Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma.

BACKGROUND: Neutrophil extracellular traps (NETs) are considered significant contributors to cancer progression, especially metastasis. However, it is still unclear whether NETs are involved in hepatitis B virus (HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma (HCC). In this study, we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical significance. METHODS: A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this study. NETs were measured in tissue specimens, freshly isolated neutrophils and blood serum from these patients, and the correlation of circulating serum NETs levels with malignancy was evaluated. The mechanism by which HBV modulates NETs formation was explored using cell-based studies. In addition, in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of HCC. RESULTS: We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients, especially those infected with HBV. NETs facilitated the growth and metastasis of HCC both in vitro and in vivo, which were mainly dominated by increased angiogenesis, epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinases (MMPs)-induced extracellular matrix (ECM) degradation and NETs-mediated cell trapping. Inhibition of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and metastasis. In addition, HBV-induced S100A9 accelerated the generation of NETs, which was mediated by activation of toll-like receptor (TLR4)/receptor for advanced glycation end products (RAGE)-reactive oxygen species (ROS) signaling. Further, circulatory NETs were found to correlate with viral load, TNM stage and metastasis status in HBV-related HCC, and the identified NETs could predict extrahepatic metastasis, with an area under the ROC curve (AUC) of 0.83 and 90.3% sensitivity and 62.8% specificity at a cutoff value of 0.32. CONCLUSIONS: Our findings indicated that activation of RAGE/TLR4-ROS signaling by HBV-induced S100A9 resulted in abundant NETs formation, which subsequently facilitated the growth and metastasis of HCC cells. More importantly, the identified circulatory NETs exhibited potential as an alternative biomarker for predicting extrahepatic metastasis in HBV-related HCC.

The Role of Inflammasomes in COVID-19: Potential Therapeutic Targets.

The coronavirus 2019 disease (COVID-19) pandemic has caused massive morbidity and mortality worldwide. In severe cases, it is mainly associated with acute pneumonia, cytokine storm, and multi-organ dysfunction. Inflammasomes play a primary role in various pathological processes such as infection, injury, and cancer. However, their role in COVID-19-related complications has not been explored. In addition, the role of underlying medical conditions on COVID-19 disease severity remains unclear. Therefore, this review expounds on the mechanisms of inflammasomes following COVID-19 infection and provides recent evidence on the potential double-edged sword effect of inflammasomes during COVID-19 pathogenesis. The assembly and activation of inflammasomes are critical for inducing effective antiviral immune responses and disease resolution. However, uncontrolled activation of inflammasomes causes excessive production of proinflammatory cytokines (cytokine storm), increased risk of acute respiratory distress syndrome, and death. Therefore, discoveries in the role of the inflammasome in mediating organ injury are key to identifying therapeutic targets and treatment modifications to prevent or reduce COVID-19-related complications.

Generation Z nursing students' online learning experiences during COVID-19 epidemic: A qualitative study.

In early 2022, the coronavirus disease 2019 (COVID-19) continued to spread quickly globally and broke out in some metropolitan areas. To stop the spread of infection, all colleges and universities were shifted to a closed model, and higher education was transformed into online learning (OL). These transitions posed numerous challenges for Generation Z students, especially those in the nursing profession that featured face-to-face practice courses. This study aimed to explore and understand the experiences of OL among Generation Z nursing students during COVID-19 epidemic. This qualitative phenomenological research design applied a purposive sampling approach to enroll 14 Generation Z nursing students from a college. Data were collected and analyzed using in-depth, semi-structured interviews and Colaizzi seven-step method. The analysis demonstrated four themes and eleven subthemes: challenges encountered during OL, advantages perceived during OL, experience of loneliness and stress, and developing resilience during OL. This study concluded that the sudden shift in learning styles presents challenges to Generation Z nursing students. Despite the adversity, the students showed tremendous resilience and endurance. During the pandemic, educators should provide support measures based on the characteristics of Generation Z to improve the effectiveness of OL and respond positively to stress.

