Expression of Foot-and-Mouth Disease Virus Capsid Proteins in Silkworm-Baculovirus Expression System and Its Utilization as a Subunit Vaccine

Background: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals. Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop. Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines. Methodology and Principal Findings: A recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed. Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette. Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle. Specific antibody was induced in all vaccinated animals. After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one. Furthermore, a PD50 (50 % bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine. The result showed the subunit vaccine could achieve 6.34 PD50 per dose

NMR and UPLC-HRMS based Metabolomics : application in Non-alcoholic fatty liver disease and Prostate Cancer Biomarker Discovery

La métabolomique consiste en l’étude approfondie du métabolome, qui correspond à l’ensemble des métabolites présent dans un organisme. Le métabolome donne un aperçu de l’état physiologique de l’organisme, de l’extrait ou des cellules étudiées. La mesure des métabolites par l’approche métabolomique est un complément important aux études sur le génome, le transcriptome et le protéome, qui peut améliorer notre compréhension sur comment la génétique, l’environnement, le microbiome, les maladies, l’exposition aux médicaments, l’alimentation et le mode de vie influencent le phénotype. L’une des applications importantes de la métabolomique en recherche clinique est la découverte de nouveaux biomarqueurs. La présente thèse porte sur la partie découverte de biomarqueurs par métabolomique. Deux études sont réalisées : (1) la première utilise l’approche métabolomique et lipidomique basée sur la RMN et l’UPLC-HRMS, pour identifier de nouveaux biomarqueurs plasmatiques qui caractérisent les différents stades de la stéatose hépatique non alcoolique (NAFLD) (2) la seconde combine la métabolomique non ciblée basée sur UPLC-HRMS avec une approche épidémiologique pour identifier les biomarqueurs plasmatiques associés au risque de développer un cancer de la prostate (PCa) au cours de la décennie suivante.Metabolomics is the science designed to comprehensively study the metabolome, the repertoire of small molecule metabolites, which gives a comprehensive snapshot of the physiological state of the biofluid, extracts or cells studied. Measuring metabolites by using metabolomics is a key complementary to genome, transcriptome and proteome studies, which may improve our understanding of how genetics, environment, the microbiome, disease, drug exposure, diet, and lifestyle influence the phenotype. One of important application of metabolomics in clinical research is the discovery of novel biomarkers. The present PhD thesis focus on biomarkers discovery by applying metabolomics, the objectives were: (1) by using NMR and UPLC-HRMS based metabolomic and lipidomic profiling, to identify novel plasma biomarkers, if any, which characterize the different stage of Non-alcoholic fatty liver disease (NAFLD), and (2) by combining UPLC-HRMS based untargeted metabolomics with epidemiology approach, to identify plasma biomarkers which associated with the risk of developing prostate cancer (PCa) within the following decade

Métabolomique par la RMN et l'UPLC-HRMS : Application dans la découverte de biomarqueurs de la stéatose hépatique non alcoolique et du cancer de la prostate

Metabolomics is the science designed to comprehensively study the metabolome, the repertoire of small molecule metabolites, which gives a comprehensive snapshot of the physiological state of the biofluid, extracts or cells studied. Measuring metabolites by using metabolomics is a key complementary to genome, transcriptome and proteome studies, which may improve our understanding of how genetics, environment, the microbiome, disease, drug exposure, diet, and lifestyle influence the phenotype. One of important application of metabolomics in clinical research is the discovery of novel biomarkers. The present PhD thesis focus on biomarkers discovery by applying metabolomics, the objectives were: (1) by using NMR and UPLC-HRMS based metabolomic and lipidomic profiling, to identify novel plasma biomarkers, if any, which characterize the different stage of Non-alcoholic fatty liver disease (NAFLD), and (2) by combining UPLC-HRMS based untargeted metabolomics with epidemiology approach, to identify plasma biomarkers which associated with the risk of developing prostate cancer (PCa) within the following decade.La métabolomique consiste en l’étude approfondie du métabolome, qui correspond à l’ensemble des métabolites présent dans un organisme. Le métabolome donne un aperçu de l’état physiologique de l’organisme, de l’extrait ou des cellules étudiées. La mesure des métabolites par l’approche métabolomique est un complément important aux études sur le génome, le transcriptome et le protéome, qui peut améliorer notre compréhension sur comment la génétique, l’environnement, le microbiome, les maladies, l’exposition aux médicaments, l’alimentation et le mode de vie influencent le phénotype. L’une des applications importantes de la métabolomique en recherche clinique est la découverte de nouveaux biomarqueurs. La présente thèse porte sur la partie découverte de biomarqueurs par métabolomique. Deux études sont réalisées : (1) la première utilise l’approche métabolomique et lipidomique basée sur la RMN et l’UPLC-HRMS, pour identifier de nouveaux biomarqueurs plasmatiques qui caractérisent les différents stades de la stéatose hépatique non alcoolique (NAFLD) (2) la seconde combine la métabolomique non ciblée basée sur UPLC-HRMS avec une approche épidémiologique pour identifier les biomarqueurs plasmatiques associés au risque de développer un cancer de la prostate (PCa) au cours de la décennie suivante

