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Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation

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Signal Transduction and Targeted Therapy 2023年第2期8卷 730-743页

作者： Zhaoyuan Fang Xiangkun Han Yueqing Chen Xinyuan Tong Yun Xue Shun Yao Shijie Tang yunjian pan Yihua Sun Xue Wang Yujuan Jin Haiquan Chen Liang Hu Lijian Hui Lin Li Luonan Chen Hongbin Ji State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Zhejiang University-University of Edinburgh Institute Zhejiang University School of MedicineHaining 314400China Department of Thoracic Surgery Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina School of Life Science and Technology ShanghaiTech UniversityShanghai 200120China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center 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 SciencesChinese Academy of SciencesHangzhou 310024China

Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation(AST).However,it remains largely unknown how Lkb1 deficiency dynamically regulates AST.Using the classical AST mouse model(Kras LSL-G12D/+;Lkb1flox/flox,KL),we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker(DNB)and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species(ROS)through its downstream effector FOXO3A.Bidirectional genetic perturbation of the Wnt pathway using two different Ctnnb1 conditional knockout mouse strains confirms its essential role in the negative regulation of AST.Importantly,pharmacological activation of the Wnt pathway before but not after the tipping point inhibits squamous transdifferentiation,highlighting the irreversibility of AST after crossing the tipping point.Through comparative transcriptomic analyses of mouse and human tumors,we find that the lineage-specific transcription factors(TFs)of adenocarcinoma and squamous cell carcinoma form a“Yin-Yang”counteracting network.Interestingly,inactivation of the Wnt pathway preferentially suppresses the adenomatous lineage TF network and thus disrupts the“Yin-Yang”homeostasis to lean towards the squamous lineage,whereas ectopic expression of NKX2-1,an adenomatous lineage TF,significantly dampens such phenotypic transition accelerated by the Wnt pathway inactivation.The negative correlation between the Wnt pathway and AST is further observed in a large cohort of human lung adenosquamous carcinoma.Collectively,our study identifies the tipping point of AST and highlights an essential role of the ROS-Wnt axis in dynamically orchestrating the homeostasis between adeno-and squamous-specific TF networks at the AST tipping point.

关键词： squamous homeostasis lung

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Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment

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National Science Review 2023年第4期10卷 37-55页

作者： Shijie Tang Yun Xue Zhen Qin Zhaoyuan Fang Yihua Sun Chongzhe Yuan yunjian pan Yue Zhao Xinyuan Tong Jian Zhang Hsinyi Huang Yuting Chen Liang Hu Dasong Huang Ruiqi Wang Weiguo Zou Yuan Li Roman K.Thomas Andrea Ventura Kwok-Kin Wong Haiquan Chen Luonan Chen Hongbin Ji Department of Pathology University Hospital Cologne Cancer Biology and Genetics Program Memorial Sloan Kettering Cancer Center Laura and Isaac Perlmutter Cancer Center New York University Langone Medical Center Key Laboratory of Systems Biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of Sciences College of Life Sciences University of Chinese Academy of Sciences Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicine The Second Affiliated Hospital Zhejiang University School of Medicine Department of Thoracic Surgery Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University School of Life Science and Technology Shanghai Tech University Department of Mathematics Shanghai University Department of Translational Genomics Center of Integrated Oncology Cologne-BonnMedical FacultyUniversity of Cologne

Human lung adenosquamous cell carcinoma(LUAS), containing both adenomatous and squamous pathologies, harbors strong plasticity and is significantly associated with poor prognosis. We established an up-to-date comprehensive genomic and transcriptomic landscape of LUAS in 109 Chinese specimens and demonstrated LUAS development via adeno-to-squamous transdifferentiation. Unsupervised transcriptomic clustering and dynamic network biomarker analysis identified an inflammatory subtype as the critical transition stage during LUAS development. Dynamic dysregulation of the counteracting lineage-specific transcription factors(TFs), containing adenomatous TFs NKX2-1 and FOXA2, and squamous TFs TP63 and SOX2, finely tuned the lineage transition via promoting CXCL3/5-mediated neutrophil infiltration. Genomic clustering identified the most malignant subtype featured with STK11-inactivation, and targeting LSD1 through genetic deletion or pharmacological inhibition almost eradicated STK11-deficient lung tumors. These data collectively uncover the comprehensive molecular landscape, oncogenic driver spectrum and therapeutic vulnerability of Chinese LUAS.

