ABSTRACT
The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects a variety of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. In addition to known host proteins, i.e. ACE2, TMPRSS2 and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spikes N-terminal domain (NTD). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in a fashion independent of ACE2. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5-capping or 3-polyadenylation, circRNA could be rapidly produced via in vitro transcription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBD elicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1m{Psi}-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicron vaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Delta could elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Delta is a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2.
ABSTRACT
Objective@#To analyze the relationship between fatigue and self- efficacy and empowerment in patients with rheumatoid arthritis.@*Methods@#A total of 219 cases of rheumatoid arthritis were investigated by general data questionnaire, Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire, Chinese Version of Patient Perception of Empowerment Scale and Chinese Version of Arthritis Self-efficacy Scale-8. SPSS 20.0 software was used for correlation analysis and AMOS software was used to construct structural equation model to test the mediating effect of self-efficacy between empowerment level and fatigue in patients with rheumatoid arthritis.@*Results@#There was a significant negative correlation between fatigue and empowerment level (r=-0.62, P <0.05), and a significant correlation between fatigue and self-efficacy (r=-0.81, P <0.05). Self-efficacy had a mediating effect on empowerment level and fatigue in patients with rheumatoid arthritis, and the mediating effect accounted for 96.41% of the total effect.@*Conclusions@#Self-efficacy has mediating effect between powerment level and fatigue in patients with rheumatoid arthritis.
ABSTRACT
Objective@#To grasp the research focus and development situation of the disease through the Web of Science database core journals of nearly ten years in nursing the lower respiratory disease is combing with visual analysis literature, as the nursing researchers further provided a reference for the research of this field.@*Method@#Using literature metrology method and information visualization software Citespace, from 2008 to 2017 Web of Science a stronger core journals on the respiratory system disease, a total of 2557 articles were visualized analysis, the hot spot and research frontier of knowledge graph were draw.@*Results@#The volume of lower respiratory disease in nursing has risen steadily in the past 10 years. The research focuses on pneumonia, asthma, mortality, self-management, risk factors for care and prevention, etc. The research frontier is mainly focused on the research of pulmonary embolism, deep vein thrombosis and other advanced diseases and children asthma. China and the United States have different research hot spots for lower respiratory disease in the same time zone, and China′s research hot spot is five years later than in the United States.@*Conclusion@#The research focus of lower respiratory disease in nursing field in the past ten years is mainly centered on the two centers of pneumonia and asthma. Lower respiratory disease in the field of nursing research China steadily rising trend, but compared with developed countries such as United States, England, the total number too little.So, China should draw lessons from foreign developed countries research hot spot and front, increase investment in the nursing of lower respiratory disease research.
ABSTRACT
Objective To analyze the relationship between fatigue and self- efficacy and empowerment in patients with rheumatoid arthritis. Methods A total of 219 cases of rheumatoid arthritis were investigated by general data questionnaire, Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire, Chinese Version of Patient Perception of Empowerment Scale and Chinese Version of Arthritis Self-efficacy Scale-8. SPSS 20.0 software was used for correlation analysis and AMOS software was used to construct structural equation model to test the mediating effect of self-efficacy between empowerment level and fatigue in patients with rheumatoid arthritis. Results There was a significant negative correlation between fatigue and empowerment level (r =－0.62, P <0.05), and a significant correlation between fatigue and self-efficacy (r=－0.81, P<0.05). Self-efficacy had a mediating effect on empowerment level and fatigue in patients with rheumatoid arthritis, and the mediating effect accounted for 96.41% of the total effect. Conclusions Self-efficacy has mediating effect between powerment level and fatigue in patients with rheumatoid arthritis.
ABSTRACT
Objective To grasp the research focus and development situation of the disease through the Web of Science database core journals of nearly ten years in nursing the lower respiratory disease is combing with visual analysis literature, as the nursing researchers further provided a reference for the research of this field. Method Using literature metrology method and information visualization software Citespace, from 2008 to 2017 Web of Science a stronger core journals on the respiratory system disease, a total of 2557 articles were visualized analysis, the hot spot and research frontier of knowledge graph were draw. Results The volume of lower respiratory disease in nursing has risen steadily in the past 10 years. The research focuses on pneumonia, asthma, mortality, self-management, risk factors for care and prevention, etc. The research frontier is mainly focused on the research of pulmonary embolism, deep vein thrombosis and other advanced diseases and children asthma. China and the United States have different research hot spots for lower respiratory disease in the same time zone, and China′s research hot spot is five years later than in the United States. Conclusion The research focus of lower respiratory disease in nursing field in the past ten years is mainly centered on the two centers of pneumonia and asthma. Lower respiratory disease in the field of nursing research China steadily rising trend, but compared with developed countries such as United States, England, the total number too little.So, China should draw lessons from foreign developed countries research hot spot and front, increase investment in the nursing of lower respiratory disease research.
