bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurotensin‐Conjugated Reduced Graphene Oxide with Multi‐Stage Near‐Infrared‐Triggered Synergic Targeted Neuron Gene Transfection In Vitro and In Vivo for Neurodegenerative Disease Therapy
Authors: Hsieh Tsung‐Ying , Huang Wei‐Chen , Kang Yi‐Da , Chu Chao‐Yi , Liao Wen‐Lin , Chen You‐Yin , Chen San‐Yuan
Published: November 2016

Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro‐specific peptide)‐conjugated polyethylenimine (PEI)‐modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two‐stage near‐infrared (NIR)‐laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First‐stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second‐stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO‐PEI‐NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC‐12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi‐stage stimuli‐responsive NIR laser treatment. The combination of neuro‐specific targeting peptide and external NIR‐laser‐triggered aid provides a nanoplatform for gene therapy in CNS diseases.
Culture on 3D Chitosan‐Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells
Authors: Wang Kui , Kievit Forrest M. , Erickson Ariane E. , Silber John R. , Ellenbogen Richard G. , Zhang Miqin
Published: November 2016

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient‐derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self‐adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial–mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold‐grown cells also display higher expression of genes that promote resistance to hypoxia‐induced oxidative stress. In accord, scaffold‐grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments.
Production of Hollow Bacterial Cellulose Microspheres Using Microfluidics to Form an Injectable Porous Scaffold for Wound Healing
Authors: Yu Jiaqing , Huang Tzu‐Rung , Lim Zhen Han , Luo Rongcong , Pasula Rupali Reddy , Liao Lun‐De , Lim Sierin , Chen Chia‐Hung
Published: November 2016

Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core–shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long‐term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal‐chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound‐healing in a Sprague Dawley rat skin model.
Molecular Force Sensors: From Fundamental Concepts toward Applications in Cell Biology
Authors: Goktas Melis , Blank Kerstin G.
Published: November 2016

Mechanical signals are central for the regulation of developmental, physiological, and pathological processes within biological systems. Force transduction across the cell–extracellular matrix (ECM) interface is highly crucial for regulating cell fate via mechanosensing and mechanotransduction cascades. The key molecules involved in these highly sophisticated processes have been identified in recent years. But little is still known about their interactions and in particular the molecular forces that determine these interactions. This is due to the limited availability of techniques that allow for investigating force propagation and mechanobiochemical signal conversion at the molecular level in live cells. In this progress report, currently available tools for measuring the molecular forces involved in cellular mechanosensing and mechanotransduction are summarized, specifically highlighting recent advances in the development of molecular force sensors (MFSs). MFSs convert the applied force into a fluorescence signal, allowing for a direct readout of tension with optical microscopy techniques. Moving from molecular design principles to applications of MFSs, important results are summarized, highlighting the new mechanistic information that has been obtained about mechanobiochemical processes at the cell–ECM interface. This progress report finishes with a critical discussion of current promises and limitations, providing perspectives for future research in this quickly evolving field.
Coral‐Like MoS2/Cu2O Porous Nanohybrid with Dual‐Electrocatalyst Performances
Authors: Zhao Xinne , Li Yang , Guo Yuqi , Chen Yajing , Su Zhiqiang , Zhang Panpan
Published: November 2016

A facile one‐step hydrothermal synthesis strategy is utilized for the preparation of 3D coral‐like structural MoS2/Cu2O porous nanohybrid which is applied as bifunctional material for biosensor and oxygen reduction reaction (ORR) applications. Due to the combination of p‐type Cu2O nanoparticles and n‐type MoS2 nanosheets, MoS2/Cu2O nanohybrid exhibits great potential in both biosensor and electrochemical catalyst. In addition, the special 3D coral‐like porous structure endows MoS2/Cu2O nanohybrid a large specific surface area which enhances its electrocatalyst performance significantly. The experimental results indicate that the hydrogen peroxide (H2O2) biosensor fabricated by MoS2/Cu2O nanohybrid shows a wide linear range, low limitation of detection, high selectivity, and long‐term stability. At the same time, the coral‐like structural MoS2/Cu2O nanohybrid also displays excellent ORR electrochemical catalysis performance. It can be anticipated that the strategies utilized in this work will not only guide the functional design of novel nanohybrid materials but also extend their potential applications in energy storage, waste water purification, and environmental engineering.
Chemically Bonded Sn Nanoparticles Using the Crosslinked Epoxy Binder for High Energy‐Density Li Ion Battery
Authors: Wang Yun‐Xiao , Xu Yanfei , Meng Qingshi , Chou Shu‐Lei , Ma Jun , Kang Yong‐Mook , Liu Hua‐Kun
Published: November 2016

An excellent integrated anode (Sn‐AB) is constructed by using epoxy (A)‐amine (B) glue binding with ultrafine Sn nanoparticles. The electrode with strong adhesion and tensile strength can effectively tolerate the large volume changes of Sn, thereby guaranteeing excellent Li‐storage properties. The development of AB binder, therefore, provides a novel and potential tactics for enhancement of electrode integration and mechanical strength.
Electrospun TiO2–rGO Composite Nanofibers with Ordered Mesopores by Molecular Level Assembly: A High Performance Anode Material for Lithium‐Ion Batteries
Authors: Chattopadhyay Shreyasi , Maiti Sandipan , Das Indranee , Mahanty Sourindra , De Goutam
Published: November 2016