关键词： LUAS ALK fusion counteracting TF regulatory network CXCL3/CXCL5 LSD1

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单兵班组供电保障装备建设发展研究

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电源技术 2022年第5期46卷 488-491页

作者：于广洲单文龙鲁文涛贾晓磊潘云剑中国人民解放军63936部队北京102202 中国人民解放军32178部队北京100012

单兵班组供电保障装备主要采用小型高效发电、储能和配电管理技术,涉及到化学电池、燃料电池、太阳电池、动能发电、配电及电源管理等诸多技术体制。面向当前及未来一段时间的单兵班组,论证其供电保障装备军事需求,构建了单兵班组供电... 详细信息

单兵班组供电保障装备主要采用小型高效发电、储能和配电管理技术,涉及到化学电池、燃料电池、太阳电池、动能发电、配电及电源管理等诸多技术体制。面向当前及未来一段时间的单兵班组,论证其供电保障装备军事需求,构建了单兵班组供电保障装备技术体系。借鉴美军相关装备及技术发展情况,初步设计了有人无人协同班组供电保障建设的方案,并对下一步发展趋势进行了展望。

关键词：单兵班组供电保障发展

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美军兵力投送保障条件建设及启示

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军事交通学院学报 2016年第7期18卷 6-10页

作者：于殿祥潘云剑张良军事交通学院汽车指挥系天津300161 军事交通学院学员旅天津300161 北京物资采购供应站北京100010

为加强我军投送基地建设,分别对美军本土和本土外部队驻地、装(卸)载港、海外军事基地、海上基地等保障兵力投送的保障条件建设情况进行了分析,提出我军要重视投送基地建设,突出投送保障设施、装备、信息和人才队伍等配套保障条件建设,... 详细信息

为加强我军投送基地建设,分别对美军本土和本土外部队驻地、装(卸)载港、海外军事基地、海上基地等保障兵力投送的保障条件建设情况进行了分析,提出我军要重视投送基地建设,突出投送保障设施、装备、信息和人才队伍等配套保障条件建设,探索、启动海外投送的相关保障条件建设等建议。

关键词：兵力投送保障条件投送基地美军

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Range-spread target detector via coherent energy accumulation and block thresholding denoising

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Journal of Systems Engineering and Electronics 2021年第4期32卷 873-880页

作者： ZHANG yunjian pan Pingping DENG Zhenmiao WU Gang School of Electronics and Communication Engineering Sun Yat-sen UniversityGuangzhou 510275China Jiuquan Satellite Launch Center Dunhuang 736200China

A range-spread target(RST)detector is proposed for wideband radar.The detector,referred to as a conjugate multiplication and block thresholding(CMBT)detector,is simple for implementation in existing radar systems and has the advantage of minor calculation.First,the target energy of adjacent stretched echoes is coherently accumulated via conjugate multiplication and Fourier transform operations.It is noted that conjugate multiplication of two complex Gaussian distributed noise is complex double Gaussian distributed,leading to a signal to noise ratio(SNR)loss.Subsequently,considering the sparsity and clustering characteristics of the conjugate multiplication amplitude spectrum(CMAS),the block thresholding method is adopted for denoising,where the noise and cross-terms are adaptively smoothed,and the signal terms can be basically preserved.Finally,numerical simulation results for both synthetic and real radar data validate the effectiveness of the proposed detector,comparing with the conventional integration detector(ID),the spatial scattering density(SSD)detector,and waveform entropy(WE)and waveform contrast(WC)based detectors.

