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New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.

Exploring urban spatial structure plays an important role in promoting urban development, but there is a lack of research on the urban spatial structure of Xinjiang ports. This paper takes the central urban area of Kashi City as the study area and integrates points of interest (POI) data with nighttime light (NTL) data using the Open Street Map (OSM) road network to perform kernel density analysis, two-factor combination mapping, and partition identification. It identifies the spatial structural characteristics of the central urban area and divides it into different functional subdivisions. This research shows that ① the overall distributions of nighttime luminance values and POI kernel density are similar, and the overall distribution pattern gradually weakens from the city centre to the surrounding area. High-value areas are distributed in groups, presenting the spatial structure characteristics of one main area and two subareas. ② The fusion of POI data with OSM road network data identifies urban single functional zones and mixed functional zones and divides different functional zones in a more detailed way, with higher accuracy in identifying functional zones. ③ The coupling of POI and nighttime light remote sensing can better characterise the spatial features of the urban structure, such as large-scale homogeneous areas, urban fringe areas, suburbs and township centres, etc. The fusion of POI and the OSM road network can better characterise single and mixed land use types of urban land use and improve the part of the city that cannot be characterised by POI and night light. The results of this study are conducive to the realisation of rational and functional zoning in Kashi City and provide a reference for promoting urban human–land coordination and sustainable development. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses. [ABSTRACT FROM AUTHOR]