Using the Skyrme density functional theory,potential energy surfaces of^(240)Pu with constraints on the axial quadrupole and octupole deformations(q_(20)and q_(30))were calculated.The volume-like and surface-like pair...Using the Skyrme density functional theory,potential energy surfaces of^(240)Pu with constraints on the axial quadrupole and octupole deformations(q_(20)and q_(30))were calculated.The volume-like and surface-like pairing forces,as well as a combination of these two forces,were used for the Hartree–Fock–Bogoliubov approximation.Variations in the least-energy fission path,fission barrier,pairing energy,total kinetic energy,scission line,and mass distribution of the fission fragments based on the different forms of the pairing forces were analyzed and discussed.The fission dynamics were studied based on the timedependent generator coordinate method plus the Gaussian overlap approximation.The results demonstrated a sensitivity of the mass and charge distributions of the fission fragments on the form of the pairing force.Based on the investigation of the neutron-induced fission of^(239)Pu,among the volume,mixed,and surface pairing forces,the mixed pairing force presented a good reproduction of the experimental data.展开更多
Xiazhuang uranium ore field,located in the southern part of the Nanling Metallogenic Belt,is considered one of the largest granite-related U regions in South China.In this paper,we contribute new apatite fission track...Xiazhuang uranium ore field,located in the southern part of the Nanling Metallogenic Belt,is considered one of the largest granite-related U regions in South China.In this paper,we contribute new apatite fission track data and thermal history modeling to constrain the exhumation history and evaluate preservation potential of the Xiazhuang Uranium ore field.Nine Triassic outcrop granite samples collected from different locations of Xiazhuang Uranium ore field yield AFT ages ranging from 43 to 24 Ma with similar mean confined fission track lengths ranging from 11.8±2.0 to 12.9±1.9μm and Dpar values between 1.01 and 1.51μm.The robustness time-temperature reconstructions of samples from the hanging wall of Huangpi fault show that the Xiazhuang Uranium ore field experienced a time of monotonous and slow cooling starting from middle Paleocene to middle Miocene(~60-10 Ma),followed by relatively rapid exhumation in the late Miocene(~10-5 Ma)and nearly thermal stability in the Pliocene-Quaternary(~5-0 Ma).The amount of exhumation after U mineralization since the Middle Paleogene was estimated as~4.3±1.8 km according to the integrated thermal history model.Previous studies indicate that the ore-forming ages of U deposits in the Xiazhuang ore field are mainly before Middle Paleocene and the mineralization depths are more than 4.4±1.2 km.Therefore,the exhumation history since middle Paleocene plays important roles in the preservation of the Xiazhuang Uranium ore field.展开更多
This article explores the transformative potential of nanotechnology and MMs(memory metals)in enhancing the design and operation of nuclear reactors,encompassing both fission and fusion technologies.Nanotechnology,wit...This article explores the transformative potential of nanotechnology and MMs(memory metals)in enhancing the design and operation of nuclear reactors,encompassing both fission and fusion technologies.Nanotechnology,with its ability to engineer materials at the atomic scale,offers significant improvements in reactor safety,efficiency,and longevity.In fission reactors,nanomaterials enhance fuel rod integrity,optimize thermal management,and improve in-core instrumentation.Fusion reactors benefit from nanostructured materials that bolster containment and heat dissipation,addressing critical challenges in sustaining fusion