bluuebunny/crossref_metadata_2025 huggingface dataset:
Furanodienone induces G0/G1 arrest and causes apoptosis via the ROS/MAPKs-mediated caspase-dependent pathway in human colorectal cancer cells: a study in vitro and in vivo
Authors: Jiang Ying , Wang Xiaoqin , Hu Daode
Published: May 2017

Furanodienone, a major bioactive constituents of sesquiterpene derived from Rhizoma Curcumae, has been proven to possess the potent anticancer efficacy on human breast cancer cells. Here, we investigated the cytotoxicity of furanodienone on human colorectal carcinoma cell lines in vitro and in vivo, as well as its underlying molecular mechanisms in the induction of apoptosis. In this study, we found that furanodienone significantly inhibited proliferation of RKO and HT-29 cells, induced mitochondrial dysfunction characterized by collapse of mitochondrial transmembrane potential and reduction of ATP level, and promoted the production of reactive oxygen species (ROS) that functions upstream of caspase-dependent apoptosis. The antioxidant N-acetyl cysteine, a ROS scavenger, abolished this apoptosis induced by furanodienone. In addition, furanodienone elevated the expression of p-p38, p-JNK, but decreased p-ERK, as a result of the produced ROS. The specific inhibitors U0126, SP600125 and SB202190 attenuated the expression of MAPKs, and regulated the expression of cleaved caspase-8, -9 and -3. Furthermore, the potential inhibitory effect of furanodienone on CRC cells was also corroborated in mouse xenograft model. In conclusion, the results demonstrated that furanodienone-triggered ROS plays a pivotal role in apoptosis as an upstream molecule-modulating activity of caspases in mitochondrial pathway via stimulating MAPKs signaling pathway. Our finding may provide a novel candidate for development of antitumor drugs targeting on colorectal cancer.
RETRACTED ARTICLE: Functional screen analysis reveals miR-3142 as central regulator in chemoresistance and proliferation through activation of the PTEN-AKT pathway in CML
Authors: Zhao Lifen , Shan Yujia , Liu Bing , Li Yang , Jia Li
Published: May 2017

Chronic myeloid leukemia (CML) is caused by the constitutively active BCR-ABL tyrosine kinase. Although great progress has been made for improvement in clinical treatment during the past decades, it is common for patients to develop chemotherapy resistance. Therefore, further exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNAs (miRNAs) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. Previously, we identified 41 miRNAs that were dysregulated in resistant compared with adriamycin (ADR)-sensitive parental cells in CML. In the present study, we reported that miR-3142 are overexpressed in ADR-resistant K562/ADR cells and CML/multiple drug resistance patients, as compared with K562 cells and CML patients. Upregulation of miR-3142 in K562 cells accelerated colony formation ability and enhanced resisitance to ADR in vitro. Conversely, inhibition of miR-3142 expression in K562/ADR cells decreased colony-formation ability and enhanced sensitivity to ADR in vitro and in vivo. Significantly, our results showed miR-3142-induced ADR resistance through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which led to downregulation of PTEN protein and activation of PI3 kinase (PI3K)/Akt pathway. Inhibition of Akt using Akt inhibitor or introduction of PTEN largely abrogated miR-3142-induced resistance. These findings indicated that miR-3142 induces cell proliferation and ADR resistance primarily through targeting the PTEN/PI3K/Akt pathway and implicate the potential application of miR-3142 in cancer therapy.
The role of extracellular histone in organ injury
Authors: Silk Eleanor , Zhao Hailin , Weng Hao , Ma Daqing
Published: May 2017

Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease. Once in the extracellular space, histones act as damage-associated molecular pattern proteins, activating the immune system and causing further cytotoxicity. They interact with Toll-like receptors (TLRs), complement and the phospholipids of cell membranes inducing endothelial and epithelial cytotoxicity, TLR2/TLR4/TLR9 activation and pro-inflammatory cytokine/chemokine release via MyD88, NFκB and NLRP3 inflammasome-dependent pathways. Drugs that block the release of histone, neutralise circulating histone or block histone signal transduction provide significant protection from mortality in animal models of acute organ injury but warrant further research to inform future clinical applications.
Engineering the haemogenic niche mitigates endogenous inhibitory signals and controls pluripotent stem cell-derived blood emergence
Authors: Rahman Nafees , Brauer Patrick M. , Ho Lilian , Usenko Tatiana , Tewary Mukul , Zúñiga-Pflücker Juan Carlos , Zandstra Peter W.
Published: May 2017

Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or inhibition. Here we show haemogenic niches can be engineered using microfabrication strategies by micropatterning hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies. CD34+VECAD+ HE cells were generated with multi-lineage potential in serum-free conditions and cultured as size-specific haemogenic niches that displayed enhanced blood cell induction over non-micropatterned cultures. Intra-colony analysis revealed radial organization of CD34 and VECAD expression levels, with CD45+ blood cells emerging primarily from the colony centroid area. We identify the induced interferon gamma protein (IP-10)/p-38 MAPK signalling pathway as the mechanism for haematopoietic inhibition in our culture system. Our results highlight the role of spatial organization in hPSC-derived blood generation, and provide a quantitative platform for interrogating molecular pathways that regulate human haematopoiesis.
Splicing modulators act at the branch point adenosine binding pocket defined by the PHF5A–SF3b complex
Authors: Teng Teng , Tsai Jennifer HC , Puyang Xiaoling , Seiler Michael , Peng Shouyong , Prajapati Sudeep , Aird Daniel , Buonamici Silvia , Caleb Benjamin , Chan Betty , Corson Laura , Feala Jacob , Fekkes Peter , Gerard Baudouin , Karr Craig , Korpal Manav , Liu Xiang , T. Lowe Jason , Mizui Yoshiharu , Palacino James , Park Eunice , Smith Peter G. , Subramanian Vanitha , Wu Zhenhua Jeremy , Zou Jian , Yu Lihua , Chicas Agustin , Warmuth Markus , Larsen Nicholas , Zhu Ping
Published: May 2017

Pladienolide, herboxidiene and spliceostatin have been identified as splicing modulators that target SF3B1 in the SF3b subcomplex. Here we report that PHF5A, another component of this subcomplex, is also targeted by these compounds. Mutations in PHF5A-Y36, SF3B1-K1071, SF3B1-R1074 and SF3B1-V1078 confer resistance to these modulators, suggesting a common interaction site. RNA-seq analysis reveals that PHF5A-Y36C has minimal effect on basal splicing but inhibits the global action of splicing modulators. Moreover, PHF5A-Y36C alters splicing modulator-induced intron-retention/exon-skipping profile, which correlates with the differential GC content between adjacent introns and exons. We determine the crystal structure of human PHF5A demonstrating that Y36 is located on a highly conserved surface. Analysis of the cryo-EM spliceosome Bact complex shows that the resistance mutations cluster in a pocket surrounding the branch point adenosine, suggesting a competitive mode of action. Collectively, we propose that PHF5A–SF3B1 forms a central node for binding to these splicing modulators.
The geography of measles vaccination in the African Great Lakes region
Authors: Takahashi Saki , Metcalf C. Jessica E. , Ferrari Matthew J. , Tatem Andrew J. , Lessler Justin
Published: May 2017

Expanded access to measles vaccination was among the most successful public health interventions of recent decades. All WHO regions currently target measles elimination by 2020, yet continued measles circulation makes that goal seem elusive. Using Demographic and Health Surveys with generalized additive models, we quantify spatial patterns of measles vaccination in ten contiguous countries in the African Great Lakes region between 2009–2014. Seven countries have ‘coldspots’ where vaccine coverage is below the WHO target of 80%. Over 14 million children under 5 years of age live in coldspots across the region, and a total of 8–12 million children are unvaccinated. Spatial patterns of vaccination do not map directly onto sub-national administrative units and transnational coldspots exist. Clustering of low vaccination areas may allow for pockets of susceptibility that sustain circulation despite high overall coverage. Targeting at-risk areas and transnational coordination are likely required to eliminate measles in the region.
Erratum: Transient birefringence of liquids induced by terahertz electric-field torque on permanent molecular dipoles
Authors: Sajadi Mohsen , Wolf Martin , Kampfrath Tobias
Published: May 2017

