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A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan He Rong liu yuan Xue yuan Quan Rongying Shi Xueying Yang Qing Lin Xun Sun Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer therapy.However,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).Here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for melanoma.The system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the combination.Our study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)infiltration.The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment.This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy Tumor immune microenvironment

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Predicting microbial extracellular electron transfer activity in paddy soils with soil physicochemical properties using machine learning

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Science China(Technological Sciences) 2024年第1期67卷 259-270页

作者： OU JiaJun LUO XiaoShan liu JunYang HUANG LinYan ZHOU LiHua yuan Yong School of Automation Guangdong University of TechnologyGuangzhou 510006China Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangzhou Key Laboratory Environmental Catalysis and Pollution ControlSchool of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China School of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China

Soil extracellular electron transfer(EET)is a pivotal biological process within the realm of soil.Unfortunately,EET suffers from a lack of predictive models.Herein,an intricately crafted machine learning model has been developed for the purpose of predicting soil EET by using the physicochemical properties of soil as independent input variables and the EET capabilities in terms of current density(j_(max))and Coulombic charge(C_(out))as dependent output variables.An autoencoder ensemble stacking(AES)model was developed to address the aforementioned issue by integrating support vector machine,multilayer perceptron,extreme gradient boosting,and light gradient boosting machine algorithms as the stacking algorithms.With 10-fold crossvalidation,the AES model exhibited notable improvements in predicting j_(max)and C_(out),with average test R^(2)values of 0.83 and 0.84,respectively,surpassing those of single machine learning(ML)models and the basic ensemble model.By utilizing partial correlation plots(PDPs),Shapley Additive explanations(SHAP)values,and SHAP decision plots,we quantitatively explained the impact and contribution of the input molecules on the AES model’s predictions of j_(max)and C_(out).In the context of the SHAP method for the AES model,total carbon(TC)was identified as the most correlated descriptor for j_(max),while total organic carbon(TOC)stood out as the most relevant descriptor for C_(out).In the prediction tasks of j_(max)and C_(out)within the AES model,employing a multitask ML approach allowed the model to benefit from the shared information of input variables,thereby enhancing its overall generalizability.This study provides a feasible tool for the prediction of soil EET from soil physiochemical properties and an advanced understanding of the relationship between soil physiochemical properties and EET capability.

关键词： extracellular electron transfer paddy soil machine learning prediction autoencoder ensemble stacking model

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Design methodology,synthesis,and control strategy of the high-speed planetary rover

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Frontiers of Mechanical Engineering 2024年第2期19卷 59-74页

作者： Renchao LU Haibo GAO Zhen liu Runze yuan Zongquan DENG State Key Laboratory of Robotics and Systems Harbin Institute of TechnologyHarbin 150001China

The planned missions to explore the surfaces of the Moon and Mars require high exploration efficiency,thus imposing new demands on the mobility system of planetary rovers.In this paper,a design method for a high-speed planetary rover(HPR)is proposed,and the representative configurations are modeled and simulated.First,the influence of the planetary surface environment on the design of HPRs is analyzed,and the design factors for HPRs are determined by studying a single-wheel suspension.Second,a design methodology for HPRs is proposed.The adaptive suspension mechanisms of a four-wheeled rover are synthesized using the all-wheel-attachment condition and position and orientation characteristics theory,which are expressed in the form of a graph theory for the increase in elastic components and active joints.Finally,a dynamic model is built,and a simulation is carried out for the proposed rover.The validity of the proposed method and rover is verified,thus highlighting their potential application in future planetary exploration.

关键词： design methodology spectrum analysis high-speed planetary rover type synthesis

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Examining the characteristics between time and distance gaps of secondary crashes

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Transportation Safety and Environment 2024年第1期6卷 116-131页

作者： Xinyuan liu Jinjun Tang Chen yuan Fan Gao Xizhi Ding Smart Transport Key Laboratory of Hunan Province School of Transport and Transportation EngineeringCentral South UniversityChangsha 410075China Department of Computer Science City University of Hong Kong999077Kowloon TongHong KongChina Department of Geography and Resource Management The Chinese University of Hong KongShatinNT 999077Hong KongChina

Understanding the characteristics of time and distance gaps between the primary(PC)and secondary crashes(SC)is crucial for preventing SC ccurrences and improving road safety.Although previous studies have tried to analyse the variation of gaps,there is limited evidence in quantifying the relationships between different gaps and various influential factors.This study proposed a two-layer stacking framework to discuss the time and distance gaps.Specifically,the framework took random forests(RF),gradient boosting decision tree(GBDT)and eXtreme gradient boosting as the base classifiers in the first layer and applied logistic regression(LR)as a combiner in the second layer.On this basis,the local interpretable model-agnostic explanations(LIME)technology was used to interpret the output of the stacking model from both local and global perspectives.Through SC dentification and feature selection,346 SCs and 22 crash-related factors were collected from California interstate freeways.The results showed that the stacking model outperformed base models evaluated by accuracy,precision,and recall indicators.The explanations based on LIME suggest that collision type,distance,speed and volume are the critical features that affect the time and distance gaps.Higher volume can prolong queue length and increase the distance gap from the SCs to PCs.And collision types,peak periods,workday,truck involved and tow away likely induce a long-distance gap.Conversely,there is a shorter distance gap when secondary roads run in the same direction and are close to the primary roads.Lower speed is a significant factor resulting in a long-time gap,while the higher speed is correlated with a short-time gap.These results are expected to provide insights into how contributory features affect the time and distance gaps and help decision-makers develop accurate decisions to prevent SCs.

