bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Heterogeneity in Early Active Multiple Sclerosis Lesions
Authors: Tham Mylyne , Frischer Josa M. , Weigand Stephen D. , Fitz‐Gibbon Patrick D. , Webb Samuel M. , Guo Yong , Adiele Reginald C. , Robinson Christopher A. , Brück Wolfgang , Lassmann Hans , Furber Kendra L. , Pushie M. Jake , Parisi Joseph E. , Lucchinetti Claudia F. , Popescu Bogdan F.
Published: November 2020

Objective

Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients' brains, suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is currently unknown.

Methods

We used synchrotron X‐ray fluorescence imaging, histology, and immunohistochemistry to compare the iron quantity and distribution between immunopattern II and III early active MS lesions. We analyzed archival autopsy and biopsy tissue from 21 MS patients.

Results

Immunopattern II early active lesions contain 64% more iron (95% confidence interval [CI] = 17–127%, p = 0.004) than immunopattern III lesions, and 30% more iron than the surrounding periplaque white matter (95% CI = 3–64%, p = 0.03). Iron in immunopattern III lesions is 28% lower than in the periplaque white matter (95% CI = −40 to −14%, p < 0.001). When normalizing the iron content of early active lesions to that of surrounding periplaque white matter, the ratio is significantly higher in immunopattern II (p < 0.001). Microfocused X‐ray fluorescence imaging shows that iron in immunopattern II lesions localizes to macrophages, whereas macrophages in immunopattern III lesions contain little iron.

Interpretation

Iron distribution and content are heterogeneous in early active MS lesions. Iron accumulates in macrophages in immunopattern II, but not immunopattern III lesions. This heterogeneity in the two most common MS immunopatterns may be explained by different macrophage polarization, origin, or different demyelination mechanisms, and paves the way for developing new or using existing iron‐sensitive magnetic resonance imaging techniques to differentiate among immunopatterns in the general nonbiopsied MS patient population. ANN NEUROL 2021;89:498–510
Assessment of a Siloxane Poly(urethane‐urea) Elastomer Designed for Implantable Heart Valve Leaflets
Authors: Jenney Chris , Millson Peter , Grainger David W. , Grubbs Robert , Gunatillake Pathiraja , McCarthy Simon J. , Runt James , Beith Jason
Published: November 2020

Synthetic polymer leaflets in prosthetic cardiac valves hold the potential to reduce calcification and thrombus, while improving blood flow, durability, and device economics. A recently developed siloxane poly(urethane‐urea) (LifePolymer, LP) exhibits properties essential for heart valve leaflets, including low dynamic modulus, high tensile strength, minimal creep, and excellent biostability. LP's properties result from carefully designed “linked co‐macrodiol” chemistry that maximizes silicone content and virtual crosslinks between soft and hard phases. Characterization of multiple commercial batches demonstrates a robust synthesis process with minimal variation. Extensive ISO 10993–based biocompatibility testing results in no observable toxicity or other adverse reactions. An ex vivo AV shunt thrombogenicity investigation reveals nearly undetectable levels of platelet attachment and thrombus formation on LP surfaces. Chronic ovine implantation of prototype heart valves with LP leaflets shows no differences in thrombogenicity or systemic tissue response when compared to a clinically standard tissue‐based valve. Toxicological risk assessment, based on extractables and leachables analysis of LP‐based heart valves, confirms minimal toxicological risk. Lastly, 24‐week, strain‐accelerated in vivo LP biostability testing confirms previous favorable in vitro biostability findings. These studies demonstrate that this newly developed elastomer exhibits ideal biomaterial properties for the flexible leaflets of a totally synthetic heart valve replacement.
Enantioselective Pd0‐Catalyzed C(sp2)–H Arylation for the Synthesis of Chiral Warped Molecules
Authors: Savary David , Baudoin Olivier
Published: November 2020

C−H activation‐based ring‐forming methods are a powerful approach for the construction of complex molecular architectures, especially those containing a congested stereocenter. Therefore, this strategy seems perfectly suited to address the synthesis of chiral polycyclic aromatic hydrocarbons (PAHs) and bowl‐shaped molecules, which are important target molecules in the field of organic electronic materials. Herein, we describe an enantioselective Pd0‐catalyzed C(sp2)−H arylation protocol for the synthesis of chiral fluoradenes and other warped molecules, which could serve to the bottom‐up construction of chiral PAHs. The current approach relies on the use of chiral bifunctional phosphine–carboxylate ligands and delivers diverse polycyclic compounds in high yield and with good to excellent enantioselectivity. The chiroptical properties of the obtained products were investigated, and some of them were found to have a strong ellipticity and an emission band located in the visible region.
Inhibition of Urease, a Ni‐Enzyme: The Reactivity of a Key Thiol With Mono‐ and Di‐Substituted Catechols Elucidated by Kinetic, Structural, and Theoretical Studies
Authors: Mazzei Luca , Contaldo Umberto , Musiani Francesco , Cianci Michele , Bagnolini Greta , Roberti Marinella , Ciurli Stefano
Published: November 2020

