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Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer

Cell and Bioscience 2023年第1期13卷 1页

作者： Fan, Yu-Ching Fong, Yu-Cin Kuo, Chun-Tse Li, Chia-Wei Chen, Wei-Yu Lin, Jian-Da Bürtin, Florian Linnebacher, Michael Bui, Quoc Thang Lee, Kuan-Der Tsai, Yuan-Chin Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Department of Pathology Wan Fang Hospital Taipei Medical University Taipei Taiwan Department of Pathology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemical Science and Technology College of Life Science National Taiwan University Taipei City 10617 Taiwan Center for Computational and Systems Biology National Taiwan University Taipei City 10617 Taiwan Clinic of General Surgery University Medical Center Rostock Schillingallee 35 Rostock 18057 Germany Clinic of General Surgery Molecular Oncology and Immunotherapy University Medical Center Rostock Schillingallee 69 Rostock 18057 Germany International Ph.D. Program for Cell Therapy and Regeneration Medicine (IPCTRM) School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Post-Baccalaureate Medicine College of Medicine Natioanl Chung Hsing University Taichung Taiwan Cell Therapy and Regenerative Medicine Center and Comprehensive Cancer Center Taichung Veterans General Hospital Taichung Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Background: Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine;however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA. Results: Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8⁺ T cells and a decrease in CD11b⁺Ly6G⁻ immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4⁺ T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8⁺ T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes. Conclusions: Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of

关键词： IFN-γ Immunosuppression interleukin-1 receptor antagonist Pancreatic adenocarcinoma Patient-derived xenograft Tumor microenvironment

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Dynamic changes of fatty acids and (R)-dichlorprop toxicity in Arabidopsis thaliana: correlation, mechanism, and implications

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Environmental science and Pollution Research 2024年第43期31卷 55522-55534页

作者： Li, Jun Zhang, Qiushui Chen, Hui Xu, Dongmei Chen, Zunwei Wen, Yuezhong MOE Key Laboratory of Environmental Remediation & amp Ecosystem Health College of Environmental and Resource Sciences Zhejiang University Hangzhou310058 China College of Science and Technology Ningbo University Ningbo315211 China Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province College of Biological and Environmental Engineering Zhejiang Shuren University Hangzhou310015 China Program in Molecular and Integrative Physiological Sciences Department of Environmental Health Harvard University T.H. Chan School of Public Health BostonMA02115 United States

Plant fatty acids (FAs) are critical components of lipids and play an important role in coping with pollution-induced stress. However, the relationship between the fluctuating changes of FAs and the toxic effects of pollutants is not clear. Here, we analyzed and identified 19 FAs, namely 14 medium and long chain fatty acids (MLCFAs) and 5 very long chain fatty acids (VLCFAs). First, a positive correlation between plant biomass and LCFA content was observed. Changes in unsaturation were inversely related to cell membrane permeability, which serves as an indicator of the toxic effects. In particular, the use of herbicides led to a reduction in total FA content, but caused a significant increase in free fatty acids (FFAs), which facilitate oxidative stress. In addition, supplementation with exogenous FAs, particularly linoleic and alpha-linolenic acids, effectively alleviated the toxic inhibition. (R)-dichlorprop causes abnormal FA metabolism that can be reversed by ferrostatin-1, a ferroptosis inhibitor. Under (R)-dichlorprop exposure, the balance of FA unsaturation in plants is disrupted by inhibition of FA desaturase activity, ultimately leading to ferroptosis and disruption of cell membrane integrity. This study aims to enhance the understanding of the ecotoxic effects of herbicides by examining changes in FAs. The findings will provide a scientific basis for controlling environmental risks associated with hazardous substances. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

关键词： Cell membranes

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Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer

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Genes & Diseases 2022年第2期9卷 393-400页

作者： Yi Zuo Shaoqiu Chen Lingling Yan Ling Hu Scott Bowler Emory Zitello Gang Huang Youping Deng Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyWuhan 430064PR China Department of Quantitative Health Sciences John A.Burns School of MedicineUniversity of Hawaii at ManoaHonoluluHI 96813USA Molecular Biosciences and Bioengineering Program College of Tropical Agriculture and Human ResourcesUniversity of Hawaii at ManoaHonoluluHI 96822USA Shanghai Key Laboratory for Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318PR China

Liver cancer presents divergent clinical *** remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been *** this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer *** performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,*** seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic ***,the model successfully categorizes patients into high-low risk *** and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.