Nature Communications 8: Article number: 14963 (2017); Published: 10 April 2017; Updated: 25 May 2017 This Article contains typographical errors in six instances in which the convolution symbol was mistakenly omitted from six equations during the production stage. Each instance is described below. The penultimate sentence of the first paragraph of the Results subsection titled ‘Model’ should read:
Cathelicidin-trypsin inhibitor loop conjugate represents a promising antibiotic candidate with protease stability
Authors: Yu Haining , Wang Chen , Feng Lan , Cai Shasha , Liu Xuelian , Qiao Xue , Shi Nannan , Wang Hui , Wang Yipeng
Published: May 2017

Cathelicidins are regarded as promising antibiotics due to their capability against antibiotic-resistant bacteria without cytotoxicity. However, some concerns about the balance of cytotoxicity and antimicrobial activity, weak stability and enzymatic susceptibility sually restrict their therapeutic use. Here, we designed a series of shortened variants, Hc1~15, based on our previously characterized Hc-CATH. Hc3, the one with the best activity, after point mutation was engineered with a trypsin inhibitor loop, ORB-C, to obtain four hybrid peptides: H3TI, TIH3, H3TIF and TIH3F. All four except TIH3 were found possessing an appreciable profile of proteases inhibitory and antimicrobial characteristics without increase in cytotoxicity. Among them, TIH3F exhibited the most potent and broad-spectrum antimicrobial and anti-inflammatory activities. Fluorescence spectroscopy has demonstrated a quick induction of bacterial membrane permeability by TIH3F leading to the cell death, which also accounts for its fast anti-biofilm activity. Such mode of antimicrobial action was mainly attributed to peptides’ amphiphilic and helical structures determined by CD and homology modeling. Besides, TIH3F exhibited good tolerance to salt, serum, pH, and temperature, indicating a much better physiological stability in vitro than Hc3, Most importantly, in the case of resistance against proteases hydrolysis, current hybrid peptides displayed a remarkable enhancement than their original templates.
Ultrasensitive Multi-Functional Flexible Sensors Based on Organic Field-Effect Transistors with Polymer-Dispersed Liquid Crystal Sensing Layers
Authors: Song Myeonghun , Seo Jooyeok , Kim Hwajeong , Kim Youngkyoo
Published: May 2017

Ultrasensitive flexible sensors with multi-sensing functions are required for various applications in flexible electronics era. Here we demonstrate flexible polymer-dispersed liquid crystal (PDLC)-integrated-organic field-effect transistors (OFETs) (PDLC-i-OFETs), which sensitively respond to various stimulations including weak gas (air) flow, direct physical touch, light, and heat. The flexible PDLC-i-OFETs were fabricated by spin-coating the poly(methyl methacrylate) (PMMA)-dispersed 4,4’-pentyl-cyanobiphenyl (5CB) layers on the poly(3-hexylthiophene) (P3HT) channel layers of OFETs with 200 μm-thick poly(ethylene naphthalate) (PEN) substrates. The flexible PDLC-i-OFET devices could sense very weak nitrogen gas flow (0.3 sccm), which cannot be felt by human skins, and stably responded to direct physical touches (0.6~4.8 g load). In addition, the present devices showed very sensitive photoresponses to a visible light and exhibited excellent heat-sensing characteristics at a temperature of 25~70 °C. In particular, the present flexible PDLC-i-OFET devices could sense two different stimulations at the same time, indicative of promising multi-sensing capabilities.
Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry
Authors: Reiser Karen , Stoller Patrick , Knoesen André
Published: May 2017

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated from the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.
Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
Authors: Hayashi Daiki , Yagi Keiko , Song Chihong , Ueda Shuji , Yamanoue Minoru , Topham Matthew , Suzaki Toshinobu , Saito Naoaki , Emoto Noriaki , Shirai Yasuhito
Published: May 2017

