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HM30181A,a potent p-glycoprotein inhibitor,potentiates the absorption and in vivo antitumor efficacy of paclitaxel in an orthotopic brain tumor model

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Cancer Biology & Medicine 2020年第4期17卷 986-1001页

作者： Wu Zeng Betty Yuen Kwan Law Vincent Kam Wai Wong Denise So Bik Chan Simon Wing Fai Mok Joyce Jia Ying Gao Rebecca Ka Yan Ho Xu Liang Jia Hao Li Ming Tsung Lee Weng Li Yoon michael p smolinski Johnson Yiu Nam Lau Christopher Wai Kei Lam Manson Fok State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina At he nex Hong Kong Irmo vative Limited Hong Kong China Faculty of Medici ne Macao Un iversity of Science and TechnologyMacaoChina Athenex Inc. New York 14203USA

Objective:Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma,owing to the presence of the blood-brain barrier and the activity of p-gp,which pumps its substrate back into the systemic *** aim of the present study was to develop an intravenous formulation of HM30181 A(HM)to inhibit p-gp in the brain to effectively deliver paclitaxel(pTX)for the treatment of malignant ***:Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies:i)spray-drying[polyvinlypyrrolidone(pVp)-HM]and ii)solvent evaporation[Hp-β-cyclodextrin(cyclodextrin)-HM].The p-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer *** and brain pharmacokinetic parameters were also determined,and the antitumor effect of cyclodextrin-HM with pTX was evaluated in an orthotopic glioma xenograft mouse ***:Although both pVp-HM and cyclodextrin-HM formulations showed promising p-gp inhibition activity in vitro,cyclodextrin-HM had a higher maximum tolerated dose in mice than did *** study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg,and the mice began to lose weight at doses above this ***-HM(10 mg/kg)administered with pTX at 10 mg/kg showed optimal antitumor activity in a mouse model,according to both tumor volume measurement and survival time(ppic brain tumor model,the intravenous co-administration of cyclodextrin-HM with pTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.

关键词： HM30181A glioma pharmacokinetics paclitaxel p-glycoprotein

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preliminary attempt to distinguish the domesticated pigs from wild boars by the methods of carbon and nitrogen stable isotope analysis

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Science China Earth Sciences 2009年第1期52卷 85-92页

作者： michael p.RICHARDS Department of Human Evolution Max-Planck Institute for Evolutionary AnthropologyDeutscher Platz 6D-04103LeipzigGermany

Despite great achievements in the origins of domestic pigs made by the methods of zooarchaeology and molecular biology,how to scientifically distinguish the domesticated pigs from wild boars during the early stage of pig domestication is still poorly *** to wild boar's diets which come from the natural environment,the diets of domestic pigs are more easily influenced by human feeding ***,in principle,exploration of the dietary differences among pigs and understanding the impact on pig diets fed by humans can have great potential to differentiate between wild boars and domesticated *** reveal dietary differences among pigs and distinguish the domesticated pigs from wild boars based on comparison with the diets of humans and other animals,we analyzed the carbon and nitrogen stable isotopes of human bones from Xiaojingshan Site and animal bones from Yuezhuang Site,both of which belong to Houli Culture in Shandong province and date to about 8500―7500 years *** mean δ 13C value((-17.8 ± 0.3)‰) and δ 15N value((9.0±0.6)‰) in human collagen indicate that although millet agriculture began it was not the main subsistence strategy as millets are typical of C4 plants and that humans made a living mainly by gathering,hunting or raising some domesticated *** δ 13C value(-16.1‰) and δ 15N value(6.9‰) in the bovine suggest that C3 plants were dominant in its diet with some C4 plants *** fish has lower δ 13C value(-24.9‰) and higher δ 15N value(8.8‰) than the bovine,which is the characteristic of the isotopic values from Eurasian freshwater *** on the differences in carbon and nitrogen isotope values,the pigs can be divided into three groups.A group,composed of two pigs,has low δ 13C values(-18.1‰,-20.0‰) and low δ 15N values(4.7‰,6.0‰).B group,only one pig,has the highest δ 13C value(-10.6‰) and mediate δ 15N value(6.4‰).As for the C group,also only one pig,low δ 13C value(-19.0‰) and the highest δ 15N value(9.1‰

