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Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood-brain barrier

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药学学报:英文版 2023年第9期13卷 3834-3848页

作者： Thuy Giang Nguyen Cao Ji Hee kang Su Jin kang Quan Truong Hoang han chang kang Won Jong Rhee Yu Shrike Zhang Young Tag Ko Min Suk Shim Division of Bioengineering Incheon National UniversityIncheon 22012Republic of Korea College of Pharmacy Gachon UniversityIncheon 21936Republic of Korea Department of Pharmacy Integrated Research Institute of Pharmaceutical Sciencesand BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future PharmacyCollege of Pharmacythe Catholic University of KoreaGyeonggi-do 14662Republic of Korea Research Center for Bio Materials&Process Development Incheon National UniversityIncheon 22012Republic of Korea Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA

Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ability.Herein,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB.To enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into bEVs.TPPconjugated Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation.Moreover,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM cells.An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis.As such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.

关键词： Extracellular vesicle Chlorin e6 Triphenylphosphonium Mitochondria-targeting photosensitizer Photodynamic therapy Blood-brain barrier Glioblastoma Transferrin receptor

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Editor Profile: Guest Editors of the Special Issue“Functional Materials, Nanocarriers,and Formulations for Targeted Therapy”

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Acta Pharmaceutica Sinica B 2016年第4期6卷 259-260页

作者： Zhonggao Gao han-chang kang the Chinese Academy of Medical Sciences the Department of Pharmaceutics Institute of Materia Medica The Catholic University of Korea The University of Utah

Interest in functional materials,nanocarriers,and formulations for targeted therapy,which can selectively deliver therapeutic or diagnostic payloads to target sites such as organs,tissues,cells,and subcellular organel... 详细信息

关键词： targeted deliver facilitate organs targeting diagnostic Editor Profile continuously pharmaceutical sustained

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Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes:current strategies and future perspectives

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Acta Pharmaceutica Sinica B 2018年第6期8卷 862-880页

作者： Gantumur Battogtokh Yeon Su Choi Dong Seop kang Sang Jun Park Min Suk Shim kang Moo Huh Yong-Yeon Cho Joo Young Lee Hye Suk Lee han chang kang Department of Pharmacy Integrated Research Institute of Pharmaceutical Sciences and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy College of Pharmacy The Catholic University of Korea Division of Bioengineering Incheon National University Department of Polymer Science and Engineering Chungnam National University

mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium(TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides,dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively,compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo, further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.

关键词： Anticancer agents Antioxidants Direct conjugation Mitochondria-targeting Sensing agents

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An Experimental Study on Response and Control of a Flapping-Wing Aerial Robot Under Wind Gusts

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Journal of Bionic Engineering 2024年第1期21卷 209-223页

作者： Kazuki Shimura Hikaru Aono chang-kwon kang Graduate School of Science and Technology Shinshu University3-15-1 TokidaUedaNagano 3868567Japan Department of Mechanical Engineering and Robotics 3-15-1 TokidaUedaNagano 3868567Japan Department of Mechanical and Aerospace Engineering University of Alabama in HuntsvilleTechnology Hall N266HuntsvilleAL35899USA

Bioinspired flapping-wing micro-air-vehicles(FWMAVs)have the potential to be useful aerial tools for gathering information in various environments.With recent advancements in manufacturing technologies and better understanding of aerodynamic mechanisms behind of the flapping flight,outdoor flights have become a reality.However,to fully realize the potential of FWMAVs,further improvements are necessary,particularly in terms of stability and robustness under gusty conditions.In this study,the response and control of a tailless two-winged FWMAV under the wind gusts are investigated.Physical experiments are conducted with a one-degree-of-freedom gimbal to focus on effects of wind gusts on the rotational motion of the FWMAV.Proportional-derivative and sliding-mode controls are adopted for the attitude control.Results present that the body angles changed in time and reached approximately 50°at the maximum due to the wing gusts.The sliding-mode controller can more effectively control the rotational angle in the presence of disturbances and both the wing speed and changes in wind speed have an impact on the effectiveness of attitude control.These results contribute to the development of of tailless two-winged,single-motor driven FWMAVs in terms of the design of attitude controller and testing apparatus.

