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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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Pathological transition as the arising mechanism for drug resistance in lung cancer

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Cancer Communications 2019年第1期39卷 469-481页

作者： yueqing chen Waiying Yvonne Tang Xinyuan Tong Hongbin Ji State Key Laboratory of Cell Biology CAS Center for Excellence on Molecular Cell ScienceInnovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031P.R.China University of Chinese Academy of Sciences Beijing 100049P.R.China Sunway Medical Centre 47500 Bandar SunwaySelangorMalaysia School of Life Science and Technology Shanghai Tech UniversityShanghai 200120P.R.China

Despite the tremendous efforts for improving therapeutics of lung cancer patients,its prognosis remains disappoint-ing.This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insuf-ficient development of effective therapeutics in clinic.Based on the current progresses of lung cancer research,we classify drug resistance mechanisms into three different levels:molecular,cellular and pathological level.All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic.Our under-standing on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis.In this review,we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.

关键词： Lung cancer Drug resistance Pathological transition

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Improvement of cloud microphysical parameterization and its advantages in simulating precipitation along the Sichuan-Xizang Railway

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Science China Earth Sciences 2024年第3期67卷 856-873页

作者： Xiaoqi XU Zhiwei HENG yueqing LI Shunjiu WANG Jian LI Yuan WANG Jinghua chen Peiwen ZHANG Chunsong LU China Meteorological Administration Transportation Meteorology Key Laboratory Nanjing Joint Institute for Atmospheric SciencesNanjing 210041China Heavy Rain and Drought-Flood Disasters in Plateau and Basin Key Laboratory of Sichuan Province Institute of Plateau MeteorologyCMAChengdu 610072China State Key Laboratory of Disaster Weather Chinese Academy of Meteorological SciencesBeijing 100081China Collaborative Innovation Center for Western Ecological Safety Lanzhou UniversityLanzhou 730000China China Meteorological Administration Aerosol-Cloud and Precipitation Key Laboratory and Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD) Nanjing University of Information Science and TechnologyNanjing 210044China

The Sichuan-Xizang Railway is an important part of the railway network in China, and geological disasters, such as mountain floods and landslides, frequently occur in this region. Precipitation is an important cause of these disasters;therefore,accurate simulation of the precipitation in this region is highly important. In this study, the descriptions for uncertain processes in the cloud microphysics scheme are improved;these processes include cloud droplet activation, cloud-rain autoconversion, rain accretion by cloud droplets, and the entrainment-mixing process. In the default scheme, the cloud water content of different sizes corresponds to the same cloud droplet concentration, which is inconsistent with the actual content;this results in excessive cloud droplet size, unreasonable related conversion rates of microphysical process(such as cloud-rain autoconversion), and an overestimation of precipitation. Our new scheme overcomes the problem of excessive cloud droplet size. The processes of cloudrain autoconversion and rain accretion by cloud droplets are similar to the stochastic collection equation, and the mixing mechanism of cloud droplets is more consistent with that occurred during the actual physical process in the cloud. Based on the new and old schemes, multiple precipitation processes in the flood season of 2021 along the Sichuan-Xizang Railway are simulated, and the results are evaluated using ground observations and satellite data. Compared to the default scheme, the new scheme is more suitable for the simulation of cloud physics, reducing the simulation deviation of the liquid water path and droplet radius from 2 times to less than 1 time and significantly alleviating the overestimation of precipitation intensity and range of precipitation center. The average root-mean-square error is reduced by 22%. Our results can provide a scientific reference for improving precipitation forecasting and disaster prevention in this region.

