SARS-CoV-2-Induced Autoimmune Hepatitis.

Few case reports discuss the incidences of autoimmune hepatitis (AIH) in patients after SARS-CoV-2 infection. Here, we present a case of SARS-CoV-2-induced AIH in a male patient who came into the emergency department with complaints of weight loss, poor oral intake, nausea, dark-colored urine, clay-colored stools, and scleral icterus, which began two weeks after he tested positive for SARS-CoV-2 PCR. Liver biopsy and subsequent histology confirmed the diagnosis of AIH with the most probable etiology being SARS-CoV-2 infection. The patient was treated with N-acetylcysteine (NAC) and steroids with clinical improvement and eventual discharge home. Our goal is to provide a clinical presentation, treatment, and outcome in a patient with SARS-CoV-2-induced AIH.

Host antiviral factors hijack furin to block SARS-CoV-2, ebola virus, and HIV-1†glycoproteins cleavage.

Viral envelope glycoproteins are crucial for viral infections. In the process of enveloped viruses budding and release from the producer cells, viral envelope glycoproteins are presented on the viral membrane surface as spikes, promoting the virus's next-round infection of target cells. However, the host cells evolve counteracting mechanisms in the long-term virus-host co-evolutionary processes. For instance, the host cell antiviral factors could potently suppress viral replication by targeting their envelope glycoproteins through multiple channels, including their intracellular synthesis, glycosylation modification, assembly into virions, and binding to target cell receptors. Recently, a group of studies discovered that some host antiviral proteins specifically recognized host proprotein convertase (PC) furin and blocked its cleavage of viral envelope glycoproteins, thus impairing viral infectivity. Here, in this review, we briefly summarize several such host antiviral factors and analyze their roles in reducing furin cleavage of viral envelope glycoproteins, aiming at providing insights for future antiviral studies.

mRNA vaccination in breast cancer: current progress and future direction.

Messenger RNA (mRNA) vaccination has proven to be highly successful in combating Coronavirus disease 2019 (COVID-19) and has recently sparked tremendous interest. This technology has been a popular topic of research over the past decade and is viewed as a promising treatment strategy for cancer immunotherapy. However, despite being the most prevalent malignant disease for women worldwide, breast cancer patients have limited access to immunotherapy benefits. mRNA vaccination has the potential to convert cold breast cancer into hot and expand the responders. Effective mRNA vaccine design for in vivo function requires consideration of vaccine targets, mRNA structures, transport vectors, and injection routes. This review provides an overview of pre-clinical and clinical data on various mRNA vaccination platforms used for breast cancer treatment and discusses potential approaches to combine appropriate vaccination platforms or other immunotherapies to improve mRNA vaccine therapy efficacy for breast cancer.

External Supports Are Associated With the COVID-19 Vaccination in Chinese Breast Cancer Patients: A Cross-Sectional Survey.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic. Breast cancer is the most commonly diagnosed malignant cancer in China. Considering the specific national conditions, no evidence is available for factors associated with COVID-19 vaccination in patients with breast cancer. Methods: This was a cross-sectional survey, fielded from June 21 through June 27, 2021. A total of 944 nationally representative samples of Chinese breast cancer patients participating in the survey were included. Participant surveys included questions addressing who finished COVID-19 vaccination with the question "Have you taken the COVID-19 vaccine?", and response options were "Yes" and "No". Results: Overall, 730 (77.33%) women with breast cancer were unvaccinated, and only 214 (22.67%) were vaccinated with the COVID-19 vaccine. After adjusting for potential confounders, including both sociodemographic and clinical characteristics, we found that external support, including positive doctor suggestions (odds ratio (OR): 5.52; 95% confidence interval (CI): 3.50 - 8.71; P < 0.0001), positive support from surrounding people (OR: 11.65; 95% CI: 7.57 - 17.91; P < 0.0001), and negative initiative from the community (OR: 0.15; 95% CI: 0.06 - 0.35; P < 0.0001), was associated with COVID-19 vaccination rates among breast cancer patients. These results remain stable in subgroup analyses. We found that most participants (82.52%) understood the necessity of COVID-19 vaccinations in China was strong; however, the recognition regarding the COVID-19 vaccine showed different patterns between vaccinated and unvaccinated participants. Conclusions: Our findings suggest external support, including vaccination suggestions from surgeons or oncologists, vaccination suggestions from associated people, and residents' committee mandated vaccinations, was associated with the COVID-19 vaccination rates. Interventions regarding these factors and improving publicity as well as education regarding COVID-19 vaccines among breast cancer patients are warranted.

