Background: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. Methods: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. Results: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). Conclusions: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. Trial registration: Chinese Clinical Trial Registry (chictr.org.cn) identifier: ChiCTR2000030464.

Rationale: Doxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is restricted because it poses a risk of severe cardiotoxicity. Previous work has established that CircITCH is a broad-spectrum tumor-suppressive circular RNA and that its host gene, ITCH, is involved in doxorubicin-induced cardiotoxicity (DOXIC). Whether CircITCH plays a role in DOXIC remains unknown. Objective: We aimed to dissect the role of CircITCH in DOXIC and further decipher its potential mechanisms. Methods and Results: Circular RNA sequencing was performed to screen the potentially involved circRNAs in doxorubicin-induced cardiotoxicity pathogenesis. Quantitative PCR (qPCR) and RNA ISH (in situ hybridization) revealed that CircITCH was downregulated in DOX-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in the autopsy specimens from cancer patients who suffered from DOX-induced cardiomyopathy. Cell death/viability assays, detection of cardiomyocyte necrosis markers, microelectrode array, and cardiomyocyte functional assays revealed that CircITCH ameliorated DOX-induced cardiomyocyte injury and dysfunction. Detection of cellular/mitochondrial oxidative stress and DNA damage markers verified that CircITCH alleviated cellular/mitochondrial oxidative stress and DNA damage induced by DOX. RNA pull-down assays, Ago2 immunoprecipitation and double fluorescent ISH (FISH) identified miR-330-5p as a direct target of CircITCH. Moreover, CircITCH was found to function by acting as an endogenous sponge that sequestered miR-330-5p. Bioinformatic analysis, luciferase reporter assays and qPCR showed that SIRT6, BIRC5 (Survivin) and ATP2A2 (SERCA2a) were direct targets of miR-330-5p and that they were regulated by the CircITCH/miR-330-5p axis in DOXIC. Further experiments demonstrated that CircITCH-mediated alleviation of DOXIC was dependent on the interactions between miR-330-5p and the 3´-UTRs of SIRT6, BIRC5 and ATP2A2 mRNA. Finally, AAV9 vector-based overexpression of the well-conserved CircITCH partly prevented DOXIC in mice. Conclusions: CircITCH represents a novel therapeutic target for DOXIC because it acts as a natural sponge of miR-330-5p, thereby upregulating SIRT6, Survivin and SERCA2a to alleviate DOX-induced cardiomyocyte injury and dysfunction.

Translocation of Nur77 from the nucleus to the mitochondria in cardiomyocytes results in the loss of mitochondrial integrity and subsequent apoptosis in response to ischaemia/reperfusion injury. Our findings identify Nur77 as a novel mediator of cardiomyocyte apoptosis and warrants further investigation of mitochondrial Nur77 translocation as a mechanism to control cell death in the treatment of ischaemic heart diseases.

Embryonic stem cells (ESCs) are pluripotent stem cells from early embryos. It has been well recognized that ESC genomes are maintained in a globally transcriptional hyperactive state, which genetically poised ESCs to the high differentiation potential. However, the transcription factors regulating the global transcription activities in ESCs are not well defined. We show here that mouse and human ESCs express two transcription factors, Aire and Deaf1. Previously known to function in the thymus stromal cells and peripheral lymphoid organs respectively, Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Differentiation of ESCs greatly reduced Aire and Deaf1 expression, in a pattern similar to the pluripotent factors, Oct4 and Nanog. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. In addition, some differentiation-associated genes that are sporadically expressed in ESCs were reduced in expression upon Aire knockdown. These results suggest that transcription factors such as Aire and Deaf1, which exert global transcriptional regulatory functions, may play important roles in self-renewal of ESCs and maintaining ESC in a transcriptionally hyperactive state.