Four embryonic stem (ES) cell lines, designated CE1, CE2, CE3 and CE4, were isolated from C57BL/6J blastocysts. The ratio of normal diploid composition of these cell lines is above 70%. To examine the differentiation...Four embryonic stem (ES) cell lines, designated CE1, CE2, CE3 and CE4, were isolated from C57BL/6J blastocysts. The ratio of normal diploid composition of these cell lines is above 70%. To examine the differentiation potential of the ES cells, the CE2 cells were injected subcutaneously into syngenic mice, and many kinds of differentiated cells were observed on the sections of the teratoma derived from this ES cell line. On the other hand, to test the chimeric ability of the ES cells, the CE2 cells were microinjected into the blastocysts of ICR mice, and a chimera was obtained among living pups. These results show that CE2 ES cells are pluripotent stem cells, which can differentiate into many kinds of cell types, and can be used as a cell system for further research.展开更多
Three-dimensional unsteady Navier-Stokes equations are numerically solved to simulate the aerodynamic interaction of rotor, canard and horizontal tail in hover based on moving chimera grid. The variations of unsteady ...Three-dimensional unsteady Navier-Stokes equations are numerically solved to simulate the aerodynamic interaction of rotor, canard and horizontal tail in hover based on moving chimera grid. The variations of unsteady aerodynamic forces and moments of the canard and horizontal tail with respect to the rotor azimuth are analyzed with the deflection angle set at 0° and 50°, respectively. The pressure map of aerodynamic surfaces and velocity vector distribution of flow field are investigated to get better understanding of the unsteady aerodynamic interaction. The result shows that the canard and horizontal tail present different characteristics under the downwash of the rotor. The canard produces much vertical force loss with low amplitude fluctuation. Contrarily, the horizontal tail, which is within the flow field induced by the down wash of the rotor, produces only less vertical force loss, but the amplitudes of the lift and pitching moment are larger, implying that a potential deflection angle scheme in hover is 50° for the canard and 0° for the horizontal tail.展开更多
Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of va...Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.展开更多
In mice,gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics.This strategy allows precise location of the site of transgene integration and is most...In mice,gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics.This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression("knock-out"),or to introduce mutant or modified alleles at the locus of interest("knock-in").The efficacy of producing live,transgenic mice challenges our understanding of this complex process,and of the factors which influence germline competence of embryonic stem cell lines.Increasingly,evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell(ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability.Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential.There are a number of options for generating chimeras from ES cells (ES chimera mice);however,each method has its advantages and disadvantages.Recent developments in induced pluripotent stem(iPS)cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies.The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines.The most recent methods for generating specifically ES and iPS chimera mice,including the advantages and disadvantages of each method are also discussed.展开更多
Dynamics of a one-dimensional array of non-locally coupled Kuramoto phase oscillators with an external potential is studied. A four-cluster chimera state is observed for the moderate strength of the external potential...Dynamics of a one-dimensional array of non-locally coupled Kuramoto phase oscillators with an external potential is studied. A four-cluster chimera state is observed for the moderate strength of the external potential. Different from the clustered chimera states studied before, the instantaneous frequencies of the oscillators in a synchronized cluster are different in the presence of the external potential. As the strength of the external potential increases, a bifurcation from the two-cluster chimera state to the four-cluster chimera states can be found. These phenomena are well predicted analytically with the help of the Ott-Antonsen ansatz.展开更多
Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediate...Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediated Autophagy Targeting Chimeras(CMATAC)peptide to knockdown endogenous ERαprotein through chaperone-mediated autophagy.The peptide contains a cell membrane-penetrating peptide(TAT)that allows the peptide to by-pass the plasma membrane,anαI peptide as a protein-binding peptide(PBD)that binds specifically to ERα,and CMA-targeting peptide(CTM)that targeting chaperone-mediated autophagy.We validated that ERαtargeting peptide was able to target and degrade ERαto reduce the viability of ERαpositive breast cancer cells.Taken together,our studies provided a new method to reduce the level of intracellular ERαprotein via CMATAC,and thus may provide a new strategy for the treatment of ERαpositive breast cancer.展开更多
