bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of the quantification of respirable crystalline silica by mass on aerosol sampling filters using Raman microscopy
Authors: Stacey Peter , Mader Kerstin T. , Sammon Christopher
Published: February 2017

Airborne respirable crystalline silica (RCS) is a hazard that can affect the health of workers, and more sensitive measurements are needed for the assessment of worker exposure. To assess the use of Raman microscopy for the analysis of RCS particulate collected on filters, aliquots of quartz or cristobalite suspended in isopropanol were pipetted onto silver filters. Samples were measured by arbitrarily selecting positions along the filter and collecting spectra at 50 discrete points. The calculated limits of quantification on test samples were between 0.066–0.161 and 0.106–0.218 μg for quartz and cristobalite, respectively. Three respirable quartz calibration dusts (A9950, NIST 1878 and Quin 1B) with different mass median aerodynamic particle sizes obtained similar Raman response relationships per unit mass. The difference between NIST 1878 and Quin 1B was not significant (p = 0.22). The intermediate measurement precision of replicate samples was 10–25% over the measured range for quartz (0.25–10 μg) and could potentially be improved. Results from mixtures of quartz and cristobalite were mostly within 10% of their theoretical values. Results from samples of 6% quartz in calcite were close to the theoretical quartz mass. The upper measurement limit for a mixture of 20% RCS in the light absorbing mineral hematite (Fe2O3) was 5 μg. These data show that Raman spectroscopy is a viable option for the quantification of the mass of respirable crystalline silica on filters with a limit of detection approaching 1/10th of that obtained with other techniques. The improvement in sensitivity may enable the measurement of particulate in samples from low concentration environments (e.g. inside a mask) or from miniature samplers operating at low flow rates. ©2017 Crown copyright. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd. © 2017 Crown copyright. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd.
Fast and simultaneous determination of 12 polyphenols in apple peel and pulp by using chemometrics‐assisted high‐performance liquid chromatography with diode array detection
Authors: Wang Tong , Wu Hai‐Long , Xie Li‐Xia , Zhu Li , Liu Zhi , Sun Xiao‐Dong , Xiao Rong , Yu Ru‐Qin
Published: February 2017

In this work, a smart chemometrics‐enhanced strategy, high‐performance liquid chromatography, and diode array detection coupled with second‐order calibration method based on alternating trilinear decomposition algorithm was proposed to simultaneously quantify 12 polyphenols in different kinds of apple peel and pulp samples. The proposed strategy proved to be a powerful tool to solve the problems of coelution, unknown interferences, and chromatographic shifts in the process of high‐performance liquid chromatography analysis, making it possible for the determination of 12 polyphenols in complex apple matrices within 10 min under simple conditions of elution. The average recoveries with standard deviations, and figures of merit including sensitivity, selectivity, limit of detection, and limit of quantitation were calculated to validate the accuracy of the proposed method. Compared to the quantitative analysis results from the classic high‐performance liquid chromatography method, the statistical and graphical analysis showed that our proposed strategy obtained more reliable results. All results indicated that our proposed method used in the quantitative analysis of apple polyphenols was an accurate, fast, universal, simple, and green one, and it was expected to be developed as an attractive alternative method for simultaneous determination of multitargeted analytes in complex matrices.
Monitoring of cefepime in human serum and plasma by micellar electrokinetic capillary chromatography: Improvement of sample preparation and validation by liquid chromatography coupled to mass spectrometry
Authors: Šestáková Nela , Theurillat Regula , Sendi Parham , Thormann Wolfgang
Published: February 2017

Cefepime monitoring in deproteinized human serum and plasma by micellar electrokinetic capillary chromatography and liquid chromatography coupled to mass spectrometry in presence of other drugs is reported. For micellar electrokinetic capillary chromatography, sample preparation comprised dodecylsulfate protein precipitation at pH 4.5 using an increased buffer concentration compared to that of a previous assay and removal of hydrophobic compounds with dichloromethane. This provided robust conditions for cefepime analysis in the presence of sulfamethoxazole and thus enabled its determination in samples of patients that receive cotrimoxazole. The liquid chromatography assay is based upon use of a column with a pentafluorophenyl‐propyl modified and multiendcapped stationary phase and the coupling to electrospray ionization with a single quadrupole detector. The performances of both assays with multilevel internal calibration were assessed with calibration and control samples and both assays were determined to be robust. Cefepime levels monitored by micellar electrokinetic capillary chromatography in samples from patients that were treated with cefepime only and with cefepime and cotrimoxazole were found to compare well with those obtained by liquid chromatography coupled to mass spectrometry. Cefepime drug levels determined by micellar electrokinetic capillary chromatography could thereby be validated.
UHPLC–MS/MS quantification combined with chemometrics for the comparative analysis of different batches of raw and wine‐processed Dipsacus asper
Authors: Tao Yi , Du Yingshan , Su Dandan , Li Weidong , Cai Baochang
Published: February 2017

