Enantioselective Effect of Chiral Small Molecules in SARS-CoV-2 Vaccine-Induced Immune Response.

Although numerous chiral small molecules have been discovered and synthesized, the investigation on their enantioselective immunological effects remains limited. In this study, we designed and synthesized a pair of small molecule enantiomers (R/S-ResP) by covalently bonding two immunostimulators (resiquimod/Res) onto a planar chiral framework (paracyclophane/P). Notably, we found that S-ResP exhibits a 4.05-fold higher affinity for toll-like receptor 7 (TLR7) than R-ResP, thereby more effectively enhancing the functions of dendritic cells and macrophages in cytokine secretion and antigen internalization. Furthermore, we observed that S-ResP significantly enhances RBD antigen-induced cross-neutralization against various SARS-CoV-2 strains compared to R-ResP. These findings demonstrate the enantioselective effects of small molecules on regulating vaccine-induced immune responses and emphasize the significance of chirality in designing small molecular adjuvants.

At-Home COVID-19 Rapid Antigen Test Down to 0.03 pg mL-1 of Nucleocapsid Protein.

Rapid and ultra-sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for early screening and management of COVID-19. Currently, the real-time reverse transcription polymerase chain reaction (rRT-PCR) is the primary laboratory method for diagnosing SARS-CoV-2. It is not suitable for at-home COVID-19 diagnostic test due to the long operating time, specific equipment, and professional procedures. Here an all-printed photonic crystal (PC) microarray with portable device for at-home COVID-19 rapid antigen test is reported. The fluorescence-enhanced effect of PC amplifies the fluorescence intensity of the labeled probe, achieving detection of nucleocapsid (N-) protein down to 0.03 pg mL-1 . A portable fluorescence intensity measurement instrument gives the result (negative or positive) by the color of the indicator within 5 s after inserting the reacted PC microarray test card. The N protein in inactivated virus samples (with cycle threshold values of 26.6-40.0) can be detected. The PC microarray provides a general and easy-to-use method for the timely monitoring and eventual control of the global coronavirus pandemic.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

Relationships Between Mental Health, Emotion Regulation, and Meaning in Life of Frontline Nurses During the COVID-19 Outbreak.

Background: The sporadic outbreak of COVID-19 and the constant mutation of the virus have put the public in panic. Frontline nurses' appropriate emotional regulation and mental health are the key to win the victory of fighting against the epidemic. The relationships between these variables directly influence the availability of human resources to combat COVID-19. Objective: To investigate the relationship between meaning in life, emotional regulation, and mental health of frontline nurses during the Delta virus epidemic. Methods: A cross-sectional survey was conducted in August 2021 among 105 nurses from the Second Xiangya Hospital, Central South University, Changsha, China, who were deployed at the COVID-19 units in Zhangjiajie People's Hospital. The Chinese Meaning in Life Questionnaire, Emotion Regulation Questionnaire, and Psychological Questionnaire for Emergent Events of Public Health were used to evaluate their meaning in life, emotion regulation, and mental health. Their correlation and the moderating effect of emotion regulation were conducted. Results: In total, 105 (100%) nurses responded. There were 14 men and 91 women and the mean age was (30.295 ± 4.653) years. The average score of meaning in life and mental health of frontline nurses was 49.971 ± 6.386 and 2.755 ± 2.580, respectively. The meaning in life of frontline nurses was positively correlated with cognitive reappraisal and negatively correlated with expressive suppression and mental health. Mental health was negatively correlated with cognitive reappraisal and positively correlated with expressive suppression. The emotional regulation of frontline nurses has a moderating effect between meaning in life and mental health. Conclusion: Meaning in life and emotion regulation of frontline nurses were significantly correlated with mental health under the effects of the COVID-19 pandemic. Changing the emotion regulation of frontline nurses, strengthening cognitive reappraisal, and weakening expressive suppression could reduce the predictive effect of meaning in life on mental health.

