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Development of NK cell-based cancer immunotherapies through receptor engineering

Cellular & Molecular Immunology 2024年第4期21卷 315-331页

作者： Audrey Page Nicolas Chuvin Jenny Valladeau-Guilemond Stéphane Depil centre de Recherche en Cancérologie de Lyon UMR INSERM U1052 CNRS 5286Centre Léon BérardLyonFrance ErVimmune LyonFrance centre Léon Bérard LyonFrance UniversitéClaude Bernard Lyon 1 LyonFrance

Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

关键词： NK cells Cell therapy Receptor engineering CAR

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Assembly of functional carboxymethyl cellulose/polyethylene oxide/anatase TiO_(2) nanocomposites and tuning the dielectric relaxation, optical, and photoluminescence performances

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Journal of Semiconductors 2024年第7期45卷 26-38页

作者： Asmaa M.Ismail Abeer A.Reffaee Fawzy G.El Desouky Spectroscopy Department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt Microwave Physics and Dielectrics Department National Research CentreDokkiCairoEgypt Solid State Physics Department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt

Nanocomposite films consisting of carboxymethyl cellulose,polyethylene oxide(CMC/PEO),and anatase titanium diox-ide(TO)were produced by the use of sol-gel and solution casting techniques.TiO2 nanocrystals were effectively incorporated into CMC/PEO polymers,as shown by X-ray diffraction(XRD)and attenuated total reflectance fourier transform infrared(ATR-FTIR)analysis.The roughness growth is at high levels of TO nanocrystals(TO NCs),which means increasing active sites and defects in CMC/PEO.In differential scanning calorimetry(DSC)thermograms,the change in glass transition temperature(Tg)val-ues verifies that the polymer blend interacts with TO NCs.The increment proportions of TO NCs have a notable impact on the dielectric performances of the nanocomposites,as observed.The electrical properties of the CMC/PEO/TO nanocomposite undergo significant changes.The nanocomposite films exhibit a red alteration in the absorption edge as the concentration of TO NCs increases in the polymer blend.The decline in the energy gap is readily apparent as the weight percentage of TO NCs increases.The photoluminescence(PL)emission spectra indicate that the sites of the luminescence peak maximums show slight variation;peaks get wider,while their intensities decrease dramatically as the concentration of TO increases.These nanocomposite materials show potential for multifunctional applications including optoelectronics,antireflection coatings,pho-tocatalysis,light emitting diodes,and solid polymer electrolytes.

关键词： anatase TiO_(2) CMC/PEO nanocomposites optical photoluminescent electrical optoelectronics

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Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

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Molecular Plant 2024年第5期17卷 824-837页

作者： Tom Schreiber Anja Prange Petra Schafer Thomas Iwen Ramona Grutzner Sylvestre Marillonnet Aurelie Lepage Marie Javelle Wyatt Paul Alain Tissier Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Limagrain Centre de RechercheRoute d’EnnezatCS 9012663720 ChappesFrance

In plants and mammals,non-homologous end-joining is the dominant pathway to repair DNA doublestrand breaks,making it challenging to generate knock-in events.In this study,we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana benthamiana.We achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation systems.In Arabidopsis thaliana,fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of transformants.In addition,we demonstrated stable and heritable knock-ins in wheat in 1%of the primary transformants.Taken together,our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

关键词： homology-directed repair knockin gene replacement CRISPR-Cas 50 exonuclease plants

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A review on the transformation of birnessite in the environment:Implication for the stabilization of heavy metals

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Journal of Environmental Sciences 2024年第5期139卷 496-515页

作者： Miao Shi Qingzhu Li Qingwei Wang Xuelei Yan Bensheng Li Linhai Feng Chao Wu Rongrong Qiu Hongkai Zhang Zhihui Yang Weichun Yang Qi Liao Liyuan Chai School of Metallurgy and Environment Central South UniversityChangsha 410083China National Engineering Research centre for Control and Treatment ofHeavy Metal Pollution Central South UniversityChangsha 410083China Water Pollution Control Technology Key Lab of Hunan Province Changsha 410083China

