Four different routes of asymmetric reduction rolling were conducted on AZ31 magnesium alloy to investigate their effect on the microstructure evolution and mechanical properties. Route A is the forward rolling; while...Four different routes of asymmetric reduction rolling were conducted on AZ31 magnesium alloy to investigate their effect on the microstructure evolution and mechanical properties. Route A is the forward rolling; while during routes B and C the sheets are rotated 180o in rolling direction and normal direction, respectively; route D is the unidirectional rolling. The strain states of rolled sheets were analyzed by the finite element method, while the microstructure and texture were observed using optical microscopy, X-ray diffraction and electron back-scattered diffraction techniques, and the mechanical properties were measured by tensile test. The results show that route D produced the largest effective strain. Compared with other samples, sample D exhibited a homogeneous microstructure with fine grains as well as a weak and tilted texture, in corresponding, it performed excellent tensile properties, which suggested that route D was an effective way to enhance the strength and plasticity of AZ31 sheet.展开更多
Mg alloy AZ31 with ~79% （volume fraction of scattering less than 30°） basal-fiber texture through hot extrusion exhibits strong grain-size dependent yield strength, Samples with grain sizes varying from 4,5 to ...Mg alloy AZ31 with ~79% （volume fraction of scattering less than 30°） basal-fiber texture through hot extrusion exhibits strong grain-size dependent yield strength, Samples with grain sizes varying from 4,5 to 22,3 μm were obtained by altering annealing time durations, The Hall-Petch relations of tension and compression are σ.2 = 86＋200d^-1/2 and σ0.2 = 17 ＋ 327d^-1/2, respectively, Considering the correlation between grain orientation and deformation modes, a novel weighted average method of calculating friction stress Cro was proposed, and results of calculation agreed with the experimental ones, which can reasonably understand the yielding behavior in tension and compression,展开更多
AIM: To construct the expression vector of B3 (scdsFv)-SEA (D227A) and to identify its binding and cytotoxic ability to B3 antigen positive carcinoma cell lines.METHODS: This fusion protein was produced by a bacterial...AIM: To construct the expression vector of B3 (scdsFv)-SEA (D227A) and to identify its binding and cytotoxic ability to B3 antigen positive carcinoma cell lines.METHODS: This fusion protein was produced by a bacterial expression system in this study. It was expressed mainly in the inclusion body. The gene product was solubilized by guanidine hydrochloride, refolded by conventional dilution method, and purified using SP-sepharose cation chromatography.RESULTS: The expression vector B3 (scdsFv)-SEA-PETwas constructed, the expression product existed mainly in the inclusion body, the refolding product retained the binding ability of the single-chain antibody and had cytotoxic effect on HT-29 colon carcinoma cells. The stability assay showed that the resulting protein was stable at 37 ℃.CONCLUSION: This genetically engineered B3 (scdsFv)-SEA fusion protein has bifunction of tumor targeting and tumor cell killing and shows its promises as an effective reagent for tumor-targeted immunotherapy.展开更多
Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence...Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.展开更多
The influence of asymmetric reduction rolling （ARR） on the microstructure, texture and mechanical properties of AZ91 was investigated. The microstructural characteristics of the AZ91 sheet processed by symmetric ro...The influence of asymmetric reduction rolling （ARR） on the microstructure, texture and mechanical properties of AZ91 was investigated. The microstructural characteristics of the AZ91 sheet processed by symmetric roiling （SR） were the twins, intersection of twins and dynamic recrystalization （DRX） grains around the coarse grains and within the twins. However, the amount of twins and DRX grains in ARRed AZ91 was much smaller than that in SRed AZ91. The SRed AZ91 after annealing exhibited fine DRX grains and some coarse grains with a size of ~ 100 pro. The grains in ARRed AZ91 after annealing were much finer and more homogeneous than those in SRed AZ91 after annealing. The intensity of basal texture of ARRed AZ91 after annealing was lower than that of SRed AZ91 rolling after annealing. The average Schmid factor of ARRed AZ91 is 0.34, which is higher than that of SRed AZ91. The yield strength and ultimate tensile strength of the ARRed AZ91 sheet were inCreased to 16.1% and 31.8% compared to SRed AZ91 sheet, from 155 to 180 MPa, and from 220 to 290 MPa, respectively. The improvement of mechanical properties in ARRed AZ91 after annealing was attributed to much finer, more homogeneous DRX grains and weaker basal texture.展开更多
Objective:Malignant peritoneal mesothelioma(MPM)is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options.This study investigated the in vitro and in vivo effi...Objective:Malignant peritoneal mesothelioma(MPM)is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options.This study investigated the in vitro and in vivo efficacy of natural killer(NK)cells for treatment of MPM.Methods:An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system,the Cell Counting Kit-8 assay,and Wright-Giemsa staining.The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays.The ability of NK cells to kill MPM cells was determined based on live cell imaging,transmission electron microscopy,and scanning electron microscopy.An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index,small animal magnetic resonance imaging,and conventional histopathologic,cytologic,and hematologic studies.Results:NK cells effectively killed MPM cells through the release of effector molecules(granzyme B,perforin,interferon-γ,and tumor necrosis factor-α)in a dose-and density-dependent manner.The NK cell killing process potentially involved four dynamic steps:chemotaxis;hitting;adhesion;and penetration.NK cells significantly reduced the tumor burden,diminished ascites production,and extended survival with no significant hematologic toxicity or organ damage in NOG mice.Conclusions:NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.展开更多