A fractional-order difference equation model of a third-order discrete phase-locked loop(FODPLL) is discussed and the dynamical behavior of the model is demonstrated using bifurcation plots and a basin of attraction. ...A fractional-order difference equation model of a third-order discrete phase-locked loop(FODPLL) is discussed and the dynamical behavior of the model is demonstrated using bifurcation plots and a basin of attraction. We show a narrow region of loop gain where the FODPLL exhibits quasi-periodic oscillations, which were not identified in the integer-order model. We propose a simple impulse control algorithm to suppress chaos and discuss the effect of the control step. A network of FODPLL oscillators is constructed and investigated for synchronization behavior. We show the existence of chimera states while transiting from an asynchronous to a synchronous state. The same impulse control method is applied to a lattice array of FODPLL, and the chimera states are then synchronized using the impulse control algorithm. We show that the lower control steps can achieve better control over the higher control steps.展开更多
The economic and financial systems consist of many nonlinear factors that make them behave as the complex systems.Recently many chaotic finance systems have been proposed to study the complex dynamics of finance as a ...The economic and financial systems consist of many nonlinear factors that make them behave as the complex systems.Recently many chaotic finance systems have been proposed to study the complex dynamics of finance as a noticeable problem in economics.In fact,the intricate structure between financial institutions can be obtained by using a network of financial systems.Therefore,in this paper,we consider a ring network of coupled symmetric chaotic finance systems,and investigate its behavior by varying the coupling parameters.The results show that the coupling strength and range have significant effects on the behavior of the coupled systems,and various patterns such as the chimera and multi-chimera states are observed.Furthermore,changing the parameters'values,remarkably influences on the oscillators attractors.When several synchronous clusters are formed,the attractors of the synchronized oscillators are symmetric,but different from the single oscillator attractor.展开更多
The rat chimera is an important animal model for the study of complex human diseases. In the present study we evaluated the chimeric potential of rat inner cell masses （ICMs） and fetal neural stem （FNS） cells. In ...The rat chimera is an important animal model for the study of complex human diseases. In the present study we evaluated the chimeric potential of rat inner cell masses （ICMs） and fetal neural stem （FNS） cells. In result, three rat chimeras were produced by day 5 （D5） Sprague-Dawley （SD） blastocysts injected with ICMs derived from day 6 （D6） and D5 Dark Agouti （DA） blastocysts; four rat chimeras had been generated by D5 DA blastocyst injected with D5 SD ICMs. For the requirement of gene modification, cultured rat inner cell mass cells were assessed to produce chimeras, but no chimeras were generated from injected embryos. The potential to generate chimeras from rFNS and transfected rFNS cells were tested, but no chimeric pups were produced. Only 2 of 41 fetuses derived from D5 DA blastocyst injection with SD LacZ transfected rFNS cells showed very low number of LacZ positive cells in the section. These results indicate that DA and SD rat ICMs arc able to contribute to chimeras, but their potential decreases significantly after culture in vitro （P〈0.05）, and rFNS cells only have the potential to contribute to early fetal development.展开更多
Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting ...Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases.展开更多
Aim: To establish techniques for producing somatic and germline chimeric chicken by transferring blastodermal cellsfused with electroporation. Methods: Stage-X blastodermal cells isolated from freshly laid fertile uni...Aim: To establish techniques for producing somatic and germline chimeric chicken by transferring blastodermal cellsfused with electroporation. Methods: Stage-X blastodermal cells isolated from freshly laid fertile unincubated whiteLeghorn and Rhode Island red chicken eggs were fused with electroporation. The treated cell suspension was transferredto the recovery medium (DMEM containing 10% FBS) and was injected into the subgenninal cavity of recipient unin-cubated embryos (stage X). Results: Of 177 recipient embryos injected with the fusing blastodermal cells, 6(3.4 %) survived to hatching. Somatic chimerism was examined in the melanocyte of the feather. The presence offeathers originating from the donor cell was observed in 1 bird (16.7%) out of the 6 hatched birds. After 21 days ofincubation two birds out of five embryos were subjected to polymerase chain reaction (PCR) analysis for W-chromo-some-specific DNA for each tissue. One bird possessed W-chromosome-specific DNA in the stomach, and the other ex-hibited the same DNA in the left and right gonads and other tissues, but not the stomach. Conclusion: Recipientembryo having electrofused blastodennal cells yields somatic and germline chimeric chickens more successfully.(Asian J Androl 2000 Dec; 2: 271-275)展开更多
