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DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui jian sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei jiang Ceshi Chen Affiliated Hospital of Guangdong Medical University Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research Center of Guizhou Medical University GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Center KunmingYunnan 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu jian sun Lian Jin Hai-Bing Xie jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and diseases.Here we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5.Interestingly,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee divergence.We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques.In addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells.Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene.These findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

Higher-order properties and extensions for indirect MRAC and APPC of linear systems

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Science China(Information Sciences) 2024年第4期67卷 218-238页

作者： Yanjun ZHANG Zhipeng ZHANG jian sun Lei WANG Kangkang ZHANG National Key Lab of Autonomous Intelligent Unmanned Systems Beijing Institute of Technology School of Automation Beijing Institute of Technology 3. Beijing Institute of Technology Chongqing Innovation Center College of Control Science and Engineering Zhejiang University Department of Electrical and Electronic Engineering Imperial College London KIOS Research and Innovation Center of Excellence University of Cyprus

Recently, a reference derived some new higher-order output tracking properties for direct model reference adaptive control(MRAC) of linear time-invariant(LTI) systems: limt→∞ e~((i))(t) = 0, i = 1,..., n~*-1, where n~* and e~((i))(t) denote the relative degree of the system and the i-th derivative of the output tracking error, respectively. However, a naturally arising question involves whether indirect adaptive control(including indirect MRAC and indirect adaptive pole placement control) of LTI systems still has higher-order tracking properties. Such properties have not been reported in the literature. Therefore, this paper provides an affirmative answer to this question. Such higher-order tracking properties are new discoveries since they hold without any additional design conditions and, in particular, without the persistent excitation condition. Given the higher-order properties, a new adaptive control system is developed with stronger tracking features.(1) It can track a reference signal with any order derivatives being unknown.(2) It has higher-order exponential or practical output tracking properties.(3) Finally, it is different from the usual MRAC system, whose reference signal’s derivatives up to the n~* order are assumed to be known. Finally, two simulation examples are provided to verify the theoretical results obtained in this paper.

关键词： higher-order tracking indirect adaptive control model reference adaptive control adaptive pole placement control

Continuous advantage learning for minimum-time trajectory planning of autonomous vehicles

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Science China(Information Sciences) 2024年第7期67卷 285-294页

作者： Zhuo LI Weiran WU Jialin WANG Gang WANG jian sun School of Automation Beijing Institute of Technology Beijing Institute of Technology Chongqing Innovation Center China Academy of Launch Vehicle Technology Intelligent Game and Decision Laboratory

This paper investigates the minimum-time trajectory planning problem of an autonomous vehicle. To deal with unknown and uncertain dynamics of the vehicle, the trajectory planning problem is modeled as a Markov decision process with a continuous action space. To solve it, we propose a continuous advantage learning(CAL) algorithm based on the advantage-value equation, and adopt a stochastic policy in the form of multivariate Gaussian distribution to encourage exploration. A shared actor-critic architecture is designed to simultaneously approximate the stochastic policy and the value function, which greatly reduces the computation burden compared to general actor-critic methods. Moreover, the shared actor-critic is updated with a loss function built as mean square consistency error of the advantage-value equation, and the update step is performed several times at each time step to improve data efficiency. Simulations validate the effectiveness of the proposed CAL algorithm and its better performance than the soft actor-critic algorithm.

关键词： trajectory planning continuous advantage learning stochastic policy shared actor-critic

Exploring changes of precipitation extremes under climate change through global variable-resolution modeling

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Science Bulletin 2024年第2期69卷 237-247页

作者： Wei sun jian Li Rucong Yu Nina Li Yi Zhang State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Institute of Tibetan Plateau Meteorology China Meteorological AdministrationChengdu 610072China Department of Atmospheric Science Yunnan UniversityKunming 650091China National Meteorological Center China Meteorological AdministrationBeijing 100081China 2035 Future Laboratory PIESAT Information Technology Co.Ltd.Beijing 100105China

Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the record-breaking precipitation over China in 2021 as an example,and study its changes under three different climate scenarios through a developed pseudo-global-warming(PGW)experimental framework with 60-3 km variable-resolution global ensemble modeling.Compared to the present climate,the precipitation extreme under a warmer(cooler)climate increased(decreased)in intensity,coverage,and total amount at a range of 24.3%-37.8%(18.7%-56.1%).With the help of the proposed PGW experimental framework,we further reveal the impacts of the multi-scale system interactions in climate change on the precipitation extreme.Under the warmer climate,large-scale water vapor transport converged from double typhoons and the subtropical high marched into central China,enhancing the convective energy and instability on the leading edge of the transport belt.As a result,the mesoscale convective system(Mcs)that directly contributed to the precipitation extreme became stronger than that in the present climate.On the contrary,the cooler climate displayed opposite changing characteristics relative to the warmer climate,ranging from the large-scale systems to local environments and to the Mcs.In summary,our study provides a promising approach to scientifically assess the response of precipitation extremes to climate change,making it feasible to perform ensemble simulations while investigating the multi-scale system interactions over the globe.

