bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons
Authors: Kwon Seung-Hwan , Lee Seoung Rak , Park Yong Joo , Ra Moonjin , Lee Yongjun , Pang Changhyun , Kim Ki Hyun
Published: November 2019

In our ongoing research to discover natural products with neuroprotective effects, hyperoside (quercetin 3-O-galactoside) was isolated from Acer tegmentosum, which has been used in Korean traditional medicine to treat liver-related disorders. Here, we demonstrated that hyperoside protects cultured dopaminergic neurons from death via reactive oxygen species (ROS)-dependent mechanisms, although other relevant mechanisms of hyperoside activity remain largely uncharacterized. For the first time, we investigated the neuroprotective effects of hyperoside on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in neurons, and the possible underlying mechanisms. Hyperoside significantly ameliorated the loss of neuronal cell viability, lactate dehydrogenase release, excessive ROS accumulation and mitochondrial membrane potential dysfunction associated with 6-OHDA-induced neurotoxicity. Furthermore, hyperoside treatment activated the nuclear erythroid 2-related factor 2 (Nrf2), an upstream molecule of heme oxygenase-1 (HO-1). Hyperoside also induced the expression of HO-1, an antioxidant response gene. Remarkably, we found that the neuroprotective effects of hyperoside were weakened by an Nrf2 small interfering RNA, which blocked the ability of hyperoside to inhibit neuronal death, indicating the vital role of HO-1. Overall, we show that hyperoside, via the induction of Nrf2-dependent HO-1 activation, suppresses neuronal death caused by 6-OHDA-induced oxidative stress. Moreover, Nrf2-dependent HO-1 signaling activation represents a potential preventive and therapeutic target in Parkinson′s disease management.
Significant Benefits of Nanoparticles Containing a Necrosis Inhibitor on Mice Testicular Tissue Autografts Outcomes
Authors: Del Vento Federico , Vermeulen Maxime , Ucakar Bernard , Poels Jonathan , des Rieux Anne , Wyns Christine
Published: November 2019

Fertility preservation for prepubertal boys relies exclusively on cryopreservation of immature testicular tissue (ITT) containing spermatogonia as the only cells with reproductive potential. Preclinical studies that used a nude mice model to evaluate the development of human transplanted ITT were characterized by important spermatogonial loss. We hypothesized that the encapsulation of testicular tissue in an alginate matrix supplemented with nanoparticles containing a necrosis inhibitor (NECINH-NPS) would improve tissue integrity and germ cells’ survival in grafts. We performed orthotopic autotransplantation of 1 mm³ testicular tissue fragments recovered form mice (aged 4–5 weeks). Fragments were either non-encapsulated, encapsulated in an alginate matrix, or encapsulated in an alginate matrix containing NECINH-NPs. Grafts were recovered 5- and 21-days post-transplantation. We evaluated tissue integrity (hematoxylin-eosin staining), germ cells survival (immunohistochemistry for promyelocytic leukemia zinc-finger, VASA, and protein-boule-like), apoptosis (immunohistochemistry for active-caspase 3), and lipid peroxidation (immunohistochemistry for malondialdehyde). NECINH-NPs significantly improved testicular tissue integrity and germ cells’ survival after 21 days. Oxidative stress was reduced after 5 days, regardless of nanoparticle incorporation. No effect on caspase-dependent apoptosis was observed. In conclusion, NECINH-NPs in an alginate matrix significantly improved tissue integrity and germ cells’ survival in grafts with the perspective of higher reproductive outcomes.
Near-Infrared Photoimmunotherapy Using a Small Protein Mimetic for HER2-Overexpressing Breast Cancer
Authors: Yamaguchi Haruka , Pantarat Namfon , Suzuki Takamasa , Evdokiou Andreas
Published: November 2019

Near-infrared photoimmunotherapy (NIR-PIT) is a new and promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer which is activated by near-infrared light irradiation, causing cell death. We investigated NIR-PIT using a small protein mimetic (6–7 kDa), Affibody molecules, instead of a monoclonal antibody for HER2-overexpressing cancer. Because of its small size, the Affibody has rapid clearance, high imaging contrast, and good tumor penetration. Due to the small size of the Affibodies, which can cross the blood–brain barrier, NIR-PIT using Affibodies has the potential to extend the target cancer of NIR-PIT, including brain metastases. In vitro, NIR-PIT using HER2 Affibody–IR700Dye conjugates induced the selective destruction of HER2-overexpressing breast cancer cells without damage to control cells having low level expression of HER2. HER2-overexpressing cancer cells showed necrotic cell death and their viability maintained at low levels, even 5 days after NIR-PIT. In contrast, treatment with high concentration of HER2 Affibody–IR700Dye conjugate alone or irradiation with high dose of NIR light alone was without effect on cell viability. Affibody and IR700Dye are currently used clinically, and therefore, we would expect the current formulation to be safely and quickly transitioned into clinical trials.
Stay-Green Trait: A Prospective Approach for Yield Potential, and Drought and Heat Stress Adaptation in Globally Important Cereals
Authors: Kamal Nasrein Mohamed , Gorafi Yasir Serag Alnor , Abdelrahman Mostafa , Abdellatef Eltayb , Tsujimoto Hisashi
Published: November 2019

