LAB ON A CHIP
·
2019
·Vol. 19
·期 16
·2651-2662
·
IF 6.914
Haili Zhao,Jin Sha,Xiaofeng Wang,Yongchao Jiang,Tao Chen,Tong Wu,Xin Chen,Huajian Ji,Yang Gao,Linsheng Xie,Yulu Ma
Spatially arranged polymer brushes provide the essential capability of precisely regulating the surface physicochemical and functional properties of various substrates. A novel and flexible polymer brush patterning methodology, which is based on employing a digital mirror device (DMD)-based light modulation technique to spatiotemporally regulate a surface-initiated photoinduced atom transfer radical polymerization (photo-ATRP) process, is presented. Various characterization techniques confirm that the spatially and/or temporally controlled brush formation results in complex PEG-derived brush patterns in accordance with a customized digital image design. A series of step-and-exposure strategies, including in situ multiple exposure, dynamic multiple exposure and dynamic sequential exposure, are developed to implement spatiotemporal regulation of the photo-ATRP process, leading to complex patterned and gradient brushes featuring binary functionalities, pyramid nanostructures and radial directional chemical gradients. Moreover, tunable and radial directional concentration gradients of various biomacromolecules (e.g., streptavidin) are obtained through preparation of height gradients of azido-functionalized brushes and subsequent orthogonal chemical activation aimed at specific protein immobilization. Finally, a unidirectional concentration gradient of fibronectin, surrounded by non-fouling PEG brushes, is fabricated and applied for human umbilical vein endothelial cell (HUVEC) adhesion experiments, whose preliminary results indicate gradient-dependent cell adhesion behavior in response to the concentration gradient of fibronectin. The presented fabrication technique could be integrated with microfluidic devices for sensors and bio-reactors, paving the way for novel approaches for lab-on-a-chip technologies.
研究领域:
材料科学
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生物医学工程
·
化学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 13.2
Dinggao Wang,Chao Zhang,Fahu Yang,Min Zhao,Feng Jiao,Zhongming Li,Haili Zhao,Tao Chen
Patterned liquid metals (LMs) are gaining significant attention as ideal candidate conductors for flexible and stretchable electronics due to their good conductivity and intrinsic deformability. In this work, a fabrication strategy was proposed for the facile and direct patterning of LM on various substrates without subsequent processing steps. Our approach utilizes stencil lithography based on the digital mirror device (DMD)-based light modulation technique to achieve selective adhesion of modified LM. Specifically, we introduced lithium magnesium sodium silicate (LiMgNaO 6 Si 2 ) particles as modifiers for eutectic gallium‑indium (EGaIn), resulting in a modified LM with enhanced adhesive properties. Concurrently, a DMD-based maskless lithography system was employed to fabricate patterned template on the substrates, enabling spatially selective adhesion of the modified LM to achieve the LM patterns with adequate resolution and customizable features. The as-fabricated LM conductive paths show good conductivity, stretchability, self-healing ability, electromechanical stability under different deformations, and reproducible printability without conductivity degradation. To evaluate the potential of this patterning method, a few applications such as flowing light-emitting diode (LED) systems and pressure-actuated sensing system have been demonstrated based on the resulting LM conductive paths, showing substantial application values in next-generation soft intelligent electronics and high-density flexible integrated circuits.
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2021
·
IF 2.694
Qiaoyan Shang,Jifa Xiao,Yan Li,Wenge Liu,Xiaojuan Liu,Guanwei Cui,Xifeng Shi,Shuqian Xia,Bo Tang
Biomass pyrolysis oil is considered to be a promising alternative to fossil energy for the synthesis of high value-added chemicals and fuels. 2-Methoxy-4-methyl phenol (MMP), 4-ethylphenol (EP), 3,5-dimethylphenol (DMP), and m-Cresol (MC) are the important phenolic compounds in pyrolysis oil. The investigation of phase equilibrium is crucial to design separation processes. In this work, the isobaric vapor–liquid equilibrium (VLE) experiment, correlation, and estimation of binary systems (cyclohexane + MMP/EP/DMP/MC) were investigated. The experimental data were verified by the Herington test and van Ness test, and all were thermodynamically consistent entirely. The binary energy interaction parameters were obtained by correlating the experimental data using NRTL, Wilson, and UNIQUAC activity coefficient models. The average absolute relative deviations (ARD %) of T, x1, and y1 correlated by NRTL, Wilson, and UNIQUAC models for four binary systems are below 0.2. In addition, the VLE data were correlated and estimated by the UNIFAC-DMD model. The new interaction parameters of the C–CH2 group in the UNIFAC-DMD model were obtained and used to estimate cyclohexane + DMP systems. The ARD % of T and y1 for cyclohexane + DMP systems were 1.02 and 0.43, respectively. The estimation accuracy of UNIFAC-DMD with new parameters was significantly improved.
