How the host immune system loses its surveillance function during the evolution from normal cell to malignancy is still largely unknown.Here,we investigate the dynamics changes of the pancreatic ductal adenocarcinoma(...How the host immune system loses its surveillance function during the evolution from normal cell to malignancy is still largely unknown.Here,we investigate the dynamics changes of the pancreatic ductal adenocarcinoma(PDAC)tumor microenvironment by profiling 132,115 single-cell transcriptomes derived from 51 tissues,including healthy pancreatic tissue,non-metastatic PDAC primary tumors,metastatic primary tumors,and patient-matched liver metastases.The cellular proportion,bio-functional,and interaction between each cell type are carefully characterized.Aberrant copy number variations(CNVs)indicating malignant intensity are identified at chromosomes 7 and 20 of epithelial cells during tumor development.A bio-functional transition of predominant genes from physiology to pancreatic oncogenesis and metastasis is observed.Combinatorial analysis of epithelial cells and immunocytes indicates a gradient loss of immune surveillance during the malignant transformation.By dissecting cellular interaction,we unravel an incremental tumor cell-triggered apoptosis of DCs through molecular pair ANXA1-FPR1/3.Consequently,the activation and infiltration of cytotoxic CD8+T cells are dampened progressively.Remarkably,we unveil a novel subtype of stress-response NK cells(strNK),which are characterized by robust proliferation,diminished cytolytic capabilities,and negative immune regulation.Notably,the presence of strNK cells is associated with poor prognosis of PDAC patients,implying a potential pro-tumor function.Taken together,our results not only shed light on the intricate mechanisms underlying step-wise evasion of immune surveillance during PDAC tumor development,but also provide a potential strategy for holding back malignant transition by reinforcing DCs’function.展开更多
Energy storage property of a dielectric is closely tied with its nanostructure.In this study,we aim to achieve a deep understanding of this relationship in high energy density ferroelectric ceramicfilms,by probing int...Energy storage property of a dielectric is closely tied with its nanostructure.In this study,we aim to achieve a deep understanding of this relationship in high energy density ferroelectric ceramicfilms,by probing into the nanograin and sub-grain nanostructures in polycrystalline BaTiO_(3)films integrated on Si.Through scanning probe acoustic microscopy analyses,it is revealed that the BaTiO_(3)films directly grown on Pt/Ti/Si mostly consist of large discontinuous columnar nanograins,while those grown on LaNiO_(3)-buffered Pt/Ti/Si substrates have a dominant microstructure of continuous columnar nanograins.Furthermore,ultrafine ferroelastic domains of~10 nm wide are revealed inside the grains of the buffered BaTiO_(3)films,while those unbufferedfilms show about~50%increase in the domain width.The dielectric properties of the BaTiO_(3)films are well correlated with their characteristic nanostructures.Under an increasing electricfield,the LaNiO_(3)-bufferedfilms display a slower decline in its dielectric constant and a later saturation of its electric polarization,leading to an improved energy storage performance.Devicelevel charge-discharge tests have verified not only the delayed polarization saturation and high energy density of the LaNiO_(3)-buffered BaTiO_(3)film capacitors,but also a high power density in the same order as those of the ferroelectric ceramics.展开更多
In the research field of energy storage dielectrics,the“responsivity”parameter,defined as the recyclable/recoverable energy density per unit electric field,has become critically important for a comprehensive evaluat...In the research field of energy storage dielectrics,the“responsivity”parameter,defined as the recyclable/recoverable energy density per unit electric field,has become critically important for a comprehensive evaluation of the energy storage capability of a dielectric.In this work,high recyclable energy density and responsivity,i.e.,W_(rec)=161.1 J·cm^(-3) and ξ=373.8 J·(kV·m^(2))^(-1),have been simultaneously achieved in a prototype perovskite dielectric,BaTiO_(3),which is integrated on Si at 500℃ in the form of a submicron thick film.This ferroelectric film features a multi-scale polar structure consisting of ferroelectric grains with different orientations and inner-grain ferroelastic domains.A LaNiO_(3) buffer layer is used to induce a{001}textured,columnar nanograin microstructure,while an elevated deposition temperature promotes lateral growth of the nanograins(in-plane diameter increases from~10-20 nm at lower temperatures to~30 nm).These preferably oriented and periodically regulated nanograins have resulted in a small remnant polarization and a delayed polarization saturation in the film’s P-E behavior,leading to a high recyclable energy density.Meanwhile,an improved polarizability/dielectric constant of the BaTiO_(3) film has produced a much larger maximum polarization than those deposited at lower temperatures at the same electric field,leading to a record-breaking responsivity for this simple perovskite.展开更多
基金funded by Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0502300[2023ZD0502304]to J.J.)National Key Research and Development Program of China(NO.2022YFA1207300 and 2022YFC2504700 to H.S.,2023ZD0502300 to X.W.L.)+5 种基金National Natural Science Foundation of China(NO.82172634 to H.S.,82473064 and 22105137 to X.W.L.)Key Program of the Science and Technology Bureau of Sichuan(NO.2021YFSY0007 to H.S.,2024NSFSC1919 to X.W.L.,and 2024NSFSC1725 to X.Y.W.)National Guidance Fund on Developing Local Science and Technology for Sichuan Province(No.2023ZYD0167 to J.J.)1.3.5 Projects for Disciplines of Excellence,West China Hospital,Sichuan University(NO.ZYYC20013 to H.S.)China Postdoctoral Science Foundation(NO.2024M762232 to J.S.)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(NO.GZB20240487 to J.S.).
