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Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

Frontiers of medicine 2024年第1期18卷 109-127页

作者： Guoqiang Li Peng Pu Mengqiao Pan Xiaoling Weng Shimei Qiu Yiming Li Sk Jahir Abbas Lu Zou Ke liu Zheng Wang Ziyu Shao Lin Jiang Wenguang Wu Yun liu Rong Shao Fatao liu Yingbin liu Department of Biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai200127China shanghai Key Laboratory of Biliary Tract Disease Shanghai200082China Department of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai200082China shanghai Tenth People’s Hospital of tongji university Shanghai200072China Department of General Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200082China Department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai200025China

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human ***,knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely ***,by taking advantage of in situ Hi-C,RNA-sequencing,and chromatin immunoprecipitation sequencing(ChIP-seq),we investigated structural reorganization and functional changes in chromosomal compartments,topologically associated domains(TADs),and CCCTC binding factor(CTCF)-mediated loops in gallbladder cancer(GBC)tissues and cell *** observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression *** inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal ***,the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial–mesenchymal transition activation were enriched in cancer compared with their control ***-specific enhancer–promoter loops,which contain multiple transcription factor binding motifs,acted as a central element to regulate aberrant gene *** of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene ***,our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

关键词： 3D genome cancer TADs loop gene regulation

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Development and Characterization of Novel FAP-Targeted Theranostic Pairs: A Bench-to-Bedside Study

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Research 2024年第3期2023卷 473-485页

作者： Wei Huang Yizhen Pang Qiufang liu Chenyi Liang Shuxian An Qianyun Wu You Zhang Gang Huang Haojun Chen Jianjun liu Weijun Wei Department of Nuclear medicine Institute of Clinical Nuclear MedicineRenj HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghai 200127China Department of Nuclear medicine and Minnan PET Center Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003China Department of Nuclear medicine Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China

Fibroblast activation protein (FAP) is among the most popular targets in nuclear medicine imaging and cancer theranostics. Several small-molecule moieties (FAPI-04, FAPI-46, etc.) are used for developing FAP-targeted theranostic agents. Nonetheless, the circulation time of FAP inhibitors is relatively short, resulting in rapid clearance via kidneys, low tumor uptake, and associated unsatisfactory treatment efficacy. To address the existing drawbacks, we engineered 3 peptides named FD1, FD2, and FD3 with different circulation times through solid-phase peptide synthesis. All the 3 reported peptides bind to human and murine FAP with single-digit nanomolar affinity measured by surface plasmon resonance. The diagnostic and therapeutic potential of the agents labeled with 68Ga and 177Lu was assessed in several tumor models exhibiting different levels of FAP expression. While radiolabeled FD1 was rapidly excreted from kidneys, radiolabeled FD2/FD3 have significantly prolonged circulation, increased tumor uptake, and decreased kidney accumulation. Our findings indicated that [68Ga]Ga-DOTA-FD1 positron emission tomography (PET) effectively detected FAP dynamics, whereas [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 exhibited remarkable therapeutic efficacy in FAP-overexpressing tumor models, including pancreatic cancer cell models characterized by abundant stroma. Moreover, a pilot translational investigation demonstrated that [68Ga]Ga-DOTA-FD1 had the capability to identify both primary and metastatic tumors with precision and distinction. In summary, we developed [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

关键词： DOTA expressing labeled

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PREDICTION OF FLOW STRESS OF HIGH-SPEED STEEL DURING HOT DEFORMATION BY USING BP ARTIFICIAL NEURAL NETWORK

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Acta Metallurgica Sinica(English Letters) 2000年第1期13卷 394-400页

作者： J. T. liu H.B. Chang R.H. Wu T. Y. Hsu(Xu Zuyao) and X.R. Ruan( 1)Department of Plasticity Technology, shanghai jiao tong university, shanghai 200030, China 2)school of Materials Science and Engineering, shanghai jiao tong university, shanghai 200030,

The hot deformation behavior of TI (18W-4Cr-1V) high-speed steel was investigated by means of continuous compression tests performed on Gleeble 1500 thermomechan- ical simulator in a wide range of tempemtures (950℃-1150℃) with strain rotes of 0.001s-1-10s-1 and true strains of 0-0. 7. The flow stress at the above hot defor- mation conditions is predicted by using BP artificial neural network. The architecture of network includes there are three input parameters:strain rate,temperature T and true strain , and just one output parameter, the flow stress ,2 hidden layers are adopted, the first hidden layer includes 9 neurons and second 10 negroes. It has been verified that BP artificial neural network with 3-9-10-1 architecture can predict flow stress of high-speed steel during hot deformation very well. Compared with the prediction method of flow stress by using Zaped-Holloman parumeter and hyperbolic sine stress function, the prediction method by using BP artificial neurul network has higher efficiency and accuracy.