关键词： origins of domestic pigs early stage of domestication differentiation of domesticated pigs from wild boars carbon and nitrogen stable isotope analysis millet agriculture

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An integrated analysis of air pollution from US coal-fired power plants

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Geoscience Frontiers 2023年第2期14卷 204-216页

作者： Mikalai Filonchyk michael p.peterson Faculty of Geomatics Lanzhou Jiaotong UniversityLanzhou 730070China Gansu provincial Engineering Laboratory for National Geographic State Monitoring Lanzhou 730070China Department of Geography/Geology University of Nebraska OmahaOmahaNE 68182USA

The United States is one of the world’s leaders in electricity production,generating about 4116 billion kWh in 2021,of which coal accounted for 21.8%of the *** study applies an integrated approach using both terrestrial and satellite data to specifically examine emissions from coal-fired power plants and its spatial *** study also highlights the effectiveness of government policies to reduce *** was found that emission of pollutants from the country’s energy sector has been steadily declining,with annual emissions of sulfur dioxide(SO_(2))and nitrogen oxides(NOx)decreasing from the US electric power sector between 1990 and 2020 by 93.4%and 84.8%,respectively,and carbon dioxide(CO_(2))by 37%between 2007 and *** overall emissions from coal-fired power plants are declining,some individual plants have yet to install environmental equipment to control *** to US government data,major emitters of SO_(2),NO_(x),and CO_(2) in the US are the Martin Lake power plant in East Texas,the Labadie power plant near ***,Missouri,and the James H Miller Jr plant near Birmingham,*** study also integrates TROpOMI satellite data to detect point emissions from individual power *** the highest levels of measured pollutants were over the country’s major cities and areas of fossil fuel extraction,TROpOMI could clearly distinguish the pollution caused by power plants in more rural *** the US has made great strides in reducing emissions from coal-fired power plants,these plants still represent a major source of pollution and remain a major *** eliminating coal as a power source will be difficult with the higher power demands resulting from the transition to electric automobiles.

关键词： Coal-fired power plants Emissions TROpOMI Air pollution Sulfur dioxide Nitrogen oxides

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New species and unexpected diversity of socially parasitic bees in the genus Inquilina Michener （Hymenoptera： Apoidea： Apidae）

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Insect Science 2009年第4期16卷 343-350页

作者： Jaclyn A. Smith michael p. Schwarz Flinders University School of Biological Sciences Adelaide South Austrafia Australia

Allodapine bees present particular problems for taxonomy due to a high level of morphological conservatism in adults, even between genera. However, this tribe of bees also presents a unique opportunity to explore the evolution of social parasitism because of the comparatively large number of origins of socially parasitic species. Morphological differences presented here, along with DNA sequence data and molecular phylogenetic analyses, indicate a much larger number of Australian social parasite species in the genus Inquilina than previously anticipated, and suggest that the final number of socially parasitic species may be considerable. We describe five new species and present sequence data that will help elucidate the delineation of further new species. Inquilina provides a unique opportunity to study the evolution of social parasitism in social insects, but further studies will need to encompass both population genetic and phylogenetic approaches.

