Since 2016, the highly pathogenic avian influenza H5N8 virus has emerged in the Central Asian flyway and Europe, causing massive deaths in poultry and wild birds. In this study, we isolated and identified three H5N8 viruses from swan goose and black swans in Hubei province during the 2016/2017 winter season. Whole-genome sequencing and phylogenetic analysis revealed that the three viruses clustered into a group of H5N8 viruses from Qinghai Lake and Europe. A novel reassortment virus from swan goose was distinguished from that of black swans, in that its PA and NP genes were distinct from those of Qinghai Lake viruses. Molecular dating revealed that the ancestral strain of these H5N8 viruses emerged around July 2015. From sequence comparison, we discovered eight amino acid substitutions in HA and NA during the adaption process from poultry to wild birds. The three viruses were isolated from wild birds in the East Asian-Australasian flyway; however, the viral genomes were similar to H5N8 viruses circulating along the Central Asian flyway. From these data, we conclude that wetlands and lakes in Central China may play a key role in disseminating H5N8 viruses between the East Asian-Australasian and Central Asian flyways.

Background: Baicalein has a significant anti-cancerous function in the treatment of cervical cancer (CC). Its functional mechanism regarding circular RNA (circRNA) hippocampus abundant transcript 1 (circHIAT1) and microRNA-19a-3p (miR-19a-3p) was explored in this research. Methods: CC cell viability and colony formation were determined using Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle progression and apoptosis were analyzed via flow cytometry. Protein markers of cell cycle, apoptosis and protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway were detected by Western blot. CircHIAT1 and miR-19a-3p levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circHIAT1 and miR-19a-3p was validated by dual-luciferase reporter and RNA pull-down assays. In vivo experiment was performed by xenograft model. Results: CC cell growth and cell cycle progression were repressed while apoptosis was enhanced by baicalein. MiR-19a-3p was downregulated in baicalein-treated CC cells and miR-19a-3p overexpression lightened the baicalein-induced CC progression inhibition. Moreover, circHIAT1 was found to be a sponge of miR-19a-3p in CC cells. Baicaleininduced cell growth inhibition, cell cycle arrest and apoptosis promotion were neutralized by knockdown of circHIAT1 via targeting miR-19a-3p. Baicalein acted on the circHIAT1/miR-19a-3p to inactivate AKT/mTOR pathway. Baicalein also reduced CC tumor growth in vivo via regulating the levels of circHIAT1 and miR-19a-3p. Conclusion: These findings demonstrated that the inhibitory function of baicalein in CC progression was dependent on the repression of AKT/mTOR pathway by upregulating circHIAT1 to sponge miR-19a-3p, showing a specific mechanism for baicalein in CC.

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After the emergence of H7N9 avian influenza viruses (AIV) in early 2013 in China, active surveillance of AIVs in migratory birds was undertaken, and two H7N7 strains were subsequently recovered from the fresh droppings of migratory birds; the strains were from different hosts and sampling sites. Phylogenetic and sequence similarity network analyses indicated that several genes of the two H7N7 viruses were closely related to those in AIVs circulating in domestic poultry, although different gene segments were implicated in the two isolates. This strongly suggested that genes from viruses infecting migratory birds have been introduced into poultry-infecting strains. A Bayesian phylogenetic reconstruction of all eight segments implied that multiple reassortments have occurred in the evolution of these viruses, particularly during late 2011 and early 2014. Antigenic analysis using a hemagglutination inhibition test showed that the two H7N7 viruses were moderately cross-reactive with H7N9-specific anti-serum. The ability of the two H7N7 viruses to remain infectious under various pH and temperature conditions was evaluated, and the viruses persisted the longest at near-neutral pH and in cold temperatures. Animal infection experiments showed that the viruses were avirulent to mice and could not be recovered from any organs. Our results indicate that low pathogenic, divergent H7N7 viruses circulate within the East Asian-Australasian flyway. Virus dispersal between migratory birds and domestic poultry may increase the risk of the emergence of novel unprecedented strains.

Newcastle disease caused by Newcastle disease virus (NDV) is one of the most serious threats to chickens and has two clinical forms, typical and atypical, caused by velogenic and lentogenic strains, respectively. To control the epidemic, many vaccines against velogenic class II NDVs have been introduced worldwide, but this has led to accelerated mutation of class II viruses under immune pressure and, on the other hand, to non-vaccine targeting class I NDVs becoming the dominant population in poultry. In this context, this study provided the first large-scale genomic epidemiological and quasispecies dynamic analysis of class I NDVs in China, and found that class I viruses that first appeared in East and South China have spread to central China and become the dominant class with an average evolutionary rate of 1.797 × 10 −3 . In addition, single nucleotide polymorphism and intra-host single nucleotide variation analyses show that HN and P genes have high mutation rates and may act as front-runners for NDV to expand their host range and enhance their virulence. This study also found that the class I NDV population has accumulated a number of mutations under positive selection and that six isolates with shortened C-terminal extensions of the HN protein are evolving toward increased virulence. These results not only enrich the research resources but also help us to better understand the dynamic evolution and mutational trends of NDV at the genomic level, which is crucial for monitoring, early warning, and controlling the outbreak of Newcastle disease.