The Neue Nationalgalerie(1968)is considered an icon of the 20th century and part of the legacy of Mies van der Rohe.Almost 50 years after its construction the building showed some physiological decay;however,it has be...The Neue Nationalgalerie(1968)is considered an icon of the 20th century and part of the legacy of Mies van der Rohe.Almost 50 years after its construction the building showed some physiological decay;however,it has been considered obsolete due to the changing standards of use and comfort of an international art gallery affected also by a growing flux of visitors.The paper investigates the future of such an icon of modern architecture moving from some open issues of the intervention carried out by David Chipperfield started up in 2015 and now in an advanced stage.The refurbishment is pursuing the modernization of the building,but trying to match the historical values with the requirements of climate control and safety.The binomials memories/requirements and authenticity/form are at the base of the investigation.Although the intervention confirms the continuity of original use and it is aimed at keeping the image of the icon,it imposes transformations that belong to very different strategies,sometimes incompatible with the preservation of material meanings and values.The restoration work on modern heritage outlines how new cultural and socio-economic needs confront themselves with respecting/reproducing the appearance of the monument.展开更多
目的:旨在评价2018年之后微创根治性子宫切除术(MIS)与开腹根治性子宫切除术(ORH)治疗宫颈癌的术后疗效,探讨MIS和ORH在治疗宫颈癌中的价值。方法:系统检索PubMed、Embase及Web of Science自2018年之后发表的相关文献,初检获得399篇研...目的:旨在评价2018年之后微创根治性子宫切除术(MIS)与开腹根治性子宫切除术(ORH)治疗宫颈癌的术后疗效,探讨MIS和ORH在治疗宫颈癌中的价值。方法:系统检索PubMed、Embase及Web of Science自2018年之后发表的相关文献,初检获得399篇研究。经双人独立去重筛选后,最终纳入11篇符合预设标准的文献。采用RevMan 5.3软件进行Meta分析,纳入的结局指标包括死亡、复发、术后淋巴结转移、术后并发症、术后辅助治疗、手术时间、术中失血量、住院时长、5年无病生存率及5年总生存率等。结果:筛选后纳入11项研究,包括9028例患者。Meta分析显示(P < 0.05具有统计学意义),MIS与较低的死亡人数相关(95%CI = 0.66~0.94, P = 0.01),MIS术后辅助治疗人数少(95%CI = 0.72~0.88, P < 0.00001),MIS患者术后淋巴结转移少(95%CI = 0.70~0.80, P = 0002),MIS和ORH在住院时间上有显著差异,即MIS术后住院时间较ORH短(95%CI = −2.53~0.63, P = 0.001),MIS和ORH在5年无病生存率上有显著差异,ORH术后5年无病生存率优于MIS (95%CI = 1.01~1.59, P = 0.04),MIS术中失血量少于ORH,MIS和ORH在术中失血量上通过敏感性分析后有统计学意义,即微创术中失血量少(95%CI = −128.45~60.04, P < 0.00001)。MIS和ORH术后复发人数无显著差异(95%CI = −0.02~0.02, P = 0.95),MIS和ORH在术后并发症上无显著差异(95%CI = 0.67~1.44, P = 0.91),MIS和ORH在操作时间上无显著差异(95%CI = −42.47~60.55, P = 0.73),MIS和ORH在5年总生存率无显著差异(95%CI = 0.78~1.63, P = 0.52)。结论:微创根治性子宫切除术在降低围手术期死亡率、减少淋巴结转移、缩短住院时间及减少术中失血方面优于开腹手术,且术后辅助治疗需求更低;然而,其5年无病生存率不及ORH。这些发现为宫颈癌的手术治疗提供了重要的临床指导,有助于医生根据患者的具体情况选择最适合的手术方法,具有十分重要的临床意义。展开更多
AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiati...AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.展开更多
Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein ef...Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.展开更多
文摘The Neue Nationalgalerie(1968)is considered an icon of the 20th century and part of the legacy of Mies van der Rohe.Almost 50 years after its construction the building showed some physiological decay;however,it has been considered obsolete due to the changing standards of use and comfort of an international art gallery affected also by a growing flux of visitors.The paper investigates the future of such an icon of modern architecture moving from some open issues of the intervention carried out by David Chipperfield started up in 2015 and now in an advanced stage.The refurbishment is pursuing the modernization of the building,but trying to match the historical values with the requirements of climate control and safety.The binomials memories/requirements and authenticity/form are at the base of the investigation.Although the intervention confirms the continuity of original use and it is aimed at keeping the image of the icon,it imposes transformations that belong to very different strategies,sometimes incompatible with the preservation of material meanings and values.The restoration work on modern heritage outlines how new cultural and socio-economic needs confront themselves with respecting/reproducing the appearance of the monument.
基金Supported by the National Natural Science Foundation of China(No.81800423)the Guangdong Medical Science and Technology Research project(No.B2022102)。
文摘AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
基金financially supported by the National Science and Technology Innovation 2030 Grants(2021ZD0201600)the National Key R&D Program of China(2021YFA0717000)+2 种基金the Intramural Joint Program Fund of State Key Laboratory of Microbial Technology(Project No.SKLMTIJP-2024-05)the Natural Science Foundation of Qingdao-Original exploration project(Project No.24-4-4-zrjj-139-jch)the National Natural Science Foundation of China(31771380)。
文摘Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.
