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Biological fate and interaction with cytochromes P450 of the nanocarrier material,D-α-tocopheryl polyethylene glycol 1000 succinate

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3156-3166页

作者： Tianming Ren Runzhi Li Liqiang Zhao j.paul fawcett Dong Sun jingkai Gu Research Center for Drug Metabolism School of Life SciencesJilin UniversityChangchun 130012China State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun 130012China Beijing Institute of Drug Metabolism Beijing 102209China

D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)*** is approved by the US Food and Drug Administration(FDA)and has found wide application in nanocarrier drug delivery systems(NDDS).Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based ***,to date,a bioassay for the simultaneous quantitation of TPGS and its metabolite,PEG1000,has not been *** the present study,we developed such an innovative bioassay and used it to investigate the pharmacokinetics,tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous *** addition,we evaluated the interaction of TPGS with cytochromes P450(CYP450s)in human liver *** results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that,after intravenous administration,TPGS and PEG1000 are mainly distributed to the spleen,liver,lung and kidney before both being slowly eliminated in urine and feces as *** vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of ***,our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

关键词： TPGS LC-MS/MS Nanocarrier materials Pharmacokinetics Tissue distribution Metabolism Excretion Cytochrome P450

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Separation and simultaneous quantitation of PGF2α and its epimer 8-iso-PGF2α using modifier-assisted differential mobility spectrometry tandem mass spectrometry

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Acta Pharmaceutica Sinica B 2018年第2期8卷 228-234页

作者： Chunsu Liang Hui Sun Xiangjun Meng Lei Yina j.paul fawcett Huaidong Yu Ting Liu jingkai Gu Research Center for Drug Metabolism School of Life Sciences Jilin University School of Pharmacy University of Otago Shanghai AB Sciex Analytical Instrument Trading Co. Ltd.

Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/m L with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.

关键词： Differential mobility spectrometry Mass spectrometry Epimer PGF2α 8-iso-PGF2α

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Quantitation of bivalirudin,a novel anticoagulant peptide,in human plasma by LC-MS/MS:Method development,validation and application to pharmacokinetics

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journal of Pharmaceutical Analysis 2013年第1期3卷 1-8页

作者： Xiao-jiao Li Yan-Tong Sun Lei Yin Xue-ju Zhang Yan Yang j.paul fawcett Yi-Min Cui jing-Kai Gu Clinical Pharmacology Center Research Institute of Translational MedicineThe First Bethune Hospital of Jilin University Research Center for Drug Metabolism College of Life ScienceJilin University School of Pharmacy University of Otago Department of Pharmacy Peking University First Hospital

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.

关键词： Bivalirudin LC-MS/MS Pharmacokinetics Human plasma Anticoagulant

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Determination of repaglinide in human plasma by high-performance liquid chromatography–tandem mass spectrometry

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Acta Pharmaceutica Sinica B 2011年第1期1卷 40-45页

作者： jie Zhang Feng Gao Xin Guan Yan-tong Sun jing-kai Gu j.paul fawcett Research Center for Drug Metabolism College of Life ScienceJilin UniversityChangchun 130012People’s Republic of China School of Pharmaceutical Sciences Jilin UniversityChangchun 130012People’s Republic of China School of Pharmacy University of OtagoDunedinNew Zealand

A rapid and sensitive method based on high-performance liquid chromatography–tandem mass spectrometry(LC–MS/MS)has been developed for the determination of repaglinide in human *** analyte and internal standard(I.S.),diazepam,were extracted from plasma(25 mL)by liquid–liquid extraction with diethyl ether–dichloromethane(60:40,v/v)and separated on a XDB-C_(18) column using acetonitrile–ammonium acetate buffer(pH 6.8,0.01 mol/L)as mobile *** retention times of repaglinide and *** 1.95 and 2.35 min,*** was carried out using API 4000 mass spectrometer with an ESI interface operating in the multiple reaction monitoring(MRM)*** assay was linear over the concentration range 0.050–50 ng/mL with a limit of detection(LOD)of 0.010 ng/***-and inter-day precisions(as relative standard deviation,R.S.D.)were ≤5.07%and ≤11.2%,respectively,and accuracy(as relative error,R.E.)was from-0.593%to -1.26%.The assay was successfully applied to a pharmacokinetic study involving a single oral administration of a tablet containing 2 mg repaglinide to each of 10 healthy volunteers.

