bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization Surface and Characterization of Three New Patients
Authors: Puisac Beatriz , Marcos-Alcalde Iñigo , Hernández-Marcos María , Tobajas Morlana Pilar , Levtova Alina , Schwahn Bernd , DeLaet Corinne , Lace Baiba , Gómez-Puertas Paulino , Pié Juan
Published: March 2018

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA synthase deficiency or mHS deficiency, OMIM #605911) is an inborn error of metabolism that affects ketone body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycemia and dicarboxylic aciduria. The diagnosis is difficult due to the relatively unspecific clinical and biochemical presentation, and fewer than 30 patients have been described. This work describes three new patients with mHS deficiency and two missense mutations c.334C>T (p.R112W) and c.430G>T (p.V144L) previously not reported. We developed a new method to express and measure the activity of the enzyme and in this work the study is extended to ten new missense variants including those of our patients. Enzymatic assays showed that three of the mutant proteins retained some but seven completely lacked activity. The identification of a patient homozygous for a mutation that retains 70% of enzyme activity opens the door to a new interpretation of the disease by demonstrating that a modest impairment of enzyme function can actually produce symptoms. This is also the first study employing molecular dynamics modelling of the enzyme mutations. We show that the correct maintenance of the dimerization surface is crucial for retaining the structure of the active center and therefore the activity of the enzyme.
Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China
Authors: Cao Yaying , Wang Tao , Wu Yiqun , Juan Juan , Qin Xueying , Tang Xun , Wu Tao , Hu Yonghua
Published: March 2018

C-Maf Inducing Protein (CMIP) gene polymorphisms were reported to be associated with type 2 diabetes mellitus (T2DM). Whether the association between CMIP and T2DM is mediated via obesity-related phenotypes is still unclear. We analyzed the association of CMIP rs2925979 with T2DM and a comprehensive set of obesity-related phenotypes in 1576 families ascertained from a Chinese population. These families included a total of 3444 siblings (1582 with T2DM, 963 with prediabetes, and 899 with a normal glucose level). Using multi-level mixed effects regression models, we found that each copy of CMIP rs2925979_T allele was associated with a 29% higher risk of T2DM in females (p = 9.30 × 10−4), while it was not significantly associated with T2DM in males (p = 0.705). Meanwhile, rs2925979_T allele was associated with lower levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), percentage of body fat (PBF), PBF of arms, PBF of legs, and PBF of trunk in nondiabetes females (all p < 0.05). The opposite associations of rs2925979_T allele with T2DM and obesity-related phenotypes suggest that CMIP may exert independent pleiotropic effects on T2DM and obesity-related phenotypes in females.
Transcriptome Analysis Reveals Molecular Signatures of Luteoloside Accumulation in Senescing Leaves of Lonicera macranthoides
Authors: Chen Zexiong , Liu Guohua , Tang Ning , Li Zhengguo
Published: March 2018

Lonicera macranthoides is an important medicinal plant widely used in traditional Chinese medicine. Luteoloside is a critical bioactive compound in L. macranthoides. To date, the molecular mechanisms underlying luteoloside biosynthesis are still largely unknown. In this work, high performance liquid chromatography (HPLC) was employed to determine the luteoloside contents in leaves, stems, and flowers at different developmental stages. Results showed that senescing leaves can accumulate large amounts of luteoloside, extremely higher than that in young and semi-lignified leaves and other tissues. RNA-Seq analysis identified that twenty-four differentially expressed unigenes (DEGs) associated with luteoloside biosynthesis were significantly up-regulated in senescing leaves, which are positively correlated with luteoloside accumulation. These DEGs include phenylalanine ammonia lyase 2, cinnamate 4-hydroxylase 2, thirteen 4-coumarate-CoA ligases, chalcone synthase 2, six flavonoid 3′-monooxygenase (F3′H) and two flavone 7-O-β-glucosyltransferase (UFGT) genes. Further analysis demonstrated that two F3′Hs (CL11828.Contig1 and CL11828.Contig2) and two UFGTs (Unigene2918 and Unigene97915) might play vital roles in luteoloside generation. Furthermore, several transcription factors (TFs) related to flavonoid biosynthesis including MYB, bHLH and WD40, were differentially expressed during leaf senescence. Among these TFs, MYB12, MYB75, bHLH113 and TTG1 were considered to be key factors involved in the regulation of luteoloside biosynthesis. These findings provide insights for elucidating the molecular signatures of luteoloside accumulation in L. macranthoides.
Preconditioning-Like Properties of Short-Term Hypothermia in Isolated Perfused Rat Liver (IPRL) System
Authors: Alva Norma , Bardallo Raquel , Basanta David , Palomeque Jesús , Carbonell Teresa
Published: March 2018