关键词： The Sichuan-Xizang Railway Cloud microphysics Precipitation Model improvement

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Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 751-764页

作者： Wen Li Jiali Huang chen Shen Weiye Jiang Xi Yang Jingxuan Huang yueqing Gu Zhiyu Li Yi Ma Jinlei Bian State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of Drug Design and Optimization Department of Medicinal ChemistrySchool of PharmacyChina Pharmaceutical UniversityNanjing 210009China

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs.To address this challenge,we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug,specifically 6-diazo-5-oxo-L-norleucine(DON),using a thioketal linkage(TK).This system enables imaging,chemotherapy,photodynamic therapy,and on-demand drug release upon radiation exposure.The optimized prodrug,DON-TK-BM3,incorporating cyanine dyes as the fluorophore,displayed potent reactive oxygen species release and efficient tumor cell killing.Unlike the parent drug DON,DON-TK-BM3 exhibited no toxicity toward normal cells.Moreover,DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects,including gastrointestinal toxicity,in mice.This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

关键词： Smart prodrug system Glutamineantagonists Immunotherapy Photodynamictherapy Reactive oxygen species Metabolicinhibitor Cyaninedye Non-small-cell lung cancer(NSCLC)

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Design and optimization of fluid lubricated bearings operated with extreme working performances——a comprehensive review

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International Journal of Extreme Manufacturing 2024年第2期6卷 325-376页

作者： Guohua Zhang Ming Huang Gangli chen Jiasheng Li Yang Liu Jianguo He yueqing Zheng Siwei Tang Hailong Cui Institute of Machinery Manufacturing Technology China Academy of Engineering PhysicsMianyangSichuan 621999People’s Republic of China

Fluid lubricated bearings have been widely adopted as support components for high-end equipment in metrology,semiconductor devices,aviation,strategic defense,ultraprecision manufacturing,medical treatment,and power generation.In all these applications,the equipment must deliver extreme working performances such as ultraprecise movement,ultrahigh rotation speed,ultraheavy bearing loads,ultrahigh environmental temperatures,strong radiation resistance,and high vacuum operation,which have challenged the design and optimization of reliable fluid lubricated bearings.Breakthrough of any related bottlenecks will promote the development course of high-end equipment.To promote the advancement of high-end equipment,this paper reviews the design and optimization of fluid lubricated bearings operated at typical extreme working performances,targeting the realization of extreme working performances,current challenges and solutions,underlying deficiencies,and promising developmental directions.This paper can guide the selection of suitable fluid lubricated bearings and optimize their structures to meet their required working performances.

关键词： fluid lubricated bearings structural design performance optimization extreme working performances

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高等护理职业教育国家规划教材立项数据信息外部特征分析

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中华护理教育 2023年第4期20卷 439-444页

作者：胡高波陈月卿饶和平衢州职业技术学院医学院衢州市324000 衢州市人民医院质量控制处

目的探讨职业教育国家规划教材高职护理类与医药卫生其他类的立项数据信息特征与差异,为护理职业教育国家规划教材建设提供参考。方法以“十三五”职业教育国家规划教材高职医药卫生大类立项教材108本为研究对象,其中护理类教材74本、... 详细信息

目的探讨职业教育国家规划教材高职护理类与医药卫生其他类的立项数据信息特征与差异,为护理职业教育国家规划教材建设提供参考。方法以“十三五”职业教育国家规划教材高职医药卫生大类立项教材108本为研究对象,其中护理类教材74本、医药卫生其他类专业教材34本。从教材总数及课程结构、重复课程教材、第一主编单位层次、教材出版版次、教材所属出版社数量与分布、教材所属立项学校分布6个维度,对比分析护理类与医药卫生其他类专业教材立项数据外部特征差异。结果高职护理类教材立项率(1.88%)高于医药卫生其他类(0.86%),差异有统计学意义(χ^(2)=15.020,P0.05);教材出版版次维度,护理类和医药卫生其他类教材版次占比的差异有统计学意义(χ^(2)=7.496,P=0.024);第一主编单位层次、教材所属出版社数量与分布2个维度,护理类与医药卫生其他类差异无统计学意义(P>0.05);人民卫生出版社和高等教育出版社在医药卫生其他类教材出版上有较强的优势,永州职业技术学院与重庆三峡医药高等专科学校等部分高校在护理类规划教材建设上表现突出。结论高职护理教育国家规划教材建设优势明显,部分课程教材建设实力较强,但存在一些不平衡,可从教材规划、编写团队、出版审核、修订完善等环节入手,切实提升护理职业教材质量。

