Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark

Porcine reproductive and respiratory syndrome (PRRS) is a severe viral disease in pigs, causing great economic losses worldwide each year. The causative agent of the disease, PRRS virus (PRRSV), is a member of the family Arteriviridae. Here we report our investigation of the unparalleled large-scale outbreaks of an originally unknown, but so-called “high fever” disease in China in 2006 with the essence of PRRS, which spread to more than 10 provinces (autonomous cities or regions) and affected over 2,000,000 pigs with about 400,000 fatal cases. Different from the typical PRRS, numerous adult sows were also infected by the “high fever” disease. This atypical PRRS pandemic was initially identified as a hog cholera-like disease manifesting neurological symptoms (e.g., shivering), high fever (40–42°C), erythematous blanching rash, etc. Autopsies combined with immunological analyses clearly showed that multiple organs were infected by highly pathogenic PRRSVs with severe pathological changes observed. Whole-genome analysis of the isolated viruses revealed that these PRRSV isolates are grouped into Type II and are highly homologous to HB-1, a Chinese strain of PRRSV (96.5% nucleotide identity). More importantly, we observed a unique molecular hallmark in these viral isolates, namely a discontinuous deletion of 30 amino acids in nonstructural protein 2 (NSP2). Taken together, this is the first comprehensive report documenting the 2006 epidemic of atypical PRRS outbreak in China and identifying the 30 amino-acid deletion in NSP2, a novel determining factor for virulence which may be implicated in the high pathogenicity of PRRSV, and will stimulate further study by using the infectious cDNA clone technique

The first salamander defensin antimicrobial peptide.

Antimicrobial peptides have been widely identified from amphibian skins except salamanders. A novel antimicrobial peptide (CFBD) was isolated and characterized from skin secretions of the salamander, Cynops fudingensis. The cDNA encoding CFBD precursor was cloned from the skin cDNA library of C. fudingensis. The precursor was composed of three domains: signal peptide of 17 residues, mature peptide of 41 residues and intervening propeptide of 3 residues. There are six cysteines in the sequence of mature CFBD peptide, which possibly form three disulfide-bridges. CFBD showed antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli. This peptide could be classified into family of β-defensin based on its sequence similarity with β-defensins from other vertebrates. Evolution analysis indicated that CFBD was close to fish β-defensin. As far as we know, CFBD is the first β-defensin antimicrobial peptide from salamanders

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s−1) and high (1800 s−1) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s−1). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition

Doxorubicin-Induced Platelet Activation and Clearance Relieved by Salvianolic Acid Compound: Novel Mechanism and Potential Therapy for Chemotherapy-Associated Thrombosis and Thrombocytopenia

Doxorubicin (Dox) is a widely utilized chemotherapeutic; however, it carries side effects, including drug-induced immune thrombocytopenia (DITP) and increased risk of venous thromboembolism (VTE). Currently, the mechanisms for Dox-associated DITP and VTE are poorly understood, and an effective inhibitor to relieve these complications remains to be developed. In this study, we found that Dox significantly induced platelet activation and enhanced platelet phagocytosis by macrophages and accelerated platelet clearance. Importantly, we determined that salvianolic acid C (SAC), a water-soluble compound derived from Danshen root traditionally used to treat cardiovascular diseases, inhibited Dox-induced platelet activation more effectively than current standard-of-care anti-platelet drugs aspirin and ticagrelor. Mechanism studies with tyrosine kinase inhibitors indicate contributions of phospholipase C, spleen tyrosine kinase, and protein kinase C signaling pathways in Dox-induced platelet activation. We further demonstrated that Dox enhanced platelet-cancer cell interaction, which was ameliorated by SAC. Taken together, these findings suggest SAC may be a promising therapy to reduce the risk of Dox-induced DITP, VTE, and the repercussions of amplified platelet-cancer interaction in the tumor microenvironment

Stoichiometric controlling of boroncarbonitride thin films with using BN-C dual-targets

High carbon-rich boroncarbonitride thin films have been grown by pulsed laser deposition (PLD) technique with using BN-C dual-targets. Fourier-transform infrared (FTIR) spectroscopy results presented B-N, B-C and C-N bonds, indicating the as-deposited thin films were new ternary compounds. B-N, B-C and C-N bonding structures were also detected by X-ray photoelectron spectroscopy (XPS), and carbon content fell into a large range of 45.8 to 85.9%. The films exhibited good thermalstability in vacuum, whereas were oxidized at 600 oC in air