Hypothermia may attenuate the progression of ischemia-induced damage in liver. Here, we determined the effects of a brief cycle of hypothermic preconditioning applied before an ischemic/reperfusion (I/R) episode in isolated perfused rat liver (IPRL) on tissue damage and oxidative stress. Rats (male, 200–250 g) were anaesthetised with sodium pentobarbital (60 mg·kg−1 i.p) and underwent laparatomy. The liver was removed and perfused in a temperature-regulated non-recirculating system. Livers were randomly divided into two groups (n = 6 each group). In the hypothermia-preconditioned group, livers were perfused with hypothermic buffer (cycle of 10 min at 22 °C plus 10 min at 37 °C) and the other group was perfused at 37 °C. Both groups were then submitted to 40 min of warm ischemia and 20 min of warm reperfusion. The level of tissue-damage indicators (alanine amino transferase, ALT; lactate dehydrogenase, LDH; and proteins), oxidative stress markers (thiobarbituric acid-reactive substances, TBARS; advanced oxidation protein products, AOPP; and glutathione, GSH) were measured in aliquots of perfusate sampled at different time intervals. Histological determinations and oxidative stress biomarkers in homogenized liver (AOPP; TBARS; nitric oxide derivatives, NOx; GSH and glutathione disulphide, GSSG) were also made in the tissue at the end. Results showed that both damage and oxidant indicators significantly decreased while antioxidant increased in hypothermic preconditioned livers. In addition, homogenized liver determinations and histological observations at the end of the protocol corroborate the results in the perfusate, confirming the utility of the perfusate as a non-invasive method. In conclusion, hypothermic preconditioning attenuates oxidative damage and appears to be a promising strategy to protect the liver against IR injury.
Disruption of PTPS Gene Causing Pale Body Color and Lethal Phenotype in the Silkworm, Bombyx mori
Authors: Tong Xiaoling , Liang Pingfeng , Wu Songyuan , Li Yuanhao , Qiao Liang , Hu Hai , Xiang Zhonghuai , Lu Cheng , Dai Fangyin
Published: March 2018

Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene or by defects in the tetrahydrobiopterin (BH4) synthesis pathway. Here, by positional cloning, we report that the 6-pyruvoyl-tetrahydropterin synthase (PTPS) gene, encoding a key enzyme of BH4 biosynthesis, is responsible for the alc (albino C) mutation that displays pale body color, head shaking, and eventually lethality after the first molting in silkworm. Compared to wild type, the alc mutant produced more substrates (phenylalanine (Phe) and tyrosine (Tyr)) and generated less DOPA and dopamine. Application of 2,4-diamino-6-hydroxypyrimidine (DAHP) to block BH4 synthesis in the wild type effectively produced the alc-like phenotype, while BH4 supplementation rescued the defective body color and lethal phenotype in both alc and DAHP-treated individuals. The detection of gene expressions and metabolic substances after drugs treatments in alc and normal individuals imply that silkworms and humans have a high similarity in the drugs metabolic features and the gene pathway related to BH4 and the dopamine biosynthesis. We propose that the alc mutant could be used as an animal model for drug evaluation for BH4-deficient PKU.
Resveratrol Suppresses the Growth and Enhances Retinoic Acid Sensitivity of Anaplastic Thyroid Cancer Cells
Authors: Li Yi-Tian , Tian Xiao-Ting , Wu Mo-Li , Zheng Xu , Kong Qing-You , Cheng Xiao-Xin , Zhu Guang-Wen , Liu Jia , Li Hong
Published: March 2018

Anaplastic thyroid cancer (ATC) is a highly lethal undifferentiated malignancy without reliable therapies. Retinoic acid (RA) has been employed to promote redifferentiation of thyroid cancers by increasing their I131 uptake and radio-sensitivity, but its effect(s) on ATCs has not yet been ascertained. Likewise, resveratrol induces cancer redifferentiation but, also in this case, its effects on ATCs remain unknown. These issues have been addresses in the current study using three human ATC cell lines (THJ-11T, THJ-16T, and THJ-21T) through multiple experimental approaches. The results reveal that RA exerts a small inhibitory effect on these cell lines. In comparison with normally cultured cells, the total cell number in resveratrol-treated THJ-16T and THJ-21T cultures significantly decreased (p < 0.05), and this effect was accompanied by reduced Cyclin D1 immuno-labeling, increased apoptotic fractions, and distinct caspase-3 activation. Resveratrol failed to inhibit growth but enhanced RA sensitivity of THJ-11T cells, suppressed peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ), and upregulated cellular retinoic acid-binding protein 2 (CRABP2) and retinoic acid receptor beta (RAR-β) expression. Increased thyroglobulin (Tg) and E-cadherin levels and appearance of membranous E-cadherin were evidenced in resveratrol-treated THJ-11T cells. Our results demonstrate for the first time: (1) the therapeutic value of resveratrol by itself or in combination with RA in the management of ATCs, (2) the capacity of resveratrol to overcome RA resistance in ATC cells by reprogramming CRABP2/RAR- and fatty acid-binding protein 5 (FABP5)/PPAR-β/δ-mediated RA signaling, and (3) the redifferentiating potential of resveratrol in ATC cells.
Genetic Variants in STAT3 Promoter Regions and Their Application in Molecular Breeding for Body Size Traits in Qinchuan Cattle
Authors: Wu Sen , Wang Yaning , Ning Yue , Guo Hongfang , Wang Xiaoyu , Zhang Le , Khan Rajwali , Cheng Gong , Wang Hongbao , Zan Linsen
Published: March 2018

