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1HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation显示文摘N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA metabolism.Autophagy activation is one of the ways by which cancer cells survive hypoxia.However,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine models.YTHDF1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients withHCC.Multiple HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and metastasis.Luciferase reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under hypoxia.The results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of HCC.Taken together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner.Our fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.Qing Li Yong Ni Liren Zhang Runqiu Jiang Jing Xu Hong Yang Yuanchang Hu Jiannan Qiu Liyong Pu Jinhai Tang Xuehao Wang 2021Signal Transduction and Targeted Therapy2021,6,3:24
2The mechanisms of sorafenib resistance in hepatocellular carcinoma:theoretical basis and therapeutic aspects显示文摘Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.Weiwei Tang Ziyi Chen Wenling Zhang Ye Cheng Betty Zhang Fan Wu Qian Wang Shouju Wang Dawei Rong F.P.Reiter E.N.De Toni Xuehao Wang 2020Signal Transduction and Targeted Therapy2020,5,1:19
3Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions显示文摘Jian Gu Xuhao Ni Xiongxiong Pan Hao Lu Yunjie Lu Jie Zhao Song Guo Zheng Keli L Hippen Xuehao Wang Ling Lu 2017Cellular & Molecular Immunology2017,14,6:6
4Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis显示文摘Objective:ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation and chromatin remodeling.Numerous studies have shown that genetic alterations in ATRX play a significant role in gliomas.This study aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms for exploring the biological significance of ATRX using large data sets.Methods:We used The Cancer Genome Atlas(TCGA)database and 130 immunohistochemical results to confirm the difference in ATRX mutations in high-and low-grade gliomas.An online analysis of the TCGA glioma datasets using the cBioPortal platform was performed to study the relationship between ATRX mutations and IDH1,TP53,CDKN2 A and CDKN2 B mutations in the corresponding TCGA glioma dataset.In combination with clinical pathology data,the biological significance of the relationships were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses and annotations of all adjacent genes in the network were performedin the Database for Annotation,Visualization and Integrated Discovery(DAVID)and R language.A protein-protein interaction(PPI)network was constructed,and the interactions of all adjacent nodes were analyzed by the String database and using Cytoscape software.Results:In the selected TCGA glioma datasets,a total of 2,228 patients were queried,21%of whom had ATRX alterations,which co-occurred frequently with TP53 and IDH1 mutations.ATRX alterations are associated with multiple critical molecular events,which results in a significantly improved overall survival(OS)rate.In low-grade gliomas,ATRX mutations are significantly associated with multiple important molecular events,such as ZNF274 and FDXR at mRNA and protein levels.A functional cluster analysis revealed that these genes played a role in chromatin binding and P53,and a link was observed between ATRX and IDH1 and TP53 in the interaction network.ATRX and TP53 are important nodes in the network and have potential links with the blood oxygen imbalance.Conclusions:ATRX mutations have clinical implications for the molecular diagnosis of gliomas and can provide diagnostic and prognostic information for gliomas.ATRX is expected to serve as a new therapeutic target.Yingbin Xie Yanli Tan Chao Yang Xuehao Zhang Can Xu Xiaoxia Qiao Jianglong Xu Shaohui Tian Chuan Fang Chunsheng Kang 2019Cancer Biology & Medicine2019,16,4:5
5Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)显示文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.Hui-Chuan Sun Jian Zhou Zheng Wang Xiufeng Liu Qing Xie Weidong Jia Ming Zhao Xinyu Bi Gong Li Xueli Bai Yuan Ji Li Xu Xiao-Dong Zhu Dousheng Bai Yajin Chen Yongjun Chen Chaoliu Dai Rongping Guo Wenzhi Guo Chunyi Hao Tao Huang Zhiyong Huang Deyu Li Gang Li Tao Li Xiangcheng Li Guangming Li Xiao Liang Jingfeng Liu Fubao Liu Shichun Lu Zheng Lu Weifu Lv Yilei Mao Guoliang Shao Yinghong Shi Tianqiang Song Guang Tan Yunqiang Tang Kaishan Tao Chidan Wan Guangyi Wang Lu Wang Shunxiang Wang Tianfu Wen Baocai Xing Bangde Xiang Sheng Yan Dinghua Yang Guowen Yin Tao Yin Zhenyu Yin Zhengping Yu Bixiang Zhang Jialin Zhang Shuijun Zhang Ti Zhang Yamin Zhang Yubao Zhang Aibin Zhang Haitao Zhao Ledu Zhou Wu Zhang Zhenyu Zhu Shukui Qin Feng Shen Xiujun Cai Gaojun Teng Jianqiang Cai Minshan Chen Qiang Li Lianxin Liu Weilin Wang Tingbo Liang Jiahong Dong Xiaoping Chen Xuehao Wang Shusen Zheng Jia Fan 2022Hepatobiliary Surgery and Nutrition2022,11,2:4
