A PEG-Fmoc conjugate as a nanocarrier for paclitaxel

We report here that a simple, well-defined, and easy-to-scale up nanocarrier, PEG5000-lysyl-(α-Fmoc-ε-t-Boc-lysine)2 conjugate (PEG-Fmoc), provides high loading capacity, excellent formulation stability and low systemic toxicity for paclitaxel (PTX), a first-line chemotherapeutic agent for various types of cancers. 9-Fluorenylmethoxycarbonyl (Fmoc) was incorporated into the nanocarrier as a functional building block to interact with drug molecules. PEG-Fmoc was synthesized via a three-step synthetic route, and it readily interacted with PTX to form mixed nanomicelles of small particle size (25–30 nm). The PTX loading capacity was about 36%, which stands well among the reported micellar systems. PTX entrapment in this micellar system is achieved largely via an Fmoc/PTX π-π stacking interaction, which was demonstrated by fluorescence quenching studies and 13C-NMR. PTX formulated in PEG-Fmoc micelles demonstrated sustained release kinetics, and in vivo distribution study via near infrared fluorescence imaging demonstrated an effective delivery of Cy5.5-labled PTX to tumor sites. The maximal tolerated dose for PTX/PEG-Fmoc (MTD > 120 mg PTX/kg) is higher than those for most reported PTX formulations, and in vivo therapeutic study exhibited a significantly improved antitumor activity than Taxol, a clinically used formulation of PTX. Our system may hold promise as a simple, safe, and effective delivery system for PTX with a potential for rapid translation into clinical study

Identification and Functional Analysis of Two New Mutant BnFAD2 Alleles That Confer Elevated Oleic Acid Content in Rapeseed

Rapeseed (Brassica napus L.) is a vital oil crop worldwide. High oleic acid content is a desirable quality trait for rapeseed oil, which makes it more beneficial to human health. However, many germplasm resources with high oleic acid content in rapeseed have not been evaluated with regard to their genotypes, making it difficult to select the best strains with this trait for the breeding of high oleic acid rapeseed variety. This work was to explore the gene-regulation mechanism of this trait using a new super-high oleic acid content (∼85%) line N1379T as genetic material. In this study, the sequences of four homologous fatty acid desaturase (BnFAD2) genes were compared between super-high (∼85%, N1379T) and normal (∼63%) oleic acid content lines. Results showed that there were two single-nucleotide polymorphisms (SNPs) in BnFAD2-1 and BnFAD2-2, respectively, which led to the amino acid changes (E106K and G303E) in the corresponding proteins. Functional analysis of both genes in yeast confirmed that these SNPs were loss-of-function mutations, thus limiting the conversion of oleic acid to linoleic acid and resulting in the considerable accumulation of oleic acid. Moreover, two specific cleaved amplified polymorphic sequences (CAPS) markers for the two SNPs were developed to identify genotypes of each line in the F2 and BC1 populations. Furthermore, these two mutant loci of BnFAD2-1 and BnFAD2-2 genes were positively associated with elevated oleic acid levels and had a similar effect with regard to the increase of oleic acid content. Taken together, these two novel SNPs in two different BnFAD2 genes jointly regulated the high oleic acid trait in this special germplasm. The study provided insight into the genetic regulation involved in oleic acid accumulation and highlighted the use of new alleles of BnFAD2-1 and BnFAD2-2 in breeding high oleic acid rapeseed varieties

Diameter effect on the heat transfer of supercritical hydrocarbon fuel in horizontal tubes under turbulent conditions

This document is the Accepted Manuscript version of the following article: Zeyuan Cheng, Zhi Tao, Jianqin Zhu, and Hongwei Wu, ‘Diameter effect on the heat transfer of supercritical hydrocarbon fuel in horizontal tubes under turbulent conditions’, Applied Thermal Engineering, Vol. 134: 39-53, April 2018. Under embargo until 31 January 2019. The final, definitive version is available online at: https://doi.org/10.1016/j.applthermaleng.2018.01.105This article presented a numerical investigation of supercritical heat transfer of the hydrocarbon fuel in a series of horizontal tubes with different diameters. The Reynolds averaging equations of mass, momentum and energy with the LS low-Reynolds number turbulence model have been solved using the pressure-based segregated solver based on the finite volume method. For the purpose of comparison, a four-species surrogate model and a ten-species surrogate model of the aviation kerosene RP-3 (Rocket Propellant 3) were tested against the published experimental data. In the current study, the tube diameter varied from 2 mm to 10 mm and the pressure was 3 MPa with heat flux to mass flux ratios ranging from 0.25 to 0.71 kJ/kg. It was found that the buoyancy has significant effect on the wall temperature non-uniformity in the horizontal tube. With the increase of the diameter, the buoyancy effect enhances and the thermal-induced acceleration effect reduces. The buoyancy effect makes wall temperature at the top and bottom generatrices of the horizontal tube increase and decrease, respectively. Due to the coupled effect of the buoyancy and thermal-induced acceleration caused by the significant change of the properties, as the diameter increases, the heat transfer deteriorates dramatically at the top generatrix but remains almost unchanged at the bottom generatrix at high heat flux to mass flux ratio. Heat transfer enhancement is observed at low heat flux to mass flux ratio when the tube diameter is less than 6 mm. Moreover, the safety analysis has been performed in order to optimally design the supercritical cooling system.Peer reviewe

