The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling.

Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells.

The stabilization of slopes by vegetation has been a topical issue for many years. Root mechanical characteristics significantly influence soil reinforcement; therefore it is necessary to research into the indicators of root tensile properties. In this study, we explored the influence of root moisture content on tensile resistance and strength with different root diameters and for different tree species. Betula platyphylla, Quercus mongolica, Pinus tabulaeformis, and Larix gmelinii, the most popular tree species used for slope stabilization in the rocky mountainous areas of northern China, were used in this study. A tensile test was conducted after root samples were grouped by diameter and moisture content. The results showedthat:1) root moisture content had a significant influence on tensile properties; 2) slightly loss of root moisture content could enhance tensile strength, but too much loss of water resulted in weaker capacity for root elongation, and consequently reduced tensile strength; 3) root diameter had a strong positive correlation with tensile resistance; and4) the roots of Betula platyphylla had the best tensile properties when both diameter and moisture content being controlled. These findings improve our understanding of root tensile properties with root size and moisture, and could be useful for slope stabilization using vegetation.

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