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Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer and is the second leading cause of cancer-related deaths worldwide. Unlike apoptosis, necroptosis (NCPS) triggers an immune response by releasing damage-related molecular factors. However, the clinical prognostic features of necroptosis-associated genes in HCC are still not fully explored.Methods: We analyzed the single-cell datasets GSE125449 and GSE151530 from the GEO database and performed weighted co-expression network analysis on the TCGA data to identify the necroptosis genes. A prognostic model was built using COX and Lasso regression. In addition, we performed an analysis of survival, immunity microenvironment, and mutation. Furthermore, the hub genes and pathways associated with HCC were localized within the single-cell atlas.Results: Patients with HCC in the TCGA and ICGC cohorts were classified using a necroptosis-related model with significant differences in survival times between high- and low-NCPS groups (p < 0.05). High-NCPS patients expressed more immune checkpoint-related genes, suggesting immunotherapy and some chemotherapies might prove beneficial to them. In addition, a single-cell sequencing approach was conducted to investigate the expression of hub genes and associated signaling pathways in different cell types.Conclusion: Through the analysis of single-cell and bulk multi-omics sequencing data, we constructed a prognostic model related to necroptosis and explored the relationship between high- and low-NCPS groups and immune cell infiltration in HCC. This provides a new reference for further understanding the role of necroptosis in HCC.

Background: Gastric cancer (GC) is the second leading cause of cancer-related mortality and the fifth most common cancer worldwide. However, the underlying mechanisms of competitive endogenous RNAs (ceRNAs) in GC are unclear. This study aimed to construct a ceRNA regulation network in correlation with prognosis and explore a prognostic model associated with GC.Methods: In this study, 1,040 cases of GC were obtained from TCGA and GEO datasets. To identify potential prognostic signature associated with GC, Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression were employed. The prognostic value of the signature was validated in the GEO84437 training set, GEO84437 test set, GEO15459 set, and TCGA-STAD. Based on the public databases, TargetScan and starBase, an mRNA-miRNA-lncRNA regulatory network was constructed, and hub genes were identified using the CytoHubba plugin. Furthermore, the clinical outcomes, immune cell infiltration, genetic variants, methylation, and somatic copy number alteration (sCNA) associated with the ceRNA network were derived using bioinformatics methods.Results: A total of 234 prognostic genes were identified. GO and GSEA revealed that the biological pathways and modules related to immune response and fibroblasts were considerably enriched in GC. A nomogram was generated to provide accurate prognostic outcomes and individualized risk estimates, which were validated in the training, test dataset, and two independent validation datasets. Thereafter, an mRNA-miRNA-lncRNA regulatory network containing 4 mRNAs, 22 miRNAs, 201 lncRNAs was constructed. The KCNQ1OT1/hsa-miR-378a-3p/RBMS1 ceRNA network associated with the prognosis was obtained by hub gene analysis and correlation analysis. Importantly, we found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may play a vital role in the diagnosis and prognosis of GC patients based on Cox regression analyses. Furthermore, our findings demonstrated that mutations and sCNA of the KCNQ1OT1/miR-378a-3p/RBMS1 axis were associated with increased immune infiltration, while the abnormal upregulation of the axis was primarily a result of hypomethylation.Conclusion: Our findings suggest that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and therapeutic target for GC. Moreover, such findings provide insights into the molecular mechanisms of GC pathogenesis.

The guarantee of cell survival under hypoxic conditions and rapid vascularization is a key in tissue engineering strategies for treating bone defects. Our study aimed to establish the protective role of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) in hypoxic conditions and realize rapid vascularization in bone defects. Resveratrol (Res), a non-flavonoid polyphenolic compound, and angiopoietin-2 (ANG2), a vascular activating factor, were applied to enhance BMSC and HUVEC survival, osteogenesis, and angiogenesis. The morphology, autophagy, viability, apoptosis, cycle, and osteogenic differentiation of BMSCs treated with Res were analyzed. The results indicated that Res could improve BMSC survival and differentiation via the autophagy pathway under hypoxic conditions. In addition, Res maintained HUVEC growth and proliferation in a hypoxic and ANG2 double-adverse environment via the autophagy pathway. To simulate a relatively hypoxic environment, small-aperture PEGDA/TCS hydrogels containing Res and ANG2 were prepared. BMSCs were cultured in the PEGDA/TCS scaffold and transplanted into a large tibial defect. CD31 immunofluorescence showed that the density and size of new blood vessels in the bone defect were significantly enhanced by ANG2 and Res at 8 weeks after surgery. H&E, Masson, and immunohistochemical staining results indicated that ANG2 combined with Res could promote new bone formation in defects. All these results suggested that Res combined with ANG2 may be a novel strategy for the targeted therapy of hypoxic bone defects with tissue engineering scaffolds.