Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.

COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.

A study of synchronous measurement of liable phosphorous and iron based on ZrO-Chelex (DGT) in the sediment of the Chaiwopu Lake, Xinjiang, Northwest China.

The water-sediment interface of lakes is an important and unique area of the water environment; the geochemical behavior of nutrients in this area has a significant impact on the quality of the water environment and ecosystems, especially in shallow lakes. However, most studies do not provide direct in situ evidence for this in shallow lakes in arid regions; in order to explore the coupling relationship between phosphorus (P) and iron (Fe) in a sediment profile, we conducted a high-resolution analysis of liable Fe and P in sediments taken from the Chaiwopu Lake using ZrO-Chelex thin film diffusion gradient technology (ZrO-Chelex DGT). The results show that (1) the vertical spatial distribution trend of the liable P and Fe in the sediments from each sampling site is essentially similar. The contents of the liable P and Fe ranged from 0.004-0.125 mg/L and 0.050-0.190 mg/L, respectively, and the synchronous distribution of the micro-interface concentration reflects the coupling relationship between them. (2) The correlation analysis of the liable P and Fe concentrations showed that there were significant linear correlations between them (P < 0.05, bilateral). (3) The diffusion fluxes of P and Fe were - 51.76~65.12 µg (m2 d)-1 and - 451.27~457.06 µg (m2 d)-1, respectively, and were shown to be negative at the sediment-water interface for most of the samples, which showed that P and Fe were released from the overlying water into the sediments. (4) This research showed that the diffusive fluxes at the different sites are quite different, which indicates that the phosphorus and iron pollution in the sediments of the Chaiwopu Lake is affected by exogenous inputs. There was no significant correlation between P release flux and pH, ORP, conductivity (EC), the TDS of the overlying water, or the pH, salinity (Ca2+, Mg2+), and nutrient (organic matter) content of the sediment. The release flux of Fe is affected by the pH of the sediment. The results of this study provide references for the research of elements in the water-sediment interface of shallow lakes in arid regions, as well as other areas.