Infectious bronchitis virus nucleocapsid protein suppressed type I interferon production by interfering with the binding of MDA5-dsRNA and interacting with LGP2.

The type I interferon (IFN-I) is a critical component of the innate immune responses, and Coronaviruses (CoVs) from both the Alphacoronavirus and Betacoronavirus genera interfere with the IFN-I signaling pathway in various ways. Of the gammacoronaviruses that mainly infect birds, little is known about how infectious bronchitis virus (IBV), evades or interferes with the innate immune responses in avian hosts since few IBV strains have been adapted to grow in avian passage cells. Previously, we reported that a highly pathogenic IBV strain GD17/04 has adaptability in an avian cell line, providing a material basis for further study on the interaction mechanism. In the present work, we describe the suppression of IBV to IFN-I and the potential role of IBV-encoded nucleocapsid (N) protein. We show that IBV significantly inhibits the poly I: C-induced IFN-I production, accordingly the nuclear translocation of STAT1, and the expression of IFN-stimulated genes (ISGs). A detailed analysis revealed that N protein, acting as an IFN-I antagonist, significantly impedes the activation of the IFN-ß promoter stimulated by MDA5 and LGP2 but does not counteract its activation by MAVS, TBK1, and IRF7. Further results showed that IBV N protein, verified to be an RNA-binding protein, interferes with MDA5 recognizing double-stranded RNA (dsRNA). Moreover, we found that the N protein targets LGP2, which is required in the chicken IFN-I signaling pathway. Taken together, this study provides a comprehensive analysis of the mechanism by which IBV evades avian innate immune responses.

Understanding post-pandemic metro commuting ridership by considering the built environment: A quasi-natural experiment in Wuhan, China

The COVID-19 pandemic has had a significant impact on metro commuting ridership. However, the exact magnitude and spatial and temporal characteristics of the impact remain unclear. In this study, we explored the impact of the COVID-19 outbreak on metro commuting ridership in Wuhan, where the novel virus was first reported. The results of interrupted time-series (ITS) analysis showed that metro commuting ridership sharply dropped in the short term under the impact of the outbreak in the epicenter, rebounded rapidly as the pandemic eased, and it returned to pre-pandemic levels in six months. Furthermore, there was a noticeable spatial heterogeneity in the rebound. Urban centers, especially employment centers, recovered faster than other areas. In addition, the number of residents, number of bus stops, number of enterprises around a metro station and being a transfer station had a positive effect on metro ridership, while street length, number of restaurants, and number of metro exits had a negative effect. These findings may help local governments and metro managers develop sustainable metro operations and infection prevention policies to better cope with the impact of the pandemic and beyond.

Associations of psychological wellbeing with COVID-19 hospitalization and mortality in adults aged 50 years or older from 25 European countries and Israel.

Background: Lower psychological wellbeing is associated with poor outcomes in a variety of diseases and healthy populations. However, no study has investigated whether psychological wellbeing is associated with the outcomes of COVID-19. This study aimed to determine whether individuals with lower psychological wellbeing are more at risk for poor outcomes of COVID-19. Methods: Data were from the Survey of Health, Aging, and Retirement in Europe (SHARE) in 2017 and SHARE's two COVID-19 surveys in June-September 2020 and June-August 2021. Psychological wellbeing was measured using the CASP-12 scale in 2017. The associations of the CASP-12 score with COVID-19 hospitalization and mortality were assessed using logistic models adjusted for age, sex, body mass index, smoking, physical activity, household income, education level, and chronic conditions. Sensitivity analyses were performed by imputing missing data or excluding cases whose diagnosis of COVID-19 was solely based on symptoms. A confirmatory analysis was conducted using data from the English Longitudinal Study of Aging (ELSA). Data analysis took place in October 2022. Results: In total, 3,886 individuals of 50 years of age or older with COVID-19 were included from 25 European countries and Israel, with 580 hospitalized (14.9%) and 100 deaths (2.6%). Compared with individuals in tertile 3 (highest) of the CASP-12 score, the adjusted odds ratios (ORs) of COVID-19 hospitalization were 1.81 (95% CI, 1.41-2.31) for those in tertile 1 (lowest) and 1.37 (95% CI, 1.07-1.75) for those in tertile 2. As for COVID-19 mortality, the adjusted ORs were 2.05 (95% CI, 1.12-3.77) for tertile 1 and 1.78 (95% CI, 0.98-3.23) for tertile 2, compared with tertile 3. The results were relatively robust to missing data or the exclusion of cases solely based on symptoms. This inverse association of the CASP-12 score with COVID-19 hospitalization risk was also observed in ELSA. Conclusion: This study shows that lower psychological wellbeing is independently associated with increased risks of COVID-19 hospitalization and mortality in European adults aged 50 years or older. Further study is needed to validate these associations in recent and future waves of the COVID-19 pandemic and other populations.

