Self-Directed Learning Predicts Online Learning Engagement in Higher Education Mediated by Perceived Value of Knowing Learning Goals

Online education has made it possible to implement the "classes suspended but learning continues" policy during the COVID-19 outbreak. However, the intangible sense of the online educational setting requires self-directed learning (SDL) and may force students to know the goals of learning that may impact their engagement. To understand the effect, based on situated expectancy-value theory, this study considered SDL as attitude and approach and constructed a research model to explore the mediating power of perceived value of knowing learning goals (PVKLG) related to participants' online learning engagement during the COVID-19 lockdown. Data were collected from 497 higher education students in China. After the confirmatory factor analysis with structural equation modeling, the results reported that SDL attitude and approach positively predicted learning engagement mediated by PVKLG. The results suggest that only when students have a high level of PVKLG will they be able to regulate their learning process through the two types of SDL and enhance their engagement in online learning contexts during the COVID-19 lockdown.

Exploring the role of online EFL learners' perceived social support in their learning engagement: a structural equation model

During the COVID-19 pandemic period, a growing number of learning activities are taking place in online contexts. Along with the adversity in the online course of target language learning, student engagement has been considered important to improve learners' academic achievements of the target language. Although there has been a growing interest in the relationship between students' perceived social support and their online learning engagement, the literature lacks an in-depth investigation of the intricate relations between these two constructs in an online English as a foreign language (EFL) learning setting during the pandemic. To address this gap, this study attempts to develop a model which depicts the relationships between students' perceived social support and their online English learning engagement. A total of 615 university students in China were invited to take part in the study. By conducting structural equation modeling, the results confirmed the mediational model in which behavioral engagement completely mediated the relationships between social support (teacher support and peer support) and three other types of student engagement (cognitive, emotional and social engagement). These findings suggest designing effective instruction and developing support strategies in online teaching to enhance EFL learners' engagement during the COVID-19 lockdown. [ FROM AUTHOR] Copyright of Interactive Learning Environments is the property of Routledge 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 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 . (Copyright applies to all s.)

Tracking B Cell Memory to SARS-CoV-2 Using Rare Cell Analysis System.

Rapid mutations within SARS-CoV-2 are driving immune escape, highlighting the need for in-depth and routine analysis of memory B cells (MBCs) to complement the important but limited information from neutralizing antibody (nAb) studies. In this study, we collected plasma samples and peripheral blood mononuclear cells (PBMCs) from 35 subjects and studied the nAb titers and the number of antigen-specific memory B cells at designated time points before and after vaccination. We developed an assay to use the MiSelect R II System with a single-use microfluidic chip to directly detect the number of spike-receptor-binding domain (RBD)-specific MBCs in PBMCs. Our results show that the number of spike-RBD-specific MBCs detected by the MiSelect R II System is highly correlated with the level of nAbs secreted by stimulated PBMCs, even 6 months after vaccination when nAbs were generally not present in plasma. We also found antigen-specific cells recognizing Omicron spike-RBD were present in PBMCs from booster vaccination of subjects, but with a high variability in the number of B cells. The MiSelect R II System provided a direct, automated, and quantitative method to isolate and analyze subsets of rare cells for tracking cellular immunity in the context of a rapidly mutating virus.

Reproduction number of SARS-CoV-2 omicron variants, China, December 2022-January 2023.

China adjusted the zero-COVID strategy in late 2022, triggering an unprecedented Omicron wave. We estimated the time-varying reproduction numbers of 32 provincial-level administrative divisions from December 2022 to January 2023. We found that the pooled estimate of initial reproduction numbers is 4.74 (95% CI: 4.41, 5.07).

Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection.

Direct in vivo investigation of human placenta trophoblast's susceptibility to SARS-CoV-2 is challenging. Here we report that human trophoblast stem cells (hTSCs) and their derivatives are susceptible to SARS-CoV-2 infection, which reveals heterogeneity in hTSC cultures. Early syncytiotrophoblasts (eSTBs) generated from hTSCs have enriched transcriptomic features of peri-implantation trophoblasts, express high levels of angiotensin-converting enzyme 2 (ACE2), and are productively infected by SARS-CoV-2 and its Delta and Omicron variants to produce virions. Antiviral drugs suppress SARS-CoV-2 replication in eSTBs and antagonize the virus-induced blockage of STB maturation. Although less susceptible to SARS-CoV-2 infection, trophoblast organoids originating from hTSCs show detectable viral replication reminiscent of the uncommon placental infection. These findings implicate possible risk of COVID-19 infection in peri-implantation embryos, which may go unnoticed. Stem cell-derived human trophoblasts such as eSTBs can potentially provide unlimited amounts of normal and genome-edited cells and facilitate coronavirus research and antiviral discovery.

Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice.

The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years.

Comparative analysis of SARS-CoV-2 Omicron BA.2.12.1 and BA.5.2 variants.

The initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries. To provide insight on the replacement of BA.2 by BA.5 as the dominant SARS-CoV-2 variant, we performed a comparative analysis of Omicron BA.2.12.1 and BA.5.2 variants in cell culture and hamster models. We found that BA.5.2 exhibited enhanced replicative kinetics over BA.2.12.1 in vitro and in vivo, which is evidenced by the dominant BA.5.2 viral genome detected at different time points, regardless of immune selection pressure with vaccine-induced serum antibodies. Utilizing reverse genetics, we constructed a mutant SARS-CoV-2 carrying spike F486V substitution, which is an uncharacterized mutation that concurrently discriminates Omicron BA.5.2 from BA.2.12.1 variant. We noticed that the 486th residue does not confer viral replication advantage to the virus. We also found that 486V displayed generally reduced immune evasion capacity when compared with its predecessor, 486F. However, the surge of fitness in BA.5.2 over BA.2.12.1 was not due to stand-alone F486V substitution but as a result of the combination of multiple mutations. Our study upholds the urgency for continuous monitoring of SARS-CoV-2 Omicron variants with enhanced replication fitness.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection (preprint)

The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblast susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs were highly susceptible to SARS-CoV-2. They expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antiviral drug tests and safety evaluation.

