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A 3D Human Liver Model of Nonalcoholic Steatohepatitis

Journal of Clinical and Translational Hepatology 2020年第4期8卷 359-370页

作者： Marion Duriez Agnes Jacquet Lucile Hoet Sandrine Roche marie-dominique bock Corinne Rocher Gilles Haussy Xavier Vigé Zsolt Bocskei Tamara Slavnic Valérie Martin Jean-Claude Guillemot Michel Didier Aimo Kannt Cécile Orsini Vincent Mikol Anne-Céline Le Fèvre Translational Sciences Sanofi1 Avenue Pierre BrossoletteChilly-MazarinFrance IT&M STATS Groupe IT&MNeuilly-sur-SeineFrance Non Clinical Biostatistics SanofiVitry sur SeineFrance Diabetes and Cardiovascular Research SanofiIndustriepark HöchstFrankfurtGermany Institute of Experimental Pharmacology Medical Faculty MannheimUniversity of HeidelbergMannheimGermany

Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. Conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.

关键词： 3D liver model Human primary cells Key features of NASH

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Towards engineering a portable platform for laparoscopic pre-training in virtual reality with haptic feedback

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虚拟现实与智能硬件（中英文） 2024年第2期6卷 83-99页

作者： Hans-Georg ENKLER Wolfgang KUNERT Stefan PFEFFER Kai-Jonas bock Steffen AXT Jonas JOHANNINK Christoph REICH Furtwangen University 78120 FurtwangenGermany University Hospital and Faculty of Medicine Tuebingen 72076 TuebingenGermany

Background Laparoscopic surgery is a surgical technique in which special instruments are inserted through small incision holes inside the *** some time,efforts have been made to improve surgical pre training through practical exercises on abstracted and reduced *** The authors strive for a portable,easy to use and cost-effective Virtual Reality-based(VR)laparoscopic pre-training platform and therefore address the question of how such a system has to be designed to achieve the quality of today's gold standard using real tissue *** VR controllers are limited regarding haptic *** haptic feedback is necessary or at least beneficial for laparoscopic surgery training,the platform to be developed consists of a newly designed prototype laparoscopic VR controller with haptic feedback,a commercially available head-mounted display,a VR environment for simulating a laparoscopic surgery,and a training *** To take full advantage of benefits such as repeatability and cost-effectiveness of VR-based training,the system shall not require a tissue sample for haptic *** is currently calculated and visually displayed to the user in the VR *** the prototype controller,a first axis was provided with perceptible feedback for test *** of the prototype VR controllers can be combined to simulate a typical both-handed use case,e.g.,laparoscopic suturing.A Unity based VR prototype allows the execution of simple standard *** The first prototype enables full operation of a virtual laparoscopic instrument in *** addition,the simulation can compute simple interaction *** challenges lie in a realistic real-time tissue simulation and calculation of forces for the haptic *** weaknesses were identified in the first hardware prototype,which will be improved in subsequent *** degrees of freedom of the controller are to be provided with haptic *** make forces t

关键词： Laparoscopic surgery Training Virtual reality Controller Haptic feedback Kinesthetic skills

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Plastid engineering with an efficient RNAi delivery system based on bacteriophage MS2 virus-like particles enhances plant resistance to cotton bollworm

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Molecular Plant 2024年第7期17卷 987-989页

作者： Chunmei Jiang Jinqiu Fu Fujun Li Kai Xia Shengchun Li Ling Chang Ralph bock Jiang Zhang State Key Laboratory of Biocatalysis and Enzyme Engineering School of Life SciencesHubei Hongshan LaboratoryHubei UniversityWuhan 430062China Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518000China Max-Planck-Institut fur Molekulare Pflanzenphysiologie Am Muhlenberg 114476Potsdam-GolmGermany

Dear Editor,RNA-based pesticides are approaching the market,offering great potential to control agricultural pests such as the coleopteran insect Diabrotica virgifera virgifera(Head et al.,2017).However,application to lepidopteran pests has been hampered by their inconsistent response to RNA interference(RNAi).As a notorious lepidoptera pest,Helicoverpa armigera feeds on over 300 species of host plants(Fu et al.,2022).Although transgenicplants expressingdouble-stranded RNAs or microRNAs that target essential insect genes can inhibit the growth of larvae,complete protection of the plants and efficient killing of this insect have not been achieved(Bally et al.,2020;Chung et al.,2021;Li et al.,2023).The relatively low RNAi efficiency in lepidopterans is mainly attributable to the degradation and intracellular sequestration of double-stranded RNA(Shukla et al.,2016;Zhu and Palli,2020).To overcome these obstacles and improve RNAi efficiency in ***,we attempted to deliver RNAi molecules using a bacteriophage MS2 virus-like particle(VLP)-based delivery system(Wang et al.,2016).

