bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphoryl‐Transfer Reaction in RNA under Alkaline Conditions
Authors: Acosta‐Silva Carles , Bertran Joan , Branchadell Vicenç , Oliva Antoni
Published: June 2018

The phosphoryl‐transfer reaction in RNA under alkaline conditions by exploring the influence of several solvents theoretically was studied. The calculations were carried out by using the M06‐2X functional and the solvents were taken as a continuum by using the solvent model density (SMD) method. The main findings show that the O2′‐P‐O5′ angle in the reactants, the free activation energies, and the reaction mechanism are clearly dependent on the dielectric constant of the environment, thus showing that the electrostatic term is the determining factor for this chemical system with two negative charges. Our study seems to indicate that water, the solvent with the greatest dielectric constant, would be the solvent that increases the reaction rate the most. As this outcome was not the case in enzymatic catalysis, one has to conclude that, in the case of proteins as well as for ribozymes, the enzymatic catalysis is not mainly due to the solvent reaction field, but to local electrical fields as a result of enzyme preorganization.
Lewis Superacids: Classifications, Candidates, and Applications
Authors: Greb Lutz
Published: June 2018

Lewis acids play a major role in all areas of chemistry. For a long time, toxic, corrosive and oxidizing SbF5 was considered as the strongest Lewis acid known. Lately, species significantly exceeding the Lewis acidity of SbF5 have been realized and were termed Lewis superacids (LSA). Prospective new candidates emerge steadily, which not only outperform SbF5 by their strength, but also in terms of their accessibility and ease of handling. In principle, Lewis superacids allow us to combine the outstanding activity of Brønsted superacids with the excellent selectivity of a common Lewis acid. However, the broad application of Lewis superacids in synthesis is all but popular. The present review deals with strong Lewis acids. First, it critically discusses Lewis acidity scaling methods and suggests an extended definition for Lewis superacidity. It then summarizes the properties and applications of the strongest currently known Lewis acids, indexed by the fluoride ion affinity (FIA). The supporting information contains a comprehensive list of experimentally and theoretically derived FIA data as a guide for the choice of Lewis acidic reagents/catalyst. This contribution shall encourage the search for new Lewis superacids and promote their application in non‐specialized laboratories.
Triply Linked Porphyrinoids
Authors: Tanaka Takayuki , Osuka Atsuhiro
Published: June 2018

Triply linked porphyrin arrays, so called porphyrin tapes, are intriguing molecules in terms of their planar structures, far red‐shifted absorption bands, multi‐charge storage abilities, and high conductivities. Recently, porphyrin tape variants such as porphyrin‐expanded porphyrin hybrid tapes, porphyrin arch‐tapes, corrole tapes, and a subporphyrin tape have been explored as novel π‐conjugated materials. These new molecules exhibit electronic and structural characteristics owing to direct triple linkages. This Minireview first discusses the fundamental properties of the parent porphyrin tapes and the peripherally functionalized porphyrin tapes. Then, a focus has been placed on the syntheses, structures, and unique properties of the recently explored porphyrin tape variants.
Towards High Performance Metal–Organic Framework–Microporous Polymer Mixed Matrix Membranes: Addressing Compatibility and Limiting Aging by Polymer Doping
Authors: Sabetghadam Anahid , Liu Xinlei , Orsi Angelica F. , Lozinska Magdalena M. , Johnson Timothy , Jansen Kaspar M. B. , Wright Paul A. , Carta Mariolino , McKeown Neil B. , Kapteijn Freek , Gascon Jorge
Published: June 2018

Membrane separation for gas purification is an energy‐efficient and environment‐friendly technology. However, the development of high performance membranes is still a great challenge. In principle, mixed matrix membranes (MMMs) have the potential to overcome current materials limitations, but in practice there is no straightforward method to match the properties of fillers and polymers (the main components of MMMs) in such a way that the final membrane performance reflects the high performance of the microporous filler and the processability of the continuous polymer phase. This issue is especially important when high flux polymers are utilized. In this work, we demonstrate that the use of small amounts of a glassy polymer in combination with high performance PIM‐1 allow for the preparation of metal–organic framework (MOF)‐based MMMs with superior separation properties and low aging rates under humid conditions, meeting the commercial target for post‐combustion CO2 capture.
Triflimide: An Overlooked High‐Performance Catalyst of the Mukaiyama Aldol Reaction of Silyl Ketene Acetals with Ketones
Authors: Bae Han Yong , List Benjamin
Published: June 2018

The Mukaiyama aldol reaction is a widely applied carbon–carbon bond forming reaction. However, despite numerous well‐established methods using aldehydes as acceptors, only few examples exist with ketones. Here we report a highly practical catalytic approach to this transformation, namely, the triflimide catalyzed Mukaiyama aldol reaction of silyl ketene acetals with ketones. This method exhibits a broad substrate scope, is very rapid, tolerates functionalized substrates, and requires only parts‐per‐million catalyst loadings with preparative scale reactions up to hundreds of grams in excellent purity (>99 %).
Synthesis and Antiviral Evaluation of TriPPPro‐AbacavirTP, TriPPPro‐CarbovirTP, and Their 1′,2′‐cis‐Disubstituted Analogues
Authors: Weising Simon , Sterrenberg Vincente , Schols Dominique , Meier Chris
Published: June 2018

Herein we describe the synthesis of lipophilic triphosphate prodrugs of abacavir, carbovir, and their 1′,2′‐cis‐substituted carbocyclic analogues. The 1′,2′‐cis‐carbocyclic nucleosides were prepared by starting from enantiomerically pure (1R,2S)‐2‐((benzyloxy)methyl)cyclopent‐3‐en‐1‐ol by a microwave‐assisted Mitsunobu‐type reaction with 2‐amino‐6‐chloropurine. All four nucleoside analogues were prepared from their 2‐amino‐6‐chloropurine precursors. The nucleosides were converted into their corresponding nucleoside triphosphate prodrugs (TriPPPro approach) by application of the H‐phosphonate route. The TriPPPro compounds were hydrolyzed in different media, in which the formation of nucleoside triphosphates was proven. While the TriPPPro compounds of abacavir and carbovir showed increased antiviral activity over their parent nucleoside, the TriPPPro compounds of the 1′,2′‐cis‐substituted analogues as well as their parent nucleosides proved to be inactive against HIV.
Generation of Vanadium Oxide Quantum Dots with Distinct Fluorescence and Antibacterial Activity via a Room‐Temperature Agitation Strategy
Authors: Huang Lei , Niu Yusheng , Xu Gengfang , Wang Yao , Yuan Lili , Xu Yuanhong , Li Ronggui
Published: June 2018

Vanadium oxide (VOx) nanomaterials have been attracting great attention recently due to their outstanding physicochemical properties. Engineering VOx into quantum dots (QDs) should bring new properties and potential for applications, but has not been reported until now. Meanwhile, the shortcomings in QDs synthesis such as needing high temperature and expensive instruments still need to be overcome. Herein, VOxQDs were generated via a simple ultrasonic and agitation strategy at room temperature using DMSO as both solvent and exfoliation agent. The VOx QDs exhibited blue fluorescence under 365 nm ultraviolet irradiation. They were with good monodispersion, narrow size distribution and average particle size of 3.3±0.3 nm. The VOxQDs can be used as a competitive fluorescent sensing probe for label‐free specific detection of Fe3+ and PPi based on the ON‐OFF or ON‐OFF‐ON fluorescent principle, respectively. Moreover, the antibacterial activity of the as‐prepared VOxQDs was found, which could damage the cell membrane and inhibit the bacterial growth of both Gram (+) (Staphylococcus aureus) and Gram (−) (Escherichia coli) bacteria, respectively.
Mitochondrial Subtype Identification and Characterization
Authors: Daniele Joseph R. , Heydari Kartoosh , Dillin Andrew
Published: June 2018

Healthy, functional mitochondria are central to many cellular and physiological phenomena, including aging, metabolism, and stress resistance. A key feature of healthy mitochondria is a high membrane potential (Δψ) or charge differential (i.e., proton gradient) between the matrix and inner mitochondrial membrane. Mitochondrial Δψ has been extensively characterized via flow cytometry of intact cells, which measures the average membrane potential within a cell. However, the characteristics of individual mitochondria differ dramatically even within a single cell, and thus interrogation of mitochondrial features at the organelle level is necessary to better understand and accurately measure heterogeneity. Here we describe a new flow cytometric methodology that enables the quantification and classification of mitochondrial subtypes (via their Δψ, size, and substructure) using the small animal model C. elegans. Future application of this methodology should allow research to discern the bioenergetic and mitochondrial component in a number of human disease and aging models, including, C. elegans, cultured cells, small animal models, and human biopsy samples. © 2018 by John Wiley & Sons, Inc.
Synthesis of Bare Iron Nanoparticles from Ferrocene Hexane Solution by Femtosecond Laser Pulses
Authors: Okamoto Takuya , Nakamura Takahiro , Kihara Ryo , Asahi Tsuyoshi , Sakota Kenji , Yatsuhashi Tomoyuki
Published: June 2018

Iron‐based nanoparticles (FeNPs) have unique and attractive properties such as superparamagnetism, biocompatibility, and catalytic activity. Although the synthesis of precious metal NPs from a metal in liquid and/or metal salt solution by a pulsed laser has been investigated, comparably little effort has been devoted to examine the production of FeNPs. Here we report the synthesis of carbon‐shell free spherical NPs of iron oxide (magnetite) from ferrocene hexane solution by femtosecond near infrared laser pulses. Nanosecond UV laser pulses are used to compare the evolution of the particle size distribution as a function of laser irradiation time. The size of NPs remains constant even for extended exposure to femtosecond laser pulses, whereas it grows with exposure to nanosecond laser pulses. The primary particles are generated by photochemical reactions regardless of pulse duration; however, the fragmentation of NPs by successive femtosecond laser pulses regulates the particle size.
Monolayer AsTe2: Stable Robust Metal in 2D, 1D and 0D
Authors: Badalov S. V. , Kandemir A. , Sahin H.
Published: June 2018

The structural, phononic, and electronic properties of the monolayer structures of AsTe2 are characterized by performing density functional theory (DFT) calculations. Total energy optimization and phonon calculations reveal that single layers of the 2H‐AsTe2 and 1T‐AsTe2 phases form dynamically stable crystal structures. Electronic structure analysis also shows that both 2H and 1T phases have nonmagnetic metallic character. It is also predicted that the metallic nature of the ultra‐thin both 2H‐AsTe2 and 1T‐AsTe2 structures remain unchanged even under high biaxial strain values. For further examination of the dimensionality effect in the robust metallicity in 2D AsTe2 phases, electronic characteristics of 1D nanoribbons and 0D quantum dots are also investigated. It is found that independent from the dimension and crystallographic orientations 0D and 1D structures of 2H‐ and 1T‐AsTe2 structures have metallic behavior. It is found that single layers of AsTe2 are quite promising materials for nanodevice applications owing to the robust metallic character.
Enhancement of Thermodynamic Gas‐Phase Acidity and Basicity of Water by Means of Secondary Interactions
Authors: Montero‐Campillo M. Merced , Alkorta Ibon , Elguero José
Published: June 2018

A series of A⋅water, B⋅water complexes (A=acid, B=base) are studied at the G4 level of theory to show that water acidity or basicity can be modulated by non‐covalent interactions. Protic and non‐protic acids interacting with water form hydrogen bonds or other kinds of non‐covalent interactions, respectively, that may dramatically change the acidity of water up to almost 360 kJ ⋅ mol−1 in terms of enthalpy. Similarly, hydrogen bonds responsible for the interaction between typical small nitrogen‐containing Lewis bases and water can enhance the proton affinity of water by almost 300 kJ ⋅ mol−1. Our results reveal that these large enhancements are linearly related with the binding energy of the charged complexes, and are determined by the Lewis acid−base properties of the molecule involved in the interaction, allowing a quite precise modulation of the corresponding acid−base properties of water.
A Compact Head‐Mounted Endoscope for In Vivo Calcium Imaging in Freely Behaving Mice
Authors: Jacob Alexander D. , Ramsaran Adam I. , Mocle Andrew J. , Tran Lina M. , Yan Chen , Frankland Paul W. , Josselyn Sheena A.
Published: June 2018

Miniaturized fluorescence microscopes for imaging calcium transients are a promising tool for investigating the relationship between behavior and population‐level neuronal activity in rodents. However, commercially available miniature microscopes may be costly and, because they are closed source, may not be easily modified based on particular experimental requirements. Here, we describe how to build and use a low‐cost compact head‐mounted endoscope (CHEndoscope) system for in vivo calcium imaging. The CHEndoscope uses an implanted gradient index lens along with the genetically encoded calcium indicator GCaMP6 to image calcium transients from hundreds of neurons simultaneously in awake behaving mice. This system is affordable, open source, and flexible, permitting modification depending on the particular experiment. This article describes in detail the assembly, surgical implantation, data collection, and processing of calcium signals using the CHEndoscope system. The aim of this open framework is to provide an accessible set of miniaturized calcium imaging tools for the neuroscience research community. © 2018 by John Wiley & Sons, Inc.
New 3D Supramolecular Ag(I) Coordination Polymer Crystal Containing 2‐Quinaldic Acid Radical Biological Ligand: Crystal Structure and Anticancer Activity
Authors: Wang Ren‐Shu , Feng Jing , Lei Yi‐Zhu , Chen Ding‐Mei , Lian Ming‐Lei
Published: June 2018

A new coordination polymer of {[Ag(Qina)(Bpp)]·(H2O)2}n (Qina = 2‐quinolinecarboxylic‐carboxylate, Bpp = 4,4'‐trimethylenedipyridine) is successfully synthesized and the structure is determined using single crystal X‐ray diffraction. The complex is crystallized in the monoclinic system with P21/c space group: Each atom of Ag(I) is chelated by one Qina group, with each Bpp ligand bridging two Ag(I) atoms to form the 1D polymer chains. Furthermore, the 3D supramolecular architecture is a costructure directed via weak stacking interactions of C–H···π and hydrogen bond. The complex shows competitive binding affinities in calf thymus DNA (ct‐DNA) interaction by fluorescence spectroscopy. In addition, the complexes’ cytotoxic activity is explored for two kinds of cancer cell lines (Hela, MCF‐7), indicating an anticancer activity and cytotoxicity. CCDC: 1553426
Effects of Electrolyte Anions on the Reduction of Carbon Dioxide to Ethylene and Ethanol on Copper (100) and (111) Surfaces
Authors: Huang Yun , Ong Cheng Wai , Yeo Boon Siang
Published: June 2018

The CO2 electroreduction reaction has been investigated on Cu(100) and Cu(111) surfaces in 0.1 m aqueous solutions of KClO4, KCl, KBr, and KI electrolyte. The formation of ethylene and ethanol on these surfaces generally increased as the electrolyte anion was changed from ClO4−→Cl−→Br−→I−. For example, on Cu(100) at −1.23 V versus RHE, as the electrolyte anion changed from ClO4− to I−, the faradaic efficiency (FE) of ethylene formation increased from 31 to 50 %, FEethanol increased from 7 to 16 %, and the associated current densities increased five‐ and sevenfold, respectively. A remarkable total FE of up to 74 % for C2 and C3 products was obtained in the presence of KI. Despite surface roughening in the presence of the electrolytes, the Cu(100) electrode still enhanced the formation of C2 compounds better than Cu(111). The favorable reduction of CO2 to C2 products in KI electrolyte was correlated with a higher *CO population on the surface, as shown using linear sweep voltammetry. In situ Raman spectroscopy indicated that the coordination environment of *CO was altered by the used electrolyte anion. Thus, apart from affecting the morphology of the electrode and local pH value, we propose that the anion plays a critical role in enhancing the formation of C2 products by tuning the coordination environment of adsorbed *CO, which gives rise to more efficient C−C coupling.
Partially Etched Ti3AlC2 as a Promising High‐Capacity Lithium‐Ion Battery Anode
Authors: Chen Xifan , Zhu Yuanzhi , Zhu Xiaoquan , Peng Wenchao , Li Yang , Zhang Guoliang , Zhang Fengbao , Fan Xiaobin
Published: June 2018

MXenes, a family of two‐dimensional transition‐metal carbide and nitride materials, are thought to be promising materials in energy storage because of their high electronic conductivity, hydrophilic surfaces, and low diffusion barriers. MXenes are generally prepared by removing the “A” elements (A=Al, Si, Sn, etc.) from their corresponding MAX phases by using hydrofluoric acid (HF) and other etching agents, although these “A” elements usually have great volumetric and gravimetric capacities. In a study of the etching progress of Ti3AlC2 and evaluation of their anode performance in lithium‐ion batteries, a partially etched sample (0.5 h‐pe Ti3C2Tx) is found to have much higher capacity (160 mAh g−1, 331.6 mAh cm−3 at 1C) when compared with the fully etched Ti3C2Tx (110 mAh g−1, 190.3 mAh cm−3 at 1C). Moreover, a 99 % capacity retention was observed even after 1000 cycles in the 0.5 h‐pe Ti3C2Tx anode. This interesting result can be explained, at least in part, by the alloying of the residual Al during lithiation.
On the problems of using linear models in ecological manipulation experiments: lessons learned from a climate experiment
Authors: Damgaard Christian , Holmstrup Martin , Schmidt Inger Kappel , Beier Claus , Larsen Klaus Steenberg
Published: June 2018

Manipulation experiments are often used to investigate ecological and environmental causal relationships and to understand and forecast impacts of anthropogenic pressures on ecosystem functioning. Such manipulation experiments often use factorial designs, and the data are analyzed using factorial linear models. Factorial designs build on the fundamental assumption that the treatment factors are independent and orthogonal. This assumption is, however, often violated because of variation within and in particular covariation between the performed experimental manipulations. For example, manipulation of temperature and precipitation in factorial setups has been widely applied in climate experiments, but manipulating soil temperature will likely have a strong impact on soil water content. Such dependency among environmental state variables will violate the assumed orthogonality in a factorial linear model and may lead to erroneous conclusions. Here, we demonstrate the importance of the assumption of orthogonality using simulated ecological responses that act on observed soil state variables from a large climate experiment with an apparent orthogonal design. More specifically, we explore the problematic consequences of analyzing ecological treatments as categorical variables in a linear model. Suitable alternative methods for the statistical analysis of manipulated ecological experiments are suggested. The key recommendation is to use the observed effects of the manipulations on the state variables directly in the analysis instead of the categories of treatments. For example, if soil water content and temperature are manipulated, then it is essential to measure the water content and temperature in the soil of all the manipulated plots.
Multi‐ethnic comparisons of diabetes in heart failure with reduced ejection fraction: insights from the HF‐ACTION trial and the ASIAN‐HF registry
Authors: Cooper Lauren B. , Yap Jonathan , Tay Wan Ting , Teng Tiew‐Hwa K. , MacDonald Michael , Anand Inder S. , Sharma Abhinav , O'Connor Christopher M. , Kraus William E. , Mentz Robert J. , Lam Carolyn S. ,   on behalf of the HF‐ACTION and ASIAN‐HF Investigators
Published: June 2018

Aim

To describe differences in patient characteristics and outcomes by ethnicity in patients with diabetes mellitus (DM) and heart failure (HF) with reduced ejection fraction (HFrEF, ejection fraction ≤35%) in a multi‐ethnic cohort.

Methods and results

Patient level data from two cohorts (HF‐ACTION and ASIAN‐HF) were combined, and patients grouped by self‐reported ethnicity. DM was defined as the presence of a clinical diagnosis and/or receiving anti‐diabetic therapy. A total of 6214 (1324 whites, 674 blacks, 1297 Chinese, 1510 Indians, 717 Malays, 692 Japanese/Koreans) patients were included. The overall prevalence of DM was 39.5% (n = 2454). The prevalence of DM was lowest in whites (29.3%), followed by Japanese/Koreans (34.1%), blacks (35.9%), Chinese (42.3%), Indians (44.2%), and highest in Malays (51.9%). The correlation between age, sex, body mass index, coronary artery disease, hypertension, atrial fibrillation, peripheral vascular disease and chronic kidney disease with DM differed significantly by ethnicity (P for interaction <0.05). The strongest correlations were seen in Malay women, whites with obesity, Indians with coronary artery disease and hypertension, and blacks with chronic kidney disease. On multivariable analyses, DM was significantly associated with the composite of 1‐year overall mortality/HF hospitalization (hazard ratio 1.37, 95% confidence interval 1.19–1.57; P < 0.001), with no interaction by ethnicity (P for interaction =0.31).

Conclusions

There is marked heterogeneity in the prevalence and correlates of DM among different ethnic groups with HF worldwide. Subgroups particularly predisposed to DM warrant special attention, since DM increases the combined risk of morbidity and mortality in all ethnicities with HF.
Family physician remuneration schemes and specialist referrals: Quasi‐experimental evidence from Ontario, Canada
Authors: Sarma Sisira , Mehta Nirav , Devlin Rose Anne , Kpelitse Koffi Ahoto , Li Lihua
Published: June 2018

Understanding how family physicians respond to incentives from remuneration schemes is a central theme in the literature. One understudied aspect is referrals to specialists. Although the theoretical literature has suggested that capitation increases referrals to specialists, the empirical evidence is mixed. We push forward the empirical research on this question by studying family physicians who switched from blended fee‐for‐service to blended capitation in Ontario, Canada. Using several health administrative databases from 2005 to 2013, we rely on inverse probability weighting with fixed‐effects regression models to account for observed and unobserved differences between the switchers and nonswitchers. Switching from blended fee‐for‐service to blended capitation increases referrals to specialists by about 5% to 7% per annum. The cost of specialist referrals is about 7 to 9% higher in the blended capitation model relative to the blended fee‐for‐service. These results are generally robust to a variety of alternative model specifications and matching techniques, suggesting that they are driven partly by the incentive effect of remuneration. Policy makers need to consider the benefits of capitation payment scheme against the unintended consequences of higher referrals to specialists.
Home enteral nutrition: Use of photo‐elicitation to capture patient and caregiver experiences
Authors: Asiedu Gladys B. , Carroll Katherine , Griffin Joan M. , Hurt Ryan T. , Mundi Manpreet
Published: June 2018

Background

Despite the importance of home enteral nutrition (HEN), there is a lack of understanding within the medical and general community of how HEN impacts the lives of patients and caregivers. Using a theoretical orientation that attends to the materiality of both everyday and medical objects, we explored patients' and family caregivers' everyday experiences of administering feeds during HEN.

Methods

Using the photo‐elicitation interviewing method, patients on HEN and their family caregivers were asked to take up to 10 photographs to portray material items and activities that they considered foundational to HEN. They subsequently narrated their experiences and the participant‐generated photographs in an interview. Participant‐generated photographs (126) and accompanying narratives were analyzed using layered analysis, and results were theorized with attention to both social and material significance of HEN.

Results

Patients and caregivers detailed overcoming misconceptions of HEN, and through their use of photographs, they conveyed their expertise in developing their own HEN feeding systems and practices, that used both the material artifacts provided by the hospital (the tube, syringe, and formula) as well as everyday material items found in the patient's home. More than this, photographs and patient narratives depicted intimate involvement of patients' families in tube feeding. This yielded a more comprehensive understanding of the material and experiential realities of HEN.

Conclusion

Home enteral nutrition was found to be a shared familial experience, that in addition to requiring medical equipment also incorporated ordinary material artifacts within the social setting of the home and family life. To more accurately convey the material, experiential, and social realities of HEN to future patients, our findings underscore the importance of drawing on both visual and textual forms of patient‐produced information in the development of HEN patient educational materials.
Inhaled corticosteroids in COPD and the risk of lung cancer
Authors: Lee Yu Min , Kim Soo Jung , Lee Jin Hwa , Ha Eunhee
Published: June 2018

Inhaled corticosteroids (ICS) might reduce the risk of lung cancer by controlling airway inflammation in patients with chronic obstructive pulmonary disease (COPD) because both are associated with chronic inflammation. The objective was to assess the impact of ICS on lung cancer risk reduction in COPD patients. We performed a nested case–control study based on the database of the National Health Insurance Service–National Sample Cohort, a nationally representative cohort of 1,125,691 participants in Korea followed over 11 years. The eligible population was patients aged 30–89 years who were newly diagnosed with COPD and initiated inhaled medications after diagnosis. Cases were defined as individuals diagnosed with lung cancer after the initiation of inhaled medications and were matched with controls by propensity score at a 1:4 ratio. We identified 265 individuals with lung cancer, matched with 1,060 controls. Use of ICS was associated with reduced risk of lung cancer (adjusted hazard ratio [aHR] 0.74, 95% CI 0.57–0.96). The high cumulative ICS dose group, defined as those above the third quartile of ICS dose distribution, had a lower risk of lung cancer than the low cumulative dose group (aHR 0.51, 95% CI 0.34–0.75). The effect of ICS on lung cancer risk reduction was more remarkable in former smokers than current smokers. Additionally, the result was consistent in men regardless of the classification according to ICS use, while it was not significant in women. ICS, particularly at high cumulative dose, might be associated with decreased risk of lung cancer in patients with COPD. Severe COPD frequently warrants treatment with inhaled corticosteroids, which exert immunomodulatory and antiproliferative effects. Despite an association between COPD and increased lung cancer risk, patients on ICS appear to have a reduced likelihood of developing lung cancer. Here, analyzing data from the National Health Insurance Service–National Sample Cohort in Korea, the authors show that ICS use is associated with decreased lung cancer risk in COPD patients. An inverse dose–response relationship was detected, whereby increasing cumulative ICS dose was associated with decreasing lung cancer risk. The effect was most pronounced in men and former smokers.
The Enduring Value of Study Skills
Authors: Fisher Douglas , Frey Nancy
Published: June 2018

This forum highlights research that literacy teachers, students, and others can explore, use, or adapt as they provide literacy instruction and develop related programs and research agendas.
Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review
Authors: Flores‐López Lucía Z. , Espinoza‐Gómez Heriberto , Somanathan Ratnasamy
Published: June 2018

The industry of nanotechnology has had a rapid development in the last decades. In particular, silver nanoparticles (AgNPs) have unique properties so they can be used in different industrial applications, mainly in areas such as electronics, environment, medicine, biosensors and biotechnology; as well as household and healthcare‐related products, like cosmetics, due to their antimicrobial properties. These beneficial effects are also offset by the higher chemical reactivity of these NPs due to their surface area to volume ratio, leading to the increased formation of reactive oxygen species (ROS) within cells. AgNPs, however, have a dark side: they increase the formation of reactive oxygen species (ROS). With increased human exposure to AgNPs, the risk and safety standards have attracted much attention. This review highlights the beneficial and toxicological effects of AgNPs in terms of cytotoxicity and genotoxicity.
Pathological cyclic strain promotes proliferation of vascular smooth muscle cells via the ACTH/ERK/STAT3 pathway
Authors: Tang Xia , Liu Yanyan , Xiao Qian , Yao Qingping , Allen Molly , Wang Yingxiao , Gao Lizhi , Qi Yingxin , Zhang Ping
Published: June 2018

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related to hyperplasia in hypertension. Our previous study suggested that adrenocorticotropic hormone (ACTH) is mechano‐responsive and may regulate VSMC proliferation. However, the molecular mechanism of VSMC abnormal proliferation induced by conditions of high cyclic strain, especially the role of ACTH in this process, is unclear. Our results revealed that ACTH and its specific receptor melanocortin receptor type 2 (MC2R) were highly expressed in hypertensive rat models. Furthermore, it was demonstrated that the expression of ACTH and MC2R was up‐regulated when exposed to high cyclic strain in vitro, accompanied by abnormal proliferation of VSMCs. Next, it was proved that ACTH‐dependent cell proliferation was related to the phosphorylation of extracellular regulated protein kinases (ERK) and signal transducer and activator of transcription 3 (STAT3). The study also found that ACTH could promote dimerization and glycosylation of melanocortin 2 receptor accessory protein (MRAP), which had a significant effect on MC2R membrane localization and signal activation. When VSMCs were treated with PD98059, a mitogen‐activated protein kinase (MAP kinase) cascade antagonist, it was determined that phosphorylation of STAT3 at Ser727 was dependent on ERK phosphorylation. In summary, these data demonstrated that the abnormal proliferation of VSMCs induced by conditions of high cyclic strain is in part attributed to ACTH and its receptor MC2R. Identifying the mechanism of ACTH‐dependent proliferation of VSMCs may help to provide new therapeutic targets for hypertension.
A novel molecular mechanism of microRNA‐21 inducing pulmonary fibrosis and human pulmonary fibroblast extracellular matrix through transforming growth factor β1–mediated SMADs activation
Authors: Zhou Jun , Xu Qianqian , Zhang Qiudi , Wang Zhigang , Guan Shuhong
Published: June 2018

Pulmonary fibrosis (PF), characterized by the destruction of lung tissue architecture and the abnormal deposition of extracellular matrix (ECM) proteins, currently has no satisfactory treatment. The role of microRNA (miR)‐21 in PF has been reported; the current study attempted to investigate a novel molecular mechanism by which miR‐21 exerted its function. Consistent with previous studies, miR‐21 inhibition reduced ECM protein levels in bleomycin (BLM)‐induced mouse model of PF. In human pulmonary fibroblast (IMR‐90), miR‐21 inhibition reduced transforming growth factor β1 (TGFβ1)–induced ECM protein expression. Regarding a novel molecular mechanism, TGFβ1 combined with TGFβ1 receptor 1 (TGFβ1RI) to activate SMAD2/3, promote SMAD4 nucleus transformation, and thus regulate miR‐21 expression and ECM. SMAD3 and SMADs complex could bind to the promoter region of miR‐21 to promote miR‐21 expression. In conclusion, miR‐21 exerts promotive effects on BLM‐induced PF and TGFβ1‐induced ECM in IMR‐90; TGFβ1 combines with TGFβ1RI to activate SMAD2/3, promote SMAD4 nucleus transformation, promote miR‐21 expression, and thus to promote BLM‐induced PF and TGFβ1‐induced ECM in IMR‐90 cells.
Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics
Authors: Esmaeili Seyed‐Alireza , Mahmoudi Mahmoud , Rezaieyazdi Zahra , Sahebari Maryam , Tabasi Nafiseh , Sahebkar Amirhossein , Rastin Maryam
Published: June 2018

Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interleukin 4 (IL‐4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM‐CSF and IL‐4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen‐antigen D Related (HLA‐DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3‐dioxygenase (IDO), IL‐10, and IL‐12 were measured using real‐time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic‐induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)‐induced MDCs. In addition, the expression of IDO and IL‐10 increased, whereas IL‐12 decreased significantly in probiotic‐induced MDCs compared with LPS‐induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis.
Increased plasma prothrombin time is associated with poor prognosis in patients with paraquat poisoning
Authors: Hu Xiao , Guo Renyong , Chen Xing , Chen Yu
Published: June 2018

Background

Paraquat can cause severe injury to vascular endothelial cells and lead to coagulation dysfunction when it is taken into the blood by oral ingestion. In this study, we aim to find a routine coagulation index to serve as an indicator of outcome in patients with acute paraquat poisoning.

Methods

Between January 2012 and December 2016, 209 patients who attempted suicide by oral ingestion of paraquat were admitted to the emergency room. Routine coagulation indices, including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), thrombin time (TT), and D‐dimer were measured to analyze the trend of changes and their relationship with prognosis.

Results

The results showed that the PT and APTT values in the ≥30 mL group were significantly greater than those in the <30 mL group (both P < .01). Within 1 week of admission, PT and APTT values gradually decreased, while Fbg levels gradually increased. Univariate and multivariate Cox regression analysis indicated that sex, ingestion volume, and PT were independent predictors of mortality within 40 days. The cumulative survival rates differed significantly (P = .001) between patients with PT <12 seconds and PT ≥12 seconds.

Conclusions

Coagulation status in patients with PQ poisoning was closely related to prognosis. Routine monitoring of coagulation function, particularly PT in plasma, is helpful for analysis of the condition and prognosis of patients with PQ poisoning.
Cleavage of caspase‐12 at Asp94, mediated by endoplasmic reticulum stress (ERS), contributes to stretch‐induced apoptosis of myoblasts
Authors: Song Jing , Zhang Qiang , Wang Shuai , Yang Fang , Chen Zhenggang , Dong Quanjiang , Ji Qiuxia , Yuan Xiao , Ren Dapeng
Published: June 2018

Mechanical overloading can lead to skeletal muscle damage instead of remodeling. This is attributed to the excessive apoptosis of myoblasts, mechanism of which remains to be elucidated. The present study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) and caspase‐12 in mediating the stretch‐induced apoptosis of myoblasts. Myoblast apoptosis was evaluated by Hoechst staining, DNA fragmentation assay, Annexin V binding, and propidium iodide staining, as well as caspase‐3 and poly‐ADP‐ribose polymerase 1 cleavage. First, our results showed that apoptosis was elevated in a time‐dependent manner when myoblasts were subjected to cyclic mechanical stretch (CMS) for 12, 24, and 36 hr. Concomitantly, CMS triggered the ERS and caspase‐12 cleavage; ERS inhibitor GSK 2606414 suppressed the CMS‐induced cleavage of caspase‐12 and myoblast apoptosis. Silencing caspase‐12 attenuated the apoptosis of myoblasts under CMS. Furthermore, CMS‐induced myoblast apoptosis was partially recovered by overexpressing wild‐type caspase‐12 in caspase‐12‐silenced myoblasts. In contrast, overexpressing mutant caspase‐12 (D94N), which cannot be cleaved into the active caspase‐12 fragments, failed to accomplish the same effect. Finally, C2C12 overexpressing truncated caspase‐12 segment (TC‐casp12‐D94), which starts from Asp94 and ends at Asn419, underwent apoptosis under both static and stretched conditions. Interestingly, C2C12 myoblasts seemed to be resistant to stretch‐induced apoptosis upon low‐serum‐induced differentiation. In conclusion, our study provided evidence that caspase‐12 cleavage at Asp94, induced by ERS under mechanical stimuli, is the key molecule in initiating the stretch‐triggered apoptosis of myoblasts.
BMAL1 and CLOCK proteins in regulating UVB‐induced apoptosis and DNA damage responses in human keratinocytes
Authors: Sun Yang , Wang Peiling , Li Hongyu , Dai Jun
Published: June 2018

A diverse array of biological processes are under circadian controls. In mouse skin, ultraviolet ray (UVR)‐induced apoptosis and DNA damage responses are time‐of‐day dependent, which are controlled by core clock proteins. This study investigates the roles of clock proteins in regulating UVB responses in human keratinocytes (HKCs). We found that the messenger RNA expression of brain and muscle ARNT‐like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) genes is altered by low doses (5 mJ/cm2) of UVB in the immortalized HaCat HKCs cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation of Rad3‐related protein kinases–checkpoint kinase 1–p53 mediated DNA damage checkpoints, it leads to suppression of UVB‐stimulated apoptotic responses, and downregulation of UVB‐elevated expression of DNA damage marker γ‐H2AX and cell cycle inhibitor p21. Diminished apoptotic responses are also observed in primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK depletion shows a suppressive effect on UVB‐induced p53 protein accumulation, depletion of either clock gene triggers early keratinocyte differentiation of HKCs at their steady state. These results suggest that UVB‐induced apoptosis and DNA damage responses are controlled by clock proteins, but via different mechanisms in the immortalized human adult low calcium temperature and primary HKCs. Given the implication of UVB in photoaging and photocarcinogenesis, mechanistic elucidation of circadian controls on UVB effects in human skin will be critical and beneficial for prevention and treatment of skin cancers and other skin‐related diseases.
Fibroblasts and mesenchymal stem cells: Two sides of the same coin?
Authors: Soundararajan Mathangi , Kannan Suresh
Published: June 2018

Mesenchymal stem/stromal cells (MSCs) have gained considerable popularity owing to the vast possibilities and lack of ethical constraints and risks normally associated with other stem cells, such as embryonic stem cells. However, they are morphologically indistinguishable from fibroblasts. This review aims to assess the similarities and differences between the two cell types, and the possible relationship between them. We found that the two cells seem almost identical with respect to their surface immunophenotype, proliferation, and differentiation capacities and even, to an extent, their gene expression profiles and immunomodulatory capacities. There are some differences in capability between the two cells, with MSCs being more efficient than fibroblasts. Even so, the similarities are so striking, that, if we were to follow the current criteria provided by the International Society for Cellular Therapy, fibroblasts ought to be named as MSCs. One promising marker is their DNA methylation profiles. Nonetheless, without any other marker to differentiate between the cells in the first place, it would be difficult to find a definitive marker. Interestingly, the differences observed between the two cells have also been observed between young and old MSCs. This also seems to be true of certain cell surface markers. Therefore, it is possible that fibroblasts are in fact aged MSCs and that the two cells are the same.
PMLIV overexpression promotes TGF‐β‐associated epithelial–mesenchymal transition and migration in MCF‐7 cancer cells
Authors: Liu Yu , Wang Jia‐Xin , Huang Di , Wang Bing , Li Liang‐Liang , Li Xiu‐Xian , Ni Ping , Dong Xing‐Li , Xia Wei , Yu Chun‐Xiao , Xu Wan‐Lu , Chu Wen‐Feng , Zhao Dan
Published: June 2018

The epithelial–mesenchymal transition (EMT) is a key event associated with metastasis and dissemination in breast tumor pathogenesis. Promyelocytic leukemia (PML) gene produces several isoforms due to alternative splicing; however, the biological function of each specific isoform has yet to be identified. In this study, we report a previously unknown role for PMLIV, the most intensely studied nuclear isoform, in transforming growth factor‐β (TGF‐β) signaling‐associated EMT and migration in breast cancer. This study demonstrates that PMLIV overexpression promotes a more aggressive mesenchymal phenotype and increases the migration of MCF‐7 cancer cells. This event is associated with activation of the TGF‐β canonical signaling pathway through the induction of Smad2/3 phosphorylation and the translocation of phospho‐Smad2/3 to the nucleus. In this study, we report a previously unknown role for PMLIV in TGF‐β signaling‐induced regulation of breast cancer‐associated EMT and migration. Targeting this pathway may be therapeutically beneficial.
P2Y12 shRNA treatment decreases SGC activation to relieve diabetic neuropathic pain in type 2 diabetes mellitus rats
Authors: Wang Shouyu , Wang Zilin , Li Lin , Zou Lifang , Gong Yingxin , Jia Tianyu , Zhao Shanhong , Yuan Huilong , Shi Liran , Liu Shuangmei , Wu Bing , Yi Zhihua , Liu Hui , Gao Yun , Li Guilin , Deussing Jan M. , Li Man , Zhang Chunping , Liang Shangdong
Published: June 2018

Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus (DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in neuropathic pain through the release of proinflammatory cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our aim was to investigate the role of the P2Y12 receptor on the pathological changes in diabetic neuropathic pain. The present study showed that diabetic neuropathic pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The results showed that the expression levels of P2Y12 messenger RNA (mRNA) and protein in DRG SGCs were increased in DM model rats compared with control rats. Glial fibrillary acidic protein (GFAP) and interleukin‐1β (IL‐1β) expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA (shRNA) decreased the upregulated expression of P2Y12 mRNA and protein, coexpression of P2Y12 and GFAP, the expression of GFAP, IL‐1β, and tumor necrosis factor‐receptor 1 in the DRG of DM rats, and relieved mechanical and thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA, the enhancing integrated OPTICAL density (IOD) ratios of p‐P38 MAPK to P38 mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA were significantly lower than that in the untreated DM rats. Therefore, P2Y12 shRNA treatment decreased SGC activation to relieve mechanical and thermal hyperalgesia in DM rats.
Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease
Authors: Gouzi Fares , Blaquière Marine , Catteau Matthias , Bughin François , Maury Jonathan , Passerieux Emilie , Ayoub Bronia , Mercier Jacques , Hayot Maurice , Pomiès Pascal
Published: June 2018

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3‐methyladenine (3‐MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3‐MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS‐induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.