bluuebunny/crossref_metadata_2025 huggingface dataset:
Liquid Crystal‐Induced Myoblast Alignment
Authors: Martella Daniele , Pattelli Lorenzo , Matassini Camilla , Ridi Francesca , Bonini Massimo , Paoli Paolo , Baglioni Piero , Wiersma Diederik S. , Parmeggiani Camilla
Published: January 2019

The ability to control cell alignment represents a fundamental requirement toward the production of tissue in vitro but also to create biohybrid materials presenting the functional properties of human organs. However, cell cultures on standard commercial supports do not provide a selective control on the cell organization morphology, and different techniques, such as the use of patterned or stimulated substrates, are developed to induce cellular alignment. In this work, a new approach toward in vitro muscular tissue morphogenesis is presented exploiting liquid crystalline networks. By using smooth polymeric films with planar homogeneous alignment, a certain degree of cellular order is observed in myoblast cultures with direction of higher cell alignment corresponding to the nematic director. The molecular organization inside the polymer determines such effects since no cell organization is observed using homeotropic or isotropic samples. These findings represent the first example of cellular alignment induced by the interaction with a nematic polymeric scaffold, setting the stage for new applications of liquid crystal polymers as active matter to control tissue growth.
Depletion Layer Built‐In Field at (1−100), (0001), and (000−1) GaN/Water Junction and Its Role in Semiconductor Nanowire Water Splitting
Authors: Stokowski Hubert , Janicki Łukasz , Serafińczuk Jarosław , Siekacz Marcin , Skierbiszewski Czesław , Kudrawiec Robert
Published: January 2019

The nature of specific GaN plane/water interfaces under external bias and illumination can influence photoelectrolysis efficiency using GaN nanowires. Studies of Ga‐polar, N‐polar, and m‐plane GaN interfaces with deionized water allow determining differences between surfaces corresponding to different nanowire facets. They are investigated under external bias conditions to reveal the profile of Fermi level localization through analysis of Franz–Keldysh oscillations using electrolyte electroreflectance (EER) technique in a specially designed measurement chamber. Calculation of the potential barrier height is also possible. EER study shows differences between surface densities of states (SDOS) at distinct GaN planes. One broad SDOS is identified near the conduction band in case of ±c‐plane and related to Ga adatom reconstruction and β‐Ga2O3 presence at the GaN electrode. Two narrow SDOS singularities are found at the m‐plane one of which is localized near the middle of the bandgap and allows to generate approximately two times higher surface potential barrier than in case of polar surfaces at zero‐bias conditions. This suggests that n‐type GaN nanowires can enhance carrier separation at sidewalls and refine the oxygen evolution rate. Additionally, a voltage‐controlled hysteresis loop of Fermi level localization is detected at the Ga‐face GaN/water interface.
Programmable Controls of Multiple Modes of Spoof Surface Plasmon Polaritons to Reach Reconfigurable Plasmonic Devices
Authors: Wang Meng , Ma Hui Feng , Tang Wen Xuan , Zhang Hao Chi , Wang Zheng Xing , Cui Tie Jun
Published: January 2019

Spoof surface plasmon polaritons (SSPPs) can be supported and propagated on metal surfaces decorated with periodic subwavelength structures, whose dispersion properties are determined by geometrical dimensions of unit structures. However, the functions of plasmonic devices made of the conventional passive SSPPs will be fixed once the devices are fabricated. Here, an electronically controlled programmable SSPP waveguide is presented, whose dispersions can be manipulated in real time at fast speed by programing the bias voltage instead of changing the dimensions of the unit structures. There are three different modes at different frequency bands, with a forbidden band existing between the first‐order (fundamental) mode and the third‐order mode, where the second‐order mode cannot be propagated. By loading varactor diodes in the unit structure, the dispersions of SSPPs can be controlled by changing the capacitance of the loaded varactor diode. The proposed programmable SSPPs have a unique advantage of designing smart plasmonic devices with reconfigurable functions. As an example, a compact plasmonic waveguide with reconfigurable rejection bands is designed, simulated, and measured, showing that the central frequency, the number, and bandwidth of the rejection bands can be freely reconfigured in real time by programming the bias voltages.
Nuts and Bolts: Microfluidics for the Production of Biomaterials
Authors: Fontana Flavia , Martins João P. , Torrieri Giulia , Santos Hélder A.
Published: January 2019

Nanotechnology holds the promise of bringing revolutionary therapeutic strategies into the clinic. However, an enormous fraction of the currently proposed nanotechnology‐based therapies suffers from lack of reproducibility, complexity, high costs, and scale‐up‐related issues. For these reasons, the research community is moving toward the miniaturization of biomaterials and fabrication methods. Customizable microfluidic‐based products have gained tremendous relevance in the development of biomedical technologies. This review provides an overview of different materials that can be used for the fabrication of microfluidic devices, as well as the other parameters influencing the production of biomaterials and biosensors. Moreover, several advanced microfluidic‐based technologies that are designed to overcome the current challenges of cancer, immunotherapy, and diabetes therapy, among others are described. Then, the pros and cons of microfluidics as alternative to conventional preparation methods, and the challenges of translating this technique to an industrial context are highlighted. Overall, microfluidic technologies and their accessibility to the research community offer a set of exciting opportunities to bridge the development of innovative therapies and their commercialization in the foreseeable future.
Advances in Reagents Storage and Release in Self‐Contained Point‐of‐Care Devices
Authors: Deng Jinqi , Jiang Xingyu
Published: January 2019