The authors report a novel strategy to fabricate electrospun anatase TiO2–rGO composite nanofibers with 3D cubic ordered mesoporosity. Such synthesis route not only ensures molecular level composite formation between rGO and TiO2 but also retains the rGO content and orders mesostructure after calcination of the nascent fiber at an optimum condition that only removes the surfactant and polymer. Transmission electron microscopic and low angle X‐ray diffraction studies confirm the presence of ordered mesoporosity within the nanofibers. Raman and X‐ray photoelectron spectroscopy studies reveal the molecular level composite formation between rGO and TiO2 with chemical bonding. This composite nanofiber with high surface area (155 m2 g–1) is tested as an anode material in lithium‐ion batteries. Intrinsically formed TiO2–rGO composite structural features with channel like interconnected 3D order mesopores within 1D fibrous morphology help in achieving 94% of the theoretical capacity (335 mAh g–1 for one electron transfer) at a current density of 16.75 mA g–1, the highest reported so far. It shows specific capacity of 212 and 168 mAh g–1 even at moderately high current densities of 335 and 838 mA g–1, respectively. Moreover, 85.3% of capacity retains after 500 continuous discharge/charge cycles at 335 mA g–1.
Understanding the Assembly of an Artificial Protein Nanotube
Authors: Nagano Soshichiro , Banwell Eleanor F. , Iwasaki Kenji , Michalak Maciej , Pałka Renata , Zhang Kam Y. J. , Voet Arnout R. D. , Heddle Jonathan G.
Published: November 2016

TRAP (trp RNA‐binding attenuation protein) is a stable, ring‐shaped protein that has proven useful in the development of artificial, self‐assembled biological structures including a protein nanotube that assembles from a cysteine‐containing mutant. While the structure of the nanotube is known in some detail, the nature of the interactions that connect the protein rings together to form tubes is not known. Here, evidence is presented that the two faces of the ring bind together using mixed interactions: On one face cysteine side chains are linked to the same face of a corresponding ring via a dithio linker molecule while the other face does not require covalent interactions and can assemble using protein–protein interactions alone. A coherent 3D model is constructed to explain the observed results, which are ultimately due to specific structural features that modulate the types of bonding that can occur. This detailed understanding offers the prospect of engineering the TRAP nanotube to endow it with bespoke properties.
The Application of Metal Sulfides in Sodium Ion Batteries
Authors: Xiao Ying , Lee Seon Hwa , Sun Yang‐Kook
Published: November 2016

The high demand for clean and renewable energy has fueled the exploration of advanced energy storage systems. As a potential alternative device for lithium ion batteries, sodium ion batteries (NIBs) have attracted extraordinary attention and are becoming a promising candidate for energy storage due to their low cost and high efficiency. Recent progress has demonstrated that metal sulfides (MSs) are very promising electrode candidates for efficient Na‐storage devices, because of their excellent redox reversibility and relatively high capacity. In this review, recent developments of MSs as anode materials for NIBs are presented. The corresponding electrochemical mechanisms are briefly discussed. We also present critical issues, challenges, and perspectives with the hope of providing a fuller understanding of the associated electrochemical processes. Such an understanding is critical for tailoring and designing metal sulfides with the desired activity and stability.
Organocatalytic, Enantioselective Synthesis of Cyclohexadienone Containing Hindered Spirocyclic Ethers through an Oxidative Dearomatization/Oxa‐Michael Addition Sequence
Authors: Reddy Reddy Rajasekhar , Gudup Satish Sonbarao , Ghorai Prasanta
Published: November 2016

An unprecedented enantioselective oxa‐Michael reaction of α‐tertiary alcohols using cinchona‐alkaloid‐based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa‐Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo‐cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity.
Hollow Chevrel‐Phase NiMo3S4 for Hydrogen Evolution in Alkaline Electrolytes
Authors: Jiang Jun , Gao Minrui , Sheng Wenchao , Yan Yushan
Published: November 2016

Electrochemical water splitting to generate molecular hydrogen requires catalysts that are cheap, active, and stable, particularly for alkaline electrolyzers, where the cathodic hydrogen evolution reaction is slower in base than in acid even on platinum. Herein, we describe the synthesis of new hollow Chevrel‐phase NiMo3S4 and its alkaline hydrogen evolution reaction (HER) performance: onset potential of −59 mV, Tafel slope of 98 mV per decade, and exchange current density of 3.9×10−2 mA cm−2. This Chevrel‐phase chalcogenide also demonstrates outstanding long‐term stability under harsh HER cycling conditions. Chevrel‐phase nanomaterials show promise as efficient, low‐cost catalysts for alkaline electrolyzers.
carbo‐Naphthalene: A Polycyclic carbo‐Benzenoid Fragment of α‐Graphyne
Authors: Cocq Kévin , Saffon‐Merceron Nathalie , Coppel Yannick , Poidevin Corentin , Maraval Valérie , Chauvin Remi
Published: November 2016

