bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrocyclic Compounds for Drug and Gene Delivery in Immune-Modulating Therapy
Authors: Bai Hongzhen , Wang Jianwei , Li Zhongbao , Tang Guping
Published: April 2019

For decades, macrocyclic compounds have been widely applied in various fields owing to essential physicochemical properties such as their rigid cyclic structures, geometric dimensions (diameter and height), hydrophobic cavity, and hydrophilic interface. This review is an attempt to summarize various research accomplishments involving macrocyclic compounds for drug and gene delivery in immune-modulating therapies: the structures and benefits of main host molecules, their mechanisms regulating the immune system from cell uptake to activation of dendritic cells and T helper lymphocytes, as well as their potential immunotherapy for different diseases. Macrocyclic compounds including cucurbiturils (CBs), calixarenes, pillararenes, cyclodextrins (CyDs), macrocyclic peptides and metallo-supramolecular compounds, have their own unique physicochemical properties and functional derivatizations that enable to improve the biocompatibility, responsiveness to stimuli, and effectiveness of immune-modulating therapy. Based on abundant clarifications of the biological immunity mechanisms, representative constructions of macrocyclic compounds for immune therapies have been conducted for the investigation of treatment of different diseases including cancer, atherosclerosis, Niemann-Pick type C1 disease (NPC1), diabetes, and inflammations. Although there are critical challenges that remain to be conquered, we believe the future of macrocyclic compounds in the immune-modulating therapy must be bright.
Mapping Semaphorins and Netrins in the Pathogenesis of Human Thoracic Aortic Aneurysms
Authors: Alebrahim Dornazsadat , Nayak Mangala , Ward Alison , Ursomanno Patricia , Shams Rebecca , Corsica Annanina , Sleiman Rayan , Hyppolite Fils Kissinger , Silvestro Michele , Boytard Ludovic , Hadi Tarik , Gelb Bruce , Ramkhelawon Bhama
Published: April 2019

Thoracic aortic aneurysm (TAA) is a complex life-threatening disease characterized by extensive extracellular matrix (ECM) fragmentation and persistent inflammation, culminating in a weakened aorta. Although evidence suggests defective canonical signaling pathways in TAA, the full spectrum of mechanisms contributing to TAA is poorly understood, therefore limiting the scope of drug-based treatment. Here, we used a sensitive RNA sequencing approach to profile the transcriptomic atlas of human TAA. Pathway analysis revealed upregulation of key matrix-degrading enzymes and inflammation coincident with the axonal guidance pathway. We uncovered their novel association with TAA and focused on the expression of Semaphorins and Netrins. Comprehensive analysis of this pathway showed that several members were differentially expressed in TAA compared to controls. Immunohistochemistry revealed that Semaphorin4D and its receptor PlexinB1, similar to Netrin-1 proteins were highly expressed in damaged areas of TAA tissues but faintly detected in the vessel wall of non-diseased sections. It should be considered that the current study is limited by its sample size and the use of internal thoracic artery as control for TAA for the sequencing dataset. Our data determines important neuronal regulators of vascular inflammatory events and suggest Netrins and Semaphorins as potential key contributors of ECM degradation in TAA.
Expanding Genetic Code Expansion through Resource Facilities, Workshops, and Conferences
Authors: Petersson E. James , Mehl Ryan A. , Ahern Christopher A.
Published: April 2019

Genetic Code Expansion (GCE) enables the encoding of amino acids with diverse chemical properties. This approach has tremendous potential to advance biological discoveries in basic research, medical, and industrial settings. Given the multiple technical approaches and the associated research activities used to achieve GCE, herein we have taken the opportunity to describe ongoing out-reach efforts in the GCE community. These include Resource Facilities that nucleate expertise and reagents within a specific GCE discipline, hands-on Workshops to provide GCE training, and GCE Conferences which bring the community together in a collegial setting. The overall goal of these activities is to accelerate the integration of GCE approaches into more research settings and to facilitate solutions to common technical hurdles.
UMP Kinase Regulates Chloroplast Development and Cold Response in Rice
Authors: Dong Qing , Zhang Ying-Xin , Zhou Quan , Liu Qun-En , Chen Dai-Bo , Wang Hong , Cheng Shi-Hua , Cao Li-Yong , Shen Xi-Hong
Published: April 2019

Pyrimidine nucleotides are important metabolites that are building blocks of nucleic acids, which participate in various aspects of plant development. Only a few genes involved in pyrimidine metabolism have been identified in rice and the majority of their functions remain unclear. In this study, we used a map-based cloning strategy to isolate a UMPK gene in rice, encoding the UMP kinase that phosphorylates UMP to form UDP, from a recessive mutant with pale-green leaves. In the mutant, UDP content always decreased, while UTP content fluctuated with the development of leaves. Mutation of UMPK reduced chlorophyll contents and decreased photosynthetic capacity. In the mutant, transcription of plastid-encoded RNA polymerase-dependent genes, including psaA, psbB, psbC and petB, was significantly reduced, whereas transcription of nuclear-encoded RNA polymerase-dependent genes, including rpoA, rpoB, rpoC1, and rpl23, was elevated. The expression of UMPK was significantly induced by various stresses, including cold, heat, and drought. Increased sensitivity to cold stress was observed in the mutant, based on the survival rate and malondialdehyde content. High accumulation of hydrogen peroxide was found in the mutant, which was enhanced by cold treatment. Our results indicate that the UMP kinase gene plays important roles in regulating chloroplast development and stress response in rice.
Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species
Authors: Usuki Seigo , Tamura Noriko , Tamura Tomohiro , Tanji Kunikazu , Mikami Daisuke , Mukai Katsuyuki , Igarashi Yasuyuki
Published: April 2019