The yield losses in cereal crops because of abiotic stress and the expected huge losses from climate change indicate our urgent need for useful traits to achieve food security. The stay-green (SG) is a secondary trait that enables crop plants to maintain their green leaves and photosynthesis capacity for a longer time after anthesis, especially under drought and heat stress conditions. Thus, SG plants have longer grain-filling period and subsequently higher yield than non-SG. SG trait was recognized as a superior characteristic for commercially bred cereal selection to overcome the current yield stagnation in alliance with yield adaptability and stability. Breeding for functional SG has contributed in improving crop yields, particularly when it is combined with other useful traits. Thus, elucidating the molecular and physiological mechanisms associated with SG trait is maybe the key to defeating the stagnation in productivity associated with adaptation to environmental stress. This review discusses the recent advances in SG as a crucial trait for genetic improvement of the five major cereal crops, sorghum, wheat, rice, maize, and barley with particular emphasis on the physiological consequences of SG trait. Finally, we provided perspectives on future directions for SG research that addresses present and future global challenges.
Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate
Authors: Haraguchi Ryuma , Kitazawa Riko , Kohara Yukihiro , Ikedo Aoi , Imai Yuuki , Kitazawa Sohei
Published: November 2019

The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the “growth plate”, is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.
A Bit Torrent Traffic Optimization Method for Enhancing the Stability of Network Traffic
Authors: Li Deguang , Zhang Yongxin , Jia Shijie , Liu Dong , Jin Yanling , Wu Yuansheng
Published: November 2019

With the extensive use of peer-to-peer applications in recent years, the network traffic becomes more dynamic and less predictable, which leads to the decline of network resource utilization and the degradation of network performance. Aiming towards the above problems, we explore how to strengthen the cooperation between peer-to-peer applications and networks, making the application adjust its own traffic mode according to current network traffic status to enhance the stability of network traffic. We improve two key algorithms of peer selection and choking/unchoking in the protocol and introduce traffic relaxation to characterize traffic state while taking the current most popular peer-to-peer application (bit torrent protocol) as an example. In our improved method, peers are selected probabilistically according their traffic relaxation, and the double-parameter selection problem that simultaneously considers the traffic relaxation and transfer rate of peers is also solved. Finally, we conduct simulation experiments in two real network typologies with real traffic matrix data and different sizes of bit torrent swarms; the experimental results show that our method can significantly improve the stability of the network traffic without sacrificing or even improving the performance of the bit torrent protocol when compared with original BT protocol.
Numerical Simulation of Flow Control around a Circular Cylinder by Installing a Wedge-Shaped Device Upstream
Authors: Han Xiaoshuang , Wang Jie , Zhou Bo , Zhang Guiyong , Tan Soon-Keat
Published: November 2019

The effect of a triangular wedge upstream of a circular cylinder has been investigated, and the findings are presented herein. The triangular wedge is equilateral in plan form, and the Reynolds number based on the diameter of the main cylinder is approximately 200. Contours of vorticity clearly show that two entirely different wake patterns exist between the wedge and the main cylinder. There also exists a critical spacing ratio and side length ratio at which the wake flow pattern shifts from one within the cavity mode to one within the wake impingement mode. For a relatively small side length ratio of l w / D = 0.20 and 0.27, where the side length refers to the length of one side of the triangular wedge, the drag and lift coefficients decrease monotonically with the spacing ratio. There is a sudden jump of the drag and lift coefficients at larger side length ratios of l w / D = 0.33 and 0.40. This study shows that at a spacing ratio of L/D = 2.8 (where L is the distance between the vertex of the wedge and the center of the cylinder) and a wedge side length of l w / D = 0.40, the reduction of the amplitude of lift and mean drag coefficient on the main cylinder are 71.9% and 60.1%, respectively.
Voltage-Induced Friction with Application to Electrovibration
Authors: Heß Markus , Popov Valentin L.
Published: November 2019