Discovery of novel bicyclic[3.3.0]proline peptidyl α-ketoamides as potent 3CL-protease inhibitors for SARS-CoV-2.

The outbreak of SARS-CoV-2 has caused global crisis on health and economics. The multiple drug-drug interaction risk associated with ritonavir warrants specialized assessment before using Paxlovid. Here we report a multiple-round SAR study to provide a novel bicyclic[3.3.0]proline peptidyl α-ketoamide compound 4a, which is endowed with excellent antiviral activities and pharmacokinetic properties. Also, in vivo HCoV-OC43 neonatal mice model demonstrated compound 4a has good in vivo efficacy. Based on these properties, compound 4a worth further SAR optimization with the goal to develop compounds with better pharmacokinetic properties and finally to realize single agent efficacy in human.

Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs; 95% confidence interval [CI]). Results: A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74-0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48-2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77-1.11). Conclusions: APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial.

Importance: Myopia is a global concern, but effective prevention measures remain limited. Premyopia is a refractive state in which children are at higher risk of myopia, meriting preventive interventions. Objective: To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia. Design, Setting, and Participants: This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 139 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of -0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤-3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Interventions: Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities. Main Outcomes and Measures: The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤-0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic. Results: There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, -0.35 [0.54] D vs -0.76 [0.60] D; difference, -0.41 D [95% CI, -0.56 to -0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group. Conclusions and Relevance: In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia. Trial Registration: ClinicalTrials.gov Identifier: NCT04825769.

IFITM3 rs12252 polymorphism and coronavirus disease 2019 severity: A meta‑analysis

Interferon-induced transmembrane protein 3 (IFITM3) serves a critical role in the immune defense against viral infection, including that of severe acute respiratory syndrome coronavirus 2. To the best of our knowledge, the association between IFITM3 rs12252 polymorphism and coronavirus disease 2019 (COVID-19) severity has not been determined. In the present study, a meta-analysis of published case-control studies assessing the association between the IFITM3 rs12252 polymorphism and COVID-19 severity was performed. PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang and preprint servers were searched up to March 30, 2022. A fixed-effect model was used to calculate odds ratio (OR) and 95% confidence interval (95% CI). Analyses were conducted for additive, dominant and recessive genetic models. A total of five studies were identified, with 1,443 mild-to-moderate cases and 667 severe cases, including 121 deaths. Overall, the CC genotype of IFITM3 rs12252 was associated with increased risk of severe COVID-19 (OR=1.97, 95% CI, 1.06-3.69) and mortality (OR=4.61, 95% CI, 1.44-14.75) compared with the CT/TT genotypes. Stratified analysis by ethnicity revealed that this association was strong in Chinese individuals (severity, OR=2.84, 95% CI, 1.34-6.04;mortality, OR=7.91, 95% CI, 1.29-48.44), but not notable in Caucasians (severity, OR=0.79, 95% CI, 0.23-2.80;mortality, OR=2.16, 95% CI, 0.37-12.55). A significant association with mortality was observed in Caucasians when comparing patients with the C allele of IFITM3 rs12252 and those without (CC/CT vs. TT: OR=1.73, 95% CI, 1.09-2.75). The results suggested that the IFTM3-rs12252 CC genotype is associated with severe COVID-19 and mortality in Chinese individuals and the IFTM3-rs12252 C allele may be associated with COVID-19 mortality in Caucasians. Large-scale studies are needed to confirm the association in different global populations. [ABSTRACT FROM AUTHOR] Copyright of Experimental & Therapeutic Medicine is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Efficacy and safety of awake prone positioning in the treatment of non-intubated spontaneously breathing patients with COVID-19-related acute respiratory failure: A systematic review and meta-analysis

Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, prone positioning has been widely applied for non-intubated, spontaneously breathing patients. However, the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear. We aimed to systematically analyze the outcomes associated with awake prone positioning (APP). Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science from January 1, 2020, to June 3, 2022. This study included adult patients with acute respiratory failure caused by COVID-19. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was the reported cumulative intubation risk across randomized controlled trials (RCTs), and the effect estimates were calculated as risk ratios (RRs;95% confidence interval [CI]). Results A total of 495 studies were identified, of which 10 fulfilled the selection criteria, and 2294 patients were included. In comparison to supine positioning, APP significantly reduced the need for intubation in the overall population (RR=0.84, 95% CI: 0.74–0.95). The two groups showed no significant differences in the incidence of adverse events (RR=1.16, 95% CI: 0.48–2.76). The meta-analysis revealed no difference in mortality between the groups (RR=0.93, 95% CI: 0.77–1.11). Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19. However, it did not significantly reduce mortality in comparison to usual care without prone positioning.

