Development of public sports and optimization of sports mode under the influence of covid-19 epidemic / Desenvolvimento de esportes públicos e otimização do modo esportivo sob influência da epidemia de covid-19 / El desarrollo del deporte público y la optimización del modelo deportivo bajo la influencia de la epidemia de covid - 19

ABSTRACT Introduction: The sports psychology of athletes and public service policies in various places have been adjusted under the influence of the epidemic of COVID-19. However, team sports also need adjustments, and the paucity of evidence prevents safe decision-making. Objective: Research the current model to outline optimizations to team sports public service during the epidemic of COVID-19. Methods: The mechanism of athletes' satisfaction was investigated, mainly involving organizing activities in sports venues, including geographical distribution, technical guidance, health services, etc. Results: According to the survey, the first concern was "organization of activities," with a score of 3.783; followed by "number of places," with a score of 3.252; and "health service," with a score of 3.142. In the athletes' satisfaction score relative to supply and demand, the first concern highlighted was "distribution of seats", with a score of 3.682; followed by "number of seats", with a score of 3.484; and "organization of activities", with a score of 3.112. Conclusion: In optimizing the public team sports service model, the actual needs of the facilities should be fully considered to achieve scientific optimization of supply and demand. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Tanto a psicologia esportiva dos atletas quanto as políticas de serviço público em vários lugares foram ajustadas sob a influência da epidemia da COVID-19. Os esportes em equipe também necessitam de adaptações e a escassez de evidências impede tomadas de decisões seguras neste aspecto. Objetivo: Pesquisar o modelo atual para traçar otimizações ao serviço público esportivo de equipe durante a epidemia da COVID-19. Métodos: O mecanismo de satisfação dos atletas foi investigado, envolvendo principalmente a organização de atividades em locais esportivos, incluindo distribuição geográfica, orientação técnica, serviços de saúde, etc. Resultados: De acordo com a pesquisa levantada, a primeira preocupação foi "organização de atividades", com pontuação de 3.783; seguido de "número de vagas", com pontuação de 3.252; e "serviço de saúde", com pontuação de 3.142. Na pontuação de satisfação das atletas relativa à oferta e demanda, a primeira preocupação destacada foi "distribuição de lugares", com pontuação de 3,682; seguida de "número de lugares", com pontuação de 3,484; e "organização de atividades", com pontuação de 3,112. Conclusão: No processo de otimização do modelo de serviço público esportivo de equipes, as necessidades reais das instalações devem ser plenamente consideradas, a fim de alcançar a otimização científica da oferta e da demanda. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Tanto la psicología deportiva de los atletas como las políticas de servicios públicos en diversos lugares se han ajustado bajo la influencia de la epidemia de COVID-19. Los deportes de equipo también necesitan ajustes y la escasez de pruebas impide tomar decisiones seguras al respecto. Objetivo: Investigar el modelo actual para delinear optimizaciones al servicio público de los deportes de equipo durante la epidemia de COVID-19. Métodos: Se investigó el mecanismo de satisfacción de los atletas, que involucra principalmente la organización de actividades en las instalaciones deportivas, incluyendo la distribución geográfica, la orientación técnica, los servicios de salud, etc. Resultados: Según la encuesta realizada, la primera preocupación era la "organización de las actividades", con una puntuación de 3,783; seguida del "número de plazas", con una puntuación de 3,252; y del "servicio sanitario", con una puntuación de 3,142. En la puntuación de satisfacción de los atletas en relación con la oferta y la demanda, la primera preocupación destacada fue la "distribución de los lugares", con una puntuación de 3,682; seguida del "número de lugares", con una puntuación de 3,484; y de la "organización de las actividades", con una puntuación de 3,112. Conclusión: En el proceso de optimización del modelo de servicio público de deportes de equipo, deben tenerse plenamente en cuenta las necesidades reales de las instalaciones para lograr una optimización científica de la oferta y la demanda. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

A dePEGylated Lipopeptide-Based Pan-Coronavirus Fusion Inhibitor Exhibits Potent and Broad-Spectrum Anti-HIV-1 Activity without Eliciting Anti-PEG Antibodies.

