检索结果-南通市图书馆

Design,synthesis,and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2021年第5期11卷 1315-1328页

作者： Liang Jiang Yuting Wang Qian Li Zhengchao Tu Sihua Zhu Sanfang Tu Zhang Zhang Ke Ding xiaoyun lu Intemational Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of Education(MOE)of ChinaSchool of PharmacyJinan UniversityGuangzhou 510632China Department of Hematology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China

Bcr-Abl threonine 315 to isoleucine 315(T315 I)gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia(CML).Chemical degradation of Bcr-AblT315 Iprotein has become a potential strategy to overcome drug ***,we first described the design,synthesis,and evaluation of a new class of selective Bcr-AblT315 I proteolysis-targeting chimeric(PROTAC)degraders based on GZD824(reported as Bcr-AblT315 Iinhibitor by our group).One of the degrader 7 o with 6-member carbon chain linkage with pomalidomide exhibits the most potent degradation efficacy with DR of 69.89%and 94.23%at 100 and 300 nmol/L,respectively,and has an IC50 value of 26.8±9.7 nmol/L against Ba/F3T315 ***,7 o also displays substantial tumor regression against Ba/F3-Bcr-AblT315 Ixenograft model in vivo.

关键词： CML PROTAC Degradation T315I mutation Clinical resistance

老年早期胃癌患者内镜治疗术后伴发营养不良的风险预测模型构建

在线全文

学校读者我要写书评

暂无评论

老年医学与保健 2024年第4期30卷 947-952页

作者：张军玲黄娟娟姜素峰卢晓云张婷江苏省中医院消化内镜中心江苏南京210036

目的分析老年早期胃癌患者行内镜黏膜下剥离术(ESD)、内镜黏膜切除术(EMR)居家伴发营养不良的影响因素。方法选取2022年1月-2023年12月在江苏省中医院接受早期胃癌行ESD或EMR治疗的80例老年患者作为研究对象,根据术后在居家环境中是... 详细信息

目的分析老年早期胃癌患者行内镜黏膜下剥离术(ESD)、内镜黏膜切除术(EMR)居家伴发营养不良的影响因素。方法选取2022年1月-2023年12月在江苏省中医院接受早期胃癌行ESD或EMR治疗的80例老年患者作为研究对象,根据术后在居家环境中是否发生营养不良,将患者分为发生营养不良组(n=45)和未发生营养不良组(n=35)。采用单因素和多因素分析方法,探讨影响营养不良发生的高危因素。结果单因素分析显示,2组高血压、血钾、血糖、血红蛋白检测值差异无统计学意义(P>0.05)。2组年龄、文化程度、焦虑得分、抑郁得分、早饱感、人格特质、术前低蛋白血症、术前血钙等均与胃癌患者术后发生营养不良有关(均P75岁、抑郁得分>35分、有早饱感、焦虑得分≥29分、术前低蛋白血症等均为导致胃癌患者术后发生营养不良的独立危险因素(P0.75,最佳临界值为0.554,提示模型具有一定的预测能力。Hosmer-Lemeshow检验评价模型校准能力(χ^(2)=0.879,P=0.761>0.05),提示模型有良好的拟合优度。DCA结果显示,当营养不良临界概率值在9%~95%时,使用该模型能够获得较高的净收益。结论本研究构建的老年早期胃癌患者术后营养不良风险预测模型,通过多因素Logistic回归分析发现,年龄>75岁、抑郁得分>35分、有早饱感、焦虑得分≥29分、术前低蛋白血症等可能为其独立危险因素。该模型经数据验证,具有较好的预测能力和校准度,且在营养不良临界概率值范围内显示出较高的净收益,可为临床实践中老年早期胃癌患者的术后营养管理提供参考。

关键词：老年胃癌营养不良影响因素人格特质低蛋白血症

Photonic neuromorphic architecture for tens-of-task lifelong learning

在线全文

学校读者我要写书评

暂无评论

Light(Science & Applications) 2024年第3期13卷 519-530页

作者： Yuan Cheng Jianing Zhang Tiankuang Zhou Yuyan Wang Zhihao Xu xiaoyun Yuan lu Fang Sigma Laboratory Department of Electronic EngineeringTsinghua UniversityBeijing 100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing 100084China Institute for Brain and Cognitive Science Tsinghua University(THUIBCS)Beijing 100084China

Scalable,high-capacity,and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning *** electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls,hindering them from the sustainable performance improvement and iterative multi-task *** to another modality of light,photonic computing has been progressively applied in high-efficient neuromorphic ***,we innovate a reconfigurable lifelong-learning optical neural network(L2 ONN),for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware *** from the inherent sparsity and parallelism in massive photonic connections,L2 ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field,while incrementally acquiring expertise on various tasks by gradually enlarging the *** multi-task optical features are parallelly processed by multi-spectrum representations allocated with different *** evaluations on freespace and on-chip architectures confirm that for the first time,L2 ONN avoided the catastrophic forgetting issue of photonic computing,owning versatile skills on challenging tens-of-tasks(vision classification,voice recognition,medical diagnosis,etc.)with a single ***,L2 ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks,and 14×larger capacity than existing optical neural networks while maintaining competitive performance on each individual *** proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme,permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

