Background. Hepatocellular carcinoma (HCC) remains a challenging medical problem. Cuproptosis is a novel form of cell death that plays a crucial role in tumorigenesis, angiogenesis, and metastasis. However, it remains unclear whether cuproptosis-related genes (CRGs) influence the outcomes and immune microenvironment of HCC patients. Method. From The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we obtained the mRNA expression file and related clinical information of HCC patients. We selected 19 CRGs as candidate genes for this study according to previous literature. We performed a differential expression analysis of the 19 CRGs between malignant and precancerous tissue. Based on the 19 CRGs, we enrolled cluster analysis to identify cuproptosis-related subtypes of HCC patients. A prognostic risk signature was created utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. We employed independent and stratification survival analyses to investigate the predictive value of this model. The functional enrichment features, mutation signatures, immune profile, and response to immunotherapy of HCC patients were also investigated according to the two molecular subtypes and the prognostic signature. Results. We found that 17 CRGs significantly differed in HCC versus normal samples. Cluster analysis showed two distinct molecular subtypes of cuproptosis. Cluster 1 is preferentially related to poor prognosis, high activity of immune response signaling, high mutant frequency of TP53, and distinct immune cell infiltration versus cluster 2. Through univariate and LASSO Cox regression analyses, we created a cuproptosis-related prognostic risk signature containing LIPT1, DLAT, MTF1, GLS, and CDKN2A. High-risk HCC patients were shown to have a worse prognosis. The risk signature was proved to be an independent predictor of prognosis in both the TCGA and ICGC datasets, according to multivariate analysis. The signature also performed well in different stratification of clinical features. The immune cells, which included regulatory T cells (Treg), B cells, macrophages, mast cells, NK cells, and aDCs, as well as immune functions containing cytolytic activity, MHC class I, and type II IFN response, were remarkably distinct between the high-risk and low-risk groups. The tumor immune dysfunction and exclusion (TIDE) score suggested that high-risk patients had a higher response rate to immune checkpoint inhibitors than low-risk patients. Conclusion. This research discovered the potential prognostic and immunological significance of cuproptosis in HCC, improved the understanding of cuproptosis, and may deliver new directions for developing more efficacious therapeutic techniques for HCC patients.

The protein encoded by CUB and Sushi Multiple Domains 2 (CSMD2) is likely involved in regulating the complement cascade reaction of the immune system. However, current scientific evidence on the comprehensive roles of CSMD2 in pan-cancer is relatively scarce. Therefore, in this study, we explored the transcriptional level of CSMD2 in pan-caner using TCGA, GEO, and International Cancer Genome Consortium databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic efficacy of CSMD2. The Kaplan-Meier Plotter and Oncolnc were used to investigate the correlation between CSMD2 expression and prognosis. Additionally, we analyzed the correlation between epigenetic methylation and CSMD2 expression in various cancers based on UALCAN, as well as, the correlation between CSMD2 and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor neoantigen burden (TNB) in tumors. TIMER2.0 database was employed to investigate the correlation between CSMD2 and immune cells in the tumor microenvironment and immune checkpoints. Based on TISIDB, the correlation between CSMD2 and MHC molecules and immunostimulators was analyzed. Ultimately, we observed with a pan-cancer analysis that CSMD2 was upregulated in most tumors and had moderate to high diagnostic efficiency, and that high expression was closely associated with poor prognosis in patients with tumors. Moreover, hypermethylation of CSMD2 promoter and high levels of m6A methylation regulators were also observed in most cancers. CSMD2 expression was negatively correlated with TMB and MSI in stomach adenocarcinoma (STAD) and stomach and esophageal carcinoma (STES), as well as with tumor mutational burden, microsatellite instability, and TNB in head-neck squamous cell carcinoma (HNSC). In most cancers, CSMD2 might be associated with immune evasion or immunosuppression, as deficient anti-tumor immunity and upregulation of immune checkpoints were also observed in this study. In conclusion, CSMD2 could serve as a promising prognostic, diagnostic and immune biomarker in pan-cancer.

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Gastric cancer (GC) is still notorious for its poor prognosis and aggressive characteristics. Though great developments have been made in diagnosis and therapy for GC, the prognosis of patient is still perishing. In this study, differentially expressed genes (DEGs) in GC were first screened using three Gene Expression Omnibus (GEO) datasets (GSE13911, GSE29998, and GSE26899). Second, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to validate expression of these DEGs and perform survival analysis. We selected seven candidate genes (CAMK2N1, OLFML2B, AKR7A3, CYP4X1, FMO5, MT1H, and MT1X) to carry out the next analysis. To construct the ceRNA network, we screened the most potential upstream ncRNAs of the candidate genes. A series of bioinformatics analyses, including expression analysis, correlation analysis, and survival analysis, revealed that the SNHG10–hsa-miR-378a-3p might be the most potential regulatory axis in GC. Then, the expression of CAMK2N1, miR-378a-3p, and SNHG10 was verified in GC cell lines (GES-1, MGC-803, BGC-823, HGC-27, MKN-45, and AGS) by qRT-PCR and Western blotting. We found that SNHG10 and CAMK2N1 were highly expressed in gastric cancer lines, and the miR-378a-3p was lowly expressed in BGC-823, HGC-27, and MKN-45. Furthermore, CAMK2N1 levels were significantly negatively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. In summary, our results suggest that the ncRNA-mediated high expression of CAMK2N1 is associated with poor prognosis and tumor immune infiltration of GC.

In order to finish the partial nitrification of wastewater with high concentration ammonia and low concentration carbon in SBR smoothly, the research had been practised in reactor that short-cut nitrification developed in depth. The relationship between concentration and nitration rate of ammonia nitrogen could be studied by degree of nitration, which controlled by alkalinity. N02'INH/ during partial nitrification need to reach 13 on condition that concentration of ammonia nitrogen and rate of nitrite accumulation was given. As it turned out, alkalinity shortage tended to bring nitrosation of ammonia nitrogen to an end by extremely low pH values. There was a linear relationship between initial alkalinity dosage and ammonia nitrogen nitration level. Alkalinity requirement that adapt to inflow of anaerobic reactor during partial nitrification could be ascertained by means of formula: .6.N C13+X) =1.3N;y (initial alkalinity) =7.744.6. N -205.2 (nitrite accumulation rate: X, ammonia nitrogen nitration demand: .6.N) .