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in leptin-mediated regulation of energy metabolism. This study investigated genetic variation in STAT3 promoter regions and verified their contribution to bovine body size traits. We first estimated the degree of conservation in STAT3, followed by measurements of its mRNA expression during fetal and adult stages of Qinchuan cattle. We then sequenced the STAT3 promoter region to determine genetic variants and evaluate their association with body size traits. From fetus to adult, STAT3 expression increased significantly in muscle, fat, heart, liver, and spleen tissues (p < 0.01), but decreased in the intestine, lung, and rumen (p < 0.01). We identified and named five single nucleotide polymorphisms (SNPs): SNP1-304A>C, SNP2-285G>A, SNP3-209A>C, SNP4-203A>G, and SNP5-188T>C. These five mutations fell significantly outside the Hardy–Weinberg equilibrium (HWE) (Chi-squared test, p < 0.05) and significantly associated with body size traits (p < 0.05). Individuals with haplotype H3H3 (CC-GG-CC-GG-CC) were larger in body size than other haplotypes. Therefore, variations in the STAT3 gene promoter regions, most notably haplotype H3H3, may benefit marker-assisted breeding of Qinchuan cattle.
Study on the Visible-Light Photocatalytic Performance and Degradation Mechanism of Diclofenac Sodium under the System of Hetero-Structural CuBi2O4/Ag3PO4 with H2O2
Authors: Chen Xiaojuan , Li Ning , Xu Song , Wang Hailong , Cai Yumin
Published: March 2018

Two kinds of CuBi2O4/Ag3PO4 with different heterojunction structures were prepared based on the combination of hydrothermal and in-situ precipitation methods with surfactant additives (sodium citrate and sodium stearate), and their characteristics were systematically resolved by X-ray Diffraction (XRD), Brunauer–Emmett–Teller (BET), X-ray Photoelectron Spectroscopy (XPS), Scanning Electron Microscope (SEM)/ High-resolution Transmission Electron Microscopy (HRTEM), UV-vis Diffuse Reflectance Spectra (DRS) and Photoluminescence (PL). Meanwhile, the photocatalytic properties of the catalysts were determined for diclofenac sodium (DS) degradation and the photocatalytic mechanism was also explored. The results indicate that both of the two kinds of CuBi2O4/Ag3PO4 exhibit higher photocatalytic efficiency, mineralization rate, and stability than that of pure CuBi2O4 or Ag3PO4. Moreover, the catalytic activity of CuBi2O4/Ag3PO4 can be further enhanced by adding H2O2. The free radical capture experiments show that in the pure CuBi2O4/Ag3PO4 photocatalytic system, the OH• and O2•− are the main species participating in DS degradation; however, in the CuBi2O4/Ag3PO4 photocatalytic system with H2O2, all OH•, h+, and O2•− take part in the DS degradation, and the contribution order is OH• > h+ > O2•−. Accordingly, the photocatalytic mechanism of CuBi2O4/Ag3PO4 could be explained by the Z-Scheme theory, while the catalysis of CuBi2O4/Ag3PO4 with H2O2 follows the heterojunction energy band theory.
Graphene Quantum Dots-ZnS Nanocomposites with Improved Photoelectric Performances
Authors: Zhang Zheng , Fang Chengyi , Bing Xin , Lei Yun
Published: March 2018

ZnS-graphene quantum dot (GQDs) composites were synthesized by a simple solvothermal method, in which GQDs were prepared by a hydrothermal cutting process. The products were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction and ultraviolet-visible absorption spectroscopy. The results show that GQDs were obtained by size tailoring of 1–4 graphene layers and combined with cubic ZnS nanoparticles to form ZnS-GQDs composites. The photocurrent and electrochemical behavior of the products were evaluated by transient photocurrent responses and electrochemical impedance spectra. The photocurrent density of ZnS-GQDs achieves the value of 2.32 × 10−5 A/cm2, which is 2.4-times as high as that of ZnS-graphene. GQDs serve as an electrical conducting material, which decreases the conductive path and accelerates the electron transfer. The charge-transfer resistance of ZnS-GQDs is much lower than that of ZnS-graphene and pure ZnS due to the effective electron separation and transfer ability upon the incorporation of GQDs.
Optimization and Characterization of Preceramic Inks for Direct Ink Writing of Ceramic Matrix Composite Structures
Authors: Franchin Giorgia , Maden Halide , Wahl Larissa , Baliello Andrea , Pasetto Marco , Colombo Paolo
Published: March 2018

