bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Neural Network for Response Inference of a Nonvolatile Resistance-Switch Array
Authors: Kim Guhyun , Kornijcuk Vladimir , Kim Dohun , Kim Inho , Hwang Cheol Seong , Jeong Doo Seok
Published: March 2019

An artificial neural network was utilized in the behavior inference of a random crossbar array (10 × 9 or 28 × 27 in size) of nonvolatile binary resistance-switches (in a high resistance state (HRS) or low resistance state (LRS)) in response to a randomly applied voltage array. The employed artificial neural network was a multilayer perceptron (MLP) with leaky rectified linear units. This MLP was trained with 500,000 or 1,000,000 examples. For each example, an input vector consisted of the distribution of resistance states (HRS or LRS) over a crossbar array plus an applied voltage array. That is, for a M × N array where voltages are applied to its M rows, the input vector was M × (N + 1) long. The calculated (correct) current array for each random crossbar array was used as data labels for supervised learning. This attempt was successful such that the correlation coefficient between inferred and correct currents reached 0.9995 for the larger crossbar array. This result highlights MLP that leverages its versatility to capture the quantitative linkage between input and output across the highly nonlinear crossbar array.
Stabilized Production of Lipid Nanoparticles of Tunable Size in Taylor Flow Glass Devices with High-Surface-Quality 3D Microchannels
Authors: Erfle Peer , Riewe Juliane , Bunjes Heike , Dietzel Andreas
Published: March 2019

Nanoparticles as an application platform for active ingredients offer the advantage of efficient absorption and rapid dissolution in the organism, even in cases of poor water solubility. Active substances can either be presented directly as nanoparticles or can be integrated in a colloidal carrier system (e.g., lipid nanoparticles). For bottom-up nanoparticle production minimizing particle contamination, precipitation processes provide an adequate approach. Microfluidic systems ensure a precise control of mixing for the precipitation, which enables a tunable particle size definition. In this work, a gas/liquid Taylor flow micromixer made of chemically inert glass is presented, in which the organic phases are injected through a symmetric inlet structure. The 3D structuring of the glass was performed by femtosecond laser ablation. Rough microchannel walls are typically obtained by laser ablation but were smoothed by a subsequent annealing process resulting in lower hydrophilicity and even rounder channel cross-sections. Only with such smooth channel walls can a substantial reduction of fouling be obtained, allowing for stable operation over longer periods. The ultrafast mixing of the solutions could be adjusted by simply changing the gas volume flow rate. Narrow particle size distributions are obtained for smaller gas bubbles with a low backflow and when the rate of liquid volume flow has a small influence on particle precipitation. Therefore, nanoparticles with adjustable sizes of down to 70 nm could be reliably produced in continuous mode. Particle size distributions could be narrowed to a polydispersity value of 0.12.
Palladium-Gold Modified Ultramicro Interdigital Array Electrode Chip for Nitrate Detection in Neutral Water
Authors: Zhao Shanshan , Tong Jianhua , Li Yang , Sun Jizhou , Bian Chao , Xia Shanhong
Published: March 2019

An ultramicro interdigital array electrode modified by palladium-gold was developed for nitrate detection in neutral water. The ultramicro interdigital array electrode was fabricated based on silicon substrate by Micro Electro-Mechanical System (MEMS) technique. The nanostructured palladium-gold (Pd-AuNPs) composite sensing film was electrodeposited on the surface of a working electrode by electrochemical method. The synergistic effect of Pd-AuNPs composite was investigated and its enhancement of the catalytic activity and stability was revealed. The Pd-AuNPs modified electrode showed good linearity (R2 = 0.99) from 1 mg/L to 15 mg/L (as N) for nitrate determination in a neutral water environment (pH = 7.2), with a sensitivity of 4.7 μA·mg−1·L. The results showed that the developed Pd-AuNPs-modified ultramicro interdigital array electrode chip can achieve sensitive and environmentally-friendly detection for nitrate in neutral water.
Hybrid Two-Scale Fabrication of Sub-Millimetric Capillary Grippers
Authors: Dehaeck Sam , Cavaiani Marco , Chafai Adam , Tourtit Youness , Vitry Youen , Lambert Pierre
Published: March 2019

Capillary gripping is a pick-and-place technique that is particularly well-suited for handling sub-millimetric components. Nevertheless, integrating a fluid supply and release mechanism becomes increasingly difficult to manufacture for these scales. In the present contribution, two hybrid manufacturing procedures are introduced in which the creation of the smallest features is decoupled from the macro-scale components. In the first procedure, small scale features are printed directly (by two-photon polymerisation) on top of a 3D-printed device (through stereolithography). In the second approach, directional ultraviolet (UV)-illumination and an adapted design allowed for successful (polydimethylsiloxane, PDMS) moulding of the microscopic gripper head on top of a metal substrate. Importantly, a fully functional microchannel is present in both cases through which liquid to grip the components can be supplied and retracted. This capability of removing the liquid combined with an asymmetric pillar design allows for a passive release mechanism with a placement precision on the order of 3% of the component size.
Polymeric Nanowires for Diagnostic Applications
Authors: Hubbe Hendrik , Mendes Eduardo , Boukany Pouyan E.
Published: March 2019

