bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoredox Alkylarylation of N‐Benzyl‐N‐(2‐ethynylaryl)‐Amides with α‐Bromoalkyl Esters: Access to Dibenzazepines
Authors: Zhang Ting‐Ting , Luo Mu‐Jia , Teng Fan , Li Yang , Hu Ming , Li Jin‐Heng
Published: August 2019

A new two‐component alkylarylation of N‐benzyl‐N‐(2‐ethynylaryl)amides with α‐bromoalkyl esters using visible light photoredox catalysis promoted by silver salts for producing substituted dibenzazepines is described. Employing α‐bromoalkyl esters to form the alkyl carbon‐centered radicals enables the alkylarylation of alkynes where two carbon‐centered functional groups are introduced across the C≡C bond in a single reaction.

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Small Gold Quantum Probes for Drug‐Free Cancer Theranostics
Authors: Agarwal Ayushi , Venkatakrishnan Krishnan , Tan Bo
Published: August 2019

Gold quantum dots (QDs) have emerged as a distinct approach for cancer theranostics by using labeled and functionalized chemotherapeutic‐drug to realize its detection and chemotherapeutic functions. However, the toxicity induced by chemical‐based synthesis, their nonspecific accumulation in healthy tissues and organs hamper its translation to clinical applications. QDs are functionalized/labeled to reduce their toxicity and helps the QDs' cellular‐uptake. In addition, labeling increases the overall hydrodynamic size of QDs, which limits the dispersion, impedes efficient renal clearance and causes the accumulation of QDs in organs. Therefore, the unique properties that arise from quantum‐size (less than 5nm) are lost. Reports on the effect of real quantum‐size on cell‐interaction are, to date, limited. In this work, the concept of a small‐sized self‐functionalized pristine bright quantum gold probe (BQGP) for cancer‐theranostics. To the best of authors' knowledge, it is the first time cell‐interaction of BQGPs has been investigated and the results suggest that it can be used for label‐free/drug‐free cancer quantum‐theranostics. The pristine BQGPs demonstrate cancer‐selective cell‐uptake, enabling dosage‐dependent fluorescent detection/differentiation of cancerous‐cells and cancer‐selective cytotoxicity. The fabricated BQGPs demonstrate fluorophore‐free illuminance at a broad‐range of excitation wavelengths and drug‐free cancer‐specific treatment. Moreover, the drug‐free BQGPs may find advantages in fighting drug‐resistant cancers.
High‐Output Triboelectric Nanogenerator Based on Dual Inductive and Resonance Effects‐Controlled Highly Transparent Polyimide for Self‐Powered Sensor Network Systems
Authors: Lee Jae Won , Jung Sungwoo , Lee Tae Won , Jo Jinhyeong , Chae Hee Young , Choi Keunsu , Kim Jae Joon , Lee Jun Hee , Yang Changduk , Baik Jeong Min
Published: August 2019

High‐output triboelectric nanogenerators (TENGs) are demonstrated based on polyimide (PI)‐based polymers by introducing functionalities (e.g., electron‐withdrawing and electron‐donating groups) into the backbone. The TENG based on 6FDA‐APS PI, possessing the most negative electrostatic potential and the low‐lying lowest unoccupied molecular orbital level, produces the highest effective charge density of about 860 µC m−2 in practical working conditions with the ion injection process. This may be ascribed to the excellent charge‐retention characteristics as well as the enhanced charge transfer capability, which increases the output power by 7 times compared to the commercially available Kapton film‐based TENG. Finally, a 6FDA‐APS‐driven sensor network system is demonstrated, providing the identity of three gases (H2, CO, and NO2) by illuminating the light‐emitting diodes within several seconds.
Role of Nonsteroidal Antiinflammatory Drugs in the Association Between Osteoarthritis and Cardiovascular Diseases: A Longitudinal Study
Authors: Atiquzzaman Mohammad , Karim Mohammad E. , Kopec Jacek , Wong Hubert , Anis Aslam H.
Published: August 2019

Objective

To elucidate the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the increased risk of cardiovascular disease (CVD) among osteoarthritis (OA) patients.

Methods

This longitudinal study was based on linked health administrative data from British Columbia, Canada. From a population‐based cohort of 720,055 British Columbians, we selected 7,743 OA patients and 23,229 age‐ and sex‐matched non‐OA controls. We used multivariable Cox proportional hazards models to estimate the risk of developing incident CVD (primary outcome) as well as ischemic heart disease, congestive heart failure, and stroke (secondary outcomes). To estimate the mediating effect of NSAIDs, defined as current use of an NSAID according to linked PharmaNet data, in the OA–CVD relationship, we implemented a marginal structural model.