关键词： secondary crash(SC) time and distance gaps stacking framework local interpretable model-agnostic explanations(LIME)

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Analysis and Optimization of Transient Mode Switching Behavior for Power Split Hybrid Electric Vehicle with Clutch Collaboration

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Automotive Innovation 2024年第1期7卷 150-165页

作者： Dehua Shi Sheng liu Yujie Shen Shaohua Wang Chaochun yuan Long Chen Automotive Engineering Research Institute Jiangsu UniversityZhenjiang 212013China Jiangsu Province Engineering Research Center of Electric Drive System and Intelligent Control for Alternative Vehicles Zhenjiang 212013China

The power split hybrid electric vehicle(HEV)adopts a power coupling configuration featuring dual planetary gearsets and multiple clutches,enabling diverse operational modes through clutch engagement and disengagement.The multi-clutch configuration usually involves the collaboration of two clutches during the transient mode switching process,thereby substantially elevating control complexity.This study focuses on power split HEVs that integrate multi-clutch mechanisms and investigates how different clutch collaboration manners impact the characteristics of transient mode switching.The powertrain model for the power-split HEV is established utilizing matrix-based methodologies.Through the formulation of clutch torque curves and clutch collaboration models,this research systematically explores the effects of clutch engagement timing and the duration of clutch slipping state on transient mode switching behaviors.Building upon this analysis,an optimization problem for control parameters pertaining to the two collaborative clutches is formulated.The simulated annealing algorithm is employed to optimize these control parameters.Simulation results demonstrate that the clutch collaboration manners have a great influence on the transient mode switching performance.Compared with the pre-calibrated benchmark and the optimal solution derived by the genetic algorithm,the maximal longitudinal jerk and clutch slipping work during the transient mode switching process is reduced obviously with the optimal control parameters derived by the simulated annealing algorithm.The study provides valuable insights for the dynamic coordinated control of the power-split HEVs featuring complex clutch collaboration mechanisms.

关键词： Power split hybrid electric vehicle Transient mode switching Clutch collaboration Simulated annealing Powertrain model

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A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

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Neuroscience Bulletin 2024年第3期40卷 310-324页

作者： Man yuan Sen Jin Gao Tan Siyuan Song Yizong liu Huadong Wang Yin Shen Eye Center Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan430060China The Brain Cognition and Brain Disease Institute Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNational Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen518055China Jan and Dan Duncan Neurological Research Institute Baylor College of MedicineHouston77030USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyCASWuhan430071China Frontier Science Center of Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan430071China

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

关键词： Parvalbumin-positive retinal ganglion cell Innate fear Superior colliculus Excitatory-excitatory neuronal connection Looming-evoked defensive response Subcortical pathway

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Numerical Simulation on Radon Retardation Behavior of Covering Floats in Radon-Containing Water

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Biomedical and Environmental Sciences 2024年第4期37卷 406-417页

作者： liu Shu yuan ZHANG Li YE Yong Jun DING Ku Ke National Institute for Radiological Protection Chinese Center for Disease Control and PreventionBeijing 100088China Office for Public Health Management Chinese Center for Disease Control and PreventionBeijing 102206China Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy University of South ChinaHengyang 421001HunanChina

Objective This study aimed to efficiently reduce the release of radon from water bodies to protect the environment.Methods Based on the sizes of the experimental setup and modular float,computational fluid dynamics(CFD)was used to assess the impact of the area coverage rate,immersion depth,diffusion coefficient,and radon transfer velocity at the gas–liquid interface on radon migration and exhalation of radon-containing water.Based on the numerical simulation results,an estimation model for the radon retardation rate was constructed.The effectiveness of the CFD simulation was evaluated by comparing the experimental and simulated variation values of the radon retardation rate with the coverage area rates.Results The effect of radon transfer velocity on radon retardation in water bodies was minor and insignificant according to the appropriate value;therefore,an estimation model of the radon retardation rate of the coverage of a radon-containing water body was constructed using the synergistic impacts of three factors:area coverage rate,immersion depth,and diffusion coefficient.The deviation between the experimental and simulated results was<4.3%.Conclusion Based on the numerical simulation conditions,an estimation model of the radon retardation rate of covering floats in water bodies under the synergistic effect of multiple factors was obtained,which provides a reference for designing covering floats for radon retardation in radoncontaining water.

