Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly.Two technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome edit...The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly.Two technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome editing(GE).Recently,these techniques were combined into a GE trait delivery system called HI-Edit(Haploid Inducer-Edit).In HI-Edit,the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety,obviating recurrent selection.For HI-Edit to operate at scale,an efficient transformable HI line is needed,but most maize varieties are recalcitrant to transformation,and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors.Leveraging marker assisted selection and a three-tiered testing scheme,we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable,have high haploid induction rates,and exhibit a robust,genetically-dominant anthocyanin native trait that may be used for rapid haploid identification.We show that transformation of these elite‘‘HI-Edit”lines is enhanced using the BABYBOOM and WUSCHEL morphogenetic factors.Finally,we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers.The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.展开更多
Transformable architecture is totally linked to the study and knowledge of geometry.There are some materials in nature,whose geometric invariants establish equivalent structural behavior regarding the scalar transform...Transformable architecture is totally linked to the study and knowledge of geometry.There are some materials in nature,whose geometric invariants establish equivalent structural behavior regarding the scalar transformations,developing different spatial typologies according to dimensional variation.Auxetic materials are characterized by their negative Poisson’s ratio.They can change their geometric configuration from a line to a surface,and from a surface to a volume or spatial framework.This paper is based on establishing and comparing those stellated reentrant auxetic geometries to be able to build new spaces defined by their capacity for architectural transformation,studying analytically geometric properties of stellated reentrant auxetic structures that,from the molecular to the macroscopic level,can be part of the architecture construction.In this investigation,a comparative study by means of CAD of stellated reentrant auxetic patterns has been realized.A Computer-Aided Design study of stellated reentrant auxetic structures will be realized to use them in architecture.The geometric behavior of the different stellated reentrant auxetic patterns is analyzed from the developed study to generate a systematic comparison,evaluating properties of these forms,such as their maximum achievable area reductions in relation to the total length of bars of the structure,in order to obtain a growth factor.展开更多
The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural ...The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.展开更多
The solar sail is one of the most promising space exploration systems due to its theoretically infinite specific impulse achieved through solar radiation pressure(SRP).Recently,researchers have proposed“transformable...The solar sail is one of the most promising space exploration systems due to its theoretically infinite specific impulse achieved through solar radiation pressure(SRP).Recently,researchers have proposed“transformable spacecraft”capable of actively reconfiguring their body configurations using actuatable joints.Transformable spacecraft,if used similarly to solar sails,are expected to significantly enhance orbit and attitude control capabilities owing to their high redundancy in control degrees of freedom.However,controlling them becomes challenging due to their large number of inputs,leading previous researchers to impose strong constraints to limit their potential control capabilities.This study focuses on novel attitude control techniques for transformable spacecraft under SRP.We developed two methods,namely,joint angle optimization to obtain arbitrary SRP force and torque,and momentum damping control driven by joint angle actuation.Our proposed methods are formulated in a general manner and can be applied to any transformable spacecraft comprising front faces that can predominantly receive the SRP on each body.The validity of our proposed method is confirmed through numerical simulations.Our study contributes to making most of the high control redundancy of transformable spacecraft without the need for expendable propellants,thus significantly enhancing the orbit and attitude control capabilities.展开更多
Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challe...Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation.This work designed a peptide-photosensitizer conjugate(PPC),which consisted of a PD-L1 antagonist peptide(CVRARTR),an MMP-2 specific cleavable sequence,a self-assembling motif,and the photosensitizer Purpurin 18.The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection.The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites,thereby initiating the cancer-specific release of the antagonist peptide.Simultaneously,the nanospheres gradually transform into co-assembled nanofibers,which promotes the retention of the remaining parts within the tumor.In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs,which sensitize 4T1 tumor cells to immune checkpoint blockade therapy.Therefore,PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases.The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.展开更多
