Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.

Population genomics study of Vibrio alginolyticus.

Vibrio alginolyticus is a Gram-negative bacillus that causes vibriosis to human and aquatic products, including fish, shrimp and shellfish. It poses a threat to public health and causes enormous economic losses to the aquaculture industry. However, research on genetic diversity and pathogenicity-related genetic elements based on whole genome is still lacking. In this study, sixty-eight strains of V. alginolyticus were collected from four provinces of China and the whole genome sequences were obtained. Combined with 113 publicly available genome sequences downloaded from NCBI, we inferred the population structure of V. alginolyticus by using fineSTRUCTURE software, and identified the virulence and antibiotic resistance factors using the VFDB, CARD and ResFinder database. The results indicated that V. alginolyticus included two main lineages, named Lineage 1 and Lineage 2. Both lineages distributed in America and Asia, but all the European genomes were classified into Lineage 1. A single cross-ocean transmission event was inferred from one of the 12 identified clonal groups in our dataset. V. alginolyticus genome contains a variety of virulence factors, such as tlh, OmpU, and IlpA, etc. The distribution of virulence factors revealed no lineage-specificity, but some of which revealed differences in their geographical distribution. A lower frequency of VP1611, vcrD, vopD, fleR/flrC and a higher frequency of IlpA were observed in genomes of Europe than other continents. In China, a lower frequency of fleR/flrC, and no IlpA were observed in genomes from Guangxi province. Among the identified antibiotic resistance genes, TxR and fos are significantly enriched in Lineage 2. In addition, TxR is more common in genomes from Asia, compared with the American and European genomes. But in China, the frequency of TxR in Sichuan genomes is much lower than in other provinces. We also found that large fragments of plasmids or ICEs that carried multiple drug resistance genes were present in five V. alginolyticus genomes (VA24, VA28, 2014V-1011, ZJ-T and Vb1833). Based on population genomics analysis, our study delineated the population structure, distribution of virulence and antibiotic resistance related factors of V. alginolyticus, which lays a foundation for future study of genetic characters and pathogenesis mechanism of this pathogen and will improve the works on monitoring, prevention and control of this pathogen.

Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone: Clinical, Virological, Immunological, and Evolutionary Analyses.

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.

[Homologous recombination among bacterial genomes: the measurement and identification].

Homologous recombination is one of important sources in shaping the bacterial population diversity, which disrupts the clonal relationship among different lineages through horizontal transferring of DNA-segments. As consequence of blurring the vertical inheritance signals, the homologous recombination raises difficulties in phylogenetic analysis and reconstruction of population structure. Here we discuss the impacts of homologous recombination in inferring phylogenetic relationship among bacterial isolates, and summarize the tools and models separately used in recombination measurement and identification. We also highlight the merits and drawbacks of various approaches, aiming to assist in the practical application for the analysis of homologous recombination in bacterial evolution research.

The sorption performance of corroded Gaomiaozi bentonite by evolved cement water at different temperatures: the case of europium removal.

In the Chinese high-level radioactive waste geological disposal program, Gaomiaozi (GMZ) bentonite has been selected as the potential buffer/backfill material. After the closure of the repository, the Ca-OH-type alkaline solution (evolved cement water) released by cement degradation may last for more than 100,000 years. The bentonite will undergo the corrosion of evolved cement water (ECW) for a long period. This work focuses on the sorption property of GMZ bentonite altered by ECW. Firstly, the corrosion experiments on compacted GMZ specimens with the dry density of 1.70 Mg/m3 were carried out under constant volume conditions at two temperatures. Then, the sorption of europium (Eu (III)) onto the corroded GMZ bentonite was studied by batch experiments. The results of batch sorption tests indicate that the altered GMZ bentonite keeps an effective removal property with the uptake of Eu (III) more than 99%. The effect of high-temperature conditions of the repository on the sorption property of bentonite is not significant. The results also suggest that the evolved cement water presents no detrimental effect on the long-term adsorption performance of bentonite even under higher temperature conditions.

[The clinical feature, diagnosis and management of splenic artery aneurysms in liver transplant patients].

OBJECTIVE: To summarize the clinical feature of splenic artery aneurysms (SAA) in OLT recipient, and review the experience in diagnosis and management. METHODS: The clinical data, results of four-phase CT scanning and CT angiography of 450 recipients, who underwent OLT from December 2001 to December 2003 were analyzed statistically. RESULTS: Twenty of 450 recipients were diagnosed as SAA, the incidence was about 4.4%. Nineteen of them were diagnosed by four-phase CT scanning. Fifteen patients did not receive any treatment for SAA during OLT, but two of them suffered SAA rupture after OLT, among which one died of hemorrhagic shock although emergency operations were performed. The five patients, who were performed splenectomy with SAA resection during transplantation, recovered successfully after OLT, and their grafts' function was satisfactory. CONCLUSIONS: Morbidity of SAA is higher in patients of liver cirrhosis. Four-phase CT scanning can diagnose SAA exactly. In the early period post-OLT, SAA rupture happens frequently, so SAA resection should be performed during transplantation.

Application of nucleoside analogues to liver transplant recipients with hepatitis B.

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.

[Ecological-geographic landscapes of natural plague foci in China VIII. Typing of natural plague foci].

Since plague is an important natural focus zoonosis, the typing of natural plague foci becomes one of the elements in understanding the nature and developing related prevention program of the disease. Natural foci of plague are composed by four fundamental parts which include Eco-geographical landscape (natural plague foci), hosts, vectors and pathogens (Yersinia pestis) that comprehensively interact through the large temporal scale of evolution. Human activities have had great impact on the foci of natural plague. Based on the published serial research papers, we tried to integrate the knowledge of each factor in natural plague foci and focusing on theoretical aspects, so as to strengthen the prevention and surveillance programs of plague to be extrapolated to other zoonosis.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues.

Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B. NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease. However, drug resistance caused by their long-term use becomes a practical problem, which influences the long-term outcomes in patients. Liver transplantation is the only choice for patients with HBV-related end-stage liver disease. But, the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients. Recently, the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA. This may complicate the antiviral therapy and bring poorly prognostic outcomes. Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR, the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy. The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies. This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

[Ecological-geographic landscapes of natural plague foci in China VII. Typing of natural plague foci].

OBJECTIVE: To group and characterize natural plague foci in China. METHODS: A novel two-class typing method as well as a three-indication nomenclature method were established to group and characterize the natural plague foci, on the basis of eco-geographical landscapes of plague foci, genetics of Yersinia pestis, zoology of rodent reservoirs and the entomology of flea vectors. RESULTS: A total of 12 distinct natural plague foci (including 19 subtypes) as well as their biological features were characterized. CONCLUSION: Natural plague foci in China were grouped and characterized in this study.