A ring carbo‐mer of naphthalene, C32Ar8 (Ar=p‐n‐pentylphenyl), has been obtained as a stable blue chromophore, after a 19‐step synthetic route involving methods inspired from those used in the synthesis of carbo‐benzenes, or specifically devised for the present target, like a double Sonogashira‐type coupling reaction. The last step is a SnCl2/HCl‐mediated reduction of a decaoxy‐carbo‐decalin, which is prepared through successive [8+10] macrocyclization steps. Two carbo‐benzene references are also described, C18Ar6 and o‐C18Ar4(C≡C‐SiiPr3)2. The carbo‐naphthalene bicycle is locally aromatic according to structural and magnetic criteria, as revealed by strong diatropic ring current effects on the deshielding of 1H nuclei of the Ar groups and on the negative value of the DFT‐calculated NICS at the center of the C18 rings (−12.8 ppm). The stability and aromaticity of this smallest fused molecular fragment of α‐graphyne allows prediction of the same properties for the carbon allotrope itself.
Excited Fluorophores Enhance the Opening of Vesicles at Electrode Surfaces in Vesicle Electrochemical Cytometry
Authors: Najafinobar Neda , Lovrić Jelena , Majdi Soodabeh , Dunevall Johan , Cans Ann‐Sofie , Ewing Andrew
Published: November 2016

Electrochemical cytometry is a method developed recently to determine the content of an individual cell vesicle. The mechanism of vesicle rupture at the electrode surface involves the formation of a pore at the interface between a vesicle and the electrode through electroporation, which leads to the release and oxidation of the vesicle's chemical cargo. We have manipulated the membrane properties using excited fluorophores conjugated to lipids, which appears to make the membrane more susceptible to electroporation. We propose that by having excited fluorophores in close contact with the membrane, membrane lipids (and perhaps proteins) are oxidized upon production of reactive oxygen species, which then leads to changes in membrane properties and the formation of water defects. This is supported by experiments in which the fluorophores were placed on the lipid tail instead of the headgroup, which leads to a more rapid onset of vesicle opening. Additionally, application of DMSO to the vesicles, which increases the membrane area per lipid, and decreasing the membrane thickness result in the same enhancement in vesicle opening, which confirms the mechanism of vesicle opening with excited fluorophores in the membrane. Light‐induced manipulation of membrane vesicle pore opening might be an attractive means of controlling cell activity and exocytosis. Additionally, our data confirm that in experiments in which cells or vesicle membranes are labeled for fluorescence monitoring, the properties of the excited membrane change substantially.
A Bis(silylenyl)pyridine Zero‐Valent Germanium Complex and Its Remarkable Reactivity
Authors: Zhou Yu‐Peng , Karni Miriam , Yao Shenglai , Apeloig Yitzhak , Driess Matthias
Published: November 2016

The synthesis, reactivity, and electronic structure of the unique germylone iron carbonyl complex [SiNSi]Ge0→Fe(CO)4 is reported. The compound was obtained in 49 % yield from the reaction of the bis(N‐heterocyclic silylenyl)pyridine pincer ligand SiNSi (1,6‐C5NH3‐[EtNSi(NtBu)2CPh]2) with GeCl2⋅(dioxane) to give the corresponding chlorogermyliumylidene chloride precursor [SiNSi]GeIICl+ Cl−, which was further reduced with K2Fe(CO)4. Single‐crystal X‐ray diffraction analysis of [SiNSi]Ge→Fe(CO)4 revealed that the Ge0 center adopts a trigonal‐pyramidal geometry with a Si‐Ge‐Si angle of 95.66(2)°. Remarkably, one of the SiII donor atoms in the complex is five‐coordinated because of additional (pyridine)N→Si coordination. Unexpectedly, the reaction of [SiNSi]Ge→Fe(CO)4 with GeCl2⋅(dioxane) (one molar equivalent) yielded the first push–pull germylone–germylene donor–acceptor complex, [SiNSi]Ge→GeCl2→Fe(CO)4 through the insertion of GeCl2 into the dative Ge0→Fe bond. The electronic features of the new compounds were investigated by DFT calculations.
A Nernstian Biosupercapacitor
Authors: Pankratov Dmitry , Conzuelo Felipe , Pinyou Piyanut , Alsaoub Sabine , Schuhmann Wolfgang , Shleev Sergey
Published: November 2016

We propose the very first “Nernstian biosupercapacitor”, a biodevice based on only one redox polymer: poly(vinyl imidazole‐co‐allylamine)[Os(bpy)2Cl], and two biocatalysts. At the bioanode PQQ‐dependent glucose dehydrogenase reduces the Os3+ moieties at the polymer to Os2+ shifting the Nernst potential of the Os3+/Os2+ redox couple to negative values. Concomitantly, at the biocathode the reduction of O2 by means of bilirubin oxidase embedded in the same redox polymer leads to the oxidation of Os2+ to Os3+ shifting the Nernst potential to higher values. Despite the use of just one redox polymer an open circuit voltage of more than 0.45 V was obtained during charging and the charge is stored in the redox polymer at both the bioanode and the biocathode. By connecting both electrodes via a predefined resistor a high power density is obtained for a short time exceeding the steady state power of a corresponding biofuel cell by a factor of 8.
Polystyrene Sulfonate Threaded through a Metal–Organic Framework Membrane for Fast and Selective Lithium‐Ion Separation
Authors: Guo Yi , Ying Yulong , Mao Yiyin , Peng Xinsheng , Chen Banglin
Published: November 2016

