Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD

A fiber beam-column model for damage assessment of traditional Chinese timber structures

This study proposes a fiber beam-column model that takes into account the anisotropy of wood and the embedment behavior of the rocking column to assess the impact of wood damage on the lateral performance of traditional Chinese timber structures. Subsequently, numerical analyses corresponding to a full-scale quasi-static test of a traditional Chinese timber framework are conducted to verify the accuracy of this fiber beam-column model. By considering factors such as residual deformation and wood decay in the column base, the degradation behavior of traditional Chinese timber structures can be evaluated. This study provides a foundation for discussing and further researching the damage assessment of traditional Chinese timber structures

Novel Matrix Proteins of <i>Pteria penguin</i> Pearl Oyster Shell Nacre Homologous to the Jacalin-Related β-Prism Fold Lectins

<div><p>Nacreous layers of pearl oyster are one of the major functional biominerals. By participating in organic compound-crystal interactions, they assemble into consecutive mineral lamellae-like photonic crystals. Their biomineralization mechanisms are controlled by macromolecules; however, they are largely unknown. Here, we report two novel lectins termed PPL2A and PPL2B, which were isolated from the mantle and the secreted fluid of <i>Pteria penguin</i> oyster. PPL2A is a hetero-dimer composed of α and γ subunits, and PPL2B is a homo-dimer of β subunit, all of which surprisingly shared sequence homology with the jacalin-related plant lectin. On the basis of knockdown experiments at the larval stage, the identification of PPLs in the shell matrix, and <i>in vitro</i> CaCO₃ crystallization analysis, we conclude that two novel jacalin-related lectins participate in the biomineralization of <i>P. penguin</i> nacre as matrix proteins. Furthermore, it was found that trehalose, which is specific recognizing carbohydrates for PPL2A and is abundant in the secreted fluid of <i>P. penguin</i> mantle, functions as a regulatory factor for biomineralization via PPL2A. These observations highlight the unique functions, diversity and molecular evolution of this lectin family involved in the mollusk shell formation.</p></div