研究领域:
化学工程
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能源科学
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2019
·
IF 2.298
Xia Yin,Chaochen Du,Jingjing Li,Wenbo Jiang,Yigang Ding,Hongmei Du,Zhiping Du,Zhiguo Yan
Carbonate esters and esters were commonly used as solvents, reaction carrier, and additives in organic synthesis, the pharmaceutical industry, and processing industries. Vapor–liquid equilibrium (VLE) data are vital to the separation process or process simulation for separating solvents. Therefore, it is necessary to enrich a VLE database for carbonate esters and esters. In this study, isobaric VLE data for three systems of isopropyl acetate + diethyl carbonate (DEC), sec-butyl acetate + DEC, and DEC + isoamyl acetate at 101.3 kPa were determined for enriching the group interaction parameters for carbonate esters. Meanwhile, the thermodynamic consistencies of the VLE data were tested using the Van Ness method modified by Fredenslund et al. The Wilson, NRTL, and UNIQUAC models were used and found to have good consistency for all binary systems between the experimental and simulated data. At the same time, the VLE data were correlated by the UNIFAC-DMD model to supplement the group parameters for carbonate esters. The average absolute deviation (AAD) of the temperature of the activity coefficient model and the UNIFAC-DMD model is not less than 0.16 K, and the AAD of the vapor phase mole fraction is not less than 0.0016. In addition, azeotropy did not occur in all binary systems.
研究领域:
化学工程
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热力学
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产品关联
DOI
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2023
·Vol. 51
·期 11
·1515-1526
·
IF 3.9
Xiaowen Wang,Yiqun Yu,Hongrui Liu,Fengjiao Bu,Chunying Shen,Qingfeng He,Xiao Zhu,Pin Jiang,Bing Han,Xiaoqiang Xiang
Ensartinib (X-396) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of ALK-positive patients with locally advanced or metastatic non–small cell lung cancer. Although in vitro experiments and molecular docking suggested its potential as a cytochrome P450 inhibitor, no further investigation or clinical trials have been conducted to assess its drug–drug interaction (DDI) risk. In this study, we conducted a series of in vitro experiments to elucidate the inhibition mechanism of ensartinib. Furthermore, a physiologically-based pharmacokinetic (PBPK) model was developed based on in vitro, in silico, and in vivo parameters, verified using clinical data, and applied to predict the clinical DDI mediated by ensartinib. The in vitro incubation experiments suggested that ensartinib exhibited strong time-dependent inhibition. Simulation results from the PBPK model indicated a significant increase in the exposure of CYP3A substrates in the presence of ensartinib, with the maximal plasma concentration and area under the plasma concentration-time curve increasing up to 12-fold and 29-fold for sensitive substrates. Based on these findings, it is evident that co-administration of ensartinib and CYP3A substrates requires careful regulatory consideration.
研究领域:
药理学
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临床药学
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生物医学工程
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2016
·Vol. 44
·期 4
·607-615
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IF 3.21
Kai Wang,Hui Wang,Ying Peng,Jiang Zheng
Benzbromarone (BBR) is a benzofuran derivative that has been quite useful for the treatment of gout; however, it was withdrawn from European markets in 2003 because of reported serious incidents of drug-induced liver injury. BBR-induced hepatotoxicity has been suggested to be associated with the formation of a quinone intermediate. The present study reported epoxide-derived intermediate(s) of BBR. An N-acetylcysteine (NAC) conjugate derived from epoxide metabolite(s) was detected in both microsomal incubations of BBR and urine samples of mice treated with BBR. The NAC conjugate was identified as 6-NAC BBR. Ketoconazole suppressed the bioactivation of BBR to the epoxide intermediate(s), and the CYP3A subfamily was the primary enzyme responsible for the formation of the epoxide(s). The present study provided new information on metabolic activation of BBR.
