This combination likely provided ancestral Bacteroidetes with a decisive competitive advantage to effectively scavenge, uptake and degrade complex organic molecules, and therefore has played a pivotal role in the successful adaptive radiation of the phylum. Aberrant activation of NLRP3 inflammasome is present in a subset of acute and chronic inflammatory diseases. The NLRP3 inflammasome has been recognized as an attractive therapeutic target for developing novel and specific anti-inflammatory inhibitors. Cellular structure-activity relationship-guided optimization resulted in the identification of 4-oxo-2-thioxo-thiazolidinone derivative 9 as a selective and direct small-molecule inhibitor of NLRP3 with IC50 of 2.4 μM, possessing favorable ex vivo and in vivo pharmacokinetic properties. Compound 9 may represent a lead for the development of anti-inflammatory therapeutics for treating NLRP3-driven diseases. A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1' ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC50 value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study. E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC50 value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development. In this work, we explored the potential of cationic solid lipid nanoparticles (cSLN) as efficient adjuvants for inactivated foot and mouth disease virus (iFMDV) vaccine. The cSLN were prepared by O/W emulsion method with Compritol 888 ATO as lipid matrix, and were modified by cationic lipid Didodecyldimethylammonium bromide (DDAB). The content of cationic lipid was optimized to produce cSLN with appropriate particle size, surface morphology, zeta potential, and polydispersity. Loading iFMDV onto cSLN by electrostatic attraction did not destruct iFMDV particle structure as measured by high performance size exclusion chromatography (HPSEC). Differential scanning fluorimetry (DSF) showed the transition temperature, Tm, related to iFMDV dissociation increased for 1.2 °C after loading on cSLN, indicating an enhanced stability of this unstable antigen. The cSLN loaded iFMDV enhanced in vitro antigen uptake and activation of bone-marrow-derived dendritic cells (BMDCs) with augmented expression of CD86, CD40, and MHC I. In animal trials, BALB/c mice were immunized with free iFMDV, antigen adjuvanted with the cSLN, and antigen adjuvanted with Montanide ISA 206 emulsion. Specific antibody titers showed cSLN could stimulate similar FMDV-specific IgG and IgG subclasses antibody level compared with the widely used ISA 206. In addition, cSLN significantly enhanced memory immune response including effector-memory T cells and central-memory T cells compared to free iFMDV antigen and antigen adjuvanted with ISA 206. Taken together the enhanced humoral and T cell immune responses and the antigen structure friendly properties, cSLN can be a potential adjuvant for iFMDV vaccines. INTRODUCTION Despite the WHO recommendation that economic evidence be considered in national vaccine recommendations, this element of decision-making has been lacking or not done routinely in Canada. This study aimed to investigate barriers and facilitators to using economic evaluations in public health immunization programs decision-making across Canadian jurisdictions. METHODS This mixed methods study consisted of a cross-sectional survey and semi-structured interviews of national, provincial and territorial public health level key informants, and of members of the national immunization research network in Canada. Barriers were categorized according to accessibility (e.g. access to human resources to conduct the evaluation) and acceptability (e.g. political resistance to using the evaluation). RESULTS Of 63 survey participants, 12 were federal, provincial or territorial key informants (response rate 12/31, 39%) and 51 were members from the research network (response rate 51/214, 24%). Eleven stakeholders gaed that facilitators to incorporating economic evidence include developing increased capacity to conduct and use economic evaluations and establishing inter-jurisdictional systems to share the work of conducting economic evaluation and/or by national leadership. Increases in vaccine hesitancy and vaccine-preventable disease outbreaks have focused attention on state laws governing school-entry vaccine mandates and the allowable exemptions (medical and nonmedical) from those mandates. There is substantial variation in the type of exemptions available in each state, and states with more rigorous or burdensome exemption requirements generally have lower exemption rates. States have little evidence, however, about how vaccine-hesitant parents respond to different requirements. Despite recent efforts to formulate "model legislation" templates for states to follow, policy evidence about optimal exemption regimes is limited to observational studies in states that have changed exemption laws. We conducted two online experiments to explore how parental attitudes and intentions responded to different school-entry vaccine mandate exemption requirements. H-1152 2HCl We randomly assigned online participants to one of four hypothetical vaccine exemption application scenarios parental signature only, a checklist of vaccines for which an exemption is requested, a lengthy (10-30+ min) video-based vaccine education module, and a requirement to write a statement justifying the exemption.