Microfluidics has emerged as a useful material for point‐of‐care testing. However, conventional microfluidic devices rely on multiple steps to complete the detection process, which may not be acceptable for untrained users. The emerging “self‐contained” point‐of‐care devices, with all necessary reagents prestored in, address this limitation. This paper summarizes the recent advances of self‐contained point‐of‐care devices, with emphasis on the approaches for reagents integration and manipulation. Due to the intrinsic similarity and relevance of these approaches in pharmaceutical applications, several examples about drug delivery in vivo are presented. Different approaches are compared and future trends for the development of self‐contained point‐of‐care devices are outlined.
Fabrication of Large Area Sub‐200 nm Conducting Electrode Arrays by Self‐Confinement of Spincoated Metal Nanoparticle Inks
Authors: Horváth Barbara , Křivová Barbora , Bolat Sami , Schift Helmut
Published: January 2019

Here, the fabrication of sub‐200 nm metal wires from commercial silver inks with 50 nm particle size, 100 times narrower than with typical low‐resolution ink‐jet and screen printing in flexible electronics, is demonstrated. Using a combination of spincoating on prepatterned polymer substrates and flash lamp annealing, nanoparticles merge to wires featuring good electrical conductivity. With this method less than 150 nm thin wires can be generated from 2 µm wide or smaller V‐grooves due to adapted dilution of particle content, self‐confinement in V‐grooves, shrinkage of line width during solvent evaporation, and sintering. After nanoimprinting, grooves made from PMMA are smoothened out by thermal reflow without affecting the wires. The resistivity of 300 µm long, 400 nm wires is similar to more conventional ink‐jet printed wires with 10–50 µm widths.
Highly Conducting, Transparent PEDOT:PSS Polymer Electrodes from Post‐Treatment with Weak and Strong Acids
Authors: Bießmann Lorenz , Saxena Nitin , Hohn Nuri , Hossain Md Asjad , Veinot Jonathan G. C. , Müller‐Buschbaum Peter
Published: January 2019

The origin of high conductivity in polymer electrodes based on poly(3,4‐ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is investigated and the resilience against water exposure is tested. Post‐treatment with weak and strong acids, namely, hydrochloric acid (HCl), formic acid (HCOOH), nitric acid (HNO3), and sulfuric acid (H2SO4), is performed and compared to the commonly used ethylene glycol treatment. PEDOT:PSS electrodes with electrical conductivities of up to ≈3000 S cm−1 and high transmittance are obtained. The underlying mechanisms for enhanced conductivity are elucidated by means of electrical (4‐point probe), optical (UV‐Vis spectroscopy), compositional (X‐ray photo‐electron spectroscopy), and structural (grazing‐incidence wide‐angle X‐ray scattering, GIWAXS) characterizations. Selective PSS removal and structural rearrangement of PEDOT‐rich domains due to an enhanced lamellar stacking is identified as major influence on the improvement in electrical conductivity. This beneficial high order is evidenced via additional signals in the GIWAXS patterns, which are altered by subsequent H2O treatment. The PSS removal and structural rearrangement is linked to the acids' strength and dielectric constant. High conductivities are reached by efficient PSS removal via HNO3 or H2SO4 treatment with the drawback of high sensitivity against H2O. By contrast, HCl and HCOOH treatment obtaining a medium enhanced conductivity differ in the amount of PSS removal but show higher H2O resistance.
Thickness‐Dependent Structural Stability and Anisotropy of Black Phosphorus
Authors: Li Qian , Huang Hao , Chen Zhongwei , Huang Xin , Deng Kerong , Luo Shuiping , Wang Zhongwu , Yu Xuefeng , Quan Zewei
Published: January 2019

Black phosphorus (BP) is emerging as a rising star in the post graphene nanomaterials, manifesting intriguing thickness‐dependent properties. However, there is little knowledge about the structural and mechanical stabilities of such BPs and their thickness dependence. Using high pressure technique, a comprehensive study was performed on the thickness‐dependent structural variations of BPs. It has been revealed from high pressure phase diagram that decrease of thickness enhances the structure stability of BPs, which is prominent between 71 and 13 nm. More importantly, an inhomogeneous distortion of the lamellar puckered structure is observed on these BPs, and the thinner ones exhibit enhanced anisotropic compressibility, with a rigid interlayer and zigzag structure and a relatively flexible armchair structure. This systematic study not only provides insights into thickness‐dependent structural nature of BPs but also lays foundation toward design and fabrication of BP‐based devices.
All‐Solid‐State Flexible Asymmetric Supercapacitors Fabricated by the Binder‐Free Hydrophilic Carbon Cloth@MnO2 and Hydrophilic Carbon Cloth@Polypyrrole Electrodes
Authors: Chen Zhiyuan , Zheng Luyao , Zhu Tao , Ma Zhihao , Yang Yongrui , Wei Chunding , Liu Lei , Gong Xiong
Published: January 2019

