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Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease

World journal of Gastroenterology 2017年第2期23卷 204-215页

作者： Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large david j hughes CN Bio Innovations Limited Welwyn Garden City AL7 3AXUnited Kingdom

AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture *** The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.

关键词： Non-alcoholic fatty liver disease Liver disease Three-dimensional cell culture Organ-on-chip Primary cell culture Fatty liver Hepatocytes

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Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

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World journal of Gastroenterology 2018年第47期24卷 5351-5365页

作者： Marcela Alcantara Proenca joice Matos Biselli Maysa Succi Fábio Eduardo Severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis david j hughes Ana Elizabete Silva Department of Biology UNESPUniv. Estadual PaulistaCampus of Sao Jose do Rio PretoSao Jose do Rio PretoSao Paulo 15054-000Brazil Department of Surgery and Orthopedics Faculty of MedicineUNESPUniv. Estadual PaulistaCampus of BotucatuBotucatuSao Paulo 18618-687Brazil Endoscopy Center of Rio Preto Sao Jose do Rio PretoSao Paulo 15015-700Brazil Molecular Oncology Research Center Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Life and Health Sciences Research Institute University of MinhoCampus GualtarBraga 4710-057Portugal ICVS/3B’s-PT Government Associate Laboratory Campus GualtarBraga 4710-057Portugal Cancer Biology and Therapeutics Group UCD Conway InstituteUniversity College DublinDublin D04 V1W8Ireland

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high *** Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

关键词： Colorectal cancer Colorectal adenoma Fusobacterium nucleatum Inflammation Cytokines MicroRNAs

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Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： david j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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美国页岩气成本被低估

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能源评论 2013年第5期 91-94页

作者： j. david hughes

美国的页岩气和页岩油产量被过度炒作，而成本则被低估了。页岩气革命的长期生命力必须在一个针对未来的、可持续的能源战略中加以考虑。

关键词：页岩气成本美国能源战略油产量

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Enhancing diabetic retinopathy screening:Non-mydriatic fundus photography-assisted telemedicine for improved clinical management

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World journal of Diabetes 2024年第8期15卷 1820-1823页

作者： Kira j Szulborski david j Ramsey Department of Ophthalmology Tufts University School of MedicineBostonMA 02111United States Lahey Department of Surgery Division of OphthalmologyUMass Chan Medical SchoolUniversity of MassachusettsBurlingtonMA 01805United States Graduate Faculty New England College of OptometryBostonMA 02115United States

The utilization of non-mydriatic fundus photography-assisted telemedicine to screen patients with diabetes mellitus for diabetic retinopathy provides an accurate,efficient,and cost-effective method to improve early detection of *** has also been shown to correlate with increased participation of patients in other aspects of diabetes *** particular,patients who undergo teleretinal imaging are more likely to meet Comprehensive Diabetes Care Healthcare Effectiveness Data and Information Set metrics,which are linked to preservation of quality-adjusted life years and additional downstream healthcare savings.

关键词： Diabetes Diabetic retinopathy Telemedicine Tele-ophthalmology Nonmydriatic fundus photography-assisted telemedicine Vision screening Preventative health services Health policy

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： Samuel S.Hardisty Xiaoqian Lin Anthony R.j.Kucernak david Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox *** via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the *** electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the *** single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating *** selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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Oryza CLIMtools:A genome–environment association resource reveals adaptive roles for heterotrimeric G proteins in the regulation of rice agronomic traits

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Plant Communications 2024年第4期5卷 145-165页

作者： Angel Ferrero-Serrano david Chakravorty Kobie j.Kirven Sarah M.Assmann Biology Department Pennsylvania State University208 Mueller LaboratoryUniversity ParkPA 16802USA Intercollege Graduate Degree Program in Bioinformatics and Genomics Pennsylvania State University208 Mueller LaboratoryUniversity ParkPA 16802USA

Modern crop varieties display a degree of mismatch between their current distributions and the suitability of the local climate for their *** address this issue,we present Oryza CLIMtools(https://***/CLIMtools/oryza_v1.0/),thefirst resource for pan-genome prediction of climate-associated genetic variants in a crop *** CLIMtools consists of interactive web-based databases that enable the user to(1)explore the local environments of traditional rice varieties(landraces)in South-East Asia and(2)investigate the environment by genome associations for 658 Indica and 283 japonica rice landrace accessions collected from georeferenced local environments and included in the 3K Rice Ge-nomes *** demonstrate the value of these resources by identifying an interplay betweenflowering time and temperature in the local environment that is facilitated by adaptive natural variation in OsHD2 and disrupted by a natural variant in *** quantitative trait locus analysis has suggested the impor-tance of heterotrimeric G proteins in the control of agronomic ***,we analyzed the climate associations of natural variants in the different heterotrimeric G protein *** identified a coordi-nated role of G proteins in adaptation to the prevailing potential evapotranspiration gradient and revealed their regulation of key agronomic traits,including plant height and seed and panicle *** conclude by highlighting the prospect of targeting heterotrimeric G proteins to produce climate-resilient crops.