关键词： Diagnosis Liver cancer Prognosis Random forests tRNA-derived small RNAs

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NMD-mediated posttranscriptional regulation fine-tunes the NLR-WRKY regulatory module to modulate bacterial defense response

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Plant science 2025年 356卷 112528页

作者： Nasim, Zeeshan Karim, Nouroz Blilou, Ikram Ahn, Ji Hoon Department of Molecular Life Sciences Korea University Seoul 02841 South Korea Plant Science Program Biological and Environmental Science and Engineering Division (BESE) King Abdullah University of Science and Technology (KAUST) Thuwal 23955-6900 Saudi Arabia

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance system that maintains transcriptome integrity by degrading aberrant RNA transcripts. NMD ensures proper growth and development by preventing autoimmunity through the direct regulation of nucleotide-binding, leucine-rich repeat (NLR) genes. Whether NMD directly regulates WRKY genes remains unclear, despite their upregulation in NMD-deficient plants, and potential feedback between NLRs and WRKYs is also poorly understood. In this study, we showed that NMD also directly regulates a subset of WRKY (WRKY15, 18, 25, 33, 46, 60, and 70) genes, particularly at lower temperatures (16°C). NMD signature-containing transcripts of WRKY46 and WRKY70, selected as representative NMD-regulated WRKY genes, showed increased half-lives in NMD-deficient mutants. Transcriptome analyses showed that these seven NMD-regulated WRKY genes are induced in response to bacterial infection. Potential homologues of these seven NMD-regulated WRKY genes in maize and rice showed similar induction in response to bacterial pathogen infection. Furthermore, these NMD-regulated WRKY genes are induced in plants overexpressing RESISTANT TO P. SYRINGAE 4 (RPS4) in a temperature-dependent manner. By using ChIP-seq and DAP-seq data of WRKY transcription factors, we showed that WRKYs potentially regulate a significant number of NLR genes by directly binding to the W-box in their promoter regions. Taken together, our findings revealed that in addition to the NLRs, the NMD machinery also regulates WRKY genes to keep the basal defense levels in check and the WRKY transcription factors directly regulate NLR genes to constitutes a positive feedback regulatory loop to optimize the plant response to invading pathogens. © 2025 Elsevier B.V.

关键词： Arabidopsis Defense NLR NMD UPF WRKY

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Suppression of Quantum Correlations in a Clean-Disordered Atom-Nanophotonic Interface

arXiv

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arXiv 2024年

作者： Handayana, I. Gusti Ngurah Yudi Tsao, Yi-Lin Jen, H.H. Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taiwan Department of Physics National Central University Taoyuan City320317 Taiwan Institute of Atomic and Molecular Sciences Academia Sinica Taipei10617 Taiwan School of Physics College of Sciences Georgia Institute of Technology Atlanta30332 United States Physics Division National Center for Theoretical Sciences Taipei10617 Taiwan

Quantum correlations are essential to the emergent behaviors of quantum systems, supporting key phenomena such as localization or delocalization of particles, quantum avalanches in many-body localized systems, and quantum information transfer. In open atom-nanophotonic systems characterized by long-range spin-exchange interactions, we examine the influence of clean system size on high-order quantum correlations among a clean-disordered atomic array with multiple atomic excitations. By initializing the system far from equilibrium, we observe a suppression of quantum correlations for localized atomic excitations in the disordered zone as the clean system size increases, showcasing the delocalization behavior in the high-order spin-exchange processes. The calculation of the entanglement entropy at the interface further substantiates this thermalizing effect. Our results manifest distinct quantum correlations enabled by long-range interactions mediated by the waveguide, enhance the theoretical comprehension of clean-disordered systems, and provide insights to nonequilibrium quantum dynamics in an atom-nanophotonic platform. Copyright © 2024, The Authors. All rights reserved.

