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Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

Signal Transduction and Targeted Therapy 2023年第5期8卷 2329-2344页

作者： Junhui Hu Ping Tan Moe Ishihara nicholas ABayley Shiruyeh Schokrpur Jeremy gReynoso Yangjun Zhang Raymond JLim Camelia Dumitras Lu Yang Steven MDubinett Parmjit SJat Jacques Van Snick Jiaoti Huang Arnold IChin Robert MPrins Thomas ggraeber Hua Xu Lily Wu Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Urology West China HospitalChengduChina Department of Hematology and Oncology University of California San DiegoSan DiegoCA92103USA Department of Neurosurgery David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Biological Repositories Department of UrologyZhongnan Hospital of Wuhan UniversityWuhanChina Department of Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Jonsson Comprehensive Cancer Center David Geffen School of Medicine at UCLAUniversity of California Los AngelesLos AngelesCA90095USA MRC Prion Unit at UCL Institute of Prion Diseases33 Cleveland StreetLondonW1W 7FFUK Ludwig Institute for Cancer Research Ltd BrusselsBelgium Department of Pathology Duke UniversityDurhamNCUSA Department of Urology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center WuhanChina

Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under *** study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic *** VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)*** tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic *** tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic *** poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+***(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular *** deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical *** work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

关键词： VHL metastasis motility

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Single nucleotide polymorphisms of OCTN1, OCTN2, and DLg5 genes in greek patients with Crohn's disease

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World Journal of gastroenterology 2005年第47期11卷 7525-7530页

作者： Maria gazouli gerassimos Mantzaris Athanassios J Archimandritis george Nasioulas nicholas P Anagnou Department of Biology School of MedicineUniversity of AthensAthens 11725Greece Department of gastroenterology Evagelismos HospitalAthens 11521Greece Department of Internal Medicine Hippokration General HospitalSchool of MedicineUniversity of AthensAthens 11527Greece Molecular Biology Department Research Center HYgEIA "Antonis Papayiannis" AthensGreece

AIM: To validate novel single nucleotide polymorphisms (SNPs) in greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. genotyping was performed by allele-specific PCR or by PCR-RFLP ***: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The g113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the greek population.

关键词： Crohn's disease SNPs OCTN1 OCTN2 DLg5

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自上而下颠覆式创新

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深圳特区科技 2005年第8期 74-77页

作者： nicholas g.Carr 王丽娜

它是创业者的梦想,同时也是CEO们的噩梦.它令Andy grove发狂,为Bill gates带来了无尽的财富.依靠它,Wal-Mart超越了Sears.它使Digital Equipment Corporation得以快速发展,随后也导致其失败.

关键词：自上而下 Digital 创新 Bill CEO

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Models and estimators linking individual-based and sample-based rarefaction, extrapolation and comparison of assemblages

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Journal of Plant Ecology 2012年第1期5卷 3-21页

作者： Robert K.Colwell Anne Chao nicholas J.gotelli Shang-Yi Lin Chang Xuan Mao Robin L.Chazdon John T.Longino Department of Ecology and Evolutionary Biology University of ConnecticutStorrsCT 06269USA Institute of Statistics National Tsing Hua UniversityHsin-Chu 30043Taiwan Department of Biology University of VermontBurlingtonVT 05405USA School of Statistics and Management Shanghai University of Finance and EconomicsShanghai 200433China Department of Biology University of UtahSalt Lake CityUT 84112USA

Aims In ecology and conservation biology,the number of species counted in a biodiversity study is a key metric but is usually a biased underestimate of total species richness because many rare species are not ***,comparing species richness among sites or samples is a statistical challenge because the observed number of species is sensitive to the number of individuals counted or the area *** individual-based data,we treat a single,empirical sample of species abundances from an investigator-defined species assemblage or community as a reference point for two estimation objectives under two sampling models:estimating the expected number of species(and its unconditional variance)in a random sample of(i)a smaller number of individuals(multinomial model)or a smaller area sampled(Poisson model)and(ii)a larger number of individuals or a larger area *** sample-based incidence(presence–absence)data,under a Bernoulli product model,we treat a single set of species incidence frequencies as the reference point to estimate richness for smaller and larger numbers of sampling *** The first objective is a problem in interpolation that we address with classical rarefaction(multinomial model)and Coleman rarefaction(Poisson model)for individual-based data and with sample-based rarefaction(Bernoulli product model)for incidence *** second is a problem in extrapolation that we address with sampling-theoretic predictors for the number of species in a larger sample(multinomial model),a larger area(Poisson model)or a larger number of sampling units(Bernoulli product model),based on an estimate of asymptotic species *** published methods exist for many of these objectives,we bring them together here with some new estimators under a unified statistical and notational *** novel integration of mathematically distinct approaches allowed us to link interpolated(rarefaction)curves and extrapolated curves to plot a unified