关键词： Repaglinide Pharmacokinetics LC–MS/MS Human plasma

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Helicobacter pylori serology in a birth cohort of New Zealanders from age 11 to 26

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World journal of Gastroenterology 2005年第21期11卷 3273-3276页

作者： j.paul fawcett Gill O.Barbezat Richie Poulton Barry j.Milne Harry H.X.Xia Nicholas j.Talley School of Pharmacy University of Otago DunedinNew Zealand Dunedin School of Medicine University of Otago DunedinNew Zealand Dunedin Multidisciplinary Health and Development Research Unit Dunedin School of Medicine University of Otago Dunedin New Zealand Department of Medicine The University of Hong Kong Queen Mary Hospital Hong Kong China Department of Medicine The University of Sydney Nepean HospitalNSW 2751Australia

AIM: To determine seroprevalence of Helicobacter pylori (Hpylori)in the Dunedin Multidisciplinary Health and Development Study (DMHDS) at age 26 in order to investigate seroconversion and seroreversion from age 11 to 26 and the association of seropositivity with risk factors for H pylori infection. METHODS: Participants in the DMHDS at age 26 and retrospectively at age 21 were tested for H pylori antibodies using two commercially available ELISA ***, socioeconomic status (SES), smoking,educational attainment and employment at age 26 were tested for association with H pylori seropositivity. RESULTS: At ages 21 and 26,seroprevalence of H pylori using one or other kit was 4.2% (n=795) and 6.3% (n=871) respectively, Seroreversion rate was lower than seroconversion rate (0.11% vs 0.53% per person-year) in contrast to the period from age 11 to 21 when seroreversion rate exceeded seroconversion rate (0.35% vs 0.11% per person-year). Serology in those tested at ages 11, 21, and 26 remained unchanged in 93.6% of the sample. Seroprevalence at age 26 was lower among those with a secondary school qualification (P=0.042) but was not associated with gender, SES, smoking or employment status. CONCLUSION: H pylori seroprevalence in a New Zealand birth cohort remains low between ages 11 and 26. H pylori infection remains stable from childhood to adulthood although seroreversion seems to be more common in the adolescent years than in young adults.

关键词： H pylori Seroprevalence Cohort

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Surface engineering with ionic polymers on membranes for boron removal

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Frontiers of Chemical Science and Engineering 2024年第5期18卷 61-69页

作者： Xiting Zhang Chenyi Fang j.paul Chen Sui Zhang Department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117576Singapore Department of Civil and Environmental Engineering National University of SingaporeSingapore 119260Singapore College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China

Removal of boric acid from seawater and wastewater using reverse osmosis membrane technologies is imperative and yet remains inadequately addressed by current commercial *** research efforts performed post-modification of reverse osmosis membranes to enhance boron rejection,which is usually accompanied by substantial sacrifice in water *** study delves into the surface engineering of low-pressure reverse osmosis membranes,aiming to elevate boron removal efficiency while maintaining optimal salt rejection and water *** were modified by the self-polymerization and co-deposition of dopamine and polystyrene sulfonate at varying ratios and *** surfaces became smoother and more hydrophilic after *** optimum membrane exhibited a water permeability of 9.2±0.1 L·m^(-2)·h^(-1)·bar^(-1),NaCl rejection of 95.8%±0.3%,and boron rejection of 49.7%±0.1% and 99.6%±0.3% at neutral and alkaline pH,*** water permeability is reduced by less than 15%,while the boron rejection is 3.7 times higher compared to the blank *** research provides a promising avenue for enhancing boron removal in reverse osmosis membranes and addressing water quality concerns in the desalination process.

关键词： membrane low-pressure reverse osmosis boron surface engineering

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A marathon,not a sprint:Increasing population physical activity as a legacy of sports mega-events

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journal of Sport and Health Science 2024年第6期13卷 732-735页

作者： Fiona C.Bull paul j.Simpson Physical Activity Unit Department of Health PromotionWorld Health OrganizationGeneva CH-1211Switzerland The BMj London WC1H 9JPUK

*** matters The withdrawal of Australia as hosts for the Commonwealth Games in 2026 demonstrates that large international sporting events are more than just sporting mastery,medals,and *** also matters.1 The cost of hosting a major international tournament is eye-wateringly *** governments need to show that the billions of dollars of investment deliver a return beyond sporting glory to justify the resources that are spent.

