A Single Vaccination of Chimeric Bivalent Virus-Like Particle Vaccine Confers Protection Against H9N2 and H3N2 Avian Influenza in Commercial Broilers and Allows a Strategy of Differentiating Infected from Vaccinated Animals.

H9N2 and H3N2 are the two most important subtypes of low pathogenic avian influenza viruses (LPAIV) because of their ongoing threat to the global poultry industry and public health. Although commercially available inactivated H9N2 vaccines are widely used in the affected countries, endemic H9N2 avian influenza remains uncontrolled. In addition, there is no available avian H3N2 vaccine. Influenza virus-like particles (VLPs) are one of the most promising vaccine alternatives to traditional egg-based vaccines. In this study, to increase the immunogenic content of VLPs to reduce production costs, we developed chimeric bivalent VLPs (cbVLPs) co-displaying hemagglutinin (HA) and neuraminidase (NA) of H9N2 and H3N2 viruses with the Gag protein of bovine immunodeficiency virus (BIV) as the inner core using the Bac-to-Bac baculovirus expression system. The results showed that a single immunization of chickens with 40µg/0.3mL cbVLPs elicited an effective immune response and provided complete protection against H9N2 and H3N2 viruses. More importantly, cbVLPs with accompanying serological assays can successfully accomplish the strategy of differentiating infected animals from vaccinated animals (DIVA), making virus surveillance easier. Therefore, this cbVLP vaccine candidate would be a promising alternative to conventional vaccines, showing great potential for commercial development.

Reference Values of Carotid Ultrafast Pulse-Wave Velocity: A Prospective, Multicenter, Population-Based Study.

BACKGROUND: Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse-wave velocity (PWV) with high reproducibility, but a lack of reference values has precluded its widespread use in clinical practice. The aims of this study were to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV. METHODS: A total of 1,544 healthy Han Chinese volunteers (581 men [38%]; age range, 18-95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). Basic clinical parameters and carotid PWV at the beginning of systole (BS) and at end-systole (ES) were measured using ultrafast ultrasound imaging techniques. RESULTS: PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. PWV at BS was significantly higher in men than in women; however, no significant difference was noted in PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with PWV at both BS and ES. PWV at BS and ES progressively increased with increases in age, BP, and BMI. Furthermore, age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established. CONCLUSIONS: Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness.

Increased carotid stiffness detected by ultrafast ultrasound imaging is associated with the Gensini score.

AIM: To test the ability of carotid stiffness evaluated by using ultrafast ultrasound imaging to indicate coronary atherosclerosis and its association with the severity of coronary artery disease (CAD). MATERIAL AND METHODS: This cross-sectional study included 131 patients with CAD and 60 normal controls. Carotid intima-media thickness (cIMT) was measured by two-dimensional ultrasound. Carotid stiffness was determined by ultrafast ultrasound imaging, with which the carotid pulse wave velocity at the beginning (PWVBS) and end (PWVES) of systole were calculated. Gensini scores based on coronary angiography were used to estimate the severity of CAD. RESULTS: Compared with normal controls, the CAD patients had higher carotid diameters, cIMT, PWVBS and PWVES (p < 0.05). In the CAD group, Gensini scores correlated significantly with cIMT, PWVBS and PWVES (r = 0.279, p = 0.001; r = 0.661, p < 0.001; r = 0.620, p < 0.001; respectively). The multivariate analysis further indicated that PWVBS, PWVES and body mass index were independently associated with the Gensini score (ß = 0.466, p < 0.001; ß = 0.308, p < 0.001; and ß = 0.209, p = 0.001; respectively). In addition, the sensitivity and specificity were 54% and 83%, respectively, for PWVBS (cutoff value, 6.9 m/s; area under the receiver operating characteristic curve, 0.70) and 64% and 83%, respectively, for PWVES (cutoff value, 8.0 m/s; area under the curve, 0.73). CONCLUSIONS: Increased carotid PWVBS and PWVES detected by ultrafast ultrasound imaging as indices of carotid stiffness might serve as promising indicators for CAD and its severity.

Endothelial function and plasma matrix metalloproteinase-2 levels and their association with the size and elastic properties of the ascending aorta in first-degree relatives of bicuspid aortic valve patients.

