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Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease(GSD)mouse model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 38-50页

作者： Dongfang ZHANG Hao XU Chi QIN Kangming CAI Jing ZHANG Xinqiu XIA Jingwen BI Li ZHANG Lianping XING Qianqian LIANG Wensheng WANG Laboratory of Molecular Medicine College of Life Science and State Key Laboratory of Cell Differentiation and RegulationHenan Normal UniversityXinxiang453007China Longhua Hospital&Spine Institute Shanghai University of Traditional Chinese MedicineShanghai200032China Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)Shanghai201203China Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochester14642USA

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow *** the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely *** this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of *** to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in *** the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in *** an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in *** found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like *** staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the *** on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

关键词： Semaphorin 3A Gorham-Stout disease Osteoclast Osteolysis Lymphatic endothelial cell

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Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3605-3623页

作者： Zehui Tan Ning Guo Zhi Cao Shuyu Liu Jiayu Zhang Deyi Ma Jiahao Zhang Wencai Lv Nan Jiang Linghe Zang Lihui Wang Xin Zhai Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung ***,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q *** most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar *** cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS *** the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in *** study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling ***,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.

关键词： DOT1L R231Q mutation Lung cancer Adenosine-containing inhibitors Epigenetics

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Robust fixed-time flight controller for a dual-system convertible UAV in the cruise mode

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Defence Technology（防务技术） 2024年第9期39卷 53-66页

作者： Lulu Chen Zhenbao Liu Qingqing Dang Wen Zhao Wenyu Chen School of Civil Aviation Northwestern Polytechnical UniversityXi'an 710072China Shenzhen Research Institute of Northwestern Polytechnical University Shenzhen 518057China Air and Missile Defense College Air Force Engineering UniversityXi'an 710051China

This paper investigates the attitude tracking control problem for the cruise mode of a dual-system convertible unmanned aerial vehicle(UAV)in the presence of parameter uncertainties,unmodeled uncertainties and wind ***,a fixed-time disturbance observer(FXDO)based on the bi-limit homogeneity theory is designed to estimate the lumped disturbance of the convertible UAV ***,a fixed-time integral sliding mode control(FXISMC)is combined with the FXDO to achieve strong robustness and chattering ***-limit homogeneity theory and Lyapunov theory are applied to provide detailed proof of the fixed-time ***,numerical simulation experimental results verify the robustness of the proposed algorithm to model parameter uncertainties and wind *** addition,the proposed algorithm is deployed in a open-source UAV autopilot and its effectiveness is further demonstrated by hardware-in-the-loop experimental results.

关键词： Convertible UAV Flight control Disturbance observer Fixed-time control

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Lignocellulose-Based Optical Biofilter with High Near-Infrared Transmittance via Lignin Capturing–Fusing Approach

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Research 2024年第3期2023卷 139-149页

作者： Shixu Yu Yifang Zhou Meixue Gan Lu Chen Yimin Xie Yuning Zhong Qinghua Feng Chaoji Chen Hubei Provincial Key Laboratory of Green Materials for Light Industry Hubei University of TechnologyWuhan 430068China.Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key LaboratorySchool of Resource and Environmental SciencesWuhan UniversityWuhan 430079China Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory School of Resource and Environmental SciencesWuhan UniversityWuhan 430079China Hubei Open University Wuhan 430074China.

Near-infrared (NIR) transparent optical filters show great promise in night vision and receiving windows. However, NIR optical filters are generally prepared by laborious, environmentally unfriendly processes that involve metal oxides or petroleum-based polymers. We propose a lignin capturing–fusing approach to manufacturing optical biofilters based on molecular collaboration between lignin and cellulose from waste agricultural biomass. In this process, lignin is captured via self-assembly in a cellulose network;then, the lignin is fused to fill gaps and hold the cellulose fibers tightly. The resulting optical biofilter featured a dense structure and smooth surface with NIR transmittance of ~90%, ultralow haze of close to 0%, strong ultraviolet-visible light blocking (~100% at 400 nm and 57.58% to 98.59% at 550 nm). Further, the optical biofilter has comprehensive stability, including water stability, solvent stability, thermal stability, and environmental stability. Because of its unique properties, the optical biofilter demonstrates potential applications in the NIR region, such as an NIR-transmitting window, NIR night vision, and privacy protection. These applications represent a promising route to produce NIR transparent optical filters starting from lignocellulose biomass waste.

