In Situ Polymerization-Mediated Antigen Presentation.

Activating antigen-presenting cells is essential to generate adaptive immunity, while the efficacy of conventional activation strategies remains unsatisfactory due to suboptimal antigen-specific priming. Here, in situ polymerization-mediated antigen presentation (IPAP) is described, in which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto the surface of dendritic cells in vivo through co-deposition with dopamine. The resulting chemically bound nanovaccines can promote antigen presentation by elevating macropinocytosis-based cell uptake and reducing lysosome-related antigen degradation. IPAP is able to prolong the duration of antigen reservation in the injection site and enhance subsequent accumulation in the draining lymph nodes, thereby eliciting robust antigen-specific cellular and humoral immune responses. IPAP is also applicable for different antigens and capable of circumventing the disadvantages of complicated preparation and purification. By implementation with ovalbumin, IPAP induces a significant protective immunity against ovalbumin-overexpressing tumor cell challenge in a prophylactic murine model. The use of the SARS-CoV-2 Spike protein S1 subunit also remarkably increases the production of S1-specific immunoglobulin G in mice. IPAP offers a unique strategy for stimulating antigen-presenting cells to boost antigen-specific adaptive responses and proposes a facile yet versatile method for immunization against various diseases.

Impact of social comparison on perceived online academic futility: A perspective from parents.

In response to the wide-ranging concern of online academic futility, the current study aimed to explore the independent variables and mediating variable from a novel perspective of parents during COVID-19. Based on the social comparison theory and the control-value theory of achievement emotions, social comparison and tutoring anxiety were incorporated into an integrated model as predictors and mediator, respectively. A total of 300 parents completed an online survey. The results of the structural equation modeling indicated that upward social comparison and downward social comparison were both positively related to tutoring anxiety, which in turn positively predicted perceived online academic futility. Notably, tutoring anxiety played a significant mediating role in the association between different social comparison and perceived online academic futility. These results highlight the consistent predictive effect of upward social comparison and downward social comparison on perceived online academic futility, shedding light on the roles of tutoring anxiety in explaining the relationship from parental perspectives.

Long-Acting Protective Ocular Surface by Instilling Adhesive Dual-Antiviral Nanoparticles.

The eye is susceptible to viral infections, causing severe ocular symptoms or even respiratory diseases. Methods capable of protecting the eye from external viral invasion in a long-term and highly effective way are urgently needed but have been proved to be extremely challenging. Here, a strategy of forming a long-acting protective ocular surface is described by instilling adhesive dual-antiviral nanoparticles. Taking pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, antiviral agent-loaded nanoparticles are coated with a "double-lock" hybrid cell membrane abundant with integrin-ß1 and angiotensin converting enzyme II (ACE2). After instillation, the presence of integrin-ß1 endows coated nanoparticles with steady adhesion via specific binding to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium, achieving durable retention on the ocular surface. In addition to loaded inhibitors, the exposure of ACE2 can trap SARS-CoV-2 and subsequently neutralize the associated spike protein, playing a dual antiviral effect of the resulting nanoparticles. Adhesive dual-antiviral nanoparticles enabled by coating with a "double-lock" hybrid cell membrane could be a versatile platform for topical long-acting protection against viral infection of the eye.

Dressing Bacteria With a Hybrid Immunoactive Nanosurface to Elicit Dual Anticancer and Antiviral Immunity.

Approaches capable of simultaneously treating cancer and protecting susceptible patients from lethal infections such as coronavirus disease 2019, are highly desirable but prove to be difficult. Here, dressing bacteria with a hybrid immunoactive nanosurface is reported to elicit dual anticancer and antiviral immunity. A combination of a checkpoint blocking antibody and a virus-specific antigen is covalently conjugated to polydopamine nanoparticles, which can be anchored onto bacterial surface, by a one-step in situ polymerization of dopamine under a cell-friendly condition. By virtue of the ability to colonize and penetrate deep tumor tissue, dressed bacteria enable sustained release and expanded exposure of carried immunoactivators to stimulate immune cells. In addition to a carrier role, bacteria are able to further provoke innate immunity due to the native immunogenicity of the pathogen-associated molecular patterns. Immunization with dressed bacteria promotes the maturation, and activation of antigen-presenting cells, which induces robust humoral and cellular immune responses in tumor-bearing mice. As evidenced by efficient production of viral-antigen-specific immunoglobulin G antibody in serum and significantly suppressed tumor growth in different models, dressing bacteria with a hybrid immunoactive nanosurface paves an avenue to prepare next-generation therapeutics for synergistic treatment and prevention.