Supercapacitors have attracted enormous attention for energy storage in both academic and industrial sectors in the past years. In this study, all‐solid‐state flexible asymmetric supercapacitors (ASCs) without any binder, incorporated with the hydrophilic carbon cloth (HCC) with MnO2 nanocomposite (HCC@MnO2) as the positive electrode, the HCC with polypyrrole (PPy) (HCC@PPy) as the negative electrode, and polyvinyl alcohol (PVA)–LiCl gel as both gel electrolyte and separator, are reported. The HCC@MnO2 and HCC@PPy electrodes are prepared by direct deposition of either MnO2 nanoparticles or PPy nanofilms on the HCC through a simple, facile, and controllable electrochemical deposition method, respectively. The HCC@MnO2 and HCC@PPy electrodes provide rich contact area for gel electrolyte, facilitating the rapid delivery of electrolyte ions, and also minimize the resistance of ASCs. As a result, all‐solid‐state flexible binder‐free HCC@MnO2//HCC@PPy ASCs exhibit a large operating voltage of 1.8 V, high energy density of 28.2 Wh kg−1 at the power density of 420.5 W kg−1, and excellent cycling stability (91.2% capacitance retention after 5000 cycles). The present study provides a facile, scalable, and efficient approach to fabricate all‐solid‐state ASCs with high electrochemical storage performance for flexible electronics.
Organic Memristor Utilizing Copper Phthalocyanine Nanowires with Infrared Response and Cation Regulating Properties
Authors: Lv Ziyu , Hu Qikun , Xu Zong‐Xiang , Wang Junjie , Chen Zhonghui , Wang Yan , Chen Meng , Zhou Kui , Zhou Ye , Han Su‐Ting
Published: January 2019

Current organic memristive devices have been suffering from unstable performance, ambiguous mechanism, and poor NIR response, thus restricting their commercial translation. Here, a near‐infrared‐sensitive (NIR) organic memristive device with high stability based on solution‐processed copper phthalocyanine nanowires (N‐CuMe2Pc NWs) is first reported. Compared with uneven thermal evaporated N‐CuMe2Pc film, the N‐CuMe2Pc NWs film possesses a uniform 3D mesh structure, which attribute to the localized cationic migration, robust formation/rupture of conductive filament and subsequent improvement of reproducibility, thermal stability, and retention characteristics. Furthermore, operating voltage and OFF current can be readily regulated by NIR illumination due to strong NIR absorption of the well‐aligned edge‐to‐edge interconnected N‐CuMe2Pc NWs and tunable potential barrier formed between active layer and Ag electrode, which are further verified by absorption spectrum and Kelvin probe force microscope analysis, respectively. This study provides a generalized method for optimizing device performance and attaching phototunable properties of organic memristive memories. In addition, compared with pristine CuPc molecules with low solubility, limitation of thermal evaporation approach that is incompatible with scaling up is expected to overcome by the solution‐processed N‐CuMe2Pc NWs.
Highly Reversible and Rechargeable Safe Zn Batteries Based on a Triethyl Phosphate Electrolyte
Authors: Naveed Ahmad , Yang Huijun , Yang Jun , Nuli Yanna , Wang Jiulin
Published: January 2019

Zinc metal is an attractive anode material for next‐generation batteries. However, dendrite growth and limited Coulombic efficiency (CE) during cycling are the major roadblocks towards the widespread commercialization of batteries employing Zn anodes. In this work we report the novel adoption of triethyl phosphate (TEP) as a solvent and co‐solvent with aqueous electrolytes to obtain a highly stable and dendrite‐free Zn anode. Stable Zn plating/stripping for over 3000 h was obtained, accompanied by a CE of 99.68 %. SEM images of the Zn anodes revealed highly porous interconnected dendrite‐free Zn deposits. The electrolyte displayed good compatibility with both Zn anodes and potassium copper hexacyanoferrate (KCuHCf) cathodes for Zn ion batteries (ZIBs). The full cell showed a long cycling stability and high rate capability. The present work is a contribution towards cost‐effective and safe battery systems.
Synthesis of a bio‐based triazine derivative and its effects on flame retardancy of polypropylene composites
Authors: Ma Dong , Li Juan
Published: January 2019

A triazine derivative CC–Cy was synthesized using cytosine (Cy) and cyanuric chloride (CC). The CC–Cy was used as a charring agent and combined with ammonium polyphosphate (APP) to form an intumescent flame‐retardant (IFR) system. The IFR system was applied to improve the flame retardancy of polypropylene (PP). Moreover, bisphenol‐A bis(diphenyl phosphate) (BDP) was introduced in the IFR system to regulate the suitability between the IFR and PP. The results showed the PP containing 20 wt % APP and 5 wt % CC–Cy achieves the UL‐94 V‐2 rating. While the PP with 18 wt % APP/CC‐Cy (4:1) and 3 wt % BDP obtains the UL‐94 V‐0 rating indicating the improved flame‐retardant efficiency. Thermal degradation behaviors and char morphology both showed that the reactions between APP and CC–Cy promote the formation of char residues, and BDP works in gas phase to enhance the flame retardancy of PP composites. Thus, a synergistic IFR system based on APP, CC–Cy, and BDP is formed, which can protect PP from fire effectively. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 47367.
Asymmetric biphasic hydrophobic/hydrophilic poly(lactic acid)–polyvinyl alcohol meshes with moisture control and noncytotoxic effects for wound dressing applications
Authors: Ribba Laura , Tamayo Laura , Flores Marcos , Riveros Ana , Kogan Marcelo Javier , Cerda Enrique , Goyanes Silvia
Published: January 2019

A noncytotoxic film was developed in this work with asymmetric biphasic properties (hydrophilic/hydrophobic) that allow for gas exchange. Among its many biomedical applications, it could be applied as a wound dressing material where the absorption of exuded fluids and control of water loss is required simultaneously. Thin meshes were developed modifying one face of poly(lactic acid) (PLA) electrospun mats with polyvinyl alcohol (PVA) using a simple photografting methodology. The contact angle of the modified face of the film was 44° while that of the other face was the original value of 122°. The chemical modification was covalent, as confirmed by X‐ray photoelectron spectroscopy, stable over time and resistant to successive washing steps. Cytotoxic assays with fibroblast cells showed that PVA photo‐grafted onto PLA meshes present a high cell viability percentage. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47369.
Metacognitive myopia and the overutilization of misleading advice
Authors: Fiedler Klaus , Hütter Mandy , Schott Malte , Kutzner Florian
Published: January 2019

