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.

[Characteristics and Source Analysis of Volatile Organic Compounds in Typical Ozone Pollution Processes During Summer in Jinan, China].

Based on a typical ozone （O3） pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds （VOCs） during different pollution periods （clean period （CP）, pollution rise period （PRP）, heavy pollution period （HPP）, and pollution decline period （PDP）） in the urban area were analyzed. Both positive matrix factorization （PMF） and an observation-based model （OBM） were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρ（O3-8h） during the HPP period in the urban area was （246.67±11.24） µg·m-3, and ρ（O3-1h） had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds （OVOCs）, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential （OFP）. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals （HO2·ï¼‰ and methyl peroxide radicals （CH3O2·ï¼‰ with NO, and the net ozone generation rate during the HPP phase [P（O3）net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.

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.