关键词： Bernoulli product model Coleman curve multinomial model Poisson model random placement species–area relation

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Molecular profiling reveals potential targets in cholangiocarcinoma

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World Journal of gastroenterology 2023年第25期29卷 4053-4071页

作者： Dan Liu Yang Shi Hongze Chen Muhammad Azhar Nisar nicholas Jabara Noah Langwinski Sophia Mattson Katsuya Nagaoka Xuewei Bai Shaolei Lu Chiung-Kuei Huang Department of gastroenterology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Pathology and Laboratory Medicine Tulane University School of MedicineNew OrleansLA 70112United States Department of Medicine Rhode Island Hospital and the Alpert Medical School of Brown UniversityProvidenceRI 02903United States Department of Pathology Alpert Medical School of Brown UniversityProvidenceRI 02903United States

BACKgROUND Cholangiocarcinoma(CCA)is a devastating malignancy and has a very poor prognosis if tumors spread outside the *** the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly *** To determine the molecular pathogenesis in CCA *** In silico analysis,in vitro cell culture,CCA transgenic animals,histological,and molecular assays were adopted to determine the molecular *** The transcriptomic data of human CCA samples were retrieved from The Cancer genome Atlas(TgCA,CHOL),European Bioinformatics Institute(EBI,gAD-00001001076),and gene Expression Omnibus(gEO,gSE107943)*** gene set enrichment analysis,the cell cycle and Notch related pathways were demonstrated to be significantly activated in CCA in TCgA and gEO ***,through differentially expressed genes,found several cell cycle and notch associated genes were significantly up-regulated in cancer tissues when compared with the non-cancerous control *** associated genes,via quantitative real-time PCR and western blotting assays,were further examined in normal human cholangiocytes,CCA cell lines,mouse normal bile ducts,and mouse CCA tumors established by specifically depleting P53 and expressing Krasg12D mutation in the ***,we validated that the cell cycle and Notch pathways are up-regulated in CCA cell lines and mouse CCA ***,targeting cell cycle and notch pathways using small molecules also exhibited significant beneficial effects in controlling tumor *** importantly,we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank *** In summary,our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are po

关键词： Bile duct cancer Notch Cell cycle Liver cancer Therapeutic target

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Rapid metabolic fingerprinting with the aid of chemometric models to identify authenticity of natural medicines: Turmeric, Ocimum, and Withania somnifera study

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Journal of Pharmaceutical Analysis 2023年第9期13卷 1041-1057页

作者： Samreen Khan Abhishek Kumar Rai Anjali Singh Saudan Singh Basant Kumar Dubey Raj Kishori Lal Arvind Singh Negi nicholas Birse Prabodh Kumar Trivedi Christopher T.Elliott Ratnasekhar Ch Metabolomics Lab Council of Scientific and Industrial Research(CSIR)-Central Institute of Medicinal and Aromatic Plants(CIMAP)Lucknow226015India Department of Crop Production&Protection Council of Scientific and Industrial Research(CSIR)-Central Institute of Medicinal and Aromatic Plants(CIMAP)Lucknow226015India Academy of Council of Scientific and Industrial Research(ACSIR) Ghaziabad201002India Department of Biotechnology Council of Scientific and Industrial Research(CSIR)-Central Institute of Medicinal and Aromatic Plants(CIMAP)Lucknow226015India genetics and Plant Breeding Department Council of Scientific and Industrial Research(CSIR)-Central Institute of Medicinal and Aromatic Plants(CIMAP)Lucknow226015India Department of Phytochemistry Council of Scientific and Industrial Research(CSIR)-Central Institute of Medicinal and Aromatic Plants(CIMAP)Lucknow226015India School of Biological Sciences Queen's UniversityBelfastBT95DLUK