关键词： Radon-containing water Radon retardation rate CFD Coverage experiment Optimized design

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High cerium content(Nd-Pr-Ce)_(2)Fe_(14)B melt-spun ribbons with high coercivity

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Journal of Rare Earths 2024年第4期42卷 690-695页

作者： Yujiang Zhong Junming Wang Zikai yuan Ruijin liu Minggang Zhu Zhe liu Xin Chen Wei Li Zhaohui Guo Division of Functional Materials Central Iron and Steel Research InstituteBeijing100081China Ningbo Jinji Strong Magnetic Material Co. Ltd.Ningbo315172China Jiangxi Jiangwu Rare Metal New Material Co. Ltd.Nanchang330013China

The effects of wheel speeds on the magnetic properties and microstructures of[(Nd,Pr)_(1-x)Ce_(x)]-Fe-B meltspun ribbons were investigated.Compared to melt-spun ribbons with low cerium(Ce)content(x=0.2),amorphous formation can be suppressed at high wheel speed in the ribbons with a relatively high Ce content(x=0.8),and with the increase of the wheel speed,the magnetic properties of the ribbons with high Ce content raise continuously.At high wheel speed,the coercivity mechanism of melt-spun ribbons is mainly pinning field,and the high wheel speed introduces a large number of defects into the matrix as pinning sites.Furthermore,ribbons with high Ce content form a fine and uniform grain structure,so the grain boundary area enlarges,which further hinders the movement of domain walls.The combined effects of the above factors enable ribbons with high Ce content to have excellent magnetic properties(Hcj=0.977 T,Mr=64 m^(2) A/kg)at the wheel speed of 35 m/s.

关键词： Wheel speed Cecontent Microstructure Magnetic properties Rare earths

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Triclosan-conjugated,Lipase-responsive Polymeric Micelles for Eradication of Staphylococcal Biofilms

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Chinese Journal of Polymer Science 2024年第6期42卷 718-728页

作者： Yan-Qiang Huang yuan-Feng Li Yong liu Lin-Qi Shi Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance Youjiang Medical University for NationalitiesBaise533000China Translational Medicine Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325035China Wenzhou Institute University of Chinese Academy of SciencesWenzhou325001China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of Educationand Institute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China

Bacterial biofilms present a significant challenge in treating drug-resistant infections,necessitating the development of innovative nanomedicines.In this study,we introduce triclosan-conjugated,lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery platform.The micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization ofε-caprolactone(CL)and triclosan-containing cyclic trimethylene carbonate(MTC-Tri).Poly(ethylene glycol)(PEG-OH)acted as the macro-initiator,resulting in micelles with a PEG shell that facilitated their penetration into bacterial biofilms.An important advantage of our micelles lies in their interaction with local bacterial lipases within biofilms.These lipases triggered rapid micelle degradation,releasing triclosan in a controlled manner.This liberated triclosan effectively eliminated bacteria embedded in the biofilms.Notably,the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts,indicating their biocompatibility and safety.This finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial biofilms.Our triclosan-conjugated,lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial biofilms.By harnessing biofilm properties and implementing a responsive drug delivery system,we seek to provide an effective solution in the fight against drug-resistant bacteria.

关键词： Self-assembly Polymer prodrug Ring-opening polymerization Biofilm eradication Cytotoxicity

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Ultra-high extinction ratio optical pulse generation with a thin film lithium niobate modulator for distributed acoustic sensing

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Photonics Research 2024年第1期12卷 40-50页

作者： yuan SHEN XIAOQIAN SHU LINGMEI MA SHAOLIANG YU GENGXIN CHEN liu liu RENYOU GE BIGENG CHEN YUNJIANG RAO Research Center for Optical Fiber Sensing Zhejiang LaboratoryHangzhou 311100China Research Center for Intelligent Optoelectronic Computing Zhejiang LaboratoryHangzhou 311100China International Research Center for Advanced Photonics College of Optical Science and EngineeringZhejiang UniversityHangzhou 310058China Fiber Optics Research Center(FORC) Key Laboratory of Optical Fiber Sensing and CommunicationsUniversity of Electronic Science and Technology of ChinaChengdu 611731China

We experimentally demonstrate ultra-high extinction ratio(ER)optical pulse modulation with an electro-optical modulator(EOM)on thin film lithium niobate(TFLN)and its application for fiber optic distributed acoustic sensing(DAS).An interface carrier effect leading to a relaxation-tail response of TFLN EOM is discovered,which can be well addressed by a small compensation component following the main driving signal.An ultrahigh ER>50 dB is achieved by canceling out the tailed response during pulse modulation using the EOM based on a cascaded Mach–Zehnder interferometer(MZI)structure.The modulated optical_(√)pulses are then utilized as a probe light for a DAS system,showing a sensitivity up to-62.9 dB·rad∕Hz~2(7 pε/Hz)for 2-km single-mode sensing fiber.Spatial crosstalk suppression of 24.9 dB along the fiber is also obtained when the ER is improved from 20 dB to 50 dB,clearly revealing its importance to the sensing performance.

关键词： modulator pulse interferometer

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