Results

OA patients had a higher risk of developing CVD than controls without OA. After adjusting for socioeconomic status, body mass index, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, and Romano comorbidity score, the adjusted hazard ratio (HR) was 1.23 (95% confidence interval [95% CI] 1.17–1.28). The adjusted HRs for congestive heart failure, ischemic heart disease, and stroke were 1.42 (95% CI 1.33–1.51), 1.17 (95% CI 1.10–1.26), and 1.14 (95% CI 1.07–1.22), respectively. Approximately 41% of the total effect of OA on increased CVD risk was mediated through NSAIDs. For the secondary outcomes, the proportion mediated through NSAIDs was 23%, 56%, and 64% for congestive heart failure, ischemic heart disease, and stroke, respectively.

Conclusion

The findings of this first study to evaluate the mediating role of NSAIDs in the relationship between OA and CVD suggest that NSAID use contributes substantially to the OA–CVD association.
A multiple‐site field study of stabilized hydrogen peroxide for drinking water disinfection
Authors: Vadasarukkai Yamuna S. , Guo Xinhai (August) , Tyssen Robert , Hares Joanna El , Feyen Ludo , Liss Steven N. , Shubat Jim , Abernethy Robert
Published: August 2019

This study examined the impact of changing the secondary disinfectant from chlorine to a stabilized hydrogen peroxide (SHP) in three full‐scale drinking water treatment plants serving small communities in the provinces of Ontario and Newfoundland, Canada. In all three communities, the SHP residuals were maintained within the limits specified by local regulators, with the exception of one of the sites in Newfoundland, where residuals were outside these limits on several occasions during the study. Following the transition to the SHP system, total coliforms and Escherichia coli consistently tested negative (nondetected) in all cases. Switching to the SHP system reduced concentrations of total trihalomethanes to 22–44 μg/L and total haloacetic acids to 47–70 μg/L, corresponding to 72 ± 9 and 67 ± 11% reductions, respectively. The present study indicated that changing the secondary disinfectant to SHP did not negatively affect the polyvinyl chloride and ductileiron pipes in the distribution systems studied.
The Obvious in a Nutshell: Science, Medicine, Knowledge, and History
Authors: De Sio Fabio , Fangerau Heiner
Published: August 2019

The scope and mission of the history of science have been constant objects of reflection and debate within the profession. Recently, Lorraine Daston has called for a shift of focus: from the history of science to the history of knowledge. Such a move is an attempt at broadening the field and ridding it of the contradictions deriving from its modernist myth of origin and principle of demarcation. Taking the move from a pluralistic concept of medicine, the present paper explores the actual and possible contributions that a history of knowledge can offer to the history of medicine in particular. As we will argue, the history of medicine has always been a history of knowledge, but for good reasons has always stuck to the concept ofmedicineas its object and problem throughout the ages, including the modern,scientificone. We argue that, in the history of medicine, the demarcation between scientific and non‐scientific represents an accident, but is not foundational as in the case of natural science. Furthermore, the history of medicine programmatically played a role in at least two academic domains (history proper and medical education), adjusting historical narratives of medical knowledge to its audience. Accordingly, we underscore that the history of both science and medicine, as traditionally defined, already provides room for almost the whole spectrum of approaches to history. Moreover, their different myths of origin can, and indeed must, be included in the reflexivity of the historical gaze. We argue that the position towards a history of science, medicine, or knowledge is not a question of narrative or theory, rather, it is a question of relevance and awareness of extant contexts.
Partisans and the Use of KnowledgeversusScience
Authors: Staley Richard
Published: August 2019

This paper explores the kind of knowledge that partisans profess in order to contribute to our studies of what has usually been thought of as the “denial of science.” Building on the research of Robert Proctor, Naomi Oreskes and Erik Conway, I show that the tobacco interests and climate science skeptics usually described as “doubt mongers” also purveyed forms of certainty and rested their arguments on three different registers of truth: that of narrowly defined “facts” that could sustain a controversy, ideological commitments to free enterprise, and the truths of self‐conscious partisans engaged in battle. Thus, in many respects they have used elements of general knowledge, as well as social, economic and political commitments, to argue against specific scientific findings. Further, at least in the case of climate skeptics, this denial has been in the service of an image of the nature of science and its proper relation to politics. Analyzing significant dichotomies in debates that cross the terrains of science and politics, and knowledge and science, I will argue that a clear articulation of the relations amongst them will be critical to our work to understand the character of climate science denial, but also of the climate sciences themselves.
Fe‐Based Complexes as Styrene Aziridination Catalysts: Ligand Substitution Tunes Catalyst Activity
Authors: Coin Guillaume , Patra Ranjan , Clémancey Martin , Dubourdeaux Patrick , Pécaut Jacques , Lebrun Colette , Castro Ludovic , Maldivi Pascale , Chardon‐Noblat Sylvie , Latour Jean‐Marc
Published: August 2019

As part of our effort to improve our understanding of aziridination mechanism, we used tetra substitution of a diphenol ligand to modify the redox properties of corresponding Fe complexes. This allowed us to confirm that aziridination catalysis by Fe‐based complexes is governed by electron affinity of the active species and further show that it correlates with the FeIII/FeII redox potential.
Mesoporous H‐ZSM‐5 for the Conversion of Dimethyl Ether to Hydrocarbons
Authors: Zimmermann Michael C. , Otto Thomas N. , Wodarz Simon , Zevaco Thomas A. , Pitter Stephan
Published: August 2019

