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Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy

Cancer Biology & Medicine 2019年第3期16卷 415-434页

作者： Yanan Li Qingrong Dong Yukun Cui Department of Radiology First Clinical Medical CollegeShanxi Medical UniversityTaiyuan030001China GuangdongProvincial Key Laboratory of Breast Cancer Diagnosis and Treatment Shantou University Medical College Cancer HospitalShantou515041China

The RAS-RAF-MEK-ERK signaling pathway(MAPK signaling pathway) plays a significant role in multiple pathological behaviors and is most frequently dysregulated in more than 30% of human cancers.As key elements in this pathway, MEK1/2 play crucial roles in tumorigenesis and the inhibition of apoptosis, which makes their inhibition an attractive antitumor strategy.Dozens of potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed that have produced substantial improvement in clinical outcomes over the past decade.However, the efficacy of these agents is limited, and response rates are variable in a wide range of tumors that harbor RAS and RAF mutations due to the development of resistance, which is derived mainly from the persistence of MAPK signaling and increased activation of the mutual feedback networks.Both intrinsic and acquired resistance to MEK inhibitors necessitates the synergistic targeting of both pathways to restore the therapeutic effects of a single agent.In this review, the significant role of the MAPK pathway in carcinogenesis and its therapeutic potential are comprehensively examined with a focus on MEK inhibitors.Then, the activation of feedback networks accompanying MEK inhibition is briefly reviewed.Combination strategies that involve the simultaneous inhibition of the original and resistance pathways are highlighted and elaborately described on the basis of the latest research progress.Finally, the obstacles to the development of MEK-related combination systems are discussed in order to lay the groundwork for their clinical application as frontline treatments for individual patients with MAPK-hyperactivated malignancies.

关键词： MAPK signaling pathway MEK inhibitor reciprocal feedback networks combination therapy malignancy

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Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiationvia downregulating frizzled class receptor 10

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Cancer Biology & Medicine 2020年第3期17卷 740-752页

作者： Jiongyu Chen Fan Zhang Xiaosha Ren Yahui Wang Wenhe Huang Jianting Zhang Yukun Cui Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment Cancer Hospital of Shantou University Medical CollegeShantou 515041China Department of Cancer Biology University of Toledo College of Medicine and Life SciencesToledoOH 43614USA

Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.

关键词： Epigallocatechin gallate fatty acid synthase frizzled class receptor 10 nasopharyngeal carcinoma radioresistance

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A 16-QAM 45-Gbps 7-m Wireless Link Using InP HEMT LNA and GaAs SBD Mixers at 220-GHz-Band

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China Communications 2021年第5期18卷 255-262页

作者： yukun Li Yong Zhang Chengkai Wu Jianhan cui Huali Zhu Bo Yan School of Electronic Science and Engineering University of Electronic Science and Technology of ChinaChengdu 611731China

This paper presents a 220-GHz-band 7-m wireless link with a 45-Gbps transmission data rate by using 16 quadrature amplitude modulation(16-QAM).Super-heterodyne transceiver modules are developed for transmission and reception of the modulated signals,which consist of a Schottky barrier diodes(SBD)based sub-harmonic mixer(SHM),an InP HEMT low noise amplifier(LNA),a waveguide band-pass filter(BPF),and a 108-GHz local oscillator(LO)multiplier chain.The transmitter features a peak transmit power of 1.41 dBm,and the IF frequency varies from 5 GHz to 20 GHz.Besides,the receiver features a conversion gain of 9.3 dB in average and a noise temperature of 3052.8 K.The measured results indicate that the transceiver modules enable data transmission of a 45-Gbps 16-QAM signal with Signal-Noise-Ratio(SNR)from 11.59 dB to 15.36 dB in a 7-m line-of-sight channel.

关键词： wireless link 16 quadrature amplitude modulation(16-QAM) super-heterodyne transceiver modules sub-harmonic mixer(SHM)

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Resection of high-grade glioma involving language areas assisted by multimodal techniques under general anesthesia:a retrospective study

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Chinese Neurosurgical Journal 2023年第4期9卷 276-289页

作者： Meng cui yukun Liu Chunhui Zhou Hewen Chen Xin Gao Jiayu Liu Qingbao Guo Bing Guan Xiaodong Ma Department of Emergency the Sixth Medical CenterChinese People’s Liberation Army General HospitalBeijingChina Department of Neurosurgery the First Medical CenterChinese People’s Liberation Army General HospitalBeijingChina Department of Neurosurgery Chinese Air Force Medical CenterBeijingChina Department of Neurosurgery the Sixth Medical CenterChinese People’s Liberation Army General HospitalBeijingChina Department of Health Economics the First Medical CenterChinese People’s Liberation Army General HospitalBeijingChina

