Laser Schlieren device was established to observe Rayleigh-Bénard-Marangoni effect produced in thick liquid depth by the diffusion of binary liquid mixtures.A recorder and a camera separately recorded dynamic and...Laser Schlieren device was established to observe Rayleigh-Bénard-Marangoni effect produced in thick liquid depth by the diffusion of binary liquid mixtures.A recorder and a camera separately recorded dynamic and static convective flow patterns during experiment.According to different signs of Ma number and Ra number,different binary liquid mixtures were selected to investigate the RBM effect induced by different driven mechanism including density gradient or surface tension gradient or combination of both.Qualitative analysis to experiment results was presented.展开更多
By utilizing optical Schlieren method, the Rayleigh Bénard Marangoni convection in mass transfer process was observed. A recorder and a camera separately recorded dynamic and static convective flow patterns dur...By utilizing optical Schlieren method, the Rayleigh Bénard Marangoni convection in mass transfer process was observed. A recorder and a camera separately recorded dynamic and static convective flow patterns during experiments . Different organic solvents were selected to investigate the RBM effects induced by different driving mechanisms including density gradient, surface tension gradient and their combination. Thermal effects produced by solvents evaporation and solute absorption/desorption are thought as an important factor in the creation of RBM convection during the mass transfer process. Qualitative analysis of experimental results is presented on the basis of photos and videotapes that were taken as direct visual evidences. Experimental results show that the thermal effect accompanying the mass transfer can be a cause at the onset of RBM convection and can′t be neglected simply in study of RBM effect driven by mass transfer.展开更多
Marangoni Benard convection, which is mainly driven by the thermocapillary （Marangoni） effect, occurs in a thin liquid layer heated uniformly from the bottom. The wavenumber of supercritical convection is studied ex...Marangoni Benard convection, which is mainly driven by the thermocapillary （Marangoni） effect, occurs in a thin liquid layer heated uniformly from the bottom. The wavenumber of supercritical convection is studied experimentally in a 160×160-mm^2 cavity that ＆ heated from the bottom block. The convection pattern ＆ visualized by an infrared thermography camera. It is shown that the onset of the Benard cell is consistent with theoretical analysis. The wavenumber decreases obviously with increasing temperature, except for a slight increase near the onset. The wavenumber gradually approaches the minimum when the supercritical number e is larger than 10. Finally, a formula is devised to describe the wavenumber selection in supercritical convection.展开更多
背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄...背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄芩苷及雷公藤甲素等中药单体治疗脊髓损伤后神经炎症的研究进展进行系统的阐述与归纳。方法:以“脊髓损伤,炎症,抗炎,中药单体,单体化合物,NF-κB信号通路,黄酮,糖苷,酚类,酯类,生物碱”为检索词在中国知网数据库中进行检索;以“Spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids”为检索词在PubMed数据库中进行检索,最终共纳入67篇文献进行综述分析。结果与结论:①核转录因子κB信号通路在神经系统中的作用复杂多样,能够调控中性粒细胞、小胶质细胞、星形胶质细胞和巨噬细胞等,介导损伤后炎症的发生与发展;②中药单体如汉黄芩苷对核转录因子κB抑制蛋白的降解、红花黄素对核转录因子κB信号通路磷酸化过程的抑制、山奈酚对核转录因子κB信号通路p65核易位的抑制等作用可以降低炎症反应对机体造成的影响,从而促进神经功能恢复;③核转录因子κB信号通路在损伤早期能够促进炎症反应和免疫细胞迁移活化,在损伤中后期能够促进损伤部位的修复和纤维化的发生等,适当的激活核转录因子κB信号通路具有促进炎症因子的释放、提高细胞的抗氧化能力及促进免疫细胞的活化等能力,但过度激活的核转录因子κB信号通路则容易导致慢性炎症的发生和持续、细胞凋亡受到抑制等;④未来的研究可以进一步探索如何准确调控核转录因子κB信号通路的活化水平、如何实现对神经系统炎症和损伤的精准干预展开,也可围绕中药单体的制备及中药单体对信号通路的作用机制展开,以期为神经系统疾病的康复和功能恢复提供更有效的治疗策略。展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which mi...Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.展开更多
文摘Laser Schlieren device was established to observe Rayleigh-Bénard-Marangoni effect produced in thick liquid depth by the diffusion of binary liquid mixtures.A recorder and a camera separately recorded dynamic and static convective flow patterns during experiment.According to different signs of Ma number and Ra number,different binary liquid mixtures were selected to investigate the RBM effect induced by different driven mechanism including density gradient or surface tension gradient or combination of both.Qualitative analysis to experiment results was presented.
