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Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3205-3217页

作者： Bing-chen Zhang Chun-Mei Lai Bang-Yue Luo Jing-Wei shao Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350116China Department of Laboratory Medicine Dongguan Institute of Clinical Cancer Researchthe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523058China College of Materials and Chemical Engineering MinjiangUniversityFuzhou350108China

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)***,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted ***,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)***@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target *** activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of *** strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor ***,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.

关键词： Ursolic acid Self-assembly Biomimetic nanoplatform Hepatocellular carcinoma CRISPR/Cas9 Immune checkpoint blockade Gene therapy Immunotherapy

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Enhancement of low-temperature toughness of Fe-Mn-C-Al alloy by rare earth Ce-modified inclusions

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Journal of Iron and Steel Research International 2024年第1期31卷 157-173页

作者： Guang-kai Yang Chang-ling Zhuang Yi-zhuang Li chen Hu shao-bo Li College of Materials and Metallurgy Guizhou UniversityGuiyang550025GuizhouChina Department of Mechanical Engineering University of Hong KongHong Kong999077China The State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang110819LiaoningChina State Key Laboratory of Public Big Data Guizhou UniversityGuiyang550025GuizhouChina

Fe-Mn-C-Al alloys have been recognized as promising materials for certain low-temperature applications due to their exceptional mechanical properties and ***,their limited low-temperature toughness restricts their large-scale applications in specific *** influence of trace amounts of rare earth cerium(Ce)on the low-temperature toughness of Fe-18Mn-0.6C-1.8Al alloys was *** addition of Ce effectively alters the inclu-sions in the alloy,transforming large-sized irregular inclusions into fine ellipsoidal rare earth *** leads to a significant reduction in both the proportion and average size of the inclusions,resulting in their effective dispersion throughout the matrix and improved cryogenic *** presence of Ce-containing inclusions within the matrix reduces stress concentration,thereby inhibiting microcrack formation and improving impact absorption ***-cally,the addition of rare earth Ce alters the fracture behavior of the material at room temperature and low temperature,changing from brittle cleavage fracture to a more ductile failure *** impact toughness of the Fe-Mn-C-Al alloy is significantly improved by the addition of 0.0048 wt.%Ce,particularly at-196℃where the impact toughness reaches 103.6 J/cm^(2),representing an impressive improvement of 87.3%.

关键词： Fe-Mn-C-Al alloy Rare earth Low-temperature toughness Inclusion Fracture

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Hydrodynamic characteristics and particle tracking of 90° lateral intakes at an inclined river slope

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Water Science and Engineering 2024年第2期17卷 197-208页

作者： Wei He Si-yuan Feng Jian Zhang Hong-wu Tang Yang Xiao sheng chen Chun-sheng Liu College of Water Conservancy and Hydropower Engineering Hohai UniversityNanjing 210098China State Key Laboratory of Hydrology Water Resources and Hydraulic Engineering Hohai UniversityNanjing 210098China Collaborative Innovation Center on Water Safety and Water Science Hohai UniversityNanjing 210098China

Lateral intakes are common in *** pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division *** hydraulic characteristics of lateral withdrawal from inclined river slopes at different intake elevations should be ***,the division width exhibits significant vertical non-uniformity at an inclined river slope,which should be ***,a three-dimensional(3-D)hydrodynamic and particle-tracking model was developed with the Open Source Field Operation and Manipulation(Open FOAM),and the model was validated with physical model tests for 90°lateral withdrawal from an inclined side *** flow fields,withdrawal sources,and division widths were investigated with different intake bottom elevations,withdrawal discharges,and main channel *** study showed that under inclined side bank conditions,water entered the intake at an oblique angle,causing significant 3-D spiral flows in the intake rather than two-dimensional closed recirculation.A lower withdrawal discharge,a lower bottom elevation of the intake,or a higher main channel velocity could further strengthen this *** average division width and turbulent kinetic energy were smaller under inclined side bank conditions than under vertical bank *** a low intake bottom elevation,a low withdrawal discharge,or a high main channel velocity,the sources of lateral withdrawal were in similar ranges near the local inclined bank in the vertical *** inclined slope conditions,sediment deposition near the intake entrance could be reduced,compared to that under vertical slope *** results provide hydrodynamic and sediment references for engineering designs for natural rivers with inclined terrains.