Diabetic nephropathy (DN) is one of vascular complications of diabetes and is caused by abnormal protein kinase C activation as a result of increased diacylglycerol (DG) production in diabetic hyperglycaemia. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. Therefore, it is expected that the activation of DGK would ameliorate DN. Indeed, it has been reported that vitamin E (VtE) ameliorates DN in rat by activating DGK, and we recently reported that VtE specifically activates DGKα isoform in vitro. However, whether DGKα is involved in the VtE-induced amelioration of DN in vivo remains unknown. Therefore, we investigated the VtE-induced amelioration of DN in wild-type (DGKα+/+) and DGKα–deficient (DGKα−/−) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGKα+/+ mice but not in the DGKα−/− mice. Moreover, transmission electron microscopy of glomeruli and immunofluorescent staining of glomerular epithelial cells (podocytes) indicated that VtE ameliorates podocyte pathology and prevents podocyte loss in the DGKα+/+ mice but not in the DGKα−/− mice. We showed that VtE can ameliorate DN in mice and that DGKα is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGKα is an attractive therapeutic target for DN.
Time-order-errors and duration ranges in the Episodic Temporal Generalization task
Authors: Mikulan Ezequiel , Bruzzone Manuel , Serodio Manuel , Sigman Mariano , Bekinschtein Tristán , García Adolfo M. , Sedeño Lucas , Ibáñez Agustín
Published: May 2017

The current model of the Episodic Temporal Generalization task, where subjects have to judge whether pairs of auditory stimuli are equal in duration, predicts that results are scale-free and unaffected by the presentation order of the stimuli. To test these predictions, we conducted three experiments assessing sub- and supra-second standards and taking presentation order into account. Proportions were spaced linearly in Experiments 1 and 2 and logarithmically in Experiment 3. Critically, we found effects of duration range and presentation order with both spacing schemes. Our results constitute the first report of presentation order effects in the Episodic Temporal Generalization task and demonstrate that future studies should always consider duration range, number of trials and presentation order as crucial factors modulating performance.
A randomised cross-over study assessing the “blue pyjama syndrome” in major depressive episode
Authors: Delmas Hélèna , Batail Jean-Marie , Falissard Bruno , Robert Gabriel , Rangé Maxence , Brousse Stéphane , Soulabaille Jacques , Drapier Dominique , Naudet Florian
Published: May 2017

This paper introduces a “blue pyjama syndrome” (whereby wearing hospital pyjamas results in an exaggerated impression of severity). We performed a 5-day, prospective, randomized, cross-over study in a French mood disorder unit for inpatients. At Day 1 (D1) and Day 5 (D5), two 5-minute video interviews were recorded with patients in pyjamas or in day clothes (the sequence was randomly allocated). Psychiatrists unaware of the study objective assessed the videos and scored their clinical global impressions (CGI, with scores ranging from 1 to 7). Of 30 participants with major depressive episode selected for inclusion, 26 participants (69% women) provided useable data for an evaluation by 10 psychiatrists. Pyjamas significantly increased the psychiatrists’ CGI ratings of disease severity by 0·65 [0·27; 1·02] points. The psychiatrists’ global impressions also rated patients as significantly less severe at D5 in comparison with D1 by −0·66 [−1·03; −0·29] points. The “blue pyjama syndrome” is in the same order of magnitude as the difference observed after a week of hospitalisation. This potentially calls into question the reliability and validity of observer ratings of depression.
Comparative de novo transcriptome profiles in Asparagus officinalis and A. kiusianus during the early stage of Phomopsis asparagi infection
Authors: Abdelrahman Mostafa , Suzumura Naoyuki , Mitoma Mai , Matsuo Satoshi , Ikeuchi Takao , Mori Mitsutaka , Murakami Kyoko , Ozaki Yukio , Matsumoto Masaru , Uragami Atsuko , Kanno Akira
Published: May 2017

