Soluble Nogo66 receptor-Fc protein(sNgR-Fc)enhances axonal regeneration following central nervous system injury.However,the underlying mechanisms remain unclear.In this study,we investigated the effects of sNgR-Fc on ...Soluble Nogo66 receptor-Fc protein(sNgR-Fc)enhances axonal regeneration following central nervous system injury.However,the underlying mechanisms remain unclear.In this study,we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells.The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats.The rats with photothrombotic cortical injury were randomized to receive infusion of 400μg/kg sNgR-Fc(sNgR-Fc group)or an equal volume of phosphate-buffered saline(photothrombotic cortical injury group)into the lateral ventricle for 3 days.The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining.Neurological function was evaluated with the Morris water maze test.To further examine the effects of sNgR-Fc treatment on neural progenitor cells,photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats.The animals were then given an infusion of phosphate-buffered saline(neural progenitor cells group)or sNgR-Fc(sNgR-Fc+neural progenitor cells group)into the lateral ventricle for 3 days.sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo,compared with phosphate-buffered saline,and it also induced the differentiation of neural progenitor cells into neurons.Compared with the photothrombotic cortical injury group,escape latency in the Morris water maze and neurological severity score were greatly reduced,and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group,indicating a substantial improvement in neurological function.Furthermore,compared with phosphate-buffered saline infusion,sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells.Our findings show that sNgR-Fc regulates neural progenitor cell proliferation,migration and differentiation.Therefore,sNgR-Fc is a potential novel therapy for stroke and neurodegenerative diseases,The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong(approval No.4560-17)in November,2015.展开更多
Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully...Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully understood.To address this issue,we first co-cultured 1.5×10^5 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1,and then intervened with cobalt chloride(CoCl2)for 24 hours.Reactive oxygen species in PC12 cells was measured by Mito-sox.Mitochondrial membrane potential(ΔΨm)in PC12 cells was determined by JC-1 staining.Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining.Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy.Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry.Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria.Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells.CoCl2-induced PC12 cell damage was dose-dependent.Co-culture with mesenchymal stem cells significantly reduced apoptosis and restoredΔΨm in the injured PC12 cells under CoCl2 challenge.Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling,the disappearance of cristae,and chromatin margination in the injured PC12 cells.After direct co-culture,mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells.The transfer efficiency was greatly enhanced in the presence of CoCl2.More importantly,inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury.Mesenchymal stem cells reduced CoCl2-induced PC12 cell injury and these effects were in part due to efficacious mitochondrial transfer.展开更多
The detection of GW170817 and its electromagnetic counterpart has revealed the speed of gravitational waves coincides with the speed of light, cT= 1. Inspired by the possibility that the physics implied by GW170817 mi...The detection of GW170817 and its electromagnetic counterpart has revealed the speed of gravitational waves coincides with the speed of light, cT= 1. Inspired by the possibility that the physics implied by GW170817 might be related with that for the primordial universe, we construct the spatially ?at stable(throughout the whole evolution)nonsingular bounce models in the beyond Horndeski theory with cT= 1 and in the degenerate higher-order scalar-tensor(DHOST) theory with cT= 1, respectively. Though it constricts the space of viable models, the constraint of cT= 1 makes the procedure of building models simpler.展开更多
This paper proposes a new customer lifetime model:the Gamma/Weibull distribution(G/W).Similar to the Pareto/NBD model,we propose a G/W/NBD model by combining the G/W distribution with a negative binomial distribution(...This paper proposes a new customer lifetime model:the Gamma/Weibull distribution(G/W).Similar to the Pareto/NBD model,we propose a G/W/NBD model by combining the G/W distribution with a negative binomial distribution(NBD)and study its properties such as(i)the probability that a customer to be alive at a time point;(ii)the expectation and variance of the number of transactions for a customer during a fixed time period;(iii)the conditional expectation and conditional variance of the number of future transactions for a customer during a fixed time period.Several simulation studies are conducted to investigate the forecasting accuracy and flexibility of the proposed model.A CDNOW data set is analyzed by the proposed model.展开更多
