bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative medical characteristics of ZDF‐T2DM rats during the course of development to late stage disease
Authors: Pang Yun‐Li , Hu Jing‐Wen , Liu Guang‐Long , Lu Shuai‐Yao 
Published: September 2018

AbstractBackgroundThere are few reports on the comparative medical characteristics of type 2 diabetes models in late stage. An analysis of comparative medical characteristics of Zucker diabetic fatty type 2 diabetes mellitus (ZDF‐T2DM) rats during the course of development to late stage disease was performed.MethodsIn this study, ZDF rats were fed with high‐sugar and high‐fat diets to raise the fasting blood glucose, and develop of type 2 diabetes. At the late stage of T2DM, the preliminary comparative medical characteristics of the T2DM model were analyzed through the detection of clinical indicators, histopathology, related cytokine levels, and insulin‐related signaling molecule expression levels.ResultsIn the T2DM group, the fasting blood glucose was higher than 6.8 mmol/L, the serum insulin, leptin, and adiponectin levels were significantly decreased, and glucose intolerance and insulin resistance were measured as clinical indicators. Regarding pathological indicators, a large number of pancreatic islet cells showed the reduction of insulin secretion, resulting in damaged glycogen synthesis and liver steatosis. At the molecular level, the insulin signal transduction pathway was inhibited by decreasing the insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), phosphatidylinositol 3 kinase (PI3K), and glycogen synthesis kinase 3β (GSK‐3β) expression levels.ConclusionThe results show that the ZDF/T2DM rats have typical clinical, histopathological, and molecular characteristics of human T2DM and thus can be used as an effective model for T2DM drug development and treatment of advanced T2DM.
Enhancer and super‐enhancer: Positive regulators in gene transcription
Authors: Peng Yanling , Zhang Yubo 
Published: September 2018

AbstractEnhancer is a positive regulator for spatiotemporal development in eukaryotes. As a cluster, super‐enhancer is closely related to cell identity‐ and fate‐determined processes. Both of them function tightly depending on their targeted transcription factors, cofactors, and genes through distal genomic interactions. They have been recognized as critical components and played positive roles in transcriptional regulatory network or factory. Recent advances of next‐generation sequencing have dramatically expanded our ability and knowledge to interrogate the molecular mechanism of enhancer and super‐enhancer for transcription. Here, we review the history, importance, advances and challenges on enhancer and super‐enhancer field. This will benefit our understanding of their function mechanism for transcription underlying precise gene expression.
Entropic Uncertainty Relation for Dirac Particles in Garfinkle–Horowitz–Strominger Dilation Space–Time
Authors: Zhang Zuo‐Yuan , Liu Jin‐Ming , Hu Zhengfeng , Wang Yuzhu 
Published: September 2018

AbstractThe quantum‐memory‐assisted entropic uncertainty relation for Dirac particles in the background of a Garfinkle–Horowitz–Strominger (GHS) dilation black hole is investigated, and the relationship between the entropy uncertainty and the quantum entanglement of a hybrid qubit–qutrit state in the GHS space–time analyzed. The results show that the physically accessible uncertainty increases while the inaccessible uncertainty decreases as the dilation parameter of the black hole enhances. Moreover, the evolution behavior of the uncertainty is inversely correlated with that of the entanglement between the quantum memory and the particle to be measured. Meanwhile, a method to steer the entropic uncertainty with the technique of weak measurement reversal is proposed. It is found that the uncertainty can be reduced effectively by adjusting the appropriate measurement strength. These findings may lead to a deeper understanding of entropy uncertainty dynamics, as well as its steering in a curved space–time.
Metallvermittelte Funktionalisierung natürlicher Peptide und Proteine: Biokonjugation mit Übergangsmetallen
Authors: Ohata Jun , Martin Samuel C. , Ball Zachary T. 
Published: September 2018