Herbal medicines are popular natural medicines that have been used for *** use of alternative medicines continues to expand rapidly across the *** World Health Organization suggests that quality assessment of natural medicines is essential for any therapeutic or health care applications,as their therapeutic potential varies between different geographic origins,plant species,and *** of herbal medicines based on a limited number of secondary metabolites is not an ideal *** quality should be considered based on a complete metabolic profile,as their pharmacological activity is not due to a few specific secondary metabolites but rather a larger group of bioactive compounds.A holistic and integrative approach using rapid and nondestructive analytical strategies for the screening of herbal medicines is required for robust *** this study,a rapid and effective quality assessment system for geographical traceability,species,and variety-specific authenticity of the widely used natural medicines turmeric,Ocimum,and Withania somnifera was investigated using Fourier transform near-infrared(FT-NIR)spectroscopy-based metabolic *** different geographical origins of turmeric,five different Ocimum species,and three different varieties of roots and leaves of Withania somnifera were studied with the aid of machine learning *** good discrimination(R^(2)>0.98,Q^(2)>0.97,and accuracy=1.0)with sensitivity and specificity of 100%was achieved using this metabolic fingerprinting *** study demonstrated that FT-NIR-based rapid metabolic fingerprinting can be used as a robust analytical method to authenticate several important medicinal herbs.

关键词： Rapid metabolic fingerprinting Natural medicines FT-NIR Chemometric models

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Influence of laser polarization on collective electron dynamics in ultraintense laser-foil interactions

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High Power Laser Science and Engineering 2016年第3期4卷 120-126页

作者： Bruno gonzalez-Izquierdo Ross J.gray Martin King Robbie Wilson Rachel J.Dance Haydn Powell David A.Mac Lellan John McCreadie nicholas M.H.Butler Steve Hawkes James S.green Chris D.Murphy Luca C.Stockhausen David C.Carroll Nicola Booth graeme g.Scott Marco Borghesi David Neely Paul McKenna SUPA Department of Physics University of Strathclyde Central Laser Facility STFC Rutherford Appleton Laboratory Department of Physics University of York Centro de Láseres Pulsados (CLPU) Centre for Plasma Physics Queens University Belfast

The collective response of electrons in an ultrathin foil target irradiated by an ultraintense(~6×10^(20)W cm^(-2)) laser pulse is investigated experimentally and via 3D particle-in-cell simulations. It is shown that if the target is sufficiently thin that the laser induces significant radiation pressure, but not thin enough to become relativistically transparent to the laser light, the resulting relativistic electron beam is elliptical, with the major axis of the ellipse directed along the laser polarization axis. When the target thickness is decreased such that it becomes relativistically transparent early in the interaction with the laser pulse, diffraction of the transmitted laser light occurs through a so called ‘relativistic plasma aperture', inducing structure in the spatial-intensity profile of the beam of energetic electrons. It is shown that the electron beam profile can be modified by variation of the target thickness and degree of ellipticity in the laser polarization.

关键词： laser–plasmas interaction ultraintense ultrashort pulse laser interaction with matters

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Operando Converting BiOCl into Bi_(2)O_(2)(CO_(3))_(x)Cl_(y) for Efficient Electrocatalytic Reduction of Carbon Dioxide to Formate

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Nano-Micro Letters 2022年第7期14卷 263-278页

作者： Huai Qin Fu Junxian Liu nicholas M.Bedford Yun Wang Joshua Wright Peng Fei Liu Chun Fang Wen Liang Wang Huajie Yin Dongchen Qi Porun Liu Hua gui Yang Huijun Zhao Centre for Catalysis and Clean Energy Gold Coast CampusGriffith UniversityGold CoastQLD 4222Australia School of Chemical Engineering University of New South WalesSydneyNSW 2052Australia Department of Physics Illinois Institute of TechnologyChicagoIL 60616USA Key Laboratory for Ultrafine Materials of Ministry of Education School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237People’s Republic of China Centre for Materials Science School of Chemistry and PhysicsQueensland University of TechnologyBrisbaneQLD 4001Australia

