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Identification and characterization of camptothecin tailoring enzymes in Nothapodytes tomentosa

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Journal of Integrative Plant Biology 2024年第6期66卷 1158-1169页

作者： Yin Chen Jian-Ping Huang Yong-Jiang Wang meng-Ling tu Junheng Li Bingyan Xu Guoqing Peng Jing Yang Sheng-Xiong Huang State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Economic Plants and Biotechnology Kunming Institute of Botany Chinese Academy of Sciences

Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity. Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan, have been approved as potent anticancer agents, there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g., C-9, C-10, etc.).However, contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold, thereby limiting the development of modified derivatives. Reported herein, we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa, via metabolomic and transcriptomic analysis. These consist of a cytochrome P450(Nt CPT9H) which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin, as well as two methyltransferases(Nt OMT1/2, converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5, decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin). Importantly, the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments. This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering. This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.

关键词： camptothecin biosynthesis enzymatic assay Nothapodytes tomentosa tailoring enzyme transcriptomic analysis

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury

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Neural Regeneration Research 2022年第12期17卷 2717-2724页

作者： Liang Wen Ya-Dong Wang Dong-Feng Shen Pei-Dong Zheng meng-di tu Wen-Dong You Yuan-Run Zhu Hao Wang Jun-Feng Feng Xiao-Feng Yang The First Affiliated Hospital School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Intensive Care Unit The First Hospital of JiaxingJiaxingZhejiang ProvinceChina Department of Neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair.However,the underlying molecular mechanism remains unclear.In this study,we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation.Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype,inhibited the expression of proinflammatory cytokines,and increased the expression of anti-inflammatory cytokines.Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury,inhibited neuroinflammation,and promoted the transformation of microglia to the anti-inflammatory phenotype.We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process.Finally,we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection.We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype.The interleukin 10/STAT3 pathway was activated during this process.These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

关键词： apoptosis bone marrow mesenchymal stem cells BV2 microglia exosome interleukin 10 lentiviral transfection microRNA-181b neuroinflammation phenotype signal transducer and activator of transcription 3 traumatic brain injury

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Maintenance,Repair,and Reinforcement Measures for dilapidated Small and Medium-Sized Bridges

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Journal of Architectural Research and Development 2024年第1期8卷 62-67页

作者： Xu meng Bo Liu Ji Li Zhi tu China Merchants Chongqing Highway Engineering Testing Center Co. Ltd.Chongqing 400060China Chongoing Construction Science Research Inspection and Testing Co. Ltd.Chongqing 400060China

The paper initiates by exploring the importance of maintaining,repairing,and reinforcing bridges.Subsequently,it delves into routine and preventative maintenance measures tailored for small to medium-sized bridges.Additionally,the paper examines repair and reinforcement techniques specifically designed for deteriorated small and medium-sized bridges,encompassing methods for fortifying both the bridge foundation and upper and lower structures.Lastly,the paper proposes suggestions aimed at fostering discussions and exchanges on the development of maintenance and repair processes for deteriorated small and medium-sized bridges.

关键词： dilapidated small and medium-sized bridges Maintenance Repair and reinforcement

Load Testing in Bridge Maintenance

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Journal of Architectural Research and Development 2024年第3期8卷 63-68页

作者： Bo Liu Xu meng Ji Li Zhi tu China Merchants Chongqing Highway Engineering Testing Center CO. LTD.Chongqing 400060China Chongqing Construction Science Research Inspection and Testing Co. Ltd.Chongqing 400060China

Highway bridges are a crucial component in road transportation networks.These bridges must be maintained according to usage requirements regularly.Test results must be considered before devising a maintenance plan.Load testing is a vital method of assessing the quality and performance of highway bridges.The outcomes of these tests facilitate the formulation of maintenance plans.This article examines the definition of load testing,its significance,and the process of execution,with the goal of providing support for bridge inspection and maintenance.

关键词： Highway bridge Load test and inspection Bridge maintenance

Defect Inspection Technology for Steel Truss Suspension Bridges

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Journal of World Architecture 2024年第2期8卷 12-16页

Steel truss suspension bridges are prone to developing defects after prolonged use.These defects may include corrosion of the main cable or the steel truss.To ensure the normal and safe functioning of the suspension bridge,it is necessary to inspect for defects promptly,understand the cause of the defect,and locate it through the use of inspection technology.By promptly addressing defects,the suspension bridge’s safety can be ensured.The author has analyzed the common defects and causes of steel truss suspension bridges and proposed specific inspection technologies.This research is intended to aid in the timely discovery of steel truss suspension bridge defects.

关键词： Steel truss suspension bridge Defect Inspection technology

Analysis of Bridge Inspection Technology for Highway Reconstruction and Expansion

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Journal of World Architecture 2024年第1期8卷 40-44页

作者： Xu meng Bo Liu Ji Li Zhi tu China Merchants Chongqing Highway Engineering Testing Center Co. Ltd.Chongqing 400060China Chonging Construction Science Research Inspection and Testing Co. Ltd.Chongqing 400060China

This article focuses on bridge testing technologies in highway construction and expansion projects.It provides an overview of the inspection process for bridges in highway reconstruction and expansion projects,the main inspections,and strategies for improving the quality of inspections.Relevant units should conduct bridge inspections using appearance inspections,special inspections,and bearing capacity assessments in highway reconstruction and expansion projects.To effectively improve testing quality,relevant units should also focus on establishing and improving testing standards,strengthening material testing,and improving the overall quality of the testing personnel.This research aims to enhance the quality of highway reconstruction and expansion projects by supporting the sensible application of bridge inspection technology.