Aqueous humor monocyte chemoattractant protein-1 predicted long-term visual outcome of proliferative diabetic retinopathy undergone intravitreal injection of bevacizumab and vitrectomy.

PurposeWe aim to investigate the risk factors associated with the prognosis of proliferative diabetic retinopathy (PDR) after a sequential treatment of intravitreal injection of bevacizumab (IVB) and pars plana vitrectomy (PPV).MethodsIn this cohort study, 63 eyes from 55 patients (21 females) diagnosed with PDR, who needed PPV for non-clearing vitreous hemorrhage or fibrovascular membrane proliferation were enrolled. All the eyes underwent IVB followed by PPV. Anterior chamber tap was performed at the beginning of both procedures to evaluate the concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1.ResultsForty-seven patients (54 eyes) were followed over six months, averaging 12±5 (6-19) months. The concentration of VEGF significantly decreased after IVB (PConclusionsMCP-1 was a predictor for the unfavorable visual outcome of PDR after IVB pretreatment and PPV

An appropriate ratio of unsaturated fatty acids is the constituent of hickory nut extract for neurite outgrowth in human SH-SY5Y cells

Hickory nuts (Carya cathayensis Sarg, CCS), a well-known Chinese medicinal nut, is thought to improve memory in Chinese folks. However, functional constituents have not been scientifically identified. In this study, human SH-SY5Y cells, combined with Q-TOF mass spectrometry (Q-TOF-MS) and standard substances, were used to evaluate the function in neuronal development and to identify constituents of CCS hydrophobic extracts (CCS-HE). Data showed that CCS-HE but not the control induced neurite outgrowth of SH-SY5Y cells in a dose-dependent manner, supported by which CCS-HE induced the expression of nerve growth factor (NGF), neurofilament 160 (NF160), and neuronal peptide Y (NPY) mRNA. Q-TOF-MS analysis with standard substances indicated that linolenic acid (LNA), linoleic acid (LA), and oleic acid (OA) were the main constituents in CCS-HE. Furthermore, mixtures of these unsaturated fatty acids (UFAs) at the natural ratio (1:8:16) significantly induced neurite outgrowth and gene expression of NGF, NF160, and NPY in a dose-dependent manner. However, the individual and alternative ratios were not effective to induce the neurite outgrowth and gene expression of NGF, NF160, and NPY. These data implicate that an appropriate ratio of UFAs is the main constituent for the neurite outgrowth

Unconditional and conditional QTL analyses of seed fatty acid composition in Brassica napus L.

Abstract Background The fatty acid composition of B. napus’ seeds determines the oil’s nutritional and industrial values, and affects seed germination. Many studies have reported correlations among C16:0, C18:0, C18:1, C18:2 and C18:3 based on phenotypic data; however, the genetic basis of the fatty acid composition in B. napus is still not well understood. Results In this study, unconditional and conditional quantitative trail locus (QTL) mapping analyses were conducted using a recombinant inbred line in six environments. In total, 21 consensus QTLs each for C16:0, C18:0 and C18:2, 16 for C18:1 and 22 for C18:3 were detected by unconditional mapping. The QTLs with overlapping confidence intervals were integrated into 71 pleiotropically unique QTLs by meta-analysis. Two major QTLs, uuqA5–6 and uuqA5–7, simultaneously affected the fatty acids, except C18:0, in most of environments, with the homologous genes fatty acid desaturase 2 (FAD2) and glycerol-3-phosphate sn-2-acyltransferase 5 (GPAT5) occurring in the confidence interval of uuqA5–6, while phosphatidic acid phosphohydrolase 1 (PAH1) was assigned to uuqA5–7. Moreover, 49, 30, 48, 60 and 45 consensus QTLs were detected for C16:0, C18:0, C18:1, C18:2 and C18:3, respectively, by the conditional mapping analysis. In total, 128 unique QTLs were subsequently integrated from the 232 conditional consensus QTLs. A comparative analysis revealed that 63 unique QTLs could be identified by both mapping methodologies, and 65 additional unique QTLs were only identified in conditional mapping. Conclusions Thus, conditional QTL mapping for fatty acids may uncover numerous additional QTLs that were inhibited by the effects of other traits. These findings provide useful information for better understanding the genetic relationships among fatty acids at the QTL level