1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

Collaborative Filtering Model of Graph Neural Network Based on Random Walk

This paper proposes a novel graph neural network recommendation method to alleviate the user cold-start problem caused by too few relevant items in personalized recommendation collaborative filtering. A deep feedforward neural network is constructed to transform the bipartite graph of user–item interactions into the spectral domain, using a random wandering method to discover potential correlation information between users and items. Then, a finite-order polynomial is used to optimize the convolution process and accelerate the convergence of the convolutional network, so that deep connections between users and items in the spectral domain can be discovered quickly. We conducted experiments on the classic dataset MovieLens-1M. The recall and precision were improved, and the results show that the method can improve the accuracy of recommendation results, tap the association information between users and items more effectively, and significantly alleviate the user cold-start problem.

The causal effect of physical activity intensity on COVID-19 susceptibility, hospitalization, and severity: Evidence from a mendelian randomization study.

The protection of physical activity (PA) against COVID-19 is a rising research interest. However, the role of physical activity intensity on this topic is yet unclear. To bridge the gap, we performed a Mendelian randomization (MR) study to verify the causal influence of light and moderate-to-vigorous PA on COVID-19 susceptibility, hospitalization, and severity. The Genome-Wide Association Study (GWAS) dataset of PA (n = 88,411) was obtained from the UK biobank and the datasets of COVID-19 susceptibility (n = 1,683,768), hospitalization (n = 1,887,658), and severity (n = 1,161,073) were extracted from the COVID-19 Host Genetics Initiative. A random-effect inverse variance weighted (IVW) model was carried out to estimate the potential causal effects. A Bonferroni correction was used for counteracting. The problem of multiple comparisons. MR-Egger test, MR-PRESSO test, Cochran's Q statistic, and Leave-One-Out (LOO) were used as sensitive analysis tools. Eventually, we found that light PA significantly reduced the risk of COVID-19 infection (OR = 0.644, 95% CI: 0.480-0.864, p = 0.003). Suggestive evidence indicated that light PA reduced the risks of COVID-19 hospitalization (OR = 0.446, 95% CI: 0.227 to 0.879, p = 0.020) and severe complications (OR = 0.406, 95% CI: 0.167-0.446, p = 0.046). By comparison, the effects of moderate-to-vigorous PA on the three COVID-19 outcomes were all non-significant. Generally, our findings may offer evidence for prescribing personalized prevention and treatment programs. Limited by the available datasets and the quality of evidence, further research is warranted to re-examine the effects of light PA on COVID-19 when new GWAS datasets emerge.

Burnout and associative emotional status and coping style of healthcare workers in COVID-19 epidemic control: A cross-sectional study.

Objective: The aim of this study was to evaluate the prevalence of burnout, clinical anxiety, depression, and insomnia and to estimate the associations of adverse emotional status, coping style, and level of self-efficacy with burnout of healthcare workers in the Shenzhen Longgang District Frontline District Headquarters of COVID-19 epidemic control, China. Methods: In this cross-sectional study, 173 staff completed the anonymous questionnaires of the Maslach Burnout Inventory, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), Insomnia Severity Index (ISI), General Self-efficacy Scale, and Simplified Coping Style Questionnaire electronically (https://www.wjx.cn/) in June 2022. Hierarchical logistic regression was used to explore the associated factors of burnout in this study. Results: The prevalence of burnout in our participants (defined as high emotional exhaustion or high depersonalization) was 47.40%, and reduced personal accomplishment was 92.49%. The prevalence of clinically significant depression (the cutoff score of ≥15), anxiety (the cutoff score of ≥10), and insomnia (the cutoff score of ≥15) was 11.56, 19.08, and 19.08%, respectively. There was a degree of overlap between burnout and other measures of adverse mental status, most notably for anxiety (odds ratio, 27.049; 95% CI, 6.125-117.732; p < 0.001). Hierarchical logistic regression demonstrated that burnout was strongly associated with anxiety (OR = 23.889; 95% CI, 5.216-109.414; p < 0.001) and negative coping style (OR = 1.869; 95% CI, 1.278-2.921; p < 0.01) independently. Conclusion: Medical staff involved in COVID-19 epidemic control in the post-epidemic era were at high risk of burnout, and most of them were in low personal accomplishment. Reducing anxiety and improving coping style by medical management institutions from the system level may be effective in alleviating burnout in healthcare workers.

Non-anticoagulant heparin derivatives for COVID-19 treatment.