6Laboratory core flooding experimental systems for CO_2 geosequestration: An updated review over the past decade显示文摘Carbon dioxide(CO_2) geosequestration in deep saline aquifers has been currently deemed as a preferable and practicable mitigation means for reducing anthropogenic greenhouse gases(GHGs) emissions to the atmosphere, as deep saline aquifers can offer the greatest potential from a capacity point of view. Hence,research on core-scale CO_2/brine multiphase migration processes is of great significance for precisely estimating storage efficiency, ensuring storage security, and predicting the long-term effects of the sequestered CO_2 in subsurface saline aquifers. This review article initially presents a brief description of the essential aspects of CO_2 subsurface transport and geological trapping mechanisms, and then outlines the state-of-the-art laboratory core flooding experimental apparatus that has been adopted for simulating CO_2 injection and migration processes in the literature over the past decade. Finally, a summary of the characteristics, components and applications of publicly reported core flooding equipment as well as major research gaps and areas in need of further study are given in relevance to laboratory-scale core flooding experiments in CO_2 geosequestration under reservoir conditions.Yankun Sun Qi Li Duoxing Yang Xuehao Liu 2016Journal of Rock Mechanics and Geotechnical Engineering2016,8,1:3
7Laser-based directed energy deposition of novel Sc/Zr-modified Al-Mg alloys:columnar-to-equiaxed transition and aging hardening behavior显示文摘The control of grain morphology is important in laser additive manufacturing(LAM),as grain morphology further affects the hot cracking resistance,anisotropy,and strength–ductility synergy of materials.To develop a solidification-control solution and achieve columnar-to-equiaxed transition(CET)in Al-based alloys during LAM,Sc-and-Zr-modified Al-Mg alloys were processed via directed energy deposition(DED).CET was achieved by introducing high potent primary Al_(3)(Sc,Zr)nucleation sites ahead of the solidification interface.Furthermore,the relationship between the solidification control parameters and precipitation behavior of primary Al_(3)(Sc,Zr)nucleation sites was established using the time-dependent nucleation theory.Then,the CET was studied according to the Hunt criterion.The results indicated that coarse columnar grain structure was still obtained at the inner region of the molten pool at low Sc/Zr contents owing to the effective suppression of the precipitation of the primary Al_(3)(Sc,Zr)nucleation sites via rapid solidification during DED.In addition,the relatively low melt temperature at the fusion boundary unavoidably promoted the precipitation of primary Al_(3)(Sc,Zr)nucleation sites,which resulted in a fine equiaxed grains band at the edge of the molten pool.As the Sc/Zr content increased,the solidification cooling rate was not sufficient to suppress the precipitation of the primary Al_(3)(Sc,Zr)nucleation sites,and a fully equiaxed grain structure was obtained.Furthermore,the effect of the layer-by-layer manufacturing process on the subsequent precipitation strengthening of secondary Al_(3)(Sc,Zr)precipitates was discussed.Both the remelting and subsequent aging during thermal cycling should be considered to achieve greater precipitation strengthening.Zihong Wang Xin Lin Yao Tang Nan Kang Xuehao Gao Shuoqing Shi Weidong Huang 2021Journal of Materials Science & Technology2021,,10:3
8IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation显示文摘Zhongming Tan Xiaofeng Qian Runqiu Jiang Qianghui Liu Youjing Wang Chen Chen Xuehao Wang Bernhard Ryffel Beicheng Sun 2013The Journal of Immunology2013,,4:2