研究领域:
药理学
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毒理学
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药物代谢
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2019
·Vol. 47
·期 8
·794-801
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IF 3.354
Hongwei Yao,Ruifeng Bai,Tianming Ren,Yani Wang,Jingkai Gu,Yingjie Guo
Clopidogrel (Clop), a thienopyridine antiplatelet prodrug, is metabolized by cytochrome P450s (CYPs) to an active metabolite, Clop-AM, and hydrolyzed by carboxylesterase (CES)1 to the inactive Clop-acid. Patients with type 2 diabetes (T2DM) tend to have a poor response to Clop due to reduced generation of Clop-AM. Whether a similar response occurs in the Zucker diabetic fatty (ZDF) rat, a commonly used animal model of T2DM, has not been explored. In this work, we compared ZDF and control rats for hepatic CES1- and CYP-mediated Clop metabolism; pharmacokinetics of Clop, Clop-AM, and Clop-acid; and the antiplatelet efficacy of Clop. In contrast to clinical findings, Clop-treated ZDF rats displayed significantly less (50%) maximum platelet aggregation at 4 hours than control rats; the enhanced efficacy was accompanied by higher formation of Clop-AM and lower formation of Clop-acid. In vitro studies showed that hepatic levels of CES1 protein and activity and Ces1e mRNA were significantly lower in ZDF than in control rats, as were the mRNA levels of CYP2B1/2, CYP2C11, and CYP3A2, and levels of CYP2B6-, CYP2C19-, and CYP3A4-related proteins and enzymatic activities in liver microsomes of ZDF rats. Interestingly, liver microsomes of ZDF rats produced higher levels of Clop-AM than that of control rats despite their lower CYP levels, although the addition of fluoride ion, an esterase inhibitor, enhanced Clop-AM formation in control rats more than in ZDF rats. These results suggest that the reduction in CES1-based Clop inactivation indirectly enhances Clop efficacy in ZDF rats by making more Clop available for CYP-mediated Clop-AM formation.
研究领域:
药理学
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糖尿病研究
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代谢
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药物动力学
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2015
·Vol. 43
·期 4
·433-443
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IF 3.252
Enxi Quan,Huailing Wang,Dong Dong,Xingwang Zhang,Baojian Wu
Active transport of glucuronide out of cells is a critical process in elimination of drugs via the glucuronidation pathway. Here, HeLa cells were stably transfected with UGT1A1 and the contributions of BCRP and MRP family transporters to the cellular efflux of chrysin glucuronide (CG) were determined. The cDNA of UGT1A1 was introduced into HeLa cells using the lentiviral transfection method. The modified cells were functional in generation of the glucuronide from chrysin. Ko143 at 10–20 μM (a dual inhibitor of BCRP and UGT1A1) caused a marked decrease (51.3%–59.7%, P < 0.01) in the excretion rate and efflux clearance of CG. Likewise, MK-571 at 5–20 μM (an inhibitor of MRPs but an activator of UGT1A1) resulted in a significant reduction in the excretion rate (18.2%–64.0%, P < 0.01) and efflux clearance (37.0%–90.2%, P < 0.001). By contrast, dipyridamole and leukotriene C4 showed no inhibitory effects on CG excretion. The chemical inhibition indicated that excretion of CG was contributed by the MRP family transporters, whereas the role of BCRP was unclear. Furthermore, short hairpin RNA–mediated silencing of a target transporter led to a marked reduction in the excretion rate of CG (38.6% for BCRP, 39.3% for MRP1, 36.4% for MRP3, and 28.7% for MRP4; P < 0.01). Transporter silencing also led to substantial decreases in the efflux clearance (44.7% for BCRP, 60.4% for MRP1, 36.7% for MRP3, and 28.7% for MRP4; P < 0.01). The gene silencing results suggested that BCRP, MRP1, MRP3, and MRP4 were significant contributors to excretion of CG.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2023
·Vol. 51
·期 12
·1651-1662
·
IF 3.9
Xue Zhang,Jianquan Pan,Xi Ye,Yunna Chen,Lei Wang,Xiangyun Meng,Weidong Chen,Fengling Wang
