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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang yueying Zhen Zhihong Wang Hesheng Zhang Richard Jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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Atomic-level coupled RuO_(2)/BaRuO_(3) heterostructure for efficient alkaline hydrogen evolution reaction

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Journal of Energy Chemistry 2024年第1期88卷 356-362,I0009页

作者： yueying Yan Tian Meng Yuting Chen Yang Yang Dewen Wang Zhicai Xing Xiurong Yang State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022JilinChina School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026AnhuiChina

The slow water dissociation is the rate-determining step that slows down the reaction rate in alkaline hydrogen evolution reaction(HER).Optimizing the surface electronic structure of the catalyst to lower the energy barrier of water dissociation and regulating the binding strength of adsorption intermediates are crucial strategy for boosting the catalytic performance of HER.In this study,RuO_(2)/BaRuO_(3)(RBRO)heterostructures with abundant oxygen vacancies and lattice distortion were in-situ constructed under a low temperature via the thermal decomposition of gel-precursor.The RBRO heterostructures obtained at 550℃ exhibited the highest HER activity in 1 M KOH,showing an ultra-low overpotential of 16 mV at 10 mA cm^(-2)and a Tafel slope of 33.37 m V dec^(-1).Additionally,the material demonstrated remarkable durability,with only 25 mV of degradation in overpotential after 200 h of stability testing at 10 mA cm^(-2).Density functional theory calculations revealed that the redistribution of charges at the heterojunction interface can optimize the binding energies of H*and OH*and effectively lower the energy barrier of water dissociation.This research offers novel perspectives on surpassing the water dissociation threshold of alkaline HER catalysts by means of a systematic design of heterogeneous interfaces.

关键词： Heterostructure Hydrogen evolution reaction Interfacial electron transfer Oxygen vacancies

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Fast-Response Fiber-Optic FPI Temperature Sensing System Based on Modulated Grating Y-Branch Tunable Laser

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Photonic Sensors 2024年第1期14卷 59-72页

作者： Yang CHEUNG zhenguo JING Qiang LIU Ang LI yueying LIU Yihang GUO Sen ZHANG Dapeng ZHOU Wei PENG School of Physics Dalian University of TechnologyDalian 116024China School of Optoelectronic Engineering and Instrumentation Science Dalian University of TechnologyDalian 116024China School of Computer and Electronic Information/School of Artificial Intelligence Nanjing Normal UniversityNanjing 210023China

In this paper,a cost-effective and miniaturized instrument is proposed,which is based on a tunable modulated grating Y-branch(MG-Y)laser for rapid temperature measurement using a Fabry-Perot interferometer(FPI)sensor.The FPI sensor with a 1463-μm cavity length is a short segment of a capillary tube sandwiched by two sections of single-mode fibers(SMFs).This system has a broad tunable range(1527 nm-1567 nm)with a wavelength interval of 8 pm and a tuning rate of 100 Hz.Temperature sensing experiments are carried out to investigate the performance of the system by demodulating the absolute cavity length of the FPI sensor using a cross-correlation algorithm.Experimental results show that the sensor can reach the response time as short as 94 ms with the sensitivity of 802 pm/C.Benefiting from the homemade and integrated essential electrical circuits,the entire system has the small size,low cost,and practical application potential to be used in the harsh environment for rapid temperature measurement.

关键词： MG-Y laser interrogator rapid temperature measurement cross-correlation algorithm

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Vacancy engineering induced reaction kinetics enhancement of cobalt metaphosphate for pH-universal hydrogen evolution

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Nano Research 2024年第5期17卷 3879-3887页

作者： Yuting Chen Tian Meng Zhicai Xing yueying Yan Yang Yang Bohan Yao Dewen Wang Xiurong Yang State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China

Developing efficient pH-universal hydrogen evolution reaction(HER)catalysts is critical in the field of water electrolysis,however,which is severely hampered by the sluggish kinetics in alkaline media.Herein,a ruthenium(Ru)incorporation induced vacancy engineering strategy is firstly proposed to precisely construct oxygen vacancy(V_(O))-riched cobalt-ruthenium metaphosphate(CRPO)for high-efficiency pH-universal HER.The V_(O) modifies the electronic structure,improves the superficial hydrophilic and gas spillover capacity,it also reduces the coordination number of Ru atoms and regulates the coordination environment.Theoretical calculations indicate that Ru tends to adsorb H_(2)O and H^(*),whereas V_(O) tends to adsorb OH^(-),which greatly promotes the H_(2)O adsorption and the dissociation of HO-H bond.Ultimately,CRPO-2 exhibits remarkable HER performance,the mass activity is about 18.34,21.73,and 38.07 times higher than that of Pt/C in acidic,neutral,and alkaline media,respectively,at the same time maintain excellent stability.Our findings may pave a new avenue for the rational design of electrocatalysts toward pH-universal water electrolysis.