A rapid and sensitive ultra‐high performance liquid chromatography with tandem mass spectrometry approach was established for the simultaneous determination of 4‐caffeoylquinic acid, loganic acid, chlorogenic acid, loganin, 3,5‐dicaffeoylquinic acid, dipsacoside B, asperosaponin VI, and sweroside in raw and wine‐processed Dipsacus asper. Chloramphenicol and glycyrrhetinic acid were employed as internal standards. The proposed approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. Intra‐ and interassay variability for all analytes were 2.8–4.9 and 1.7–4.8%, respectively. The standard addition method determined recovery rates for each analytes (96.8–104.6%). In addition, the developed approach was applied to 20 batches of raw and wine‐processed samples of Dipsacus asper. Principle component analysis and partial least squares‐discriminate analysis revealed a clear separation between the raw group and wine‐processed group. After wine‐processing, the contents of loganic acid, chlorogenic acid, dipsacoside B, and asperosaponin VI were upregulated, while the contents of 3,5‐dicaffeoylquinic acid, 4‐caffeoylquinic acid, loganin, and sweroside were downregulated. Our results demonstrated that ultra‐high performance liquid chromatography with tandem mass spectrometry quantification combined with chemometrics is a viable method for quality evaluation of the raw Dipsacus asper and its wine‐processed products.
Extraction and separation of lactate dehydrogenase inhibitors from Poria cocos (Schw.) Wolf based on a hyphenated technique and in vitro methods
Authors: Li Sainan , Zhang Jianxu , Li Senlin , Liu Chunming , Liu Shu , Liu Zhiqiang
Published: February 2017

Stroke is one of the most common diseases worldwide. Lactate dehydrogenase inhibitors are widely used in the treatment of ischemic stroke, with natural products considered a promising source of lactate dehydrogenase inhibitors. In this study, ultrafiltration liquid chromatography coupled with mass spectrometry was used for the screening and identification of lactate dehydrogenase inhibitors from Poria cocos. Five lactate dehydrogenase inhibitors were selected: dehydropachymic acid, pachymic acid, dehydrotrametenolic acid, trametenolic acid, and eburicoic acid. The inhibitors were extracted and isolated with purities of 96.75, 98.15, 97.25, 95.46, and 94.88%, respectively, by using a new “hyphenated” strategy of microwave‐assisted extraction coupled with counter‐current chromatography and centrifugal partition chromatography by a two‐phase solvent system of n‐hexane/ethyl acetate/ethanol/water at the volume ratio 0.965:1.000:0.936:0.826 v/v/v/v. The bioactivity of the isolated compounds was assessed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay in PC12 cells. The results also showed that the hyphenated technique of microwave‐assisted extraction coupled with counter‐current chromatography and centrifugal partition chromatography was an efficient method for the continuous extraction and online isolation of chemical constituents from medicinal herbs. Furthermore, the research route based on the activity screening, extraction, separation, and activity verification of the compounds offered advantages of efficiency, orientation, and objectivity.
Room Temperature Self‐Healing Methyl Phenyl Silicone Rubbers Based on the Metal–Ligand Cross‐Link: Synthesis and Characterization
Authors: Yu Dajiang , Zhao Xinxin , Zhou Chuanjian , Zhang Chen , Zhao Shigui
Published: February 2017

Novel self‐healing silicone rubbers are prepared by a two‐step procedure: aminopropyl methyl phenyl polysiloxanes is first reacted with salicylaldehyde and then with copper acetate. The reversible nature of the metal–ligand coordination interaction between polysiloxanes with pendent Schiff‐base groups and Cu2+ has endowed silicone rubbers with superior self‐healing properties. As compared with other self‐healing silicone rubbers based on hydrogen bonds or Diels–Alder reaction, this cross‐linked system shows high healing power. The materials are cut into two parts and put together in a mold for 1 h at 30 °C, observing a macroscopic healing and a strength recovery up to 87.0%.

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Coassembly Modulated pH‐Responsive Hydrogel for Dye Absorption and Release
Authors: Wang Fang , Ji Wei , Liu Jinying , He Jiye , Feng Chuanliang
Published: February 2017

Hydrogel as a carrier for drug delivery system has been developed, but it is hard to change the load and release of drugs through a simple way. Herein, the authors report a novel pH‐sensitive supramolecular binary hydrogel based on Phe‐Gly derivative gelator (LPPG) and 4,4′‐dipyridine disulfide (DPDS). Fourier transform infrared spectroscopy, circular dichroism, and 1H NMR confirm that the driving force for the coassembly process is intermolecular hydrogen bonds. The composite hydrogel can improve the dye adsorption capacity relative to LPPG hydrogel. Moreover, the controllable absorption of the dyes is studied by varying the pH and concentration of dye solutions. LPPG‐DPDS hydrogel can also release of entrapped dyes at physiological pH. The two‐component hydrogel should be a promising system for controllable drug delivery.