AbstractDie selektive Modifikation natürlicher Proteine stellt eine enorme methodologische Herausforderung dar und bedarf einer strikten Kontrolle der Selektivität und des Umfangs einer Reaktion. Demnach existiert ein fortwährender Bedarf an neuen Reaktivitäts‐ sowie Selektivitätskonzepten. Übergangsmetalle zeichnen sich durch ihre Fülle einzigartiger Reaktivitäten aus, welche biologischen Reaktionen und Prozessen gegenüber orthogonal sind. Folglich spielen metallbasierte Methoden eine zunehmend wichtige Rolle in der Biokonjugationschemie. In diesem Aufsatz werden metallbasierte Methoden sowie deren Reaktivitäten und Selektivitäten bei der Funktionalisierung natürlicher Proteine und Peptide diskutiert.
Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study
Authors: López‐Mejías Raquel , Carmona F. David , Genre Fernanda , Remuzgo‐Martínez Sara , González‐Juanatey Carlos , Corrales Alfonso , Vicente Esther F. , Pulito‐Cueto Verónica , Miranda‐Filloy José A. , Ramírez Huaranga Marco A. , Blanco Ricardo , Robustillo‐Villarino Montserrat , Rodríguez‐Carrio Javier , Alperi‐López Mercedes , Alegre‐Sancho Juan J. , Mijares Verónica , Lera‐Gómez Leticia , Pérez‐Pampín Eva , González Antonio , Ortega‐Castro Rafaela , López‐Pedrera Chary , García Vivar Mari L. , Gómez‐Arango Catalina , Raya Enrique , Narvaez Javier , Balsa Alejandro , López‐Longo Francisco J. , Carreira Patricia , González‐Álvaro Isidoro , Rodríguez‐Rodríguez Luis , Fernández‐Gutiérrez Benjamín , Ferraz‐Amaro Iván , Gualillo Oreste , Castañeda Santos , Martín Javier , Llorca Javier , González‐Gay Miguel A. 
Published: September 2018

ObjectiveTo investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA).MethodsWe performed a genome‐wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima‐media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals.ResultsA genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome‐wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 10−8). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein–protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate–adjusted P = 4.01 × 10−3). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10−4, P = 5.94 × 10−4, and P = 2.46 × 10−4, respectively).ConclusionThe present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.
The pearl necklace model in protein A chromatography: Molecular mechanisms at the resin interface
Authors: L. Silva Goncalo , Plewka Jacek , Lichtenegger Helga , Dias‐Cabral Ana C. , Jungbauer Alois , Tscheließnig Rupert 
Published: September 2018

AbstractStaphylococcal protein A chromatography is an established core technology for monoclonal antibody purification and capture in the downstream processing. MabSelect SuRe involves a tetrameric chain of a recombinant form of the B domain of staphylococcal protein A, called the Z‐domain. Little is known about the stoichiometry, binding orientation, or preferred binding. We analyzed small‐angle X‐ray scattering data of the antibody–protein A complex immobilized in an industrial highly relevant chromatographic resin at different antibody concentrations. From scattering data, we computed the normalized radial density distributions. We designed three‐dimensional (3D) models with protein data bank crystallographic structures of an IgG1 (the isoform of trastuzumab, used here; Protein Data Bank: 1HZH) and the staphylococcal protein A B domain (the native form of the recombinant structure contained in MabSelect SuRe resin; Protein Data Bank: 1BDD). We computed different binding conformations for different antibody to protein A stoichiometries (1:1, 2:1, and 3:1) and compared the normalized radial density distributions computed from 3D models with those obtained from the experimental data. In the linear range of the isotherm we favor a 1:1 ratio, with the antibody binding to the outer domains in the protein A chain at very low and high concentrations. In the saturation region, a 2:1 ratio is more likely to occur. A 3:1 stoichiometry is excluded because of steric effects.
Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
Authors: Ma Wanru , Ma Juan , Ma Ping , Lei Ting , Zhao Man , Zhang Man 
Published: September 2018