In a previous work, an ink based on a preceramic polymer, SiC fillers, and chopped carbon fibers was proposed for the production of Ceramic Matrix Composite (CMC) structures by Direct Ink Writing (DIW) and subsequent pyrolysis. Thanks to the shear stresses generated at the nozzle tip during extrusion, carbon fibers can be aligned along the printing direction. Fumed silica was added to the ink in order to enhance its rheological properties; however, the printed structures still showed some deformation in the Z direction. In this work, a second ink was successfully developed to limit deformation and at the same time avoid the addition of fumed silica, which limited the potential temperature of application of the composites. Instead, the positive role of the preceramic polymer on the ink rheology was exploited by increasing its concentration in the ink. Rheological characterization carried out on both inks confirmed that they possessed Bingham shear thinning behavior and fast viscosity recovery. Single filaments with different diameters (~310 µm and ~460 µm) were produced with the latter ink by DIW and subsequent pyrolysis. Tested under a four-point flexural test, the filaments showed a mean flexural strength above 30 MPa, graceful failure, and fiber pull-out. The results of this work suggest that CMC components can effectively be fabricated via DIW of a preceramic ink with embedded short fibers; the preceramic polymer is able to provide the desired rheology for the process and to develop a dense matrix capable of incorporating both fibers and ceramic particles, whereas the fibers addition contributes to an increase of the fracture toughness of the material and to the development of a graceful failure mode.
Synthesis and Characterization of Sulfonated Graphene Oxide Reinforced Sulfonated Poly (Ether Ether Ketone) (SPEEK) Composites for Proton Exchange Membrane Materials
Authors: Cao Ning , Zhou Chaofan , Wang Yong , Ju Hong , Tan Dongyang , Li Jin
Published: March 2018

As a clean energy utilization device, full cell is gaining more and more attention. Proton exchange membrane (PEM) is a key component of the full cell. The commercial-sulfonated, tetrafluoroethylene-based fluoropolymer-copolymer (Nafion) membrane exhibits excellent proton conductivity under a fully humidified environment. However, it also has some disadvantages in practice, such as high fuel permeability, a complex synthesis process, and high cost. To overcome these disadvantages, a low-cost and novel membrane was developed. The sulfonated poly (ether ether ketone) (SPEEK) was selected as the base material of the proton exchange membrane. Sulfonated graphene (SG) was cross-linked with SPEEK through the elimination reaction of hydrogen bonds. It was found that the sulfonic acid groups and hydrophilic oxygen groups increased obviously in the resultant membrane. Compared with the pure SPEEK membrane, the SG-reinforced membrane exhibited better proton conductivity and methanol permeability prevention. The results indicate that the SG/SPEEK could be applied as a new proton exchange membrane in fuel cells.
The Influence of Metakaolinite on the Development of Thermal Cracks in a Cement Matrix
Authors: Szeląg Maciej
Published: March 2018

In the paper the cluster cracks of cement paste that has been modified with metakaolinite was analyzed. The samples were loaded with an elevated temperature based on a thermal shock. To describe the crack structure, three stereological parameters were proposed to measure: (i) the cluster average area ( A ¯ ); (ii) the cluster average perimeter ( L ¯ ); and (iii) the crack average width ( I ¯ ). The computer image analysis was implemented in the study, and 4 series of samples were subjected to the examination. In two series, metakaolinite was used as a substitute for 10% of a cement’s mass. An assessment of the basic physico-mechanical characteristics of the cement matrix was also carried out. The structure of the cement paste was considered as a highly concentrated dispersion system, in which the interactions between the cement’s grains at the initial stage of the structure self-assembly affect the crack characteristics. The study has been supplemented with microstructural investigations using a scanning electron microscope and an X-ray microanalyzer. The conducted research indicated the direction of changes in the geometrical characteristics of thermal cracks if the technological variables of the material are subjected to modification. It was also confirmed that the cluster structures have fractal character and can be analyzed and observed on many levels of a structural heterogeneity.
Porous Polyethylene Coated with Functionalized Hydroxyapatite Particles as a Bone Reconstruction Material
Authors: Fouad H. , AlFotawi Randa , Alothman Othman , Alshammari Basheer , Alfayez Musaad , Hashem Mohamed , Mahmood Amer
Published: March 2018