Abstract Previous studies have suggested that cortical functional reorganization is associated with motor recovery after stroke and that normal afferent sensory information is very important in that process. In this s...Abstract Previous studies have suggested that cortical functional reorganization is associated with motor recovery after stroke and that normal afferent sensory information is very important in that process. In this study, we selected patients who had a stroke in or under the thalamus, with potentially impaired afferent sensory information and analyzed the differences between these patients and healthy controls at three levels： brain regions, the functional con- nectivity between brain areas, and the whole-brain func- tional network. Compared with healthy controls, regionalhomogeneities in the left middle temporal gyrus decreased and functional connectivity between the left middle tem- poral gyrus and the stroke area increased in the patients. However, there was no significant change in the whole- brain functional network. By focusing on stroke located in or under the thalamus, our study contributes to wider inquiries into understanding and treating stroke.展开更多
目的:探讨鸟苷酸结合蛋白α亚基(guanine nucleotide binding protein alpha subunit,Gsα)表达与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)主要临床病理特征及预后的相关性。方法:收集首都医科大学附属北京世纪坛医院65例PMP患者病理...目的:探讨鸟苷酸结合蛋白α亚基(guanine nucleotide binding protein alpha subunit,Gsα)表达与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)主要临床病理特征及预后的相关性。方法:收集首都医科大学附属北京世纪坛医院65例PMP患者病理标本,行常规组织病理学和定量免疫组织化学检测Gsα蛋白表达,研究Gsα蛋白表达与主要临床病理特征及预后的相关性。结果:65例PMP肿瘤行定量免疫组织化学分析,Gsα高表达者35例(53.8%),低表达者30例(46.2%)。单因素分析显示,Gsα高表达与下列5个临床病理指标呈正相关:术前肿瘤标志物(χ^(2)=3.68,P=0.087)、术中腹水量(χ^(2)=3.69,P=0.055)、腹膜癌指数评分(peritoneal cancer index,PCI)(χ^(2)=3.12,P=0.077)、肿瘤细胞减灭程度评分(completeness of cytoreduction,CC)(χ^(2)=2.72,P=0.099)、组织病理分级(χ^(2)=5.85,P=0.016)。多因素分析显示,Gsα蛋白高表达仅与组织病理分级呈独立正相关:高级别或高级别伴印戒细胞的组织病理类型(OR=3.47,95%CI:1.1~15.6,P=0.029)。Cox多因素分析显示,年龄(HR=8.08,95%CI:2.42~26.97,P=0.001)、既往手术(HR=0.24,95%CI:0.07~0.81,P=0.022)、组织病理分级(HR=3.92,95%CI:1.12~13.70,P=0.032);Gsα蛋白表达(HR=3.25,95%CI:1.01~10.5,P=0.048)为独立预后因素。结论:Gsα蛋白高表达与高级别或高级别伴印戒细胞的组织病理类型呈正相关,提示PMP预后不良。展开更多
Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long i...Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long interspersed element-1(LINE-1)is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development.In this review,we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency.We also explore the critical function of LINE-1 activation and its rich functional reservoir,which is exploited by the host to provide cis-regulatory elements and functional proteins.Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation,histone methylation,ubiquitination,and RNA methylation.The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages.Accordingly,the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes,including the opening of chromatin architecture,zygotic genome activation,aging,and age-related disorders.It may reflect an effect on totipotency and pluripotency of mammalian development.Underscoring its pivotal significance,the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.展开更多
This paper analyzes the development of spatial concentration of various innovation activities in China from 2000 to 2015 by using a generalized Theil index based on a balanced provincial dataset.It tracks concentratio...This paper analyzes the development of spatial concentration of various innovation activities in China from 2000 to 2015 by using a generalized Theil index based on a balanced provincial dataset.It tracks concentration development back to the developing heterogeneity within and between regions in general and the mega-economic zones in particular.Results show that innovation activities tend to be distributed unequally across provinces in China,with more pronounced unequal distribution of innovation outcomes than innovation inputs.Over the research period,the innovation activities considered became more and more equally distributed across provinces.The between-region inequality of innovation activities has,however,not yet significantly improved,despite the implementation of Chinese regional policies to encourage more equal regional development.Instead,more equal distribution of innovation activities within megaeconomic zones is observed.展开更多
基金Project(51471041)supported by the National Natural Science Foundation of China
文摘Four different routes of asymmetric reduction rolling were conducted on AZ31 magnesium alloy to investigate their effect on the microstructure evolution and mechanical properties. Route A is the forward rolling; while during routes B and C the sheets are rotated 180o in rolling direction and normal direction, respectively; route D is the unidirectional rolling. The strain states of rolled sheets were analyzed by the finite element method, while the microstructure and texture were observed using optical microscopy, X-ray diffraction and electron back-scattered diffraction techniques, and the mechanical properties were measured by tensile test. The results show that route D produced the largest effective strain. Compared with other samples, sample D exhibited a homogeneous microstructure with fine grains as well as a weak and tilted texture, in corresponding, it performed excellent tensile properties, which suggested that route D was an effective way to enhance the strength and plasticity of AZ31 sheet.