reactions.The integration of SMAs(shape memory alloys),or MMs,further amplifies these advancements.These materials,characterized by their ability to revert to a pre-defined shape under thermal conditions,provide self-healing capabilities,adaptive structural components,and enhanced magnetic confinement.The synergy between nanotechnology and MMs represents a paradigm shift in nuclear reactor technology,promising a future of cleaner,more efficient,and safer nuclear energy production.This innovative approach positions the nuclear industry to meet the growing global energy demand while addressing environmental and safety concerns.展开更多
This article proposes to associate a Deuterium-Deuterium (D-D) fusion reactor with a PWR (fission Pressurized Water Reactor) in a hybrid reactor. Even if the mechanical gain (Q factor) of the D-D fusion reactor is bel...This article proposes to associate a Deuterium-Deuterium (D-D) fusion reactor with a PWR (fission Pressurized Water Reactor) in a hybrid reactor. Even if the mechanical gain (Q factor) of the D-D fusion reactor is below the unity and consequently consumes more energy than it supplies, due to the high energy amplification factor of the PWR fission reactor, the global yield is widely superior to 1. As the energy supplied by the fusion reactor is relatively low and as the neutrons supplied are mainly issued from D-D fusions (at 2.45 MeV), the problems of heat flux and neutrons damage connected with materials, as with D-T fusion reactors are reduced. Of course, there is no need to produce Tritium with this D-D fusion reactor. This type of reactor is able to incinerate any mixture of natural Uranium, natural Thorium and depleted Uranium (waste issued from enrichment plants), with natural Thorium being the best choice. No enriched fuel is needed. So, this type of reactor could constitute a source of energy for several thousands of years because it is about 90 more efficient than a standard fission reactor, such as a PWR or a Candu one, by extracting almost completely the energy from the fertile materials U238 and Th232. For the fission part, PWR technology is mature. For the fusion part, it is based on a reasonable hypothesis done on present Stellarators projects. The working of this reactor is continuous, 24 hours a day. In this paper, it will be targeted a reactor able to provide net electric power of about 1400 MWe, as a big fission power plant.展开更多
Neutron-induced fission is an important research object in basic science.Moreover,its product yield data are an indispensable nuclear data basis in nuclear engineering and technology.The fission yield tensor decomposi...Neutron-induced fission is an important research object in basic science.Moreover,its product yield data are an indispensable nuclear data basis in nuclear engineering and technology.The fission yield tensor decomposition(FYTD)model has been developed and used to evaluate the independent fission product yield.In general,fission yield data are verified by the direct comparison of experimental and evaluated data.However,such direct comparison cannot reflect the impact of the evaluated data on application scenarios,such as reactor transport-burnup simulation.Therefore,this study applies the evaluated fission yield data in transport-burnup simulation to verify their accuracy and possibility of application.Herein,the evaluated yield data of235U and239Pu are applied in the transport-burnup simulation of a pressurized water reactor(PWR)and sodium-cooled fast reactor(SFR)for verification.During the reactor operation stage,the errors in pin-cell reactivity caused by the evaluated fission yield do not exceed 500 and 200 pcm for the PWR and SFR,respectively.The errors in decay heat and135Xe and149Sm concentrations during the short-term shutdown of the