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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang liu Dongchao Shen qing liu Mingsheng liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration

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Genes & Diseases 2024年第3期11卷 351-367页

作者： Xinzhu Quiu Hongbo He Hao Zeng Xiaopeng Tongg Can Zhang Yupeng liu Zhan Liao qing liu Department of Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalChangshaHunan 410008China Department of Sports Medicine Research Center of Sports MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China

MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated.We constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus.Subsequently,we calcu-lated the extent of MYBL2 activation in malignant proliferative osteoblasts.We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma.Furthermore,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy prognosis.Finally,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict prognosis.MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways.MYBL2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines.Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.

关键词： Biomarker Immunecheckpoint MYBL2 Osteosarcoma Pan-cancer

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Relationship between hydrogenation degree and pyrolysis performance of jet fuel

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Chinese Journal of Chemical Engineering 2024年第4期68卷 35-42页

作者： qing liu Tinghao Jia Lun Pan Jijun Zou Xiangwen Zhang Key Laboratory for Green Chemical and Technology School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192China Zhejiang Institute of Tianjin University Ningbo 315201China Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China

Understanding the relationship between the chemical composition and pyrolysis performance of endothermic hydrocarbon fuel(EHF)is of great significance for the design and optimization of advanced EHFs.In this work,the effect of deep hydrogenation on the pyrolysis of commercial RP-3 is investigated.Fuels with different hydrogenation degrees were obtained by the partially and completely catalytic hydrogenation and their pyrolysis performances were investigated using an apparatus equipped with an electrically heated tubular reactor.The results show that with the increase of hydrogenation degree,fuel conversion almost remains constant during the pyrolysis process(500e650C,4 MPa);however,the heat sink increases slightly,and the anti-coking performance significantly improves,which are highly related to their H/C ratios.Detailed characterisations reveal that the difference of the pyrolysis performance can be ascribed to the content of aromatics and cycloalkanes:the former are prone to initiate secondary reactions to form coking precursors,while the latter could act as the hydrogen donor and release hydrogen,which will terminate the radical propagation reactions and suppress the coke deposition.This work should provide the guidance for upgrading EHFs by modulating the composition of EHFs.

关键词： RP-3 Fuel Pyrolysis Hydrogenation Deposition

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Whose Aid is Beneficial to Firms'Exports?Evidence from a Post-disaster Aid Experiment in China

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China & World Economy 2024年第2期32卷 73-96页

作者： Tan Li qing liu Lihe Xu School of International Business Southwestern University of Finance and EconomicsChina School of Economics Renmin University of ChinaChina Institute of Studies for the Greater Bay Area Guangdong University of Foreign StudiesChina

Post-disaster aid is widely regarded as important in helping local recovery and development.This paper examines the effectiveness of post-disaster aid on exports,which are a driving factor of economic development.It reports a natural experiment in China–the case of post-disaster aid following the Wenchuan earthquake in 2008–to examine how donors'experiences affected the exports of manufacturing firms in disaster-stricken counties.The export experience of the donor was important.Aid coming from donors with more export experience was more beneficial to the exports of firms in recipient counties than aid from less experienced donors.“Learning from the donor”is a potential channel through which this effect occurred.That is,firms in recipient counties learned from donors'export experience by exporting more products similar to those of donors,exporting more to the destination countries of donors,and participating in the donors'supply-chain networks by exporting more of the donors'exports.Such“learning from the donor”effects show that knowledge spillover can occur between spatially distant parties,which complements the literature.

关键词： China export knowledge spillover post-disaster aid

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Hi-TOM 2.0:an improved platform for high-throughput mutation detection

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Science China(Life Sciences) 2024年第7期67卷 1532-1534页

作者： Tingting Sun qing liu Xi Chen Fengyue Hu Kejian Wang State Key Laboratory of Rice Biology and Breeding China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou 310006China Hainan Seed Industry Laboratory Sanya 572025China

Dear Editor,CRISPR/Cas systems,which can create novel mutations by manipulating the genome or transcriptome,have been developed as a powerful molecular tool for gene editing in various organisms(Cheng et al.,2022;Gao,2021).However,identifying mutations in large samples and decoding chimeric mutations are time-consuming,labor-intensive.

关键词： CRISPR/Cas consuming mutation

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Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway

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Food Science and Human Wellness 2024年第2期13卷 1040-1054页

作者： Xiaomin Li qing liu Songyu Xie Xiaoping Wu Junsheng Fu College of Life Sciences Mycological Research CenterFujian Agriculture and Forestry UniversityFuzhou 350002China

Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.

