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Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Journal of Pharmaceutical Analysis 2024年第3期14卷 308-320页

作者： Mengxin Wang Stephen Vulcano changlu xu Renjian Xie Weijie Peng Jie Wang Qiaojun Liu Lee Jia Zhi Li Yumei Li Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province Gannan Medical UniversityGanzhouJiangxi341000China School of Rehabilitation Medicine Gannan Medical UniversityGanzhouJiangxi341000China Autoimmunity and Inflammation Program HSS Research InstituteHospital for Special Surgery New YorkNew YorkNY10021USA Division of Oral and Systemic Health Sciences School of DentistryUniversity of CaliforniaLos AngelesCA90095USA School of Medical Information Engineering Gannan Medical UniversityGanzhouJiangxi341000China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsInstitute for Liver Diseases of Anhui Medical UniversitySchool of PharmacyAnhui Medical UniversityHefei230032China School of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Institute of Oceanography Minjiang UniversityFuzhou350108China

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

关键词： Ribosome biogenesis Ribosomopathy gene Cancer treatment target Pharmaceutical target

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Long non-coding RNAs during normal erythropoiesis

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Blood Science 2019年第2期1卷 137-140页

作者： changlu xu Lihong Shi State Key Laboratory of Experimental Hematology National Clinical Research Center for Hematological DisordersInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina Center for Stem Cell Medicine Chinese Academy of Medical Sciences&Department of Stem Cells and Regenerative MedicinePeking Union Medical CollegeTianjinChina

The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding RNAs.Among them,long noncoding RNAs(lncRNAs)consist of a significant portion that widely exists across mammal genome,generating from high-throughput transcriptomic studies in the last decade.Although the functions of most lncRNAs remain to be further investigated,many of them have already been shown to play critical roles during normal development and disease conditions.Increasing evidence indicates that lncRNAs involve in versatile biological processes during erythroid proliferation and differentiation,including erythroid cell survival,heme metabolism,globin switching and regulation,erythroid enucleation,etc,via cis-or trans-mediated molecular mechanisms.In this review,we focus on recent advances regarding the functions and mechanisms of lncRNAs in normal erythropoiesis.

关键词： Erythropoiesis Globin regulation Heme biosynthesis Long non-coding RNAs

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A Green Biocompatible Fabrication of Highly Porous Functional Ceramics with High Strength and Controllable Pore Structures

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Journal of Materials Science & Technology 2016年第8期32卷 729-732页

作者： changlu xu Haoran Liu Huilin Yang Lei Yang Orthopaedic Institute and Department of Orthopaedics The First Affiliated Hospital Soochow University International Research Center for Translational Orthopaedics (IRCTO) Soochow University

A green biocompatible foaming method utilizing natural coconut oil and cornstarch was developed to fabricate highly porous functional ceramics with controllable strengths and pore structures. The poros- ity of A1203 ceramics prepared via this method reached 79.6%-86.9% while these ceramics maintained high compressive strengths of 2.2-5.5 MPa. More importantly, porous A1203 ceramic with a pore size gra- dient was also readily fabricated by casting serial layers of foams that were set for different time periods. The potential applications of porous Al2O3 and HA ceramics fabricated by this green foaming method in- cluding scaffolds for oil cleaning and cell culture, respectively, were also demonstrated.

关键词： Porous ceramic Pore structure Bioceramics Hydroxyapatite Alumina

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Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells

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Journal of Molecular Cell Biology 2021年第2期13卷 104-115页

作者： Guohui Bian Yanzheng Gu changlu xu Wenyu Yang xu Pan Yijin Chen Mowen Lai Ya Zhou Yong Dong Bin Mao Qiongxiu Zhou Bo Chen Tatsutoshi Nakathata Lihong Shi Min Wu Yonggang Zhang Feng Ma Center for Stem Cell Research and Application Institute of Blood TransfusionChinese Academy of Medical Sciences&Peking Union Medical College(CAMS&PUMC)Chengdu 610052China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalCAMS&PUMCTianjin 300020China Stem Cell Key Laboratory of Jiangsu Province Institute of Medical BiotechnologySuzhou UniversitySuzhou 215123China Center for iPS Cell Research and Application(CiRA) Kyoto UniversityKyoto 606-8507Japan Department of Biomedical Sciences School of Medicine and Health SciencesUniversity of North DakotaGrand ForksND 58203US

Mast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34+ cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34+c-kit+ cell population, which appeared prior to the emergence of CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase+Chymase+ MCs (MCTCs). Single-cell analysis revealed dual development directions of CD34+c-kit+ progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MCTCs derived from early CD34+c-kit+ cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MCTCs could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTCs and have significant therapeutic implications.

