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101.
Hao Liu Yawen You Yanjuan Sang Dr. Fang Pu Prof. Jinsong Ren Prof. Xiaogang Qu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(72):18201-18207
Off-target toxicity and insufficient hydroxyl radicals (.OH) generation limit the further clinical application of nanozymes in chemodynamic therapy (CDT). Herein, we designed and constructed a microRNA-triggered nanozyme cascade platform for enhanced tumor-specific chemodynamic therapy. The nanozyme-based cascade reaction could be triggered successfully by the high expression of microRNA in cancer cells to generate more .OH, thus exhibiting excellent tumor-specific therapeutic performance. Our work provides a new dimension for tumor-specific chemodynamic therapy. 相似文献
102.
服务外包下,由于客户企业参与程度、服务提供商的努力水平以及专用性资产投入水平都难以让合作双方有效验证,这三种不可验证性风险因素可能引发道德风险,从而降低服务外包的绩效,甚至导致服务外包的失败。为此,本文建立了服务外包下的委托—代理框架,设计了客户企业参与下的服务外包激励机制模型,运用最优化理论分析了客户企业的参与程度以及服务提供商的专用性资产投入水平等因素对激励机制契约设计的影响,并运用数值仿真验证客户企业参与程度和服务提供商专用性资产投入水平对激励系数和服务提供商的努力水平的影响。研究分析表明:在服务外包活动中客户企业更多的投入到合作生产中时,对服务提供商的激励也会增加但是增加的幅度较慢,同时服务提供商付出的努力将会加速的提高;服务提供商投入的专用性资产投入水平越高时,其自身的努力水平也会加速增长,客户企业对其的激励系数也会增长,当专用性资产投入水平达到某一程度时,激励系数增长速度达到最大。 相似文献
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Influenza is one of the great plagues which is not yet under control. The reason for this is the immense variability of the infecting agent, the influenza A viruses. These viruses behave like a chameleon: they adapt very rapidly to varying environments. New strains are “synthesized,” which can escape the immune response of the host, cross species barriers, and become highly pathogenic. We are beginning to understand the molecular background of this extraordinarily high variability. The genome of influenza A viruses consists of eight single-stranded RNA segments, each of which constitutes a gene. The total base sequence of the eight RNA segments of several strains is known. If a suitable organism becomes doubly infected with two different influenza A strains, each of the RNA segments behaves like a chromosome. This means that by reassortment of the 16 RNA segments, 28 ?2 = 254 new combinations (= reassortants) are theoretically possible, each having different properties. Furthermore, mutations in the various RNA segments are relatively easily tolerated. Another great problem resides in the enormous reservoir of different influenza A viruses in the animal kingdom, especially in feral waterbirds. In these birds the avian influenza A viruses normally cause at most mild symptoms, and therefore these viruses are distributed over and between continents. Bearing this in mind it appears to be necessary to develop new ideas as to how to overcome this great plague. 相似文献
106.
Qiaoqiao Zhou Shaochen Wang Peng Hu Shuling Yu Jiahua Shi Jintao Yuan 《Particle & Particle Systems Characterization》2021,38(4):2000333
A targeting and specific fluorescent gold nanoparticle is prepared for tracing of drug and effective treatment of cancers. First, 4-carboxybenzeneboronic acid (CBPA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) are used to modify cyclodextrins (CDs), then modified cyclodextrins and polyethylene glycol (PEG) are used to stabilize gold nanoclusters to prepare fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG). CBPA has targeting and TPGS can induce apoptosis, therefore, AuNCs@CD-TPGS-CBPA/PEG has targeting and certain anti-tumor activity. The structure and morphology of the nanomaterial are characterized by using nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscope (TEM). Paclitaxel (PTX) is loaded into the hydrophobic cavity of CDs to form targeting specific drug-loaded fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG/PTX). Biological performances of AuNCs@CD-TPGS-CBPA/PEG are studied by in vitro and in vivo experiments. In vitro test results confirm that AuNCs@CD-TPGS-CBPA/PEG could be internalized by tumor cells, and effectively against tumor cells, but it is biocompatible to normal cells. In vivo experiments prove that AuNCs@CD-TPGS-CBPA/PEG has excellent targeting, biocompatibility, and enhanced antitumor capability, could enrich and stay for a long time in the tumor regions, effectively prolong the lifetime of tumor-bearing mice. Therefore, this work provides an insight into the development of fluorescent gold nanomaterials for practical biomedical application. 相似文献
107.