Chiral-Selective Antigen-Presentation by Supramolecular Chiral Polymer Micelles.

Chirality is ubiquitous in biological systems, which is closely related to biological functions, life process, and even pathogenesis of diseases. However, the interface between the chirality of synthetic materials and organisms, particularly the immune system, remains poorly understood. Here, supramolecular chiral polymer micelles (SCPMs) are prepared by complexing antigenic proteins with chiral amino acid modified polyethyleneimine. The introduction of chirality not only reduces the toxicity of cationic polymer, but also benefits cell uptake and antigen presentation. Especially, D-chirality presents the lowest cytotoxicity, while promotes the highest expression level of costimulatory molecules on dendritic cells compared to L-chirality and achirality. The superiority of D-chirality to stimulate dendritic cell maturation is supported by immunization with D-SCPMs, which achieves significant antigen-specific proliferation of T cells in the spleen, lymph nodes and tumor of mice. Chirality-mediated antigen processing and presentation is demonstrated by D-SCPMs self-assembled from chiral alkaline histidine or neutral phenylalanine modified polyethyleneimine and tumor associated ovalbumin or severe acute respiratory syndrome coronavirus 2 spike 1 antigenic protein. Immunoactivation enabled by D-chirality opens a window to prepare potent nanotherapeutics for disease prevention and treatment. This article is protected by copyright. All rights reserved.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Impact of social comparison on perceived online academic futility: A perspective from parents

In response to the wide-ranging concern of online academic futility, the current study aimed to explore the independent variables and mediating variable from a novel perspective of parents during COVID-19. Based on the social comparison theory and the control-value theory of achievement emotions, social comparison and tutoring anxiety were incorporated into an integrated model as predictors and mediator, respectively. A total of 300 parents completed an online survey. The results of the structural equation modeling indicated that upward social comparison and downward social comparison were both positively related to tutoring anxiety, which in turn positively predicted perceived online academic futility. Notably, tutoring anxiety played a significant mediating role in the association between different social comparison and perceived online academic futility. These results highlight the consistent predictive effect of upward social comparison and downward social comparison on perceived online academic futility, shedding light on the roles of tutoring anxiety in explaining the relationship from parental perspectives.

Where Is the Way Forward for New Media Empowering Public Health? Development Strategy Options Based on SWOT-AHP Model.

(1) Background: In recent years, new media and the integration of sport and medicine have promoted the rapid integration and development of the two fields of health and, to a certain extent, the pursuit of public health knowledge and the promotion of health concepts. However, the overall development process is at an early stage and the aim of this paper is to make an empirical analysis of its development through a SWOT-AHP model and give corresponding recommendations. (2) Methods: The SWOT-AHP model was constructed to quantitatively and qualitatively analyse the four dimensions of strengths, weaknesses, opportunities and threats obtained through the Delphi method, with regard to development and to determine the strategic direction of its development. (3) Results: The strategic azimuth θ is -13.243° and the strategic coefficient p is 0.53699, in the diversification zone. (4) Conclusions: New media, as a fast track to empowering the integration of sport and medicine for health, is a field with a bright future, but its own strengths and external threats coexist and should be maximised to overcome the disruptions caused by external threats through a variety of measures.

An active learning-based approach for screening scholarly articles about the origins of SARS-CoV-2.

To build a full picture of previous studies on the origins of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), this paper exploits an active learning-based approach to screen scholarly articles about the origins of SARS-CoV-2 from many scientific publications. In more detail, six seed articles were utilized to manually curate 170 relevant articles and 300 nonrelevant articles. Then, an active learning-based approach with three query strategies and three base classifiers is trained to screen the articles about the origins of SARS-CoV-2. Extensive experimental results show that our active learning-based approach outperforms traditional counterparts, and the uncertain sampling query strategy performs best among the three strategies. By manually checking the top 1,000 articles of each base classifier, we ultimately screened 715 unique scholarly articles to create a publicly available peer-reviewed literature corpus, COVID-Origin. This indicates that our approach for screening articles about the origins of SARS-CoV-2 is feasible.