AbstractObjectiveB7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐CD3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells (ATC) to kill bladder cancer cells.MethodsHigh expressions of B7‐H3 on human bladder cancer cells were detected, including Pumc‐91 and T24 cells, and their chemotherapeutic drug‐resistant counterparts. ATC generated from healthy donors were stimulated with anti‐CD3 monoclonal antibody and interleukin‐2 (IL‐2) for 13 days. The ability of ATC armed with B7‐H3Bi‐Ab to kill bladder cancer cells was detected by flow cytometry, LDH, Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7‐H3Bi‐Ab to verity the cell killing by the methods as previously described.ResultsCompared with unarmed ATC, a significant increased cytotoxicity of B7‐H3Bi‐Ab‐armed ATC against bladder cancer cells was discovered. The B7‐H3Bi‐Ab‐armed ATC secreted more IFN‐γ, TNF‐α, and expressed high levels of activation marker CD69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug‐resistant cancer cell lines, B7‐H3Bi‐Ab‐armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug‐resistant counterparts.ConclusionB7‐H3 is an effective target for bladder cancer. B7‐H3Bi‐Ab enhances the ability of ATC to kill bladder cancer cells. B7‐H3Bi‐Ab‐armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy.
Phytochemical Composition, Antioxidant Potential and Cholinesterase Inhibition Potential of Extracts from Mentha pulegium L.
Authors: Politeo Olivera , Bektašević Mejra , Carev Ivana , Jurin Mladenka , Roje Marin 
Published: September 2018

AbstractThe aim of this work was to perform the phytochemical analysis as well as antioxidant and anticholinesterase potential of hot water and methanolic extracts from Mentha pulegium L., Lamiaceae, wild growing in Bosnia and Herzegovina. It is a plant that is traditionally used in Bosnia and Herzegovina medicine to treat gastrointestinal and neurological disorders. By HPLC‐DAD analysis of tested extracts, 15 phenol compounds were identified and quantified. Rosmarinic acid was the most abundant compound in both extracts, followed by ellagic acid, eriodictyol, naringenin and chlorogenic acid. Both extracts were demonstrated good radical scavenging potential, reducing power and ability to inhibit lipid oxidation. The tested extracts also showed low ability to inhibit protein oxidation and low or no acetylcholinesterase and butyrylcholinesterase inhibition potential. The promising radical scavenging potential, reducing power and lipid protection potential of tested extracts indicates that the extracts of M. pulegium could be useful in preventing free radical linked diseases, as well as food protecting antioxidants.
An Alcohol Dehydrogenase from the Short‐Chain Dehydrogenase/Reductase Family of Enzymes for the Lactonization of Hexane‐1,6‐diol
Authors: Dithugoe Choaro D. , van Marwijk Jacqueline , Smit Martha S. , Opperman Diederik J. 
Published: September 2018

AbstractBiocatalytic production of lactones, and in particular ϵ‐caprolactone (CL), have gained increasing interest as a greener route to polymer building blocks, especially through the use of Baeyer–Villiger monooxygenases (BVMOs). Despite several advances in the field, BVMOs, however, still suffer several practical limitations. Alcohol dehydrogenase (ADH)‐mediated lactonization of diols in turn has received far less attention and very few enzymes have been identified for the conversion of diols to lactones, with horse‐liver ADH (HLADH) remaining the catalyst of choice. Screening of a diverse panel of ADHs, AaSDR‐1, a member of the short‐chain dehydrogenase/reductase family, was found to produce ϵ‐caprolactone from hexane‐1,6‐diol. Moreover, cofactor regeneration by an NADH oxidase eliminated the requirement of co‐substrates, yielding water as the sole by‐product. Despite lower turnover frequencies as compared to HLADH, higher selectivity was found for the production of CL, with HLADH forming significant amounts of 6‐hydroxyhexanoic acid and adipic acid through aldehyde dehydrogenation/oxidation of the gem‐diol intermediates. Also, CL yield were shown to be dependent on buffer choice, as structural elucidation of a Tris adduct confirmed the buffer amine to react with aliphatic aldehydes forming a Schiff‐base intermediate which through further ADH oxidation, forms a tricyclic acetal product.
Silver Oxide‐Based Semiconductors for Solar Fuels Production and Environmental Remediation: a Solid‐State Chemistry Approach
Authors: Galante Miguel T. , Sotelo Paola , Hossain Mohammad K. , Vali Abbas , Raamann Asti , Longo Claudia , Macaluso Robin T. , Rajeshwar Krishnan 
Published: September 2018