Due to the growing interest in robotic and haptic applications, voltage-induced friction has rapidly gained in importance in recent years. However, despite extensive experimental investigations, the underlying principles are still not sufficiently understood, which complicates reliable modeling. We present a macroscopic model for solving electroadhesive frictional contacts which exploits the close analogy to classical adhesion theories, like Johnson-Kendall-Roberts (JKR) and Maugis, valid for electrically neutral bodies. For this purpose, we recalculate the adhesion force per unit area and the relative surface energy from electrostatics. Under the assumption of Coulomb friction in the contact interface, a closed form equation for the friction force is derived. As an application, we consider the frictional contact between the fingertip and touchscreen under electrovibration in more detail. The results obtained with the new model agree well with available experimental data of the recent literature. The strengths and limitations of the model are clearly discussed.
Intercalated Intermetallic Compounds AlTi3 and Fe2Ti in Microrods and Microtubes Obtained by Invariant Reaction of Mechanically Milled System Al43Ti36Fe21
Authors: Díaz Barriga Arceo Lucía G. , González Reyes Leonardo , Rivera Olvera Jesús Noé , Medina Ovando Abraham , Garibay Febles Vicente
Published: November 2019

This paper reports the production of intermetallic microrods and microtubes from the decomposition of an intermetallic compound in an AlTiFe system. The intermetallic compound was obtained by mechanosynthesis of elemental powders of Al, Ti and Fe over 300 h at 400 rpm, sintering from compacted powder particles at 300 MPa per minute and at 900 °C for 3600 s in an argon atmosphere. The milled and sintered samples were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The intermetallic AlTi3 and Fe3Al phases were obtained during the milling process. After sintering, a decomposition of these intermetallic phases was found—Al3Ti0.75Fe0.25, Al3Ti, FeTi, AlTi3, Ti9Al23, Fe2Ti, Al86Fe14 and Al0.4Fe0.6. As a result of the decomposition, we observed the formation of hexagonal rods with intercalated phases of AlTi3 and Fe2Ti.
Activation and Repassivation of Stainless Steels in Artificial Brines as a Function of pH
Authors: Mujanović Emir , Zajec Bojan , Kosec Tadeja , Legat Andraž , Hönig Stefan , Zehethofer Gerald , Mori Gregor
Published: November 2019

When planning oil wells with stainless steel components, two possible reasons for depassivation have to be considered—chemical depassivation caused by acidizing jobs and mechanical depassivation caused by various tools and hard particles. The study explores conditions causing chemical activation of investigated steels and circumstances under which repassivation occurs after activation. The main focus of the study is to determine, how quickly various steels can repassivate under different conditions and to find pH values where repassivation will occur after depassivation. The investigated steels were ferritic (martensitic or bainitic) in the cases of 13Cr, 13Cr6Ni2Mo, and 17Cr4Ni2Mo, austenitic in the case of 17Cr12Ni2Mo, and duplex (austenitic and ferritic) in the case of 22Cr5Ni3Mo. Potentiodynamic experiments were employed to obtain electrochemical properties of investigated steels, followed by immersion tests to find ultimate conditions, where the steels still retain their passivity. After obtaining this information, scratch tests were performed to study the repassivation kinetics. It was found that repassivation times are similar for nearly all investigated steels independent of their chemical composition and microstructure.
Performance Degradation of Large-Sized Asphalt Mixture Specimen under Heavy Load and Its Affecting Factors Using Multifunctional Pavement Material Tester
Authors: Li Jiasheng , Yu Jianying , Xie Jun , Ye Qunshan
Published: November 2019

With the increase of heavy traffic transportation, it is meaningful to study the performance change of pavements under heavy loads. To study the development of asphalt mixture under heavy load, an AC-13 asphalt mixture was prepared and a large-sized specimen wheel tracking test was conducted. Samples from different periods were extracted to research the influence of the cumulative load times under heavy load on asphalt mixtures. It was found that there were different variation rules on the performance of the asphalt mixture under different load conditions. The failure time on skid resistance was predicted by the fitting curve. Heavy load conditions would greatly speed up the failure of skid resistance. According to the sieving results, the stable gradation of 10–16 mm, 5–10 mm, 3–5 mm, and 0–3 mm after heavy load grinding was 10%, 37%, 23%, and 30%. It was found that the content of 10–16 mm had a significant correlation with the permanent deformation of the asphalt mixture, while there were no significant correlation between aggregate and skid resistance.
Oxide Thin-Film Transistor-Based Vertically Stacked Complementary Inverter for Logic and Photo-Sensor Operations
Authors: Joo Hyo-Jun , Shin Min-Gyu , Jung Hwan-Seok , Cha Hyun-Seok , Nam Donguk , Kwon Hyuck-In
Published: November 2019

