The current COVID-19 pandemic, caused by SARS-CoV-2, poses a serious public health threat. Effective therapeutic and prophylactic treatments are urgently needed. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, which binds to the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Here, we developed recombinant human ACE2-Fc fusion protein (hACE2-Fc) and a hACE2-Fc mutant with reduced catalytic activity. hACE2-Fc and the hACE2-Fc mutant both efficiently blocked entry of SARS-CoV-2, SARS-CoV, and HCoV-NL63 into hACE2-expressing cells and inhibited SARS-CoV-2 S protein-mediated cell–cell fusion. hACE2-Fc also neutralized various SARS-CoV-2 strains with enhanced infectivity including D614G and V367F mutations, as well as the emerging SARS-CoV-2 variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.1 (Kappa), and B.1.617.2 (Delta), demonstrating its potent and broad-spectrum antiviral effects. In addition, hACE2-Fc proteins protected HBE from SARS-CoV-2 infection. Unlike RBD-targeting neutralizing antibodies, hACE2-Fc treatment did not induce the development of escape mutants. Furthermore, both prophylactic and therapeutic hACE2-Fc treatments effectively protected mice from SARS-CoV-2 infection, as determined by reduced viral replication, weight loss, histological changes, and inflammation in the lungs. The protection provided by hACE2 showed obvious dose-dependent efficacy in vivo. Pharmacokinetic data indicated that hACE2-Fc has a relative long half-life in vivo compared to soluble ACE2, which makes it an excellent candidate for prophylaxis and therapy for COVID-19 as well as for SARS-CoV and HCoV-NL63 infections.
Dietary thiamin requirement of juvenile grass carp, Ctenopharyngodon idella, was to investigate in this experiment. Eight purified diets were formulated with graded levels of thiamin (0.1, 0.6, 1.1, 2.1, 5.5, 9.8, 21.2, and 41.8 mg/kg, respectively). Each diet was fed to triplicate groups of 40 fish (initial average weight 10.7 ± 0.2 g) for 12 wk in 400‐L aquaria (R = 1 m, h = 0.6 m). Results showed that weight gain rate, specific growth rate, feed efficiency, protein efficiency ratio, and hepatosomatic indice of fish increased before dietary thiamin increased to the optimum level, then remained similar thereafter (P > 0.05). Thiamin concentration in fish liver was positively correlated with dietary thiamin and it stayed in stable when dietary thiamin level exceed 5.0 mg/kg. The serum biochemical indices analysis showed that dietary thiamin had significant effects on serum triglycerides, total cholesterol, glucose, pyruvate contents, and lactate dehydrogenase activity. Body composition was unaffected by dietary thiamin. Broken‐line regression analysis showed that, a dietary thiamin level of 1.3 mg/kg diet was adequate for optimum growth, and 5.0 mg/kg for maximum liver thiamin accumulation.
Herein, Ti3C2Tx (MXene) was synthesized and mixed with polyvinyl alcohol (PVA) to fabricate PVA/MXene nanocomposites. The results confirmed that delaminated MXene was successfully synthesized. The nanocomposites were obtained via casting/evaporation method. The thermal stability was evaluated by thermogravimetric analysis (TGA). For the PVA composites with content of 2 wt% MXene (PVA‐MXene2), the thermal decomposition was retarded by approximately 20°C when the temperature was lower than 350°C compared with that of pure PVA. Moreover, the evolved gas products of the PVA/MXene composite were lower than those of pure PVA. For the first time, the flame retardancy of PVA/MXene nanocomposite was investigated using a microscale combustion calorimeter. The peak heat release rate (PHRR) and total heat release of the PVA composite were reduced by 25.7% and 25.5%, respectively, with 1 wt% of MXene. The temperatures at PHRR of PVA/MXene composites were improved with the addition of MXene. Moreover, the addition of MXene resulted in PVA composites with a higher tensile strength and elongation at break than those of a pure PVA film. The improvements in the flame retardancy, thermal and mechanical properties of PVA/MXene composites should enable a wide range of potential applications of MXenes in polymer matrices.
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