The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the ef...The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.展开更多
Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large...Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large FOV and DOF microscope imaging technology based on a chip-scale metalens device that is implemented by a SiNxmetalens array with a co-and cross-polarization multiplexed dual-phase design and dispersive spectrum zoom effect.A 4-mm×4-mm FOV is obtained with a resolution of 1.74μm and DOF of200μm within a wavelength range of 450 to 510 nm,which definitely exceeds the performance of traditional microscopes with the same resolution.Moreover,it is realized in a miniaturized compact prototype,showing an overall advantage for portable and convenient microscope technology.展开更多
Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune system.In the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medaw...Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune system.In the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological pregnancy.Immune cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy establishment.However,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.展开更多
Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to expl...Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.展开更多
Influenza epidemics and pandemics are constant threats to global public health.Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection,the effic...Influenza epidemics and pandemics are constant threats to global public health.Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection,the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant strains.Our previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus infections.However,one notable drawback ofγδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with phosphoantigens.Here,we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation.CD137^(+)Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137−counterparts in vitro and in Rag2^(-/-)γc^(-/-)mice.We further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation,proliferation,survival and effector functions.In humanized mice reconstituted with human peripheral blood mononuclear cells,CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza virus.Our study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.展开更多
基金This work was supported by the Research fund of Anhui Institute of Translation Medicine(No.2021zhyx-C49)the Foundation of Anhui Medical University(No.2021xkj030)+2 种基金the Anhui Provincial Natural Science Foundation(No.2208085QC81)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(No.2021xkjT028)Grants for Scientific Research of BSKY from Anhui Medical University(No.1406012201).
文摘The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.
基金financial support from the National Key R&D Program of China(2017YFA0303701)the National Natural Science Foundation of China(91850204 and 12174186)support from the Dengfeng Project B of Nanjing University。
文摘Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large FOV and DOF microscope imaging technology based on a chip-scale metalens device that is implemented by a SiNxmetalens array with a co-and cross-polarization multiplexed dual-phase design and dispersive spectrum zoom effect.A 4-mm×4-mm FOV is obtained with a resolution of 1.74μm and DOF of200μm within a wavelength range of 450 to 510 nm,which definitely exceeds the performance of traditional microscopes with the same resolution.Moreover,it is realized in a miniaturized compact prototype,showing an overall advantage for portable and convenient microscope technology.
基金the Shenzhen Healthcare Research Project(Grant No.SZXJ2018004)Clinical Research Fund of Chinese Medical Association(Grant No.18010110740)+2 种基金National Key R&D Program of China(Grant Nos.2018YFC1003900 and 2018YFC1003904)Sanming Project of Medicine in Shenzhen(Grant No.SZSM201502035)General Research Fund,Research Grants Council of Hong Kong(Grant Nos.17122519,17126317,17115015,and 17121214),China。
文摘Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune system.In the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological pregnancy.Immune cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy establishment.However,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.
基金This work was supported by the Shenzhen Healthcare Research Project,China(SZXJ2018004)Clinical Research Program of Chinese Medical Association,China(17020340703)the Sanming Project of Medicine in Shenzhen,China(SZSM201502035).
文摘Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.
基金supported in part by the General Research Fund,Research Grants Council of Hong Kong(17115015,17121214,17126317,17122519)Theme-based Research Scheme from the Research Grants Council of the Hong Kong SAR,China(Project No.T11-705/14N)+1 种基金Chinese National Natural Science Foundation of China(31570898)Natural Science Foundation of Guangdong Province,China(2016A030313112).
文摘Influenza epidemics and pandemics are constant threats to global public health.Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection,the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant strains.Our previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus infections.However,one notable drawback ofγδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with phosphoantigens.Here,we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation.CD137^(+)Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137−counterparts in vitro and in Rag2^(-/-)γc^(-/-)mice.We further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation,proliferation,survival and effector functions.In humanized mice reconstituted with human peripheral blood mononuclear cells,CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza virus.Our study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.