Birnessite is ubiquitous in the natural environment where heavy metals are retained and easily transformed.The surface properties and structure of birnessite change with the changes in external environmental conditions,which also affects the fate of heavy metals.Clarifying the effect and mechanism of the birnessite phase transition process on heavy metals is the key to taking effective measures to prevent and control heavy metal pollution.Therefore,the four transformation pathways of birnessite are summarized first in this review.Second,the relationship between transformation pathways and environmental conditions is proposed.These relevant environmental conditions include abiotic(e.g.,co-existing ions,pH,oxygen pressure,temperature,electric field,light,aging,pressure)and biotic factors(e.g.,microorganisms,biomolecules).The phase transformation is achieved by the key intermediate of Mn(Ⅲ)through interlayer-condensation,folding,neutralizationdisproportionation,and dissolution-recrystallization mechanisms.The AOS(average oxidation state)of Mn and interlayer spacing are closely correlated with the phase transformation of birnessite.Last but not least,the mechanisms of heavy metals immobilization in the transformation process of birnessite are summed up.They involve isomorphous substitution,redox,complexation,hydration/dehydration,etc.The transformation of birnessite and its implication on heavy metals will be helpful for understanding and predicting the behavior of heavy metals and the crucial phase of manganese oxides/hydroxides in natural and engineered environments.

关键词： Birnessite Transformation Heavy metals Pathways Mechanism

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Fabrication of ceramic coatings on the biodegradable ZM21 magnesium alloy by PEO coupled EPD followed by laser texturing process

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Journal of Magnesium and Alloys 2021年第3期9卷 910-926页

作者： Hariprasad Sampatirao Saikiran Amruthaluru Premchand Chennampalli Rama Krishna Lingamaneni Rameshbabu Nagumothu Department of Metallurgical and Materials Engineering National Institute of TechnologyTiruchirappalli 620015India centre for engineered coatings International Advanced Research Centre for Powder Metallurgy and New Materials(ARCI)Hyderabad 500005India

Zirconia(ZrO_2)incorporated ceramic coatings were fabricated on biodegradable ZM21 Mg alloy by the PEO coupled with EPD process.Subsequently,the sample surface was modified by laser texturing to improve the corrosion resistance,roughness and cell proliferation and growth properties.The corrosion performance of the fabricated samples along with the substrate was studied by electrochemical measurements under simulated body fluid(SBF)environment.The cell direct contact assay was conducted for the substrate and fabricated samples using L-929 mouse fibroblast cells for 24 h.The phase contrast images of cell direct contact assay revealed that fabricated samples exhibited better contact and response with the fibroblast cells,compared to the substrate.The addition of nanoparticles in the PEO process,called PEO coupled EPD process,resulted in attaining a higher thickness and improved corrosion performance of the samples than the PEO coated samples.Among all the samples,laser surface textured PEO,and PEO-EPD coated samples unveiled enhanced corrosion resistance,cell growth,thereby enabling it as a suitable prototype for biodegradable implant applications.

关键词： ZM21 ZrO_(2)nanoparticle PEO-EPD Laser texturing Corrosion resistance L-929 cells

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Arbuscular mycorrhizal fungi regulate plant mineral nutrient uptake and partitioning in iron ore tailings undergoing eco-engineered pedogenesis

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Pedosphere 2024年第2期34卷 385-398页

作者： Zhen LI Songlin WU Yunjia LIU Qing YI Merinda HALL Narottam SAHA Junjian WANG Yuanfang HUANG Longbin HUANG College of Land Science and Technology China Agricultural UniversityBeijing 100193China centre for Mined Land Rehabilitation Sustainable Minerals InstituteThe University of QueenslandBrisbaneQLD 4072Australia Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control School of Environmental Science and EngineeringSouthern University of Science and TechnologyShenzhen 518055China

