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Viral diseases of the central nervous system (CNS) represent a major global health concern. Difficulties in treating these diseases are caused mainly by the biological tissues and barriers, which hinder the transport of drugs into the CNS. To counter this, a nanobody-mediated virus-targeting drug delivery platform (SWCNTs-P-A-Nb) is constructed for CNS viral disease therapy. Viral encephalopathy and retinopathy (VER), caused by nervous necrosis virus (NNV), is employed as a disease model. SWCNTs-P-A-Nb is successfully constructed by employing single-walled carbon nanotubes, amantadine, and NNV-specific nanobody (NNV-Nb) as the nanocarrier, anti-NNV drug, and targeting ligand, respectively. Results showed that SWCNTs-P-A-Nb has a good NNV-targeting ability in vitro and in vivo, improving the specific distribution of amantadine in NNV-infected sites under the guidance of NNV-Nb. SWCNTs-P-F-A-Nb can pass through the muscle and gill and be excreted by the kidney. SWCNTs-P-A-Nb can transport amantadine in a fast manner and prolong the action time, improving the anti-NNV activity of amantadine. Results so far have indicated that the nanobody-mediated NNV-targeting drug delivery platform is an effective method for VER therapy, providing new ideas and technologies for control of the CNS viral diseases. IMPORTANCE CNS viral diseases have resulted in many deadly epidemics throughout history and continue to pose one of the greatest threats to public health. Drug therapy remains challenging due to the complex structure and relative impermeability of the biological tissues and barriers. Therefore, development in the intelligent drug delivery platform is highly desired for CNS viral disease therapy. In the study, a nanobody-mediated virus-targeting drug delivery platform is constructed to explore the potential application of targeted therapy in CNS viral diseases. Our findings hold great promise for the application of targeted drug delivery in CNS viral disease therapy.

To understand surface soil heavy metal pollution characteristics, and the spatial distribution and sources of pollution in the main sedimentary features of the Qaidam Basin, a total of 129 topsoil samples(0-10 cm) were collected within a 25 km radius. The concentrations of As, Ba, Cr, Mn, Nb, Ni, Pb, Ti, Zn, Zr, and ten kinds of heavy metals were determined, the degree of contamination and potential sources quantitatively analyzed based on enrichment factors(EFs), the ground accumulation index(

Iridovirus of Taiwan (TGIV) has been threatening the grouper farming since 1997, effective prophylaxis method is urgently needed. Subunit vaccine was proved to be useful to against the virus. Bath is the simplest method of vaccination and easy to be administrated without any stress to fish. In this research, we constructed a prokaryotic expression vector of TGIV's major capsid protein (MCP) to acquire the vaccine. Single-walled carbon nanotubes (SWCNTs) were used as the carrier to enhance the protective effect of bath vaccination for juvenile pearl gentian grouper (bath with concentrations of 5, 10, 20 mg/L for 6 h). Virus challenge was done after 28 days. Survival rates were calculated after 14 days. The level of antibody, activities of related enzymes in serums and expression of immune-related genes in kidneys and spleens were test. The results showed that vaccine with SWCNTs as carrier induced a higher level of antibody than that without. In addition, the activities of related enzymes (acid phosphatase, alkaline phosphatase, superoxide dismutase) and the expression of immune-related genes (Mx1, IgM, TNFαF, Lysozyme, CC chemokine 1, IL1-β, IL-8) had a significantly increase. What's more, higher survival rates (42.10%, 77.77%, 89.47%) were provided by vaccine with SWCNTs than vaccine without SWCNTs (29.41%, 38.09%, 43.75%). This study suggests that the protective effect of vaccine that against TGIV with the method of bath vaccination could be enhanced by SWCNTs and SWCNTs could be a potential carrier for other subunit vaccines.

Spring viraemia of carp virus (SVCV), a highly pathogenic fish rhabdovirus, caused an acute hemorrhagic and highly contagious disease in cyprinids. In this study, a new strain of SVCV was isolated from diseased zebrafish in Yangling, Shaanxi Province, China, and named SVCV-CG01. Tissue filtrates of diseased fish were detected by Nest PCR using the specific 714 bp and 606 bp fragments from the glycoprotein gene of SVCV. The genes encoding for the N, P, M and G protein were amplified, and the fragments were inserted into pMD-19T vectors to determine the genome of SVCV. Based on phylogenetic analysis of G protein gene, the isolated virus was classified into the Ia genogroup. The titer of the new strain at 48 h and 72 h was approximately 108 and 109 times higher than that of the 0504 strain, respectively. The virus could produce typical cytopathic effects (CPE) and induce apoptosis in EPC cells at 48 and 72 h post infection (hpi). Healthy zebrafish were injected with different doses of SVCV and mass mortality of fish was detected after 4 d infection, with a cumulative death rate of 100% from 107 TCID50 group at 7 d post infection (dpi). Using cultured mammalian 293T cells, an average transfection efficiency of the four structural proteins was 49.1% and 69.6% at 24 and 48 h post transfection (hpt), respectively. This study could be served as a reference for the research on the molecular epidemiology, evolution and pathogenicity of fish viruses.

Chinese herbal medicines, as the natural and innocuous compounds, have been used commonly as immunostimulants to increase growth performance, immune response and disease resistance in fish. This study aimed to investigate the effects of dietary geniposide on the immune response and disease resistance in crucian carp. The fish were fed with three different levels of geniposide-supplemented diets, including 1 mg/kg (low level group, LLG), 10 mg/kg (medium level group, MLG), 100 mg/kg (high level group, HLG) geniposide, respectively. Innate immune response, immune-related genes expression, and disease resistance against Aeromonas hydrophila infection were detected to evaluate the immunostimulant effect of dietary geniposide. The results showed that compared with control group, crucian carp fed with different levels of geniposide showed significant (p