Integrated Bioinformatics Analysis and Verification of Gene Targets for Myocardial Ischemia-Reperfusion Injury.

Background: Myocardial ischemia-reperfusion injury (MIRI) has become a thorny and unsolved clinical problem. The pathological mechanisms of MIRI are intricate and unclear, so it is of great significance to explore potential hub genes and search for some natural products that exhibit potential therapeutic efficacy on MIRI via targeting the hub genes. Methods: First, the differential expression genes (DEGs) from GSE58486, GSE108940, and GSE115568 were screened and integrated via a robust rank aggregation algorithm. Then, the hub genes were identified and verified by the functional experiment of the MIRI mice. Finally, natural products with protective effects against MIRI were retrieved, and molecular docking simulations between hub genes and natural products were performed. Results: 230 integrated DEGs and 9 hub genes were identified. After verification, Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be the most significant genes during MIRI. A total of 75 natural products were discovered. Most of them (especially araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) showed good ability to bind the hub genes. Conclusions: Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.

A look back at the first wave of COVID-19 in China: A systematic review and meta-analysis of mortality and health care resource use among severe or critical patients.

BACKGROUND: To investigate the mortality and health care resource use among patients with severe or critical coronavirus disease of 2019 (COVID-19) in the first wave of pandemic in China. METHODS: We performed a systematic review and meta-analysis to investigate the mortality, discharge rate, length of hospital stay, and use of invasive ventilation in severe or critical COVID-19 cases in China. We searched electronic databases for studies from China with no restrictions on language or interventions patients received. We screened records, extracted data and assessed the quality of included studies in duplicate. We performed the meta-analysis using random-effect models through a Bayesian framework. Subgroup analyses were conducted to examine studies by disease severity, study location and patient enrolment start date. We also performed sensitivity analysis using various priors, and assessed between-study heterogeneity and publication bias for the primary outcomes. RESULTS: Out of 6,205 titles and abstracts screened, 500 were reviewed in full text. A total of 42 studies were included in the review, of which 95% were observational studies (n = 40). The pooled 28-day and 14-day mortalities among severe or critical patients were 20.48% (7,136 patients, 95% credible interval (CrI), 13.11 to 30.70) and 10.83% (95% CrI, 6.78 to 16.75), respectively. The mortality declined over time and was higher in patients with critical disease than severe cases (1,235 patients, 45.73%, 95% CrI, 22.79 to 73.52 vs. 3,969 patients, 14.90%, 95% CrI, 4.70 to 39.57) and patients in Hubei compared to those outside Hubei (6,719 patients, 26.62%, 95% CrI, 13.11 to 30.70 vs. 244 patients, 5.88%, 95% CrI 2.03 to 14.11). The length of hospital stay was estimated at 18.48 days (6,847 patients, 95% CrI, 17.59 to 21.21), the 28-day discharge rate was 50.48% (3,645 patients, 95% CrI, 26.47 to 79.53), and the use of invasive ventilation rate was 13.46% (4,108 patients, 95% CrI, 7.61 to 22.31). CONCLUSIONS: Our systematic review and meta-analysis found high mortality among severe and critical COVID-19 cases. Severe or critical COVID-19 cases consumed a large amount of hospital resources during the outbreak.

Impact of Face-Recognition-Based Access Control System on College Students' Sense of School Identity and Belonging During COVID-19 Pandemic.

In the context of coronavirus pandemic (COVID-19), the face-recognition-based access control system (FACS) has been intensively adopted to protect students' and teachers' health and safety in school. However, the impact of FACS, as a new technology, on students' attitude toward accepting FACS has remained unknown from the psychological halo effect. Drawn on "halo effect" theory where psychological effects affect the sense of social identity and belonging, the present study explored college students' sense of school identity and belonging in using FACS during COVID-19 based on the technology acceptance model (TAM). Data collected from 391 college students was analyzed using SEM to verify the relationship among perceived usefulness (PU), perceived ease of use (PEU), intention to use (IU), school identity, and school belonging. The results show that PU and PEU can positively predict IU, and consequentially can positively predict school identity and school belonging. Our study expands the application of halo effect theory to study FACS acceptance based on TAM, and provides strong evidence to support the effect of school FACS during the pandemic. The findings of this study also suggest that FACS acceptance can enhance students' sense of school identity and belonging.

