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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai wanqi chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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光学体表监测技术引导的放射治疗应用现状与前景

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协和医学杂志 2024年第1期15卷 135-140页

作者：沈晶陈琬琦侯晓荣邱杰中国医学科学院北京协和医院放射治疗科北京100730 中山大学肿瘤防治中心核医学科广东中山510060

光学体表监测技术(surface guided radiation therapy,SGRT)是一种在放射治疗过程中对患者进行连续体位监测的无辐射、无创性技术,通过先进的3D光学表面定位及追踪技术,快速获取患者的体表轮廓信息,生成高精度的3D体表轮廓,可在放射治... 详细信息

光学体表监测技术(surface guided radiation therapy,SGRT)是一种在放射治疗过程中对患者进行连续体位监测的无辐射、无创性技术,通过先进的3D光学表面定位及追踪技术,快速获取患者的体表轮廓信息,生成高精度的3D体表轮廓,可在放射治疗期间对患者进行实时监测,保证放射治疗的精准性。SGRT已广泛应用于乳腺、颅内、头颈和四肢等不同部位肿瘤的放射治疗中,其优势在于减少初始摆位误差、实时监测治疗过程,并与呼吸门控和深吸气屏气治疗技术相结合。SGRT还可通过减少锥形束CT的使用进而降低辐射剂量,提高患者应用固定装置的舒适性,提升临床工作效率和安全性等。本文阐述SGRT常用系统及其临床应用,并探讨其局限性和未来发展前景。

关键词：光学体表监测技术表面成像放射治疗表面引导放射治疗

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多糖铁复合物胶囊联合复方硫酸亚铁叶酸片治疗妊娠期缺铁性贫血孕妇的疗效研究

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世界临床药物 2024年第4期45卷 380-384,390页

作者：陈婉琪熊琼英孝感市中心医院产科湖北孝感432000

目的观察多糖铁复合物胶囊联合复方硫酸亚铁叶酸片对妊娠期缺铁性贫血(iron deficiency anemia,IDA)孕妇的疗效。方法将本院于2022年1月至2023年4月期间收治的114例妊娠期IDA孕妇分为观察组和对照组,每组57例。对照组服用多糖铁复合物胶... 详细信息

目的观察多糖铁复合物胶囊联合复方硫酸亚铁叶酸片对妊娠期缺铁性贫血(iron deficiency anemia,IDA)孕妇的疗效。方法将本院于2022年1月至2023年4月期间收治的114例妊娠期IDA孕妇分为观察组和对照组,每组57例。对照组服用多糖铁复合物胶囊,观察组在对照组基础上加服复方硫酸亚铁叶酸片。比较两组孕妇的疗效、贫血指标、铁代谢指标、免疫功能、安全性指标及不良反应情况。结果治疗后,两组孕妇红细胞计数、血红蛋白、红细胞压积、血清铁蛋白、血清铁、CD3^(+)、CD4^(+)以及CD4^(+)/CD8^(+)均显著升高,且观察组高于对照组,转铁蛋白及CD8^(+)均较治疗前明显下降,观察组低于对照组(P<0.05)。观察组治疗总有效率(55/57,96.49%)高于对照组(47/57,82.46%,P<0.05)。结论多糖铁复合物胶囊联合复方硫酸亚铁叶酸片对妊娠期IDA具有较好的疗效。

关键词：妊娠期缺铁性贫血多糖铁复合物胶囊复方硫酸亚铁叶酸片

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A Model for Evaluation of Grain Sizes of Aluminum Alloys with Grain Refinement Additions

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Journal of Materials Science & Technology 2007年第5期23卷 619-622页

作者： Zhongwei chen Zhi HE wanqi JIE State Key Laboratory of Solidification Processing Northwestern Polytechnical University Xi＇an 710072 China

Based on the assumption that the nucleation substrates are activated by constitutional undercooling generated by an adjacent grain growth and solute distribution during the initial solidification, a model for calculation of the grain size of aluminum alloys with the grain refinement is developed, where the nucleation is dominated by two parameters, i.e. growth restriction factor Q and the undercooling parameter P. The growth restriction factor Q is proportional to the initial rate of constitutional undercooling development and can be used directly as a criterion of the grain refinement in the alloys with strong potential nucleation particles. The undercooling parameter P can be regarded as the maximum of constitutional undercooling △Tc. For weak potential nucleation particles, the use of RGS would be more accurate. The experimental data of the grain refinement of pure aluminum and AlSi7 alloys are coincident predicted results with the model.