A high-order upwind scheme has been developed to capture the vortex wake of a helicopter rotor in the hover based on chimera grids. In this paper, an improved fifth-order weighted essentially non-oscillatory （WENO） ...A high-order upwind scheme has been developed to capture the vortex wake of a helicopter rotor in the hover based on chimera grids. In this paper, an improved fifth-order weighted essentially non-oscillatory （WENO） scheme is adopted to interpolate the higher-order left and right states across a cell interface with the Roe Riemann solver updating inviscid flux, and is compared with the monotone upwind scheme for scalar conservation laws （MUSCL）. For profitably capturing the wake and enforcing the period boundary condition, the computation regions of flows are discretized by using the struc- tured chimera grids composed of a fine rotor grid and a cylindrical background grid. In the background grid, the mesh cells located in the wake regions are refined after the so- lution reaches the approximate convergence. Considering the interpolation characteristic of the WENO scheme, three layers of the hole boundary and the interpolation boundary are searched. The performance of the schemes is investigated in a transonic flow and a subsonic flow around the hovering rotor. The results reveal that the present approach has great capabilities in capturing the vortex wake with high resolution, and the WENO scheme has much lower numerical dissipation in comparison with the MUSCL scheme.展开更多
Chimera state is a peculiar spatiotemporal pattern,wherein the coherence and incoherence coexist in the network of coupled identical oscillators.In this paper,we study the chimera states in a network of impact oscilla...Chimera state is a peculiar spatiotemporal pattern,wherein the coherence and incoherence coexist in the network of coupled identical oscillators.In this paper,we study the chimera states in a network of impact oscillators with nonlocal coupling.We investigate the effects of the coupling strength and the coupling range on the network behavior.The results reveal the emergence of the chimera state for significantly small values of coupling strength,and higher coupling strength values lead to unbounded motions in the oscillators.We also study the network in the case of excitation failure.We observe that the coupling helps in the maintenance of an oscillatory motion with a lower amplitude in the failed oscillator.展开更多
Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimer...Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo.In chimeric brains,human neural and immune cells can maintain human-specific features,undergo maturation,and functionally integrate into host brains,allowing scientists to study how human cells impact neural circuits and animal behaviors.The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease,elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels,and testing the efficacy of cell therapy interventions.Here,we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders,including disease modeling and cell therapy.展开更多
Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr...Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.展开更多
文摘Four embryonic stem (ES) cell lines, designated CE1, CE2, CE3 and CE4, were isolated from C57BL/6J blastocysts. The ratio of normal diploid composition of these cell lines is above 70%. To examine the differentiation potential of the ES cells, the CE2 cells were injected subcutaneously into syngenic mice, and many kinds of differentiated cells were observed on the sections of the teratoma derived from this ES cell line. On the other hand, to test the chimeric ability of the ES cells, the CE2 cells were microinjected into the blastocysts of ICR mice, and a chimera was obtained among living pups. These results show that CE2 ES cells are pluripotent stem cells, which can differentiate into many kinds of cell types, and can be used as a cell system for further research.
文摘Three-dimensional unsteady Navier-Stokes equations are numerically solved to simulate the aerodynamic interaction of rotor, canard and horizontal tail in hover based on moving chimera grid. The variations of unsteady aerodynamic forces and moments of the canard and horizontal tail with respect to the rotor azimuth are analyzed with the deflection angle set at 0° and 50°, respectively. The pressure map of aerodynamic surfaces and velocity vector distribution of flow field are investigated to get better understanding of the unsteady aerodynamic interaction. The result shows that the canard and horizontal tail present different characteristics under the downwash of the rotor. The canard produces much vertical force loss with low amplitude fluctuation. Contrarily, the horizontal tail, which is within the flow field induced by the down wash of the rotor, produces only less vertical force loss, but the amplitudes of the lift and pitching moment are larger, implying that a potential deflection angle scheme in hover is 50° for the canard and 0° for the horizontal tail.
基金financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030503)National Key Research and Development Program of China(2017YFA0105103)+5 种基金Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104004)Science and Technology Planning Project of Guangdong Province,China(2014A030312001,2017B020231001,2017A050501059,2017B030314056)Science and Technology Program of Guangzhou,China(201704030034)Research Unit of Generation of Large Animal Disease Models,Chinese Academy of Medical Sciences(2019-I2M-5-025)the Science and Technology Planning Project of Jiangmen(2017TD02)the Young People Fund of Wuyi University(2019TD05)。
文摘Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.