Genomic Analysis of the Suspicious SARS-CoV-2 Sequences in the Public Sequencing Database.

SARS-CoV-2 has infected more than 600 million people. However, the origin of the virus is still unclear; knowing where the virus came from could help us prevent future zoonotic epidemics. Sequencing data, particularly metagenomic data, can profile the genomes of all species in the sample, including those not recognized at the time, thus allowing for the identification of the progenitor of SARS-CoV-2 in samples collected before the pandemic. We analyzed the data from 5,196 SARS-CoV-2-positive sequencing runs in the NCBI's SRA database with collection dates prior to 2020 or unknown. We found that the mutation patterns obtained from these suspicious SARS-CoV-2 reads did not match the genome characteristics of an unknown progenitor of the virus, suggesting that they may derive from circulating SARS-CoV-2 variants or other coronaviruses. Despite a negative result for tracking the progenitor of SARS-CoV-2, the methods developed in the study could assist in pinpointing the origin of various pathogens in the future. IMPORTANCE Sequences that are homologous to the SARS-CoV-2 genome were found in numerous sequencing runs that were not associated with the SARS-CoV-2 studies in the public database. It is unclear whether they are derived from the possible progenitor of SARS-CoV-2 or contamination of more recent SARS-CoV-2 variants circulated in the population due to the lack of information on the collection, library preparation, and sequencing processes. We have developed a computational framework to infer the evolutionary relationship between sequences based on the comparison of mutations, which enabled us to rule out the possibility that these suspicious sequences originate from unknown progenitors of SARS-CoV-2.

SARS-CoV-2 Pattern Provides a New Scoring System and Predicts the Prognosis and Immune Therapeutic Response in Glioma.

OBJECTIVE: Glioma is the most common primary malignancy of the adult central nervous system (CNS), with a poor prognosis and no effective prognostic signature. Since late 2019, the world has been affected by the rapid spread of SARS-CoV-2 infection. Research on SARS-CoV-2 is flourishing; however, its potential mechanistic association with glioma has rarely been reported. The aim of this study was to investigate the potential correlation of SARS-CoV-2-related genes with the occurrence, progression, prognosis, and immunotherapy of gliomas. METHODS: SARS-CoV-2-related genes were obtained from the human protein atlas (HPA), while transcriptional data and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Glioma samples were collected from surgeries with the knowledge of patients. Differentially expressed genes were then identified and screened, and seven SARS-CoV-2 related genes were generated by LASSO regression analysis and uni/multi-variate COX analysis. A prognostic SARS-CoV-2-related gene signature (SCRGS) was then constructed based on these seven genes and validated in the TCGA validation cohort and CGGA cohort. Next, a nomogram was established by combining critical clinicopathological data. The correlation between SCRGS and glioma related biological processes was clarified by Gene set enrichment analysis (GSEA). In addition, immune infiltration and immune score, as well as immune checkpoint expression and immune escape, were further analyzed to assess the role of SCRGS in glioma-associated immune landscape and the responsiveness of immunotherapy. Finally, the reliability of SCRGS was verified by quantitative real-time polymerase chain reaction (qRT-PCR) on glioma samples. RESULTS: The prognostic SCRGS contained seven genes, REEP6, CEP112, LARP4B, CWC27, GOLGA2, ATP6AP1, and ERO1B. Patients were divided into high- and low-risk groups according to the median SARS-CoV-2 Index. Overall survival was significantly worse in the high-risk group than in the low-risk group. COX analysis and receiver operating characteristic (ROC) curves demonstrated excellent predictive power for SCRGS for glioma prognosis. In addition, GSEA, immune infiltration, and immune scores indicated that SCRGS could potentially predict the tumor microenvironment, immune infiltration, and immune response in glioma patients. CONCLUSIONS: The SCRGS established here can effectively predict the prognosis of glioma patients and provide a potential direction for immunotherapy.

