Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Anxiety and its relationship with sleep disturbance and problematic smartphone use among Chinese medical students during COVID-19 home confinement - A structural equation model analysis.

BACKGROUND: The majority of medical students in China have experienced home confinement and a reliance on online resources to study medicine since the outbreak of COVID-19. More time spent studying online during the COVID-19 pandemic may be a potential risk factor for problematic smartphone use, since smartphones have become the most commonly used device for accessing the internet. The objective of the present study was to explore the association between anxiety, smartphone problematic use and sleep disturbance among medical students during the enforced COVID-19 home confinement. METHODS: Altogether, 666 medical students validly answered a self-administered questionnaire, which included the Chinese version of the Generalized Anxiety Disorder scale, Smartphone addiction scale - short version, and the PROMIS Sleep Disturbance scale (short form). Hierarchical multiple regression analyses were employed to explore the associated factors of anxiety. Structural equation modeling was conducted to test hypothesized associations. RESULTS: Anxiety was significantly associated with problematic smartphone use and sleep disturbance among medical students during the COVID-19 pandemic. Problematic smartphone use not only directly affected anxiety, but also exerted a significant indirect effect on anxiety via sleep disturbance. A significant decrease of the path coefficient of problematic smartphone use on anxiety (from ß=0.53 to ß=0.22, P<0.01) was observed with sleep disturbance being modeled as a mediator. LIMITATIONS: Limitations include its cross-sectional design and samples recruited from only one medical school. CONCLUSIONS: The detrimental impact of problematic smartphone use and the importance of sleep health on mitigating anxiety should be highlighted and incorporated into medical education.

The Influence of L2 Proficiency on Bilinguals' Creativity: The Key Role of Adaptive Emotion Regulation Strategies During the COVID-19 Pandemic.

The COVID-19 pandemic has brought severe impact on language learners' emotional states and their performance in creativity. Yet, their ability to regulate emotions is crucial for everyday functioning during times of crisis. The question of how adaptive emotion regulation (ER) strategies, which help an individual maintain appropriate and stable mood states, might affect bilinguals' creativity remains unexplored. The present study investigated this issue by measuring various indicators of the psychological impact of the COVID-19 pandemic, L2 proficiency, adaptive ER strategies, and bilinguals' cognitive creativity (CC) and emotional creativity (EC) during the pandemic. Results from a sample of 235 bilingual participants who completed a battery of survey instruments showed that: (1) bilinguals' negative mood significantly increased during the pandemic compared with their mood state before the pandemic; (2) their negative mood during the pandemic was positively associated with their adaptive ER strategies; (3) L2 proficiency had a direct effect on bilinguals' cognitive flexibility, CC, and EC; (4) L2 proficiency also indirectly influenced bilinguals' CC through cognitive flexibility. These results suggest that cognitive flexibility had a simple mediation effect on the association between L2 proficiency and CC. However, the current study further found that bilinguals had different cognitive patterns in EC. L2 proficiency influenced bilinguals' EC through cognitive flexibility indirectly only when adaptive ER strategies had a moderation effect on the association between cognitive flexibility and EC. However, this moderated mediation effect was not significant in CC. The current study implies that bilinguals' adaptive ER strategies played a distinct role in bilinguals' EC during the COVID-19 pandemic.

A Positive Role of Negative Mood on Creativity: The Opportunity in the Crisis of the COVID-19 Epidemic.

The COVID-19 epidemic is associated with negative mood, which has the potential to be a powerful driver of creativity. However, the influence of negative mood on cognitive creativity and emotional creativity remains elusive. Previous research has indicated that self-focused attention is likely to be related to both negative mood and creativity. The current study introduced two self-focused attention variables (i.e., rumination, reflection) to explore how negative mood might contribute to cognitive creativity and emotional creativity. Based on a sample of 351 participants, our study found that (1) negative mood during the outbreak of COVID-19 was associated with cognitive creativity and emotional creativity. Meanwhile, there were significant serial mediation effects of rumination and reflection in the relationship between negative mood and creativity and (2) the psychological impact after exposure to the COVID-19 epidemic was positively correlated with emotional creativity but not with cognitive creativity. These results suggested that individuals, in real life and work, could achieve better creative performance through moderate self-focus. Moreover, individuals with different mood states can be induced to enhance their creativity in times of crisis through intervention training to promote reflection.

Psychological Impact of Health Risk Communication and Social Media on College Students During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: The outbreak of COVID-19 began in 2019 and is expected to impact the psychological health of college students. Few studies have investigated the associations among health risk communication, social media, and psychological symptoms during a major pandemic. OBJECTIVE: The aim of this research was to assess the prevalence of psychological symptoms among college students and explore their associations with health risk communication and social media. METHODS: A web-based survey was distributed through the Wenjuanxing platform among Chinese college students from March 3-15, 2020. In addition to demographics, information on health risk communication and social media was collected, and the Symptom Checklist 90 Phobia and Health Anxiety Inventory subscale was used to assess psychological symptoms among 1676 college students in China. Multivariable logistic regression was performed to examine these independent risk factors. RESULTS: The prevalence of panic and health anxiety was 17.2% (288/1676) and 24.3% (408/1676), respectively. Regarding risk communication, understanding the risk of COVID-19 (odds ratio [OR] 0.480, 95% CI 0.367-0.627) was a protective factor against panic. Knowledge of prognosis (OR 0.708, 95% CI 0.551-0.910), preventive measures (OR 0.380, 95% CI 0.195-0.742), and wearing face masks (OR 0.445, 95% CI 0.230-0.862) were shown to be protective factors in predicting health anxiety. Perceived lethality (OR 1.860, 95% CI 1.408-2.459), being affected by the global spread (OR 1.936, 95% CI 1.405-2.669), and impact on social contacts (OR 1.420, 95% CI 1.118-1.802) were identified as significant risk factors associated with health anxiety. In terms of social media, trust in mainstream media (OR 0.613, 95% CI 0.461-0.816) was considered to be a protective factor against health anxiety. CONCLUSIONS: There was a high prevalence of psychological symptoms among college students. Health risk communication and social media use were important in predicting psychological symptoms, especially health anxiety. Scientific and evidence-based information should be reported by social media platforms. Web-based consultation and intervention measures should be the focus of future studies.

A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge.

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.