Integrin αvβ3 expression is altered in various diseases and has been proposed as a drug target. Here we use a rational design approach to develop a therapeutic protein, which we call ProAgio, that binds to integrin αvβ3 outside the classical ligand-binding site. We show ProAgio induces apoptosis of integrin αvβ3-expressing cells by recruiting and activating caspase 8 to the cytoplasmic domain of integrin αvβ3. ProAgio also has anti-angiogenic activity and strongly inhibits growth of tumour xenografts, but does not affect the established vasculature. Toxicity analyses demonstrate that ProAgio is not toxic to mice. Our study reports a new integrin-targeting agent with a unique mechanism of action, and provides a template for the development of integrin-targeting therapeutics.

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Experimental investigation on seismic performance of RC shear walls reinforced with CFRP bars in boundary elements to enhance the resilience was presented which is expected for stable resistance capacity and small residual deformation. Six RC shear walls reinforced with CFRP bars as longitudinal tensile materials in boundary elements were tested under reversed cyclic lateral loading while subjected to constant axial compression with different axial load ratios of 0.17, 0.26 and 0.33, respectively. Two forms of stirrups were used for each axial load ratio, which were rectangular and circular stirrups in boundary elements. A reference specimen, ordinary RC shear walls, was also introduced to certify the excellence of CFRP bars. The test results indicated that the walls utilizing CFRP bars had small residual deformations and residual crack widths. Lower crack propagation height and larger concrete crushing region, bearing capacity and equivalent viscous damping coefficient (EVDC) could be observed with the increase of axial load ratios. The effects of stirrup forms on experimental results had a relation to the axial load ratio. When the axial load ratio was small, the shear walls with circular stirrups had better energy dissipation than that with rectangular stirrups at a given drift level, while the cumulative energy dissipation (CED) were similar. With the increase of axial load ratio, the walls exhibited similar energy dissipation at the same drift level, however, the shear walls with rectangular stirrups had larger CED.