Name: an intestine/liver microphysiological system for drug pharmacokinetic and toxicological assessment
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Description: Watch this Scientific Journal Video about An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment at JoVE.com

我们感谢克里斯蒂·古根-吉卢佐博士、INSERM 522单元的菲利普·格里邦博士和271 INSERM单元的克里斯蒂安·特雷波博士使用生物材料（Hepa RG细胞），并随后提供给我们进行学术研究。

1. 生产组织等价物，用于2-OC的栽培
<ol><li>小肠屏障当量生产<ol>
<li>使用肠道等效介质维持 Caco-2 和 HT-29 细胞：DMEM 辅以 10% FBS、1% 青霉素和链霉素，以及 1% 非必需氨基酸，本手稿中称为"DMEM S"。</li>
		<li>取出培养基，用1x DPBS洗涤两次，并加入8 mL的0.25%的尝试素/EDTA，以分离细胞培养瓶中生长的Caco-2细胞（175厘米2）。在37°C下孵育5分钟，通过添加至少双量的三辛抑制剂来停止反应。对HT-29?...

<ol>
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M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shp2+negatively+regulates+growth+in+cardiomyocytes+by+controlling+focal+adhesion+kinase/src+and+mTOR+pathways.">Shp2 negatively regulates growth in cardiomyocytes by controlling focal adhesion kinase/src and mTOR pathways.</a> Circulation Research. 103 (8), 813-824 (2008).</li><li>Linkert, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metadata+matters:+Access+to+image+data+in+the+real+world.">Metadata matters: Access to image data in the real world.</a> Journal of Cell Biology. 189 (5), 777-782 (2010).</li><li>OECD. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=OECD+TG+491+-+Short+Time+Exposure+In+vitro+Test+Method+for+Identifying+i)+Chemicals+Inducing+Serious+Eye+Damage+and+ii)+Chemicals+Not+Requiring+Classification+for+Eye+Irritation+or+Serious+Eye+Damage.">OECD TG 491 - Short Time Exposure In vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage.</a> OECD. 14, (2018).</li><li>Fernandes, M. 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准确、可靠地评估研究性新药的药理特性，对于降低以下开发步骤的风险至关重要。MPS 是一项相对较新的技术，旨在提高预测能力，减少临床前测试的成本和时间。我们的团队正在推进对铅优化所需的药代动力学和毒理学特性的评估。我们与2-OC微流体装置合作，该装置有两个腔室，允许两个器官的整合。APAP之所以被选中，是因为它拥有大量高质量的人类数据，大部分是肝脏代谢的，并且也表现?...

由于基因组和蛋白质组的差异，动物模型对几种人类结果的预测价值有限。此外，它们既费时又昂贵，而且在道德上也值得怀疑。MPS 是一项相对较新的技术，旨在提高预测能力，减少临床前测试的成本和时间。它们是在媒体流下培养器官（器官的人工模仿功能单元）的微流体装置，促进器官-器官通信。由人类细胞制造的有机体增加转化相关性2，3，4。MPS 预期性能优于动物试验，因为它们是基因人类，并重述组织之间的相互作用。当完全正常运行时，MPS 将提供更有意义的结果，以更高的速度和更低的成本和风险 4。许多团体正在开发MPS，用于多种目的，特别是疾病模型，以测试药物的疗效。
暴露水平是评估药物疗效和毒性的最关键参数之一5，6，7，8，9，10，11，12。MPS 允许有机体整合，模拟全身暴露，预期性能优于传统的 2D 人体组织培养。该技术可显著提高复合肠道吸收和肝代谢的预测。
考虑到这两个器官在药物生物利用度和全身暴露13、14、15等的中心作用，整合肠道和肝脏等量模型的MPS是一个很好的起点。APAP是一种有吸引力的药物，用于研究没有肾脏等价物的MPS，因为它的代谢主要由肝脏16，17完成。
2-OC是一种双室微流体装置，适用于由微通道16连接的两种不同人体等效组织/器官的培养。为了模拟体外人类口服/静脉注射药物，并评估肠道和肝脏等价物之间的交代对APAP药代动力学的影响， 除了器官的功能和生存能力外，还进行了三种不同的MPS组件：（1） 一个"肠2-OC MPS"，由一个肠道等效物组成，其培养物中含有一个包含Caco-2+HT-29细胞共培养的培养物，并集成到2-OC装置中;（2） 由肝球类组成、由 HepaRG + HHSteC （人类肝状斯特拉特细胞） 组成的"肝脏 2-OC MPS"，集成在 2-OC 器件中;和 （3） 由一个设备隔间中的肠道等效物组成的"肠/肝脏 2-OC MPS"，通过介质流经微流体通道与肝脏等效物通信。
由于机械刺激（压缩、拉伸和剪切）对细胞的生存能力和功能18、19、20的影响，所有测定都是在静态（无流动）和动态（带流量）条件下进行的。本文介绍了APAP口服/静脉注射给药模拟的方案，以及含有人类肠道和肝脏等效模型的2-OC MPS中各自的吸收/代谢和毒理学分析。