关键词： Expressway Reconstruction and expansion Bridge engineering Detection technology

High-timing-precision detection of single X-ray photons by superconducting nanowires

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National Science Review 2024年第1期11卷 194-203页

作者： Shuya Guo Jingrou Tan Hengbin Zhang Jinguang Wang Tianhao Ji Labao Zhang Xiaolong Hu Jian Chen Jun Xie Kai Zou Yun meng Xiaomin Bei Ling-An Wu Qi Chen Hao Wang Xuecou tu Xiaoqing Jia Qing-Yuan Zhao Lin Kang Peiheng Wu Research Institute of Superconductor Electronics Nanjing University Qian Xuesen Laboratory of Space Technology Beijing National Laboratory of Condensed Matter Physics Institute of Physics Chinese Academy of Sciences Hefei National Laboratory School of Precision Instrument and Optoelectronic Engineering Tianjin University Key Laboratory of Optoelectronic Information Science and Technology Ministry of Education

Precisely acquiring the timing information of individual X-ray photons is important in both fundamental research and practical applications. The timing precision of commonly used X-ray single-photon detectors remains in the range of one hundred picoseconds to microseconds. In this work, we report on high-timing-precision detection of single X-ray photons through the fast transition to the normal state from the superconductive state of superconducting nanowires. We successfully demonstrate a free-running X-ray single-photon detector with a timing resolution of 20.1 ps made of 100-nm-thick niobium nitride film with an active area of 50 μm by 50 μm. By using a repeated differential timing measurement on two adjacent X-ray single-photon detectors, we demonstrate a precision of 0.87 ps in the arrival-time difference of X-ray photon measurements. Therefore, our work significantly enhances the timing precision in X-ray photon counting, opening a new niche for ultrafast X-ray photonics and many associated applications.

关键词： single-photon detection timing precision superconductor ultrafast phenomenon pulsar X-ray navigation

Reachability-Based Confidence-Aware Probabilistic Collision Detection in Highway Driving

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Engineering 2024年第2期33卷 90-107页

作者： Xinwei Wang Zirui Li Javier Alonso-Mora meng Wang School of Engineering and Materials Science Queen Mary University of LondonLondon E14NSUK Department of Cognitive Robotics Delft University of TechnologyDelft 2628 CDNetherlands School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China Chair of Traffic Process Automation “Friedrich List”Faculty of Transport and Traffic SciencesTU DresdenDresden 01069Germany

Risk assessment is a crucial component of collision warning and avoidance systems for intelligent vehicles.Reachability-based formal approaches have been developed to ensure driving safety to accurately detect potential vehicle collisions.However,they suffer from over-conservatism,potentially resulting in false–positive risk events in complicated real-world applications.In this paper,we combine two reachability analysis techniques,a backward reachable set(BRS)and a stochastic forward reachable set(FRS),and propose an integrated probabilistic collision–detection framework for highway driving.Within this framework,we can first use a BRS to formally check whether a two-vehicle interaction is safe;otherwise,a prediction-based stochastic FRS is employed to estimate the collision probability at each future time step.Thus,the framework can not only identify non-risky events with guaranteed safety but also provide accurate collision risk estimation in safety-critical events.To construct the stochastic FRS,we develop a neural network-based acceleration model for surrounding vehicles and further incorporate a confidence-aware dynamic belief to improve the prediction accuracy.Extensive experiments were conducted to validate the performance of the acceleration prediction model based on naturalistic highway driving data.The efficiency and effectiveness of the framework with infused confidence beliefs were tested in both naturalistic and simulated highway scenarios.The proposed risk assessment framework is promising for real-world applications.

关键词： Probabilistic collision detection Confidence awareness Probabilistic acceleration prediction Reachability analysis Risk assessment

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复杂环境下输电线路鸟巢目标图像检测模型

计算机工程 2024年第7期50卷 216-226页

作者：屠乃威焦猛阎馨辽宁工程技术大学电气与控制工程学院辽宁葫芦岛125105

为了解决复杂环境下电力巡检无人机对输电线路鸟巢识别精度低、错检漏检率高、定位不准等问题,在YOLOv5s模型的基础上,提出一种用于输电线路鸟巢目标检测的改进YOLO-nc-kd模型。设计一种高效的多尺度卷积特征融合模块(MCFFM),实现不同... 详细信息

为了解决复杂环境下电力巡检无人机对输电线路鸟巢识别精度低、错检漏检率高、定位不准等问题,在YOLOv5s模型的基础上,提出一种用于输电线路鸟巢目标检测的改进YOLO-nc-kd模型。设计一种高效的多尺度卷积特征融合模块(MCFFM),实现不同尺度下的高效特征提取,使模型能获得更加丰富和多样化的特征表示。引入注意力机制,提升主干网络在相似环境背景下的鸟巢特征提取能力。设计改进的定位损失函数,提高边界框的定位精度和小目标检测能力。使用知识蒸馏技术,进一步提升模型精度。实验结果表明,改进YOLO-nc-kd模型的准确率、召回率以及平均精度均值(m AP)相较于YOLOv5s模型分别提升了7.3、5.6、4.9个百分点,具有较好的输电线路鸟巢目标图像检测效果。

关键词：鸟巢检测 YOLOv5s模型注意力机制损失函数知识蒸馏

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