关键词： transparent starting waste

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PSRDP:A Parallel Processing Method for Pulsar Baseband Data

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Research in Astronomy and Astrophysics 2024年第1期24卷 300-310页

作者： Ya-Zhou Zhang Hai-Long Zhang Jie Wang Xin-Chen Ye Shuang-Qiang Wang Xu Du Han Wu Ting Zhang Shao-Cong Guo Meng Zhang Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China University of chinese Academy of Sciences Beijing 100049China Key Laboratory of Radio Astronomy Chinese Academy of SciencesNanjing 210008China National Astronomical Data Center Beijing 100101China Southeast University Nanjing 211189China School of Cyber Science and Engineering Qufu Normal UniversityQufu 273165China

To address the problem of real-time processing of ultra-wide bandwidth pulsar baseband data,we designed and implemented a pulsar baseband data processing algorithm(PSRDP)based on GPU parallel computing *** can perform operations such as baseband data unpacking,channel separation,coherent dedispersion,Stokes detection,phase and folding period prediction,and folding integration in GPU *** tested the algorithm using the J0437-4715 pulsar baseband data generated by the CASPSR and Medusa backends of the Parkes,and the J0332+5434 pulsar baseband data generated by the self-developed backend of the Nan Shan Radio *** obtained the pulse profiles of each baseband *** experimental analysis,we have found that the pulse profiles generated by the PSRDP algorithm in this paper are essentially consistent with the processing results of Digital Signal Processing Software for Pulsar Astronomy(DSPSR),which verified the effectiveness of the PSRDP ***,using the same baseband data,we compared the processing speed of PSRDP with DSPSR,and the results showed that PSRDP was not slower than DSPSR in terms of *** theoretical and technical experience gained from the PSRDP algorithm research in this article lays a technical foundation for the real-time processing of QTT(Qi Tai radio Telescope)ultra-wide bandwidth pulsar baseband data.

关键词： (stars:)pulsars:general methods:data analysis techniques:miscellaneous

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Transcriptome Analysis of Inflorescence Development at the Five-Leaf Stage in Castor(Ricinus communis L.)

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Phyton-International Journal of Experimental Botany 2024年第4期93卷 713-723页

作者： Yong Zhao Yaxuan Jiang Li Wen Rui Luo Guorui Li Jianjun Di Mingda Yin Zhiyan Wang Fenglan Huang Fanjuan Meng College of Life Science Baicheng Normal UniversityBaicheng137000China College of Life Science and Food Inner Mongolia University for the NationalitiesTongliao028000China College of Life Science Northeast Forestry UniversityHarbin150040China Key Laboratory of Castor Breeding of the State Ethnic Affairs Commission Inner Mongolia Minzu UniversityTongliao028043China Inner Mongolia Industrial Engineering Research Center of Universities for Castor Inner Mongolia Minzu UniversityTongliao028043China Inner Mongolia Key Laboratory of Castor Breeding and Comprehensive Utilization Inner Mongolia Minzu UniversityTongliao028000China Inner Mongolia Engineering Research Center of Industrial Technology innovation of Castor Inner Mongolia Minzu UniversityTongliao028000China

The yield of castor is influenced by the type of inflorescence and the proportion of female ***,there are few studies on the genetic mechanism involved in the development and differentiation of castor *** this study,we performed transcriptomic analyses of three different phenotypes of inflorescences at the five-leaf *** comparison to the MI(complete pistil without willow leaves),290 and 89 differentially expressed genes(DEGs)were found in the SFI(complete pistil with willow leaves)and the BI(monoecious inflorescence),*** the DEGs,104 and 88 were upregulated in the SFI and BI,respectively,compared to the *** addition,186 DEGs and 1 DEG were downregulated in the SFI and BI compared to the ***,we conducted GO and KEGG enrichment analyses of the *** comparison to the MI,the SFI and BI exhibited the enrichment of functional branches in DEGs,specifically in pollen wall assembly,pollen development,and cellular component assembly involved in *** our study,RADL5 showed low expression levels between SFI-vs.-MI *** addition,we found that the expression of NAC in the SFI differed from that in MI and BI,and some genes related to hormonal signaling changed their expression levels during inflorescence *** results reveal the genetic mechanism of sex genotypes in castor,which will not only guide researchers in the breeding of castor but also provide a reference for genetic research on other flowering plants.

