[Numerical Response Analysis of PM2.5-O3 Compound Pollution in Beijing].

The multi-scale variation trend of PM2.5-O3 compound pollution events was analyzed based on air quality data, meteorological data, and COVID-19 data in Beijing from 2015 to 2020. For the threshold of compound pollution, a compound pollution index was proposed, and the numerical response trend was evaluated based on the generalized additive model. A distributed lag nonlinear model was introduced to analyze the risk response relationship between compound pollution and influencing factors. The results showed that the events of PM2.5-O3 compound pollution in Beijing decreased annually. At the same time, due to the influence of pollutant emissions and meteorological conditions, there were obvious seasonal effects, week effects, holiday effects, and epidemic effects. The composite pollution index had no correlation with rainfall but had a linear positive correlation with O3 and air temperature and a nonlinear correlation with other explanatory variables. Air pollutants and meteorological conditions had obvious lag effects on the composite pollution index, and the lag effects were mainly concentrated in 1-3 d. PM2.5, PM10, O3, SO2, and air temperature in high-value areas significantly increased the risk of compound pollution. The CO (1-6 mg·m-3), NO2 (38-118 µg·m-3), and relative humidity (54%-87%) in the median section would also increase the risk of compound pollution, as would low wind speed. The compound pollution events showed a trend of multi-day continuous pollution in the numerical response. Compared with PM2.5 and PM10, compound pollution events were more dependent on O3, and the compound pollution rate in high-value areas was 30.7%-47.5%. CO and relative humidity had little effect on compound pollution events. The air temperature had the greatest impact, and 84.7% of the composite pollution incidents occurred at 20-30℃.

A Nanobody-Mediated Virus-Targeting Drug Delivery Platform for the Central Nervous System Viral Disease Therapy.

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.

Evaluation on antiviral activity of a novel arctigenin derivative against multiple rhabdoviruses in aquaculture.

Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro. By comparing inhibitory concentration at half-maximal activity (IC 50), we found that BOA (IC50 = 1.11 µM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2-6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.

An evaluation study of research efficiency of the Guangzhou institute of respiratory diseases based on malmquist index.

BACKGROUND: This study aimed to analyze the dynamic changes of the scientific research innovation efficiency of Guangzhou Institute of Respiratory Diseases (GIRD) during the year 2009-2013 to explore the reason for these changes and give some suggestions on how to improve the overall efficiency of the Institute. METHODS: The panel data used in this study were taken from 19 research teams of GIRD during 2009 to 2013. Data envelopment analysis (DEA) based on Malmquist index (MI) was used to analyze the performance of each research team in terms of productivity changes over time. Data were analyzed using DEAP 2.1 software. RESULTS: The annual average increase rate of total factor productivity (TFP), technological progress, technical efficiency, pure technical efficiency, and scale efficiency was 30.4%, 22.5%, 6.4%, 0.9%, and 5.4%, respectively from 2009 to 2013. The scientific research innovation efficiency of the GIRD was generally high and kept on growing. The increase of TFP was mainly caused by the progress of tech, the descending of TFP in some teams should be mainly attributable to the declining pure technical efficiency, and scale efficiency on the whole, maintaining a stable growth at a low speed. CONCLUSIONS: To achieve higher scientific research innovation, GIRD not only needs to further improve the management level and introduce advanced management mode, but also needs to focus on optimization of resource allocation, as well as to strengthen the talent introduction, and continue to maintain the absorption of new technologies and innovation.

Effects of three strains of intestinal autochthonous bacteria and their extracellular products on the immune response and disease resistance of common carp, Cyprinus carpio.

The study isolated three strains of intestinal autochthonous bacteria Aeromonas veronii BA-1, Vibrio lentus BA-2, and Flavobacterium sasangense BA-3 from the intestinal tract of the common carp (Cyprinus carpio). To reveal the effects of these three strains of bacteria on the innate immunity of carp, the lysozyme, complement C3, total serum protein, albumin and globulin levels, respiratory burst activity, phagocytic activity by blood leucocytes and the expression of IL-1b, lysozyme-C, and TNF-α were examined after feeding with seven different diets for up to 28 days. Also the survival of carp against Aeromonas hydrophila was challenged for 14 days. The carp were fed seven different diets: one control, three diets supplemented with 1 × 10(8) cell g(-1) of carp intestinal bacteria BA-1 (Group D-I), BA-2 (Group D-II) and BA-3 (Group D-III), and three diets supplemented with extracellular products FA-1 (Group E-I), FA-2 (Group E-II) and FA-3 (Group E-III) which were corresponding to the strains BA-1, BA-2, and BA-3, respectively, up to 28 days. For groups D-I, D-III, E-I and E-III, the innate immune parameters of carp were significantly increased, the expression of three immune-related genes in blood was significantly up-regulated examined during 7, 14, and 21 days of feeding, and the survival rate was improved. The study indicates that the two isolated intestinal autochthonous bacteria A. veronii BA-1 and F. sasangense BA-3 could positively influence immune response and enhance disease resistance of carp against A. hydrophila infection.

Identification of a virus-specific and conserved B-cell epitope on NS1 protein of Japanese encephalitis virus.