关键词： Cordycepin Hepatocellular carcinoma Hippo signaling pathway GBP3 ETV5

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Hybrid model for BOF oxygen blowing time prediction based on oxygen balance mechanism and deep neural network

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 106-117页

作者： Xin Shao qing liu Zicheng Xin Jiangshan Zhang Tao Zhou Shaoshuai Li State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China Engineering Research Center of MES Technology for Iron&Steel Production Ministry of EducationBeijing 100083China Laiwu Iron and Steel Group Yinshan Section Steel Co. Ltd.Jinan 271104China

The amount of oxygen blown into the converter is one of the key parameters for the control of the converter blowing process,which directly affects the tap-to-tap time of converter. In this study, a hybrid model based on oxygen balance mechanism (OBM) and deep neural network (DNN) was established for predicting oxygen blowing time in converter. A three-step method was utilized in the hybrid model. First, the oxygen consumption volume was predicted by the OBM model and DNN model, respectively. Second, a more accurate oxygen consumption volume was obtained by integrating the OBM model and DNN model. Finally, the converter oxygen blowing time was calculated according to the oxygen consumption volume and the oxygen supply intensity of each heat. The proposed hybrid model was verified using the actual data collected from an integrated steel plant in China, and compared with multiple linear regression model, OBM model, and neural network model including extreme learning machine, back propagation neural network, and DNN. The test results indicate that the hybrid model with a network structure of 3 hidden layer layers, 32-16-8 neurons per hidden layer, and 0.1 learning rate has the best prediction accuracy and stronger generalization ability compared with other models. The predicted hit ratio of oxygen consumption volume within the error±300 m^(3)is 96.67%;determination coefficient (R^(2)) and root mean square error (RMSE) are0.6984 and 150.03 m^(3), respectively. The oxygen blow time prediction hit ratio within the error±0.6 min is 89.50%;R2and RMSE are0.9486 and 0.3592 min, respectively. As a result, the proposed model can effectively predict the oxygen consumption volume and oxygen blowing time in the converter.

关键词： basic oxygen furnace oxygen consumption oxygen blowing time oxygen balance mechanism deep neural network hybrid model

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Recent progresses of exosome-liposome fusions in drug delivery

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Chinese Chemical Letters 2024年第2期35卷 107-117页

作者： Lulu Zheng Bo Hu Deyao Zhao Wenjing liu qing liu Yuanyu Huang Shaobo Ruan School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Beijing Key Laboratory of Drug Resistance Tuberculosis Research Beijing Tuberculosis and Thoracic Tumor Research Instituteand Beijing Chest HospitalCapital Medical UniversityBeijing 101149China

Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.

关键词： Exosome Liposome Membrane fusion Drug delivery Disease treatment

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Neuromorphic circuits based on memristors: endowing robots with a human-like brain

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Journal of Semiconductors 2024年第6期45卷 47-63页

作者： Xuemei Wang Fan Yang qing liu Zien Zhang Zhixing Wen Jiangang Chen Qirui Zhang Cheng Wang Ge Wang Fucai liu School of Optoelectronic Science and Engineering University of Electronic Science and Technology of ChinaChengdu 610054China Yangtze Delta Region Institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou 313099China

Robots are widely used,providing significant convenience in daily life and production.With the rapid development of artificial intelligence and neuromorphic computing in recent years,the realization of more intelligent robots through a pro-found intersection of neuroscience and robotics has received much attention.Neuromorphic circuits based on memristors used to construct hardware neural networks have proved to be a promising solution of shattering traditional control limita-tions in the field of robot control,showcasing characteristics that enhance robot intelligence,speed,and energy efficiency.Start-ing with introducing the working mechanism of memristors and peripheral circuit design,this review gives a comprehensive analysis on the biomimetic information processing and biomimetic driving operations achieved through the utilization of neuro-morphic circuits in brain-like control.Four hardware neural network approaches,including digital-analog hybrid circuit design,novel device structure design,multi-regulation mechanism,and crossbar array,are summarized,which can well simulate the motor decision-making mechanism,multi-information integration and parallel control of brain at the hardware level.It will be definitely conductive to promote the application of memristor-based neuromorphic circuits in areas such as intelligent robotics,artificial intelligence,and neural computing.Finally,a conclusion and future prospects are discussed.

关键词： neuromorphic devices neuromorphic circuits hardware networks memristors humanlike robots

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Revealing the role of pyramidal slip in the high ductility of Mg-Li alloy

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Journal of Magnesium and Alloys 2024年第3期12卷 1021-1025页

作者： Jing Xu Bo Guan Yunchang Xin Guangjie Huang Peidong Wu qing liu International Joint Laboratory for Light Alloys College of Materials Science and EngineeringChongqing UniversityChongqing 400030China Key Laboratory for Light-weight Materials Nanjing Tech UniversityNanjing 210009China Department of Mechanical Engineering McMaster UniversityHamiltonON L8S 4L7Canada

The high ductility of Mg-Li alloy has been mainly ascribed to a high activity of pyramidalslip to accommodate plastic strain.In the present study,however,a quantitative analysis reveals that Li-addition can only slightly stimulate the activation of pyramidalslip under compression along the normal direction of a hot-rolled Mg-4.5 wt.%Li plate,with a relative activity of approximately 18%.Although the limited activity of pyramidalslip alone cannot accommodate a large plastic strain,it effectively reduces the number of{10.11}−{10.12}double twins,which are believed to be favorable sites for crack initiation.The evidently reduced activity of double twins leads to a lower cracking tendency,and therefore improves ductility.

关键词： Mg alloy Plasticity Plastic deformation Slip Twinning.

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