Numerous studies have addressed the utilization of oxide thin-film transistor (TFT)-based complementary logic circuits that are based on two-dimensional (2D) planar structures. However, there are fundamental limits to the 2D planar structured complementary logic circuits, such as a large dimension and a large parasitic resistance. This work demonstrated a vertically stacked three-dimensional complementary inverter composed of a p-channel tin monoxide (SnO) TFT and an n-channel indium-gallium-zinc oxide (IGZO) TFT. A bottom-gate p-channel SnO TFT was formed on the top-gate n-channel IGZO TFT with a shared common gate electrode. The fabricated vertically stacked complementary inverter exhibited full swing characteristics with a voltage gain of ~33.6, a high noise margin of 3.13 V, and a low noise margin of 3.16 V at a supplied voltage of 10 V. The achieved voltage gain of the fabricated complementary inverter was higher than that of the vertically stacked complementary inverters composed of other oxide TFTs in previous works. In addition, we showed that the vertically stacked complementary inverter exhibited excellent visible-light photoresponse. This indicates that the oxide TFT-based vertically stacked complementary inverter can be used as a sensitive photo-sensor operating in the visible spectral range with the voltage read-out scheme.
FE Analysis of Critical Testing Parameters in Kolsky Bar Experiments for Elastomers at High Strain Rate
Authors: Chaudhry Muhammad Salman , Czekanski Aleksander
Published: November 2019

The main aim of this research is to present complete methodological guidelines for dynamic characterization of elastomers when subjected to strain rates of 100/s–10,000/s. We consider the following three aspects: (i) the design of high strain rate testing apparatus, (ii) finite element analysis for the optimization of the experimental setup, and (iii) experimental parameters and validation for the response of an elastomeric specimen. To test low impedance soft materials, design of a modified Kolsky bar is discussed. Based on this design, the testing apparatus was constructed, validated, and optimized numerically using finite element methods. Furthermore, investigations on traditional pulse shaping techniques and a new design for pulse shaper are described. The effect of specimen geometry on the homogeneous deformation has been thoroughly accounted for. Using the optimized specimen geometry and pulse shaping technique, nitrile butadiene rubber was tested at different strain rates, and the experimental findings were compared to numerical predictions.
Fabrication of High Permittivity Resin Composite for Vat Photopolymerization 3D Printing: Morphology, Thermal, Dynamic Mechanical and Dielectric Properties
Authors: Malas Asish , Isakov Dmitry , Couling Kevin , Gibbons Gregory J.
Published: November 2019

The formulation of a high dielectric permittivity ceramic/polymer composite feedstock for daylight vat photopolymerization 3D printing (3DP) is demonstrated, targeting 3DP of devices for microwave and THz applications. The precursor is composed of a commercial visible light photo-reactive polymer (VIS-curable photopolymer) and dispersed titanium dioxide (TiO2, TO) ceramic nano-powder or calcium copper titanate (CCT) micro-powder. To provide consistent 3DP processing from the formulated feedstocks, the carefully chosen dispersant performed the double function of adjusting the overall viscosity of the photopolymer and provided good matrix-to-filler bonding. Depending on the ceramic powder content, the optimal viscosities for reproducible 3DP with resolution better than 100 µm were η(TO) = 1.20 ± 0.02 Pa.s and η(CCT) = 0.72 ± 0.05 Pa.s for 20% w/v TO/resin and 20% w/v CCT/resin composites at 0.1 s−1 respectively, thus showing a significant dependence of the “printability” on the dispersed particle sizes. The complex dielectric properties of the as-3D printed samples from pure commercial photopolymer and the bespoke ceramic/photopolymer mixes are investigated at 2.5 GHz, 5 GHz, and in the 12–18 GHz frequency range. The results show that the addition of 20% w/v of TO and CCT ceramic powder to the initial photopolymer increased the real part of the permittivity of the 3DP composites from ε’ = 2.7 ± 0.02 to ε’(TO) = 3.88 ± 0.02 and ε’(CCT) = 3.5 ± 0.02 respectively. The present work can be used as a guideline for high-resolution 3DP of structures possessing high-ε.
Second Order Semilinear Volterra-Type Integro-Differential Equations with Non-Instantaneous Impulses
Authors: Benchohra Mouffak , Rezoug Noreddine , Samet Bessem , Zhou Yong
Published: November 2019

We consider a non-instantaneous system represented by a second order nonlinear differential equation in a Banach space E. We use the family of linear bounded operators introduced by Kozak, Darbo fixed point method and Kuratowski measure of noncompactness. A new set of sufficient conditions is formulated which guarantees the existence of the solution of the non-instantaneous system. An example is also discussed to illustrate the efficiency of the obtained results.
Simulation of an Adaptive Fluid-Membrane Piezoelectric Lens
Authors: Bettaswamy Gowda Hitesh Gowda , Wallrabe Ulrike
Published: November 2019