Extraction of lithium ions from salt‐lake brines is very important to produce lithium compounds. Herein, we report a new approach to construct polystyrene sulfonate (PSS) threaded HKUST‐1 metal–organic framework (MOF) membranes through an in situ confinement conversion process. The resulting membrane PSS@HKUST‐1‐6.7, with unique anchored three‐dimensional sulfonate networks, shows a very high Li+ conductivity of 5.53×10−4 S cm−1 at 25 °C, 1.89×10−3 S cm−1 at 70 °C, and Li+ flux of 6.75 mol m−2 h−1, which are five orders higher than that of the pristine HKUST‐1 membrane. Attributed to the different size sieving effects and the affinity differences of the Li+, Na+, K+, and Mg2+ ions to the sulfonate groups, the PSS@HKUST‐1‐6.7 membrane exhibits ideal selectivities of 78, 99, and 10296 for Li+/Na+, Li+/K+, Li+/Mg2+ and real binary ion selectivities of 35, 67, and 1815, respectively, the highest ever reported among ionic conductors and Li+ extraction membranes.
Contrasting Magnetic Behaviors in Rhodium‐ and Ruthenium‐Doped Cubic Perovskite SrFeO3: Nearly Ferromagnetic Metal versus Spin‐Glass Insulator
Authors: Kinoshita Masataka , Sakai Hideaki , Hayashi Naoaki , Tokura Yoshinori , Takano Mikio , Ishiwata Shintaro
Published: November 2016

The effects of Rh and Ru doping for SrFeO3, a helimagnetic metal with a cubic perovskite structure, are studied by magnetic and resistivity measurements. Although SrRhO3 is a paramagnetic metal and SrRuO3 is a ferromagnetic one, the Rh doping induces a nearly ferromagnetic metallic state, whereas the Ru doping induces a spin‐glass insulating state. Mössbauer measurements evidence a marked difference between SrFe0.8Rh0.2O3 and SrFe0.8Ru0.2O3 in the formal valences of Fe, which are estimated to be 4+ and 3.75+, respectively. The contrasting magnetic behaviors of Rh‐ and Ru‐doped SrFeO3 are discussed in terms of the subtle balance between the double‐exchange ferromagnetism and the superexchange antiferromagnetism.
Debugging Eukaryotic Genetic Code Expansion for Site‐Specific Click‐PAINT Super‐Resolution Microscopy
Authors: Nikić Ivana , Estrada Girona Gemma , Kang Jun Hee , Paci Giulia , Mikhaleva Sofya , Koehler Christine , Shymanska Nataliia V. , Ventura Santos Camilla , Spitz Daniel , Lemke Edward A.
Published: November 2016

Super‐resolution microscopy (SRM) greatly benefits from the ability to install small photostable fluorescent labels into proteins. Genetic code expansion (GCE) technology addresses this demand, allowing the introduction of small labeling sites, in the form of uniquely reactive noncanonical amino acids (ncAAs), at any residue in a target protein. However, low incorporation efficiency of ncAAs and high background fluorescence limit its current SRM applications. Redirecting the subcellular localization of the pyrrolysine‐based GCE system for click chemistry, combined with DNA‐PAINT microscopy, enables the visualization of even low‐abundance proteins inside mammalian cells. This approach links a versatile, biocompatible, and potentially unbleachable labeling method with residue‐specific precision. Moreover, our reengineered GCE system eliminates untargeted background fluorescence and substantially boosts the expression yield, which is of general interest for enhanced protein engineering in eukaryotes using GCE.
Indenylmetal Catalysis in Organic Synthesis
Authors: Trost Barry M. , Ryan Michael C.
Published: November 2016

Synthetic organic chemists have a long‐standing appreciation for transition metal cyclopentadienyl complexes, of which many have been used as catalysts for organic transformations. Much less well known are the contributions of the benzo‐fused relative of the cyclopentadienyl ligand, the indenyl ligand, whose unique properties have in many cases imparted differential reactivity in catalytic processes toward the synthesis of small molecules. In this Review, we present examples of indenylmetal complexes in catalysis and compare their reactivity to their cyclopentadienyl analogues, wherever possible.
Spectroscopic andin silicostudy of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin
Authors: Gao Xin , Bi Hongna , Jia Jingjing , Tang Lin
Published: November 2016

The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding propertiesin vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes.
Dendrimeric Guanidinoneomycin for Cellular Delivery of Bio‐macromolecules
Authors: Sganappa Aurora , Wexselblatt Ezequiel , Bellucci Maria Cristina , Esko Jeffrey D. , Tedeschi Gabriella , Tor Yitzhak , Volonterio Alessandro
Published: November 2016

