Porcine Deltacoronavirus Infection Disrupts the Intestinal Mucosal Barrier and Inhibits Intestinal Stem Cell Differentiation to Goblet Cells via the Notch Signaling Pathway.

Goblet cells and their secreted mucus are important elements of the intestinal mucosal barrier, which allows host cells to resist invasion by intestinal pathogens. Porcine deltacoronavirus (PDCoV) is an emerging swine enteric virus that causes severe diarrhea in pigs and causes large economic losses to pork producers worldwide. To date, the molecular mechanisms by which PDCoV regulates the function and differentiation of goblet cells and disrupts the intestinal mucosal barrier remain to be determined. Here, we report that in newborn piglets, PDCoV infection disrupts the intestinal barrier: specifically, there is intestinal villus atrophy, crypt depth increases, and tight junctions are disrupted. There is also a significant reduction in the number of goblet cells and the expression of MUC-2. In vitro, using intestinal monolayer organoids, we found that PDCoV infection activates the Notch signaling pathway, resulting in upregulated expression of HES-1 and downregulated expression of ATOH-1 and thereby inhibiting the differentiation of intestinal stem cells into goblet cells. Our study shows that PDCoV infection activates the Notch signaling pathway to inhibit the differentiation of goblet cells and their mucus secretion, resulting in disruption of the intestinal mucosal barrier. IMPORTANCE The intestinal mucosal barrier, mainly secreted by the intestinal goblet cells, is a crucial first line of defense against pathogenic microorganisms. PDCoV regulates the function and differentiation of goblet cells, thereby disrupting the mucosal barrier; however, the mechanism by which PDCoV disrupts the barrier is not known. Here, we report that in vivo, PDCoV infection decreases villus length, increases crypt depth, and disrupts tight junctions. Moreover, PDCoV activates the Notch signaling pathway, inhibiting goblet cell differentiation and mucus secretion in vivo and in vitro. Thus, our results provide a novel insight into the mechanism underlying intestinal mucosal barrier dysfunction caused by coronavirus infection.

Non-commuting intentions during COVID-19 in Nanjing, China: A hybrid latent class modeling approach.

Non-commuting travel is essential for people to meet daily demands and regulate mental health, which is greatly disrupted due to the COVID-19 pandemic. To explore non-commuting intentions during COVID-19 across different groups of residents, this paper uses online survey data in Nanjing and constructs a hybrid latent class choice model that combines sociodemographic characteristics and psychological factors. Results showed that the respondents can be divided into two groups: the "cautious" group versus the "fearless" group. The "cautious" group with lower willingness to travel tend to be older, higher-income, higher-educated, female and full-time employees. Furthermore, the "cautious" group with higher perceived susceptibility is more obedient to government policies. In contrast, the "fearless" group is significantly affected by perceived severity and is more inclined to turn to personal protection against the pandemic. These results suggested that non-commuting trips were influenced not only by individual characteristics but also by psychological factors. Finally, the paper provides implications for the government to formulate COVID-19 management measures for the heterogeneity of different groups.

Non-commuting intentions during COVID-19 in Nanjing, China: A hybrid latent class modeling approach

Non-commuting travel is essential for people to meet daily demands and regulate mental health, which is greatly disrupted due to the COVID-19 pandemic. To explore non-commuting intentions during COVID-19 across different groups of residents, this paper uses online survey data in Nanjing and constructs a hybrid latent class choice model that combines sociodemographic characteristics and psychological factors. Results showed that the respondents can be divided into two groups: the "cautious” group versus the "fearless” group. The "cautious” group with lower willingness to travel tend to be older, higher-income, higher-educated, female and full-time employees. Furthermore, the "cautious” group with higher perceived susceptibility is more obedient to government policies. In contrast, the "fearless” group is significantly affected by perceived severity and is more inclined to turn to personal protection against the pandemic. These results suggested that non-commuting trips were influenced not only by individual characteristics but also by psychological factors. Finally, the paper provides implications for the government to formulate COVID-19 management measures for the heterogeneity of different groups.

