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ARTICLE OPEN Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer

Signal Transduction and Targeted Therapy 2021年第5期6卷 1498-1510页

作者： Huashan Liu Zhenxing liang Chi Zhou Ziwei Zeng Fengwei Wang Tuo Hu Xiaowen He xiaojian Wu Xianrui Wu Ping Lan Department of Coloreaal Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Clinical Innovation Department Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouChina Department of Colorectal Surgery Sun Yat-sen University Cancer CenterGuangzhouChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdongChina

Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of KRAS,where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages(TAMs).In human CRC specimens,mutant KRAS positively correlates with the presence of *** activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and *** turn,KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab ***,KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-la(HIF-1a),a transcription factor that controls the expression of CSF2 and glycolytic *** KRAS increased the production of reactive oxygen species,an inhibitor of prolyl hydroxylase activity which decreases HIF-1a hydroxylation,leading to enhanced HIF-1a *** cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy,and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.

关键词： KRAS colorectal programming

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Experimental investigation on the deformation characteristics of locking-steel-pipe(LSP)pile retaining structure during excavation in sand

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Underground Space 2022年第6期7卷 1098-1114页

作者： Shi Wei Rongzhu liang Guoxiong Mei M.Hesham El Naggar Lianwei Sun Jinqing Jia Xiaohua Bao xiaojian Wu Wenbing Wu Faculty of Engineering China University of GeosciencesWuhanHubei 430074China Guangxi Key Laboratory of Disaster Prevention and Engineering Safety College of Civil Engineering and ArchitectureGuangxi UniversityNanningGuangxi 530004China Geotechnical Research Centre Faculty of EngineeringThe University of Western OntarioLondonON N6A 5B9Canada Shanghai Construction Group Co. Ltd.Shanghai 200080China School of Civil Engineering Dalian University of TechnologyDalian 116024China College of Civil and Transportation Engineering Shenzhen UniversityShenzhenGuangdong 518060China

Locking-steel-pipe(LSP)piles connect with adjacent joints to form a pile row enclosure *** to the advantages of quick construction,efficiency in installation,and recycle utilization,the connected LSP piles are frequently used as retaining structure in deep ***,systematic studies of the deformation mechanism of the LSP pile retaining structure are rarely reported,and it still lack of experimental evidence to optimize the *** this study,a braced supported excavation experimental model test in sand was designed and conducted to investigate the deformation characteristics of LSP pile retaining *** dimensional(3D)printing technique was creatively applied to manufacture LSP model *** experimental results show that,a“S”shaped distribution of bending moments is observed along pile shaft when excavation is executed;the deflection of pile shaft develops deep-seated movements toward the excavation side as excavation went deeper,resulting in a“bowl”ground *** the deflection of LSP piles,a rotating trend was occurred between pairs of locking joint,and the severe open deformation of locking joint arose on excavation *** was a gradual reduction in earth pressure behind the LSP pile retaining wall with excavation *** earth pressure between two struts level had no obvious changing,owing to the supported effect of inner struts.

关键词： Locking-steel-pipe(LSP)piles Deep excavation Model test Deformation characteristics Three dimensional(3D)printing

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Modeling and Global Conflict Analysis of Firewall Policy

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China Communications 2014年第5期11卷 124-135页

作者： liang Xiaoyan XIA Chunhe JIAO Jian HU Junshun LI xiaojian Beij ing Key Laboratory of Network Technology Beihang University Beijing 100191 R R. China Beijing Information Science & Technology University Beijing 100192 P. R. China Software Development Center of China Agricultural Bank Beijing 100073 P. R. China College of Computer Science and Information Technology Guangxi Normal University Guilin 541004 Guangxi Province P. R. China

The global view of firewall policy conflict is important for administrators to optimize the *** has been lack of appropriate firewall policy global conflict analysis,existing methods focus on local conflict *** research the global conflict detection algorithm in this *** presented a semantic model that captures more complete classifications of the policy using knowledge concept in rough *** on this model,we presented the global conflict formal model,and represent it with OBDD(Ordered Binary Decision Diagram).Then we developed GFPCDA(Global Firewall Policy Conflict Detection Algorithm) algorithm to detect global *** experiment,we evaluated the usability of our semantic model by eliminating the false positives and false negatives caused by incomplete policy semantic model,of a classical *** compared this algorithm with GFPCDA *** results show that GFPCDA detects conflicts more precisely and independently,and has better performance.