We present the synthesis of polymeric amino‐ and guanidinoglycosides prepared by tethering neomycin and guanidinoneomycin to PAMAM dendrimers of generations 2 and 4. The ability of these conjugates to promote cellular uptake of high‐molecular‐weight cargo is discussed, together with their cytotoxicity and mechanisms of entry. We demonstrate that the presence of multiple guanidinoneomycin carriers on the PAMAM surface plays an important role in promoting cellular uptake of the dendrimers, maintaining the heparan sulfate specificity and negligible cytotoxicity typical of monomeric guanidinoglycoside molecular transporters.
Activation of Chlorinated Methanes at the Surface of Nanoscopic Lewis Acidic Aluminum Fluorides
Authors: Siwek Agnieszka K. , Ahrens Mike , Feist Michael , Braun Thomas , Kemnitz Erhard
Published: November 2016

We report on the activation of chlorinated methanes by the heterogeneous catalysts aluminum chlorofluoride (ACF) and high‐surface aluminum fluoride (HS‐AlF3) under moderate conditions. For comparison, chlorinated toluenes and 1,2‐dichloroethane were also tested. The strong Lewis acids are able to promote the cleavage of C−Cl bonds in the presence of Et3SiH. The C−Cl bonds were converted into C−H bonds through hydrodechlorination reactions or, in the presence of benzene, into C−C bonds through Friedel–Crafts type reactions. The catalytic reactions show high conversions.
Defect Engineering, Electronic Structure, and Catalytic Properties of Perovskite Oxide La0.5Sr0.5CoO3−δ
Authors: Wang Xiyang , Huang Keke , Ma Wei , Cong Yingge , Ge Chengda , Feng Shouhua
Published: November 2016

The electronic structures of transition metal oxides play a crucial role in the physical and chemical properties of solid materials. Defect engineering is an efficient way to regulate the electronic structure and improve the performance of materials. Here, we develop a defect engineering route that is implemented by controlling the topochemical reactions between cobalt perovskite and urea to optimize the electronic structure of La0.5Sr0.5CoO3−δ (LSCO). Urea pyrolysis is able to increase the oxygen defect concentration and cause octahedral distortions. Furthermore, we can distinctly observe that the introduction of oxygen vacancies narrows the hybridization orbital between O 2p and Co 3d and optimizes the O p‐band center near the Fermi level by X‐ray absorption spectroscopy, which greatly improves the catalytic activity of CO oxidation and photocatalytic water splitting. These results highlight the relationship between oxygen defects, electronic structure, and catalytic activity of perovskite LSCO, and demonstrate a rational approach to defect design and reveal the importance of anion redox chemistry for the structures and properties of perovskite oxides.
Copper‐Catalyzed Remote para‐C−H Functionalization of Anilines with Sodium and Lithium Sulfinates
Authors: Liang Shuai , Bolte Michael , Manolikakes Georg
Published: November 2016

A copper‐catalyzed, cross‐dehydrogenative coupling of anilines with sodium and lithium sulfinates was developed. By using a cooperative reaction system with Mn(OAc)3 as stoichiometric co‐oxidant a highly selective para‐functionalization of anilines was accomplished. Various functional groups were tolerated and the desired products were obtained in high yields. This method not only provides a novel approach for the synthesis of arylsulfones but might also offer new opportunities for the development of copper‐catalyzed para‐selective C−H functionalizations.
Exercise test predictors of severe coronary artery disease: Role of ST‐segment elevation in lead aVR
Authors: Russo Giulio , Ravenna Salvatore Emanuele , De Vita Antonio , Aurigemma Cristina , Lamendola Priscilla , Lanza Gaetano Antonio , Crea Filippo
Published: November 2016

Background

The role of exercise stress test (EST)‐induced ST‐segment elevation (STE) in electrocardiographic lead aVR in predicting severe coronary artery disease (CAD) is controversial.

Hypothesis

Assessment of lead aVR during EST can be helpful to identify patients with severe CAD.

Methods

We performed maximal EST in 200 patients undergoing coronary angiography for suspect of CAD. Four angiographic findings of severe CAD were considered: (1) left main (LM) disease; (2) LM or equivalent LM (LM/EQLM) disease; (3) LM or proximal left anterior descending (LAD) artery (LM/proxLAD) disease; and (4) LM or 3‐vessel (LM/3V) disease.

Results

LM, LM/EQLM, LM/proxLAD, and LM/3V disease were shown in 6 (3%), 13 (6.5%), 33 (16.5%), and 27 (13.5%) patients, respectively. EST‐induced STE in aVR occurred in 41 patients (20.5%). ST‐segment depression (STD) in ≥5 leads was the only predictor of LM stenosis (odds ratio [OR]: 6.18, 95% confidence interval [CI]: 1.19‐32.2, P = 0.03) and the most significant variable associated with LM/proxLAD stenosis (OR: 4.73, 95% CI: 2.0‐11.2, P = 0.0001); maximal STD ≥3 mm was the most significant variable associated with LM/EQLM (OR: 7.58, 95% CI: 2.31‐24.9, P = 0.001) and LM/3V (OR: 3.86, 95% CI: 1.47‐10.1, P = 0.006) CAD. EST‐induced STE in aVR was associated with LM/proxLAD disease only (OR: 3.23, 95% CI: 1.44‐7.24, P = 0.004). At multivariate analysis, STD in ≥5 leads was the only independent predictor of LM/proxLAD disease (OR: 3.99, 95% CI: 1.58‐10.1, P = 0.003).