We previously identified a lipopeptide, EK1C4, by linking cholesterol to EK1, a pan-CoV fusion inhibitory peptide via a polyethylene glycol (PEG) linker, which showed potent pan-CoV fusion inhibitory activity. However, PEG can elicit antibodies to PEG in vivo, which will attenuate its antiviral activity. Therefore, we designed and synthesized a dePEGylated lipopeptide, EKL1C, by replacing the PEG linker in EK1C4 with a short peptide. Similar to EK1C4, EKL1C displayed potent inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses. In this study, we found that EKL1C also exhibited broad-spectrum fusion inhibitory activity against human immunodeficiency virus type 1 (HIV-1) infection by interacting with the N-terminal heptad repeat 1 (HR1) of viral gp41 to block six-helix bundle (6-HB) formation. These results suggest that HR1 is a common target for the development of broad-spectrum viral fusion inhibitors and EKL1C has potential clinical application as a candidate therapeutic or preventive agent against infection by coronavirus, HIV-1, and possibly other class I enveloped viruses.

A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients.

Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs). Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied. Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group. Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.

"Buffering traumatic reactions to COVID-19: Mindfulness moderates the relationship between the severity of the pandemic and posttraumatic stress symptoms": Correction.

Reports an error in "Buffering traumatic reactions to COVID-19: Mindfulness moderates the relationship between the severity of the pandemic and posttraumatic stress symptoms" by Xiaoyan Liu, Xue Wen, Qian Zhang and Wei Xu (Psychological Trauma: Theory, Research, Practice, and Policy, Advanced Online Publication, Mar 21, 2022, np). In the original article, the first affiliation was incorrectly listed as "Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education, Beijing Normal University" and was corrected to read "Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University." All versions of this article have been corrected. (The following abstract of the original article appeared in record 2022-45143-001). OBJECTIVE: As an international public health emergency panic, Corona Virus Disease-19 (COVID-19) has caused substantial impacts on economic and daily life. The public were at high risk of mental health problems and posttraumatic stress symptoms (PTSS). This study aimed to evaluate the association between objective/subjective severity of COVID-19 pandemic and PTSS, and explore the moderating role of mindfulness. METHOD: Using longitudinal and 7-day ecological momentary assessment (EMA) designs, we gathered data from 109 college students who were home-quarantined to examined study hypotheses. In the EMA phase, participants completed questionnaires measuring subjective severity, mindfulness and PTSS three times per day. Objective severity was indicated using the daily new confirmed cases. Then participants completed a follow-up measure of PTSS 2 months later, when the epidemic initially became stable. RESULTS: The results of structural equation modeling showed that state mindfulness moderated the relationship between subjectivity severity of COVID-19 and PTSS. Specifically, the association between subjective severity of COVID-19 and PTSS was positive at the low level of state mindfulness, and negative at the high level of state mindfulness. Trait mindfulness did not moderate the relationship between objectivity severity of COVID-19 and PTSS. CONCLUSION: Mindfulness-based interventions can be used as preventive mental health education to the daily lives of the general public, and to deal with unpredictable crisis events. Implications of this study are drawn for theory, practice, and research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo.

The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin-converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.

A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.

Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication and transcription and represents an attractive drug target for fighting COVID-19. Many SARS-CoV-2 Mpro inhibitors have been reported, including covalent and noncovalent inhibitors. The SARS-CoV-2 Mpro inhibitor PF-07321332 (Nirmatrelvir) designed by Pfizer has been put on the market. This paper briefly introduces the structural characteristics of SARS-CoV-2 Mpro and summarizes the research progress of SARS-CoV-2 Mpro inhibitors from the aspects of drug repurposing and drug design. These information will provide a basis for the drug development of treating the infection of SARS-CoV-2 and even other coronaviruses in the future.

An HR2-Mimicking Sulfonyl-γ-AApeptide Is a Potent Pan-coronavirus Fusion Inhibitor with Strong Blood-Brain Barrier Permeability, Long Half-Life, and Promising Oral Bioavailability.

Neutralizing antibodies and fusion inhibitory peptides have the potential required to combat the global pandemic caused by SARS-CoV-2 and its variants. However, the lack of oral bioavailability and enzymatic susceptibility limited their application, necessitating the development of novel pan-CoV fusion inhibitors. Herein we report a series of helical peptidomimetics, d-sulfonyl-γ-AApeptides, which effectively mimic the key residues of heptad repeat 2 and interact with heptad repeat 1 in the SARS-CoV-2 S2 subunit, resulting in inhibiting SARS-CoV-2 spike protein-mediated fusion between virus and cell membranes. The leads also displayed broad-spectrum inhibitory activity against a panel of other human CoVs and showed strong potency in vitro and in vivo. Meanwhile, they also demonstrated complete resistance to proteolytic enzymes or human sera and exhibited extremely long half-life in vivo and highly promising oral bioavailability, delineating their potential as pan-CoV fusion inhibitors with the potential to combat SARS-CoV-2 and its variants.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real-clinical experience study.

Background: Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab. Methods: In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively. Results: 233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events). Conclusions: Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.