基金supported by the National Natural Science Foundation of China,No.81671882,81471832(to XL)the Natural Science Foundation of Guangdong Province of China,No.2016A030311039(to XL)+1 种基金the Science and Technology Foundation of Guangdong Province of China,No.2015A020212012,2017A020224012(to XL)the Science and Technology Foundation of Guangzhou City of China,No.201707010373(to XL)
文摘Soluble Nogo66 receptor-Fc protein(sNgR-Fc)enhances axonal regeneration following central nervous system injury.However,the underlying mechanisms remain unclear.In this study,we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells.The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats.The rats with photothrombotic cortical injury were randomized to receive infusion of 400μg/kg sNgR-Fc(sNgR-Fc group)or an equal volume of phosphate-buffered saline(photothrombotic cortical injury group)into the lateral ventricle for 3 days.The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining.Neurological function was evaluated with the Morris water maze test.To further examine the effects of sNgR-Fc treatment on neural progenitor cells,photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats.The animals were then given an infusion of phosphate-buffered saline(neural progenitor cells group)or sNgR-Fc(sNgR-Fc+neural progenitor cells group)into the lateral ventricle for 3 days.sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo,compared with phosphate-buffered saline,and it also induced the differentiation of neural progenitor cells into neurons.Compared with the photothrombotic cortical injury group,escape latency in the Morris water maze and neurological severity score were greatly reduced,and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group,indicating a substantial improvement in neurological function.Furthermore,compared with phosphate-buffered saline infusion,sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells.Our findings show that sNgR-Fc regulates neural progenitor cell proliferation,migration and differentiation.Therefore,sNgR-Fc is a potential novel therapy for stroke and neurodegenerative diseases,The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong(approval No.4560-17)in November,2015.
基金supported by the National Natural Science Foundation of China,No.81671882,81471832the Natural Science Foundation of Guangdong Province of China,No.2016A030311039+1 种基金the Science and Technology Foundation of Guangdong Province of China,No.2015A020212012,2017A020224012the Science and Technology Foundation of Guangzhou City of China,No.201707010373(all to XL)
文摘Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully understood.To address this issue,we first co-cultured 1.5×10^5 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1,and then intervened with cobalt chloride(CoCl2)for 24 hours.Reactive oxygen species in PC12 cells was measured by Mito-sox.Mitochondrial membrane potential(ΔΨm)in PC12 cells was determined by JC-1 staining.Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining.Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy.Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry.Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria.Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells.CoCl2-induced PC12 cell damage was dose-dependent.Co-culture with mesenchymal stem cells significantly reduced apoptosis and restoredΔΨm in the injured PC12 cells under CoCl2 challenge.Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling,the disappearance of cristae,and chromatin margination in the injured PC12 cells.After direct co-culture,mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells.The transfer efficiency was greatly enhanced in the presence of CoCl2.More importantly,inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury.Mesenchymal stem cells reduced CoCl2-induced PC12 cell injury and these effects were in part due to efficacious mitochondrial transfer.
基金Supported by National Natural Science Foundation of China under Grant Nos.11575188 and 11690021
文摘The detection of GW170817 and its electromagnetic counterpart has revealed the speed of gravitational waves coincides with the speed of light, cT= 1. Inspired by the possibility that the physics implied by GW170817 might be related with that for the primordial universe, we construct the spatially ?at stable(throughout the whole evolution)nonsingular bounce models in the beyond Horndeski theory with cT= 1 and in the degenerate higher-order scalar-tensor(DHOST) theory with cT= 1, respectively. Though it constricts the space of viable models, the constraint of cT= 1 makes the procedure of building models simpler.
文摘This paper proposes a new customer lifetime model:the Gamma/Weibull distribution(G/W).Similar to the Pareto/NBD model,we propose a G/W/NBD model by combining the G/W distribution with a negative binomial distribution(NBD)and study its properties such as(i)the probability that a customer to be alive at a time point;(ii)the expectation and variance of the number of transactions for a customer during a fixed time period;(iii)the conditional expectation and conditional variance of the number of future transactions for a customer during a fixed time period.Several simulation studies are conducted to investigate the forecasting accuracy and flexibility of the proposed model.A CDNOW data set is analyzed by the proposed model.
