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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song suah yang Jinseong Kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon Kim Man Kyu Shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Cathepsin B-responsive prodrugs for cancer-targeted therapy:Recent advances and progress for clinical translation

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Nano Research 2022年第8期15卷 7247-7266页

作者： Seong Ik Jeon suah yang Man Kyu Shim Kwangmeyung Kim Biomedical Research Institute Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea

The cathepsin B-responsive prodrugs are promising strategies to reduce the serious adverse effects of anticancer drugs by improving the cancer selectivity that can be specifically activated by overexpressed cathepsin B in targeted cancer ***,clinical translation of such therapeutic approaches has been restricted by low antitumor efficacy that is mainly attributable to undesirable pharmacokinetic profiles and inefficient tumor-targeting of cathepsin B-responsive prodrugs,due to their small-molecule *** recent decades,many researchers have widely investigated the drug delivery system(DDS)to improve the in vivo pharmacokinetic profiles and tumor-targeting efficiency of cathepsin B-responsive prodrugs via the application of polymers,dendrimers,antibodies,lipids,and inorganic nanoparticles as drug *** addition,the potential therapeutic efficacy of DDS for cathepsin B-responsive prodrugs is demonstrated in multiple studies and combinatorial treatment with typical therapeutic modalities can effectively overcome the challenges of tumor heterogeneity and multidrug *** this review,recent advances and progress of new DDS for cathepsin B-responsive prodrugs are outlined,and their clinical trials are ***,potential challenges and the outlooks for clinical translation of cathepsin B-responsive prodrugs are highlighted.

关键词： cathepsin B prodrug chemotherapy drug delivery system targeted cancer therapy

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All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy

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Bioactive Materials 2023年第10期28卷 358-375页

作者： Sukyung Song Man Kyu Shim suah yang Jaewan Lee Wan Su Yun Hanhee Cho Yujeong Moon Jin Young Min Eun Hee Han Hong Yeol Yoon Kwangmeyung Kim College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul03760Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul02841Republic of Korea Department of Bioengineering Korea UniversitySeoul02841Republic of Korea Research Center for Bioconvergence Analysis Korea Basic Science Institute(KBSI)Cheongju28119Republic of Korea Department of Toxicology College of PharmacyChungnam National UniversityDaejeon34134Republic of Korea

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.

关键词： Chitosan nanoparticle Synergistic immunotherapy Immune checkpoint blockade Multivalent binding Immunogenic cell death

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Vibration properties of Paulownia wood for Ruan sound quality using machine learning methods

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Journal of Forestry Research 2024年第5期35卷 216-222页

作者： yang yang College of Art and Design Harbin UniversityHarbin 150076People’s Republic of China College of Mechanical and Electrical Engineering Northeast Forestry UniversityHarbin 150040People’s Republic of China

As an important material for manufacturing resonant components of musical instruments,Paulownia has an important influence on the sound quality of *** this paper,a model for evaluating the sound quality of Ruan based on the vibration characteristics of wood is developed using machine learning ***,the selection of materials for Ruan manufacturing relies primarily on manually weighing,observing,striking,and listening by the instrument *** in scientific theory have hindered the quality of the finished *** this study,nine Ruans were manufactured,and a prediction model of Ruan sound quality was proposed based on the raw material information of *** of a total of 180 data sets,145 and 45 sets were chosen for training and validation,*** this paper,typical correlation analysis was used to determine the correlation between two single indicators in two adjacent pairwise combinations of the measured objects in each stage of the production process in *** vibra-tion characteristics of the wood were tested,and a model for predicting the evaluation of Ruan’s acoustic qualities was developed by measuring the vibration characteristics of the resonating plate *** acoustic quality of the Ruan sound board wood was evaluated and predicted using machine learning model generalized regression neural *** results show that the prediction of Ruan sound quality can be achieved using Matlab simulation based on the vibration characteristics of the soundboard *** the model-predicted values were compared with the tradi-tional predicted results,it was found that the generalized regression neural network had good performance,achieving an accuracy of 93.8%which was highly consistent with the experimental *** was concluded that the model can accurately predict the acoustic quality of the Ruan based on the vibration performance of the soundboards.