关键词： firewall policy semantic model conflict analysis conflict detection

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On the Assessment of Generative AI in Requirements Analysis and Modeling Tasks with UML:An Exploratory Study

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计算机教育 2023年第12期 2-10页

作者： Chong Wang Peng liang xiaojian Li Jian Wang Zhong Luo the School of Computer Science Wuhan UniversityWuhan430072China the College of Naval Architecture and Ocean Engineering Naval University of EngineeringWuhan430033China

Generative AI is rapidly employed by software developers to generate code or other software ***,the analysis and assessment of generative AI with respect to requirements analysis and modeling tasks,especially with UML,has received little *** paper investigates the capabilities of generative AI to aid in the creation of three types of UML models:UML use case models,class diagrams,and sequence *** this purpose,we designed an AI-aided UML modeling task in our course on software requirements modeling.50 undergraduates who majored in Software Engineering at Wuhan University completed the modeling task and the corresponding online *** findings show that generative AI can help create these three types of UML models,but its performance is limited to identifying essential modeling elements of these UML models.

关键词： AI-aided education UML modeling Generative AI Requirements engineering

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Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD^(+)acute myeloid leukemia

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2185-2196页

作者： Dan Li Tongjuan Li Zhen Shang Lei Zhao Qian Xu Jiaqi Tan Yun Qin Yuanyuan Zhang Yang Cao Na Wang liang Huang xiaojian Zhu Kuangguo Zhou Liting Chen Chunrui Li Ting Xie Yi Yang Jue Wang Jianfeng Zhou Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Division of Pathology and Experimental Hematology and Cancer Biology Cincinnati Children’s Hospital Medical CenterCincinnatiOH 45248USA Immunotherapy Research Center for Hematologic Diseases of Hubei Province WuhanHubei 430030China Department of geriatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Medical Research Institute Wuhan UniversityWuhan 430071China

Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor ***3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains *** signaling is important in numerous types of ***,the role of Notch signaling in FLT3/ITD^(+)AML remains to be *** the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary *** Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular *** a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML ***,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML ***,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK *** findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.

关键词： FLT3 Notch treatment

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Classification and treatment strategy for Moyamoya disease-related aneurysms

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Chinese Neurosurgical Journal 2024年第1期10卷 1-7页

作者： Yangchun Hu xiaojian Wang Chao Li liang Zhao Jing Luo Lei Ye Baochun Cheng Department of Neurosurgery The First Affiliated Hospital of Anhui Medical UniversityJixi 218Hefei 230022People’s Republic of China

Background Moyamoya disease(MMD)is a cerebrovascular disorder characterized by progressive unilateral or bilateral stenosis of the distal internal carotid *** hemodynamic features in MMD patients alter,the comorbidity of intracranial aneurysm(IA)is sometimes observed *** aim to investigate clinical characteristics and therapeutic strategies for the comorbidity of Moyamoya disease with intracranial aneurysms(MMD-IA).Methods A total of 13 MMD-IA patients were recruited in this study and were manifested to be intracranial *** reviewed the surgical technique notes for all *** According to the locations of an aneurysm,MMD-IA could be divided into several categories:(1)MMD-IA at a circle of Willis—aneurysms usually located at the trunk of Willis circle;(2)MMD-IA at collateral anastomosis—aneurysms located at the distal end of collateral anastomosis;and(3)MMA-IA at basal ganglia *** this report,aneurysms in 10 patients located at Willis circle,2 at the pericallosal artery,and 1 at the basal ganglia *** them,endovascular embolism was performed among 5 *** clipping was conducted among 7 patients.A patient with an aneurysm at the basal ganglia region just accepted revascularization *** the treatments were ***-up studies,ranging from 6 to 24 months,demonstrated all patients received satisfactory curative *** Diverse clinical presentations could be observed among MMD-IA *** neurosurgical treatments should be chosen according to the locations of the aneurysm.

