No abstract

In a recent study, the PD-1 inhibitor has been widely used in clinical trials and shown to improve various cancers. However, PD-1/PD-L1 inhibitors showed a low response rate and were effective for only a small number of cancer patients. Thus, it is important to figure out the issue about the low response rate of immunotherapy. Here, we performed ssGSEA and unsupervised clustering analysis to identify three clusters (clusters A, B, and C) according to different immune cell infiltration status, prognosis, and biological action. Of them, cluster C showed a better survival rate, higher immune cell infiltration, and immunotherapy effect, with enrichment of a variety of immune active pathways including T and B cell signal receptors. In addition, it showed more significant features associated with immune subtypes C2 and C3. Furthermore, we used WGCNA analysis to confirm the cluster C-associated genes. The immune-activated module highly correlated with 111 genes in cluster C. To pick candidate genes in SD/PD and CR/PR patients, we used the least absolute shrinkage (LASSO) and SVM-RFE algorithms to identify the targets with better prognosis, activated immune-related pathways, and better immunotherapy. Finally, our analysis suggested that there were six genes with KLRC3 as the core which can efficiently improve immunotherapy responses with greater efficacy and better prognosis, and our study provided clues for further investigation about target genes associated with the higher response rate of immunotherapy.

Ecological pollution caused by heavy metals released by sediments is a worldwide concern. However, the effect of changes in sediment speciation on their release of heavy metals has not been adequately reported. This study analysed changes in the sediment speciation of Pb and Cr before and after a release experiment by varying the temperature, pH, and salinity of the water column. The results show that the release of Pb and Cr from sediments increases with increasing water temperature, mainly due to the conversion of the residual fraction of Pb to the Fe-Mn oxide fraction and Cr converting more residual fraction to the organic matter and sulfide fraction. The release of sediment Pb and Cr decreased with increasing pH, with Pb converting more acid extractable fraction to the residual fraction and Cr converting more organic matter and sulfide fraction to the residual fraction. In contrast, the release of Pb and Cr increased and then decreased with increasing salinity, with the acid extractable and residual fractions of Pb interconverting, and the organic matter and sulfide fraction and the residual fraction of Cr showing higher interconversion. For Pb, the acid extractable fraction was more susceptible to conversion to the residual fraction by environmental influences, whereas for Cr, the organic matter and sulfide fraction was susceptible to conversion to the residual fraction. This study highlights the influence of environmental factors on the sediment speciation of heavy metals, which can help reveal the transport and transformation of heavy metals in cold and arid lake sediments.