Nataliya E. Kuzmina Sergey V. Moiseev Mikhail D. Khorolskiy Anna I. Lutceva 《Molecules (Basel, Switzerland)》2021,26(6)
The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods. 相似文献
108.
The biodegradation of N-alkyl polypropylene polyamines (NAPPs) was studied using pure and mixed cultures to enable read-across of ready biodegradability test results. Two Pseudomonas spp. were isolated from activated sludge with N-oleyl alkyl propylene diamine and N-coco alkyl dipropylene triamine, respectively. Both strains utilized all NAPPs tested as the sole source of carbon, nitrogen and energy for growth. Mineralization of NAPPs was independent of the alkyl chain length and the size of the polyamine moiety. NAPPs degraded in closed bottle tests (CBTs) using both river water and activated sludge. However, ready biodegradability of NAPPs with alkyl chain lengths of 16–18 carbon atoms and polyamine moieties with three and four nitrogen atoms could not be demonstrated. Biodegradation in the CBT was hampered by their limited bioavailability, making assessment of the true ready biodegradability of these highly adsorptive surfactants impossible. All NAPPs are therefore classified as readily biodegradable through read-across. Read-across is justified by the broad substrate specificity of NAPP-degrading microorganisms, their omnipresence and the mineralization of NAPPs. 相似文献
109.
Conversion of Anthranilate Synthase into Isochorismate Synthase: Implications for the Evolution of Chorismate‐Utilizing Enzymes
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Maximilian G. Plach Patrick Löffler Prof. Dr. Rainer Merkl Prof. Dr. Reinhard Sterner 《Angewandte Chemie (International ed. in English)》2015,54(38):11270-11274
Chorismate‐utilizing enzymes play a vital role in the biosynthesis of metabolites in plants as well as free‐living and infectious microorganisms. Among these enzymes are the homologous primary metabolic anthranilate synthase (AS) and secondary metabolic isochorismate synthase (ICS). Both catalyze mechanistically related reactions by using ammonia and water as nucleophiles, respectively. We report that the nucleophile specificity of AS can be extended from ammonia to water by just two amino acid exchanges in a channel leading to the active site. The observed ICS/AS bifunctionality demonstrates that a secondary metabolic enzyme can readily evolve from a primary metabolic enzyme without requiring an initial gene duplication event. In a general sense, these findings add to our understanding how nature has used the structurally predetermined features of enzyme superfamilies to evolve new reactions. 相似文献
110.
《Journal of computational chemistry》2017,38(32):2791-2801
What factors favor protein folding? This is a textbook question. Parsing the experimental free energies of folding/unfolding into diverse enthalpic and entropic components of solute and solvent favoring or disfavoring folding is not an easy task. In this study, we present a computational protocol for estimating the free energy contributors to protein folding semi‐quantitatively using ensembles of unfolded and native states generated via molecular dynamics simulations. We tested the methodology on 35 proteins with diverse structural motifs and sizes and found that the calculated free energies correlate well with experiment (correlation coefficient ∼ 0.85), enabling us to develop a consensus view of the energetics of folding. As a more sensitive test of the methodology, we also investigated the free energies of folding of an additional 33 single point mutants and obtained a correlation coefficient of 0.8. A notable observation is that the folding free energy components appear to carry signatures of the fold (SCOP classification) of the protein. © 2017 Wiley Periodicals, Inc. 相似文献