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
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
In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone int...In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi- tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the iscbemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-spe- cific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi- tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.展开更多
The Shanghai advanced proton therapy facility is a proton cancer treatment device designed and built by the Shanghai Institute of applied physics at the Chinese academy of sciences.The accelerator part comprises a pro...The Shanghai advanced proton therapy facility is a proton cancer treatment device designed and built by the Shanghai Institute of applied physics at the Chinese academy of sciences.The accelerator part comprises a proton linear accelerator(linac)injector and a circular synchrotron.An alternating current current transformer(ACCT)is used for non-intercepting beam current measurement at the drift tube linac exit.According to the beam characteristics,the ACCT is required to complete real-time beam current and pulse width measurements at currents of3-30 mA,frequencies of 1-10 Hz,and pulse widths of40-400μs.In this paper,we report the design and development of an ACCT.The designed ACCT was simulated using CST Microwave Studio,and calibrated using an oscilloscope and signal generator.Variations in the output signal of the ACCT were investigated as a function of ceramic gap size,number of coil turns,and resistance.According to the simulation and experimental results,the optimal number of coil turns was found to be 30.In addition,a low-pass filter was adopted to filter the noise introduced during long-distance signal transmission using a coaxial cable with the length of 20 m.The calibration results show that the corresponding rise time of the ACCT is 800 ns with the sensitivity of 8.2 V/A and a droop of less than 1%,meeting the design requirements.展开更多
Objective:The clinical treatment of brain diseases is urgent. Xingnaojing (XNJ) injection is often used in combination with other injection drugs. Due to the possible interaction between the injections in vivo, the pa...Objective:The clinical treatment of brain diseases is urgent. Xingnaojing (XNJ) injection is often used in combination with other injection drugs. Due to the possible interaction between the injections in vivo, the particle size, osmotic pressure, pH value change and component stability decrease, that is one of the important factors causing various adverse reactions. Based on the above situation, this study investigated the physical properties and chemical composition changes of XNJ injection and its compatibility solvent and 13 kinds of clinical injection, speculated the possible interactions between the drugs in vivo from the perspective of in vitro compatibility stability, find out the safety risks of adverse reactions and provide guidance for the safe and rational use of XNJ injection. Methods:According to the clinical application, XNJ injection was mixed with 13 combination injections based on 250 mL 5% glucose injection, and placed at room temperature for 6 h. Then, the clarity, particle size, pH, osmolality, and the contents of camphor, d-borneol, and muscone of the compatible solutions were detected at 0, 1, 2, 4, and 6 h, respectively. Results:The results showed that the physical-chemical properties of compatibility solution were slightly influenced when XNJ was combined with Alprostadil injection and Danhong injection. The change of particle size and the degradation of muscone content were the main factors affecting the compatibility stability of XNJ injection, indicating that there are some problems in compatibility stability, which may be one of the causes of clinical adverse reactions. Conclusion:This study suggests that XNJ injection in combination with other injections during intravenous administration should be performed cautiously.展开更多
Electric-field control of topological magnetic states in thinfilm heterostructures is promising for applications in nextgeneration memory or logic devices with ultrahigh density and low-power consumption.Multiferroic ...Electric-field control of topological magnetic states in thinfilm heterostructures is promising for applications in nextgeneration memory or logic devices with ultrahigh density and low-power consumption.Multiferroic materials,where spin and polar degrees of freedom coexist,provide a versatile playground to manipulate magnetism(converse magnetoelectric effect).Here,we report that the topological spin textures can be controlled by electric field in rhombohedral BiFeO_(3)/monoclinic La_(0.67)Sr_(0.33)MnO_(3)thin-film heterostructure at room temperature.展开更多
目的对间质性肺疾病的发展趋势及其国际研究热点进行可视化文献计量分析,为我国间质性肺疾病科研领域的发展提供参考信息。方法利用Citespace 5.5软件,以Web of Science数据库为数据来源,对2011年~2020年间质性肺疾病发表文献的年份、...目的对间质性肺疾病的发展趋势及其国际研究热点进行可视化文献计量分析,为我国间质性肺疾病科研领域的发展提供参考信息。方法利用Citespace 5.5软件,以Web of Science数据库为数据来源,对2011年~2020年间质性肺疾病发表文献的年份、国家、期刊、关键词进行可视化分析。结果共检索到6098条文献,2011年以来发文量逐渐增加,发文量最多的国家为美国;被引率最高的期刊为Am J Resp Crit Care;发文量及引文量最高的作者分别为Toby M Maher和Raghu G;该领域研究重点为流行病学,炎症与发病机制,诊断及治疗。结论国际间质性肺疾病关注度与研究水平逐渐增加,探索该领域研究热点及发展趋势,可为我国紧跟国际间质性肺疾病研究提供方向和依据。展开更多
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 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funded by a grant from Shaanxi Provincial Support Project of Scientific Research Development Plan of China,No.2012KCT-16
文摘In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi- tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the iscbemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-spe- cific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi- tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.