Konjac ceramide (kCer), which consists of plant-type molecular species of characteristic shingoid bases and fatty acids, is prepared from konjac glucosylceramide GlcCer by chemoenzymatical deglucosylation. kCer activates the semaphorin 3A (Sema3A) signaling pathway, inducing collapsin response mediator protein 2 (CRMP2) phosphorylation. This results in neurite outgrowth inhibition and morphological changes in remaining long neurites in PC12 cells. Whether a specific molecular species of kCer can bind to the Sema3A receptor (Neuropilin1, Nrp1) and activate the Sema3A signaling pathway remains unknown. Here, we prepared kCer molecular species using endoglycoceramidase I-mediated deglucosylation and examined neurite outgrowth and phosphorylation of collapsin response mediator protein 2 in nerve growth factor (NGF)-primed cells. The 8-trans unsaturation of sphingadienine of kCer was essential for Sema3A-like signaling pathway activation. Conversely, 8-cis unsaturation of kCer molecular species had no effect on Sema3A-like activation, and neurite outgrowth inhibition resulted in remaining short neurites. In addition, α-hydroxylation of fatty acids was not associated with the Sema3A-like activity of the kCer molecular species. These results suggest that 8-trans or 8-cis isomerization of sphingadienine determines the specific interactions at the ligand-binding site of Nrp1.
A Viral Polymerase Inhibitor Reduces Zika Virus Replication in the Reproductive Organs of Male Mice
Authors: Jacobs Sofie , Delang Leen , Verbeken Eric , Neyts Johan , Kaptein Suzanne J.F.
Published: April 2019

In humans, Zika virus and viral RNA have been detected in semen up to 2.2 months and 6 months post infection (pi), respectively. Although the contribution of sexual transmission to the spread of ZIKV is too low to sustain an outbreak, it can increase the risk of infection and the epidemic size as well as prolong the duration of an outbreak. In this study, we explored the potential of antivirals to serve as an effective strategy to prevent sexual transmission. Male AG129 mice infected with a ZIKV isolate from Suriname were treated with the nucleoside analog, 7-deaza-2′-C-methyladenosine (7DMA), that was previously shown to be efficacious in reducing ZIKV viremia and delaying ZIKV-induced disease in mice. Following treatment, viral RNA and infectious virus titers were consistently reduced in the male reproductive organs compared to vehicle-treated mice. This reduction of ZIKV loads in the testis was confirmed by the detection of lower levels of ZIKV antigens. Our data illustrate the value of this mouse model to validate the efficacy of new potential ZIKV drugs at the level of the male reproductive system.
Evaluation of Wireless Phosphine Sensors for Monitoring Fumigation Gas in Wheat Stored in Farm Bins
Authors: Brabec Daniel , Campbell James , Arthur Frank , Casada Mark , Tilley Dennis , Bantas Sotiris
Published: April 2019

Fumigation of grain bins with phosphine tablets is one method of insect control for stored products. Monitoring the concentration of the toxic gas at many locations over several days for a given structure or container can be challenging. In this study, a commercially-available system that wirelessly measures phosphine was evaluated in small-scale and large-scale tests. Small-scale testing was performed to study the repeatability and accuracy of the sensors. The wireless sensors were within 30 ppm of each other, over a range of 700 ppm phosphine. Large-scale testing evaluated the system during the fumigation of wheat stored in 7 m diameter, 120 metric ton, steel grain bins. As a reference, monitoring lines were distributed at several positions and depths in the bin in order to sample phosphine gas concentrations. A series of three fumigation trials were performed, with each lasting for over six days. The wireless devices collected local phosphine concentrations and temperatures every two hours without assistance from personnel. Although the fumigation trials were significantly different in terms of patterns in gas concentration over time, the two sampling methods gave similar trendlines. However, the automated data provided a more detailed picture of the fumigation process. This information may help fumigation managers to better evaluate fumigations and assure successful insect control.
Feasibility of Agricultural Biomass Fly Ash Usage for Soil Stabilisation of Road Works
Authors: Barišić Ivana , Netinger Grubeša Ivanka , Dokšanović Tihomir , Marković Berislav
Published: April 2019