关键词：教材教育,护理院校,卫生职业外部特征

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Neutralization of SARS-CoV-2 infection by antibodies targeting diverse epitopes

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Genes & Diseases 2024年第4期11卷 134-137页

作者： Shusheng Wang Yunji Liao Kaiyong Yang Hang Ma Zhangyi Song Haiqiu Huang Li Zhang Ailing Wang Lei Han Jiawei Zhang Hui chen Haiyang Yin Yantin Bian Hua Jiang Xiaodong Xiao yueqing Xie Yunsheng Yuan Jianwei Zhu Engineering Research Center of Cell and Therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Jecho Laboratories Inc.FrederickMD 21704USA Jecho Institute Co. Ltd.Shanghai 200240China

The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic lives.Previous and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 infections.Using a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike protein.Many of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.

关键词： antibodies inhibited monoclonal

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试析建筑工程项目暖通空调工程的节能设计

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智能建筑 2022年第9期 86-88,91页

作者：陈月庆河北建研建筑设计有限公司

随着建筑居住水平的提高,暖通空调数量越来越多,规模越来越大,得到了越来越多人的支持。在建筑工程中,不仅要保证建筑美观,还要保证建筑具有节能性。在此基础上,根据暖通空调实际情况,采用更有效的手段来提高效率,达到理想的节能效果。... 详细信息

随着建筑居住水平的提高,暖通空调数量越来越多,规模越来越大,得到了越来越多人的支持。在建筑工程中,不仅要保证建筑美观,还要保证建筑具有节能性。在此基础上,根据暖通空调实际情况,采用更有效的手段来提高效率,达到理想的节能效果。对此,本文对建筑工程项目暖通空调节能设计进行了分析和探讨。

关键词：建筑工程暖通空调节能设计

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AN IMPROVEMENT ON ESTIMATE OF d_0/d~* FOR STARLIKE FUNCTIONS

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Systems Science and Mathematical Sciences 1989年第4期2卷 329-336页

作者：陈跃庆 Huaqiao University QuanzhouChina

Let S* be the class of starlike functions in unit disc.For f∈S*,denote its radiusof convexity by r0 and let d0=（?）|f（z）|,d*=inf{|β||f（z）≠β,|z|0/d*≥0.45,thus improving the result of d0/d*≥0.38 by McCarty,C.... 详细信息

关键词： Starlike function radius of convexity 2/3 conjecture

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Atomically Dispersed Ruthenium Catalysts with Open Hollow Structure for Lithium-Oxygen Batteries

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Nano-Micro Letters 2024年第2期16卷 154-164页

作者： Xin chen Yu Zhang Chang chen Huinan Li Yuran Lin Ke Yu Caiyun Nan chen chen Beijing Advanced Innovation Center for Materials Genome Engineering Institute of Solid State ChemistryUniversity of Science and Technology BeijingBeijing 100083People’s Republic of China Engineering Research Center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084People’s Republic of China Beijing Key Laboratory of Energy Conversion and Storage Materials Institution College of ChemistryBeijing Normal UniversityBeijing 100875People’s Republic of China

Lithium–oxygen battery with ultrahigh theoretical energy density is considered a highly competitive next-generation energy storage device,but its practical application is severely hindered by issues such as difficult decomposition of discharge products at present.Here,we have developed N-doped carbon anchored atomically dispersed Ru sites cathode catalyst with open hollow structure(h-RuNC)for Lithium–oxygen battery.On one hand,the abundance of atomically dispersed Ru sites can effectively catalyze the formation and decomposition of discharge products,thereby greatly enhancing the redox kinetics.On the other hand,the open hollow structure not only enhances the mass activity of atomically dispersed Ru sites but also improves the diffusion efficiency of catalytic molecules.Therefore,the excellent activity from atomically dispersed Ru sites and the enhanced diffusion from open hollow structure respectively improve the redox kinetics and cycling stability,ultimately achieving a high-performance lithium–oxygen battery.

关键词： Atomically dispersed Open hollow structure Discharge product Lithium Oxygen battery

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