In this paper, we present a finite-element simulation of an adaptive piezoelectric fluid-membrane lens for which we modelled the fluid-structure interaction and resulting membrane deformation in COMSOL Multiphysics®. Our model shows the explicit coupling of the piezoelectric physics with the fluid dynamics physics to simulate the interaction between the piezoelectric and the fluid forces that contribute to the deformation of a flexible membrane in the adaptive lens. Furthermore, the simulation model is extended to describe the membrane deformation by additional fluid forces from the fluid thermal expansion. Subsequently, the simulation model is used to study the refractive power of the adaptive lens as a function of internal fluid pressure and analyze the effect of the fluid thermal expansion on the refractive power. Finally, the simulation results of the refractive power are compared to the experimental results at different actuation levels and temperatures validating the coupled COMSOL model very well. This is explicitly proven by explaining an observed positive drift of the refractive power at higher temperatures.
Root-Associated Fungal Communities in Two Populations of the Fully Mycoheterotrophic Plant Arachnitis uniflora Phil. (Corsiaceae) in Southern Chile
Authors: Herrera Hector , Soto Javiera , de Bashan Luz E. , Sampedro Inmaculada , Arriagada Cesar
Published: November 2019

The microbiological interactions of the roots of non-photosynthetic plants in South America have been scarcely explored. This study analyzes culturable fungal diversity associated with the mycoheterotrophic plant Arachnitis uniflora Phil. (Corsiaceae) in southern Chile, growing in two different understoreys of native (Nothofagus-dominated) and mixed forest (native, Cupressus sempervirens, and Pinus radiata). Rhizospheric and endophytic fungi were isolated, cultured, and purified to identify microorganisms associated with A. uniflora roots. We showed the different fungi associated with the plant, and that these distributions are influenced by the sampling site. We isolated 410 fungal strains (144 endophytic and 266 from the rhizosphere). We identified 13 operative taxonomical units from plants sampled in the mixed forest, while 15 were from the native forest. Rhizospheric microorganisms were mainly related to Penicillium spp., whereas some pathogenic and saprophytic strains were more frequent inside the roots. Our results have also shown that the fungal strains are weak for phosphate solubilization, but other pathways such as organic acid exudation and indole acetic acid production can be considered as major mechanisms to stimulate plant growth. Our results point to new fungal associates of A. uniflora plants reported in Andean ecosystems, identifying new beneficial endophytic fungi associated with roots of this fully mycoheterotrophic plant.
A Mesophilic Aeromonas salmonicida Strain Isolated from an Unsuspected Host, the Migratory Bird Pied Avocet
Authors: Vincent Antony T. , Bernatchez Alex , Frey Joachim , Charette Steve J.
Published: November 2019

Aeromonas salmonicida is a Gram-negative bacterium, known as a fish pathogen since its discovery. Although the species was initially considered psychrophilic, a mesophilic subspecies (pectinolytica) and many other mesophilic strains still not attributed to subspecies have been described in the last two decades. These mesophilic strains were sampled from various sources, including humans, and some of them are known to be pathogenic. In this study, we describe a strain, JF2480, which was isolated from the spleen, and also found the kidney and liver of a dead pied avocet (Recurvirostra avosetta), a type of migratory bird inhabiting aquatic environments. A core genome phylogenomic analysis suggests that JF2480 is taxonomically distant from other known A. salmonicida subspecies. The genome sequence confirms that the strain possesses key virulence genes that are present in the typical A. salmonicida psychrophilic subspecies, with the exception of the genes encoding the type three secretion system (T3SS). Bacterial virulence assays conducted on the surrogate host Dictyostelium discoideum amoeba confirmed that the strain is virulent despite the lack of T3SS. Bacterial growth curves showed that strain JF2480 grow well at 40 °C, the body temperature of the pied avocet, and even faster at 41 °C, compared to other mesophilic strains. Discovery of this strain further demonstrates the extent of the phylogenomic tree of this species. This study also suggests that A. salmonicida can infect a wider array of hosts than previously suspected and that we need to rethink the way we perceive A. salmonicida’s natural environment.
Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus
Authors: Wu Chung-Ze , Ou Shih-Hsiang , Chang Li-Chien , Lin Yuh-Feng , Pei Dee , Chen Jin-Shuen
Published: November 2019

Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. Methods: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and β cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. Results: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, β cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.
Late-Stage Copper-Catalyzed Radiofluorination of an Arylboronic Ester Derivative of Atorvastatin
Authors: S. Clemente Gonçalo , Zarganes-Tzitzikas Tryfon , Dömling Alexander , H. Elsinga Philip
Published: November 2019

There is an unmet need for late-stage 18F-fluorination strategies to label molecules with a wide range of relevant functionalities to medicinal chemistry, in particular (hetero)arenes, aiming to obtain unique in vivo information on the pharmacokinetics/pharmacodynamics (PK/PD) using positron emission tomography (PET). In the last few years, Cu-mediated oxidative radiofluorination of arylboronic esters/acids arose and has been successful in small molecules containing relatively simple (hetero)aromatic groups. However, this technique is sparsely used in the radiosynthesis of clinically significant molecules containing more complex backbones with several aromatic motifs. In this work, we add a new entry to this very limited database by presenting our recent results on the 18F-fluorination of an arylboronic ester derivative of atorvastatin. The moderate average conversion of [18F]F− (12%), in line with what has been reported for similarly complex molecules, stressed an overview through the literature to understand the radiolabeling variables and limitations preventing consistently higher yields. Nevertheless, the current disparity of procedures reported still hampers a consensual and conclusive output.
A Subcellular Quantitative Proteomic Analysis of Herpes Simplex Virus Type 1-Infected HEK 293T Cells
Authors: Wan Weiwei , Wang Liangjie , Chen Xi , Zhu Shenglin , Shang Weijuan , Xiao Gengfu , Zhang Lei-Ke
Published: November 2019