Agricultural biomass ash is a waste material produced by incineration of residue from fields after harvesting crops. The use of agricultural biomass in industry produces large quantities of ash that represent an ecological problem. Another ecological problem is the dependency of road building on natural materials, which has been traditionally used for all pavement layers. Today, roads are built on less accessible and suitable terrains, increasing the need for improving the mechanical characteristics of locally available materials by various means of stabilisation. Within this research, three agricultural biomass fly ashes are used as lime substitutes for hydraulically stabilised soil. The purpose of this research is evaluation of potential use of agricultural biomass fly ash for the soil stabilisation of road works, i.e., for embankment and subgrade purposes. The results indicate that there is a potential of using barley, sunflower seed shells and wheat fly ash as lime substitutes in the soil stabilisation of road works. The strength characteristics of stabilised soil incorporating biomass fly ash are highly dependent on its chemical composition. Using a three-dimensional digital image correlation technique, it is concluded that the elastic properties of stabilised soil correlate to a fracture mechanism that can be efficiently defined by this modern research tool.
Impacts of Low Atmospheric Pressure on Properties of Cement Concrete in Plateau Areas: A Literature Review
Authors: Huo Jinyang , Wang Zhenjun , Chen Huaxin , He Rui
Published: April 2019

Low atmospheric pressure (LAP) can enormously affect properties of cement concrete in plateau areas. There are fewer studies and attendances on this issue than those of cement concrete in normal atmospheric pressure (AP), because of the limitations of both environmental conditions and instruments. In order to improve properties of cement concrete under LAP, influences of LAP on properties of cement concrete were reviewed in this work. The influence rules and mechanism on properties of cement concrete were summarized. The corresponding mechanism and techniques were put forward for enhancing the properties of cement concrete. The results of researchers show that LAP can significantly reduce the air entraining ability of the air entraining agent (AEA). Air content in concrete linearly decreases with the decrease of AP when other conditions are constant. If the initial air content is high, the decrease rate of air content increases with the decrease of AP. When the initial air content in cement concretes is similar, the greater the slump of cement concrete, the stronger its resistance to the decrease of air content caused by the decrease of AP. In addition, the condition of the bubble characteristics of hardened cement concrete under LAP is worse than that under normal AP. Therefore, the change of concrete properties under LAP is mainly attributed to these bubble characteristics, such as air content, bubble spacing coefficient, bubble radius and bubble specific surface area. In this work, nano-silica (negative charges) with cationic oligomeric surfactants is recommended as a new type of AEA to optimize the bubble characteristics under LAP in plateau areas.
The Influence of Process Parameters and Build Orientation on the Creep Behaviour of a Laser Powder Bed Fused Ni-based Superalloy for Aerospace Applications
Authors: Hilal Hani , Lancaster Robert , Jeffs Spencer , Boswell John , Stapleton David , Baxter Gavin
Published: April 2019

Additive Layer Manufacturing (ALM) is an innovative net shape manufacturing technology that offers the ability to produce highly intricate components not possible through traditional wrought and cast procedures. Consequently, the aerospace industry is becoming ever more attentive in exploiting such technology for the fabrication of nickel-based superalloys in an attempt to drive further advancements within the holistic gas turbine. Given this, the requirement for the mechanical characterisation of such material is rising in parallel, with limitations in the availability of material processed restricting conventional mechanical testing; particularly with the abundance of process parameters to evaluate. As such, the Small Punch Creep (SPC) test method has been deemed an effective tool to rank the elevated temperature performance of alloys processed through ALM, credited to the small volumes of material utilised in each test and the ability to sample material from discrete locations. In this research, the SPC test will be used to assess the influence of a number of key process variables on the mechanical performance of Laser Powder Bed Fused (LPBF) Ni-based superalloy CM247LC. This will also include an investigation into the influence of build orientation and post-build treatment on creep performance, whilst considering the structural integrity of the different experimental builds.
Microstructure Characterization and Corrosion Resistance of Zinc Coating Obtained on High-Strength Grade 10.9 Bolts Using a New Thermal Diffusion Process
Authors: Kania Henryk , Sipa Jacek
Published: April 2019

The article presents the results of research on the application of innovative thermal diffusion zinc coating technology with the recirculation of the reactive atmosphere to high-strength grade 10.9 bolts. The innovation of this method consists in the introduction of reactive atmosphere recirculation and the application of coating powder mix which contains zinc powder and activator. Recirculation of the reactive atmosphere ensures its uniform composition, while the presence of an activator intensifies the process of saturating steel surface with zinc, which boosts the efficiency of active agents. Coatings were created at 440 °C and a heat soaking time of 30–240 min. Coating structure (SEM) was exposed, chemical composition in microsites (EDS) was defined, and coating phase structure (XRD) was identified. The kinetics of coating growth were defined. It was found that the increment of coating thickness was controlled by square root of soaking time. Coatings obtained using innovative thermal diffusion zinc coating technology had a two-layer structure. At the substrate, a compact layer of phase Γ1 (Fe11Zn40) was created, which was covered with a layer of phase δ1 (FeZn10). The new method of thermal diffusion zinc coating will alow for the creation of coatings of very good corrosion resistance while maintaining strength properties of bolts defined as strength class 10.9.
Numerical Reckoning Fixed Points of (ρE)-Type Mappings in Modular Vector Spaces
Authors: Kassab Wissam , Ţurcanu Teodor
Published: April 2019

In this paper, we study an iteration process introduced by Thakur et al. for Suzuki mappings in Banach spaces, in the new context of modular vector spaces. We establish existence results for a more recent version of Suzuki generalized non-expansive mappings. The stability and data dependence of the scheme for ρ -contractions is studied as well.
A Quantitative Validation Method of Kriging Metamodel for Injection Mechanism Based on Bayesian Statistical Inference
Authors: You Dongdong , Shen Xiaocheng , Zhu Yanghui , Deng Jianxin , Li Fenglei
Published: April 2019