<table>
	<tbody>
		<tr>
			<td>1x DPBS</td>
			<td>Thermo Fisher Scientific</td>
			<td>14190235</td>
			<td>No calcium, no magnesium</td>
		</tr>
		<tr>
			<td>2-OC</td>
			<td>TissUse GmbH</td>
			<td></td>
			<td>Two-organ chip</td>
		</tr>
		<tr>
			<td>384-well Spheroid Microplate</td>
			<td>Corning</td>
			<td>3830</td>
			<td>Black/Clear, Round Bottom, Ultra-Low Attachment</td>
		</tr>
		<tr>
			<td>4% Paraformaldehyde</td>
			<td></td>
			<td></td>
			<td>Use to fix cell</td>
		</tr>
		<tr>
			<td>Acetaminophen</td>
			<td>Sigma Aldrich</td>
			<td>A7085</td>
			<td>Use to MPS assays</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>Tedia</td>
			<td></td>
			<td>Used to perform HPLC</td>
		</tr>
		<tr>
			<td>Alexa Fluor 647 phalloidin</td>
			<td>Thermo Fisher Scientific</td>
			<td></td>
			<td>confocal experiment</td>
		</tr>
		<tr>
			<td>Ammonium acetate</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td>Used to perform HPLC</td>
		</tr>
		<tr>
			<td>Caco-2 cells</td>
			<td>Sigma Aldrich</td>
			<td>86010202</td>
			<td></td>
		</tr>
		<tr>
			<td>Cacodylate buffer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cell culture flasks</td>
			<td>Sarstedt</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Confocal Fluorescence microscope</td>
			<td>Leica</td>
			<td>DMI6000</td>
			<td></td>
		</tr>
		<tr>
			<td>Cryostat</td>
			<td>Leica</td>
			<td>CM1950</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM high glucose</td>
			<td>Thermo Fisher Scientific</td>
			<td>12800017</td>
			<td>Add supplements: 10% fetal bovine serum, 100 units per mL penicillin, 100 &#181;g/mL streptomycin, and 1% non-essential amino acids</td>
		</tr>
		<tr>
			<td>DMSO</td>
			<td>Sigma Aldrich</td>
			<td>D4540</td>
			<td>Add 2% to HepaRG media</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Synth</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal Bovine Serum</td>
			<td>Thermo Fisher Scientific</td>
			<td>12657029</td>
			<td></td>
		</tr>
		<tr>
			<td>Freezing medium OCT</td>
			<td>Tissue-Tek</td>
			<td></td>
			<td>Tissue-Tek&#174; O.C.T.&#8482; Compound is a formulation of watersoluble glycols and resins, providing a convenient specimen matrix for cryostat sectioning at temperatures of -10&#176;C and below.</td>
		</tr>
		<tr>
			<td>Hematoxylin &#38; Eosin</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>HepaRG cells</td>
			<td>Biopredic International</td>
			<td>HPR101</td>
			<td>Undifferentiated cells</td>
		</tr>
		<tr>
			<td>HHSTeC</td>
			<td>ScienCell Research Laboratories</td>
			<td>5300</td>
			<td>Cells and all culture supplements</td>
		</tr>
		<tr>
			<td>Hoechst 33342</td>
			<td></td>
			<td></td>
			<td>HCA experiments</td>
		</tr>
		<tr>
			<td>HT-29 cells</td>
			<td>Sigma Aldrich</td>
			<td>85061109</td>
			<td></td>
		</tr>
		<tr>
			<td>Human Insulin</td>
			<td>Invitrogen - Thermo Fisher Scientific</td>
			<td>12585014</td>
			<td></td>
		</tr>
		<tr>
			<td>Hydrocortisone</td>
			<td>Sigma Aldrich</td>
			<td>H0888</td>
			<td></td>
		</tr>
		<tr>
			<td>Isopropanol</td>
			<td>Merck</td>
			<td>278475</td>
			<td></td>
		</tr>
		<tr>
			<td>Karnovsky&#8217;s fixative</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>L-glutamine</td>
			<td>Thermo Fisher Scientific</td>
			<td>A2916801</td>
			<td></td>
		</tr>
		<tr>