PWR are all less than 1%;the errors in decay heat and activity of the spent fuel of the PWR and SFR during the temporary storage stage are all less than 2%.For the PWR,the errors in important nuclide concentrations in spent fuel,such as90Sr,137Cs,85Kr,and99Tc,are all less than 6%,and a larger error of 37%is observed on129I.For the SFR,the concentration errors of ten important nuclides in spent fuel are all less than 16%.A comparison of various aspects reveals that the transport-burnup simulation results using the FYTD model evaluation have little difference compared with the reference results using ENDF/B-Ⅷ.0 data.This proves that the evaluation of the FYTD model may have application value in reactor physical analysis.展开更多
Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spi...Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spinal cord injury.However,the precise mechanism remains unclear.To investigate the effect of photo biomodulation on mitochondrial fission imbalance after spinal cord injury,in this study,we treated rat models of spinal co rd injury with 60-minute photo biomodulation(810 nm,150 mW) every day for 14 consecutive days.Transmission electron microscopy results confirmed the swollen and fragmented alte rations of mitochondrial morphology in neurons in acute(1 day) and subacute(7 and 14 days) phases.Photo biomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase,reduced neuronal cell death,and improved rat posterior limb motor function in a time-dependent manner.These findings suggest that photobiomodulation targets neuronal mitochondria,alleviates mitochondrial fission imbalance-induced neuronal apoptosis,and thereby promotes the motor function recovery of rats with spinal cord injury.展开更多
Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(...Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.展开更多
Uplift and exhumation are important factors affecting the preservation of deposits.The anatomy of uplift-cooling evolution and exhumation in the East Longshou Mountain is of significant research value in understanding...Uplift and exhumation are important factors affecting the preservation of deposits.The anatomy of uplift-cooling evolution and exhumation in the East Longshou Mountain is of significant research value in understanding changes in the Jinchuan Ni-Cu-PGE deposit since its formation.This study uses apatite fission track(AFT)thermochronology to reconstruct the thermal history of the East Longshou Mountain,including the Jinchuan mine,revealing the uplift and exhumation history of the East Longshou Mountain and elucidating the preservation status of the Jinchuan deposit.The AFT ages in the East Longshou Mountain are distributed from 62.3±3.0 Ma to 214.7±14 Ma,with significant differences in ages in distinct areas,the central and pooled ages being consistent within the margin of error.Inverse thermal history models reveal two rapid cooling events associated with exhumation from the Early Jurassic to the Early Cretaceous(200–100 Ma)and since the Miocene(15–0 Ma),the former attributable to the far-afield response to the closure of the PaleoTethys Ocean and plate assembly at the southern margin of Eurasia,the latter associated with the initial India-Eurasia plate collision.A slow cooling event from the Early Cretaceous to the Miocene(100–15 Ma)is thought to be related to the arid environment in northwest China since the Cretaceous.These cooling events have diverse responses and cooling rates in different blocks of the East Longshou Mountain:the southwest and centre of which are mainly cooled over 200–120 Ma and 120–0 Ma,with cooling rates of~0.25 and~0.33°C/Ma(~1.25 and~0.33°C/Ma in the centre);the Jinchuan mine primarily cooled over 160–100 Ma,100–15 Ma and 15–0 Ma,with cooling rates of~1.33,~0.25 