A Bayesian framework-based approach is proposed for the quantitative validation and calibration of the kriging metamodel established by simulation and experimental training samples of the injection mechanism in squeeze casting. The temperature data uncertainty and non-normal distribution are considered in the approach. The normality of the sample data is tested by the Anderson–Darling method. The test results show that the original difference data require transformation for Bayesian testing due to the non-normal distribution. The Box–Cox method is employed for the non-normal transformation. The hypothesis test results of the calibrated kriging model are more reliable after data transformation. The reliability of the kriging metamodel is quantitatively assessed by the calculated Bayes factor and confidence. The Bayesian factor and the confidence level results indicate that the kriging model demonstrates improved accuracy and is acceptable after data transformation. The influence of the threshold ε on both the non-normally and normally distributed data in the model is quantitatively evaluated. The threshold ε has a greater influence and higher sensitivity when applied to the normal data results, based on the rapid increase within a small range of the Bayes factors and confidence levels.
Influence of Welding on Dynamic Fracture Toughness of Strenx 700MC Steel
Authors: Schmidová Eva , Bozkurt Fatih , Culek Bohumil , Kumar Sunil , Kuchariková Lenka , Uhríčik Milan
Published: April 2019

Thermomechanically processed high-strength steels feature specific fracture behavior. One of the decisive criteria for their application is their stability against internal defects during impact loads, especially in connection with the welding. The work is focused on experimental analyses of the influence of welding on static and dynamic fracture toughness of Strenx 700MC steel. The fracture toughness was determined using the circumferentially notched round bar specimens during static loads and two dynamic load levels. To achieve a homogeneous zone for the requirements of fracture toughness tests, simulation of the welding influence was performed. Fractographic and metallographic analyses described a specific fracture behavior controlled by the internal structural heterogeneity. A limiting degradation process due to welding was identified by the microstructural analysis.
Modeling Thermomechanical Stress with H13 Tool Steel Material Response for Rolling Die under Hot Milling
Authors: Tolcha Mesay Alemu , Lemu Hirpa Gelgele
Published: April 2019

For the extreme pressure and temperature arising in the hot rolling process, thermomechanical (TM) models are used to predict the residual stresses on the surface of the die because a quantification of the TM stresses allows a prediction of the life span of the rolling die. As the accuracy and consistency of models developed in this area show a large variation due to the considered parameters, conditions, and assumptions, the capability of the developed models needs to be verified for a particular set of circumstances. In this study, new constitutive equations are proposed and a model consisting of five sub-models that computes temperature distribution, thermal stresses, mechanical stresses, and thermomechanical stress for the rolling die under continuous casting application has been developed and presented in this paper. The first sub-model describes the temperature distribution on the rolling die surface by accounting for the effects of different process parameters such as the initial temperature of the slab, reduction ratio, and the rolling speed, while the second and the third sub-models describe the thermal cyclic stress and the elasticity deformation of mechanical stress, respectively. Furthermore, the fourth sub-model describes the TM stress generation through inheriting numerical approaches, and the last sub-model is developed for the H13 tool material response at a high temperature. To verify the developed analytical models, a finite element simulation and the experimental data are considered. The analytical models are computed using Python, and the ABAQUS software has been used for the finite element simulations. The results show a good agreement with the finite element simulation and experimental data.
Effect of Rolling Speed on Microstructural and Microtextural Evolution of Nb Tubes during Caliber-Rolling Process
Authors: Lee Jongbeom , Jeong Haguk
Published: April 2019

This study investigated the fabrication of Nb tubes via the caliber-rolling process at various rolling speeds from 1.4 m/min to 9.9 m/min at ambient temperature, and the effect of the caliber-rolling speed on the microstructural and microtextural evolution of the Nb tubes. The caliber-rolling process affected the grain refinement when the Nb tube had a higher fraction of low angle grain boundaries. However, the grain size was identical regardless of the rolling speed. The dislocation density of the Nb tubes increased with the caliber-rolling speed according to the Orowan equation. The reduction of intensity for the <111> fiber texture and the development of the <112> fiber texture with the increase of the strain rate are considered to have decreased the internal energy by increasing the fraction of the low-energy Σ3 boundaries.
Small-Scale Mechanical Testing of Cemented Carbides from the Micro- to the Nano-Level: A Review
Authors: Naughton-Duszová Annamária , Csanádi Tamás , Sedlák Richard , Hvizdoš Pavol , Dusza Ján
Published: April 2019