The potential of hierarchical H‐ZSM‐5 zeolites was studied for the conversion of DME to fuel‐compatible hydrocarbons. For this purpose, hierarchical H‐ZSM‐5 zeolites have been prepared from commercial H‐ZSM‐5 by desilication and organosilane‐directed hydrothermal synthesis. The zeolites were characterized by X‐ray diffraction, NH3‐TPD, DRIFTS, and N2 physisorption measurements. The catalysts have been tested in a tube reactor (1 bar, 648 K). The results indicate important structural changes in framework and acidic sites, which are significant for the synthesis of gasoline‐range hydrocarbons.
In Situ Derivatization for Boosted Lithium Storage Performance of Fe7S8/C Hollow Nanospheres
Authors: Dai Lanxuan , Tang Dongmei , Shen Chao , Han Yue , Wu Xiaoyu , Wu Huayu , Diao Guowang , Chen Ming
Published: August 2019

In this paper, Fe3O4 nanoparticles (Fe3O4 NPs) with an average diameter of 10 nm were grown in situ on the shell of hollow mesoporous carbon nanospheres (HMCNs) to form a new type of sesame balls‐like Fe3O4/C hollow nanospheres (HNSs) by thermal decomposition. After vulcanization and phosphating, Fe3O4/C HNSs are transformed into Fe7S8/C HNSs and Fe(PO3)2/Fe2O3/C HNSs, respectively. Compared with Fe3O4/C HNSs and Fe(PO3)2/Fe2O3/C HNSs, Fe7S8/C HNSs display good cycling stability as anode material for lithium ion batteries. When the current density is 1 A g−1, the reversible specific capacity of Fe7S8/C HNSs is 1006 mA h g−1 after 250 cycles. The rate performance and electrochemical properties of Fe7S8/C HNSs are significantly improved. Research shows that the capacitive behavior plays a major role in specific capacity contribution of Fe7S8/C HNSs electrode. The anchoring of Fe7S8 NPs on the shell of HMCNs avoids the aggregation of Fe7S8 NPs, promote the conductivity of composite and boost the delivery of electrons. This idea and expedient method of construction can be broadened to synthesize other hollow nanostructured material with preferable electrochemistry performance.
Synergistic Effects of ppm Levels of Palladium on Natural Clinochlore for Reduction of Nitroarenes
Authors: Gholinejad Mohammad , Oftadeh Erfan , Shojafar Mohammad , Sansano José M. , Lipshutz Bruce H.
Published: August 2019

Augmenting the modified naturally occurring clay clinochlore with ppm amounts of palladium leads to a new and very effective reagent for the reduction of numerous aromatic nitro species. When palladium nanoparticles are supported on pyridyltriazole‐modified clinochlore, iron within clinochlore acts synergistically with palladium to catalyze the reduction of a wide variety of nitroarenes at room temperature in aqueous media. Based on E‐factor calculations, the catalyst system is found to be in line with green chemistry standards and can be recycled up to five times.
Montelukast modifies simvastatin‐induced myopathy and hepatotoxicity
Authors: Hareedy Mohammad S. , Ahmed Esraa A. , Ali Marwa F.
Published: August 2019

Montelukast (MNK) has prominent anti‐inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV‐induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co‐treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co‐administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that produce muscle and hepatic protective effects.
Spidroin in carbopol‐based gel promotes wound healing in earthworm's skin model
Authors: Abd Ellah Noura H. , Abd El‐Aziz Fatma El‐Zahraa A. , Abouelmagd Sara A. , Abd El‐Hamid Basma N. , Hetta Helal F.
Published: August 2019

Spider silk's regenerative, biocompatible, and antimicrobial properties render it a promising biomaterial for wound healing promotion. Spidroin as the main protein component of spider silks was used in this study to evaluate the potential effects on wound healing via topical application of novel spidroin‐containing carbopol 934 (CP934) gel. Spidroin was extracted, formulated into CP934 gel, and characterized both in vitro and in vivo. Spidroin gel was translucent and brownish‐yellow in color. An optimum viscosity was obtained at 0.6% CP934 at neutral pH. Optimized spidroin gel (0.6% CP934) effectively inhibited the growth of clinical bacterial isolates of methicillin‐sensitive Staphylococcus aureus (MSSA), methicillin‐resistant S. aureus (MRSA) and Escherichia coli at 440 μg/mL with MIC values of 0.98, 4.6, and 8.2 μg/mL, respectively. Optimized spidroin gel was evaluated for wound healing via topical application on wounds surgically induced in Allolobophora caliginosa earthworms used as a robust human skin model. After application for three consecutive days, dramatic reductions in wound closure and reepithelialization duration were observed macroscopically and via histological studies (light and electron microscopy) when compared with control. In conclusion, these results show that spidroin gel is a promising promoter for wound healing, and further studies would be directed toward investigating mechanisms underlying this effect.
Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta‐analyses
Authors: Alhajraf Falah , Ness Deborah , Hye Abdul , Strydom Andre
Published: August 2019