关键词： wideband radar detection range-spread target conjugate multiplication block thresholding denoising

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儿童抗γ-氨基丁酸A型受体脑炎1例

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中华儿科杂志 2022年第9期60卷 948-950页

作者：张敏张林妹潘岗沈瑾张赟健周水珍复旦大学附属儿科医院神经内科上海201102 复旦大学附属儿科医院放射科上海201102

抗γ-氨基丁酸A型受体(GABAAR)脑炎患儿1例,男,2岁,急性起病,主要表现为快速进展的难治性癫痫、癫痫持续状态、不自主运动及认知功能障碍,脑脊液常规生化正常,头颅磁共振成像提示弥漫性脑萎缩样改变,血清及脑脊液抗GABAAR抗体阳性,不伴... 详细信息

抗γ-氨基丁酸A型受体(GABAAR)脑炎患儿1例,男,2岁,急性起病,主要表现为快速进展的难治性癫痫、癫痫持续状态、不自主运动及认知功能障碍,脑脊液常规生化正常,头颅磁共振成像提示弥漫性脑萎缩样改变,血清及脑脊液抗GABAAR抗体阳性,不伴肿瘤,抗癫痫药物对癫痫发作控制效果不佳,免疫治疗有效,但遗留严重神经系统功能障碍。提示对不明原因急性起病的儿童难治性癫痫、癫痫持续状态患者,需重视自身免疫性脑炎的筛查。

关键词：脑脊液常规不自主运动抗癫痫药物难治性癫痫自身免疫性脑炎癫痫持续状态不明原因脑萎缩

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Effects of annealing temperature on electrochemical performance of SnSx embedded in hierarchical porous carbon with N-carbon coating by in-situ structural phase transformation as anodes for lithium ion batteries

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Journal of Materials Science & Technology 2021年第25期84卷 191-199页

作者： Qianqian Hu Biao Wang Shiyong Chang Chun Yang yunjian Hu Shubin Cao Jiqun Lu Lingzhi Zhang Ye Hong Guangzhou Institute of Energy Conversion Chinese Academy of SciencesCAS Key Laboratory of Renewable EnergyGuangdong Provincial Key Laboratory of New and Renewable Energy Research and DevelopmentGuangzhouGuangdong 510640China GAC Automotive Research&Development Center Guangzhou 511434China University of Chinese Academy of Sciences Beijing 100049China Nano Science and Technology Institute University of Science and Technology of ChinaSuzhou 215123China Industrial Training Center Guangdong Polytechnic Normal University510665China

Tuned tin chalcogenides rooted in hierarchical porous carbon(HPC)with N-carbon coating layers are prepared by thermal shock under various temperatures(denoted as HPC-SnS_(2)-pan-Various T).With the increase of annealing temperature,the morphology and phase structure of Sn S_(2),as well as the cyclization degree of polyacrylonitrile(pan),are significantly changed,which leads to the formation of rod-like Sn S and ordered structure of conductive N-carbon layer.By combining HPC,N-carbon coating derived from the cyclization of pan,with 1D Sn S nanorods generated from structural phase transformation of SnS_(2),the optimized composite(HPC-SnS_(2)-pan-500)as anode for lithium ion batteries(LIBs)provides buffer space for volume changes during alloying/dealloying process,builds a highly conductive network as well as decreases irreversible capacity from solid electrolyte interphase and enhances the ion/electron transport.Attributed to the above merits from composition regulation and architecture modification by sulfur depletion and pan cyclization,this target anode exhibits an extraordinary cycling stability with a high specific capacity of 652.5 m A h/g at 0.5 A/g after 900 cycles.It suggests that rod-like Sn S embedded in HPC with cyclized pan layers by thermal treatment approach renders a potential structural design of anode materials for LIBs.

