bluuebunny/crossref_metadata_2025_split huggingface dataset:
microRNA‐34a aggravates coxsackievirus B3‐induced apoptosis of cardiomyocytes through the SIRT1‐p53 pathway
Authors: Jiang Dehua , Li Minghui , Yu Ying , Shi Hui , Chen Ruizhen 
Published: April 2019

AbstractViral myocarditis is inflammation of the myocardium mainly caused by a viral infection, and coxsackievirus B3 (CVB3) infection is one of the most common. It is well known that cardiomyocyte apoptosis is involved in the pathogenesis of viral myocarditis. microRNAs (miRNAs, miRs) are endogenous noncoding oligoribonucleotides involved in various pathological conditions, and miR‐34a is one of the miRNAs causing apoptosis. Whether miR‐34a participates in cardiomyocyte apoptosis during CVB3 infection and the underlying mechanisms is still unclear. In this in vitro study, we found that miR‐34a expression increased in cardiomyocytes after CVB3 infection. Furthermore, we found that CVB3 infection augmented histone deacetylase 1 (HDAC1) and Bax expression while inhibiting sirtuin 1 (SIRT1) and Bcl‐2 expression, along with the acetylated p53 (Ac‐p53) upregulation in cardiomyocytes. The above‐mentioned phenomenon was reversed by a miR‐34a inhibitor after CVB3 infection. In addition, the Ac‐p53 amount increased in CVB3‐infected cardiomyocytes, and SRT1720 and trichostatin A (TSA) pretreatment decreased Ac‐p53 levels. After pifithrin‐α pretreatment of CVB3‐infected cardiomyocytes, the protein expression level of HDAC1 decreased while that of SIRT1 increased. Moreover, miR‐34a expression and CVB3‐induced apoptosis of cardiomyocytes were attenuated by pretreatment with SRT1720, TSA, or pifithrin‐α, accompanied with Bax downregulation and Bcl‐2 upregulation. In summary, these data indicate that miR‐34a induces cardiomyocyte apoptosis by downregulating SIRT1, and the activation of the SIRT1‐p53 pathway contributes to CVB3‐induced apoptosis of cardiomyocytes. Thus, miR‐34a might serve as a potential therapeutic target because it promotes cardiomyocyte apoptosis through the SIRT1‐p53 signaling pathway.
Long noncoding RNA TSPOAP1 antisense RNA 1 negatively modulates type I IFN signaling to facilitate influenza A virus replication
Authors: Wang Qi , Zhang Daining , Feng Wenjing , Guo Yidi , Sun Xiaoning , Zhang Maolin , Guan Zhenhong , Duan Ming 
Published: April 2019

AbstractAlthough the expression of thousands of host long noncoding RNAs (lncRNAs) can be regulated by viral infection, the number of lncRNAs with experimentally verified function is limited. In this study, the expression of host lncRNA TSPOAP1‐AS1 was significantly induced by influenza A virus (IAV) infection in a dose‐ and time‐dependent manner. Polyinosine‐polycytidylic acid (﻿p﻿﻿oly (I:C))﻿, a synthetic analog of double‐stranded RNA, also increased TSPOAP1‐AS1 expression. RNA fractionation revealed that TSPOAP1‐AS1 was a nucleocytoplasmic lncRNA, and an increased nuclear/cytoplasmic ratio was detected after IAV infection. The nuclear factor‐κB signaling acting as a critical factor in the transcription of TSPOAP1‐AS1 was determined through the use of pharmacological and genetic approaches. Functionally, overexpression of TSPOAP1‐AS1 resulted in a significant increase in IAV replication. In contrast, the abolition of TSPOAP1‐AS1 by RNA interference restricted viral replication. Furthermore, we demonstrated that TSPOAP1‐AS1 negatively modulated the IAV‐induced Ifnb1 transcription, i﻿nterferon‐sensitive response element (﻿ISRE)﻿ activation, and downstream interferon‐stimulated genes expression. Collectively, our data provides evidence for the host lncRNA utilized by viruses to support its replication.
Deep neuromuscular blockade for endolaryngeal procedures: A multicenter randomized study
Authors: Laosuwan Prok , Songarj Phuriphong , Lapisatepun Worawut , Boonsri Settapong , Rodanant Oraluxna , Wasinwong Wirat , Sriraj Wimonrat , Watcharotayangul Jittiya , Wongyingsinn Mingkwan 
Published: April 2019