Bismuth-based materials(e.g., metallic, oxides and subcarbonate) are emerged as promising electrocatalysts for converting CO_(2) to formate. However, Bio-based electrocatalysts possess high overpotentials, while bismuth oxides and subcarbonate encounter stability issues. This work is designated to exemplify that the operando synthesis can be an effective means to enhance the stability of electrocatalysts under operando CO_(2)RR conditions. A synthetic approach is developed to electrochemically convert Bi^(O)Cl into Cl-containing subcarbonate(Bi_(2)O_(2)(CO_(3))_(x)Cl_(y)) under operando CO_(2)RR conditions. The systematic operando spectroscopic studies depict that BiOCl is converted to Bi_(2)O_(2)(CO_(3))_(x)Cl_(y) via a cathodic potential-promoted anion-exchange process. The operando synthesizedBi_(2)O_(2)(CO_(3))_(x)Cl_(y) can tolerate-1.0 V versus RHE, while for the wet-chemistry synthesized pure Bi_(2)O_(2)CO_(3),the formation of metallic Bio occurs at-0.6 V versus RHE. At-0.8 V versus RHE, Bi_(2)O_(2)(CO_(3))_(x)Cl_(y) can readily attain a FEHCOO-of 97.9%,much higher than that of the pure Bi_(2)O_(2)CO_(3)(81.3%). DFT calculations indicate that differing from the pure Bi_(2)O_(2)CO_(3)-catalyzed CO_(2)RR, where formate is formed via a *OCHO intermediate step that requires a high energy input energy of 2.69 eV to proceed, the formation of H COO-over Bi_(2)O_(2)(CO_(3))_(x)Cl_(y) has proceeded via a *COOH intermediate step that only requires low energy input of 2.56 eV.

关键词： Carbon dioxide reduction Chloride-containing bismuth subcarbonate Cathodic potential-promoted anion-exchange Stability

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空军航空电子设备实验室的电子战技术

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系统工程与电子技术 1983年第12期 55-62页

作者： g.nicholas ,C.H.Krueger ,刘鲁勤

在过去十年里,机载电子战飞速发展中最引人注目的变化之一是认识到电子战技术再也不能脱离航空电子设备的其他组成部分而单独发展了。人们曾经把电子战技术看成是由少数人秘密进行的一种法术和通常装在飞机上的最新设备,而现在它已作为... 详细信息

在过去十年里,机载电子战飞速发展中最引人注目的变化之一是认识到电子战技术再也不能脱离航空电子设备的其他组成部分而单独发展了。人们曾经把电子战技术看成是由少数人秘密进行的一种法术和通常装在飞机上的最新设备,而现在它已作为一个年青的伙伴出现在空军大力推行的把所有机载电子设备并入全集成化系统的运动中。将电子战设备并到总的航空电子设备中,这种动向是由下面两个因素决定的:(1)电子战探测器和其他机载电子设备探测器之间的信息联系是完成任务的根本条件;(2)由于微电子学、计算机和数据总线方面的大变革带来航空电子设备体系结构的可能改进,为高效

关键词：航空电子设备接收机带宽电子战技术电子战系统电子对抗系统实验室空军军队

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Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study

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World Journal of Transplantation 2021年第4期11卷 114-128页

作者： nicholas V Mendez Yehuda Raveh Joshua J Livingstone gaetano Ciancio giselle guerra george W Burke III Vadim B Shatz Fouad g Souki Linda J Chen Mahmoud Morsi Jose M Figueiro Tony M Ibrahim Werviston L DeFaria Ramona Nicolau-Raducu Department of Anesthesiology University of Miami/Jackson Memorial HospitalMiamiFL 33136United States Department of Surgery Miami Transplant Institute/University of Miami/Jackson Memorial HospitalMiamiFL 33136United States Division of Nephrology of the Department of Medicine University of Miami/Jackson Memorial HospitalMiamiFL 33136United States

BACKgROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney *** exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is *** To identify risk factors associated with delayed graft function(DgF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 *** primary outcome was the occurrence of *** The incidence of DgF was 27%.Under logistic regression,eight independent risk factors for DgF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressureg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/*** We delineate the association between DgF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine.

关键词： Delayed graft function Outcome Kidney transplant Risk factors Phenylephrine Mean arterial pressure

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