Authority or Autonomy? Exploring Interactions between Central and Peer Punishments in Risk-Resistant Scenarios.

Game theory provides a powerful means to study human cooperation and better understand cooperation-facilitating mechanisms in general. In classical game-theoretic models, an increase in group cooperation constantly increases people's gains, implying that individual gains are a continuously varying function of the cooperation rate. However, this is inconsistent with the increasing number of risk-resistant scenarios in reality. A risk-resistant scenario means once a group does not successfully resist the risk, all individuals lose their resources, such as a community coping with COVID-19 and a village resisting a flood. In other words, individuals' gains are segmented about the collaboration rate. This paper builds a risk-resistant model to explore whether punishment still promotes collaboration when people resist risk. The results show that central and peer punishments can both encourage collaboration but with different characteristics under different risk-resistant scenarios. Specifically, central punishment constrains the collaboration motivated by peer punishment regardless of risk, while peer punishment limits the collaboration induced by central punishment only when the risk is high. Our findings provide insights into the balance between peer punishment from public autonomy and central punishment from central governance, and the proposed model paves the way for the development of richer risk-resistant models.

Tasks of COVID-19 prevention and control management teams at primary health care facilities in mainland China: a nationwide online cross-sectional survey.

BACKGROUND: This research aimed to investigate the tasks performed by Coronavirus Disease 2019(COVID-19) prevention and control management teams at primary healthcare (PHC) facilities during COVID-19 pandemic across the mainland China. METHODS: An online survey was performed and COVID-19 prevention and control management teams at PHC facilities were invited to participate in this research. The top 7 most important tasks in the three different periods of COVID-19 containment were selected and ranked. Participations of tasks were surveyed. RESULTS: A total of 998 valid responses (an effective rate of 99.11%) were collected. The respondents were divided into Group A (≤5 respondents within each PHC facility, n1 = 718) and Group B (> 5 respondents within each PHC facility, n2 = 280). The consensus was selected from top 7 most important tasks including screening at travel centers/intervals and screening at entry centers, at-home/centralized quarantine management, transferring, pre-examination/triage and fever sentinel surveillance clinic/fever clinic. Pre-examination/triage and fever sentinel surveillance clinic/fever clinic works became more significant in the regular prevention and control period. Adjusted analysis found that team members of Group A with a college, undergraduate college and graduate school educational background were less involved in pre-examination/triage works (aOR: 0.28; 95%CI: 0.09-0.86, P = 0.026; aOR: 0.30; 95%CI: 0.10-0.90, P = 0.031; aOR: 0.21; 95%CI: 0.05-0.82, P = 0.024). Those who were over the median age were twice more likely to be engaged in managing fever sentinel surveillance of clinic/fever clinic visitors (aOR: 2.18; 95%CI: 1.16-4.08, P = 0.015). Those being specialized in nursing and other specialties were less likely to participate in fever sentinel surveillance of clinic/fever clinic works (aOR: 0.44; 95%CI: 0.24-0.81, P = 0.009; aOR: 0.30; 95%CI: 0.16-0.58, P < 0.001). Those came from central and western China were less likely to participate in centralized quarantine management (aOR: 0.61; 95%CI: 0.38-0.98, P = 0.042; aOR: 0.64; 95%CI: 0.42-0.97, P = 0.037). Team members came from central and western China were twice less likely to participate in screening at travel centers/intervals (aOR: 1.75; 95%CI: 1.14-2.70, P = 0.011; aOR: 1.63; 95%CI: 1.07-2.48, P = 0.024). CONCLUSION: In mainland China, team members of COVID-19 prevention and control at PHC facilities are mainly responsible for screening, quarantine, transferring and monitoring during the COVID-19 pandemic. Pre-examination/triage and the fever sentinel surveillance clinic/fever clinic were gradually valued. Team members with lower educational background are competent in pre-examination/triage works, but more experienced general practitioners are more likely to be in charge of fever sentinel surveillance clinic/fever clinics work. The necessity of COVID-19 prevention and control management teams to participate in screening at travel centers/intervals is subjected to further discussions.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS: LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

Peramivir, an Anti-Influenza Virus Drug, Exhibits Potential Anti-Cytokine Storm Effects.

