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Severe acute respiratory syndrome coronavirus 2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination

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Chinese Medical Journal 2024年第22期137卷 2734-2744页

作者： Xiuwen Wang Yongzheng Li Junyan Jin Xiaoran Chai zhenglai Ma Junyi Duan Guanghui Zhang Tao Huang Xin Zhang Tong Zhang Hao wu Yunlong Cao Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for HIV/AIDS ResearchClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100069China Cancer and Stem Cell Biology Program Duke-NUS Medical SchoolSingapore Changping Laboratory Beijing 102299China

Background:T-cell-mediated immunity is crucial for the effective clearance of viral infection,but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines in people living with human immunodeficiency virus(PLWH)remain ***:Forty-five PLWH who had received antiretroviral therapy(ART)for more than two years and 29 healthy controls(HCs)at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose(week 0)and 4 or 12 weeks(week 4 or week 12)after receiving the third dose of inactivated SARS-CoV-2 *** cytometry,enzyme-linked immunospot(ELISpot),and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this ***:The results of the ELISpot and activation-induced marker(AIM)assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine,and a similar magnitude of immune response was induced against the Omicron(B.1.1.529)variant compared to the wild-type *** detail,spike-specific T-cell responses(measured by the ELISpot assay for interferonγ[IFN-γ]release)in both PLWH and HCs significantly increased in week 4,and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third *** the AIM assay,spike-specific CD4+T-cell responses peaked in both PLWH and HCs in week ***,significantly higher spike-specific CD8+T-cell responses were induced in PLWH than in HCs in week *** PLWH,the release of the cytokines interleukin-2(IL-2),tumour necrosis factor-alpha(TNF-α),and IL-22 by peripheral blood mononuclear cells(PBMCs)that were stimulated with spike peptides increased in week *** addition,the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week ***,the magnit

关键词： HIV People living with HIV SARS-CoV-2 vaccine T-cell responses Omicron variant

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Fargeted elimination of mutant mitochondria DNA in MELAS-iPSCs by mitoTALENs

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Protein & Cell 2018年第3期9卷 283-297页

作者： Yi Yang Han wu Xiangjin Kang Yanhui Liang Ting Lan Tianjie Li Tao Tan Jiangyun Peng Quanjun Zhang Geng An Yali Liu Qian Yu zhenglai Ma Ying Lian Boon Seng Soh Qingfeng Chen Ping Liu Yaoyong Chen Xiaofang Sun Rong Li Xiumei Zhen Yang Yu Xiaoping Li Yong Fan Key Laboratory for Major Obstetric Diseases of Guangdong Province Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 China Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China Center of Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 China Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 China Disease Modeling and Therapeutics Laboratory A'STAR Institute of Molecular and Cell Biology 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Biological Sciences National University of Singapore Singapore 117543 Singapore

Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells （MiPSCs） that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes （MELAS）. We engineered mitochondrial-targeted transcription activator-like effector nucleases （mitoTALENs） and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

关键词： mitochondria iPSCs TALEN MELAS

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Changing roles of CD3^(+)CD8^(low) T cells in combating HIV-1 infection

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Chinese Medical Journal 2023年第4期136卷 433-445页

作者： Xin Zhang Xiuwen Wang Ling Qin Xiaofan Lu Zhiying Liu Zhen Li Lin Yuan Rui Wang Junyan Jin zhenglai Ma Hao wu Yonghong Zhang Tong Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Research Center for Biomedical Resources Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into ***:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 ***:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of *** HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually ***,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection *** classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic ***,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of ***,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in ***,the nonincrease i

关键词： Acute human immunodeficiency virus-1 infection HIV CD3^(+)CD8^(low)T cells Immune activation Programmed cell death protein 1 T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains

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Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8^(+)T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine

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Chinese Medical Journal 2023年第24期136卷 2938-2947页

作者： Junyan Jin Xiuwen Wang Yongzheng Li Xiaodong Yang Hu Wang Xiaoxu Han Jin Sun zhenglai Ma Junyi Duan Guanghui Zhang Tao Huang Tong Zhang Hao wu Xin Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100871China Tian Yuan Studio Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor ***,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated ***:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this *** amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third ***:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in ***,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker *** with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in ***,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T ***,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was in

关键词： HIV TIGIT T-lymphocytes SARS-CoV-2 Booster vaccination Immunity

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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA

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Chinese Medical Journal 2024年第6期137卷 729-736页

作者： Lin Yuan Zhiying Liu Xin Zhang Feili Wei Shan Guo Na Guo Lifeng Liu zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao wu Tong Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV *** digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard ***,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV ***:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV *** coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,*** assay linear dynamic range and lower limit of detection(LLOD)were also ***:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA *** the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit *** HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell ***:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and *** can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials.