Reduced enzyme activity in hepatocellular carcinoma (HCC) and poor targeting limit the application of enzyme-activating prodrugs, which is also detrimental to the effective treatment of HCC. Here, we investigated whether accelerated blood clearance (ABC) phenomenon occurs in HCC models following repeated injections of PEGylated liposomes (PEG-L), thus inducing prodrug accumulation and activation in the liver and exerting highly effective and low-toxicity therapeutic effects on HCC. First, PEGylated liposomal cyclophosphamide was prepared by solvent injection and characterized. Importantly, preinjection of PEG-L induced the ABC phenomenon and activation of CYP3A in both HCC rats and HCC mice by studying the effects of repeated injections of PEG-L on pharmacokinetics and tissue distribution. Next, the efficacy and toxicity of repeated injections of PEG-L in HCC mice were examined, and our data indicate that repeated injections are administered in a manner that significantly enhances the antitumor effect compared with controls, with little or no toxicity to other organs. To further reveal the pharmacokinetic mechanism of PEG-L repeated administration for the treatment of HCC, the protein expression of hepatic CYP3A and the concentration of cyclophosphamide in the liver and spleen of HCC mice by inhibiting CYP3A were analyzed. These results revealed that inducing CYP3A to accelerate the rapid conversion of prodrugs that accumulate significantly in the liver is a key mechanism for the treatment of HCC with repeated injections of PEG-L. Collectively, this work taps into the application potential of the ABC phenomenon and provides new insights into the clinical application of PEGylated nanoformulations.
研究领域:
药理学
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肿瘤学
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纳米医学
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药物递送系统
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 8
·911-918
·
IF 4.4
Jingyu Zhang,Weiwei Li,Ying Liu,Yan He,Zihao Cheng,Ximei Li,Yu Chen,Aihua Zhang,Ying Peng,Jiang Zheng
Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug–drug interactions.
研究领域:
毒理学
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药理学
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药学
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 7
·597-605
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IF 4.4
Ting Wu,Lu Li,Wenhong Zhou,Guofang Bi,Xiaowen Jiang,Manlan Guo,Xiao Yang,Jianhong Fang,Jianxin Pang,Shicheng Fan,Huichang Bi
Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly.
研究领域:
药理学
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微生物学
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肝脏病学
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分子生物学
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 2
·106-117
·
IF 4.4
Yufan Zhou,Hongjiao Dong,Jiang Fan,Mingshe Zhu,Lu Liu,Yongbin Wang,Pingming Tang,Xiaoyan Chen
Ciprofol (HSK3486) is a novel intravenous agent for general anesthesia. In humans, HSK3486 mainly undergoes glucuronidation to form M4 [fraction of clearance (fCL): 62.6%], followed by the formation of monohydroxylated metabolites that further undergo glucuronidation and sulfation to produce M5-1, M5-2, M5-3, and M3 (summed fCL: 35.2%). However, the complete metabolic pathways of HSK3486 in humans remain unclear. In this study, by comparison with chemically synthesized reference standards, three monohydroxylated metabolites [M7-1, 4-hydroxylation with an unbound intrinsic clearance (CLint,u) of 2211 μl/min/mg; M7-2, ω-hydroxylation with a CLint,u of 600 μl/min/mg; and M7-3, (ω-1)-hydroxylation with a CLint,u of 78.4 μl/min/mg] were identified in human liver microsomes, and CYP2B6 primarily catalyzed their formation. In humans, M7-1 was shown to undergo glucuronidation at the 4-position and 1-position by multiple UDP-glucuronosyltransferases (UGTs) to produce M5-1 and M5-3, respectively, or was metabolized to M3 by cytosolic sulfotransferases. M7-2 was glucuronidated at the ω position by UGT1A9, 2B4, and 2B7 to form M5-2. UGT1A9 predominantly catalyzed the glucuronidation of HSK3486 (M4). The CLint,u values for M4 formation in human liver and kidney microsomes were 1028 and 3407 μl/min/mg, respectively. In vitro to in vivo extrapolation analysis suggested that renal glucuronidation contributed approximately 31.4% of the combined clearance. In addition to HSK3486 glucuronidation (M4), 4-hydroxylation (M7-1) was identified as another crucial oxidative metabolic pathway (fCL: 34.5%). Further attention should be paid to the impact of CYP2B6- and UGT1A9-mediated drug interactions and gene polymorphisms on the exposure and efficacy of HSK3486.
研究领域:
药理学
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生物化学
·
临床医学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）