SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril.

Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics.

Selective Catalytic Epoxidation-Hydration of α-Pinene with Hydrogen Peroxide to Sobrerol by Durable Ammonium Phosphotungstate Immobilized on Imidazolized Activated Carbon.

It is presented that the activated carbon was carboxylated with hydrogen peroxide and then acylated with 2-methylimidazole to prepare the porous carbon support with a surface imidazolated modification. Through the adsorption of phosphotungstic acid on the fundamental site of an imidazolyl group and then adjusting the acid strength with the ammonia molecule, a catalytic carbon material immobilized with ammonium phosphotungstate (AC-COIMO-NH4PW) was obtained, which was used to catalyze a one-pot reaction of convenient α-pinene and hydrogen peroxide to sobrerol. The bifunctional active site originated from the dual property of ammonium phosphotungstate, as the oxidant and acid presenting a cooperatively catalytic performance, which effectively catalyzes the tandem epoxidation-isomerization-hydration of α-pinene to sobrerol, in which the solvent effect of catalysis simultaneously exists. The sobrerol selectivity was significantly improved after the acid strength weakening by ammonia. Monomolecular chemical bonding and anchoring of ammonium phosphotungstate at the basic site prevented the loss of the active catalytic species, and the recovered catalyst showed excellent catalytic stability in reuse. Using acetonitrile as the solvent at 40 °C for 4 h, the conversion of α-pinene could reach 90.6%, and the selectivity of sobrerol was 40.5%. The results of five cycles show that the catalyst presents excellent stability due to the tight immobilization of ammonium phosphotungstate bonding on the imidazolized activated carbon, based on which a catalytic-cycle mechanism is proposed for the tandem reaction.

Physician education on World Asthma Day aids in disease management during the COVID-19.

Anxiety and depression can negatively affect the management of asthma. The study aimed to assess the psychosocial effects of asthma patients during COVID-19 and analyze potential risk factors and interventions.In June 2022, the "Questionnaire Star" electronic questionnaire system was used to collect data. A total of 98 asthma patients from the affiliated hospital of the medical school of Ningbo University were invited to complete the questionnaires. According to our study, the prevalence of symptoms of anxiety and depression in the asthma patients in the institution was 91.8 and 77.6%, respectively. Patients who had an asthma exacerbation in the previous two months were more likely to have anxiety symptoms (OR = 0.142 95%CI 0.025-0.820), while patients who did not participate in asthma day activities were more likely to have anxiety symptoms than those who did (OR = 0.130 95%CI 0.022-0.762).This study found that routine disease educational lectures on asthma day can successfully alleviate asthma sufferers' anxiety and depression.

Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), has infected hundreds of millions of people and caused millions of deaths. Looking for valid druggable targets with minimal side effects for the treatment of COVID-19 remains critical. After discovering host genes from multiscale omics data, we developed an end-to-end network method to investigate drug-host gene(s)-coronavirus (CoV) paths and the mechanism of action between the drug and the host factor in a directional network. We also inspected the potential side effect of the candidate drug on several common comorbidities. We established a catalog of host genes associated with three CoVs. Rule-based prioritization yielded 29 Food and Drug Administration (FDA)-approved drugs via accounting for the effects of drugs on CoVs, comorbidities, and drug-target confidence information. Seven drugs are currently undergoing clinical trials as COVID-19 treatment. This catalog of druggable host genes associated with CoVs and the prioritized repurposed drugs will provide a new sight in therapeutics discovery for severe COVID-19 patients.

Evaluation and driving factors of land use economic efficiency in China's urban agglomerations under the impact of COVID-19 epidemic.

Land is an indispensable factor of production and the basic support for all social and economic activities. The COVID-19 epidemic has a great impact on China's macro-economy and land market. As a unit with a high concentration of economic entities, urban agglomeration is closely related to its land use economic efficiency. Under the impact of epidemic and the rigid constraints of the relative scarcity of land resources, improving the land use economic efficiency is crucial to the sustainable development of urban agglomerations. Taking the 10 major urban agglomerations in China as a case study, this paper constructs a theoretical and empirical analysis framework for the land use economic efficiency and its driving mechanism of urban agglomerations, and measures the land use economic efficiency of urban agglomerations from the aspects of single factor productivity and total factor productivity. The results show that the COVID-19 epidemic has a great impact on the land market of various cities in China's urban agglomerations. Whether single factor productivity or total factor productivity is used to measure land use economic efficiency of urban agglomerations, the driving effects of industrial agglomeration, industrial structure change, technological progress, and transportation infrastructure are all significant. It is necessary to take a series of measures to reform the market-oriented allocation of land elements, and improve a long-term mechanism for the smooth operation of the land market. It is necessary to improve the land use economic efficiency through a combination of industrial agglomeration, industrial structure adjustment, technological progress, and transportation infrastructure.

Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice.

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

Has Tourism Industry Agglomeration Improved the Total Factor Productivity of Chinese Urban Agglomerations?-The Moderating Effect of Public Epidemic.