PURPOSE: To explore endothelial function and plasma matrix metalloproteinase-2 levels and their association with the size and elastic properties of the ascending aorta in the first-degree relatives (FDRs) with tricuspid aortic valve (TAV) of individuals with bicuspid aortic valve (BAV). METHODS: Twenty-six patients with BAV without significant valvular dysfunction, 35 FDRs with TAV, and 29 matched healthy controls were analyzed. Two-dimensional echocardiography and high-resolution ultrasound were applied to evaluate the size and elasticity of the ascending aorta and the flow-mediated vasodilation (FMD) of the brachial artery in response to hyperemia. RESULTS: The aortic diameter was larger in the BAV patients than in the FDRs and controls, and the aortic elastic properties showed larger decreases in the BAV patients. The FDRs had a larger aortic diameter and more impaired elastic properties than the controls. The BAV patients had a significantly lower FMD than the FDRs and controls (P < .001), while the FMD was lower in the FDRs than in the controls (P < .001). The plasma MMP-2 levels were significantly higher in the BAV patients than in the FDRs (P = .001) and controls (P < .001). Additionally, the FDRs had higher plasma MMP-2 levels than the controls (P < .001). Pearson correlation analysis revealed that the aortic diameter, distensibility, stiffness index, and strain were significantly associated with FMD and plasma MMP-2 levels. CONCLUSION: Aortic enlargement and impaired elasticity in the FDRs with TAV were associated with impaired endothelial function and increased plasma MMP-2 concentrations.

Schisandrin A and B affect subventricular zone neurogenesis in mouse.

Schisandrin A and B (Sch A and B) are the main effective components extracted from the oriental medicine Schisandra chinensis which is traditionally used to enhance mental and intellectual function. Although their neuroprotective effects have been demonstrated, their influences on neurogenesis are still unknown. In the brain, new neural cells born in the subventricular zone (SVZ) next to the lateral ventricles migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB). To investigate the effects of Sch A and B on neurogenesis in the SVZ-RMS-OB system, Sch A and B were intragastrically administrated at dosages of 1, 10 and 20 mg/kg d respectively. The dose of 10 mg/kg d was selected for further analysis based on the preliminary analysis. In the SVZ, significant increases of phosphohistone H3 positive proliferating cells and the intensity of glial fibrillary acidic protein (GFAP+) cells were noticed in Sch B group. In the RMS, Sch A treatment augmented the intensity of doublecortin positive neuroblasts. In the OB, Sch A decreased tyrosine hydroxylase cells and Calbindin (CalB+) cells, while Sch B increased CalB+ cells and Calretinin (CalR+) cells. These results suggest that Sch B stimulates SVZ proliferation by enhancing GFAP+ cells and improves the survival of OB interneurons, while Sch A promotes neuroblast formation in the RMS but impairs the survival of OB interneurons. The present study provides the first evidence that Sch B exerts neuroprotective functions by enhancing neurogenesis, but Sch A mainly negatively regulates neurogenesis, in the adult SVZ-RMS-OB system.

Protective immunity conferred by porcine circovirus 2 ORF2-based DNA vaccine in mice.

Post-weaning multisystemic wasting syndrome (PMWS) associated with porcine circovirus type 2 (PCV2) has caused the swine industry significant health challenges and economic damage. Although inactivated and subunit vaccines against PMWS have been used widely, so far no DNA vaccine is available. In this study, with the aim of exploring a new route for developing a vaccine against PCV2, the immunogenicity of a DNA vaccine was evaluated in mice. The pEGFP-N1 vector was used to construct a PCV2 Cap gene recombinant vaccine. To assess the immunogenicity of pEGFP-Cap, 80 BALB/c mice were immunized three times at 2 weekly intervals with pEGFP-Cap, LG-strain vaccine, pEGFP-N1 vector or PBS and then challenged with PCV2. IgG and cytokines were assessed by indirect ELISA and ELISA, respectively. Specimens stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC) techniques were examined histopathologically. It was found that vaccination of the mice with the pEGFP-Cap induced solid protection against PCV2 infection through induction of highly specific serum IgG antibodies and cytokines (IFN-γ and IL-10), and a small PCV2 viral load. The mice treated with the pEGFP-Cap and LG-strain developed no histopathologically detectable lesions (HE stain) and IHC techniques revealed only a few positive cells. Thus, this study demonstrated that recombinant pEGFP-Cap substantially alleviates PCV2 infection in mice and provides evidence that a DNA vaccine could be an alternative to PCV2 vaccines against PMWS.