			<td>Luna C18 guard column SS</td>
			<td>Phenomenex</td>
			<td></td>
			<td>Used to perform HPLC</td>
		</tr>
		<tr>
			<td>Microscope</td>
			<td>Leica</td>
			<td>DMi4000</td>
			<td></td>
		</tr>
		<tr>
			<td>Microtome</td>
			<td>Leica</td>
			<td>RM2245</td>
			<td></td>
		</tr>
		<tr>
			<td>Millicell 0.4 &#181;m pore size inserts</td>
			<td>Merck</td>
			<td>PIHP01250</td>
			<td></td>
		</tr>
		<tr>
			<td>Millicell ERS-2 meter</td>
			<td>Merck</td>
			<td>MERS00002</td>
			<td>Used to TEER measurement</td>
		</tr>
		<tr>
			<td>MitoTracker Deep Red</td>
			<td></td>
			<td></td>
			<td>HCA experiments</td>
		</tr>
		<tr>
			<td>MTT</td>
			<td>Thermo Fisher Scientific</td>
			<td>M6494</td>
			<td></td>
		</tr>
		<tr>
			<td>MX3000P system</td>
			<td>Agilent Technologies</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Neubauer chamber</td>
			<td></td>
			<td></td>
			<td>Counting cells</td>
		</tr>
		<tr>
			<td>Operetta High Content Imaging System</td>
			<td>Perkin Elmer</td>
			<td></td>
			<td>Used to perform HCA</td>
		</tr>
		<tr>
			<td>P450-Glo CYP3A4 Assay with Luciferin-IPA</td>
			<td>Promega</td>
			<td>Cat.# V9001</td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin/Streptomycin</td>
			<td>Thermo Fisher Scientific</td>
			<td>15070063</td>
			<td>Cell culture</td>
		</tr>
		<tr>
			<td>Permount</td>
			<td>Thermo Fisher Scientific</td>
			<td></td>
			<td>Histology</td>
		</tr>
		<tr>
			<td>Primers</td>
			<td></td>
			<td></td>
			<td>RT-qPCR</td>
		</tr>
		<tr>
			<td>PVDF membrane</td>
			<td>BioRad</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PVDF Syringe filter</td>
			<td></td>
			<td></td>
			<td>0.22 &#956;m pore size</td>
		</tr>
		<tr>
			<td>Reversed-phase Luna C18 column</td>
			<td>Phenomenex</td>
			<td></td>
			<td>Used to perform HPLC</td>
		</tr>
		<tr>
			<td>Shaker (IKA VXR Basic Vibrax)</td>
			<td>IKA Works GmbH &#38; Co</td>
			<td>2819000</td>
			<td>Used for spheroids to improve MTT assay</td>
		</tr>
		<tr>
			<td>Stellate Cell Media (STeC CM)</td>
			<td>ScienCell</td>
			<td>5301</td>
			<td>Add STeC CM supplements</td>
		</tr>
		<tr>
			<td>SuperScriptIITM Reverse Transcriptase</td>
			<td>Thermo Fisher Scientific</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>SYBR Green PCR Master Mix</td>
			<td>Thermo Fisher Scientific</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>TRizol TM reagent</td>
			<td>Thermo Fisher Scientific</td>
			<td></td>
			<td>Trizol is a monophasic solution of phenol and guanidine isothiocyanate.</td>
		</tr>
		<tr>
			<td>Trypsin/EDTA solution</td>
			<td>Thermo Fisher Scientific</td>
			<td>R001100</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultra-low-attachment plates</td>
			<td>Corning</td>
			<td>CLS3471-24EA</td>
			<td>6 wells</td>
		</tr>
		<tr>
			<td>Vectashield plus DAPI mounting media</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>White Opaque 96-well Microplate</td>
			<td>PerkinHelmer</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Wide-bore tips</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Williams E</td>
			<td>Pan Biotech</td>
			<td>P04-29510</td>
			<td>Add supplements: 10% fetal bovine serum, 2 mM L-glutamine, 100 units per ml penicillin, 100 &#181;g/mL streptomycin and 5 &#181;g/mL human insulin</td>
		</tr>
	</tbody>
</table>