关键词： cobalt metaphosphate pH-universal hydrogen evolution reaction(HER) vacancy engineering low-coordination atoms oxygen vacancy

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Long-term functional maintenance of primary hepatocytes in vitro using macroporous hydrogels engineered through liquid-liquid phase separation

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Nano Research 2024年第3期17卷 1725-1736页

作者： Yang Sun Sheng Yin Jian Cui Zhongxia Wang yueying Han Ding Ma Shuo Wang Junhua Wu Yi Cao Chunping Jiang Xiaosong Gu Jinan Microecological Biomedicine Shandong Laboratory Jinan 250021China Collaborative Innovation Center of Advanced Microstructures National Laboratory of Solid State MicrostructureKey Laboratory of Intelligent Optical Sensing and ManipulationMinistry of EducationDepartment of PhysicsNanjing UniversityNanjing 210093China Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210093China National Institute of Healthcare Data Science at Nanjing University Nanjing UniversityNanjing 210093China

Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.

关键词： liver tissue engineering phase separation hepatocytes macroporous hydrogel

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Prescreening of large-effect markers with multiple strategies improves the accuracy of genomic prediction

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Journal of Integrative Agriculture 2024年第5期23卷 1634-1643页

作者： Keanning Li Bingxing An Mang Liang Tianpeng Chang Tianyu Deng Lili Du Sheng Cao yueying Du Hongyan Li Lingyang Xu Lupei Zhang Xue Gao Junya LI Huijiang Gao Laboratory of Molecular Biology and Bovine Breeding Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193China Shaanxi Key Laboratory of Molecular Biology for Agriculture College of Animal Science and TechnologyNorthwest A&F UniversityYangling712100China College of Computer and Information Engineering Tianjin Agricultural UniversityTianjin 300384China College of Animal Science and Technology Qingdao Agricultural UniversityQingdao 266109China Tongliao Animal Agriculture Development Service Center Tongliao 028000China

Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as the training population data,using BSLMM,TWAS,and eQTL mapping to prescreen features according to |β_(b)|>0,top 1%of phenotypic variation explained(PVE),expression-associated single nucleotide polymorphisms(eSNPs),and egenes(false discovery rate(FDR)<0.01),where these loci were set as extra fixed effects(named GBLUP-Fix)and random effects(GFBLUP)to improve the prediction accuracy in the validation population,respectively.The results suggested that both GBLUP-Fix and GFBLUP models could improve the accuracy of longissimus dorsi muscle(LDM),water holding capacity(WHC),shear force(SF),and pH in Huaxi cattle on average from 2.14 to 8.69%,especially the improvement of GFBLUP-TWAS over GBLUP was 13.66%for SF.These methods also captured more genetic variance than GBLUP.Our study confirmed that multi-omics-assisted large-effects loci prescreening could improve the accuracyofgenomic prediction.

关键词： multi-omics data features prescreening eQTL mapping Huaxi cattle genomic selection

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抗肿瘤治疗相关高血压

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中华心血管病杂志 2024年第6期52卷 718-722页

作者：王玥莹陈子良郑屹李朋莎刘彤天津医科大学第二医院心脏科、天津市心血管病离子与分子机能重点实验室、天津心脏病学研究所天津300211

高血压是肿瘤患者最常见的合并疾病,也是抗肿瘤治疗常见的不良反应,多种抗肿瘤药物可引起高血压的发生发展。因此,重视抗肿瘤治疗相关高血压的有效管理,不仅可以预防严重心血管事件,也能避免肿瘤患者因高血压而中断或终止抗肿瘤治疗。... 详细信息