Developing bulk metallic glass composites(BMGCs)with high toughness is vital for their practical application.However,the influence of different microstructures on the impact toughness of BMGCs is still unclear.The eff...Developing bulk metallic glass composites(BMGCs)with high toughness is vital for their practical application.However,the influence of different microstructures on the impact toughness of BMGCs is still unclear.The effects of Al addition and cryogenic cyclic treatment(CCT)on the Charpy impact toughness,a K,at 298 and 77 K of a series of phase-transformable BMGCs are investigated in this work.It is found that deformation-induced martensitic transformation(DIMT)of theβ-Ti dendrites is the dominant toughening mechanism in the phase-transformable BMGCs at 298 K,but at 77 K,the toughness of BMGCs is primarily determined by the intrinsic toughness of the glass matrix.The addition of Al can moderately tune theβ-Ti phase stability,which then affects the amount of DIMT and impact toughness of the BMGCs at 298 K.However,at 77 K,Al addition causes a monotonic decrease in the toughness of the BMGCs due to the embrittlement of the glass matrix.It is found that CCT can effectively rejuvenate the phase-transformable BMGCs,which results in an enhanced impact toughness at 298 K.However,the toughness at 77 K monotonously decreases with increasing the number of CCT cycles,suggesting that the rejuvenation of the glass matrix affects the toughness at both 298 and 77 K of BMGCs,but in dramatically different ways.These findings reveal the influence of microstructures and CCT on the impact toughness of BMGCs and provide insights that could be useful for designing tougher BMGs and BMGCs.展开更多
When a transformable B2 precipitate is embedded in an amorphous matrix,it is often experimentally observed that the crystalline-amorphous interface not only serves as an initiation site for the martensitic transformat...When a transformable B2 precipitate is embedded in an amorphous matrix,it is often experimentally observed that the crystalline-amorphous interface not only serves as an initiation site for the martensitic transformation due to local stress concentrations,but also as an inhibitor to stabilize the transformation,the latter being attributed to the“confinement effect”exerted by the amorphous matrix,according to the Eshelby solution.These two seemingly incongruous factors are examined in this study using molecular dynamics simulations from an atomic interaction perspective.An innate strain gradient in the vicinity of the crystalline-amorphous interface is identified.The actual interface,the compressive/dilatative transition,and the interfacial maximum strain are investigated to differentiate from the conventional“interface”located within a distance of a few nanometers.Our innate interfacial elastic strain field model is applicable for the design of materials with a higher degree of martensitic transformation and controllable stress concentration,even in cryogenic environments.展开更多
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
文摘The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly.Two technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome editing(GE).Recently,these techniques were combined into a GE trait delivery system called HI-Edit(Haploid Inducer-Edit).In HI-Edit,the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety,obviating recurrent selection.For HI-Edit to operate at scale,an efficient transformable HI line is needed,but most maize varieties are recalcitrant to transformation,and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors.Leveraging marker assisted selection and a three-tiered testing scheme,we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable,have high haploid induction rates,and exhibit a robust,genetically-dominant anthocyanin native trait that may be used for rapid haploid identification.We show that transformation of these elite‘‘HI-Edit”lines is enhanced using the BABYBOOM and WUSCHEL morphogenetic factors.Finally,we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers.The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.
文摘Transformable architecture is totally linked to the study and knowledge of geometry.There are some materials in nature,whose geometric invariants establish equivalent structural behavior regarding the scalar transformations,developing different spatial typologies according to dimensional variation.Auxetic materials are characterized by their negative Poisson’s ratio.They can change their geometric configuration from a line to a surface,and from a surface to a volume or spatial framework.This paper is based on establishing and comparing those stellated reentrant auxetic geometries to be able to build new spaces defined by their capacity for architectural transformation,studying analytically geometric properties of stellated reentrant auxetic structures that,from the molecular to the macroscopic level,can be part of the architecture construction.In this investigation,a comparative study by means of CAD of stellated reentrant auxetic patterns has been realized.A Computer-Aided Design study of stellated reentrant auxetic structures will be realized to use them in architecture.The geometric behavior of the different stellated reentrant auxetic patterns is analyzed from the developed study to generate a systematic comparison,evaluating properties of these forms,such as their maximum achievable area reductions in relation to the total length of bars of the structure,in order to obtain a growth factor.
基金We acknowledge financial support by the National Natural Science Foundation of China(32071374,32000985,81761148029,81620108028)Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100)+3 种基金Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan,One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province(2019C04024)the Zhejiang Provincial Natural Science Foundation of China(LR22C100001,LGF19C100002,LQ21H300003)Zhejiang Province Medical and Health Science Research Project(2021KY666),and Zhejiang Pharmaceutical Association(2019ZYY12)Open access funding provided by Shanghai Jiao Tong University
文摘The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.