关键词： mast cells human pluripotent stem cells(hPSCs) development tryptase chymase

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Single-cell transcriptomic landscape of human blood cells

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National Science Review 2021年第3期8卷 42-52页

作者： Xiaowei Xie Mengyao Liu Yawen Zhang Bingrui Wang Caiying Zhu Chenchen Wang Qing Li Yingying Huo Jiaojiao Guo changlu xu Linping Hu Aiming Pang Shihui Ma Lina Wang Wenbin Cao Shulian Chen Qiuling Li Sudong Zhang xueying Zhao Wen Zhou Hongbo Luo Guoguang Zheng Erlie Jiang Sizhou Feng Lixiang Chen Lihong Shi Hui Cheng Sha Hao Ping Zhu Tao Cheng State Key Laboratory of Experimental Hematology and National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences &Peking Union Medical College Center for Stem Cell Medicine and Department of Stem Cell & Regenerative Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Research Institute School of Basic Medical Science Central South University School of Life Sciences Zhengzhou University

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis.However,an elaborate and comprehensive transcriptome reference of the whole blood system is lacking.Here,we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types,including hematopoietic stem cells,progenitors and mature blood cells derived from 21 healthy donors.With high sequencing depth and coverage,we constructed a single-cell transcriptional atlas of blood cells(ABC) on the basis of both protein-coding genes and long noncoding RNAs(lncRNAs),and showed a high consistence between them.Notably,putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified.While common transcription factor regulatory networks were activated in neutrophils and monocytes,lymphoid cells dramatically changed their regulatory networks during differentiation.Furthermore,we showed a subset of nucleated erythrocytes actively expressing immune signals,suggesting the existence of erythroid precursors with immune functions.Finally,a web portal offering transcriptome browsing and blood cell type prediction has been established.Thus,our work provides a transcriptional map of human blood cells at single-cell resolution,thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

关键词： human hematopoietic cells lncRNAs transcription factor single-cell RNA-seq

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Micro/nano flow chemistry by Beyond Limits Manufacturing

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Chinese Chemical Letters 2024年第5期35卷 3-12页

作者： Peiwen Liu Fang Zhao Jing Zhang Yunpeng Bai Jinxing Ye Bo Bao Xinggui Zhou Li Zhang changlu Zhou Xinhai Yu Peng Zuo Jianye Xia Lian Cen Yangyang Yang Guoyue Shi Lin xu Weiping Zhu Yufang xu xuhong Qian State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Chemical Engineering School of Chemical EngineeringEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for BiomanufacturingEast China University of Science and TechnologyShanghai 200237China School of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China School of Mechanical and Power Engineering East China University of Science and TechnologyShanghai 200237China Shanghai Key Laboratory of Green Chemistry and Chemical Processes Department of ChemistrySchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

In September 2018,we proposed the cutting-edge concept of“Beyond Limits Manufacturing”(BLM).BLM technology is based on the three-dimensional inner engraving or precise outer engraving of ultra-fast laser,to invent micro/nano scale flow chips or devices,which makes it possible for the microform,integration,economy,safety,high efficiency,green and intelligence of research,development and manufacturing process,so as to realize transformational manufacturing in the era of Industry 4.0.In this paper,we reviewed the representative results we made in the field of micro/nano flow chemistry during the implementation of the BLM major project(December 2019 to August 2023),and discussed its application prospects in micro/nano flow chemistry.

关键词： Beyond Limits Manufacturing Flow chemistry Pharmaceutical manufacturing Microreactor

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Riverine sulfate sources and behaviors in arid environment,Northwest China:Constraints from sulfur and oxygen isotopes

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Journal of Environmental Sciences 2024年第3期137卷 716-731页

作者： Yifu xu Wenjing Liu Bing xu Zhifang xu Key Laboratory of Cenozoic Geology and Environment Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China Innovation Academy for Earth Science Chinese Academy of SciencesBeijing 100029China University of Chinese Academy of Sciences Beijing 100049China

