ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease.
ABSTRACT
Objective To evaluate the effect of BinaxNOW rapid diagnostic devices for malaria in the field. Methods The symptomatic patients were detected by using the BinaxNOW devices and the results were compared with the microscopic examination of Giemsa-stained blood smears(as a golden standard). The sensitivity and specificity were calculated. The double-blind method was used in this study. Results In 443 symptomatic patients,151 cases were positive for malaria. The sensitivity was 98.69% and the specificity was 100%,and the coincidence rate of BinaxNOW with the microscopic examination was 99.55%. The sensitivity and specificity of Plasmodium falciparum were 100% and 99.66%,respectively,and the coincidence rate was 99.76%. The sensitivity and specificity of non-falciparum Plasmodium were 90.91% and 100%,respectively,and the coincidence rate was 99.36%. Conclusion The BinaxNOW rapid diagnostic devices for malaria are sensitive,specific,and stable for malaria diagnosis in the field.
