Hillock Related Degradation Mechanism for AlGaN-Based UVC LEDs.

Heteroepitaxial growth of high Al-content AlGaN often results in a high density of threading dislocations and surface hexagonal hillocks, which degrade the performance and reliability of AlGaN-based UVC light emitting diodes (LEDs). In this study, the degradation mechanism and impurity/defect behavior of UVC LEDs in relation to the hexagonal hillocks have been studied in detail. It was found that the early degradation of UVC LEDs is primarily caused by electron leakage. The prominent contribution of the hillock edges to the electron leakage is unambiguously evidenced by the transmission electron microscopy measurements, time-of-flight secondary ion mass spectrometry, and conductive atomic force microscopy. Dislocations bunching and segregation of impurities, including C, O, and Si, at the hillock edges are clearly observed, which facilitate the trap-assisted carrier tunneling in the multiple quantum wells and subsequent recombination in the p-AlGaN. This work sheds light on one possible degradation mechanism of AlGaN-based UVC LEDs.

Protocol for high-throughput screening of ACE2 enzymatic activators to treat COVID-19-induced metabolic complications.

Drug repositioning represents a cost- and time-efficient strategy for drug development. Here, we present a workflow of in silico screening of ACE2 enzymatic activators to treat COVID-19-induced metabolic complications. By using structure-based virtual screening and signature-based off-target effect identification via the Connectivity Map database, we provide a ranked list of the repositioning candidates as potential ACE2 enzymatic activators to ameliorate COVID-19-induced metabolic complications. The workflow can also be applied to other diseases with ACE2 as a potential target. For complete details on the use and execution of this protocol, please refer to Li et al. (2022).

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry.

Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.