关键词： Flapping-wing micro-air vehicles Sliding-mode control Pitch and roll angle-Wind gus

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Confluence of asymmetric catalysis and electrosynthesis in sustainable chemical transformations

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Science China Chemistry 2024年第3期67卷 755-758页

作者： Qinglin Zhang kang Liang chang Guo Hefei National Research Center for Physical Sciences at the Microscale and Department of Chemistry University of Science and Technology of ChinaHefei 230026China

Electrosynthesis has gained widespread recognition for its extraordinary ability to precisely control the redox process.This outstanding capability enables the direct conversion of non-functionalized substrates into reactive intermediates by utilizing easily accessible starting materials, eliminating the need for preliminary functionalization procedures and allowing for unconventional bond activations.

关键词： Confluence of asymmetric catalysis and electrosynthesis in sustainable chemical transformations

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Research on Optimal Preload Method of Controllable Rolling Bearing Based on Multisensor Fusion

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 3329-3352页

作者： Kuosheng Jiang Chengrui han Yasheng chang School of Mechanical and Electrical Engineering Anhui University of Science and TechnologyHuainan232001China School of Optical and Electronic Information Suzhou City University&Suzhou Key Laboratory of BiophotonicsSuzhou215104China State Key Laboratory for Manufacturing Systems Engineering Xi’an Jiaotong UniversityXi’an710054China

Angular contact ball bearings have been widely used in machine tool spindles,and the bearing preload plays an important role in the performance of the spindle.In order to solve the problems of the traditional optimal preload prediction method limited by actual conditions and uncertainties,a roller bearing preload test method based on the improved D-S evidence theorymulti-sensor fusion method was proposed.First,a novel controllable preload system is proposed and evaluated.Subsequently,multiple sensors are employed to collect data on the bearing parameters during preload application.Finally,a multisensor fusion algorithm is used to make predictions,and a neural network is used to optimize the fitting of the preload data.The limitations of conventional preload testing methods are identified,and the integration of complementary information frommultiple sensors is used to achieve accurate predictions,offering valuable insights into the optimal preload force.Experimental results demonstrate that the multi-sensor fusion approach outperforms traditional methods in accurately measuring the optimal preload for rolling bearings.

关键词： Multi-sensor information fusion neural network preload force

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CFD-DEM study on the synergistic effect of coke consumption and particle dynamics in the blast furnace raceway

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Particuology 2024年第6期89卷 270-278页

作者： Peng Xu Peng han Zhijun He Xizhong An kang Sun Lihua Gao Key Laboratory of Green Low-Carbon and Intelligent Metallurgy School of Materials and MetallurgyUniversity of Science and Technology LiaoningAnshan 114000China Key Laboratory for Ecological Metallurgy of Multimetallic Mineral of Ministry of Education School of MetallurgyNortheastern UniversityShenyang110819China

In this study,the gas-solid flow process in the blast furnace raceway is numerically simulated using coupled computational fluid dynamics and the discrete element method(CFD-DEM).The coke reaction kinetics data are imported into the DEM model to reproduce the consumption process of each coke particle.The effects of inlet gas velocity and angle on the morphology of the raceway,coke consumption rate,coke bed temperature,and particle size distribution in the blast process are systematically investigated and analyzed.The results show that the consumption of coke particles promotes the formation of raceways during the blast process.At the same time,a coke mixture layer is produced at the edge of the raceway.The higher the inlet gas velocity,the thicker the coke mixture layer in the middle and upper parts of the raceway region,and the larger the proportion of small particles in the coke mixture layer.The effect of the inlet gas angle on the raceway region is less than the inlet gas velocity.However,with the increase in the inlet gas angle,the high-temperature region of the coke bed extends downward gradually,which is conducive to activating the hearth.

关键词： Blast furnace Raceway Multiphase flow CFD-DEM Modeling

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Molecular Chaperone-Dependent Polymer Translocation through Nanopores: The Effects of Chaperone Concentration and Chaperone-Polymer Interaction

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Chinese Journal of Polymer Science 2024年第1期42卷 125-132,I0011页

作者： chang-Sheng Zuo kang Wang Li-Zhen Sun Ting-Ting Sun Department of Physics Zhejiang University of Science and TechnologyHangzhou 310023China Department of Applied Physics Zhejiang University of TechnologyHangzhou 310014China

The polymer translocation through a nanopore from a donor space(or named cis side) to a receiver space(trans side) in the chaperone-induced crowded environment has attracted increasing attention in recent years due to its significance in biological systems and technological applications. In this work, we mainly focus on the effects of chaperone concentration and chaperone-polymer interaction on the polymer translocation. By assuming the polymer translocation to be a quasi-equilibrium process, the free energy F of the polymer can be estimated by Rosenbluth-Rosenbluth method and then the translocation time τ can be calculated by Fokker-Plank equation based on the obtained free energy landscape. Our calculation results show that the translocation time can be controlled by independently tuning the chaperone concentration and chaperone-polymer interaction at the cis side or the trans side. There exists a critical chaperone-polymer attraction ε~*=-0.2 at which the volume exclusion and interaction effects of the chaperone can balance each other. Additionally, we also find that at large chaperone-polymer attraction, the translocation time is mainly governed by the diffusion coefficient of the polymer.

