An improved LC–MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients

Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC–MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid-phase extraction-protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C₁₈ column using water containing 0.05% acetic acid along with 20 μM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m/z 830.3 → 548.8 and m/z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1–500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from −4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.     

A DNA Switch for Detecting Single Nucleotide Polymorphism within a Long DNA Sequence Under Denaturing Conditions

DNA detection is usually conducted under nondenaturing conditions to favor the formation of Watson–Crick base-paring interactions. However, although such a setting is excellent for distinguishing a single-nucleotide polymorphism (SNP) within short DNA sequences (15–25 nucleotides), it does not offer a good solution to SNP detection within much longer sequences. Here we report on a new detection method capable of detecting SNP in a DNA sequence containing 35–90 nucleotides. This is achieved through incorporating into the recognition DNA sequence a previously discovered DNA molecule that forms a stable G-quadruplex in the presence of 7 molar urea, a known condition for denaturing DNA structures. The systems are configured to produce both colorimetric and fluorescent signals upon target binding.     

Lipase‐Supported Metal–Organic Framework Bioreactor Catalyzes Warfarin Synthesis

A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase‐supported metal–organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors.     

Lithium Insertion Mechanism in Iron-Based Oxyfluorides with Anionic Vacancies Probed by PDF Analysis

The mechanism of lithium insertion that occurs in an iron oxyfluoride sample with a hexagonal–tungsten–bronze (HTB)-type structure was investigated by the pair distribution function. This study reveals that upon lithiation, the HTB framework collapses to yield disordered rutile and rock salt phases followed by a conversion reaction of the fluoride phase toward lithium fluoride and nanometer-sized metallic iron. The occurrence of anionic vacancies in the pristine framework was shown to strongly impact the electrochemical activity, that is, the reversible capacity scales with the content of anionic vacancies. Similar to FeOF-type electrodes, upon de-lithiation, a disordered rutile phase forms, showing that the anionic chemistry dictates the atomic arrangement of the re-oxidized phase. Finally, it was shown that the nanoscaling and structural rearrangement induced by the conversion reaction allow the in situ formation of new electrode materials with enhanced electrochemical properties.     

The single-polarization filter composed of gold-coated photonic crystal fiber

A single-polarization filter comprising a gold-coated photonic crystal fiber based on surface plasmon resonance is designed and investigated. The pattern matching and coupled polarization characteristics analyzed by the full-vector finite element method (FEM) and losses at 1,540 nm are achieved to 1,016.01739 dB/cm (x-pol core mode) and 33.81917 dB/cm (y-pol core mode). The crosstalk (CT) value of the 1,540 nm band is ?853.12653 dB for fiber length $L=1,000\mathrm{\mu }\text{m}$ and the bandwidth is 850 nm. The working wavelength of the filter ranges from 1,280 nm to 1,540 nm by varying the diameter of outer air holes ($d_1$), the diameter of inner air holes ($d_4$), the metal film thickness (t), as well as the liquid refractive index (n).     

Bimetallic Covalent Organic Frameworks for Constructing Multifunctional Electrocatalyst

Covalent organic frameworks (COFs) are a new class of crystalline porous polymers comprised mainly of carbon atoms, and are versatile for the integration of heteroatoms such as B, O, and N into the skeletons. The designable structure and abundant composition render COFs useful as precursors for heteroatom-doped porous carbons for energy storage and conversion. Herein, we describe a multifunctional electrochemical catalyst obtained through pyrolysis of a bimetallic COF. The catalyst possesses hierarchical pores and abundant iron and cobalt nanoparticles embedded with standing carbon layers. By integrating these features, the catalyst exhibits excellent electrochemical catalytic activity in the oxygen reduction reaction (ORR), with a 50 mV positive half-wave potential, a higher limited diffusion current density, and a much smaller Tafel slope than a Pt-C catalyst. Moreover, the catalyst displays superior electrochemical performance toward the hydrogen evolution reaction (HER), with overpotentials of −0.26 V and −0.33 V in acidic and alkaline aqueous solution, respectively, at a current density of 10 mA cm⁻². The overpotential in the catalysis of the oxygen evolution reaction (OER) was 1.59 V at the same current density.     

Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites

Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing [U-¹³C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.     

A Hydroperoxide-Mediated Decarboxylation of α-Ketoacids Enables the Chemoselective Acylation of Amines

Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the synthesis of peptides from amino acid derived α-ketoacids under preservation of the stereochemical information.     

A posteriori error estimation for a singularly perturbed Volterra integro-differential equation

Numerical Algorithms - A singularly perturbed Volterra integro-differential equation with an integrable singularity in the integral term is considered. The upwind difference method is used to...     

On Fermat Diophantine functional equations,little Picard theorem and beyond

Aequationes mathematicae - We discuss equivalence conditions for the non-existence of non-trivial meromorphic solutions to the Fermat Diophantine equation $$f^m(z)+g^n(z)=1$$ with integers $$m,n\ge...