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS.

Null-free False Discovery Rate Control Using Decoy Permutations.

The traditional approaches to false discovery rate (FDR) control in multiple hypothesis testing are usually based on the null distribution of a test statistic. However, all types of null distributions, including the theoretical, permutation-based and empirical ones, have some inherent drawbacks. For example, the theoretical null might fail because of improper assumptions on the sample distribution. Here, we propose a null distribution-free approach to FDR control for multiple hypothesis testing in the case-control study. This approach, named target-decoy procedure, simply builds on the ordering of tests by some statistic or score, the null distribution of which is not required to be known. Competitive decoy tests are constructed from permutations of original samples and are used to estimate the false target discoveries. We prove that this approach controls the FDR when the score function is symmetric and the scores are independent between different tests. Simulation demonstrates that it is more stable and powerful than two popular traditional approaches, even in the existence of dependency. Evaluation is also made on two real datasets, including an arabidopsis genomics dataset and a COVID-19 proteomics dataset.

Vaccination coverage among COVID-19 prevention and control management teams at primary healthcare facilities in China and their attitudes towards COVID-19 vaccine: a cross-sectional online survey.

OBJECTIVE: To investigate the COVID-19 vaccination coverage rate and differences among various COVID-19 prevention primary healthcare (PHC) facilities in China and understand their attitudes towards COVID-19 vaccine. These findings are helpful to provide important suggestions to further improve national COVID-19 vaccination rate. DESIGN: A nationwide cross-sectional online survey was designed and conducted among COVID-19 prevention and control management teams at PHC facilities in mainland China. In the self-designed questionnaires, each subject was asked to evaluate on a 1-10 scale (10=extremely important/acceptable/influential) the COVID-19 vaccination importance, acceptance and factors related to vaccine hesitancy. SETTING: Subjects from 31 provinces and autonomous regions including minorities across mainland China were invited to complete the questionnaire between 22 February 2021 and 2 March 2021. PARTICIPANTS: Were selected by multistage stratified sampling, 998 valid questionnaires (valid rate 99.11%) were collected. The respondents were divided into group A (≤5 respondents within each PHC facility, n1=718) and group B (>5 respondents within each PHC facility, n2=280). OUTCOME MEASURES: Survey on vaccination rate and attitude towards COVID-19 vaccine included the following: (1) if the subjects think the vaccination is important in containment of COVID-19 pandemic (1-10 scale, 10=extremely important), (2) if they would accept COVID-19 vaccine (1-10 scale, 10=extremely acceptable) and (3) their opinions on 7 factors possibly related to vaccine hesitancy (1-10 scale, 10=extremely influential). All the items were designed based on the previous expert interviews. RESULTS: Our results showed vaccination rate was greater in group A (85.93%) than in group B (66.43%) (p<0.001). Detailed analyses revealed that in group A, male members were twice as likely to get vaccinated as compared with female members (adjusted OR (aOR): 2.07; 95% CI: 1.26 to 3.43, p=0.004). In group B, those who were at or under the median age had twice the odds of vaccination coverage compared with those who were over the median age (aOR: 2.29; 95% CI: 1.22 to 4.33, p=0.010). In addition, those who were specialised in traditional Chinese medicine were less likely to get vaccinated against COVID-19 compared with those who were specialised in general medicine, with the aOR: 0.10 (95% CI: 0.01 to 0.83, p=0.033). By analysing the factors that influenced the vaccination attitudes among the 998 respondents, we found no significant difference between the vaccinated and unvaccinated participants. However, further detailed analyses found that team members with undergraduate college education were less likely to score higher in COVID-19 vaccination importance than those with technical secondary school education (aOR: 0.35; 95% CI: 0.13 to 0.93, p=0.035); Furthermore, those with non-medical job titles had nearly twice the odds of giving a higher score for the uncertainty of vaccine efficacy compared with those with junior medical titles (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.016). Team members with a non-medical title were more likely to give a higher score for advice on social sources compared with those with a junior medical title (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.042). CONCLUSION: In PHC facilities, although there was a higher COVID-19 vaccination rate among COVID-19 prevention and control teams, some subgroups with different descriptive characters showed negative attitudes towards COVID-19 vaccination. Because primary care workers in China are highly expected to receive the vaccination, and support and educate the public for COVID-19 vaccination. Thus, it is important and necessary to continue to educate them about their vaccination concerns and change their attitudes towards vaccination. Our findings are highly beneficial for designing public vaccination education strategies.