and~2.00°C/Ma.These differentiated coolings imply that the uplift of the East Longshou Mountain before the Miocene(~15 Ma)was integral.Strong uplift then occurred in the vicinity of the mining area,which is a critical period for the uplift of the Jinchuan deposit to the surface,meaning that the Jinchuan deposit was exposed no earlier than the Miocene(~15 Ma).Based on mineralization depth information obtained by previous researchers,in conjunction with the calculation and simulation results of this study,it can be seen that the bulk of the Jinchuan intrusion may still be preserved at depth.展开更多
目的:研究线粒体分裂抑制剂1(Mdivi-1)在实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘保护中的作用,探讨Mdivi-1抑制髓鞘变性的机制。方法:小鼠经髓磷脂少突胶质细胞糖蛋白第35~55位肽段(MOG35-55)免疫后,随机分为DMSO模型组和Mdivi-1干预组...目的:研究线粒体分裂抑制剂1(Mdivi-1)在实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘保护中的作用,探讨Mdivi-1抑制髓鞘变性的机制。方法:小鼠经髓磷脂少突胶质细胞糖蛋白第35~55位肽段(MOG35-55)免疫后,随机分为DMSO模型组和Mdivi-1干预组。于免疫后第28天处死小鼠,行Luxol fast blue染色分析髓鞘丢失情况,免疫荧光染色和TUNEL染色小鼠脊髓组织和体外细胞实验分析Mdivi-1髓鞘保护机制。结果:与DMSO模型组比较,Mdivi-1处理明显减少EAE小鼠脊髓组织白质区髓鞘丢失,减少少突胶质细胞凋亡及线粒体凋亡相关蛋白cleaved caspase-3、caspase-9、cytochrome C和Bax的表达;体外MO3.13少突胶质细胞培养实验发现,Mdivi-1可以明显阻止星形孢菌素(staurosporine)处理诱导的线粒体膜电位去极化,减轻细胞损伤,增强细胞活力。结论:Mdivi-1可能通过抑制少突胶质细胞线粒体相关凋亡信号通路发挥髓鞘保护作用。展开更多
线粒体是细胞内能量代谢的中心,对于维持细胞稳态而言,其形态和功能的调控至关重要。小分子泛素相关修饰物蛋白(small ubiquitin-related modifier protein,SUMO)修饰和发动蛋白相关蛋白1(dynamin-related protein 1,DRP1)在细胞调控中...线粒体是细胞内能量代谢的中心,对于维持细胞稳态而言,其形态和功能的调控至关重要。小分子泛素相关修饰物蛋白(small ubiquitin-related modifier protein,SUMO)修饰和发动蛋白相关蛋白1(dynamin-related protein 1,DRP1)在细胞调控中扮演着重要角色,尤其与线粒体动力学密切相关。SUMO修饰是一种重要的蛋白质修饰形式,通过将靶蛋白与SUMO相连来调节这些蛋白质的功能。而DRP1是线粒体分裂蛋白,负责调节线粒体的形态和功能。近年来研究发现,SUMO修饰与DRP1之间存在复杂的相互作用网络,对于线粒体的分裂、融合、自噬等起着重要作用。在DRP1的可变结构域中,有8个赖氨酸残基可以在线粒体锚定蛋白连接酶(mitochondrial-anchored protein ligase,MAPL)的作用下完成SUMO修饰。并且不同亚型的SUMO蛋白对于DRP1功能的调节也不同。SUMO1修饰会使DRP1向线粒体富集,促进线粒体的分裂;SUMO2/3修饰会使DRP1向细胞质转移,减少线粒体的分裂。在实际的细胞程序中,不同亚型SUMO的修饰水平往往是由SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)的类型决定。线粒体作为细胞中重要的能量供应细胞器,其动力学的异常往往会导致诸多疾病的发生,例如:心肌缺血再灌注性损伤、阿尔茨海默病、脑血栓、视网膜病变等。本文综述了SUMO修饰与DRP1之间相互作用对于线粒体动力学调控的研究进展,为进一步揭示细胞调控机制和发展相关疾病的治疗策略提供一定的参考。展开更多
基金supported by the National Key R&D Program of China(No.2022YFA1602000)National Natural Science Foundation of China(Nos.12275081,U2067205,11790325,and U1732138)the Continuous-support Basic Scientific Research Project。
文摘Using the Skyrme density functional theory,potential energy surfaces of^(240)Pu with constraints on the axial quadrupole and octupole deformations(q_(20)and q_(30))were calculated.The volume-like and surface-like pairing forces,as well as a combination of these two forces,were used for the Hartree–Fock–Bogoliubov approximation.Variations in the least-energy fission path,fission barrier,pairing energy,total kinetic energy,scission line,and mass distribution of the fission fragments based on the different forms of the pairing forces were analyzed and discussed.The fission dynamics were studied based on the timedependent generator coordinate method plus the Gaussian overlap approximation.The results demonstrated a sensitivity of the mass and charge distributions of the fission fragments on the form of the pairing force.Based on the investigation of the neutron-induced fission of^(239)Pu,among the volume,mixed,and surface pairing forces,the mixed pairing force presented a good reproduction of the experimental data.
基金the Foundation of State Key Laboratory of Nuclear Resources and Environment(Grant Nos.NRE2021-01,2022NRE34)the National Natural Science Foundation of China(Grant No.42162013)+1 种基金the Third Xinjiang Scientific Expedition Program(Grant No.2022xjkk1301)the Fund of National Key Laboratory of Science and Technology on Remote Sensing Information and imagery Analysis,Beijing Research Institute of Uranium Geology(Grant No.6142A01210405).
