Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Intra-Host Co-Existing Strains of SARS-CoV-2 Reference Genome Uncovered by Exhaustive Computational Search.

The COVID-19 pandemic caused by SARS-CoV-2 has had a severe impact on people worldwide. The reference genome of the virus has been widely used as a template for designing mRNA vaccines to combat the disease. In this study, we present a computational method aimed at identifying co-existing intra-host strains of the virus from RNA-sequencing data of short reads that were used to assemble the original reference genome. Our method consisted of five key steps: extraction of relevant reads, error correction for the reads, identification of within-host diversity, phylogenetic study, and protein binding affinity analysis. Our study revealed that multiple strains of SARS-CoV-2 can coexist in both the viral sample used to produce the reference sequence and a wastewater sample from California. Additionally, our workflow demonstrated its capability to identify within-host diversity in foot-and-mouth disease virus (FMDV). Through our research, we were able to shed light on the binding affinity and phylogenetic relationships of these strains with the published SARS-CoV-2 reference genome, SARS-CoV, variants of concern (VOC) of SARS-CoV-2, and some closely related coronaviruses. These insights have important implications for future research efforts aimed at identifying within-host diversity, understanding the evolution and spread of these viruses, as well as the development of effective treatments and vaccines against them.

Impact of the COVID-19 outbreak on tourists' real-time on-site emotional experience in reopened tourism destinations

The COVID-19 pandemic that caused unprecedented havoc on global tourism industry will all blow over, however whether the tourists' real-time on-site emotional experience in the reopened tourism destinations is higher or lower than that of the period before the pandemic outbreak has not been studied. Since this is an important basis for managers to design tourist win-back strategies, this study empirically examines the impact of the COVID-19 outbreak on tourists' real-time on-site emotional experience using geo-tagged check-in user-generated content data in China's National 5A scenic spots from November 7, 2019 to April 8, 2020. Results show that although the COVID-19 pandemic doesn't destroy the tourist attractions, tourists' real-time on-site emotional experience after the outbreak of COVID-19 is significantly lower than that of the period before the COVID-19 outbreak, suggesting that tourism destinations should not only focus on the recovery of tourist arrivals, but also pay attention to the tourist experience recovery during the tourism recovery stage. Results also provide empirical evidence and practical implications for destinations in tourist experience management during and after the COVID-19 pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Combined Analysis of the Whole Transcriptome of Piglets Infected with SADS-CoV Virulent and Avirulent Strains.

When piglets are infected by virulent and avirulent strains of swine acute diarrhea syndrome coronavirus (SADS-CoV), there are obvious differences in their clinical symptoms; however, the specific mechanisms of pathogenicity and the immune regulation of highly pathogenic and low pathogenic strains are unknown. We collected intestinal tissues from SADS-CoV-infected piglets, performed a whole transcriptome sequencing analysis, including mRNA, miRNA, lncRNA, cicrRNA, and TUCP, and performed functional and correlation analyses of differentially expressed RNAs. Our results showed that the differentially expressed RNAs in group A versus group B (AvsB), group A versus group C (AvsC), and group B versus group C (BvsC) were relevant to immune and disease-related signaling pathways that participate in the organisms' viral infection and immune regulation. Furthermore, data obtained from the HAllA analysis suggested that there was a strong correlation between the differentially expressed RNAs. Specifically, LNC_011487 in the P set was significantly negatively correlated with ssc-miR-215, and LNC_011487 was positively correlated with PI3. Moreover, we also constructed a differentially expressed RNA association network map. This study provides a valuable resource for studying the SADS-CoV transcriptome and pathogenic mechanism from the perspective of RNA to understand the differences in and consistency of the interaction between virulent and attenuated SADS-CoV strains and hosts.

A non-contact oxygen saturation detection method based on dynamic spectrum.