基金the support of the National Natural Science Foundation of China(51271046 and 51471041)
文摘Mg alloy AZ31 with ~79% （volume fraction of scattering less than 30°） basal-fiber texture through hot extrusion exhibits strong grain-size dependent yield strength, Samples with grain sizes varying from 4,5 to 22,3 μm were obtained by altering annealing time durations, The Hall-Petch relations of tension and compression are σ.2 = 86＋200d^-1/2 and σ0.2 = 17 ＋ 327d^-1/2, respectively, Considering the correlation between grain orientation and deformation modes, a novel weighted average method of calculating friction stress Cro was proposed, and results of calculation agreed with the experimental ones, which can reasonably understand the yielding behavior in tension and compression,
基金Supported by the National Natural Science Foundation of China,No. 30271478
文摘AIM: To construct the expression vector of B3 (scdsFv)-SEA (D227A) and to identify its binding and cytotoxic ability to B3 antigen positive carcinoma cell lines.METHODS: This fusion protein was produced by a bacterial expression system in this study. It was expressed mainly in the inclusion body. The gene product was solubilized by guanidine hydrochloride, refolded by conventional dilution method, and purified using SP-sepharose cation chromatography.RESULTS: The expression vector B3 (scdsFv)-SEA-PETwas constructed, the expression product existed mainly in the inclusion body, the refolding product retained the binding ability of the single-chain antibody and had cytotoxic effect on HT-29 colon carcinoma cells. The stability assay showed that the resulting protein was stable at 37 ℃.CONCLUSION: This genetically engineered B3 (scdsFv)-SEA fusion protein has bifunction of tumor targeting and tumor cell killing and shows its promises as an effective reagent for tumor-targeted immunotherapy.
基金supported by the General Program of the National Natural Science Foundation of China (Grant No. 82073376)。
文摘Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.
基金financially supported by the National Natural Science Foundation of China(No.51271046)
文摘The influence of asymmetric reduction rolling （ARR） on the microstructure, texture and mechanical properties of AZ91 was investigated. The microstructural characteristics of the AZ91 sheet processed by symmetric roiling （SR） were the twins, intersection of twins and dynamic recrystalization （DRX） grains around the coarse grains and within the twins. However, the amount of twins and DRX grains in ARRed AZ91 was much smaller than that in SRed AZ91. The SRed AZ91 after annealing exhibited fine DRX grains and some coarse grains with a size of ~ 100 pro. The grains in ARRed AZ91 after annealing were much finer and more homogeneous than those in SRed AZ91 after annealing. The intensity of basal texture of ARRed AZ91 after annealing was lower than that of SRed AZ91 rolling after annealing. The average Schmid factor of ARRed AZ91 is 0.34, which is higher than that of SRed AZ91. The yield strength and ultimate tensile strength of the ARRed AZ91 sheet were inCreased to 16.1% and 31.8% compared to SRed AZ91 sheet, from 155 to 180 MPa, and from 220 to 290 MPa, respectively. The improvement of mechanical properties in ARRed AZ91 after annealing was attributed to much finer, more homogeneous DRX grains and weaker basal texture.
基金supported by the General Program of National Natural Science Foundation of China(Grant No.82073376)。
文摘Objective:Malignant peritoneal mesothelioma(MPM)is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options.This study investigated the in vitro and in vivo efficacy of natural killer(NK)cells for treatment of MPM.Methods:An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system,the Cell Counting Kit-8 assay,and Wright-Giemsa staining.The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays.The ability of NK cells to kill MPM cells was determined based on live cell imaging,transmission electron microscopy,and scanning electron microscopy.An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index,small animal magnetic resonance imaging,and conventional histopathologic,cytologic,and hematologic studies.Results:NK cells effectively killed MPM cells through the release of effector molecules(granzyme B,perforin,interferon-γ,and tumor necrosis factor-α)in a dose-and density-dependent manner.The NK cell killing process potentially involved four dynamic steps:chemotaxis;hitting;adhesion;and penetration.NK cells significantly reduced the tumor burden,diminished ascites production,and extended survival with no significant hematologic toxicity or organ damage in NOG mice.Conclusions:NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.