关键词： overcome offering approaching

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The tri-band high spectral resolution spectrometer with gratings in tandem for the charge-exchange recombination spectroscopy diagnostic system on HL-2A tokamak

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Plasma Science and Technology 2024年第6期26卷 103-110页

作者：刘亮余德良马倩何小斐 Maarten DE bock Manfred von HELLERMANN Michael WALSH 陈文锦何小雪魏彦玲张能李栋魏会领 the HL-2A Team Southwestern Institute of Physics Chengdu 610041People’s Republic of China College of Physics and Optoelectronic Technology Baoji University of Arts and SciencesBaoji 721000People’s Republic of China ITER Organization Route de Vinon-sur-VerdonCS 90046St.Paul Lez Durance Cedex 13067France Fusion Spectroscopy Markgraf-Albrecht Str.14Berlin 10711Germany

Charge-exchange(CX) recombination spectroscopy is a powerful tool monitoring ion temperature and plasma rotation with good temporal and spatial resolutions. A compact, new design for a high-throughput, tri-band high spectral resolution spectrometer has been developed for the charge-exchange recombination spectroscopy measurement on the HL-2A tokamak. The simultaneous measurements of He II(468.57 nm), C VI(529.1 nm), and Dα(656.1 nm accompanied by beam emission spectra) with an acquisition frequency up to 400 Hz are achieved by vertically binning the spectrum from each fiber in experiments. Initial results indicate that the system can provide radial profiles of not only ion temperature and rotation velocity,but also concentration of carbon. For the case of helium, the measurements for the ion temperature and rotation velocity are straightforward but the apparent concentration associated with the observed CX intensity is obviously too high. Modeling of the active He II CX feature including plume contributions needs to be carried out to extract the true helium *** spectrometer could become a prototype for the ITER charge-exchange recombination spectroscopy diagnostic and the pilot experiments, as presented here, demonstrate the possibility of impurity concentrations measurements based on the combined measurement of local beam emission and charge-exchange recombination spectroscopy spectra.

关键词： CXRS ion temperature plasma rotation impurity concentration

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Haplotype-based phylogenetic analysis and population genomics uncover the origin and domestication of sweetpotato

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Molecular Plant 2024年第2期17卷 277-296页

作者： Mengxiao Yan Ming Li Yunze Wang Xinyi Wang M-Hossein Moeinzadeh Dora G.Quispe-Huamanquispe Weijuan Fan Yijie Fang Yuqin Wang Haozhen Nie Zhangying Wang Aiko Tanaka Bettina Heider Jan F.Kreuze Godelieve Gheysen Hongxia Wang Martin Vingron Ralph bock Jun Yang Shanghai Key Laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai 201602China College of Life Sciences Chongqing Normal UniversityChongqing 401331China Biotechnology and Nuclear Technology Research Institute Sichuan Academy of Agricultural SciencesChengdu 610061China College of Life Sciences Shanghai Normal UniversityShanghai 200234China Department of Computational Molecular Biology Max Planck Institute for Molecular GeneticsIhnestraBe 63-7314195 BerlinGermany Department of Biotechnology Ghent University9000 GhentBelgium Guangdong Provincial Key Laboratory of Crops Genetics and Improvement Crop Research InstituteGuangdong Academy of Agricultural SciencesGuangzhou 510640China Graduate School of Bioagricultural Sciences Nagoya UniversityChikusaNagoya 464-8601Japan international Potato Center(CIP) LimaPeru CAS Center for Excellence of Molecular Plant Sciences Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200233China Max-Planck-Institut fur Molekulare Pflanzenphysiologie Am Muhlenberg 114476 Potsdam-GolmGermany