Polymer nanowire-related research has shown considerable progress over the last decade. The wide variety of materials and the multitude of well-established chemical modifications have made polymer nanowires interesting as a functional part of a diagnostic biosensing device. This review provides an overview of relevant publications addressing the needs for a nanowire-based sensor for biomolecules. Working our way towards the detection methods itself, we review different nanowire fabrication methods and materials. Especially for an electrical signal read-out, the nanowire should persist in a single-wire configuration with well-defined positioning. Thus, the possibility of the alignment of nanowires is discussed. While some fabrication methods immanently yield an aligned single wire, other methods result in disordered structures and have to be manipulated into the desired configuration.
Design, Fabrication, and Testing of a Monolithically Integrated Tri-Axis High-Shock Accelerometer in Single (111)-Silicon Wafer
Authors: Cai Shengran , Li Wei , Zou Hongshuo , Bao Haifei , Zhang Kun , Wang Jiachou , Song Zhaohui , Li Xinxin
Published: March 2019

In this paper, a monolithic tri-axis piezoresistive high-shock accelerometer has been proposed that has been single-sided fabricated in a single (111)-silicon wafer. A single-cantilever structure and two dual-cantilever structures are designed and micromachined in one (111)-silicon chip to detect Z-axis and X-/Y-axis high-shock accelerations, respectively. Unlike the previous tri-axis sensors where the X-/Y-axis structure was different from the Z-axis one, the herein used similar cantilever sensing structures for tri-axis sensing facilitates design of uniform performance among the three elements for different sensing axes and simplifies micro-fabrication for the multi-axis sensing structure. Attributed to the tri-axis sensors formed by using the single-wafer single-sided fabrication process, the sensor is mechanically robust enough to endure the harsh high-g shocking environment and can be compatibly batch-fabricated in standard semiconductor foundries. After the single-sided process to form the sensor, the untouched chip backside facilitates simple and reliable die-bond packaging. The high-shock testing results of the fabricated sensor show linear sensing outputs along X-/Y-axis and Z-axis, with the sensitivities (under DC 5 V supply) as about 0.80–0.88 μV/g and 1.36 μV/g, respectively. Being advantageous in single-chip compact integration of the tri-axis accelerometers, the proposed monolithic tri-axis sensors are promising to be embedded into detection micro-systems for high-shock measurement applications.
Kinetic Analysis of the Thermal Decomposition of a Synthetic Mercury Jarosite
Authors: Flores Mizraim U. , Reyes Iván A. , Palacios Elia G. , Patiño Francisco , Juárez Julio C. , Reyes Martín , Teja Aislinn M. , Islas Hernán , Gutiérrez Emmanuel J.
Published: March 2019

Jarosites are widely used in the hydrometallurgical industry of zinc to eliminate iron and other impurities contained in the concentrates. However, these compounds can also incorporate elements of significant environmental concern such as Tl+, Hg2+, Pb2+, Cd2+, Cr(VI), and As(V). In this work, the characterization of a synthetic mercury jarosite and its thermal decomposition kinetics are reported. XRD and FTIR analyses confirm that a mercury jarosite—Hg0.40(H3O)0.2]Fe2.71(SO4)2.17(OH)4.79(H2O)0.44—was successfully synthesized. Four mass loss events were observed by thermogravimetric analysis at 290 °C, 365 °C, 543 °C, and 665 °C. The third event corresponds to mercury decomposition into mercury oxide, whilst the forth is related to the jarosite to hematite transformation determined by X-ray diffraction starting at around 600 °C. According to the kinetic parameters (activation energy and frequency factor) of the thermal decomposition process, the fourth stage required the highest energy (Ea = 234.7 kJ∙mol−1), which corresponds to elimination of sulfur and oxygen from the jarosite lattice. Results show that jarosite-type compounds have the capability to incorporate heavy metals into their structure, retaining them even at high temperatures. Therefore, they can be used as a remediation strategy for heavy metals, such as mercury and others elements of environmental concern.
Mechanism Study of Xanthate Adsorption on Sphalerite/Marmatite Surfaces by ToF-SIMS Analysis and Flotation
Authors: Lai Hao , Deng Jiushuai , Fan Guixia , Xu Hongxiang , Chen Wenxiang , Li Shimei , Huang Lingyun
Published: March 2019

In this work, the active sites and species involved in xanthate adsorption on sphalerite/marmatite surfaces were studied using adsorption capacity measurements, single mineral flotation, and time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis. The effects of Fe concentration on the xanthate adsorption capacity, Cu activation, and the flotation response of sphalerite/marmatite were determined. A discovery was that xanthate can interact with Fe atoms in the crystal of sphalerite/marmatite, as well as with Zn and Cu on the surface. We detected C2S2− fragment ions from dixanthogen, and dixanthogen may have been adsorbed on the surface of marmatite. The amounts of Cu and copper xanthate adsorbed on the marmatite surface were lower than those on the sphalerite surface, because Fe occupies Cu and Zn exchange sites. These results help to address the long-standing controversy regarding the products and mechanisms of xanthate adsorption on Fe-bearing sphalerite surfaces.
Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology
Authors: Lee Hyun Tae , Lee Sang Hyung , Heo Yong-Seok
Published: March 2019

Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), cemiplimab (Libtayo®), atezolizumab (Tecentriq®), durvalumab (Imfinzi®), and avelumab (Bavencio®), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology.
Graphene Oxide Tablets for Sample Preparation of Drugs in Biological Fluids: Determination of Omeprazole in Human Saliva for Liquid Chromatography Tandem Mass Spectrometry
Authors: Zohdi Zeynab , Hashemi Mahdi , Uheida Abdusalam , Moein Mohammad , Abdel-Rehim Mohamed
Published: March 2019

In this study, a novel sort of sample preparation sorbent was developed, by preparing thin layer graphene oxide tablets (GO-Tabs) utilizing a mixture of graphene oxide and polyethylene glycol on a polyethylene substrate. The GO-Tabs were used for extraction and concentration of omeprazole (OME) in human saliva samples. The determination of OME was carried out using liquid chromatography-tandem mass spectrometry (LC–MS/MS) under gradient LC conditions and in the positive ion mode (ESI+) with mass transitions of m/z 346.3→198.0 for OME and m/z 369.98→252.0 for the internal standard. Standard calibration for the saliva samples was in the range of 2.0–2000 nmol L−1. Limits of detection and quantification were 0.05 and 2.0 nmol L−1, respectively. Method validation showed good method accuracy and precision; the inter-day precision values ranged from 5.7 to 8.3 (%RSD), and the accuracy of determinations varied from −11.8% to 13.3% (% deviation from nominal values). The extraction recovery was 60%, and GO-Tabs could be re-used for more than ten extractions without deterioration in recovery. In this study, the determination of OME in real human saliva samples using GO-Tab extraction was validated.
Multielemental Analysis of Various Kinds of Whisky
Authors: Pawlaczyk Aleksandra , Gajek Magdalena , Jozwik Krzysztof , Szynkowska Malgorzata Iwona
Published: March 2019

Whisky (whiskey) consists of many trace elements coming from the raw materials used in its fermentation, distillation and maturation processes. These ingredients assure the exceptional organoleptic characteristics of the beverage. Their analysis is important to better control the stages of fermentation, distillation, taste repeatability and for product quality assurance as well as from the brand protection point of view. This article presents the usefulness of modern analytical techniques based on elemental analysis. ICP mass spectrometry and CV atomic absorption spectroscopy were applied to distinguish whisky produced in Scotland from whisky coming from Ireland and the United States. The collected semi-quantitative data were used for multivariate analysis performed using the Statistica 10.0 software. The results showed that Irish whiskey is characterized by quite a high amount of Ba and Ti compared with other samples, which made it possible to distinguish this sample from the others. No strict correlation was found between the type of whisky and the amount of trace elements, however, the projection of objects on the first two components revealed that single malt samples created one cluster.
A Complete Assessment of Dopamine Receptor- Ligand Interactions through Computational Methods
Authors: Bueschbell Beatriz , Barreto Carlos A. V. , Preto António J. , Schiedel Anke C. , Moreira Irina S.
Published: March 2019

Background: Selectively targeting dopamine receptors (DRs) has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases involving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like). Fifteen structurally diverse ligands were docked. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for selective binding to DR subtypes. Results: Residues of the aromatic microdomain were shown to be responsible for the majority of ligand interactions established to all DRs. Hydrophobic contacts involved a huge network of conserved and non-conserved residues between three transmembrane domains (TMs), TM2-TM3-TM7. Hydrogen bonds were mostly mediated by the serine microdomain. TM1 and TM2 residues were main contributors for the coupling of large ligands. Some amino acid groups form electrostatic interactions of particular importance for D1R-like selective ligands binding. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, which will support mutagenesis studies to improve the design of subtype-specific ligands.
Characterization of Inulin-Type Fructan from Platycodon grandiflorus and Study on Its Prebiotic and Immunomodulating Activity
Authors: Pang De-Jiang , Huang Chao , Chen Mei-Ling , Chen Yu-Long , Fu Yu-Ping , Paulsen Berit Smestad , Rise Frode , Zhang Bing-Zhao , Chen Zheng-Li , Jia Ren-Yong , Li Li-Xia , Song Xu , Feng Bin , Ni Xue-Qin , Yin Zhong-Qiong , Zou Yuan-Feng
Published: March 2019

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a β-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2–10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.
Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breast Cancer Cells
Authors: Luparello Claudio
Published: March 2019