Insight into Degrading Effects of Two Fungi on Polyurethane Coating Failure in a Simulated Atmospheric Environment

Two different fungi, Talaromyces funiculosus (T. funiculosus) and Phanerochaete chrysosporium (P. chrysosporium), were collected from the Xishuangbanna atmospheric corrosion site and incubated on a polyurethane (PU) coating at 30 °C for two weeks under 95% relative humidity (RH). The biodegrading effects of these fungi on the coating failure were investigated from aspects of metabolism and electrochemistry. The results showed that T. funiculosus contributed more to the degradation of the PU coating failure than P. chrysosporium, and two factors played dominant roles. First, the weight of the T. funiculosus mycelium was nearly 3 times more than that of P. chrysosporium, indicating there was more substrate mycelium of T. funiculosus deep into the coatings to get more nutrition in atmospheric during colonization. Second, T. funiculosus secreted carboxylic acids, such as citric, propanoic, succinic, and tartaric acids, and accelerated the hydrolysis of the ester and urethane bonds in the PU coatings. As a result, the mycelium of T. funiculosus readily penetrated the interface of the coating and substrate resulting in a rapid proliferation. Thus, the |Z|0.01Hz value of the coating decreased to 5.1 × 104 Ω·cm2 after 14 days of colonization by T. funiculosus while the value remained at 7.2 × 107 Ω·cm2 after colonization by P. chrysosporium. These insights suggest that the biodegradation process in simulated atmospheric environments would provide theoretical guidance and directions for the design of antifungal PU coatings

Simultaneous Quantification of Pioglitazone and Omarigliptin in Rat Plasma by UHPLC-MS/MS and Its Application to Pharmacokinetic Study after Coadministration of the Two Drugs

Combination therapy is a common approach for clinical treatment of type 2 diabetes mellitus, especially for patients with poor monotherapy. Meta-analysis suggested that omarigliptin, a long-acting DPP-4 inhibitor, combined with pioglitazone might improve the side effects of pioglitazone. However, little is known about the pharmacokinetic properties after a coadministration. In this study, a rapid and reliable method for the simultaneous determination of the pioglitazone and omarigliptin in rat plasma by UHPLC-MS/MS was established and validated for the first time. An exsil mono C18 column (2.0 × 50 mm, 3 μm) was used to separate the analytes and the column temperature was kept at 30°C. Sitagliptin was selected as the internal standard. 0.02% formic acid aqueous solution (A) and methanol-acetonitrile (B) were used as mobile phases with gradient elution at a flow rate of 0.3 mL/min. The elution procedure was as follows: 20%B (0–0.1 min), 80%B (0.1–0.3 min), 80%B (0.3–2.0 min), and 20%B (2.1–3.0 min). A multiple reaction monitor (MRM) was used under positive ionization mode with electrospray ion source to detect pioglitazone (357.1 ⟶ 134.1), omarigliptin (399.2 ⟶ 153.0), and sitagliptin (408.2 ⟶ 235.0). The linear ranges of pioglitazone and omarigliptin were 5–2000 ng/mL and 10–4000 ng/mL, respectively. Good linear relationships were exhibited in the corresponding linear ranges (r ≥ 0.9944). The bioanalytical method was validated, and the selectivity, linearity, sensitivity, accuracy, precision, stability, recovery, and matrix effect were acceptable. The validated method was then successfully applied to pharmacokinetic study of pioglitazone combined with omarigliptin in rats. Results suggested that the combination of the two drugs had little effect on the pharmacokinetic parameters of each other in rats