Understanding the influence of technological capability and exogenous pressure on business model dynamics: insights from a longitudinal case study

PurposeThe purpose of the study is to explore how technological capability and exogenous pressure interactively influence business model (BM) dynamics over time in new technology-based ventures.Design/methodology/approachThe study adopts a longitudinal case study of the BM innovations of a Chinese financial technology venture. The structural approach and temporal bracket are used to analyze and theorize the data.FindingsThe findings indicate that distinct contextual changes impel a firm to refine or abandon existing BMs over time. In different stages, the antecedents interactively influence BM dynamics with three successive patterns, namely pressure dominance, parallel influence and hybrid influence. While both antecedents trigger changes during the initiation and implementation of new BMs, they also serve as the filter and the enabler, respectively, during the ideation and integration of BMs.Research limitations/implicationsThe study inductively develops three propositions regarding the relationship between BM dynamics and its antecedents, which is based on the data collected from one single firm. Future research should test the propositions in other domains and take more cross-level antecedents into consideration.Originality/valueThe study contributes to the nascent research stream of BM dynamics by offering in-depth insights into the interaction of internal and external antecedents and by linking the differentiated roles of antecedents to the BM innovation process. The research offers some practical implications for new technology-based ventures seeking to develop BMs in a fast-changing environment.

Supply Chain Resilience of Mineral Resources Industry in China

Improving the supply chain resilience of the mineral resources industry is crucial for ensuring national economic security in China. Based on the supply and demand data of China's mineral resources industry from 2002 to 2018, this study adopts system dynamics model to simulate the supply chain resilience of the mineral resources industry, the mining industry, and the smelting and processing industry under the scenario of steady economic development and the scenario of supply chain crisis. From the simulation results, the reserves of the mineral resources industry and the smelting and processing industry under the two scenarios are nearly the same, indicating that they are weakly affected by the foreign market, and both have strong resilience. The mining industry has a high dependence on imports and a lack of supply chain resilience. Under the condition of steady economic development, the output of the mining industry needs to develop at a low speed to reduce production capacity. More attention should be paid to the high level of import dependence and insufficient supply chain resilience of the mining industry. In the stable international trade situation, reserves of important minerals should be increased to alleviate the resource shortage during the supply chain crisis.

A comparative study about attitudes towards the efficiency, effectiveness, and atmosphere of offline and online learning among medical students.

Background: In recent decades, the mode of education has changed, and online learning via the Internet has gradually entered the medical education system. During the Coronavirus disease 2019 pandemic, online learning rapidly became one of the main learning methods for medical students, this has impacted medical undergraduates and postgraduates to varying degrees; however, currently, little is known about its effectiveness as a learning mode. Methods: This study included undergraduates and postgraduates in medical schools at some universities in China. The student participants were asked to complete a questionnaire survey in which they self-evaluated the learning effectiveness, learning efficiency, learning atmosphere, and other issues associated with online and offline learning. SPSSAU was used to analyze the acquired data. Results: Most medical students expressed the view that offline learning was superior to online learning in terms of effectiveness, efficiency, and atmosphere. However, online learning was better in terms of the acquisition of learning resources and flexibility. The attitudes of medical undergraduates and postgraduates participating in this research were largely similar (P>0.05); however, undergraduates placed a higher value on offline learning than postgraduates (P<0.05). Conclusions: Both online and offline learning have advantages and disadvantages. The differences between undergraduates and postgraduates may be related to subtle differences in the training objectives at these 2 levels of medical education. Combining the advantages of online and offline learning may improve the learning of medical students.

Changes in Physical Activity and Health Indicators among Koreans during the COVID-19 Pandemic: Comparison between 2019 and 2020.