We examined the dose–response effect of MnCl2 on the proliferative behavior of triple-negative breast cancer MDA-M231 cells vs. immortalized HB2 cells from breast epithelium taken as nontumoral counterparts. We also tested the effect of MnCl2 on tumor cell invasiveness in vitro by evaluating the relative invasion indexes through Boyden chamber assays. Moreover, we checked whether cotreatment with both MnCl2 and CdCl2 could modify the observed biological response by MDA-MB231 cells. Our results show a promotional impact of MnCl2 on cell proliferation, with 5 µM concentration inducing the more pronounced increase after 96-h exposure, which is not shared by HB2 cells. Exposure to 5 µM MnCl2 induced also an elevation of the relative invasion index of cancer cells. The Mn-mediated stimulatory effects were counteracted by cotreatment with CdCl2. These data support the concept that human exposure to high environmental concentrations of Mn may increase the risk of carcinogenesis and metastasis by prompting the expansion and dissemination of triple-negative breast cancer cells. On the other hand, the Mn-counteracting anticancer property of Cd looks promising and deserves a more detailed characterization of the involved intracellular targets aimed to the molecular modeling of specific antineoplastic agents against malignant breast cancer spreading.
In Vitro Toxicity Study of a Porous Iron(III) Metal‒Organic Framework
Authors: Chen Gongsen , Leng Xin , Luo Juyuan , You Longtai , Qu Changhai , Dong Xiaoxv , Huang Hongliang , Yin Xingbin , Ni Jian
Published: March 2019

A MIL series metal‒organic framework (MOF), MIL-100(Fe), was successfully synthesized at the nanoscale and fully characterized by TEM, TGA, XRD, FTIR, DLS, and BET. A toxicological assessment was performed using two different cell lines: human normal liver cells (HL-7702) and hepatocellular carcinoma (HepG2). In vitro cytotoxicity of MIL-100(Fe) was evaluated by the MTT assay, LDH releasing rate assay, DAPI staining, and annexin V/PI double staining assay. The safe dose of MIL-100(Fe) was 80 μg/mL. It exhibited good biocompatibility, low cytotoxicity, and high cell survival rate (HL-7702 cells’ viability >85.97%, HepG2 cells’ viability >91.20%). Therefore, MIL-100(Fe) has a potential application as a drug carrier.
A Combined ELONA-(RT)qPCR Approach for Characterizing DNA and RNA Aptamers Selected against PCBP-2
Authors: Moreno Miguel , Fernández-Algar María , Fernández-Chamorro Javier , Ramajo Jorge , Martínez-Salas Encarnación , Briones Carlos
Published: March 2019

Improvements in Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology and DNA sequencing methods have led to the identification of a large number of active nucleic acid molecules after any aptamer selection experiment. As a result, the search for the fittest aptamers has become a laborious and time-consuming task. Herein, we present an optimized approach for the label-free characterization of DNA and RNA aptamers in parallel. The developed method consists in an Enzyme-Linked OligoNucleotide Assay (ELONA) coupled to either real-time quantitative PCR (qPCR, for DNA aptamers) or reverse transcription qPCR (RTqPCR, for RNA aptamers), which allows the detection of aptamer-target interactions in the high femtomolar range. We have applied this methodology to the affinity analysis of DNA and RNA aptamers selected against the poly(C)-binding protein 2 (PCBP-2). In addition, we have used ELONA-(RT)qPCR to quantify the dissociation constant (Kd) and maximum binding capacity (Bmax) of 16 high affinity DNA and RNA aptamers. The Kd values of the high affinity DNA aptamers were compared to those derived from colorimetric ELONA performed in parallel. Additionally, Electrophoretic Mobility Shift Assays (EMSA) were used to confirm the binding of representative PCBP-2-specific RNA aptamers in solution. We propose this ELONA-(RT)qPCR approach as a general strategy for aptamer characterization, with a broad applicability in biotechnology and biomedicine.
Recycled Polyethylene/Paraffin Wax/Expanded Graphite Based Heat Absorbers for Thermal Energy Storage: An Artificial Aging Study
Authors: Abdelrazeq Haneen , Sobolčiak Patrik , Al-Ali Al-Maadeed Mariam , Ouederni Mabrouk , Krupa Igor
Published: March 2019

An artificial aging study of novel heat absorbers based on phase change materials (PCMs) prepared from recycled high-density polyethylene (HDPE), paraffin wax (PW), and expanded graphite (EG) was investigated. The optimal composition of PCMs contained 40 wt% HDPE, whereas the paraffin wax content ranged from 40 to 60 wt% and the expanded graphite content ranged from 5 to 15 wt%. PCMs were artificially aged through exposure to UV irradiation, enhanced temperature, and humidity. It was clearly demonstrated that the addition of EG to PCMs led to the suppression of PW leakage and improved the photooxidation stability of the PCMs during the aging process. The best performance was achieved by adding 15 wt% of EG to the PCMs. The sample shows a leakage of paraffin wax below 10%, retaining a melting enthalpy of PW within PCMs of 54.8 J/g, a thermal conductivity of 1.64 W/mK and the lowest photooxidation, characterized by an increase in the concentration of carbonyl groups from all investigated materials after artificial aging. Furthermore, PCMs mixed with EG exhibited good mechanical properties, even after 100 days of exposure to artificial aging. Finally, this work demonstrates a justification for the use of recycled plastics in the formation of PCMs.
Challenges in Translating from Bench to Bed-Side: Pro-Angiogenic Peptides for Ischemia Treatment
Authors: Petrak Karel , Vissapragada Ravi , Shi Siyu , Siddiqui Zain , Kim Ka Kyung , Sarkar Biplab , Kumar Vivek A.
Published: March 2019