Individuals with Down syndrome (DS) are at high risk of developing Alzheimer's disease (AD). Discovering reliable biomarkers which could facilitate early AD diagnosis and be used to predict/monitor disease course would be extremely valuable. To examine if analytes in blood related to amyloid plaques may constitute such biomarkers, we conducted meta‐analyses of studies comparing plasma amyloid beta (Aβ) levels between DS individuals and controls, and between DS individuals with and without dementia. PubMed, Embase, and Google Scholar were searched for studies investigating the relationship between Aβ plasma concentrations and dementia in DS and 10 studies collectively comprising >1,600 adults, including >1,400 individuals with DS, were included. RevMan 5.3 was used to perform meta‐analyses. Meta‐analyses showed higher plasma Aβ40 (SMD = 1.79, 95% CI [1.14, 2.44], Z = 5.40, p < .00001) and plasma Aβ42 levels (SMD = 1.41, 95% CI [1.15, 1.68], Z = 10.46, p < .00001) in DS individuals than controls, and revealed that DS individuals with dementia had higher plasma Aβ40 levels (SMD = 0.23, 95% CI [0.05, 0.41], Z = 2.54, p = .01) and lower Aβ42/Aβ40 ratios (SMD = −0.33, 95% CI [−0.63, −0.03], Z = 2.15, p = .03) than DS individuals without dementia. Our results indicate that plasma Aβ40 levels may constitute a promising biomarker for predicting dementia status in individuals with DS. Further investigations using new ultra‐sensitive assays are required to obtain more reliable results and to investigate to what extent these results may be generalizable beyond the DS population.
A Boron Doped Diamond Electrode Modified with Nano‐carbon Black for the Sensitive Electrochemical Determination of Chlorogenic Acid
Authors: Teker Tugçe , Hasan Ali Mahmood Hasan , Aslanoglu Mehmet
Published: August 2019

An electrochemical method was developed for the sensitive determination of chlorogenic acid using a boron doped diamond electrode (BDDE) modified with nano‐carbon black (nano‐CB). The active surface areas were found to be 0.059 and 0.146 cm2 for the unmodified BDDE, and nano‐CB/BDDE, respectively. Compared with a BDDE, the nano‐CB/BDDE exhibited a well‐defined redox couple for chlorogenic acid. In addition, the plot of the peak current response changing from a square root to a linear dependence on scan rate is attributed to the transition from planar diffusion to surface behaviour. The anodic and cathodic peak separations (ΔEp) were 97 mV and 14 mV at BDDE and nano‐CB/BDDE, respectively. The decrease in ΔEp at the proposed electrode indicated that the process of chlorogenic acid was greatly accelerated. Square wave voltammetry (SWV) exhibited a dynamic range in which the current versus the concentration of chlorogenic acid were linear from 2.0×10−8 to 2.0×10−6 M with a LOD of 4.1×10−9 M (based on 3Sb/m). The nano‐CB modified BDDE provided improved electrochemical behavior, high electrocatalytic activity, high sensitivity and good reproducibility.
Electrochemical Sensing of Ovalbumin Based on the Interaction between Lysozyme Origin/Tyrosine‐rich Peptides Modified on Magnetic Beads and Oligothreonine/Ovalbumin‐origin Peptide
Authors: Sugawara Kazuharu , Ishizaki Sora , Kuramitz Hideki , Kadoya Toshihiko
Published: August 2019

We developed a highly sensitive electrochemical system for the sensing of ovalbumin (OVA). Lysozyme origin/tyrosine‐rich peptides (RNRCKGTDVQAWY4C) were immobilized on magnetic beads, and the competitive reaction between OVA and oligothreonine/OVA origin peptide probe (T8VLLPDEVSG) could then be measured. In a previous study, the detection of OVA at the 10−13 M level was achieved using RNRCKGTDVQAWY4C‐modified beads via a cross‐linker. To improve the sensitivity to OVA, this system uses T8VLLPDEVSG peptide probe to measure the interaction to RNRCKGTDVQAWY4C immobilized on magnetic beads. The peak of Y4C actually was an electron‐transfer peptide, which represented the oxidation of a phenolic hydroxyl group. First, we confirmed that the oxidation response of Y4C was increased based on an improvement in the electron transfer accessibility by oligothreonine. Next, T8VLLPDEVSG peptide probe was used for the electrochemical sensing of OVA in solutions that contained consistent amounts of RNRCKGTDVQAWY4C on magnetic beads. As a result, the peak current decreased as the concentration of OVA increased. The sensitivity to OVA was improved compared with the use of only RNRCKGTDVQAWY4C on magnetic beads. The OVA detection level was 10−14 M, which approximates the results from antibody‐antigen reactions. Consequently, the proposed system is a powerful new concept in protein sensing.
Square‐wave Voltammetry of Two‐step Surface Electrode Mechanisms Coupled with Chemical Reactions – A Theoretical Overview
Authors: Janeva Milkica , Kokoskarova Pavlinka , Maksimova Viktorija , Gulaboski Rubin
Published: August 2019