关键词： Moyamoya disease Aneurysm Clipping Revascularization Endovascular embolism

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时变环境下RCS测量中的精确背景抵消处理技术

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北京航空航天大学学报 2018年第10期44卷 2193-2199页

作者：原赛赛梁丽雅许小剑北京航空航天大学电子信息工程学院北京100083

在外场雷达散射截面(RCS)测量中,受随时间变化的环境因素影响,不同时刻测得到的数据其幅度和相位不完全相干,导致直接采用背景矢量相减技术难以有效地抑制背景杂波。建立了测量系统-测试场时变传递函数的参数化模型来表征环境变化对雷... 详细信息

在外场雷达散射截面(RCS)测量中,受随时间变化的环境因素影响,不同时刻测得到的数据其幅度和相位不完全相干,导致直接采用背景矢量相减技术难以有效地抑制背景杂波。建立了测量系统-测试场时变传递函数的参数化模型来表征环境变化对雷达接收回波的影响,并在此基础上提出了一种改进的精确背景抵消处理技术。首先,从现场测量回波数据中提取辅助校准区域数据;然后,利用降噪互相关法和优化相干函数法估计出时变传递函数模型参数,并据此对不同时刻测得的回波数据进行幅度和相位补偿,使得两者完全相干;最后,做精确的背景矢量相减处理。实验结果验证了本文技术和算法的有效性。

关键词：背景抵消雷达雷达散射截面(RCS)测量时变环境相干补偿

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复杂背景下目标散射信号测量与提取技术

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北京航空航天大学学报 2018年第10期44卷 2232-2237页

作者：梁丽雅原赛赛许小剑北京航空航天大学电子信息工程学院北京100083

在复杂环境条件下的宽带雷达目标散射特性测量中,场地周围环境产生的零多普勒杂波(ZDC)会严重影响目标测量数据的准确性。为了有效地抑制背景杂波、提高目标散射信号的测量精度,提出了一种基于最大概率提取技术。该技术首先通过方位滑... 详细信息

在复杂环境条件下的宽带雷达目标散射特性测量中,场地周围环境产生的零多普勒杂波(ZDC)会严重影响目标测量数据的准确性。为了有效地抑制背景杂波、提高目标散射信号的测量精度,提出了一种基于最大概率提取技术。该技术首先通过方位滑窗平均得到每个频点的初始固定背景杂波估计,然后对每个频点的杂波初始估计进行统计直方图处理得到最大概率幅度统计量,并依据该统计量完成门限处理得到最终的杂波估计值,从而消除方位滑窗平均处理中的剩余目标信号分量、实现精确的背景提取与抵消。对典型目标的外场测量数据处理结果验证了本文方法的有效性。

关键词：目标散射零多普勒杂波(ZDC) 背景杂波背景相减雷达散射截面(RCS)

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng liang Susu Liu Ke Deng liangfu Chen Shangwu Chen Guohui Wan xiaojian Wu Yonggui Fu Anlong Xu State Key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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基于网络中心性视角的股指增强投资策略研究

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世界经济文汇 2020年第6期 104-120页

作者：牛晓健梁张诚复旦大学经济学院上海市200433

本文利用最小生成树法构建沪深300成分股网络序列,并从网络中心性视角进行分析,结果显示股票的行业属性和特质性因素均会影响网络中心性,核心股票更可能出现在有色金属、采掘、公用事业、机械设备等产业链中上游的行业。我们分别利用核... 详细信息

本文利用最小生成树法构建沪深300成分股网络序列,并从网络中心性视角进行分析,结果显示股票的行业属性和特质性因素均会影响网络中心性,核心股票更可能出现在有色金属、采掘、公用事业、机械设备等产业链中上游的行业。我们分别利用核心股票与边缘股票构建投资组合,发现两种投资组合的收益率均优于市场指数,核心股票组合在市场快速上行期表现优异,边缘股票组合在市场震荡或下行阶段能够获得超额收益。我们认为将两个组合进行等权重投资,可实现指数增强的效果。

关键词：网络中心性核心组合边缘组合指数增强

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