an intestine/liver microphysiological system for drug pharmacokinetic and toxicological assessment

最近引进的培养人体器官的微生理系统（MPS）在药物开发过程的临床前测试阶段有望比动物表现更好，因为它们是遗传人类，并重述组织之间的相互作用。在这项研究中，将人类肠道屏障（由Caco-2和HT-29细胞的共培养物模拟）和肝脏当量（由分化的肝细胞和人类肝硬质细胞的球类模拟）整合到双器官芯片（2-OC）微流体装置中，以评估一些乙酰氨基酚（APAP）药理动力学（PK）和毒理学特性。MPS有三个组件：肠道只有2-OC，肝脏只有2-OC，和肠/肝脏2-OC与相同的介质细读两个器官。对于 PK 评估，我们在通过肠道屏障（模拟口腔路线）或介质（模拟静脉路线）后，在介质中以预设的时间点对 APAP 进行加注，分别值 12 μM 和 2 μM。通过反相高压液相色谱（HPLC）对介质样品进行分析。对器官分析为基因表达，TEER值，蛋白质表达和活性，然后收集，固定，并提交一组形态学评估。MTT 技术在评估器官生存能力方面表现良好，但高含量分析 （HCA） 能够检测出非常早期的毒性事件，以响应 APAP 治疗。我们验证，介质流没有显著影响APAP吸收，但它显著改善肝脏等效功能。APAP人类肠道吸收和肝代谢可以在MPS中模拟。MPS 数据与硅建模之间的关联在提高体外方法的可预测性方面有很大的潜力，并且比在药代动力学和毒理学研究中的动物模型具有更高的准确性。

要在 2-OC MPS 中执行 PK APAP 测试，第一步是制造人肠和肝脏等价物（器官）。在开始PKAPAP检测之前，它们被集成到2-OC微流体装置（图1A）24小时。第二天，介质被更改，模型将暴露在 APAP。图 1显示了放置在 2-OC 设备（图1B）和APAP PK 实验时间过程（图1C）内的肠道和肝脏等价物。我们在 2D 培养物和 3D 器官中进?...

