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Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in nonalcoholic steatohepatitis patients

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Acta Pharmaceutica Sinica B 2023年第1期13卷 1-28页

作者： Solène Marie kayla l.frost Raymond K.Hau lucy Martinez-Guerrero Jailyn M.Izu Cassandra M.Myers Stephen H.Wright Nathan J.Cherrington College of Pharmacy Department of Pharmacology&ToxicologyUniversity of ArizonaTucsonAZ 85721USA College of Medicine Department of PhysiologyUniversity of ArizonaTucsonAZ 85724USA

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and ***-alcoholic steatohepatitis(NASH)causes disease-specific alterations to the absorption,distribution,metabolism,and excretion(ADME)processes,including a decrease in protein expression of basolateral uptake transporters,an increase in efflux transporters,and modifications to enzyme *** can result in increased drug exposure and adverse drug reactions(ADRs).Our goal was to predict drugs that pose increased risks for ADRs in NASH *** research identified 71 drugs with reported ADRs in patients with liver disease,mainly non-alcoholic fatty liver disease(NAFlD),54 of which are known substrates of transporters and/or metabolizing *** NASH is the progressive form of NAFlD but is most frequently undiagnosed,we identified other drugs at risk based on NASH-specific alterations to ADME ***,we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH,based on their transport and/or metabolism *** encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients,especially when eliminated through multiple pathways altered by the ***,these results may inform clinicians regarding the selection of drugs for use in NASH patients.

关键词： Non-alcoholic steatohepatitis Hepatic elimination Transporter Enzyme Pharmacokinetics Drug-drug interaction liver Adverse drug reaction

Nitrogen-doped graphene quantum dots: Optical properties modification and photovoltaic applications

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Nano Research 2019年第5期12卷 1041-1047页

作者： Md Tanvir Hasan Roberto Gonzalez-Rodriguez Conor Ryan Kristof Pota kayla Green Jeffery l.Coffer Anton V.Naumov Department of Physics and Astronomy Texas Christian UniversityTCU Box 298840Fort WorthTexas 76129USA Department cf Chemistry and Eiochemistry Texas Christian UniversityTCU Box 298860Fort WorthTexas 76129USA

In this work,we utilize a bottom-up approach to synthesize nitrogen self-doped graphene quantum dots (NGQDs) from a single glucosamine precursor via an eco-friendly microwave-assisted hydrothermal *** and optical properties of as-produced NGQDs are further modified using controlled ozone ***-treated NGQDs (Oz-NGQDs) are reduced in size to 5.5 nm with clear changes in the lattice structure and/D//G Raman ratios due to the introduction/alteration of oxygen-containing functional groups detected by Fourier-transform infrared (FTIR) spectrometer and further verified by energy dispersive X-ray spectroscopy (EDX) showing increased atomic/weight percentage of oxygen *** with structural modifications,GQDs experience decrease in ultraviolet-visible (UV-vis) absorption coupled with progressive enhancement of visible (up to 16 min treatment) and near-infrared (NIR)(up to 45 min treatment) *** allows fine-tuning optical properties of NGQDs for solar cell applications yielding controlled emission increase,while controlled emission quenching was achieved by either blue laser or thermal *** Oz-NGQDs were further used to form a photoactive layer of solar calls with a maximum efficiency of 2.64% providing a 6-fold enhancement over untreated NGQD devices and a 3-fold increase in fill factor/current *** study suggests simple routes to alter and optimize optical properties of scalably produced NGQDs to boost the photovoltaic performance of solar cells.