关键词： Hierarchical porous carbon SnSx Conducting medium Cycling stability Lithium ion batteries

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Data-Driven User Complaint Prediction for Mobile Access Networks

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Journal of Communications and Information Networks 2018年第3期3卷 9-19页

作者： Huimin pan Sheng Zhou yunjian Jia Zhisheng Niu Meng Zheng Lu Geng Department of Electronic Engineering Tsinghua UniversityBeijing 100084China College of Communication Engineering Chongqing UniversityChongqing 400044China Hitachi(China)Research&Development Cooperation Beijing 100190China

In this paper,we present a user-complaint prediction system for mobile access networks based on network monitoring data.By applying machine-learning models,the proposed system can relate user complaints to network performance indicators,alarm reports in a data-driven fashion,and predict the complaint events in a fine-grained spatial area within a specific time window.The proposed system harnesses several special designs to deal with the specialty in complaint prediction;complaint bursts are extracted using linear filtering and threshold detection to reduce the noisy fluctuation in raw complaint events.A fuzzy gridding method is also proposed to resolve the inaccuracy in verbally described complaint locations.Furthermore,we combine up-sampling with down-sampling to combat the severe skewness towards negative samples.The proposed system is evaluated using a real dataset collected from a major Chinese mobile operator,in which,events due to complaint bursts account approximately for only 0:3%of all recorded events.Re-sults show that our system can detect 30%of complaint bursts 3 h ahead with more than 80%precision.This will achieve a corresponding proportion of quality of experi-ence improvement if all predicted complaint events can be handled in advance through proper network maintenance.

关键词： data-driven complaint prediction complaint location network management machine learning pipeline

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ZnCr_(2)O_(4)表面CO加氢反应活性位点的探测

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Chinese Journal of Catalysis 2022年第8期43卷 2017-2025页

作者：凌云健冉义华邵伟鹏李娜焦峰潘秀莲傅强刘志杨帆包信和中国科学院大连化学物理研究所催化基础国家重点实验室辽宁大连11602 中国科学院大学北京100039 上海科技大学物质科学与技术学院上海201210 上海科技大学上海市高分辨电子显微学重点实验室上海201210

CO加氢转化为高附加值化学品是煤、天然气和生物质等清洁利用的核心过程之一.近年来,氧化物催化剂越来越多地被用于加氢反应,其中ZnCrO_(x)催化剂广泛应用于Cl分子催化加氢反应,并且是氧化物分子筛(OXZEO)合成气转化催化剂的主要活性组... 详细信息