关键词： Grain refinement Constitutional undercooling Nucleation Aluminum alloys

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Electromagnetic wave absorption performance of Ti_(2)O_(3)and vacancy enhancement effective bandwidth

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Journal of Materials Science & Technology 2021年第17期76卷 166-173页

作者： Xiankai Fu Bo Yang wanqi chen Zongbin Li Haile Yan Xiang Zhao Liang Zuo Key Laboratory for Anisotropy and Texture of Materials(Ministry of Education) School of Material Science and Engineering.Northeastern UniversityShenyang110819China

The microwave absorption properties of Ti_(2)O_(3)were systematically *** results indicate that Ti_(2)O_(3)has microwave absorption performance with a minimum reflection loss value of-37.6 d B at 18.6 GHz and an effective absorption bandwidth(RL<-10 d B)of 2 ***,vacancy defects were introduced into Ti_(2)O_(3)by carbothermal ***,the effective absorption bandwidth of Ti_(2)O_(3)with vacancy defects reach 3.2 ***-principles calculations provide evidence that vacancy defects result in the changes of electric dipole state,leading to a wider effective absorption *** results have significance in understanding the origin of electromagnetic phenomena and developing electromagnetic wave absorption materials.

关键词： Ti_(2)O_(3) Microwave absorption Vacancy Electric dipoles First-principles

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基于^(18)F-FDG PET/CT影像组学在食管癌诊疗中的应用进展

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医学综述 2024年第8期30卷 1001-1005页

作者：李冬园黄伟鹏陈淮陈婉琪林杨皓揭阳市人民医院医学影像中心广东揭阳522000

食管癌是消化道常见的恶性肿瘤之一,我国食管癌的治疗模式逐步向精准医学理念指导下的个体化多学科综合治疗模式演化。^(18)F-氟代脱氧葡萄糖(^(18)F-FDG)正电子发射体层成像(PET)/CT在食管癌的诊断及精准分期中起重要作用。但传统PET/C... 详细信息

食管癌是消化道常见的恶性肿瘤之一,我国食管癌的治疗模式逐步向精准医学理念指导下的个体化多学科综合治疗模式演化。^(18)F-氟代脱氧葡萄糖(^(18)F-FDG)正电子发射体层成像(PET)/CT在食管癌的诊断及精准分期中起重要作用。但传统PET/CT图像仍存在一定局限性。近年来,影像组学发展迅猛,采用PET/CT影像组学方法提取食管癌相应区域的图像特征获得了海量数据特征,并将其与患者的病灶信息、疗效、预后、生存期等临床参数结合后建立定量关系,最终将其应用于食管癌早期诊断、疗效评估及预测预后等方面。未来还需深入研究^(18)F-FDG PET/CT影像组学在食管癌诊疗中的应用。

关键词：食管癌 ^(18)F-氟代脱氧葡萄糖正电子发射体层成像 CT 影像组学

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Effects of hot-pressing parameters on microstructure and mechanical properties of composites synthesized by Al-TiO_(2) in-situ reaction

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中国科学:技术科学英文版 2023年第9期66卷 2725-2734页

作者： LIU Yin chen wanqi GU LiMing LI XiaoNan ZAN YuNing WANG QuanZhao WANG Dong XIAO BoLv MA ZongYi School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China Key Laboratory of Nuclear Materials and Safety Assessment Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Shi-changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Nuclear Equipment Division Beijing Institute of Nuclear EngineeringChina Nuclear Power Engineering Co.Ltd.Beijing 100840China

As a classic in-situ reaction, the Al-TiO_(2) reaction is expected to prepare aluminum matrix composites with high thermal *** this study, it was found that the preparation method of ensuring sufficient reaction using higher temperatures in previous studies was not conducive to acquiring optimized high-temperature strength. With the increase of hot-pressing temperature and the extension of holding time, the in-situ reaction became more thorough, but the strength of the composites first increased and then decreased. Coarsening of the microstructure at high temperatures would lead to degradation of strength and controlling the in-situ reaction process by the hot-pressing parameters could optimize the mechanical properties of the composites. Strengthening mechanisms at room and high temperatures were studied, and it was found that the load-transfer and Orowan strengthening mechanisms are the main strengthening effects at room temperature, while the pinning effect of fine particles became more crucial at elevated temperatures. As a result, the coarsening of the reinforcing phases was more detrimental to the hightemperature strength. Therefore, an insufficient in-situ reaction led to more excellent mechanical properties, and the composite hot-pressed at 605℃ and held for 2 h exhibited the highest strength, which was 367 MPa at room temperature and 170 MPa at 350℃.