AbstractA solid‐state perspective is offered for a discussion of silver‐based ternary and quaternary oxide semiconductors for applications related to solar fuels photogeneration and environmental remediation. The rather unique d10 electron configuration in these compounds is shown to impart interesting effects on their optoelectronic properties, and in turn, the photocatalytic activity of these compounds. This Minireview focuses on the structural aspects, electronic band structures, synthetic advances, and finally photoelectrochemical and photocatalytic applications of 32 compounds within the two oxide families, of the generic formula: AgxByOz or AgxByCnOz, where B and C are metals or non‐metals other than silver.
Layered Bimetallic Metal‐Organic Material Derived Cu2SnS3/SnS2/C Composite for Anode Applications in Lithium‐Ion Batteries
Authors: Foley Sarah , Geaney Hugh , Bree Gerard , Mukherjee Soumya , Zaworotko Michael J. , Ryan Kevin M. 
Published: September 2018

AbstractHere, we report the synthesis of a bimetallic 2D interpenetrated metal‐organic material (MOM) and its use as a sacrificial precursor for the formation of a Cu2SnS3/SnS2/C composite. The one‐step sulfurisation of the novel Sn/Cu‐MOM represents a facile method for the preparation of an effective anode material for Li‐ion battery applications. The Cu2SnS3/SnS2/C composite was characterised by XRD, TGA, TEM and SEM. Electrochemical analysis was conducted on SnCu2SnS3/SnS2/C anodes in half cell configurations between 0–3 V and 0–1 V. Anodes cycled between 0–1 V exhibited markedly more stable capacity retention (315 mAh/g after 100 cycles), as only alloying of the Li with Sn took place within this potential window, compared to a combination of conversion and alloying for the wider potential range. This stability of the Li alloying based capacity was further enhanced by replacing the planar Cu foil with a rough dendritic Cu foil as the current collector, resulting in an improved capacity retention of 84 % after 100 cycles.
To Loop or Not to Loop: Influence of Hinge Flexibility on Self‐Assembly Outcomes for Acridine‐Based Triazolylpyridine Chelates with Zinc(II), Iron(II), and Copper(II)
Authors: Miron Caitlin E. , Fleischel Olivier , Petitjean Anne 
Published: September 2018

AbstractCoordination‐driven self‐assembly has been established as an effective strategy for the efficient construction of intricate architectures in both natural and artificial systems, for applications ranging from gene regulation to metal–organic frameworks. Central to these systems is the need for carefully designed organic ligands, generally with rigid components, that can undergo self‐assembly with metal ions in a predictable manner. Herein, we report the synthesis and study of three novel organic ligands that feature 3,6‐disubstituted acridine as a rigid spacer connected to two 2‐(1,2,3‐triazol‐4‐yl)pyridine “click” chelates through hinges of the same length but differing flexibility. The flexibility of these “three‐atom” hinges was modulated by i) moving from secondary to tertiary amide functional groups and ii) replacing an sp2 amide carbon with an sp3 methylene carbon. In an effort to understand the role of hinge flexibility in directing self‐assembly into mononuclear loops or dinuclear cylinders, the impact of these changes on self‐assembly outcomes with zinc(II), iron(II), and copper(II) ions is described.
Protein Glycosylation through Sulfur Fluoride Exchange (SuFEx) Chemistry: The Key Role of a Fluorosulfate Thiolactoside
Authors: Marra Alberto , Dong Jiajia , Ma Tiancheng , Giuntini Stefano , Crescenzo Elisa , Cerofolini Linda , Martinucci Marco , Luchinat Claudio , Fragai Marco , Nativi Cristina , Dondoni Alessandro 
Published: September 2018

AbstractProtein glycosylation is the most complex post‐translational modification process. More than 50 % of human cells proteins are glycosylated, whereas bacteria such as E. coli do not have this modification machinery. Indeed, the carbohydrate residues in natural proteins affect their folding, immunogenicity, and stability toward proteases, besides controlling biological properties and activities. It is therefore important to introduce such structural modification in bioengineered proteins lacking the presence of carbohydrate residues. This is not trivial as it requires reagents and conditions compatible with the protein's stability and reactivity. This work reports on the introduction of lactose moieties in two natural proteins, namely ubiquitin (Ub) and l‐asparaginase II (ANSII). The synthetic route employed is based on the sulfur(VI) fluoride exchange (SuFEx) coupling of a lactose tethered arylfluorosulfate (Lact‐Ar‐OSO2F) with the ϵ‐NH2 group of lysine residues of the proteins. This metal‐free click SuFEx reaction relies on the properties of the fluorosulfate employed, which is easily prepared in multigram scale from available precursors and reacts chemoselectively with the ϵ‐NH2 group of lysine residues under mild conditions. Thus, iterative couplings of Lact‐Ar‐OSO2F to Ub and ANSII, afforded multiple glycosylations of these proteins so that up to three and four Lact‐Ar‐OSO2 groups were introduced in Ub and ANSII, respectively, via the formation of a sulfamoyl (OSO2‐NH) linkage.
Retracted: A Temperature‐, pH‐ and Voltage‐Responsive Nanogate with a Remarkably High Factor of Change in Ion Currents due to ON/OFF Switching
Authors: Dettori Riccardo , Yang Quan , Achenie Luke E. K. , Schwarz Roland D. 
Published: September 2018