Conclusions

EST‐induced STE in lead aVR does not significantly increase the prediction of severe CAD compared with severity and extension of STD as assessed in the other electrocardiographic leads.
Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis
Authors: Somnay Yash R. , Yu Xiao‐Min , Lloyd Ricardo V. , Leverson Glen , Aburjania Zviadi , Jang Samuel , Jaskula‐Sztul Renata , Chen Herbert
Published: November 2016

BACKGROUND

Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1‐4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact.

METHODS

Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients. The functional role of Notch3 was then investigated by upregulating its expression in a follicular thyroid cancer (FTC) cell line.

RESULTS

Notch3 expression regressed across decreasingly differentiated, increasingly malignant thyroid specimens, correlated with clinicopathological attributes reflecting poor prognosis, and independently predicted survival following univariate and multivariate analyses. Overexpression of the active Notch3 intracellular domain (NICD3) in a gain‐of‐function FTC line led to functional activation of centromere‐binding protein 1, while increasing thyroid‐specific gene transcription. NICD3 induction also reduced tumor burden in vivo and initiated the intrinsic apoptotic cascade, alongside suppressing cyclin and B‐cell lymphoma 2 family expression.

CONCLUSIONS

Loss of Notch3 expression may be fundamental to the process of dedifferentiation that accompanies thyroid oncogenesis. Conversely, activation of Notch3 in thyroid cancer exerts an antiproliferative effect and restores elements of a differentiated phenotype. These findings provide preclinical rationale for evaluating Notch3 as a disease prognosticator and therapeutic target in advanced thyroid cancer. Cancer 2017;123:769–82. © 2016 American Cancer Society.
Assessment of the treatment approach and survival outcomes in a modern cohort of patients with atypical teratoid rhabdoid tumors using the National Cancer Database
Authors: Fischer‐Valuck Benjamin W. , Chen Ishita , Srivastava Amar J. , Floberg John M. , Rao Yuan James , King Allison A. , Shinohara Eric T. , Perkins Stephanie M.
Published: November 2016

BACKGROUND

Atypical teratoid rhabdoid tumors (ATRTs) are rare brain tumors that occur primarily in children under the age of 3 years. This report evaluates the treatment approach and survival outcomes in a large cohort of patients treated in the United States.

METHODS

Using the National Cancer Database, the analysis included all ATRT patients aged 0 to 18 years who were diagnosed between 2004 and 2012 and had complete treatment data.

RESULTS

Three hundred sixty‐one ATRT patients were evaluated. The 5‐year overall survival (OS) rate was 29.9%, and it was significantly lower for children who were less than 3 years old (5‐year OS, 27.7%) versus those who were 3 years old or older (5‐year OS, 37.5%; P < .001). The best outcome was seen for patients with localized disease who received trimodality therapy (surgery, chemotherapy, and radiation therapy [RT]) with a 5‐year OS rate of 46.8%. The utilization of trimodality therapy significantly increased during the study period (27.7% in 2004‐2008 vs 45.1% in 2009‐2012; P < .01), largely because of the increased use of RT. In a multivariate analysis, treatment that did not utilize trimodality therapy was associated with significantly worse OS (hazard ratio, 2.52; 95% confidence interval (1.82–3.51). Children aged 0 to 2 years were significantly less likely to receive trimodality therapy because of decreased utilization of RT in this age group.

CONCLUSIONS

The use of trimodality therapy significantly increased during the study period and was associated with improved outcomes. For patients with localized disease who received trimodality therapy, the OS rate at 5 years approached 50%. However, further research into the optimal management of children less than 3 years old is needed because of their significantly worse OS in comparison with older children. Cancer 2017;123:682–687. © 2016 American Cancer Society.
A Computational Investigation of the Equilibrium Constants for the Fluorescent and Chemiluminescent States of Coelenteramide
Authors: Min Chun‐Gang , Pinto da Silva Luís , Esteves da Silva Joaquim C. G. , Yang Xi‐Kun , Huang Shao‐Jun , Ren Ai‐Min , Zhu Yan‐Qin
Published: November 2016

In spite of recent advances in understanding the mechanism of coelenterate bioluminescence, there is no consensus about which coelenteramide specie and/or state are the light emitter. In this study, a systematic investigation of the geometries and spectra of all possible light emitters has been performed at the TD ωB97XD/6‐31+G(d) level of theory, including various fluorescent and chemiluminescent states in vacuum, in a hydrophobic environment and in aqueous solution. To deduce the most probable form of the fluorescent and chemiluminescent coelenteramide emitter, the equilibrium constants for the fluorescent and chemiluminescent states connecting the various species have been calculated. ωB97XD gives a qualitatively good description of fluorescent and chemiluminescent structures. Coelenteramide is formed in a “dark” chemiluminescent state and must evolve to a bright fluorescent state. Moreover, the photoacidity of the phenol group is significantly higher in the fluorescent state than in the chemiluminescent state, which allows the formation of phenolate coelenteramide and clarifies its role as the bioluminescent emitter.
Tailored Fabrication of Transferable and Hollow Weblike Titanium Dioxide Structures
Authors: Hiltunen Arto , Lahtonen Kimmo , Saari Jesse , Ojanperä Anniina , Sarlin Essi , Wondraczek Holger , Efimov Alexander , Kaunisto Kimmo , Vivo Paola , Maccato Chiara , Barreca Davide , Fardim Pedro , Tkachenko Nikolai , Valden Mika , Lemmetyinen Helge
Published: November 2016