关键词： life neural versatile

Strategies of polyhydroxyalkanoates modification for the medical application in neural regeneration/nerve tissue engineering

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Advances in Bioscience and Biotechnology 2013年第6期4卷 731-740页

作者： xiaoyun lu Leilei Wang Zhiqian Yang Haixia lu Institute of Neurobiology Xi’an Jiaotong University College of Medicine Xi’an China Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi’an Jiaotong University Xi’an China

Neural regeneration was once considered to be impossible, especially in the central nervous system where neural regeneration comprise the generation of new neurons, glia, axons, myelin, and synapses. Until recently, neural stem cells/neural progenitor cells (NSCs/NPCs) were identified from various areas of brain and brought hopes to the neural repair and regeneration. Tissue engineering has revolutionized the current neural regeneration technology and it has become a pioneering interdisciplinary field in the areas of biomedical research. Polyhydoxyalkanoate (PHA) as one of biodegradable material has been successfully used as tissue engineering materials. It has also been applied in nerve tissue engineering due to the high biocompatibility and low cytotoxicity. Over the past 10 years, different kinds of modification strategies have been undertaken to improve the properties of PHA to fit the requirements from various fields. Several members of PHA family have been attempted for neural regeneration. This article reviewed the recent modification strategies for improving the properties of PHA and highlighted the pioneer applications in neural regeneration.

关键词： PHA Modification Neural Regeneration Nerve Tissue Engineering

GA-LSTM speed prediction-based DDQN energy management for extended-range vehicles

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Energy and AI

Energy and AI 2024年第3期17卷 11-28页

作者： Laiwei lu Hong Zhao Fuliang Xv Yong luo Junjie Chen xiaoyun Ding College of Mechanical and Electrical Engineering Qingdao UniversityQingdao266071Shandong ProvinceChina

In this paper,a dual deep Q-network(DDQN)energy management model based on long-short memory neural network(LSTM)speed prediction is proposed under the model predictive control(MPC)*** initial learning rate and neuron dropout probability of the LSTM speed prediction model are optimized by the genetic algorithm(GA).The prediction results show that the root-mean-square error of the GA-LSTM speed prediction method is smaller than the SVR method in different speed prediction *** predicted demand power,the state of charge(SOC),and the demand power at the current moment are used as the state input of the agent,and the real-time control of the control strategy is realized by the MPC *** simulation results show that the proposed control strategy reduces the equivalent fuel consumption by 0.0354 kg compared with DDQN,0.8439 kg compared with ECMS,and 0.742 kg compared with the power-following control *** difference between the proposed control strategy and the dynamic planning control strategy is only 0.0048 kg,0.193%,while the SOC of the power battery remains ***,the hardware-in-the-loop simulation verifies that the proposed control strategy has good real-time performance.

关键词： Extended-range vehicle LSTM speed prediction Genetic algorithm Model predictive control(MPC) Deep reinforcement learning Double deep Q-network(DDQN)

2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidines as new reversible inhibitors of EGFR C797S(Cys797 to Ser797)mutant

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2020年第5期31卷 1281-1287页

作者： Xianglong Hu Qiuju Xun Tao Zhang Su-Jie Zhu Qian Li Linjiang Tong Mengzhen Lai Tao Huang Cai-Hong Yun Hua Xie Ke Ding xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJinan UniversityGuangzhou 510632China Division of Antitumor Pharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Institute for Translational Medicine College of MedicineQingdao UniversityQingdao 266021China Department of Biochemistry and Biophysics Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China

Extensive structure-activity relationships(SARs)study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFRC797 S *** of the most potent compound 6 i potently suppressed EGFRL858 R/T790 M/C797 S kinase with an IC50 value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S mutants with IC50 values of 290 nmol/L and 316 nmol/L,***,6 i dose-dependently induced suppression of the phosphorylation of EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S in BaF3 *** 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC)patients.

关键词： EGFRC797S mutant SARs 2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidine Clinical resistance Fourth-generation inhibitors

Study of vascular smooth muscle cell calcification induced by hyperphosphate and intervented by phosphonoformic acid

在线全文

学校读者我要写书评

暂无评论

Journal of Nanjing Medical University 2007年第6期21卷 377-381页

作者： Weiping lu xiaoyun Wang Xiufen Zhao Department of Nephrology the First Affiiated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