The ongoing pandemic of COVID-19, caused by the infection of SARS-CoV-2, has generated significant harm to the world economy and taken numerous lives. This syndrome is characterized by an acute inflammatory response, mainly in the lungs and kidneys. Accumulated evidence suggests that exogenous heparin might contribute to the alleviation of COVID-19 severity through anticoagulant and various non-anticoagulant mechanisms, including heparanase inhibition, chemokine and cytokine neutralization, leukocyte trafficking interference, viral cellular-entry obstruction, and extracellular cytotoxic histone neutralization. However, the side effects of heparin and potential drawbacks of administering heparin therapy need to be considered. Here, the current heparin therapy drawbacks were covered in great detail: structure-activity relationship (SAR) mystery, potential contamination, and anticoagulant activity. Considering these unfavorable effects, specific non-anticoagulant heparin derivatives with antiviral activity could be promising candidates to treat COVID-19. Furthermore, a structurally diverse library of non-anticoagulant heparin derivatives, constructed by chemical modification and enzymatic depolymerization, would contribute to a deeper understanding of SAR mystery. In short, targeting non-anticoagulant mechanisms may produce better therapeutic effects, overcoming the side effects in patients suffering from COVID-19 and other inflammatory disorders.

How will actual wearing time influence the protective effect of surgical masks?

The protection effects of wearing masks against viruses and bacteria have been verified many times over previous pandemics and infectious diseases. However, the supply of the surgical masks can barely meet the surging demand at the early stage (first 12 months) of the outbreak of a pandemic. Thus, it is essential to use surgical masks wisely in such urgent times. In this work, we selected two types of surgical masks and systematically explored how actual wearing time influences the protective performances of the masks. Each type of surgical masks was worn for 4, 10, 24, 32 and 48 h, respectively, and the results show that with the increase of actual wearing time, both particulate filtration efficiency (PFE) and bacterial filtration efficiency (BFE) of the masks decline. After wearing for 32 h, the PFEs of both types of masks were still far above the corresponding standard (>= 30%, according to YY0469-2011). After wearing for 10 h, the BFEs of both masks were over 95% (which is regarded as the safe value), whereas after 24 and 32 h of wearing, the BFE of one type of mask decreased obviously to 91.6% and 80.0%, respectively. Based on these results, it is rational to conclude that the wearing time of surgical masks should be no more than 10 h.

Clinical Characteristics of 254 COVID-19 Inpatients in Yichang, Hubei, China, and Efficacy of Integrated Chinese and Western Medicine Treatment.

Introduction: There is no effective treatment plan for coronavirus disease 2019 (COVID-19). We employed a combination of Chinese and Western medicine treatment for some COVID-19 inpatients. Methods: This study was a prospective cohort study that observed non-critical COVID-19 inpatients. The differences will be observed in the time from admission to two consecutive 2019-nCoV nucleic acid test negatives and the Visual Analog Scale (VAS) score between the two groups. Results: A total of 254 confirmed COVID-19 patients were included in this study. The median time from the admission to two consecutive negative nucleic acid tests was 14 days for the integrated Chinese and Western Medicine (ICWM) group, while the Western Medicine (WM) group was 16 days. Besides, the median VAS score of the ICWM group was 0, which was an average decrease of 2 points compared to the time of admission. Conclusion: For non-critical COVID-19 patients, it was safe and have more benefits to add traditional Chinese medicine decoction based on WM treatment.

Elevated levels of fructosamine are independently associated with SARS-CoV-2 reinfection: A 12-mo follow-up study.

BACKGROUND: The association between blood levels of fructosamine (FMN) and recurrent coronavirus disease 2019 (COVID-19) is currently unclear. AIM: To investigate a prospective relationship between blood levels of FMN and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. METHODS: A total of 146 Chinese hospitalized patients infected with SARS-CoV-2 were consecutively collectively recruited and followed from January 2020 to May 2021. Diagnosis of COVID-19 and SARS-CoV-2 reinfection was based on the diagnostic criteria and treatment protocol in China. The levels of FMN were determined in blood and divided into tertiles based on their distribution in the cohort of COVID-19 patients. Multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for SARS-CoV-2 reinfection across the tertiles of FMN levels. A Cox regression model was used to generate the HR for SARS-CoV-2 reinfection in the participants in the top tertile of FMN levels compared with those at the bottom. Disease-free survival was used as the time variable, and relapse was used as the state variable, adjusted for age, gender, influencing factors such as diabetes mellitus, hypertension, and corticosteroid therapy, and clinical indexes such as acute liver failure, acute kidney failure, white blood cell (WBC) count, C-reactive protein, prognostic nutritional index (PNI), and blood lipids. Kaplan-Meier analysis with log-rank tests was used to compare the survival rate between patients with elevated FMN levels (FMN > 1.93 mmol/L, the top tertile) and those with nonelevated levels. RESULTS: Clinical data for the 146 patients with confirmed COVID-19 [age 49 (39-55) years; 49% males] were analyzed. Eleven patients had SARS-CoV-2 reinfection. The SARS-CoV-2 reinfection rate in patients with elevated FMN levels was significantly higher than that in patients with nonelevated FMN (17% vs 3%; P = 0.008) at the end of the 12-mo follow-up. After adjustments for gender, age, diabetes mellitus, hypertension, corticosteroid therapy, WBC count, PNI, indexes of liver and renal function, and blood lipids, patients with nonelevated FMN levels had a lower risk of SARS-CoV-2 reinfection than those with elevated FMN levels (HR = 6.249, 95%CI: 1.377-28.351; P = 0.018). Kaplan-Meier analysis showed that the cumulative survival rate of patients infected with SARS-CoV-2 was higher in patients with nonelevated FMN levels than in those with elevated FMN levels (97% vs 83%; log rank P = 0.002). CONCLUSION: Elevated levels of FMN are independently associated with SARS-CoV-2 reinfection, which highlights that patients with elevated FMN should be cautiously monitored after hospital discharge.

Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction.

Circular RNAs (circRNAs) as novel regulatory molecules have been recognized in diverse species, including viruses. The virus-derived circRNAs play various roles in the host biological process and the life cycle of the viruses. This review summarized the circRNAs from the DNA and RNA viruses and discussed the biogenesis of viral and host circRNAs, the potential roles of viral circRNAs, and their future perspective. This review will elaborate on new insights gained on viruses encoded circRNAs during virus infection.

A DNA-Cu nanocluster and exonuclease I integrated label-free reporting system for CRISPR/Cas12a-based SARS-CoV-2 detection with minimized background signals.

CRISPR-driven biosensing is developing rapidly, but current studies mostly adopt dye-labeled ssDNA as the signal reporter, which is costly and unstable. Herein, we developed a label-free and low-background reporter for CRISPR/Cas12a signaling by integrating DNA-templated copper nanoclusters (DNA-CuNCs) and exonuclease I (EXO I). The template of the DNA-CuNCs was rationally designed as a ds-/ss-DNA hybrid, ensuring that after a quick and nonpersistent cut of Cas12a, a majority of the template can be digested by EXO I. Based on this novel reporter, a biosensor termed CRISPR-CNS (cost-effective, nimble, and sensitive copper nanocluster sensor integrating CRISPR) was developed. Due to the high signal-to-background ratio of our proposed reporter, CRISPR-CNS shows excellent performances for nucleic acid detection, yielding a detection limit of 20 copies for SARS-CoV-2 RNA. Considering its facile synthesis, robust fluorescence, effective cost, and good sensitivity, this combination shall serve as a highly potential output for CRISPR-based point-of-care testing.

Resilience and Prosocial Behavior Among Chinese University Students During COVID-19 Mitigation: Testing Mediation and Moderation Models of Social Support.

Purpose: Suffering during events such as the COVID-19 pandemic threatens university students' physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation. Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior. Results: Pearson's correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students' prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts. Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students' prosocial behavior.

How social support predicts anxiety among university students during COVID-19 control phase: Mediating roles of self-esteem and resilience.

Public health emergency, such as COVID-19 pandemic, generally has severe impacts on mental health in public. One of the often-neglected negative consequences is that the control and prevention measures of COVID-19 in the post-epidemic can pose psychological threats to public mental health. This study aimed to seek the factors and mechanisms to alleviate this mental health threat based on a sample of university students in China. Accordingly, this study proposed an environmental-individual interaction model examining the multiple mediating effects of self-esteem and resilience in the association between social support and anxiety among university students during COVID-19 control phase. A questionnaire containing multiple scales were administered on the sample of 2734 Chinese university students. Results indicated that social support negatively predicted anxiety through the serial mediating effects of self-esteem and resilience sequentially. Our results highlight the impact of social support and the internal factors on relieving anxiety among university students in COVID-19 control phase. Findings suggest that effective psychological intervention tools should be designed and offered to college students to reduce anxiety distress and improve mental health in the post-epidemic era or the similar situations in the future.

Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

Before and after the Chinese gene-edited human babies: Multiple discourses of gene editing on social media.

This study examines discourses in Chinese online discussions of gene editing by multiple social actors on Weibo before and after a significant scientific crisis, the 2018 scandal of Chinese gene-edited human babies. A content analysis of 2074 posts was done to identify frames, emotions, and metaphors. Findings reveal that Chinese social media have opened up new spaces for multiple social actors to generate multiple discourses. This has resulted in a more participatory public engagement with science and technology on Chinese social media, potentially influencing the online agenda and policy decisions on science and technology. Finally, findings indicate that a scientific crisis can serve as a trigger for significant changes in public attitudes and opinions regarding gene editing.

Prevention and Control of COVID-19 after Resuming General Hospital Functions.

During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare systems, especially for these designated facilities, is how to safely resume hospital function after these patients have been discharged. Here, we take a designated COVID-19-care facility in Wuhan, China, as an example to share our experience in resuming hospital function while ensuring the safety of patients and medical workers. After more than 1200 patients with COVID-19 infections were discharged in late March, 2020, our hospital resumed function by setting up a three-level hospital infection management system with four grades of risk of exposure. Moreover, we also took measures to ensure the safety of medical personnel in different departments including clinics, wards, and operation rooms. After all patients with COVID-19 infections were discharged, during the five months of regular function from April to September in 2020, no positive cases have been found among more than 40,000 people in our hospital, including hospital staff and patients.

Business Cycle and Public Health: The Moderating Role of Health Education and Digital Economy.

The cyclicality of public health in the emerging market is underexplored in existing literature. In this study, we used a fixed effect model and provincial data to document how public health varies with the business cycle in China over the period of 2010-2019. The estimated results showed that the business cycle is negatively correlated with the mortality of infectious disease, a proxy variable of public health, thus indicating that public health exhibits a countercyclical pattern in China. Furthermore, we investigated the potential moderating role of public health education and digital economy development in the relationship between business cycle and public health. Our findings suggested that public health education and digital economy development can mitigate the damage of economic conditions on public health in China. Health education helps the public obtain more professional knowledge about diseases and then induces effective preventions. Compared with traditional economic growth, digital economy development can avoid environmental pollution which affects public health. Also, it ensures that state-of-the-art medical services are available for the public through e-health. In addition, digitalization assures that remote working is practicable and reduces close contact during epidemics such as COVID-19. The conclusions stand when subjected to several endogeneity and robustness checks. Therefore, the paper implies that these improvements in public health education and digitalization can help the government in promoting public health.

Internet Rumors During the COVID-19 Pandemic: Dynamics of Topics and Public Psychologies.

The capturing of social opinions, especially rumors, is a crucial issue in digital public health. With the outbreak of the COVID-19 pandemic, the discussions of related topics have increased exponentially in social media, with a large number of rumors on the Internet, which highly impede the harmony and sustainable development of society. As human health has never suffered a threat of this magnitude since the Internet era, past studies have lacked in-depth analysis of rumors regarding such a globally sweeping pandemic. This text-based analysis explores the dynamic features of Internet rumors during the COVID-19 pandemic considering the progress of the pandemic as time-series. Specifically, a Latent Dirichlet Allocation (LDA) model is used to extract rumor topics that spread widely during the pandemic, and the extracted six rumor topics, i.e., "Human Immunity," "Technology R&D," "Virus Protection," "People's Livelihood," "Virus Spreading," and "Psychosomatic Health" are found to show a certain degree of concentrated distribution at different stages of the pandemic. Linguistic Inquiry and Word Count (LIWC) is used to statistically test the psychosocial dynamics reflected in the rumor texts, and the results show differences in psychosocial characteristics of rumors at different stages of the pandemic progression. There are also differences in the indicators of psychosocial characteristics between truth and disinformation. Our results reveal which topics of rumors and which psychosocial characteristics are more likely to spread at each stage of progress of the pandemic. The findings contribute to a comprehensive understanding of the changing public opinions and psychological dynamics during the pandemic, and also provide reference for public opinion responses to major public health emergencies that may arise in the future.

Can Viewing Nature Through Windows Improve Isolated Living? A Pathway Analysis on Chinese Male Prisoners During the COVID-19 Epidemic.

Nature exposure is known to promote life satisfaction and well-being, and indirect exposure through windows is likely to benefit isolated populations. However, whether such type of exposure can benefit prisoners, the extremely isolated population, is unknown. In the current study, we investigated 326 male prisoners from three prisons in southwest China. Psychological variables including depression, anxiety, loneliness, distress tolerance, life satisfaction, and well-being were measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), short-form UCLA Loneliness Scale (ULS-6), Distress Tolerance Scale (DTS), Satisfaction with Life Scale (SWLS), and 5-item World Health Organization Well-Being Index (WHO-5), respectively. Structural equation modeling was employed to identify the pathways from the visibility of nature through windows to prisoners' life satisfaction and well-being. Our results demonstrated that visibility of nature promoted the frequency and duration of viewing nature through windows. The frequency directly affected well-being, but the duration did not effectively affect any measured variables. The visibility of nature enhanced life satisfaction mainly via direct effects but enhanced well-being mainly via indirect effects. Regarding the indirect pathways, the visibility of nature increased distress tolerance and thus reduced loneliness and mental health problems. The reduced mental health problem, in turn, promoted life satisfaction and well-being. Our findings suggest that nature exposure through windows is effective in enhancing prisoners' life satisfaction and well-being. The policymaker may need to consider nature-based solutions such as indirect nature exposure in prions to benefit isolated populations.