Excess available K and Fe in Fe ore tailings with organic matter amendment and water-deficiencies may restrain plant colonization and growth,which hinders the formation of eco-engineered soil from these tailings for sustainable and cost-effective mine site rehabilitation.Arbuscular mycorrhizal(AM)fungi are widely demonstrated to assist plant growth under various unfavorable environments.However,it is still unclear whether AM symbiosis in tailings amended with different types of plant biomass and under different water conditions could overcome the surplus K and Fe stress for plants in Fe ore tailings,and if so,by what mechanisms.Here,host plants(Sorghum sp.Hybrid cv.Silk),either colonized or noncolonized by the AM fungi(Glomus spp.),were cultivated in lucerne hay(LH,C:N ratio of 18)-or sugarcane mulch(SM,C:N ratio of 78)-amended Fe ore tailings under well-watered(55%water-holding capacity(WHC)of tailings)or water-deficient(30%WHC of tailings)conditions.Root mycorrhizal colonization,plant growth,and mineral elemental uptake and partitioning were examined.Results indicated that AM fungal colonization improved plant growth in tailings amended with plant biomass under water-deficient conditions.Arbuscular mycorrhizal fungal colonization enhanced plant mineral element uptake,especially P,both in the LH-and SM-amended tailings regardless of water condition.Additionally,AM symbiosis development restrained the translocation of excess elements(i.e.,K and Fe)from plant roots to shoots,thereby relieving their phytotoxicity.The AM fungal roles in P uptake and excess elemental partitioning were greater in LH-amended tailings than in SM-amended tailings.Water deficiency weakened AM fungal colonization and functions in terms of mineral element uptake and partitioning.These findings highlighted the vital role AM fungi played in regulating plant growth and nutrition status in Fe ore tailings technosol,providing an important basis for involvement of AM fungi in the eco-engineered pedogenesis of Fe ore tailings.

关键词： Fe stress fungal symbiosis K stress mine site rehabilitation mycorrhizal colonization plant biomass amendment plant nutrition water deficiency

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Development and application of feature engineered geological layers for ranking magmatic,volcanogenic,and orogenic system components in Archean greenstone belts

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Geoscience Frontiers 2024年第2期15卷 251-273页

作者： R.M.Montsion S.Perrouty M.D.Lindsay M.W.Jessell R.Sherlock Mineral Exploration Research centre Harquail School of Earth SciencesGoodman School of MinesLaurentian UniversitySudburyOntario P3E 2C6Canada centre for Exploration Targeting School of Earth SciencesThe University of Western Australia35 Stirling HighwayCrawley 6009Australia Commonwealth Scientific and Industrial Research Organization Mineral Resources26 Dick Perry AveKensingtonWA 6151Australia ARC centre for Data Analytics for Resources and Environments(DARE) Perth and SydneyAustralia

Geologically representative feature engineering is a crucial component in geoscientific applications of machine learning.Many commonly applied feature engineering techniques used to produce input variables for machine learning apply geological knowledge to generic data science techniques,which can lead to ambiguity,geological oversimplification,and/or compounding subjective bias.Workflows that utilize minimally processed input variables attempt to overcome these issues,but often lead to convoluted and uninterpretable results.To address these challenges,new and enhanced feature engineering methods were developed by combining geological knowledge,understanding of data limitations,and a variety of data science techniques.These include non-Euclidean fluid pre-deformation path distance,rheological and chemical contrast,geologically constrained interpolation of characteristic host rock geochemistry,interpolation of mobile element gain/loss,assemblages,magnetic intensity,structural complexity,host rock physical properties.These methods were applied to compiled open-source and new field observations from Archean greenstone terranes in the Abitibi and western Wabigoon sub-provinces of the Superior Province near Timmins and Dryden,Ontario,respectively.Resulting feature maps represent conceptually significant components in magmatic,volcanogenic,and orogenic mineral systems.A comparison of ranked feature importance from random forests to conceptual mineral system models show that the feature maps adequately represent system components,with a few exceptions attributed to biased training data or limited constraint data.The study also highlights the shared importance of several highly ranked features for the three mineral systems,indicating that spatially related mineral systems exploit the same features when available.Comparing feature importance when classifying orogenic Au mineralization in Timmins and Dryden provides insights into the possible cause of contrasting endowment being related to fluid source.The study demonstrat

