Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Rational development of multicomponent mRNA vaccine candidates against mpox.

The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.

Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice.

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.

How Emotional Intelligence Influences Cognitive Outcomes Among University Students: The Mediating Role of Relational Engagement During the Covid-19 Pandemic.

This study investigated the relationships among emotional intelligence (EI), relational engagement (RE), and cognitive outcomes (COs). A survey questionnaire containing 34 statements was completed by 338 undergraduate students from the four universities of China, with responses recorded on a 7-point Likert-type scale. The relationships were examined using the partial least squares structural equation modeling. The findings showed that EI influenced the COs directly and indirectly during the pandemic. In the forms of self-regulation (SR) and social skills (SS), the high levels of EI improved the COs of the students. Further, the aspects of EI, such as SR, self-awareness (SA), empathy (E), motivation (M), and SS were found to improve the RE of the students. The RE was positively correlated with the COs, indicating its potential for improving critical thinking among university students. Finally, the RE was a key mediator of the relationship between the EI and COs. It is concluded that the students with higher levels of EI and RE may achieve better COs. The implications of the research and suggestions for future studies are also discussed.

Machine learning based early warning system enables accurate mortality risk prediction for COVID-19.

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.

O2-Type Li0.78[Li0.24Mn0.76]O2 Nanowires for High-Performance Lithium-Ion Battery Cathode

Continued improvement in the electrochemical performance of Li-Mn-O oxide cathode materials is key to achieving advanced low-cost Li-ion batteries with high energy densities. In this study, O2-type Li0.78[Li0.24Mn0.76]O2 nanowires were synthesized by a solvothermal reaction to produce P2-type Na5/6[Li1/4Mn3/4]O2 nanowires, which were then subjected to molten salt Li-ion exchange. The resulting nanowires have diameters less than 20 nm and lengths of several micrometers. The full-Mn-based nanowires cathode material delivers a reversible capacity of 275 mAh g-1 at 0.1 C and 200 mAh g-1 at a high current rate of 15 C with a capacity retention of more than 80% and the voltage decay was dramatically suppressed after 100 cycles. This excellent performance is ascribed to the highly stable oxygen redox reaction and lack of layered-to-spinel phase transition in the O2-type structure during cycling.

Risk factors for developing into critical COVID-19 patients in Wuhan, China: A multicenter, retrospective, cohort study.

BACKGROUND: The ferocious global assault of COVID-19 continues. Critically ill patients witnessed significantly higher mortality than severe and moderate ones. Herein, we aim to comprehensively delineate clinical features of COVID-19 and explore risk factors of developing critical disease. METHODS: This is a Mini-national multicenter, retrospective, cohort study involving 2,387 consecutive COVID-19 inpatients that underwent discharge or death between January 27 and March 21, 2020. After quality control, 2,044 COVID-19 inpatients were enrolled. Electronic medical records were collected to identify the risk factors of developing critical COVID-19. FINDINGS: The severity of COVID-19 climbed up straightly with age. Critical group was characterized by higher proportion of dyspnea, systemic organ damage, and long-lasting inflammatory storm. All-cause mortality of critical group was 85•45%, by contrast with 0•58% for severe group and 0•18% for moderate group. Logistic regression revealed that sex was an effect modifier for hypertension and coronary heart disease (CHD), where hypertension and CHD were risk factors solely in males. Multivariable regression showed increasing odds of critical illness associated with hypertension, CHD, tumor, and age ≥ 60 years for male, and chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), tumor, and age ≥ 60 years for female. INTERPRETATION: We provide comprehensive front-line information about different severity of COVID-19 and insights into different risk factors associated with critical COVID-19 between sexes. These results highlight the significance of dividing risk factors between sexes in clinical and epidemiologic works of COVID-19, and perhaps other coronavirus appearing in future. FUNDING: 10.13039/100000001 National Science Foundation of China.