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Development of NK cell-based cancer immunotherapies through receptor engineering

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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

Hydrometallurgy two stage process for preparation of (Nd,La,Ce)_(2)O_(3) from end-of-life NiMH batteries

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Journal of Rare Earths 2024年第2期42卷 415-423,I0007页

作者： Karim Tanji Khalid Ouzaouit Mohamed Belghiti Isam Lamsayety Hakim Faqir Intissar Benzakour centre de recherche REMINEX-Groupe MANAGEM MarrakechMorocco

The present work aims to investigate the recovery of light rare earth elements(LREEs) oxides from end-oflife NiMH batteries using a hydro metallurgical process followed by effective precipitation.The operational leaching parameters such as phosphoric acid concentration,temperature,and the solid-liquid ratio were first optimized by Box-Behnken design.The results reveal that under optimum conditions([H_(3)PO_(4)]=2 mol/L,T=80℃,and S/L=1:10 g/mL) the leaching efficiencies of Ni,Co reach 98.1% and99.3%.While La,Ce,and Nd elements remain in the leaching residue as(La,Ce,Nd)PO_(4) with yields of 98.2%,98.6%,and 99.6% for La,Ce,and Nd,respectively.Afterward,the(La,Ce,Nd)PO_(4) is leached with HCl acid,then the rare earth oxalate was precipitated using oxalic acid at a pH of 1.8 and then the product was calcined at 800℃ for 2 h in order to synthesize the(Nd,La,Ce)_(2)O_(3).The analysis using scanning electron microscopy(SEM) coupled with energy dispersive X-ray spectroscopy(EDX) confirms the homogeneity of(Nd,La,Ce)_(2)O_(3) particles that have two morphologies,i.e.,flower and sticks with a particle size between 3and 6 μm.The unit cell parameters of(Nd,La,Ce)_(2)O_(3) were calculated after Rietveld refinement of the XRD patterns,in the space group of Fm-3m are a=b=c=0.57921 nm and the volume equal to 0.194322 nm^(3).

关键词： NiMH batteries Hydrometallurgical process Leaching Phosphoric acid Box-Behnken Light rare earth oxides

Unveiling protein corona composition:predicting with resampling embedding and machine learning

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Regenerative Biomaterials 2024年第1期3卷 27-33页

作者： Rong Liao Yan Zhuang Xiangfeng Li Ke Chen Xingming Wang Cong Feng Guangfu Yin Xiangdong Zhu Jiangli Lin Xingdong Zhang College of Biomedical Engineering National Engineering Research Centre for BiomaterialsSichuan UniversityChengdu610065China

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration.When nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs.However,achieving accurate predictions remains a significant challenge.Although several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution.In this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data.Various ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were obtained.Our ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random Oversampling.Additionally,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

关键词： nanoparticles protein corona machine learming resampling technique feature analysis

In-situ synthesis of quantum dots in the nucleus of live cells

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National Science Review 2024年第3期11卷 172-182页

作者： Yusi Hu Zhi-Gang Wang Haohao Fu Chuanzheng Zhou Wensheng Cai Xueguang Shao Shu-Lin Liu Dai-Wen Pang State Key Laboratory of Medicinal Chemical Biology Frontiers Science Centre for New Organic MatterTianjin Key Laboratory of Biosensing and Molecular Recognition Research Centre for Analytical Sciences College of Chemistry School of Medicine and Frontiers Science Centre for Cell Responses Nankai University Haihe Laboratory of Sustainable Chemical Transformations

The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However,whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdSxSe1-xquantum dots（QDs） in the nucleus by regulation of the glutathione（GSH） metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced ‘supercells’.

关键词： glutathione live cell nucleus quantum dot intracellular synthesis

Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1077-1097页

作者： Lindokuhle Cindy Nene Heidi Abrahamse Laser Research centre Faculty of Health SciencesUniversity of JohannesburgDoornfontein 2028South Africa

Cancer remains one of the diseases with the highest incidence and mortality globally.Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and surgery.Sono-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach.SPDT combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer eradication.The use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT.This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

关键词： Sonodynamic therapy Photodynamic therapy Combinatorial therapy Phthalocyanines Sensitizer Cancer

Snow and regolith albedo variations using CRISM data at McMurdo crater,Mars

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Earth and Planetary Physics 2024年第2期8卷 338-355页

作者： Sehajpal Singh Deepak Singh centre of Studies in Resources Engineering Indian Institute of Technology BombayMumbaiIndia

The cryosphere component provides the most reliable and insightful indications of any planet’s climate dynamics.Using data from the Compact Reconnaissance Imaging Spectrometer for Mars(CRISM),we develop a novel approach to determining the broadband Visible and Near Infrared(VNIR)albedo of the Martian surface.This study focuses on albedo changes in the McMurdo crater,part of Mars’s south polar layer deposits.We compare seasonal and interannual variations of the McMurdo surface albedo before,during,and after the Global Dust Storm(GDS)of Martian Year(MY)34.As the seasons progressed from spring to summer,the mean albedo in MY 32 and 34 plunged by over 40%,by about 35%in MY 33,and by slightly more than 30%in MY 35.Compared interannually,however,mean albedo values within both seasons(spring and summer)exhibited no significant differences in those same years.Notably,interannual albedo difference maps reveal albedo variation of more than±0.3 in certain regions of the crater.Considering only snow-covered pixels,interannual albedo differences suggest that Mars dust had a pervasive impact on Mars’s cryosphere.Variations in maximum and minimum albedo values as high as 0.5 were observed,depending upon differences in the dust levels in Martian snow/ice.The maximum and the minimum snow albedo values were lowest in MY 34,indicating the effect of the intense dust storm event that year.The average snow albedo decreased from 0.45 in MY 32 to 0.40 in MY 33 and to 0.33 in MY 34,and then rose back to 0.40 in MY 35.This trajectory suggests a temporary deposition of dust,partially reversed after the GDS by self-cleaning mechanisms(local aeolian process and CO_(2)sublimation/deposition cycle).

