Na Qiang,Weihong Yang,Longfei Li,Peng Dong,Jixiang Zhu,Tao Wang,Chenguang Zeng,Daping Quan
abstract Nano-fibrous scaffolds modified with biological peptides, which can mimic the physical and chemical characteristics of an extracellular matrix (ECM), have been considered good candidate matrices for cell culture in tissue engineering application. In this study, a series of semicrystalline block copolymers, specifically pendent carboxyl-containing poly( ε -caprolactone- co - β -malic acid)-block-poly( l -lactide), were synthesized to fabricate nano-fibrous scaffolds via thermal induced liquid–liquid phase separation process. Random prepolymers P(CL- co -BMD) were first synthesized through ring-opening copolymerization of ε-CL and 3(S)-[(benzyloxycarbony)methyl]-1,4-dioxane-2,5-dione (BMD) in the presence of dodecanol as initiator and stannous octoate(Sn(Oct) 2 ) as catalyst. The terminal hydroxyl of P(CL- co -BMD)-OH was subsequently added to initiate the ring-opening of l -LA catalyzed by Sn(Oct) 2 . After deprotection, a series of block copolymers, poly( ε -caprolactone- co - β -malic acid)-block-poly( l -lactide)(PCM- b -P L LA), were obtained and fabricated into nanofibrous scaffolds through thermally induced phase separation (TIPS) technique using tetrahydrofuran (THF) as solvent at a gelation temperature of −40 °C. The structure of the copolymers was characterized Nuclear Magnetic Resonance ( 1 H NMR, 13 C NMR), Gel Permeation Chromatography (GPC), and Differential Scanning Calorimetry (DSC). The crystallinity of the PCL segment generally decreased when the amount of BMD segment in P(CL- co -BMD) was increased. However, for PCM- b -P L LA, aside from the crystal melting peak of P L LA at 170 °C–180 °C, no indication of PCL section crystallization occurred because the crystallization of the PCL segment was interrupted by PLLA segment. The nanofiber size of the matrices was in the range of 180 nm–650 nm, similar to the architecture of ECM at the nanometer scale. These nanofibrous matrices have design potential to conjugate covalently to bioactive molecules for tissue engineering.
Wang Aimin,Fan Yuting,Fu Jun,Song Fengrui,Liu Zhiqiang,Liu Shu
Metabolomics is a biochemical analysis tool for identifying metabolic phenotypes and used to reveal the pathogenic mechanisms of disease and to inform drug-targeted therapies. Carboxyl-containing metabolites (CCMs) account for an important proportion of the metabolome, but because of the diversity of physical and chemical properties of CCMs in biological samples, traditional liquid chromatography–mass spectrometry (LC-MS) targeted metabolome analysis methods cannot achieve simultaneous quantification of multiple types of CCMs. Therefore, we proposed for the first time a targeted metabolomics strategy using isoniazid derivatization combined with LC-MS/MS to simultaneously quantify 39 CCMs of 5 different types (short-chain fatty acids, amino acids, bile acids, phenylalanine and tryptophan metabolic pathway acids) with large polarity differences associated with Alzheimer’s disease (AD) and significantly improve the detection coverage and sensitivity. The yields of isoniazid derivative CCMs were high and could guarantee the accuracy of CCM quantification. The LODs of CCMs increased significantly (1.25–2000-fold) after derivatization. The method showed good selectivity, intra-day and inter-day accuracies and precisions, and repeatability. There was no significant effect on the determination of CCMs in terms of matrix effect and recovery. CCMs showed good stability. And CCMs showed good stability under short-term storage and freeze-thaw cycles. At the same time, the regulatory effects of Schisandrae chinensis Fructus and Ginseng Radix et Rhizoma (SG) herb pair on CCM metabolic disorders in feces, urine, serum, and the brain of AD rats were elucidated from the perspective of targeted metabolomics. In combination with pharmacodynamic evaluation and gut microbiota analysis, the mechanism of SG herb pair on AD rats was comprehensively understood. In summary, this innovative isoniazid derivatization combined with a targeted metabolomics method has great potential for trace biological lineage analysis. Graphical
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