Thermal-annealing-regulated plasmonic enhanced fluorescence platform enables accurate detection of antigen/antibody against infectious diseases.

Plasmonic enhanced fluorescence (PEF) technology is a powerful strategy to improve the sensitivity of immunofluorescence microarrays (IFMA), however, current approaches to constructing PEF platforms are either expensive/time-consuming or reliant on specialized instruments. Here, we develop a completely alternative approach relying on a two-step protocol that includes the self-assembly of gold nanoparticles (GNPs) at the water-oil interface and subsequent annealing-assisted regulation of gold nanogap. Our optimized thermal-annealing GNPs (TA-GNP) platform generates adequate hot spots, and thus produces high-density electromagnetic coupling, eventually enabling 240-fold fluorescence enhancement of probed dyes in the near-infrared region. For clinical detection of human samples, TA-GNP provides super-high sensitivity and low detection limits for both hepatitis B surface antigen and SARS-CoV-2 binding antibody, coupled with a much-improved detection dynamic range up to six orders of magnitude. With fast detection, high sensitivity, and low detection limit, TA-GNP could not only substantially improve the outcomes of IFMA-based precision medicine but also find applications in fields of proteomic research and clinical pathology. Electronic Supplementary Material: Supplementary material (UV-Vis absorption and transmission spectra of GNPs, SEM, microscopy and digital images of PEF platforms, and fluorescence images of IFMA on PEF platforms) is available in the online version of this article at 10.1007/s12274-022-5035-6.

Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment.

Coronaviruses (CoVs) are a family of RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of CoVs to illustrate the reciprocal regulation between CoV infection and pyroptosis. For the first time, we elucidate the molecular mechanism of porcine gasdermin D (pGSDMD)-mediated pyroptosis and demonstrate that amino acids R238, T239, and F240 within pGSDMD-p30 are critical for pyroptosis. Furthermore, 3C-like protease Nsp5 from SARS-CoV-2, MERS-CoV, PDCoV, and PEDV can cleave pGSDMD at the Q193-G194 junction to produce two fragments unable to trigger pyroptosis. The two cleaved fragments could not inhibit PEDV replication. In addition, Nsp5 from SARS-CoV-2 and MERS-CoV also cleave human GSDMD (hGSDMD). Therefore, we provide clear evidence that PEDV may utilize the Nsp5-GSDMD pathway to inhibit pyroptosis and, thus, facilitate viral replication during the initial period, suggesting an important strategy for the coronaviruses to sustain their infection. IMPORTANCE Recently, GSDMD has been reported as a key executioner for pyroptosis. This study first demonstrates the molecular mechanism of pGSDMD-mediated pyroptosis and that the pGSDMD-mediated pyroptosis protects host cells against PEDV infection. Notably, PEDV employs its Nsp5 to directly cleave pGSDMD in favor of its replication. We found that Nsp5 proteins from other coronaviruses, such as porcine deltacoronavirus, severe acute respiratory syndrome coronavirus 2, and Middle East respiratory syndrome coronavirus, also had the protease activity to cleave human and porcine GSDMD. Thus, we provide clear evidence that the coronaviruses might utilize Nsp5 to inhibit the host pyroptotic cell death and facilitate their replication during the initial period, an important strategy for their sustaining infection. We suppose that GSDMD is an appealing target for the design of anticoronavirus therapies.

Buffering traumatic reactions to COVID-19: Mindfulness moderates the relationship between the severity of the pandemic and posttraumatic stress symptoms.

[Correction Notice: An Erratum for this article was reported online in Psychological Trauma: Theory, Research, Practice, and Policy on Sep 15 2022 (see record 2023-01896-001). In the original article, the first affiliation was incorrectly listed as "Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education, Beijing Normal University" and was corrected to read "Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University." All versions of this article have been corrected.] Objective: As an international public health emergency panic, Corona Virus Disease-19 (COVID-19) has caused substantial impacts on economic and daily life. The public were at high risk of mental health problems and posttraumatic stress symptoms (PTSS). This study aimed to evaluate the association between objective/subjective severity of COVID-19 pandemic and PTSS, and explore the moderating role of mindfulness. METHOD: Using longitudinal and 7-day ecological momentary assessment (EMA) designs, we gathered data from 109 college students who were home-quarantined to examined study hypotheses. In the EMA phase, participants completed questionnaires measuring subjective severity, mindfulness and PTSS three times per day. Objective severity was indicated using the daily new confirmed cases. Then participants completed a follow-up measure of PTSS 2 months later, when the epidemic initially became stable. RESULTS: The results of structural equation modeling showed that state mindfulness moderated the relationship between subjectivity severity of COVID-19 and PTSS. Specifically, the association between subjective severity of COVID-19 and PTSS was positive at the low level of state mindfulness, and negative at the high level of state mindfulness. Trait mindfulness did not moderate the relationship between objectivity severity of COVID-19 and PTSS. CONCLUSION: Mindfulness-based interventions can be used as preventive mental health education to the daily lives of the general public, and to deal with unpredictable crisis events. Implications of this study are drawn for theory, practice, and research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Acriflavine and proflavine hemisulfate as potential antivirals by targeting Mpro.

