The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a lipid-enveloped virus that acquires its lipid bilayer from the host cell it infects. SARS-CoV-2 can spread from cell to cell or from patient to patient by undergoing assembly and budding to form new virions. The assembly and budding of SARS-CoV-2 is mediated by several structural proteins known as envelope (E), membrane (M), nucleoprotein (N) and spike (S), which can form virus-like particles (VLPs) when co-expressed in mammalian cells. Assembly and budding of SARS-CoV-2 from the host ER-Golgi intermediate compartment is a critical step in the virus acquiring its lipid bilayer. To date, little information is available on how SARS-CoV-2 assembles and forms new viral particles from host membranes. In this study, we find the N protein can strongly associate with anionic lipids including phosphoinositides and phosphatidylserine. Moreover, lipid binding is shown to occur in the N protein C-terminal domain, which is supported by extensive in silico analysis. Anionic lipid binding occurs for both the free and N oligomeric forms suggesting N can associate with membranes in the nucleocapsid form. Herein we present a lipid-dependent model based on in vitro, cellular and in silico data for the recruitment of N to M assembly sites in the lifecycle of SARS-CoV-2.

Investigating the Relationship between Users' Behavioral Intentions and Learning Effects of VR System for Sustainable Tourism Development

Macao is a tourist city. It is home to the Ruins of Saint Paul's, a unique 100-year-old landmark, which is still standing with manual maintenance, even after three fires and reconstruction events. Therefore, the continuous preservation of its culture, heritage education, and construction are important issues for Macao. With the development of digital technology in recent years, users can quickly search historical sites and save two-dimensional and three-dimensional images and videos through smartphones. These methods also enhance the communication power of culture. Virtual browsing on a smartphone requires computing power and storage space;yet, virtual reality devices are not widely used. Therefore, augmented reality and virtual reality are rarely used simultaneously for three-dimensional interactive guided tours and operation experiences on the same theme. However, by quickly creating virtual reality scenarios and preserving historical sites on mobile devices, 4DAGE's 4DKanKan technology can provide augmented reality and metaverse virtual reality experiences. 4DKanKan can also integrate mobile guides and navigation software to connect mobile devices and assist in cultural inheritance and conduct sustainable education. This research linked this technology to the web by incorporating augmented reality and virtual reality technology to make designs and discussed the influences among service design, behavioral intentions, and learning effects. We collated and analyzed relevant data and text materials through systematic testing, observation, operation processes, and semi-structured interviews. The PLS multigroup structural model was used to explore and analyze the degree of influence and explanatory power of system quality, information quality, behavioral intention, and learning effects among themselves. The results of this study show that most users accepted the proposed innovative mode of operation and found it to be interesting and fun. Augmented reality is not limited by space or time;however, virtual reality devices taking too long to operate, switching too frequently, and having too many functional interfaces can cause operational problems. This study identified and modified the influencing factors and problems of the proposed system, with the aim of continuing to expand the applications of 4DKanKan to other cultural attractions or museums in the future. In addition, the research results can provide a reference for the sustainable development of related cultural sites.

Physical activity and depressive symptoms among community-dwelling older adults in the COVID-19 pandemic era: A three-wave cross-lagged study

The aim of the study is to determine the trajectories of physical activity and depressive symptoms and their reciprocal relationship among community-dwelling older adults in the COVID-19 pandemic era. The study population consisted of a cohort of 511 participants aged 60 years and over, who were recruited from eight community health centers in Ya'an, China. The Physical Activity Scale for the Elderly and the Patient Health Questionnaire were respectively used to measure physical activity and depressive symptoms at three time points: before the COVID-19 outbreak (T0), during the outbreak period (T1), and after the subsidence of COVID-19 (T2). The results revealed that physical activity and depressive symptoms fluctuated substantially across T0, T1, and T2. In addition, more severe depressive symptoms at T0 and T1 were significantly associated with lower levels of physical activity at T1 and T2, but the obverse direction of physical activity being associated with subsequent depressive symptoms was not observed in the current study. These findings highlight the importance of supporting old people to remain physically active and combat mental distress early in a pandemic, and prevention and management of depressive symptoms may also be beneficial to promote physical activity.

Clinical Characteristics of Coronavirus Disease 2019 (COVID-19): A Comparison Between Laboratory-Confirmed and Clinically Suspected Patients.