Background Multimodal techniques-assisted resection of glioma under general anesthesia(GA)has been shown to achieve similar clinical outcomes as awake craniotomy(AC)in some studies.In this study,we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas(HGILAs)under GA.Methods HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center.Patients were separated into multimodal group(using neuronavigation,intraoperative MRI combined with direct electrical stimulation[DES]and neuromonitoring[IONM])and conventional group(neuronavigation alone)and clinical outcomes were compared between groups.Studies of HGILAs were reviewed systematically and the meta-analysis results of previous(GA or AC)studies were compared with our results.Results Finally,there were 263 patients in multimodal group and 137 patients in conventional group.Compared to the conventional group,the multimodal group achieved the higher median EOR(100%versus 94.32%,P<0.001)and rate of gross total resection(GTR)(73.8%versus 36.5%,P<0.001)and the lower incidence of permanent language deficit(PLD)(9.5%versus 19.7%,P=0.004).The multimodal group achieved the longer median PFS(16.8 versus 10.3 months,P<0.001)and OS(23.7 versus 15.7 months,P<0.001)than the conventional group.The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC(73.8%versus 55.7%[95%CI 32.0-79.3%]versus 53.4%[35.5-71.2%]).The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA(9.5%versus 14.0%[5.8-22.1%])and our incidence of PLD was a little higher than that of previous multimodal studies under AC(9.5%versus 7.5%[3.7-11.2%]).Our multimodal group also achieved a relative longer survival than previous studies.Conclusions Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA.Further prospective studies are needed to compare GA with AC for

关键词： High-grade glioma Language Multimodal techniques Intraoperative MRI General anesthesia

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职业本科院校机械类专业课程思政育人效果提升研究与实践

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模具制造 2023年第7期23卷 59-62页

作者：崔海花解玉坤河南科技职业大学机电工程学院河南周口466000

长期以来,职业院校理工科类专业教育和思想政治教育形成为“两张皮”现象,专业“课程思政”教育出现了刻意“贴标签”的情形,不能形成良好的协同育人合力,难以发挥“课程思政”育人作用。因此,研究如何提升机械类专业课程思政育人效果... 详细信息

长期以来,职业院校理工科类专业教育和思想政治教育形成为“两张皮”现象,专业“课程思政”教育出现了刻意“贴标签”的情形,不能形成良好的协同育人合力,难以发挥“课程思政”育人作用。因此,研究如何提升机械类专业课程思政育人效果有着十分重要的现实意义:一方面,有助于推进机械类专业人才培养方案的修订和完善工作;另一方面,有助于提升学生的职业精神和社会责任感。结合河南科技职业大学机电工程学院机械类专业“课程思政”育人现状,从育人模式、课程体系、教师观念、实践路径、评价体系等几方面出发,探讨了提升机械类专业“课程思政”的有效性的策略与措施。

关键词：课程思政机械类专业课程育人模式策略与措施评价体系

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Relational graph location network for multi-view image localization

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系统工程与电子技术：英文版 2023年第2期34卷 460-468页

作者： YANG yukun LIU Xiangdong School of Automation Beijing Institute of TechnologyBeijing 100081China

In multi-view image localization task,the features of the images captured from different views should be fused properly.This paper considers the classification-based image localization problem.We propose the relational graph location network(RGLN)to perform this task.In this network,we propose a heterogeneous graph construction approach for graph classification tasks,which aims to describe the location in a more appropriate way,thereby improving the expression ability of the location representation module.Experiments show that the expression ability of the proposed graph construction approach outperforms the compared methods by a large margin.In addition,the proposed localization method outperforms the compared localization methods by around 1.7%in terms of meter-level accuracy.

关键词： multi-view image localization graph construction heterogeneous graph graph neural network

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测电阻常用方法浅析

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无线互联科技 2016年第22期13卷 109-110页

作者：崔煜坤成都棠湖外国语学校四川成都610000

电阻是电磁学中常见的物理量之一,测量电阻的方法很多。文章主要介绍了常见的伏安法、电桥法和万用表法的基本原理,分析了3种方法在使用中经常会出现的误差。

关键词：伏安法电桥法万用表法

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高效热管理用鳞片石墨/铝复合材料的研究进展

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功能材料 2022年第1期53卷 1025-1032页

作者：刘园崔岩杨宇坤杨继鹏北方工业大学机械与材料工程学院北京100144

鳞片石墨由于其较高的石墨化度、高结晶度和纯度,具有很高的平面热导率而成为制备定向高导热复合材料的重要原料。其与铝基体复合制备的鳞片石墨/铝复合材料具有优异的热综合性能,更是在电子通讯和航空航天领域有更显著的应用优势。介... 详细信息