IFITM3 rs12252 polymorphism and coronavirus disease 2019 severity: A meta­analysis.

Interferon-induced transmembrane protein 3 (IFITM3) serves a critical role in the immune defense against viral infection, including that of severe acute respiratory syndrome coronavirus 2. To the best of our knowledge, the association between IFITM3 rs12252 polymorphism and coronavirus disease 2019 (COVID-19) severity has not been determined. In the present study, a meta-analysis of published case-control studies assessing the association between the IFITM3 rs12252 polymorphism and COVID-19 severity was performed. PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang and preprint servers were searched up to March 30, 2022. A fixed-effect model was used to calculate odds ratio (OR) and 95% confidence interval (95% CI). Analyses were conducted for additive, dominant and recessive genetic models. A total of five studies were identified, with 1,443 mild-to-moderate cases and 667 severe cases, including 121 deaths. Overall, the CC genotype of IFITM3 rs12252 was associated with increased risk of severe COVID-19 (OR=1.97, 95% CI, 1.06-3.69) and mortality (OR=4.61, 95% CI, 1.44-14.75) compared with the CT/TT genotypes. Stratified analysis by ethnicity revealed that this association was strong in Chinese individuals (severity, OR=2.84, 95% CI, 1.34-6.04; mortality, OR=7.91, 95% CI, 1.29-48.44), but not notable in Caucasians (severity, OR=0.79, 95% CI, 0.23-2.80; mortality, OR=2.16, 95% CI, 0.37-12.55). A significant association with mortality was observed in Caucasians when comparing patients with the C allele of IFITM3 rs12252 and those without (CC/CT vs. TT: OR=1.73, 95% CI, 1.09-2.75). The results suggested that the IFTM3-rs12252 CC genotype is associated with severe COVID-19 and mortality in Chinese individuals and the IFTM3-rs12252 C allele may be associated with COVID-19 mortality in Caucasians. Large-scale studies are needed to confirm the association in different global populations.

Network connectivity between anxiety, depressive symptoms and psychological capital in Chinese university students during the COVID-19 campus closure.

BACKGROUND: In the context of the outbreak of COVID-19 within mainland China, to understand the mental health status of university students during campus closure, this study analyzes the relationship between anxiety, depressive symptoms, and psychological capital and to reveals their central symptoms. METHODS: A total of 12,945 university students were included in this study from April 10 to 19, 2022. Anxiety and depressive symptoms were measured by the seven-item Generalized Anxiety Disorder Scale (GAD-7) and two-item Patient Health Questionnaires (PHQ-2). Psychological capital was measured using the Psychological Capital Questionnaire (PCQ-24). The centrality and bridge centrality indexes were used to identify central and bridge symptoms, respectively. Network Comparison Test (NCT) was also administered to check whether network traits differed by gender and place of residence. RESULTS: The most influential node in this study was Trouble relaxing (GAD4), followed by Uncontrollable worry (GAD2) and Excessive worry (GAD3). The main bridging symptoms were Depressed mood (PHQ2), Psychological capital. There are no differences in the network structure of students by place of residence, while there are more significant differences in the network structure of students by gender. CONCLUSION: Central and bridging symptoms may be the core symptoms that trigger or maintain the development of anxiety and depression among university students during the COVID-19 campus closure. Timely and reasonable interventions targeting these symptoms may help reduce depression and anxiety in this population. In addition, improving university students' psychological capital may likewise contribute to the development of their good mental health.