CO加氢转化为高附加值化学品是煤、天然气和生物质等清洁利用的核心过程之一.近年来,氧化物催化剂越来越多地被用于加氢反应,其中ZnCrO_(x)催化剂广泛应用于Cl分子催化加氢反应,并且是氧化物分子筛(OXZEO)合成气转化催化剂的主要活性组分之一.由于复合氧化物表面结构的复杂性,在CO加氢反应中,ZnCrO_(x)上的活性位点和活化过程尚存在争议.本文采用原位傅里叶变换红外光谱(FT-IR)和X射线光电子能谱(XPS)研究了不同条件预处理的ZnCr_(2)O_(4)尖晶石催化剂在CO/H_(2)中的原位吸附和反应过程.XPS结果表明,相较氧化的ZnCr_(2)O_(4),使用H_(2)还原的ZnCr_(2)O_(4)中Cr^(6+)的含量会下降,同时带来更多的表面氧空位或羟基物种.Cr^(6+)的还原也能由FT-IR谱中位于1013 cm^(-1)铬酸盐的Cr=O振动峰的消失来证明.利用CO作为探针分子,FT-IR结果表明还原的ZnCr_(2)O_(4)比氧化的ZnCr_(2)O_(4)具有更多的CO吸附位点.通过对比ZnO和Cr_(2)O_(3)上的CO吸附波数发现,这些CO吸附位点并非还原ZnCr_(2)O_(4)相分离产生的ZnO和Cr_(2)O_(3),而是通过直接还原表面Cr位点,在其周围产生氧空位而产生的新位点.在室温下,ZnCr_(2)O_(4)与CO能反应形成碳酸盐,还原的ZnCr_(2)O_(4)产生碳酸盐的表面吸附量以及结合碳酸盐的稳定性要明显高于氧化的ZnCr_(2)O_(4).真空室温下,H_(2)能在还原的ZnCr_(2)O_(4)上异裂解离形成氢化物,并可在373 K稳定存在;而ZnO表面H_(2)异裂产生的氢化物在低于室温即已脱附.还原的ZnCr_(2)O_(4)表面形成的氢化物在423 K以上会有部分转化为羟基,这些羟基具有较高的热稳定性,在673 K以上才开始脱附.相比ZnO或Cr_(2)O_(3),还原的ZnCr_(2)O_(4)表面与CO和H_(2)的作用都要更强.在CO/H_(2)(1:1)混合气氛下,还原的ZnCr_(2)O_(4)表面能发生CO加氢反应,在373 K发现CO加氢产物甲酸盐形成.然而,在只有羟基存在的还原的ZnCr_(2)O_(4)表面上,羟基只能通过水气变换反应氧化CO,通过羟基含量的减少判断该反应,发生在523 K以上;而ZnCr_(2)O_(4)表面H_(2)异裂形成的氢化物在373-473K下就能使CO加氢形成甲酰基或甲酸盐.因此,H_(2)异裂形成的表面氢化物才是CO加氢的活性物种.综上,本文通过探测ZnCr_(2)O_(4)上的CO和H_(2)活化和反应过程,为复合氧化物表面的CO加氢的基元过程提供了更深入的理解.

关键词： ZnCr_(2)O^(4) 傅里叶变换红外光谱 CO吸附氢化物羟基

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CD44 receptor targeted Paclitaxel-loaded amphiphilic hyaluronic acid polymeric micelle with tunable pH and redox-sensitive property for breast cancer therapy

CD44 receptor targeted Paclitaxel-loaded amphiphilic hyaluro...

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2018年第十二届中国药物制剂大会

作者：杨月 Jinyu Li yunjian Li Fen Chen Weisan pan 沈阳药科大学药学院 Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications Liaoning University of Traditional Chinese Medicine

Paclitaxel（PTX） is a naturally occurring alkaloid against a wide spectrum of cancers. However, its potential in clinical uses is severely hindered by low tumor selectivity, poor water solubility and distinct side effects. Polymer micelles, tough structure self-assembled from amphiphilic copolymers, are a class of nanocarrier systems with potential application in cancer therapy by enhancing the water solubility of anticancer drugs, prolonging the blood circulation and good biocompatibility. Here, histidine（His） and vitamin E succinate（VES） grafted hyaluronic acid（HA） tripolymer using a disulfide bond as the linker（HisHA-SS-VES） was synthesized in the presence of 1-Ethyl-3-（3-dimethylaminopropyl） carbodiimide（EDC） and N-Hydroxysuccinimide（NHS）. The chemical structure of His-HA-SS-VES conjugate was determined by H1-nuclear magnetic resonance（H1-NMR） and Fourier transform infrared spectroscopy（FTIR）. The degree of substitution of His and VES were assayed through H1-NMR spectrum, which were 4.59% and 15.76%, respectively. The water-insoluble anticancer drug PTX was successfully entrapped into into the core via probe ultrasonication method. The near-spherical PTX-loaded micelle was formed in aqueous media with diameter 108 ± 0.126 nm and a drug loading of 12.54 ± 0.523%. Moreover, the redox and pH-sensitivity of the micelle were confirmed by the particle size change under the simulated tumor environment. These results demonstrate the potential of His-HA-SS-VES micelles as a promising delivery system for pooly soluble antitumor drugs or their derivatives in cancer therapy.

关键词： Paclitaxel Polymer micelle hyaluronic acid vitamin E succinate pH and redox-sensitive H~1-nuclear magnetic resonance

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