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Promoting Endothelialization of Polymeric Cardiovascular Biomaterials
Authors: Heath Daniel E.
Published: February 2017

The lack of a blood compatible synthetic interface is one of the largest unaddressed challenges in the field of biomaterials science. This technological shortcoming hinders the successful clinical application of small diameter vascular grafts and other cardiovascular devices such as stents and artificial heart valves. Therefore, intensive research activities are ongoing to develop polymer materials with improved blood compatibility. One attractive strategy to improve the blood compatibility of an interface is to design surfaces that promote the development of an endothelium, the monolayer of endothelial cells that line our native vasculature and is responsible for blood compatibility. This article describes the recent strategies that have been used to generate polymeric materials that promote the development of an endothelium, discusses shortcomings in the field, and proposes future directions of research that can be undertaken to design next generation polymeric biomaterial that promote endothelialization.

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A comprehensive phylogenetic analysis of copper transporting P1B ATPases from bacteria of the Rhizobiales order uncovers multiplicity, diversity and novel taxonomic subtypes
Authors: Cubillas Ciro , Miranda‐Sánchez Fabiola , González‐Sánchez Antonio , Elizalde José Pedro , Vinuesa Pablo , Brom Susana , García‐de los Santos Alejandro
Published: February 2017

The ubiquitous cytoplasmic membrane copper transporting P1B‐1 and P1B‐3‐type ATPases pump out Cu+ and Cu2+, respectively, to prevent cytoplasmic accumulation and avoid toxicity. The presence of five copies of Cu‐ATPases in the symbiotic nitrogen‐fixing bacteria Sinorhizobium meliloti is remarkable; it is the largest number of Cu+‐transporters in a bacterial genome reported to date. Since the prevalence of multiple Cu‐ATPases in members of the Rhizobiales order is unknown, we performed an in silico analysis to understand the occurrence, diversity and evolution of Cu+‐ATPases in members of the Rhizobiales order. Multiple copies of Cu‐ATPase coding genes (2–8) were detected in 45 of the 53 analyzed genomes. The diversity inferred from a maximum‐likelihood (ML) phylogenetic analysis classified Cu‐ATPases into four monophyletic groups. Each group contained additional subtypes, based on the presence of conserved motifs. This novel phylogeny redefines the current classification, where they are divided into two subtypes (P1B‐1 and P1B‐3). Horizontal gene transfer (HGT) as well as the evolutionary dynamic of plasmid‐borne genes may have played an important role in the functional diversification of Cu‐ATPases. Homologous cytoplasmic and periplasmic Cu+‐chaperones, CopZ, and CusF, that integrate a CopZ‐CopA‐CusF tripartite efflux system in gamma‐proteobacteria and archeae, were found in 19 of the 53 surveyed genomes of the Rhizobiales. This result strongly suggests a high divergence of CopZ and CusF homologs, or the existence of unexplored proteins involved in cellular copper transport.
DKK3 attenuates the cytotoxic effect of natural killer cells on CD133+ gastric cancer cells
Authors: Xia Pu , Xu Xiao‐Yan
Published: February 2017

Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem‐like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D‐dependent manner. DKK3 has been demonstrated as a suppressor in many cancers. Interestingly, we found that DKK3 suppressed CD133‐induced activation in NK cells by inhibiting Erk pathway and immunological synapse (IS) formation. NK cells‐based CSCs immunotherapy may be a novel approach for cancer therapy.
Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas
Authors: Fedirko Veronika , McKeown‐Eyssen Gail , Serhan Charles N. , Barry Elizabeth L. , Sandler Robert S. , Figueiredo Jane C. , Ahnen Dennis J. , Bresalier Robert S. , Robertson Douglas J. , Anderson Carlton W. , Baron John A.
Published: February 2017

Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA4 and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub‐set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC‐MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA4 and RvD1 were not associated with the risk of adenoma occurrence. LXA4 at the end of study follow‐up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non‐significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA4 or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA4 may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed.
Divergent roles of p120‐catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen‐induced rat skin tumors
Authors: Wang Rong , Chen Ying‐Shiuan , Dashwood Wan‐Mohaiza , Li Qingjie , Löhr Christiane V. , Fischer Kay , Ho Emily , Williams David E. , Dashwood Roderick H.
Published: February 2017

The heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) targets multiple organs for tumorigenesis in the rat, including the colon and the skin. PhIP‐induced skin tumors were subjected to mutation screening, which identified genetic changes in Hras (7/40, 17.5%) and Tp53 (2/40, 5%), but not in Ctnnb1, a commonly mutated gene in PhIP‐induced colon tumors. Despite the absence of Ctnnb1 mutations, β‐catenin was overexpressed in nuclear and plasma membrane fractions from PhIP‐induced skin tumors, coinciding with loss of p120‐catenin from the plasma membrane, and the appearance of multiple p120‐catenin‐associated bands in the nuclear extracts. Real‐time RT‐PCR revealed that p120‐catenin isoforms 1 and 4 were upregulated in PhIP‐induced skin tumors, whereas p120‐catenin isoform 3 was expressed uniformly, compared with adjacent normal‐looking tissue. In human epidermoid carcinoma and colon cancer cells, transient transfection of p120‐catenin isoform 1A enhanced the viability and cell invasion index, whereas transient transfection of p120‐catenin isoform 4A increased cell viability and cell proliferation. Knockdown of p120‐catenin revealed a corresponding reduction in the expression of β‐catenin and a transcriptionally regulated target, Ccnd1/Cyclin D1. Co‐immunoprecipitation experiments identified associations of β‐catenin with p120‐catenin isoforms in PhIP‐induced skin tumors and human cancer cell lines. The results are discussed in the context of therapeutic strategies that might target different p120‐catenin isoforms, providing an avenue to circumvent constitutively active β‐catenin arising via distinct mechanisms in skin and colon cancer.
Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair‐deficiency and Lynch syndrome
Authors: Maletzki Claudia , Huehns Maja , Bauer Ingrid , Ripperger Tim , Mork Maureen M. , Vilar Eduardo , Klöcking Sabine , Zettl Heike , Prall Friedrich , Linnebacher Michael
Published: February 2017

Mismatch‐repair deficient (MMR‐D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood‐form of constitutional mismatch repair‐deficiency (CMMR‐D); caused by bi‐allelic MMR gene mutations. A hallmark of LS‐associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR‐D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR‐D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR‐D. CMMR‐D‐associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR‐D cases. MSI‐target gene analysis revealed mutations in CMMR‐D‐associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR‐D tumorigenesis.
Curcumin analog L48H37 induces apoptosis through ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells
Authors: Feng Chen , Xia Yiqun , Zou Peng , Shen Miaoshan , Hu Jie , Ying Shilong , Pan Jialing , Liu Zhiguo , Dai Xuanxuan , Zhuge Weishan , Liang Guang , Ruan Yeping
Published: February 2017

Lung cancer is the leading cause of cancer‐related deaths. Curcumin is a well‐known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously, we reported that L48H37, a novel analog of curcumin with higher bioavailability, ameliorated LPS‐induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells. Our results show that L48H37 decreases lung cancer cell growth and colony formation. These alterations were mediated through induction of G2/M cell cycle arrest and apoptosis in lung cancer cells. After L48H37 treatment, ER stress‐related proteins were increased, and the expression of p‐STAT3 was decreased in a dose‐dependent manner. L48H37 also induced the accumulation of ROS in lung cancer cells, and pretreatment with NAC could fully reverse L48H37‐induced reactive oxygen species (ROS) increase. Blocking ROS was able to reverse L48H37‐induced endoplasmic reticulum (ER) stress, cell cycle arrest, and apoptosis. Finally, we show that L48H37 inhibits the growth of lung cancer xenografts without exhibiting toxicity. Treatment of mice bearing human lung cancer xenografts with L48H37 was also associated with indices of ER stress activation. In summary, our results provide evidence for a novel anti‐tumor candidate for the treatment of lung cancer.
Profound changes in miRNA expression during cancer initiation by aflatoxin B1 and their abrogation by the chemopreventive triterpenoid CDDO‐Im
Authors: Livingstone Merricka C. , Johnson Natalie M. , Roebuck Bill D. , Kensler Thomas W. , Groopman John D.
Published: February 2017

Aflatoxin B1 (AFB1) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next‐generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 μg/kg per day AFB1 for 4 week. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno‐miR‐434‐3p, rno‐miR‐411‐5p, rno‐miR‐221‐3p, rno‐miR‐127‐3p, rno‐miR‐205, rno‐miR‐429, rno‐miR‐34a‐5p, rno‐miR‐181c‐3p, rno‐miR‐200b‐3p, and rno‐miR‐541‐5p. Analysis of rat livers exposed to AFB1 plus the chemopreventive triterpenoid CDDO‐Im revealed a striking abrogation of this upregulation. These changes were validated by real‐time PCR. We also explored the temporal variation in expression of the candidate miRNAs during the 4‐week dosing period. Most of the candidate miRNAs were upregulated at week 1 and increased for the duration of AFB1 dosing over the 4‐week period. Treatment with CDDO‐Im ameliorated these effects at all time points. All candidate miRNAs were detectable in serum from aflatoxin treated animals; however, there was no significant difference in expression for 7 of the 11 miRNAs examined. Exposure to AFB1 upregulated miR‐122‐5p (fivefold), 34a‐5p (13‐fold), and 181c‐3p (170‐fold) compared with controls. The findings from this study give insight into epigenetic changes induced by aflatoxin taking place during the initial step of carcinogenesis.
Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation
Authors: Benešová Martina , Trejbalová Kateřina , Kučerová Dana , Vernerová Zdenka , Hron Tomáš , Szabó Arpád , Amouroux Rachel , Klézl Petr , Hajkova Petra , Hejnar Jiří
Published: February 2017

Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells (PGCs), including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1‐3 enzymes and the level of their product, 5‐hydroxymethylcytosine (5hmC), in a panel of histologically characterized seminomas and non‐seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real‐time PCR. TET1 expression and the level of 5hmC were examined immunohistochemically. Quantitative assessment of 5‐methylcytosine (5mC) and 5hmC levels was done by the liquid chromatography‐mass spectroscopy technique. We found highly increased expression of TET1 dioxygenase in most seminomas and strong TET1 staining in seminoma cells. Isocitrate dehydrogenase 1 and 2 mutations were not detected, suggesting the enzymatic activity of TET1. The levels of 5mC and 5hmC in seminomas were found decreased in comparison to non‐seminomatous germ cell tumors and healthy testicular tissue. We propose that TET1 expression should be studied as a potential marker of seminomas and mixed germ cell tumors and we suggest that elevated expression of TET dioxygenase enzymes is associated with the maintenance of low DNA methylation levels in seminomas. This “anti‐methylator” phenotype of seminomas is in contrast to the CpG island methylator phenotype (CIMP) observed in a fraction of tumors of various types.
Chromium IV exposure, via Src/Ras signaling, promotes cell transformation
Authors: Ganapathy Suthakar , Li Ping , Lafontant Jean , Xiong Rui , Yu Tianqi , Zhang Guojun , Chen Changyan
Published: February 2017

Hexavalent chromium [Cr(VI)] is a well‐known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles, and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)‐mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS‐2B or keratinocytes. These cells were formed colonies in soft agar cultures following the persistent Cr(VI) treatment. Furthermore, anti‐apoptotic factor Bcl‐2 was upregulated and activated in the colonies. Thus, our study suggests that Cr(VI), though activating the src and Ras signaling axis, perturbs redox state and invokes ER stress for the establishment of carcinogenic actions in the cells. In this process, Bcl‐2 appears playing an important role. By uncovering these intracellular targets, our study may help developing novel strategies for better environmental protection, especially in areas contaminated or polluted by Cr(VI) as well as for effective cancer treatments.
Physiologically based kinetic modeling of hesperidin metabolism and its use to predict in vivo effective doses in humans
Authors: Boonpawa Rungnapa , Spenkelink Albertus , Punt Ans , Rietjens Ivonne M. C. M.
Published: February 2017

Scope

To develop a physiologically based kinetic (PBK) model that describes the absorption, distribution, metabolism, and excretion of hesperidin in humans, enabling the translation of in vitro concentration–response curves to in vivo dose–response curves.

Methods and results

The PBK model for hesperidin in humans was developed based on in vitro metabolic parameters. Hesperidin was predicted to mainly occur in the systemic circulation as different monoglucuronides. The plasma concentrations of hesperidin aglycone (hesperetin) was predicted to be <0.02 mg/L at an oral dose of 50 mg/kg bw. The developed PBK model allowed conversion of in vitro concentration–response curves for different effects to in vivo dose–response curves. The BMD05 (benchmark dose for 5% response) values for protein kinase A inhibition ranged between 135 and 529 mg/kg bw hesperidin, and for inhibition of endothelial cell migration and prostaglandin E2 and nitric oxide production ranged between 2.19 and 44 mg/kg bw hesperidin. These values are in line with reported human data showing in vivo effects by hesperidin and show that these effects may occur at Western dietary and supplementary intake of hesperidin.

Conclusions

The developed PBK model adequately predicts absorption, distribution, metabolism, and excretion of hesperidin in humans and allows to evaluate the human in vivo situation without the need for human intervention studies.
Specific inulin‐type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis
Authors: Chen Kang , Chen Hao , Faas Marijke M. , de Haan Bart J. , Li Jiahong , Xiao Ping , Zhang Hao , Diana Julien , de Vos Paul , Sun Jia
Published: February 2017

Scope

Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin‐type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice.

Methods and results

Female nonobese diabetic mice were weaned to long‐ and short‐chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic‐gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T‐cell responses, as evidenced by increased CD25+Foxp3+CD4+ regulatory T cells, decreased IL17A+CD4+ Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase‐1‐p20‐IL‐1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin‐2, antimicrobial peptides β‐defensin‐1, and cathelicidin‐related antimicrobial peptide as well as short‐chain fatty acid production were enhanced by ITF(l). Next‐generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli.

Conclusion

Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut‐pancreatic immunity, barrier function, and microbiota homeostasis.
Chronic supplementation with dietary proanthocyanidins protects from diet‐induced intestinal alterations in obese rats
Authors: Gil‐Cardoso Katherine , Ginés Iris , Pinent Montserrat , Ardévol Anna , Arola Lluís , Blay Mayte , Terra Ximena
Published: February 2017

Scope

Increased attention has been paid to the link between altered intestinal function and elevated incidence of metabolic disorders, such as in obesity. This study investigated in obese rats the role of grape seed proanthocyanidin extract (GSPE) chronic treatment, taken in a low, moderate, or high dose, on obesity‐associated intestinal alterations in response to a cafeteria diet (CAF).