关键词： Ricinus communis L RNA-Seq inflorescence

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Enhanced optical imaging and fluorescent labeling for visualizing drug molecules within living organisms

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2428-2446页

作者： Ting Sun Huanxin Zhao Luyao Hu Xintian Shao Zhiyuan Lu Yuli Wang Peixue Ling Yubo Li Kewu Zeng Qixin Chen School of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery SystemMedical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Institute of Biochemical and Biotechnological Drugs School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Biopharmaceuticals Postdoctoral Scientific Research WorkstationShandong Academy of Pharmaceutical ScienceJinan 250098China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China School of Life Sciences Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China School of chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China Tianjin Pharmaceutical DA REN TANG Group Corporation Limited Traditional chinese Pharmacy Research Institute Tianjin 300457China Key Laboratory of Systems Bioengineering(ministry of education) School of Chemistry Engineering and TechnologyTianjin UniversityTianjin 300072China

The visualization of drugs in living systems has become key techniques in modern *** advancements in optical imaging technologies and molecular design strategies have revolutionized drug *** the subcellular level,super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to *** beyond subcellular imaging,researchers have integrated multiple modes,like optical near-infrared II imaging,to study the complex spatiotemporal interactions between drugs and their *** combining these visualization approaches,researchers gain supplementary information on physiological parameters,metabolic activity,and tissue composition,leading to a comprehensive understanding of drug *** review focuses on cutting-edge technologies in drug visualization,particularly fluorescence imaging,and the main types of fluorescent molecules ***,we discuss current challenges and prospects in targeted drug research,emphasizing the importance of multidisciplinary cooperation in advancing drug *** the integration of advanced imaging technology and molecular design,drug visualization has the potential to redefine our understanding of pharmacology,enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

关键词： Optical imaging Drug visualization Fluorophore labeling Therapeutics

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Two-color emissive AIEgens with anti-Kasha property for dual-organelle imaging and phototherapy

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Science China Chemistry 2024年第5期67卷 1740-1752页

作者： Pu Chen Guogang Shan Qingli Nie Yuting Yan Pengfei Zhang Zujin Zhao Hai-Tao Feng Ben Zhong Tang AIE Research Center Shaanxi Key Laboratory of PhytochemistryCollege of Chemistry and Chemical EngineeringBaoji University of Arts and SciencesBaoji 721013China Institute of Functional Material Chemistry and National&Local United Engineering Lab for Power Battery Faculty of ChemistryNortheast Normal UniversityChangchun 130024China College of Chemistry&Materials Science Northwest UniversityXi’an 710127China Guangdong Key Laboratory of Nanomedicine CAS-HK Joint Lab of BiomaterialsCAS Key Laboratory of Biomedical Imaging Science and SystemShenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State Key Laboratory of Luminescent Materials and Devices Key Laboratory of Luminescence from Molecular Aggregates of Guangdong ProvinceSouth China University of TechnologyGuangzhou 510640China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Despite the rapid development of probes for targeting single organelle, the construction of robust dual-organelle targeting probes with multicolor emission was rarely reported. Herein, two dual-emissive aggregation-induced emission luminogens(AIEgens)with donor-π-acceptor structures were designed and synthesized, namely QT-1 and QF-2. Both two AIEgens exhibited excitation wavelength-dependence defying the Kasha's rule, and could stain lipid droplets(LDs) and mitochondria in blue and red fluorescence, respectively. Moreover, thanks to the near-infrared emission and abundant reactive oxygen species(ROS) generation efficiency of QT-1, it was chosen as a photodynamic therapy agent to selectively kill cancer cells from normal cells. Upon light irradiation, an obvious decrease of mitochondrial membrane potential(MMP) and serious change of mitochondrial shape in cells were observed, which corresponded to the efficient inhibition of tumor growth in vivo. This work afforded a promising strategy for the construction of multicolor emission by tuning anti-Kasha behaviors and expanding their application in dualorganelle targeting-based phototheranostics.