Response of Natural Gas Consumption to Temperature and Projection under SSP Scenarios during Winter in Beijing

The present study investigates the response of natural gas consumption to temperature on the basis of observations during heating season (middle November–middle March) for the period 2002–2021 in Beijing, China, and then estimates temperature-related changes in the gas consumption under future scenarios by using climate model simulations from the Coupled Model Intercomparison Project Phase 6. Observational evidence suggests that the daily natural gas consumption normalized by gross domestic product is linearly correlated with the daily average temperature during heating season in the past two decades in Beijing. Hence, a linear regression model is built to estimate temperature-related changes in the natural gas consumption under future scenarios. Corresponding to a rising trend in the temperature, the natural gas consumption shows a decrease trend during 2015–2100 under both the SSP245 and the SSP585 scenarios. In particular, the temperature would increase rapidly from early 2040s to the end of 21st century under the SSP585 scenario, leading to an obvious reduction in the natural gas consumption for heating in Beijing. Relative to that in the present day (1995–2014), the natural gas consumption would show a reduction of approximately 9% (±4%) at the end of 21st century (2091–2100) under the SSP245 scenario and approximately 22% (±7%) under the SSP585 scenario.

Lung Organoids as Model to Study SARS-CoV-2 Infection.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has severely affected socio-economic conditions and people's life. The lung is the major target organ infected and (seriously) damaged by SARS-CoV-2, so a comprehensive understanding of the virus and the mechanism of infection are the first choices to overcome COVID-19. Recent studies have demonstrated the enormous value of human organoids as platforms for virological research, making them an ideal tool for researching host-pathogen interactions. In this study, the various existing lung organoids and their identification biomarkers and applications are summarized. At the same time, the seven coronaviruses currently capable of infecting humans are outlined. Finally, a detailed summary of existing studies on SARS-CoV-2 using lung organoids is provided and includes pathogenesis, drug development, and precision treatment. This review highlights the value of lung organoids in studying SARS-CoV-2 infection, bringing hope that research will alleviate COVID-19-associated lung infections.

Multiscale characterization reveals oligomerization dependent phase separation of primer-independent RNA polymerase nsp8 from SARS-CoV-2.

RNA replication and transcription machinery is an important drug target for fighting against coronavirus. Non-structure protein nsp8 was proposed harboring primase activity. However, the RNA primer synthesis mechanism of nsp8 is still largely unknown. Here, we purified dimer and tetramer forms of SARS-CoV-2 nsp8. Combined with dynamic light scattering, small-angle neutron scattering and thermo-stability analysis, we found that both dimer and tetramer become loosened and destabilized with decreasing salt concentration, and the dimer form is more stable than the tetramer form. Further investigation showed that nsp8 dimer and tetramer can undergo phase separation but exhibit different phase separation behaviors. Nsp8 dimer can form liquid-like droplets in the buffer with a low concentration of NaCl; phase separation of nsp8 tetramer depends on the assistance of RNA. Our findings on different phase separation behaviors of nsp8 dimer and tetramer may provide insight into the functional studies of nsp8 in coronavirus.

Illegitimate tasks and nurses' work engagement: The role of ego depletion

This study explored whether ego depletion mediated the relationship between illegitimate tasks and nurses' work engagement. We recruited 760 Chinese nurses at three tertiary hospitals and a general hospital to complete a survey on illegitimate tasks, ego depletion, and work engagement. The results show that illegitimate tasks were negatively related to work engagement and that ego depletion partially mediated this relationship. These results provide a theoretical reference to improve nurses' work engagement through avoiding illegitimate tasks.

The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage.

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 are comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.

Production of single-cycle infectious SARS-CoV-2 through a trans-complemented replicon.

Single-cycle infectious virus can elicit close-to-natural immune response and memory. One approach to generate single-cycle severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is through deletion of structural genes such as spike (S) and nucleocapsid (N). Transcomplementation of the resulting ΔS or ΔN virus through enforced expression of S or N protein in the cells gives rise to a live but unproductive virus. In this study, ΔS and ΔN BAC clones were constructed and their live virions were rescued by transient expression of S and N proteins from the ancestral and the Omicron strains. ΔS and ΔN virions were visualized by transmission electron microscopy. Virion production of ΔS was more efficient than that of ΔN. The coated S protein from ΔS was delivered to infected cells in which the expression of N protein was also robust. In contrast, expression of neither S nor N was detected in ΔN-infected cells. ΔS underwent viral RNA replication, induced type I interferon (IFN) response, but did not form plaques. Despite RNA replication in cells, ΔS infection did not produce viral progeny in culture supernatant. Interestingly, viral RNA replication was not further enhanced upon overexpression of S protein. Taken together, our work provides a versatile platform for development of single-cycle vaccines for SARS-CoV-2.

Coronaviruses exploit a host cysteine-aspartic protease for replication.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.

Phosphatidic acid phosphatase 1 impairs SARS-CoV-2 replication by affecting the glycerophospholipid metabolism pathway.

Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming in vitro and in vivo using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients' plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects' plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.