Methods and results

To evaluate the degree of intestinal inflammation, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity were measured as well as the expression of inflammatory‐related genes. The barrier integrity was assessed by quantifying the gene expression of tight‐junction components and measuring the plasma LPS. GSPE decreased the ROS levels and MPO activity, without substantial differences among the doses. The supplementation with moderate and high GSPE doses significantly decreased iNOS expression compared to the CAF group, and the same pattern was observed in the low‐dose animals with respect to IL‐1β expression. Moreover, the results show that GSPE significantly increases zonulin‐1 expression with respect to the CAF animals.

Conclusion

This study provides evidence for the ameliorative effect of a proanthocyanidin extract on high‐fat/high‐carbohydrate diet‐induced intestinal alterations, specifically reducing intestinal inflammation and oxidative stress and suggesting a protection against a barrier defect.
Kinetics and mechanism of the thermal degradation for the synthesis of poly(norbornene sulfone)s by two different polymerization methods
Authors: Liu Xin , Guo Xuewen , Zhi Yunfei , Shan Shaoyun , Ni Yonghao , Jia Qingming
Published: February 2017

The recent development of sulfur dioxide (SO2) polymerization has seen a renaissance in its chemistry, especially poly(olefin sulfone)s from the copolymerization of SO2, and unsaturated hydrocarbons can be found to have many applications, including transient electronic packaging, drug delivery, and electron beam‐resistant materials. In this work, a type of functional poly(norbornene sulfone) was synthesized via two different polymerization methods. Aiming to understanding the effects of different polymerization methods on poly(olefin sulfone)s and gain further understanding on the kinetics of poly(olefin sulfone)s's thermal instability, we investigated their detailed thermal degradation behaviors using thermogravimetry and analyzed the resultant kinetics in accordance with three kinetic models. The results supported the conclusion that although the poly(norbornene sulfone)s obtained have different activation energy, the thermal degradation kinetics are the same and also obey the Dn type. Copyright © 2017 John Wiley & Sons, Ltd.
Synthesis of poly(silmethylene)s via ring‐opening polymerization of benzocyclobutene functionalized disilacyclobutene and their low‐dielectric and thermal properties
Authors: Huang Yawen , Zhang Shengbo , Hu Huan , Wei Xiaonan , Yu Hongtao , Yang Junxiao
Published: February 2017

In this work, benzocyclobutene‐introduced poly(silmethylene)s were synthesized by ring‐opening copolymerization of benzocyclobutene (BCB) functionalized disilacyclobutene with phenyldisilacyclobutene. The incorporation ratio of BCB was tailored by changing feeding ratio of 1,3‐dimethyl‐1,3‐dibenzocyclobutene‐1,3‐disilacyclobutane and 1,3‐dimethyl‐1,3‐diphenyl‐1,3‐disilacyclobutane, thus enabling the control of ultimate properties of cured resins. With increasing the incorporation ratios of BCB from 9.5 to 28.9 mol%, T5% of cured resins is improved from 404°C to 462°C, while the dielectric constant is decreased from 2.59 to 2.41 at 10 MHz. The excellent thermal stability and low‐dielectric performance make such thermosets potential inter‐layered or inter‐lined low‐dielectric media. Copyright © 2017 John Wiley & Sons, Ltd.
Influence of Na on grain boundary and properties of Cu(In,Ga)Se2 solar cells
Authors: Raghuwanshi Mohit , Cadel Emmanuel , Duguay Sébastien , Arzel Ludovic , Barreau Nicolas , Pareige Philippe
Published: February 2017

Whether added from external sources or supplied via substrate, incorporation of Na has always improved the conversion efficiency of polycrystalline thin‐film Cu(In,Ga)Se2 (CIGS) solar cells. Segregation of Na along grain boundary (GB) is thought to be one of the main reasons for better efficiency, and changing its concentration levels may tune the device properties accordingly. Our previous works have shown that changes in GB chemistry over various Ga/In concentrations are the main reason for poor performance of Ga‐rich (18%) CIGS, besides its optimum band gap (1.4 eV) for energy conversion. It was suspected that changes in GB chemistry or device performance or both could be driven by variation in Na concentration at GB. In this research, atomic level fluctuations of Na atoms at GB for various CuIn1−xGaxSe2 thin films were measured accurately with atom probe tomography technique. Fluctuations observed in Na concentration at GB are restricted to the range 0.5–6.5 atoms per nm2 and is irrespective of x value (GGI) and GB surface density. Results also show that changes in GB chemistry for similar CIGS compositions are not necessary due to changes in Na concentration levels at GB. However, an increased density of GBs per unit volume with GGI may indicate an overall rise in Na in thin films and could explain the drop in CIGS performance. Copyright © 2017 John Wiley & Sons, Ltd.
Novel field‐effect passivation for nanostructured Si solar cells using interfacial sulfur incorporation
Authors: Kim Dae Woong , Song Jae‐Won , Park Young Min , Lee Jung‐Ho , Park Tae Joo
Published: February 2017