The inhibition of urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) by a class of six aromatic poly‐hydroxylated molecules, namely mono‐ and dimethyl‐substituted catechols, was investigated on the basis of the inhibitory efficiency of the catechol scaffold. The aim was to probe the key step of a mechanism proposed for the inhibition of SPU by catechol, namely the sulfanyl radical attack on the aromatic ring, as well as to obtain critical information on the effect of substituents of the catechol aromatic ring on the inhibition efficacy of its derivatives. The crystal structures of all six SPU‐inhibitors complexes, determined at high resolution, as well as kinetic data obtained on JBU and theoretical studies of the reaction mechanism using quantum mechanical calculations, revealed the occurrence of an irreversible inactivation of urease by means of a radical‐based autocatalytic multistep mechanism, and indicate that, among all tested catechols, the mono‐substituted 3‐methyl‐catechol is the most efficient inhibitor for urease.
Non‐Coordinative Binding of O2 at the Active Center of a Copper‐Dependent Enzyme
Authors: Leisinger Florian , Miarzlou Dzmitry A. , Seebeck Florian P.
Published: November 2020

Molecular oxygen (O2) is a sustainable oxidation reagent. O2 is strongly oxidizing but kinetically stable and its final reaction product is water. For these reasons learning how to activate O2 and how to steer its reactivity along desired reaction pathways is a longstanding challenge in chemical research.[1] Activation of ground‐state diradical O2 can occur either via conversion to singlet oxygen or by one‐electron reduction to superoxide. Many enzymes facilitate activation of O2 by direct fomation of a metal‐oxygen coordination complex concomitant with inner sphere electron transfer. The formylglycine generating enzyme (FGE) is an unusual mononuclear copper enzyme that appears to follow a different strategy. Atomic‐resolution crystal structures of the precatalytic complex of FGE demonstrate that this enzyme binds O2 juxtaposed, but not coordinated to the catalytic CuI. Isostructural complexes that contain AgI instead of CuI or nitric oxide instead of O2 confirm that formation of the initial oxygenated complex of FGE does not depend on redox activity. A stepwise mechanism that decouples binding and activation of O2 is unprecedented for metal‐dependent oxidases, but is reminiscent of flavin‐dependent enzymes.
Sulfur‐Coordinated Organoiridium(III) Complexes Exert Breast Anticancer Activity via Inhibition of Wnt/β‐Catenin Signaling
Authors: Sun Qi , Wang Yi , Fu Qiuxia , Ouyang Ai , Liu Shanshan , Wang Zhongyuan , Su Zijie , Song Jiaxing , Zhang Qianling , Zhang Pingyu , Lu Desheng
Published: November 2020

The sulfur‐coordinated organoiridium(III) complexes pbtIrSS and ppyIrSS, which contain C,N and S,S (dithione) chelating ligands, were found to inhibit breast cancer tumorigenesis and metastasis by targeting Wnt/β‐catenin signaling for the first time. Treatment with pbtIrSS and ppyIrSS induces the degradation of LRP6, thereby decreasing the protein levels of DVL2, β‐catenin and activated β‐catenin, resulting in downregulation of Wnt target genes CD44 and survivin. Additionally, pbtIrSS and ppyIrSS can suppress cell migration and invasion of breast cancer cells. Furthermore, both complexes show the ability to inhibit sphere formation and mediate the stemness properties of breast cancer cells. Importantly, pbtIrSS exerts potent anti‐tumor and anti‐metastasis effects in mouse xenograft models through the blockage of Wnt/β‐catenin signaling. Taken together, our results indicate that pbtIrSS has great potential to be developed as a breast cancer therapeutic agent with a novel mechanism.
Polymorphism of 2D Imine Covalent Organic Frameworks
Authors: Li Yusen , Guo Linshuo , Lv Yongkang , Zhao Ziqiang , Ma Yanhang , Chen Weihua , Xing Guolong , Jiang Donglin , Chen Long
Published: November 2020

We designed and synthesized A2B2 type tetraphenyl benzene monomers (p‐, m‐, and o‐TetPB) which have the para‐, meta, and ortho‐substituted isomeric structures, for the direct construction of isomeric frameworks. Interestingly, both kagome (kgm) and monoclinic square (sql) framework isomers are produced from either p‐TetPB (C2h symmetry) or m‐TetPB (C2v symmetry) by changing reaction solvents, while their isomeric structures are characterized by X‐ray diffraction, computational simulation, microscopy, and sorption isotherm measurements. Only sql frameworks was formed for o‐TetPB (C2v symmetry), irrespective of reaction solvents. These results disclose a unique feature in the framework structural formation, that is, the geometry of monomers directs and dominates the lattice growth process while the solvent plays a role in the perturbation of chain growth pattern. The isomeric frameworks exhibit highly selective adsorption of vitamin B12 owing to pore shape and size differences.
Teerfarben‐basierte Koordinationskäfige und ‐helikate
Authors: Regeni Irene , Chen Bin , Frank Marina , Baksi Ananya , Holstein Julian J. , Clever Guido H.
Published: November 2020

Wir berichten über den Einbau klassischer Teerfarben (Michlers Keton, Methylen Blau, Rhodamin B und Kristallviolett) in selbstassemblierte Strukturen der Formel [Pd2L4]. Die Chromophore wurden unter Verwendung von Piperazin‐Linkern in bis‐monodentate Liganden integriert. Dies erlaubt die Erhaltung der für die intensive Farbgebung verantwortlichen auxochromen Dialkylamin‐Funktionen. Liganden mit Pyridin‐Donoren bilden laternenförmige dinukleare Käfige, während Chinolin‐Donoren stark gewundene [Pd2L4]‐Helikate ergeben. In einem Fall konnte mittels Röntgenstrukturanalyse eine [Pd3L6]‐Ringstruktur im Festkörper nachgewiesen werden. Für neun untersuchte Derivate, in Farben von Gelb bis Dunkelviolett, konnte mittels CD‐Spektroskopie chirale Induktion durch einen enantiomerenreinen Gast gezeigt werden. Ionenmobilitäts‐Massenspektrometrie erlaubt die Unterscheidung zweier Bindungsmodi. Nanostrukturen basierend auf dieser neuen Ligandenklasse versprechen Anwendungen in chiropitscher Erkennung, Photo‐Redox‐Katalyse und funktionalen Materialien.
A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes
Authors: Yanai Hikaru , Hoshikawa Shoki , Moriiwa Yukiko , Shoji Atsushi , Yanagida Akio , Matsumoto Takashi
Published: November 2020

