Human angiotensin‐converting enzyme 2 (ACE2) facilitates cellular entry of severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARS‐CoV‐2 as their common receptor. During infection, ACE2‐expressing tissues become direct targets, resulting in serious pathological changes and progressive multiple organ failure or even death in severe cases. However, as an essential component of renin‐angiotensin system (RAS), ACE2 confers protective effects in physiological circumstance, including maintaining cardiovascular homeostasis, fluid, and electrolyte balance. The absence of protective role of ACE2 leads to dysregulated RAS and thus acute changes under multiple pathological scenarios including SARS. This potentially shared mechanism may also be the molecular explanation for pathogenesis driven by SARS‐CoV‐2. We reasonably speculate several potential directions of clinical management including host‐directed therapies aiming to restore dysregulated RAS caused by ACE2 deficiency. Enriched knowledge of ACE2 learned from SARS and COVID‐19 outbreaks can provide, despite their inherent tragedy, informative clues for emerging pandemic preparedness.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to have higher pathogenicity among patients with obesity. Obesity, termed as body mass index greater than 30 kg/m 2 , has now been demonstrated to be important comorbidity for disease severity during coronavirus disease 2019 (COVID-19) pandemic and associated with adverse events. Unraveling mechanisms behind this phenomenon can assist scientists, clinicians, and policymakers in responding appropriately to the COVID-19 pandemic. In this review, we systemically delineated the potential mechanistic links between obesity and worsening COVID-19 from altered physiology, underlying diseases, metabolism, immunity, cytokine storm, and thrombosis. Problematic ventilation caused by obesity and preexisting medical disorders exacerbate organ dysfunction for patients with obesity. Chronic metabolic disorders, including dyslipidemia, hyperglycemia, vitamin D deficiency, and polymorphisms of metabolism-related genes in obesity, probably aid SARS-CoV-2 intrusion and impair antiviral responses. Obesity-induced inadequate antiviral immunity (interferon, natural killer cells, invariant natural killer T cell, dendritic cell, T cells, B cell) at the early stage of SARS-CoV-2 infection leads to delayed viral elimination, increased viral load, and expedited viral mutation. Cytokine storm, with the defective antiviral immunity, probably contributes to tissue damage and pathological progression, resulting in severe symptoms and poor prognosis. The prothrombotic state, driven in large part by endothelial dysfunction, platelet hyperactivation, hypercoagulability, and impaired fibrinolysis in obesity, also increases the risk of severe COVID-19. These mechanisms in the susceptibility to severe condition also open the possibility for host-directed therapies in population with obesity. By bridging work done in these fields, researchers can gain a holistic view of the paths forward and therapeutic opportunities to break the vicious cycle of obesity and its devastating complications in the next emerging pandemic.

Burns are tissue injuries caused by high temperature, chemicals or electricity. Severe burns may involve all of the organs and tissues of the human body, leading to a series of pathophysiological processes and even death. The present study reviewed the clinical data of burn patients, including cases of burn-associated death, to provide evidence for the strategy of burn prevention. Basic information from 13,205 inpatients treated between January 1, 2009 and December 31, 2016 was extracted from the database of the Institute of Burn Research at Southwest Hospital (Chongqing, China). After excluding 3,426 inpatients who were not primarily treated for burns, 9,779 patients remained; among them, 68 cases (0.7%) had died as a direct consequence of the burns. Based on baseline data, the mortality rate, total body surface area of the burn (TBSA), age, sex, cause of injury and complications were analysed. In general, males accounted for a higher percentage than female burn patients. Of the patients, 95.54% had a TBSA of <50%, and the rate of mortality of the patients was increased when the TBSA was ≥50%. The major causes of injury were scalds (41.60%), fire (26.92%) and electricity (15.29%), and the majority of victims were 14 years or younger. With improvements in burn treatment technology in recent years, burn patient mortality was significantly reduced. Complications, including multiple organ failure and severe systemic infection, may reduce the survival rate of patients. The major risk factors for death included burns resulting from explosions, as well as shock, age (aged 0-1 or ≥50 years), greater TBSA and full-thickness burn area. With increasing length of stay at the hospital, patient mortality decreased. The renewal of treatment concepts and refined patient management contributed to the shorter LOS and lower mortality in 2015 and 2016.

Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF‐biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Initially, we found that electrical signals directed keratinocytes to the cathode with enhanced motility parameters [i.e., trajectory distance, trajectory speed, displacement distance, and displacement speed (Td/t)] and more efficient migration (directionality and Td/t along the x axis, among others). Meanwhile, EFs induced a time‐dependent increase in autophagic activity in keratinocytes, with constant autophagic flux, accompanied by increased transcription of numerous autophagy‐related genes. Deficiency in Atg5, a key protein necessary for autophagosome formation, led to significant reduction of autophagy, which was accompanied by a substantial reduction in EF‐stimulated directed motility. These results demonstrated a causal relationship between autophagy and EF‐directed migratory speed. In addition, both cell migration under normal conditions and EF‐biased directionality were autophagy independent. Thus, our findings define autophagy as an important functional regulator of electrically enhanced directed motility, adding to a growing understanding of EFs.—Yan, T., Jiang, X., Lin, G., Tang, D., Zhang, J., Guo, X., Zhang, D., Zhang, Q., Jia, J., Huang, Y. Autophagy is required for the directed motility of keratinocytes driven by electric fields. FASEB J. 33, 3922–3935 (2019). http://www.fasebj.org