Stereoselective Crystallization of Chiral Pharmaceuticals Aided by Cellulose Derivatives through Helical Pattern Matching.

Stereoselective inhibition aided by "tailor-made" polymeric additives is an efficient approach to obtain enantiopure compounds through conglomerate crystallization. The chemical and configurational match between the side groups of polymers and the molecules of undesired enantiomer is considered to be a necessary condition for successful stereoseparation. Whereas in this contribution, we present an effective resolution of chiral pharmaceuticals by using cellulose acetates as the additives, which stereoselectively reside on the specific crystal faces of one enantiomer and inhibit its crystal nucleation and growth through helical pattern and supramolecular interaction complementarity.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel.

A Double Mutation in the Gene Confers a High Level of Resistance to Mesosulfuron-Methyl in Shepherd's-Purse.

Shepherd's-purse (), a globally distributed noxious weed species often found in wheat, has evolved resistance to ALS-inhibiting herbicides mainly due to single mutations in the gene. In the present study, dose-response bioassays showed that a shepherd's-purse population (R), collected from Xinghua, Jiangsu Province, China, had high level of resistance to the ALS-inhibiting herbicide, mesosulfuron-methyl (800-fold), and even much higher resistance levels to other reported ALS-inhibiting herbicides, tribenuron-methyl (1313-fold), bensulfuron-methyl (969-fold) and penoxsulam (613-fold). Sequencing of the open reading frame of the gene revealed a double gene mutation (Pro197-Ser plus Trp574-Leu) conferring the high resistance in the R plants.

Differential Mobility Spectrometry-Tandem Mass Spectrometry with Multiple Ion Monitoring Coupled with in Source-Collision Induced Dissociation: A New Strategy for the Quantitative Analysis of Pharmaceutical Polymer Excipients in Rat Plasma.

Polylactic acids (PLAs) are synthetic polymers composed of repeating lactic acid subunits. For their good biocompatibility, PLAs have been approved and widely applied as pharmaceutical excipients and scaffold materials. Liquid chromatography-tandem mass spectrometry is a powerful analytical tool not only for pharmaceutical ingredients but also for pharmaceutical excipients.

Recrystallization of Hot-Rolled 2A14 Alloy during Semisolid Temperature Annealing Process.

In this study, in order to provide proper parameters for the preparation of semisolid billets, the semisolid annealing of hot-rolled 2A14 Al alloy was investigated. The microstructure was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) with an X-ray energy dispersive spectrometer (EDS) and electron backscattered diffraction (EBSD), and scanning transmission electron microscopy (STEM). The XRD results showed that, with an increase in temperature, the θ-Al2Cu equilibrium gradually dissolved in the matrix.

C,N co-doped TiO hollow nanofibers coated stainless steel meshes for oil/water separation and visible light-driven degradation of pollutants.

Complex pollutants are discharging and accumulating in rivers and oceans, requiring a coupled strategy to resolve pollutants efficiently. A novel method is proposed to treat multiple pollutants with C,N co-doped TiO hollow nanofibers coated stainless steel meshes which can realize efficient oil/water separation and visible light-drove dyes photodegradation. The poly(divinylbenzene-co-vinylbenzene chloride), P(DVB-co-VBC), nanofibers are generated by precipitate cationic polymerization on the mesh framework, following with quaternization by triethylamine for N doping.

Fabrication of Rigid Isocyanate-Based Polyimide Foam Achieved Excellent Use Safety via Synergy between Expandable Graphite and Phosphorus-Containing Polyol.

For the advantages of low cost, excellent thermal insulation, and sound absorption properties, the rigid isocyanate-based polyimide foam (RPIF) presents great application prospects as a building insulation material. However, its inflammability and the accompanying toxic fumes create huge safety hazard. In this paper, reactive phosphate-containing polyol (PPCP) is synthesized and employed with expandable graphite (EG) to obtain RPIF with excellent use safety.

Numerical Simulation and Experimental Validation of Squeeze Casting of AlSi9Mg Aluminum Alloy Component with a Large Size.