Influence des caractéristiques aérodynamiques d'un écoulement en conduite sur la réponse d'un débitmètre à ultrasons

Les débitmètres à ultrasons présentent de nombreux avantages par rapport aux technologies concurrentes (diaphragme, turbine,...) dans le domaine gazier notamment. Néanmoins, leur coût d exploitation et la dégradation de la qualité de mesure du débit en écoulement perturbé limitent leur utilisation. Cette étude expérimentale vise à mieux comprendre l'impact des conditions d'installation de ces débitmètres sur la qualité de la mesure du débit. L étude de la réponse de ces débitmètres requière une analyse ne de l'écoulement auquel ils sont soumis. Ainsi, diverses perturbations de l'écoulement (rotation de la veine, dissymétrie du champ de vitesse axiale et modi cation de l état de surface interne de la conduite) ont été étudiées. L'écoulement complexe obtenu en aval d un té suivi d un coude a aussi été caractérisé expérimentalement. Des simulations numériques complètent l'approche expérimentale effectuée. Dans le cadre de ces travaux, un modèle de comportement de ces débitmètres est testé. Ce modèle est basé sur la connaissance du champ aérodynamique le long des trajets acoustiques composant le débitmètre à ultrasons. Les hypothèses nécessaires à l'élaboration du modèle sont discutées. Entre autres, ce modèle nécessite une reconstruction du champ aérodynamique dans le débitmètre. L'impact de cette reconstruction sur la précision du modèle est quanti é grâce à une approche analytique. L'analyse des perturbations élémentaires montre que pour une con guration acoustique donnée, il existe des corrélations entre la perturbation aérodynamique et la réponse du débitmètre. Ces résultats permettent d envisager une auto correction de la mesure du débit par ultrasons.TOULOUSE-ISAE (315552318) / SudocSudocFranceF

Three-dimensional parallel recording with a Debye diffraction-limited and aberration-free volumetric multifocal array

In this Letter, we report on the generation of high-quality Debye diffraction-limited volumetric multifocal arrays. The multifocal arrays with a uniformity of 0.99 over the entire focal region of a high numerical-aperture objective are volumetrically generated by using the vectorial Debye-based three-dimensional (3D) Fourier-transform method, through the accurate phase modulation on an Ewald cap. Thus, this method is capable of dynamic spherical aberration compensation. Applying this feature into 3D parallel aberration-free optical recording reveals a significant increase in the throughput by two orders of magnitude

Investigating Different Local Polyurethane Coatings Degradation Effects and Corrosion Behaivors by <i>Talaromyces funiculosus</i> via Wire Beam Electrodes

The degradation effect of mold on the coating in a hot and humid environment is one of the important factors that cause layer failure. Combined with the wire beam electrode (WBE) and the traditional surface analysis technique, the local biodegradation of the coatings and the corrosion behaviors of metal substrates can be characterized accurately by a WBE. Herein, a WBE was used to study the degradation impact of Talaromyces funiculosus (T. funiculosus) isolated from a tropical rainforest environment on the corrosion of polyurethane (PU) coating. After immersion for 14 days, the local current density distribution of the WBE surface can reach ~10−3 A/cm2 in the fungal liquid mediums but maintains ~10−7 A/cm2 in sterile liquid mediums. The |Z|0.01Hz value of the high current densities area (#85 electrode) was 1.06 × 109 Ω cm2 in a fungal liquid medium after 14 days of immersion. After being attacked by T. funiculosus, the degradation of the PU was more severe, and there were wrinkles, cracks, blisters, and even micro-holes distributed randomly on the surface of electrodes. This resulted from the self-corrosion caused by the T. funiculosus degradation of the coating; the corrosion caused by the electric coupling effect of the coating was introduced. Energy dispersive spectroscopy (EDS) and Raman spectra results showed that the corrosion products were flakey and globular, which consisted of γ-FeOOH, γ-Fe2O3, and α-FeOOH