays, lactate dehydrogenase (LDH) level measurements, and analysis of receptor-interacting protein kinase 1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) pathway-related proteins. The impact of CYLD on RIPK1 protein stability and ubiquitination was also investigated, along with the interaction between VPO1 and CYLD. Additionally, cardiac structure and function were assessed using echocardiography, Hematoxylin-eosin (HE) staining, Masson staining, and measurements of myocardial injury-related factors, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), Aspartate aminotransferase (AST), LDH, and creatine kinase-myocardial band (CK-MB).Results:VPO1 expression was upregulated in CHF rats and in H9c2 cells treated with adriamycin. In cellular experiments, VPO1 knockdown improved cell viability, inhibited necrosis and the expression of proteins associated with the RIPK1/RIPK3/MLKL pathway. Mechanistically, VPO1 promoted cardiomyocyte programmed necrosis by interacting with the deubiquitinating enzyme CYLD, which enhanced RIPK1 ubiquitination and degradation, leading to activation of the RIPK1/RIPK3/MLKL signaling pathway. At animal level, overexpression of CYLD counteracted the cardiac failure, cardiac hypertrophy, myocardial injury, myocardial fibrosis, and tissue necrosis caused by VPO1 knockdown.Conclusions:VPO1 exacerbates cardiomyocyte programmed necrosis in CHF rats by upregulating CYLD, which activates the RIPK1/RIPK3/MLKL signaling pathway. Thus, VPO1 may represent a potential therapeutic target for CHF.