Huntington disease (HD) is an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (HTT). PolyQ length determines disease onset and severity with a longer expansion causing earlier onset. The mechanisms of mutant HTT-mediated neurotoxicity remain unclear; however, mitochondrial dysfunction is a key event in HD pathogenesis1,2. Here we tested whether mutant HTT impairs the mitochondrial fission/fusion balance and thereby causes neuronal injury. We show that mutant HTT triggers mitochondrial fragmentation in neurons and fibroblasts of HD individuals in vitro and HD mice in vivo before the presence of neurological deficits and HTT aggregates. Interestingly, mutant HTT abnormally interacts with the mitochondrial fission GTPase dynamin-related protein 1 (DRP1) in HD mice and individuals which in turn stimulates its enzymatic activity. Importantly, mutant HTT-mediated mitochondrial fragmentation, defects in anterograde and retrograde mitochondrial transport, and neuronal cell death are all rescued by reducing DRP1 GTPase activity with the dominant-negative DRP1K38A mutant. Thus, DRP1 might represent a new therapeutic target to combat neurodegeneration in HD.

Background: Since December 2019, China has been affected by a severe outbreak of coronavirus disease 2019 (COVID-19). Frontline medical workers experienced difficulty due to the high risk of being infected and long and distressing work shifts. The current study aims to evaluate psychological symptoms in frontline medical workers during the COVID-19 epidemic in China and to perform a comparison with the general population. Methods: An online survey was conducted from 14 February 2020 to 29 March 2020. A total of 899 frontline medical workers and 1104 respondents in the general population participated. Depression, anxiety, insomnia, and resilience were assessed via the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), Insomnia Severity Index (ISI), and abbreviated Connor–Davidson Resilience Scale (CD-RISC-10), respectively. Results: Overall, 30.43%, 20.29%, and 14.49% of frontline medical workers in Hubei Province and 23.13%, 13.14%, and 10.64% of frontline medical workers in other regions reported symptoms of depression, anxiety, and insomnia, respectively. In addition, 23.33%, 16.67%, and 6.67% of the general population in Hubei Province and 18.25%, 9.22%, and 7.17% of the general population in other regions reported symptoms of depression, anxiety, and insomnia, respectively. The resilience of frontline medical staff outside Hubei Province was higher than that of the general population outside Hubei Province. Conclusion: A large proportion of frontline medical workers and the general public experienced psychological symptoms during the COVID-19 outbreak. Psychological services for frontline medical workers and the general public are needed.

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D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.