Regulation of IL-10 expression and function by JAK-STAT in CD8+ T cells.

IL-10 is a pleiotropic cytokine that plays a significant role in antiviral and antitumor immunity. Potent CD8+ T cells express IL-10 after stimulation by strong TCR signaling, which promotes the killing effect of CD8+ T cells. However, the regulation of IL-10 expression in CD8+ T cells and its signaling pathway to enhance CD8+ T cell function are largely unknown. In this study, we investigated the JAK-STAT signaling molecules that regulate IL-10 expression in CD8+ T cells and the JAK-STAT signaling pathway that IL-10 enhances the function of CD8+ T cells through its receptor, using small molecule inhibitors and CRISPR-Cas9 gene editing. Our findings provide new insights and a theoretical basis for the immunotherapy of tumors.

Assessing the impact of governance and health expenditures on carbon emissions in China: Role of environmental regulation.

The current study tries to summarize the leading factors and their behavior toward the environmental quality. Therefore, this study investigates the environment-development linkage in China's economy covering the period of 1984-2018. In order to investigate the proposed objectives, the current study uses the dynamic ordinary least square, fully modified ordinary least square and canonical co-integration regression with granger causality test. The results reveal that there exists an inverted U-shaped relationship in China's economy. Likewise, urbanization positively contributes to environmental deterioration. Furthermore, the health expenditures also cause to deteriorate the environmental quality. In contrast, there exists the negative association between good governance and carbon emissions, while the rule of law in China's economy does not secure the environmental quality. Therefore, environmental regulation policies need to be revised in order to achieve a sustainable environment. As a result, we recommend that China continue to expand its economy and invest in health care and environmental initiatives.

MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/ß-catenin signaling pathway.

MICAL1 has been reported to be involved in the malignant processes of several types of cancer cells, however, the roles of MICAL1 in colorectal cancer (CRC) have not been well-characterized. This study aims to investigate the cellular functions and molecular mechanisms of MICAL1 in CRC cells. Here, we found that both mRNA and protein levels of MICAL1 were down-regulated in colorectal cancer tissues compared with matched adjacent non-tumor tissues, and the expression level of MICAL1 was correlated with the metastatic status of colorectal cancer. Importantly, overexpression of MICAL1 significantly inhibited colorectal cancer cell migration and growth, and increased the level of E-cadherin and Occludin, and suppressed the expression level of Vimentin and N-cadherin; while silencing of MICAL1 promoted CRC cell migration and enhanced EMT. In addition, MICAL1 overexpression significantly inhibited the proliferation and growth of CRC in vitro and in vivo. Moreover, RNA sequencing and bioinformatics analysis identified that MICAL1 was closely correlated with "cell migration", "cell cycle" and "ß-catenin signaling" genesets. Mechanistically, overexpression of MICAL1 downregulated the mRNA level of EGR1 and ß-catenin, decreased the protein level and nuclear translocation of ß-catenin, and inhibited the transcriptions of ß-catenin downstream targets, c-myc and cyclin D1. The ectopic expression of EGR1 or ß-catenin can significantly block the MICAL1-mediated inhibitory effects. Collectively, MICAL1 is down-regulated in CRC, and plays an inhibitory role in the migration and growth of CRC cells by suppressing the ERG1/ß-catenin signaling pathway.