In this study, porous polyethylene scaffolds were examined as bone substitutes in vitro and in vivo in critical-sized calvarial bone defects in transgenic Sprague-Dawley rats. A microscopic examination revealed that the pores appeared to be interconnected across the material, making them suitable for cell growth. The creep recovery behavior of porous polyethylene at different loads indicated that the creep strain had two main portions. In both portions, strain increased with increased applied load and temperature. In terms of the thermographic behavior of the material, remarkable changes in melting temperature and heat fusion were revealed with increased the heating rates. The tensile strength results showed that the material was sensitive to the strain rate and that there was adequate mechanical strength to support cell growth. The in vitro cell culture results showed that human bone marrow mesenchymal stem cells attached to the porous polyethylene scaffold. Calcium sulfate–hydroxyapatite (CS–HA) coating of the scaffold not only improved attachment but also increased the proliferation of human bone marrow mesenchymal stem cells. In vivo, histological analysis showed that the study groups had active bone remodeling at the border of the defect. Bone regeneration at the border was also evident, which confirmed that the polyethylene acted as an osteoconductive bone graft. Furthermore, bone formation inside the pores of the coated polyethylene was also noted, which would enhance the process of osteointegration.
Comparative Analysis of Machining Procedures
Authors: Kundrak Janos , Molnar Viktor , Deszpoth Istvan
Published: March 2018

The in-depth analysis of cutting procedure is a topic of particular interest in manufacturing efficiency because in large-scale production the effective use of production capacities and the revenue-increasing capacity of production are key conditions of competitiveness. That is why the analysis of time and material removal rate, which are in close relation to production, are important in planning a machining procedure. In the paper three procedures applied in hard cutting are compared on the basis of these parameters and a new parameter, the practical parameter of material removal rate, is introduced. It measures not only the efficiency of cutting but also that of the whole machining process because it includes the values measured by time analysis as well. In the investigations the material removal rate was analyzed, first on the basis of geometrical data of the component. After that different machining procedures (hard machining) were compared for some typical surfaces. The results can give some useful indications about machining procedure selection.
Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity
Authors: Li Qing , Sun Xueqi , Gu Guodong , Guo Zhanyong
Published: March 2018

Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating “click reaction” with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL−1) was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.
New Eudesmane-Type Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus Penicillium sp. J-54
Authors: Qiu Liuming , Wang Pei , Liao Ge , Zeng Yanbo , Cai Caihong , Kong Fandong , Guo Zhikai , Proksch Peter , Dai Haofu , Mei Wenli
Published: March 2018

Four new eudesmane-type sesquiterpenoids, penicieudesmol A–D (1–4), were isolated from the fermentation broth of the mangrove-derived endophytic fungus Penicillium sp. J-54. Their structures were determined by spectroscopic methods, the in situ dimolybdenum CD method, and modified Mosher’s method. The bioassays results showed that 2 exhibited weak cytotoxicity against K-562 cells.
Influence of Scandium Addition on Stress Corrosion Cracking Susceptibility of Al-Zn-Mg Alloy in Different Corrosive Environments
Authors: Li Zhaoming , Jiang Haichang , Yan Desheng , Rong Lijian
Published: March 2018

Stress corrosion cracking (SCC) susceptibilities of Al-Zn-Mg alloys without and with Scandium addition were evaluated in 3.5% NaCl solution at different pH and different strain rate, using slow strain rate test technique. The results indicate that Sc addition reduces grain size and width of precipitation free zones, and transforms grain boundary precipitates from continuous distribution into interrupted distribution by inhibiting recrystallization. In solution at pH 1, pH 3 and pH 7, Sc addition reduces the degree of localized corrosion of alloy surface and SCC susceptibility of Al-Zn-Mg alloy. However, in solution at pH 10 and pH 12, grain refinement significantly promotes the diffusion of hydrogen atoms into matrix, thus Sc addition increases SCC susceptibility of Al-Zn-Mg alloy. Under different strain rate conditions, Sc addition can all reduce SCC susceptibility of Al-Zn-Mg alloy in solution at pH 1, pH 3 and pH 7, and can all increase SCC susceptibility of Al-Zn-Mg alloy in solution at pH 10 and pH 12. As a result, Sc modified Al-Zn-Mg alloy in practical applications should be avoided in alkaline environments.
DC-25 GHz and Low-Loss MEMS Thermoelectric Power Sensors with Floating Thermal Slug and Reliable Back Cavity Based on GaAs MMIC Technology
Authors: Zhang Zhiqiang , Ma Yao
Published: March 2018