Progress and Challenges in Modeling Dynamics–Microphysics Interactions: From the Pi Chamber to Monsoon Convection

The CAIPEEX (Cloud Aerosol Interaction and Precipitation Enhancement Experiment) monsoon convective clouds case was designed to explore the impacts of environmental and cloud condensation nuclei (CCN) conditions on monsoon convection. Pi chamber warm cloud case The scientific objectives are 1) to demonstrate the model capability of representing the detailed microphysical processes happening in the cloud chamber and how different models behave in different aerosol injection rates, 2) to reveal the model uncertainties and limitations in the existing modeling tools, and 3) to provide guidance and recommendations for future work to improve cloud chamber simulations and model–laboratory comparisons. The comparison was performed among a diverse set of model categories, including four types of LES models (Dziekan et al. 2019;Shima et al. 2009, 2020;Niedermeier et al. 2020;Khairoutdinov and Randall 2003) performed by the University of Warsaw, University of Hyogo, Leibniz Institute for Tropospheric Research, and Brookhaven National Laboratory;two types of direct numerical simulation (DNS) models (Chen et al. 2021;Richter et al. 2021) by the National Center for Atmospheric Research (NCAR) and the University of Notre Dame;and the Linear Eddy Model (LEM;Su et al. 1998) by the University of Utah. Interestingly, however, the amount of updraft tilting was sensitive not only to the vertical wind shear used in the model, but also to the method of cloud initiation, i.e., forcing using warm bubbles or surface heat fluxes.

Relationships Between Mental Health, Emotion Regulation, and Meaning in Life of Frontline Nurses During the COVID-19 Outbreak

Background The sporadic outbreak of COVID-19 and the constant mutation of the virus have put the public in panic. Frontline nurses' appropriate emotional regulation and mental health are the key to win the victory of fighting against the epidemic. The relationships between these variables directly influence the availability of human resources to combat COVID-19. Objective To investigate the relationship between meaning in life, emotional regulation, and mental health of frontline nurses during the Delta virus epidemic. Methods A cross-sectional survey was conducted in August 2021 among 105 nurses from the Second Xiangya Hospital, Central South University, Changsha, China, who were deployed at the COVID-19 units in Zhangjiajie People's Hospital. The Chinese Meaning in Life Questionnaire, Emotion Regulation Questionnaire, and Psychological Questionnaire for Emergent Events of Public Health were used to evaluate their meaning in life, emotion regulation, and mental health. Their correlation and the moderating effect of emotion regulation were conducted. Results In total, 105 (100%) nurses responded. There were 14 men and 91 women and the mean age was (30.295 ± 4.653) years. The average score of meaning in life and mental health of frontline nurses was 49.971 ± 6.386 and 2.755 ± 2.580, respectively. The meaning in life of frontline nurses was positively correlated with cognitive reappraisal and negatively correlated with expressive suppression and mental health. Mental health was negatively correlated with cognitive reappraisal and positively correlated with expressive suppression. The emotional regulation of frontline nurses has a moderating effect between meaning in life and mental health. Conclusion Meaning in life and emotion regulation of frontline nurses were significantly correlated with mental health under the effects of the COVID-19 pandemic. Changing the emotion regulation of frontline nurses, strengthening cognitive reappraisal, and weakening expressive suppression could reduce the predictive effect of meaning in life on mental health.

Amantadine-assembled nanostimulator enhances dimeric RBD antigen-elicited cross-neutralization against SARS-CoV-2 strains.

There is an urgent need to develop new vaccination strategies to elevate the cross-neutralization against different SARS-CoV-2 strains. In this study, we construct the spherical amantadine-assembled nanostimulator (AAS). Amantadine as immunostimulating molecules are displayed on the outermost layer of AAS. Molecular mechanism analysis reveals that AAS can activate RIG-I-like receptor (RLR) signaling pathway to increase the expression of type I interferons in vivo. AAS-mediated activation of RLR signaling pathway further promotes the maturation and proliferation of dendritic cells (DCs) and T helper cells (Ths), finally activating B cells to produce potent antibody responses. In performance evaluation experiments, the mixture of AAS and dimeric RBD significantly enhances RBD-specific humoral responses (4-fold IgG, 3.5-fold IgG2a, 3.3-fold IgG2b, 3.8-fold IgG3 and 1.3-fold IgM), in comparison to aluminum adjuvant-assistant dimeric RBD. Importantly, AAS dramatically elevates dimeric RBD-elicited cross-neutralization against different SARS-CoV-2 strains such as Wuhan-Hu-1 (9-fold), B.1.1.7 (UK variant, 15-fold), B.1.351 (South African variant, 4-fold) and B.1.617.2 (India variant, 7-fold). Our study verifies the mechanism of AAS in activating RLR signaling pathway in host immune system and highlights the power of AAS in improving antigen-elicited cross-neutralization against different SARS-CoV-2 strains.

Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus.

Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4+ and CD8+ T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.

D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study.

BACKGROUND: Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome. METHODS: We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. RESULTS: Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10-94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau-b = 0.374, P = 0.000) and chest CT staging (Kendall's tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77-0.92). CONCLUSIONS: D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.