Characterization of Murine Intestinal Mucus Layer Gene Expression during Postnatal Maturation

The objective of this work was to characterize the expression pattern of the main intestinal mucin and glycosyltransferases genes in the distal ileum, caecum, proximal and distal colon of 5, 10, 15, 21, 25 and 32 days old mouse pups by real-time PCR. We found that all genes considered, except for Muc13 followed a spatio-temporal expression pattern. As a potential modulator of mucin gene expression, gut microbiota composition was also analyzed in the same animals. We found that neither the total bacterial numbers nor the relative abundance of the main microbial phyla vary after 21 days of age. The characterization of the postnatal intestinal mucus layer gene expression may aid to understand disease-related deviations and help designing nutritional interventions to sustain the intestinal barrier.MAS

Novel Insights in Ankylosing Spondylitis Biology: Mouse and Human Studies

Little is known about the mechanisms underlying the clinical overlap of ankylosing spondylitis (AS) and inflammatory bowel disease (IBD). There is also a lack of reliable serological biomarkers to guide AS management. AS is a complex, male-dominant disease with HLA-B27 being the strongest genetic association. The ank/ank mouse is a murine model with serological and pathological features similar to human AS. Lipocalin 2 (murine Lcn2/human LCN2) is a secreted anti-microbial glycoprotein produced in multiple tissues including joint and gut. Given the functions of lipocalin 2 in infection, inflammation and bone remodeling, our aim is to assess whether lipocalin 2 is a key mediator of the gut-joint axis in AS and whether it would serve a better marker for treatment outcomes. The association of LCN2 with HLA-B27 and sex in patients is also analyzed. Chapter 2 shows that aberrant levels of Lcn2 are associated with ankylosis and gut pathology in ank/ank mice, indicating a potential mechanism underlying the overlap of AS and IBD. The interplay of gut inflammation and ankylosis in contributing to elevated Lcn2 levels suggests that the ank/ank mouse is a relevant animal model for the gut-joint interactions, as seen in AS. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in aberrant Lcn2 pathway in this AS model. Chapter 3 confirms the elevation of serum LCN2 in AS patients. Levels of LCN2 are associated with coexisting IBD and with the degree of ankylosis. The relationship of HLA-B27 positivity and sex with LCN2 implicates a host-microbe interaction underlying the gut-joint axis in AS. Chapter 4 demonstrates that normalization of LCN2 could be viewed as a treatment target in AS. Serum LCN2 served a more sensitive biomarker for treatment outcome in 89% of AS patients. HLA-B27 status and sex does affect LCN2 as a readout for assessing treatment outcome. The discovery of aberrant Lcn2/LCN2 reveals a relevant mechanism underlying the gut-joint axis in AS. The effect of PPARγ on aberrant Lcn2 pathway sheds lights on novel therapeutic targets for the disease. More knowledge of the dysregulation of Lcn2/LCN2 pathways will contribute to better AS management and more effective treatment strategies.Ph.D

Multi-feature Co-learning for Image Inpainting

Image inpainting has achieved great advances by simultaneously leveraging image structure and texture features. However, due to lack of effective multi-feature fusion techniques, existing image inpainting methods still show limited improvement. In this paper, we design a deep multi-feature co-learning network for image inpainting, which includes Soft-gating Dual Feature Fusion (SDFF) and Bilateral Propagation Feature Aggregation (BPFA) modules. To be specific, we first use two branches to learn structure features and texture features separately. Then the proposed SDFF module integrates structure features into texture features, and meanwhile uses texture features as an auxiliary in generating structure features. Such a co-learning strategy makes the structure and texture features more consistent. Next, the proposed BPFA module enhances the connection from local feature to overall consistency by co-learning contextual attention, channel-wise information and feature space, which can further refine the generated structures and textures. Finally, extensive experiments are performed on benchmark datasets, including CelebA, Places2, and Paris StreetView. Experimental results demonstrate the superiority of the proposed method over the state-of-the-art. The source codes are available at https://github.com/GZHU-DVL/MFCL-Inpainting

Identification of Novel Hydrogen-Substituted Polyfluoroalkyl Ether Sulfonates in Environmental Matrices near Metal-Plating Facilities

Environmental occurrence and behaviors of 6:2 chlorinated polyfluoroalkyl ether sulfonate (Cl-6:2 PFESA, with trade name F-53B) have been receiving increased attention recently. Nevertheless, its potential fates under diversified conditions remain concealed. In this study, susceptibility of Cl-6:2 PFESA to reductive dehalogenation was tested in an anaerobic super-reduced cyanocobalamin assay. A rapid transformation of dosed Cl-6:2 PFESA was observed, with a hydrogen-substituted polyfluoroalkyl ether sulfonate (1H-6:2 PFESA) identified as the predominant product by a nontarget screening workflow. With the aid of laboratory-purified standards, hydrogen-substituted PFESA analogues (i.e., 1H-6:2 and 1H-8:2 PFESA) were further found in river water and sediment samples collected from two separate regions near metal-plating facilities. Geometric mean concentrations of 560 pg/L (river water) and 11.1 pg/g (sediment) for 1H-6:2 PFESA and 11.0 pg/L (river water) and 7.69 pg/g (sediment) for 1H-8:2 PFESA were measured, and both analytes consisted average compositions of 1% and 0.1% among the 18 monitored per- and polyfluoroalkyl sulfonate and carboxylate pollutants, respectively. To our knowledge, this is the first to report existence of polyfluoroalkyl sulfonates with both hydrogen and ether functional group in the environment

Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins

In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (< 2 nm) and small mesopores (2 nm < diameter < 10 nm) of HP20 resin decreased after adsorption of toxins in seawater at high and low salinity but not in seawater at medium salinity, which demonstrated that the toxin molecules entered into micropores and mesopores (below 10 m in size) in seawaters of high and low salinity. More toxin or other matrix agglomerates were displayed on the surface of resin deployed in the seawater of medium salinity. Taking into consideration the pore-size distribution and surface images, it appears that intra-particle diffusion governs toxin adsorption in seawater at high salinity while film diffusion mainly controls the adsorption process in seawater at medium salinity. This is the first study to confirm that molecules of OA and DTX1 are able to enter into micropores (< 2 nm) and small mesopores (2 - 10 nm) of HP20 resin in estuarine seawater with high salinity (∼27 %)

Identification of Novel Hydrogen-Substituted Polyfluoroalkyl Ether Sulfonates in Environmental Matrices near Metal-Plating Facilities

Environmental occurrence and behaviors of 6:2 chlorinated polyfluoroalkyl ether sulfonate (Cl-6:2 PFESA, with trade name F-53B) have been receiving increased attention recently. Nevertheless, its potential fates under diversified conditions remain concealed. In this study, susceptibility of Cl-6:2 PFESA to reductive dehalogenation was tested in an anaerobic super-reduced cyanocobalamin assay. A rapid transformation of dosed Cl-6:2 PFESA was observed, with a hydrogen-substituted polyfluoroalkyl ether sulfonate (1H-6:2 PFESA) identified as the predominant product by a nontarget screening workflow. With the aid of laboratory-purified standards, hydrogen-substituted PFESA analogues (i.e., 1H-6:2 and 1H-8:2 PFESA) were further found in river water and sediment samples collected from two separate regions near metal-plating facilities. Geometric mean concentrations of 560 pg/L (river water) and 11.1 pg/g (sediment) for 1H-6:2 PFESA and 11.0 pg/L (river water) and 7.69 pg/g (sediment) for 1H-8:2 PFESA were measured, and both analytes consisted average compositions of 1% and 0.1% among the 18 monitored per- and polyfluoroalkyl sulfonate and carboxylate pollutants, respectively. To our knowledge, this is the first to report existence of polyfluoroalkyl sulfonates with both hydrogen and ether functional group in the environment

Intracellular Survival and Persistence of <i>Chlamydia muridarum</i> Is Determined by Macrophage Polarization

<div><p>Macrophages can display a number of distinct phenotypes, known collectively as polarized macrophages. The best defined of these phenotypes are the classically-activated, interferon gamma (IFNγ)/LPS induced (M1) and alternatively-activated, IL-4 induced (M2) macrophages. The goal of this study is to characterize macrophage-<i>Chlamydia</i> interactions in the context of macrophage polarization. Here we use <i>Chlamydia muridarum</i> and murine bone-marrow derived macrophages to show <i>Chlamydia</i> does not induce M2 polarization in macrophages as a survival strategy. Unexpectedly, the infection of macrophages was silent with no upregulation of M1 macrophage-associated genes. We further demonstrate that macrophages polarized prior to infection have a differential capacity to control <i>Chlamydia</i>. M1 macrophages harbor up to 40-fold lower inclusion forming units (IFU) than non-polarized or M2 polarized macrophages. Gene expression analysis showed an increase in <i>16sRNA</i> in M2 macrophages with no change in M1 macrophages. Suppressed <i>Chlamydia</i> growth in M1 macrophages correlated with the induction of a bacterial gene expression profile typical of persistence as evident by increased <i>Euo</i> expression and decreased <i>Omp1</i> and <i>Tal</i> expression. Observations of permissive <i>Chlamydia</i> growth in non-polarized and M2 macrophages and persistence in M1 macrophages were supported through electron microscopy. This work supports the importance of IFNγ in the innate immune response to <i>Chlamydia</i>. However, demonstration that the M1 macrophages, despite an antimicrobial signature, fail to eliminate intracellular <i>Chlamydia</i> supports the notion that host–pathogen co-evolution has yielded a pathogen that can evade cellular defenses against this pathogen, and persist for prolonged periods of time in the host.</p> </div