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A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na Ma Weikang Xu Xuan Yi Xinyu lu Xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao jiang Yajing He Sha Wu Yukai He Yongyin Li jinlin Hou State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK Department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key Laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

Synchronized off-harmonic probe laser with highly variable pulse duration for laser-plasma interaction experiments

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High Power Laser Science and Engineering 2024年第1期12卷 99-107页

作者： j.Hornung Y.Zobus H.Lorenté C.Brabetz B.Zielbauer V.Bagnoud GSI Helmholtzzentrum für Schwerionenforschung GmbH DarmstadtGermany Institut d’Optique UniversitéParis-SaclayPalaiseauFrance Institut für Angewandte Physik Technische Universität DarmstadtDarmstadtGermany

This paper presents the development and experimental utilization of a synchronized off-harmonic laser system designed as a probe for ultra-intense laser±plasma interaction experiments. The system exhibits a novel seed-generation design,allowing for a variable pulse duration spanning over more than three orders of magnitude, from 3.45 picoseconds to 10 nanoseconds. This makes it suitable for various plasma diagnostics and visualization techniques. In a side-view configuration, the laser was employed for interferometry and streaked shadowgraphy of a laser-induced plasma while successfully suppressing the self-emission background of the laser±plasma interaction, resulting in a signal-to-self-emission ratio of 110 for this setup. These properties enable the probe to yield valuable insights into the plasma dynamics and interactions at the PHELIX facility and to be deployed at various laser facilities due to its easy-to-implement design.

关键词： interferometry laser-plasma interaction off-harmonic probe laser streaked shadowgraphy

The initial stages of Li_(2)O_(2) formation during oxygen reduction reaction in Li-O_(2) batteries:The significance of Li_(2)O_(2) in charge-transfer reactions within devices

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journal of Energy Chemistry 2024年第1期88卷 223-231,I0006页

作者： Daniela M.josepetti Bianca P.Sousa Simone A.j.Rodrigues Renato G.Freitas Gustavo Doubek Advanced Energy Storage Division LABCenter for Innovation on New EnergiesSchool of Chemical EngineeringUniversity of CampinasAv Albert Einstein 50013083-852CampinasSPBrazil Institute of Physics&Department of Chemistry Laboratory of Computational MaterialsFederal University of Mato Grosso78060-900CuiabáMTBrazil

Lithium-oxygen batteries are a promising technology because they can greatly surpass the energy density of lithium-ion ***,this theoretical characteristic has not yet been converted into a real device with high *** with air contamination,metallic lithium reactivity,and complex discharge and charge reactions are the main issues for this technology.A fast and reversible oxygen reduction reaction(ORR)is crucial for good performance of secondary batteries',but the partial knowledge of its mechanisms,especially when devices are concerned,hinders further *** this perspective,the present work uses operando Raman experiments and electrochemical impedance spectroscopy(EIS)to assess the first stages of the discharge processes in porous carbon electrodes,following their changes cycle by cycle at initial operation.A growth kinetic formation of the discharge product signal(Li_(2)O_(2))was observed with operando Raman,indicating a first-order reaction and enabling an analysis by a microkinetic *** solution mechanism in the evaluated system was ascribed for an equivalent circuit with three time *** the time constant for the anode interface reveals to remain relatively constant after the first discharge,its surface seemed to be more *** model indicated that the reaction occurs at the Li_(2)O_(2) surface,decreasing the associated resistance during the initial discharge ***,the growth of Li_(2)O_(2) forms a hetero-phase between Li_(2)O_(2)/electrolyte,while creating a more compact and homogeneous on the Li_(2)O_(2)/cathode *** methodology here described thus offers a way of directly probing changes in surface chemistry evolution during cycling from a device through EIS analysis.

关键词： Li-O_(2)battery Operando Raman analysis Equivalent circuit modeling Time-constant distribution

Interactive mechanism and friction modelling of transient tribological phenomena in metal forming processes: A review

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Friction 2024年第3期12卷 375-395页

作者： Xiao YANG Heli LIU Lemeng ZHANG Yiran HU Denis j.POLITIS Mohammad M.GHARBI Liliang WANG Department of Mechanical Engineering Imperial College LondonLondon SW72AZUK Department of Mechanical and Manufacturing Engineering University of CyprusNicosia 1678Cyprus Quaker Houghton Deutschland GmbH Dortmund 44319Germany

The accurate representation of tribological boundary conditions at the tool–workpiece interface is crucial for analysis and optimization of formability,material flow,and surface quality of components during metal forming *** has been found that these tribological conditions vary spatially and historically with process parameters and contact *** time-dependent tribological behaviours are also known as transient tribological phenomena,which are widely observed during forming processes and many other manufacturing application ***,constant friction values are usually assigned to represent complex and dynamic interfacial conditions,which would introduce deviations in the relevant *** this paper,transient tribological phenomena and the contemporary understanding of the interaction between friction and wear are reviewed,and it has been found that these phenomena are induced by the transitions of friction mechanisms and highly dependent on complex loading conditions at the *** modelling techniques for transient behaviours for metal forming applications are also *** accurately describe the evolutionary friction values and corresponding wear during forming,the advanced interactive friction modelling has been established for different application scenarios,including lubricated condition,dry sliding condition(metal-on-metal contact),and coated system.

