Fluvoxamine alleviates bleomycin-induced lung fibrosis via regulating the cGAS-STING pathway.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9-5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-ß1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.

Turnover at the Top: The Digital Transformation and Dismissal of Chairman and CEO.

Companies increasingly implement digital transformation strategies to promote efficiency. Nevertheless, there are few concerns about employees' acceptance of the changes, especially the executives' adaptability, which is an important part of digital transformation strategy implementation. By utilizing the "searching-matching" in keywords of the annual reports of public listed companies in China, we measured the degree of corporate digital transformation to analysis its influence on the turnover rate of the Chairman and CEO. We found that digital transformation decreases the possibility of Chairman and CEO's turnover. Derived from the dynamic managerial capital theory, we demonstrated that executives' social network and political connections both have a moderate effect on the relationship between digital transformation and the turnover rate of executives. These findings will contribute to the digital transformation research by integrating with executives' dynamic managerial capital which is attained through social networks and political connections.