Chitosan particle-emulsion complex adjuvants: The effect of particle distribution on the immune intensity and response type.

Particle-emulsion complex adjuvants as a new trend in the research of vaccine formulation, can improve the immune strength and balance the immune type. However, the location of the particle in the formulation is a key factor that has not been investigated extensively and its type of immunity. In order to investigate the effect of different combining modes of emulsion and particle on the immune response, three types of particle-emulsion complex adjuvant formulations were designed with the combination of chitosan nanoparticles (CNP) and an o/w emulsion with squalene as the oil phase. The complex adjuvants included the CNP-I group (particle inside the emulsion droplet), CNP-S group (particle on the surface of emulsion droplet) and CNP-O group (particle outside the emulsion droplet), respectively. The formulations with different particle locations behaved with different immunoprotective effects and immune-enhancing mechanisms. Compared with CNP-O, CNP-I and CNP-S significantly improve humoral and cellular immunity. CNP-O was more like two independent systems for immune enhancement. As a result, CNP-S triggered a Th1-type immune bias and CNP-I had more of a Th2-type of the immune response. These data highlight the key influence of the subtle difference of particle location in the droplets for immune response.

Optimization of Laser-MAG Hybrid Welding Parameters of Ship Steel Based on Response Surface Methodology.

In this paper, the optimization of laser-MAG hybrid welding parameters of 10CrNi3MoV ship steel was developed. Using the Box-Behnken Design (BBD) model in Response Surface Methodology (RSM) and taking laser power, welding speed and welding current as response factors, the design matrix was completed and verified by experiment. The regression model associated with welding parameters was established by measuring the response indices, such as penetration, tensile strength and impact absorption energy. Through the model check, it was found that the accuracy of penetration and tensile strength of the model was high, and the optimized parameters were as follows: laser power (P) = 3700 W, welding speed (V) = 0.8 m/min, wire feeding speed (Vs) = 7 m/min. On the premise of meeting mechanical performance inspection standards, the maximum penetration was 8 mm.

Second Primary Malignancy in Patients with Hypopharyngeal Carcinoma: A SEER-Based Study.

BACKGROUND: A population-based analysis of the risk of secondary primary malignancy (SPM) in patients with hypopharyngeal carcinoma (HPC) has been lacking in the literature. Therefore, we conducted this study to determine the risk factors and assess the effects of SPM on the overall survival (OS) and cancer-specific survival (CSS) of patients with HPC. METHODS: Data on selected patients diagnosed with HPC from the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015 were examined through logistic regression, Cox regression and nomogram methods. RESULTS: The overall risk of SPM in patients with HPC was higher than that in the general population (SIR: 2.77; P < 0.05). The specific-site, including the oral cavity, pharynx, digestive system, respiratory system and endocrine system, had a relatively higher risk of SPM. The overall risks of the subgroup of people 55-75 years of age and all subgroups of sex, race and latency were significantly elevated. In addition, patients with HPC were more likely to have been diagnosed in 2010-2015 (vs 2004-2009; P = 0.002), to be unmarried (vs married; P = 0.008), to have distant metastasis (vs no metastasis; P = 0.016) and to have had no surgery for the first tumor (vs surgery for the first tumor; P = 0.021), and these aspects were associated with a significantly elevated risk of developing SPM. SPM was independently associated with better OS and CSS. The OS and CSS in patients with HPC with SPM were better than those in patients without SPM (log rank P < 0.0001). The C indexes of the nomogram constructed with ten influencing factors including SPM were 0.681:0.699 for OS and 0.705:0.724 for CSS (training cohort:validation cohort). CONCLUSION: Although the overall risk of SPM in patients with HPC was elevated, SPM did not decrease the OS and CSS in patients with HPC. This finding is inconsistent with clinical observations and thus requires further research and exploration. It possibly because HPC might have a shorter survival time, or the follow-up time was not long enough.

Hydroxypropyltrimethyl ammonium chloride chitosan-based hydrogel as the split H5N1 mucosal adjuvant: Structure-activity relationship.