This study aimed to compare the changes in physical activity (PA), chronic disease, and mental health indicators of Koreans before and after the COVID-19 outbreak, using raw data from more than 400,000 representative samples from the 2019-2020 Community Health Survey by the Korea Centers for Disease Control and Prevention, and to explore the correlations among them. We used two-way ANOVA to analyze changes and differences in PA and obesity levels. We assessed the influence of gender and recurrent PA using chi-square tests for mental health status and chronic disease. Finally, we performed a correlation analysis to determine the relationships among PA days, mental health, and chronic disease. The results showed that, compared to the levels before the COVID-19 period, moderate-intensity (Days: 1.415~1.217; Time: 114.688~107.321) and high-intensity (Days: 0.798~0.671; Time: 112.866~106.110) PA significantly decreased in Koreans during the COVID-19 period, while low-intensity (Time: 60.305~61.735) PA increased. Before and during the COVID-19 period, men (18,436 (8.1%)~16,124 (7.0%)) performed PA more regularly than women (13,207 (5.8%)~9382 (4.1%)). Compared to the number of regular PA participants before the COVID-19 period, regular PA participants (male, female) decreased from 31,643 (13.8%) to 25,506 (11.1%) during the COVID-19 period. Compared with the levels before the COVID-19 period, the experience rates of stress (3.1%~2.6%), depression (0.8%~0.6%), HBP (3.0%~2.2%), and diabetes (1.2%~0.9%) significantly changed under different levels of conventional PA intervention. In addition, the obesity rate during the COVID-19 period (23.957) was higher than it was before COVID-19 (23.477). During the COVID-19 period, the PA of Koreans was greatly restricted, but low-intensity PA was maintained and increased. PA is an effective activity for maintaining mental health and for preventing and reducing chronic diseases. Recommendations for appropriate intensity or a combination of high-, moderate-, and low-intensity PA should be based on the health status of Koreans to help them maintain mental health and to reduce the risk of chronic diseases during COVID-19 social distancing.

The impact of COVID-19 pandemic on treatment delay and short-term neurological functional prognosis for acute ischemic stroke during the lockdown period

Background Preventive strategies implemented during the COVID-19 pandemic may negatively influence the management of patients with acute ischemic stroke (AIS). Nowadays, studies have demonstrated that the pandemic has led to a delay in treatment among patients with AIS. Whether this delay contributes to meaningful short-term outcome differences warranted further exploration. Objective The objective of this study was to evaluate the impacts of the COVID-19 pandemic on treatment delay and short-term outcomes of patients with AIS treated with IVT and MT. Methods Patients admitted before (from 11/1/2019 to 1/31/2020) and during the COVID-19 pandemic (from 2/1/2020 to 3/31/2020) were screened for collecting sociodemographic data, medical history information, and symptom onset status, and comparing the effect of treatment delay. The patients treated with IVT or MT were compared for delay time and neurological outcomes. Multivariable logistic regression was used to estimate the effect of treatment delay on short-term neurological prognosis. Results In this study, 358 patients receiving IVT were included. DTN time increased from 50 min (IQR 40–75) before to 65 min (IQR 48–84), p = 0.048. 266 patients receiving MT were included. The DTP was 120 (112–148) min vs. 160 (125-199) min before and during the pandemic, p = 0.002. Patients with stroke during the pandemic had delays in treatment due to the need for additional PPE (p < 0.001), COVID-19 screening processes (p < 0.001), multidisciplinary consultation (p < 0.001), and chest CT scans (p < 0.001). Compared with pre-COVID-19, during the pandemic, patients had a higher likelihood of spontaneous intracranial hemorrhage after IVT (OR: 1.10;95% CI, 1.03–1.30) and a lower likelihood of mRS scores 0–2 at discharge (OR: 0.90;95% CI, 0.78–0.99). In logistic regression analysis, high NIHSS score at admission, increasing age, worse pre-admission mRS, large vessel occlusion, admission during the lockdown period, and low mTICI grade after MT were associated with an mRS ≥ 3. Conclusion The COVID-19 pandemic has had remarkable impacts on the management of AIS. The pandemic might exacerbate certain time delays and play a significant role in early adverse outcomes in patients with AIS.