The preparation of weblike titanium dioxide thin films by atomic layer deposition on cellulose biotemplates is reported. The method produces a TiO2 web, which is flexible and transferable from the deposition substrate to that of the end application. Removal of the cellulose template by calcination converts the amorphous titania to crystalline anatase and gives the structure a hollow morphology. The TiO2 webs are thoroughly characterized using electron microscopy, X‐ray diffraction, and X‐ray photoelectron spectroscopy to give new insight into manufacturing of porous titanium dioxide structures by means of template‐based methods. Functionality and integrity of the TiO2 hollow weblike thin films were successfully confirmed by applying them as electrodes in dye‐sensitized solar cells.
Complete Conversion of PbI2 to Methyl Ammonium PbI3 Improves Perovskite Solar Cell Efficiency
Authors: Wang Lili , Lin Wei‐Chun , McCleese Christopher , Kovalsky Anton , Zhao Yixin , Burda Clemens
Published: November 2016

One major disadvantage to the two‐step deposition method of perovskite films is the incomplete conversion from PbI2 to perovskite resulting in the presence of a thick PbI2 layer, which hinders charge carrier transportation. In this study, a quaternary ammonium salt has been used to manipulate the crystallization of PbI2 in the first deposition step, which leads to facile incorporation of the methylammonium iodide into the Pb‐I lattice and promotes the conversion of PbI2 to perovskite leading to improved device performance.
Catalytic Macroporous Biohydrogels Made of Ferritin‐Encapsulated Gold Nanoparticles
Authors: Kumari Sushma , Häring Marleen , Gupta Sayam Sen , Díaz Díaz David
Published: November 2016

Reported is a modular approach for the incorporation and stabilization of gold nanoparticles inside a three‐dimensional macroporous hydrogel made of ferritin. The strategy, which involves the dynamic templating of surfactant H1 domains, demineralization, and remineralization helps to overcome aggregation and degradation issues usually associated with bare‐metal‐based nanocatalysts. The catalytic activity of the so‐synthesized bionanocomposite hydrogel was demonstrated in both nitroaldol (Henry) and nitroreduction model reactions in aqueous solution at room temperature. An interesting synergistic effect between basic residues of the protein and the gold nanoparticles was found in the nitroaldol reaction when carried out in water in the presence of a phase‐transfer catalyst. Furthermore, the reduction of 4‐nitrophenol and 4‐nitroaniline catalyzed by the nanocomposite scaffold in the presence of NaBH4 proceeded significantly faster than that using other known Au‐ and Ag‐based catalysts under similar conditions.
The Conflict Family: Storytelling as an Activity and a Method for Locally Led, Community‐Based Peacebuilding
Authors: Linabary Jasmine R. , Krishna Arunima , Connaughton Stacey L.
Published: November 2016

Researchers and practitioners are beginning to look to community‐based participatory research (CBPR) approaches in their efforts to address social problems with those directly affected by them. Yet additional methods and tools are needed. In this article, we propose storytelling as a participatory method in the context of peacebuilding. Drawing on the Conflict Family, an example of cultural storytelling from a locally led peacebuilding initiative in Ghana, we illustrate the ways in which storytelling emerged as a co‐constructed, culturally relevant, collaborative, reflexive, and memorable participatory strategy that functioned as a catalyst for action. Storytelling helped create a dialogic space for participants to discuss land disputes in their communities. This study contributes to what is known about storytelling by showcasing how cultural storytelling can promote local citizens’ ownership for CBPR approaches. It also reveals the ways storytelling can serve as a CBPR method that encourages a relational orientation and the co‐construction of meaning, as well as inspire transformation among local citizens, particularly in conflict situations and peacebuilding contexts.
1,1′‐Bis(pyrazol‐4‐yl)ferrocenes: Potential Clip Ligands and Their Supramolecular Structures
Authors: Veronelli Mattia , Dechert Sebastian , Schober Anne , Demeshko Serhiy , Meyer Franc
Published: November 2016

