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SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang sheng Hu min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses

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Electroacupuncture activates AMPKa1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics

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Journal of Integrative Medicine 2024年第5期22卷 588-599页

作者： Wei-wei Jia Hua-wei Lin min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of Rehabilitation Medicine Fujian University of Traditional Chinese Medicine The Institute of Rehabilitation Industry Fujian University of Traditional Chinese Medicine National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese Medicine Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese Medicine

Objective: Studies have shown that electroacupuncture(EA) can alleviate cognitive impairments from Alzheimer's disease(AD) by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial ***: The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKa1-subunit conditional knockout(AMPKa1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition,chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 ***: Both APP/PS1 mice and AMPKa1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferatoractivated receptor-γ coactivator-1a(PGC-1a) pathway increased pathological amyloid-β(Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1a pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by ***: The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1a pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

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Milestone progress of the HEPS booster commissioning

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Nuclear Science and Techniques 2024年第1期35卷 170-177页

作者： Yue-Mei Peng Jian-She Cao Jin-Hui Chen Hai-Yi Dong Ping He Yi Jiao Ling Kang Wen Kang Jian Li Jing-Yi Li Guo-Ping Lin Fang Liu Feng-Li Long Cai Meng Xin Qi Hua-min Qu Yan-Feng Sui sheng Wang Gang Xu Qiang Ye Jing Zhang Pei Zhang Wei-min Pan Key Laboratory of Particle Acceleration Physics and Technology Institute of High Energy PhysicsChinese Academy of Sciences19B Yuquan RoadShijingshan DistrictBeijing 100049China University of the Chinese Academy of Sciences 19A Yuquan RoadShijingshan DistrictBeijing 100049China

The high-energy photon source(HEPS)is the first fourth-generation synchrotron light source facility in *** HEPS injector consists of a linear accelerator(Linac)and a full energy *** booster captures the electron beam from the Linac and increases its energy to the value required for the storage *** full-energy beam could be injected to the storage ring directly or after“high-energy accumulation.”On November 17,2023,the key booster parameters successfully reached their corresponding target *** milestone results were achieved based on numerous contributions,including nearly a decade of physical design,years of equipment development and installation,and months of beam *** measured at the extraction energy of 6 GeV,the averaged beam current and emittance reached 8.57 mA with 5 bunches and 30.37 nm rad with a single-bunch charge of 5.58 nC,compared with the corresponding target values of 6.6 mA and 35 nm rad,*** paper presents the physical design,equipment development,installation,and commissioning process of the HEPS booster.

关键词： High energy photon source Booster Beam commissioning

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“义”在宋代的应用与价值

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河北学刊 2024年第4期44卷 92-102页

作者：程民生河南大学历史文化学院

宋代是义观念实践的一个历史高潮。宋代之义具有崇高神圣的精神地位,受到上至皇帝、下及盗贼的追捧。宋代强调君臣以义立,皇帝以义结天下人心,以义对内理政、对外交好。士大夫之公义指正义、刚正的气概,是高尚情操,其小义主要体现在对... 详细信息

宋代是义观念实践的一个历史高潮。宋代之义具有崇高神圣的精神地位,受到上至皇帝、下及盗贼的追捧。宋代强调君臣以义立,皇帝以义结天下人心,以义对内理政、对外交好。士大夫之公义指正义、刚正的气概,是高尚情操,其小义主要体现在对社会、朋友的责任担当与无私帮助,个人之间也多称兄道弟以及结拜兄弟。武人之公义通常都是忠于朝廷,慷慨赴义,其私义多表现于结拜兄弟。民间之义除公益之义外,还有更多样的表现形式,如互济互助、扶正驱邪,包括义居、复仇杀人,结义现象更为普遍,既有义兄弟,也有义父子,均受到法律的承认。义观念的强化和实践,体现着宋人的奉献精神、自律精神、契约精神。从开国皇帝赵匡胤传下来的以义治国策略,是宋代政治文明的重要组成部分。

关键词：义义举结义宋代

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运动界面的电磁波相位匹配

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物理学报 2024年第13期73卷 121-125页

作者：袁金健顾民黄润生南京大学物理学院南京210093

电磁波在运动物体表面的折射反射和内部的传播研究中,运动界面的电磁场相位匹配作为一个重要问题,只有用Galileo变换的讨论,但运动边界对电磁波传播的相对论效应是不应被忽略的.本文从空间曲面方程的定义和相对性原理出发导出了运动曲... 详细信息

电磁波在运动物体表面的折射反射和内部的传播研究中,运动界面的电磁场相位匹配作为一个重要问题,只有用Galileo变换的讨论,但运动边界对电磁波传播的相对论效应是不应被忽略的.本文从空间曲面方程的定义和相对性原理出发导出了运动曲面单位法向量的变换式,基于该变换式导出了运动边界的电磁场边界条件.同时基于单位法向量的变换式导出考虑相对论效应时电磁波在运动边界的相位匹配.虽然该工作不涉及量子效应的影响,但可以为电磁波通讯和电磁遥感遥测的理论分析提供一些参考.