Installation of a carbanionic substituent, that is strongly stabilized by two (trifluoromethyl)sulfonyl (Tf=SO2CF3) groups, into several fluorescence dyes including boron‐dipyrromethenes (BODIPYs), fluoresceins, and aminocoumarins has been achieved by the 2,2‐bis(triflyl)ethylation reaction of the dye frameworks with highly electrophilic Tf2C=CH2, followed by neutralization with NaHCO3. Despite the contradiction between water solubility and lipophilicity, the carbanion‐decorated dyes thus obtained showed significant enhancement of not only water solubility but also lipophilicity. This work clearly demonstrates that the fluorinated, highly stabilized carbanionic substituent is a new option for controlling the macroscopic property of chemical materials.
Fast Li‐Ion Conductivity in Superadamantanoid Lithium Thioborate Halides
Authors: Kaup Kavish , Assoud Abdeljalil , Liu Jue , Nazar Linda F.
Published: November 2020

Lithium thioborates are promising fast Li‐ion conducting materials, with similar properties to their lithium thiophosphate counterparts that have enabled the development of solid‐state Li‐ion batteries. By comparison, thioborates have scarcely been developed, however, offering new space for materials discovery. Here we report a new class of lithium thioborate halides that adopt a so‐called supertetrahedral adamantanoid structure that houses mobile lithium ions and halide anions within interconnected 3D structural channels. Investigation of the structure using single‐crystal XRD, neutron powder diffraction, and neutron PDF reveals significant lithium and halide anion disorder. The phases are non‐stoichiometric, adopting slightly varying halide contents within the materials. These new superadamantanoid materials exhibit high ionic conductivities up to 1.4 mS cm−1, which can be effectively tuned by the polarizability of the halide anion within the channels.
Modular Synthesis of Organoboron Helically Chiral Compounds: Cutouts from Extended Helices
Authors: Full Julian , Panchal Santosh P. , Götz Julian , Krause Ana‐Maria , Nowak‐Król Agnieszka
Published: November 2020

Two types of helically chiral compounds bearing one and two boron atoms were synthesized by a modular approach. Formation of the helical scaffolds was executed by the introduction of boron to flexible biaryl and triaryl derived from small achiral building blocks. All‐ortho‐fused azabora[7]helicenes feature exceptional configurational stability, blue or green fluorescence with quantum yields (Φfl) of 18–24 % in solution, green or yellow solid‐state emission (Φflup to 23 %), and strong chiroptical response with large dissymmetry factors of up to 1.12×10−2. Azabora[9]helicenes consisting of angularly and linearly fused rings are blue emitters exhibitingΦflof up to 47 % in CH2Cl2and 25 % in the solid state. As revealed by the DFT calculations, their P–M interconversion pathway is more complex than that ofH1. Single‐crystal X‐ray analysis shows clear differences in the packing arrangement of methyl and phenyl derivatives. These molecules are proposed as primary structures of extended helices.
Charge‐Promoted Self‐Metalation of Porphyrins on an Oxide Surface
Authors: Egger Larissa , Hollerer Michael , Kern Christian S. , Herrmann Hannes , Hurdax Philipp , Haags Anja , Yang Xiaosheng , Gottwald Alexander , Richter Mathias , Soubatch Serguei , Tautz F. Stefan , Koller Georg , Puschnig Peter , Ramsey Michael G. , Sterrer Martin
Published: November 2020

Metalation and self‐metalation reactions of porphyrins on oxide surfaces have recently gained interest. The mechanism of porphyrin self‐metalation on oxides is, however, far from being understood. Herein, we show by a combination of results obtained with scanning tunneling microscopy, photoemission spectroscopy, and DFT computations, that the self‐metalation of 2H‐tetraphenylporphyrin on the surface of ultrathin MgO(001) films is promoted by charge transfer. By tuning the work function of the MgO(001)/Ag(001) substrate, we are able to control the charge and the metalation state of the porphyrin molecules on the surface.
Coal‐Tar Dye‐based Coordination Cages and Helicates
Authors: Regeni Irene , Chen Bin , Frank Marina , Baksi Ananya , Holstein Julian J. , Clever Guido H.
Published: November 2020