Wideband and low-loss microwave power measurements are becoming increasingly important for microwave communication and radar systems. To achieve such a power measurement, this paper presents the design and measurement of wideband DC-25 GHz and low-loss MEMS thermoelectric power sensors with a floating thermal slug and a reliable back cavity. In the sensors, the microwave power is converted to thermovoltages via heat. The collaborative design of the thermal slug and the back cavity, i.e., two thermal flow paths, is utilized to improve the efficiency of heat transfer and to ensure reliable applications. These sensors are required to operate up to 25 GHz. In order to achieve low microwave losses at the bandwidth, the floating thermal slug is designed instead of the grounded one. The effects of the floating slug on the reflection losses are analyzed by the simulation. The fabrication of these sensors is completed by GaAs monolithic microwave integrated circuits (MMIC) and micro-electro-mechanical systems (MEMS) technology. Measured reflection losses are less than −25.6 dB up to 12 GHz and −18.6 dB up to 25 GHz. The design of the floating thermal slug reduces the losses, which is equivalent to improving the sensitivity. At 10 and 25 GHz, experiments exhibit that the sensors result in sensitivities of about 51.13 and 35.28 μV/mW for the floating slug and 81.68 and 55.20 μV/mW for the floating slug and the cavity.
Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness
Authors: Farra Rossella , Musiani Francesco , Perrone Francesca , Čemažar Maja , Kamenšek Urška , Tonon Federica , Abrami Michela , Ručigaj Aleš , Grassi Mario , Pozzato Gabriele , Bonazza Deborah , Zanconati Fabrizio , Forte Giancarlo , El Boustani Maguie , Scarabel Lucia , Garziera Marica , Russo Spena Concetta , De Stefano Lucia , Salis Barbara , Toffoli Giuseppe , Rizzolio Flavio , Grassi Gabriele , Dapas Barbara
Published: March 2018

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.
Synthesis of Novel Amino Acid–Fipronil Conjugates and Study on Their Phloem Loading Mechanism
Authors: Sheng Qingqing , Liu Xinxin , Xie Yun , Lin Fei , Zhang Zhixiang , Zhao Chen , Xu Hanhong
Published: March 2018

To develop a new pesticide with phloem mobility, a series of new amino acid–fipronil conjugates were designed and synthesized based on derivatization at the 3-position of the pyrazole ring of fipronil. Experiments using a Ricinus communis seedling system showed that all tested conjugates were phloem mobile except for the isoleucine–fipronil conjugate, and that the serine–fipronil conjugate (4g) exhibited the highest concentration in phloem sap (52.00 ± 5.80 μM). According to prediction with log Cf values and uptake experiments with Xenopus oocytes, the phloem loading process of conjugate 4g involved both passive diffusion and an active carrier system (RcANT15). In particular, compared with for a previously reported glycinergic–fipronil conjugate (GlyF), passive diffusion played a more important role for conjugate 4g in the enhancement of phloem mobility. This study suggests that associating a nutrient at a different position of an existing pesticide structure could still be effective in obtaining phloem-mobile derivatives, but the distinct physicochemical properties of resultant conjugates may lead to different phloem loading mechanisms.
Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical Approach
Authors: Makarov Vladimir , Khmelinskii Igor , Javadov Sabzali
Published: March 2018

Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier.
Investigation of Absorption Routes of Meloxicam and Its Salt Form from Intranasal Delivery Systems
Authors: Bartos Csilla , Ambrus Rita , Kovács Anita , Gáspár Róbert , Sztojkov-Ivanov Anita , Márki Árpád , Janáky Tamás , Tömösi Ferenc , Kecskeméti Gábor , Szabó-Révész Piroska
Published: March 2018

The aim of this article was to study the trans-epithelial absorption to reach the blood and to target the brain by axonal transport using nasal formulations with nanonized meloxicam (nano MEL spray) and its salt form known as meloxicam potassium monohydrate (MELP spray). The physicochemical properties and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out. These forms were first investigated in “nose-to-brain” relation. It was found that the in vitro study and in vivo study did not show any significant correlation. In vitro experiments demonstrated faster dissolution rate and higher diffusion of MELP from the spray compared with the nano MEL spray. The administration of the nano MEL spray resulted in faster absorption and constant plasma concentration of the drug after five minutes of administration as compared to MELP. The axonal transport of the drug was justified. MEL appeared in the brain tissues after the first five minutes of administration in the case of both spray forms, but its amount was too small in comparison with the total plasma concentration. The application of the nano MEL spray resulted in the same AUC in the brain as the intravenous injection. The “nose-to-blood” results predicted the nasal applicability of MEL and MELP in pain management. The “nose-to-brain” pathway requires further study.
Dissipation and Migration of Pyrethroids in Auricularia polytricha Mont. from Cultivation to Postharvest Processing and Dietary Risk
Authors: Xiao Jin-Jing , Duan Jin-Sheng , Wu Yan-Can , Shi Yan-Hong , Fang Qing-Kui , Liao Min , Hua Ri-Mao , Cao Hai-Qun
Published: March 2018

