Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl) in DPP4 gene knockout (gko) mice. DPP4 gko had less liver fibrosis and inflammation and fewer B cell clusters than wild type mice in the fibrosis model. DPP4 inhibitor-treated mice also developed less liver fibrosis. DNA microarray and PCR showed that many immunoglobulin (Ig) genes and some metabolism-associated transcripts were differentially expressed in the gko strain compared with wild type. CCl-treated DPP4 gko livers had more IgM and IgG intrahepatic lymphocytes, and fewer CD4, IgD and CD21 intrahepatic lymphocytes. These data suggest that DPP4 is pro-fibrotic in CCl-induced liver fibrosis and that the mechanisms of DPP4 pro-fibrotic action include energy metabolism, B cells, NK cells and CD4 cells.

Formalin-fixed (FF) autopsy tissue comprises the bulk of existing Multiple Sclerosis (MSc) pathology archives, providing a rich pool of material for biomarker discovery and disease characterization. Here, we present the development of a heat-induced extraction protocol for the proteomic analysis of FF brain tissue, its application to the study of lesion remyelination and its failure in MSc. A 4-round extraction strategy was optimized using FF tissue leading to a 35% increase in the number of proteins identified compared to a single extraction; and a 65% increase in proteins identified with ≥4 peptides. Histological staining of sections with oil red O and luxol fast blue-periodic acid Schiff, required to characterize MSc lesions was found to have minimal effect on LC-MS/MS. The application of the optimized protocol to chronic demyelinated and remyelinated FF MSc lesions and the adjacent periplaque white matter, isolated through laser guided manual dissection from 3 patients, identified 428 unique proteins (0.2% FDR) using LC-MS/MS. Comparison of the lesion types using iTRAQ and 2-D LC-MS/MS revealed 82 differentially expressed proteins. Protein quantitation by iTRAQ and spectral counting was well-correlated (r(s)= 0.7653; p < 10(-30)). The data generated from this work illustrates the scope of the methodology and provides insights into the pathogenesis of MSc and remyelination.

The design of Superstructure constructed with aluminum alloy do not have to follow the traditional standard design method. It can be designed by applying strength theory and ANSYS program or MSC Patran / Nastran program, which can ensure the strength requirements with the selected aluminum alloy components and make the weight of the ship lightest. In this paper, the 42.4m catamaran sightseeing boat is used as an example. The structural strength of the superstructure constructed with aluminum alloy is calculated by MSC Patran / Nastran program. The distribution of the superstructure stress is obtained, which proved the size of the selected components of the superstructure can meet the requirements of the local strength and can be the reference of selecting the structure size. As the other conditions are unchanged, the the local thickness of the junction of the front wall and the side wall of the compass deck is changed. the relationship between plate thickness and stress is obtained. It is found that as The plate thickness is thicker, the stress there decreases; and as the thickness is smaller, it is obvious to reduce stress as the plate thickness Increase. when the thickness increases to a certain extent, the effect of the plate stress decreases is not obvious.