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LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

World Journal of Gastroenterology 2008年第5期14卷 758-763页

作者： gang-shi wang meng-wei wang ben-yan wu xin-yan yang wei-hua wang wei-di you Department of Gerontal Gastroenterology General Hospital of Chinese PLA Beijing 100853 China

AIM： To analyze the expression profiles of a human gastriccancer-related gene, GCRG123, in human gastric signetring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123.METHODS： In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information （NCBI） and the University of California Santa Cruz （UCSC） databases were used for the analyses.RESULTS： The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons （LINE-1, L1）. BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and -23 of Rb, 5＇ flanking region of IL-2 and clotting factor Ⅸ genes.CONCLUSION： GCRG123, an active member of the Lt family, was up-regulated in human gastric signet-ring cell carcinoma.

关键词： Stomach Signet-ring cell carcinoma GCRG123 LINE-1 In situ hybridization Bioinformatics

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taBOX: A water-soluble tetraanionic rectangular molecular container for conjugated molecules and taste masking for berberine and palmatine

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Chinese Chemical Letters 2024年第5期35卷 175-178页

作者： Qihan Lin Jiabin xing Yue-yang Liu gang wu shi-Jia Liu Hui wang wei Zhou Zhan-Ting Li Dan-wei Zhang Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsFudan UniversityShanghai 200438China

A water-soluble macrocycle that bears four carboxylate anions has been designed and prepared,which forms a rectangular cavity that can efficiently encapsulate discrete electron-deficient aromatic compounds,including berberine and *** macrocycle is revealed to be highly biocompatible and able to inhibit the bitter taste of the two drugs.

关键词： Macrocycle Multianion Molecular container Molecular recognition Bitter taste masking

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The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-gang yang Hai-yan XU Dong YIN wei-hua SONG Hong-Jian wang Cheng-gang ZHU Lei FENG wei wu Kai-HongCHEN yan-yan ZHAO Ye LU Ke-Fei DOU Yue-Jin yang on behalf of the CAMI Registry Investigators Cardiometabolic Medicine Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research&Biometrics Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart disease Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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Stratigraphic framework and sedimentary evolution during the Cryogenian-Ediacaran transition in northeastern Sichuan Basin,South China

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Petroleum Science 2024年第2期21卷 823-835页

作者： Yi Zhang Hong-wei Kuang Yong-Qing Liu Qiang shi Dong-Ge wang Ke-Ning Qi Yu-Chong wang Da-wei Qiao Xiao-Shuai Chen Li-Zhi wu meng Tian Long Chen Yi wei Liao-Yuan Song Jian Li Zi-gang wu Yun-Qian Liu Xuan-Chun Liu An-Qing Chen Zhi-wei Liao Institute of Geology Chinese Academy of Geological SciencesBeijing100037China State Key Laboratory of Coal Mine disaster Dynamics and Control School of Resources and Safety EngineeringChongqing UniversityChongqing400044China No.205 Geological Team Chongqing Bureau of Geology and Minerals ExplorationChongqing401121China Chongqing Institute of Geological Survey Chongqing401122China Key Laboratory of Deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources Chengdu University of TechnologyChengdu610059SichuanChina

The northeastern Sichuan area in the northern yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent ***,the Cryogenian-Ediacaran(C-E)boundary has not been precisely identified,which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the yangtze Block and even the global paleogeographic *** study conducted stratigraphy,sedimentology,and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern *** results showed that the Ediacaran sediments,without the cap dolomite,unconformably overlaid the Cryogenian sediments in the studied *** Member II of the DST,characterized by 50-160 m of red-green sandstone(approximately equivalent to the original Chengkou“Guanyinya Formation”),directly overlaid the Cryogenian sediments and displayed a 623±2.3 Ma maximum depositional age from the detrital zircon U-Pb *** stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three ***,the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top,then change upward to DST barrier coast *** proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite:(i)Member II purple-red,gray-green sandstone strata,(ii)MemberⅢblack mudstone strata,and(iii)Member IV P-Mn bearing *** the C-E transition,the study area experienced(i)the global deglaciation stage in the terminal Marinoan glaciation and(ii)the filling-leveling up stage with clastic rocks in the early ***,the early Ediacaran

关键词： Marinoan glaciation Doushantuo formation Cap dolomite Deglacial and coastal deposits Detrital zircon U-Pb dating

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Lithium-Ion Charged Polymer Channels Flattening Lithium Metal Anode

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Nano-Micro Letters 2024年第4期16卷 379-393页

作者： Haofan Duan Yu you gang wang Xiangze Ou Jin Wen Qiao huang Pengbo Lyu Yaru Liang Qingyu Li Jianyu huang Yun‑Xiao wang hua‑Kun Liu shi Xue Dou wei‑Hong Lai Hunan Provincial Key Laboratory of Thin Film Materials and Devices School of Material Sciences and EngineeringXiangtan UniversityXiangtan 411105People’s Republic of China Guangxi Key Laboratory of Low Carbon Energy Materials School of Chemical and Pharmaceutical ScienceGuangxi Normal UniversityGuilin 541004People’s Republic of China Institute for Superconducting and Electronic Materials Australian Institute of Innovative MaterialsUniversity of WollongongInnovation CampusSquires WayNorth WollongongNSW 2500Australia Institute of Energy Materials Science University of Shanghai for Science and TechnologyShanghai 200093People’s Republic of China

The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite *** this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged *** channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium *** stretched molecular channels can also accelerate the transport of Li *** combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 ***,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of *** facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.

