kr.Oxidative stress and its associated lipid peroxidation play a key role in nonalcoholic steatohepatitis (NASH). Ferroptosis is a recently recognized type of cell death characterized by an iron-dependent and lipid peroxidationemediated nonapoptotic cell death. We demonstrate the impact of ferroptosis on the progression of NASH induced by methionine/choline-deficient diet (MCD) feeding for 10 days. RSL-3 (a ferroptosis inducer) treatment showed decreased hepatic expression of glutathione peroxidase 4 (GPX4) and conversely increased 12/15-lipoxygenase, and apoptosis-inducing factor, indicating that ferroptosis plays a key role in NASH-related lipid peroxidation and its associated cell death. Consistently, levels of serum biochemical, hepatic steatosis, inflammation, and apoptosis in MCD-fed mice were exacerbated with RSL-3 treatment. However, MCD-fed mice treated with sodium selenite (a GPX4 activator) showed increase of hepatic GPX4, accompanied by reduced NASH severity. To chelate iron, deferoxamine mesylate salt was used. Administration of deferoxamine mesylate salt significantly reduced NASH severity and abolished the harmful effects of RSL-3 in MCD-fed mice. Finally, treatment with liproxstatin-1 (a ferroptosis inhibitor) repressed hepatic lipid peroxidation and its associated cell death, resulting in decreased NASH severity. Consistent with the in vivo findings, modulation of ferroptosis/GPX4 affected hepatocellular death in palmitic acideinduced in vitro NASH milieu. We conclude that GPX4 and its related ferroptosis might play a major role in the development of NASH.

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Arthropod-borne viruses (Arboviruses) are transmitted by arthropods such as Culicoides biting midges and cause abortion, stillbirth, and congenital malformation in ruminants, apparently leading to economic losses to farmers. To monitor the distribution of Culicoides and to determine their relationship with different environmental conditions (temperature, humidity, wind speed, and altitude of the farms) on 5 cattle farms, Culicoides were collected during summer season (May-September) in 2016 and 2017, and analyzed for identification of species and detection of arboviruses. About 35% of the Culicoides were collected in July and the collection rate increased with increase in temperature and humidity. The higher altitude where the farms were located, the more Culicoides were collected on inside than outside. In antigen test of Culicoides against 5 arboviruses, only Chuzan virus (CHUV) (2.63%) was detected in 2016. The Akabane virus (AKAV), CHUV, Ibaraki virus and Bovine ephemeral fever virus (BEFV) had a positive rate of less than 1.8% in 2017. In antigen test of bovine whole blood, AKAV (12.96%) and BEFV (0.96%) were positive in only one of the farms. As a result of serum neutralization test, antibodies against AKAV were generally measured in all the farms. These results suggest that vaccination before the season in which the Culicoides are active is probably best to prevent arbovirus infections.

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