A strategy to implement four members of the classic coal‐tar dye family, Michler's ketone, methylene blue, rhodamine B, and crystal violet, into [Pd2L4] self‐assemblies is introduced. Chromophores were incorporated into bis‐monodentate ligands using piperazine linkers that allow to retain the auxochromic dialkyl amine functionalities required for intense colors deep in the visible spectrum. Upon palladium coordination, ligands with pyridine donors form lantern‐shaped dinuclear cages while quinoline donors lead to strongly twisted [Pd2L4] helicates in solution. In one case, single crystal X‐ray diffraction revealed rearrangement to a [Pd3L6] ring structure in the solid state. For nine examined derivatives, showing colors from yellow to deep violet, CD spectroscopy discloses different degrees of chiral induction by an enantiomerically pure guest. Ion mobility mass spectrometry allows to distinguish two binding modes. Self‐assemblies based on this new ligand class promise application in chiroptical recognition, photo‐redox catalysis and optical materials.
The analysis of cannabinoids in cannabis samples by supercritical fluid chromatography and ultra‐high‐performance liquid chromatography: A comparison study
Authors: Deidda Riccardo , Schelling Cédric , Roussel Jean‐Marc , Dispas Amandine , De Bleye Charlotte , Ziemons Éric , Hubert Philippe , Veuthey Jean‐Luc
Published: November 2020

The aim of this work was to develop a supercritical fluid chromatographic method to study the applicability of this emerging technique to cannabinoid analysis and showcase its advantages. During method development, the authors focused on nine phyto‐cannabinoids to assess the selectivity needed to potentially perform the quantitation of each cannabinoid. After method development, robustness studies were carried out on this method to gain more information about its qualitative behavior (in terms of critical resolutions) when varying some crucial parameters (concentration of additive, column temperature, starting gradient conditions and column batch). Once the robustness was evaluated and the parameters most affecting the selected responses were individuated, the SFC method was applied for a simulated routine use to generate quantitative results concerning the concentrations of the main cannabinoids in real cannabis samples. The samples were also analyzed by means of an ultra‐high‐performance liquid chromatographic method currently used in the laboratory for the same objective. Finally, the results obtained with both analytical methods were compared to evaluate their accordance. The Bland–Altman method was applied as a statistical strategy to evaluate the degree of accordance between the results generated and display the data in a difference plot. The ultra‐high performance supercritical fluid chromatography quantitative results were in accordance with the ultra‐high performance liquid chromatography results, demonstrating the applicability of this technique for cannabinoid analysis.
Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX‐2 inhibitors
Authors: Kaya Çavuşoğlu Betül , Sağlık Begüm N. , Acar Çevik Ulviye , Osmaniye Derya , Levent Serkan , Özkay Yusuf , Kaplancıklı Zafer A.
Published: November 2020

A new series of chalcones (1−9) possessing an SO2CH3 COX‐2 pharmacophore at the para position of the C‐1 phenyl ring was synthesized via the Claisen–Schmidt condensation reaction and examined for their inhibition potential against cyclooxygenase (COX) enzymes. Their structures were elucidated by infrared, 1H NMR (nuclear magnetic resonance), 13C NMR, and high‐resolution mass spectroscopic methods. Enzyme inhibition studies revealed that most of the compounds showed a moderate‐to‐strong inhibitory activity (IC50 = 0.18−0.34 μM) against the COX‐2 enzyme as compared with celecoxib (IC50 = 0.12 μM), ibuprofen (IC50 = 5.33 μM), and nimesulide (IC50 = 1.68 μM). Among these compounds, 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2,3‐dichlorophenyl)prop‐2‐en‐1‐one (5), 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2,4‐dichlorophenyl)prop‐2‐en‐1‐one (6), and 1‐[4‐(methylsulfonyl)phenyl]‐3‐(2‐chloro‐6‐fluorophenyl)prop‐2‐en‐1‐one (8) became prominent with IC50 values of 0.21, 0.19, and 0.18 μM, respectively. According to molecular docking studies of the most effective compounds, it was found that the compounds interact with amino acids that are important in COX‐2 selectivity, such as Arg499 and Phe504.
The influence of distance between decoy and target on context effect: Attraction or repulsion?
Authors: Liao Jiejie , Chen Yujie , Lin Wuji , Mo Lei
Published: November 2020

The attraction effect in decision making refers to how preferences are influenced by an inferior option in the choice set. Recent studies challenged the robustness of attraction effect by manipulating the distance between decoy and target in perceptual decision‐making tasks. However, previous manipulation of the distance was not comprehensive and systematic enough. Whether the influence of distance between decoy and target on attraction effect would occur in high‐level decisions remains unclear. The present study conducted five experiments (two on perceptual decisions and three on preferential decisions) where the distance of the decoy to the target option was systematically manipulated. We found that the distance of the decoy to the target systematically changes the strength and the direction of the attraction effect and sometimes causes its opposite: repulsion effect. Specifically, such change of the context effect (from attraction to repulsion) follows a U‐shape function (technically regarding the relative choice share of the target option [RST] as a function of the target–decoy distance), which is in the shape of convex in the perceptual decisions but concave in the domain of preferential decisions. Our findings show how the distance of decoy to target influences the robustness of attraction effect in preferential and perceptual decisions.
A Review on Metabolites from Onchidium Genus: Chemistry and Bioactivity
Authors: Wang Bowen , Chen Deli , Yu Meng , Liu Yangyang , Liu Pinghuai , Zhang Xiaopo
Published: November 2020