Square‐wave voltammetry (SWV) of so‐called “surface redox reactions” is seen as a simple and efficient tool to quantify large number of drugs, physiologically active substances and other important chemicals. It also provides elegant methods to get access to relevant kinetic and thermodynamic parameters related to many lipophilic compounds. Moreover, with this technique we can study activity of various enzymes by exploring the “protein‐film voltammetry” set up. In this work, we focus on theoretical SWV features of four complex surface electrode mechanisms, in which the electron exchange between the working electrode and the studied redox substrate takes place in two successive steps. While we present large number of calculated square‐wave voltammograms, we give hints to recognize particular two‐step surface mechanism, but also to distinguish it from other similar mechanisms. We present plenty of relevant aspects of surface two‐step surface EE, two‐step surface ECE and surface catalytic EEC’ mechanisms. Moreover, we present for the first time a series of theoretical results related to two‐step surface EECrev mechanism (i. e. two‐step surface reaction coupled to follow‐up reversible chemical step). The simulated voltammetric patterns presented in this work can bring relevant aspects to resolve some experimental situations met in voltammetry of many redox enzymes and other important substances whose electrochemical transformation occurs in two‐steps.
Enhanced Electrochemical Performance of LiNi0.6Co0.2Mn0.2O2 by Expanded Graphite
Authors: Peng Zhenfeng , Tang Wenjie , Peng Yujia , Qiu Yang , Shuai Hantao , Wang Guixin
Published: August 2019

High‐capacity ternary materials are attractive for the development of electric vehicles for long‐distance driving, but they still face some challenges. To improve the performance, expanded graphite (EG) with a unique loose‐layered structure is mixed with (Ni0.6Co0.2Mn0.2)(OH)2 and LiOH·H2O aqueous solution to supply microscale reaction space and limit grain growth via hydrothermal treatment as well as accommodate LiNi0.6Co0.2Mn0.2O2 (NCM622) particles between the graphene layers. The key factors affecting electrochemical performance are investigated using various techniques. The NCM622 sample synthesized by adding 6.6 wt% of EG (PEG6.6%) exhibits the best performance. EG improves the discharge capacity of NCM622 from 156 to 175 mAh g−1 after 50 cycles at 1 C. As the surrounding temperature increases to 60 °C, the sample also shows good cyclability at 1 C, the 50th discharge specific capacity remains 153 mAh g−1 and the capacity retention rate is 82.3%, which is much higher than that of NCM622. Also, the columbic efficiency of NCM622 after 50 cycles improves from 69% to 99% with EG. The possible enhanced mechanism of NCM622 by EG is discussed. The effective way to enhance the performance using the layered structure of EG is promising for other energy materials.
Hybrid Taguchi–Fuzzy‐based performance‐exhaust emission trade‐off study of variable compression ratio diesel engine fueled with undi‐diesel blends
Authors: Madane Pravin A. , Bhowmik Subrata , Panua Rajsekhar
Published: August 2019

The present investigation highlights the effect of variable compression ratio (VCR) on the performance and exhaust emission characteristics of a single cylinder, direct injection diesel engine fueled with undi‐diesel blends. 10%, 20%, 30%, 40%, and 50% undi fuel have been added to diesel in volumetric proportions and tested by varying compression ratio (CR) from 16:1 to 20:1. Undi addition to diesel fuel significantly improves the brake thermal efficiency (BTE) and brake specific energy consumption (BSEC) of the engine. In addition, higher CR facilitates to improve unburned hydrocarbon (UHC), carbon monoxide (CO) and smoke opacity of the diesel engine with the penalties of higher oxides of nitrogen (NOX) emissions. In perspective of the engine experimental outputs, a Taguchi assisted Fuzzy based trade off study has been conducted to screen and locate the optimal diesel engine operating conditions, namely, CR, undi share, and load. The optimum process parameter has been found to be A2B6C2 with a multi performance characteristics index (MPCI) value of 0.683 indicating the optimum operating conditions of 17:1 CR, 50% (by volume) undi share at 50% load.
The Psychoactive Drug Escitalopram Affects Foraging Behavior in Zebrafish (Danio rerio)
Authors: Nielsen Sebastian Vedel , Frausing Marie , Henriksen Per Guldhammer , Beedholm Kristian , Baatrup  Erik
Published: August 2019