Objectives/HypothesisThe aim of the present study was to compare the surgical condition between deep neuromuscular blockade (NMB) and moderate NMB.Study DesignMulticenter, randomized, parallel intervention trial.MethodsOne hundred two patients underwent microscopic endolaryngeal surgery at four university hospitals. The patients were randomized into moderate NMB (train‐of‐four 1‐2) (M group) or deep NMB (post‐tetanic count 1‐2) (D group) with moderate or high doses of rocuronium, respectively. Surgical rating conditions (SRCs) were evaluated during the surgery. Sugammadex was given to the M group at 2 mg/kg and the D group at 4 mg/kg. Perioperative clinical signs and conditions were recorded until discharge from the postanesthesia care unit.ResultsClinically acceptable SRC was observed in 49 patients (100%) in the D group and 43 patients (89.6%) in the M group (P = .027). The frequency of notable vocal fold movement in the M group was significantly higher than the D group (70.8% vs. 32.7%). The patients in the M group required more additional doses of rocuronium (47.9%) than the D group (20.4%) to maintain full relaxation (P = .005). The median time (interquartile range) from administration of sugammadex to train‐of‐four ratio 0.9 in the D group was shorter than the M group (120 [109–180 minutes] vs. 180 minutes [120–240 minutes], P = .034).ConclusionsDeep NMB with high doses of rocuronium combined with 4 mg/kg of sugammadex for reversal during endolaryngeal surgery provided better SRC and anesthetic conditions than moderate NMB of rocuronium with 2 mg/kg of sugammadex.Level of Evidence1b Laryngoscope, 130:437–441, 2020
The High‐Order Toroidal Moments and Anapole States in All‐Dielectric Photonics
Authors: Gurvitz Egor A. , Ladutenko Konstantin S. , Dergachev Pavel A. , Evlyukhin Andrey B. , Miroshnichenko Andrey E. , Shalin Alexander S. 
Published: April 2019

AbstractAll‐dielectric nanophotonics attracts ever increasing attention nowadays due to the possibility of controlling and configuring light scattering on high‐index semiconductor nanoparticles. It opens a room of opportunities for designing novel types of nanoscale elements and devices, and paves the way for advanced technologies of light energy manipulation. One of the exciting and promising prospects is associated with utilizing the so‐called toroidal moment, being the result of poloidal currents excitation, and anapole states, corresponding to the interference of dipole and toroidal electric moments. Here, higher‐order toroidal moments of both types (up to the electric octupole toroidal moment) are presented and investigated in detail via the direct Cartesian multipole decomposition allowing new near‐ and far‐field configurations to be obtained. Poloidal currents can be associated with vortex‐like distributions of the displacement currents inside nanoparticles, revealing the physical meaning of the high‐order toroidal moments and the convenience of the Cartesian multipoles as an auxiliary tool for analysis. High‐order nonradiating anapole states accompanied by the excitation of intense near‐fields are demonstrated. It is believed that the results are of high importance for both the fundamental understanding of light scattering by high‐index particles and a variety of nanophotonics applications and light governing on nanoscale.
Utilization of 4‐(trifluoromethyl)benzenesulfonates as Counter Ions Tunes the Initiator Efficiency of Sophisticated Initiators for the Preparation of Well‐Defined poly(2‐oxazoline)s
Authors: Engel Nora , Dirauf Michael , Seupel Susanne , Leiske Meike N. , Schubert Stephanie , Schubert Ulrich S. 
Published: April 2019

AbstractDuring the last decades, poly(2‐oxazoline)s (POx) have gained increased interest due to their versatility. In particular, cationic ring‐opening polymerization (CROP) enables the synthesis of well‐defined polymers bearing quantitative α‐ and ω‐functionalities. In contrast to small initiating groups, the introduction of more sophisticated, respectively demanding groups remains challenging. To fulfill this challenge, the initiator should comply with one major requirement in order to yield well‐defined polymers: a fast and complete initiation. The straight forward two‐step synthesis of a novel initiator containing a 4‐(trifluoromethyl)benzenesulfonate (fluorylate, TosCF3) counter‐ion is herein presented to accomplish the introduction of a sophisticated functional 3‐(2‐(2‐ethoxy)ethoxy)ethoxy)prop‐1‐ene (TEG) initiating group. Kinetic studies are conducted in acetonitrile and chlorobenzene using the hydrophilic 2‐ethyl‐2‐oxazoline (EtOx) as well as the hydrophobic 2‐octyl‐2‐oxazoline (OctOx) as monomers to examine the influences of the solvent as well as the different monomers. In particular, the initiator efficiency is determined by 1H and 19F nuclear magnetic resonance spectroscopy and compared to the corresponding tosylate (TEGTos) and triflate (TEGTf). It is shown that the fluorylate combines the stability of the tosylate and an enhanced propagation rate comparable to the triflate.
Coarse‐Grained Dendrimers in a Good Solvent: Comparison of Monte Carlo Simulations, Self‐Consistent Field Theory, and a Hybrid Modeling Strategy
Authors: Bergsma Johan , van der Gucht Jasper , Leermakers Frans A. M. 
Published: April 2019

AbstractRecently, a hybrid method has been developed, wherein the positions of some polymer segments are constrained to a small volume. The volume's position is sampled with a Monte Carlo algorithm. The distribution of the remaining segments is determined with Scheutjens–Fleer self‐consistent field theory (SF‐SCF). This incorporates thermal fluctuations into the model. Here it is investigated whether this also leads to an improved treatment of the excluded volume interactions. Dendrimers, with f = 1⋅⋅⋅7 generations, g = 2⋅⋅⋅5 spacers per branch point, and spacers of 20 or 50 segments, are used as a model system. The focus is on the radius of gyration, the asphericity, the radial density, and the end point and first branch point distribution. As expected, both SCF methods underestimate the radius of gyration due to underestimating the short range excluded volume. The SF‐SCF model, however, also gives a slightly different scaling and, in contrast to the other models, also predicts a bimodal distribution for first generation branch points for large f and g. This difference is attributed to overestimating the excluded volume at long ranges. As the hybrid method does not show this, localizing just a few segments largely compensates this shortcoming in the SF‐SCF theory.
Novel mutations of COL4A3, COL4A4, and COL4A5 genes in Chinese patients with Alport Syndrome using next generation sequence technique
Authors: Zhao Xuechao , Chen Chen , Wei Yanfu , Zhao Ganye , Liu Lina , Wang Conghui , Zhang Junjun , Kong Xiangdong 
Published: April 2019

AbstractBackgroundAlport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes. The large sizes of these genes and the absence of mutation hot spots have complicated mutational analysis by routine PCR‐based approaches. In recent years, the development of next‐generation sequencing (NGS) has made possible the time‐ and cost‐effective and accurate analysis of the three genes in a single step.MethodsHere, we analyze COL4A3, COL4A4, and COL4A5 simultaneously in 29 AS patients using NGS. Candidate mutations were validated by classic Sanger sequencing and Real‐time PCR.ResultsTwenty two new mutations and 10 known mutations were detected. Of those novel mutations, 18, 3, and 1 mutations were detected in COL4A5, COL4A4, and COL4A3, respectively. Twenty six patients showed X‐linked inheritance, one showed autosomal recessive inheritance and two showed digenic inheritance (DI).ConclusionA comparison of the clinical manifestations caused by different types of mutations in COL4A5 suggested that large fragment mutations are relatively more severe than the other missense mutations and AS by some mutations may show inter‐ and intra‐familial phenotypic variability. It is important to consider these transmission patterns in the clinical evaluation according to the results of genetic testing, especially for DI. Twenty two new mutations can expand the genotypic spectrum of AS.
QSAR Analysis of a Series of Hydantoin‐based Androgen Receptor Modulators and Corresponding Binding Affinities
Authors: Wang Xin , Han Wenya , Li Jiazhong 
Published: April 2019

AbstractAndrogen receptor (AR), a member of the nuclear hormone receptor superfamily of intracellular ligand‐dependent transcription factors, plays an indispensable role in normal male development through the regulation of androgen through the binding with endogenous androgens. Inappropriate amounts of androgens have a severe adverse effect on men. Excessive androgen may contribute to accelerate prostatic hypertrophy, even prostate cancer, while the absence of androgen may result in reduced muscle mass and strength, decreased bone mass, low energy, diminished sexual function and an increased risk of osteoporosis and fracture. In these cases, androgen receptor modulators are important to maintain the normal biological function of AR. So androgen receptor modulators are necessary for human being to improve their happy life index. To explore the relationships between molecular structures and corresponding binding abilities to aid the new AR modulator design, multiple linear regressions (MLR) are employed to analyze a series of hydantoin analogues, which can bind to androgen receptor acting as AR modulators. The obtained optimum model presents wonderful reliabilities and strong predictive abilities with R2=0.858,
=0.822,
=0.813,
=0.840,
=0.807,
=0.814, CCC=0.893, respectively. The derived model can be used to predict the binding abilities of unknown chemicals and may help to design novel molecules with better AR affinity activity.
The nursing work environment and quality of care: Content analysis of comments made by registered nurses responding to the Essentials of Magnetism II scale
Authors: Oshodi Titilayo O. , Bruneau Benjamin , Crockett Rachel , Kinchington Francia , Nayar Shoba , West Elizabeth 
Published: April 2019

AbstractAimTo report a qualitative study of themes Registered Nurses raised spontaneously about their work environment, in a cross‐sectional survey study when responding to the Essentials of Magnetism II (EOMII) scale.DesignQualitative descriptive survey.MethodsAt the end of the EOMII scale, a free form text section was included asking nurses to add comments about their ward/work environment. Of the 247 nurses who completed the EOMII scale, 30% (N = 75) provided comments. Inductive content analysis was used to analyse the textual information generated.ResultsThree key themes emerged: “nurses need nurses to nurse”; working as a team and workplace environment. Participants described issues they were facing which comprised high turnover rates, inadequate staffing levels, increasing workload and high stress levels. Particular attention was drawn to the role of the ward manager in promoting a positive work environment, good teamwork and quality patient care.
Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events
Authors: Miller Tamara P. , Fisher Brian T. , Getz Kelly D. , Sack Leah , Razzaghi Hanieh , Seif Alix E. , Bagatell Rochelle , Adamson Peter C. , Aplenc Richard 
Published: April 2019

AbstractBackgroundAdverse events (AEs) on Children's Oncology Group (COG) trials are reported manually by clinical research assistants (CRAs). The Common Terminology Criteria for Adverse Events (CTCAE) was developed to provide standardized definitions for identifying and grading AEs. The CTCAE has expanded significantly over its five versions, but the impact of CTCAE definitional changes has not been examined.ProcedureThis study compared AE number and ascertainment among the first four CTCAE versions using a case vignette. Each CTCAE version was used to create a list of AEs and grades by two separate CRAs.ResultsThe CTCAE expanded from 9 categories and 49 AEs in v1.0 to 26 categories and 790 AEs in v4.0. CRAs independently selected different approaches to AE ascertainment—comprehensive and parsimonious. The number of AEs identified in the parsimonious approach was stable with 10–14 in each CTC version. The comprehensive approach identified 9, 20, 29, and 37 AEs in CTC versions 1.0, 2.0, 3.0, and 4.0, respectively. Only approximately 65% of AEs were conclusively graded in versions 2.0 to 4.0 using the comprehensive approach.ConclusionsCTCAE has increased in complexity. Although this increased complexity allows for more granular AE reporting, these data demonstrate potential unintended negative consequences of increasing CTC AE complexity, including the risk of varying approaches to AE capture. A comprehensive evaluation of CTC AE definitions and CRA reporting practices across COG institutions and AEs are needed to improve the accuracy and efficiency of AE reporting.
Proteomics Approaches to Define Senescence Heterogeneity and Chemotherapy Response
Authors: Petit Coralie , Guillon Jordan , Toutain Bertrand , Boissard Alice , Patsouris Anne , Lelièvre Eric , Guette Catherine , Coqueret Olivier 
Published: April 2019

AbstractIn primary cells, senescence induces a permanent proliferative arrest to prevent the propagation of malignant cells. However, the outcome of senescence is more complex in advanced cancer cells where senescent states are heterogeneous. Here, this heterogeneity is discussed and it is proposed that proteomic analysis should be used to identify specific signatures of cancer cells that use this pathway as an adaptive mechanism. Since senescent cells produce an inflammatory secretome, MRM approaches and quantification with internal standards might be particularly suited to follow the expression of the corresponding markers in body fluids. Used in combination with imaging medical technics, a better characterization of senescence heterogeneity should help to monitor the response to chemotherapy treatment.
Morphology diagram of PE gel films in wide range temperature‐strain space: An in situ SAXS and WAXS study
Authors: Lv Fei , Wan Caixia , Chen Xiaowei , Meng Lingpu , Chen Xin , Wang Daoliang , Li Liangbin 
Published: April 2019