The evolving SARS-CoV-2 epidemic buffets the world, and the concerted efforts are needed to explore effective drugs. M^pro is an intriguing antiviral target for interfering with viral RNA replication and transcription. In order to get potential anti-SARS-CoV-2 agents, we established an enzymatic assay using a fluorogenic substrate to screen the inhibitors of M^pro. Fortunately, Acriflavine (ACF) and Proflavine Hemisulfate (PRF) with the same acridine scaffold were picked out for their good inhibitory activity against M^pro with IC₅₀ of 5.60 ± 0.29 µM and 2.07 ± 0.01 µM, respectively. Further evaluation of MST assay and enzymatic kinetics experiment in vitro showed that they had a certain affinity to SARS-CoV-2 M^pro and were both non-competitive inhibitors. In addition, they inhibited about 90 % HCoV-OC43 replication in BHK-21 cells at 1 µM. Both compounds showed nano-molar activities against SARS-CoV-2 virus, which were superior to GC376 for anti-HCoV-43, and equivalent to the standard molecule remdesivir. Our study demonstrated that ACF and PRF were inhibitors of M^pro, and ACF has been previously reported as a PL^pro inhibitor. Taken together, ACF and PRF might be dual-targeted inhibitors to provide protection against infections of coronaviruses.

A pan-sarbecovirus vaccine based on RBD of SARS-CoV-2 original strain elicits potent neutralizing antibodies against XBB in non-human primates.

The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma. Therefore, it is essential to develop broad-spectrum COVID-19 vaccines to combat current and future emerging variants. Here, we found that the human IgG Fc-conjugated RBD of the original SARS-CoV-2 strain (WA1) plus a novel STING agonist-based adjuvant CF501 (CF501/RBD-Fc) could induce highly potent and durable broad-neutralizing antibody (bnAb) responses against Omicron subvariants, including BQ.1.1 and XBB in rhesus macaques with NT50s ranging from 2,118 to 61,742 after three doses. A decline of 0.9- to 4.7-fold was observed in the neutralization activity of sera in the CF501/RBD-Fc group against BA.2.2, BA.2.9, BA.5, BA.2.75, and BF.7 relative to D614G after three doses, while a significant decline of NT50 against BQ.1.1 (26.9-fold) and XBB (22.5-fold) relative to D614G. However, the bnAbs were still effective in neutralizing BQ.1.1 and XBB infection. These results suggest that the conservative but nondominant epitopes in RBD could be stimulated by CF501 to generate bnAbs, providing a proof-of-concept for using "nonchangeable against changeables" strategy to develop pan-sarbecovirus vaccines against sarbecoviruses, including SARS-CoV-2 and its variants.

The Collateral Impact of the COVID-19 Pandemic on HPV-positive Oropharyngeal Cancer Diagnosis

Purpose We aim to assess the potential impact of the COVID-19 pandemic on diagnostic delays in HPV-positive oropharyngeal cancer (OPC), and to describe their underlying reasons. Methods All HPV+ OPC referred to a tertiary cancer centre and diagnosed between June-December 2019 (Pre-Pandemic cohort) vs June-December 2020 (Pandemic cohort) were reviewed. TNM classification, gross-tumor-volumes (GTV) and intervals between sign/symptom onset and treatment initiation were compared between the cohorts. Reasons for delay (>6 months from onset of signs/symptoms to a positive biopsy of the primary tumor, or a delay specifically mentioned in the patient chart) in establishing the diagnosis were recorded per clinician's documentation, and categorized as COVID-related or non-COVID-related. Results A total of 157 consecutive HPV+ OPC patients were identified (Pre-Pandemic: 92;Pandemic: 65). Compared to the Pre-Pandemic cohort, Pandemic cohort patients had a higher proportion of N2-N3 (32% vs 15%, p=0.019) and stage III (38% vs 23%, p=0.034) disease at presentation. The differences in proportions with >6 months delay from symptom onset to establishing the diagnosis (29% vs 20%, p=0.16) or to first treatment (49% vs 38%, p=0.22) were not statistically different. 47% of diagnostic delays in the Pandemic cohort were potentially attributable to COVID-19. Conclusion We observed a collateral impact of the COVID-19 pandemic on HPV+ OPC care through more advanced stage at presentation and a non-significant but numerically longer interval to diagnosis. This could adversely impact patient outcomes and future resource allocation. Both COVID-19-related or unrelated factors contribute to diagnostic delay. Tailored interventions to reduce delays are warranted.