Controlling effect of TiO2 carrier on formed vanadium species for effective catalytic oxidization of chlorobenzene

Catalytic oxidization of the dioxins is critical to the atmosphere since medical-waste incineration is globally increased due to COVID-19. Vanadium supported TiO2 is the most-widely investigated catalyst. However, previous reports usually investigated V-Ti relationships after vanadate was loaded on TiO2 and an activation was completed. In comparison, this work emphasizes on the influence of TiO2 surface chemistries on properties of formed vanadium species during a thermal activation. The vanadate loaded TiO2 are detailedly analyzed by both experimental characterizations and theoretical calculations. As a result, TiO2 with more Ti4+ is inclined to be reductive, and promotes the formation of more low-valence vanadium and surface vacancies. On the contrary, TiO2 with more Ti3+ is inclined to be oxidative, and promotes the formation of more lattice oxygens and high-valence vanadium. When they were compared in catalytic oxidization of chlorobenzene, the Ti4+-induced catalyst attains a conversion of 98.0 % at 250 °C, far bigger than that (11.3 %) of the Ti3+-induced catalyst. The main result of this work helps readers to understand the process of the catalyst preparation, which is in favor of producing a more effective catalyst by regulating the catalyst carrier.

Mechanisms of host type I interferon response modulation by the nucleocapsid proteins of alpha- and betacoronaviruses.

Coronaviruses can have a devastating impact on the health of humans and animals. Porcine epidemic diarrhea virus (PEDV) causes extremely high fatality rates in neonatal piglets, whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic in humans. As a critical component of the host antiviral innate immune response, type I interferon production and signaling play a very important role, especially in the initial phase of the antiviral responses. Coronaviruses have evolved multiple ways to counteract type I interferon responses. Although the primary functions of the nucleocapsid protein are to facilitate viral RNA replication and package viral genomic RNA into virions, recent studies have shown that the nucleocapsid protein is also involved in virus-host interactions. The aim of this review is to summarize our current understanding of how the nucleocapsid proteins of PEDV and SARS-CoV-2 modulate type I interferon responses. This knowledge will be useful for developing strategies to combat coronavirus infections.

Product Market Competition and Firm Performance: Business Survival Through Innovation and Entrepreneurial Orientation Amid COVID-19 Financial Crisis.

The product market competition has become a global challenge for business organizations in the challenging and competitive market environment in the influx of the COVID-19 outbreak. The influence of products competition on organizational performance in developed economies has gained scholars' attention, and numerous studies explored its impacts on business profitability. The existing studies designate mixed findings between the linkage of CSR practices and Chinese business firms' healthier performance in emerging economies; however, the current global crisis due to the coronavirus has made product market completion fierce, which ultimately affects business firms' performance. This study focuses on this logical global challenge, investigates the rationale, and examines product-market completion impact on firms' performance operating in the Chinese markets. The study collected data from the annual reports of Chinese business organizations with A-share listing and registered with the database of China Stock Markets and Accounting Research (CSMAR). The study employed a Generalized Method of Moment technique and investigated the connection between product market competition and Chinese firm performance. The empirical analysis of this study highlights the conclusion that market competition positively and significantly affected business firms' performance. This study specified that product market competition play a dynamic and indispensable role in achieving healthier firm performance in the Chinese markets. This study provides valuable insights on practical implications and future research directions for the scholars to draw interesting results with new study models.