关键词： Lateral withdrawal Hydrodynamic characteristics Particle tracking Inclined river slope Bottom elevation of intake OpenFOAM

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A comprehensive review of the modeling of transport phenomenon in the flow channels of polymer electrolyte membrane fuel cells

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Frontiers of Chemical Science and Engineering 2024年第8期18卷 123-161页

作者： Niyi Olukayode Shenrong Ye Mingruo Hu Yanjun Dai Rui chen sheng Sui Institute of Fuel Cell Shanghai Jiao Tong UniversityShanghai 200240China Institute of Refrigeration and Cryogenics Shanghai Jiao Tong UniversityShanghai 200240China Low Carbon Engineering Loughborough UniversityLoughborough Leicestershire LE113TUUK

Reactant gas and liquid water transport phenomena in the flow channels are complex and critical to the performance and durability of polymer electrolyte membrane fuel *** polymer membrane needs water at an optimum level for proton *** management involves the prevention of dehydration,waterlogging,and the cell’s subsequent performance decline and *** process requires the study and understanding of internal two-phase *** experimental visualization techniques are used to study two-phase flows in polymer electrolyte membrane fuel ***,the experiments have limitations in in situ measurements;they are also expensive and time *** contrast,numerical modeling is cheaper and faster,providing insights into the complex multiscale processes occurring across the components of the polymer electrolyte membrane fuel *** paper introduces the recent design of flow *** reviews the numerical modeling techniques adopted for the transport phenomena therein:the two-fluid,multiphase mixture,volume of fluid,lattice Boltzmann,and pressure drop ***,this work describes,compares,and analyses the models’approaches and reviews the representative results of some selected ***,the paper summarizes the modeling perspectives,emphasizing future directions with some recommendations.

关键词： two-phase flows numerical model flow channel polymer electrolyte membrane fuel cells water management

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Accelerating H^(*)desorption of hollow Mo_(2)C nanoreactor via in-situ grown carbon dots for electrocatalytic hydrogen evolution

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Journal of Energy Chemistry 2024年第9期96卷 464-471页

作者： Mengmeng Liu Yuanyuan Jiang Zhuwei Cao Lulu Liu Hong chen sheng Ye School of Materials and Chemistry Anhui Agricultural UniversityHefei 230036AnhuiChina

Molybdenum carbide(Mo_(2)C)is a promising non-noble metal electrocatalyst with electronic structures similar to Pt for hydrogen evolution reaction(HER).However,strong H^(*)adsorption at the Mo sites hinders the improvement of HER ***,we synthesized monodisperse hollow Mo_(2)C nanoreactors,in which the carbon dots(CD)were in situ formed onto the surface of Mo_(2)C through carburization *** to finite element simulation and analysis,the CD@Mo_(2)C possesses better mesoscale diffusion properties than Mo_(2)C *** optimized CD@Mo_(2)C nanoreactor demonstrates superior HER performance in alkaline electrolyte with a low overpotential of 57 mV at 10 mA cm^(−2),which is better than most Mo_(2)C-based ***,CD@Mo_(2)C exhibits excellent electrochemical stability during 240 h,confirmed by operando Raman and X-ray diffraction(XRD).Density functional theory(DFT)calculations show that carbon dots cause the d-band center of CD@Mo_(2)C to shift away from Fermi level,promoting water dissociation and the desorption of H^(*).This study provides a reasonable strategy towards high-activity Mo-based HER eletrocatalysts by modulating the strength of Mo–H bonds.

关键词： Mo_(2)C nanoreactor Carbon dots H^(*)desorption Electrocatalytic hydrogen evolution

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Multi-layered effects of Codonopsis Radix on the immune system

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Acupuncture and Herbal Medicine 2024年第3期4卷 405-419页

作者： Xiyu chen Rui shao Yu Wang School of Integrative Medicine Tianjin University of Traditional Chinese MedicineTianjinChina State Key Laboratory of Component-Based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina

Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and ***,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still *** knowledge gap hinders its widespread utilization in clinical ***,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying ***,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.

关键词： Active ingredients Codonopsis Radix Immune system Immunomodulation herbal medicine Traditional Chinese medicine

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In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

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Journal of Pharmaceutical Analysis 2024年第6期14卷 840-850页

作者： Zhenjie Yu Huarong shao Xintian shao Linyan Yu Yanan Gao Youxiao Ren Fei Liu Caicai Meng Peixue Ling Qixin chen Key Laboratory for Biotechnology Drugs of National Health Commission School of Pharmaceutical Sciences&Institute of Materia MedicaMedical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Key Laboratory of Biopharmaceuticals Engineering Laboratory of Polysaccharide DrugsNational-Local Joint Engineering Laboratory of Polysaccharide DrugsShandong Academy of Pharmaceutical ScienceJinan250101China Shenzhen Research Institute of Xiamen University ShenzhenGuangdong518057China School of Life Sciences Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore School of Pharmaceutical Sciences Shandong UniversityJinan250101China

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and *** address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of *** a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured *** recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the ***,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid *** drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related ***,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and ***,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug ***,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.