Prevention and control of COVID-19 by primary health care facilities in China: a field-survey-based qualitative study in three typical cities.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.

Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases.

Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy.

SARS-CoV-2 targets the lysosome to mediate airway inflammatory cell death.

As the coronavirus disease 2019 (COVID-19) pandemic continues to wreak havoc, researchers around the globe are working together to understand how the responsible agent - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) damages the respiratory system and other organs. Macroautophagy/autophagy is an innate immune response against viral infection and is known to be manipulated by positive-strand RNA viruses, including SARS-CoV-2. Nevertheless, the link between autophagic subversion and cell death or inflammation in COVID-19 remains unclear. Emerging evidence suggests that SARS-CoV-2 could trigger pyroptosis, a form of inflammatory programmed cell death characterized by the activation of inflammasomes and CASP1 (caspase 1) and the formation of transmembrane pores by GSDMD (gasdermin D). In this connection, autophagic flux impairment is a known activator of inflammasomes. This prompted us to investigate if SARS-CoV-2 could target autophagy to induce inflammasome-dependent pyroptosis in lung epithelial cells.Abbreviations: ATP6AP1: ATPase H+ transporting accessory protein 1; CASP1: caspase 1; COVID-19: coronavirus disease 2019; GSDMD: gasdermin D; IL1B: interleukin 1 beta; IL18: interleukin 18; KRT 18: keratin 18; NLRP3: NLR family pyrin domain containing 3; NOD: nucleotide oligomerization domain; NSP6: non-structural protein 6; TFEB: transcription factor EB; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1.

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

Anticoagulation treatment for patients with coronavirus disease 2019 (COVID-19) and its clinical effectiveness in 2020: A meta-analysis study.

BACKGROUND: To better inform efforts to treat and control the current outbreak with effective anticoagulant treatment strategies for coronavirus disease 2019 patients. METHODS: We searched Cochrane Library, Pubmed, EMBASE, MEDLINE, SCIEXPANDED, Web of Science, Google Scholar, CNKI (Chinese Database), WanFang (Chinese Database), CBM (Chinese Database), VIP (Chinese Database) for studies published from November 1, 2019 to October 1, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using funnel plot. RESULTS: Fourteen studies involving 7681 patients were included. We meta-analyzed the bleeding, deep vein thrombosis, and pulmonary embolism risk between no anticoagulation and prophylactic anticoagulation, and found no significant difference. The same trend occurred in the comparison between with and without anticoagulation. However, when compared with no anticoagulation, both prophylactic anticoagulation (odd ratio [OR] = 0.80, 95% confidence interval [CI]: 0.69-0.93) and therapeutic anticoagulation (OR = 0.91, 95% CI: 0.80-1.05) had lower risk of mortality. Furthermore, the risk of overall bleeding among patients with therapeutic anticoagulation was 3.11 times (95% CI: 2.29-4.24) than that of patients with prophylactic anticoagulation. On the contrary, therapeutic anticoagulation had lower risk of deep vein thrombosis than prophylactic anticoagulation (OR = 0.34, 95% CI: 0.19-0.63). CONCLUSIONS: Among coronavirus disease 2019 patients, preventive and therapeutic anticoagulation were more beneficial than no anticoagulation for reducing mortality rate. The result will inform healthcare providers and public health policy makers in efforts to treat and control the current outbreak.