关键词： T1 high-speed steel flow stress prediction of flow stress back propagation (BP) artificial neural network (ANN)

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VELOCITY MEASUREMENT OF DRAG-REDUCING FLOW USING PDA

VELOCITY MEASUREMENT OF DRAG-REDUCING FLOW USING PDA

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多相流研究进展国际会议

作者： ~*Songping Wang ~+Shan Sun ~*Dezhong Wang ~*Jingyu Zhou ~*Yingzheng liu *school of Mechanical Engineering shanghai jiao tong university shanghai 200030 +school of Electrical and Information Engineering shanghai jiao tong university shanghai 200030

＜正＞ Velocity measurements of the drag-reducing flow were performed extensively using Phase Doppler Anemometry （PDA）. Three dimensional velocity distribution of the turbulent boundary layer flow in two-dimensional water channel was measured. System error due to the refractive index difference between Acrylic resin plate and water was analyzed.

关键词： PDA drag-reducing flow refractive index

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Surface Topological Glycosylation-Mediated Mucoadhesion of Bacteria

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Chinese Journal of Chemistry 2024年第13期42卷 1447-1455页

作者： Xiao Kuang Xiaobing liu Ju Chen Wenyan Lv Mengmeng Zhang Huan Chen Feng Wu Jinyao liu school of Life Sciences Shanghai UniversityShanghai 200444China shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Institute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China school of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China College of Chemistry and Materials Science Shanghai Normal UniversityShanghai 200234China

Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial *** adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior,but has been proven to be ***,surface topological glycosylation is reported to mediate the interaction of bacteria with mucous *** functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation *** a copper-catalyzed azide-alkyne cycloaddition,the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido *** a proof-of-concept study,a set of topologically glycosylated probiotics(TGPs)is prepared using linear,two-branched,and tetra-branched compounds,*** interaction between mucin and TGPs was studied and the results demonstrate that,compared to unmodified bacteria,TGPs exhibit an enhanced adhesive capacity to mucin,which increases with the branching *** binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding *** work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria,providing unique significant insights into the manipulation of bacterial behavior through surface modification.

关键词： Topochemistry Bacteria Glycosylation Surface modification Mucoadhesion Click chemistry

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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Responses of the Southern Ocean mixed layer depth to the eastern and central Pacific El Niño events during austral winter

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Acta Oceanologica Sinica 2024年第7期43卷 1-14页

作者： Yuxin Shi Hailong liu Xidong Wang Quanan Zheng school of Oceanography Shanghai Jiao Tong UniversityShanghai 200240China Yunnan Key Laboratory of Meteorological Disasters and Climate Resources in the Greater Mekong Subregion Yunnan UniversityKunming 600650China College of Oceanography Hohai UniversityNanjing 210098China Department of Atmospheric and Oceanic Science University of Maryland at College ParkCollege Park 20742USA

Based on the Ocean Reanalysis System version 5(ORAS5)and the fifth-generation reanalysis datasets derived from European Centre for Medium-Range Weather Forecasts(ERA5),we investigate the different impacts of the central Pacific(CP)El Niño and the eastern Pacific(EP)El Niño on the Southern Ocean(SO)mixed layer depth(MLD)during austral *** MLD response to the EP El Niño shows a dipole pattern in the South Pacific,namely the MLD dipole,which is the leading El Niño-induced MLD variability in the *** tropical Pacific warm sea surface temperature anomaly(SSTA)signal associated with the EP El Niño excites a Rossby wave train propagating southeastward and then enhances the Amundsen Sea low(ASL).This results in an anomalous cyclone over the Amundsen *** a result,the anomalous southerly wind to the west of this anomalous cyclone advects colder and drier air into the southeast of New Zealand,leading to surface cooling through less total surface heat flux,especially surface sensible heat(SH)flux and latent heat(LH)flux,and thus contributing to the mix layer(ML)*** east of the anomalous cyclone brings warmer and wetter air to the southwest of Chile,but the total heat flux anomaly shows no significant *** warm air promotes the sea ice melting and maintains fresh water,which strengthens *** results in a shallower *** the CP El Niño,the response of MLD shows a separate negative MLD anomaly center in the central South *** Rossby wave train triggered by the warm SSTA in the central Pacific Ocean spreads to the Amundsen Sea,which weakens the ***,the anomalous anticyclone dominates the Amundsen ***,the anomalous northerly wind to the west of anomalous anticyclone advects warmer and wetter air into the central and southern Pacific,causing surface warming through increased SH,LH,and longwave radiation flux,and thus contributing to the ML ***,to the east of the anomalous anticyclone,there is n

关键词： Southern Ocean mixed layer depth Central Pacific El Niño Eastern Pacific El Niño Rossby wave train

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AI for tribology:Present and future

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Friction 2024年第6期12卷 1060-1097页

作者： Nian YIN Pufan YANG Songkai liu Shuaihang PAN Zhinan ZHANG State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong UniversityShanghai 200240China school of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai 200240China Department of Mechanical Engineering University of UtahSalt Lake CityUT 84112USA