Blood oxygen saturation (SpO2) is an important monitoring indicator for many respiratory diseases. Non-contact oximetry offers outstanding advantages in both coronavirus pandemic monitoring and sleep monitoring, but at the same time poses both challenges regarding technology and environment. Therefore, we propose a method for non-contact SpO2 measurement based on the principle of DS (dynamic spectrum) in this paper. A multispectral camera with 24 wavelengths (range in 660 nm-950 nm) is used to capture video of the people's cheek region, and then the two-dimensional images are converted into a one-dimensional temporal PPG signal. After pre-processing the PPG signal, the 24 wavelengths DS values are extracted. The optimal wavelength combination is obtained by wavelength screening using the one-by-one elimination method, and a PLS (partial least squares) model is established using the SpO2 values measured simultaneously by pulse oximetry as the modeled true values. The facial videos of eight healthy subjects were collected, and a total of 140 valid samples were obtained. By analyzing the modeling results, the regression coefficient (R) and root mean square error (RMSE) of the modeled set were 0.6366 and 0.9906, respectively. This method can significantly respond to the variation of SpO2, and the prediction results are approaching to the prediction accuracy (±2%) of most pulse oximeters in the market. Using DS theory in this method eliminates in principle the interference of static tissue, individual differences, and environment. It fully meets the strong demand for non-contact oximetry and provides a new measurement idea.

Density-based detection of cell transition states to construct disparate and bifurcating trajectories.

Tree- and linear-shaped cell differentiation trajectories have been widely observed in developmental biologies and can be also inferred through computational methods from single-cell RNA-sequencing datasets. However, trajectories with complicated topologies such as loops, disparate lineages and bifurcating hierarchy remain difficult to infer accurately. Here, we introduce a density-based trajectory inference method capable of constructing diverse shapes of topological patterns including the most intriguing bifurcations. The novelty of our method is a step to exploit overlapping probability distributions to identify transition states of cells for determining connectability between cell clusters, and another step to infer a stable trajectory through a base-topology guided iterative fitting. Our method precisely re-constructed various benchmark reference trajectories. As a case study to demonstrate practical usefulness, our method was tested on single-cell RNA sequencing profiles of blood cells of SARS-CoV-2-infected patients. We not only re-discovered the linear trajectory bridging the transition from IgM plasmablast cells to developing neutrophils, and also found a previously-undiscovered lineage which can be rigorously supported by differentially expressed gene analysis.

Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain.

Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

Impact of the COVID-19 outbreak on tourists’ real-time on-site emotional experience in reopened tourism destinations

The COVID-19 pandemic that caused unprecedented havoc on global tourism industry will all blow over, however whether the tourists' real-time on-site emotional experience in the reopened tourism destinations is higher or lower than that of the period before the pandemic outbreak has not been studied. Since this is an important basis for managers to design tourist win-back strategies, this study empirically examines the impact of the COVID-19 outbreak on tourists' real-time on-site emotional experience using geo-tagged check-in user-generated content data in China's National 5A scenic spots from November 7, 2019 to April 8, 2020. Results show that although the COVID-19 pandemic doesn't destroy the tourist attractions, tourists' real-time on-site emotional experience after the outbreak of COVID-19 is significantly lower than that of the period before the COVID-19 outbreak, suggesting that tourism destinations should not only focus on the recovery of tourist arrivals, but also pay attention to the tourist experience recovery during the tourism recovery stage. Results also provide empirical evidence and practical implications for destinations in tourist experience management during and after the COVID-19 pandemic.

Mental health status of primary school students during the coronavirus disease 2019 epidemic and its influencing factors

Objective To study the mental health status of primary school students and the factors influencing the mental health status during the coronavirus disease 2019 (COVID-19) epidemic. Methods Online questionnaire surveys were conducted among 3 600 primary school students aged 6-12 years in Jilin Province, China in April, 2020 (during the epidemic) and 3 089 primary school students in September, 2020 (during the regular epidemic prevention and control). The general information and the data related to the Mental Health Scale for Child and Adolescent were collected by the questionnaire surveys. The multivariate logistic regression analysis was used to evaluate the factors influencing the mental health status of the students during the epidemic. Results The students during the epidemic had a significantly poorer mental health status in the emotional experience and volitional behavior than those during the regular epidemic prevention and control (P<0.05). The multivariate logistic regression analysis showed the risk of psychological problems of the students decreased with age (OR=0.895). The girls were at a higher risk of psychological problems than boys (OR=1.453). The students with father's and mother's charater between irritability and gentle were at a lower risk of psychological problems (OR=0.496 and 0.470 respectively). The students from a family with a parental education style of a combination of encouraging and scolding were at a lower risk of psychological problems (OR=0.263). The students from a single-parent family or an extended family were at a higher risk of psychological problems (OR=2.995 and 3.446 respectively). Conclusions The COVID-19 epidemic has a certain impact on emotional experience and volitional behavior of primary school students. During the epidemic, particular attention should be paid to the mental health of primary school students, especially girls, younger students, and students from single-parent families, extended families or families with impatient parents and improper parental education.

