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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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In vivofluorescenceflow cytometry reveals that the nanoparticle tumor vaccine OVA@HA-PEI effectively clears circulating tumor cells

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Journal of Innovative Optical health Sciences 2024年第6期17卷 107-123页

作者： Wei Jin Yuting Fu Sisi Ge Han Sun Kai Pang Xunbin Wei The Department of biomedical Engineering institute of Advanced Clinical Medicine Peking University Beijing 100191P.R.China institute of Medical Technology Peking University health Science Center Beijing 100191 P.R.China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Peking University Cancer Hospital&InstituteBeijing 100142P.R.China School of Instrument Science and Opto-Electronics Engineering Beijing Information Science&Technology University Beijing 100192 P.R.China

Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side ***,it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery *** vaccines often fail to elicit a su±ciently robust immune response against progressive tumors,thereby limiting their clinical e±*** this study,we developed a nanoparticle-based tumor vaccine,OVA@HA-PEI,utilizing ovalbumin(OVA)as the presenting antigen and hyaluronic acid(HA)and polyethyleneimine(PEI)as adjuvants and *** formulation significantly enhanced the proliferation of immune cells and cytokines,such as CD3,CD8,interferon-,and tumor necrosis factor-,in vivo,effectively activating an immune response against B16–F10 *** vivofluorescenceflow cytometry(IVFC)has already become an effective method for monitoring circulating tumor cells(CTCs)due to its direct,noninvasive,and long-term detection *** study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1(PD-1)*** results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment ***,this combination therapy substantially reduced the number of CTCs in vivo,increased the clearance rate of CTCs by the immune system,and slowed tumor *** greatly enhance the clinical application prospects of IVFC and tumor vaccines.

关键词： Tumor vaccines circulating tumor cells in vivofluorescenceflow cytometry.

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Electrochemical anodization of cast titanium alloys in oxalic acid for biomedical applications

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Frontiers of Chemical Science and Engineering 2024年第1期18卷 13-24页

作者： Engie M.Safwat Soha A.Abdel-Gawad Madiha A.Shoeib Shimaa El-Hadad Restorative and Dental Materials Department National Research CentreGiza 12622Egypt Chemistry Department Faculty of ScienceCairo UniversityGiza 12613Egypt Central Metallurgical research and Development institute Helwan 11421Egypt

Titanium and its alloys have numerous biomedical applications thanks to the composition and morphology of their oxide *** this study,the colorful oxide films were formed by anodizing cast Ti-6Al-4V and Ti-6Al-7Nb alloys in a 10%oxalic acid solution for 30 s at different voltages(20–80 V)of a direct current power *** force microscopy was used as an accurate tool to measure the surface roughness of thin films on the nanometer *** electron microscopy and X-ray diffraction were performed to analyze surface morphology and phase *** to the results,the produced titanium oxide layer showed high surface roughness,which increased with increasing anodizing *** impact of anodizing voltages on the color and roughness of anodized layers was *** corrosion resistance of the anodized samples was studied in simulated body fluid at pH 7.4 and a temperature of 37℃ utilizing electrochemical impedance spectroscopy and the potentiodynamic polarization *** anodized samples for both alloys at 40 V were at the optimal voltage,leading to a TiO_(2) layer formation with the best compromise between oxide thickness and corrosion ***,findings showed that TiO_(2) films produced on Ti-6Al-7Nb alloys had superior surface roughness properties compared to those of Ti-6Al-4V alloys,making them more appropriate for orthopedic *** the obtained data and the fruitful discussion,it was found that the utilized procedure is simple,low-cost,and ***,anodization in 10%oxalic acid proved a viable alternative for the surface finishing of titanium alloys for biomedical applications.

关键词： DC anodization Ti-6Al-4V alloy Ti-6Al-7Nballoy oxidefilm corrosion

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Dynamic Organization of Large-scale Functional Brain Networks Supports Interactions Between Emotion and Executive Control

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Neuroscience Bulletin 2024年第7期40卷 981-991页

作者： Haiyang Geng Pengfei Xu Andre Aleman Shaozheng Qin Yue-Jia Luo State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Tianqiao and Chrissy Chen Institute for Translational ResearchShanghai 200040China Beijing Key Laboratory of Applied Experimental Psychology National Demonstration Center for Experimental Psychology Education(BNU)Faculty of PsychologyBeijing Normal UniversityBeijing 100875China Center for Neuroimaging Shenzhen Institute of NeuroscienceShenzhen 518107China University of Groningen Department of Biomedical Sciences of Cells and SystemsSection Cognitive NeuroscienceUniversity Medical Center GroningenGroningenThe Netherlands institute for Neuropsychological Rehabilitation University of Health and Rehabilitation SciencesQingdao 266113China Shenzhen Key Laboratory of Affective and Social Neuroscience Magnetic Resonance ImagingCenter for Brain Disorders and Cognitive SciencesShenzhen UniversityShenzhen 518060China Chinese institute for Brain research Beijing 102206China

Emotion and executive control are often conceptualized as two distinct modes of human brain ***,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their *** amygdala and prefrontal systems have long been thought to play crucial roles in these *** advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their ***,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based *** this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain *** model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.

关键词： Dynamic brain network Emotion Executive control Salience network Executive control network Default mode network

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O_(2)-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

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Chinese Chemical Letters 2024年第7期35卷 394-399页

作者： Yu Qin Mingyang Huang Chenlu Huang Hannah LPerry Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Molecular Sciences research Hub Department of ChemistryWhite City CampusImperial College LondonLondon W120BZUnited Kingdom

Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor ***,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor *** drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective *** address these issues,a MnO_(2)doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and MnO_(2)*** surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell *** internalization,HTIM-PMs showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO_(2)and *** released MnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT *** PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS *** PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of *** promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.