关键词： Atoms

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pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy

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Bioactive Materials 2024年第4期34卷 414-421页

作者： Jianhua Zou Zheng Li Yang Zhu Yucen Tao Qing You Fangfang Cao Qinghe Wu Min Wu Junjie Cheng Jianwei Zhu Xiaoyuan Chen Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore119074Singapore Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore117597Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore117599Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)61 Biopolis DriveProteosSingapore138673Singapore Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiaotong UniversityShanghai200011PR China Department of Chemistry Center for Bioanalytical Chemistry University of Science and Technology of ChinaHefei230026PR China College of Life Science Nanjing Normal University1 Wenyuan RoadNanjing210023PR China

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy(PDT)due to oxygen *** I PDT,which can operate independently of oxygen,is a viable option for treating hypoxic *** this study,we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment(TME)to enhance type I PDT through glutathione(GSH)*** approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals(O_(2)^(-).)while minimizing their *** diisopropyl group within PEG-IR820 serves a dual purpose:it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820,facilitating efficient O_(2)^(-).***,the release of JSK leads to GSH depletion,resulting in the generation of nitric oxide(NO).This,in turn,contributes to the formation of highly cytotoxic peroxynitrite(ONOO^(-).),thereby enhancing the therapeutic efficacy of these ***-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

关键词： TME responsive NO gas therapy NIR-II imaging Type I PDT

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Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

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Bioactive Materials 2023年第6期24卷 387-400页

作者： Yufeng Shou Ling Liu Qimin Liu Zhicheng Le Khang Leng Lee Hua Li Xianlei Li Dion Zhanyun Koh Yuwen Wang Tong Ming Liu Zheng Yang Chwee Teck Lim Christine Cheung Andy Tay Department of Biomedical Engineering National University of Singapore117583Singapore Institute for Health Innovation&Technology National University of Singapore117599Singapore School of Civil Engineering and Architecture Wuhan University of Technology430070WuhanChina NUS Tissue Engineering Program National University of Singapore117510Singapore Lee Kong Chian School of Medicine Nanyang Technological University636921Singapore School of Mechanical and Aerospace Engineering Nanyang Technological University639798Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)138648Singapore Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore119288Singapore Mechanobiology Institute National University of Singapore117411Singapore

Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory *** cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in *** overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to *** our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and *** addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK *** our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.

关键词： Mesenchymal stem cell Dynamic mechanical stimulation Magnetic hydrogel Stem cell manufacturing Cell therapy

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Ultrahigh zT from strong electron-phonon interactions and a low-dimensional Fermi surface

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Energy and Environmental science 2024年第5期17卷 1904-1915页

作者： Ranganayakulu, V.K. Wang, Te-Hsien Chen, Cheng-Lung Huang, Angus Ma, Ma-Hsuan Wu, Chun-Min Tsai, Wei-Han Hung, Tsu-Lien Ou, Min-Nan Jeng, Horng-Tay Lee, Chih-Hao Chen, Kuei-Hsien Li, Wen-Hsien Brod, Madison K. Snyder, G. Jeffrey Chen, Yang-Yuan Institute of Physics Academia Sinica Taipei11529 Taiwan Department of Engineering and System Science National Tsing Hua University Hsinchu30013 Taiwan Taiwan International Graduate Program Taipei11529 Taiwan Department of Physics National Chung Hsing University Taichung City40227 Taiwan Graduate School of Materials Science National Yunlin University of Science and Technology Yunlin64002 Taiwan Bachelor Program in Semiconductor Materials and Fabrication Ming Chi University of Technology New Taipei City243303 Taiwan Department of Physics National Tsing Hua University Hsinchu30013 Taiwan Center for Theory and Computation National Tsing Hua University Hsinchu30013 Taiwan Physics Division National Center for Theoretical Sciences Taipei10617 Taiwan Department of Physics National Central University Jhongli32001 Taiwan National Synchrotron Radiation Research Center Hsinchu Science Park Hsinchu30076 Taiwan Institute of Atomic and Molecular Sciences Academia Sinica Taipei10617 Taiwan Department of Materials Science and Engineering Northwestern University EvanstonIL60208 United States Graduate Institute of Applied Physics National Chengchi University Taipei11605 Taiwan

The outstanding thermoelectric performance of GeTe has attracted significant attention in the research community in recent years. However, many of the underlying physical mechanisms that contribute to GeTe's exceptionally high figure of merit (zT) remain not fully understood. In this study, an Sb-Bi codoped GeTe single crystal (Ge0.86Sb0.08Bi0.06)Te with an ultrahigh zT of 2.7 at 700 K and a record high device zT of 1.41 in the temperature range of 300-773 K was synthesized and investigated. The ultrahigh zT is attributed to the extremely low lattice thermal conductivity induced by strong electron-phonon (EP) interactions as revealed by the experimentally observed Kohn anomaly, through inelastic neutron scattering (INS) measurements. First-principles calculations further demonstrate that the remarkable EP interaction arises from the Fermi surface nesting featured in a one-dimensional (double-walled) topology. Our finding unravels the ultrahigh-zT mechanism in GeTe-based materials, serving as an inspiring guide toward high thermoelectric performance. © 2024 The Royal Society of Chemistry.