The squeeze casting process for an AlSi9Mg aluminum alloy flywheel housing component was numerically simulated using the ProCAST software, and orthogonal simulation tests were designed according to the L16 (4) orthogonal test table to investigate the alloy melt flow rule under four factors and four levels each of the pouring temperature, mold temperature, pressure holding time and specific pressure, as well as the distributions of the temperature fields, stress fields and defects. The results showed that the flywheel housing castings in all 16 test groups were fully filled, and the thinner regions solidified more quickly than the thicker regions. Hot spots were predicted at the mounting ports and the convex platform, which could be relieved by adding a local loading device.

Study on the Interaction between Deuterium Clopidogrel and Omeprazole.

Introduction: Dual antiplatelet therapy with aspirin in combination with a P2Y12 receptor antagonist is a cornerstone for treating patients with acute coronary syndrome and in percutaneous coronary intervention. However, as this combination of antiplatelet therapy increases the risk of bleeding, proton pump inhibitors (PPIs) are currently recommended to prevent gastrointestinal ulcers and bleeding. The cytochrome P450 (CYP450) isoenzyme system metabolizes both clopidogrel (CLP) and PPIs.

Evaluation of efficacy and safety after replacement of methyl hydrogen with deuterium at methyl formate of Clopidogrel.

Background And Purpose: Despite being a first-line clinical drug, thienopyridines have many unsatisfactory aspects, including the low bioavailability of clopidogrel(CLP) and the high bleeding risk of prasugrel. We synthesized deuterium clopidogrel(D-CL, patented in China) to alleviate the deficiency of CLP in clinical, such as a slow onset, a greater influence of gene polymorphism, and a high frequency of drug-drug interaction.

Experimental Approach: Molecular docking was used to analyze the affinity between D-CL and the P2Y receptor.

Zwitterionic Polymer Hairy Coating onto Mesh toward Easy Oil/Water Separation.

A zwitterionic polymeric hair-coated stainless steel mesh membrane is fabricated, which demonstrates efficient separation of oil/water mixtures and emulsions. The hairy coating of poly(divinylbenzene-co-vinylbenzene chloride) is generated by precipitation cationic polymerization, and subsequently grafting a zwitterionic polymer layer by atom transfer radical polymerization of sulfobetaine methacrylate. The microstructure of the hairy coating is tunable from an array of individual nanofibers to porous networks by interweaving of the hairs.

High-throughput bioanalysis of sitagliptin in plasma using direct analysis in real time mass spectrometry and its application in the pharmacokinetic study thereof.

Sitagliptin is a dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes mellitus. In the present study, a sensitive and high-throughput quantitative method based on the direct analysis in real time tandem mass spectrometry has been developed and validated for the bioanalysis of sitagliptin in rat plasma without chromatographic separation. Sitagliptin and its internal standard retagliptin were detected in positive ion mode by multiple reaction monitoring transitions at m/z 408.

Effects of Isothermal Temperature and Soaking Time on Water Quenched Microstructure of Nickel-Based Superalloy GH3536 Semi-Solid Billets.

Semi-solid billets of GH3536 alloy were prepared by semi-solid isothermal treatment of wrought superalloy method. GH3536 samples were soaked at several semi-solid temperatures (1350 °C, 1360 °C, 1364 °C, and 1367 °C) for 5-120 min. The effects of temperature and soaking time on the microstructure of GH3536 billets were studied.

Fabrication of PεCL-AuNP-BSA core-shell-corona nanoparticles for flexible spatiotemporal drug delivery and SERS detection.

Nanoparticles with protein coronae can be used as promising multifunctional platforms for nanomedicine due to the possibility of performing surface functionalization on protein molecules and the achievement of biomedical properties. In this research, nanoparticles (NPs) with poly(ε-caprolactone) (PεCL) cores, gold NP (AuNP) shells and BSA coronae were fabricated by a self-assembly approach. The hydrophobic PεCL cores were used to encapsulate curcumin (CUR), the AuNP shells were decorated with a Raman probe, and the protein molecules in the coronae were functionalized with folic acid (FA).

Janus Surface Micelles on Silica Particles: Synthesis and Application in Enzyme Immobilization.