In this study, 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC)-based hydrogel was devised as a mucosal adjuvant for H5N1 vaccine. Aimed to investigate the structure activity relationship between HTCC hydrogel and immune response, we prepared a series of HTCC hydrogel with defined quaternization degrees (DQs, 0%, 21%, 41%, 60%, 80%). Results suggested that with DQ increasing, the positive charge and gelation time of HTCC hydrogel increased but the viscosity decreased. We applied in vivo imaging system and found that the moderate DQ 41% prolonged antigen residence time in nasal cavity, resulting in the most potent systemic responses (IgG, IgG1, IgG2a, HI). While, the lowest DQ 0% produced the best mucosal IgA antibody responses, most likely due to the closer contact with mucosa. Furthermore, the influence of animal gender was also discussed. These data add to the growing understanding of the relationship between physicochemical features of chitosan-based hydrogel and how they influence the immune responses.

A novel multiple emulsion enhanced immunity via its biomimetic delivery approach.

To generate effective immunity post-vaccination, antigens need to be effectively captured and taken up by antigen-presenting cells (APCs) as a prerequisite. Biomimetic designs that mimic natural pathogen-like properties have provided platforms for antigen delivery. However, the structural dynamic properties of pathogens leading to their efficient internalization have been neglected in most platforms. Herein, we redesigned a special multiple emulsion with chitosan hydrogel nanoparticles inside, mimicking the configurational flexibility and deformational flexibility of pathogens. With the assistance of chitosan-antigen particles, the novel emulsion exhibited amplified deformability and the vaccine-cell contact zone was increased. Additionally, its configurational transitions, which offered sustained exposure of sheltered uptake signals including antigens and stimulator chitosan during endocytosis, resulted in efficient antigen delivery to APCs. Prolonged antigen depot effect, versatile antigen presentation, multiple immunocyte activation, and marked adjuvant-sparing effects were achieved as compared with those in the control groups. As a result, the intracellular emulsion formulation robustly induced both humoral and cellular immunity, especially CTL response, against the foot-and-mouth disease virus (FMDV) with improved biosafety. Our study highlights the positive impact of biomimetic structural dynamic properties on robust vaccine-cell interactions and provides a promising FMDV vaccine candidate.

Bridging Systemic Immunity with Gastrointestinal Immune Responses via Oil-in-Polymer Capsules.

As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, "immunoticket" capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all-trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut-homing receptors (CCR9). By hitchhiking on the concentration gradient of the CC-motif chemokine ligand 25 (CCL25), the primed DCs would home to the gut associated lymphoid tissues (GALTs) and induce antigen-specific IgA secretion and T cell engagements. Compared with the currently employed RA-involving formulations, the immunoticket capsules stimulate enhanced RA-mediated gut-tropism by mounting the inflammatory innate immunity. Through controlling the RA payload, the potential regulatory T cell engagement is circumvented. In ovalbumin (OVA) and EV71 vaccinations, the immunoticket capsules induce potent serum IgG titer and antigen-specific cytotoxic T cells in the peripheral lymph tissues, as well as robust IgA secretion and T cell engagements on gastrointestinal sites. The data suggest the potential of the immunotickets to serve as a facile, effective, and safe strategy to provide comprehensive immune responses against gastrointestinal infections and diseases.

Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination.

A major challenge in vaccine formulations is the stimulation of both the humoral and cellular immune response for well-defined antigens with high efficacy and safety. Adjuvant research has focused on developing particulate carriers to model the sizes, shapes and compositions of microbes or diseased cells, but not antigen fluidity and pliability. Here, we develop Pickering emulsions-that is, particle-stabilized emulsions that retain the force-dependent deformability and lateral mobility of presented antigens while displaying high biosafety and antigen-loading capabilities. Compared with solid particles and conventional surfactant-stabilized emulsions, the optimized Pickering emulsions enhance the recruitment, antigen uptake and activation of antigen-presenting cells, potently stimulating both humoral and cellular adaptive responses, and thus increasing the survival of mice upon lethal challenge. The pliability and lateral mobility of antigen-loaded Pickering emulsions may provide a facile, effective, safe and broadly applicable strategy to enhance adaptive immunity against infections and diseases.

Collaborative Localization and Location Verification in WSNs.

Localization is one of the most important technologies in wireless sensor networks. A lightweight distributed node localization scheme is proposed by considering the limited computational capacity of WSNs. The proposed scheme introduces the virtual force model to determine the location by incremental refinement. Aiming at solving the drifting problem and malicious anchor problem, a location verification algorithm based on the virtual force mode is presented. In addition, an anchor promotion algorithm using the localization reliability model is proposed to re-locate the drifted nodes. Extended simulation experiments indicate that the localization algorithm has relatively high precision and the location verification algorithm has relatively high accuracy. The communication overhead of these algorithms is relative low, and the whole set of reliable localization methods is practical as well as comprehensive.