No abstract

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.

No abstract

Limited by reduction radio, heavy plates manufactured from slabs are always subjected to deterioration of soundness and mechanical properties. For overcoming these defects, in the current works, a new approach, named heavy reduction process to improve segregation and porosity, was presented. The aim this study was to fix the dividing position of improving centerline segregation or porosity. Based on the world's maximum thickness vertical‐bending type caster, a two‐step strategy was preceded using software THERCAST, which was coupled macroscopic segregation with thermal‐mechanical GNS method firstly. According to the real production condition of superheat, casting speed and spray intensity, the depth of mushy zone and the terminal end of solidification in width direction were modeled. After this, the distribution of pressure and bulging were presented, and four positions were preliminarily determined based on the curves. Finally, the element concentration, cracks and reduction rate at these different reduction positions were discussed further. The results indicate that the division point of improving centerline segregation or porosity is confirmed ultimately.