关键词： Mars Martian ice albedo dust storm Mars surface Martian climate

Air traffic monitoring using optimized ADS-B CubeSat constellation

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Astrodynamics 2024年第1期8卷 189-208页

作者： Ghulam Jaffer Rameez AMalik Elias Aboutanios Nazish Rubab Ronnie Nader Hans U.Eichelberger Guy A.E.Vandenbosch Interdisciplinary centre for Security Reliability and Trust(SnT)University of LuxembourgLuxembourg1855Luxembourg

The primary technique used for air traffic surveillance is radar.However,nowadays,its role in surveillance is gradually being replaced by the recently adopted Automatic Dependent Surveillance-Broadcast(ADS-B).ADS-B offers a higher accuracy,lower power consumption,and longer range than radar,thus providing more safety to aircraft.The coverage of terrestrial radar and ADS-B is confined to continental parts of the globe,leaving oceans and poles uncovered by real-time surveillance measures.This study presents an optimized Low-Earth Orbit(LEO)-based ADS-B constellation for global air traffic surveillance over intercontinental trans-oceanic flight routes.The optimization algorithm is based on performance evaluation parameters,i.e.,coverage time,satellite availability,and orbit stability(precession and perigee rotation),and communication analysis.The results indicate that the constellation provides ample coverage in the simulated global oceanic regions.The constellation is a feasible and cost-effective solution for global air supervision,which can supplement terrestrial ADS-B and radar systems.

关键词： constellation automatic dependent surveillance-broadcast (ADS-B) air traffic surveillance precession perigee rotation.

Background removal from global auroral images:Data-driven dayglow modeling

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Earth and Planetary Physics 2024年第1期8卷 247-257页

作者： A.Ohma M.Madelaire K.M.Laundal J.P.Reistad S.M.Hatch S.Gasparini S.J.Walker Birkeland centre for Space Science Department of Physics and TechnologyUniversity of BergenBergenNorway

Global images of auroras obtained by cameras on spacecraft are a key tool for studying the near-Earth environment.However,the cameras are sensitive not only to auroral emissions produced by precipitating particles,but also to dayglow emissions produced by photoelectrons induced by sunlight.Nightglow emissions and scattered sunlight can contribute to the background signal.To fully utilize such images in space science,background contamination must be removed to isolate the auroral signal.Here we outline a data-driven approach to modeling the background intensity in multiple images by formulating linear inverse problems based on B-splines and spherical harmonics.The approach is robust,flexible,and iteratively deselects outliers,such as auroral emissions.The final model is smooth across the terminator and accounts for slow temporal variations and large-scale asymmetries in the dayglow.We demonstrate the model by using the three far ultraviolet cameras on the Imager for Magnetopause-to-Aurora Global Exploration(IMAGE)mission.The method can be applied to historical missions and is relevant for upcoming missions,such as the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.

关键词： aurora dayglow modeling global auroral images far ultraviolet images dayglow removal

Heterogeneous integration of 2D materials on Si charge-coupled devices as optical memory

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Science China(Information Sciences) 2024年第6期67卷 190-197页

作者： Zheng BIAN Feng TIAN Zongwen LI Xiangwei SU Tianjiao ZHANG Jialei MIAO Bin YU Yang XU Yuda ZHAO College of Integrated Circuits Hangzhou Global Scientific and Technological Innovation CentreZhejiang University

Optical memory integrates the function of optical sensing in memory devices, remarkably promoting the interconnection between sensory and memory terminals. Silicon charge-coupled photodetectors and floating gate memory have been widely used in imaging and storage technologies, respectively. However,the heterogeneous integration of the two devices requires technological innovation and complex electrical connections. In this work, we adopt a three-dimensional layer stacking method to design a novel optical memory device. On the top of Si charge-coupled photodetectors, we successively deposit two-dimensional graphene,hexagonal boron nitride, and molybdenum disulfide as a floating gate layer, a tunneling layer, and a readout layer, respectively. By applying a gate bias on lightly doped Si, a deep depletion layer is formed with a high voltage potential drop. Under dark conditions, the depletion layer cannot be filled, and the electric field across the h-BN tunnel barrier is relatively small. Under light irradiation, the deep depletion layer is gradually filled, and the h-BN tunneling layer withstands the increasing electric field, resulting in charge storage in the floating gate layer. Based on this mechanism, the device exhibits a gate voltage-dependent operation mode, including an integrated optical sensing-memory mode and an electrically driven storage mode. Under moderate gate voltage, the device can effectively detect the optical information with varied intensity and store the optical information in the floating gate, displaying optically controlled memory characteristics. Our work demonstrates a compact device structure for optical memory and displays excellent optically controlled memory performance, which can be applied in artificial vision systems.

关键词： heterogeneous integration charge-coupled device floating gate optical memory molybdenum disulfide lightly doped silicon