We describe progress and obstacles in the development of novel peptide-hydrogel therapeutics for unmet medical needs in ischemia treatment, focusing on the development and translation of therapies specifically in peripheral artery disease (PAD). Ischemia is a potentially life-threatening complication in PAD, which affects a significant percentage of the elderly population. While studies on inducing angiogenesis to treat PAD were started two decades ago, early results from animal models as well as clinical trials have not yet been translated into clinical practice. We examine some of the challenges encountered during such translation. We further note the need for sustained angiogenic effect involving whole growth factor, gene therapy and synthetic growth factor strategies. Finally, we discuss the need for tissue depots for de novo formation of microvasculature. These scaffolds can act as templates for neovasculature development to improve circulation and healing at the preferred anatomical location.
Analysis of Non-Ionic Surfactant Triton X-100 Using Hydrophilic Interaction Liquid Chromatography and Mass Spectrometry
Authors: Farsang Evelin , Gaál Violetta , Horváth Ottó , Bárdos Erzsébet , Horváth Krisztián
Published: March 2019

It is well known that surfactants increase the solubility of hydrophobic organic compounds and cause adverse environmental effects. The removal of these compounds from the contaminated soil or ground-water is particularly difficult due to their water soluble feature. In this work, an ultra-high performance hydrophilic interaction liquid chromatographic method was developed for the separation of oligomers of Triton X-100 octylphenol-polyethoxylate non-ionic surfactant. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the Triton X-100 compounds. There was a 44 mass unit difference between two adjacent peaks that is the molar mass of one ethylene oxide group (–CH 2 CH 2 O–). A quadratic retention model was applied for the estimation of retention of the examined non-ionic surfactant and the optimization of gradient elution conditions. The optimized method was suitable for the baseline separation of 28 Triton X-100 oligomers in five minutes.
Liquid Phase and Microwave-Assisted Extractions for Multicomponent Phenolic Pattern Determination of Five Romanian Galium Species Coupled with Bioassays
Authors: Mocan Andrei , Diuzheva Alina , Bădărău Sabin , Moldovan Cadmiel , Andruch Vasil , Carradori Simone , Campestre Cristina , Tartaglia Angela , De Simone Marta , Vodnar Dan , Tiecco Matteo , Germani Raimondo , Crișan Gianina , Locatelli Marcello
Published: March 2019

Background: Galium is a plant rich in iridoid glycosides, flavonoids, anthraquinones, and small amounts of essential oils and vitamin C. Recent works showed the antibacterial, antifungal, antiparasitic, and antioxidant activity of this plant genus. Methods: For the determination of the multicomponent phenolic pattern, liquid phase microextraction procedures were applied, combined with HPLC-PDA instrument configuration in five Galium species aerial parts (G. verum, G. album, G. rivale, G. pseudoaristatum, and G. purpureum). Dispersive Liquid–Liquid MicroExtraction (DLLME) with NaCl and NAtural Deep Eutectic Solvent (NADES) medium and Ultrasound-Assisted (UA)-DLLME with β-cyclodextrin medium were optimized. Results: The optimal DLLME conditions were found to be: 10 mg of the sample, 10% NaCl, 15% NADES or 1% β-cyclodextrin as extraction solvent—400 μL of ethyl acetate as dispersive solvent—300 μL of ethanol, vortex time—30 s, extraction time—1 min, centrifugation at 12000× g for 5 min. Conclusions: These results were compared with microwave-assisted extraction procedures. G. purpureum and G. verum extracts showed the highest total phenolic and flavonoid content, respectively. The most potent extract in terms of antioxidant capacity was obtained from G. purpureum, whereas the extract obtained from G. album exhibited the strongest inhibitory effect against tyrosinase.
In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Lysimachia capillipes Hemsl
Authors: Zhang Xu , Cheng Xiao , Wu Yali , Feng Di , Qian Yifan , Chen Liping , Yang Bo , Gu Mancang
Published: March 2019

The goal of this investigation was to determine the processes and mechanism of intestinal absorption for capilliposide B (CAPB) and capilliposide C (CAPC) from the Chinese herb, Lysimachia capillipes Hemsl. An analysis of basic parameters, such as drug concentrations, time, and behavior in different intestinal segments was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The susceptibility of CAPB and CAPC to various inhibitors such as P-glycoprotein (P-gp) inhibitor (verapamil); multidrug resistance-associated protein 2 (MRP2) inhibitor (indomethacin); cytochrome P450 protein 3A4 (CYP3A4) inhibitor (ketoconazole); and the co-inhibitor of P-gp, MRP2 and CYP3A4 (cyclosporine A) were assessed using both caco-2 cell monolayer and single-pass intestinal perfusion (SPIP) models. As a result, CAPB and CAPC are both poorly absorbed in the intestines and exhibited segment-dependent permeability. The intestinal permeability of CAPB and CAPC were significantly increased by the co-treatment of verapamil, indomethacin. In addition, the intestinal permeability of CAPB was also enhanced by ketoconazole and cyclosporine A. It can be concluded that the intestinal absorption mechanisms of CAPB and CAPC involve processes such as facilitated passive diffusion, efflux transporters, and enzyme-mediated metabolism. Both CAPB and CAPC are suggested to be substrates of P-gp and MRP2. However, CAPB may interact with the CYP3A4 system.
Possible Role of the Ca2+/Mn2+ P-Type ATPase Pmr1p on Artemisinin Toxicity through an Induction of Intracellular Oxidative Stress
Authors: Pongwattanakewin Onnicha , Phyu The , Suesattayapirom Suchanya , Jensen Laran T. , Jensen Amornrat N.
Published: March 2019