Surface passivation of a nanostructured Si solar cells plays a crucial role in collecting photogenerated carriers by mitigating carrier recombination at surface defect sites. Interface modification by additional sulfur (S) incorporation is proposed to enhance the field‐effect passivation performance. Here, we report that simple annealing in a H2S ambient induced additional negative fixed charges at the interface between atomic‐layer‐deposited Al2O3 and nanostructured Si. Annealing at various temperatures allowed us to control the S concentration and the fixed charge density. The optimized S incorporation at the interface significantly enhanced the negative fixed charge density and the minority carrier lifetime up to ~5.9 × 1012 cm−2 and ~780 μs, respectively. As a result, the internal quantum efficiency was nearly two times higher in the blue response region than that of control cells without S incorporation. Copyright © 2017 John Wiley & Sons, Ltd.
Effect of Pre‐strain Aging on the Damage Properties of Composite Solid Propellants based on a Constitutive Equation
Authors: Zhou Dongmo , Liu Xiangyang , Sui Xin , Wei Zhijun , Wang Ningfei
Published: February 2017

Accelerated aging tests under pre‐strain were conducted on HTPB‐based composite solid propellant with the goal of investigating the effect of pre‐strain aging on its damage properties. A statistical damage constitutive model based on continuum damage theory and statistical strength theory was established. The aging damage coefficient, making aging process of propellant equivalent to a form of damage, was introduced to correct the damage variable. Experimental results show that theoretical model has good agreement with experimental results and can accurately describe the mechanical behavior of propellant during pre‐strain aging. Further analysis indicated that the damage effects caused by pre‐strain can be identified from the equation of the aging damage coefficient. Aging time influences both tensile strength and shape characteristics of the stress‐strain curve of propellant in the damage stage, while pre‐strain only decreased the tensile strength. The strain damage threshold value decreased linearly over the aging period and with increasing pre‐strain level during the aging process.
Partial Reparametrization of the BKW Equation of State for DNAN‐Based Melt‐Cast Explosives
Authors: Li Dongwei , Zhou Lin , Zhang Xiangrong
Published: February 2017

DNAN‐based melt‐cast explosives are a type of new, insensitive munitions (IM) explosives. Quickly determining munitions’ explosive properties is extremely important during the formulation design stage. The aim of this study was to partially reparameterize BKW‐EOS (only β and κ were reparameterized on the basis of the parameters (α, β, κ, and θ) of classical BKW‐RDX set and BKW‐TNT set) to more accurately predict the properties of DNAN‐based melt‐cast explosives. A new set of parameters β and κ was obtained (β=0.19, κ=9.81) according to measured detonation velocity and detonation pressure for ideal DNAN‐based melt‐cast formulations (DNAN/RDX and DNAN/HMX). For non‐ideal DNAN‐based melt‐cast formulations (DNAN/RDX/Al and DNAN/HMX/Al), aluminum oxidation degree was first determined according to the measured detonation heat; then, another new set of parameters β and κ was obtained in the same way as the ideal formulations (β=0.24, κ=8.5). The predicted detonation properties with BKW reparametrization for DNAN‐based melt‐cast explosives agreed with the measured data.
Introducing Novel Tetrazole Derivatives as High Performance Energetic Compounds for Confined Explosion and as Oxidizer in Solid Propellants
Authors: Keshavarz Mohammad Hossein , Abadi Yasin Hayat , Esmaeilpour Karim , Damiri Sajjad , Oftadeh Mohsen
Published: February 2017

This paper introduces five novel high‐nitrogen content (N>50%) tetrazole derivatives with desirable physicothermal properties, high detonation and combustion performance as well as suitable sensitivities with respect to external stimuli electric spark and heat. Suitable density functional theory (DFT) and empirical methods were used to predict their crystal density, melting point, condensed phase heat of formation, enthalpy of fusion, Gibbs free energy of formation, velocity of detonation, detonation pressure, Gurney velocity, heat of detonation, power (strength), brisance, impact sensitivity, electric spark sensitivity, heat sensitivity and specific impulse. Two compounds 5,5′‐[(1Z,5Z)‐3,4‐dinitrohexaaza‐1,5‐diene‐1,6‐diyl]bis(1‐nitro‐1H‐tetrazole) and 3,3′,7,7′‐tetranitro‐3,3a,3′,3′a‐tetrahydro‐7H,7′H‐6,6′‐bitetrazolo[1,5‐e]pentazine as compared to the other new derivatives can be introduced as high performance explosives for confined explosion and oxidizers in solid propellants.
Structural and biochemical characterization of the nucleoside hydrolase from C. elegans reveals the role of two active site cysteine residues in catalysis
Authors: Singh Ranjan Kumar , Steyaert Jan , Versées Wim
Published: February 2017