NS1 protein of Japanese encephalitis virus (JEV) is an important non-structural protein, which is able to induce protective immune response in target animals and can be used as specific serological diagnosis tool, but the epitopes on NS1 of JEV have not been identified. For epitope mapping, in this study, a series of 51 partially overlapping fragments covering entire NS1 protein were expressed with a GST-tag and then screened by a monoclonal antibody (mAb). Through enzyme-linked immunosorbent assay (ELISA), linear epitope-containing fragment, the overlapping region of NS1-18 and NS1-19 (residues 145-152), was located. Then a set of peptides derived from that overlapping region with deletions were expressed and subjected to ELISA and Western blot for further mapping purpose. Results indicated that the motif of (146)EHARW(150) is the minimal unit of the linear epitope recognized by that monoclonal antibody (mAb). Western blot showed that this epitope could be recognized by JEV-positive serum from pigs. Furthermore, it was found that the epitope is highly conserved among JEV strains through sequence alignments analysis. Notably, none of the homologous regions on NS1 proteins of other flavivirus could react with the mAb when they were tested for cross-reactivity, suggesting the potential clinical application of this epitope in differential diagnosis.

Fusion of C3d with hemagglutinin enhances protective immunity against swine influenza virus.

H1N1 and H3N2 are the dominant subtypes causing swine influenza in China and other countries. It is important to develop effective vaccines against both H1N1 and H3N2 subtypes of swine influenza virus (SIV). We examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine complement C3d in mice. Plasmids encoding soluble HA (sHA), complete HA (tmHA), or a soluble fused form of HA (sHA-mC3d3) were constructed from the H3N2 subtype of SIV. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI) assays, and virus neutralization tests. Analysis of antibody titers indicated that immunization with HA-mC3d3 resulted in higher titers of anti-HA antibodies and higher antibody affinities, compared with serum from mice immunized with sHA or tmHA. Furthermore, the C3d fusion increased the Th2-biased immune response, by inducing IL-4 production. Splenocytes from mice immunized with sHA-mC3d3 produced about three-fold more IL-4 than did splenocytes from mice immunized with sHA or tmHA. Seven days post-challenge with homologous virus (H3N2), no virus was isolated from the mice immunized with HA-expressing plasmids. However, 10 days post-challenge with heterologous virus (H1N1), only mice immunized with sHA-mC3d3 had no virus or microscopic lesions in the kidneys and cerebrum. In conclusion, C3d enhanced antibody responses to hemagglutinin and protective immunity against SIV of different subtypes.

Isolation and genetic characterization of avian origin H9N2 influenza viruses from pigs in China.

As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the adaptation of avian influenza viruses to humans. In April 2006, a disease caused by highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) occurred in several pig farms and subsequently overwhelmed almost half of China with more than 2,000,000 cases of pig infection. Here we report a case in which four swine H9N2 influenza viruses were isolated from pigs infected by highly pathogenic PRRSVs in Guangxi province in China. All the eight gene segments of the four swine H9N2 viruses are highly homologous to A/Pigeon/Nanchang/2-0461/00 (H9N2) or A/Wild Duck/Nanchang/2-0480/00 (H9N2). Phylogenetic analyses of eight genes show that the swine H9N2 influenza viruses are of avian origin and may be the descendants of A/Duck/Hong Kong/Y280/97-like viruses. Molecular analysis of the HA gene indicates that our H9N2 isolates might have high-affinity binding to the alpha2,6-NeuAcGal receptor found in human cells. In conclusion, our finding provides further evidence about the interspecies transmission of avian influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus (SIV) surveillance, especially after the emergence of highly pathogenic PRRSVs in pigs in China.

Genetic evolution of swine influenza A (H3N2) viruses in China from 1970 to 2006.

Pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts, or mixing vessels, for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we summarize and report for the first time the coexistence of wholly human-like H3N2 viruses, double-reassortant H3N2 viruses, and triple-reassortant H3N2 viruses in pigs in China by analyzing the eight genes of swine influenza A (H3N2) viruses found in China from 1970 to 2006. In 1970, the first wholly human-like H3N2 (Hong Kong/68-like) viruses were isolated from pigs in Taiwan, and then in the next years Victoria/75-like, Sydney/97-like, New York/99-like, and Moscow/99-like swine H3N2 viruses were regularly isolated in China. In the 1980s, two triple-reassortant viruses were isolated from pigs. Recently, the double-reassortant viruses containing genes from the human (HA and NA) and avian (PB2, PB1, PA, NP, M, and NS) lineages and the triple-reassortant viruses containing genes from the human (HA and NA), classical swine (NP), and avian (PB2, PB1, PA, M, and NS) lineages emerged in pigs in China. The coexistence of wholly human-like and reassortant viruses provides further evidence that pigs serve as intermediate hosts, or mixing vessels, and emphasizes the importance of reinforcing swine influenza virus surveillance in China.

Isolation and genetic analysis of human origin H1N1 and H3N2 influenza viruses from pigs in China.

Influenza A viruses of subtypes H1N1 and H3N2 have been reported widely in pigs, associated with clinical disease. These mainly include classical swine H1N1, avian-like H1N1, and human-like or avian-like H3N2 viruses. From 2005 to 2006, we carried out swine influenza virus surveillance in eight provinces of China. Here we report, for the first time, the isolation and genetic analysis of a human-like influenza H1N1 virus from a pig in a farm of Guangdong province of southern China, a host suspected to generate new pandemic strains through genetic reassortment. Each of the eight gene segments is of human origin. Phylogenetic analysis indicates that these genes form a human lineage, suggesting that this virus is the descendant of recent human H1N1 influenza viruses. In addition, four swine H3N2 viruses were also isolated. The three H3N2 viruses from Guangdong province are descendants of recent human viruses, while an H3N2 virus from Heilongjiang province derives from early human viruses. Isolation and genetic analysis of human H1N1 and H3N2 influenza viruses from pigs in China provides further evidence about the interspecies transmission of human influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus surveillance.