The sub-health status of different social roles and the analysis of its influencing factors during the 2019 coronavirus disease pandemic

Aim: This paper aims at investigating the sub-health status (SHS) of different social roles during the 2019 coronavirus disease (COVID-19) pandemic and analyzing its influencing factors. Design: A cross-sectional, convenience sampling including 1062 Chinese was conducted in March 2020. Statistical analysis was then performed for the data using SPSS 22.0.

Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism.

Thirty-two clofazimine derivatives, of which twenty-two were new, were synthesized and evaluated for their antiviral effects against both rabies virus and pseudo-typed SARS-CoV-2, taking clofazimine (1) as the lead. Among them, compound 15f bearing 4-methoxy-2-pyridyl at the N5-position showed superior or comparable antiviral activities to lead 1, with the EC50 values of 1.45 µM and 14.6 µM and the SI values of 223 and 6.1, respectively. Compound 15f inhibited rabies and SARS-CoV-2 by targeting G or S protein to block membrane fusion, as well as binding to L protein or nsp13 to inhibit intracellular biosynthesis respectively, and thus synergistically exerted a broad-spectrum antiviral effect. The results provided useful scientific data for the development of clofazimine derivatives into a new class of broad-spectrum antiviral candidates.

Three doses of an inactivation-based COVID-19 vaccine induces cross-neutralizing immunity against the SARS CoV-2 Omicron variant.

The immunity potency upon natural infection or vaccination is the main concern for the vaccine strategy of severe acute respiratory syndrome coronavirus 2 (SARS COV-2 variant), especially the recently reported Omicron variant (B.1.1.529). In this study, 200 recipients immunized with three doses of a COVID-19-inactivated vaccine were enrolled, whose serum samples were collected within 2 months after the third immunization. The neutralizing activity of sera against the pseudotyped Omicron variant, prototype, and Delta variant was determined. Our results demonstrated that the positive neutralization activity was 95.5% for the Omicron variant, 99.5% for the prototype, and 98.5% for the Delta variant. The geometric mean titers (GMT) for the Omicron variant was 49 and maintained sustained immune levels for 2 months, which decreased by 4.9-fold and 3.0-fold compared with the prototype (GMT, 239) and Delta variant (GMT, 148), respectively. In summary, our study demonstrated that three doses of a COVID-19-inactivated vaccine effectively yielded potent cross-neutralizing activity against the Omicron variant at 2 months after the third vaccination.

Exploring Rapid and Effective Screening Methods for Anti-SARS-CoV-2 Neutralizing Antibodies in COVID-19 Convalescent Patients and Longitudinal Vaccinated Populations.

Assessing the duration of neutralizing antibodies (nAbs) following SARS-CoV-2 infection or vaccination is critical to evaluate the protective immunity and formulate public health strategies. In this study, SARS-CoV-2 Ab ELISA (enzyme-linked immunosorbent assay), chemiluminescent microparticle immunoassay (CMIA), as well as pseudovirus neutralization test (PVNT) were performed in two cohorts, convalescent patients (CP) from coronavirus disease 2019 (COVID-19) and BBIBP-CorV vaccinated population. It was found that nAbs and binding antibodies emerged at 14 days post the 1st dose of vaccination, reached peaks at 28 days after 2nd dose vaccination and then gradually declined over time. CP-6M (convalescent patients up to 6 months) from COVID-19 presented stronger nAbs or binding antibodies responses than vaccinees 90 days or 180 days after 2nd dose vaccination. CMIA or SARS-CoV-2 Ab ELISA correlated well with PVNT with high consistency in the two cohorts. It shown that nAbs and binding antibodies can keep 6 months both in CP and vaccinees. Most importantly, our data show the application of using CMIA and SARS-CoV-2 Ab ELISA as rapid screening tests for nAb titer and could be used as alternative strategies for quickly evaluating SARS-CoV-2 nAbs responses in vaccine research.

Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries.

Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries. Each library was constructed synthetically with shuffled complementarity-determining region loops from natural llama and human antibody repertoires. While most candidates targeted the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike protein, we also identified a neutralizing IgG candidate that binds a unique epitope on the N-terminal domain. A select number of antibodies retained binding to SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa and Delta. Overall, our data show that synthetic phage libraries can rapidly yield SARS-CoV-2 S1 antibodies with therapeutically desirable features, including high affinity, unique binding sites, and potent neutralizing activity in vitro, and a capacity to limit disease in vivo.

Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost.

ABSTRACTThe emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant.Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters.Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the "priming" shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Shock effect of COVID-19 infection on environmental quality and economic development in China: causal linkages (Health Economic Evaluation).

Since coronavirus disease 2019 (COVID-19) was first reported on December 2019 in Wuhan, it fast spread to the rest of China, which has turned into a global public health problem later and generated global stock markets to violently shake. We inspect the causal relationships between economic development (ED) and environmental quality (EQ) during the period from January 2019 to May 2020 with the structural break for China and investigate the causal linkages between ED and EQ in subgroup of before and after the outbreak of COVID-19 with a semi-parametric model. The empirical tests show that smoothing structural transforms matter for the linkages of causality between ED and EQ, especially after COVID-19 infection. While the Toda-Yamamoto causality analysis supports unidirectional causality between ED and EQ before the outbreak of COVID-19, under structural shifts by the causality supplies of bidirectional casual linkages after the outbreak of COVID-19. Our results further clarified the proof that the economic activity gives rise to the environmental pollution and energy utilization mainly via the shock of COVID-19 in China. The emphasis on nonlinear causality between economic development and environmental quality may be an opportunity for China's economic recovery under considering the factor of COVID-19 infection.

Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies.

The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology.

Correction to: Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit.

The original version of this article unfortunately contained a mistake. There was an error in Xiaorong Hu's name. The original article has been corrected. The authors apologize for the mistake.

Digital twins-based remote semi-physical commissioning of flow-type smart manufacturing systems.

The COVID-19 has become a global pandemic that dramatically impacted human lives and economic activities. Due to the high risk of getting affected in high-density population areas and the implementation of national emergency measures under the COVID-19 pandemic, both travel and transportation among cities become difficult for engineers and equipment. Consequently, the costly physical commissioning of a new manufacturing system is greatly hindered. As an emerging technology, digital twins can achieve semi-physical simulation to avoid the vast cost of physical commissioning of the manufacturing system. Therefore, this paper proposes a digital twins-based remote semi-physical commissioning (DT-RSPC) approach for open architecture flow-type smart manufacturing systems. A digital twin system is developed to enable the remote semi-physical commissioning. The proposed approach is validated through a case study of digital twins-based remote semi-physical commissioning of a smartphone assembly line. The results showed that combining the open architecture design paradigm with the proposed digital twins-based approach makes the commissioning of a new flow-type smart manufacturing system more sustainable.

Rapid exploration of the epitope coverage produced by an Ebola survivor to guide the discovery of therapeutic antibody cocktails.

BACKGROUND: Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences. METHODS AND RESULTS: A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. A focused set of antibodies was selected from representative clones per bin to guide a second-pass binning that revealed previously unassigned epitopes, confirmed epitopes known to be associated with neutralizing antibodies, and demonstrated asymmetric blocking of EBOV GP from allosteric effectors reported from literature. CONCLUSIONS: Critically, this workflow allows us to probe the epitope landscape of EBOV GP without any prior structural knowledge of the antigen or structural benchmark clones. Incorporating epitope binning on hundreds of antibodies during early stage antibody characterization ensures access to a library's full epitope coverage, aids in the identification of high quality reagents within the library that recapitulate this diversity for use in other studies, and ultimately enables the rational development of therapeutic cocktails that take advantage of multiple mechanisms of action such as cooperative synergistic effects to enhance neutralization function and minimize the risk of mutagenic escape. The use of high-throughput epitope binning during new outbreaks such as the current COVID-19 pandemic is particularly useful in accelerating timelines due to the large amount of information gained in a single experiment.