To investigate the characteristic findings between laboratory-confirmed and clinically suspected patients with COVID-19. In this retrospective study, we included patients admitted to the Xiangya Hospital from Jan 24 to Feb 10, 2020. Two researchers separately collected and sorted out the patients' epidemiological, demographic, clinical, laboratory, and radiologic findings. SPSS was performed to analyze the collected data. 241 patients were admitted, including 28 (45.5; IQR, 34.0-52.5) confirmed and 213 (42.0; IQR, 30.0-57.0) suspected patients. The prevalence of COVID-19 disease in males was significantly higher than in females (64.3% vs. 35.7%, P = 0.033). Before admission of the confirmed and suspected undiagnosed cases, the onset of symptoms is often manifested as respiratory symptoms such as fever (35.7% vs. 27.7%) and cough (30.7% vs. 32.1%). Twenty patients (71.4%) had an exposure history to high-risk areas, and 14 patients (50.0%) traveled or lived in a high-risk area in the confirmed group, which was significantly different from the suspected group. The pulmonary imaging of the patients in the confirmed group was primarily manifested as ground-glass opacity (89.3%). A total of 499 nucleic acid testing (NAT) was performed to determine the 28 COVID-19 positive throat swabs among the 241 patients. Whether there is a history of high-risk area exposure in the epidemiological investigation is essential in distinguishing the suspected patients from the confirmed patients. Multiple nucleic acid tests were used as the basis for the diagnosis of COVID-19, and during CT examination, ground-glass opacity was used as a COVID-19 indicator. Trail registration Trail registration number. 202012195, Date of registration: 2020.12.22 "retrospectively registered".

SARS-CoV-2 viral budding and entry can be modeled using virus-like particles (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in December 2019 in Wuhan, China and expeditiously spread across the globe causing a global pandemic. While a select agent designation has not been made for SARS-CoV-2, closely related SARS-CoV-1 and MERS coronaviruses are classified as Risk Group 3 select agents, which restricts use of the live viruses to BSL-3 facilities. Such BSL-3 classification make SARS-CoV-2 research inaccessible to the majority of functioning research laboratories in the US; this becomes problematic when the collective scientific effort needs to be focused on such in the face of a pandemic. In this work, we assessed the four structural proteins from SARS-CoV-2 for their ability to form virus-like particles (VLPs) from human cells to form a competent system for BSL-2 studies of SARS-CoV-2. Herein, we provide methods and resources of producing, purifying, fluorescently and APEX2-labeling of SARS-CoV-2 VLPs for the evaluation of mechanisms of viral budding and entry as well as assessment of drug inhibitors under BSL-2 conditions.

Temporal Dynamics in Clinical and Laboratory Manifestations During COVID-19 Progression (preprint)

BAckground Severe COVID-19 patients account for most of the mortality of this disease. Early detection of severe cases of the disease remains a major challenge. Here, we performed clinical and laboratory profiling of COVID-19 to explore the early warning indicators of severe cases.Methods An analysis of the evolution during the hospitalization of clinical and laboratory findings from 78 confirmed COVID-19 patients and the associated risk factors.Results Of the 78 patients who were classified as un-severe at admission, 60 patients(stable group) were stable as mild cases until discharge, and the remaining 18 patients progressed to severe cases(exacerbated group) during hospitalization. Compared with stable patients, exacerbated patients exhibited older, higher BMI values and higher proportion of smokers. In the exacerbated patients, the median time from onset to deterioration was 7.5 days. Before the time point(days 0–7 from onset), we observed higher-levels of White blood cells(WBC), neutrophil, Neutrophi-Lymphocyte-Ratio(NLR), Lactose-dehydrogenase(LDH), D-dimer, and lower-levels of albumin in the exacerbated group, compared with the stable group. In the second week after the time point, the exacerbated patients displayed lower numbers of lymphocytes, CD3+, and CD8+T-cells, and higher-levels of C-reactive protein(CRP), erythrocyte-sedimentation-rate(ESR), Alanine-aminotransferase(ALT),Aspartate-aminotransferase(AST), and Interleukin-6. In the third week, the highest temperature and the proportion of febrile patients declined. All of the laboratory indicators gradually improved.Conclusions Advanced age and smoking history could be risk factors for COVID-19 progression. In the early stage, high-levels of WBC and neutrophils, with noticeably increased LDH and D-dimer, could be early indicators of the disease’s conversion from mild to severe, followed by elevated inflammatory markers, liver enzymes, and decreased T-lymphocytes in the next week.