基金Supported by Grants from EU FP6("MEDRAT"-LSHG-CT-2005-518240"Artemis",LSHM-CT-2006-037862+5 种基金"AGLAEA",LSHM-CT-2006-037554,"CLONET",MRTN-CT-2006-035468),EU FP7("PartnErS",PIAP-GA-2008-218205"InduHeart",EUFP7-PEOPL E-IRG-2008-234390"InduStem",PIAP-GA-2008-230675"Plurisys",HEALTH-F4-2009-223485)NKFP_07_1-ES2HEART-HU,No.OM-00202-2007 NKTH/ANRTET Franco-Hungarian Bilateral Scientific and Technological Collaborative Project"Plurabit"
文摘In mice,gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics.This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression("knock-out"),or to introduce mutant or modified alleles at the locus of interest("knock-in").The efficacy of producing live,transgenic mice challenges our understanding of this complex process,and of the factors which influence germline competence of embryonic stem cell lines.Increasingly,evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell(ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability.Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential.There are a number of options for generating chimeras from ES cells (ES chimera mice);however,each method has its advantages and disadvantages.Recent developments in induced pluripotent stem(iPS)cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies.The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines.The most recent methods for generating specifically ES and iPS chimera mice,including the advantages and disadvantages of each method are also discussed.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.10875011 and 11075016)the 973 Project(Grant No.2007CB814805)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Foundation for Doctoral Training from the Ministry of Education of China
文摘Dynamics of a one-dimensional array of non-locally coupled Kuramoto phase oscillators with an external potential is studied. A four-cluster chimera state is observed for the moderate strength of the external potential. Different from the clustered chimera states studied before, the instantaneous frequencies of the oscillators in a synchronized cluster are different in the presence of the external potential. As the strength of the external potential increases, a bifurcation from the two-cluster chimera state to the four-cluster chimera states can be found. These phenomena are well predicted analytically with the help of the Ott-Antonsen ansatz.
基金the National Natural Science Foundation of China(Grant Nos:81272260&81572712 to L.Chen)Natural Science Fund for Distinguished Young Scholars of Jiangsu Province(SBK2020010058)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediated Autophagy Targeting Chimeras(CMATAC)peptide to knockdown endogenous ERαprotein through chaperone-mediated autophagy.The peptide contains a cell membrane-penetrating peptide(TAT)that allows the peptide to by-pass the plasma membrane,anαI peptide as a protein-binding peptide(PBD)that binds specifically to ERα,and CMA-targeting peptide(CTM)that targeting chaperone-mediated autophagy.We validated that ERαtargeting peptide was able to target and degrade ERαto reduce the viability of ERαpositive breast cancer cells.Taken together,our studies provided a new method to reduce the level of intracellular ERαprotein via CMATAC,and thus may provide a new strategy for the treatment of ERαpositive breast cancer.
基金Project supported by the Center for Nonlinear Systems,Chennai Institute of Technology,India (Grant No. CIT/CNS/2020/RD/061)。
文摘A fractional-order difference equation model of a third-order discrete phase-locked loop(FODPLL) is discussed and the dynamical behavior of the model is demonstrated using bifurcation plots and a basin of attraction. We show a narrow region of loop gain where the FODPLL exhibits quasi-periodic oscillations, which were not identified in the integer-order model. We propose a simple impulse control algorithm to suppress chaos and discuss the effect of the control step. A network of FODPLL oscillators is constructed and investigated for synchronization behavior. We show the existence of chimera states while transiting from an asynchronous to a synchronous state. The same impulse control method is applied to a lattice array of FODPLL, and the chimera states are then synchronized using the impulse control algorithm. We show that the lower control steps can achieve better control over the higher control steps.
文摘The economic and financial systems consist of many nonlinear factors that make them behave as the complex systems.Recently many chaotic finance systems have been proposed to study the complex dynamics of finance as a noticeable problem in economics.In fact,the intricate structure between financial institutions can be obtained by using a network of financial systems.Therefore,in this paper,we consider a ring network of coupled symmetric chaotic finance systems,and investigate its behavior by varying the coupling parameters.The results show that the coupling strength and range have significant effects on the behavior of the coupled systems,and various patterns such as the chimera and multi-chimera states are observed.Furthermore,changing the parameters'values,remarkably influences on the oscillators attractors.When several synchronous clusters are formed,the attractors of the synchronized oscillators are symmetric,but different from the single oscillator attractor.
