Rotenone, a widely used pesticide, causes dopaminergic neurons loss and increase the risk of Parkinson's disease (PD). However, few studies link the role of PARP1 to neuroinflammatory response and autophagy dysfunction in rotenone-induced neurodegeneration. Here, we identified that PARP1 overactivation caused by rotenone led to autophagy dysfunction and NLRP3-mediated inflammation. Further results showed that PARP1 inhibition could reduce NLRP3-mediated inflammation, which was effectively eliminated by TFEB knockdown. Moreover, PARP1 poly(ADP-ribosyl)ated TFEB that reduced autophagy. Of note, PARP1 inhibition could rescue rotenone-induced dopaminergic neurons loss. Overall, our study revealed that PARP1 blocks autophagy through poly (ADP-ribosyl)ating TFEB and inhibited NLRP3 degradation, which suggests that intervention of PARP1-TFEB-NLRP3 signaling can be a new treatment strategy for rotenone-induced neurodegeneration.

Objective:To study the mechanism of mitochondrial calcium uniporter (MCU) in regulating rotenone induced ferroptosis in dopaminergic neurons.Methods:Immunoblotting test and lipid oxidation kit were used to detect the expression of MCU protein and the level of ferroptosis before and after rotenone treatment. The changes of the expression of MCU protein and the level of ferroptosis after rotenone treatment were detected.Results:After rotenone treatment, the expression of glutathione peroxidase - 4 and ferritin heavy chain polypeptide - 1 protein in dopaminergic neurons were decreased, and the level of intracellular oxidative stress was increased; the expression of MCU protein and the level of ferroptosis were decreased after the recovery of MCU protein expression.Conclusions:Rotenone can promote ferroptosis of dopaminergic neurons by reducing the expression of MCU protein.

Objective:To investigate the impact of the 2019 novel coronavirus disease (COVID-19) pandemic on the willingness to change dietary habits among young adults in Shenzhen.Methods:With an anonymous network sampling method, we conducted a questionnaire survey among 22,459 residents aged 15 to 45 years living in Shenzhen in March 2020. The questionnaire included socio-demographic information, subjective impact of the epidemic on individuals, and willingness to change dietary habits due to COVID-19. Multivariable linear regression model was used to analyzed the influencing factors of willingness to change dietary habits.Results:Average age of the subjects was 27.9±7.8 years old. The mean score of willingness to change dietary habits was 2.17 (ranges from -9 to 9). Among them, the female, ≥35 years old people, with (bachelor degree or above education, married, non-medical staff, and with BMI of (18.5~23.9)kg/m2 had a good performance of the score, which were 2.84, 2.96, 2.52, 2.70, 2.19 and 2.34, respectively (P＜0.05). Multivariate regression analysis showed that the impact of the COVID-19 pandemic (epidemic concern, impact of psychology, impact of work or study) are associated with a higher score of willingness to change dietary habits among female, the older, non-medical worker, and individuals married or with higher education level, normal BMI.Conclusions:After experiencing the impact of COVID-19, there was a positive improvement on the willingness to adopt a proper diet among young adults in Shenzhen. We should strengthen the health education and promotion of reasonable diet. Individual subjective influence, gender, age, education level, occupation, marital status and BMI are the factors that influence the willingness.

Abstract Background: To investigate impact of the 2019 novel coronavirus disease (COVID-19) pandemic on willingness to adopt healthy dietary habits in China. Methods: A survey was carried out, and subjective perception of impact due to COVID-19 and willingness to change dietary habits were obtained. Results: A total of 22,459 subjects were derived from China, with an average age of 27.9±7.8 years old. Of them, the mean score of willingness to adopt healthy dietary habits was 2.2 (ranges from -9 to 9). Multivariate regression analysis showed that the impact of the COVID-19 pandemic (epidemic concern, impact of psychology, impact of work or study) are associated with a higher score of willingness to adopt healthy dietary habits among female, the older, on-medical worker, and individuals married or with higher education level, normal BMI. Conclusions: There was a positive improvement to a proper diet, so the changing features of diets should be considered in nutritional interventions for maintaining health, and prevention and control COVID-19 during the pandemic period.

Rotenone, a component of pesticides, is widely used in agriculture and potentially causes Parkinson's disease (PD). However, the regulatory mechanisms of rotenone-induced PD are unclear. Here, we revealed a novel feedback mechanism of p38-Parkin-ROS regulating rotenone-induced PD. Rotenone treatment led to not only the activation of p38 but also Parkin inactivation and reactive oxygen species (ROS) overproduction in SN4741 cells. Meanwhile, p38 activation regulated Parkin phosphorylation at serine 131 to disrupt Parkin-mediated mitophagy. Notably, both p38 inhibition and Parkin overexpression decreased ROS levels. Additionally, the ROS inhibitor N-acetyl-l-cysteine (NAC) inhibited p38 and activated Parkin-mediated mitophagy. Both p38 inhibition and the ROS inhibitor NAC exerted a protective effect by restoring cell death and mitochondrial function in rotenone-induced PD models. Based on these results, the p38-Parkin-ROS signaling pathway is involved in neurodegeneration. This pathway represents a valuable treatment strategy for rotenone-induced PD, and our study provides basic research evidence for the safe use of rotenone in agriculture.