关键词： aggregation-induced emission anti-Kasha luminescence fluorescent probe bioimaging photodynamic therapy

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残余胆固醇与心血管、癌症死亡率的相关性:一项全国性队列研究

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Science Bulletin 2024年第4期69卷 526-534页

作者：田原武依戚敏杰宋莉娟陈伯望王椿淇路甲鹏杨阳张小艳崔建兰许巍杨皓贺文彦张岩郑昕张海波郭远林李希 National Clinical Research Center of Cardiovascular Diseases State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Henan Provincial Center for Disease Control and Prevention Zhengzhou 450000China Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Shenzhen Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical SciencesShenzhen 501800China Central China Sub-Center of the National Center for Cardiovascular Diseases Zhengzhou 450000China

The health significance of triglyceride-rich lipoproteins,also known as remnant cholesterol,has been increasingly ***,evidence of their associations with cause-specific mortality in the general population was previously *** explore these associations and their heterogeneities across subgroups,a prospective cohort study was conducted including 3,403,414 community-based participants from China HEART,an ongoing government-funded public health program throughout China,from November 2014 through December *** study assessed mortality risk of all-cause mortality,cardiovascular disease(CVD)mortality(including mortality from ischemic heart diseases(IHD),ischemic stroke(IS),and hemorrhagic stroke(HS),separately),and cancer mortality(including lung cancer,stomach cancer,and liver cancer,separately).During the 4-year follow-up,23,646 individuals died from CVD(including 8807 from IHD,3067 from IS,and 5190 from HS),and 20,318 from cancer(including 6208 from lung cancer,3013 from liver cancer,and 2174 from stomach cancer).Compared with individuals with remnant cholesterol<17.9 mg/d L,multivariable-adjusted mortality hazard ratios(HRs)for individuals with remnant cholesterol≥27.7 mg/d L were 1.03(1.00–1.05)for all-cause mortality,1.17(1.12–1.21)for CVD(1.19(1.12–1.27)for IHD mortality,and 1.22(1.09–1.36)for IS mortality),and 0.90(0.87–0.94)for allcancer mortality(0.94(0.87–1.02)for lung cancer,0.59(0.53–0.66)for liver cancer,and 0.73(0.64–0.83)for stomach cancer).In summary,this study revealed a correlation between increased remnant cholesterol levels and an elevated risk of cardiovascular disease mortality,as well as a reduced risk of mortality for certain types of cancer.

关键词： Remnant cholesterol Mortality Cardiovascular disease Cancer

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Effects of Heterologously Overexpressing PIP5K-Family Genes in Arabidopsis on Inflorescence Development

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Phyton-International Journal of Experimental Botany 2024年第1期93卷 97-117页

作者： Mingda Yin Rui Luo Tana Liang Qi Wen Xiaotian Liang Yanpeng Wen Xuemei Hu Zhiyan Wang Chang Gao Wenjing Ren Fenglan Huang College of Life Science and Food Engineering Inner Mongolia Minzu UniversityTongliao028000China Key Laboratory of Castor Breeding of the State Ethnic Affairs Commission Inner Mongolia Minzu UniversityTongliao028000China Inner Mongolia Industrial Engineering Research Center of Universities for Castor Inner Mongolia Minzu UniversityTongliao028043China Inner Mongolia Key Laboratory of Castor Breeding and Comprehensive Utilization Inner Mongolia Minzu UniversityTongliao028000China Inner Mongolia Engineering Research Center of Industrial Technology innovation of Castor Inner Mongolia Minzu UniversityTongliao028000China

Castor is one of the top 10 oil crops in the world and has extremely valuable *** inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor *** previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence *** this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor *** PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in ***,and the relationships among the PIP5Ks in castor were *** expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were *** relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual *** PIP5Ks were heterologously overexpressed in ***,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were *** tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)*** plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique *** correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.

关键词： Castor inflorescence development PIP5K gene family gene overexpression

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