Previous research on advice taking has explained the failure to exploit collective wisdom in terms of the egocentric underweighting of advice provided by independent others. The present research is concerned with an opposite and more radical source of irrational advice taking, namely, the failure to critically assess the validity of advice due to metacognitive myopia. Participants could use the advice of one or two experts when estimating health risks. They read sketches of the study samples that experts had drawn to estimate conditional probabilities (e.g., of HIV‐given drug addiction). Whether samples were valid or seriously biased, subsequent judgments were strongly affected by any advice (Experiment 1). Uncritical reliance on any advice persisted when participants were sensitized to the contrast of valid and invalid advice in a repeated measures design (Experiment 2), when participants themselves believed advice not to be valid (Experiment 3), and even after full debriefing about invalid advice (Experiment 4). Lay advice exerted a similar influence as expert advice (Experiment 5). Although these provocative results are independent of numeracy and consensus (Experiment 6), they highlight the impact of metacognitive myopia as an impediment of social rationality.
Fluorescence and absorption studies of DNA–Pd(II) complex interaction: Synthesis, spectroanalytical investigations and biological activities
Authors: Thakor Khyati P. , Lunagariya Miral V. , Bhatt Bhupesh S. , Patel Mohan N.
Published: January 2019

Novel palladium(II) complexes (7a–7e) of substituted quinoline derivatives were synthesized. The complexes were characterized using various techniques such as thermogravimetric analysis (TGA), elemental analysis, conductance measurement, mass, absorption, infra‐red (IR), 1H NMR, 13C NMR and energy‐dispersive X‐ray spectroscopy (EDX). Complexes for herring sperm DNA (HS DNA) binding were explored and absorption titration and the binding constant (Kb) as well as Gibb's free energy were evaluated. Complex 7d exhibited the highest binding constant, therefore the thermodynamic parameters of 7d at different temperatures were evaluated. To support the results of the absorption titration, fluorescence titration, viscosity measurement and molecular docking studies were performed. The fluorescence quenching data as evaluated from Stern–Volmer equation were used to calculate KSV, Kf and the number of binding sites. The results of all these studies were in good agreement with the absorption study. DNA electrophoretic mobility was performed to explore the possible application of metal complexes as artificial metallonucleases. The antibacterial activity of the complexes was accessed against different pathogenic bacteria and cytotoxicity was measured using brine shrimp and S. pombe.
Acetyl Coenzyme A Analogues as Rationally Designed Inhibitors of Citrate Synthase
Authors: Bello Davide , Rubanu Maria Grazia , Bandaranayaka Nouchali , Götze Jan P. , Bühl Michael , O'Hagan David
Published: January 2019

In this study, we probed the inhibition of pig heart citrate synthase (E.C. 4.1.3.7) by synthesising seven analogues either designed to mimic the proposed enolate intermediate in this enzyme reaction or developed from historical inhibitors. The most potent inhibitor was fluorovinyl thioether 9 (Ki=4.3 μm), in which a fluorine replaces the oxygen atom of the enolate. A comparison of the potency of 9 with that of its non‐fluorinated vinyl thioether analogue 10 (Ki=68.3 μm) revealed a clear “fluorine effect” favouring 9 by an order of magnitude. The dethia analogues of 9 and 10 proved to be poor inhibitors. A methyl sulfoxide analogue was a moderate inhibitor (Ki=11.1 μm), thus suggesting hydrogen bonding interactions in the enolate site. Finally, E and Z propenoate thioether isomers were explored as conformationally constrained carboxylates, but these were not inhibitors. All compounds were prepared by the synthesis of the appropriate pantetheinyl diol and then assembly of the coenzyme A structure according to a three‐enzyme biotransformation protocol. A quantum mechanical study, modelling both inhibitors 9 and 10 into the active site indicated short CF⋅⋅⋅H contacts of ≈2.0 Å, consistent with fluorine making two stabilising hydrogen bonds, and mimicking an enolate rather than an enol intermediate. Computation also indicated that binding of 9 to citrate synthase increases the basicity of a key aspartic acid carboxylate, which becomes protonated.
A novel technique for coronary bifurcation intervention: Double rewire crush technique and its clinical outcomes after 2 years of follow‐up
Authors: Zhang Dong , He Yuan , Yan Ruohua , Yin Dong , Feng Lei , Xu Bo , Yang Yuejin , Zhu Chenggang , Dou Kefei
Published: January 2019

Objectives

To describe procedural details of the double rewire (DR) crush technique, a novel modified crush technique, and report the clinical outcomes of patients who underwent the procedure.

Background

In the management of complex bifurcation lesions, there is a need to use elective two‐stent techniques that stent the side branch (SB) before main vessel (MV) stenting and keep SB open.

Methods

We studied 48 patients with 49 bifurcation lesions who underwent percutaneous coronary intervention (PCI) using the DR‐crush technique between January and December 2013. Baseline, postprocedural, and follow‐up quantitative coronary angiographic analyses were performed. Procedural characteristics and clinical outcomes at follow‐up were assessed.

