Search

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy., Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course., Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.., Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19., Funding: Amsterdam UMC Corona Research Fund., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Porcine Reproductive and Respiratory Syndrome (PRRS), an acute infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is one of the most devastating diseases affecting the global swine industry. In order to establish a multiplex real-time PCR method for the simultaneous detection of the classical PRRSV (C-PRRSV) strain, the highly pathogenic PRRSV (HP-PRRSV) strain and NADC30-like PRRSV (NL-PRRSV) strain, we designed specific primers and TaqMan fluorescent probes based on the Nsp2 target gene sequence of these three different PRRSV strains, and designed American-type PRRSV (PRRSV-U) special primers and probes based on the relatively conserved target gene sequence of ORF7. The method established in this study can quickly and accurately detect and differentiate three types of strains of clinical tissue samples, respectively. This method plays a key role in the rapid diagnosis and determination of PRRSV., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF 6 ])-modified magnetic graphene oxide (MGO-IL) was prepared for the first time, and was used to adsorb and remove arsenic (As(Ⅲ) and As(V)) ions from aqueous solution. MGO-IL was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and magnetization curves. Effects of ionic liquid type, solution pH, initial arsenic concentration and contact time on the adsorption performance of MGO-IL for As(Ⅲ) and As(V) were studied. The experimental results showed that the adsorption equilibrium was achieved within 30 min, with maximum adsorption capacities of 160.65 mg g -1 for As(Ⅲ) and 104.13 mg g -1 for As(V), respectively, and MGO-IL could be rapidly isolated from solution by applying a magnetic field. MGO-IL was reused for 5 times, without marked decrease in its adsorption capacities. Moreover, common coexisting anions did not interfere with the absorption of As(Ⅲ) and As(V). Compared with MGO, the sorption quantities of MGO-IL for As(Ⅲ) and As(V) were greatly enhanced, and the equilibrium time was significantly reduced. Therefore, MGO-IL can potentially serve as an excellent adsorbent for the simultaneous separation and removal of As(Ⅲ) and As(V) from water., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Atrazine contamination of water is of considerable concern because of the potential hazard to human health. In this study, a magnetic molecularly imprinted polymer for atrazine was prepared by the surface-imprinting technique using Fe 3 O 4 as the core, mesoporous silica as the carrier, atrazine as the template, and itaconic acid as the functional monomer. The magnetic molecularly imprinted polymer was characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and vibration-sample magnetometry. The binding properties of the magnetic molecularly imprinted polymer toward atrazine were investigated by adsorption isotherms, kinetics, and competitive adsorption. It was found that the adsorption equilibrium was achieved within 2 h, the maximum adsorption capacity of atrazine was 8.8 μmol/g, and the adsorption process could be well described by the Langmuir isotherm model and pseudo-second-order kinetic model. The magnetic molecularly imprinted polymer exhibited good adsorption selectivity for atrazine with respect to structural analogues, such as cyanazine, simetryne, and prometryn. The reusability of the magnetic molecularly imprinted polymer was demonstrated for at least five repeated cycles without a significant decrease in adsorption capacity. These results suggested that the magnetic molecularly imprinted polymer could be used as an efficient material for the selective adsorption and removal of atrazine from water samples., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epidemiological investigations were conducted on recently emerging porcine reproductive and respiratory syndrome virus (PRRSV) strains in Shandong province in 2014-2015. The proportion of the NADC30 strain identified by ORF7 sequence alignment has been gradually increasing. Three emerging PRRSV strains were successfully isolated, and the complete genomic sequences were determined. Our results indicate the importance of recombinant strains in Shandong province, China. There was a varied degree of recombination of two or three strains (classical, HP-PRRSV and/or NADC30). Moreover, the recombination strains affected the pathogenicity of newly emerged strains.

Porcine reproductive and respiratory syndrome (PRRS), a highly contagious disease, has been constantly causing huge economic losses all over the world. PRRS virus (PRRSV) infection results in immunosuppression and IL-10 up-regulation. The relationship between them is still in dispute. Previous studies demonstrated the protein of PRRSV nucleocapsid (N) protein is able to up-regulate IL-10, yet the underlying molecular mechanisms remain unknown. In this study, the expression kinetics of IL-10 up-regulation induced by PRRSV N protein were analyzed in immortalized porcine alveolar macrophages (PAMs). N protein induced IL-10 expression in a time- and dose-dependent manner. Inhibition experiments of signaling pathways suggested NF-κB and p38 MAPK pathways are both involved in N protein-induced IL-10 up-regulation. Besides, the integrity of N protein is essential for significant IL-10 up-regulation. This research is beneficial for further understanding of the interplay between PRRSV and host immune system., (Copyright © 2017. Published by Elsevier Ltd.)

