Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.

Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.

Water clarity mapping of global lakes using a novel hybrid deep-learning-based recurrent model with Landsat OLI images.

Information regarding water clarity at large spatiotemporal scales is critical for understanding comprehensive changes in the water quality and status of ecosystems. Previous studies have suggested that satellite observation is an effective means of obtaining such information. However, a reliable model for accurately mapping the water clarity of global lakes (reservoirs) is still lacking due to the high optical complexity of lake waters. In this study, by using gated recurrent units (GRU) layers instead of full-connected layers from Artificial Neural Networks (ANNs) to capture the efficient sequence information of in-situ datasets, we propose a novel and transferrable hybrid deep-learning-based recurrent model (DGRN) to map the water clarity of global lakes with Landsat 8 Operational Land Imager (OLI) images. We trained and further validated the model using 1260 pairs of in-situ measured water clarity and surface reflectance of Landsat 8 OLI images with Google Earth Engine. The model was subsequently utilized to construct the global pattern of temporal and spatial changes in water clarity (lake area>10 km2) from 2014 to 2020. The results show that the model can estimate water clarity with good performance (R2 = 0.84, MAE = 0.55, RMSE = 0.83, MAPE = 45.13%). The multi-year average of water clarity for global lakes (16,475 lakes) ranged from 0.0004 to 9.51 m, with an average value of 1.88 ± 1.24 m. Compared to the lake area, elevation, discharge, residence time, and the ratio of area to depth, water depth was the most important factor that determined the global spatial distribution pattern of water clarity. Water clarity of 15,840 global lakes between 2014 and 2020 remained stable (P ≥ 0.05); while there was a significant increase in 243 lakes (P < 0.05) and a decrease in 392 lakes (P < 0.05). However, water clarity in 2020 (COVID-19 period) showed a significant increase in most global lakes, especially in China and Canada, suggesting that the worldwide lockdown strategy due to COVID-19 might have improved water quality, espically water clarity, dueto the apparent reduction of anthropogenic activities.

Food-trade-associated COVID-19 outbreak from a contaminated wholesale food supermarket in Beijing.

The re-emerging outbreak of COVID-19 in Beijing, China, in the summer of 2020 originated from a SARS-CoV-2-infested wholesale food supermarket. We postulated that the Xinfadi market outbreak has links with food-trade activities. Our Susceptible to the disease, Infectious, and Recovered coupled Agent Based Modelling (SIR-ABM) analysis for studying the diffusion of SARS-CoV-2 particles suggested that the trade-distancing strategy effectively reduces the reproduction number (R0). The retail shop closure strategy reduced the number of visitors to the market by nearly half. In addition, the buy-local policy option reduced the infection by more than 70% in total. Therefore, retail closures and buy-local policies could serve as significantly effective strategies that have the potential to reduce the size of the outbreak and prevent probable outbreaks in the future.

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome: Report of two cases and review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a worldwide pandemic. Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure. In such cases, extracorporeal membrane oxygenation (ECMO) treatment is a necessary life-saving procedure. CASE SUMMARY: Two special COVID-19 cases-one full-term pregnant woman and one elderly (72-year-old) man-were treated by veno-venous (VV)-ECMO in the Second People's Hospital of Zhongshan, Zhongshan City, Guangdong Province, China. Both patients had developed refractory hypoxemia shortly after hospital admission, despite conventional support, and were therefore managed by VV-ECMO. Although both experienced multiple ECMO-related complications on top of the COVID-19 disease, their conditions improved gradually. Both patients were weaned successfully from the ECMO therapy. At the time of writing of this report, the woman has recovered completely and been discharged from hospital to home; the man remains on mechanical ventilation, due to respiratory muscle weakness and suspected lung fibrosis. As ECMO itself is associated with various complications, it is very important to understand and treat these complications to achieve optimal outcome. CONCLUSION: VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome. However, it is crucial to understand and treat ECMO-related complications.

First successful treatment of a COVID-19 pregnant woman with severe ARDS by combining early mechanical ventilation and ECMO.

The novel coronavirus (COVID-19) has become a global pandemic outbreak. Patients with COVID-19 are prone to progress to acute respiratory distress syndrome (ARDS), and even severe ARDS with ineffective mechanical ventilation, and an extremely high mortality. Extracorporeal membrane oxygenation (ECMO) provides effective respiratory support and saves time for the treatment of severe COVID-19. The present study reports that a 31-year-old pregnant female infected by COVID-19, who suffered from fever, dyspnea, and rapid ARDS. The patient's pulmonary function gradually recovered by combining early mechanical ventilation and ECMO, and finally, this patient was successfully weaned from ECMO and the ventilator. No fibrosis lesions were found in the chest CT, and the patient recovered very well after leaving from the hospital for one month.