In this overview, we summarize the results published to date concerning the small-scale mechanical testing of WC–Co cemented carbides and similar hardmetals, describing the clear trend in the research towards ever-smaller scales (currently at the nano-level). The load-size effect during micro/nanohardness testing of hardmetals and their constituents and the influence of the WC grain orientation on their deformation, hardness, indentation modulus, fracture toughness, and fatigue characteristics are discussed. The effect of the WC grain size/orientation, cobalt content, and testing environment on damage accumulation, wear mechanisms, and wear parameters are summarized. The deformation and fracture characteristics and mechanical properties, such as the yield and compression strength, of WC–Co composites and their individual WC grains at different orientations during micropillar compression tests are described. The mechanical and fracture properties of micro-cantilevers milled from WC–Co hardmetals, single WC grains, and cantilevers containing WC/WC boundaries with differently-oriented WC grains are discussed. The physical background of the deformation and damage mechanisms in cemented carbides at the micro/nano-levels is descri and potential directions for future research in this field are outlined.
Sparse-TFM Imaging of Lamb Waves for the Near-Distance Defects in Plate-Like Structures
Authors: Zhang Haiyan , Liu Yaqun , Fan Guopeng , Zhang Hui , Zhu Wenfa , Zhu Qi
Published: April 2019

The ultrasonic phased array total focusing method (TFM) has the advantages of high imaging resolution and high sensitivity to small defects. However, it has a long imaging time and cannot realize near-distance defect imaging, which limits its application for industrial detection. A sparse-TFM algorithm is adopted in this work to solve the problem regarding rapid imaging of near- distance defects in thin plates. Green’s function is reconstructed through the cross-correlation of the diffuse full matrix captured by the ultrasonic phased array. The reconstructed full matrix recovers near-distance scattering information submerged by noise. A sparse array is applied to TFM for rapid imaging. In order to improve the imaging resolution, the location of active array elements in the sparse array can be optimized using the genetic algorithm (GA). Experiments are conducted on three aluminium plates with near-distance defects. The experimental results confirm that the sparse-TFM algorithm of Lamb waves can be used for near-distance defects imaging, which increases the computational efficiency by keeping the imaging accuracy. This paper provides a theoretical guidance for Lamb wave non-destructive testing of the near-distance defects in plate-like structures.
Design, Fabrication and Mass-spectrometric Studies of a Micro Ion Source for High-Field Asymmetric Waveform Ion Mobility Spectrometry
Authors: Li Hua , Yun Hongmei , Du Xiaoxia , Guo Chaoqun , Zeng Ruosheng , Jiang Yongrong , Chen Zhencheng
Published: April 2019

A needle-to-cylinder electrode, adopted as an ion source for high-field asymmetric ion mobility spectrometry (FAIMS), is designed and fabricated by lithographie, galvanoformung and abformung (LIGA) technology. The needle, with a tip diameter of 20 μm and thickness of 20 μm, and a cylinder, with a diameter of 400 μm, were connected to the negative high voltage and ground, respectively. A negative corona and glow discharge were realized. For acetone with a density of 99.7 ppm, ethanol with a density of 300 ppm, and acetic ether with a density of 99.3 ppm, the sample gas was ionized by the needle-to-cylinder chip and the ions were detected by an LTQ XL™ (Thermo Scientific Corp.) mass spectrometer. The mass spectra show that the ions are mainly the protonated monomer, the proton bound dimer, and an ion-H2O molecule cluster. In tandem with a FAIMS system, the FAIMS spectra show that the resolving power increases with an increase in the RF voltage. The obtained experimental results showed that the micro needle-to-cylinder chip may serve as a miniature, low cost and non-radioactive ion source for FAIMS.
Petrogenesis of the Early Cretaceous Tiantangshan A-Type Granite, Cathaysia Block, SE China: Implication for the Tin Mineralization
Authors: Jia Ru-Ya , Wang Guo-Chang , Geng Lin , Pang Zhen-Shan , Jia Hong-Xiang , Zhang Zhi-Hui , Chen Hui , Liu Zheng
Published: April 2019

The newly discovered Tiantangshan tin polymetallic deposit is located in the southeast Nanling Range, Cathaysia block, Southeast China. The tin orebodies are mainly hosted in the greisen and the fractured alteration zones of the tufflava and trachydacite. However, the genetic relationship between the hidden alkali-feldspar granite and volcanic rocks and the tin mineralization remains poorly understood. This paper presents SHRIMP zircon U–Pb dating, whole-rock major and trace element analyses, as well as Nd isotopic data of the trachydacite and alkali-feldspar granite. The SHRIMP zircon U–Pb dating of the alkali-feldspar granite and trachydacite yields weight mean 206Pb/238U ages of 138.4 ± 1.2, and 136.2 ± 1.2 Ma, respectively. These granitic rocks have high levels of SiO2 (64.2–75.4 wt%, mostly > 68 wt%), alkalis (K2O + Na2O > 8.3 wt%), REE (except for Eu), HFSE (Zr + Nb + Ce + Y > 350 ppm) and Ga/Al ratios (10,000 × Ga/Al > 2.6), suggesting that they belong to the A-type granite. According to the high Y/Nb and Yb/Ta ratios, they can be further classified into A1 subtype. Their εNd (T) range from −3.8 to −6.5. They were likely generated by the assimilation-fractional crystallization (AFC) of the coeval oceanic island basalts -like basaltic magma. This study suggests that the A1 type granite is also a potential candidate for the exploration of tin deposits.
He-Ar Isotopes and Trace Gas Compositions of Fluid Inclusions in Massive Sulphides from the Yushui Copper-Polymetallic Deposit, South China: Metallogenic Implications
Authors: Huang Yi , Wu Zhongwei , Sun Xiaoming , Wang Yan , Shi Guiyong , Zhai Wei , Guan Yao
Published: April 2019

