MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of a variety of biological processes. However, the role of miRNAs in TGF-β-regulated biological processes is poorly addressed. In this study, we found that miR-24 was upregulated during myoblast differentiation and could be inhibited by TGF-β1. Using both a reporter assay and Northern blot analysis, we showed that TGF-β1 repressed miR-24 transcription which was dependent on the presence of Smad3 and a Smads binding site in the promoter region of miR-24. TGF-β1 was unable to inhibit miR-24 expression in Smad3-deficient myoblasts, which exhibited accelerated myogenesis. Knockdown of miR-24 led to reduced expression of myogenic differentiation markers in C2C12 cells, while ectopic expression of miR-24 enhanced differentiation, and partially rescued inhibited myogenesis by TGF-β1. This is the first study demonstrating a critical role for miRNAs in modulating TGF-β-dependent inhibition of myogenesis, and provides a novel mechanism of the genetic regulation of TGF-β signaling during skeletal muscle differentiation.

The Hebei Province Medical Science Special Major Projects Research Fund.

www.eymj.orgAs of February 26, 2020, 78195 cases of the 2019-new coronavirus were reported in China, and among these, 2718 resulted in death. 1 Like SARS and MERS, the coronavirus can lead to severe respiratory problems, and human-to-human transmission has been confirmed. 2 The outbreak, which began in Wuhan, has now spread across China to different parts of the country and the world. Panic has spread throughout China. 3 More alarming than the number of deaths is that several doctors and nurses have also died while fighting against the virus, despite their expertise.Under normal conditions, people try to maintain a stable state of mind and harmony between themselves and the environment. However, when faced with an urgent event, this internal balance is lost. The body immediately mobilizes physiological and psychological responses in an attempt to deal with the emergency. This is referred to as the stress response. An appropriate stress response can assist people in paying adequate attention to the epidemic and actively preventing and remedying it; however, an excessive response can drive people to exaggerate the seriousness of the epidemic and live in constant fear. Causal factorsMental disorders related to COVID-19 are the result of biological, social, and psychological factors. Biological factorsBiological factors include the virus, its metabolites, and the body's excessive immune response to these foreign substances, which results in fever, dyspnea, and other clinical symptoms. This can lead to brain hypoxia and/or carbon dioxide retention, edema, vascular dysfunction, and other pathological changes. These, in turn, can disrupt the brain's higher neural activity. In addition, some drugs used in treatment, such as antiviral drugs, can cause drug-induced mental disorders: for example, glucocorticoids can lead to excitement, depression, tension, insomnia, hallucinations, and other symptoms. 4 Social factorsPublic psychology is often very fragile during outbreaks of infectious diseases. Amid a lack of psychological endurance in the public, inappropriate or excessive release of panic-triggering information by television, radio, newspaper, magazine, Internet, and other media sources can have a negative impact on the population. From the perspective of communication psychology, during such times, people tend to carry an affinity for negative, threatening, or informal information and for ignoring or doubting positive and formal information. Furthermore,

Edited by Tamas DalmayKeywords: Hypoxia Hypoxia-inducible factor 1a (HIF-1a) MicroRNA miR-21 Cardiomyocytes a b s t r a c t Accumulating evidence suggests that hypoxia-inducible factor 1a (HIF-1a) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF-1a and miR-21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF-1a and miR-21 expression. HIF-1a knockdown increased cell apoptosis and reduced miR-21 expression. Furthermore, we found that HIF-1a transcriptionally enhanced miR-21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR-21 inhibition increased cell apoptosis and reduced HIF-1a expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF-1a-miR-21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.

As a safe application, the use of a tourniquet during TKA may be effective for reducing intraoperative blood loss, but not for reducing the postoperative blood loss and actual total blood loss. However, no uniform guideline can be made based on the current evidence because of the very low evidence quality and lower GRADE recommendation strength.