An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

<p>Abstract</p> <p>Background</p> <p>A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses.</p> <p>Results</p> <p>Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses.</p> <p>Conclusions</p> <p>These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.</p

A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses

Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus

Existence results for impulsive neutral stochastic functional integro-differential inclusions with nonlocal initial conditions

AbstractIn this paper, we prove the existence of mild solutions for a class of impulsive neutral stochastic functional integro-differential inclusions with nonlocal initial conditions and resolvent operators. Sufficient conditions for the existence are derived with the help of the fixed point theorem for multi-valued operators due to Dhage and the fractional power of operators. An example is provided to illustrate the theory

Effect of esketamine on the EC50 of remifentanil for suppression of choking cough during extubation

Summary: Choking cough during awakening from anesthesia is common (15%–94%) and can cause severe discomfort and complications, especially in neck surgery. This study compared the median effective concentration (EC50) of remifentanil combined with esketamine versus remifentanil alone for suppressing cough during extubation in male patients undergoing anterior cervical spine surgery. Group E received 0.25 mg/kg esketamine intravenously 30 min before surgery ended, while group D received a placebo. We observed that the EC50 values were 1.88 ng/mL for group E and 2.55 ng/mL for group D. No significant differences were observed in intraoperative hemodynamics or extubation time. Additionally, group E had lower postoperative pain scores at 2 and 24 h. Findings suggest that combining esketamine with remifentanil reduces the EC50 for cough suppression and effectively lowers early postoperative pain, providing reference for perioperative safety and improvement of prognosis in patients undergoing anterior cervical surgery

High-Permeability Wood with Microwave Remodeling Structure

This paper presents the development of a microwave puffed wood (MPW) with novel and unique structural features in its internal structure that are based on natural wood (NW). The focus of the research was on the comprehensive visualization of the structural characteristics of MPW from the macroscopic to the microscopic scale followed by an exploration of its impregnation capabilities. The results showed that the volume of MPW increased by about 9% compared to NW due to the presence of a large number of cracked cavities. The CT images indicated that there was a significant difference between the macroscopic cracks produced by microwave processing and the natural cracks in the wood. The mercury intrusion test results showed that macro-pores increased while the micro-pores decreased in the MPW compared to in the NW. The MPW showed good fluid permeability and liquid absorption performance. The phenolic resin penetration rate of the MPW was about 20 times that of the NW, and the material absorption was more than 2 times that of the NW. The crack space enabled the MPW to serve as a fluid transportation and a storage warehouse. MPW is a super container based on natural materials. It has broad potential in more fields, such as in wood composite materials.</jats:p

Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis

The current meta-analysis analyzed the prognostic impact of elevated platelet count before the treatment of malignant mesothelioma (MM). We performed a search for articles published up to April 15, 2016 in PubMed, MEDLINE, EMBASE, and Web of Science, which evaluated elevated platelet count and survival outcome of MM. STATA version 12 was used for statistical analysis. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were combined to calculate overall effects. The assessment of heterogeneity was tested by the Cochran Q and I2 statistics. The sensitivity and meta-regression analyses were performed to explore the origin of heterogeneity. We analyzed 18 eligible studies (3602 patients) that evaluated the correlation between pretreatment platelet count and overall survival (OS). Elevated platelet count was a prognostic factor of poor OS, with a pooled HR of 1.56 (95% CI = 1.36–1.77). However, significant heterogeneity was observed in the included studies (I2 = 86.0%, p < 0.001). Sensitivity and meta-regression analyses were performed to trace the origin of heterogeneity. Only the variable type (multivariable or univariate model) was traced as the origin of heterogeneity. Hence, we conducted a subgroup analysis of variable type. The HR was 1.66 (95% CI = 1.41–1.91) in the multivariable group and no significant heterogeneity was observed (I2 = 0.0%, p = 0.476). In conclusion, high pretreatment platelet count resulted in poor OS in MM. Therefore, platelet count could be an adequate and useful factor of prognosis for MM

High-Permeability Wood with Microwave Remodeling Structure

This paper presents the development of a microwave puffed wood (MPW) with novel and unique structural features in its internal structure that are based on natural wood (NW). The focus of the research was on the comprehensive visualization of the structural characteristics of MPW from the macroscopic to the microscopic scale followed by an exploration of its impregnation capabilities. The results showed that the volume of MPW increased by about 9% compared to NW due to the presence of a large number of cracked cavities. The CT images indicated that there was a significant difference between the macroscopic cracks produced by microwave processing and the natural cracks in the wood. The mercury intrusion test results showed that macro-pores increased while the micro-pores decreased in the MPW compared to in the NW. The MPW showed good fluid permeability and liquid absorption performance. The phenolic resin penetration rate of the MPW was about 20 times that of the NW, and the material absorption was more than 2 times that of the NW. The crack space enabled the MPW to serve as a fluid transportation and a storage warehouse. MPW is a super container based on natural materials. It has broad potential in more fields, such as in wood composite materials

Improvement of Mechanical, Hydrophobicity and Thermal Properties of Chinese Fir Wood by Impregnation of Nano Silica Sol

In this paper, a wood-SiO2 composite material was prepared via in-situ polymerization using vacuum/pressure impregnation technology using commercial scale nano silica sol and Chinese Fir (Cunninghamia lanceolate (Lamb.) Hook.). Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), and water contact angle were used to study the changes in the microstructure and physical and mechanical properties of this composite. The results showed that silica sol can penetrate and distribute into the wood cell cavities and surface of cell walls and hence combine with the substances of wood materials. FTIR results indicated that the –OH groups of wood can polycondense in-situ with silica sol to form Si–O–C covalent bonds, and amorphous SiO2 formed from Si–O–Si bonds between the –OH groups of silica sol did not change the crystalline structure of wood cell walls. This in-situ formulating composite significantly improved the compact microstructure, thermal and mechanical properties, and hydrophobicity of the composites.</jats:p