AbstractIn biological cells, nuclear pore complexes (NPCs) embedded in cell membranes are capable of controlling the flow of ions, for example, Na+, K+, and Ca2+ by responding to stimuli, for example, pH and voltage. Inspired by NPCs, researchers have been endeavoring to develop nanogates to achieve the control of ion transport, but the developed nanogates only have a low factor of change in ion currents due to ON/OFF switching. As such nanopores with high temperature and pH responsivities were developed in this work. According to the experimental results, at a voltage of 3 V, the change in ion currents due to pH change is up to a factor of 170, which is remarkably high compared to other nanogates reported. Quantum chemical (QC) calculation results show that a protonated cytosine molecule (C+) and an unprotonated cytosine molecule (C) form three pairs of hydrogen bonds and consequently a nucleobase pair, CC+, leading to the binding of various strands, assembly of a strand net, and blockage of ion transport. The nanogate developed is capable of responding to temperature change. At a voltage of 3 V, the factor of change in ion currents in response to temperature variation is as high as 110. Further experiments were performed to investigate the influence of the NaCl concentrations and small opening diameters exerted on nanogate performance.
Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro‐inflammatory cytokines in human breast adenocarcinoma cells
Authors: Vaidya Foram U. , Sharma Rakesh , Shaikh Sofiya , Ray Debes , Aswal Vinod K. , Pathak Chandramani 
Published: September 2018

AbstractBackgroundCurcumin is a natural derivative, which exhibits broad spectrum biological activities including anti‐oxidant, anti‐inflammatory, and anti‐cancer. Since ancient times, it has been used for the treatment of various diseases. Many reports highlighted its potential as a chemopreventive and chemotherapeutic agent. Despite its imperative properties, the pharmacological application had been limited due to low solubility in the aqueous medium, limited tissue absorption, and rapid degradation at physiological pH.AimsCytotoxicity of drugs and their undesirable side effects are major obstacles in the regimens of cancer therapy. Therefore, natural plant derivatives‐based anti‐cancer drug delivery systems are getting more attention as they are less toxic, safer, and effective. In the present study, Pluronic block copolymer encapsulated curcumin was developed as an improved curcumin delivery system with the aim to improve its efficacy and biological response against cancer cells.Methods and ResultsPluronic micelles encapsulated curcumin was synthesized, and its characterization was done by particle size analysis, Fourier transform infrared spectroscopy, small‐angle neutron scattering analysis, PXRD, and differential scanning calorimetry. Further, its biological activities were corroborated in cancer cells. Results indicate that Pluronic micelles encapsulated curcumin exemplify solubility and stability of curcumin in the aqueous medium. Biophysical characterization indicated that Pluronic F127 forms nanoparticle, and its micellar core radius was increased after incorporation of curcumin. Furthermore, biological studies show that Pluronic micelles encapsulated curcumin inhibits cell proliferation, improves cellular uptake of curcumin, arrests the cell cycle in G0/G1 phase, and inhibits the activation of NF‐kB and release of pro‐inflammatory cytokines to manifest apoptotic cell death rather than necrotic. This formulation was non‐toxic to normal cells.ConclusionThis study suggests that Pluronic micelles encapsulated curcumin is stable that can effectively inhibit cell proliferation and release of pro‐inflammatory cytokines in cancer cells as compared with the free curcumin. This approach could be applied to improve the therapeutic index of anti‐cancer agents.