Repair of Sciatic Nerve Defect in Rats With Acellular Nerve Allograft Carrying Vascular Endothelial Cells.

BACKGROUND: Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. METHODS: A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. RESULTS: All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. CONCLUSION: ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.

Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration.

Large segmental bone defects are commonly operated with autologous bone grafting, which has limited bone sources and poses additional surgical risks. In this study, we fabricated poly(lactide-co-glycolic acid) (PLGA)/ß-tricalcium phosphate (ß-TCP) composite membranes by electrostatic spinning and further promoted osteogenesis by regulating the release of ß-TCP in the hope of replacing autologous bone grafts in the clinical practice. The addition of ß-TCP improved the mechanical strength of PLGA by 2.55 times. Moreover, ß-TCP could accelerate the degradation of PLGA and neutralize the negative effects of acidification of the microenvironment caused by PLGA degradation. In vitro experiments revealed that PLGA/TCP10 membranes are biocompatible and the released ß-TCP can modulate the activity of osteoblasts by enhancing the calcium ions concentration in the damaged area and regulating the pH of the local microenvironment. Simultaneously, an increase in ß-TCP can moderate the lactate content of the local microenvironment, synergistically enhancing osteogenesis by promoting the tube-forming effect of human umbilical vein endothelial cells. Therefore, it is potential to utilize PLGA/TCP bioactive membranes to modulate the microenvironment at the site of bone defects to promote bone regeneration.

Activation of the cGAS-STING-IRF3 Axis by Type I and II Interferons Contributes to Host Defense.

Interferons (IFNs) activate JAK-STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (ß) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3-deficiency impairs transcription of a subset of downstream effector genes induced by IFN-ß and IFN-γ. Mechanistically, IFN-induced activation of IRF3 is dependent on the cGAS-STING-TBK1 axis. Both IFN-ß and IFN-γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1-mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN-ß- or IFN-γ-mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS-STING-IRF3 axis in host defense.

Retarded sodium alloying interface reaction for stable anode-less sodium metal batteries.

Improving the sodiophilicity of the substrate is essential to enhance the reversibility of anode-less sodium metal batteries. Here, we have prepared a sodiophilic nano-Pb coating on aluminum-based collectors by magnetron sputtering. The slow alloying kinetics between Pb and sodium allows prolonged Pb retention in the coating, endowing the coating with a durable sodiophilicity.