关键词： nitrogen-doped graphene quantum dots ozone treatment optical properties photovoltaics solar cells

iStent inject trabecular microbypass stent implantation with cataract extraction in open-angle glaucoma:early clinical experience

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Eye and Vision 2020年第3期7卷 266-274页

作者： Tanner J.Ferguson Zachary Dockter Adam Bleeker kayla l.Karpuk Justin Schweitzer Mitch J.Ibach John P.Berdahl Cole Eye Institute Cleveland ClinicClevelandOHUSA University of South Dakota Sanford School of Medicine Sioux FallsSDUSA Cleveland Eye Clinic ClevelandOHUSA Vance Thompson Vision Sioux FallsSDUSA

Background:Retrospective,consecutive case series to evaluate the implantation of two second-generation trabecular microbypass stents in combination with cataract surgery in a real-world,clinical ***:The series included 56 eyes implanted with the iStent inject device with *** series consisted of eyes with primary open-angle glaucoma(n=52)and pseudoexfoliative glaucoma(n=4).Primary outcome measures included intraocular pressure(IOP)and number of glaucoma *** outcomes included the need for secondary surgical intervention and the incidence of IOP spikes≥10 mmHg and≥15 ***:IOP was reduced by 21%to 14.7±2.9 mmHg(plaucoma medications was 1.5±0.9 and reduced by 39%to 0.9±1.2(pline.55%of eyes were medication-free at 6 months,up from 18%at *** were no severe postoperative *** eyes underwent an additional glaucoma ***:Implantation of the iStent inject device with concomitant cataract surgery effectively provides a sustained reduction in IOP with a markedly improved medication burden out to 6 months *** safety profile is excellent.

关键词： Micro-invasive glaucoma surgery Minimally invasive glaucoma surgery MIGS Trabecular microbypass stent Open-angle glaucoma

Synthesis of a-SnWO_4 thin-film electrodes by hydrothermal conversion from crystalline WO_3

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Chinese Chemical letters 2015年第4期26卷 474-478页

作者： kayla J.Pyper Taylor C.Evans Bart M.Bartlett Department of Chemistry University of Michigan

Thin film electrodes of the orthorhombic form of tin tungstate （α-SnWO4） were prepared using a hydrothermal method to convert thin films of WO3 in aqueous SnCI2. The pH dependence of the growth mechanism was identified by scanning electron microscopy （SEM） and X-ray diffraction （XRD）. The XRD patterns show complete conversion of WO3（s） to SnWO4（s） at pH 1, 4, and 7. SEM images reveal a morphology change from sponge-like platelets to sharp nanowires as the pH increases from 1 to 7. The α-SnWO4 thin films were reddish brown in color, and display an indirect band gap of 1.9 eV by diffuse reflectance UV-vis spectroscopy. α-SnWO4 is therefore solar-responsive, and a chopped light linear sweep voltammogram recorded under 100 mW/cm2 AM1.5 simulated solar illumination in a pH 5 0.1 mol/l KPi buffer show a visible light response for photoelectrochemical water oxidation, producing 32 μA/cm2 at 1.23 V vs. RHE.

关键词： Alpha tin tungstateHydrothermal conversionMicrostructureHydrothermal method

钠钾氯共转运体在γ-氨基丁酸引起的肠神经元兴奋中的作用

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生理学报 2020年第3期72卷 263-273页

作者：刘素梅郑丽飞 NEITZEl kayla 纪托 REN Wei 曲梅花美国威斯康星大学拉克罗斯分校科学与健康学院生物学系威斯康星州拉克罗斯市54601 美国俄亥俄州立大学医学院生理学与细胞生物学系俄亥俄州哥伦布市43210 首都医科大学基础医学院生理学与病理生理学系北京100069 潍坊市第二人民医院转化医学中心潍坊261053

γ-氨基丁酸(γ-aminobutyric acid, GABA)是成年个体中枢神经系统(central nervous system, CNS)的一种抑制性神经递质,但对未成熟CNS神经元有兴奋作用。出生后GABA对CNS神经元的作用由去极化逐渐转为超极化,这种转变主要是由于大脑Na^... 详细信息