关键词： Polymer ionic channel Li metal batteries Artificial protective layer Uniform Li deposition Electrochemical performances

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Inhibiting the phase transition of WO_(3)for highly stable aqueous electrochromic battery

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Journal of Energy Chemistry 2024年第8期95卷 86-95,I0003页

作者： Zhisheng wu Zhendong Lian Ting ding Jielei Li Jincheng Xu Jinxiao wang Liangxing Zhang Bo wang shi Chen Peng Xiao hua Xu Shuang-Peng wang Kar wei Ng Joint Key Laboratory of the Ministry of Education Institute of Applied Physics and Materials EngineeringUniversity of MacaoAvenida da UniversidadeMacao 999078China School of Applied Physics and Materials Wuyi UniversityJiangmen 529020GuangdongChina Guangdong-Hong Kong-Macao Joint Laboratory for Intelligent Micro-Nano Optoelectronic Technology School of Physics and Optoelectronic EngineeringFoshan UniversityFoshan 528225GuangdongChina Guangzhou New Vision Optoelectronic Technology Co. Ltd.Guangzhou 510530GuangdongChina

Aqueous electrochromic battery(ECB)has shown intense potential for achieving energy storage and saving *** tungsten oxide(WO_(3))is the most promising EC material for commercialization,the cycling stability of WO_(3)-based aqueous ECBs is currently unsatisfactory due to the repeated phase transition during the redox process and the corrosion by acidic ***,we present a titanium-tungsten oxide alloy(Ti-WO_(3))with controllable morphology and crystal phase synthesized by a facile hot injection method to overcome the *** contrast to conventional monoclinic WO_(3),the Ti-WO_(3)nanorods can stably maintain their cubic crystal phase during the redox reaction in an acidic electrolyte,thus leading to dramatically enhanced response speed and cycling stability,Specifically,when working in a well-matched hybrid Al^(3+)/Zn^(2+)aqueous electrolyte,our phasetransition-free cubic Ti-WO_(3)exhibits an ultra-high cycling stability(>20000 cycles),fast response speed(3,95 s/4,65 s for bleaching/coloring),as well as excellent discharge areal capacity of 214.5 mA h m^(-2),We further fabricate a fully complementa ry aqueous electrochromic device,for the first time,using a Ti-WO_(3)/Prussian blue device ***,the complementary ECB shows>10000 stable operation cycles,attesting to the feasibility of our Ti-WO_(3)for practical *** work validates the significance of inhibiting the phase transitions of WO_(3)during the electrochromic process for realizing highly cyclable aqueous ECB,which can possibly provide a generalized design guidance for other high-quality metallic oxides for electrochemical applications.

关键词： Aqueous electrochromic battery Ti-WO_(3) Phase transition Long-term stability

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Frontiers in high entropy alloys and high entropy functional materials

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Rare Metals 2024年第10期43卷 4639-4776页

作者： Wen-Tao Zhang Wen huang Fu-Jie Yu Qi Zhao xin-Dong Zhu Tao Feng Yao Jiang Xiao-Ming Li Xue-Fei Miao He Zhu Si Lan Xue-Qian wang Bao-Long Shen Zhe Jia Feng-Qi Zhang wei wang Qi Liu yang Ren Xun-Li wang Xiao-Ya Cui Xiao-yang wang Ya-Nan Chen Bing-Bing Fan meng-Ru Li Qi-Long Gao Jia-Ming Guo Zeng-Bao Jiao Zhi-Min Guo Yu-Ping Zhao Qian Yu Rui huang Ling-Kun Zhang Yi-Ping Lu Xu-Bo Li huai-Jun Lin yan Ma wei-Ming yang Zhi-hua Shen Hai-yan He Yong-gang Sun Yong-Jiang huang De-Zhuang wang Qing-Feng Liu Fei-yang wang Hui Liu Hong-Hui wu Li-Qiang wang yang Lu Nan wang Tian-Li wang wei-Bing Liao Yi-Han wang Yuan wu Yu-Zhen Yin Jie Pan Yi Zhang Qing wang Jian-yang Zhang Tao yang Yasir Sohail Jin-Yu Zhang hua Ji Qiang Li wei-di Liu Zhi-gang Chen Xiong-Jun Liu Wen Ma Liang Mao Zhen-Duo wu School of Materials Science and Engineering Nanjing University of Science and Technology Jiangsu Key Laboratory for Advanced Metallic Materials School of Materials Science and Engineering Southeast University Department of Physics City University of Hong Kong School of Materials Science and Engineering Tianjin University School of Physics and Microelectronics Zhengzhou University Department of Mechanical Engineering Research Institute for Advanced Manufacturing The Hong Kong Polytechnic University Center of Electron Microscopy and State Key Laboratory of Silicon Materials School of Materials Science and Engineering Zhejiang University Key Laboratory of Solidification Control and digital Preparation Technology (Liaoning Province) School of Materials Science and Engineering Dalian University of Technology Institute of Advanced Wear & Corrosion Resistance and Functional Materials Jinan University School of Mechanics and Civil Engineering China University of Mining and Technology School of Physical Sciences Great Bay University School of Materials Science andEngineering Harbin Institute of Technology State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University Beijing Advanced Innovation Center for Materials Genome Engineering Research Institute for Carbon Neutrality University of Science and Technology Beijing Department of Mechanical Engineering The University of Hong Kong School of Computing Macquarie University Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic Engineering Shenzhen University State Key Laboratory for Advanced Metals and Materials University of Science and Technology Beijing State Key Laboratory of Materials Processing and die & Mould Technology School of Materials Science and Engineering Huazhong University of Science and Technology Institute of materials Shanghai University Department of Materials Science and Engineering C