高血压是肿瘤患者最常见的合并疾病,也是抗肿瘤治疗常见的不良反应,多种抗肿瘤药物可引起高血压的发生发展。因此,重视抗肿瘤治疗相关高血压的有效管理,不仅可以预防严重心血管事件,也能避免肿瘤患者因高血压而中断或终止抗肿瘤治疗。该文综述多种抗肿瘤治疗方法与高血压关系的最新进展,旨在强调抗肿瘤治疗相关高血压诊断、监测和治疗的重要性。

关键词：高血压化疗靶向治疗内分泌治疗蛋白酶体抑制剂

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计及实时交通特征的电动公交车备用率与充电桩联合优化

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电力自动化设备 2024年第4期44卷 127-134,150页

作者：曹昉郑怡馨王斯琪王淳奕齐玥莹华北电力大学电气与电子工程学院北京102206

为了提高电动公交车及充电站总投资和运营的经济性,需综合考虑公交车和充电桩的购置成本以及充电成本。以道路特征、实时交通特征、环境温度为主要影响因素,计算电动公交车的行驶时间和能耗;在满足公交车运营基本需求和保证车内温度的... 详细信息

为了提高电动公交车及充电站总投资和运营的经济性,需综合考虑公交车和充电桩的购置成本以及充电成本。以道路特征、实时交通特征、环境温度为主要影响因素,计算电动公交车的行驶时间和能耗;在满足公交车运营基本需求和保证车内温度的前提下,以日公交车购置成本、日充电桩建造成本、日充电成本之和最小为目标进行优化,建立电动公交车备用率与充电桩的联合优化模型,并采用改进的离散型自适应粒子群优化算法进行计算,得到公交车和充电桩的最优购置方案以及各季节和全年的日均投资及运营成本。以某公交线路上电动公交车年内多种运营条件为算例,验证所建优化模型的正确性。

关键词：电动公交车充电桩充电站公交车备用率实时交通特征联合优化环境温度

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Effects of propofol on ammonium chloride-exposed astrocyte morphology and aquaporin-4 expression

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Neural Regeneration Research 2011年第5期6卷 383-387页

作者： Hanjian Chen Caifei Pan Peng Guo yueying zheng Shengmei Zhu Department of Anesthesiology First Affiliated Hospital Zhejiang University Medical School Hangzhou 310003 Zhejiang Province China Department of Anesthesiology Shaoxing Central Hospital Shaoxing 312030 Zhejiang Province China

Ammonia induces astrocyte swelling, which is strongly associated with overexpression of aquaporin-4. However, the mechanisms by which ammonia induces astrocyte swelling, and subsequently upregulating aquaporin-4 expression, remain unknown. In the present study, astrocytes were cultured in vitro and exposed to ammonium chloride （NH4CI）, followed by propofol protein kinase C agonist, or antagonist, respectively. Astrocyte morphology was observed by light microscopy, and aquaporin-4 expression was detected by western blot analysis. Results showed that propofol or protein kinase C agonist significantly attenuated the degree of NH4CI-induced astrocyte swelling and inhibited increased aquaporin-4 expression. Propofol treatment inhibited aquaporin-4 overexpression in cultured astrocyte induced by NH4CI; protein kinase C pathway activation is potentially involved.

关键词： ammonium chloride aquaporin-4 astrocytes propofol protein kinase C

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俯仰异观睹著知微——约翰·凯奇学术研讨会综述

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人民音乐 2024年第5期 76-79页

作者：宋月盈中央音乐学院音乐学系

约翰·凯奇(John Cage,1912—1992)作为20世纪美国乃至世界现代音乐中无可取代的独特存在,以其颠覆性的音乐实践被国内外的音乐界乃至多个领域共同关注并被讨论。当下,人们对凯奇的关注也逐渐从感性的评价转向了学术研究,对其认识也日... 详细信息

约翰·凯奇(John Cage,1912—1992)作为20世纪美国乃至世界现代音乐中无可取代的独特存在,以其颠覆性的音乐实践被国内外的音乐界乃至多个领域共同关注并被讨论。当下,人们对凯奇的关注也逐渐从感性的评价转向了学术研究,对其认识也日益深入和多元。

关键词： Cage 现代音乐无可取代音乐实践学术研究研讨会综述颠覆性

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