γ-氨基丁酸(γ-aminobutyric acid, GABA)是成年个体中枢神经系统(central nervous system, CNS)的一种抑制性神经递质,但对未成熟CNS神经元有兴奋作用。出生后GABA对CNS神经元的作用由去极化逐渐转为超极化,这种转变主要是由于大脑Na^+-K^+-2Cl^-共运体1 (Na^+-K^+-2Cl^-symporter 1, NKCC1)表达逐渐减少和K^+-Cl^-共运体2 (K^+-Cl^-cotransporter 2, KCC2)表达增加。与CNS神经元不同,肠神经系统(enteric nervous system, ENS)中未成熟和成体神经元都可被GABA去极化。GABA激发ENS神经元兴奋的分子机制尚不清楚,但与ENS神经元内的高Cl^-浓度有关。本研究目的是检验一个假设,即ENS神经元的细胞内高Cl^-浓度是由NKCCs活动维持的。结果显示,NKCC2免疫反应性(immunoreactivity, IR)在出生后第1天(P1)大鼠结肠ENS中出现,随后持续升高,在P14达到稳定的高水平,并在成年后保持在这一水平。NKCC1的IR出现在P14大鼠的ENS中,并维持到成年。在任何发育阶段的大鼠ENS中都检测不到KCC2的IR。在ENS神经元中,NKCC1和NKCC2均与GABAA受体共同表达。外源性GABA (1 mmol/l)可引起ENS神经元膜去极化。GABA诱导的去极化逆转电位约为-16 m V。NKCC抑制剂布美他尼(50μmol/l)或速尿(300μmol/l)可显著抑制GABA诱导的去极化。布美他尼(50μmol/l)使GABA诱导的去极化逆转电位向超极化方向移动。无论是KCC抑制剂DIOA (20μmol/l)还是Cl^-/HCO3-交换抑制剂DIDS (200μmol/l)对GABA诱发的去极化都没有明显影响。以上结果提示,ENS表达NKCC1和NKCC2,但是不表达KCC2。NKCC1和NKCC2在GABA引起的肠神经元兴奋中起重要作用。

关键词：钠钾氯共转运体钾氯共转运体 γ-氨基丁酸肠神经系统胃肠道

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如何更好地为在线学生服务?

中国教育网络 2018年第12期 43-44页

作者： kayla l.Westra 俊琳不详

截至2016年,每年有600多万学生参加在线课程,其中三分之二以上是在公共机构。2016年之前的剧增之后,人数目前正在趋于稳定。其部分原因是学习管理系统和辅助结构已经巩固完善,而且更多高校也开始提供线上的辅导。在线课程多种多样,从相... 详细信息

截至2016年,每年有600多万学生参加在线课程,其中三分之二以上是在公共机构。2016年之前的剧增之后,人数目前正在趋于稳定。其部分原因是学习管理系统和辅助结构已经巩固完善,而且更多高校也开始提供线上的辅导。在线课程多种多样,从相对独立的学习课程到强大的互动课程,从完全异步的课程到带有一些同步组件的课程。部分机构已经完全接纳在线学习为一种新的学习形式,而另外一些机构也明确表示他们不会采用这种方式。虽然许多高校都提供在线学生服务来支持他们的在线学习者,但支持的类型和程度有很大的差异。

关键词：学生服务学习管理系统公共机构在线学习部分机构课程高校

Determination of Optimal Hormone and Mineral Salts levels in Tissue Culture Media for Callus Induction and Growth of Industrial Hemp (<i>Cannabis sativa</i>l.)