De novo vasculitis after COVID-19 vaccination.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to spread around the world. Vaccinations have been administered globally and have been proven to be safe and effective. However, vasculitis has been reported as an adverse event occurring after COVID-19 vaccination. METHODS: In this review, we analyzed the literature to identify original articles that reported on patients who developed vasculitis following COVID-19 vaccination and summarized their clinical manifestations. PubMed and Web of Knowledge were searched to identify relevant studies. RESULTS: A total of 27 patients who developed vasculitis following COVID-19 vaccination were identified from 21 studies. The involved organs included the skin and kidney. The main clinical features of patients whose skin was affected were papules, maculopapular rashes, and plaques. Most of the patients exhibited small vessel vasculitis and single-organ vasculitis; these were resolved within one month. Patients whose kidneys were affected exhibited vasculitis, including anti-neutrophil cytoplasmic antibody glomerulonephritis and IgA nephritis. Most patients were treated with corticosteroid, rituximab, and cyclophosphamide, and one patient needed hemodialysis. The renal function of most patients was improved or recovered, but one patient needed maintenance dialysis. CONCLUSION: Vasculitis was rarely reported after COVID-19 vaccine administration. It often manifested as cutaneous small-vessel vasculitis or glomerulonephritis. Notably, when a patient demonstrates hematuria, proteinuria, and acute kidney injury after COVID-19 vaccination, there is a possibility that the patient could have developed vasculitis. Skin-related problems were quickly resolved, while kidney-related problems may progress to chronic kidney disease.

How does imported pork regulate the supply and demand of China's pig market during the epidemic?-based on the analysis of African swine fever and COVID-19.

The pig industry is primarily a domestic industry in China is focused on ensuring the domestic pork supply. This paper analyzed changes in Chinese pork imports following the outbreaks of African Swine Fever (ASF) and COVID-19 between January 2017 to November 2020 and evaluated the impact of imported pork on the development of the swine industry in China. The results demonstrated that the shortage of domestic pork supply changed the import volume. ASF transformed imported pork from a complementary product to meet the diversified needs of domestic consumers into a critical substitute required to fill the supply gap. Following the COVID-19 outbreak, the substitution effect of imported pork decreased. ASF, has caused the supply capacity of pork in China to decrease, the price of pork to increase, leading to increased pork import in January 2019. At the end of 2019, pig slaughter decreased, while China cut tariffs on imported pork. The COVID-19 outbreak did not reduce China's pork imports in China, which declined after the global COVID-19 outbreak. Imported pork has made up for the supply gap during COVID-19, not impacting the level of production of the swine industry in China.

Changes in Agri-Food Export Competitiveness Based on the Sophistication Analysis: The Case of Xinjiang, China

The Xinjiang Uygur Autonomous Region is a major agri-food export contributor within China. Growing quality requirements for agri-food export, increasing green trade barriers, and a desire to emphasize sustainable trade at regional levels have prompted Xinjiang to pay increased attention to agri-food export competitiveness. The paper uses the export sophistication index to investigate the overall and classificatory export competitiveness of Xinjiang's Agricultural Products (APs). The results are compared to the national average within China by calculating the relative export sophistication. The research finds that (1) Xinjiang's APs exports are predominant in medium and medium-low-sophistication products. Along with the expanding scale, its structure has been optimized overall. (2) Horticultural products keep a leading position, not having strong competitiveness in Xinjiang but also far exceeding the national average. However, the bulk APs, livestock products, aquatic products, beverages and tobacco, and other APs have no significant export competitiveness compared to the national average. (3) The export structure of Xinjiang's APs is highly concentrated in horticultural products, showing an adverse trend in export competitiveness distribution-';the strong getting stronger and the weak getting weaker,';and a slower upgrading than the national average since the outbreak of COVID-19, which requires the attention of policymakers.

COVID-19 Breakthrough Infections in Vaccinated Kidney Transplant Recipients.

Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among kidney transplant recipients (KTRs). The administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the only reliable strategy to prevent COVID-19 and alleviate the severity of COVID-19 in this particular population. The aim of this article was to evaluate the clinical protection by vaccines (breakthrough infections, deaths, and hospitalizations) in KTRs. There were 135 KTRs with COVID-19 breakthrough infections for whom patient-level data were available in PubMed and Web of Science. There was a male predominance (61.4%), 97 were given the standard vaccination regimen, and 38 received three or four doses of the vaccine. The median age was 59.0 (IQR: 49.0-69.0) years. A total of 67 patients were hospitalized, and 10 patients died. In 72.6% of cases, triple-maintenance immunosuppression was employed. The deceased patients were older than the survivors (p < 0.05); an age over 60 years was a risk factor for death (p < 0.05). The KTRs with booster vaccines had a longer time interval from the last vaccine to COVID-19 infection and lower hospitalization rates than the individuals who received the standard vaccination regimen (33.3% vs. 54.8%, p < 0.05). The hospitalized patients were older than the outpatients (p < 0.05). Among 16,820 fully vaccinated or boosted KTRs from 14 centers, there were 633 breakthrough infections (3.58%) and 73 associated deaths (0.41%). The center-level breakthrough infection rates varied from 0.21% to 9.29%. These findings highlight the need for booster doses for KTRs. However, more research is needed to define the long-term effectiveness and immunogenicity of booster doses and to identify methods to boost the protective response to vaccination in these immunocompromised patients.