关键词：电磁波运动界面相位匹配相对性原理

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Non-proteolytic ubiquitination of HBx controls HBV replication

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Virologica Sinica 2024年第2期39卷 338-342页

作者： Xiangpeng sheng Yi Yang min Zhu Linlin Zhou Fang Zhu Yuanfei Zhu Siying Dong Hui Kong Honghua Wang Ji Jiang mingyue Wan mingyang Feng Qiang Deng Yumin Xu Qing You Ronggui Hu State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Thoracic Surgery Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Shanghai Key Laboratory of Plant Molecular Sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China Department of Pathogenic Biology West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China School of Medicine Guizhou UniversityGuiyang 550025China Key Laboratory of Medical Molecular Virology(MOE&MOH) School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Hospital Infection Management Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Dear Editor,Although effective vaccines and antiviral therapies are available,hepatitis B virus(HBV)infection is still a serious global health *** HBV infection remains the principal cause of liver cirrhosis and hepatocellular carcinoma(HCC).HBV is a small DNA virus,owning a~3.2 kb genome that encodes several proteins:viral DNA polymerase,core antigen(HBcAg),E antigen(HBeAg),three surface antigens(PreS1/PreS2/HBsAg),and a regulatory X protein(HBx)(Lamontagne et al.,2016).X protein,named for its lack of homology with any known proteins,is a 154 aa protein that plays an essential role in HBV biology and regulates the development of HCC(Yang et al.,2022).Although previous studies have strongly expanded our understanding of HBx,the regulation of HBx is not completely elucidated.

关键词： infection cirrhosis

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Oxidation behavior of low-grade vanadiferous titanomagnetite concentrate with high titanium

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Journal of Iron and Steel Research International 2024年第2期31卷 329-341页

作者： Jin-sheng Liu Zhen-xing Xing Gong-jin Cheng Xue-yong Ding Xiang-xin Xue School of Metallurgy Northeastern UniversityShenyang110819LiaoningChina Liaoning Key Laboratory of Recycling Science for Metallurgical Resources Shenyang110819LiaoningChina Innovation Research Institute of Vanadium and Titanium Resource Industry Technology Northeastern UniversityShenyang110819LiaoningChina

In order to clarify the oxidation mechanisms and make better use of the low-grade vanadiferous titanomagnetite concentrate with high titanium(LVTC),the oxidation behavior of LVTC was *** results showed that oxidation degree was achieved within 90 min when temperature was not lower than 700°C,and the main phases of the oxidized LVTC consisted of Fe9TiO15,Fe2O3,CaSiTiO5 and a small amount of *** temperature is favorable to the formation of *** surface of LVTC gradually becomes rough,with fine particles of needle-like and granular shape appearing on the surface,which finally turn from laminar to creamy,spread out,and are interspersed with many tiny *** phase oxidation paths in LVTC were as follows:(1)Fe2.75Ti0.25O4→Fe9TiO15+Fe2O3;(2)Fe2.75Ti0.25O4→Fe2O3+FeTiO3→Fe2TiO5;(3)FeTiO3→Fe2O3+Fe2Ti3O9→*** is predominantly mesoporous whether oxidized or not,with the pores mainly distributed in the range of 2–40 nm,and the specific surface area of LVTC decreases significantly with increasing temperature.

关键词： Low-grade vanadiferous titanomagnetite concentrate Oxidation degree Phase transformation Micromorphology Oxidation path Pore structure

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In situ calibrated angle between the quantization axis and the propagating direction of the light field for trapping neutral atoms

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Chinese Physics B 2024年第2期33卷 318-323页

作者：郭瑞军何晓东盛诚王坤鹏许鹏刘敏王谨孙晓红曾勇詹明生 Henan Key Laboratory of Laser and Optoelectronic Information National Center for International Joint Research of Electronic Materials and SystemsSchool of Electrical and Information EngineeringZhengzhou UniversityZhengzhou 450001China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan 430071China

The recently developed magic-intensity trapping technique of neutral atoms efficiently mitigates the detrimental effect of light shifts on atomic qubits and substantially enhances the coherence time. This technique relies on applying a bias magnetic field precisely parallel to the wave vector of a circularly polarized trapping laser field. However, due to the presence of the vector light shift experienced by the trapped atoms, it is challenging to precisely define a parallel magnetic field, especially at a low bias magnetic field strength, for the magic-intensity trapping of85Rb qubits. In this work, we present a method to calibrate the angle between the bias magnetic field and the trapping laser field with the compensating magnetic fields in the other two directions orthogonal to the bias magnetic field direction. Experimentally, with a constantdepth trap and a fixed bias magnetic field, we measure the respective resonant frequencies of the atomic qubits in a linearly polarized trap and a circularly polarized one via the conventional microwave Rabi spectra with different compensating magnetic fields and obtain the corresponding total magnetic fields via the respective resonant frequencies using the Breit–Rabi formula. With known total magnetic fields, the angle is a function of the other two compensating magnetic ***, the projection value of the angle on either of the directions orthogonal to the bias magnetic field direction can be reduced to 0(4)° by applying specific compensating magnetic fields. The measurement error is mainly attributed to the fluctuation of atomic temperature. Moreover, it also demonstrates that, even for a small angle, the effect is strong enough to cause large decoherence of Rabi oscillation in a magic-intensity trap. Although the compensation method demonstrated here is explored for the magic-intensity trapping technique, it can be applied to a variety of similar precision measurements with trapped neutral atoms.