Two ferrocene derivatives with pyrazoles appended at their C‐4 position to both cyclopentadienyl (Cp) rings have been synthesized, namely, 1,1′‐bis(1H‐pyrazol‐4‐yl)ferrocene (H2HL) and 1,1′‐bis(3,5‐dimethyl‐1H‐pyrazol‐4‐yl)ferrocene (H2MeL). In the solid state, these are shown crystallographically to form supramolecular aggregates through intermolecular NH···N hydrogen bonds in either a dimeric (H2HL) or trimeric (H2MeL) arrangement. Variable‐temperature NMR spectroscopy and diffusion‐ordered spectroscopy (DOSY) evidenced the presence of [H2MeL]3 trimers in [D8]toluene solution, whereas both H2HL and H2MeL exist as monomers in deuterated N,N‐dimethylformamide ([D7]DMF) even at low temperatures. The kinetic parameters for the NH tautomerism have been determined. In their dianionic forms, both of these hybrid ferrocene/pyrazole molecules serve as ligands towards CuI, AgI, and AuI ions. Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS) revealed the formation of [M2RL]3 hexametallic complexes, the structures of which are suggested to have D3h symmetry with two metallomacrocyclic [M(µ‐pz)]3 (pz = pyrazolate) decks connected by three ferrocene clips. Mössbauer spectra and preliminary luminescence data were collected for the proligands and the resulting complexes. Owing to the insolubility of the coinage‐metal complexes, the electrochemical properties could be measured only for the two H2RL proligands.
Arene–Ruthenium(II) Complexes with Bioactive ortho‐Hydroxydibenzoylmethane Ligands: Synthesis, Structure, and Cytotoxicity
Authors: Pettinari Riccardo , Petrini Agnese , Marchetti Fabio , Pettinari Claudio , Riedel Tina , Therrien Bruno , Dyson Paul J.
Published: November 2016

The synthesis of a series of neutral arene–ruthenium(II) complexes (arene = p‐cymene, hexamethylbenzene, and benzene) [(arene)Ru(HDB)Cl] derived from the reaction of the appropriate arene–ruthenium(II) dimers and ortho‐hydroxydibenzoylmethane (HDBH), a potent inhibitor of cell proliferation, is described. In addition, related ionic complexes [(arene)Ru(HDB)(PTA)](SO3CF3) (PTA = 1,3,5‐triaza‐7‐phosphaadamantane) have been prepared. The structure of three complexes has been confirmed by X‐ray crystallography. The cytotoxicity of the complexes has been evaluated against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against nontumorigenic human embryonic kidney (HEK293) cells, and compared to the free ligand and cisplatin. Two of the complexes, that is from the first series with p‐cymene and hexamethylbenzene, display relevant activities against the cisplatin‐resistant A2780cisR cancer cell line.
Discrimination of Octahedral versus Trigonal Bipyramidal Coordination Geometries of Homogeneous TiIV, VV, and MoVI Amino Triphenolate Complexes through Nitroxyl Radical Units
Authors: Badetti Elena , Lloveras Vega , Romano Francesco , Di Lorenzo Rosalia , Veciana Jaume , Vidal‐Gancedo José , Zonta Cristiano , Licini Giulia
Published: November 2016

Invited for the cover of this issue is the group of Giulia Licini at Università di Padova, Italy, in collaboration with the NANOMOL research group at the Institute of Materials Science of Barcelona, Spain. The cover image shows the change in geometry of an amino triphenolate vanadium(V) complex, which is detected by EPR spectroscopy.
Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?
Authors: Kristensen P.J. , Heegaard A.M. , Hestehave S. , Jeggo R.D. , Bjerrum O.J. , Munro G.
Published: November 2016

Background

Outbred Sprague–Dawley (SD) rats are a commonly used strain in preclinical pain research. Here, we established empirically how SD rats obtained from different vendors might vary in sensitivity to injury and pharmacotherapy.

Methods

Chronic Constriction Injury (CCI) or complete Freund's adjuvant (CFA) hindpaw inflammation was induced in male SD rats sourced from three to four different vendors, respectively. Neuropathic hypersensitivity was evaluated over 58 days using von Frey filaments, pinprick stimulation and the hot plate test. Pharmacological sensitivity was evaluated by treatment with gabapentin (100 mg/kg, p.o.) or morphine (3 mg/kg, s.c.). CFA‐induced hyperalgesia and sensitivity to morphine (0.3–6 mg/kg, s.c.) was measured using a digital Randall–Selitto device. In addition, paw weight gain was used as an index of peripheral oedema.

Results

Significant differences between the vendor‐supplied SD rats in relation to onset, magnitude and resolution of hypersensitivity after CCI were observed. Although all sub‐strains eventually developed a robust and reversible neuropathic hypersensitivity to mechanical stimulation, the thermal hypersensitivity varied. Whereas pharmacological response to gabapentin varied enormously, the response to morphine was both robust and much more consistent between sub‐strains. Despite a similar degree of CFA‐induced hypersensitivity, the paw oedema level differed between sub‐strains. Here, morphine dose‐dependently alleviated the CFA‐induced hypersensitivity, with only a subtle difference in sensitivity between sub‐strains observed.

Conclusions

Our data reveal that the source of vendor used to obtain SD rats may be one key factor responsible for ‘between laboratory variation’ in reproducing sensitivity to some drugs targeting various pathophysiological mechanisms in specific animal pain models.

Significance

The choice of vendor used to source the same strain of rat for use in preclinical pain research can profoundly affect the level of nociceptive hypersensitivity and response to reference analgesics in neuropathic versus inflammatory models.