Results

Majority of the patients (60.4%, 29/48) had acute coronary syndrome. Most bifurcation lesions (77.6%, 38/49) were classified as Medina 1, 1, 1. Final kissing balloon inflation was successfully performed in all patients. After PCI, MV and SB of all patients had Thrombolysis In Myocardial Infarction 3 blood flow. None of the patients had MV or SB diameter stenosis ≥50% after PCI. At a mean follow‐up period of 2.4 years, target vessel revascularization occurred in 2.1% and myocardial infarction in 2.1%. No deaths occurred in this period.

Conclusions

The DR‐crush technique is feasible in coronary bifurcation stenting. Patients who underwent this procedure had relatively low incidence of adverse events. Larger studies are warranted for further confirmation of the findings.
Sulfur‐Rich Colloidal Nickel Sulfides as Bifunctional Catalyst for All‐Solid‐State, Flexible and Rechargeable Zn‐Air Batteries
Authors: Sumboja Afriyanti , Chen Jingwei , Ma Yuanyuan , Xu Yijie , Zong Yun , Lee Pooi See , Liu Zhaolin
Published: January 2019

Earth‐abundant and high‐performance catalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are highly desirable in development of energy‐efficient rechargeable Zn‐air batteries. In this work, sulfur‐rich colloidal nickel sulfides (NiSx) are prepared as OER/ORR bifunctional catalysts via a two‐step hydrothermal process. The NiSx nanoparticles (NPs) with large surface area show high OER activity and excellent stability, as evidenced by low overpotential of 301 mV, small Tafel slope of 41 mV dec−1 and high stability over 20 h of chronopotentiometry test. Due to their sulfur‐rich nature (i. e. Ni3S4 and NiS2), the obtained NiSx also exhibit good ORR activity. The introduction of graphene oxide (GO) in the starting materials leads to the formation of a composite catalyst composed of conductive sulfur‐doped reduced graphene oxide (S‐rGO) and NiSx. A high ORR onset potential of 0.91 V (vs. RHE) is obtained from the sulfur‐rich NiSx NPs coupled with the S‐rGO which facilitates the electron‐transfer and furnishes the bifunctional catalytic activity. Rechargeable Zn‐air batteries with NiSx/S‐rGO bifunctional catalyst deliver stable charge and discharge voltages of 2.1 and 1.1 V over 590 cycles. Furthermore, all‐solid‐state and foldable Zn‐air batteries using pliable and robust air cathodes of NiSx/S‐rGO show similar voltage profile as their non‐foldable counterparts. The foldable batteries exhibit stable cycling performance for up to 120 discharge/charge cycles at either flat or folded state, proving their high electrochemical and mechanical stability.
Bioleaching von Rostasche der thermischen Abfallbehandlung im Jahreszyklus
Authors: Lewandowski Birgit , Knoll Thomas , Gärtner Tobias
Published: January 2019

Das Recycling der Fraktion < 10 mm von Rostaschen der thermischen Abfallverwertung ist aus Gründen des Umweltschutzes zukünftig unumgänglich und zugleich ein Zugang zu Rohstoffen, die Deutschland bei der Versorgung unabhängiger machen können. Aufgrund der Inhomogenität von Rostaschen liefern Stichproben keine verlässlichen Gehaltsmittelwerte, weshalb nur eine Langzeitstudie mittels Rücklösung über das Potenzial Aufschluss gibt. Daher wird zur Einschätzung des Potenzials nicht die Konzentration der Rostasche herangezogen, sondern die Menge an Metallen (Al, Fe, Cu, Zn), die aus der Rostasche mittels Bioleaching gelöst werden kann.
Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1‐Activated Prodrugs as Antiviral Agents
Authors: Richter Michael , Boldescu Veaceslav , Graf Dominik , Streicher Felix , Dimoglo Anatoli , Bartenschlager Ralf , Klein Christian D.
Published: January 2019

Recent studies indicate that tubulin can be a host factor for vector‐borne flaviviruses like dengue (DENV) and Zika (ZIKV), and inhibitors of tubulin polymerization such as colchicine have been demonstrated to decrease virus replication. However, toxicity limits the application of these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed by the esterase in vitro. In contrast to previous reports, the phenylglycine esters were not cleaved by human carboxylesterase. The antiviral activity of combretastatin, colchicine, and selected prodrugs against DENV and ZIKV in cell culture was observed at low micromolar and sub‐micromolar concentrations. In addition, docking studies were performed to understand the binding mode of the studied compounds to tubulin.
Investigation of the Pentathiepin Functionality as an Inhibitor of Feline Immunodeficiency Virus (FIV) via a Potential Zinc Ejection Mechanism, as a Model for HIV Infection
Authors: Asquith Christopher R. M. , Laitinen Tuomo , Konstantinova Lidia S. , Tizzard Graham , Poso Antti , Rakitin Oleg A. , Hofmann‐Lehmann Regina , Hilton Stephen T.
Published: January 2019

A small diverse library of pentathiepin derivatives were prepared to evaluate their efficacy against the nucleocapsid protein function of the feline immunodeficiency virus (FIV) as a model for HIV, using an in vitro cell culture approach. This study led to the development of nanomolar active compounds with low toxicity.
The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer
Authors: Sharma Manvi , Holmes Holly M. , Mehta Hemalkumar B. , Chen Hua , Aparasu Rajender R. , Shih Ya‐Chen T. , Giordano Sharon H. , Johnson Michael L.
Published: January 2019

Background

The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug‐drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI‐PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer.

Methods

This retrospective study used linked Surveillance, Epidemiology, and End Results‐Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI‐PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional‐hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome.