9Insights into flavonoid biosynthesis during cucumber fruit peel coloration based on metabolite profiling and transcriptome analyses显示文摘The fruit peel color is a crucial trait of cucumber.To better understand the molecular mechanisms underlying cucumber peel coloration,we compared the UPLC-ESI-MS/MS-based flavonoid metabolomic and RNA sequencing-based transcriptomic profiling of the brown peeled cucumber line‘PW’at six developmental stages.A total of 210 flavonoid metabolites were identified.Of which,117 flavonoid metabolites were differentially accumulated.In this study,weighted gene co-expression network analysis combined with Kyoto Encyclopedia of Gene and Genomes enrichment analysis revealed key genes coding for seven enzymes and eight transcription factors(TFs)associated with flavonoid biosynthesis.Among them,the R2R3MYB CsaV3_4G001130 is the best candidate gene that is responsible for controlling mature fruit colors in cucumber.Sanger sequencing revealed one nonsynonymous SNP in the exon of CsaV3_4G001130 among the selected 11 cucumber lines,which introduced a premature stop codon,generating a truncated protein in pale yellow or creamy peeled fruits.Yeast two-hybrid assays showed a direct interaction of CsaV3_4G001130 with the bHLH TF CsaV3_1G002260 and the WD40 protein CsaV3_5G001800.However,the interactions were influenced by the nonsynonymous SNP we identified.Our finding revealed that the integrated transcriptome and metabolome analysis further demonstrated that the abundance of some pigmented flavonoids(especially anthocyanins and chalcones)contributed to the coloration of‘PW’fruits.These findings pave the way for elucidation of flavonoid biosynthesis and improvement of cucumber peel color in the future.Shuying He Yi Ye Ying Yuan Mai Lv Meixing Wang Qiang Xu Xuewen Xu Xuehao Chen 2023Horticultural Plant Journal2023,9,4:2
10All-trans retinoic acid preconditioning protects against liver ischemia/reperfusion injury by inhibiting the nuclear factor kappa B signaling pathway显示文摘Jianhua Rao Xiaofeng Qian Ping Wang Liyong Pu Yuan Zhai Xuehao Wang Feng Zhang Ling Lu 2012Journal of Surgical Research2012,,:2
11Molecularly tagged genes and quantitative trait loci in cucumber with recommendations for QTL nomenclature显示文摘Cucumber,Cucumis sativus L.(2n=2x=14),is an important vegetable crop worldwide.It was the first specialty crop with a publicly available draft genome.Its relatively small,diploid genome,short life cycle,and selfcompatible mating system offers advantages for genetic studies.In recent years,significant progress has been made in molecular mapping,and identification of genes and QTL responsible for key phenotypic traits,but a systematic review of the work is lacking.Here,we conducted an extensive literature review on mutants,genes and QTL that have been molecularly mapped or characterized in cucumber.We documented 81 simply inherited trait genes or major-effect QTL that have been cloned or fine mapped.For each gene,detailed information was compiled including chromosome locations,allelic variants and associated polymorphisms,predicted functions,and diagnostic markers that could be used for marker-assisted selection in cucumber breeding.We also documented 322 QTL for 42 quantitative traits,including 109 for disease resistances against seven pathogens.By alignment of these QTL on the latest version of cucumber draft genomes,consensus QTL across multiple studies were inferred,which provided insights into heritable correlations among different traits.Through collaborative efforts among public and private cucumber researchers,we identified 130 quantitative traits and developed a set of recommendations for QTL nomenclature in cucumber.This is the first attempt to systematically summarize,analyze and inventory cucumber mutants,cloned or mapped genes and QTL,which should be a useful resource for the cucurbit research community.Yuhui Wang Kailiang Bo Xingfang Gu Junsong Pan Yuhong Li Jinfeng Chen Changlong Wen Zhonghai Ren Huazhong Ren Xuehao Chen Rebecca Grumet Yiqun Weng 2020Horticulture Research2020,7,1:2
