Search for: All records

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation–induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light. Pulsed light stimulation of human cardiomyocytes showed that the optoelectronically active scaffold could increase their beating rates (>40%), maintain high cell viability under light stimulation (>96%), and negligibly affect the electrocardiogram morphology. The seeded scaffolds, termed optoelectronically active tissues, were able to successfully accelerate heart beating in vivo in rats. Our work demonstrates a viable wireless, printable, and optically controllable tissue, suggesting a transformative step in future therapy of electrically active tissues/organs. 

Hepatitis C Virus (HCV) is reported to develop GS-461203 resistance because of multiple mutations within the RNA-dependent RNA Polymerase (RdRp) of HCV. The lack of a high-resolution structure of these RdRp mutants in complex with GS-461203 hinders efforts to understand the drug resistance. Here we decipher the binding differences of GS-461203 in the wild type and mutated systems T179A or M289L of HCV RdRp Genotype 2a using homology modeling, molecular docking, and molecular dynamics simulation. Key residues responsible for GS-461203 binding were identified to be Arg48, Arg158, Asp318, Asp319, and Asp220, and that mutations T179A or M289L have caused conformational changes of GS-461203 in the RdRp active site. The affinities of GS-461203 were reduced in T179A system, but it became slightly stronger in the M289L system. Furthermore, we designed two new analogues of GS-461203 which encouragingly induced more stable interactions than GS-461203, and thus resulted in much better binding energies. This present study reveals how a single mutation, T179A or M289L, will modulate GS-461203 binding in HCV RdRp Genotype 2a, while introducing two novel analogues to overcome the drug resistance which may be good candidate for further experimental verification.