Industry agglomeration has become a prominent feature of tourism industry development in developed and developing countries and regions in the world. According to the literature analysis, the development of industrial agglomeration has both agglomeration effect and congestion effect. This paper constructs a theoretical and empirical analysis framework for the impact of tourism industry agglomeration on the total factor productivity of Chinese urban agglomerations, and analyze the moderating effect of the public epidemic on this impact. From results of empirical analysis, a U-shaped relationship exists between tourism industry agglomeration and the total factor productivity of Chinese urban agglomerations. The public epidemic positively moderated (enhanced) the negative effect (congestion effect) of tourism industry agglomeration on total factor productivity, and negatively moderated (weakened) the positive effect (agglomeration effect) of tourism industry agglomeration on total factor productivity.

The Psychological Impact of the Tertiary Hospital Reappraisal on Resident Doctors in the Post-pandemic Era: A Cross-sectional Study in Ningbo.

PARTICIPANTS: Competent resident doctor were expected to help the patients, advance medical knowledge, and promote public health. The time and effort necessary for residents to devote to standarized training is extensive. Anxiety and depression can negatively affect professional development and work efficacy. The study aimed to assess the psychosocial effects of the hospital reappraisal during the post-pandemic era of COVID-19 and analyze potential risk factors leading to their symptoms of anxiety and depression. METHOD: In March 2021, the "Questionnaire Star" electronic questionnaire system was used to collect data. A total of 96 resident doctors from the affiliated hospital of the medical school of Ningbo University were invited to complete the questionnaires. RESULTS: According to our study, the prevalence of symptoms of anxiety and depression in the resident doctors in the institution was 61.5 and 59.4%, respectively. The residents who were worried about clinical skills tend to have anxiety symptoms under online education (OR = 3.436, 95%CI: 1.122-10.526). Compared with participants who were assigned by other hospitals, social trainees (OR: 7.579, 95%CI: 1.747-32.885), and full-time masters (OR: 5.448, 95% CI: 1.586-18.722) were more likely to have anxiety symptoms. Participants without a labor contract (OR = 3.257, 95% CI: 1.052-10.101) had a high risk of depression symptoms. Participants who spent more time learning the details prepared for the tertiary hospital reappraisal were significantly more likely to develop anxiety and depressive symptoms. CONCLUSION: This study suggested that the tertiary hospital reappraisal program has an impact on the high incidence of anxiety and depression of the young resident doctors during the post-pandemic era of the COVID-19 in Ningbo.

The Impact of Network Embeddedness on the Innovation Performance of New Generation of Employees in the Post-COVID-19 Era-The Mediating Role of Psychological Contract.

The innovation activities of new generation of employees have the characteristics of double network embeddedness, and the degree of psychological contract fulfilment is an important factor that affects their innovation performance. Based on the attributes of internal network embeddedness and external network embeddedness, this paper builds a hypothesis model of the relationship between network embeddedness, psychological contract and innovation performance. It explores the impact and mechanism of network embeddedness on the innovation performance of new generation of employees and the mediating role of the psychological contract. Empirical research shows that network embeddedness has a positive effect on the innovation performance of new generation of employees. The psychological contract has a mediating role in network embeddedness on innovation performance of new generation of employees. These conclusions continue and deepen the research on network embeddedness and innovation performance and further enrich and expand the application of social networks in the research of individual innovation performance of new generation of employees.

The Impact of Network Embeddedness on the Innovation Performance of New Generation of Employees in the Post-COVID-19 Era—The Mediating Role of Psychological Contract

The innovation activities of new generation of employees have the characteristics of double network embeddedness, and the degree of psychological contract fulfilment is an important factor that affects their innovation performance. Based on the attributes of internal network embeddedness and external network embeddedness, this paper builds a hypothesis model of the relationship between network embeddedness, psychological contract and innovation performance. It explores the impact and mechanism of network embeddedness on the innovation performance of new generation of employees and the mediating role of the psychological contract. Empirical research shows that network embeddedness has a positive effect on the innovation performance of new generation of employees. The psychological contract has a mediating role in network embeddedness on innovation performance of new generation of employees. These conclusions continue and deepen the research on network embeddedness and innovation performance and further enrich and expand the application of social networks in the research of individual innovation performance of new generation of employees.

SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury.

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. In this study, we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation altered various signaling pathways in alveolar epithelial cells, particularly, the induction of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

Longitudinal Peripheral Blood Transcriptional Analysis Reveals Molecular Signatures of Disease Progression in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients developing severe illness or even death. Disease severity has been associated with increased levels of proinflammatory cytokines and lymphopenia. To elucidate the atlas of peripheral immune response and pathways that might lead to immunopathology during COVID-19 disease course, we performed a peripheral blood RNA sequencing analysis of the same patient's samples collected from symptom onset to full recovery. We found that PBMCs at different disease stages exhibited unique transcriptome characteristics. We observed that SARS-CoV-2 infection caused excessive release of inflammatory cytokines and lipid mediators as well as an aberrant increase of low-density neutrophils. Further analysis revealed an increased expression of RNA sensors and robust IFN-stimulated genes expression but a repressed type I IFN production. SARS-CoV-2 infection activated T and B cell responses during the early onset but resulted in transient adaptive immunosuppression during severe disease state. Activation of apoptotic pathways and functional exhaustion may contribute to the reduction of lymphocytes and dysfunction of adaptive immunity, whereas increase in IL2, IL7, and IL15 may facilitate the recovery of the number and function of lymphocytes. Our study provides comprehensive transcriptional signatures of peripheral blood response in patients with moderate COVID-19.