Results

The overall prevalence of TKI‐PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI‐PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05‐1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04‐1.18) but was not associated with discontinuation.

Conclusions

Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.
No Effect of Plazomicin on the Pharmacokinetics of Metformin in Healthy Subjects
Authors: Choi Taylor , Komirenko Allison S. , Riddle Valerie , Kim Aryun , Dhuria Shyeilla V.
Published: January 2019

Plazomicin is an aminoglycoside that was engineered to overcome aminoglycoside‐modifying enzymes, which are the most common aminoglycoside resistance mechanism in Enterobacteriaceae. Because plazomicin is predominantly eliminated via renal pathways, an in vitro study was conducted to determine whether plazomicin inhibits the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion (MATE1 and MATE2‐K) transporters, using metformin as a probe substrate. Plazomicin inhibited OCT2, MATE1, and MATE2‐K transporters with half‐maximal inhibition of the transporter values of 5120, 1300, and 338 µg/mL, respectively. To determine whether this in vitro inhibition translates in vivo, an open‐label, randomized, 2‐period, 2‐treatment crossover study (NCT03270553) was carried out in healthy subjects (N = 16), who received a single oral dose of metformin 850 mg alone and in combination with a single intravenous infusion of plazomicin 15 mg/kg. Geometric least‐squares mean ratios of the test treatment (combination) vs the reference treatment (metformin alone) and 90% confidence intervals were within the equivalence interval of 80% to 125% (peak plasma concentration, 104.5 [95.1–114.9]; area under the plasma concentration–time curve from time zero to time of last quantifiable concentration, 103.7 [93.5–115.0]; area under the plasma concentration–time curve from time zero to infinity, 104.0 [94.2–114.8]). The results demonstrate that there is no clinically significant drug‐drug interaction resulting from coadministration of single doses of intravenous plazomicin 15 mg/kg and oral metformin 850 mg in healthy subjects. Coadministration of plazomicin and metformin was well tolerated in healthy subjects.
Conservation of Critical Elements of the Periodic Table
Authors: Supanchaiyamat Nontipa , Hunt Andrew J.
Published: January 2019

Since its conception, the periodic table and the elements contained within it have shaped our modern lives. The use of many elements is now ubiquitous and essential for the modern technologies we have now become accustomed to. However, our use of some elements may be considered as unsustainable and their current use may create both economic and environmental pressures. The United Nations have designated 2019 the “International Year of the Periodic Table”. As such this Essay presents some important points on “critical elements” and the importance of adopting sustainable practices in the use of all elements of the periodic table. This article also highlights a number of examples of green technologies for elemental recovery and some of the challenges we must overcome to become truly sustainable across the whole periodic table.
Single‐cell redox states analyzed by fluorescence lifetime metrics and tryptophan FRET interaction with NAD(P)H
Authors: Cao Ruofan , Wallrabe Horst , Siller Karsten , Rehman Alam Shagufta , Periasamy Ammasi
Published: January 2019

Redox changes in live HeLa cervical cancer cells after doxorubicin treatment can either be analyzed by a novel fluorescence lifetime microscopy (FLIM)‐based redox ratio NAD(P)H‐a2%/FAD‐a1%, called fluorescence lifetime redox ratio or one of its components (NAD(P)H‐a2%), which is actually driving that ratio and offering a simpler and alternative metric and are both compared. Auto‐fluorescent NAD(P)H, FAD lifetime is acquired by 2‐ photon excitation and Tryptophan by 3‐photon, at 4 time points after treatment up to 60 min demonstrating early drug response to doxorubicin. Identical Fields‐of‐view (FoV) at each interval allows single‐cell analysis, showing heterogeneous responses to treatment, largely based on their initial control redox state. Based on a discrete ROI selection method, mitochondrial OXPHOS and cytosolic glycolysis are discriminated. Furthermore, putative FRET interaction and energy transfer between tryptophan residue carrying enzymes and NAD(P)H correlate with NAD(P)H‐a2%, as does the NADPH/NADH ratio, highlighting a multi‐parametric assay to track metabolic changes in live specimens. © 2019 International Society for Advancement of Cytometry
Angiotensin‐converting enzyme 2 inhibits endoplasmic reticulum stress–associated pathway to preserve nonalcoholic fatty liver disease
Authors: Cao Xi , Song Li‐Ni , Zhang Yi‐Chen , Li Qi , Shi Ting‐Ting , Yang Fang‐Yuan , Yuan Ming‐Xia , Xin Zhong , Yang Jin‐Kui
Published: January 2019

Background

Previous works indicated that the stress on the endoplasmic reticulum (ER) affected nonalcoholic fatty liver disease (NAFLD). However, there is no clear evident on the effect of the regulation of ER stress by angiotensin‐converting enzyme 2 (ACE2) on the prevention of NAFLD.

Methods

HepG2 cells were treated with thapsigargin (Tg) or palmitic acid (PA). We analysed ACE2 expression using Western‐blotting analyses. ER stress–related proteins were detected in ACE2 knockout mice and Ad‐ACE2‐treated db/db mice by immunofluorescence or Western‐blotting analyses. In ACE2‐overexpression HepG2 cells, the triglyceride (TG), total cholesterol (TC), and glycogen content were detected by assay kits. Meanwhile, the expression of hepatic lipogenic proteins (ACCα, SREBP‐1c, FAS, and LXRα), enzymes for gluconeogenesis (PEPCK, G6Pase, and IRS2), and IKKβ/NFκB/IRS1/Akt pathway were analysed by Western‐blotting analyses.