Impact of glycemia and insulin treatment in fatal outcome of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. METHODS: A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] ≥7 mmol/L), postadmission hyperglycemia (admission FPG <7 mmol/L but FPG ≥7 mmol/L after admission), and euglycemia (FPG <7 mmol/L throughout hospitalization) were compared for their clinical progress and outcomes. RESULTS: A total of 3225 patients were included in this study, 37.9% of whom developed acute hyperglycemia and 7.6% postadmission hyperglycemia. The presence of acute hyperglycemia, with or without known diabetes, was associated with increased risk of death (odds ratio [OR]: 1.63; 95% confidence interval [CI]: 1.29-2.05) compared with euglycemia. This effect, however, was only determined in female patients (OR: 2.15; 95% CI: 1.54-2.93). Insulin treatment of patients with SFTS and acute hyperglycemia without previous diabetes was associated with significantly increased mortality (OR: 1.58; 95% CI: 1.16-2.16). CONCLUSION: Acute hyperglycemia can act as a strong predictor of SFTS-related death in female patients. Insulin treatment of hyperglycemia in patients with SFTS without pre-existing diabetes has adverse effects.

Immune Responses Induced by Recombinant Bacillus subtilis Expressing the PEDV Spike Protein Targeted at Microfold Cells.

Bacillus subtilis (B. subtilis), a probiotic bacterium and feeding additive, is widely used for heterologous antigen expression and protective immunisation. Porcine epidemic diarrhoea virus (PEDV) invades swine via mucosal tissue. To enhance the mucosal immune response to PEDV, we modified B. subtilis to express a PEDV antigen and used it as a mucosal vaccine delivery system. Initially, we constructed a recombinant B. subtilis strain (B.s-RCL) that expressed the PEDV spike protein and L-Lectin-ß-GF, with the goal of inducing mucosal secretory immunoglobulin A (sIgA) and anti-PEDV serum immunoglobulin G (IgG) production, as well as to increase the number of microfold cells (M cells). Following the oral administration of B.s-RCL to mice, the small intestinal PEDV-specific sIgA expression levels significantly increased, as well as the increased number of B.s-RCL adhered to M cells. Moreover, we found that mice administered B.s-RCL exhibited markedly higher percentages of CD4+ and CD8+ T cells in the mesenteric lymph nodes and spleen compared to the control mice. Furthermore, we found that intestinal mucosa sIgA and serum anti-PEDV IgG levels were higher in mice orally immunised with B.s-RCL, suggesting that the mice could be more resistant to PEDV. In this study, we developed a novel oral vaccine to prevent porcine diarrhoea epidemics.

Destination Personality and Behavioral Intention in Hainan's Golf Tourism during COVID-19 Pandemic: Mediating Role of Destination Image and Self-Congruity

The aim of this study was (a) to investigate the relationship between destination personality (DP), destination image (DI), self-congruity (SC), and behavioral intention (BI) in the context of golf tourism and (b) to examine the mediating roles of DI and SC in the relationship between DP and BI. We collected valid data about 519 golf tourists who visited Hainan, China in 2021. The results show that DP positively affected DI, DP positively affected BI, DP positively affected SC, SC positively affected BI, and DI positively affected BI. In addition, DI positively mediated the relationship between DP and BI, and SC positively mediated the relationship between DP and BI. The findings enrich the tourism literature, contribute to the exploration of golf tourism theory, and provide recommendations for golf tourism researchers and marketers.