The Yushui ore deposit, located in the middle section of the Yong’an-Meixian Hercynian depression, is a medium-sized Cu-polymetallic massive sulphide deposit in Eastern Guangdong Province, South China. This deposit is characterized by unusually high copper grade (up to 50–60 wt. % Cu). Other metallic elements, such as lead, zinc and silver, are also economically important in the Yushui ore bodies. The aim of this study was to apply N2–Ar–He systematics, together with organic gases (light-hydrocarbon tracers), to constrain the origin and evolution of ore-forming fluids. The helium-argon isotopes and trace gas compositions of fluid inclusions trapped within metal sulphide minerals were measured for a number of bonanza ores from the Yushui deposit. The noble gas concentrations in the studied samples vary over one to two orders of magnitude (4He: 2.27–160.00 × 10−5 cm3 STP g−1; 3He: 0.53–34.88 × 10−12 cm3 STP g−1; 40Ar: 6.28–37.82 × 10−7 cm3 STP g−1; 36Ar: 1.25–10.40 × 10−9 cm3 STP g−1). Our data show a narrow range of 3He/4He ratios from 0.006 to 0.056 Ra (~0.026 Ra on average, n = 8), which are considerably lower than the modern atmospheric end-member value; whereas the 40Ar/36Ar ratios (ranging from 333.76 to 501.68, with an average of 397.53) are significantly greater than that of air-saturated water. Most of the bornite samples have somewhat higher 3He/4He ratios of trapped fluids when compared to chalcopyrite. Overall, these He-Ar results are well within the range of crustal reservoir, thus implying a predominantly crustal source (originated from Caledonian basement) for ore-forming solutions, with little contribution from mantle-derived fluids. Analysis of the N2–Ar–He composition in Cu-rich sulphides indicates that the Yushui ore-forming fluids were probably derived from formation water (or basinal hot brines). Moreover, organic gas species identified in sulphide-hosted fluid inclusions are mainly composed of C1–C4 alkanes, while the concentrations of unsaturated olefins and aromatic hydrocarbons are very low. In particular, most chalcopyrite samples with relatively low 3He/4He ratios (0.006–0.016 Ra) and 40Ar*/4He values (0.0002–0.0012) are generally characterized by very high CO2/CH4 ratios (~60–102). All these suggest that main-stage Cu-Ag metallogenic processes might have not been affected by high-temperature magmatic activities or superimposed by strong metamorphic overprinting, although some chalcopyrite-rich ores appear to be influenced by later stage hydrothermal processes. In summary, neither magmatic input nor convecting seawater has played an important role in the formation of Yushui copper-polymetallic deposit. The massive sulphide ore bodies were products of water–rock interaction between metal-bearing basinal brines and the host sedimentary strata.
Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells
Authors: Xia Mengmeng , Fang Yajing , Cao Weiwei , Liang Fuqiang , Pan Siyi , Xu Xiaoyun
Published: April 2019

P-glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance (MDR) in cancer cells. In order to enhance the uptake of chemotherapy drugs, larger amounts of P-gp inhibitors are required. Besides several chemically synthesized P-gp inhibitors, flavonoids as P-gp inhibitors are being investigated, with their advantages including abundance in our daily diet and a low toxicity. The cytotoxicity of daunorubicin (as a substrate of P-gp) to KB/MDR1 cells and the parental KB cells was measured in the presence or absence of flavonoids. A two-dimensional quantitative structure–activity relationship (2D-QSAR) model was built with a high cross-validation coefficient (Q2) value of 0.829. Descriptors including vsurf_DW23, E_sol, Dipole and vsurf_G were determined to be related to the inhibitory activity of flavonoids. The lack of 2,3-double bond, 3′-OH, 4′-OH and the increased number of methoxylated substitutions were shown to be beneficial for the inhibition of P-gp. These results are important for the screening of flavonoids for inhibitory activity on P-gp.
Fabrication and Application of Novel Porous Scaffold in Situ-Loaded Graphene Oxide and Osteogenic Peptide by Cryogenic 3D Printing for Repairing Critical-Sized Bone Defect
Authors: Zhang Yidi , Wang Chong , Fu Li , Ye Shan , Wang Min , Zhou Yanmin
Published: April 2019

Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide’s biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.
Preparation of Pincer Hafnium Complexes for Olefin Polymerization
Authors: Kwon Su Jin , Baek Jun Won , Lee Hyun Ju , Kim Tae Jin , Ryu Ji Yeon , Lee Junseong , Shin Eun Ji , Lee Ki Soo , Lee Bun Yeoul
Published: April 2019