Green spaces, especially nearby forest, may reduce the SARS-CoV-2 infection rate: A nationwide study in the United States

The coronavirus pandemic is an ongoing global crisis that has profoundly harmed public health. Although studies found exposure to green spaces can provide multiple health benefits, the relationship between exposure to green spaces and the SARS-CoV-2 infection rate is unclear. This is a critical knowledge gap for research and practice. In this study, we examined the relationship between total green space, seven types of green space, and a year of SARS-CoV-2 infection data across 3,108 counties in the contiguous United States, after controlling for spatial autocorrelation and multiple types of covariates. First, we examined the association between total green space and SARS-CoV-2 infection rate. Next, we examined the association between different types of green space and SARS-CoV-2 infection rate. Then, we examined forest–infection rate association across five time periods and five urbanicity levels. Lastly, we examined the association between infection rate and population-weighted exposure to forest at varying buffer distances (100m to 4km). We found that total green space was negative associated with the SARS-CoV-2 infection rate. Furthermore, two forest variables (forest outside park and forest inside park) had the strongest negative association with the infection rate, while open space variables had mixed associations with the infection rate. Forest outside park was more effective than forest inside park. The optimal buffer distances associated with lowest infection rate are within 1,200m for forest outside park and within 600m for forest inside park. Altogether, the findings suggest that green spaces, especially nearby forest, may significantly mitigate risk of SARS-CoV-2 infection.

Differential expression analysis of mRNAs, lncRNAs, and miRNAs expression profiles and construction of ceRNA networks in PEDV infection.

BACKGROUND: Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that seriously affects the swine industry. MicroRNAs and long noncoding RNAs are two relevant non-coding RNAs (ncRNAs) class and play crucial roles in a variety of physiological processes. Increased evidence indicates a complex interaction between mRNA and ncRNA. However, our understanding of the function of ncRNA involved in host-PEDV interaction is limited. RESULTS: A total of 1,197 mRNA transcripts, 539 lncRNA transcripts, and 208 miRNA transcripts were differentially regulated at 24 h and 48 h post-infection. Gene ontology (GO) and KEGG pathway enrichment analysis showed that DE mRNAs and DE lncRNAs were mainly involved in biosynthesis, innate immunity, and lipid metabolism. Moreover, we constructed a miRNA-mRNA-pathway network using bioinformatics, including 12 DE mRNAs, 120 DE miRNAs, and 11 pathways. Finally, the target genes of DE miRNAs were screened by bioinformatics, and we constructed immune-related lncRNA-miRNA-mRNA ceRNA networks. Then, the selected DE genes were validated by qRT-PCR, which were consistent with the results from RNA-Seq data. CONCLUSIONS: This study provides the comprehensive analysis of the expression profiles of mRNAs, lncRNAs, and miRNAs during PEDV infection. We characterize the ceRNA networks which can provide new insights into the pathogenesis of PEDV.

What caregivers believe affected the quality of implementation of asthma-related family management models (AFMM) during COVID-19: A phenomenological qualitative study.

PURPOSE: The recurrent COVID-19 epidemic in China has disrupted many aspects of daily life for children with asthma and their caregivers, while negatively impacting their asthma family management models (AFMM). This phenomenological qualitative study identifies what affects the quality of implementation of AFMM in this population and outlines potential coping strategies for the caregivers. METHODS: We used purposive sampling to conduct semistructured interviews with primary caregivers of school-age children with asthma from community healthcare centers (CHCs), which focused on understanding what factors influenced caregivers' implementation of AFMM during quarantine. The Colaizzi seven-step method was used to independently code and categorize the transcript and to generate themes and identify associated key subthemes. RESULTS: Twenty-four caregivers were interviewed, and they provided greater insight into barriers and motivators to implement AFMM. The three themes and nine relevant subthemes generated, (a) the "individual-family" internal-level factors: weak health literacy and beliefs, quietly changing family relationships, the dramatic increase in the care burden, gradual adjustment of negative psychology; (b) the "hospital-community" external-level factors: the endless power of peer support, strict community quarantine policy; and (c) the "health system-public" social-level factors: the enormous potential of internet-based telemedicine, improved public awareness of prevention, government's prompt assistance. CONCLUSIONS: This qualitative study reveals that the quality of AFMM implementation during pandemic is impacted by three different levels. Therefore, a targeted and comprehensive caring model that provides caregivers with the necessary coping strategies around these three levels is needed to achieve better asthma control outcomes.