The Onchidium genus (Mollusca, Gastropoda, Pulmonata, Systellommatophora, Onchidiidae family) is used as the important economical shellfish, due to the high nutritional value and medicinal value. Research over the previous decades indicated that Onchidium sp. mainly contains polypropionates, depsipeptides, terpenoids and other chemical components. Many biological activities of Onchidium (e. g., cytotoxic activities against tumor cells, anti‐viral and anti‐bacterial activities) have been reported. This review reports a total of 60 compounds, synthetic work and biological studies on Onchidium genus, covering the literature from 1978 to date, with a view to providing a reference and helping for the in‐depth research of this genus.
Antimicrobial and Anticancer Properties of Synthetic Peptides Derived from the Wasp Parachartergus fraternus
Authors: Muller Jessica A. I. , Lawrence Nicole , Chan Lai Yue , Harvey Peta J. , Elliott Alysha G. , Blaskovich Mark A. T. , Gonçalves Jacqueline C. , Galante Priscilla , Mortari Marcia R. , Toffoli‐Kadri Mônica C. , Koehbach Johannes , Craik David J.
Published: November 2020

Agelaia‐MPI and protonectin are antimicrobial peptides isolated from the wasp Parachartergus fraternus that show antimicrobial and neuroactive activities. Previously, two analogues of these peptides, neuroVAL and protonectin‐F, were designed to reduce nonspecific toxicity and improve potency. Here, the three‐dimensional structures of neuroVAL, protonectin and protonectin‐F were determined by using circular dichroism and NMR spectroscopy. Antibacterial, antifungal, cytotoxic and hemolytic activities were tested for the parent peptides and analogues. All peptides showed moderate antimicrobial activity against Gram‐positive bacteria, with agelaia‐MPI being the most active. Protonectin and protonectin‐F were found to be toxic to cancerous and noncancerous cell lines. Internalization experiments revealed that these peptides accumulate inside both cell types. By contrast, neuroVAL was nontoxic to all tested cells and was able to enter cells without accumulating. In summary, neuroVAL has potential as a nontoxic cell‐penetrating peptide, while protonectin‐F needs further modification to realize its potential as an antitumor peptide.
CHRDL2 promotes osteosarcoma cell proliferation and metastasis through the BMP‐9/PI3K/AKT pathway
Authors: Chen Houping , Pan Runsang , Li Hao , Zhang Wenguang , Ren Chong , Lu Qiaoying , Chen Hui , Zhang Xiangyan , Nie Yingjie
Published: November 2020

Various studies demonstrated that bone morphogenetic proteins (BMPs) and their antagonists contribute to the development of cancers. Chordin‐like 2 (CHRDL2) is a member of BMP antagonists. However, the role and its relative mechanism of CHRDL2 in osteosarcoma remains unclear. In the present study, we demonstrated that the expression of CHRDL2 was significantly upregulated in osteosarcoma tissues and cell lines compared with adjacent tissues and human normal osteoblast. Inhibition of CHRDL2 decreased the proliferation and colony formation of osteosarcoma cells in vitro, as well as the migration and invasion. CHRDL2 overexpression induced the opposite effects. CHRDL2 can bind with BMP‐9, thus decreasing BMP‐9 expression and the combination to its receptor protein kinase ALK1. It was predicted that BMP‐9 regulates PI3K/AKT pathways using gene set enrichment analysis. Inhibition of CHRDL2 decreased the activation of PI3K/AKT pathway, while overexpression of CHRDL2 upregulated the activation. Increasing the expression of BMP‐9 reversed the effects of CHRDL2 overexpression on the activation of PI3K/AKT pathway, as well as the proliferation and metastasis of osteosarcoma cells. Take together, our present study revealed that CHRDL2 upregulated in osteosarcoma tissues and cell lines, and promoted osteosarcoma cell proliferation and metastasis through the BMP‐9/PI3K/AKT pathway. CHRDL2 maybe an oncogene in osteosarcoma, as well as novel biomarker for the diagnosis of osteosarcoma.
Effect of processing on the phenolics content and antioxidant properties of mung bean
Authors: Zhang Shu , Feng Yu‐Chao , Fu Tian‐Xin , Sheng Ya‐Nan , Diao Jing‐Jing , Wang Chang‐Yuan
Published: November 2020

Background and objectives

Health benefits of cereals depend not only on the intake levels but also on their processing methods and conditions. In this work, effects of processing treatments, including steaming, cooking, and roasting on the free and bound phenolics content and antioxidant properties of mung bean, were investigated.

Findings

The free phenolics content of mung bean significantly decreased (p < .05), while the bound phenolics content significantly increased after processing. The loss in the free phenolics content was found to be greater after cooking, followed by steaming, and roasting. However, cooked mung bean samples showed greater bound phenolics content than that of steamed or roasted ones. Antioxidant activity of mung bean phenolics retained or even enhanced after processing depending processing method, duration, and temperature as well as phenolics type, that is, free and bound. Furthermore, a positive correlation was found between the free or bound phenolics content and antioxidant activity of mung bean.

Conclusions

The processing of whole mung bean grain resulted in the change of the composition content of phenolics and changed the antioxidant activity. It was feasible to maintain the active by adjusting the processing mode and conditions of grain.