Herpes simplex virus type 1 (HSV-1) is widespread double-stranded DNA (dsDNA) virus that establishes life-long latency and causes diverse severe symptoms. The mechanisms of HSV-1 infection and HSV-1’s interactions with various host cells have been studied and reviewed extensively. Type I interferons were secreted by host cells upon HSV infection and play a vital role in controlling virus proliferation. A few studies, however, have focused on HSV-1 infection without the presence of interferon (IFN) signaling. In this study, HEK 293T cells with low toll-like receptor (TLR) and stimulator of interferon genes protein (STING) expression were infected with HSV-1 and subjected to a quantitative proteomic analysis. By using a subcellular fractionation strategy and high-performance mass spectrometry, a total of 6607 host proteins were quantified, of which 498 proteins were differentially regulated. A bioinformatics analysis indicated that multiple signaling pathways might be involved in HSV-1 infection. A further functional study indicated the role of Interferon-induced transmembrane protein 3 (IFITM3), Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), and Tripartite motif-containing protein 27 (TRIM27) in inhibiting viral DNA replication and proliferation. Our data provide a global view of host responses to HSV-1 infection in HEK 293T cells and identify the proteins involved in the HSV-1 infection process.
Bixa orellana L. (Bixaceae) and Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) Essential Oils Formulated in Nanocochleates against Leishmania amazonensis
Authors: Machín Laura , Tamargo Beatriz , Piñón Abel , Atíes Regla C. , Scull Ramón , Setzer William N. , Monzote Lianet
Published: November 2019

Leishmaniasis is a group of neglected tropical diseases caused by protozoan parasites of the Leishmania genus. The absence of effective vaccines and the limitations of current treatments make the search for effective therapies a real need. Different plant-derived essential oils (EOs) have shown antileishmanial effects, in particular from Bixa orellana L. (EO-Bo) and Dysphania ambrosioides (L.) Mosyakin & Clemants (EO-Da). In the present study, the EO-Bo and EO-Da, formulated in nanocochleates (EO-Bo-NC and EO-Da-NC, respectively), were evaluated in vitro and in vivo against L. amazonensis. The EO-Bo-NC and EO-Da-NC did not increase the in vitro inhibitory activity of the EOs, although the EO-Bo-NC showed reduced cytotoxic effects. In the animal model, both formulations (30 mg/kg/intralesional route/every 4 days/4 times) showed no deaths or weight loss greater than 10%. In the animal (mouse) model, EO-Bo-NC contributed to the control of infection (p < 0.05) in comparison with EO-Bo treatment, while the mice treated with EO-Da-NC exhibited larger lesions (p < 0.05) compared to those treated with EO-Da. The enhanced in vivo activity observed for EO-Bo-NC suggests that lipid-based nanoformulations like nanocochleates should be explored for their potential in the proper delivery of drugs, and in particular, the delivery of hydrophobic materials for effective cutaneous leishmaniasis treatment.
The Frontiers of Nanomaterials (SnS, PbS and CuS) for Dye-Sensitized Solar Cell Applications: An Exciting New Infrared Material
Authors: Meyer Edson L. , Mbese Johannes Z. , Agoro Mojeed A.
Published: November 2019

To date, extensive studies have been done on solar cells on how to harness the unpleasant climatic condition for the binary benefits of renewable energy sources and potential energy solutions. Photovoltaic (PV) is considered as, not only as the future of humanity’s source of green energy, but also as a reliable solution to the energy crisis due to its sustainability, abundance, easy fabrication, cost-friendly and environmentally hazard-free nature. PV is grouped into first, second and third-generation cells. Dye-sensitized solar cells (DSSCs), classified as third-generation PV, have gained more ground in recent times. This is linked to their transparency, high efficiency, shape, being cost-friendly and flexibility of colour. However, further improvement of DSSCs by quantum dot sensitized solar cells (QDSSCs) has increased their efficiency through the use of semiconducting materials, such as quantum dots (QDs), as sensitizers. This has paved way for the fabrication of semiconducting QDs to replace the ideal DSSCs with quantum dot sensitized solar cells (QDSSCs). Moreover, there are no absolute photosensitizers that can cover all the infrared spectrum, the infusion of QD metal sulphides with better absorption could serve as a breakthrough. Metal sulphides, such as PbS, SnS and CuS QDs could be used as photosensitizers due to their strong near infrared (NIR) absorption properties. A few great dependable and reproducible routes to synthesize better QD size have attained much ground in the past and of late. The injection of these QD materials, which display (NIR) absorption with localized surface plasmon resonances (SPR), due to self-doped p-type carriers and photocatalytic activity could enhance the performance of the solar cell. This review will be focused on QDs in solar cell applications, the recent advances in the synthesis method, their stability, and long term prospects of QDSSCs efficiency.
Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
Authors: Delort Laetitia , Bougaret Lauriane , Cholet Juliette , Vermerie Marion , Billard Hermine , Decombat Caroline , Bourgne Céline , Berger Marc , Dumontet Charles , Caldefie-Chezet Florence
Published: November 2019

Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.
Grain Foods in US Infants Are Associated with Greater Nutrient Intakes, Improved Diet Quality and Increased Consumption of Recommended Food Groups
Authors: Papanikolaou Yanni , Fulgoni Victor L.
Published: November 2019

There are limited data providing guidance on grain foods as part of a healthy dietary pattern in infants and may represent a gap in knowledge for the development of the 2020–2025 Dietary Guidelines for Americans Scientific Advisory Committee report currently in progress. An analysis using infant data from the National Health and Nutrition Examination Survey was conducted to assess grain food relationships with nutrient and energy intakes, diet quality, and food group consumption in infant consumers relative to non-consumers. Grain consumers were defined as infants consuming foods from the main grain food group, as defined by the US Department of Agriculture, and included whole and refined/enriched grains. All infants consuming grain foods had greater energy (kcal) vs. grain non-consumers (p’s < 0.0047). While infant grain consumers 6- to 12-months-old (N = 942) had higher daily intakes of sodium and added and total sugars, these infants also had significantly higher dietary fiber, calcium, folate, potassium, magnesium, zinc, phosphorus, choline, thiamin, riboflavin, and vitamin B6 compared to non-consumers. In 13- to 23-month-olds (N = 1668), grain consumption was associated with greater daily dietary fiber, iron, zinc, magnesium, phosphorus, folate, riboflavin, niacin, thiamin, vitamin A, vitamin B6, and vitamin B12 relative to non-consumers. Diet quality scores were significantly higher in all infant grain consumers examined in comparison to non-consumers (p’s < 0.0065). Grain intake was also linked with greater daily intake of several recommended food groups in both younger and older infants versus non-consumption of grains. The current analysis provides evidence to substantiate the inclusion of whole and enriched grain foods as part of the infant dietary pattern as beneficial associations between grain food consumption and dietary quality are apparent. Eliminating and/or reducing grain foods in infant dietary patterns may lead to unintended nutrient and health consequences.
Changes in Human Milk Fatty Acid Composition during Lactation: The Ulm SPATZ Health Study
Authors: Siziba Linda  P. , Lorenz Leonie , Stahl Bernd , Mank Marko , Marosvölgyi Tamas , Decsi Tamas , Rothenbacher Dietrich , Genuneit Jon
Published: November 2019

The lipid fraction of human milk provides the infant with the fatty acids that are necessary for optimal growth and development. The aim of this study was to investigate the fatty acid composition of human milk at three time points during lactation and its change over time using appropriate statistical methods. Human milk samples from breastfeeding mothers at 6 weeks (n = 706), 6 months (n = 483), and 12 months (n = 81 with all three time points) were analyzed. Centered log-ratio (clr) transformation was applied to the fatty acid data. Principal component analysis (PCA) and generalized linear model-based repeated measure analysis were used to assess changes over time. The total lipid content was significantly higher at 6 months (β = 0.199, p < 0.029) and 12 months of lactation (β = 0.421, p < 0.001). The constituents of C20:3n-6 and C20:3n-3 were lower at 6 months (p < 0.001). Four distinct sub-compositional fatty acid groups were only identified at 12 months of lactation. The inclusion of small fatty acids of small constituent size in the analysis resulted in a shift in the balance between fatty acid constituents. Human milk fatty acid composition during prolonged lactation is different from that of human milk during a short duration of lactation. Our findings support the hypothesis that a combination of multiple fatty acids is important in fatty acid profiling beyond the presentation of individual fatty acids. Furthermore, the high variability of small fatty acids warrants attention because a compositional analysis may show more pronounced changes.
Multi-Micronutrient Fortified Rice Improved Serum Zinc and Folate Concentrations of Cambodian School Children. A Double-Blinded Cluster-Randomized Controlled Trial
Authors: Kuong Khov , Tor Pety , Perignon Marlene , Fiorentino Marion , Chamnan Chhoun , Berger Jacques , Burja Kurt , Dijkhuizen Marjoleine A. , Parker Megan , Roos Nanna , Wieringa Frank T.
Published: November 2019