Selective serotonin reuptake inhibitors (SSRIs) are psychoactive pharmaceuticals that have been detected intact in natural waters globally. Laboratory experiments have reported that several SSRIs inhibit fish foraging behavior, but data for the SSRI escitalopram are lacking. The objectives of the present study were to determine whether escitalopram affects feeding behavior in zebrafish and whether possible sex differences exist. We exposed female and male zebrafish (Danio rerio) to 0.00, 0.10, and 1.50 µg/L of escitalopram in flow-through tanks for a 3-wk exposure period. We used a video tracking system with high temporal and spatial resolution to collect data on zebrafish swimming patterns in test tanks containing a food source. The results show a more pronounced effect of escitalopram in males compared with females. At the assumed most environmentally relevant concentration (0.10 µg/L), male average feeding time/visit and maximum feeding duration were significantly reduced by 27 and 42%, respectively. In addition, male total feeding duration was also significantly reduced (by 73%) at the highest concentration (1.50 µg/L). In females, only the maximum feeding duration was significantly reduced (by 41%) in the 0.10 µg/L treatment group. Hence, we reject our initial hypothesis that female feeding behavior is more vulnerable to escitalopram. There was no effect of escitalopram on length or weight among the experimental groups. The present study demonstrates that escitalopram, like other SSRIs, can inhibit fish foraging behavior and therefore potentially disturb natural food chains. Finally, our study suggests that SSRIs can both be sex and behavior specific. Environ Toxicol Chem 2019;38:1902–1910. © 2019 SETAC.

Abstract

The feeding behavior of zebrafish was quantified after treatment with the pharmaceutical escitalopram. Escitalopram affected feeding behavior more in males (•) than in females (▴). Different letters indicate significant differences (analysis of variance; Tukey post hoc test) with the significance level at 0.05. Different letters indicate significant differences. AOI = area of interest; ROI = region of interest.
Effects of hypogonadism on brain development during adolescence in girls with Turner syndrome
Authors: Li Min , Zhao Chenxi , Xie Sheng , Liu Xiwei , Zhao Qiuling , Zhang Zhixin , Gong Gaolang
Published: August 2019

Gonadal steroids play an important role in brain development, particularly during puberty. Girls with Turner syndrome (TS), a genetic disorder characterized by the absence of all or part of the second X chromosome, mostly present a loss of ovarian function and estrogen deficiency, as well as neuroanatomical abnormalities. However, few studies have attempted to isolate the indirect effects of hormones from the direct genetic effects of X chromosome insufficiency. Brain structural (i.e., gray matter [GM] morphology and white matter [WM] connectivity) and functional phenotypes (i.e., resting‐state functional measures) were investigated in 23 adolescent girls with TS using multimodal MRI to assess the role of hypogonadism in brain development in TS. Specifically, all girls with TS were divided into a hormonally subnormal group and an abnormal subgroup according to their serum follicle‐stimulating hormone (FSH) levels, with the karyotypes approximately matched between the two groups. Statistical analyses revealed significant effects of the “group‐by‐age” interaction on GM volume around the left medial orbitofrontal cortex and WM diffusion parameters around the bilateral corticospinal tract, anterior thalamic radiation, left superior longitudinal fasciculus, and cingulum bundle, but no significant “group‐by‐age” or group differences were observed in resting‐state functional measures. Based on these findings, estrogen deficiency has a nontrivial impact on the development of the brain structure during adolescence in girls with TS. Our present study provides novel insights into the mechanism by which hypogonadism influences brain development during adolescence in girls with TS, and highlights the important role of estrogen replacement therapy in treating TS.
FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study
Authors: Vink Frederique J. , Meijer Chris J.L.M. , Clifford Gary M. , Poljak Mario , Oštrbenk Anja , Petry Karl Ulrich , Rothe Beate , Bonde Jesper , Pedersen Helle , de Sanjosé Silvia , Torres Montserrat , del Pino Marta , Quint Wim G.V. , Cuschieri Kate , Boada Elia Alcañiz , van Trommel Nienke E. , Lissenberg‐Witte Birgit I. , Floore Arno N. , Hesselink Albertus T. , Steenbergen Renske D.M. , Bleeker Maaike C.G. , Heideman Daniëlle A.M.
Published: August 2019

Widespread adoption of primary human papillomavirus (HPV)‐based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124‐2 genes has shown promise for the triage of high‐risk (hr) HPV‐positive women. In our study, we assessed the consistency of FAM19A4/miR124‐2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation‐specific PCR (qMSP)‐based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124‐2 methylation‐positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer.
Toxicological safety evaluation of the human‐identical milk oligosaccharide 6′‐sialyllactose sodium salt
Authors: Phipps Kirt R. , Baldwin Nigel J. , Lynch Barry , Stannard Diane R. , Šoltésová Alica , Gilby Ben , Mikš Marta H. , Röhrig Christoph H.
Published: August 2019

