N 6-methyladenosine (m 6 A) mRNA modifications play critical roles in various biological processes. However, no study addresses the role of m 6 A in macroautophagy/autophagy. Here, we show that m 6 A modifications are increased in H/R-treated cardiomyocytes and ischemia/reperfusion (I/R)-treated mice heart. We found that METTL3 (methyltransferase like 3) is the primary factor involved in aberrant m 6 A modification. Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes. However, overexpression of METTL3 or inhibition of the RNA demethylase ALKBH5 has an opposite effect, suggesting that METTL3 is a negative regulator of autophagy. Mechanistically, METTL3 methylates TFEB, a master regulator of lysosomal biogenesis and autophagy genes, at two m 6 A residues in the 3ʹ-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. Further experiments show that autophagic flux enhanced by METTL3 deficiency is TFEB dependent. In turn, TFEB regulates the expression levels of METTL3 and ALKBH5 in opposite directions: it induces ALKBH5 and inhibits METTL3. TFEB binds to the ALKBH5 promoter and activates its transcription. In contrast, inhibition of METTL3 by TFEB does not involve transcriptional repression but rather downregulation of mRNA stability, thereby establishing a negative feedback loop. Together, our work uncovers a critical link between METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m 6 A methylation and its modulators in ischemic heart disease.

The coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. In order to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs, we conducted a molecular epidemiological study among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. Nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) detection were performed to confirm SARS-CoV-2 infection among those HCWs. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 15, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. These HCWs were provided with adequate supply of PPE as committed by their original institutions or provinces. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. In conclusion, our findings indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection.

Secondary prevention is an important strategy in gastric cancer. Low-grade intraepithelial neoplasia (LGIN) is the last stage of precancerous lesion, and its timely diagnosis can greatly improve the detection rate of early gastric cancer. We performed a prospective study to analyze the risk factors of gastric LGIN in asymptomatic subjects undergoing physical examination. A total of 3437 subjects were included in this study, and 2259 asymptomatic subjects were investigated from March 2015 to April 2018. Risk factors were evaluated, and the endoscopic features of LGIN and prognosis were described. The overall incidence of LGIN was 19.73% (678/3437), while the incidence of LGIN in the asymptomatic and symptomatic groups was 19.65% (444/2259) and 19.86% (234/1178), respectively (P = 0:884). The rate of Helicobacter pylori infection in this physical examination population was 39.13% (35.8% asymptomatic group, 45.5% symptomatic group; P ≤ 0:001). Risk factors including age, H. pylori infection, history of antibiotic misuse, and spicy and high-fat diet (all P < 0:05) were further verified by multivariate analysis as independent risk factors. History of antibiotic misuse and H. pylori infection showed significant associations with LGIN (odds ratio ðORÞ = 6:767, 95% confidence interval (CI) 3.873-11.825 and OR = 3:803, 95% CI 3.009-4.808, respectively). The most common endoscopic classification of LGIN was erosive gastritis (50.78%), and the major endoscopic appearance was Paris IIa (flat with slight elevation located mostly in the antrum). During the mean follow-up period of 15.02 months, 49.4% of LGIN regressed, 0.61% of LGIN progressed, and 50% of LGIN remained unchanged. History of antibiotic misuse and H. pylori infection were predominant risk factors of LGIN in asymptomatic subjects, and those individuals should consider early screening for gastric cancer.