The hexaploid sweetpotato(lpomoea batatas)is one of the most important root crops ***,its genetic origin remains controversial,and its domestication history remains *** this study,we used a range of genetic evidence and a newly developed haplotype-based phylogenetic analysis to identify two probable progenitors of *** diploid progenitor was likely closely related to lpomoea ae-quatoriensis and contributed the B,subgenome,IbT-DNA2,and the lineage 1 type of chloroplast genome to *** tetraploid progenitor of sweetpotato was most likely *** 4x,which donated the B2 subgenome,IbT-DNA1,and the lineage 2 type of chloroplast *** most likely originated from reciprocal crosses between the diploid and tetraploid progenitors,followed by a subsequent whole-genome *** addition,we detected biased gene exchanges between the subgenomes;the rate of B,to B2 subgenome conversions was nearly three times higher than that of B2 to B subgenome *** analyses revealed that genes involved in storage root formation,maintenance of genome stabil-ity,biotic resistance,sugar transport,and potassium uptake were selected during the speciation and domestication of *** study sheds light on the evolution of sweetpotato and paves the way forimprovementofthiscrop.

关键词： sweetpotato origin gene conversion domestication IbT-DNA HPA

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The Translational Apparatus of Plastids and Its Role in Plant Development

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Molecular Plant 2014年第7期7卷 1105-1120页

作者： Nadine Tiller Ralph bock Max-Planck-Institut for Molekulare Pflanzenphysiologie Am Muhlenberg 1 D-14476 Potsdam-Golm Germany

Chloroplasts （plastids） possess a genome and their own machinery to express it. Translation in plastids occurs on bacterial-type 70S ribosomes utilizing a set of tRNAs that is entirely encoded in the plastid genome. In recent years, the components of the chloroplast translational apparatus have been intensely studied by proteomic approaches and by reverse genetics in the model systems tobacco （plastid-encoded components） and Arabidopsis （nucleus-encoded components）. This work has provided important new insights into the structure, function, and biogenesis of chloroplast ribosomes, and also has shed fresh light on the molecular mechanisms of the translation process in plastids. In addition, mutants affected in plastid translation have yielded strong genetic evidence for chloroplast genes and gene products influencing plant develop- ment at various levels, presumably via retrograde signaling pathway（s）. In this review, we describe recent progress with the functional analysis of components of the chloroplast translational machinery and discuss the currently available evidence that supports a significant impact of plastid translational activity on plant anatomy and morphology.

关键词： plastid translation ribosome ribosomal protein evolution plastid transformation retrograde signaling leaf development palisade cell.

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Visual rating and the use of image analysis for assessing canopy density in a pecan provenance collection during leaf fall

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林业研究:英文版 2023年第6期34卷 1843-1854页

作者： Cristina Pisani Clive H.bock Jennifer Randall United States Department of Agriculture−Agricultural Research Service (USDA-ARS)Southeastern Fruit and Tree Nut Research Station(SEFTNRS)ByronGA 31008USA Department of Entomology Plant Pathology and Weed ScienceNew Mexico State UniversityLas CrucesNM 88003USA

A collection representing the native range of pecan was planted at the US DA-ARS Southeastern Fruit and Tree Nut Research Station,Byron,*** collection(867 trees)is a valuable genetic resource for characterizing important horticultural *** density during leaf fall is important as the seasonal canopy dynamics provides insights to environmental cues and breeding potential of *** ability of visual raters to estimate canopy density on a subset of the provenance collection(76 trees)as an indicator of leaf shed during autumn along with image analysis values was *** canopy density using the image analysis software was less compared to visual estimates(11.9%vs 18.4%,respectively).At higher canopy densities,the raters overestimated foliage density,but overall agreement between raters and measured values was good(ρc=0.849 to 0.915),and inter-rater reliability was high(R^(2)=0.910 to 0.953).The provenance from Missouri(MOL),the northernmost provenance,had the lowest canopy density in November,and results show that the higher the latitude of the provenance,the lower the canopy *** on regression,the source provenance latitude explained 0.609 of the variation using image analysis,and0.551 to 0.640 when based on the rater estimates of canopy *** assessment of pecan canopy density due to late season leaf fall for comparing pecan genotypes provides accurate and reliable estimates and could be used in future studies of the whole provenance collection.

