Site-specific qualitative and quantitative analysis of the N- and O-glycoforms in recombinant human erythropoietin

Recombinant human erythropoietin (rhEPO) has been extensively used as a pharmaceutical product for treating anemia. Glycosylation of rhEPO affects the biological activity, immunogenicity, pharmacokinetics, and in-vivo clearance rate of rhEPO. Characterization of the glycosylation status of rhEPO is of great importance for quality control. In this study, we established a fast and comprehensive approach for reliable characterization and relative quantitation of rhEPO glycosylation, which combines multiple-enzyme digestion, hydrophilic-interaction chromatography (HILIC) enrichment of glycopeptides, and tandem mass spectrometry (MS) analysis. The N-linked and O-linked intact glycopeptides were analyzed with high-resolution and high-accuracy (HR–AM) mass spectrometry using an Orbitrap. In total, 74 intact glycopeptides from four glycosylation sites at N₂₄, N₃₈, N₈₃, and O₁₂₆ were identified, with the simultaneous determination of peptide sequences and glycoform compositions. The extracted ion chromatograms based on the HR–AM data enabled relative quantification of glycoforms. Our results could be extended to quality control of rhEPO or could help establish detection approaches for glycosylation of other proteins. Graphical Abstract

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Biological evaluation of 2-methylpyrimidine derivatives as active pan Bcr-Abl inhibitors

We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT,Bcr-Abl E255K,Bcr-Abl Q252H,Bcr-Abl G250E and Bcr-Abl T315I,with IC50 values of 0.13 nM,0.17 nM,0.24 nM,0.19 nM and 0.65μM,respectively.This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM,thus representing a new lead for further optimization.     

Extraction of coal-tar pitch using NMP/ILs mixed solvents

Coal-tar pitch(CP)is a promising carbon raw material for producing needle coke,carbon fiber etc.During processing,the H/C ratio,ash content,and quinoline insoluble(QI)in the CP are the key factors that influence the material preparation.In this study,NMP was selected to extract CP first;then[BMIM]Cl/NMP mixed solvent was used;and finally a series of ionic liquids(ILs)mixtures with NMP were developed for the extraction of CP to obtain the refined pitch.The extracts were analyzed via elemental analysis,TGA,FT-IR,and 13C-NMR.Results indicate that different NMP/IL mass ratios or different kinds of ILs have impact on the extraction yield.The relationship of the hydrogen to carbon(H/C)ratio changed with different solvents and QI extracts were obtained.Results showed that the H/C ratios changed little between NMP extracts and could be adjusted by changing the NMP/ILs mass ratio or using different ILs.The extracts are suitable for preparation mesophase pitch because of no ash content,low QI,and appropriate H/C ratios.As a result,NMP can be used to refine pitch.In addition,[BMIM]Cl is good mixed with NMP for CP extraction,because it can obtain a relatively high yield under the same extraction conditions.     

Thermo-responsive gelatin-functionalized PCL film surfaces for improvement of cell adhesion and intelligent recovery of gene-transfected cells

Efficient local gene transfection on a tissue scaffold is dependent on good cell-adhesion characteristics. In this work, the thermo-responsive gelatin-functionalized polycaprolactone (PCL) films were proposed for improvement of cell adhesion and intelligent recovery of gene-transfected cells. Functional copolymer brushes (PCL-g-P(NIPAAm-co-MAAS)) were first prepared via surface-initiated ATRP of N-isopropylacrylamide (NIPAAm) and methacrylic acid sodium salt (MAAS) from the initiator-funcationalized PCL surfaces. The pendant carboxyl end-groups of the PCL-g-P(NIPAAm-co-MAAS) surface were subsequently coupled with gelatin via carbodiimide chemistry to produce the thermo-responsive gelatin-functionalized PCL surface. The thermo-responsive gelatin-functionalized PCL film surface can improve cell adhesion and proliferation above the LCST of P(NIPAAm) without destroying cell detachment properties at lower temperatures. The dense transfected cells can be recovered simply by lowering culture temperature. The thermo-responsive gelatin-functionalized PCL films are potentially useful as intelligent adhesion modifiers for directing cellular functions within tissue scaffolds.     

2 D Manganese Vanadate Nanoflakes as High‐Performance Anode for Lithium‐Ion Batteries

Nanometer‐sized flakes of MnV₂O₆ were synthesized by a hydrothermal method. No surfactant, expensive metal salt, or alkali reagent was used. These MnV₂O₆ nanoflakes present a high discharge capacity of 768 mA h g^?1 at 200 mA g^?1, good rate capacity, and excellent cycling stability. Further investigation demonstrates that the nanoflake structure and the specific crystal structure make the prepared MnV₂O₆ a suitable material for lithium‐ion batteries.     