文摘The solar sail is one of the most promising space exploration systems due to its theoretically infinite specific impulse achieved through solar radiation pressure(SRP).Recently,researchers have proposed“transformable spacecraft”capable of actively reconfiguring their body configurations using actuatable joints.Transformable spacecraft,if used similarly to solar sails,are expected to significantly enhance orbit and attitude control capabilities owing to their high redundancy in control degrees of freedom.However,controlling them becomes challenging due to their large number of inputs,leading previous researchers to impose strong constraints to limit their potential control capabilities.This study focuses on novel attitude control techniques for transformable spacecraft under SRP.We developed two methods,namely,joint angle optimization to obtain arbitrary SRP force and torque,and momentum damping control driven by joint angle actuation.Our proposed methods are formulated in a general manner and can be applied to any transformable spacecraft comprising front faces that can predominantly receive the SRP on each body.The validity of our proposed method is confirmed through numerical simulations.Our study contributes to making most of the high control redundancy of transformable spacecraft without the need for expendable propellants,thus significantly enhancing the orbit and attitude control capabilities.
基金This work was supported by the National Key R&D Program of China(2017YFA0205600)Natural Science Foundation of Hebei Province(H2022206171)。
文摘Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation.This work designed a peptide-photosensitizer conjugate(PPC),which consisted of a PD-L1 antagonist peptide(CVRARTR),an MMP-2 specific cleavable sequence,a self-assembling motif,and the photosensitizer Purpurin 18.The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection.The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites,thereby initiating the cancer-specific release of the antagonist peptide.Simultaneously,the nanospheres gradually transform into co-assembled nanofibers,which promotes the retention of the remaining parts within the tumor.In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs,which sensitize 4T1 tumor cells to immune checkpoint blockade therapy.Therefore,PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases.The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.
基金supported by the National Natural Science Foundation of China(Nos.52171164 and 51790484)National Key Laboratory of Science and Technology on Materials under Shock and Impact(WDZC2022-13)+4 种基金the National Key Research and Development Program of China(No.2021YFA0716303)Start-up research grant(No.SRG/2020/000095)of Science and Engineering Research Board,DST,GoI.A∗STAR,Singapore via the Structural Metals and Alloys Program(No.A18B1b0061)the Natural Science Foundation of Liaoning Province(No.2021-MS-009)the China Manned Space Engineering,the Chinese Academy of Sciences(ZDBS-LY-JSC023)the Youth Innovation Promotion Association CAS(No.2021188).
文摘Developing bulk metallic glass composites(BMGCs)with high toughness is vital for their practical application.However,the influence of different microstructures on the impact toughness of BMGCs is still unclear.The effects of Al addition and cryogenic cyclic treatment(CCT)on the Charpy impact toughness,a K,at 298 and 77 K of a series of phase-transformable BMGCs are investigated in this work.It is found that deformation-induced martensitic transformation(DIMT)of theβ-Ti dendrites is the dominant toughening mechanism in the phase-transformable BMGCs at 298 K,but at 77 K,the toughness of BMGCs is primarily determined by the intrinsic toughness of the glass matrix.The addition of Al can moderately tune theβ-Ti phase stability,which then affects the amount of DIMT and impact toughness of the BMGCs at 298 K.However,at 77 K,Al addition causes a monotonic decrease in the toughness of the BMGCs due to the embrittlement of the glass matrix.It is found that CCT can effectively rejuvenate the phase-transformable BMGCs,which results in an enhanced impact toughness at 298 K.However,the toughness at 77 K monotonously decreases with increasing the number of CCT cycles,suggesting that the rejuvenation of the glass matrix affects the toughness at both 298 and 77 K of BMGCs,but in dramatically different ways.These findings reveal the influence of microstructures and CCT on the impact toughness of BMGCs and provide insights that could be useful for designing tougher BMGs and BMGCs.
基金supported by the National Natural Science Foundation of China(No.51601019,52001184,52071089,52071217)the Guangdong Major Project of Basic and Applied Basic Research(Grant No.2019B030302010)the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010233,2019A1515110472).
文摘When a transformable B2 precipitate is embedded in an amorphous matrix,it is often experimentally observed that the crystalline-amorphous interface not only serves as an initiation site for the martensitic transformation due to local stress concentrations,but also as an inhibitor to stabilize the transformation,the latter being attributed to the“confinement effect”exerted by the amorphous matrix,according to the Eshelby solution.These two seemingly incongruous factors are examined in this study using molecular dynamics simulations from an atomic interaction perspective.An innate strain gradient in the vicinity of the crystalline-amorphous interface is identified.The actual interface,the compressive/dilatative transition,and the interfacial maximum strain are investigated to differentiate from the conventional“interface”located within a distance of a few nanometers.Our innate interfacial elastic strain field model is applicable for the design of materials with a higher degree of martensitic transformation and controllable stress concentration,even in cryogenic environments.