文摘Xiazhuang uranium ore field,located in the southern part of the Nanling Metallogenic Belt,is considered one of the largest granite-related U regions in South China.In this paper,we contribute new apatite fission track data and thermal history modeling to constrain the exhumation history and evaluate preservation potential of the Xiazhuang Uranium ore field.Nine Triassic outcrop granite samples collected from different locations of Xiazhuang Uranium ore field yield AFT ages ranging from 43 to 24 Ma with similar mean confined fission track lengths ranging from 11.8±2.0 to 12.9±1.9μm and Dpar values between 1.01 and 1.51μm.The robustness time-temperature reconstructions of samples from the hanging wall of Huangpi fault show that the Xiazhuang Uranium ore field experienced a time of monotonous and slow cooling starting from middle Paleocene to middle Miocene(~60-10 Ma),followed by relatively rapid exhumation in the late Miocene(~10-5 Ma)and nearly thermal stability in the Pliocene-Quaternary(~5-0 Ma).The amount of exhumation after U mineralization since the Middle Paleogene was estimated as~4.3±1.8 km according to the integrated thermal history model.Previous studies indicate that the ore-forming ages of U deposits in the Xiazhuang ore field are mainly before Middle Paleocene and the mineralization depths are more than 4.4±1.2 km.Therefore,the exhumation history since middle Paleocene plays important roles in the preservation of the Xiazhuang Uranium ore field.
文摘This article explores the transformative potential of nanotechnology and MMs(memory metals)in enhancing the design and operation of nuclear reactors,encompassing both fission and fusion technologies.Nanotechnology,with its ability to engineer materials at the atomic scale,offers significant improvements in reactor safety,efficiency,and longevity.In fission reactors,nanomaterials enhance fuel rod integrity,optimize thermal management,and improve in-core instrumentation.Fusion reactors benefit from nanostructured materials that bolster containment and heat dissipation,addressing critical challenges in sustaining fusion reactions.The integration of SMAs(shape memory alloys),or MMs,further amplifies these advancements.These materials,characterized by their ability to revert to a pre-defined shape under thermal conditions,provide self-healing capabilities,adaptive structural components,and enhanced magnetic confinement.The synergy between nanotechnology and MMs represents a paradigm shift in nuclear reactor technology,promising a future of cleaner,more efficient,and safer nuclear energy production.This innovative approach positions the nuclear industry to meet the growing global energy demand while addressing environmental and safety concerns.
文摘This article proposes to associate a Deuterium-Deuterium (D-D) fusion reactor with a PWR (fission Pressurized Water Reactor) in a hybrid reactor. Even if the mechanical gain (Q factor) of the D-D fusion reactor is below the unity and consequently consumes more energy than it supplies, due to the high energy amplification factor of the PWR fission reactor, the global yield is widely superior to 1. As the energy supplied by the fusion reactor is relatively low and as the neutrons supplied are mainly issued from D-D fusions (at 2.45 MeV), the problems of heat flux and neutrons damage connected with materials, as with D-T fusion reactors are reduced. Of course, there is no need to produce Tritium with this D-D fusion reactor. This type of reactor is able to incinerate any mixture of natural Uranium, natural Thorium and depleted Uranium (waste issued from enrichment plants), with natural Thorium being the best choice. No enriched fuel is needed. So, this type of reactor could constitute a source of energy for several thousands of years because it is about 90 more efficient than a standard fission reactor, such as a PWR or a Candu one, by extracting almost completely the energy from the fertile materials U238 and Th232. For the fission part, PWR technology is mature. For the fusion part, it is based on a reasonable hypothesis done on present Stellarators projects. The working of this reactor is continuous, 24 hours a day. In this paper, it will be targeted a reactor able to provide net electric power of about 1400 MWe, as a big fission power plant.
基金the National Natural Science Foundation of China(Nos.11875328,12075327 and 12105170)the Key Laboratory of Nuclear Data foundation(No.JCKY2022201C157)+1 种基金the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.22lgqb39)the Open Project of Guangxi Key Laboratory of Nuclear Physics and Nuclear Technology(No.NLK2020-02).