关键词： Photodynamic therapy Photothermal therapy Oxygen generating One-step self-assembly Stimuli-responsive nanoparticles

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Mathematics of multi-agent learning systems at the interface of game theory and artificial intelligence

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Science China(Information Sciences) 2024年第6期67卷 445-447页

作者： Long WANG Feng FU Xingru CHEN Center for Systems and Control College of EngineeringPeking University Center for Multi-Agent research Institute for Artificial IntelligencePeking University Department of Mathematics Dartmouth College Department of biomedical Data Science Geisel School of Medicine at Dartmouth School of Science Beijing University of Posts and Telecommunications

Evolutionary game theory (EGT) and artificial intelligence(AI) are two fields that,at first glance,might seem distinct,but they have notable connections and *** former focuses on the evolution of behaviors (or strategies)in a population,where individuals interact with others and update their strategies based on imitation (or social learning).

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The Mechanics of Tumor Cells Dictate Malignancy via Cytoskeleton-Mediated APC/Wnt/β-Catenin Signaling

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research 2024年第2期2023卷 659-673页

作者： Xi Chen Zichen Xu Kai Tang Guanshuo Hu Pengyu Du Junfang Wang Cunyu Zhang Ying Xin Keming Li Qiantang Zhang Jianjun Hu Zhuxue Zhang Mo Yang Guixue Wang Youhua Tan The Hong Kong Polytechnic University Shenzhen research institute Shenzhen518057China Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing400030China research institute of Smart Ageing The Hong Kong Polytechnic UniversityHong KongChina Department of biomedical Engineering The Hong Kong Polytechnic UniversityHong KongChina Department of Pathology Guizhou Provincial People's HospitalGuiyangGuizhou550002China

Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression,implicating the correlation between cell mechanics and ***,the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely *** report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in ***/strengthening actin cytoskeleton impairs/reinforces the interaction between adenomatous polyposis coli(APC)andβ-catenin,which facilitatesβ-catenin nuclear/cytoplasmic ***β-catenin binds to the promoter of Oct4,which enhances its transcription that is crucial in sustaining self-renewal and *** results demonstrate that the mechanics of tumor cells dictate self-renewal through cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling,which are correlated with tumor differentiation and patient *** study unveils an uncovered regulatory role of cell mechanics in self-renewal and malignancy,and identifies tumor cell mechanics as a hallmark not only for cancer diagnosis but also for mechanotargeting.

关键词： diagnosis skeleton APC

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Distinct SARS-CoV-2 populational immune backgrounds tolerate divergent RBD evolutionary preferences

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national Science Review 2024年第7期11卷 95-105页

作者： Wentai Ma Haoyi Fu Fanchong Jian Yunlong Cao Mingkun Li Beijing institute of Genomics Chinese Academy of Sciencesand China National Center for Bioinformation University of Chinese Academy of Sciences biomedical Pioneering Innovation Center(BIOPIC) Peking University Changping Laboratory

Immune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct(less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of the newly derived mutations that occurred in BA.5.2.48, BF.7.14 and BA.5.2.49—variants prevalent in China—with their counterparts in other countries. We found that the emerging mutations in the receptor-binding-domain region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher angiotensin-converting enzyme 2(ACE2) binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them outcompeted the original strain until the arrival of the XBB variant, which had stronger immune evasion and subsequently outcompeted all circulating variants. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.

关键词： SARS-CoV-2 evolution mutation population immunity

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Challenges and Suggestions of Ethical Review on Clinical research Involving Brain-Computer Interfaces

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Chinese Medical Sciences Journal 2024年第2期39卷 131-139页

作者： Xue-Qin Wang Hong-Qiang Sun Jia-Yue Si Zi-Yan Lin Xiao-Mei Zhai Lin Lu Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Chinese Academy of Medical Sciences Research Unit(No.2018RU006)Beijing 100191China Department of Psychology University of CaliforniaDavis 95616USA Department of Psychology University of TorontoToronto M5S 1A1Canada School of Population Medicine and Public health Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Academy for Advanced Interdisciplinary Studies Peking-Tsinghua Centre for Life Sciences and Peking University-International Development Group/McGovern Institute for Brain ResearchPeking UniversityBeijing 100871China

Brain-computer interface(BCI)technology is rapidly advancing in medical research and *** an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental ***,BCI also raises several challenges and ethical concerns in clinical *** this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical *** the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in *** ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.

关键词： brain-computer interface clinical research bioethics ethical governance ethical review

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Defined hydrogels for spinal cord organoids:challenges and potential applications

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Neural Regeneration research 2024年第11期19卷 2329-2330页

作者： Wai Hon Chooi Yuewen Wu Shi-Yan Ng institute of Molecular and Cell Biology(IMCB) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Department of Physiology Yong Loo Lin School of MedicineNational University of Singapore(NUS)SingaporeSingapore

Organoids of the central nervous system,primarily derived from pluripotent stem cells or neural stem cells,are three-dimensional tissue cultures with self-organizing *** exposed to the right combinations of signals,they differentiate into a 3D tissue consisting of complex cytoarchitecture and native cell types,including various neuron subtypes and glial *** features closely mimic native tissues,making them invaluable for developmental studies and disease *** recent years,spinal cord organoids(SCOs)have been developed to investigate spinal cord development,injuries,and various neurological *** an integral part of the central nervous system,SCOs play a vital role and serve as a site for studying both neurodevelopment and neurodegenerative diseases.

关键词： properties injuries primarily

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