关键词： metal matrix composites high energy ball milling high-temperature properties nanoparticles in-situ reaction

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Radiotherapy in combination with systemic therapies for brain metastases:current status and progress

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Cancer Biology & Medicine 2020年第4期17卷 910-922页

作者： Lei Liu wanqi chen Ruopeng Zhang Yuekun Wang Penghao Liu Xin Lian Fuquan Zhang Yu Wang Wenbin Ma Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Radiotherapy Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Brain metastases(BMs)are the most common cause of intracranial neoplasms in adults with poor *** BMs originate from lung cancer,breast cancer,or ***(RT),including whole brain radiotherapy(WBRT)and stereotactic radiation surgery(SRS),has been widely explored and is considered a mainstay anticancer treatment for *** the past decade,the advent of novel systemic therapies has revolutionized the treatment of *** this context,there is a strong rationale for using a combination of treatments based on RT,with the aim of achieving both local disease control and extracranial disease *** review focuses on describing the latest progress in RT as well as the synergistic effects of the optimal combinations of RT and systemic treatment modalities for BMs,to provide perspectives on current treatments.

关键词： supported by grants from Beijing Municipal Natural Science Foundation(Grant No.7202150) Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.2016-I2M-2-001)

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食管鳞癌患者临床病理特征及^(18)F-FDG PET/CT代谢参数与PD-L1的相关性

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国际医药卫生导报 2024年第11期30卷 1821-1827页

作者：陈婉琪王震汕曾丽婷洪邓辉陈杰文黄伟鹏揭阳市人民医院核医学科揭阳522000 揭阳市人民医院医学影像中心揭阳522000

目的探讨食管鳞癌(ESCC)患者临床病理特征及^(18)F-氟代脱氧葡萄糖(^(18)F-FDG)正电子发射计算机体层显像仪(PET/CT)代谢参数与程序性死亡受体配体-1(PD-L1)表达的相关性。方法回顾性分析2019年1月至2022年8月期间在揭阳市人民医院经手... 详细信息

目的探讨食管鳞癌(ESCC)患者临床病理特征及^(18)F-氟代脱氧葡萄糖(^(18)F-FDG)正电子发射计算机体层显像仪(PET/CT)代谢参数与程序性死亡受体配体-1(PD-L1)表达的相关性。方法回顾性分析2019年1月至2022年8月期间在揭阳市人民医院经手术治疗的91例ESCC患者临床病理特征及术前^(18)F-FDG PET/CT检查资料。其中,男性66例,女性25例,中位年龄65岁,PD-L1表达阳性45例、阴性46例。分析患者性别、年龄、发病部位、肿瘤分化程度、神经束侵犯、脉管癌栓、T分期、N分期、TNM分期、原发灶最大标准摄取值(SUV_(max))、代谢体积(MTV)、病灶糖酵解总量(TLG)与PD-L1表达水平的相关性。统计学方法采用Mann-Whitney U非参数检验、χ^(2)检验、Spearman相关分析及受试者操作特征曲线(ROC)。结果ESCC T分期、SUV_(max)、TLG均与其PD-L1阳性存在正相关关系,相关系数r分别为0.215、0.297、0.264(均P<0.05)。ROC显示,SUV_(max)、TLG预测PD-L1阳性的曲线下面积(AUC)为0.671、0.623。结论ESCC T分期及SUVmax、TLG与PD-L1表达水平存在相关性,可在一定程度上反映肿瘤的PD-L1表达情况。

关键词：食管鳞癌正电子发射计算机体层显像仪 ^(18)F-氟代脱氧葡萄糖程序性死亡受体配体-1

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Metal–organic framework wafer enabled fast response radiation detection with ultra-low dark current

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Nano Research 2024年第4期17卷 2988-2993页

作者： Meng Xu Jianxi Liu Wei Wu Yang chen Donghao Ma Sixin chen wanqi Jie Menghua Zhu Yadong Xu State Key Laboratory of Solidification Processing MIIT Key Laboratory of Radiation Detection Materials and Devices&School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China

Semiconductive metal–organic frameworks(MOFs)have attracted great interest for the electronic ***,dark currents of present hybrid organic–inorganic materials are 1000–10,000 times higher than those of commercial inorganic detectors,leading to poor charge ***,we demonstrate a ZIF-8(Zn(mim)_(2),mim=2-methylimidazolate)wafer with ultra-low dark current of 1.27 pA·mm^(-2) under high electric fields of 322 V·mm^(-1).The isostatic pressing preparation process provides ZIF-8 wafers with good ***,the presence of redox-active metals and small spatial separation between components promotes the charge *** ZIF-8-based semiconductor detector shows promising X-ray detection sensitivity of 70.82μC·Gy^(-1)·cm^(-2) with low doses exposures,contributing to superior X-ray imaging capability with a relatively high spatial resolution of 1.2 lp·mm^(-1).Simultaneously,good peak discrimination with the energy resolution of~43.78%is disclosed when the detector is illuminated by uncollimated 241Am@5.48 MeVα-*** results provide a broad prospect of MOFs for future radiation detection applications.

关键词： MOFs lead-free α-particles X-ray detection and imaging dark current fast response

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