COVID-19 and Eating Problems in Daily Life: The Mediating Roles of Stress, Negative Affect and Posttraumatic Stress Symptoms.

BACKGROUND: The COVID-19 pandemic poses a challenge to individuals' mental health. People worldwide are experiencing increased stress, negative affect, and posttraumatic stress symptoms, which may lead to eating problems. The purpose of this study was to explore the impact of the perceived severity of COVID-19 on eating problems and the mediating effects of stress/negative affect/posttraumatic stress symptoms both at the personal level and interpersonal level. Methods: During the COVID-19 outbreak, a total of 108 college students were recruited to report their perceived severity of COVID-19, stress, negative affect, posttraumatic stress symptoms, and eating problems three times a day for seven consecutive days using Ecological Momentary Assessment. Results: State perceived severity of COVID-19 predicted fewer subsequent eating problems in daily life at the personal level. Both state negative affect and posttraumatic stress symptoms were positively associated with eating problems in daily life. At the interpersonal level, trait-like perceived severity of COVID-19, stress, negative affect, and posttraumatic stress symptoms were positively associated with overall eating problems. There were no mediating effects of stress/negative affect/posttraumatic stress symptoms on the relations between perceived severity of COVID-19 and eating problems at the personal/interpersonal level. Conclusions: The perceived severity of COVID-19, stress, negative affect, and posttraumatic stress symptoms might increase the risk of eating problems.

Bibliometric analyses of social media for educational purposes over four decades.

The unexpected outbreak of COVID-19 pandemic has led students to frequently use social media to receive education, which brought about both positive and negative learning outcomes (Oliveira et al., 2022). To address the issue of integrating social media into education, this study conducted both quantitative and qualitative studies using VOSviewer and CitNetExplorer. The qualitative study through CitNetExplorer, involving 1780 publications, concluded that while social media might have gained popularity in education based on the classic theoretical framework of the zone of proximal development, there might be many challenges such as teacher resistance, data privacy, costs, and ethical and social issues. Besides, this study conducted bibliometric analyses using VOSviewer (N = 1841) to identify the top cited authors, organizations, documents, references, sources, countries, and keywords with high occurrences based on the citation networks. In the future, researchers could enhance the studies on how to guide students and teachers to properly integrate social media into education.

SARS-CoV-2 Omicron subvariants exhibit distinct fusogenicity, but similar sensitivity, to pan-CoV fusion inhibitors.

Continuous emergence of the Omicron variant, along with its subvariants, has caused an increasing number of infections, reinfections, and vaccine-breakthrough infections, seriously threatening human health. Recently, several new Omicron subvariants, such as BA.5, BA.2.75, BA.4.6, and BF.7, bearing distinct mutation profiles in their spike (S) proteins, have significantly increased their capacity to evade vaccine-induced immunity and have shown enhanced infectivity and transmissibility, quickly becoming dominant sublineages. In this study, we found the S proteins of these Omicron subvariants to have 2- to 4-fold more efficient membrane fusion kinetics than that of the original Omicron variant (BA.1), indicating that these novel Omicron subvariants might possess increased pathogenicity. We also identified that peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, showed equal efficacy against membrane fusion mediated by S proteins of the noted Omicron subvariants and infection by their pseudoviruses. Additionally, either immune sera induced by wild-type (WT) SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed potent synergism with EK1 against both WT SARS-CoV-2 and various Omicron subvariants, further suggesting that EK1-based fusion inhibitors are promising candidates for development as clinical antiviral agents against the currently circulating Omicron subvariants.

Development of variant-proof severe acute respiratory syndrome coronavirus 2, pan-sarbecovirus, and pan-ß-coronavirus vaccines.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first-generation SARS-CoV-2 vaccines. Other sarbecoviruses, such as SARS-CoV and SARS-related coronaviruses (SARSr-CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant-proof SARS-CoV-2, pan-sarbecovirus or pan-ß-CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad-spectrum neutralizing antibody responses and protective immunity to combat the current SARS-CoV-2 and its variants, other sarbecoviruses, as well as other ß-CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS-CoV-2 vaccines and summarized recent advances in broad-spectrum vaccines against sarbecoviruses and ß-CoVs.