Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway

Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.

A Monte Carlo method for quantitatively calculating the neutron sensitivity of rhodium self-powered neutron detectors in reactors

Purpose Self-powered neutron detectors(SPNDs)with rhodium emitters exhibit high thermal neutron sensitivity and extensively equipped in nuclear reactors for core monitoring.The neutron sensitivity of SPND is the most significant criterion that directly determines the measured neutron flux and power and thereby needs to be accurately calibrated.Methods In this presented paper,the physical characteristics of rhodium SPND and its reaction mechanism with in-core neutrons were described thoroughly.Based on the inherent space electric field of concentric cylindrical SPND,three formulas with different approaches were proposed to quantitatively calculate the effective signal of SPND.The neutron sensitivity of rhodium SPND was then calculated quantitatively using the Monte Carlo(MC)methods.In order to expand the application scope of rhodium SPND,its sensitivity performance in four different types of pressurized water reactors(PWRs)was also been simulated and compared.Results and improvements The effectiveness and correctness of the model have been verified through experiments and comparisons with previous studies.The methods proposed in this paper have been successfully applied to industrial applications of reactor monitoring,and have demonstrated considerable reliability and accuracy.

NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors,but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown.Besides,the WW domain containing proteins can be recognized by NDFIP1,resulted in the loading of the target proteins into exosomes.However,whether WW domain-containing transcription regulator 1(WWTR1,also known as TAZ)can be packaged into exosomes by NDFIP1 and if so,whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent.Here,we first found that NDFIP1 was low expressed in NSCLC samples and cell lines,which is associated with shorter OS.Then,we confirmed the interaction between TAZ and NDFIP1,and the existence of TAZ in exosomes,which requires NDFIP1.Critically,knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate.And the cellular TAZ level could be altered by exosome secretion.Furthermore,NDFIP1 inhibited proliferation in vitro and in vivo,and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout.Moreover,TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples,and the serum exosomal TAZ level was lower in NSCLC patients.In summary,our data uncover a new tumor suppressor,NDFIP1 in NSCLC,and a new exosome-related regulatory mechanism of TAZ.