Different associations of parental involvement with children's learning of Chinese, English, and math: a three-wave longitudinal study

Due to the impact of COVID-19, children and their parents are spending more time at home, which increases parent–child interactions. The goals of the present study were to examine the mediating effects of children's learning engagement on the relationships of parental involvement in Chinese, English, and math performance and to investigate whether parent-perceived parental involvement and child-perceived parental involvement consistently affected children's academic performance. Data were collected from 253 Chinese primary school students (117 boys, Mage = 10.53) during the COVID-19 pandemic. We included parental involvement perceived by the parents and by the children to comprehensively describe parental involvement (in wave 2);we collected children's learning engagement (wave 2);and we compared children's Chinese, English and math academic performances before (wave 1) and after (wave 3) China's first wave of COVID-19 in 2020. The results showed that after controlling for gender, age, and SES, the parental involvement perceived by parents could be directly and positively related to children's learning engagement, and it also indirectly influenced children's learning engagement through the children's perceived parental involvement. Learning engagement was a mediator of the relationship between parental involvement and children's academic performance. Parental involvement significantly predicted children's Chinese and English performances through their learning engagement, while parental involvement failed to predict children's mathematics performances during the COVID-19 pandemic. The current research provides insights into the underlying mechanisms of how parental involvement affects children's academic performances during school closures and hopes to guide parents and schools to consider how to cooperate and continue to use rapidly developing digital education resources amid the long-term impact of COVID-19 to provide children using more effective and suitable guidance in the future. [ FROM AUTHOR]

Specific Pupylation as IDEntity Reporter (SPIDER) for the identification of Protein-Biomolecule interactions (preprint)

Protein-biomolecule interactions play pivotal roles in almost all biological processes, the identification of the interacting protein is essential. By combining a substrate-based proximity labelling activity from the pupylation pathway of Mycobacterium tuberculosis , and the streptavidin (SA)-biotin system, we developed S pecific P upylation as IDE ntity R eporter (SPIDER) for identifying protein-biomolecular interactions. As a proof of principle, SPIDER was successfully applied for global identification of interacting proteins, including substrates for enzyme (CobB), the readers of m 6 A, the protein interactome of mRNA, and the target proteins of drug (lenalidomide). In addition, by SPIDER, we identified SARS-CoV-2 Omicron variant specific receptors on cell membrane and performed in-depth analysis for one candidate, Protein-g. These potential receptors could explain the differences between the Omicron variant and the Prototype strain, and further serve as target for combating the Omicron variant. Overall, we provide a robust technology which is applicable for a wide-range of protein-biomolecular interaction studies.

Polymerized Porin as a Novel Delivery Platform for Coronavirus Vaccine (preprint)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. Here, we designed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We use surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane in this study. More importantly, the polymerized RBD displayed on ClyA-RBD polymerized porin (RBD-PP) already has some correct spatial structures of virus spikes. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies and systemic cellular immune responses and immune memory. We applied ofthis PP-based vaccine platform to make an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to be applied to more fields, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.

COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters (preprint)

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters (preprint)

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the START button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

SARS-CoV-2 Antibody Signatures for Predicting the Outcome of COVID-19 (preprint)

Background: The COIVD-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies remain elevated with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome.Method: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgM/IgG responses against 20 SARS-CoV-2 proteins in 1,034 hospitalized COVID-19 patients on admission, who were followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality.Results: We found that high level of IgM against ORF7b at the time of hospitalization is an independent predictor of patient survival ( p  trend = 0.002), while levels of IgG responses to 6 non-structural proteins and 1 accessory protein, i. e., NSP4, NSP7, NSP9, NSP10, RdRp (NSP12), NSP14, and ORF3b, possess significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory markers for disease severity (all with p trend < 0.05). Spline regression analysis indicated that the correlation between ORF7b IgM, NSP9 IgG, and NSP10 IgG and the risk of COVID-19 mortality shows linear ( p = 0.0013, 0.0073 and 0.0003, respectively). Their AUCs for predictions, determined by computational cross-validations (validation1), were 0.74 (cut-off = 7.59), 0.66 (cut-off = 9.13), and 0.68 (cut-off = 6.29), respectively. Further validations were conducted in the second and third serial samples of these cases (validation2A, n = 633, validation2B, n = 382), with high accuracy of prediction for outcome.Conclusion: These findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.Funding Statement: This work was supported by grants from the Fundamental Research Funds for the Central Universities (HUST COVID-19 Rapid Response Call No. 2020kfyXGYJ040) and Wuhan Bureau of Science and Technology (No. 2020020601012218).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (IRB ID:TJ-C20200128).

