RESUMEN
A novel donor-acceptor-donor (D-A-D) type compound containing pyrazine as the acceptor and triphenylamine as the donor has been designed and synthesized. The photophysical properties and biocompatibility of this probe, namely (OMeTPA)2-Pyr for live cell imaging were systematically investigated, with observed large Stokes shifts, high photostability, and low cytotoxicity. Furthermore, we demonstrated that (OMeTPA)2-Pyr could permeate live cell membranes for labeling. The proposed mechanism of this probe was the binding and shafting through membrane integral transport proteins by electrostatic and hydrophobic interactions. These salient and novel findings can facilitate the strategic design of new pyrazine-fused charge-neutral molecular platforms as fluorescent probes, for long-term in situ dynamic monitoring in live cells.
RESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC) with high immunogenicity. Research on immune-related gene (IRG) is of great significance in ccRCC in identifying new therapeutic targets and improving patient prognosis. In this study, the IRG patterns of ccRCC were investigated and correlated these patterns with tumor microenvironment infiltrating characteristics in immunotherapy. Moreover, an IRG score was constructed to quantify the pattern of individual tumors through the principal component analysis algorithm. Two distinct molecular subtypes (C1 and C2) were identified based on the IRGs expression profile. Subtype C1 was characterized with significantly high level of immune-checkpoint, immune score, stromal score, showed high drug sensitivity in Sorafenib, Sunitinib, Cisplatin, Vinblastine, Vinorelbine, Vorinostat, and Gemcitabine. Cytokine-cytokine receptor pathway, chemokine signaling pathway, and JAK signaling pathways were found enriched in the subtype C1 account for the poor prognosis. Subtype C2 was linked to a better survival outcome. By using the Connective Map database, subtype specific small molecular drugs identified that could facilitate the treatment of ccRCC patients. In addition, A immune index that used to evaluated the immune modification patterns and further validated in the other types RCC dataset, such as papillary renal cell carcinoma (pRCC) and chromophobe renal cell carcinoma (chRCC). Together, this study identified two distinct molecular subtypes with immune index, aid to the treatment of ccRCC and enhancing our cognition of the tumor microenvironment infiltration characterization in ccRCC immunotherapy.