In order to ensure raw consumption safety the dissipation behavior, migration, postharvest processing, and dietary risk assessment of five pyrethroids in mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field conditions. Half-lives (t1/2) of pyrethroids in fruiting body and substrate samples were 3.10–5.26 and 17.46–40.06 d, respectively. Fenpropathrin dissipated rapidly in fruiting bodies (t1/2 3.10 d); bifenthrin had the longest t1/2. At harvest, pyrethroid residues in A. polytricha (except fenpropathrin) were above the respective maximum residue limits (MRLs). Some migration of lambda-cyhalothrin was observed in the substrate-fruit body system. In postharvest-processing, sun-drying and soaking reduced pyrethroid residues by 25–83%. We therefore recommend that consumers soak these mushrooms in 0.5% NaHCO3 at 50 °C for 90 min. Pyrethroids exhibit a particularly low PF value of 0.08–0.13%, resulting in a negligible exposure risk upon mushroom consumption. This study provides guidance for the safe application of pyrethroids to edible fungi, and for the establishment of MRLs in mushrooms to reduce pesticide exposure in humans.
UHPLC-MS Metabolome Fingerprinting: The Isolation of Main Compounds and Antioxidant Activity of the Andean Species Tetraglochin ameghinoi (Speg.) Speg.
Authors: Luna Lorena , Simirgiotis Mario , Lima Beatriz , Bórquez Jorge , Feresin Gabriela , Tapia Alejandro
Published: March 2018

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4′,6′,-dihydroxy-2′-O-(6″-acetyl)-β-d-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant.
The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose Homeostasis in a Diet-Induced Pre-Diabetic Rat Model
Authors: Gamede Mlindeli , Mabuza Lindokuhle , Ngubane Phikelelani , Khathi Andile
Published: March 2018

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this compound on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects OA on a diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were treated with OA in both the presence and absence of dietary intervention for a period of 12 weeks. The administration of OA with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, plasma ghrelin concentration and glycated haemoglobin by comparison to the pre-diabetic control. These results suggest that OA may be used to manage pre-diabetes as it was able to restore glucose homeostasis and prevented the progression to overt type 2 diabetes.
Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity
Authors: Ma Qingyu , Liu Qiuming , Yuan Ling , Zhuang Yongliang
Published: March 2018

A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) identified in the hydrolysate had a high hydroxyl radical scavenging activity. In this study, activities of LSGYGP were further evaluated using ultraviolet B (UVB)-induced mouse embryonic fibroblasts (MEFs). UVB irradiation significantly increased the intercellular reactive oxygen species (ROS) production and matrix metalloproteinases (MMPs) activities and decreased the content of collagen in MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs. Meanwhile, the decrease of superoxide dismutase (SOD) activity and the increase of malondiaidehyde (MDA) content were inhibited by LSGYGP. LSGYGP reduced MMP-1 and MMP-9 activities in a dose-dependent manner. Molecular docking simulation indicated that LSGYGP inhibited MMPs activities by docking the active sites of MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular phosphorylation of UVB-induced the mitogen-activated protein kinase pathway. LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by inhibiting oxidative stress and regulating MMPs activities.
The Modal—Amodal Distinction in the Debate on Conceptual Format
Authors: Haimovici Sabrina
Published: March 2018

In this paper, I review the main criteria offered for distinguishing the modal and amodal approaches to conceptual format: the type of input to which the representations respond, the relation they bear to perceptual states, and the specific neural systems to which they belong. I evaluate different interpretations of them and argue that they all face difficulties. I further show that they lead to cross-classifications of certain types of representations, using approximate number representations as an example.
Spatiotemporal Fusion of Multisource Remote Sensing Data: Literature Survey, Taxonomy, Principles, Applications, and Future Directions
Authors: Zhu Xiaolin , Cai Fangyi , Tian Jiaqi , Williams Trecia
Published: March 2018

Satellite time series with high spatial resolution is critical for monitoring land surface dynamics in heterogeneous landscapes. Although remote sensing technologies have experienced rapid development in recent years, data acquired from a single satellite sensor are often unable to satisfy our demand. As a result, integrated use of data from different sensors has become increasingly popular in the past decade. Many spatiotemporal data fusion methods have been developed to produce synthesized images with both high spatial and temporal resolutions from two types of satellite images, frequent coarse-resolution images, and sparse fine-resolution images. These methods were designed based on different principles and strategies, and therefore show different strengths and limitations. This diversity brings difficulties for users to choose an appropriate method for their specific applications and data sets. To this end, this review paper investigates literature on current spatiotemporal data fusion methods, categorizes existing methods, discusses the principal laws underlying these methods, summarizes their potential applications, and proposes possible directions for future studies in this field.
Flexible Gas Sensors Employing Octahedral Indium Oxide Films
Authors: Alvarado Miriam , Navarrete Èric , Romero Alfonso , Ramírez José Luis , Llobet Eduard
Published: March 2018