文摘How the host immune system loses its surveillance function during the evolution from normal cell to malignancy is still largely unknown.Here,we investigate the dynamics changes of the pancreatic ductal adenocarcinoma(PDAC)tumor microenvironment by profiling 132,115 single-cell transcriptomes derived from 51 tissues,including healthy pancreatic tissue,non-metastatic PDAC primary tumors,metastatic primary tumors,and patient-matched liver metastases.The cellular proportion,bio-functional,and interaction between each cell type are carefully characterized.Aberrant copy number variations(CNVs)indicating malignant intensity are identified at chromosomes 7 and 20 of epithelial cells during tumor development.A bio-functional transition of predominant genes from physiology to pancreatic oncogenesis and metastasis is observed.Combinatorial analysis of epithelial cells and immunocytes indicates a gradient loss of immune surveillance during the malignant transformation.By dissecting cellular interaction,we unravel an incremental tumor cell-triggered apoptosis of DCs through molecular pair ANXA1-FPR1/3.Consequently,the activation and infiltration of cytotoxic CD8+T cells are dampened progressively.Remarkably,we unveil a novel subtype of stress-response NK cells(strNK),which are characterized by robust proliferation,diminished cytolytic capabilities,and negative immune regulation.Notably,the presence of strNK cells is associated with poor prognosis of PDAC patients,implying a potential pro-tumor function.Taken together,our results not only shed light on the intricate mechanisms underlying step-wise evasion of immune surveillance during PDAC tumor development,but also provide a potential strategy for holding back malignant transition by reinforcing DCs’function.
基金Natural Science Foundation of Shandong Province(Grant No.ZR2022ZD39,ZR2020QE042,ZR2022ME031,ZR2022QB138)the National Natural Science Foundation of China(NSFC)(Grant nos.51772175,52002192)+2 种基金the Science,Education and Industry Integration Pilot Projects of Qilu University of Technology(Shandong Academy of Sciences)(Grant Nos.2022GH018,2022PY055).J.Ouyang acknowledges the support from the Jinan Science and Technology Bureau(Grant No.2021GXRC055)the Education Department of Hunan Province/Xiangtan University(Grant No.KZ0807969)the seed funding for top talents at Qilu University of Technology(Shandong Academy of Sciences).
文摘Energy storage property of a dielectric is closely tied with its nanostructure.In this study,we aim to achieve a deep understanding of this relationship in high energy density ferroelectric ceramicfilms,by probing into the nanograin and sub-grain nanostructures in polycrystalline BaTiO_(3)films integrated on Si.Through scanning probe acoustic microscopy analyses,it is revealed that the BaTiO_(3)films directly grown on Pt/Ti/Si mostly consist of large discontinuous columnar nanograins,while those grown on LaNiO_(3)-buffered Pt/Ti/Si substrates have a dominant microstructure of continuous columnar nanograins.Furthermore,ultrafine ferroelastic domains of~10 nm wide are revealed inside the grains of the buffered BaTiO_(3)films,while those unbufferedfilms show about~50%increase in the domain width.The dielectric properties of the BaTiO_(3)films are well correlated with their characteristic nanostructures.Under an increasing electricfield,the LaNiO_(3)-bufferedfilms display a slower decline in its dielectric constant and a later saturation of its electric polarization,leading to an improved energy storage performance.Devicelevel charge-discharge tests have verified not only the delayed polarization saturation and high energy density of the LaNiO_(3)-buffered BaTiO_(3)film capacitors,but also a high power density in the same order as those of the ferroelectric ceramics.
基金the National Natural Science Foundation of China(Grant Nos.51772175 and 52002192)Natural Science Foundation of Shandong Province(Grant Nos.ZR2022ZD39,ZR2022ME075,ZR2020QE042,ZR2022ME031,and ZR2022QB138)+3 种基金the Science,Education and Industry Integration Pilot Projects of Qilu University of Technology(Shandong Academy of Sciences)(Grant Nos.2022GH018 and 2022PY055)the Jinan City Science and Technology Bureau(Grant No.2021GXRC055)the Education Department of Hunan Province/Xiangtan University(Grant No.KZ0807969)funding for top talents at Qilu University of Technology(Shandong Academy of Sciences).
文摘In the research field of energy storage dielectrics,the“responsivity”parameter,defined as the recyclable/recoverable energy density per unit electric field,has become critically important for a comprehensive evaluation of the energy storage capability of a dielectric.In this work,high recyclable energy density and responsivity,i.e.,W_(rec)=161.1 J·cm^(-3) and ξ=373.8 J·(kV·m^(2))^(-1),have been simultaneously achieved in a prototype perovskite dielectric,BaTiO_(3),which is integrated on Si at 500℃ in the form of a submicron thick film.This ferroelectric film features a multi-scale polar structure consisting of ferroelectric grains with different orientations and inner-grain ferroelastic domains.A LaNiO_(3) buffer layer is used to induce a{001}textured,columnar nanograin microstructure,while an elevated deposition temperature promotes lateral growth of the nanograins(in-plane diameter increases from~10-20 nm at lower temperatures to~30 nm).These preferably oriented and periodically regulated nanograins have resulted in a small remnant polarization and a delayed polarization saturation in the film’s P-E behavior,leading to a high recyclable energy density.Meanwhile,an improved polarizability/dielectric constant of the BaTiO_(3) film has produced a much larger maximum polarization than those deposited at lower temperatures at the same electric field,leading to a record-breaking responsivity for this simple perovskite.