Human milk oligosaccharides (HMOs) are abundant in breastmilk, but their presence in infant formula is negligible. Sialylated HMOs, such as 6′‐sialyllactose, constitute a significant portion of the HMO fraction of human milk and are linked to important biological functions. To produce infant formula that is more comparable with human milk, biosynthesized sialyllactoses known as human‐identical milk oligosaccharides (structurally identical counterparts to their respective naturally occurring HMOs in breastmilk) are proposed for use in infant formula and other functional foods for the general population. To support the safety of 6′‐sialyllactose sodium salt (6′‐SL), a 90‐day oral (gavage) toxicity study and in vitro genotoxicity tests were conducted. The 90‐day study is the first to be conducted with 6′‐SL using neonatal rats (day 7 of age at the start of dosing), thus addressing safety of 6′‐SL for consumption by the most sensitive age group (infants). In the 90‐day study, neonatal rats received 6′‐SL at doses up to 5000 mg/kg body weight (BW)/day and reference controls received 5000 mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in infant formula) for comparison with the high‐dose 6′‐SL group, followed by a 4‐week recovery period. There was no evidence of genotoxicity in vitro. No test item‐related adverse effects were observed on any parameter in the 90‐day study, thus the high dose (5000 mg/kg BW/day) was established as the no‐observed‐adverse‐effect level. These results confirm that 6′‐SL is safe for use in formula milk for infants and in other functional foods for the general population.
Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes
Authors: Singh Shilpi , Singh Shio Kumar
Published: August 2019

Perfluoroalkyl acids (PFAAs) are widely used in commercial products and are found in many goods of daily use. Perfluorononanoic acid (PFNA) is one of the PFAAs that possesses endocrine disrupting properties and we have recently shown that PFNA affects testicular functions in Parkes mice. Exposure to environmental endocrine disruptors during fetal life is believed to affect gonadal development and they might produce reproductive abnormalities in males. Therefore, the present study examined the effect of gestational exposure to PFNA on the testes of neonatal mice offspring. Pregnant Parkes mice were orally administered PFNA (2 and 5 mg/kg body weight) or distilled water from gestational day 12 until parturition. Male pups were killed on postnatal day 3. PFNA treatment decreased testosterone biosynthesis by inhibiting expression of steroidogenic acute regulatory protein, cytochrome P450scc, and 3β‐ and 17β‐hydroxysteroid dehydrogenase; proliferation of testicular cells was also affected in treated mice. Furthermore, a marked decrease in expression of Wilms tumor 1, steroidogenic factor 1 and insulin‐like factor 3 was noted in neonatal mice testes, indicating that the PFNA treatment may affect the development of the testis. Moreover, observation of the dose‐related expression of anti‐müllerian hormone and c‐Kit in neonatal mice testes is also suggestive of an interference with gonadal development by PFNA exposure. In conclusion, the results suggest that the gestational exposure to PFNA decreased testosterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health.
Targeted and stimuli–responsive mesoporous silica nanoparticles for drug delivery and theranostic use
Authors: Aquib Md , Farooq Muhammad A. , Banerjee Parikshit , Akhtar Fahad , Filli Mensura S. , Boakye‐Yiadom Kofi O. , Kesse Samuel , Raza Faisal , Maviah Mily B. J. , Mavlyanova Rukhshona , Wang Bo
Published: August 2019

For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs‐based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug‐loaded MPSNPs using targeting ligands and stimuli‐sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi‐stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery.
Grayscale mask‐assisted photochemical crosslinking for a dense collagen construct with stiffness gradient
Authors: Hong Hyeonjun , Park Sang Min , Kim Dohui , Park Sung Jea , Kim Dong Sung
Published: August 2019

Despite the potential of a collagen construct with a stiffness gradient for investigating cell–extracellular matrix (ECM) stiffness interaction or recapitulating an in vivo tissue interface, it has been developed in a limited way due to the low and poorly controllable mechanical properties of the collagen. This study proposes a novel fabrication process to achieve a compressed collagen construct with a stiffness gradient, named COSDIENT, at a level of ~ 1 MPa while maintaining in vivo ECM‐like dense collagen fibrillar structures. The COSDIENT was fabricated by collagen compression followed by grayscale mask‐assisted UV–riboflavin crosslinking. The collagen compression process enabled the remarkable increase in the stiffness of the collagen gel from ~ 1–10 kPa to ~ 1 MPa by physical compaction. The subsequent UV–riboflavin crosslinking with a continuous‐tone grayscale mask could simply generate a gradual change of UV irradiation followed by modulating riboflavin‐mediated crosslinking, thereby resulting in a continuous stiffness gradient with a range of 1.16–4.38 MPa in the single compressed collagen construct. The suggested grayscale mask‐assisted photochemical crosslinking had no effect on the physical and optical properties of the original compressed collagen construct, while inducing gradual changes of chemical bonds among collagen fibrils. A skin wound healing assay with epidermal keratinocytes was finally applied as an application example of the COSDIENT to examine the effect of stiffness on the skin keratinocyte behavior.
Controlled cross‐linking of porcine cholecyst extracellular matrix for preparing tissue engineering scaffold
Authors: Mony Manjula P. , Anilkumar Thapasimuthu V.
Published: August 2019