12Diagnosis and treatment of biliary sludge,cast and stone following liver transplantation显示文摘Objective:To investigate etiological facts and treatment of biliary sludge,cast and stone following orthotopic liver transplantation(OLT).Methods:A review was made using data collected from 81 cases with OLTs performed in our center from February 2003 to January 2004,and confirmed by retrospective study.Etiological factors of biliary sludge,cast and stone following OLT were analyzed,and treatment of biliary sludge,cast and stone following OLT were discussed.Result:Nine cases of biliary sludge,cast and stone were diagnosed and the incidence rate was 11.1%.Of these,five were biliary sludge and cast,2 were bile stone and 2 were necrotic debris.Two cases with hepatic artery embolism received retransplantation and survived.The other one with hepatic artery embolism was ameliorated with nasobiliary drainage by ERCP.Two cases with biliary sludge and cast were resolved by non-operative treatment.Four cases were reoperated,2 resolved and 2 cases died.Conclusion:Biliary injury and ischemia reperfusion injury,reject reaction,infection and changes of bile kinetics are the important factors causing biliary sludge,cast and stone following OLT.Shortening the time of cold and heat ischemia reperfusion injury of liver,reducing the injury of the blood supply of donor bile duct,actively preventing and early treating of infection and rejection reaction might reduce the incidence rate of biliary sludge,cast and stone following OLT.Lianbao Kong Xuehao Wang Fen Zhang 2006Journal of Nanjing Medical University2006,20,4:1
13Microstructure and compressive/tensile characteristic of large size Zr-based bulk metallic glass prepared by laser solid forming显示文摘The large size, crack-free Zr_(55)Cu_(30)Al_(10)Ni_(5) bulk metallic glass(BMGs) with the diameter of 54 mm and the height of 15 mm was built by laser solid forming additive manufacturing technology, whose size is larger than the critical diameter by casting. The microstructure, tensile and compressive deformation behaviors and fracture morphology of laser solid formed Zr_(55)Cu_(30)Al_(10)Ni_5 BMGs were investigated. It is found that the crystallization mainly occurs in the heat-affected zones of deposition layers, which consist of Al_5Ni_3Zr_2, NiZr_2, ZrCu, CuZr_2 phases. The content of amorphous phase in the deposit is about 63%.Under the compressive loading, the deposit presents no plasticity before fracture occurs. The fracture process is mainly controlled by the shear stress and the compressive shear fracture angles of about39?. The compressive strength reaches 1452 MPa, which is equivalent to that of as-Cast Zr_(55)Cu_(30)Al_(10)Ni_5 BMGs, and there exist vein-like patterns, river-like patterns and smooth regions at the compressive fractography. Under the tensile loading, the deposit presents the brittle fracture pattern without plastic deformation. The fracture process exhibits normal fracture model, and the tensile shear fracture angle of about 90?. The tensile strength is only about 609 MPa, and the tensile fractography mainly consists of micro-scaled cores and vein-like patterns, dimple-like patterns, chocolate-like patterns and smooth regions. The results further verified the feasibility and large potential of laser additive manufacturing on fabrication and industrial application of large-scale BMGs parts.Xin Lin Yuanyuan Zhang Gaolin Yang Xuehao Gao Qiao Hu Jun Yu Lei Wei Weidong Huang 2019Journal of Materials Science & Technology2019,35,2:1
14Ozonation as an efficient pretreatment method to alleviate reverse osmosis membrane fouling caused by complexes of humic acid and calcium ion显示文摘Humic acid has been considered as one of the most significant sources in feed water causing organic fouling of reverse osmosis (RO) membranes, but the relationship between the fouling behavior of humic acid and the change of its molecular structure has not been well developed yet. In this study, the RO membrane fouling behavior of humic acid was studied systematically with ozonation as a pretreatment method to control RO membrane fouling. Furthermore, the effect of ozone on the structure ofhumic acid was also explored to reveal the mechanisms. Humic acid alone (10-90 mg/L, in deionized water) was found not to cause obvious RO membrane fouling in 45-h operation. However, the presence of Ca^2+ aggravated significantly the RO membrane fouling caused by humic acid, with significant flux reduction and denser fouling layer on RO membrane, as it was observed by scanning electron microscope (SEM) and atomic force microscope (AFM). However, after the pretreatment by ozone, the influence of Ca^2+ was almost eliminated. Further analysis revealed that the addition of Ca^2+ increased the particle size of humic acid solution significantly, while ozonation reduced the SUVA254, particle size and molecular weight of the complexes of humic acid and Ca^2+(HA-Ca^2+ complexes). According to these results and literature, the bridge effect of Ca^2+ aggregating humic acid molecules and the cleavage effect of ozone breaking HA-Ca^2+ complexes were summarized. The change of the structure of humic acid under the effect of Ca^2+ and ozone is closely related to the change of its membrane fouling behavior.Xuehao Zhao Yinhu Wu Xue Zhang Xin Tong Tong Yu Yunhong Wang Nozomu Ikuno Kazuki Ishii Hongying Hu 2019Frontiers of Environmental Science & Engineering2019,13,4:1