Pincer-type [Cnaphthyl, Npyridine, Namido]HfMe2 complex is a flagship among the post-metallocene catalysts. In this work, various pincer-type Hf-complexes were prepared for olefin polymerization. Pincer-type [Namido, Npyridine, Namido]HfMe2 complexes were prepared by reacting in situ generated HfMe4 with the corresponding ligand precursors, and the structure of a complex bearing 2,6-Et2C6H3Namido moieties was confirmed by X-ray crystallography. When the ligand precursors of [(CH3)R2Si-C5H3N-C(H)PhN(H)Ar (R = Me or Ph, Ar = 2,6-diisopropylphenyl) were treated with in situ generated HfMe4, pincer-type [Csilylmethyl, Npyridine, Namido]HfMe2 complexes were afforded by formation of Hf-CH2Si bond. Pincer-type [Cnaphthyl, Sthiophene, Namido]HfMe2 complex, where the pyridine moiety in the flagship catalyst was replaced with a thiophene unit, was not generated when the corresponding ligand precursor was treated with HfMe4. Instead, the [Sthiophene, Namido]HfMe3-type complex was obtained with no formation of the Hf-Cnaphthyl bond. A series of pincer-type [Cnaphthyl, Npyridine, Nalkylamido]HfMe2 complexes was prepared where the arylamido moiety in the flagship catalyst was replaced with alkylamido moieties (alkyl = iPr, cyclohexyl, tBu, adamantyl). Structures of the complexes bearing isopropylamido and adamantylamido moieties were confirmed by X-ray crystallography. Most of the complexes cleanly generated the desired ion-pair complexes when treated with an equivalent amount of [(C18H37)2N(H)Me]+[B(C6F5)4]−, which showed negligible activity in olefin polymerization. Some complexes bearing bulky substituents showed moderate activities, even though the desired ion-pair complexes were not cleanly afforded.
Modulating the Chemical and Biological Properties of Cancer Stem Cell-Potent Copper(II)-Nonsteroidal Anti-Inflammatory Drug Complexes
Authors: Shin Jimin , Eskandari Arvin , Suntharalingam Kogularamanan
Published: April 2019

Copper(II) complexes bearing nonsteroidal anti-inflammatory drugs (NSAIDs) are known to potently kill cancer stem cells (CSCs), a subpopulation of tumour cells with high metastatic and relapse fidelity. One of the major disadvantages associated to these copper(II) complexes is their instability in the presence of strong cellular reductants (such as ascorbic acid). Here we present a biologically stable copper(II)-NSAID complex containing a bathocuproinedisulfonic acid disodium ligand and two indomethacin moieties, Cu(bathocuproinedisulfonic acid disodium)(indomethacin)2, 2. The copper(II) complex, 2 kills bulk breast cancer cells and breast CSC equally (in the sub-micromolar range) and displays very low toxicity against non-tumorigenic breast and kidney cells (IC50 value > 100 µM). Three-dimensional cell culture studies show that 2 can significantly reduce the number and size of breast CSC mammospheres formed (from single suspensions) to a similar level as salinomycin (an established anti-breast CSC agent). The copper(II) complex, 2 is taken up reasonably by breast CSCs and localises largely in the cytoplasm (>90%). Cytotoxicity studies in the presence of specific inhibitors suggest that 2 induces CSC death via a reactive oxygen species (ROS) and cyclooxygenase isoenzyme-2 (COX-2) dependent apoptosis pathway.
SERS-Active Substrate with Collective Amplification Design for Trace Analysis of Pesticides
Authors: Sitjar Jaya , Liao Jiunn-Der , Lee Han , Liu Bernard Haochih , Fu Wei-en
Published: April 2019

Health risks posed by the exposure to trace amounts of pesticide residue in agricultural products have gained a lot of concerns, due to their neurotoxic nature. The applications of surface-enhanced Raman Scattering (SERS) as a detection technique have consistently shown its potential as a rapid and sensitive means with minimal sample preparation. In this study, gold nanoparticles (Au NPs) in elliptical shapes were collected into a layer of ordered zirconia concave pores. The porous zirconia layer (pZrO2) was then deposited with Au NPs, denoted as Au NPs (x)/pZrO2, where x indicates the deposition thickness of Au NPs in nm. In the concave structure of pZrO2, Au-ZrO2 and Au-Au interactions provide a synergistic and physical mechanism of SERS, which is anticipated to collect and amplify SERS signals and thereafter improve the enhancement factor (EF) of Au NPs/pZrO2. By taking Rhodamine 6G (R6G) as the test molecule, EF of Au NPs/pZrO2 might reach to 7.0 × 107. Au NPs (3.0)/pZrO2 was then optimized and competent to detect pesticides, e.g., phosmet and carbaryl at very low concentrations, corresponding to the maximum residue limits of each, i.e., 0.3 ppm and 0.2 ppm, respectively. Au NPs (3.0)/pZrO2 also showed the effectiveness of distinguishing between phosmet and carbaryl under mixed conditions. Due to the strong affinities of the phosphoric groups and sulfur in phosmet to the Au NPs (3.0)/pZrO2, the substrate exhibited selective detection to this particular pesticide. In this study, Au NPs (3.0)/pZrO2 has thus demonstrated trace detection of residual pesticides, due to the substrate design that intended to provide collective amplification of SERS.
Structural Influence on the Post-Clustering Stability of DNA/AgNCs Fluorescence
Authors: Nagda Riddhi , Shah Pratik , Lee Chang Seop , Park Sooyeon , Yang Seong Wook
Published: April 2019

