IntroductionLung metastasis occurs in parts of the bladder carcinoma (BC) patients but represents the highest severity and a poor outcome of the disease. The molecular mechanism underlying lung metastasis of BC is not fully understood. Fibroblast growth factor receptor 2 (FGFR2) signaling plays a substantial role in the BC cell growth and invasion. In this study, we assessed the regulation of the alternative splicing of FGFR2 by epithelial splicing regulatory proteins (ESRPs) in lung metastasis of BC.MethodsGene profile of BC in comparison with adjacent non-tumor bladder tissue was obtained from GEO public database to analyze the levels of differentiated genes and pathways. Moreover, the association of ESRP1 or ESRP2 with lung metastasis of BC was analyzed on our own clinic samples. The effects of altered expression of ESRP1 or ESRP2 on alternative splicing of FGFR2 IIIb and IIIc, which represents epithelial and mesenchymal-like splicing, were analyzed on BC cell lines T24 and RT4. The in vivo effects of ESRP1 or ESRP2 on lung metastasis of BC were assessed in mice subcutaneously grafted with ESRP1/2-modified BC labeled with fluorescent and luciferase reporters.ResultsWe detected significant reduction of ESRP1 and ESRP2 in BC in public database of BC specimens. Moreover, analysis on our own specimens also showed strong downregulation of ESRP1 or ESRP2 in BC, and the latter was more pronounced in cases with lung metastasis. In vitro, altered levels of ESRP1 or ESRP2 caused a switch of FGFR2 splicing between FGFR2-IIIb and FGFR2-IIIc, resulting in changes in tumor cell growth and metastatic potential. In vivo, re-expression of ESRP1 or ESRP2 in BC cells not only inhibited the growth of the xenografted tumor formation in nude mice, but also reduced the occurrence of lung metastasis, partially through altering polarization of tumor-associated macrophages.ConclusionOur data thus suggest that reduction in ESRP1 or ESRP2 promotes lung metastasis of BC through altering FGFR2 splicing and macrophage polarization.

The purpose of this paper was to investigate the relationship between board independence and the firm performance of Chinese firms listed in the Shanghai Stock Exchange, under the moderating role of Corporate Social Responsibility (CSR). A total of 860 firm-year observations over a period of ten years, that is from 2010 to 2019 was collected. The panel data regression technique was employed to analyze the data and determine the relationship between board independence and the firm performance of the Chinese firms under investigation. After a robustness check, the empirical results showed that the level of the CSR moderated (reduced) the positive relationship between board independence and firm performance. Therefore, the results seemed to imply that although the CSR has been seen as a useful business strategy, the level of the CSR in China still needed to be improved. In order to improve firm performance through practicing the CSR, the Chinese government and enterprises should be encouraged to continuously improve the level of the CSR.

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Aims Biodiversity is found to have a significant promotion effect on ecosystem functions in manipulation experiments on grassland communities. However, its relative role compared with stand factors or functional identity is still controversial in natural forests. Here we examined their relative effects on biomass and productivity during forest restoration. Methods We investigated stand biomass and productivity for 24 plots (600 m 2) across restoration stages in the subtropical forests of Mt. Shennongjia, central China. We measured five key functional traits and calculated functional diversity (functional richness, evenness, and dispersion) and community-weighted mean (CWM) of traits. We used general linear models (GLMs), variation partitioning methods to test the relative importance of stand factors (density, stand age, maximum height, etc.), functional identity, species and functional diversity on biomass and productivity. Important Findings Our results illustrated that stand biomass and productivity increased significantly as forest restoration, and that community species richness increased significantly, while functional dispersion decreased significantly. Variation partitioning analyses showed that diversity had no significant pure effects on biomass and productivity. However, diversity can affect biomass and productivity through the joint effect with stand factors and functional identity. Overall, we found that stand factors had the strongest effect on biomass and productivity, while functional identity significantly affects productivity but not biomass, suggesting that modulating stand structure and species identity are effective ways to enhance forest carbon storage and sequestrations potential in forest management.