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
Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study ai...Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.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
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
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
Based on analysis of pore features and pore skeleton composition of shale,a“rigid elastic chimeric”pore skeleton model of shale gas reservoir was built.Pore deformation mechanisms leading to increase of shale porosi...Based on analysis of pore features and pore skeleton composition of shale,a“rigid elastic chimeric”pore skeleton model of shale gas reservoir was built.Pore deformation mechanisms leading to increase of shale porosity due to the pore skeleton deformation under overpressure were sorted out through analysis of stress on the shale pore and skeleton.After reviewing the difficulties and defects of existent porosity measurement methods,a dynamic deformed porosity measurement method was worked out and used to measure the porosity of overpressure Silurian Longmaxi Formation shale under real formation conditions in southern Sichuan Basin.The results show:(1)The shale reservoir is a mixture of inorganic rock particles and organic matter,which contains inorganic pores supported by rigid skeleton particles and organic pores supported by elastic-plastic particles,and thus has a special“rigid elastic chimeric”pore structure.(2)Under the action of formation overpressure,the inorganic pores have tiny changes that can be assumed that they don’t change in porosity,while the organic pores may have large deformation due to skeleton compression,leading to the increase of radius,connectivity and ultimately porosity of these pores.(3)The“dynamic”deformation porosity measurement method combining high injection pressure helium porosity measurement and kerosene porosity measurement method under ultra-high variable pressure can accurately measure porosity of unconnected micro-pores under normal pressure conditions,and also the porosity increment caused by plastic skeleton compression deformation.(4)The pore deformation mechanism of shale may result in the"abnormal"phenomenon that the shale under formation conditions has higher porosity than that under normal pressure,so the overpressure shale reservoir is not necessarily“ultra-low in porosity”,and can have porosity over 10%.Application of this method in Well L210 in southern Sichuan has confirmed its practicality and reliability.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
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.
基金supported by the National Natural Science Foundation of China(82260716)the Key Research and Development Program of Ningxia(2023BEG02010).
文摘Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
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.
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Supported by the National Science and Technology Major Project of China(2017ZX05035).
文摘Based on analysis of pore features and pore skeleton composition of shale,a“rigid elastic chimeric”pore skeleton model of shale gas reservoir was built.Pore deformation mechanisms leading to increase of shale porosity due to the pore skeleton deformation under overpressure were sorted out through analysis of stress on the shale pore and skeleton.After reviewing the difficulties and defects of existent porosity measurement methods,a dynamic deformed porosity measurement method was worked out and used to measure the porosity of overpressure Silurian Longmaxi Formation shale under real formation conditions in southern Sichuan Basin.The results show:(1)The shale reservoir is a mixture of inorganic rock particles and organic matter,which contains inorganic pores supported by rigid skeleton particles and organic pores supported by elastic-plastic particles,and thus has a special“rigid elastic chimeric”pore structure.(2)Under the action of formation overpressure,the inorganic pores have tiny changes that can be assumed that they don’t change in porosity,while the organic pores may have large deformation due to skeleton compression,leading to the increase of radius,connectivity and ultimately porosity of these pores.(3)The“dynamic”deformation porosity measurement method combining high injection pressure helium porosity measurement and kerosene porosity measurement method under ultra-high variable pressure can accurately measure porosity of unconnected micro-pores under normal pressure conditions,and also the porosity increment caused by plastic skeleton compression deformation.(4)The pore deformation mechanism of shale may result in the"abnormal"phenomenon that the shale under formation conditions has higher porosity than that under normal pressure,so the overpressure shale reservoir is not necessarily“ultra-low in porosity”,and can have porosity over 10%.Application of this method in Well L210 in southern Sichuan has confirmed its practicality and reliability.
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)