Nucleoside hydrolases (NHs) catalyze the hydrolysis of the N‐glycoside bond in ribonucleosides and are found in all three domains of life. Although in parasitic protozoa a role in purine salvage has been well established, their precise function in bacteria and higher eukaryotes is still largely unknown. NHs have been classified into three homology groups based on the conservation of active site residues. While many structures are available of representatives of group I and II, structural information for group III NHs is lacking. Here, we report the first crystal structure of a purine‐specific nucleoside hydrolase belonging to homology group III from the nematode Caenorhabditis elegans (CeNH) to 1.65Å resolution. In contrast to dimeric purine‐specific NHs from group II, CeNH is a homotetramer. A cysteine residue that characterizes group III NHs (Cys253) structurally aligns with the catalytic histidine and tryptophan residues of group I and group II enzymes, respectively. Moreover, a second cysteine (Cys42) points into the active site of CeNH. Substrate docking shows that both cysteine residues are appropriately positioned to interact with the purine ring. Site‐directed mutagenesis and kinetic analysis proposes a catalytic role for both cysteines residues, with Cys253 playing the most prominent role in leaving group activation.
Stepwise assembly of functional C‐terminal REST/NRSF transcriptional repressor complexes as a drug target
Authors: Inui Ken , Zhao Zongpei , Yuan Juan , Jayaprakash Sakthidasan , Le Le T. M. , Drakulic Srdja , Sander Bjoern , Golas Monika M.
Published: February 2017

In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)‐silencing transcription factor/neuron‐restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non‐neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C‐terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes. Therefore, the aim of this study was to express and purify human REST/NRSF and its C‐terminal interactors in a baculovirus multiprotein expression system as individual proteins and coexpressed complexes. All proteins were enriched in the nucleus, and REST/NRSF was isolated as a slower migrating form, characteristic of nuclear REST/NRSF in mammalian cells. Both REST/NRSF alone and its C‐terminal repressor complex were functionally active in histone deacetylation and histone demethylation and bound to RE1/neuron‐restrictive silencer element (NRSE) sites. Additionally, the mechanisms of inhibition of the small‐molecule drugs 4SC‐202 and SP2509 were analyzed. These drugs interfered with the viability of medulloblastoma cells, where REST/NRSF has been implicated in cancer pathogenesis. Thus, a resource for molecular REST/NRSF studies and drug development has been established.
Effect of micromorphology on transport properties of Nb‐doped anatase TiO2 films: A transmission electron microscopy study
Authors: Ogawa Daisuke , Nakao Shoichiro , Morikawa Kazuo , Ebisawa Mizue , Hirose Yasushi , Hasegawa Tetsuya
Published: February 2017

We investigate the transport properties and micromorphology of polycrystalline Nb‐doped anatase TiO2 (TNO) transparent conductive films, as a function of working pressure (pw) during sputtering. The TNO films were crystallized from amorphous precursors sputter‐deposited on unheated glass substrates. The micromorphologies of the TNO films were observed using a transmission electron microscope. The film deposited at a high pw of 1 Pa showed an inhomogeneous micromorphology, and a substantially low Hall mobility (μH) of 2.0 cm2V−1s−1. However, films deposited at a low pw of 0.75 and 0.5 Pa exhibited less inhomogeneity in the micromorphologies and a high μH of 3.8 and 9.2 cm2V−1s−1, respectively. These results indicate that the inhomogeneous micromorphology acts as an additional carrier scattering source. The pw dependence of the micromorphology demonstrates that the inhomogeneous micromorphology originates from density fluctuation rather than sputter damage.

The working pressure (pw) of sputtering significantly affects the micromorphology and, thus, the Hall mobility (μH) of Nb‐doped anatase TiO2 (TNO) transparent conductive thin films.
Influence of AlN buffer layer on growth of AlGaN by HVPE
Authors: Fleischmann Simon , Richter Eberhard , Mogilatenko Anna , Weyers Markus , Tränkle Günther
Published: February 2017

To the end of improvement of layer morphology and crystalline perfection of thick AlGaN layers grown by hydride vapor phase epitaxy (HVPE) as well as for the suppression of crystallite formation during growth, the impact of AlN buffer layer properties on AlGaN growth was investigated. While the surface morphology of 500 nm thick AlN layer improves with higher V/III ratio toward 50 and lower growth temperatures of 1020 °C, its use as a buffer layer for thick AlGaN layers leads to strong degradation of AlGaN surface and even to formation of different crystallites during growth. Best surface morphology and crystalline perfection of thick AlGaN layers was observed for the growth on an AlN buffer layer with a higher crystal quality disregarding its 3D morphology and high surface roughness. Best results were achieved at medium V/III ratio of about 10–20 and AlN buffer growth temperature of 1060 °C.