关键词： Sound quality Wood vibration performance Paulownia wood Machine learning methods

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Overview of radar detection methods for low altitude targets in marine environments

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Journal of Systems Engineering and Electronics 2024年第1期35卷 1-13页

作者： yang Yong yang Boyu School of Electronic Science National University of Defense TechnologyChangsha 410073China

In this paper,a comprehensive overview of radar detection methods for low-altitude targets in maritime environments is presented,focusing on the challenges posed by sea clutter and multipath *** performance of the radar detection methods under sea clutter,multipath,and combined conditions is categorized and summarized,and future research directions are outlined to enhance radar detection performance for low-altitude targets in maritime environments.

关键词： radar sea clutter multipath scattering detection low altitude target

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Fresh-Keeping Decision and Coordination of Fresh Agricultural Product Supply Chain Considering Carbon Cap-and-Trade under Different Dominance

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Journal of Systems Science and Systems Engineering 2024年第1期33卷 30-51页

作者： yang yang Guanxin Yao China Institute for Agricultural Equipment Industrial Development Jiangsu UniversityZhenjiang212013China Jiangsu Modern Logistics Research Base Yangzhou UniversityYangzhou225009China

In the context of low carbon,this paper discussed the impact of the carbon cap-and-trade policy on the fresh-keeping decision-making of two-echelon fresh agricultural product supply chains under different dominance,and designed cost-sharing contracts to coordinate the supply chain of fresh agricultural products dominated by suppliers and retailers *** results showed that:dominance has no effect on the fresh-keeping decision and total revenue of fresh agricultural product supply chain,but it affects the internal income distribution,and dominance does not always bring more benefits;the implementation of carbon cap-and-trade reduces the fresh-keeping decision-making of fresh agricultural products supply chain and reduces the free-rider income of followers;the role of higher carbon trading price is twofold,which not only brings about the speculation of leading enterprises,but also promotes the application of low-carbon technologies;consumers’high preference for freshness,low-cost and high-efficiency low-carbon technology are all conducive to improving the fresh-keeping efforts and benefits of the supply chain;cost-sharing contracts can coordinate the supply chain of fresh agricultural products.

关键词： Dominant power carbon cap-and-trade policy fresh agricultural product supply chain fresh-keeping decision-making

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Selective nano-buckling improves the performance of graphene logic transistors

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National Science Review 2024年第2期11卷 95-96页

作者： Tong yang Ming yang Department of Applied Physics The Hong Kong Polytechnic University Research Centre for Nanoscience and Nanotechnology The Hong Kong Polytechnic University

The massive integration of silicon-based transistors into modern electronic devices greatly increases power consumption and heat generation/dissipation[1]. In this concern, transistors based on atomically-thin graphene that exhibit high electric and thermoelectric conductivities with negligible contact resistance,

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Design Optimization and Operating Performance of S-CO_(2) Brayton Cycle under Fluctuating Ambient Temperature and Diverse Power Demand Scenarios

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Journal of Thermal Science 2024年第1期33卷 190-206页

作者： yang Jingze yang Zhen DUAN Yuanyuan Key Laboratory for Thermal Science and Power Engineering of MOE Beijing Key Laboratory for CO_(2) Utilization and Reduction TechnologyTsinghua UniversityBeijing 100084China