鳞片石墨由于其较高的石墨化度、高结晶度和纯度,具有很高的平面热导率而成为制备定向高导热复合材料的重要原料。其与铝基体复合制备的鳞片石墨/铝复合材料具有优异的热综合性能,更是在电子通讯和航空航天领域有更显著的应用优势。介绍了近年来鳞片石墨/铝复合材料的主流制备技术及其导热性能,从碳-铝两相润湿性、界面反应出发,分析了鳞片石墨表面改性的方法及其对复合材料界面微结构和导热性能的影响规律。最后展望了今后鳞片石墨/铝复合材料的研究方向及发展趋势。

关键词：鳞片石墨/铝复合材料热导率界面润湿镀层

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我国大型线状文化遗产的研究态势——基于核心期刊的统计分析

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城市发展研究 2015年第7期22卷 92-100页

作者：崔卫华胡玉坤东北财经大学产业组织研究中心日本东亚大学东亚文化研究所

作为遗产研究的前沿领域,大型线状文化遗产与城市规划和区域经济发展息息相关,"一带一路"战略的提出为其发展带来全新机遇。从年代、期刊、作者、学科背景、研究内容等方面进行文献统计分析后发现,国内研究始于2001年,经过近十五年的快... 详细信息

作为遗产研究的前沿领域,大型线状文化遗产与城市规划和区域经济发展息息相关,"一带一路"战略的提出为其发展带来全新机遇。从年代、期刊、作者、学科背景、研究内容等方面进行文献统计分析后发现,国内研究始于2001年,经过近十五年的快速发展,已初步形成核心刊物群,但尚未形成稳定的核心作者群;学科背景以城市发展规划、文化遗产学为主,表现出跨学科、多视角的研究态势;在研究内容上,个案研究数量占51.6%,基础理论研究的不足成为当前国内研究的瓶颈。通过对国内代表性文献的梳理和分析,以期为我国大型线状文化遗产的后续研究提供参考。

关键词：大型线状文化遗产研究态势文献统计中国

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Enabling an Inorganic-Rich Interface via Cationic Surfactant for High-Performance Lithium Metal Batteries

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NANO-MICRO LETTERS 2024年第1期16卷 1-17页

作者： Sun, Zejun Yang, Jinlin Xu, Hongfei Jiang, Chonglai Niu, Yuxiang Lian, Xu Liu, Yuan Su, Ruiqi Liu, Dayu Long, Yu Wang, Meng Mao, Jingyu Yang, Haotian cui, Baihua Xiao, yukun Chen, Ganwen Zhang, Qi Xing, Zhenxiang Pan, Jisheng Wu, Gang Chen, Wei Natl Univ Singapore Dept Chem 3 Sci Dr 3 v 117543 Singapore Tianjin Univ Joint Sch Natl Univ Singapore & Tianjin Univ Int Campus Fuzhou 350207 Peoples R China Natl Univ Singapore Dept Phys 2 Sci Dr 3 Singapore 117542 Singapore ASTAR Inst High Performance Comp 1 Fusionopolis Way16-16 Connexis Singapore 138632 Singapore ASTAR Inst Mat Res & Engn 2 Fusionopolis Way 08-03 Singapore 138634 Singapore

An anion-rich electric double layer (EDL) region is favorable for fabricating an inorganic-rich solid-electrolyte interphase (SEI) towards stable lithium metal anode in ester electrolyte. Herein, cetyltrimethylammonium bromide (CTAB), a cationic surfactant, is adopted to draw more anions into EDL by ionic interactions that shield the repelling force on anions during lithium plating. In situ electrochemical surface-enhanced Raman spectroscopy results combined with molecular dynamics simulations validate the enrichment of NO3-/FSI- anions in the EDL region due to the positively charged CTA(+). In-depth analysis of SEI structure by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry results confirmed the formation of the inorganic-rich SEI, which helps improve the kinetics of Li+ transfer, lower the charge transfer activation energy, and homogenize Li deposition. As a result, the Li||Li symmetric cell in the designed electrolyte displays a prolongated cycling time from 500 to 1300 h compared to that in the blank electrolyte at 0.5 mA cm(-2) with a capacity of 1 mAh cm(-2). Moreover, Li||LiFePO4 and Li||LiCoO2 with a high cathode mass loading of > 10 mg cm(-2) can be stably cycled over 180 cycles.

关键词： Cationic surfactant Lithium nitrate additive Solid-electrolyte interphase Electric double layer Lithium metal batteries ELECTROLYTES

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