关键词： return dollar sport

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A vectorial model for the nonlinear gradient force exerted on metallic Rayleigh nanoparticles

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Chinese Optics Letters 2024年第2期22卷 207-213页

作者：朱政张聿全闵长俊 Aurèle j.LAdam H.paul Urbach 袁小聪 Research Center for Humanoid Sensing Research Institute of Intelligent SensingZhejiang LabHangzhou 311100China Nanophotonics Research Center Institute of Microscale Optoelectronics&State Key Laboratory of Radio Frequency Heterogeneous IntegrationShenzhen UniversityShenzhen 518060China Optics Research Group ImPhys DepartmentFaculty of Applied SciencesDelft University of TechnologyDelft 2628 CJThe Netherlands

Optical tweezers have proved to be a powerful tool with a wide range of *** gradient force plays a vital role in the stable optical trapping of *** scalar method is convenient and effective for analyzing the gradient force in traditional optical ***,when the third-order nonlinear effect of the nano-object is stimulated,the scalar method cannot adequately present the optical response of the metal nanoparticle to the external optical ***,we propose a theoretical model to interpret the nonlinear gradient force using the vector *** combining the optical Kerr effect,the polarizability vector of the metallic nanoparticle is derived.A quantitative analysis is obtained for the gradient force as well as for the optical potential *** vector method yields better agreement with reported experimental *** suggest that this method could lead to a deeper understanding of the physics relevant to nonlinear optical trapping and binding phenomena.

关键词： gradient forces nonlinear effect metallic nanoparticles

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Quasi-static and dynamic compressive behaviour of additively manufactured Menger fractal cube structures

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Defence Technology（防务技术） 2024年第7期37卷 39-49页

作者： Damith Mohotti Dakshitha Weerasinghe Madhusha Bogahawaththa Hongxu Wang Kasun Wijesooriya paul jHazell School of Engineering and Technology UNSWCanberraACT2600Australia School of Civil Mining and Environmental EngineeringFaculty of Engineering and Information SciencesUniversity of WollongongWollongongNSWAustralia

This paper presents the first-ever investigation of Menger fractal cubes'quasi-static compression and impact *** cubes with different void ratios were 3D printed using polylactic acid(PLA)with dimensions of 40 mm×40 mm×40 *** different orders of Menger cubes with different void ratios were considered,namely M1 with a void ratio of 0.26,M2 with a void ratio of 0.45,and M3with a void ratio of ***-static Compression tests were conducted using a universal testing machine,while the drop hammer was used to observe the behaviour under impact *** fracture mechanism,energy efficiency and force-time histories were *** the structured nature of the void formation and predictability of the failure modes,the Menger geometry showed some promise compared to other alternatives,such as foams and *** the increasing void ratio,the Menger geometries show force-displacement behaviour similar to hyper-elastic materials such as rubber and *** third-order Menger cubes showed the highest energy absorption efficiency compared to the other two geometries in this *** findings of the present work reveal the possibility of using additively manufactured Menger geometries as an energy-efficient system capable of reducing the transmitting force in applications such as crash barriers.

关键词： Additive manufacturing Fractal geometries Menger cube Energy absorption Quasi-static

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Effects of pyrethroid and organophosphate insecticides on reared black soldier fly larvae(Hermetia illucens)

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Insect Science 2024年第3期31卷 817-834页

作者： Nathan Meijer Lisa Zoet Theo de Rijk paul Zomer Deborah Rjkers H.j.van der Fels-Klerx joop j.A.van Loon Wageningen Food Safety Research(WFSR) Part of Wageningen University and ResearchWageningenThe Netherlands Bestico B.V. Industrieweg 6Berkel en RodenrjsThe Netherlands Plant Sciences Group Laboratory of EntomologyWageningen UniversityWageningenTheNetherlands

Black soldier fly larvae(Hermetia illucens)receive growing interest as a potential alternative animal feed *** insects may be exposed to insecticide residues in the rearing *** study aimed to investigate the effects of six different pyrethroid and organophosphate insecticides on this insect species'*** toxicity of two"model"substances for each of these classes(cypermethrin;pirimiphosmethyl)was quantified,with and without the synergist piperonyl butoxide(PBO).Critical effect doses corresponding to 10%yield(CED10)for cypermethrin(0.4 mg/kg)and pirimiphos-methyl(4.8 mg/kg)were *** addition of PBO to cypermethrin enhanced its relative potency with a factor *** data were compared against the relative toxicity of two analogue substances in each class(permethrin,deltamethrin;chlorpyrifosmethyl,malathion).Results suggest that exposure to concentrations complying with legal limits can cause significant reductions in *** to multiple substances at lower concentrations resulted in negative additive and synergistic *** the tested substances,deltamethrin was most toxic,causing 94%yield at 0.5 mg/*** results suggested that transfer of tested substances to the larval biomass was substance-and concentration-specific,but appeared to be correlated to reduced yields and the presence of *** of organophosphates was overall low(justing legally allowed maximum residue levels in insect feed.

关键词： feed insects pesticides rearing substrate

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