文摘Neutron-induced fission is an important research object in basic science.Moreover,its product yield data are an indispensable nuclear data basis in nuclear engineering and technology.The fission yield tensor decomposition(FYTD)model has been developed and used to evaluate the independent fission product yield.In general,fission yield data are verified by the direct comparison of experimental and evaluated data.However,such direct comparison cannot reflect the impact of the evaluated data on application scenarios,such as reactor transport-burnup simulation.Therefore,this study applies the evaluated fission yield data in transport-burnup simulation to verify their accuracy and possibility of application.Herein,the evaluated yield data of235U and239Pu are applied in the transport-burnup simulation of a pressurized water reactor(PWR)and sodium-cooled fast reactor(SFR)for verification.During the reactor operation stage,the errors in pin-cell reactivity caused by the evaluated fission yield do not exceed 500 and 200 pcm for the PWR and SFR,respectively.The errors in decay heat and135Xe and149Sm concentrations during the short-term shutdown of the PWR are all less than 1%;the errors in decay heat and activity of the spent fuel of the PWR and SFR during the temporary storage stage are all less than 2%.For the PWR,the errors in important nuclide concentrations in spent fuel,such as90Sr,137Cs,85Kr,and99Tc,are all less than 6%,and a larger error of 37%is observed on129I.For the SFR,the concentration errors of ten important nuclides in spent fuel are all less than 16%.A comparison of various aspects reveals that the transport-burnup simulation results using the FYTD model evaluation have little difference compared with the reference results using ENDF/B-Ⅷ.0 data.This proves that the evaluation of the FYTD model may have application value in reactor physical analysis.
基金supported by the National Natural Science Foundation of China,Nos.81070996 (to ZW) and 815 72151 (to XYH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05 (to ZW),2021ZDLSF02-10 (to XYH)。
文摘Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spinal cord injury.However,the precise mechanism remains unclear.To investigate the effect of photo biomodulation on mitochondrial fission imbalance after spinal cord injury,in this study,we treated rat models of spinal co rd injury with 60-minute photo biomodulation(810 nm,150 mW) every day for 14 consecutive days.Transmission electron microscopy results confirmed the swollen and fragmented alte rations of mitochondrial morphology in neurons in acute(1 day) and subacute(7 and 14 days) phases.Photo biomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase,reduced neuronal cell death,and improved rat posterior limb motor function in a time-dependent manner.These findings suggest that photobiomodulation targets neuronal mitochondria,alleviates mitochondrial fission imbalance-induced neuronal apoptosis,and thereby promotes the motor function recovery of rats with spinal cord injury.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82103208,and 82002948)the Guangdong Basic and Applied Basic Research Foundation(Grant Nos.:2022A1515220212,and 2023A1515030115)+1 种基金National Key R&D Program of China(Grant No.:2020YFE0202200)Jinan University National College Students'Innovation and Entrepreneurship Training Program(Program No.:202110559085).
文摘Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.
基金jointly funded by the National Natural Science Foundation Project(Grant No.92162213)The Fundamental Research Funds for the Central Universities,CHD(Grant No.300102272205)。
文摘Uplift and exhumation are important factors affecting the preservation of deposits.The anatomy of uplift-cooling evolution and exhumation in the East Longshou Mountain is of significant research value in understanding changes in the Jinchuan Ni-Cu-PGE deposit since its formation.This study uses apatite fission track(AFT)thermochronology to reconstruct the thermal history of the East Longshou Mountain,including the Jinchuan mine,revealing the uplift and exhumation history of the East Longshou Mountain and elucidating the preservation status of the Jinchuan deposit.The AFT ages in the East Longshou Mountain are distributed from 62.3±3.0 Ma to 214.7±14 Ma,with significant differences in ages in distinct areas,the central and pooled ages being consistent within the margin of error.Inverse thermal history models reveal two rapid cooling events associated with exhumation from the Early Jurassic to the Early Cretaceous(200–100 Ma)and since the Miocene(15–0 Ma),the former attributable to the far-afield response to the closure of the PaleoTethys Ocean and plate assembly at the southern margin of Eurasia,the latter associated with the initial India-Eurasia plate collision.A slow cooling event from the Early Cretaceous to the Miocene(100–15 Ma)is thought to be related to the arid environment in northwest China since the Cretaceous.These cooling events have diverse responses and cooling rates in different blocks of the East Longshou Mountain:the southwest and centre of which are mainly cooled over 200–120 Ma and 120–0 Ma,with cooling rates of~0.25 and~0.33°C/Ma(~1.25 and~0.33°C/Ma in the centre);the Jinchuan mine primarily cooled over 160–100 Ma,100–15 Ma and 15–0 Ma,with cooling rates of~1.33,~0.25 and~2.00°C/Ma.These differentiated coolings imply that the uplift of the East Longshou Mountain before the Miocene(~15 Ma)was integral.Strong uplift then occurred in the vicinity of the mining area,which is a critical period for the uplift of the Jinchuan deposit to the surface,meaning that the Jinchuan deposit was exposed no earlier than the Miocene(~15 Ma).Based on mineralization depth information obtained by previous researchers,in conjunction with the calculation and simulation results of this study,it can be seen that the bulk of the Jinchuan intrusion may still be preserved at depth.