关键词： transient tribological phenomena interactive friction mechanism modelling techniques metal forming

Stochastic seismic inversion and Bayesian facies classification applied to porosity modeling and igneous rock identification

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Petroleum Science 2024年第2期21卷 918-935页

作者： Fábio júnior Damasceno Fernandes Leonardo Teixeira Antonio Fernando Menezes Freire Wagner Moreira lupinacci Exploratory Interpretation and Reservoir Characterization Group(GIECAR) Department of Geology and GeophysicsFederal Fluminense UniversityNiter oiRJ24210-346Brazil Petrobras Rio de JaneiroRJ20231-030Brazil National Institute of Science and Technology of Petroleum Geophysics(INCT-GP/CNPQ) Niter oiRJ24210-346Brazil

We apply stochastic seismic inversion and Bayesian facies classification for porosity modeling and igneous rock identification in the presalt interval of the Santos Basin. This integration of seismic and well-derived information enhances reservoir characterization. Stochastic inversion and Bayesian classification are powerful tools because they permit addressing the uncertainties in the model. We used the ES-MDA algorithm to achieve the realizations equivalent to the percentiles P10, P50, and P90 of acoustic impedance, a novel method for acoustic inversion in presalt. The facies were divided into five: reservoir 1,reservoir 2, tight carbonates, clayey rocks, and igneous rocks. To deal with the overlaps in acoustic impedance values of facies, we included geological information using a priori probability, indicating that structural highs are reservoir-dominated. To illustrate our approach, we conducted porosity modeling using facies-related rock-physics models for rock-physics inversion in an area with a well drilled in a coquina bank and evaluated the thickness and extension of an igneous intrusion near the carbonate-salt interface. The modeled porosity and the classified seismic facies are in good agreement with the ones observed in the wells. Notably, the coquinas bank presents an improvement in the porosity towards the top. The a priori probability model was crucial for limiting the clayey rocks to the structural lows. In Well B, the hit rate of the igneous rock in the three scenarios is higher than 60%, showing an excellent thickness-prediction capability.

关键词： Stochastic inversion Bayesian classification Porosity modeling Carbonate reservoirs Igneous rocks

Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： jiang-Hui Wang Dominic j.Gessler Wei Zhan Thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

Coordinate-wise monotonic transformations enable privacy-preserving age estimation with 3D face point cloud

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Science China(Life Sciences) 2024年第7期67卷 1489-1501页

作者： Xinyu Yang Runhan Li Xindi Yang Yong Zhou Yi Liu jing-Dong j.Han School of Life Sciences Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Beijing Key Lab of Traffic Data Analysis and Mining School of Computer and Information TechnologyBeijing Jiaotong UniversityBeijing 100044China Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy *** we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic *** first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and *** show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial *** visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is *** study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.

关键词： face point cloud age estimation face verification privacy coordinate-wise monotonic transformation

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基于LES的压气机叶栅通道非定常流动结构研究

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热能动力工程 2024年第1期39卷 98-107页

作者：黄明珂周玲季路成北京理工大学宇航学院北京100081 清华大学航空发动机研究院北京100084

为了进一步理解压气机叶栅通道内的非定常流动结构,采用大涡模拟(LES)方法研究了来流附面层厚度和稠度变化对叶栅通道内涡系结构及总压损失系数的影响。研究表明:来流附面层增厚将导致端壁处流体的轴向动能降低,使得马蹄涡压力面分支更... 详细信息

为了进一步理解压气机叶栅通道内的非定常流动结构,采用大涡模拟(LES)方法研究了来流附面层厚度和稠度变化对叶栅通道内涡系结构及总压损失系数的影响。研究表明:来流附面层增厚将导致端壁处流体的轴向动能降低,使得马蹄涡压力面分支更早地流向相邻叶片吸力面;来流附面层越厚,通道涡在叶栅尾缘沿展向抬升的高度越高,角区分离的范围也越大;叶栅的总压损失随附面层增厚而增加,附面层损失增加显著,二次流损失有所增大;稠度较低时叶栅吸力面表面存在分离,会对通道涡及角区分离产生影响;稠度增大,横向压力梯度减小,叶栅流道的速度分布更均匀,通道涡的强度和尺度减小,角区分离的范围减小;稠度增大使叶表不再分离时,总压损失显著降低,但稠度继续增大会使气流与叶片表面的摩擦损失增加。

关键词：压气机叶栅大涡模拟附面层厚度稠度角区分离

Four Late-type Galaxies with Double Radio Lobes and Properties of Such Galaxies

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Research in Astronomy and Astrophysics 2024年第4期24卷 84-90页

作者： Z.S.Yuan X.Y.Gao Z.L.Wen j.L.Han National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China CAS Key Laboratory of FAST National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China School of Astronomy and Space Sciences University of Chinese Academy of SciencesBeijing 100049China

The triggering mechanism for radio lobes from late-type galaxies is not fully *** samples are desired for a thorough investigation and *** utilizing the optical data from the newly released Dark Energy Spectroscopic Instrument imaging surveys and the radio sources from the NRAO VLA Sky Survey and the Faint Images of the Radio Sky at Twenty-centimeter,we identify four Late-type Galaxies with double Radio Lobes(La GRLs):j0217-3645,j0947+6220,j1412+3723 and j1736+*** previously known La GRLs,we confirm the correlation between radio power P_(1.4GHz)and stellar mass M_(*)of host ***(25/35)La GRLs belong to the blue cloud galaxies,while the newly identified cases in this work are located within the region of the red *** find a clear correlation between the differential radio power,i.e.,the offset from the P_(1.4GHz)-M_(*)relation,and the galaxy color,indicating that bluer galaxies at a fixed M_(*)tend to host more powerful radio ***,the majority(31/36)of La GRLs are either located in a galaxy group or displaying a disturbed *** suggest that all of the galaxy mass,color and surrounding environment could play important roles in triggering radio lobes in late-type galaxies.

关键词： galaxies:active galaxies:jets galaxies:spiral radio continuum:galaxies