Clinical Characteristics and CT Imaging Features of COVID-19 on Admission: A Retrospective Study.

BACKGROUND AND AIMS: Coronavirus Disease 2019 (COVID-19) pandemic has become a global health issue. This study aimed to explore the clinical characteristics and CT imaging features of patients with COVID-19 on admission. METHODS: Consecutive patients with laboratory-confirmed COVID-19 were retrospectively recruited to this study from January 2020 to March 2020. According to the disease severity status on admission, patients were divided into two groups, the common group, and the severe group. RESULTS: Forty-four patients (F/M 20/24) who were COVID-19 positive were enrolled in this study. The most common onset symptom was fever (90.9%), followed by cough (43.2%). As for the laboratory tests, common findings included increased C reactive protein (47.7%) and erythrocyte sedimentation rate (43.2%) and decreased lymphocyte (34.1%). The frequency of decreased lymphocyte count and increased lactate dehydrogenasewas higher in the severe group (n=14) than in the common group (n=30). About 86% of patients showed typical imaging findings of COVID-19 infection, including ground-glass opacity with ill-defined margins, air bronchogram, interlobular septal thickening, and consolidation. Lesions were mainly located in the peripheral and subpleural regions with diffused distribution and multiple lung lobes were found to be affected. CONCLUSION: Fever and cough were the most common onset symptoms of COVID-19. Increased C reactive protein and erythrocyte sedimentation rate were the most common laboratory findings. Typical signs of chest CT imaging of COVID-19 included ground-glass opacity with ill-defined margins, air bronchogram, interlobular septal thickening, and consolidation.

Systemic antiviral immunization by virus-mimicking nanoparticles-decorated erythrocytes.

New vaccine technologies are urgently needed to produce safe and effective vaccines in a more timely manner to prevent future infectious disease pandemics. Here, we describe erythrocyte-mediated systemic antiviral immunization, a versatile vaccination strategy that boosts antiviral immune responses by using erythrocytes decorated with virus-mimetic nanoparticles carrying a viral antigen and a Toll-like receptor (TLR) agonist. As a proof of concept, polydopamine nanoparticles were synthesized via a simple in situ polymerization in which the nanoparticles were conjugated with the SARS-CoV-2 spike protein S1 subunit and the TLR7/8 agonist R848. The resulting SARS-CoV-2 virus-mimetic nanoparticles were attached to erythrocytes via catechol groups on the nanoparticle. Erythrocytes naturally home to the spleen and interact with the immune system. Injection of the nanoparticle-decorated erythrocytes into mice resulted in greater maturation and activation of antigen-presenting cells, humoral and cellular immune responses in the spleen, production of S1-specific immunoglobulin G (IgG) antibodies, and systemic antiviral T cell responses than a control group treated with the nanoparticles alone, with no significant negative side effects. These results show that erythrocyte-mediated systemic antiviral immunization using viral antigen- and TLR agonist-presenting polydopamine nanoparticles-a generalizable method applicable to many viral infections-is effective new approach to developing vaccines against severe infectious diseases.

The Effects of Scientific Self-efficacy and Cognitive Anxiety on Science Engagement with the "Question-Observation-Doing-Explanation" Model during School Disruption in COVID-19 Pandemic.

Game-based learning supported by mobile intelligence technology has promoted the renewal of teaching and learning models. Herein, a model of Question-Observation-Doing-Explanation (QODE) based on smart phones was constructed and applied to science learning during school disruption in COVID-19 pandemic. In this study, from the theoretical perspective of cognitive-affective theory of learning with media, Bandura's motivation theory and community of inquiry model, self-report measure was used to verify the effect of students' scientific self-efficacy and cognitive anxiety on science engagement. A total of 357 valid questionnaires were used for structural equation model research. The results indicated that two types of scientific self-efficacy, as indicated by scientific learning ability and scientific learning behavior, were negatively associated with cognitive anxiety. In addition, cognitive anxiety was also negatively correlated to four types of science engagement, as indicated by cognitive engagement, emotional engagement, behavioral engagement, and social engagement through smartphone interactions. These findings provide further evidence for game-based learning promoted by smart phones, contributing to a deeper understanding of the associations between scientific self-efficacy, cognitive anxiety, and science engagement. This study points out that the QODE model is suitable for implementing smart mobile devices to students' science learning.