关键词： Polymer translocation Rosenbluth-Rosenbluth method Fokker-Plank equation Free energy landscapes

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A semantic segmentation-based underwater acoustic image transmission framework for cooperative SLAM

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Defence Technology（防务技术） 2024年第3期33卷 339-351页

作者： Jiaxu Li Guangyao han Shuai chang Xiaomei Fu School of Marine Science and Technology Tianjin UniversityTianjin 300072China

With the development of underwater sonar detection technology,simultaneous localization and mapping(SLAM)approach has attracted much attention in underwater navigation field in recent years.But the weak detection ability of a single vehicle limits the SLAM performance in wide areas.Thereby,cooperative SLAM using multiple vehicles has become an important research direction.The key factor of cooperative SLAM is timely and efficient sonar image transmission among underwater vehicles.However,the limited bandwidth of underwater acoustic channels contradicts a large amount of sonar image data.It is essential to compress the images before transmission.Recently,deep neural networks have great value in image compression by virtue of the powerful learning ability of neural networks,but the existing sonar image compression methods based on neural network usually focus on the pixel-level information without the semantic-level information.In this paper,we propose a novel underwater acoustic transmission scheme called UAT-SSIC that includes semantic segmentation-based sonar image compression(SSIC)framework and the joint source-channel codec,to improve the accuracy of the semantic information of the reconstructed sonar image at the receiver.The SSIC framework consists of Auto-Encoder structure-based sonar image compression network,which is measured by a semantic segmentation network's residual.Considering that sonar images have the characteristics of blurred target edges,the semantic segmentation network used a special dilated convolution neural network(DiCNN)to enhance segmentation accuracy by expanding the range of receptive fields.The joint source-channel codec with unequal error protection is proposed that adjusts the power level of the transmitted data,which deal with sonar image transmission error caused by the serious underwater acoustic channel.Experiment results demonstrate that our method preserves more semantic information,with advantages over existing methods at the same compression ratio.It also improves the error

关键词： Semantic segmentation Sonar image transmission Learning-based compression

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Artificial intelligence optimization and controllable slow-release iron sulfide realizes efficient separation of copper and arsenic in strongly acidic wastewater

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Journal of Environmental Sciences 2024年第5期139卷 293-307页

作者： Xingfei Zhang Chenglong Lu Jia Tian Liqiang Zeng Yufeng Wang Wei Sun Haisheng han Jianhua kang School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China Centre for Mined Land Rehabilitation Sustainable Minerals InstituteThe University of QueenslandBrisbane 4072Australia

Iron sulfide(FeS)is a promising material for separating copper and arsenic from strongly acidic wastewater due to its S^(2-)slow-release effect.However,uncertainties arise because of the constant changes in wastewater composition,affecting the selection of operating parameters and FeS types.In this study,the aging method was first used to prepare various controllable FeS nanoparticles to weaken the arsenic removal ability without affecting the copper removal.Orthogonal experiments were conducted,and the results identified the Cu/As ratio,H_(2)SO_(4) concentration,and FeS dosage as the three main factors influencing the separation efficiency.The backpropagation artificial neural network(BP-ANN)model was established to determine the relationship between the influencing factors and the separation efficiency.The correlation coefficient(R)of overall model was 0.9923 after optimizing using genetic algorithm(GA).The BP-GA model was also solved using GA under specific constraints,predicting the best solution for the separation process in real-time.The predicted results show that the high temperature and long aging time of FeS were necessary to gain high separation efficiency,and the maximum separation factor can reached 1,400.This study provides a suitable sulfurizing material and a set of methods and models with robust flexibility that can successfully predict the separation efficiency of copper and arsenic from highly acidic environments.

关键词： FeS nanoparticles Aging Sulfide precipitation Orthogonal experiment Artificial neural network Prediction

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