Asparagus kiusianus, an important wild relative of cultivated asparagus (A. officinalis), exhibits resistance to stem blight disease caused by Phomopsis asparagi. However, the mechanisms underlying this resistance are not understood and no transcriptomic or genetic resources are available for this species. De novo transcriptome sequencing of A. officinalis and A. kiusianus stems was performed 24 h after inoculation with P. asparagi. In total, 35,259 and 36,321 transcripts were annotated in A. officinalis and A. kiusianus, respectively. 1,027 up-regulated and 752 down-regulated transcripts were differentially expressed in the two Asparagus species. RNA sequencing data were validated using quantitative real-time reverse transcription PCR. Several defense-related genes including peroxidase 4, cationic peroxidase SPC4-like, pathogenesis-related protein-1-like, and jasmonic acid biosynthesis and signaling-related genes including phospholipase D alpha 1, 12-oxophytodienoate reductase and jasmonate-induced protein 23 KD were up-regulated in A. kiusianus relative to A. officinalis. In addition, infected A. kiusianuns exhibited a substantial increase in jasmonic acid and methyl jasmonate relative to A. officinalis. Peroxidase activity was significantly elevated in infected A. kiusianus compared with infected A. officinalis. Our transcriptomic database provides a resource for identifying novel genes and molecular markers-associated with Phomopsis disease resistance and will facilitate breeding and improvement of cultivated asparagus varieties.
Structures and thermodynamics of water encapsulated by graphene
Authors: Jiao Shuping , Duan Chuanhua , Xu Zhiping
Published: May 2017

Understanding phase behaviors of nanoconfined water has driven notable research interests recently. In this work, we examine water encapsulated under a graphene cover that offers an ideal testbed to explore its molecular structures and thermodynamics. We find layered water structures for up to ~1000 trapped water molecules, which is stabilized by the spatial confinement and pressure induced by interfacial adhesion. For monolayer encapsulations, we identify representative two-dimensional crystalline lattices as well as defects therein. Free energy analysis shows that the structural orders with low entropy are compensated by high formation energies due to the pressurized confinement. There exists an order-to-disorder transition for this condensed phase at ~480–490 K, with a sharp reduction in the number of hydrogen bonds and increase in the entropy. Fast diffusion of the encapsulated water demonstrates anomalous temperature dependence, indicating the solid-to-fluid nature of this structural transition. These findings offer fundamental understandings of the encapsulated water that can be used as a pressurized cell with trapped molecular species, and provide guidance for practical applications with its presence, for example, in the design of nanodevices and nanoconfined reactive cells.
Comparisons of microvascular and macrovascular changes in aldosteronism-related hypertension and essential hypertension
Authors: Varano Monica , Iacono Pierluigi , Tedeschi Massimiliano M. , Letizia Claudio , Curione Mario , Savoriti Claudio , Baiocco Erika , Zinnamosca Laura , Marinelli Cristiano , Boccassini Barbara , Parravano Mariacristina
Published: May 2017

Case-control observational study to evaluate the microvascular and macrovascular changes in patients with hypertension secondary to primary aldosteronism (PA), essential hypertension (EH) and healthy subjects. Measurements of arterial stiffness including augmentation index (AIx) and pulse wave velocity (PWV) were assessed using a TensioClinic arteriograph system. Retinal microcirculation was imaged by a Retinal Vessel Analyzer (RVA) and a non-midriatic camera (Topcon-TRC-NV2000). IMEDOS software analyzed the retinal artery diameter (RAD), retinal vein diameters (RVD) and arteriole-to-venule ratio (AVR) of the vessels coming off the optic disc. Thirty, 39 and 35 patients were included in the PA, EH and control group, respectively. The PA group showed higher PWV values compared only with the control group. The mean brachial and aortic AIx values did not show significant difference between groups. In the PA group, the mean RVD and AVR values were significantly lower than in the EH and control groups, whereas the parameters did not differ between the EH and control groups. In conclusion, AVR appears significantly modified in the PA group compared with the EH group and could represent an early and more reliable indicator of microvascular remodeling.
Perioperative and anesthesia-related cardiac arrests in geriatric patients: a systematic review using meta-regression analysis
Authors: Braghiroli Karen S. , Braz José R. C. , Rocha Bruna , El Dib Regina , Corrente José E. , Braz Mariana G. , Braz Leandro G.
Published: May 2017