Owing to their exceptional properties, high-entropy alloys(HEAs) and high-entropy materials have emerged as promising research areas and shown diverse applications. Here,the recent advances in the field are comprehensively reviewed,organized into five sections. The first section introduces the background of HEAs, covering their definition, significance,application prospects, basic properties, design principles, and microstructure. The subsequent section focuses on cutting-edge high-entropy structural materials, highlighting developments such as nanostructured alloys, grain boundary engineering,eutectic systems, cryogenic alloys, thin films, micro-nano-lattice structures, additive manufacturing, high entropy metallic glasses, nano-precipitate strengthened alloys, composition modulation, alloy fibers, and refractory systems. In the following section, the emphasis shifts to functional materials, exploring HEAs as catalysts, magneto-caloric materials, corrosion-resistant alloys, radiation-resistant alloys, hydrogen storage systems, and materials for biomedicine. Additionally, the review encompasses functional high-entropy materials outside the realm of alloys, including thermoelectric, quantum dots, nanooxide catalysts, energy storage materials, negative thermal expansion ceramics,and high-entropy wave absorption materials. The paper concludes with an outlook, discussing future directions and potential growth areas in the field. Through this comprehensive review,researchers, engineers, and scientists may gain valuable insights into the recent progress and opportunities for further exploration in the exciting domains of high-entropy alloys and functional materials.

关键词： Cutting-edge structural materials Cutting-edgefunctional materials High entropy alloys

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Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2673-2682页

作者： huang Chen Rui-Ying Jiang Zhan hua Xiao-wei wang Xiao-Li shi Ye wang Qian-Qian Feng Jie Luo wu Ning yan-Fen shi Da-Kui Zhang Bei wang Jian-Zheng Jie ding-Rong Zhong Department of Pathology China-Japan Friendship HospitalBeijing 100029China Department of Gastrointestinal Surgery China-Japan Friendship HospitalBeijing 100029China Department of Scientific Research GeneisBeijing 100012China

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly *** To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in *** We enrolled 2271 Chinese CRC patients at the China-Japan Friendship *** proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain *** status was determined using an MSI detection *** analyses were conducted using SPSS software and logistic *** The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,*** mutations were more likely to occur in patients with moderate-to-high *** mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural *** MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous ***,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,*** dMMR was more likely to occur in patients with a family history of CRC,ageddifferentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II *** This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

关键词： Colorectal cancer Deficient mismatch repair Microsatellite instability Gene mutation Comprehensive analysis

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A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： meng-Jie Tang Xiao-Li Ma Xiang-Ling He wei-hua Pan Xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Li wei Yao Song Gu wei-Ling Zhang Qiang Zhao shi-Hao huang Yong-Jun Fang wei Liu Hui-Zhong Niu Chun-Mei wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen huang Zhi-Yong Zhong Xi-Ge wang Zhong-Rong Li Liang-Chun yang Ye-Ming wu huan-Min wang xin Sun Xiao-Jun Yuan Department of Pediatric Hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of Hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of Hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of Hematology/Oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

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TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

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Zoological Research 2024年第4期45卷 937-950页

作者： Yi-Fu Zhu Rong-hua Yu Shuai Zhou Pei-Pei Tang Rui Zhang Yu-xin wu Ran Xu Jia-Ming wei Ying-Ying wang Jia-Li Zhang meng-Ke Li Xiao-Jing shi Yu-wei Zhang Guang-Zhi Liu Rick FThorne Xu Dong Zhang Mian wu Song Chen School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Translational Research Institute of Henan Provincial People’s Hospital and People'’s Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450053China Institute of Medicinal Biotechnology Jiangsu College of NursingHuai’anJiangsu 223300China Laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China Henan Key Laboratory of Stem cell differentiation and Modification Henan Provincial People’s HospitalHenan UniversityZhengzhouHenan 450053China School of Biomedical Sciences and Pharmacy The University of NewcastleNSW 2308Australia

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental *** highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained ***,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in *** deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse ***,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate ***,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this ***,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO ***,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

关键词： Non-canonical autophagy TAX1BP1 FIP200 p62 Aggregates Neural stem cell

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