The mechanism of phenanthridines synthesis from the nitrogenation of 2-acetylbiphenyls (1) by TMSN 3 in TFA has been studied by DFT calculations. Results at the B3LYP/6-311G(d) level showed that: 1) reaction of TMSN 3 /HN 3 with the protonated form of 1 (1H + ), which generates the key intermediate C x+ by removal of TMSOH/H 2 O, is the rate determining step, and TMSN 3 as the nitrogen source is certainly preferred over HN 3 . 2) from C x+ , the two pathways leading to 2 x H + and 3 x H + are both thermodynamically and kinetically feasible and competitive to each other. 3) The high barriers of the reverse reactions suggest that the ratio of the final products 2 x :3 x is determined by the branching ratio of reaction rates of C x+ to intermediates D x+ in pass_I and E x+ in pass_II. Graphical Abstract DFT results indicate that the replacement of -OH by -N 3 which generates C x+ controls the consumption rate of 1 x H + , and the ratio of C x+ transforms to D x+ and C x+ transforms to E x+ (k:k') determines the final ratio of products 2x:3x.

Unlabelled: Foot-and-mouth disease virus (FMDV) causes a highly contagious, debilitating disease in cloven-hoofed animals with devastating economic consequences. To survive in the host, FMDV has evolved to antagonize the host type I interferon (IFN) response. Previous studies have reported that the leader proteinase (L(pro)) and 3C(pro) of FMDV are involved in the inhibition of type I IFN production. However, whether the proteins of FMDV can inhibit type I IFN signaling is less well understood. In this study, we first found that 3C(pro) of FMDV functioned to interfere with the JAK-STAT signaling pathway. Expression of 3C(pro) significantly reduced the transcript levels of IFN-stimulated genes (ISGs) and IFN-stimulated response element (ISRE) promoter activity. The protein level, tyrosine phosphorylation of STAT1 and STAT2, and their heterodimerization were not affected. However, the nuclear translocation of STAT1/STAT2 was blocked by the 3C(pro) protein. Further mechanistic studies demonstrated that 3C(pro) induced proteasome- and caspase-independent protein degradation of karyopherin α1 (KPNA1), the nuclear localization signal receptor for tyrosine-phosphorylated STAT1, but not karyopherin α2, α3, or α4. Finally, we showed that the protease activity of 3C(pro) contributed to the degradation of KPNA1 and thus blocked STAT1/STAT2 nuclear translocation. Taken together, results of our experiments describe for the first time a novel mechanism by which FMDV evolves to inhibit IFN signaling and counteract host innate antiviral responses., Importance: We show that 3C(pro) of FMDV antagonizes the JAK-STAT signaling pathway by blocking STAT1/STAT2 nuclear translocation. Furthermore, 3C(pro) induces KPNA1 degradation, which is independent of proteasome and caspase pathways. The protease activity of 3C(pro) contributes to the degradation of KPNA1 and governs the ability of 3C(pro) to inhibit the JAK-STAT signaling pathway. This study uncovers a novel mechanism evolved by FMDV to antagonize host innate immune responses.

The limit of Riemann solutions to the nonsymmetric system of Keyfitz-Kranzer type with a scaled pressure is considered for both polytropic gas and generalized Chaplygin gas. In the former case, the delta shock wave can be obtained as the limit of shock wave and contact discontinuity when u - > u + and the parameter ϵ tends to zero. The point is, the delta shock wave is not the one of transport equations, which is obviously different from cases of some other systems such as Euler equations or relativistic Euler equations. For the generalized Chaplygin gas, unlike the polytropic or isothermal gas, there exists a certain critical value ϵ 2 depending only on the Riemann initial data, such that when ϵ drops to ϵ 2, the delta shock wave appears as u - > u +, which is actually a delta solution of the same system in one critical case. Then as ϵ becomes smaller and goes to zero at last, the delta shock wave solution is the exact one of transport equations. Furthermore, the vacuum states and contact discontinuities can be obtained as the limit of Riemann solutions when u - < u + and u - = u +, respectively.

This study was aimed at determining the effect of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) on Haemophilus parasuis (HPS) in co-infection. A quantitative real-time PCR targeting infB gene, which is conserved among different HPS serotypes, was developed to improve the accuracy and speed of the detection of HPS. A total of 32 four-week-old conventional pigs were distributed randomly into four groups: pigs in group I were intranasally infected with HP-PRRSV first, and were then intraperitoneally inoculated with HPS on 5 days after HP-PRRSV infection; pigs in group II were intranasally inoculated with HP-PRRSV alone; pigs in group III were intraperitoneally inoculated with HPS alone; pigs in group IV were intraperitoneally inoculated with physiological saline. The amount of HPS in serum on 0, 3, 6, 9 and 12 days post-inoculation (dpi) with HPS were detected using the established quantitative real-time PCR. Clinical signs, pathological changes and histopathological lesions were observed. The amount of HPS in serum reached 10(6)copies/μl at 3 dpi with HPS in pigs of group I, while it arrived 10(5.7)copies/μl at 9 dpi with HPS in pigs of group III. The HPS loads in hearts and lungs were much higher than in other tissues. The study showed that HP-PRRSV was able to accelerate HPS infection and loads., (Copyright © 2012 Elsevier B.V. All rights reserved.)