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Agricultural Sciences 2018年第10期9卷 1250-1268页

作者： Xoe Thacker kayla Thomas Matthew Fuller Shannon Smith John DuBois Department of Biology and the Tennessee Center for Botanical Medicine Research Middle Tennessee State University Murfreesboro TN USA

Historically, industrial hemp (Cannabis sativa l.) has been a valuable source of metabolites and compounds, such as cannabidiols. There is a need for large amounts of plant tissue to be grown under controlled environments, and plant tissue culture is one unique way to yield this tissue. The purposes of this study were to determine: 1) the optimal concentrations (μM)/ratios of auxin:cytokinin in media and;2) the optimal mineral salts formulation for callus induction and callus growth in select hemp cultivars. To find the optimal concentration/ratios, 16 different combinations of auxin:cytokinin and three different mineral salts formulations were evaluated. The three mineral salts formulations tested were MS salts, MB5D1K and an MTSU formulation. The top performing hormone formulations were determined to be equal concentrations (1:1, 2:2, 3:3 μM) of auxin and cytokinin. The top performing media hormone formulations for callus induction were determined to be 2:1, 2:2, 2:3, and 3:2 μM (auxin:cytokinin). The optimal mineral salts formulation was determined to be MD5D1K. Therefore, the overall optimal media formulation for hemp callus production would be MB5D1K salts with the concentration/ratio of 2:2 μM (auxin:cytokinin).

关键词： Industrial Hemp Cannabis Sativa Tissue Culture Hormones Mineral Salts Callus

Microgeographic Variation and Inter-Riffle Migration of <i>Rhinichthys atratulus</i>(Pisces: Cyprinidae) in a Small Connecticut Stream, United States

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Open Journal of Ecology 2020年第7期10卷 460-481页

作者： Sage J. loomis kayla Anatone laura Bither Sarah J. Kang Nola Neri David Machado Michelle l. Kraczkowski Barry Chernoff College of the Environment Wesleyan University Middletown USA Department of Biology Wesleyan University Middletown USA Department of Molecular Biology and Biochemistry Wesleyan University Middletown USA Department of Biology University of Saint Joseph West Hartford USA Department of Earth & Environmental Sciences Wesleyan University Middletown USA

We examined the genetic diversity on a microgeographic scale of Rhinichthys atratulus (Eastern Blacknose Dace) in Allyn Brook, a small tributary in the upper Coginchaug River drainage in Connecticut. By looking at gene flow on a microgeographic scale among populations that had no physical barriers to migration, we tested the null hypothesis that the populations should be homogeneous. We resolved seven polymorphic microsatellite loci and one mitochondrial gene, nd2, in three adjacent populations (llyn Brook and compared these populations to the two closest populations (>5 km) in the Coginchaug River. A dam from the 1920’s in lower Allyn Brook has isolated Allyn-Brook populations from Coginchaug-River populations. Allyn Brook was selected because there are only three riffle habitats in the brook and, therefore, there can be no immigration from upstream populations. Each population has private (i.e., unique) alleles and haplotypes, and there are significant genetic differences between all sites. The Allyn Brook populations are almost as different from one another as they are from the distant populations in the Coginchaug River from which they have been isolated for more than 80 years. These results point to in situ evolution and little migration or gene flow among populations on a microgeographic scale. This raises interesting questions for conservation of genetic diversity of stream fishes.

关键词： Migration Microgeographic Differentiation Population Ecology Gene Flow Rhinichthys atratulus

Interaction of Immune System Protein with PEGylated and Un-PEGylated Polymeric Nanoparticles

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Advances in Nanoparticles 2017年第3期6卷 103-113页

作者： Matthewos Eshete kayla Bailey Tuyen Duong Thanh Nguyen Santosh Aryal Seong-O Choi Department of Chemistry Mississippi Valley State University Itta Bena MS USA Nanotechnology Innovation Center of Kansas State (NICKS) Kansas State University Manhattan KS USA Department of Chemistry Kansas State University Manhattan KS USA Department of Anatomy and Physiology Kansas State University Manhattan KS USA

Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PlGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PlGA-COOH and PlGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DlS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PlGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PlGA-PEG-NH2 indicating conformational changes in the protein structure.

关键词： Nanoparticles Mannose-Binding Protein Poly (l-lactic-Co-Glycolic Acid) Nanoparticle Protein Interaction