The fate of riverine sulfate ion (SO_(4)^(2-)) and its environmental effects in arid environment are difficult to evaluate due to its complicated sources and strongly coupled behaviors with water cycle which is significantly modified by humans.To understand the sulfur cycle in aquatic systems in arid environment,the chemical and sulfur and oxygen isotopic compositions (δ^(34)S_(SO4)and δ^(18)O_(SO4)) of major rivers around the Badain Jaran Desert,northwestern China,were investigated.These rivers had averaged SO_(4)^(2-)content at 1336μmol/L,over 10times higher than the global average.The δ^(34)S_(SO4)and δ^(18)O_(SO4)values ranged from-5.3‰to+11.8‰and+1.6‰to+12.8‰,respectively.The end-member analysis and the inverse model showed that riverine sulfate was mainly derived from evaporites dissolution (0-87%),sulfide oxidation (13%-100%) and precipitation (0-33%),indicating heterogeneity in sulfur sources and behaviors along the river drainage with the lithology variations and climate gradients.Multiple isotopic tools combining with hydro-chemistry compositions could be applied to reveal sulfur cycle in arid environment.Based on the calculation,sulfide oxidation plays the primary role in the headwater and upstream in the Qilian-Mountains area,where sulfide is widely exposed.While the proportion of evaporites dissolution contributing to riverine sulfate is much higher in downstream in a drier environment.Besides,less precipitation and higher temperature can lead to more intensive evaporation,affecting the process of sulfide oxidation and enhancing the rates of evaporites dissolution and sulfate precipitation in the basin.

关键词： Sulfur and oxygen isotopes Source apportionment Inverse model Arid environment Inland rivers Northwestern China

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Biohythane production from two-stage anaerobic digestion of food waste:A review

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Journal of Environmental Sciences 2024年第5期139卷 334-349页

作者： Xiaona An Ying xu Xiaohu Dai State Key Laboratory of Pollution Control and Resource Reuse School of Environmental Science and EngineeringTongji UniversityShanghai 200092China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China

The biotransformation of food waste(FW)to bioenergy has attracted considerable research attention as a means to address the energy crisis and waste disposal problems.To this end,a promising technique is two-stage anaerobic digestion(TSAD),in which the FW is transformed to biohythane,a gaseous mixture of biomethane and biohydrogen.This review summarises the main characteristics of FW and describes the basic principle of TSAD.Moreover,the factors influencing the TSAD performance are identified,and an overview of the research status;economic aspects;and strategies such as pre-treatment,co-digestion,and regulation of microbial consortia to increase the biohythane yield from TSAD is provided.Additionally,the challenges and future considerations associated with the treatment of FW by TSAD are highlighted.This paper can provide valuable reference for the improvement and widespread implementation of TSAD-based FW treatment.

关键词： Two-stage anaerobic digestion(TSAD) Food waste(FW) Methane production Hydrogen production

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Identification of high oxygen-consuming substances in stormwater drainage systems illicitly connected with sewage system

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Journal of Environmental Sciences 2024年第4期138卷 132-140页

作者： Chen xu Zuxin xu Wenhai Chu Shanshan Wu Rong Xiao Lei Su State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China Ministry of Education Key Laboratory of Yangtze River Water Environment Tongji UniversityShanghai 200092China Guangzhou Resource Environmental Protection Technology Co. Ltd.Guangzhou 510030China

The dissolved oxygen content in water is an important indicator for assessing the quality of the water environment,and maintaining a certain amount of dissolved oxygen is essential for the healthy development of the ecological environment.When a water body is anoxic,the activity of anaerobic microorganisms increases and organic matter is decomposed to produce a large number of blackening and odorizing substances,resulting in black and odorous water bodies,which is a very common and typical phenomenon in China.Presently,there is still a relatively universal occurrence of illicitly connected stormwater and sewage pipes in the urban drainage pipe network in China,which makes oxygen-consuming substances be directly discharged into rivers through stormwater pipes and consume the dissolved oxygen in the water bodies,resulting in an oxygen deficiency of the water.This induces seasonal or year-round black and stink phenomena in urban rivers.Hence,identifying high oxygen-consuming substances,which lays the foundation for the subsequent removal of oxygen-consuming substances,is essential.Through a series of comparisons of water quality indicators and analysis of organic characteristics,it was found that the oxygen consumption capacity of domestic sewage was higher than that of industrial wastewater in the selected area of this study,and the oxygen-consuming substances of domestic sewage were small molecular amino acids.By comparing 20 conventional free amino acids,it was found that seven of them consumed oxygen easily,and compared with chemical oxygen consumption,biological oxygen consumption was in a leading position.

关键词： Urban drainage system Oxygen-consuming substances Domestic sewage Amino acid

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Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

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Science China Chemistry 2024年第6期67卷 2079-2091页

作者： Liwei xu Xinxin xu Hua Kuang Chuanlai xu Xiaoling Wu State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and Technology Jiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu Province Jiangnan UniversityWuxi214122China

Chiral pollutants often pose significant differential environmental health risks.In this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically investigated.Firstly,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was revealed.The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of S-configuration.Meanwhile,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine.Thirdly,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.

关键词： neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk

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