NetNMSP: Nonoverlapping maximal sequential pattern mining

Nonoverlapping sequential pattern mining, as a kind of repetitive sequential pattern mining with gap constraints, can find more valuable patterns. Traditional algorithms focused on finding all frequent patterns and found lots of redundant short patterns. However, it not only reduces the mining efficiency, but also increases the difficulty in obtaining the demand information. To reduce the frequent patterns and retain its expression ability, this paper focuses on the Nonoverlapping Maximal Sequential Pattern (NMSP) mining which refers to finding frequent patterns whose super-patterns are infrequent. In this paper, we propose an effective mining algorithm, Nettree for NMSP mining (NetNMSP), which has three key steps: calculating the support, generating the candidate patterns, and determining NMSPs. To efficiently calculate the support, NetNMSP employs the backtracking strategy to obtain a nonoverlapping occurrence from the leftmost leaf to its root with the leftmost parent node method in a Nettree. To reduce the candidate patterns, NetNMSP generates candidate patterns by the pattern join strategy. Furthermore, to determine NMSPs, NetNMSP adopts the screening method. Experiments on biological sequence datasets verify that not only does NetNMSP outperform the state-of-the-arts algorithms, but also NMSP mining has better compression performance than closed pattern mining. On sales datasets, we validate that our algorithm guarantees the best scalability on large scale datasets. Moreover, we mine NMSPs and frequent patterns in SARS-CoV-1, SARS-CoV-2 and MERS-CoV. The results show that the three viruses are similar in the short patterns but different in the long patterns. More importantly, NMSP mining is easier to find the differences between the virus sequences.

Identification of Novel COVID-19 Biomarkers by Multiple Feature Selection Strategies.

Coronavirus disease 2019 (COVID-19) arising from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic since its first report in December 2019. So far, SARS-CoV-2 nucleic acid detection has been deemed as the golden standard of COVID-19 diagnosis. However, this detection method often leads to false negatives, thus triggering missed COVID-19 diagnosis. Therefore, it is urgent to find new biomarkers to increase the accuracy of COVID-19 diagnosis. To explore new biomarkers of COVID-19 in this study, expression profiles were firstly accessed from the GEO database. On this basis, 500 feature genes were screened by the minimum-redundancy maximum-relevancy (mRMR) feature selection method. Afterwards, the incremental feature selection (IFS) method was used to choose a classifier with the best performance from different feature gene-based support vector machine (SVM) classifiers. The corresponding 66 feature genes were set as the optimal feature genes. Lastly, the optimal feature genes were subjected to GO functional enrichment analysis, principal component analysis (PCA), and protein-protein interaction (PPI) network analysis. All in all, it was posited that the 66 feature genes could effectively classify positive and negative COVID-19 and work as new biomarkers of the disease.

Characterizing the COVID-19 Infodemic on Chinese Social Media: Exploratory Study.

BACKGROUND: The COVID-19 infodemic has been disseminating rapidly on social media and posing a significant threat to people's health and governance systems. OBJECTIVE: This study aimed to investigate and analyze posts related to COVID-19 misinformation on major Chinese social media platforms in order to characterize the COVID-19 infodemic. METHODS: We collected posts related to COVID-19 misinformation published on major Chinese social media platforms from January 20 to May 28, 2020, by using PythonToolkit. We used content analysis to identify the quantity and source of prevalent posts and topic modeling to cluster themes related to the COVID-19 infodemic. Furthermore, we explored the quantity, sources, and theme characteristics of the COVID-19 infodemic over time. RESULTS: The daily number of social media posts related to the COVID-19 infodemic was positively correlated with the daily number of newly confirmed (r=0.672, P<.01) and newly suspected (r=0.497, P<.01) COVID-19 cases. The COVID-19 infodemic showed a characteristic of gradual progress, which can be divided into 5 stages: incubation, outbreak, stalemate, control, and recovery. The sources of the COVID-19 infodemic can be divided into 5 types: chat platforms (1100/2745, 40.07%), video-sharing platforms (642/2745, 23.39%), news-sharing platforms (607/2745, 22.11%), health care platforms (239/2745, 8.71%), and Q&A platforms (157/2745, 5.72%), which slightly differed at each stage. The themes related to the COVID-19 infodemic were clustered into 8 categories: "conspiracy theories" (648/2745, 23.61%), "government response" (544/2745, 19.82%), "prevention action" (411/2745, 14.97%), "new cases" (365/2745, 13.30%), "transmission routes" (244/2745, 8.89%), "origin and nomenclature" (228/2745, 8.30%), "vaccines and medicines" (154/2745, 5.61%), and "symptoms and detection" (151/2745, 5.50%), which were prominently diverse at different stages. Additionally, the COVID-19 infodemic showed the characteristic of repeated fluctuations. CONCLUSIONS: Our study found that the COVID-19 infodemic on Chinese social media was characterized by gradual progress, videoization, and repeated fluctuations. Furthermore, our findings suggest that the COVID-19 infodemic is paralleled to the propagation of the COVID-19 epidemic. We have tracked the COVID-19 infodemic across Chinese social media, providing critical new insights into the characteristics of the infodemic and pointing out opportunities for preventing and controlling the COVID-19 infodemic.