Antibody Landscape Against SARS-CoV-2 Proteome Revealed Significant Differences between Non-Structural/ Accessory Proteins and Structural Proteins (preprint)

The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.Funding: This work was partially supported by the National Key Research and Development Program of China Grant (No.2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, 31370813, 31900112 and 21907065).Conflict of Interest: The authors declare no competing interests.Ethical Approval: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (ITJ-C20200128). Written informed consent was obtained from all participants enrolled in this study.

Linear Epitope Landscape of SARS-CoV-2 Spike Protein Constructed from 1,051 COVID-19 Patients (preprint)

Neutralization antibodies and vaccines for treating COVID-19 are desperately needed. For precise development of antibodies and vaccines, the key is to understand which part of SARS-CoV-2 Spike protein is highly immunogenic on a systematic way. We generate a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions that rich of linear epitopes, i.e., CTD and a region close to the S2’ cleavage site and fusion peptide. Unexpectedly, we find RBD is lack of linear epitope. Besides 3 moderate immunogenic peptides from RBD, 16 highly immunogenic peptides from other regions of Spike protein are determined. These peptides could serve as the base for precise development of antibodies and vaccines for COVID-19 on a systematic level.Funding: This work was partially supported by National Key Research and Development Program of China Grant (No. 2016YFA0500600), Science and Technology Commission of Shanghai Municipality (No. 19441911900), Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2020YQ10), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813).Conflict of Interest: The authors declare no competing interest.

Chemokine Receptor Inhibitor vMIP-II Promoting Lymphocytes in COVID-19 Patients and Its Related Mechanism In Vitro (preprint)

Coronavirus disease (COVID-19) accompanies severe immune injury as well as a decrease and overactivation of T lymphocytes. We observed that vMIP-Ⅱ, a broad-spectrum chemokine receptor inhibitor, could improve the lymphocyte decrease of COVID-19. Comparisons of T cell populations in PBMCs showed that the effects of vMIP-II on the subsets of T cells and cytokine secretion stimulated by SARS-CoV-2 S protein were the same as those in the asymptomatic infection group: the proportion of CD8+ TCM cells in the vMIP-II treatment and asymptomatic groups was significantly higher than that in the symptomatic control group. Differential gene expression of effector CD8+ T cells suggested that vMIP-II inhibits multiple chemokine receptors and related signal pathway and strengthens their stem proliferating capacity. Thus, vMIP-II reconstitutes cellular immunity lost due to acute infection of SARS-CoV-2 by modulating effector CD8+ T cells to produce more TCM cells.

Chemokine Receptor Inhibitor vMIP-II Promoting Lymphocytes in COVID-19 Patients and Its Related Mechanism In Vitro (preprint)

Coronavirus disease (COVID-19) accompanies severe immune injury as well as a decrease and overactivation of T lymphocytes. We observed that vMIP-Ⅱ, a broad-spectrum chemokine receptor inhibitor, could improve the lymphocyte decrease of COVID-19. Comparisons of T cell populations in PBMCs showed that the effects of vMIP-II on the subsets of T cells and cytokine secretion stimulated by SARS-CoV-2 S protein were the same as those in the asymptomatic infection group: the proportion of CD8+TCM cells in the vMIP-II treatment and asymptomatic groups was significantly higher than that in the symptomatic control group. Differential gene expression of effector CD8+ T cells suggested that vMIP-II inhibits multiple chemokine receptors and related signal pathway and strengthens their stem proliferating capacity. Thus, vMIP-II reconstitutes cellular immunity lost due to acute infection of SARS-CoV-2 by modulating effector CD8+ T cells to produce more TCM cells.