关键词： Human immunodeficiency virus HIV Integrated HIV-1 DNA Total HIV DNA Droplet digital polymerase chain reaction HIV reservoir Antiretroviral therapy

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铝电解生产中偏心阳极的研究与应用

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甘肃冶金 2023年第5期45卷 84-86,90页

作者：张正来周德堂武文奇兰州铝业有限公司生产运行部甘肃兰州730089

为了减少铝电解生产中铝电解槽A、B面阳极碳块之间散热大的问题,对炭素成型机进行改造生产出碳碗中心距尺寸向左偏移的阳极碳块,经组装进入电解槽后实现电解槽A、B面上阳极碳块之间的距离的缩短,从而使铝电解槽垂直电流向中心部位收拢,... 详细信息

为了减少铝电解生产中铝电解槽A、B面阳极碳块之间散热大的问题,对炭素成型机进行改造生产出碳碗中心距尺寸向左偏移的阳极碳块,经组装进入电解槽后实现电解槽A、B面上阳极碳块之间的距离的缩短,从而使铝电解槽垂直电流向中心部位收拢,炉帮增厚,提高电流效率,降低直流电耗。

关键词：铝电解电解槽阳极碳块电流分布

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同心套管与异心套管管排余热回收装置的实验研究

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制冷学报 2016年第3期37卷 48-52页

作者：张正来韩晓星王亚雄吴伟李棚辉内蒙古科技大学化学与化工学院包头014010

本文设计了一套以铝为壳体,丙酮为工质的新型热管换热器。研究了不同热负荷,其系统倾角分别为30°、45°、60°、75°、90°,工质充液率为30%条件下的运行特性。通过改变倾斜角度及加热段长度和操作温度来测试余热回收系统的最佳传热性... 详细信息

本文设计了一套以铝为壳体,丙酮为工质的新型热管换热器。研究了不同热负荷,其系统倾角分别为30°、45°、60°、75°、90°,工质充液率为30%条件下的运行特性。通过改变倾斜角度及加热段长度和操作温度来测试余热回收系统的最佳传热性能和效率。结果显示:在实验条件下,最大传热量随着操作温度的升高、蒸发段长度的增长而增大,最佳倾斜角度为60°,最佳长度为270 mm。

关键词：重力热管余热回收传热性能

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思政引领下新农科复合型创新人才培养探索——以“作物栽培学”课程改革为例

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中国农业教育 2023年第6期24卷 29-35页

作者：张文静武立权黄正来安徽农业大学安徽合肥230036

在教育部《关于加快新农科建设推进高等农林教育创新发展的意见》和“农业强国”精神引领下,文章提出以现代农业发展需求为导向、以学生发展为中心,加强专业课程思政建设,探索构建新农科复合型创新人才培养模式。以农学专业核心课程“... 详细信息

在教育部《关于加快新农科建设推进高等农林教育创新发展的意见》和“农业强国”精神引领下,文章提出以现代农业发展需求为导向、以学生发展为中心,加强专业课程思政建设,探索构建新农科复合型创新人才培养模式。以农学专业核心课程“作物栽培学”为例,在课程教学过程中与时俱进增加思政元素,培养专业自信和“知农爱农”情怀;将课程讲授内容纵向重构为“基础知识、专业知识、应用专业知识解决实际问题”等模块;建立“学生创新/创业研究+课堂研讨”的知识提升教学模式;联合试验站,构建“教学内容+田间实物”相结合的虚拟实物化课堂;基于OBE理念,组建“校内专业教师+校外企业导师”双师培养团队。以上课程改革,为培养高素质农学复合型创新人才提供了实践经验,提升了地方农业院校服务乡村振兴战略水平。

关键词：新农科思政教育复合型创新人才教学模式

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性别差异对自身免疫性肝炎患者临床特征及预后的影响

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临床肝胆病杂志 2021年第7期37卷 1636-1643页