关键词： Allodapine bee molecular phylogenetics social parasite

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Divergent pathways of β,γ-unsaturated α-diazocarbonyl compounds catalyzed by dirhodium and Lewis acids catalysts separately or in combination

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Chinese Chemical Letters 2015年第2期26卷 227-232页

作者： Xin-Fang Xu michael p.Doyle Key Laboratory of Organic Synthesis of Jiangsu province College of ChemistryChemical Engineering and Materials ScienceDushu Lake CampusSoochow University Department of Chemistry and Biochemistry.University of Maryland College Park

β,γ-Unsaturated a-diazocarbonyl compounds possess two reactive sites for electrophilic addition-one at the diazo carbon and the other at the vinylogous γ-*** by catalyst,divergent transformations are achieved starting from the same starting materials,either by Lewis acid-catalyzed addition or by dirhodium-catalyzed metal carbene *** select cases two catalysts working in combination or in sequence provide a relay for cascade *** this review,we summarize advances in catalyst-dependent divergent transformations of β,γ-unsaturated α-diazocarbonyl compounds and highlight the potential of this exciting research area and the many challenges that remain.

关键词： Divergent synthesis β γ-Unsaturated α-diazocarbonyl compounds Metal carbene(carbenoid) Dirhodium Lewis acid catalyst

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Cellular automaton simulation and experimental validation of eutectic transformation during solidification of Al-Si alloys

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npj Computational Materials 2022年第1期8卷 1245-1253页

作者： Cheng Gu michael p.Moodispaw Alan A.Luo Department of Materials Science and Engineering The Ohio State UniversityColumbusOHUSA Department of Integrated Systems Engineering The Ohio State UniversityColumbusOHUSA

The morphology of eutectic silicon in solidification microstructure is critical to the performance of Al-Si-based *** eutectic Si phase formation has been a challenge in ICME (integrated computational materials engineering) based design and manufacturing of solidification products of Al-Si-based *** this study,our previous three-dimensional (3-D) cellular automaton (CA) model for α-Al dendritic growth was extended to include eutectic (α-Al + Si) transformation in multi-dendrite domains,providing a complete solidification simulation of critically important Al-Si based *** quantitative results of the Si phase in the eutectic microstructure were experimentally validated using scanning electron microscopy and deep etching *** simulation results show a good agreement with the experimental observations and calculations by the Scheil model and lever *** 3-D CA model is useful for predicting and optimizing the solidification microstructure including eutectic transformation during solidification processing such as casting,potentially welding,and additive manufacturing.

关键词： solidification eutectic transformation

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Compressional origin of the Aegean Orogeny,Greece

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Geoscience Frontiers 2022年第2期13卷 383-404页

作者： michael p.Searle Thomas N.Lamont Dept Earth Sciences Oxford UniversitySouth Parks RoadOxfordOX13ANUK School of Earth and Environmental Sciences University of St AndrewsSt AndrewsKY169ALUK

The Aegean Sea area is thought to be an actively extending back-arc region,north of the present day Hellenic volcanic arc and north-dipping subduction zone in the Eastern *** area shows extensive normal faulting,ductile‘extensional’shear zones and extensional S-C fabrics throughout the islands that have previously been related to regional Aegean extension associated with slab rollback on the Hellenic Subduction *** this paper,we question this interpretation,and suggest the Cenozoic geodynamic evolution of the Aegean region is associated with a Late Cretaceous-Eocene NE-dipping subduction zone that was responsible for continentcontinent collision between Eurasia and Adria-Apulia/*** of eclogite and blueschist facies rocks in the Cyclades and kyanite-sillimanite grade gneisses in the Naxos core complex have pressures that are far greater than could be accounted for purely by lithospheric extension and isostatic *** identify four stages of crustal shortening that affected the region prior to regional lithospheric extension,herein called the Aegean *** orogeny followed a classic Wilson cycle from early ophiolite obduction(ca.74 Ma)onto a previously passive continental margin,to attempted crustal subduction with Hp eclogite and blueschist facies metamorphism(ca.54-45 Ma),through crustal thickening and regional kyanite-sillimanite grade Barroviantype metamorphism(ca.22-14 Ma),to orogenic collapse(periods of‘extensional’fabrics relate to:(1)Exhumation of blueschists and eclogite facies rocks showing tight-isoclinal folds and top-NE,base-SW fabrics,recording return flow along a subduction channel in a compressional tectonic setting(ca.50-35 Ma).(2)Extensional fabrics within the core complexes formed by exhumation of kyanite-and sillimanite gneisses showing thrust-related fabrics at the base and‘extensional’fabrics along the top(ca.18.5-14 Ma).(3)Regional ductile-brittle‘extensional’fabrics and low-angle