ABSTRACTDeformation‐induced structural evolution of polyethylene (PE) gel films were investigated by in situ synchrotron radiation SAXS and WAXS techniques during stretching at temperatures from 25°C to 110°C. The structural evolutions along tensile strains showed distinct behaviors in the four temperature regions divided by and given by DMA and the onset point of melting measured by DSC, respectively, which was determined by the coupling effects of external stretching field and temperature. Finally, the morphological diagrams of PE gel films on distinct scales including long period of lamellae, crystallinity, and crystal size in 2D temperature‐strain space were established, which can give a direct sight of membrane morphologies and act as a map for processing parameters selection. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 748–757
Polycystic Ovary Syndrome and Insulin Physiology: An Observational Quantitative Serum Proteomics Study in Adolescent, Normal‐Weight Females
Authors: Manousopoulou Antigoni , Al‐Daghri Nasser M. , Sabico Shaun , Garay‐Baquero Diana J. , Teng Jie , Alenad Amal , Alokail Majed S. , Athanasopoulos Nikos , Deligeoroglou Efthymios , Chrousos George P. , Bacopoulou Flora , Garbis Spiros D. 
Published: April 2019

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal‐weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols.MethodsNon‐depleted serum from normal‐weight (BMI: 18–23 kg m−2), adolescent females (13–21 years old) with PCOS (n = 20) is compared to BMI‐ and age‐matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool).ResultsOne‐hundred and twenty‐six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin‐like growth factor receptor signaling pathway. Circulating levels of IGF‐1 and ‐2 and IGFBP‐2, ‐3, and ‐4 are found to be lower in females with PCOS compared to healthy controls.ConclusionsThe present serum proteomics study provides insight into the pro‐inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols.
A structural and functional analysis of the glycosyltransferase BshA from Staphylococcus aureus: Insights into the reaction mechanism and regulation of bacillithiol production
Authors: Royer Christopher J. , Cook Paul D. 
Published: April 2019

AbstractBacillithiol is a glucosamine‐derived antioxidant found in several pathogenic Gram‐positive bacteria. The compound is involved in maintaining the appropriate redox state within the cell as well as detoxifying foreign agents like the antibiotic fosfomycin. Bacillithiol is produced via the action of three enzymes, including BshA, a retaining GT‐B glycosyltransferase that utilizes UDP‐N‐acetylglucosamine and l‐malate to produce N‐acetylglucosaminyl‐malate. Recent studies suggest that retaining GT‐B glycosyltransferases like BshA utilize a substrate‐assisted mechanism that goes through an SNi‐like transition state. In a previous study, we relied on X‐ray crystallography as well as computational simulations to hypothesize the manner in which substrates would bind the enzyme, but several questions about substrate binding and the role of one of the amino acid residues persisted. Another study demonstrated that BshA might be subject to feedback inhibition by bacillithiol, but this phenomenon was not analyzed further to determine the exact mechanism of inhibition. Here we present X‐ray crystallographic structures and steady‐state kinetics results that help elucidate both of these issues. Our ligand‐bound crystal structures demonstrate that the active site provides an appropriate steric and geometric arrangement of ligands to facilitate the substrate‐assisted mechanism. Finally, we show that bacillithiol is competitive for UDP‐N‐acetylglucosamine with a Ki value near 120–130 μM and likely binds within the BshA active site, suggesting that bacillithiol modulates BshA activity via feedback inhibition. The work presented here furthers our understanding of bacillithiol metabolism and can aid in the development of inhibitors to counteract resistance to antibiotics such as fosfomycin.
Stabilization of SecA ATPase by the primary cytoplasmic salt of Escherichia coli
Authors: Roussel Guillaume , Lindner Eric , White Stephen H. 
Published: April 2019

AbstractMuch is known about the structure, function, and stability of the SecA motor ATPase that powers the secretion of periplasmic proteins across the inner membrane of Escherichia coli. Most studies of SecA are carried out in buffered sodium or potassium chloride salt solutions. However, the principal intracellular salt of E. coli is potassium glutamate (KGlu), which is known to stabilize folded proteins and protein‐nucleic acid complexes. Here we report that KGlu stabilizes SecA, including its dimeric state, and increases its ATPase activity, suggesting that SecA is likely fully folded, stable, and active in vivo at 37°C. Furthermore, KGlu also stabilizes a precursor form of the secreted maltose‐binding protein.