Objective： To evaluate the effects of different concentrations of phosphate on calcium deposition and osteocalcin level in cultured bovine aortic smooth muscle cell, investigate the mechanism of hyperphosphatemia to evoke calcification of vascular smooth muscle cell and observe the effects of phosphonoformic acid（PFA） in different concentrations on vascular calcification. Methods： The bovine aortic smooth muscle cells （BASMC） were *** deposition and the expression of osteocalcin of BASMC in different concentrations of phosphate （1.5 mmol/L and 2.0 mmol/L） and PFA were determined by o-cresolphthalein complexone and radioimmunity methods, respectively. Osteocalcin mRNA expressions were determined by RT-PCR. Results： After six or nine days of BASMC cultured, the calcium deposition in Pi 2.0 mmol/L group was more than that in Pi 1.5 mmol/L group[（77.187 ± 11.692） lag/（mg · protein） vs（25.768 ± 1.750）lag/（mg · protein）, P 〈 0.01 and（125.399 ± 16.677）lag/（mg · protein） vs（29.046 ± 2.635）lag/（mg · protein）, P 〈 0.01 respectively]. The calcium deposition was dependent on time and dosage of phosphate treatment. After 72 h culture the osteocalcin in Pi 2.0 mmol/L group was more than that in Pi 1.5 mmol/L grouplin supematant,（1.503 ± 10^-2 ± 2.601 × 10^-3）ng/（ lag o protein） vs（2.981 × 10-3 ± 8.382 × 10-34）ng/（ lag · protein）, P 〈 0.001], the same was found in osteocalcin mRNA expression[OC/GAPDH, （1.906 ± 0.132） vs（0.748 ± 0.037）, P〈 0.001]. Compared to Pi 1.5mmol/L group,bovine smooth muscle cells（BSMC） cultured in media containing Pi 2.0 mmol/L phosphate levels increased calcium deposition[On day 6,（77.187 ± 11.692） la g/（mg · protein） vs （25.768 ±1.750） la g/（mg · protein）, P 〈 0.001]. Elevated phosphate treatment of BSMCs also enhanced the expression of the osteoblastic differentiation marker osteocalcin[On day 3, Pi 2.0 mmol/L group vs Pi 1.5mmol/L group,（1.503 × 10^-2 ± 2.601 × 10^-3 ）ng/（ lag · protein） vs（2.981× 10^-3 ± 8.382 × 10^-4）ng/（ μg · protein）

关键词： vascular smooth muscle cell phosphate calcification osteocalcin phosphonoformic acid

Studies on the Relationship between Neuroendocrine Cellular Differentiation in Gastric Cancers and Post-operative Survival Time

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Clinical Oncology 2007年第6期4卷 416-419页

作者： Song He Qiao Yan Xudong Chen Jianbing Zhang xiaoyun lu Hongjia Pan Li Chen Department of Pathology Nantong CancerHospital Nantong Jiangsu 226361 China Department of Pathology Nantong University Nantong Jiangsu China

OBJECTIVE To examine the ultrastructure of gastric cancer ceils by the electron microscope, in order to assess the relationship between neuroendocrine differentiation and post-operative survival time. METHODS NSE, Syn and CgA immunohistochemical labeling was conducted in 168 cases with a common-type of gastric cancer. Electron microscopy was performed in 80 cases with positive immunohistochemical labeling. These cases were followed-up for over 5 years and the post-operative survival data analyzed. RESULTS Neuroendocrine granules were found by electron microscopy in 39 cases. The rate of neuroendocrine differentiation found was 23% （39/168）, using routine diagnostic criteria and electron microscopy （REM）. The post-operative survival time of gastric cancer patients with neuroendocdne differentiation was significantly shorter （P=-0.0032） compared to those without neuroendocrine differentiation. CONCluSION It is of significant clinical importance to determine if the neuroendocrine cells are differentiated in gastdc cancers. The gastric cancer patients with neuroendocrine differentiation have a shorter post-operative survival time and a poorer prognosis. Electron microscopy is a reliable method of providing a diagnosis.

关键词： gastric cancer neuroendocrine electron microscopy post-operative survival time.

在线全文

学校读者我要写书评

暂无评论

犹豫模糊粒计算中信息熵研究

计算机工程与应用 2017年第7期53卷 171-176页

作者：鲁小云青海师范大学计算机学院西宁810008

基于犹豫模糊粒度结构理论,结合Shannon熵和梁吉业等人提出的新熵概念,给出Ι型和Π型犹豫模糊信息熵、联合熵、条件熵概念,讨论了两类犹豫模糊信息熵的偏序性,分析了给出的犹豫模糊信息熵、联合熵、条件熵与已存在的各类相关熵之间的... 详细信息

基于犹豫模糊粒度结构理论,结合Shannon熵和梁吉业等人提出的新熵概念,给出Ι型和Π型犹豫模糊信息熵、联合熵、条件熵概念,讨论了两类犹豫模糊信息熵的偏序性,分析了给出的犹豫模糊信息熵、联合熵、条件熵与已存在的各类相关熵之间的关系。

关键词：犹豫模糊粒度结构犹豫模糊信息熵犹豫模糊信息联合熵犹豫模糊信息条件熵