Utilization of Environmentally Benign Dicyandiamide as a Precursor for the Synthesis of Ordered Mesoporous Carbon Nitride and its Application in Base‐Catalyzed Reactions

Assisted by a new dissolution procedure, dicyandiamide (DCDA), an environmentally benign and cheap precursor, has been employed for the synthesis of mesoporous carbon nitride (CN) materials through a nanocasting approach. The synthesized mesoporous materials possessed high specific surface areas (269–715 m² g^?1) with narrow pore‐size distributions (about 5 nm) and faithfully replicated the mesostructures of the SBA‐15 and FDU‐12 templates. Several characterization techniques, including XRD, SAXS, TEM, Raman and FTIR spectroscopy, XPS, and CO₂‐TPD, were used to analyze the physicochemical properties of these materials and the results showed that the mesoporous CND materials had graphitic‐like structures and consisted of CN heterocycles, as well as amino groups. In a series of Knoevenagel condensation reactions, as exemplified by the reaction of various aldehydes and nitriles, these mesoporous CND materials demonstrated high and stable catalytic activities, owing to an abundance of basic sites.     

A Highly Selective and Sensitive Turn-On Fluorescent Chemosensor Based on Rhodamine 6G for Iron(III)

Recently, more and more rhodamine derivatives have been used as fluorophores to construct sensors due to their excellent spectroscopic properties. A rhodamine-based fluorescent and colorimetric Fe³⁺ chemosensor 3’,6’-bis(ethylamino)-2-acetoxyl-2’,7’-dimethyl-spiro[1H-isoindole-1,9’-[9H]xanthen]-3(2H)-one (RAE) was designed and synthesized. Upon the addition of Fe³⁺, the dramatic enhancement of both fluorescence and absorbance intensity, as well as the color change of the solution, could be observed. The detection limit of RAE for Fe³⁺ was around 7.98 ppb. Common coexistent metal ions showed little or no interference in the detection of Fe³⁺. Moreover, the addition of CN⁻ could quench the fluorescence of the acetonitrile solution of RAE and Fe³⁺, indicating the regeneration of the chemosensor RAE. The robust nature of the sensor was shown by the detection of Fe³⁺ even after repeated rounds of quenching. As iron is a ubiquitous metal in cells and plays vital roles in many biological processes, this chemosensor could be developed to have applications in biological studies.     

Novel Red Phosphorescent Polymers Bearing Both Ambipolar and Functionalized IrIII Phosphorescent Moieties for Highly Efficient Organic Light‐Emitting Diodes

A series of novel red phosphorescent polymers is successfully developed through Suzuki cross‐coupling among ambipolar units, functionalized Ir^III phosphorescent blocks, and fluorene‐based silane moieties. The photophysical and electrochemical investigations indicate not only highly efficient energy‐transfer from the organic segments to the phosphorescent units in the polymer backbone but also the ambipolar character of the copolymers. Benefiting from all these merits, the phosphorescent polymers can furnish organic light‐emitting diodes (OLEDs) with exceptional high electroluminescent (EL) efficiencies with a current efficiency (η _L) of 8.31 cd A⁻¹, external quantum efficiency (η _ext) of 16.07%, and power efficiency (η _P) of 2.95 lm W⁻¹, representing the state‐of‐the‐art electroluminescent performances ever achieved by red phosphorescent polymers. This work here might represent a new pathway to design and synthesize highly efficient phosphorescent polymers.

     

Morphological Investigation of Midblock‐Sulfonated Block Ionomers Prepared from Solvents Differing in Polarity

Recent developments regarding charged multiblock copolymers that can form physical networks and exhibit robust mechanical properties herald new and exciting opportunities for contemporary technologies requiring amphiphilic attributes. Due to the presence of strong interactions, however, control over the phase behavior of such materials remains challenging, especially since their morphologies can be solvent‐templated. In this study, transmission electron microscopy and microtomography are employed to examine the morphological characteristics of midblock‐sulfonated pentablock ionomers prepared from solvents differing in polarity. Resultant images confirm that discrete, spherical ion‐rich microdomains form in films cast from a relatively nonpolar solvent, whereas an apparently mixed morphology with a continuous ion‐rich pathway is generated when the casting solvent is more highly polar. Detailed 3D analysis of the morphological characteristics confirms the coexistence of hexagonally‐packed nonpolar cylinders and lamellae, which facilitates the diffusion of ions and/or other polar species through the nanostructured medium.

     

Recent Progress on Transition Metal Catalyst Separation and Recycling in ATRP

Atom transfer radical polymerization (ATRP) is a versatile and robust tool to synthesize a wide spectrum of monomers with various designable structures. However, it usually needs large amounts of transition metal as the catalyst to mediate the equilibrium between the dormant and propagating species. Unfortunately, the catalyst residue may contaminate or color the resultant polymers, which limits its application, especially in biomedical and electronic materials. How to efficiently and economically remove or reduce the catalyst residue from its products is a challenging and encouraging task. Herein, recent advances in catalyst separation and recycling are highlighted with a focus on (1) highly active ppm level transition metal or metal free catalyzed ATRP; (2) post‐purification method; (3) various soluble, insoluble, immobilized/soluble, and reversible supported catalyst systems; and (4) liquid‐liquid biphasic catalyzed systems, especially thermo‐regulated catalysis systems.