30Qing Mao (Phone +86 135 9418 0020;Abstract: An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 5 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these 10 highly pathogenic coronaviruses. Short Title: SARS-CoV N over-activates complement by MASP-2One Sentence Summary: The lectin pathway of complement activation is a promising target for 15 the treatment of highly pathogenic coronavirus induced pneumonia.All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Background The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. Methods A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. Results CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. Conclusion Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients. Keywords 2019 novel coronavirus. Viral pneumonia. Artificial intelligence (AI). Computed tomography (CT). Ground glass opacity (GGO) Hai-tao Zhang, Jin-song Zhang and Hai-hua Zhang contributed equally to this work.
Viral diseases constitute a major constraint to high yield and high quality production of potato. Potato leafroll virus (PLRV) and Potato virus Y (PVY) are among the most damaging potato viruses and are prevalent in most potato growing areas. In the present study, attempts were made to eliminate PLRV and PVY by three cryogenic protocols, i.e., encapsulation-dehydration, encapsulation-vitrification and droplet. Results showed that both PLRV and PVY could be efficiently eliminated by cryogenic treatments with 83-86% and 91-95% of frequencies of virus-free plantlets obtained for the former and latter, respectively. Frequencies of virus-free plantlets produced by cryogenic treatments were higher than those by meristem culture (56% for PLRV and 62% for PVY) and thermotherapy (50% for PLRV and 65% for PVY), and similar to those by thermotherapy followed by meristem culture (90% for PLRV and 93% for PVY). Survival (75-85%) and regrowth (83-89%) from cryo-treated shoot tips were higher than those from meristem culture (50-55%) and thermotherapy followed by meristem culture (40-50%), but similar to those from thermotherapy (80-87%). The morphology of the plantlets regenerated from cryo-treated shoot tips was similar to that of non-treated plantlets. Thus, cryotherapy would provide an alternative method for efficient elimination of potato viruses, and can be simultaneously used for long-term storage of potato germplasm and for production of virusfree plants.
Neutrophil-mediated lung injury is a potential complication of trauma and sepsis. Concomitant with trauma and sepsis, there is an immediate and sustained systemic elevation of catecholamines including epinephrine. In the absence of trauma or sepsis, we examined whether epinephrine contributes to the accumulation of neutrophils in the lung. Eight- to 12-week-old male CF-1 mice were injected i.p. with 0.2 mL of normal saline or epinephrine (0.1-5.0 mg/kg). An unmanipulated control group was included to examine the stress of i.p. injection. Animals were sacrificed at predetermined time points, and lung and spleen were harvested. PMN accumulation was assessed by using a myeloperoxidase (MPO) assay, which is an indirect marker for neutrophil presence. Morphometric analysis of lung tissue was performed by a pathologist blinded to the groups. Increasing epinephrine doses resulted in a significantly increased accumulation of pulmonary neutrophils compared with normal saline. The stress of normal saline injection also resulted in a significantly greater pulmonary neutrophil accumulation than unmanipulated controls. The effects of epinephrine on pulmonary neutrophil accumulation were greatest at 2 h, but they were not significantly different from saline-injected controls by 12 h. These results correlated with histological analysis. There were no significant differences in spleen MPO activity between groups, suggesting an organ-specific mechanism of epinephrine-induced pulmonary neutrophil sequestration. In the absence of trauma, shock, or infection, epinephrine results in the accumulation of neutrophils in murine lungs. The finding that "injection stress" increased lung neutrophil sequestration suggests the possibility that this mechanism may be physiologically relevant. Thus, epinephrine release in trauma may set the stage for development of neutrophil-mediated acute lung injury.
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