Background: Within Cambodia, micronutrient deficiencies continue to be prevalent in vulnerable groups, such as women and children. Fortification of staple foods such as rice could be a promising strategy for Cambodia to improve micronutrient status. Objective: Our objective was to investigate the impact of multiple-micronutrient fortified rice (MMFR), distributed through a World Food Program school-meals program (WFP-SMP) on serum zinc concentrations and folate status in a double-blind, cluster-randomized, placebo-controlled trial. Methods: Sixteen schools were randomly assigned to receive one of three different types of extruded-fortified rice (UltraRice Original (URO), UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. A total of 1950 schoolchildren (6–16 years old) participated in the study. Serum zinc (all groups) and folate (only in NutriRice and placebo group) concentrations were assessed from morning non-fasting antecubital blood samples and were measured at three time points (baseline and after three and six months). Results: After six months of intervention, serum zinc concentrations were significantly increased in all fortified rice group compared to placebo and baseline (0.98, 0.85 and 1.40 µmol/L for URO, URN and NutriRice, respectively) (interaction effect: p < 0.001 for all). Children in the intervention groups had a risk of zinc deficiencies of around one third (0.35, 039, and 0.28 for URO, URN, and NutriRice, respectively) compared to the placebo (p < 0.001 for all). The children receiving NutriRice had higher serum folate concentrations at endline compared to children receiving normal rice (+2.25 ng/mL, p = 0.007). Conclusions: This study showed that the high prevalence of zinc and folate deficiency in Cambodia can be improved through the provision of MMFR. As rice is the staple diet for Cambodia, MMFR should be considered to be included in the school meal program and possibilities should be explored to introduce MMFR to the general population.
Served Portion Sizes Affect Later Food Intake Through Social Consumption Norms
Authors: Raghoebar Sanne , Haynes Ashleigh , Robinson Eric , Van Kleef Ellen , De Vet Emely
Published: November 2019

Portion sizes of commercially available foods have increased, and there is evidence that exposure to portion sizes recalibrates what is perceived as ‘normal’ and subsequently, how much food is selected and consumed. The present study aims to explore the role of social (descriptive and injunctive) and personal portion size norms in this effect. Across two experiments, participants were either visually exposed to (Study 1, N = 329) or actually served (Study 2, N = 132) a smaller or larger than normal food portion. After 24 h, participants reported their intended consumption (Study 1) or served themselves and consumed (Study 2) a portion of that food and reported perceived portion size norms. In Study 1, visual exposure to portion size did not significantly affect intended consumption and perceived portion size norms. In Study 2, participants consumed a smaller portion of food when they were served a smaller rather than a larger portion the previous day, which was mediated by perceived descriptive and injunctive social (but not personal) portion size norms. Results suggest that being served (but not mere visual exposure to) smaller (relative to larger) portions changes perceived social norms about portion size and this may reduce future consumption of that food.
The Effect of Marine n-3 Polyunsaturated Fatty Acids on Heart Rate Variability in Renal Transplant Recipients: A Randomized Controlled Trial
Authors: Lilleberg Hanne Sether , Cichosz Simon Lebech , Svensson My , Christensen Jeppe Hagstrup , Fleischer Jesper , Eide Ivar , Jenssen Trond
Published: November 2019

Resting heart rate (rHR) and heart rate variability (HRV) are non-invasive measurements that predict the risk of sudden cardiac death (SCD). Marine n-3 polyunsaturated fatty acid (PUFA) supplementation may decrease rHR, increase HRV, and reduce the risk of SCD. To date, no studies have investigated the effect of marine n-3 PUFA on HRV in renal transplant recipients. In a randomized controlled trial, 132 renal transplant recipients were randomized to receive either three 1 g capsules of marine n-3 PUFA, each containing 460 mg/g EPA and 380 mg/g DHA, or control (olive oil) for 44 weeks. HRV was calculated in the time and frequency domains during a conventional cardiovascular reflex test (response to standing, deep breathing, and Valsalva maneuver) and during 2 min of resting in the supine position. There was no significant effect of marine n-3 PUFA supplementation on time-domain HRV compared with controls. rHR decreased 3.1 bpm (± 13.1) for patients receiving marine n-3 PUFA compared to 0.8 (± 11.0) in controls (p = 0.28). In the frequency domain HRV analyses, there was a significant change in response to standing in both high and low frequency measures, 2.9 (p = 0.04, 95% CI (1.1;8)) and 2.7 (p = 0.04, 95% CI (1.1;6.5)), respectively. In conclusion, 44 weeks of supplemental marine n-3 PUFAs in renal transplant recipients significantly improved the cardiac autonomic function, assessed by measuring HRV during conventional cardiovascular reflex tests.