DNA-encapsulated Silver Nanoclusters (DNA/AgNCs) based sensors have gained increasing attention in past years due to their diverse applications in bioimaging, biosensing, and enzymatic assays. Given the potential of DNA/AgNCs for practical applications, the systematic studies of the fluorescent stability over an extended period is necessary. However, the correlation between nucleic acid properties and the long-term stability of DNA/AgNCs is less known. With locking-to-unlocking sensors, in which the secondary structure of DNA template is standardized, we investigated the correlation between the DNA structure and the fluorescence stability of AgNCs. Post-synthesis of DNA/AgNCs, the fluorescence, and structures of templates were monitored over three weeks. By combining the fluorescence spectroscopy with the in-gel fluorescent assay, we found that AgNCs encapsulated by dimer-structured DNA/AgNCs templates were more stable than those of hairpin-structured DNA/AgNCs templates. While the orange fluorescence from the dimer templates increased over three weeks, the red fluorescence from the hairpin templates was diminished by >80% within two days at room temperature. Further tests revealed that hairpin-encapsulated red-emissive AgNCs is more sensitive to oxidation by atmospheric oxygen compared to dimer encapsulated orange AgNCs. Our observations may provide an important clue in encapsulating photophysically more stable AgNCs by tuning the DNA secondary structures. The proposed strategy here can be essential for pragmatic applications of DNA/AgNCs templates.
The Association of Breakfast Frequency and Cardiovascular Disease (CVD) Risk Factors among Adolescents in Malaysia
Authors: Mustafa Norashikin , Abd Majid Hazreen , Toumpakari Zoi , Carroll Harriet Amy , Yazid Jalaludin Muhammad , Al Sadat Nabilla , Johnson Laura
Published: April 2019

Breakfast frequency is associated with cardiovascular disease (CVD) risk in Western populations, possibly via the types of food eaten or the timing of food consumption, but associations in Malaysian adolescents are unknown. While the timing of breakfast is similar, the type of food consumed at breakfast in Malaysia differs from Western diets, which allows novel insight into the mechanisms underlying breakfast–CVD risk associations. We investigated foods eaten for breakfast and associations between breakfast frequency and CVD risk factors in the Malaysian Health and Adolescents Longitudinal Research Team study (MyHeARTs). Breakfast (frequency of any food/drink reported as breakfast in 7-day diet history interviews) and CVD risk factors (body mass index (BMI), waist circumference, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and systolic and diastolic blood pressure) were cross-sectionally associated using linear regression adjusting for potential confounders (n = 795, age 13 years). Twelve percent of adolescents never ate breakfast and 50% ate breakfast daily, containing mean (SD) 400 (±127) kilocalories. Commonly consumed breakfast foods were cereal-based dishes (primarily rice), confectionery (primarily sugar), hot/powdered drinks (primarily Milo), and high-fat milk (primarily sweetened condensed milk). After adjustment, each extra day of breakfast consumption per week was associated with a lower BMI (−0.34 kg/m2, 95% confidence interval (CI) −0.02, −0.66), and serum total (−0.07 mmol/L 95% CI −0.02, −0.13) and LDL (−0.07 mmol/L 95% CI −0.02, −0.12) cholesterol concentrations. Eating daily breakfast in Malaysia was associated with slightly lower BMI and total and LDL cholesterol concentrations among adolescents. Longitudinal studies and randomized trials could further establish causality.
The Effect of Vitamin C (Ascorbic Acid) in the Treatment of Patients with Cancer: A Systematic Review
Authors: van Gorkom Gwendolyn N.Y. , Lookermans Eline L. , Van Elssen Catharina H.M.J. , Bos Gerard M.J.
Published: April 2019

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.
Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats
Authors: Lee Geum-Hwa , Hoang The-Hiep , Jung Eun-Soo , Jung Su-Jin , Chae Soo-Wan , Chae Han-Jung
Published: April 2019

Dyslipidemia is associated with endothelial dysfunction, which is linked to nitric oxide (NO) biology. The coupling of endothelial NO synthase with cofactors is a major step for NO release. This study is aimed to investigate the vascular pharmacology effects of mulberry in rat thoracic aorta and human vascular endothelial cells. In vitro, we investigated the protective effects of the mulberry extract and its main component cyanidin-3-rutinoside (C-3-R), against oxidized low-density lipoprotein (ox-LDL)-induced endothelial nitric oxide synthase (eNOS) uncoupling. Whereas ox-LDL significantly decreased NO levels in endothelial cells, mulberry extract, and C-3-R significantly recovered NO levels and phospho-eNOS Thr495 and Ser1177 expression. In vivo, mulberry was administered to 60% of high-fat diet (w/w)-fed Sprague Dawley (SD) rats for six weeks, in which endothelium-dependent relaxations were significantly improved in organ bath studies and isometric tension recordings. Consistently, aortic expressions of phospho-eNOS and nitrotyrosine were increased. Mulberry also raised serum NO levels, increased phosphorylation of eNOS, and reduced nitrotyrosine and intracellular reactive oxygen species (ROS) in aortas, showing that mulberry preserves endothelium-dependent relaxation in aortas from high-fat diet rats. We suggest that this effect is mediated through enhanced NO bioavailability, in which the regulation of ROS and its reduced eNOS uncoupling are involved.