Watch this Scientific Journal Video about An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment at JoVE.com

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

我们向对乙酰氨基酚（APAP）暴露了含有肠道和肝脏器官的微生理系统（MPS）。本文介绍了MPS中器官生产和APAP药代动力学和毒理学属性评估的方法。它还描述了验证结果所需的组织功能分析。

药物药代动力学和毒理学评估的肠道/肝脏微生理系统

The recently introduced microphysiological systems (MPS) cultivating human organoids are expected to perform better than animals in the preclinical tests ...

微生理系统能够模拟药代动力学和人体对特定兴趣治疗的毒理学反应。微生理系统有可能取代动物试验，因为其使用可以提高体外方法的预测能力，并降低药理学和毒理学研究的成本和时间。在测试物质被检出前24小时，在两个器官芯片的较大和更小的隔间之间分离出800微升的Will william ES介质，并在准备的24个孔板中从每个肠道屏障中吸气。使用无菌钳子，将每两个器官芯片电路中的一个插入物集成到较大的隔间中，并将 200 微升 DMEMS 添加到阴性侧。使用宽孔尖端，将每个电路的 20 个肝脏当量集成到两个器官芯片的较小隔间中，并将系统连接到控制单元。然后将控制单元连接到加压空气供应，将压力设置为大约正负 300 条，泵送频率为 0.3 赫兹。第二天，将库存对乙酰氨基酚溶液稀释至12微摩尔浓度。为了取代系统中的介质，从两个器官芯片中的肠道屏障当量中吸气基质和阴极介质，并在器官基质侧大隔间中加入500微升新鲜合适的培养基，将300微升添加到小隔间。检查气泡后，模拟口服给药，在肠道培养物插入的一端添加200微升12微摩尔醋氨酚溶液，并将微生理系统连接到控制单元。从肠道和基础侧以及在指示时间点三边的小隔间收集总体积。收集所有样品后，按表中所示设置 HPLC 分析的所有相关参数，并在真空下通过 0.4 微米膜过滤器过滤移动相。然后通过 0.22 微米孔径 PVDF 注射器过滤器过滤样品，并在开始 HPLC UV 测量之前将样品存放在小瓶中。为了评估有机体的可行性，将每个复制的所有20个球类转移到96孔板的单个孔中，并将细胞培养插入物转移到24孔板的单个孔中。每次洗涤用新鲜 DPBS 清洗组织等价物三次，并在每个实验井中加入 300 微升每毫升 MTT 溶液 1 毫克。在细胞培养箱中孵育三个小时后，将 MTT 溶液替换为每口200微升异丙醇，在4摄氏度下进行夜间孵育，从肠道和肝脏当量中提取MTT formazan。第二天早上，将每个上流液的200微升转移到96井板中的适当井中，并在570纳米的板读卡器上读取前体，以便计算细胞的相对能力，使用与负对比相比，每个时间点的平均光密度来降低MTT。对于样品的细胞化学和组织学分析，首先在室温下将肠道和肝脏当量在0.1摩尔PBS中4%半甲醛中固定25分钟。在孵化结束时，每次洗涤用PBS洗五次有机物10分钟，然后用四甲苯胺甲胺聚丙酮亚历克萨氟647 phaloidin在室温下染色1小时。在孵育结束时，将样品转移到冷冻介质上几分钟，然后将组织在液氮中捕捉冷冻。接下来，使用低温恒温器获取 10 至 12 微米厚的肝球类低温截面，并使用 DAPI 将组织部分安装到安装介质中，通过共声荧光显微镜进行成像。对于线粒体和核染色，用线粒体染色溶液完全覆盖样品，在37摄氏度的加湿环境中用5%的二氧化碳孵育15至45分钟。在孵育结束时，在室温下小心地将染色溶液用PBS中的2至4%甲状甲醛替换15分钟。固定后，用新鲜 PBS 轻轻冲洗两次细胞，每次洗涤五分钟，然后用核酸染色工作溶液标记样品，在室温下冲洗 10 分钟。在孵化结束时，用三、五分钟在PBS中清洗样品，防止光线产生光，并使用核酸染色，以利于用适当的过滤器在荧光显微镜上量化线粒体染色表达细胞的数量。将人类肠道屏障和肝脏等价物整合到两个器官芯片微流体装置中，可以评估感兴趣的治疗的药代动力学和毒理学特性。经过处理，HPLC 可分析介质样本。可以分析器官的基因表达、跨上皮电阻值、蛋白质表达和活性，以及它们的形态特征。MTT 分析可以进行评估器官的生存能力，以及检测对乙酰氨基酚治疗的早期毒性事件。介质流对对乙酰氨基酚的吸收没有显著影响，同时显著改善肝脏等效功能，表明人类肠道对乙酰氨基酚吸收和肝代谢可以在这个微观生理系统中进行模拟。微型生理系统有可能取代药物开发和发现中的动物模型，因为它们能更好地模仿人类生理学，并可用于以更高的速度和更低的风险和复杂性成本促进药物开发。