关键词： Cyclades Ophiolite High-pressure metamorphism Core complex Compressional tectonics

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I Don’t peer-Review for Non-Open Journals,and Neither Should You

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Journal of Data and Information Science 2022年第2期7卷 1-3页

作者： michael p.Taylor Department of Earth Sciences University of BristolBristol BS81RJEngland

“The reasonable man adapts himself to the world;the unreasonable one persists in trying to adapt the world to *** all progress depends on the unreasonable man.”-Maxims for Revolutionists,George Bernard Shaw(1903).In the twenty years since the Budapest Open Access Initiative(BOAI,2002)defined the term“open access”(OA)and laid out the unanswerable case in its favour,the growth of OA has been *** publishers,dependent on the revenue stream provided by subscriptions,have repeatedly attempted to stem this tide,and have certainly succeeded in delaying it-to no-one’s benefit but their *** OA progresses despite this rearguard action,especially in recent years through the adoption by many major research funders of the plan S declaration(plan S,2018),that open-access publication is a condition of grant *** the time of writing,over half of all newly published papers are open access either immediately or within a few months(piwowar,priem,&Orr,2019),and the proportion continues to increase rapidly.

关键词： Open repeatedly continue

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Immunotherapy for hepatocellular carcinoma:Current and future

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World Journal of Gastroenterology 2019年第24期25卷 2977-2989页

作者： michael p Johnston Salim I Khakoo Department of Hepatology Southampton General HospitalUniversity Hospital SouthamptonSouthampton SO16 6YDUnited Kingdom Department of Clinical and Experimental Sciences Faculty of MedicineSouthampton General HospitalUniversity of SouthamptonSouthampton SO16 6YDUnited Kingdom

Hepatocellular carcinoma(HCC)arises on the background of chronic liver *** the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fatty liver *** patients present with advanced disease out with the criteria for transplant,resection or even locoregional *** available therapeutics for HCC are effective in a small minority of ***,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers,great opportunities now exist for treating HCC with newer and more sophisticated *** checkpoint inhibitors are at the forefront of this revolution,other therapeutics such as inhibitory cytokine blockade,oncolytic viruses,adoptive cellular therapies and vaccines are *** these may be categorized as either boosting existing immune response or stimulating de novo immune *** some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional *** these agents are likely to generate new and exciting opportunities for treating HCC,which are summarized in this review.

关键词： Adoptive cell therapy Cancer vaccine Checkpoint inhibitor Hepatocellular carcinoma Immunotherapy Liver cancer Oncolytic virus

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Enhanced electrogastrography: A realistic way to salvage a promise that was never kept?

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World Journal of Gastroenterology 2017年第25期23卷 4517-4528页

作者： michael D poscente Martin p Mintchev Department of Electrical and Computer Engineering University of Calgary

To enhance the clinical utility of electrogastrography (EGG), which has been recorded since 1922, but is clinically unutilized. METHODSAn innovative method to salvage the promise of EGG is proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegratable, biocompatible pseudobesoar residing in the stomach for the duration of the test. The benefits of the proposed approach are outlined, tested and discussed in details. RESULTSExperiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. pharmacologically facilitated gastric motility revealed a significant (p pearson correlation between gastric motility indices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments which already utilize standard EGG testing. The expanded intragastric pseudobezoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. CONCLUSIONEnhancing standard EGG by an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electronic oscillator can be an important avenue for clinical applicability of this test.

关键词： Electrogastrography Functional dyspepsia Gastroparesis Ingestible oscillator pseudobesoar

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