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Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea and high mortality in neonatal piglets. Pseudorabies causes acute and often fatal infections in young piglets, respiratory disorders in growing pigs, and reproductive failure in sows. In late 2011, pseudorabies virus (PRV) variants occurred in Bartha-K61-vaccine-immunized swine herds, resulting in economic losses to the global pig industry. Therefore, it is essential to develop a safe and effective vaccine against both PEDV and PRV infections. In this study, we constructed a recombinant virus rPRV-PEDV S1 expressing the major neutralizing epitope region (COE, SS2, and SS6) of the PEDV S1 protein by homologous recombination technology and CRISPR/Cas9 gene editing technology, and then evaluated its biological characteristics in vitro and immunogenicity in pigs. The recombinant virus rPRV-PEDV S1 had similar growth kinetics in vitro to the parental rPRV NY-gE−/gI−/TK− strain, and was proven genetically stable in swine testicle (ST) cells and safe for piglets. PEDV S1-specific antibodies were detected in piglets immunized with rPRV-PEDV S1 on the 7th day post-immunization (dpi), and the antibody level increased rapidly at 14–21 dpi. Moreover, the immunized piglets receiving the recombinant virus exhibited alleviated clinical signs and reduced viral load compared to the unvaccinated group following a virulent PEDV HN2021 strain challenge. Also, piglets immunized with rPRV-PEDV S1 developed a PRV-specific humoral immune response and elicited complete protection against a lethal PRV NY challenge. These data indicate that the recombinant rPRV-PEDV S1 is a promising vaccine candidate strain for the prevention and control of PEDV and PRV infections.

Abstract. Background. The global spread of coronavirus disease 2019 (COVID-19) continues to threaten human health security, exerting considerable pressure on healthcare systems worldwide. While prognostic models for COVID-19 hospitalized or intensive care patients are currently available, prognostic models developed for large cohorts of thousands of individuals are still lacking. Methods. Between February 4 and April 16, 2020, we enrolled 3,974 patients admitted with COVID-19 disease in the Wuhan Huo-Shen-Shan Hospital and the Maternal and Child Hospital, Hubei Province, China. (1) Screening of key prognostic factors: A univariate Cox regression analysis was performed on 2,649 patients in the training set, and factors affecting prognosis were initially screened. Subsequently, a random survival forest model was established through machine analysis to further screen for factors that are important for prognosis. Finally, multivariate Cox regression analysis was used to determine the synergy among various factors related to prognosis. (2) Establishment of a scoring system: The nomogram algorithm established a COVID-19 patient death risk assessment scoring system for the nine selected key prognostic factors, calculated the C index, drew calibration curves and drew training set patient survival curves. (3) Verification of the scoring system: The scoring system assessed 1,325 patients in the test set, splitting them into high- and low-risk groups, calculated the C-index, and drew calibration and survival curves. Results. The cross-sectional study found that age, clinical classification, sex, pulmonary insufficiency, hypoproteinemia, and four other factors (underlying diseases: blood diseases, malignant tumor; complications: digestive tract bleeding, heart dysfunction) have important significance for the prognosis of the enrolled patients with COVID-19. Herein, we report the discovery of the effects of hypoproteinemia and hematological diseases on the prognosis of COVID-19. Meanwhile, the scoring system established here can effectively evaluate objective scores for the early prognoses of patients with COVID-19 and can divide them into high- and low-risk groups (using a scoring threshold of 117.77, a score below which is considered low risk). The efficacy of the system was better than that of clinical classification using the current COVID-19 guidelines (C indexes, 0.95 vs. 0.89). Conclusions. Age, clinical typing, sex, pulmonary insufficiency, hypoproteinemia, and four other factors were important for COVID-19 survival. Compared with general statistical methods, this method can quickly and accurately screen out the relevant factors affecting prognosis, provide an order of importance, and establish a scoring system based on the nomogram model, which is of great clinical significance.

Zn-based alloys are considered as new kind of potential biodegradable implanted biomaterials recently. The difficulty of metal implanted biomaterials and bone tissue integration seriously affects the applications of metal implanted scaffolds in bone tissue-related fields. Herein, we self-designed Zn0.8Mn and Zn0.8Mn0.1Li alloys and CaP coated Zn0.8Mn and Zn0.8Mn0.1Li alloys, then evaluated the degradation property and cytocompatibility. The results demonstrated that the Zn0.8Mn0.1Li alloys had profoundly modified the degradation property and cytocompatibility, but Zn0.8Mn0.1Li alloys had particularly adverse effects on the surface morphology of osteoblasts. The results furtherly showed that the CaP-coated Zn0.8Mn and Zn0.8Mn0.1Li alloys scaffold had better biocompatibility, which would further guarantee the biosafety of this new kind of biodegradable Zn-based alloys implants for future clinical applications.

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.

Porcine epidemic diarrhea virus (PEDV) is the major pathogen that causes diarrhea and high mortality in newborn piglets, with devastating impact on the pig industry. To further understand the molecular epidemiology and genetic diversity of PEDV field strains, in this study the complete genomes of four PEDV variants (HN2021, CH-HNYY-2018, CH-SXWS-2018, and CH-HNKF-2016) obtained from immunized pig farms in central China between 2016 to 2021 were characterized and analyzed. Phylogenetic analysis of the genome and S gene showed that the four strains identified in the present study had evolved into the subgroup G2a, but were distant from the vaccine strain CV777. Additionally, it was noteworthy that a new PEDV strain (named HN2021) belonging to the G2a PEDV subgroup was successfully isolated in vitro and it was further confirmed by RT-PCR that this isolate had a large natural deletion at 207–373 nt of the ORF3 gene, which has never been reported before. Particularly, in terms of pathogenicity evaluation, colostrum deprivation piglets challenged with PEDV HN2021 showed severe diarrhea and high mortality, confirming that PEDV HN2021 was a virulent strain. Hence, PEDV strain HN2021 of subgroup G2a presents a promising vaccine candidate for the control of recurring porcine epidemic diarrhea (PED) in China. This study lays the foundation for better understanding of the genetic evolution and molecular pathogenesis of PEDV.

MN1 C-terminal truncation (MCTT) syndrome was first reported in 2020 and only 28 patients have been recorded to date. Since MCTT syndrome is a newly defined and rare syndrome with many clinical features, the present study reviewed the manifestations and management of oral and dental anomalies. Gene variants of MCTT syndrome and their positive phenotypes were summarised. The phenotypes of variants in two exons differed from each other mainly in the craniomaxillofacial region, including brain MRI abnormalities and palatal morphology. Pathogenic mechanisms, especially in craniofacial and oral anomalies, were discussed. Appropriate treatments in the stomatology and respiratory departments could improve the symptoms of MCTT syndrome. The different sites of MN1 gene variants may influence the clinical symptoms and there may be racial differences in MCTT syndrome. We recommend oral and pulmonary evaluations for the multidisciplinary treatment of MCTT syndrome. [ABSTRACT FROM AUTHOR]