作者：伍慧丽时红波刘燕敏丁美马正来刘霜陈煜段钟平首都医科大学附属北京佑安医院疑难肝病及人工肝中心北京100069 首都医科大学附属北京佑安医院肝病研究所北京100069 首都医科大学附属北京佑安医院肝病免疫科北京100069 首都医科大学附属北京佑安医院肝衰竭与人工肝治疗研究北京市重点实验室北京100069

目的自身免疫性肝炎(AIH)主要发生在女性,目前对男性AIH患者的研究甚少,本研究比较不同性别AIH之间的临床差异。方法收集2009年10月—2019年10月在北京佑安医院住院并确诊为AIH的患者398例进行回顾性研究,分为男(n=48)、女(n=350)两组,... 详细信息

目的自身免疫性肝炎(AIH)主要发生在女性,目前对男性AIH患者的研究甚少,本研究比较不同性别AIH之间的临床差异。方法收集2009年10月—2019年10月在北京佑安医院住院并确诊为AIH的患者398例进行回顾性研究,分为男(n=48)、女(n=350)两组,对一般情况、临床特点及预后等影响因素进行分析。主要研究终点为死亡或肝移植治疗。正态分布的计量资料2组间比较采用t检验,非正态分布计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ^(2)检验或Fisher精确概率法。采用Cox比例风险模型进行单变量和多变量分析。结果年龄方面,51-60岁是两组的发病高峰,但是男性在21-30岁时段确诊率明显高于女性(8/48 vs 24/334,χ^(2)=4.915,P=0.027),而在41-50岁时段则低于女性(7/48 vs 97/334,χ^(2)=4.428,P=0.035)。AIH分类方面,男性特发性AIH占比更高(31/48 vs 170/350,χ^(2)=4.329,P=0.037),但男性合并其他自身免疫性疾病尤其是甲状腺功能亢进比例低于女性(0/48 vs 39/348,P=0.008)。实验室检查方面,男性ANA≥1∶100(42/48 vs 325/340,χ^(2)=5.375,P=0.020)和SSA/SSB(2/48 vs 76/340,χ^(2)=7.566,P=0.006)阳性率显著低于女性患者;男性ANA≥1∶1000的比率显著低于女性(P42μmol/L、淋巴细胞计数<1.2×10^(9)/L以及补体C3<0.588 g/L(P值均<0.05)。结论性别差异对AIH患者临床表现和预后有一定影响,主要表现在男性患者更年轻、预后更差。

关键词：肝炎,自身免疫性性别体征和症状预后

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基于全球文献计量的小麦响应气候变暖的研究

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中国农学通报 2019年第23期35卷 142-151页

作者：刘秋霞吴汉卿黄正来安徽农业大学农学院合肥230036 中国农业大学资源与环境学院北京100193 江苏省现代农作物生产协同创新中心南京210095

基于Web of ScienceTM核心合集数据库,利用R语言Bibliometrix包,从高被引论文、来源期刊、高频关键词、高产作者等方面对21世纪以来(2000—2018)发表的有关气候变化对小麦影响的研究文献进行计量分析,并构建了文献共被引、关键词共现、... 详细信息

基于Web of ScienceTM核心合集数据库,利用R语言Bibliometrix包,从高被引论文、来源期刊、高频关键词、高产作者等方面对21世纪以来(2000—2018)发表的有关气候变化对小麦影响的研究文献进行计量分析,并构建了文献共被引、关键词共现、国家共被引、文献历史被引网络图谱以及关键词的聚类分析概念图,进而研究小麦对气候变化响应的最新研究进展、热点及趋势。结果表明:从高产国家来看,中国发文量最多,其次是美国和印度。该领域TOP 10的高产作者中,中国占有四位。该领域论文主要发表在《Agricultural and Forest Meteorology》、《Field Crops Research》和《Climatic Change》期刊。关键词的共现和聚类分析表明,目前气候变暖对小麦的影响研究主要集中在温度变化对小麦生长及其产量的影响、气候变化对小麦影响的模型研究、小麦对气候变化的响应及CO2浓度、温度升高对小麦生长和产量的影响等方面。文献历史被引分析发现,Local Citations (LCS)高的文章均与模型研究有关,说明利用模型来研究气候变化对小麦的影响也是目前的热点及趋势之一。

关键词：小麦气候变暖 Web of Science 研究热点文献计量分析 R语言

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