文摘The rat chimera is an important animal model for the study of complex human diseases. In the present study we evaluated the chimeric potential of rat inner cell masses （ICMs） and fetal neural stem （FNS） cells. In result, three rat chimeras were produced by day 5 （D5） Sprague-Dawley （SD） blastocysts injected with ICMs derived from day 6 （D6） and D5 Dark Agouti （DA） blastocysts; four rat chimeras had been generated by D5 DA blastocyst injected with D5 SD ICMs. For the requirement of gene modification, cultured rat inner cell mass cells were assessed to produce chimeras, but no chimeras were generated from injected embryos. The potential to generate chimeras from rFNS and transfected rFNS cells were tested, but no chimeric pups were produced. Only 2 of 41 fetuses derived from D5 DA blastocyst injection with SD LacZ transfected rFNS cells showed very low number of LacZ positive cells in the section. These results indicate that DA and SD rat ICMs arc able to contribute to chimeras, but their potential decreases significantly after culture in vitro （P〈0.05）, and rFNS cells only have the potential to contribute to early fetal development.
基金This work was supported by the National Natural Science Foundation of China,No.81870975(to SLZ)the Nantong Science and Technology Innovation Program,China,No.JC2019028(to XMY).
文摘Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases.
文摘Aim: To establish techniques for producing somatic and germline chimeric chicken by transferring blastodermal cellsfused with electroporation. Methods: Stage-X blastodermal cells isolated from freshly laid fertile unincubated whiteLeghorn and Rhode Island red chicken eggs were fused with electroporation. The treated cell suspension was transferredto the recovery medium (DMEM containing 10% FBS) and was injected into the subgenninal cavity of recipient unin-cubated embryos (stage X). Results: Of 177 recipient embryos injected with the fusing blastodermal cells, 6(3.4 %) survived to hatching. Somatic chimerism was examined in the melanocyte of the feather. The presence offeathers originating from the donor cell was observed in 1 bird (16.7%) out of the 6 hatched birds. After 21 days ofincubation two birds out of five embryos were subjected to polymerase chain reaction (PCR) analysis for W-chromo-some-specific DNA for each tissue. One bird possessed W-chromosome-specific DNA in the stomach, and the other ex-hibited the same DNA in the left and right gonads and other tissues, but not the stomach. Conclusion: Recipientembryo having electrofused blastodennal cells yields somatic and germline chimeric chickens more successfully.(Asian J Androl 2000 Dec; 2: 271-275)
基金supported by the National Natural Science Foundation of China(No.10802046)
文摘A high-order upwind scheme has been developed to capture the vortex wake of a helicopter rotor in the hover based on chimera grids. In this paper, an improved fifth-order weighted essentially non-oscillatory （WENO） scheme is adopted to interpolate the higher-order left and right states across a cell interface with the Roe Riemann solver updating inviscid flux, and is compared with the monotone upwind scheme for scalar conservation laws （MUSCL）. For profitably capturing the wake and enforcing the period boundary condition, the computation regions of flows are discretized by using the struc- tured chimera grids composed of a fine rotor grid and a cylindrical background grid. In the background grid, the mesh cells located in the wake regions are refined after the so- lution reaches the approximate convergence. Considering the interpolation characteristic of the WENO scheme, three layers of the hole boundary and the interpolation boundary are searched. The performance of the schemes is investigated in a transonic flow and a subsonic flow around the hovering rotor. The results reveal that the present approach has great capabilities in capturing the vortex wake with high resolution, and the WENO scheme has much lower numerical dissipation in comparison with the MUSCL scheme.
基金Project supported by the Polish National Science Centre,MAESTRO Programme(No.2013/08/A/ST8/00780)the OPUS Programme(No.2018/29/B/ST8/00457)。
文摘Chimera state is a peculiar spatiotemporal pattern,wherein the coherence and incoherence coexist in the network of coupled identical oscillators.In this paper,we study the chimera states in a network of impact oscillators with nonlocal coupling.We investigate the effects of the coupling strength and the coupling range on the network behavior.The results reveal the emergence of the chimera state for significantly small values of coupling strength,and higher coupling strength values lead to unbounded motions in the oscillators.We also study the network in the case of excitation failure.We observe that the coupling helps in the maintenance of an oscillatory motion with a lower amplitude in the failed oscillator.
文摘Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo.In chimeric brains,human neural and immune cells can maintain human-specific features,undergo maturation,and functionally integrate into host brains,allowing scientists to study how human cells impact neural circuits and animal behaviors.The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease,elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels,and testing the efficacy of cell therapy interventions.Here,we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders,including disease modeling and cell therapy.
基金supported by the National Natural Science Foundation of China Fund Project(82272956).
文摘Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
