Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use

Genome-resolved metagenomics provides insights into the microbial-mediated sulfur and nitrogen cycling in temperate seagrass meadows

The presence of seagrasses facilitates numerous microbial-mediated biogeochemical cycles, with sulfur- and nitrogen-cycling microorganisms playing crucial roles as regulators. Despite efforts to comprehend the diversity of microbes in seagrass ecosystems, the metabolic functions of these benthic microorganisms in seagrass sediments remain largely unknown. Using metagenomics, we provide insights into the sulfur- and nitrogen-cycling pathways and key metabolic capacities of microorganisms in both Z. japonica-colonized and unvegetated sediments over a seasonal period. Taxonomic analysis of N and S cycling genes revealed that δ- and γ- proteobacteria dominated the benthic sulfate-reducing bacteria, while α- and γ-proteobacteria played a significant role in the sulfur-oxidation processes. The proteobacterial lineages were also major contributors to the benthic nitrogen cycling. However, at a finer taxonomic resolution, microbial participants in different processes were observed to be highly diverse and mainly driven by environmental factors such as temperature and salinity. The gene pools of sulfur and nitrogen cycles in the seagrass sediments were dominated by genes involved in sulfide oxidation (fccA) and hydroxylamine oxidation (hao), respectively. Seagrass colonization elevated the relative abundance of genes responsible for sulfite production (phsC), hydroxylamine oxidation (hao), and nitrogen fixation (nifK), but suppressed sulfur oxidation (soxXYZ) and denitrification (nosZ and nirS). The prevalence of proteobacterial lineages functioned with versatile capabilities in both sulfur and nitrogen cycles in seagrass ecosystems, highlighting tight couplings between these processes, which was further supported by the recovery of 83 metagenome-assembled genomes (MAGs). These findings broaden our understanding of the biogeochemical processes that are mediated by microorganisms in seagrass ecosystems

Generation and Comprehensive Analysis of Host Cell Interactome of the PA Protein of the Highly Pathogenic H5N1 Avian Influenza Virus in Mammalian Cells

Accumulating data have identified the important roles of PA protein in replication and pathogenicity of influenza A virus (IAV). Identification of host factors that interact with the PA protein may accelerate our understanding of IAV pathogenesis. In this study, using immunoprecipitation assay combined with liquid chromatography-tandem mass spectrometry, we identified 278 human cellular proteins that might interact with PA of H5N1 IAV. Gene Ontology annotation revealed that the identified proteins are highly associated with viral translation and replication. Further KEGG pathway analysis of the interactome profile highlighted cellular pathways associated with translation, infectious disease, and signal transduction. In addition, Diseases and Functions analysis suggested that these cellular proteins are highly related with Organismal Injury and Abnormalities and Cell Death and Survival. Moreover, two cellular proteins (nucleolin and eukaryotic translation elongation factor 1-alpha 1) identified both in this study and others were further validated to interact with PA using co-immunoprecipitation and co-localization assays. Therefore, this study presented the interactome data of H5N1 IAV PA protein in human cells which may provide novel cellular target proteins for elucidating the potential molecular functions of PA in regulating the lifecycle of IAV in human cells

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy

Experimental Investigation into the Friction Coefficient of Ball-on-Disc in Dry Sliding Contact Considering the Effects of Surface Roughness, Low Rotation Speed, and Light Normal Load

The friction coefficient is one of the key parameters in the tribological performance of mechanical systems. In the condition of light normal load and low rotation speed, the friction coefficients of ball-on-disc with rough surface in dry sliding contact are experimentally investigated. Friction tests are carried out under normal load 2–9 N, rotation speed 20–48 rpm at room temperature, and surface roughness 0.245–1.010 μm produced by grinding, milling, and turning. Results show that the friction coefficient increases first and then becomes stable, in which the running-in and steady-state periods are included. With the growth of normal load and rotation speed, or the decline of surface roughness, the duration and fluctuation of the running-in period verge to reduce. The whole rising slope of the friction coefficient in the running-in period goes up more quickly with the increment of rotation speed, and it ascends more slowly as normal load enlarges. In terms of the steady-state period, the deviation of the friction coefficient shows a dwindling trend when normal load or rotation speed grows, or surface roughness descends. As normal load or rotation speed rises, the value of the friction coefficient rises first and then drops. Additionally, the mean value of the friction coefficient in steady-state is approximately independent of surface roughness

Experimental Investigation into the Friction Coefficient of Ball-on-Disc in Dry Sliding Contact Considering the Effects of Surface Roughness, Low Rotation Speed, and Light Normal Load

The friction coefficient is one of the key parameters in the tribological performance of mechanical systems. In the condition of light normal load and low rotation speed, the friction coefficients of ball-on-disc with rough surface in dry sliding contact are experimentally investigated. Friction tests are carried out under normal load 2–9 N, rotation speed 20–48 rpm at room temperature, and surface roughness 0.245–1.010 μm produced by grinding, milling, and turning. Results show that the friction coefficient increases first and then becomes stable, in which the running-in and steady-state periods are included. With the growth of normal load and rotation speed, or the decline of surface roughness, the duration and fluctuation of the running-in period verge to reduce. The whole rising slope of the friction coefficient in the running-in period goes up more quickly with the increment of rotation speed, and it ascends more slowly as normal load enlarges. In terms of the steady-state period, the deviation of the friction coefficient shows a dwindling trend when normal load or rotation speed grows, or surface roughness descends. As normal load or rotation speed rises, the value of the friction coefficient rises first and then drops. Additionally, the mean value of the friction coefficient in steady-state is approximately independent of surface roughness

Discovering the Characteristics of Community Structures and Functional Properties of Epiphytic Bacteria on Spartina alterniflora in the Coastal Salt Marsh Area

The invasive submerged Spartina alterniflora is dominant in the coastal Yellow River Delta wetland. Although sediment microorganisms have been found to mediate the nutrient cycle in wetlands, the role of epiphytic bacteria on submerged S. alterniflora has rarely drawn attention. In the present study, we analyzed the characteristics of epiphytic microbial community diversity and functional properties related to S. alterniflora in summer and winter by Illumina MiSeq sequencing and functional prediction. Marked high abundances of Proteobacteria, Actinobacteriota, Planctomycetota, Cyanobacteria and Desulfobacterota were found in S. alterniflora epiphytic microbiome. Beta diversity based on NMDS and LDA analysis revealed that the distribution of these epiphytic microbial communities clustered according to the leaf locations and variation in seasons. Environmental factors, including temperature, salinity, DO and total organic matter, exert important roles in impacting the microbial community. Significantly higher abundances of chemoheterotrophy, aerobic_chemoheterotrophy, hydrocarbon degradation, fermentation, nitrate reduction and nitrate respiration were correlated with the submerged S. alterniflora epiphytic microbiome. Collectively, the results indicated that S. alterniflora epiphytic bacterial community diversity and functional guilds varied greatly with variations in leaf locations and seasons. These results will also provide guidance for the isolation of functional bacteria in controlling plant spread