Artemisinins are widely used to treat Plasmodium infections due to their high clinical efficacy; however, the antimalarial mechanism of artemisinin remains unresolved. Mutations in P. falciparum ATPase6 (PfATP6), a sarcoplasmic endoplasmic reticulum Ca2+-transporting ATPase, are associated with increased tolerance to artemisinin. We utilized Saccharomyces cerevisiae as a model to examine the involvement of Pmr1p, a functional homolog of PfATP6, on the toxicity of artemisinin. Our analysis demonstrated that cells lacking Pmr1p are less susceptible to growth inhibition from artemisinin and its derivatives. No association between sensitivity to artemisinin and altered trafficking of the drug efflux pump Pdr5p, calcium homeostasis, or protein glycosylation was found in pmr1∆ yeast. Basal ROS levels are elevated in pmr1∆ yeast and artemisinin exposure does not enhance ROS accumulation. This is in contrast to WT cells that exhibit a significant increase in ROS production following treatment with artemisinin. Yeast deleted for PMR1 are known to accumulate excess manganese ions that can function as ROS-scavenging molecules, but no correlation between manganese content and artemisinin resistance was observed. We propose that loss of function mutations in Pmr1p in yeast cells and PfATP6 in P. falciparum are protective against artemisinin toxicity due to reduced intracellular oxidative damage.
A Resolution-Free Parallel Algorithm for Image Edge Detection within the Framework of Enzymatic Numerical P Systems
Authors: Yuan Jianying , Guo Dequan , Zhang Gexiang , Paul Prithwineel , Zhu Ming , Yang Qiang
Published: March 2019

Image edge detection is a fundamental problem in image processing and computer vision, particularly in the area of feature extraction. However, the time complexity increases squarely with the increase of image resolution in conventional serial computing mode. This results in being unbearably time consuming when dealing with a large amount of image data. In this paper, a novel resolution free parallel implementation algorithm for gradient based edge detection, namely EDENP, is proposed. The key point of our method is the introduction of an enzymatic numerical P system (ENPS) to design the parallel computing algorithm for image processing for the first time. The proposed algorithm is based on a cell-like P system with a nested membrane structure containing four membranes. The start and stop of the system is controlled by the variables in the skin membrane. The calculation of edge detection is performed in the inner three membranes in a parallel way. The performance and efficiency of this algorithm are evaluated on the CUDA platform. The main advantage of EDENP is that the time complexity of O ( 1 ) can be achieved regardless of image resolution theoretically.
Ethical, Stigma, and Policy Implications of Food Addiction: A Scoping Review
Authors: Cassin Stephanie E. , Buchman Daniel Z. , Leung Samantha E. , Kantarovich Karin , Hawa Aceel , Carter Adrian , Sockalingam Sanjeev
Published: March 2019

The concept of food addiction has generated much controversy. In comparison to research examining the construct of food addiction and its validity, relatively little research has examined the broader implications of food addiction. The purpose of the current scoping review was to examine the potential ethical, stigma, and health policy implications of food addiction. Major themes were identified in the literature, and extensive overlap was identified between several of the themes. Ethics sub-themes related primarily to individual responsibility and included: (i) personal control, will power, and choice; and (ii) blame and weight bias. Stigma sub-themes included: (i) the impact on self-stigma and stigma from others, (ii) the differential impact of substance use disorder versus behavioral addiction on stigma, and (iii) the additive stigma of addiction plus obesity and/or eating disorder. Policy implications were broadly derived from comparisons to the tobacco industry and focused on addictive foods as opposed to food addiction. This scoping review underscored the need for increased awareness of food addiction and the role of the food industry, empirical research to identify specific hyperpalatable food substances, and policy interventions that are not simply extrapolated from tobacco.
A Durum Wheat Variety-Based Product Is Effective in Reducing Symptoms in Patients with Non-Celiac Gluten Sensitivity: A Double-Blind Randomized Cross-Over Trial
Authors: Ianiro Gianluca , Rizzatti Gianenrico , Napoli Marco , Matteo Maria Valeria , Rinninella Emanuele , Mora Vincenzina , Fanali Caterina , Leonetti Alessia , Benedettelli Stefano , Mele Maria Cristina , Cammarota Giovanni , Gasbarrini Antonio
Published: March 2019

Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but their symptoms improve after a gluten-free diet (GFD). However, to date, it is uncertain if gluten or other components of wheat are responsible for these symptoms. The aim of this study was to compare the effects of an organic durum wheat variety with those of standard commercial wheat in patients with known NCGS. We performed a double-blind randomized cross-over trial of 42 patients (mean age 45 years, 8 men) with NCGS diagnosed according to the Salerno criteria and adherence to GFD for at least 12 weeks from screening. Enrolled subjects were randomly assigned to one the following groups of treatment: (A) a two-week diet with Senatore Cappelli wheat variety pasta; (B) a two-week diet with standard commercial pasta. Then, after a two-week washout period on gluten-free diet, each patient crossed over to the other treatment group. Symptoms were assessed through a modified version of the Gastrointestinal Symptom Rating Scale (GSRS), tailored on NCGS. Between April 2018 and July 2018, 42 patients with NCGS were enrolled in the study (70.6% females), and 34 patients completed the study. Patients reported lower overall symptoms scores after eating Senatore Cappelli pasta than standard pasta (p = 0.03) and also significantly lower scores in several specific gastrointestinal and extra-intestinal symptoms after eating Senatore Cappelli pasta than standard pasta, specifically, bloating (p = 0.04), abdominal distention (p = 0.004), eructation (p = 0.01), flatus (p = 0.02), feeling of incomplete evacuation (p = 0.001), dermatitis (p = 0.01), and limb numbness (p = 0.03). In our study, patients with NCGS experienced lower gastrointestinal and extra-intestinal symptom scores after eating the Senatore Cappelli wheat variety than a standard commercial wheat. Should our preliminary results be confirmed by further studies, new dietary alternatives may be available to patients with NCGS, with consequent health, economic, and social benefits.
Usability and Engagement Evaluation of an Unguided Online Program for Promoting a Healthy Lifestyle and Reducing the Risk for Eating Disorders and Obesity in the School Setting
Authors: Nitsch Martina , Adamcik Tanja , Kuso Stefanie , Zeiler Michael , Waldherr Karin
Published: March 2019

Implementing integrated online prevention to reduce the risk of both obesity and eating disorders, in the school setting, is a promising approach. The challenge is to develop highly user-friendly and motivating programs, to foster adherence and effectiveness. The purpose of this study was to evaluate the usability of such a universal prevention program for students aged 14–19 years, and to address engagement issues. A mixed-methods approach was chosen, consisting of a think-aloud task, a semi-structured interview, and a questionnaire including items on sociodemographic characteristics and the System Usability Scale (SUS). Usability tests were conducted in two rounds, with five adolescents participating per round. Mean score in the SUS was 92.5 of 100 points (range 85–100), in the second round, after some adaptations from the participants’ feedback. In the course of the think-aloud tasks and interviews, five major themes emerged—visual design, navigation, mode of transfer, content, and engagement conditions. Interesting headlines, gamification, and monitoring tools are crucial for engagement. Apart from the importance of using the program during school hours, the study showed that problems currently perceived as important by the target group, need to be considered and addressed, prior to offering them prevention programs, which highlights the importance of a user-centered design.
Hericium erinaceus Improves Recognition Memory and Induces Hippocampal and Cerebellar Neurogenesis in Frail Mice during Aging
Authors: Ratto Daniela , Corana Federica , Mannucci Barbara , Priori Erica Cecilia , Cobelli Filippo , Roda Elisa , Ferrari Beatrice , Occhinegro Alessandra , Di Iorio Carmine , De Luca Fabrizio , Cesaroni Valentina , Girometta Carolina , Bottone Maria Grazia , Savino Elena , Kawagishi Hirokazu , Rossi Paola
Published: March 2019

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, implicated in both poor quality of life and negative health outcomes. One central question surrounding frailty is whether phenotypic frailty is associated with the cognitive impairment during aging. Using spontaneous behavioral tests and by studying the dynamic change during aging, we demonstrated that the two form of vulnerability, locomotor and recognition memory decline, develop in parallel and therefore, integration of the motoric and cognitive evaluations are imperative. We developed an integrated frailty index based on both phenotypic and recognition memory performances. Hericium erinaceus (H. erinaceus) is a medicinal mushroom that improves recognition memory in mice. By using HPLC-UV-ESI/MS analyses we obtained standardized amounts of erinacine A and hericenones C and D in H. erinaceus extracts, that were tested in our animal model of physiological aging. Two-month oral supplementation with H. erinaceus reversed the age-decline of recognition memory. Proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunohistochemistry in the hippocampus and cerebellum in treated mice supported a positive effect of an H. erinaceus on neurogenesis in frail mice.
Palatability of Goat’s versus Cow’s Milk: Insights from the Analysis of Eating Behavior and Gene Expression in the Appetite-Relevant Brain Circuit in Laboratory Animal Models
Authors: Klockars Anica , Wood Erin L. , Gartner Sarah N. , McColl Laura K. , Levine Allen S. , Carpenter Elizabeth A. , Prosser Colin G. , Olszewski Pawel K.
Published: March 2019