基金supported by the Ministry of Education of the People's Republic of China(MOE)(No.021312921002)。
文摘The Shanghai advanced proton therapy facility is a proton cancer treatment device designed and built by the Shanghai Institute of applied physics at the Chinese academy of sciences.The accelerator part comprises a proton linear accelerator(linac)injector and a circular synchrotron.An alternating current current transformer(ACCT)is used for non-intercepting beam current measurement at the drift tube linac exit.According to the beam characteristics,the ACCT is required to complete real-time beam current and pulse width measurements at currents of3-30 mA,frequencies of 1-10 Hz,and pulse widths of40-400μs.In this paper,we report the design and development of an ACCT.The designed ACCT was simulated using CST Microwave Studio,and calibrated using an oscilloscope and signal generator.Variations in the output signal of the ACCT were investigated as a function of ceramic gap size,number of coil turns,and resistance.According to the simulation and experimental results,the optimal number of coil turns was found to be 30.In addition,a low-pass filter was adopted to filter the noise introduced during long-distance signal transmission using a coaxial cable with the length of 20 m.The calibration results show that the corresponding rise time of the ACCT is 800 ns with the sensitivity of 8.2 V/A and a droop of less than 1%,meeting the design requirements.
文摘Objective:The clinical treatment of brain diseases is urgent. Xingnaojing (XNJ) injection is often used in combination with other injection drugs. Due to the possible interaction between the injections in vivo, the particle size, osmotic pressure, pH value change and component stability decrease, that is one of the important factors causing various adverse reactions. Based on the above situation, this study investigated the physical properties and chemical composition changes of XNJ injection and its compatibility solvent and 13 kinds of clinical injection, speculated the possible interactions between the drugs in vivo from the perspective of in vitro compatibility stability, find out the safety risks of adverse reactions and provide guidance for the safe and rational use of XNJ injection. Methods:According to the clinical application, XNJ injection was mixed with 13 combination injections based on 250 mL 5% glucose injection, and placed at room temperature for 6 h. Then, the clarity, particle size, pH, osmolality, and the contents of camphor, d-borneol, and muscone of the compatible solutions were detected at 0, 1, 2, 4, and 6 h, respectively. Results:The results showed that the physical-chemical properties of compatibility solution were slightly influenced when XNJ was combined with Alprostadil injection and Danhong injection. The change of particle size and the degradation of muscone content were the main factors affecting the compatibility stability of XNJ injection, indicating that there are some problems in compatibility stability, which may be one of the causes of clinical adverse reactions. Conclusion:This study suggests that XNJ injection in combination with other injections during intravenous administration should be performed cautiously.
基金financially supported by the Basic Science Center Program of National Natural Science Foundation of China(No.51788104)the National Natural Science Foundation of China(Nos.11974052,12074365)the National Key R&D Program of China(No.2021YFA0718700)。
文摘Electric-field control of topological magnetic states in thinfilm heterostructures is promising for applications in nextgeneration memory or logic devices with ultrahigh density and low-power consumption.Multiferroic materials,where spin and polar degrees of freedom coexist,provide a versatile playground to manipulate magnetism(converse magnetoelectric effect).Here,we report that the topological spin textures can be controlled by electric field in rhombohedral BiFeO_(3)/monoclinic La_(0.67)Sr_(0.33)MnO_(3)thin-film heterostructure at room temperature.