Significance and novelty

The antioxidant activity modification promoted by the processing treatment could increase the potential applications of mung bean.
Phosphorus‐Doped CuCo2O4 Oxide with Partial Amorphous Phase as a Robust Electrocatalyst for the Oxygen Evolution Reaction
Authors: Guo Zhen , Pang Yongyu , Xie Huan , He Guanjie , Parkin Ivan P. , Chai Guo‐Liang
Published: November 2020

It is highly desirable to develop efficient and low‐cost electrocatalysts for the oxygen evolution reaction (OER) to improve the efficiency of water electrolysis. Here, we report a strategy doping with a small amount of phosphorus to make inactive and low‐cost spinel CuCo2O4 (CCO) turn into high‐efficiency and superior to the noble metal catalyst RuO2. The spinel CuCo2O4−P0.5 (CCP0.5) shows the best OER performance with a small overpotential of 290 mV at a current density of 10 mA cm−2 and a low Tafel slope of 68 mV dec−1 in an alkaline electrolyte. The phosphorus doping induces the production of an amorphous phase that provides a large number of active sites, and the synergistic effect of the crystalline phase and amorphous phase significantly improves the OER activity of CCO. It is also revealed that the conductivity of CCO is improved compared with pristine CCO. Our work highlights that non‐metallic element doping is an effective strategy to greatly enhance the OER performance of spinel transition metal oxide electrocatalysts.
Forty Years after the Discovery of Its Nucleolytic Activity: [Cu(phen)2]2+ Shows Unattended DNA Cleavage Activity upon Fluorination
Authors: Lüdtke Carsten , Sobottka Sebastian , Heinrich Julian , Liebing Phil , Wedepohl Stefanie , Sarkar Biprajit , Kulak Nora
Published: November 2020

[Cu(phen)2]2+ (phen=1,10‐phenanthroline) is the first and still one of the most efficient artificial nucleases. In general, when the phen ligand is modified, the nucleolytic activity of its CuII complex is significantly reduced. This is most likely due to higher steric bulk of such ligands and thus lower affinity to DNA. CuII complexes with phen ligands having fluorinated substituents (F, CF3, SF5, SCF3) surprisingly showed excellent DNA cleavage activity—in contrast to the unsubstituted [Cu(phen)2]2+—in the absence of the otherwise required classical, bioabundant external reducing agents like thiols or ascorbate. This nucleolytic activity correlates well with the half‐wave potentials E1/2 of the complexes. Cancer cell studies show cytotoxic effects of all complexes with fluorinated ligands in the low μm range, whereas they were less toxic towards healthy cells (fibroblasts).
Catalytic Benzylation Reactions: From C—H Bond Activation to C—N Bond Activation
Authors: Jiang Tianxiao , Liu Hongchi , Zhang Haocheng , Huang Hanmin
Published: November 2020

Transition‐metal mediated activation of inert chemical bonds is an ongoing topic in homogeneous catalysis. In view of the abundance and accessibility of alkylarenes and benzylamines, the use of them as benzyl source in catalytic benzylation reactions via benzylic C—H and C—N bond activation is highly desirable. Indeed, compared with the traditional approaches with benzyl halide as the substrates, benzylation reactions via C—H and C—N bond cleavage provide more efficient, atom‐economic strategies to access myriads of synthetically important molecules. In this account, our group's efforts on catalytic benzylation reactions via directed C—H activation, nondirected C—H activation and C—N bond activation are summarized.

What is the most favorite and original chemistry developed in your research group?

Palladium‐catalyzed aminal chemistry.

How do you supervise your students?

Discuss with my students and encourage them to think about where the scientific problem is.

What is the most important personality for scientific research?

Honesty, curiosity and passion.

What are your hobbies?

Reading and playing badminton.

Who influences you mostly in your life?

My parents, who always inspire me to go forward.

What is your favorite journal(s)?

Journals that fairly review the manuscripts and publish inspiring, innovative research results.
Pharmacokinetics of Belimumab in Children With Systemic Lupus Erythematosus
Authors: Dimelow Richard , Ji Beulah , Struemper Herbert
Published: November 2020

The phase 2 placebo‐controlled, double‐blind PLUTO trial characterized the pharmacokinetics of belimumab plus standard systemic lupus erythematosus (SLE) therapy in patients with childhood‐onset SLE (cSLE) and demonstrated similar efficacy and safety to that in adult SLE. Patients with active cSLE aged 5‐17 years were randomized to intravenous belimumab 10 mg/kg every 4 weeks (n = 53). A linear 2‐compartment population pharmacokinetics (popPK) model with first‐order elimination was developed, and an exploratory exposure‐response analysis assessed the impact of between‐patient exposure variability on clinical response (SLE Responder Index 4 [SRI4]) in week 52, and occurrence of serious adverse events during the study. The popPK model estimated clearance of 158 mL/day, steady‐state volume of distribution of 3.5 L, terminal half‐life of 16.3 days, and distribution half‐life of 0.8 days in the overall population. Fat‐free mass (FFM) better characterized the pharmacokinetics than total body weight and was more consistent with allometric scaling theory; belimumab pharmacokinetics were largely determined by FFM. Age, sex, disease activity, and concomitant medication had no impact on pediatric belimumab exposure after accounting for body size. Individual and median steady‐state pediatric pharmacokinetic profiles were similar to known adult profiles and pediatric exposure estimates for belimumab 10 mg/kg intravenously were consistent with adult exposures. Exposures were similar between SRI4 responders and nonresponders, and patients who did or did not experience a serious adverse event. There was no clinically relevant correlation between exposure and efficacy or safety, confirming belimumab 10 mg/kg intravenous dose every 4 weeks as appropriate for pediatric patients with cSLE.
An operative constellation rate for smart safety units using Internet of Things
Authors: Manoharan Hariprasath
Published: November 2020

