Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the complexity of the genetic and immunologic background has not been fully explored. METHODS: Single-cell sequencing data were acquired from a healthy dataset and three UM datasets. The differentially expressed genes between primary and metastatic UM in The Cancer Genome Atlas (TCGA) data were attributed to specific cell types and explained with functional annotation. The analysis for cell-cell communication was conducted by "CellChat" to understand the cell crosstalk among the cell clusters and to delineate the dysfunctional signaling pathways in metastatic UM. CCK-8, EdU and transwell assays were performed to verify the function of the genes of interest. RESULTS: We revealed aberrant signaling pathways with distinct functional statuses between primary and metastatic UM by integrating multiple datasets. The crucial signals contributing most to outgoing or incoming signaling of metastasis were identified to uncover the potential targeting genes. The association of these genes with disease risk was estimated based on survival data from TCGA. The key genes associated with proliferation and metastasis were verified. CONCLUSIONS: Conclusively, we discovered the potential key signals for occurrence and metastasis of UM and provided a theoretical basis for potential clinical application.

Bioelectrocatalysis for CO2 reduction: recent advances and challenges to develop a sustainable system for CO2 utilization.

Activation and turning CO2 into value added products is a promising orientation to address environmental issues caused by CO2 emission. Currently, electrocatalysis has a potent well-established role for CO2 reduction with fast electron transfer rate; but it is challenged by the poor selectivity and low faradic efficiency. On the other side, biocatalysis, including enzymes and microbes, has been also employed for CO2 conversion to target Cn products with remarkably high selectivity; however, low solubility of CO2 in the liquid reaction phase seriously affects the catalytic efficiency. Therefore, a new synergistic role in bioelectrocatalysis for CO2 reduction is emerging thanks to its outstanding selectivity, high faradic efficiency, and desirable valuable Cn products under mild condition that are surveyed in this review. Herein, we comprehensively discuss the results already obtained for the integration craft of enzymatic-electrocatalysis and microbial-electrocatalysis technologies. In addition, the intrinsic nature of the combination is highly dependent on the electron transfer. Thus, both direct electron transfer and mediated electron transfer routes are modeled and concluded. We also explore the biocompatibility and synergistic effects of electrode materials, which emerge in combination with tuned enzymes and microbes to improve catalytic performance. The system by integrating solar energy driven photo-electrochemical technics with bio-catalysis is further discussed. We finally highlight the significant findings and perspectives that have provided strong foundations for the remarkable development of green and sustainable bioelectrocatalysis for CO2 reduction, and that offer a blueprint for Cn valuable products originate from CO2 under efficient and mild conditions.