The supercritical CO_(2)(S-CO_(2)) Brayton cycle is expected to replace steam cycle in the application of solar power tower system due to the attractive potential to improve efficiency and reduce *** the concentrated solar power plant with thermal energy storage is usually located in drought area and used to provide a dispatchable power output,the S-CO_(2) Brayton cycle has to operate under fluctuating ambient temperature and diverse power demand *** addition,the cycle design condition will directly affect the off-design *** this work,the combined effects of design condition,and distributions of ambient temperature and power demand on the cycle operating performance are analyzed,and the off-design performance maps are proposed for the first time.A cycle design method with feedback mechanism of operating performance under varied ambient temperature and power demand is introduced *** show that the low design value of compressor inlet temperature is not conductive to efficient operation under low loads and sufficient output under high ambient *** average yearly efficiency is most affected by the average power demand,while the load cover factor is significantly influenced by the average ambient *** multi-objective optimization,the optimal solution of designed compressor inlet temperature is close to the minimum value of35℃ in Delingha with low ambient temperature,while reaches 44.15℃ in Daggett under the scenario of high ambient temperature,low average power demand,long duration and large value of peak load during the peak temperature *** the cycle designed with compressor inlet temperature of 35℃ instead of 44.15℃ in Daggett under light industry power demand,the reduction of load cover factor will reach 0.027,but the average yearly efficiency can barely be improved.

关键词： supercritical CO_(2)Brayton cycle ambient temperature fluctuating power demand scenarios design optimization off-design performance

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A physics-informed deep learning framework for spacecraft pursuit-evasion task assessment

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Chinese Journal of Aeronautics 2024年第5期37卷 363-376页

作者： Fuyunxiang yang Leping yang Yanwei ZHU College of Aerospace Science and Engineering National University of Defense TechnologyChangsha 410073China

Qualitative spacecraft pursuit-evasion problem which focuses on feasibility is rarely studied because of high-dimensional dynamics,intractable terminal constraints and heavy computational *** this paper,A physics-informed framework is proposed for the problem,providing an intuitive method for spacecraft threat relationship determination,situation assessment,mission feasibility analysis and orbital game rules *** the first time,situation adjustment suggestions can be provided for the weak player in orbital ***,a dimension-reduction dynamics is derived in the line-of-sight rotation coordinate system and the qualitative model is determined,reducing complexity and avoiding the difficulty of target set presentation caused by individual ***,the Backwards Reachable Set(BRS)of the target set is used for state space partition and capture zone ***-time analysis can eliminate the influence of changeable initial state and enable the proposed framework to analyze plural situations ***,a time-dependent Hamilton-Jacobi-Isaacs(HJI)Partial Differential Equation(PDE)is established to describe BRS evolution driven by dimension-reduction dynamics,based on level set ***,Physics-Informed Neural Networks(PINNs)are extended to HJI PDE final value problem,supporting orbital game rules summarization through capture zone evolution ***,numerical results demonstrate the feasibility and efficiency of the proposed framework.

关键词： Spacecraft pursuit-evasion Qualitative differential game Physics-Informed Neural Networks(PINNs) Reachability analysis Hamilton-Jacobi-Isaacs(HJI) Partial Differential Equations(PDEs)

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Processing,microstructure,and properties of porous ceramic composites with directional channels

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Journal of Materials Science & Technology 2024年第1期168卷 1-15页

作者： Bo Zhang yang yang Xueling Fan Key Laboratory of Service Performance and Protection Technology in Extreme Environments Xi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Strength and Vibration of Mechanical Structures School of Aerospace EngineeringXi’an Jiaotong UniversityXi’an 710049China

Porous ceramic composites with directional microchannels from micrometer to dozens of micrometer levels have attracted more and more attention in various fields including aerospace,biomedicines,and thermal insulation due to their excellent fluid permeability,mechanical properties,*** this article,we summarize the recent directional porous ceramics developments including their main processing routes and respective ***,the properties get from different processing routes have been com-pared and analyzed in terms of microstructures,mechanical properties,and *** has been given to the deeper understanding which can allow one to control the microstructural features of these porous ceramic composites to obtain the desired *** work can provide a useful reference for the development and application of porous ceramic composites with directional microchan-nels.

关键词： Porous ceramic composites Directional microchannels Processing routes Permeability

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