This paper focuses on implementing an intelligent decision‐making automated device for providing safety to all individuals. In India, during every year it has been observed that an average of 36% of the people is dying due to road accidents in highways. Till now, there are no intelligent devices to monitor the above‐mentioned conditions. Even if the devices are available the distance of installation is observed to be small and as a result cost of installation is higher. Therefore, the monitoring devices are not integrated in proper position and the safety units which are divided and placed in highways for providing indication to the drivers are not appropriate. To provide higher safety to each individual in highways, the proposed method incorporates a Minimized Cluster Rate for partitioning the highway patterns and for understanding the congestion problem to identify appropriate highway lanes with Enhanced Level protocol for proper operation in emergency conditions. Also, this new flanged model is monitored using Thing speak and for real‐time analysis the results are plotted in MATLAB. Moreover, it has been observed that the projected method provide more safety to each individual with minimization of cost and error in control process.
Drug‐Drug Interaction Surveillance Study: Comparing Self‐Controlled Designs in Five Empirical Examples in Real‐World Data
Authors: Bykov Katsiaryna , Li Hu , Kim Sangmi , Vine Seanna M. , Lo Re Vincent , Gagne Joshua J.
Published: November 2020

Self‐controlled designs, specifically the case‐crossover (CCO) and the self‐controlled case series (SCCS), are increasingly utilized to generate real‐world evidence (RWE) on drug‐drug interactions (DDIs). Although these designs share the advantages and limitations of within‐individual comparison, they also have design‐specific assumptions. It is not known to what extent the differences in assumptions lead to different results in RWE DDI analyses. Using a nationwide US commercial healthcare insurance database (2006–2016), we compared the CCO and SCCS designs, as they are implemented in DDI studies, within five DDI‐outcome examples: (1) simvastatin + clarithromycin and muscle‐related toxicity; (2) atorvastatin + valsartan, and muscle‐related toxicity; and (3–5) dabigatran + P‐glycoprotein inhibitor (clarithromycin, amiodarone, and verapamil) and bleeding. Analyses were conducted within person‐time exposed to the object drug (statins and dabigatran) and adjusted for bias associated with the inhibiting drugs via control groups of individuals unexposed to the object drug. The designs yielded similar estimates in most examples, with SCCS displaying better statistical efficiency. With both designs, results varied across sensitivity analyses, particularly in CCO analyses with small number of exposed individuals. Analyses in controls revealed substantial bias that may be differential across DDI‐exposed and control individuals. Thus, both designs showed no association between amiodarone or verapamil and bleeding in dabigatran‐exposed but revealed strong positive associations in controls. Overall, bias adjustment via a control group had a larger impact on results than the choice of a design, highlighting the importance and challenges of appropriate control group selection for adequate bias control in self‐controlled analyses of DDIs.
Is conflict adaptivity better than cooperation? The effects of adaptive conflict behaviors on job‐related well‐being in South Korea
Authors: Kim Regina , Coleman Peter T. , Kugler Katharina G.
Published: November 2020

Given the pervasiveness of conflict at work and its potential negative consequences, it is important to know how managers can deal with conflicts constructively. Employees and managers are often required to navigate through a multiplicity of conflicts, including disputes with their supervisors and supervisees of either a cooperative, win–win or competitive, win–lose nature. The goal of this study was to examine how the capacity of South Korean workers to respond adaptively to different or changing types of conflict situations impacts their job‐related well‐being and turnover intentions. Specifically, we hypothesized and found that more adaptive responses to conflict—those that utilize different behavioral strategies that are aligned with the normative demands of presenting conflict situations—were positively related to satisfaction with conflict outcomes, job‐related well‐being, and lower intentions to quit one's job among managers and employees in South Korea. These findings are consistent with those from similar studies in the United States, providing support for the generalizability of the model to other cultural contexts. Theoretical and practical implications of the results as well as directions for future research are discussed.
Does religion improve corporate environmental responsibility? Evidence from China
Authors: Chen Kejing , Guo Wenqi , Kang Yanling , Wan Qingqing
Published: November 2020

We examine how religion influences corporate environmental responsibility (CER). With the existing literature, we analyse how Buddhism and Taoism, the most traditional and influential religion of the Chinese, could act on individual and organizational behaviours and corporate culture, and then improve CER. Taking Chinese listed companies that disclose environmental governance information from 2007 to 2016 as our sample, we find that religion contributes to the improvement of CER on corporate environmental governance, and the effect is still significant after controlling for endogenous problems and robustness tests. Furthermore, we find that religion can enhance the positive role of CER by reducing unit energy consumption and promoting local pollution prevention.
LC‐HRMS characterization of the skin pigmentation and sexual enhancers melanotan II and bremelanotide sold on the black market of performance and image enhancing drugs
Authors: Mestria Serena , Odoardi Sara , Frison Giampietro , Strano Rossi Sabina
Published: November 2020

The spread of performance and image enhancing drugs (PIEDs) often requires forensic toxicology laboratories to identify unknown compounds without reference standards. We characterized the PIEDs melanotan II and bremelanotide, not legally marketed, in eight unknown samples confiscated by police together with anabolic steroids, hormone modulators, sexual enhancers and stimulants, intended for the black market of bodybuilders, using liquid chromatography–high resolution/high accuracy Orbitrap mass spectrometry (LC‐HRMS). The characterization was carried out by the accurate mass measurements of MH+ ionic species, the study of their isotopic patterns and the associated relative isotopic abundance (RIA) values, as well as the accurate mass measurements of collision‐induced product ions obtained in fragmentation experiments. LC‐HRMS confirmed itself as a powerful analytical tool to elucidate the elemental composition and structural characteristics of unknown compounds.
Distancing from a stigmatized social identity: State of the art and future research agenda on self‐group distancing
Authors: van Veelen Ruth , Veldman Jenny , Van Laar Colette , Derks Belle
Published: November 2020