With remarkable learning capabilities and swift operational speeds,artificial intelligence(AI)can assist researchers in swiftly extracting valuable patterns,trends,and associations from subjective *** behaviors are characterized by dependence on systems,evolution with time,and multidisciplinary *** friction process involves a variety of phenomena,including mechanics,thermology,electricity,optics,magnetics,and so ***,tribological information possesses the distinct characteristics of being multidisciplinary,multilevel,and multiscale,so that the application of AI in tribology is highly *** delineate the scope,classification,and recent trends of AI implementation in tribology,this review embarks on exploration of the tribology research *** comprehensively outlines the utilization of AI in basic theory of tribology,intelligent tribology,component tribology,extreme tribology,bio-tribology,green tribology,and other ***,considering the emergence of"tribo-informatics"as a novel interdisciplinary field,which combines tribology with informatics,this review elucidates the future directions and research framework of"AI for tribology".In this paper,tribo-system information is divided into 5 categories:input information(I),system intrinsic information(S),output information(O),tribological state information(Ts),and derived state information(Ds).Then,a fusion method among 5 types of tribo-system information and different AI technologies(regression,classification,clustering,and dimension reduction)has been proposed,which enables tribo-informatics methods to solve common problems such as tribological behavior state monitoring,behavior prediction,and system *** purpose of this review is to offer a systematic comprehension of tribo-informatics and to inspire new research ideas of ***,it aspires to enhance the efficiency of problem-solving in tribology.

关键词： artificial intelligence(AI) tribology machine learning tribo-informatics AI for tribology

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A novel interpretable multilevel wavelet decomposition deep network for actual heartbeat classification

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Science China(Technological Sciences) 2024年第6期67卷 1842-1854页

作者： JIN YanRui LI ZhiYuan TIAN YuanYuan WEI XiaoYang liu ChengLiang school of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai200240China

Arrhythmias may lead to sudden cardiac death if not detected and treated in time.A supraventricular premature beat(SPB)and premature ventricular contraction(PVC)are important categories of arrhythmia ***,deep learning methods have been applied to the PVC/SPB heartbeats ***,most researchers have focused on time-domain information of the electrocardiogram and there has been a lack of exploration of the interpretability of the *** this study,we design an interpretable and accurate PVC/SPB recognition algorithm,called the interpretable multilevel wavelet decomposition deep network(IMWDDN).Wavelet decomposition is introduced into the deep network and the squeeze and excitation(SE)-Residual block is designed for extracting time-domain and frequency-domain ***,inspired by the idea of residual learning,we construct a novel loss function for the constant updating of the multilevel wavelet decomposition ***,the IMWDDN is evaluated on the Third China Physiological Signal Challenge Dataset and the MIT-BIH Arrhythmia *** comparison results show IMWDDN has better detection performance with 98.51%accuracy and a 93.75%F1-macro on average,and its areas of concern are similar to those of an expert diagnosis to a certain ***,the IMWDDN has good application value in the clinical screening of PVC/SPB heartbeats.

关键词： actual heartbeat classification electrocardiogram interpretable deep network multilevel discrete wavelet decomposition layer SE-Residual block

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Nurrl is essential for the differentiation of DA neurons during zebrafish embryogenesis

Nurrl is essential for the differentiation of DA neurons dur...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Guang-Rui LUO,Yi CHEN,Xu-Ping LI,Ting-Xi liu~*,Wei-Dong LE~* Institute of Health Sciences,shanghai Institutes for Biological Sciences,Chinese Academy of Sciences and shanghai jiao tong university school of medicine,200025,shanghai,China State Key Laboratory for Medical Genomics, RuiJin Hospital,jiao tong university school of medicine,200025,shanghai,China Institute of Neurology,RuiJin Hospital,jiao tong university school of medicine,200025,shanghai.China odel Organism Division E-Institutes of shanghai Universities,shanghai,China

＜正＞Nurrl has been recently found to be critical for the development and maintenance of mesencephalic dopamine （DA） *** uncover the molecular mechanisms by which Nurr 1 contributes to the development of DA neurons,we have applied zebrafish to study the topographic distribution of nurrl transcripts during the early embryogenesis because of its ectogenesis and transparent,as well as its correlation with neuron progenitor marker（ngn1） and DA neuron markers （tyrosine hydroxylase,TH and DA transporter,DAT）.Our studies show that although nurrl transcripts did not co-localize with TH and DAT transcripts in the basal forebrain,it partially co-expressed with ngn1 in the region before 36 hpf. Knockdown of Nurr1 resulted in significant decrease of TH+ and DAT+ DA neurons,accompanied by reduction of DA transmitter and locomotive *** number of DA neurons and reduced DA transmitter in Nurr1-deficient embryos were significantly rescued by the injection of mouse Nurrl ***,the number of nurrl + cells in Nurr1-deficient embryos was increased by 1.6 *** results suggest that Nurrl plays a crucial role in the differentiation and maturation rather than the survival of DA progenitors during zebrafish early embryogenesis.

关键词： nurr1 DA progenitors and zebrafish

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