关键词： Precipitation extreme Climate change Pseudo-global-warming experiment Variable-resolution modeling Multi-scale system interaction

Noninvasive Detection of Cerebral Blood Flow and Blood Oxygen Based on Inductive Sensing Technology and Near Infrared Spectroscopy

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Journal of Beijing Institute of Technology 2024年第3期33卷 204-212页

作者： Cheng Zhou Zexiang Lyu Maoting Zhang Xin Zou Liang Wei Feng Wang Mingxin Qin Jia Xu jian sun College of Biomedical Engineering Army Medical UniversityChongqing 400038China School of Pharmacy and Bioengineering Chongqing University of TechnologyChongqing 400054China Department of Medical Engineering Xinqiao HospitalChongqing 400037China

The synchronous monitoring of cerebral blood flow and blood oxygen levels plays a pivotal role in the prevention,diagnosis,and treatment of cerebrovascular diseases.This study introduces a novel noninvasive device utilizing inductive sensing and near-infrared spectroscopy technology to facilitate simultaneous monitoring of cerebral blood flow and blood oxygen levels.The device consists of modules for cerebral blood flow monitoring,cerebral blood oxygen monitoring,control,communication,and a host machine.Through experiments conducted on healthy subjects,it was confirmed that the device can effectively achieve synchronous monitoring and recording of cerebral blood flow and blood oxygen signals.The results demonstrate the device’s capability to accurately measure these signals simultaneously.This technology enables dynamic monitoring of cerebral blood flow and blood oxygen signals with potential clinical applications in preventing,diagnosing,treating cerebrovascular diseases while reducing their associated harm.

关键词： cerebrovascular disease synchronous monitoring inductive sensing near infrared spec-troscopy(NIRS)

Substrate screening for superclean graphene growth using firstprinciples calculations

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Nano Research 2024年第4期17卷 2216-2222页

作者： Zhihao Li Xiucai sun Xiaoli sun Wan-jian Yin Zhongfan Liu College of Energy Soochow Institute for Energy and Materials InnovationS(SIEMIS)and Jiangsu Provincial Key Laboratory for Advanced Carbon Materials and Wearable Energy TechnologiesSoochow UniversitySuzhou 215006China Graphene Basic Science Research Center Beijing Graphene Institute(BGI)Beijing 100095China Center for Nanochemistry Beijing Science and Engineering Center for NanocarbonsBeijing National Laboratory for Molecular ScienceCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

Suppressing the formation of amorphous surface carbon and contaminants during the preparation of graphene by chemical vapor deposition remains an ongoing issue.Herein,we analyzed how substrate characteristics affect graphene quality by simulating margin extension,the nucleation process,and defect pegging configurations on mono-crystalline oriented metal substrates with the aim of enhancing graphene cleanliness.Defect formation energy and nucleation potential,which are indirect substrate–graphene interaction features,were found to appropriately evaluate graphene quality.The crystallographic orientation of the metal substrate was discovered to be critical for producing superclean graphene.A low graphene defect density and high nucleation rate on the Cu(100)facet guarantee growth of high-quality graphene,especially in terms of suppressing the formation of amorphous carbon.In addition,rapid kink growth and self-healing on the Cu(100)facet facilitate rapid graphene synthesis,which is also promoted by rapid kink splicing and margin self-repair on this facet.This study provides theoretical insight useful for the synthesis of superclean graphene.

关键词： superclean graphene defects nucleation metal substrates density functional theory calculations

Prediction of lime utilization ratio of dephosphorization in BOF steelmaking based on online sequential extreme learning machine with forgetting mechanism

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 508-517页

作者： Runhao Zhang jian Yang Han sun Wenkui Yang State Key Laboratory of Advanced Special Steel School of Materials Science and EngineeringShanghai UniversityShanghai 200444China

The machine learning models of multiple linear regression(MLR),support vector regression(SVR),and extreme learning ma-chine(ELM)and the proposed ELM models of online sequential ELM(OS-ELM)and OS-ELM with forgetting mechanism(FOS-ELM)are applied in the prediction of the lime utilization ratio of dephosphorization in the basic oxygen furnace steelmaking process.The ELM model exhibites the best performance compared with the models of MLR and SVR.OS-ELM and FOS-ELM are applied for sequential learning and model updating.The optimal number of samples in validity term of the FOS-ELM model is determined to be 1500,with the smallest population mean absolute relative error(MARE)value of 0.058226 for the population.The variable importance analysis reveals lime weight,initial P content,and hot metal weight as the most important variables for the lime utilization ratio.The lime utilization ratio increases with the decrease in lime weight and the increases in the initial P content and hot metal weight.A prediction system based on FOS-ELM is applied in actual industrial production for one month.The hit ratios of the predicted lime utilization ratio in the error ranges of±1%,±3%,and±5%are 61.16%,90.63%,and 94.11%,respectively.The coefficient of determination,MARE,and root mean square error are 0.8670,0.06823,and 1.4265,respectively.The system exhibits desirable performance for applications in actual industrial pro-duction.

关键词： basic oxygen furnace steelmaking machine learning lime utilization ratio dephosphorization online sequential extreme learning machine forgetting mechanism

Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun sun Qi Lin Dapeng Wang jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of Pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit