bluuebunny/crossref_metadata_2025 huggingface dataset:
In Situ Assembly of 2D Conductive Vanadium Disulfide with Graphene as a High‐Sulfur‐Loading Host for Lithium–Sulfur Batteries
Authors: Zhu Xingyu , Zhao Wen , Song Yingze , Li Qiucheng , Ding Feng , Sun Jingyu , Zhang Li , Liu Zhongfan
Published: April 2018

Lithium–sulfur (Li–S) batteries are deemed to be one of the most promising energy storage technologies because of their high energy density, low cost, and environmental benignancy. However, existing drawbacks including the shuttling of intermediate polysulfides, the insulating nature of sulfur, and the considerable volume change of sulfur cathode would otherwise result in the capacity fading and unstable cycling. To overcome these challenges, herein an in situ assembly route is presented to fabricate VS2/reduced graphene oxide nanosheets (G–VS2) as a sulfur host. Benefiting from the 2D conductive and polar VS2 interlayered within a graphene framework, the obtained G–VS2 hybrids can effectively suppress the polysulfide shuttling, facilitate the charge transport, and cushion the volume expansion throughout the synergistic effect of structural confinement and chemical anchoring. With these advantageous features, the obtained sulfur cathode (G–VS2/S) can deliver an outstanding rate capability (≈950 and 800 mAh g−1 at 1 and 2 C, respectively) and an impressive cycling stability at high rates (retaining ≈532 mAh g−1 after 300 cycles at 5 C). More significantly, it enables superior cycling performance of high‐sulfur‐loading cathodes (achieving an areal capacity of 5.1 mAh cm−2 at 0.2 C with a sulfur loading of 5 mg cm−2) even at high current densities.
Enhancing Optical, Electronic, Crystalline, and Morphological Properties of Cesium Lead Halide by Mn Substitution for High‐Stability All‐Inorganic Perovskite Solar Cells with Carbon Electrodes
Authors: Liang Jia , Liu Zonghao , Qiu Longbin , Hawash Zafer , Meng Lingqiang , Wu Zhifang , Jiang Yan , Ono Luis K. , Qi Yabing
Published: April 2018

In this work all‐inorganic perovskite CsPbIBr2 are doped with Mn to compensate their shortcomings in band structure for the application of perovskite solar cells (PSCs). The novel Mn‐doped all‐inorganic perovskites, CsPb1−xMnxI1+2xBr2−2x, are prepared in ambient atmosphere. As the concentration of Mn2+ ions increases, the bandgaps of CsPb1−xMnxI1+2xBr2−2x decrease from 1.89 to 1.75 eV. Additionally, when the concentration of Mn dopants is appropriate, this novel Mn‐doped all‐inorganic perovskite film shows better crystallinity and morphology than its undoped counterpart. These advantages alleviate the energy loss in hole transfer and facilitate the charge‐transfer in perovskites, therefore, PSCs based on these novel CsPb1−xMnxI1+2xBr2−2x perovskite films display better photovoltaic performance than the undoped CsPbIBr2 perovskite films. The reference CsPbIBr2 cell reaches a power conversion efficiency (PCE) of 6.14%, comparable with the previous reports. The CsPb1−xMnxI1+2xBr2−2x cells reach the highest PCE of 7.36% (when x = 0.005), an increase of 19.9% in PCE. Furthermore, the encapsulated CsPb0.995Mn0.005I1.01Br1.99 cells exhibit good stability in ambient atmosphere. The storage stability measurements on the encapsulated PSCs reveal that PCE is dropped by only 8% of the initial value after >300 h in ambient. Such improved efficiency and stability are achieved using low‐cost carbon electrodes (without expensive hole transport materials and Au electrodes).
Application of bone transgenic zebrafish in anti‐osteoporosis chemical screening
Authors: Huang Hong‐xin , Lin Hao , Lan Fen , Wu Yong‐fu , Yang Zhen‐guo , Zhang Jing‐jing
Published: April 2018

Background

The zebrafish (Danio rerio) has recently been shown to be an ideal model to study bone disease including osteoporosis. The zebrafish osteoporosis model could be induced by glucocorticoid treatment with chemical staining for reflecting the level of bone mineralization. However, this methodology was unstable. Here, we developed a novel methodology to directly evaluate the bone mass and density.

Methods

We generated and used the bone of transgenic zebrafish Tg (ola.sp7:nlsGFP) to evaluate the bone mass and density by measuring the areal extent and the integrated optical density (IOD) of enhanced green fluorescent protein (eGFP). This methodology was further compared with the traditional chemically stained method showing the bone mineralization. Furthermore, genes related to zebrafish osteoporosis were analyzed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR).

Results

Our results of new methods were consistent with those from chemically stained fish, following glucocorticoid‐induction or epimedium flavonoid (FE)‐rescue treatments. qRT‐PCR analyses on mRNA levels revealed that glucocorticoid induces osteoporosis by downregulating the expression of osteoblast‐related factors osterix, osteocalcin, and osteopontin, and upregulating the expression of osteoclast‐related factor tartrate‐resistant acid phosphatase. In FE‐rescued fish, the expression of osteogenic factors osterix, osteocalcin, and osteopontin were increased.

Conclusion

Compared to the traditional chemical staining methods, the new osteoporosis model using Tg(ola.sp7:nlsGFP) is more convenient and efficient for studying osteoporosis in vivo, and especially for high‐throughput anti‐osteoporosis drug screening.
Redox imbalance stress in diabetes mellitus: Role of the polyol pathway
Authors: Yan Liang‐jun
Published: April 2018

In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase (AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+ redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed.
Homeobox genes for embryo implantation: From mouse to human
Authors: He Bo , Ni Zhang‐li , Kong Shuang‐bo , Lu Jin‐hua , Wang Hai‐bin
Published: April 2018

The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation, which is considered to be a critical event for successful pregnancy. Like many developmental processes, a large number of transcription factors, such as homeobox genes, have been shown to orchestrate this complicated but highly organized physiological process during implantation. In this review, we focus on progress in studies of the role of homeobox genes, especially the Hox and Msx gene families, during implantation, together with subsequent development of post‐implantation uterus and related reproductive defects in both mouse models and humans, that have led to better understanding of how implantation is precisely regulated and provide new insights into infertility.
Dhcr24 activates the PI3K/Akt/HKII pathway and protects against dilated cardiomyopathy in mice
Authors: Dong Wei , Guan Fei‐fei , Zhang Xu , Gao Shan , Liu Ning , Chen Wei , Zhang Lian‐feng , Lu Dan
Published: April 2018

Background

24‐dehydrocholesterol reductase (Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and anti‐apoptotic activities of tissues. We found that Dhcr24 expression decreased in the cTnTR141W dilated cardiomyopathy (DCM) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of DCM and its possible mechanism.

Methods

Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to cTnTR141W mouse to obtain the double transgenic mouse (DTG). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and TUNEL assay in vivo and in vitro.

Results

We find that Dhcr24 decreased in hearts tissues of cTnTR141W and LMNAE82K DCM mice. The transgenic overexpression of Dhcr24 significantly improves DCM phenotypes in cTnTR141W mice, and activates PI3K/Akt/HKII pathway, followed by a reduction of the translocation of Bax and release of cytochrome c, caspase‐9 and caspase‐3 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of PI3K/Akt/HKII pathway and inhibition of the mitochondrial‐dependent apoptosis. The anti‐apoptotic effect of Dhcr24 could be completely removed by the inhibition of PI3K pathway and partly removed by the HKII inhibitor in H9c2 cell line.

Conclusion

Compensatory expression of Dhcr24 protect against DCM through activated PI3K/Akt/HKII pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of DCM.
Mouse models of porcine circovirus 2 infection
Authors: Ouyang Ting , Liu Xiao‐hui , Ouyang Hong‐sheng , Ren Lin‐zhu
Published: April 2018

PCV2 is considered the main pathogen of porcine circovirus diseases and porcine circovirus‐associated diseases (PCVD/PCVAD). However, the exact mechanism underlying PCVD/PCVAD is currently unknown. Mouse models of PCV2 are valuable experimental tools that can shed light on the pathogenesis of infection and will enable the evaluation of antiviral agents and vaccine candidates. In this review, we discuss the current state of knowledge of mouse models used in PCV2 research that has been performed to date, highlighting their strengths and limitations, as well as prospects for future PCV2 studies.
Instant Locking of Molecular Ordering in Liquid Crystal Elastomers by Oxygen‐Mediated Thiol–Acrylate Click Reactions
Authors: Xia Yu , Zhang Xinyue , Yang Shu
Published: April 2018

Liquid crystal elastomers (LCEs) with intrinsic anisotropic strains are reversible shape‐memory polymers of interest in sensor, actuator, and soft robotics applications. Rapid gelation of LCEs is required to fix molecular ordering within the elastomer network, which is essential for directed shape transformation. A highly efficient photo‐cross‐linking chemistry, based on two‐step oxygen‐mediated thiol–acrylate click reactions, allows for nearly instant gelation of the main‐chain LCE network upon exposure to UV light. Molecular orientation from the pre‐aligned liquid crystal oligomers can be faithfully transferred to the LCE films, allowing for preprogrammed shape morphing from two to three dimensions by origami‐ (folding‐only) and kirigami‐like (folding with cutting) mechanisms. The new LCE chemistry also enables widely tunable physical properties, including nematic‐to‐ isotropic phase‐transition temperatures (TN‐I), glassy transition temperatures (Tg), and mechanical strains, without disrupting the LC ordering.
A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible‐Light Photoredox Catalysis
Authors: Xue Fei , Wang Falu , Liu Jiazhen , Di Jiamei , Liao Qi , Lu Huifang , Zhu Min , He Liping , He Huan , Zhang Dan , Song Hao , Liu Xiao‐Yu , Qin Yong
Published: April 2018

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible‐light photoredox catalysis. A process that involves the generation of N‐centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional‐group tolerance.
Stereoretentive Reactions at the Anomeric Position: Synthesis of Selenoglycosides
Authors: Zhu Feng , O'Neill Sloane , Rodriguez Jacob , Walczak Maciej A.
Published: April 2018

Reported is the stereospecific cross‐coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono‐, di‐, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross‐coupling method presented herein can find use in the synthesis of selenium‐containing glycomimetics and glycoconjugates.
A Nanohelicoidal Nematic Liquid Crystal Formed by a Non‐Linear Duplexed Hexamer
Authors: Mandle Richard J. , Goodby John W.
Published: April 2018

The twist‐bend modulated nematic liquid‐crystal phase exhibits formation of a nanometre‐scale helical pitch in a fluid and spontaneous breaking of mirror symmetry, leading to a quasi‐fluid state composed of chiral domains despite being composed of achiral materials. This phase was only observed for materials with two or more mesogenic units, the manner of attachment between which is always linear. Non‐linear oligomers with a H‐shaped hexamesogen are now found to exhibit both nematic and twist‐bend modulated nematic phases. This shatters the assumption that a linear sequence of mesogenic units is a prerequisite for this phase, and points to this state of matter being exhibited by a wider range of self‐assembling structures than was previously envisaged. These results support the double helix model of the TB phase as opposed to the simple heliconical model. This new class of materials could act as low‐molecular‐weight surrogates for cross‐linked liquid‐crystalline elastomers.
Enantioselective Rhodium‐Catalyzed Dimerization of ω‐Allenyl Carboxylic Acids: Straightforward Synthesis of C2‐Symmetric Macrodiolides
Authors: Steib Philip , Breit Bernhard
Published: April 2018

Herein, we report on the first enantioselective and atom‐efficient catalytic one‐step dimerization method to selectively transform ω‐allenyl carboxylic acids into C2‐symmetric 14‐ to 28‐membered bismacrolactones (macrodiolides). This convenient asymmetric access serves as an attractive route towards multiple naturally occuring homodimeric macrocyclic scaffolds and demonstrates excellent efficiency to construct the complex, symmetric core structures. By utilizing a rhodium catalyst with a modified chiral cyclopentylidene‐diop ligand, the desired diolides were obtained in good to high yields, high diastereoselectivity, and excellent enantioselectivity.
Trifluoromethanesulfonic Anhydride as a Low‐Cost and Versatile Trifluoromethylation Reagent
Authors: Ouyang Yao , Xu Xiu‐Hua , Qing Feng‐Ling
Published: April 2018

A large number of reagents have been developed for the synthesis of trifluoromethylated compounds. However, an ongoing challenge in trifluoromethylation reaction is the use of less expensive and practical trifluoromethyl sources. We report herein the unprecedented direct trifluoromethylation of (hetero)arenes using trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent by merging photoredox catalysis and pyridine activation. Furthermore, introduction of both the CF3 and OTf groups of the trifluoromethanesulfonic anhydride into internal alkynes to access tetrasubstituted trifluoromethylated alkenes was achieved. Since trifluoromethanesulfonic anhydride is a low‐cost and abundant chemical, this method provides a cost‐efficient and practical route to trifluoromethylated compounds.
Polycyclic Indoline‐Benzodiazepines through Electrophilic Additions of α‐Imino Carbenes to Tröger Bases
Authors: Bosmani Alessandro , Guarnieri‐Ibáñez Alejandro , Goudedranche Sébastien , Besnard Céline , Lacour Jérôme
Published: April 2018

Polycyclic indoline‐benzodiazepines can be accessed through the intermolecular reaction of Tröger bases with N‐sulfonyl‐1,2,3‐triazoles. Under RhII catalysis, α‐imino carbenes are generated and a subsequent cascade of [1,2]‐Stevens, Friedel–Crafts, Grob, and aminal formation reactions yield the polycyclic heterocycles as single isomers (d.r.>49:1, four stereocenters including two bridgehead N atoms). Further ring expansion by insertion of a second α‐imino carbene leads to elaborated polycyclic 9‐membered‐ring triazonanes.
Bottom‐up Synthesis and Self‐Assembly of Copper Clusters into Permanent Excimer Supramolecular Nanostructures
Authors: Santiago‐Gonzalez Beatriz , Monguzzi Angelo , Capitani Chiara , Prato Mirko , Santambrogio Carlo , Meinardi Francesco , Brovelli Sergio
Published: April 2018

Metal clusters with appropriate molecular ligands have been shown to be suitable subnanometer building blocks for supramolecular architectures with controlled secondary interactions, providing access to physical regimes not achievable with conventional intermolecular motifs. An example is the excimer photophysics exhibited by individual cluster‐based superstructures produced by top‐down etching of gold nanoparticles. Now, a supramolecular architecture of copper clusters is presented with controlled optical properties and efficient non‐resonant luminescence produced via a novel bottom‐up synthesis using mild green reductants followed by a ligand exchange reaction and spontaneous supramolecular assembly. Spectroscopic experiments confirm the formation of the intercluster network and reveal the permanent nature of their excimer‐like behavior, thus extending the potential impact and applicability of metal cluster superstructures as efficient and stable non‐resonant single‐particle emitters.
Interfacial interactions and properties of natural rubber–silica composites with liquid natural rubber as a compatibilizer and prepared by a wet‐compounding method
Authors: He Fan , Yuan Tianyuan , Li Chaoqun , Sun Long , Liao Shuangquan
Published: April 2018

Natural rubber–silica [W(NR–SiO2)] composites were prepared by wet‐compounding technology with liquid natural rubber (LNR) as a compatibilizer. The effects of the LNR content and wet‐compounding technology on the filler dispersion, Payne effect, curing characteristics, mechanical properties, and interfacial interactions were investigated. The results show that the incorporation of LNR promoted vulcanization and decreased the Payne effect of the W(NR–SiO2) composites. With the addition of 5 phr LNR, the remarkable improvements in the mechanical properties of the W(NR–SiO2) vulcanizates were correlated with the improved silica dispersion and strengthened interfacial bonding. Furthermore, the W(NR–SiO2) vulcanizates containing LNR exhibited improvements in both the wet‐skid resistance and rolling‐resistance performance. The interfacial interactions, quantitatively evaluated by the Mooney–Rivlin equation and Lorenz–Park equation on the basis of the rubber elasticity and reinforcement theory, were strengthened in the presence of LNR. Accordingly, an interfacial structural model was proposed to illustrate the improvements in the mechanical properties of the W(NR–SiO2) composites. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46457.
Formation of G‐wires, bimolecular and tetramolecular quadruplex: Cation‐induced structural polymorphs of G‐rich DNA sequence of human SYTX gene
Authors: Ahmed Saami , Kaushik Mahima , Chaudhary Swati , Kukreti Shrikant
Published: April 2018

An exceptional property of auto‐folding into a range of intra‐ as well as intermolecular quadruplexes by guanine‐rich oligomers (GROs) of promoters, telomeres and various other genomic locations is still one of the most attractive areas of research at present times. The main reason for this attention is due to their established in vivo existence and biological relevance. Herein, the structural status of a 20‐nt long G‐rich sequence with two G5 stretches (SG20) is investigated using various biophysical and biochemical techniques. Bioinformatics analysis suggested the presence of a 17‐nt stretch of this SG20 sequence in the intronic region of human SYTX (Synaptotagmin 10) gene. The SYTX gene helps in sensing out the Ca2+ ion, causing its intake in the pre‐synaptic neuron. A range of various topologies like bimolecular, tetramolecular and guanine‐wires (nano‐wires) was exhibited by the studied sequence, as a function of cations (Na+/K+) concentration. UV‐thermal denaturation, gel electrophoresis, and circular dichroism (CD) spectroscopy showed correlations and established a cation‐dependent structural switch. The G‐wire formation, in the presence of K+, may further be explored for its possible relevance in nano‐biotechnological applications.
Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration
Authors: Chen Ying‐ling , Li Dong‐ping , Jiang Hong‐yue , Yang Yang , Xu Li‐li , Zhang Shun‐cai , Gao Hong
Published: April 2018

HACE1 E3 ligase was discovered to be down‐regulated in several cancers while its role in regulating tumors was merely understood. This study aimed to explore the specific effect of HACE1 played in gastric tumorigenesis and its potential mechanism. HACE1's expression was found significantly lower in gastric cancer tissues compared with the adjacent normal tissues (P < 0.001). Its protein level in gastric cancer negatively correlated to tumor pathological differentiation (P = 0.019). And in gastric cancer patients with TNM I‐IIIa, those with lower HACE1 protein level had poorer overall survival (P = 0.025). Studies, in vivo and in vitro, showed that overexpressing HACE1 inhibited tumor proliferation and migration, and enhanced cell apoptosis. Besides, ectopic expression of HACE1 down‐regulated the protein level of β‐catenin and inhibited the activity of the Wnt/β‐catenin signaling pathway. All the cellular functions were abolished when we overexpressed inactive HACE1‐deltaHECT. Above all, we demonstrated that HACE1 E3 ligase played a suppressive role in gastric tumorigenesis and inhibited the activity of the Wnt/β‐catenin signaling pathway. Circumventing the decline of HACE1 in early stage of carcinoma may impede the tumorigenesis and malignant process of gastric cancer.
Optogenetics: A Primer for Chemists
Authors: O'Banion Colin P. , Lawrence David S.
Published: April 2018

The field of optogenetics uses genetically encoded, lightresponsive proteins to control physiological processes. This technology has been hailed as the one of the ten big ideas in brain science in the past decade, the breakthrough of the decade, and the method of the year in 2010 and again in 2014. The excitement evidenced by these proclamations is confirmed by a couple of impressive numbers. The term “optogenetics” was coined in 2006. As of December 2017, “optogenetics” is found in the title or abstract of almost 1600 currently funded National Institutes of Health grants. In addition, nearly 600 reviews on optogenetics have appeared since 2006, which averages out to approximately one review per week! However, in spite of these impressive numbers, the potential applications and implications of optogenetics are not even close to being fully realized. This is due, in large part, to the challenges associated with the design of optogenetic analogues of endogenous proteins. This review is written from a chemist's perspective, with a focus on the molecular strategies that have been developed for the construction of optogenetic proteins.
Phase Behavior and Aggregation in a Catanionic System Dominated by an Anionic Surfactant Containing a Large Rigid Group
Authors: Zhai Zhaolan , Yan Xinyan , Xu Ji , Song Zhanqian , Shang Shibin , Rao Xiaoping
Published: April 2018

The phase behavior and aggregates of a catanionic system have been investigated. The anionic surfactants in the mixed systems were sodium N‐alkylmaleimidepimaric carboxylate (Cn‐MPA‐Na, n=12, 14, 16), which were prepared from rosin and contain a large rigid skeleton and a flexible alkane chain, and the cationic surfactant was cetyltrimethylammonium bromide (CTAB). The phase behavior of the C14‐MPA‐Na/CTAB system transformed sequentially from a viscoelastic solution to an aqueous surfactant two‐phase system (ASTP), an aqueous surfactant three‐phase system (AS3P), and an anisotropic homogeneous phase as the concentration of C14‐MPA‐Na was continuously increased from 10 to 35 mm. The C16‐MPA‐Na/CTAB system showed similar phase behavior, whereas the C12‐MPA‐Na/CTAB system did not form the AS3P system. The corresponding microstructures in the different phases were investigated by using rheology and cryogenic transmission electron microscopy (Cryo‐TEM). The aggregates in the viscoelastic solutions are thread‐like, annular, and worm‐like micelles. The microstructures in the upper phase of the ASTP are worm‐like micelles, and in the lower phase are spherical and rod‐like micelles. The aggregates in the upper and lower phases of the AS3P are worm‐like micelles and spherical and rod‐like micelles, respectively. The aggregates in the middle phase of the AS3P and the anisotropic homogeneous phase are sponge‐like micelles. The clear Cryo‐TEM images of the sponge‐like micelles are presented.
Potent 3‐Hydroxy‐2‐Pyridine Aldoxime Reactivators of Organophosphate‐Inhibited Cholinesterases with Predicted Blood–Brain Barrier Penetration
Authors: Zorbaz Tamara , Braïki Anissa , Maraković Nikola , Renou Julien , de la Mora Eugenio , Maček Hrvat Nikolina , Katalinić Maja , Silman Israel , Sussman Joel L. , Mercey Guillaume , Gomez Catherine , Mougeot Romain , Pérez Belén , Baati Rachid , Nachon Florian , Weik Martin , Jean Ludovic , Kovarik Zrinka , Renard Pierre‐Yves
Published: April 2018

A new series of 3‐hydroxy‐2‐pyridine aldoxime compounds have been designed, synthesised and tested in vitro, in silico, and ex vivo as reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by organophosphates (OPs), for example, VX, sarin, cyclosarin, tabun, and paraoxon. The reactivation rates of three oximes (16–18) were determined to be greater than that of 2‐PAM and comparable to that of HI‐6, two pyridinium aldoximes currently used by the armies of several countries. The interactions important for a productive orientation of the oxime group within the OP‐inhibited enzyme have been clarified by molecular‐modelling studies, and by the resolution of the crystal structure of the complex of oxime 17 with Torpedo californica AChE. Blood–brain barrier penetration was predicted for oximes 15–18 based on their physicochemical properties and an in vitro brain membrane permeation assay. Among the evaluated compounds, two morpholine‐3‐hydroxypyridine aldoxime conjugates proved to be promising reactivators of OP‐inhibited cholinesterases. Moreover, efficient ex vivo reactivation of phosphylated native cholinesterases by selected oximes enabled significant hydrolysis of VX, sarin, paraoxon, and cyclosarin in whole human blood, which indicates that the oximes have scavenging potential.
Hexakis(3,6‐di‐tert‐butyl‐4‐oxo‐2,5‐cyclohexadien‐1‐ylidene)cyclohexane: Closed‐Shell [6]Radialene or Open‐Shell Hexa‐Radicaloid?
Authors: Feng Jiaqi , Gopalakrishna Tullimilli Y. , Phan Hoa , Wu Jishan
Published: April 2018

A star‐shaped hexaquinocyclohexane molecule 4 c is reported, which turns out to be a closed‐shell extended [6]radialene with a twisted‐boat conformation according to X‐ray crystallographic analysis. It was formed by an unusually slow decay of its in situ generated open‐shell valence isomer, the hexa‐radicaloid 4 o, with a half‐life time of about 156 min at room temperature. Reaction progress kinetic analysis revealed a large energy barrier of about 95.5±4.3 kJ mol−1 at room temperature from the hexa‐radical form 4 o to the contorted [6]radialene form 4 c, because the transformation needs to overcome large steric repulsion between the neighboring phenoxyl units. Compound 4 c can be chemically reduced to radical anion and dianion, and the dianion is actually a diradical dianion, with a calculated diradical character of 71.9 %. This study demonstrates the unique chemical bonding nature of contorted quinoidal π‐conjugated molecules and a very unusual valence isomerization process.
Construction of Polycyclic π‐Conjugated Systems Incorporating an Azulene Unit Following the Oxidation of 1,8‐Diphenyl‐9,10‐bis(phenylethynyl)phenanthrene
Authors: Konishi Akihito , Morinaga Atsushi , Yasuda Makoto
Published: April 2018

Polycyclic aromatic hydrocarbons (PAHs) that incorporate either heptagons or pentagons consist of non‐planar molecular structures with unusual optoelectronic properties, and the design of a relatively simple and efficient method to construct these highly fused π‐conjugated systems with odd‐membered rings is in high demand. This work describes the use of silver(I) cations to promote the efficient synthesis of azulene‐embedded PAH 2, which is a structural isomer of tribenzo[fg,ij,rst]pentaphene 3, via tandem oxidative transannulation between the phenyl and arylethynyl moieties. This method involves a carbophilic interaction of the silver(I) cation with the acetylene units, which facilitates an electron transfer in the initial step. The synthesized PAH 2 and the protonated cation 2 H⋅BF4 were fully characterized by X‐ray crystallographic analysis, electronic absorption, electrochemical measurement, and quantum chemical calculation. The azulene‐embedded PAH 2 exhibited a low‐energy absorption band and amphoteric redox events, which were characterized as non‐alternant characteristics originating from the azulene unit.
Redox‐Flow‐Batterien im Unterricht
Authors: Quarthal Dominik , Novotny Jana , Oetken Marco
Published: April 2018

Der Beitrag stellt Redox‐Flow‐Batterien vor, welche den didaktischen Vorteil besitzen, dass man ihren Ladezustand anhand ihrer Farbigkeit erkennen kann.
Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study
Authors: Rosenberg Michael A. , Shores Molly M. , Matsumoto Alvin M. , Bůžková Petra , Lange Leslie A. , Kronmal Richard A. , Heckbert Susan R. , Mukamal Kenneth J.
Published: April 2018

Background

Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.

Hypothesis

Low serum androgens are associated with an increased risk of AF.

Methods

We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone–binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.

Results

After median follow‐up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT‐proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01–2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint‐specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9–65.3 nmol/L) had increased risk.

Conclusions

Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association.
Electrocardiography scar quantification correlates with scar size of hypertrophic cardiomyopathy seen by multidetector computed tomography
Authors: Bignoto Tiago Costa , Moreira Dalmo Antônio Ribeiro , Habib Ricardo Garbe , de Barros Correia Edileide , Amarante Ricardo Carneiro , Jatene Tannas , Nunes Mario Barbosa Guedes , Senra Tiago , Mastrocolla Luiz Eduardo
Published: April 2018

Background

Hypertrophic cardiomyopathy (HCM), a genetically transmitted disease, is the most common genetic cardiovascular disease. Current strategies to stratify risk are expensive and concentrated in wealthy centers. Twelve‐lead electrocardiography (ECG) is inexpensive, universally available, and can be readily used for Selvester QRS scoring, which estimates scar size. This study aimed to establish the relation between ECG scar quantification and myocardial fibrosis (extent of myocardial delayed enhancement) in multidetector computed tomography (MDCT).

Hypothesis

There is a significant association between ECG scar quantification and the extent of myocardial delayed enhancement in MDCT.

Methods

Seventy‐five patients with HCM underwent a routine clinical evaluation and echocardiography, 12‐lead ECG, and MDCT study. Patients with and without an implantable cardioverter‐defibrillator were included.

Results

The estimated Selvester QRS score of myocardial fibrosis was correlated significantly (R = 0.70; P < 0.01) with the quantified MDCT fibrosis. Compared with MDCT, the QRS score had 84.8% sensitivity and 88.8% specificity. Myocardial fibrosis was present in 88% of these patients with HCM (fibrotic mass, 9.87 ±10.8 g) comprising 5.66% ±6.16% of the total myocardial mass seen on the MDCT images. The Selvester QRS score reliably predicted the fibrotic mass in 76% of patients, which estimated 8.44% ±7.39% of the total myocardial mass.

Conclusions

The Selvester QRS score provides reliable quantification of myocardial fibrosis and was well correlated with MDCT in patients with HCM.
Targeting autophagy in cancer
Authors: Onorati Angelique V. , Dyczynski Matheus , Ojha Rani , Amaravadi Ravi K.
Published: April 2018

Autophagy is a conserved, self‐degradation system that is critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, in cancer, autophagy plays a dichotomous role by inhibiting tumor initiation but supporting tumor progression. Early results from clinical trials that repurposed hydroxychloroquine for cancer have suggested that autophagy inhibition may be a promising approach for advanced cancers. In this review of the literature, the authors present fundamental advances in the biology of autophagy, approaches to targeting autophagy, the preclinical rationale and clinical experience with hydroxychloroquine in cancer clinical trials, the potential role of autophagy in tumor immunity, and recent developments in next‐generation autophagy inhibitors that have clinical potential. Autophagy is a promising target for drug development in cancer.Cancer2018.©2018 American Cancer Society.
Immunotherapy and the role of imaging
Authors: Carter Brett W. , Bhosale Priya R. , Yang Wei T.
Published: April 2018

Significant advances in the genetic and molecular characterization of cancer have led to the development of effective immunotherapies. These therapeutics help the host immune system recognize cancer as foreign, promote the immune system, and relieve the inhibition that allows growth and spread of tumors. Experience with various immunotherapies, particularly the immunomodulatory monoclonal antibody ipilimumab, has demonstrated that unique patterns of response may be encountered that cannot be adequately captured by traditional response criteria, such as the World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), which have been used primarily with cytotoxic chemotherapies. In response to these observations, several novel response criteria have been developed to evaluate patients who receive immunotherapy, including immune‐related response criteria (irRC), immune‐related RECIST (irRECIST), and immune RECIST (iRECIST). These criteria are typically used in conjunction with RECIST version 1.1 in the clinical trial setting, because approval of new therapeutics by the US Food and Drug Administration relies on the responses derived from RECIST version 1.1. Finally, a wide variety of immune‐related adverse events may affect patients who receive immunotherapy, many of which can be identified on imaging studies such as computed tomography, magnetic resonance imaging, and 2‐deoxy‐2‐(fluorine‐18)fluoro‐D‐glucose–positron emission tomography/computed tomography. In this review, the authors present the role of imaging in the evaluation of patients treated with immunotherapy, including the background and application of irRC, irRECIST, and iRECIST; the imaging of immune‐related adverse events; and future directions in advanced imaging of immunotherapy. Cancer 2018;124:2906‐22. © 2018 American Cancer Society.
Sustainable development and pollutant outcomes: The case of ISO 14001 in Korea
Authors: Baek Kyungmin
Published: April 2018

ISO 14001 is one of the best known and most common globally adopted environmental management system‐based standards under current sustainable development schemes. This paper investigates the impact of ISO 14001 on the level of pollutant emissions across manufacturing facilities in Korea. The level of pollutant emissions in 22 ISO 14001‐certified facilities in Korea is compared with that of 52 non‐certified ones. Through statistical analyses based on the Shapiro‐Wilk and Mann‐Whitney U tests, it is concluded that ISO 14001‐certified facilities and non‐certified facilities are not significantly different in terms of the level of pollutant emissions produced. These statistical results indicate that ISO 14001 may not contribute to the actual improvement of environmental performance in Korea.
Soccer fields? What for? Effectiveness of corporate social responsibility initiatives in the mining industry
Authors: Devenin Veronica , Bianchi Constanza
Published: April 2018

While there is significant research regarding corporate social responsibility (CSR) practices in the mining industry, there is a lack of understanding in terms of the actual effectiveness of CSR initiatives disclosed by these companies. This paper aims to examine the perceptions of stakeholders in the mining industry regarding the intended results of CSR initiatives. Results show three ineffective situations that emerged from empirical contrasts of CSR initiatives declared by mining companies in sustainability reports and the actual impact on beneficiaries in communities: (1) failure of the CSR initiatives to contribute to real community beneficiary needs; (2) failure of the CSR initiatives to adjust to the socio‐cultural characteristics of the beneficiary group; and (3) failure of the CSR initiatives to ensure sustainability in the long run. This study contributes to the literature on CSR initiative effectiveness and provides suggestions for mining managers, government, and policymakers.
High Water Tolerance of a Core–Shell‐Structured Zeolite for CO2 Adsorptive Separation under Wet Conditions
Authors: Miyamoto Manabu , Ono Shumpei , Kusukami Kodai , Oumi Yasunori , Uemiya Shigeyuki
Published: April 2018

Dehumidification in CO2 adsorptive separation processes is an important issue, owing to its high energy consumption. However, available adsorbents such as low‐silica zeolites show a significant decrease in CO2 adsorption capacity when water vapor is present. A core–shell‐structured MFI‐type zeolite with a hydrophilic ZSM‐5 coated with a hydrophobic silicalite‐1 shell layer was applied in CO2 adsorptive separation under wet conditions. This hybrid material demonstrated remarkably high water tolerance with stable CO2 adsorption performance without additional thermal treatment for regeneration, whereas a significant decrease in the CO2 adsorption amount because of water vapor was observed on the parent ZSM‐5. The core–shell structure of zeolites with high pore volumes, such as LTA or CHA, could also be suitable candidates for high CO2 adsorption capacity and high water tolerance for practical applications.
Newly diagnosed type 2 diabetes may serve as a potential marker for pancreatic cancer
Authors: Dankner Rachel , Freedman Laurence S. , Gerstein Hertzel C. , Roth Jesse , Keinan‐Boker Lital
Published: April 2018

Pancreatic cancer has an extremely highly case fatality. Diabetes is a well‐established strong risk factor for pancreatic cancer. Compared with a nondiabetic population, we previously reported a 15‐ and 14‐fold greater risk for detecting pancreatic cancer during the first year after diagnosing diabetes in adult women and men, respectively, which dropped during the second year to 5.4‐fold and 3.5‐fold, respectively, and stabilized around 3‐fold for the rest of the 11‐year follow‐up in our historical cohort. The population attributable risk during the 11‐year period was 13.3% and 14.1% in prevalent diabetic women and men, respectively. This means that one out of about every 8 patients diagnosed with pancreatic cancer has been previously diagnosed with diabetes. The globally high prevalence of diabetes and the aggravating implications of a delayed pancreatic cancer diagnosis call for newly‐onset diabetes to be considered a potential marker for an underlying pancreatic cancer and addressed accordingly.
Synthesis, analytical characterization, and monoamine transporter activity of the new psychoactive substance 4‐methylphenmetrazine (4‐MPM), with differentiation from its ortho‐ and meta‐ positional isomers
Authors: McLaughlin Gavin , Baumann Michael H. , Kavanagh Pierce V. , Morris Noreen , Power John D. , Dowling Geraldine , Twamley Brendan , O'Brien John , Hessman Gary , Westphal Folker , Walther Donna , Brandt Simon D.
Published: April 2018

The availability of new psychoactive substances (NPS) on the recreational drug market continues to create challenges for scientists in the forensic, clinical and toxicology fields. Phenmetrazine (3‐methyl‐2‐phenylmorpholine) and an array of its analogs form a class of psychostimulants that are well documented in the patent and scientific literature. The present study reports on two phenmetrazine analogs that have been encountered on the NPS market following the introduction of 3‐fluorophenmetrazine (3‐FPM), namely 4‐methylphenmetrazine (4‐MPM), and 3‐methylphenmetrazine (3‐MPM). This study describes the syntheses, analytical characterization, and pharmacological evaluation of the positional isomers of MPM. Analytical characterizations employed various chromatographic, spectroscopic, and mass spectrometric platforms. Pharmacological studies were conducted to assess whether MPM isomers might display stimulant‐like effects similar to the parent compound phenmetrazine. The isomers were tested for their ability to inhibit uptake or stimulate release of tritiated substrates at dopamine, norepinephrine and serotonin transporters using in vitro transporter assays in rat brain synaptosomes. The analytical characterization of three vendor samples revealed the presence of 4‐MPM in two of the samples and 3‐MPM in the third sample, which agreed with the product label. The pharmacological findings suggest that 2‐MPM and 3‐MPM will exhibit stimulant properties similar to the parent compound phenmetrazine, whereas 4‐MPM may display entactogen properties more similar to 3,4‐methylenedioxymethamphetamine (MDMA). The combination of test purchases, analytical characterization, targeted organic synthesis, and pharmacological evaluation of NPS and their isomers is an effective approach for the provision of data on these substances as they emerge in the marketplace.
Cre‐driver lines used for genetic fate mapping of neural crest cells in the mouse: An overview
Authors: Debbache Julien , Parfejevs Vadims , Sommer Lukas
Published: April 2018

The neural crest is one of the embryonic structures with the broadest developmental potential in vertebrates. Morphologically, neural crest cells emerge during neurulation in the dorsal folds of the neural tube before undergoing an epithelial‐to‐mesenchymal transition (EMT), delaminating from the neural tube, and migrating to multiple sites in the growing embryo. Neural crest cells generate cell types as diverse as peripheral neurons and glia, melanocytes, and so‐called mesectodermal derivatives that include craniofacial bone and cartilage and smooth muscle cells in cardiovascular structures. In mice, the fate of neural crest cells has been determined mainly by means of transgenesis and genome editing technologies. The most frequently used method relies on the Cre‐loxP system, in which expression of Cre‐recombinase in neural crest cells or their derivatives genetically enables the expression of a Cre‐reporter allele, thus permanently marking neural crest‐derived cells. Here, we provide an overview of the Cre‐driver lines used in the field and discuss to what extent these lines allow precise neural crest stage and lineage‐specific fate mapping.
At the tipping point: Differential influences of warming and deoxygenation on the survival, emergence, and respiration of cosmopolitan clams
Authors: Kim Tae Won , Park Shinyeong , Sin Eunchong
Published: April 2018

Although warming and low dissolved oxygen (DO) levels are co‐occurring significant climatic stressors in the ocean, the combined effects of these stressors on marine benthic animals have not been well established. Here, we tested the effects of elevated temperatures and low dissolved oxygen levels on the survival, emerging behavior from sediment, and the respiration of juvenile cosmopolitan Manila clams (Venerupis philippinarum) by exposing them to two temperatures (20 and 23.5°C) and DO levels (3.5 and 6–7 mg/L). Although within previously described tolerable ranges of temperature and DO, this 3.5°C increase in temperature combined with a 50% decrease in DO had a devastating effect on the survival of clams (85% mortality after 8 days). The mortality of clams under normoxia at 23.5°C appeared to be higher than under the low DO condition at 20°C. On the other hand, more clams emerged from sediment under the low DO condition at 20°C than under any other conditions. Oxygen consumption rates were not significantly affected by different conditions. Our results suggest temperature elevation combined with low oxygen additively increases stress on Manila clams and that warming is at least as stressful as low DO in terms of mortality. However, low DO poses another threat as it may induce emergence from sediment, and, thus increase predation risk. This is the first evidence that a combination of warming and deoxygenation stressors should reduce population survival of clams much more so than changes in a single stressor.
Community differentiation of bacterioplankton in the epipelagic layer in the South China Sea
Authors: Zhang Yi , Li Jie , Cheng Xuhua , Luo Yinfeng , Mai Zhimao , Zhang Si
Published: April 2018

The South China Sea (SCS) is the largest marginal sea in the western tropical Pacific Ocean and is characterized by complex physicochemical environments. To date, the biogeographic patterns of the microbial communities have rarely been reported at a basin scale in the SCS. In this study, the bacterial assemblages inhabiting the epipelagic zone across 110°E to 119°E along 14°N latitude were uncovered. The vertical stratification of both bacterial taxa and their potential functions were revealed. These results suggest that the water depth‐specific environment is a driver of the vertical bacterioplankton distribution. Moreover, the bacterial communities were different between the eastern stations and the western stations, where the environmental conditions were distinct. However, the mesoscale eddy did not show an obvious effect on the bacterial community due to the large distance between the sampling site and the center of the eddy. In addition to the water depth and longitudinal location of the samples, the heterogeneity of the phosphate and salinity concentrations also significantly contributed to the variance in the epipelagic bacterial community in the SCS. To the best of our knowledge, this study is the first to report that the variability in epipelagic bacterioplankton is driven by the physicochemical environment at the basin scale in the SCS. Our results emphasize that the ecological significance of bacterioplankton can be better understood by considering the relationship between the biogeographic distribution of bacteria and the oceanic dynamics processes.