Research

Education

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Pharmacology

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Unit 1

Pharmacokinetics

SCIENTISTS IN ACTION

Preparation and Characterization of SDF-1&#945;-Chitosan-Dextran Sulfate Nanoparticles

Preparation and Characterization of SDF-1ÃƒÅ½Ã‚Â±-Chitosan-Dextran Sulfate Nanoparticles

SDF-1α - 壳聚糖硫酸葡聚糖纳米粒子的制备与表征

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under ...

科研

化学

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

制备及个体表征和多载药物理截留聚合物胶束

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

协议的合成<em&gt;邻</em&gt; -trifluoromethoxylated苯胺类化合物

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

PTR-ToF-MS Coupled with an Automated Sampling System and Tailored Data Analysis for Food Studies: Bioprocess Monitoring, Screening and Nose-space Analysis

PTR-ToF-MS结合自动采样系统和食品研究定制数据分析：生物过程监测，筛选和鼻空间分析

Proton Transfer Reaction (PTR), combined with a Time-of-Flight (ToF) Mass Spectrometer (MS) is an analytical approach based on chemical ionization that ...

An Aptamer-based Sensor for Unchelated Gadolinium(III)

An Aptamer-based Sensor for Unchelated GadoliniumIII

对于未螯合钆基于核酸适配体传感器（III）

A method for determining the presence of unchelated trivalent gadolinium ion (Gd3+) in aqueous solution is demonstrated. Gd3+ is often present in samples ...

Real-time Breath Analysis by Using Secondary Nanoelectrospray Ionization Coupled to High Resolution Mass Spectrometry

利用二次 Nanoelectrospray 电离耦合高分辨质谱的实时呼吸分析

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental ...

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling

用于化学诱导的 DNA 化和表观遗传重塑的基因工程 Split-TET2 酶

DNA methylation is a stable and heritable epigenetic modification in the mammalian genome and is involved in regulating gene expression to control ...

Generation of Electronic Cigarette Aerosol by a Third-Generation Machine-Vaping Device: Application to Toxicological Studies

第三代机械 Vaping 装置生成电子烟气溶胶: 毒理学研究的应用

Electronic-cigarette (e-cig) devices use heat to produce an inhalable aerosol from a liquid (e-liquid) composed mainly of humectants, nicotine, and ...

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry

New analytical methods are urgently needed to enable high-throughput, yet comprehensive drug screening, given an alarming opioid and prescription drug ...

An Electrochemical Cholesteric Liquid Crystalline Device for Quick and Low-Voltage Color Modulation

一种用于快速和低压彩色调制的电化学胆固醇液晶器件

We demonstrate a method for fabricating a prototype reflective display device that contains cholesteric liquid crystal (LC) as an active component. The ...