Goat’s (GM) and cow’s milk (CM) are dietary alternatives with select health benefits shown in human and animal studies. Surprisingly, no systematic analysis of palatability or preference for GM vs. CM has been performed to date. Here, we present a comprehensive investigation of short-term intake and palatability profiles of GM and CM in laboratory mice and rats. We studied consumption in no-choice and choice scenarios, including meal microstructure, and by using isocaloric milks and milk-enriched solid diets. Feeding results are accompanied by qPCR data of relevant genes in the energy balance-related hypothalamus and brain stem, and in the nucleus accumbens, which regulates eating for palatability. We found that GM and CM are palatable to juvenile, adult, and aged rodents. Given a choice, animals prefer GM- to CM-based diets. Analysis of meal microstructure using licking patterns points to enhanced palatability of and, possibly, greater motivation toward GM over CM. Most profound changes in gene expression after GM vs. CM were associated with the brain systems driving consumption for reward. We conclude that, while both GM and CM are palatable, GM is preferred over CM by laboratory animals, and this preference is driven by central mechanisms controlling eating for pleasure.
Gamma-oryzanol Prevents LPS-induced Brain Inflammation and Cognitive Impairment in Adult Mice
Authors: Mastinu Andrea , Bonini Sara Anna , Rungratanawanich Wiramon , Aria Francesca , Marziano Mariagrazia , Maccarinelli Giuseppina , Abate Giulia , Premoli Marika , Memo Maurizio , Uberti Daniela
Published: March 2019

Background: Rice (Oryza sativa L.) is the main food source for more than half of humankind. Rice is rich in phytochemicals and antioxidants with several biological activities; among these compounds, the presence of γ-oryzanol is noteworthy. The present study aims to explore the effects of γ-oryzanol on cognitive performance in a mouse model of neuroinflammation and cognitive alterations. Methods: Mice received 100 mg/kg γ-oryzanol (ORY) or vehicle once daily for 21 consecutive days and were then exposed to an inflammatory stimulus elicited by lipopolysaccharide (LPS). A novel object recognition test and mRNA expression of antioxidant and neuroinflammatory markers in the hippocampus were evaluated. Results: ORY treatment was able to improve cognitive performance during the neuroinflammatory response. Furthermore, phase II antioxidant enzymes such as heme oxygenase-1 (HO-1) and NADPH-dehydrogenase-quinone-1 (NQO1) were upregulated in the hippocampi of ORY and ORY+LPS mice. Lastly, γ-oryzanol showed a strong anti-inflammatory action by downregulating inflammatory genes after LPS treatment. Conclusion: These results suggest that chronic consumption of γ-oryzanol can revert the LPS-induced cognitive and memory impairments by promoting hippocampal antioxidant and anti-inflammatory molecular responses.
Frequency of Use of Added Sugar, Salt, and Fat in Infant Foods up to 10 Months in the Nationwide ELFE Cohort Study: Associated Infant Feeding and Caregiving Practices
Authors: Bournez Marie , Ksiazek Eléa , Charles Marie-Aline , Lioret Sandrine , Brindisi Marie-Claude , de Lauzon-Guillain Blandine , Nicklaus Sophie
Published: March 2019

The consumption of sugar, salt, and fat in infancy may influence later health. The objective of this study was to describe the frequency of use of added sugar, salt, and fat during the complementary feeding period and the associated infant caregiving practices. Data were obtained from a monthly questionnaire filled by parents for 10,907 infants from the French Etude Longitudinale Française depuis l’Enfance (ELFE) cohort. A score of frequency of use (SU) for added sugar, salt, and fat (oil, margarine, butter, and/or cream) was calculated from the age at complementary feeding introduction (CFI) to the 10th month. Associations between the SU of each added ingredient with infant feeding and caregiving practices were studied with multivariable linear regressions adjusted for familial characteristics. Only 28% of the parents followed the recommendation of adding fat and simultaneously not adding sugar or salt. Breastfeeding mothers were more prone to add sugar, salt, and fat than non-breastfeeding mothers. CFI before four months was positively associated with the SU of added sugar and salt and negatively associated with the SU of added fat. The use of commercial baby food was negatively related to the SU of added salt and fat. The use of these added ingredients was mainly related to breastfeeding, age at CFI, and use of commercial food, and it was independent of the household socioeconomic characteristics.
Maternal and Early Life Iron Intake and Risk of Childhood Type 1 Diabetes: A Danish Case-Cohort Study
Authors: Thorsen Steffen Ullitz , Halldorsson Thorhallur I. , Bjerregaard Anne A. , Olsen Sjurdur F. , Svensson Jannet
Published: March 2019

Background: Iron overload has been associated with diabetes. Studies on iron exposure during pregnancy and in early life and risk of childhood type 1 diabetes (T1D) are sparse. We investigated whether iron supplementation during pregnancy and early in life were associated with risk of childhood T1D. Methods: In a case-cohort design, we identified up to 257 children with T1D (prevalence 0.37%) from the Danish National Birth Cohort through linkage with the Danish Childhood Diabetes Register. The primary exposure was maternal pure iron supplementation (yes/no) during pregnancy as reported in interview two at 30 weeks of gestation (n = 68,497 with iron supplement data). We estimated hazard ratios (HRs) using weighted Cox regression adjusting for multiple confounders. We also examined if offspring supplementation during the first 18 months of life was associated with later risk of T1D. Results: Maternal iron supplementation was not associated with later risk of T1D in the offspring HR 1.05 (95% CI: 0.76–1.45). Offspring intake of iron droplets during the first 18 months of life was inversely associated with risk of T1D HR 0.74 (95% CI: 0.55–1.00) (ptrend = 0.03). Conclusions: Our large-scale prospective study demonstrated no harmful effects of iron supplementation during pregnancy and in early life in regard to later risk of childhood T1D in the offspring.