Despite equal rights, minority groups such as ethnic minorities, LGBTQ + people, and people with mental or physical disabilities face discrimination on a day‐to‐day basis in subtle and hard‐to‐recognize forms. As discrimination slips beneath the surface, it becomes difficult to fight the stigma using collective social identity coping mechanisms. Instead, individual mobility responses such as distancing the self from the stigmatized identity (“self‐group distancing”) become more viable as a way to improve one's individual standing. In this overview of the state of the art, we take a social identity lens to reflect on the current empirical knowledge base on self‐group distancing as a coping mechanism and provide a framework on what self‐group distancing is; when, where and why self‐group distancing likely occurs; and what its consequences are at the individual and the collective level. The contributions in this special issue provide novel insights into how these processes unfold, and serve as a basis to set a future research agenda, for example on what can be done to prevent self‐group distancing (i.e., interventions). Together, the insights highlight that while self‐group distancing may seem effective to (strategically and temporarily) alleviate discomfort or to improve one's own position, on a broader collective level and over time self‐group distancing tends to keep the current unequal social hierarchy in place.
Understanding allies’ participation in social change: A multiple perspectives approach
Authors: Kutlaca Maja , Radke Helena R. M. , Iyer Aarti , Becker Julia C.
Published: November 2020

The introduction to the EJSP special issue brings together recent literature on allyship. We present and discuss different definitions of allyship and highlight a multiple perspectives approach to understanding the predictors and consequences of allyship. This approach suggests that engagement in allyship can be driven by egalitarian and non‐egalitarian motivations and that the behaviours identified as allyship can have different meanings, causes and consequences depending on whether researchers take into account the allies’ perspective or the disadvantaged groups’ perspective. We use this approach as an organizing principle to identify themes that emerge in the papers included in this special issue. We start with four papers that consider the perspective of the advantaged group, followed by two papers that consider the perspective of the disadvantaged group. Finally, we introduce two theoretical papers that examine the relations between disadvantaged groups and allies, and we set out directions for future research.
Morphometric Assessment of Golden Mahseer Populations in the Ganga River Basin, India
Authors: Dwivedi Arvind Kumar
Published: November 2020

River fragmentation has adverse effects on fish populations due to restricted migratory pattern, resulting in risk of population extinction. It has been hypothesized that river fragmentation has led to changes in fish population structure. To test the hypothesis, 149 Golden Mahseer Tor putitora were collected from seven locations, including the Ganga River and upstream and downstream of two impounded headwater tributaries: the Bhagirathi and the Alaknanda rivers. Landmark–based “Truss” and “Geometric” morphometric differentiation was investigated to determine if variations in Golden Mahseer populations exist due to river impoundments. Truss network modeling yielded 90 size–corrected distance variables from 14 landmarks, following which analysis of variance (ANOVA), principal component analysis (PCA) and discriminant function analysis (DFA) were performed. Geometric morphometric modeling included relative warps, PCA, and canonical variate analysis (CVA). Both DFA and CVA plot illustrated overlapping, with DFA suggesting low percentage of classification between populations. Mahalanobis and Procrustes distances extracted from CVA were non-significant (P > 0.001) among populations. Results indicated the existence of single homogenous population of Golden Mahseer in the Ganga River. This study provides a basis for stock identification useful in developing a suitable plan towards conservation and restoration of Golden Mahseer populations in the fragmented Ganga River.
Juice of Citrullus lanatus var. citroides (wild watermelon) inhibits the entry and propagation of influenza viruses in vitro and in vivo
Authors: Morimoto Ryosuke , Yoshioka Kae , Nakayama Miyu , Nagai Emiko , Okuno Yoshinobu , Nakashima Ayaka , Ogawa Taro , Suzuki Kengo , Enomoto Toshiki , Isegawa Yuji
Published: November 2020

Vaccines and various anti‐influenza drugs are clinically used to prevent and treat influenza infections. However, with the antigenic mismatch of vaccines and the emergence of drug‐resistant viral strains, new approaches for treating influenza are warranted. This study focused on natural foods as potential candidates for the development of new treatment options for influenza infections. The screening of plants from the Cucurbitaceae family revealed that the juice of Citrullus lanatus var. citroides (wild watermelon) had the strongest ability to inhibit the replication of influenza virus in Madin–Darby canine kidney cells. The results of a time‐of‐addition assay indicated that wild watermelon juice (WWMJ) inhibits the adsorption and late stages of viral replication, suggesting that WWMJ contains multiple constituents with effective anti‐influenza activity. A viral adsorption analysis showed that WWMJ reduces the amount of viral RNA in the cells at 37°C but not at 4°C, confirming that WWMJ inhibits viral entry into the host cells at 37°C. These results suggest that a mechanism other than the inhibition of viral attachment is involved in the anti‐influenza action of WWMJ, which is perhaps responsible for a reduction in internalization of the virus. Administration of WWMJ into the nasal mucosa of BALB/c mice infected with the A/PR/8/34 mouse‐adapted influenza virus was seen to significantly improve the survival rate. The findings of this study, therefore, demonstrate the anti‐influenza potential of WWMJ in vitro and in vivo, thereby suggesting the candidature of WWMJ as a functional food product that can be used to develop anti‐influenza agents and drugs.