Results

ACE2 was significantly increased in Tg/PA‐induced cultured hepatocytes. Additionally, ACE2 knockout mice displayed elevated levels of ER stress, while Ad‐ACE2‐treated db/db mice showed reduced ER stress in liver. Furthermore, activation of ACE2 can ameliorate ER stress, accompanied by decreased TG content, increased intracellular glycogen, and downregulated expression of hepatic lipogenic proteins and enzymes for gluconeogenesis in Tg/PA‐induced hepatocytes. As a consequence of anti‐ER stress, the activation of ACE2 led to improved glucose and lipid metabolism through the IKKβ/NFκB/IRS1/Akt pathway.

Conclusions

This is the first time documented that ACE2 had a notable alleviating role in ER stress–induced hepatic steatosis and glucose metabolism via the IKKβ/NFκB/IRS1/Akt‐mediated pathway. This study may further provide insight into a novel underlying mechanism and a strategy for treating NAFLD.
Cardiovascular effects of SGLT‐2 inhibitors: What we have learned from cardiovascular outcome trials and what we still need to understand
Authors: Cavallari Ilaria , Maddaloni Ernesto
Published: January 2019

The recent results of the DECLARE‐TIMI 58 trial forces a profound reflection about the cardiovascular protection conferred by SGLT‐2 inhibitors. DECLARE‐TIMI 58, the largest cardiovascular outcome trial in diabetes, failed to show a significant reduction in the risk of major adverse cardiovascular events (MACEs) conferred by dapagliflozin compared with placebo. However, a lower rate of hospitalization for heart failure was reported. Whilst the lack of benefits on MACE may seem in contrast with the results of previous SGLT‐2 inhibitors cardiovascular outcome trials, DECLARE clearly delineates the real cardiovascular effects of SGLT‐2 inhibitors, which mainly tackle heart failure. Differences in study design and population enrolled are crucial to correctly value each molecule and to translate results of clinical trials in daily clinical practise.
Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair
Authors: Arbouche Nadia , Raul Jean‐Sebastien , Garnier Delphine , Kintz Pascal , Ameline Alice
Published: January 2019

Synthetic cannabinoid receptor agonists were first identified in herbal products in 2008 advertised as a legal replacement for cannabis. These herbal incense are usually called “spice” and among these, one product in particular has gained popularity: AB‐PINACA (N‐[(2S)‐1‐Amino‐3‐methyl‐1‐oxobutan‐2‐yl]‐1‐pentyl‐1H‐indazole‐3‐carboxamide). This drug has been discovered to have a stronger binding to human cannabinoid CB1 and CB2 receptors than ∆9‐THC.While some articles have been published regarding the presence of AB‐PINACA in biological fluids such as blood and urine, none reports the presence of AB‐PINACA in hair. We have developed and validated a method for detection of AB‐PINACA in hair using a liquid chromatography−tandem mass spectrometry system and applied it to head and pubic hair obtained in a case of intoxication. The validation procedure demonstrated a limit of detection and a limit of quantification of 0.5 and 1 pg/mg, respectively and acceptable linearity, repeatability, and reproducibility. AB‐PINACA tested positive in the blood (5.7 ng/mL) and less than 1 ng/mL was found in urine. The analysis of the hair specimens resulted in an unusual distribution of the drug between head and pubic hair. AB‐PINACA was identified at a higher concentration in head hair (195 pg/mg) versus in pubic hair (5 pg/mg). The very low concentration of AB‐PINACA in the urine after consumption, due to rapid metabolism, could explain this infrequent distribution, as pubic hair can be contaminated by urine. In any case, it cannot be excluded that the high concentration in head hair may be due to environmental contamination.
Mild and Practical Indole C2 Allylation by Allylboration of in situ Generated 3‐Chloroindolenines
Authors: Saya Jordy M. , van Wordragen Ellen D. H. , Orru Romano V. A. , Ruijter Eelco
Published: January 2019

C2 allylation of indole derivatives is a challenging but important transformation given the biological relevance of the products. Herein we report a selective C2 allylation strategy that proceeds via allylboration of in situ‐generated 3‐chloroindolenines. The reaction is mild, practical, and compatible with a wide range of C3‐substituted indoles. As allylboronates are readily accessible from commercial precursors, various substituted allyl moieties can be introduced using the same protocol. To showcase the utility of this method we applied it to the synthesis of the natural product, tryprostatin B.
Enantioselective Synthesis and X‐ray Structure of (+)((4aS,5S,8aS)‐5,8a‐Dimethyl‐7‐methyleneoctahydro‐2H‐spiro[naphthalene‐1,2′‐[1,3]dioxolan]‐5‐yl)methyl‐4‐iodobenzoate
Authors: Leonelli Francesca , Trombetta Andrea , La Bella Angela , Lucarelli Giulio , Demitri Nicola , Lamba Doriano , Migneco Luisa Maria , Marini Bettolo Rinaldo
Published: January 2019

