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
·
2016
·Vol. 44
·期 1
·40-49
·
IF 3.21
Ning Zhou,Yuanting Zheng,Junfen Xing,Huiying Yang,Hanmei Chen,Xiaoqiang Xiang,Jing Liu,Shanshan Tong,Bin Zhu,Weimin Cai
Currently used in vitro models for estimating liver metabolism do not take into account the physiologic structure and blood circulation process of liver tissue. The Bio-PK metabolic system was established as an alternative approach to determine the in vitro intrinsic clearance of the model drug tolbutamide. The system contained a peristaltic pump, recirculating pipeline, reaction chamber, and rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogel. The metabolism of tolbutamide at initial concentrations of 100, 150, and 200 μM was measured in both the FAB hydrogel and the circular medium. The data from the FAB hydrogel and the circular medium were fitted to a mathematical model to obtain the predicted intrinsic clearance of tolbutamide after different periods of preincubation. The in vitro clearance value for tolbutamide was incorporated into Simcyp software and used to predict both the in vivo clearance value and the dynamic process of elimination. The predicted in vivo clearance of tolbutamide was 0.107, 0.087, and 0.095 L/h/kg for i.v. injection and 0.113, 0.095, and 0.107 L/h/kg for oral administration. Compared with the reported in vivo clearance of 0.09 L/h/kg (i.v.) and 0.10 L/h/kg (oral), all the predicted values differed by less than twofold. Thus, the Bio-PK metabolic system is a reliable and general in vitro model, characterized by three-dimensional structured RLM and circulation and perfusion processes for predicting the in vivo intrinsic clearance of low-extraction compounds, making the system more analogous with the rat in terms of both morphology and physiology
研究领域:
药代动力学
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药物代谢
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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
·
2020
·Vol. 48
·期 11
·1129-1136
·
IF 3.231
Jian Lu,Ang Chen,Xinrun Ma,Xuyang Shang,Yuanjin Zhang,Yuanqing Guo,Mingyao Liu,Xin Wang
Cytochrome P450 2J2 (CYP2J2) enzyme attracts more attention because it not only metabolizes clinical drugs but also mediates the biotransformation of important endogenous substances and the regulation of physiologic function. Although CYP2J2 is very important, few animal models are available to study its function in vivo. In particular, a CYP2J gene knockout (KO) rat model for drug metabolism and pharmacokinetics is not available. In this report, the CRISPR/Cas9 technology was used to delete rat CYP2J3/10, the orthologous genes of CYP2J2 in humans. The CYP2J3/10 KO rats were viable and fertile and showed no off-target effect. Compared with wild-type (WT) rats, the mRNA and protein expression of CYP2J3/10 in liver, small intestine, and heart of KO rats were completely absent. At the same time, CYP2J4 mRNA expression and protein expression were significantly decreased in these tissues. Further in vitro and in vivo metabolic studies of astemizole, a typical substrate of CYP2J, indicated that CYP2J was functionally inactive in KO rats. The heart function indexes of WT and KO rats were also measured and compared. The myocardial enzymes, including creatine kinase–muscle brain type (CK-MB), creatine kinase (CK), and CK-MB/CK ratio, of KO rats increased by nearly 140%, 80%, and 60%, respectively. In conclusion, this study successfully developed a new CYP2J3/10 KO rat model, which is a useful tool to study the function of CYP2J in drug metabolism and cardiovascular disease.
研究领域:
药理学
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分子生物学
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遗传学
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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
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 3
·188-197
·
IF 4.4
Ying Liu,Yu Chen,Jingyu Zhang,Guangyun Ran,Zihao Cheng,Xin Wang,Yufen Liao,Xu Mao,Ying Peng,Weiwei Li,Jiang Zheng
Dihydrotanshinone I (DHTI) is a pharmacologically active component occurring in the roots of the herbal medicine Salvia miltiorrhiza Bunge. This study investigated DHTI-induced inhibition of CYP1A1, CYP1A2, and CYP1B1 with the aim to determine the potential effects of DHTI on the bioactivation of estradiol (E2), possibly related to preventive/therapeutic strategy for E2-associated breast cancer. Ethoxyresorufin as a specific substrate for CYP1s was incubated with human recombinant CYP1A1, CYP1A2, or CYP1B1 in the presence of DHTI at various concentrations. Enzymatic inhibition and kinetic behaviors were examined by monitoring the formation of the corresponding product. Molecular docking was further conducted to define the interactions between DHTI and the three CYP1s. The same method and procedure were employed to examine the DHTI-induced alteration of E2 metabolism. DHTI showed significant inhibition of ethoxyresorufin O-deethylation activity catalyzed by CYP1A1, CYP1A2 and CYP1B1 in a concentration-dependent manner (IC50 = 0.56, 0.44, and 0.11 μM, respectively). Kinetic analysis showed that DHTI acted as a competitive type of inhibitor of CYP1A1 and CYP1B1, whereas it noncompetitively inhibited CYP1A2. The observed enzyme inhibition was independent of NADPH and time. Molecular docking analysis revealed hydrogen bonding interactions between DHTI and Asp-326 of CYP1B1. Moreover, DHTI displayed preferential activity to inhibit 4-hydroxylation of E2 (a genotoxic pathway) mediated by CYP1B1. Exposure to DHTI could reduce the risk of genotoxicity induced by E2.
研究领域:
药理学
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生物化学
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癌症研究
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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
·
药物递送系统
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2020
·Vol. 48
·期 1
·52-62
·
IF 3.231
Chong Chen,Qingqing Ding,Boyu Shen,Tengjie Yu,He Wang,Yangfan Xu,Huimin Guo,Kangrui Hu,Lin Xie,Guangji Wang,Yan Liang
Glutathione (GSH) has been reported to be closely related to various diseases of the central nervous system, yet its authentic active ingredients and action sites remain unclear. In the present study, oral exogenous GSH significantly alleviated ischemic brain injury, but this result was inconsistent with its low bioavailability and blood-brain barrier (BBB) permeability. To ascertain the exposure of GSH-derived ingredients, including GSH, cysteine (CYS), glutamate (Glu), glycine (GLY), CYS-GLY, and γ-glutamylcysteine (γ-GC) were systematically studied both in vitro and in vivo. The outcomes demonstrated that oral GSH not only increases the GSH and CYS levels in rat striatum and cortex, but it also can decrease the rise of intracerebral Glu concentration caused by ischemia/reperfusion surgery. Then the influence of GSH on the BBB was investigated via measuring IgG leakage, intracerebral endotoxin, and tight-junction proteins. All indicators showed that GSH dosing can repair the destroyed BBB. Oral GSH greatly enhances the exposure of GSH, CYS, CYS-GLY, and γ-GC in rat duodenum, jejunum, ileum, and colon. Accumulating evidence reveals a close link between brain injury and gastrointestinal dysfunction. Our findings further suggest that oral GSH significantly improves intestinal inflammatory damage and barrier disruptions. In conclusion, oral GSH can have a direct therapeutic role in brain injury by stabilizing intracerebral levels of GSH, CYS, and Glu. It can also play an indirect therapeutic role by enhancing the intestinal exposure of GSH, CYS, CYS-GLY, and γ-GC and improving intestinal barrier disruptions.
研究领域:
神经科学
·
药理学
·
药代动力学
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药效学
·
中枢神经系统疾病
·
胃肠生理学
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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）