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Mycophenolic acid (MPA), a frequently used immunosuppressant, exhibits large inter‐patient pharmacokinetic variability. This study (a) developed and validated a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for MPA and metabolites [MPA glucuronide (MPAG) and acyl‐glucuronide (AcMPAG)] in the culture medium of HepaRG cells; and (b) characterized the metabolism interaction between MPA and p‐cresol (a common uremic toxin) in this in vitro model as a potential mechanism of pharmacokinetic variability. Chromatographic separation was achieved with a C18 column (4.6 × 250 mm,5 μm) using a gradient elution with water and methanol (with 0.1% formic acid and 2 mm ammonium acetate). A dual ion source ionization mode with positive multiple reaction monitoring was utilized. Multiple reaction monitoring mass transitions (m/z) were: MPA (320.95 → 207.05), MPAG (514.10 → 303.20) and AcMPAG (514.10 → 207.05). MPA‐d3 (323.95 → 210.15) and MPAG‐d3 (517.00 → 306.10) were utilized as internal standards. The calibration curves were linear from 0.00467 to 3.2 μg/mL for MPA/MPAG and from 0.00467 to 0.1 μg/mL for AcMPAG. The assay was validated based on industry standards. p‐Cresol inhibited MPA glucuronidation (IC50 ≈ 55 μm ) and increased MPA concentration (up to >2‐fold) at physiologically relevant substrate‐inhibitor concentrations (n = 3). Our findings suggested that fluctuations in p‐cresol concentrations might be in part responsible for the large pharmacokinetic variability observed for MPA in the clinic. 相似文献
3.
The covalent boron–diol interaction enables elaborate design of boronic acid‐based saccharide sensors. Over the last decade, this research topic has been well developed thanks to the integration of boronic acid chemistry with a range of techniques, including supramolecular chemistry, materials chemistry, surface modification, and nanotechnology. New sensing strategies and platforms have been introduced and remarkable progress has been achieved to fully utilize the unique property of boron–diol interaction and to improve the binding affinity towards different targets, especially under physiological conditions. In this review, the latest progress over the past 30 months (from late 2012 to early 2015) is highlighted and discussed to shed light on this versatile and promising platform for saccharide sensing. 相似文献
4.
John R. Britnell Neil Saunders Tony Skyner 《Journal of Pure and Applied Algebra》2017,221(11):2647-2665
A finite group G is exceptional if it has a quotient Q whose minimal faithful permutation degree is greater than that of G. We say that Q is a distinguished quotient.The smallest examples of exceptional p-groups have order . For an odd prime p, we classify all pairs where G has order and Q is a distinguished quotient. (The case has already been treated by Easdown and Praeger.) We establish the striking asymptotic result that as p increases, the proportion of groups of order with at least one exceptional quotient tends to 1/2. 相似文献
5.
Tony Huynh Andrew D. King Sang‐il Oum Maryam Verdian‐Rizi 《Journal of Graph Theory》2017,84(2):158-175
A graph is strongly even‐cycle decomposable if the edge set of every subdivision with an even number of edges can be partitioned into cycles of even length. We prove that several fundamental composition operations that preserve the property of being Eulerian also yield strongly even‐cycle decomposable graphs. As an easy application of our theorems, we give an exact characterization of the set of strongly even‐cycle decomposable cographs. 相似文献
6.
Jan-Frederik Mai Steffen Schenk Matthias Scherer 《Journal of Theoretical Probability》2017,30(1):365-383
Two novel characterizations of self-decomposable Bernstein functions are provided. The first one is purely analytic, stating that a function \(\varPsi \) is the Bernstein function of a self-decomposable probability law \(\pi \) on the positive half-axis if and only if alternating sums of \(\varPsi \) satisfy certain monotonicity conditions. The second characterization is of probabilistic nature, showing that \(\varPsi \) is a self-decomposable Bernstein function if and only if a related d-variate function \(C_{\psi ,d}\), \(\psi :=\exp (-\varPsi )\), is a d-variate copula for each \(d \ge 2\). A canonical stochastic construction is presented, in which \(\pi \) (respectively \(\varPsi \)) determines the probability law of an exchangeable sequence of random variables \(\{U_k\}_{k\in {\mathbb {N}}}\) such that \((U_1,\ldots ,U_d) \sim C_{\psi ,d}\) for each \(d \ge 2\). The random variables \(\{U_k\}_{k\in {\mathbb {N}}},\) are i.i.d. conditioned on an increasing Sato process whose law is characterized by \(\varPsi \). The probability law of \(\{U_k\}_{k \in {\mathbb {N}}}\) is studied in quite some detail. 相似文献
7.
We consider random subgraphs of a fixed graph with large minimum degree. We fix a positive integer k and let Gk be the random subgraph where each independently chooses k random neighbors, making kn edges in all. When the minimum degree then Gk is k‐connected w.h.p. for ; Hamiltonian for k sufficiently large. When , then Gk has a cycle of length for . By w.h.p. we mean that the probability of non‐occurrence can be bounded by a function (or ) where . © 2016 Wiley Periodicals, Inc. Random Struct. Alg., 50, 143–157, 2017 相似文献
8.
Shubo Geng Hang Xu Chun-Shuai Cao Prof. Tony Pham Prof. Bin Zhao Prof. Zhenjie Zhang 《Angewandte Chemie (International ed. in English)》2023,62(32):e202305390
Adsorption-based removal of carbon dioxide (CO2) from gas mixtures has demonstrated great potential for solving energy security and environmental sustainability challenges. However, due to similar physicochemical properties between CO2 and other gases as well as the co-adsorption behavior, the selectivity of CO2 is severely limited in currently reported CO2-selective sorbents. To address the challenge, we create a bioinspired design strategy and report a robust, microporous metal–organic framework (MOF) with unprecedented [Mn86] nanocages. Attributed to the existence of unique enzyme-like confined pockets, strong coordination interactions and dipole-dipole interactions are generated for CO2 molecules, resulting in only CO2 molecules fitting in the pocket while other gas molecules are prohibited. Thus, this MOF can selectively remove CO2 from various gas mixtures and show record-high selectivities of CO2/CH4 and CO2/N2 mixtures. Highly efficient CO2/C2H2, CO2/CH4, and CO2/N2 separations are achieved, as verified by experimental breakthrough tests. This work paves a new avenue for the fabrication of adsorbents with high CO2 selectivity and provides important guidance for designing highly effective adsorbents for gas separation. 相似文献
9.
Dr. Vasily G. Panferov Nikita A. Ivanov Dr. Tony Mazzulli Dr. Davor Brinc Dr. Vathany Kulasingam Prof. Sergey N. Krylov 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2023,135(2):e202215548
Lateral flow immunoassay (LFIA) is a rapid, simple, and inexpensive point-of-need method. A major limitation of LFIA is a high limit of detection (LOD), which impacts its diagnostic sensitivity. To overcome this limitation, we introduce a signal-enhancement procedure that is performed after completing LFIA and involves controllably moving biotin- and streptavidin-functionalized gold nanoparticles by electrophoresis. The nanoparticles link to immunocomplexes forming multilayer aggregates on the test strip, thus, enhancing the signal. Here, we demonstrate lowering the LOD of hepatitis B surface antigen from approximately 8 to 0.12 ng mL−1, making it clinically acceptable. Testing 118 clinical samples for hepatitis B showed that signal enhancement increased the diagnostic sensitivity of LFIA from 73 % to 98 % while not affecting its 95 % specificity. Electrophoresis-driven enhancement of LFIA is universal (antigen-independent), takes two minutes, and can be performed by an untrained person. 相似文献
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