基金supported by grants from the National Natural Science Foundation of China(31230032,31171083, and 31471071)Fundamental Research Funds for the Central Universities of China(WK2070000033)+1 种基金the Natural Science Foundation of Anhui Province,China(1208085MH179)Hefei Science Center,CAS "User with Potential"(2015HSC-UP017)
文摘Abstract Previous studies have suggested that cortical functional reorganization is associated with motor recovery after stroke and that normal afferent sensory information is very important in that process. In this study, we selected patients who had a stroke in or under the thalamus, with potentially impaired afferent sensory information and analyzed the differences between these patients and healthy controls at three levels： brain regions, the functional con- nectivity between brain areas, and the whole-brain func- tional network. Compared with healthy controls, regionalhomogeneities in the left middle temporal gyrus decreased and functional connectivity between the left middle tem- poral gyrus and the stroke area increased in the patients. However, there was no significant change in the whole- brain functional network. By focusing on stroke located in or under the thalamus, our study contributes to wider inquiries into understanding and treating stroke.
文摘目的:探讨鸟苷酸结合蛋白α亚基(guanine nucleotide binding protein alpha subunit,Gsα)表达与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)主要临床病理特征及预后的相关性。方法:收集首都医科大学附属北京世纪坛医院65例PMP患者病理标本,行常规组织病理学和定量免疫组织化学检测Gsα蛋白表达,研究Gsα蛋白表达与主要临床病理特征及预后的相关性。结果:65例PMP肿瘤行定量免疫组织化学分析,Gsα高表达者35例(53.8%),低表达者30例(46.2%)。单因素分析显示,Gsα高表达与下列5个临床病理指标呈正相关:术前肿瘤标志物(χ^(2)=3.68,P=0.087)、术中腹水量(χ^(2)=3.69,P=0.055)、腹膜癌指数评分(peritoneal cancer index,PCI)(χ^(2)=3.12,P=0.077)、肿瘤细胞减灭程度评分(completeness of cytoreduction,CC)(χ^(2)=2.72,P=0.099)、组织病理分级(χ^(2)=5.85,P=0.016)。多因素分析显示,Gsα蛋白高表达仅与组织病理分级呈独立正相关:高级别或高级别伴印戒细胞的组织病理类型(OR=3.47,95%CI:1.1~15.6,P=0.029)。Cox多因素分析显示,年龄(HR=8.08,95%CI:2.42~26.97,P=0.001)、既往手术(HR=0.24,95%CI:0.07~0.81,P=0.022)、组织病理分级(HR=3.92,95%CI:1.12~13.70,P=0.032);Gsα蛋白表达(HR=3.25,95%CI:1.01~10.5,P=0.048)为独立预后因素。结论:Gsα蛋白高表达与高级别或高级别伴印戒细胞的组织病理类型呈正相关,提示PMP预后不良。
基金supported by grants from the National Natural Science Foundation of China(No.32371217,32070860)the National Key R&D Plan of China(No.2021YFA1101002)+1 种基金Tianjin Natural Science Foundation(China)(No.22JCYBJC01220)the National Students'Platform for Innovation and Entrepreneurship Training Program(China)(No.202410055320,202410055676).
文摘Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long interspersed element-1(LINE-1)is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development.In this review,we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency.We also explore the critical function of LINE-1 activation and its rich functional reservoir,which is exploited by the host to provide cis-regulatory elements and functional proteins.Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation,histone methylation,ubiquitination,and RNA methylation.The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages.Accordingly,the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes,including the opening of chromatin architecture,zygotic genome activation,aging,and age-related disorders.It may reflect an effect on totipotency and pluripotency of mammalian development.Underscoring its pivotal significance,the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.
文摘This paper analyzes the development of spatial concentration of various innovation activities in China from 2000 to 2015 by using a generalized Theil index based on a balanced provincial dataset.It tracks concentration development back to the developing heterogeneity within and between regions in general and the mega-economic zones in particular.Results show that innovation activities tend to be distributed unequally across provinces in China,with more pronounced unequal distribution of innovation outcomes than innovation inputs.Over the research period,the innovation activities considered became more and more equally distributed across provinces.The between-region inequality of innovation activities has,however,not yet significantly improved,despite the implementation of Chinese regional policies to encourage more equal regional development.Instead,more equal distribution of innovation activities within megaeconomic zones is observed.