In these years, synthesis and applications of Janus structures have aroused great interest for large-scale applications in chemistry and materials science. Up to now, Janus particles with different morphologies and different functionalities have been synthesized in solutions, but the synthesis of Janus particles on solid surfaces has not been touched. In this research, Janus surface micelles (JSMs) are fabricated on the surfaces of silica particles by polymerization induced surface self-assembly (PISSA) approach, and the JSMs are used for enzyme immobilization.

Biosurfaces Fabricated by Polymerization-Induced Surface Self-Assembly.

Surface biofunctionalization provides an approach to the fabrication of surfaces with improved biological and clinical performances. Biosurfaces have found increasing applications in many areas such as sensing, cell growth, and disease detection. Efficient synthesis of biosurfaces without damages to the structures and functionalities of biomolecules is a great challenge.

Surface Nanostructures Based on Assemblies of Polymer Brushes.

Studies on the fabrication of hierarchical surface nanostructures have significantly promoted the development of materials with new surface properties and functionalities. In this Minireview, progress on the fabrication of surface nanostructures based on surface organization of polymer brushes are outlined. In the past decades, self-assemblies of polymer brushes, including homopolymer, block-copolymer and mixed-polymer brushes, have aroused great interest in the fields of chemistry and materials science.

Biomimetic Mineralization of Protein Nanogels for Enzyme Protection.

Protein nanogels have found a wide variety of applications, ranging from biocatalysis to drug/protein delivery. However, in practical applications, proteins in nanogels may suffer from enzymic hydrolysis and denaturation. Inspired by the structure and functionalities of the fowl eggshells, biomimetic mineralization of protein nanogels was studied in this research.

Absorption, distribution, metabolism and excretion of the biomaterials used in Nanocarrier drug delivery systems.

Nanocarriers (NCs) are a type of drug delivery system commonly used to regulate the pharmacokinetic and pharmacodynamic properties of drugs. Although a wide variety of NCs has been developed, relatively few have been registered for clinical trials and even fewer are clinically approved. Overt or potential toxicity, indistinct mechanisms of drug release and unsatisfactory pharmacokinetic behavior all contribute to their high failure rate during preclinical and clinical testing.

Recent advances in single-cell analysis by mass spectrometry.

Cells are the most basic structural units that play vital roles in the functioning of living organisms. Analysis of the chemical composition and content of a single cell plays a vital role in ensuring precise investigations of cellular metabolism, and is a crucial aspect of lipidomic and proteomic studies. In addition, structural knowledge provides a better understanding of cell behavior as well as the cellular and subcellular mechanisms.

A Unique Collision-Induced Dissociation Reaction of Cholamine Derivatives of Certain Prostaglandins.

Prostaglandins (PGs) are biologically active metabolites of arachidonic acid containing 20 carbon atoms, a cyclic moiety, and two side chains (A and B) in common. The bioassay of PGs requires high sensitivity because of their low concentration in tissues and blood and has usually been carried out by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative ion mode. Chemical derivatization of PG carboxylic acid groups to introduce positive charge-carrying groups is an established strategy to improve the sensitivity and selectivity of such assays.

Analytical methods for investigating fate of nanoliposomes: A review.

Nanoliposomes are considered to be the most successful nanoparticle drug delivery system, but their fate in vivo has not been fully understood due to lack of reliable bioanalytical methods, which seriously limits the development of liposomal drugs. Hence, an overview of currently used bioanalytical methods is imperative to lay the groundwork for the need of developing a bioanalytical method for liposome measurements in vivo. Currently, major analytical methods for nanoliposomes measurement in vivo include fluorescence labeling, radiolabeling, magnetic resonance imaging (MRI), mass spectrometry and computed tomography.

Cu(OAc) /TEMPO Cooperative Promoted Hydroamination Cyclization and Oxidative Dehydrogenation Cascade Reaction of Homopropargylic Amines.

A novel and efficient Cu(OAc) -catalyzed hydroamination cyclization and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidative dehydrogenation cascade reaction of homopropargylic amines has been developed. A library of 1,2-disubstituted pyrrole derivatives were obtained in good-to-high yields in one pot with no step-by-step feeding process. This reaction involved TEMPO playing dual roles as both an oxidative dehydrogenation reagent and a ligand.