关键词： Neutron scattering

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Steady-state phases and interaction-induced depletion in a driven-dissipative chirally-coupled dissimilar atomic array

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Physical Review Research 2024年第2期6卷 023232-023232页

作者： Shao-Hong Chung I Gusti Ngurah Yudi Handayana Yi-Lin Tsao Chun-Chi Wu G.-D. Lin H. H. Jen Department of Physics and Center for Quantum Science and Engineering Taipei 10617 Taiwan Molecular Science and Technology Program Taiwan International Graduate Program Department of Physics Physics Division National Center for Theoretical Sciences Taipei 10617 Taiwan Trapped-Ion Quantum Computing Laboratory Hon Hai Research Institute Taipei 11492 Taiwan

A nanophotonic waveguide coupled with an atomic array forms one of the strongly coupled quantum interfaces to showcase many fascinating collective features of quantum dynamics. In particular, for a dissimilar array of two different interparticle spacings with competing photon-mediated dipole-dipole interactions and directionality of couplings, we study the steady-state phases of atomic excitations under a weakly driven condition of laser field. We identify a partial set of steady-state phases of the driven system composed of combinations of steady-state solutions in a homogeneous array. We also reveal the intricate role of the atom at the interface of the dissimilar array in determining the steady-state phases and find an alteration in the dichotomy of the phases strongly associated with steady-state distributions with crystalline orders. We further investigate in detail the interaction-induced depletion in half of the dissimilar array, where the blockaded region results from two contrasting interparticle spacings near the reciprocal coupling regime. This can be further evidenced from the analytical solutions under the reciprocal coupling. Our results can provide insights in the driven-dissipative quantum phases of atomic excitations with nonreciprocal couplings and pave the avenues toward quantum simulations of exotic many-body states essential for quantum information applications.

关键词： Collective behavior Dissipative dynamics Nanophotonics Phase diagrams Dipole approximation Two-level models

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Efficient synthesis method of CsPbBr3/Al2O3 composite powders for scalable production: Augmented green emission and thermal stability

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Journal of Industrial and Engineering Chemistry 2025年

作者： Kim, Seok-Hun Shin, Weon Ho Oh, Jong-Min Kim, Sang-Wook Kim, Sunghoon Center for Brain Busan 21 Plus Program Dong-Eui University Busan47340 Korea Republic of Department of Electronic Materials Engineering Kwangwoon University Seoul01897 Korea Republic of Department of Molecular Science and Technology Ajou University Suwon16499 Korea Republic of

Metal halide perovskites (MHPs) have gained significant attention for their exceptional optoelectronic properties, particularly in displays. However, their practical utility is severely limited by their intrinsic instability, including poor thermal stability, photostability, and susceptibility to moisture-induced degradation. This study introduces scalable synthesis of CsPbBr3/Al2O3 green-emitting phosphors, using submicron Al2O3 as a support, comparing mechanochemical reaction (MRM) and dissolution-evaporation (DEM) methods. DEM is the optimal route, enabling the formation of monoclinic CsPbBr3/Al2O3 with high photoluminescence quantum yield (PLQY) and enhanced stability. The influence of the CsPbBr3 to Al2O3 mass ratio on PLQY was quantitatively analyzed using the Halder-Wagner method, which indirectly calculated crystallite size and its correlation with PLQY. The composite demonstrated exceptional thermal stability, maintaining over 90 % of its initial PL intensity after 200 °C exposure for 15 days and showed excellent photostability, maintaining nearly its initial luminous efficiency under the currents of 20 mA and 70 mA for 10000-seconds. When integrated as a green phosphor in a white LED package with K2SiF6:Mn+4 as a red phosphor, it achieved a luminous efficiency of 25 lm W−1 and a color gamut of 112.4 % NTSC. These results highlight the potential of CsPbBr3/Al2O3 composites for cost-effective, stable, and high-performance optoelectronic applications. © 2025 The Korean Society of Industrial and Engineering Chemistry

关键词： Perovskite

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