Treatment with cross‐linking agents for stabilizing biomolecules is an integral step during the preparation of many extracellular matrix‐based tissue engineering scaffolds from mammalian organs. However, excess cross‐linking may cause nonavailability of biomolecules and consequent deterioration of bioinductive properties of the scaffold. The present study considered controlling the extent of cross‐linking in a porcine cholecyst extracellular matrix scaffold prepared by a nonenzymatic and nondetergent method, by ex situ incubation of the source organ in varying concentrations of neutral buffered formaldehyde (10, 4, 1 or 0%; v/v) for in situ cross‐linking of biomolecules. Reduction of the formaldehyde concentration resulted in an increase in the extent of biodegradation and a decrease in the compactness of the mesh‐like surface microarchitecture of the scaffold. Retention of collagen was maximum when treated with 10% neutral buffered formaldehyde without any variation in the content of elastin and sulphated glycosaminoglycans. Although there was a reduction in the quantity of growth factors following the cross‐linking, fibroblasts remained viable on the scaffolds. The retention of major biomolecule was maximum and autodigestion was minimum in the scaffold prepared by the ex situ treatment of cholecyst in 10% neutral buffered formalin and found suitable for preparing the tissue engineering scaffold.
The Impact of Testosterone on Metformin Action on Hypothalamic‐Pituitary‐Thyroid Axis Activity in Men: A Pilot Study
Authors: Krysiak Robert , Szkróbka Witold , Okopień Bogusław
Published: August 2019

The effect of metformin on thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic‐pituitary‐thyroid axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550‐3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA‐GT. Metformin‐induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA‐GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
Modulation of the dual‐faced effects of miR‐141 with chitosan/miR‐141 nanoplexes in breast cancer cells
Authors: Kaban Kubra , Salva Emine , Akbuga Julide
Published: August 2019

Background

miR‐141, known as a tumor suppressive microRNA, is downregulated in breast cancer. However, recent contrasting studies report that it also acts as oncogene when it is upregulated. The present study aimed to investigate whether miR‐141 is a tumor suppressor or oncogenic when it reaches normal levels in chitosan/miR‐141 nanoplexes.

Methods

Chitosan nanoplexes were prepared using simple complexation method. Nanoplexes were characterized by a gel retardation assay and zeta potential and particle size measurements. To determine the expression level of miR‐141, a quantitative real‐time polymerase chain reaction was performed. The effects of miR‐141 mimics were investigated with respect to angiogenesis by vascular endothelial growth factor (VEGF), epithelial–mesenchymal transition (EMT) by E‐cadherin, metastasis by Igfbp‐4 and Tinagl1 enzyme‐linked immunosorbent assays, invasion by an invasion chamber, and apoptosis by Annexin V.

Results

The miR‐141 expression levels of MDA‐MB‐231 and MDA‐MB‐435 cells by administration of chitosan/mimic miR‐141 nanoplexes reached endogenous miR‐141 levels of a non‐tumorigenic epithelial breast cell line, MCF‐10A. According to our results, metastasis, VEGF, EMT and invasion in breast cancer cells were diminished, whereas apoptosis increased by 1.5‐ and 2.4‐fold in breast cancer cell lines as a result of the miR‐141 mimics.

Conclusions

In conclusion, we have demonstrated that administration of miR‐141 mimics at the determined doses to breast cancer cells revealed a tumor suppressor effect, and not the oncogenic face. The delivery of miR‐141 by chitosan nanoplexes presents a promising approach for the suppression of breast cancer.
Facile Synthesis, Antimicrobial Activity and Molecular Docking of Novel 2,4,5‐Trisubstituted‐1H‐Imidazole–Triazole Hybrid Compounds
Authors: Chauhan Sunil , Verma Vikas , Kumar Devinder , Kumar Ashwani
Published: August 2019

In the present work, a series of 18 imidazole–triazole hybrids (4a–r) has been synthesized in good yield from substituted naphthaldehydes and 1,2‐diketones in the presence of ammonium acetate. The synthesized imidazole–triazole hybrid compounds were characterized by spectral techniques and screened in vitro for their antimicrobial activity. Compound 4h was found to be most active against Staphylococcus epidermidis, and compound 4e exhibited promising activity against Escherichia coli. In the fungal species under test, compound 4q was most potent against Aspergillus niger, even better than the fluconazole. Further, compound 4e was docked in the binding site of DNA gyrase topoisomerase II of E. coli.
Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal
Authors: Kuypers Jane , Perchetti Garrett A. , Chu Helen Y. , Newman Kira L. , Katz Joanne , Khatry Subarna K. , LeClerq Steven C. , Jerome Keith R. , Tielsch James M. , Englund Janet A.
Published: August 2019

Problem

Rhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically.

Objective

To characterize the RV types detected with respiratory illness episodes in infants in Nepal.

Study methods

Infants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household‐based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types.

Results

Among 547 RV‐only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV‐A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV‐A, 11 RV‐B, and 31 RV‐C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV‐A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care‐seeking.

Conclusions

Among very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV‐A was detected most frequently. There was no association between RV species and disease severity.