The d and l amino acid mediated enantioselective intramolecular aldol reaction of 4‐((1‐methyl‐2,6‐dioxo‐cyclohexyl)methyl)‐pent‐4‐enal 1 leading, after dehydration, to (‐)‐(R) and (+)‐(S) 4a‐methyl‐3‐methylene‐5‐oxo‐2,3,4,4a,5,6,7,8‐octahydro‐naphthalene‐1‐carbaldehyde 2 was explored. It was found that (‐)‐(R) carbaldehyde 2 is enantioselectively formed in the presence of l‐amino acids while (+)‐(S) carbaldehyde 2 is enantioselectively formed in the presence of d‐amino acids. (‐)‐(R) Carbaldehyde 2 was then transformed into (+)‐22. The absolute configuration and relative stereochemistry of the latter was established by single‐crystal X‐ray diffraction analysis of p‐iodobenzoate (+)‐23.
A Carbon‐Free Li2TiO3/Li2MTi3O8 (M═Zn1/3Co2/3) Nanocomposite as High‐Rate and Long‐Life Anode for Lithium‐Ion Batteries
Authors: Yin Jiangmei , Sun Pengxiao , Yang Hongcen , Wei Yunrui , Hou Peiyu , Xu Xijin
Published: January 2019

A carbon‐free biphasic Li2TiO3/Li2MTi3O8 (M═Zn1/3Co2/3) nanocomposite has been rationally designed and successfully synthesized via co‐precipitation and solid‐state reactions, which can effectively improve the Li+ kinetics of lithium titanium oxide anodes. The biphasic intergrowth is beneficial to the size decrease of primary grains and further shortens the Li+ migration path. Cyclic voltammetry (CV) analyses confirm the enhanced Li+ diffusion coefficient as high as 4.22 × 10−11 cm2 s−1. Furthermore, the biphasic nanocomposite delivers a large reversible capacity of ≈200 mAh g−1 at a rate of 0.1 C with a low average voltage of 0.8 V (vs Li/Li+) and an outstanding cycling stability of the capacity (≈100% retention even after 500 cycles at 0.5 C). Furthermore, a superior high‐rate capability, ≈133 mAh g−1 even at a high rate of 20 C, can be achieved. The biphasic intergrowth strategy gives a new insight into developing high‐rate and durable titanium‐based anode for lithium‐ion batteries.
Trends in ecology: shifts in ecological research themes over the past four decades
Authors: McCallen Emily , Knott Jonathan , Nunez‐Mir Gabriela , Taylor Benjamin , Jo Insu , Fei Songlin
Published: January 2019

As ecology enters a critical era, more comprehensive studies are needed to improve our understanding of the key themes, major trends, and potential gaps within the discipline. However, as the number of published scientific papers continues to grow, tracking the ever‐expanding body of work becomes increasingly challenging. To identify trends in ecological research, we used recently developed machine learning techniques to perform an automated content analysis on over 84,841 articles published in 33 top‐ranked scientific journals over the past four decades. We detected a clear decline in the relative frequency of classical theoretical research, and increases in data‐intensive research at both micro‐ and macroscales and on anthropogenic themes. Scattered around the periphery of the expanding thematic space, themes such as microbial ecology, genetics, biogeochemistry, and management and policy have all increased in relative frequency. New educational and research frameworks, as well as funding priorities, should incorporate these contemporary themes so that the field of ecology can better address societal challenges.
MR‐PET head motion correction based on co‐registration of multicontrast MR images
Authors: Chen Zhaolin , Sforazzini Francesco , Baran Jakub , Close Thomas , Shah Nadim Jon , Egan Gary F.
Published: January 2019

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous magnetic resonance‐positron emission tomography (MR‐PET) makes it possible to estimate head motion information from high‐resolution MR images and then correct motion artefacts in PET images. In this article, we introduce a fully automated PET motion correction method, MR‐guided MAF, based on the co‐registration of multicontrast MR images. The performance of the MR‐guided MAF method was evaluated using MR‐PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18‐F]FDG). Compared with conventional methods, MR‐guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR‐PET scanners. The fully automated motion estimation method has been implemented as a publicly available web‐service.
Amyloid burden accelerates white matter degradation in cognitively normal elderly individuals
Authors: Vipin Ashwati , Ng Kwun Kei , Ji Fang , Shim Hee Youn , Lim Joseph K. W. , Pasternak Ofer , Zhou Juan Helen ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: January 2019

Alterations in parietal and temporal white matter microstructure derived from diffusion tensor imaging occur in preclinical and clinical Alzheimer's disease. Amyloid beta (Aβ) deposition and such white matter alterations are two pathological hallmarks of Alzheimer's disease. However, the relationship between these pathologies is not yet understood, partly since conventional diffusion MRI methods cannot distinguish between cellular and extracellular processes. Thus, we studied Aβ‐associated longitudinal diffusion MRI changes in Aβ‐positive (N = 21) and Aβ‐negative (N = 51) cognitively normal elderly obtained from the Alzheimer's Disease Neuroimaging Initiative dataset using linear mixed models. Aβ‐positivity was based on Alzheimer's Disease Neuroimaging Initiative amyloid‐PET recommendations using a standardized uptake value ratio cut‐off of 1.11. We used free‐water imaging to distinguish cellular and extracellular changes. We found that Aβ‐positive subjects had increased baseline right uncinate fasciculus free‐water fraction (FW), associated with worse baseline Alzheimer's disease assessment scale scores. Furthermore, Aβ‐positive subjects showed faster decrease in fractional anisotropy (FW‐corrected) in the right uncinate fasciculus and faster age‐dependent right inferior longitudinal fasciculus FW increases over time. Right inferior longitudinal fasciculus FW increases were associated with greater memory decline. Importantly, these results remained significant after controlling for gray and white matter volume and hippocampal volume. This is the first study to illustrate the influence of Aβ burden on early longitudinal (in addition to baseline) white matter changes in cognitively normal elderly individuals at‐risk of Alzheimer's disease, thus underscoring the importance of longitudinal studies in assessing microstructural alterations in individuals at risk of Alzheimer's disease prior to symptoms onset.