Shear Localization and Mechanical Properties of Cu/Ta Metallic Nanolayered Composites: A Molecular Dynamics Study

With their excellent mechanical properties, Cu/Ta metallic nanolayered composites (MNCs) are extensively applied in aerospace and nuclear industry facilities. However, shear localization severely disrupts the ability of these materials to deform uniformly, attracting many researchers. The necessary time and length conditions of experiments limit the investigation of shear localization; thus, relevant studies are insufficient. The molecular dynamics simulation perfectly corresponds to the short duration and high strain rate of the deformation process. Therefore, in this study, we used molecular dynamics simulations to explore the effect of layer thickness on the shear localization of Cu/Ta MNCs with Kurdjumov–Sachs (KS) orientation–related interfaces. Our research demonstrates that shear localization occurs in samples with layer thicknesses below 2.5 nm, resulting in an inverse size effect on the flow strength. The quantitative analysis indicates that the asymmetry of dislocations in the slip transmission across the interface causes interface rotation. This activates dislocations parallel to the interface to glide beyond the distance of individual layer thicknesses, eventually forming shear bands. Both interface rotation and sliding dominate the plastic deformation in the shear band region. In addition, the dislocation density and amorphous phase increase with decreasing layer thickness

Oxidation Mechanism of Core-Shell Structured Al@PVDF Powders Synthesized by Solvent/Non-Solvent Method

Micron-sized aluminum (Al) powders are extensively added to energy-containing materials to enhance the overall reactivity of the materials. However, low oxidation efficiency and energy release limit the practical application of Al powders. Polyvinylidene fluoride (PVDF), the most common fluoropolymer, can easily react with Al to form aluminum fluoride (AlF3), thus promoting the oxidation of Al powders. In this paper, core-shell structured Al@PVDF powders were synthesized by solvent/non-solvent method. Thermal analysis results show that the weight and exothermic enthalpy of Al@PVDF powders are 166.10% and 11,976 J/g, which are superior to pure Al powders (140.06%, 6560 J/g). A detailed description of the oxidation mechanisms involved is provided. Furthermore, constant volume pressure results indicate that Al@PVDF powders have outstanding pressure output ability in the environment of 3 MPa oxygen. The study provides a valuable reference for the application of Al powders in energetic materials

Microstructure and Oxidation Behavior of Metal V Films Deposited by Magnetron Sputtering

Direct-current magnetron sputtering (DCMS) was applied to prepare vanadium (V) films on Si substrate. The influence of substrate temperature (Ts) and target⁻substrate distance (Dt⁻s) on phase structure and surface morphology of V films were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscope (AFM) and transmission electron microscopy (TEM). The results show that the crystallinity of the V films increases with increasing Ts and decreasing Dt⁻s. The film deposited at Ts = 400 °C and Dt⁻s = 60 mm exhibits the best crystallinity and <111> preferred orientation with a regular tetrahedral surface morphology. Oxidation behavior of the V thin films has also been studied by X-ray photoelectron spectroscopy (XPS)

Tailoring the Grain Size of Bi-Layer Graphene by Pulsed Laser Deposition

Improving the thermoelectric efficiency of a material requires a suitable ratio between electrical and thermal conductivity. Nanostructured graphene provides a possible route to improving thermoelectric efficiency. Bi-layer graphene was successfully prepared using pulsed laser deposition in this study. The size of graphene grains was controlled by adjusting the number of pulses. Raman spectra indicated that the graphene was bi-layer. Scanning electron microscopy (SEM) images clearly show that graphene changes from nanostructured to continuous films when more pulses are used during fabrication. Those results indicate that the size of the grains can be controlled between 39 and 182 nm. A detailed analysis of X-ray photoelectron spectra reveals that the sp2 hybrid state is the main chemical state in carbon. The mobility is significantly affected by the grain size in graphene, and there exists a relatively stable region between 500 and 800 pulses. The observed phenomena originate from competition between decreasing resistance and increasing carrier concentration. These studies should be valuable for regulating grains sizes for thermoelectric applications of graphene

Antimicrobial activity of β-defensin CFDB.

<p>Minimal peptide concentration required for total inhibition of cell growth in liquid medium; these concentrations represent mean values (±20%) of three replicates.</p