文摘目的:研究线粒体分裂抑制剂1(Mdivi-1)在实验性自身免疫性脑脊髓炎(EAE)小鼠髓鞘保护中的作用,探讨Mdivi-1抑制髓鞘变性的机制。方法:小鼠经髓磷脂少突胶质细胞糖蛋白第35~55位肽段(MOG35-55)免疫后,随机分为DMSO模型组和Mdivi-1干预组。于免疫后第28天处死小鼠,行Luxol fast blue染色分析髓鞘丢失情况,免疫荧光染色和TUNEL染色小鼠脊髓组织和体外细胞实验分析Mdivi-1髓鞘保护机制。结果:与DMSO模型组比较,Mdivi-1处理明显减少EAE小鼠脊髓组织白质区髓鞘丢失,减少少突胶质细胞凋亡及线粒体凋亡相关蛋白cleaved caspase-3、caspase-9、cytochrome C和Bax的表达;体外MO3.13少突胶质细胞培养实验发现,Mdivi-1可以明显阻止星形孢菌素(staurosporine)处理诱导的线粒体膜电位去极化,减轻细胞损伤,增强细胞活力。结论:Mdivi-1可能通过抑制少突胶质细胞线粒体相关凋亡信号通路发挥髓鞘保护作用。
文摘线粒体是细胞内能量代谢的中心,对于维持细胞稳态而言,其形态和功能的调控至关重要。小分子泛素相关修饰物蛋白(small ubiquitin-related modifier protein,SUMO)修饰和发动蛋白相关蛋白1(dynamin-related protein 1,DRP1)在细胞调控中扮演着重要角色,尤其与线粒体动力学密切相关。SUMO修饰是一种重要的蛋白质修饰形式,通过将靶蛋白与SUMO相连来调节这些蛋白质的功能。而DRP1是线粒体分裂蛋白,负责调节线粒体的形态和功能。近年来研究发现,SUMO修饰与DRP1之间存在复杂的相互作用网络,对于线粒体的分裂、融合、自噬等起着重要作用。在DRP1的可变结构域中,有8个赖氨酸残基可以在线粒体锚定蛋白连接酶(mitochondrial-anchored protein ligase,MAPL)的作用下完成SUMO修饰。并且不同亚型的SUMO蛋白对于DRP1功能的调节也不同。SUMO1修饰会使DRP1向线粒体富集,促进线粒体的分裂;SUMO2/3修饰会使DRP1向细胞质转移,减少线粒体的分裂。在实际的细胞程序中,不同亚型SUMO的修饰水平往往是由SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)的类型决定。线粒体作为细胞中重要的能量供应细胞器,其动力学的异常往往会导致诸多疾病的发生,例如:心肌缺血再灌注性损伤、阿尔茨海默病、脑血栓、视网膜病变等。本文综述了SUMO修饰与DRP1之间相互作用对于线粒体动力学调控的研究进展,为进一步揭示细胞调控机制和发展相关疾病的治疗策略提供一定的参考。