Comparison of clinical characteristics among younger and elderly deceased patients with COVID-19: a retrospective study.

We aimed to compare the age-related clinical characteristics between younger and elderly deceased COVID-19 patients. This single-center retrospective study included 163 adult deceased COVID-19 patients who were admitted to Wuhan Union Hospital West Campus from January 12, 2020, to March 30, 2020. Demographic and clinical features were collected by reviewing the medical records. The median age of the 163 deceased patients was 69 (interquartile range [IQR], 62-78) years. They were classified as younger (age 18-69 years; 86/163, 52.8%) and elderly (≥70 years; 77/163, 47.2%) subjects. Younger deceased patients were more likely to develop fever (72/86 vs 54/77, P=0.039) than elderly deceased patients were while anorexia was (29/77 vs 19/86, P=0.029) more common in elderly deceased patients than in younger deceased patients. In multivariate analyses, age was a protective factor for acute cardiac injury of deceased COVID-19 patients (odds ratio [OR] 0.968, [95% confidence interval (CI), 0.940-0.997]; P=0.033) while chronic cardiac disease was a risk factor for acute cardiac injury of deceased COVID-19 patients (OR 2.660 [95%CI, 1.034-6.843]; P=0.042). Our study described the clinical characteristics of younger and elderly deceased COVID-19 patients and demonstrated that younger deceased patients were more likely to develop an acute cardiac injury.

Nucleic acid detection analysis of 71 cases of COVID-19 with biological samples of diferent disease course

Objective: To study the nucleic acid detection results of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in different biological samples of COVID-19 (coronavirus disease 2019, COVID-19) patients in different stages, and we analyze the results and clinical significance.

Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan, China: a multicentre retrospective cohort study.

OBJECTIVES: To describe the fraction of asymptomatic health-care workers (HCWs) in two designated hospitals for coronavirus disease 2019 (COVID-19) treatment in Wuhan and explore the factors associated with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: All HCWs in Wuhan Union Hospital and Wuhan Red Cross Hospital with either positive SARS-CoV-2 nucleic acid or positive antibody test before 18 April 2020 were included. Exposure, epidemiological and demographic information were retrospectively collected by a structured questionnaire. Medical records were also reviewed for clinical characteristics and CT images of HCWs. RESULTS: As of 18 April 2020, a total of 424 HCWs were identified. Among them, 276 (65.1%) were symptomatic and 148 (34.9%) were asymptomatic. Fifty-five (19.9%) families of the symptomatic HCWs and 16 (10.8%) families of the asymptomatic HCWs were infected with SARS-CoV-2. HCWs with infected family members tended to be symptomatic (OR 2.053, 95% CI 1.130-3.730; p 0.018). Multivariable logistic regression analysis exhibited that performing tracheal intubation or extubation (OR 4.057, 95% CI 1.183-13.909; p 0.026) was associated with an increased likelihood of symptomatic SARS-CoV-2 infection, whereas consistent use of N95 respirators (OR 0.369, 95% CI 0.201-0.680; p 0.001) and eye protection (OR 0.217, 95% CI 0.116-0.404; p < 0.001) were associated with an increased likelihood of asymptomatic SARS-CoV-2 infection. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection in HCWs comprised a considerable proportion of HCW infections during the pandemic of COVID-19. Those who performed tracheal intubation or extubation were most likely to develop related symptoms, whereas those taking aggressive measures, including consistent use of N95 masks and eye protection, tended to be asymptomatic cases.