Prenatal anxiety and the associated factors among Chinese pregnant women during the COVID-19 pandemic——a smartphone questionnaire survey study

Backgrounds The uncertainty of the pandemic of Coronavirus Disease 2019 (COVID-19) brought about tremendous psychological harm for pregnant women, causing their high rates of prenatal anxiety. The impacts of COVID-19 pandemic and symptoms of pregnant status are highly linked with prenatal anxiety. Whereas, self-efficacy and support from family and friends could attenuate the development of prenatal anxiety. Thus, the purpose of the study is to evaluate the prevalence of prenatal anxiety and its influence factors among pregnant women during the pandemic of COVID-19 in Shenyang, China. Methods A cross-sectional study with face-to-face interview between April 24, 2020 and May 3, 2020 during the COVID-19 pandemic was applied among pregnant women in Shenyang Women’s and Children’s Hospital. Chi-square tests were calculated to determine the differences in prenatal anxiety among categorical variables. Multivariable logistic regression was employed to investigate the risk factors of prenatal anxiety. Results The percentage of prenatal anxiety (GAD-7 score ≥ 7) among pregnant women during the pandemic of COVID-19 was 34/304 (11.18%). Logistic regression indicated that vomiting (OR 4.454, 95% CI 1.113–17.821) and feeling susceptible to SARS-CoV-2 infection (OR 2.966, 95% CI 1.151–7.642) increased the odds of prenatal anxiety. Satisfaction with medical care (OR 0.303, 95% CI 0.113–0.813) and self-efficacy (OR 0.253, 95% CI 0.100–0.639) decreased the odds of prenatal anxiety. High monthly income (OR 0.246, 95% CI 0.078 ~ 0.780) reduced the chances of suffering from prenatal anxiety. Conclusion The pregnant women in China exerted a higher prevalence of prenatal anxiety during the COVID-19 pandemic than that without COVID-19 pandemic. Effective management on symptoms of pregnant status should be delivered to relieve prenatal anxiety for the pregnant women. Furthermore, interventions on self-efficacy enhancement and high-quality medical prenatal care should be provided to prevent from the susceptibility of SARS-CoV-2 infection and reduce prenatal anxiety.

Social Media Exposure, Psychological Distress, Emotion Regulation, and Depression During the COVID-19 Outbreak in Community Samples in China.

The outbreak of coronavirus disease 2019 (COVID-19) has been a global emergency, affecting millions of individuals both physically and psychologically. The present research investigated the associations between social media exposure and depression during the COVID-19 outbreak by examining the mediating role of psychological distress and the moderating role of emotion regulation among members of the general public in China. Participants (N = 485) completed a set of questionnaires online, including demographic information, self-rated physical health, and social media exposure to topics related to COVID-19. The Impact of Event Scale-Revised (IES-R), the Beck Depression Inventory-II (BDI-II), and the Emotion Regulation Questionnaire (ERQ) were utilized to measure psychological distress about COVID-19, depression, and emotion regulation strategies, respectively. Results found that older age and greater levels of social media exposure were associated with more psychological distress about the virus (r = 0.14, p = 0.003; r = 0.22, p < 0.001). Results of the moderated mediation model suggest that psychological distress mediated the relationship between social media exposure and depression (ß = 0.10; Boot 95% CI = 0.07, 0.15). Furthermore, expressive suppression moderated the relationship between psychological distress and depression (ß = 0.10, p = 0.017). The findings are discussed in terms of the need for mental health assistance for individuals at high risk of depression, including the elderly and individuals who reported greater psychological distress and those who showed preference usage of suppression, during the COVID-19 crisis.