关键词： quantization axis trapping laser angle compensating magnetic fields

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强吸收纳米粒子团簇的光泳力悬浮及热泳力下的迁移行为

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物理学报 2024年第13期73卷 164-174页

作者：黄雪峰刘敏卢山张敏琦李盛姬罗丹杭州电子科技大学物理系杭州310018 杭州电子科技大学材料与环境工程学院杭州310018

为了探索空气中强吸收纳米粒子团簇在激光作用下的悬浮以及迁移行为,提出采用反向传输的双贝塞尔光束对纳米粒子团簇进行捕获及悬浮,而后释放团簇,观察和计算分析团簇的迁移行为.两束贝塞尔光束由锥透镜和偏振分光方式产生,进行反向水... 详细信息

为了探索空气中强吸收纳米粒子团簇在激光作用下的悬浮以及迁移行为,提出采用反向传输的双贝塞尔光束对纳米粒子团簇进行捕获及悬浮,而后释放团簇,观察和计算分析团簇的迁移行为.两束贝塞尔光束由锥透镜和偏振分光方式产生,进行反向水平布置,形成三维光阱,光阱刚度可通过调节两束贝塞尔光束的功率比进行控制.悬浮室内的粒子通过微弱气流进行流化,而后被光阱捕获和悬浮.采用高速摄像仪对团簇的悬浮及迁移过程进行记录,然后通过图像分析来获取粒子运动参数.以强吸收性超细煤粉粒子团簇为对象,首先对其进行悬浮和释放迁移的实验研究,而后对团簇所受的光泳力、重力、浮力、曳力以及热泳力进行计算和分析.实验和计算的结果表明:强吸收性纳米粒子团簇在激光作用下产生的光泳力占主导作用;团簇能够被稳定地悬浮在反向传输的双贝塞尔光束形成的三维势阱中,通过调整悬浮的位置而达到与重力、浮力、曳力等的动态平衡;利用悬浮的相对不稳定度分析评价强吸收性粒子团簇的稳定性,超细煤粉粒子团簇的最小相对不稳定度可达0.075;通过对团簇释放后的高速图像进行分析,可获得团簇的迁移运动参数,从而测量出团簇所受的热泳力;对于等效粒径为13—21μm的超细煤粉粒子团簇,其热泳力量级为10-11—10-10N,随着团簇粒径的增大,热泳力线性增大,与理论计算结果趋势一致.通过利用激光对粒子进行悬浮和释放的方式为热泳力的测量和研究提供了一种新的研究思路,也为气体介质中粒子的控制和输运展现了一种新的操控手段.

关键词：激光悬浮光泳力热泳力强吸收性纳米团簇

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2种乳酸菌发酵酸面团对馒头品质与风味的影响

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中国食品学报 2024年第2期24卷 200-209页

作者：邢倩刘敏柯胜周中凯石河子大学农产品加工与质量安全控制重点实验室新疆石河子832003 天津科技大学食品科学与工程学院天津300457

选取融合魏斯氏菌、植物乳酸杆菌2种乳酸菌分别与酵母发酵以及共同与酵母发酵(LP+WC)制备酸面团,与仅添加酵母的酸面团(CK)对比,研究不同酸面团的乳酸菌菌落数变化、有机酸含量及其对馒头面团水分分布、流变学特性以及馒头品质和风味的... 详细信息

选取融合魏斯氏菌、植物乳酸杆菌2种乳酸菌分别与酵母发酵以及共同与酵母发酵(LP+WC)制备酸面团,与仅添加酵母的酸面团(CK)对比,研究不同酸面团的乳酸菌菌落数变化、有机酸含量及其对馒头面团水分分布、流变学特性以及馒头品质和风味的影响。结果表明,添加乳酸菌发酵的酸面团24 h后pH值保持稳定,WC+LP组乳酸菌菌落数在24 h达到最高,为9.34 lg(CFU/g酸面团)。发酵24 h后,LP组乳酸含量最多,为7.75 mg/g酸面团;LP+WC组乙酸含量最多,为0.49 mg/g酸面团。添加酸面团的馒头面团T2弛豫时间为235.43 ms,CK组为252.35 ms,低于未添加酸面团的馒头面团的T2弛豫时间289.94 ms,且使馒头面团黏弹性下降。酸面团的加入增加了馒头的比容,LP+WC组比容最大为2.17 mL/g,较普通干酵母面包(OSB)增长了20.56%,降低了馒头的硬度,LP+WC组的硬度较OSB降低了25.89%,提升了馒头的弹性,LP+WC组弹性较普通干酵母面包(OSB)增长了4.5%。GC-MS分析表明,在LP+WC组中检出35种风味物质,种类最多,表明融合魏斯氏菌和植物乳酸杆菌复合发酵酸面团对馒头品质及风味有改善作用。

关键词：融合魏斯氏菌植物乳酸杆菌酸面团馒头品质风味

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