15Pressurized water reactor nuclear power plant(NPP) modeling and the midterm dynamic simulation after NPP has been introduced into power system显示文摘Hu Xuehao Zheng Xuecheng etc IEEE0,93,:1
16Cucumber glossy fruit 1 (CsGLF1) encodes the zinc finger protein 6 that regulates fruit glossiness by enhancing cuticular wax biosynthesis显示文摘Cucumber glossiness is an important visual quality trait that affects consumer choice.Accumulating evidence suggests that glossy trait is associated with cuticular wax accumulation.However,the molecular genetic mechanism controlling cucumber glossiness remains largely unknown.Here,we report the map-based cloning and functional characterization of CsGLF1,a locus that determines the glossy trait in cucumber.CsGLF1 encodes a homolog of the Cys_(2)His_(2)-like fold group(C2H2)-type zinc finger protein 6(ZFP6)and its deletion leads to glossier pericarp and decreased cuticular wax accumulation.Consistently,transcriptomic analysis demonstrated that a group of wax biosynthetic genes were downregulated when CsZFP6 was absent.Further,transient expression assay revealed that CsZFP6 acted as a transcription activator of cuticular wax biosynthetic genes.Taken together,our findings demonstrated a novel regulator of fruit glossiness,which will provide new insights into regulatory mechanism of fruit glossiness in cucumber.Yan Yang Congxi Cai Yipeng Wang Yanran Wang Haolun Ju Xuehao Chen 2023Horticulture Research2023,10,1:1
17Characterization of chars from pyrolysis of lignin显示文摘Ramesh K Sharma Jan B Wooten Vicki L Baliga Xuehao Lin W Geoffrey Chan Mohammad R Hajaligol 2004Fuel2004,,11:1
18Revenue-sharing con- tracts in an N-stage supply chain with reliability consid- erations 显示文摘Feng Xuehao Moon I Ryu K 2014International Journal of Production Eco- nomics2014,147,1:1
19Comparative proteomic analysis of cucumber powdery mildew resistance between a singlesegment substitution line and its recurrent parent显示文摘Powdery mildew(PM)is considered a major cause of yield losses and reduced quality in cucumber worldwide,but the molecular basis of PM resistance remains poorly understood.A segment substitution line,namely,SSL508-28,was developed with dominant PM resistance in the genetic background of PM-susceptible cucumber inbred line D8.The substituted segment contains 860 genes.An iTRAQ-based comparative proteomic technology was used to map the proteomes of PM-inoculated and untreated(control)D8 and SSL508-28.The number of differentially regulated proteins(DRPs)in SSL508-28 was almost three times higher than that in D8.Fourteen DRPs were located in the substituted segment interval.Comparative gene expression analysis revealed that nodulin-related protein 1(NRP1)may be a good candidate for PM resistance.Gene Ontology enrichment analysis showed that DRPs functioning in tetrapyrrole biosynthetic process,sulfur metabolic process and cell redox homeostasis were specifically enriched in the resistant line SSL508-28.DRPs categorized in the KEGG term photosynthesis increased in both lines upon PM infection,suggesting that the strategies used by cucumber may be different from those used by other crops to react to PM attacks at the initial stage.The measurement of hydrogen peroxide and superoxide anion production and net photosynthetic rate were consistent with the changes in protein abundance,suggesting that the proteomic results were reliable.There was a poor correlation between DRPs measured by iTRAQ and the corresponding gene expression changes measured by RNA-seq with the same experimental design.Taken together,these findings improve the understanding of the molecular mechanisms underlying the response of cucumber to PM infection.Xuewen Xu Xueli Liu Yali Yan Wei Wang Kiros Gebretsadik Xiaohua Qi Qiang Xu Xuehao Chen 2019Horticulture Research2019,6,1:1
20Production of lipase by repeated batch fermentation with immobilized Rhizop us arrhizus显示文摘Yang Xuehao Wang Bingwu Cui Fengnan 2005Process Biochemistry2005,40,:1
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