关键词： Oryza sativa rice G by E adaptation flowering time GWAS OsHD2 OsSOC1 heterotrimeric G pro-tein OsRGA1 d1 OsGS3 OsDEP1 OsGGC2

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Integrating petrophysical data into efficient iterative cluster analysis for electrofacies identification in clastic reservoirs

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Energy Geoscience 2024年第4期5卷 291-305页

作者： Mohammed A.Abbas Watheq j.Al-Mudhafar Aqsa Anees david A.Wood Basrah Oil Company BasrahIraq Institute of International Rivers and Eco-Security Yunnan UniversityKunming650500China Institute for Ecological Research and Pollution Control of Plateau Lakes School of Ecology and Environmental ScienceYunnan UniversityKunming650500China DWA Energy Limited LincolnUK

Efficient iterative unsupervised machine learning involving probabilistic clustering analysis with the expectation-maximization(EM)clustering algorithm is applied to categorize reservoir facies by exploiting latent and observable well-log variables from a clastic reservoir in the Majnoon oilfield,southern *** observable well-log variables consist of conventional open-hole,well-log data and the computer-processed interpretation of gamma rays,bulk density,neutron porosity,compressional sonic,deep resistivity,shale volume,total porosity,and water saturation,from three wells located in the Nahr Umr *** latent variables include shale volume and water *** EM algorithm efficiently characterizes electrofacies through iterative machine learning to identify the local maximum likelihood estimates(MLE)of the observable and latent variables in the studied *** optimized EM model developed successfully predicts the core-derived facies classification in two of the studied *** EM model clusters the data into three distinctive reservoir electrofacies(F1,F2,and F3).F1 represents a gas-bearing electrofacies with low shale volume(Vsh)and water saturation(Sw)and high porosity and permeability values identifying it as an attractive reservoir *** results of the EM model are validated using nuclear magnetic resonance(NMR)data from the third studied well for which no cores were *** NMR results confirm the effectiveness and accuracy of the EM model in predicting *** utilization of the EM algorithm for electrofacies classification/cluster analysis is ***,the clusters it establishes are less rigidly constrained than those derived from the more commonly used K-means clustering *** EM methodology developed generates dependable electrofacies estimates in the studied reservoir intervals where core samples are not ***,once calibrated with core data in some wells,the model is suitable for

关键词： Cluster analysis Electrofacies classification Expectation-maximization(EM)algorithm Clastic reservoir Maximum likelihood estimate(MLE)

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Storylines of family medicine Ⅺ:professional identity formation—nurturing one’s own story

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Family Medicine and Community Health 2024年第S3期12卷 99-108页

作者： William B Ventres Leslie A Stone Hamish j Wilson Sumi M Sexton david j Doukas jessica P Cerdena david M Kelley Michael D Fetters jeffrey j Haney john j Frey III Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA General Practice and Rural Health University of Otago Dunedin School of MedicineDunedinNew Zealand Family Medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Family and Community Medicine Tulane University School of MedicineNew OrleansLouisianaUSA Family Medicine Residency Program Middlesex HealthMiddletownConnecticutUSA Family Medicine University of Michigan Medical SchoolAnn ArborMichiganUSA Medical Education and Clinical Sciences Washington State UniversitySpokaneWashingtonUSA Family Medicine and Community Health University of Wisconsin-Madison School of Medicine and Public HealthMadisonWisconsinUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅺ:professional identity formation—nurturing one’s own story’,authors address the following themes:‘The social construction of professional identity’,‘On becoming a family physician’,‘What’s on the test?—professionalism for family physicians’,‘The ugly doc-ling’,‘Teachers—the essence of who we are’,‘Family medicine research—it starts in the clinic’,‘Socially accountability in medical education’,‘Personal philosophy and how to find it’and‘Teaching and learning with Storylines of Family Medicine’.May these essays encourage readers to find their own creative spark in medicine.

关键词： own becoming professional

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Influence of Local Cation Order on Electronic Structure and Optical Properties of Cation-Disordered Semiconductor AgBiS_(2)

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Chinese Physics Letters 2024年第10期41卷 61-69页

作者： Xiaoyu Wang Muhammad Faizan Yuhao Fu Kun Zhou Yilin Zhang Xin He david j.Singh Lijun Zhang State Key Laboratory of Superhard Materials College of PhysicsJilin UniversityChangchun 130012China State Key Laboratory of Integrated Optoelectronics Key Laboratory of Automobile Materials of MOECollege of Materials Science and EngineeringJilin UniversityChangchun 130012China Department of Physics and Astronomy University of MissouriColumbiaMissouri 65211-7010USA

Site disorder exists in some practical semiconductors and can significantly impact their intrinsic properties both beneficially and ***,the uncertain local order and structure pose a challenge for experimental and theoretical ***,it hinders the investigation of the effects of the diverse local atomic environments resulting from the site *** employ the special quasi-random structure method to perform first-principles research on connection between local site disorder and electronic/optical properties,using cationdisordered AgBiS_(2)(rock salt phase)as an *** predict that cation-disordered AgBiS_(2)has a bandgap ranging from 0.6 to 0.8 eV without spin-orbit coupling and that spin-orbit coupling reduces this by approximately 0.3 *** observe the effects of local structural features in the disordered lattice,such as the one-dimensional chain-like aggregation of cations that results in formation of doping energy bands near the band edges,formation and broadening of band-tail states,and the disturbance in the local electrostatic potential,which significantly reduces the bandgap and *** influence of these ordered features on the optical properties is confined to alterations in the bandgap and does not markedly affect the joint density of states or optical *** study provides a research roadmap for exploring the electronic structure of site-disordered semiconductor materials,suggests that the ordered chain-like aggregation of cations is an effective way to regulate the bandgap of AgBiS_(2),and provides insight into how variations in local order associated with processing can affect properties.

关键词： stability. structure ordered

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