[Analysis of clinical characteristics of patients with different vaccines and underlying diseases infected with novel coronavirus Omicron variant].

OBJECTIVE: To analyze the clinical characteristics of patients inoculated with different vaccines and underlying diseases, infected with the novel coronavirus Omicron variant. METHODS: The data of 430 patients infected with the novel coronavirus Omicron variant who were admitted to Tianjin First Center Hospital from January 21, 2022 to March 7, 2022 were collected. A total of 108 patients with Omicron variant infection with underlying diseases were selected and enrolled. The gender, age, body mass index (BMI), history of underlying diseases, vaccination status (vaccination times, vaccination type), clinical symptoms, laboratory test indicators, imaging data, hospitalization time, nucleic acid negative conversion time, re-positivity and antibody titer from the two groups of the patients were collected and analyzed. RESULTS: In the 108 patients, 93 cases received inactivated vaccine and 15 cases received adenovirus vaccine. There was no statistically significant difference between the two groups in terms of gender, age, BMI, disease types, whether completed the fully vaccinated, whether had prime boost and underlying diseases. Both groups had fever, dry cough, sore throat, runny nose and other clinical symptoms, but there were no statistical difference between the two groups. There were no statistically significant differences in laboratory blood routine tests, biochemical indexes, C-reactive protein (CRP) level and the results of chest computed tomography (CT) imaging between the two groups. There were no statistically significant differences in hospitalization days, nucleic acid negative conversion time, whether admission to intensive care unit (ICU), turn re-positive on nucleic acid tests and immunoglobulin M (IgM) antibody titer expression between the two groups, but immunoglobulin G (IgG) antibody titer in adenovirus group was higher than that in inactivated group (g/L: 229.67±26.13 vs. 194.33±61.56, P = 0.020). There were also no significant differences in laboratory examinations, hospitalization days, nucleic acid negative conversion time, turn re-positive on nucleic acid tests and Novel coronavirus antibody titers expression of the patients with booster shots between the inactivated vaccine group and the adenovirus vaccine group. CONCLUSIONS: The protection of inactivated virus vaccine is equivalent to adenovirus vaccine in patients with underlying disease Omicron variant infection, and the titer of IgG antibody in patients with adenovirus vaccine is higher than that in patients with inactivated virus vaccine after one week of recovery.

Engineered disulfide reveals structural dynamics of locked SARS-CoV-2 spike.

The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct "S-R/x3" to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.

Relationships among thriving at work, organisational commitment and job satisfaction among Chinese front-line primary public health workers during COVID-19 pandemic: a structural equation model analysis.

OBJECTIVES: This study aims to explore the mediating effect and influence mechanism of organisational commitment on the association among thriving at work and job satisfaction among frontline primary public health workers (PHWs) in China during the COVID-19 pandemic. DESIGN: This study is a cross-sectional written survey. SETTING: We included 20 primary care units in northern provinces of China. PARTICIPANTS: A total of 601 PHWs who worked in primary organisations and against COVID-19 on the front line were included. METHODS: We collected the data from the participants' written questionnaire (Minnesota Satisfaction Questionnaire, thriving at work scale and organisational commitment scale), and programmed AMOS V.26.0 to develop a structural equation model (SEM) based on the relationships among the three variables. RESULTS: The thriving at work scores of the primary PHWs were (M=3.17, SD=0.65), and job satisfaction was (M=3.05, SD=0.69); the scores of their thriving at work, organisational commitment and job satisfaction were all significantly correlated (p<0.01); and the SEM indicated that organisational commitment had a significant partial mediating effect between thriving at work and job satisfaction. The overall effect value was 0.867, and the mediated effect value was 0.422, accounting for 48.7% of the total effect size. CONCLUSION: The thriving at work and job satisfaction scores of primary PHWs in China are moderate, and thriving at work not only affects job satisfaction directly, but also indirectly through organisational commitment. This study suggests that health policy-makers should promote job satisfaction among PHWs through relative inventions aiming to improve their thriving at work and organisational commitment.