关键词： Machine learning Random forests Mineral systems Magmatic Ni-Cu-PGE Volcanogenic Massive Sulfide(VMS)Cu-Zn-Pb-Ag(-Au) Orogenic Au Abitibi Wabigoon

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未热解厚热障涂层的隔热能力和黏接强度

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Transactions of Nonferrous Metals Society of China 2024年第4期34卷 1226-1236页

作者： Mohammad IZADINIA Reza SOLTANI Mahmoud HEYDARZADEH SOHI Javad MOSTAGHIMI School of Metallurgy and Materials Engineering College of EngineeringUniversity of TehranTehranIran centre for Advanced Coating Technologies Department of Mechanical and Industrial EngineeringUniversity of TorontoTorontoOntarioCanada

对比研究使用未热解粉末制备的厚热障涂层(UPTTBC)和传统TBC、厚TBC(TTBC)及密集垂直裂纹(DVC)TTBC 4种涂层的隔热能力和黏接强度。采用降温法测试涂层的隔热能力;根据ASTM C633标准,采用拉拔试验检测涂层的黏接强度。结果显示,UPTTBC和... 详细信息

对比研究使用未热解粉末制备的厚热障涂层(UPTTBC)和传统TBC、厚TBC(TTBC)及密集垂直裂纹(DVC)TTBC 4种涂层的隔热能力和黏接强度。采用降温法测试涂层的隔热能力;根据ASTM C633标准,采用拉拔试验检测涂层的黏接强度。结果显示,UPTTBC和DVC TTBC的黏接强度分别比TTBC高35%和25%。这可能是由于UPTTBC结构中存在亚微米尺度的未熔化区域,起到了阻止裂纹扩展的作用。此外,隔热测试的结果表明,DVCTTBC涂层的隔热能力最差,为0.28℃/μm,而UPTTBC涂层的隔热能力最强,为0.40℃/μm。由于UPTTBCs显微组织中存在亚微米区域,使涂层展现出优越的隔热能力。相反,DVCTTBC因其致密的结构,具有最低的隔热能力。

关键词：厚热障涂层密集垂直裂纹热障涂层未热解粉末黏接强度隔热能力

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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A STAMP-Game model for accident analysis in oil and gas industry

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Petroleum Science 2024年第3期21卷 2154-2167页

作者： Huixing Meng Xu An Daiwei Li Shijun Zhao Enrico Zio Xuan Liu Jinduo Xing State Key Laboratory of Explosion Science and Safety Protection Beijing Institute of Technology School of Emergency Management and Safety Engineering China University of Mining and Technology (Beijing) Energy Department Politecnico di Milano Mines Paris PSL Centre de Recherche sur les Risques et les Crises School of Mechanical-Electronic and Vehicle Engineering Beijing University of Civil Engineering and Architecture

Accidents in engineered systems are usually generated by complex socio-technical factors. It is beneficial to investigate the increasing complexity and coupling of these factors from the perspective of system safety. Based on system and control theories, System-Theoretic Accident Model and Processes(STAMP) is a widely recognized approach for accident analysis. In this paper, we propose a STAMP-Game model to analyze accidents in oil and gas storage and transportation systems. Stakeholders in accident analysis by STAMP can be regarded as players of a game. Game theory can, thus, be adopted in accident analysis to depict the competition and cooperation between stakeholders. Subsequently, we established a game model to study the strategies of both supervisory and supervised entities. The obtained results demonstrate that the proposed game model allows for identifying the effectiveness deficiency of the supervisory entity, and the safety and protection altitudes of the supervised entity. The STAMP-Game model can generate quantitative parameters for supporting the behavior and strategy selections of the supervisory and supervised entities. The quantitative data obtained can be used to guide the safety improvement, to reduce the costs of safety regulation violation and accident risk.

关键词： Accident analysis STAMP System engineering Game theory Oil and gas storage and transportation systems

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