Fig 2: (A) Increased expression of HK2 in PH induced by MCT. (B) Overexpress HK2 lentivirus and differential MICRORNA screening. PASMCs were transfected in vitro and screened for negatively correlated miRNA molecules with HK-II expression. The control group and PASMCs overexpressing HK2 were detected by miRNA gene expression profiling. (C) Regulated gene expression of cell proliferation was significantly active. Sequence-based miRNA target gene prediction method was applied. The number of target genes predicted by this differential miRNA using MIRANDA was 2432. Based on the number of genes contained in differentially significant function and their degree of enrichment in the database, a targeted map can be created for significant function according to enrichment order. In the figure, the ordinate is the function of differential gene, and the abscissa is enrichment. Each column on the graph represents a significant differential gene function. The greater the difference in gene function, the higher the ranking. (D) Tumor-associated metabolism was active through expression. Pathway analysis was based on the KEGG database. Fisher's exact test and chi-square test were used for differential genes. Based on the analysis results, significantly up-regulated gene pathway can be used to construct a map of differential gene pathways. The ordinate is the name of differential gene pathway, and the abscissa is negative logarithm of p value (-LgP). The larger the value, the smaller the p value.

Fig 3: Model of RIPK3-dependent programmed necrosis and caspase 8-dependent apoptosis in Mf infected with MtbIn Mf infected with virulent Mtb RIPK3 and pro-caspase 8 present in the cytosol translocate to the mitochondria in presence of Bcl-xL and RIPK3 is activated RIPK3 enhances binding of HKII to VDAC on the outer mitochondrial membrane controlling mitochondrial glycolysis. At the same time activated RIPK3 triggers CypD-dependent formation of the mitochondrial permeability transition (MPT) pore via interaction between ANT and VDAC leading to leakage of the electron chain. Both mechanisms seem to be required for increasing ROS-dependent necrosis (right). In Mf infected with avirulent Mtb the RIPK3 and caspase 8 also translocate to the mitochondria but this step is quickly followed by activation of caspase 8 and degradation of RIPK3. Oligomerization of BAX and BAK, which in turn allows the release of pro-apoptotic molecules (e.g. cytochrome c) leads to apoptosis (left). The exact action mechanism of Bcl-xL function is unknown.

Fig 4: HK2 expression was correlated with the level of immune marker genes in RCC patients. (a) Hazard ratios for RCC patients with high expression of HK2 and low expression of HK2 were defined by the CIBERSORT P value. Boxes represent hazard ratios, and vertical lines are 95% confidence intervals. (b) The bar plot of the top of the heat map indicates HK2 mRNA expression levels. The colors on the bar indicate the HK2 copy number status. The bar plot on the right represents the negative log10 of the Wilcoxon signed-rank test P value of individual immune checkpoint receptors. The expression levels are log2 transformed and mean normalized.

Fig 5: The relationship between HK2 expression and prognosis in RCC patients. (a) Overall survival rates between RCC patients with low expression of HK2 and high expression of HK2. (b) RFS between RCC patients with low expression of HK2 and high expression of HK2. (c) ROC curves between RCC patients with low expression of HK2 (area = 0.62) and high expression of HK2 (area = 0.73).