Translating daily COVID-19 screening into a simple glucose test: a proof of concept study.

Home testing is an attractive emerging strategy to combat the COVID-19 pandemic and prevent overloading of healthcare resources through at-home isolation, screening and monitoring of symptoms. However, current diagnostic technologies of SARS-CoV-2 still suffer from some drawbacks because of the tradeoffs between sensitivity, usability and costs, making the test unaffordable to most users at home. To address these limitations, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPRs) and a portable glucose meter (PGM), we present a proof-of-concept demonstration of a target-responsive CRISPR-PGM system for translating SARS-CoV-2 detection into a glucose test. Using this system, a specific N gene, N protein, and pseudo-viruses of SARS-CoV-2 have been detected quantitatively with a PGM. Given the facile integration of various bioreceptors into the CRISPR-PGM system, the proposed method provides a starting point to provide patients with a single-device solution that can quantitatively monitor multiple COVID-19 biomarkers at home.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-ß production via blocking IPS-1 and RIG-I.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly emerging enteric coronavirus, is considered to be associated with swine acute diarrhea syndrome (SADS) which has caused significantly economic losses to the porcine industry. Interactions between SADS-CoV and the host innate immune response is unclear yet. In this study, we used IPEC-J2 cells as a model to explore potential evasion strategies employed by SADS-CoV. Our results showed that SADS-CoV infection failed to induce IFN-ß production, and inhibited poly (I:C) and Sendai virus (SeV)-triggered IFN-ß expression. SADS-CoV also blocked poly (I:C)-induced phosphorylation and nuclear translocation of IRF-3 and NF-κB. Furthermore, SADS-CoV did not interfere with the activity of IFN-ß promoter stimulated by IRF3, TBK1 and IKKε, but counteracted its activation induced by IPS-1 and RIG-I. Collectively, this study is the first investigation that shows interactions between SADS-CoV and the host innate immunity, which provides information of the molecular mechanisms underlying SASD-CoV infection.

Microfluidic-RT-LAMP chip for the point-of-care detection of emerging and re-emerging enteric coronaviruses in swine.

Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are three emerging and re-emerging coronaviruses (CoVs). Symptoms caused by these three viruses are extremely similar, including acute diarrhea, vomiting and even death in piglets. To date, strict biosecurity is still the most effective disease prevention and control measures, and the early detection of pathogens is the most important link. Here, we developed a microfluidic-RT-LAMP chip detection system for the first time, which could detected PEDV, PDCoV and SADS-CoV simultaneously, and had advantages of rapid, simple, sensitive, high-throughput, and accurate at point-of-care settings. The lowest detection limits of the microfluidic-RT-LAMP chip method are 101 copies/µL, 102 copies/µL and 102 copies/µL for PEDV, PDCoV and SADS-CoV, respectively. The whole detection procedure can be finished rapidly in 40 min without any cross-reaction with other common swine viruses. A total of 173 clinical swine fecal samples characterized with diarrheal symptoms were used to evaluate the performance of the newly developed system, which presented good stabilities (C.V.s<5%) and specificities (100%), and possessed sensitivities of 92.24%, 92.19% and 91.23% for PEDV, PDCoV and SADS-CoV respectively. In summary, the established microfluidic-RT-LAMP chip detection system could satisfy the demanding in field diagnoses, which was suitable for promotion in remote areas due to its fast, portable and cost-effective characters.