Indium oxide octahedral nanopowders were obtained from an ionic precursor compound after an oxidation process conducted under a low-oxygen atmosphere. This method was found to produce contamination-free indium oxide nanomaterial with very similar morphological and crystalline properties to the one produced by vapor-phase transport, but at significantly lower temperatures and higher yield. The as-synthesized indium oxide was mixed to an organic vehicle and microdrop deposited to form a film bridging the interdigitated silver electrodes patterned on top of a flexible, polyimide (Kapton®), substrate. The gas sensing properties of the flexible chemoresistors towards ammonia vapors, hydrogen, and nitrogen dioxide were investigated. It was found that these sensors were remarkably sensitive to nitrogen dioxide at a low operating temperature of 150 °C. These results are consistent with the performance of vapor-phase transport synthesized indium oxide octahedra sensors on rigid, ceramic substrates. Therefore, the results presented here pave the way for the mass production of inexpensive gas sensors onto flexible substrates via additive manufacturing.
Direct Printing of Stretchable Elastomers for Highly Sensitive Capillary Pressure Sensors
Authors: Liu Wenguang , Yan Chaoyi
Published: March 2018

We demonstrate the successful fabrication of highly sensitive capillary pressure sensors using an innovative 3D printing method. Unlike conventional capacitive pressure sensors where the capacitance changes were due to the pressure-induced interspace variations between the parallel plate electrodes, in our capillary sensors the capacitance was determined by the extrusion and extraction of liquid medium and consequent changes of dielectric constants. Significant pressure sensitivity advances up to 547.9 KPa−1 were achieved. Moreover, we suggest that our innovative capillary pressure sensors can adopt a wide range of liquid mediums, such as ethanol, deionized water, and their mixtures. The devices also showed stable performances upon repeated pressing cycles. The direct and versatile printing method combined with the significant performance advances are expected to find important applications in future stretchable and wearable electronics.
Linear Feature Projection-Based Sensory Event Detection from the Multiunit Activity of Dorsal Root Ganglion Recordings
Authors: Han Sungmin , Youn Inchan
Published: March 2018

Afferent signals recorded from the dorsal root ganglion can be used to extract sensory information to provide feedback signals in a functional electrical stimulation (FES) system. The goal of this study was to propose an efficient feature projection method for detecting sensory events from multiunit activity-based feature vectors of tactile afferent activity. Tactile afferent signals were recorded from the L4 dorsal root ganglion using a multichannel microelectrode for three types of sensory events generated by mechanical stimulation on the rat hind paw. The multiunit spikes (MUSs) were extracted as multiunit activity-based feature vectors and projected using a linear feature projection method which consisted of projection pursuit and negentropy maximization (PP/NEM). Finally, a multilayer perceptron classifier was used to detect sensory events. The proposed method showed a detection accuracy superior to those of other linear and nonlinear feature projection methods and all processes were completed within real-time constraints. Results suggest that the proposed method could be useful to detect sensory events in real time. We have demonstrated the methodology for an efficient feature projection method to detect real-time sensory events from the multiunit activity of dorsal root ganglion recordings. The proposed method could be applied to provide real-time sensory feedback signals in closed-loop FES systems.
A Sparsity-Promoted Method Based on Majorization-Minimization for Weak Fault Feature Enhancement
Authors: Ren Bangyue , Hao Yansong , Wang Huaqing , Song Liuyang , Tang Gang , Yuan Hongfang
Published: March 2018

Fault transient impulses induced by faulty components in rotating machinery usually contain substantial interference. Fault features are comparatively weak in the initial fault stage, which renders fault diagnosis more difficult. In this case, a sparse representation method based on the Majorzation-Minimization (MM) algorithm is proposed to enhance weak fault features and extract the features from strong background noise. However, the traditional MM algorithm suffers from two issues, which are the choice of sparse basis and complicated calculations. To address these challenges, a modified MM algorithm is proposed in which a sparse optimization objective function is designed firstly. Inspired by the Basis Pursuit (BP) model, the optimization function integrates an impulsive feature-preserving factor and a penalty function factor. Second, a modified Majorization iterative method is applied to address the convex optimization problem of the designed function. A series of sparse coefficients can be achieved through iterating, which only contain transient components. It is noteworthy that there is no need to select the sparse basis in the proposed iterative method because it is fixed as a unit matrix. Then the reconstruction step is omitted, which can significantly increase detection efficiency. Eventually, envelope analysis of the sparse coefficients is performed to extract weak fault features. Simulated and experimental signals including bearings and gearboxes are employed to validate the effectiveness of the proposed method. In addition, comparisons are made to prove that the proposed method outperforms the traditional MM algorithm in terms of detection results and efficiency.