Farnesoid X Receptor Protects Murine Lung against IL-6-promoted Ferroptosis Induced by Polyriboinosinic-Polyribocytidylic Acid.

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Mental Health Problems Among School-Aged Children After School Reopening: A Cross-Sectional Study During the COVID-19 Post-pandemic in East China.

Background: Most studies on mental health problems caused by COVID-19 crisis in children were limited to the period of home quarantine. It remained unclear what adverse impact of the psychosocial stressors caused by school reopening, as well as the transitions in daily activities and social interactions had on mental health in children. Methods: A total of 6400 students in primary schools were enrolled in a cross-sectional study conducted in East China, between June 26 and July 6, 2020, when schools reopened. Children's mental health status was assessed by the parent version of Strengths and Difficulties Questionnaire (SDQ). Ultimately, data on a total of 6017 children with completed information on mental health, psychosocial stressors, daily activities, and social interactions were eligible for analysis. The associations of mental health with psychosocial stressors, daily activities, and social interactions were determined by ordinal logistic regression models. Stratified analyses were conducted according to grade, gender, school level, area, and caregiver-child relationship to further observe the effects of stressors on mental status. Results: The prevalence of borderline, moderately abnormal, and prominently abnormal scores were 7.16, 3.34, and 1.96% for total difficulties, and 13.83, 13.45, and 17.85% for prosocial behavior, respectively. Children with psychological stressors had a significantly higher risk of being in a worse category of mental health status, with the maximum adjusted OR of 7.90 (95% CI 3.33-18.75) in those definitely afraid of inadaptation to study and life styles. Time used in home work and computer games was positively related to mental health problems, while physical exercises and frequency of communication with others was negatively related. The effects of psychological stressors on total difficulties were more evident in middle-high grade students (OR = 7.52, 95% CI 4.16-8.61), boys (OR = 6.95, 95% CI 4.83-8.55), those who lived in Taizhou (OR = 7.62, 95% CI 4.72-8.61) and with poor caregiver-child relationship (OR = 7.79, 95% CI 2.26-8.65). Conclusion: Emotional and behavioral difficulties, especially less prosocial behavior, were prevalent in primary school children after schools reopened. The Chinese government, communities, schools, and families need to provide more effective support for students' transition back into the school building and address emotional and behavioral problems for children with difficulties.

Study problems and depressive symptoms in adolescents during the COVID-19 outbreak: poor parent-child relationship as a vulnerability.

BACKGROUND: Little is known about the prevalence of and risk factors for adolescent mental health problems during the COVID-19 outbreak. We aimed to investigate the prevalence of depressive symptoms, their association with study-relevant problems, and the moderating effect of parent-child relationship among Chinese adolescents during the school closures. METHODS: We performed a cross-sectional analysis with data collected in middle and high schools in Taizhou, China. Students completed an online survey between April 16 and May 14, 2020. Depressive symptoms were assessed using the Children's Depression Inventory. Three types of study problems were recorded, including having difficulty in studying at home, dislike of remote learning, and excessive screen entertainment time. Parental relationships were categorized into good or normal relationship and poor relationship. Linear regression and logistic regression analyses were conducted to investigate the associations between study-relevant problems and depressive symptoms. RESULTS: Using data from 6435 adolescents, we found that the prevalence of depressive symptoms was 17.7%. All the study problem measures were associated with more severe depressive symptoms. There was a moderating effect of the parental relationship on the associations between study problems and depressive symptoms. The association between number of study problems and depressive symptoms was stronger in adolescents with a poor parent-child relationship (regression coefficient 4.34 [95% CI 2.97, 5.72]) than those with a good or normal relationship (2.55 [2.35, 2.75]), p for interaction 0.002, on multivariable adjustment. CONCLUSIONS: Study problems due to school closures were particularly problematic for adolescents who had poor parent-child relationships. Public health initiatives could help students to adjust study habits and improve parent-child relationships, thereby protecting against the development of depression.

Impact of psychosocial stressors on emotional and behavioral problems in Chinese adolescents during the COVID-19 period: the explanatory value of loneliness.

BACKGROUND: Chinese adolescents experienced a variety of stressors during the COVID-19 home confinement period. This study aimed to investigate the prevalence of emotional and behavioral problems (EBPs) among adolescents during the COVID-19 period. The study also examined the relationships between psychosocial stressors and adolescents' EBPs, and explored the potential explanatory value of loneliness for any associations observed. METHODS: We conducted a cross-sectional study which included 6,587 adolescents in Taizhou, China between April 16 and May 14, 2020. Adolescents' EBPs were assessed by the Strengths and Difficulties Questionnaire (SDQ), while subjective feelings of loneliness were assessed using one item from the Children's Depression Inventory. We applied structural equation modelling to assess direct and indirect associations (explained by loneliness) between psychosocial stressors (study problems, parent-child relationship, and family or friends with COVID-19) and the total difficulties and prosocial scores. RESULTS: The prevalence of EBPs in the sample was 31.6% for total difficulties and 37.5% for prosocial problems. After adjustment for a range of covariates, the presence of study problems, poor parent-child relationship and family or friends with COVID-19 were significantly associated with a higher SDQ total difficulties score (ß=6.20, 21.46, 5.21; P<0.01) and a lower prosocial score (ß=-0.79, -4.35, -1.65; P<0.01). There was an explanatory effect of loneliness on these associations, which explained 27-37% of the total effect on the total difficulties score and 11-37% on the prosocial score. CONCLUSIONS: The presence of psychosocial stressors during the home confinement period was related to higher EBPs in adolescents, and the relationship was partially explained by loneliness. Targeted psychosocial interventions towards loneliness and COVID-19 related stressors may improve adolescents' psychological health.

COVID-19 control strategies in Taizhou city, China.

PROBLEM: On 21 January 2020, the city of Taizhou, China, reported its first imported coronavirus disease 2019 (COVID-19) case and subsequently the number of cases rapidly increased. APPROACH: To organize the emergency responses, the government of Taizhou established on 23 January 2020 novel headquarters for prevention and control of the COVID-19 outbreak, by coordinating different governmental agencies. People at high risk of acquiring COVID-19, as well as probable and confirmed cases, were identified and quarantined. The government closed public venues and limited gatherings. The Taizhou Health Commission shared information about identified COVID-19 patients and probable cases with affected agencies. To timely track and manage close contacts of confirmed cases, Taizhou Center for Disease Control and Prevention did epidemiological investigations. Medical institutions or local centers for disease control and prevention reported confirmed cases to the national Center for Disease Control and Prevention. LOCAL SETTING: Taizhou, a city in Zhejiang province with about 6 million residents, reported 18 confirmed COVID-2019 cases by 23 January 2020, which ranked it third globally in number of cases after Wuhan and Xiaogan cities in the Hubei province. RELEVANT CHANGES: In total, 146 confirmed cases (85 cases imported and 61 cases through community transmission) and no deaths due to COVID-19 had been reported in Taizhou by 1 June 2020. Between 16 February and 1 June 2020, no confirmed case had been reported. LESSON LEARNT: Identifying and managing imported cases and people at risk for infection, timely information sharing, limiting gatherings and ensuring collaborations between different agencies were important in controlling COVID-19.