关键词： Carya illinoinensis Accuracy Reliability Canopy Foliage density Leaf area density Leaf area index

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Water hammer in the pump-rising pipeline system with an air chamber

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Journal of Hydrodynamics 2014年第6期26卷 960-964页

作者： KIM Sang-Gyun LEE Kye-bock KIM Kyung-Yup Korea Water Resources Corporation School of Mechanical Engineering Chungbuk National University School of Mechanical Engineering Korea Polytechnic University

Water hammer following the tripping of pumps can lead to overpressure and negative pressure. Reduction in overpressure and negative pressure may be necessary to avoid failure, to improve the efficiency of operation and to avoid fatigue of system components. The field tests on the water hammer have been conducted on the pump rising pipeline system with an air chamber. The hydraulic transient was simulated using the method of characteristics. Minimizing the least squares problem representing the difference between the measured and predicted transient response in the system performs the calibration of the simulation program. Among the input variables used in the water hammer analysis, the polytropic exponent, the discharge coefficient and the wave speed were calibrated. The computer program developed in this study will be useful in designing the optimum parameters of an air chamber for the real pump pipeline system. The correct selection of air chamber size and the effect of the inner diameter of the orifice to minimize water hammer have been investigated by both field measurements and numerical modeling.

关键词： air chamber design parameter field test pump pipeline system water hammer

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Factors affecting trace element content in periurban market garden subsoil in Yunnan Province,China

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Journal of Environmental Sciences 2011年第3期23卷 488-496页

作者： Yanqun zu Laurent bock Christian Schvartz Gilles Colinet Yuan Li College of Resources and Environment Yunnan Agricultural University Kunming 650201 China Laboratory of Soil Science Gembloux Agro-bio Technology University Liege University Gembloux Belgium Laboratory of Soil and Environment Institute of Advanced Agriculture Catholic University Lille France

Field investigations were conducted to measure subsoil trace element content and factors influencing content in an intensive periurban market garden in Chenggong County, Yunnan Province, South-West China. The area was divided into three different geomorphological units： specifically, mountain （M）, transition （T） and lacustrine （L）. Mean trace element content in subsoil were determined for Pb （58.2 mg/kg）, Cd （0.89 mg/kg）, Cu （129.2 mg/kg）, and Zn （97.0 mg/kg）. Strong significant relationships between trace element content in topsoil and subsoil were observed. Both Pb and Zn were accumulated in topsoil （RTS （ratio of mean trace element in topsoil to subsoil） of Pb and Zn ≥1.0） and Cd and Cu in subsoil （RTS of Cd and Cu≤1.0）. Subsoil trace element content was related to relief, stoniness, soil color, clay content, and cation exchange capacity. Except for 7.5 YR （yellow-red） color, trace element content increased with color intensity from brown to reddish brown. Significant positive relationships were observed between Fe content and that of Pb and Cu. Trace element content in mountain unit subsoil was higher than in transition and lacustrine units （M 〉 T 〉 L）, except for Cu （T 〉 M 〉 L）. Mean trace element content in calcareous subsoil was higher than in sandstone and shale. Mean trace element content in clay texture subsoil was higher than in sandy and sandy loam subsoil, and higher Cu and Zn content in subsoil with few mottles. It is possible to model Pb, Cd, Cu, and Zn distribution in subsoil physico-chemical characteristics to help improve agricultural practice.

关键词： trace elements subsoil topsoil relationships

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The Chlamydomonas Chloroplast HLP Protein Is Required for Nucleoid Organization and Genome Maintenance

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Molecular Plant 2009年第6期2卷 1223-1232页

作者： Daniel Karcher Dietrich Koster Anne Schadach Anja Klevesath Ralph bock Max-Planck-lnstitut fur Molekulare Pflanzenphysiologie Am Muhlenberg 1 D-14476 Potsdam-Golm Germany

The chloroplasts genome （plastome） occurs at high copy numbers per cell. Several chloroplast genome copies are densely packed into nucleoprotein particles called nucleoids. How genome packaging occurs and which proteins organize chloroplast nucleoids are largely unknown. Here, we have analyzed the Chlamydornonas reinhardtii homolog of the bacterial architectural DNA-binding protein HU, the histone-like protein HLP. We show that the Chlarnydornonas HLP protein is targeted to chloroplasts and associates with nucleoids. Knockdown of HLP gene expression by RNA interference （RNAi） alters the structure of chloroplast nucleoids and appears to reduce the level of compaction of chloroplast DNA. Unexpectedly, also chloroplast genome copy numbers are significantly decreased in the RNAi strains, suggesting that, in addition to its architectural role in nucleoid formation, the HIP protein is also involved in chloroplast genome maintenance.

关键词： Chloroplast nucleoid Chlamydomonas reinhardtii HLP DNA-binding protein genome maintenance

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