Intestinal microbiota has important effect on severity of hand foot and mouth disease in children.

BACKGROUND: The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. METHODS: We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. RESULTS: We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. CONCLUSIONS: Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

A newly developed real-time PCR assay for discriminating influenza B virus Yamagata and Victoria lineages.

Currently, two distinct lineages of influenza B virus (IBV), B/Victoria and B/Yamagata lineage, have been co-circulating in human beings. Assessment of the prevalent lineage is key for the recommendation of the seasonal influenza vaccine composition and the evaluation of its efficacy. In this study, a multiplex qRT-PCR assay for the discrimination of the IBV lineages was designed based on the genetic differences of the hemagglutinin genes between B/Yamagata and B/Victoria lineages. The assay was highly specific and able to discriminate the lineages of IBV without any non-specific reaction against other influenza A viruses. The detection limit of the assay was determined to be 10 genome-equivalent copies and 2.8 × 10-2 50% tissue culture infectious doses (TCID50 ) of live IBV per reaction. Moreover, our assay was able to discriminate the lineages of IBVs in clinical samples with 100% accuracy, when compared with pyrosequencing. Our results indicate that this assay may represent an update of the existing qRT-PCR assays and will be of great use for the rapid and accurate diagnosis and surveillance of the circulating IBVs.

Enzymatic reporting of peste des petits ruminants virus genes ligating two specific probes on nanoparticles.

An alternative strategy for the detection of nucleic acid derived from peste des petits ruminants virus was developed omitting amplification. The assay is based on two probes complementary to the target sequences, one conjugated to magnetic microparticles the second to gold nanoparticles labeled with horseradish peroxidase. In the presence of target gene the two particles ligate via the probes and the complex can be magnetically separated. Applying substrate and chromogen a color reaction results for a positive case. Under optimized conditions, the approach had a linear detection range from 10 fM to 1 µM for ssDNA corresponding to an RNA low detection limit of 17.6 ng/µl. The quick performance (45 min) and not requiring expensive instrumentations offer a new way of detecting nucleic acids for the clinical diagnosis in our case for peste des petits ruminants virus.

Metaphorical Description and Model Description of Complex Systems.

From metaphorical description to model description is the symbol of the maturity of complexity science. This paper focuses on two model description methods of complex systems: formal system model and relevance theory model, and compares their advantages and disadvantages. These two models are descriptions of complex systems from different perspectives and have important and irreplaceable significance in the theoretical research and practical application of complex systems. The future research direction of complex systems is not the "integration" of the two models but the alternation of the two models, which scientifically reveals the essence of complex systems from multiple perspectives. In view of the complexity of education and the scientificity of educational evaluation, a fuzzy evaluation method is proposed. Fuzzy evaluation is a mathematical thinking mode based on fuzzy theory and mathematical methods, which studies fuzzy and complex phenomena, and provides quantitative relationship and description for educational evaluation.

Generation of Chicken IgY against SARS-COV-2 Spike Protein and Epitope Mapping.

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.

Delayed peak of human infections and ongoing reassortment of H7N9 avian influenza virus in the newly affected western Chinese provinces during Wave Five.

OBJECTIVES: Eight additional provinces in western China reported human infections for the first time during the fifth wave of human H7N9 infections. The aim of this study was to analyze the epidemiological and virological characteristics of this outbreak. METHODS: The epidemiological data of H7N9 cases from the newly affected western Chinese provinces were collected and analyzed. Full-length genome sequences of H7N9 virus were downloaded from the GenBank and GISAID databases, and phylogenetic, genotyping, and genetic analyses were conducted. RESULTS: The peak of human infections in the newly affected western Chinese provinces was delayed by 4 months compared to the eastern Chinese provinces, and both low pathogenic (LP) and highly pathogenic (HP) H7N9-infected cases were found. The LP- and HP-H7N9 virus belonged to 10 different genotypes (including four new genotypes), of which G11 and G3 were the dominant genotypes, respectively. Almost all of these viruses originated from eastern and southern China and were most probably imported from neighboring provinces. Genetic characteristics of the circulating viruses were similar to those of the viruses from previously affected provinces during Wave Five. CONCLUSIONS: A delayed peak of human infections was observed in the newly affected western Chinese provinces, and reassortment has been ongoing since the introduction of H7N9 viruses. This study highlights the importance of continued surveillance of the circulation and evolution of H7N9 virus in western China.

Complete genome sequence of a highly pathogenic porcine reproductive and respiratory syndrome virus variant isolated from a backyard piglet.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) isolates have showed accelerating evolution under the great immune pressure in China in recent years. Here, we report the complete genome sequence of the HP-PRRSV variant GX1001 isolated from a vaccinated backyard piglet.

Recombinant adenovirus expressing F and H fusion proteins of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in goats.

Peste des petits ruminants (PPR) is an acute and contagious disease of some small ruminants caused by peste des petits ruminants virus (PPRV). Fusion (F) protein and hemagglutinin (H) protein are two glycoproteins of PPRV that might induce a protective immune response. In this study, three replication-defective recombinant adenoviruses were constructed and the immunogenicity was evaluated in goats (the natural host). The recombinant adenoviruses (rAds) expressing F, H, and F-H fusion protein were named rAd-F, rAd-H, and rAd-F-H, respectively. In vitro, the proteins expressed in AAV-293 cells infected with different rAds were identified by Western blotting and immunofluorescence. The results showed that the proteins could be expressed in vitro. Three groups of goats (6 goats per group) were inoculated subcutaneously twice at 3-week intervals with the rAds. As negative controls, two additional groups were inoculated with wild-type adenovirus (wtAd) or PBS. In vivo, goats immunized with the rAds developed PPRV-specific virus neutralizing antibody (VNA) by 3 weeks after primary immunization. Moreover, the seroconversions were maintained for approximately 21 weeks after primary immunization. Stronger lymphocyte proliferation responses were induced in goats immunized with the three rAds than in the negative controls (P<0.05). Notably, goats inoculated with rAd-F-H developed significantly higher VNA titers (P<0.05) and stronger cell-mediated immune responses than did goats inoculated with rAd-F or rAd-H alone. The results suggest that the three rAds might be attractive candidate differentiating infected from vaccinated animals (DIVA) vaccines for preventing PPRV infection. Notably, the rAd-F-H expressing F-H fusion protein is likely the most potent candidate of the rAds.