文摘By utilizing optical Schlieren method, the Rayleigh Bénard Marangoni convection in mass transfer process was observed. A recorder and a camera separately recorded dynamic and static convective flow patterns during experiments . Different organic solvents were selected to investigate the RBM effects induced by different driving mechanisms including density gradient, surface tension gradient and their combination. Thermal effects produced by solvents evaporation and solute absorption/desorption are thought as an important factor in the creation of RBM convection during the mass transfer process. Qualitative analysis of experimental results is presented on the basis of photos and videotapes that were taken as direct visual evidences. Experimental results show that the thermal effect accompanying the mass transfer can be a cause at the onset of RBM convection and can′t be neglected simply in study of RBM effect driven by mass transfer.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11502271 and 11372328the Strategic Priority Research Program on Space Science of the Chinese Academy of Sciences under Grant Nos XDA04020405 and XDA04020202-05the China Manned Space Engineering Program
文摘Marangoni Benard convection, which is mainly driven by the thermocapillary （Marangoni） effect, occurs in a thin liquid layer heated uniformly from the bottom. The wavenumber of supercritical convection is studied experimentally in a 160×160-mm^2 cavity that ＆ heated from the bottom block. The convection pattern ＆ visualized by an infrared thermography camera. It is shown that the onset of the Benard cell is consistent with theoretical analysis. The wavenumber decreases obviously with increasing temperature, except for a slight increase near the onset. The wavenumber gradually approaches the minimum when the supercritical number e is larger than 10. Finally, a formula is devised to describe the wavenumber selection in supercritical convection.
文摘背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄芩苷及雷公藤甲素等中药单体治疗脊髓损伤后神经炎症的研究进展进行系统的阐述与归纳。方法:以“脊髓损伤,炎症,抗炎,中药单体,单体化合物,NF-κB信号通路,黄酮,糖苷,酚类,酯类,生物碱”为检索词在中国知网数据库中进行检索;以“Spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids”为检索词在PubMed数据库中进行检索,最终共纳入67篇文献进行综述分析。结果与结论:①核转录因子κB信号通路在神经系统中的作用复杂多样,能够调控中性粒细胞、小胶质细胞、星形胶质细胞和巨噬细胞等,介导损伤后炎症的发生与发展;②中药单体如汉黄芩苷对核转录因子κB抑制蛋白的降解、红花黄素对核转录因子κB信号通路磷酸化过程的抑制、山奈酚对核转录因子κB信号通路p65核易位的抑制等作用可以降低炎症反应对机体造成的影响,从而促进神经功能恢复;③核转录因子κB信号通路在损伤早期能够促进炎症反应和免疫细胞迁移活化,在损伤中后期能够促进损伤部位的修复和纤维化的发生等,适当的激活核转录因子κB信号通路具有促进炎症因子的释放、提高细胞的抗氧化能力及促进免疫细胞的活化等能力,但过度激活的核转录因子κB信号通路则容易导致慢性炎症的发生和持续、细胞凋亡受到抑制等;④未来的研究可以进一步探索如何准确调控核转录因子κB信号通路的活化水平、如何实现对神经系统炎症和损伤的精准干预展开,也可围绕中药单体的制备及中药单体对信号通路的作用机制展开,以期为神经系统疾病的康复和功能恢复提供更有效的治疗策略。
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by grants from the National Key Research and Development Program of China,No.2017YFA0105400(to LR)the Key Research and Development Program of Guangdong Province,No.2019B020236002(to LR)the National Natural Science Foundation of China,Nos.81972111(to LZ),81772349(to BL).
文摘Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.