关键词： Cellular imaging Fluorescence labeling Mussel oligosaccharide Lipid metabolism

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Metal and ligand modification modulates the electrocatalytic HER,OER,and ORR activity of 2D conductive metal-organic frameworks

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Nano Research 2024年第9期17卷 7984-7990页

作者： Yanan Zhou Li sheng Lanlan chen Wenhui Zhao Wenhua Zhang Jinlong Yang School of Material Science and Chemical Engineering Institute of Mass SpectrometryNingbo UniversityNingbo 315211China Department of Chemical Physics University of Science and Technology of ChinaHefei 230026China Department of Material Science and Engineering University of Science and Technology of ChinaHefei 230026China Department of Physics Ningbo UniversityNingbo 315211China Hefei National Laboratory for Physical Sciences at the Microscale CAS Key Laboratory of Materials for Energy Conversion and Synergetic Innovation Centre of Quantum Information and Quantum PhysicsUniversity of Science and Technology of ChinaHefei 230026China

It is highly desirable to design efficient and stable hydrogen evolution reaction(HER)and oxygen evolution/reduction reaction(OER/ORR)electrocatalysts for the development of renewable energy ***,density functional theory(DFT)calculations were conducted to systematically investigate a series of TMN_(x)O_(4-x)-HTT(TM=Fe,Co,Ni,Ru,Rh,Pd,Ir and Pt;HTT=hexahydroxy tetraazanaphthotetraphene)analogs of two-dimensional(2D)conductive metal-organic frameworks(MOFs)as potential electrocatalysts for the HER,OER and *** thermodynamic and electrochemical stability simulations suggest that these designed catalysts are ***,CoO_(4)-HTT,RhN_(3)O_(1)-HTT and IrN3O1-HTT are predicted to be the most promising catalysts for the HER,OER and ORR,respectively,surpassing the catalytic activity of corresponding benchmark *** volcano plots were established based on the scaling relationship of adsorption Gibbs free energy of *** results reveal that regulating combinations of metal active centers and local coordination environments could effectively balance the interaction strength between intermediates and catalysts,thus achieving optimal catalytic *** findings not only opt for the promising HER/OER/ORR electrocatalysts but also guide the design of efficient electrocatalysts based on 2D MOFs materials.

关键词： hydrogen evolution reaction(HER) oxygen evolution/reduction reaction(OER/ORR) electrocatalysts design twodimensional(2D)conductive metal-organic frameworks(MOFs) density functional theory(DFT)

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Enhancing cancer immunotherapy:Nanotechnology-mediated immunotherapy overcoming immunosuppression

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3834-3854页

作者： Yunna chen Qianqian Zhou Zongfang Jia Nuo cheng sheng Zhang Weidong chen Lei Wang Key Laboratory of Molecular Biology(Brain diseases) Anhui University of Chinese MedicineHefei 230012China MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials Hefei 230012China Anhui Province Key Laboratory of Chinese Medicinal Formul1 Hefei 230012China

Immunotherapy is an important cancer treatment method that offers hope for curing cancer *** immunotherapy has achieved initial success,a major obstacle to its widespread adoption is the inability to benefit the majority of *** success or failure of immunotherapy is closely linked to the tumor’s immune ***,there has been significant attention on strategies to regulate the tumor immune microenvironment in order to stimulate anti-tumor immune responses in cancer *** distinctive physical properties and design flexibility of nanomedicines have been extensively utilized to target immune cells(including tumor-associated macrophages(TAMs),T cells,myeloid-derived suppressor cells(MDSCs),and tumor-associated fibroblasts(TAFs)),offering promising advancements in cancer *** this article,we have reviewed treatment strategies aimed at targeting various immune cells to regulate the tumor immune *** focus is on cancer immunotherapy models that are based on nanomedicines,with the goal of inducing or enhancing anti-tumor immune responses to improve *** is worth noting that combining cancer immunotherapy with other treatments,such as chemotherapy,radiotherapy,and photodynamic therapy,can maximize the therapeutic ***,we have identified the challenges that nanotechnology-mediated immunotherapy needs to overcome in order to design more effective nanosystems.

关键词： Immunotherapy Nanomedicine Tumor immunosuppressive microenvironment Cancer T cells Immunogenic cell death Immune checkpoint inhibitors Extracellular matrix

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Application of Ice Pigging in a Drinking Water Distribution System:Impacts on Pipes and Bulk Water Quality

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Engineering 2024年第9期40卷 122-130页

作者： Yujing Huang Zhiwei chen Guilin He Yu shao Shuang Song Feilong Dong Tuqiao Zhang College of Civil Engineering and Architecture Zhejiang UniversityHangzhou 310027China Suzhou Wuzhong Water Co. Ltd.Suzhou 215128China School of Municipal and Environmental Engineering Shandong Jianzhu UniversityJi’nan 250101China College of Environment Zhejiang University of TechnologyHangzhou 310014China

Ice pigging is an emerging technique for pipe cleaning in drinking water distribution ***,substantial confusion and controversy exist on the potential impacts of ice pigging on bulk water *** study monitored the microstructural features and composition of sediments and microbial community structures in bulk water in eight multimaterial Chinese *** concentration analysis demonstrated that separate cleaning of pipes with different materials in complex networks could mitigate the risk of losing ice pigs and degrading water *** microstructural and trace element characterization results showed that ice pigs would scarcely disturb the inner surfaces of long-used *** bacterial richness and diversity of bulk water decreased significantly after ice ***,correlations were established between pipe service age,temperature,and chloride and total iron concentrations,and the 15 most abundant taxa in bulk water,which could be used to guide practical ice pigging operations.

关键词： Ice pigging Pipe cleaning Drinking water distribution system Bacterial community Sediments

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