The worldwide population is aging, and the number of surgeries performed in geriatric patients is increasing. This systematic review evaluated anesthetic procedures to assess global data on perioperative and anesthesia-related cardiac arrest (CA) rates in geriatric surgical patients. Available data on perioperative and anesthesia-related CA rates over time and by the country’s Human Development Index (HDI) were evaluated by meta-regression, and a pooled analysis of proportions was used to compare perioperative and anesthesia-related CA rates by HDI and time period. The meta-regression showed that perioperative CA rates did not change significantly over time or by HDI, whereas anesthesia-related CA rates decreased over time (P = 0.04) and in high-HDI (P = 0.015). Perioperative and anesthesia-related CA rates per 10,000 anesthetic procedures declined in high-HDI, from 38.6 before the 1990s to 7.7 from 1990–2017 (P < 0.001) and from 9.2 before the 1990s to 1.3 from 1990–2017 (P < 0.001), respectively. The perioperative CA rate from 1990–2017 was higher in low-HDI than in high-HDI countries (P < 0.001). Hence, a reduction in anesthesia-related CA rates over time was observed. Both perioperative and anesthesia-related CA rates only decreased with a high-HDI between time periods, and perioperative CA rates during 1990–2017 were 4-fold higher with low- compared to high-HDI in geriatric patients.
Independent and cumulative effects of resting heart rate and pulse pressure with type 2 diabetes mellitus in Chinese rural population
Authors: Wang Panpan , Li Yuqian , Liu Xiaotian , Wang Quanxin , Guo Ying , Zhao Yang , Li Linlin , Fan Jingjing , Zhou Hao , Mao Zhenxing , Zhang Gongyuan , Wang Chongjian
Published: May 2017

The purpose was to explore the effects of resting heart rate (RHR) and pulse pressure (PP) independently as well as their cumulative effects on the risk of type 2 diabetes mellitus (T2DM) through cross-sectional study plus meta-analysis. A total of 8276 subjects aged 35–74 years from the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study were included in the study. Meanwhile, two meta-analyses were conducted to validate the results of the epidemiological research. The results showed that RHR and PP were associated with higher risk of T2DM, and the corresponding adjusted OR(95%CI) for each quartiles were 1.00, 0.99(0.68–1.42), 1.58(1.13–2.20), 2.93(2.15–3.98) and 1.00, 1.06(0.75–1.48), 1.11(0.79–1.56), 1.45(1.03–2.03), respectively. The cumulative effect analysis indicated that the adjusted OR(95%CI) in the fast RHR-high PP were 3.36(2.26–4.99), 2.60(1.47–4.59), and 3.60(2.09–6.20) compared with the slow RHR-low PP for total population, male and female, respectively. Meta-analysis showed that the pooled effect values for RHR and PP were 1.94(1.64–2.31) and 1.25(1.04–1.51), respectively. This study demonstrated that elevated RHR and PP are independently associated with the risk of T2DM as well as the influences of conventional confounders, and fast RHR with high PP might cumulatively increase the risk of T2DM. However, the potential clinical application remains to be determined.
Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients
Authors: Ye Huan , Shao Meiqin , Shi Xiaohong , Wu Lifeng , Xu Bing , Qu Qiang , Qu Jian
Published: May 2017

The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed that GSTP1 IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087–2.332, P = 0.017). The Asian patients bearing the favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192–1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084–1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.
GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation
Authors: Carlessi Rodrigo , Chen Younan , Rowlands Jordan , Cruzat Vinicius F. , Keane Kevin N. , Egan Lauren , Mamotte Cyril , Stokes Rebecca , Gunton Jenny E. , Bittencourt Paulo Ivo Homem de , Newsholme Philip
Published: May 2017

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of β-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression.
Room-Temperature Superplasticity in an Ultrafine-Grained Magnesium Alloy
Authors: Edalati Kaveh , Masuda Takahiro , Arita Makoto , Furui Mitsuaki , Sauvage Xavier , Horita Zenji , Valiev Ruslan Z.
Published: May 2017

Superplasticity, a phenomenon of high tensile elongation in polycrystalline materials, is highly effective in fabrication of complex parts by metal forming without any machining. Superplasticity typically occurs only at elevated homologous temperatures, where thermally-activated deformation mechanisms dominate. Here, we report the first observation of room-temperature superplasticity in a magnesium alloy, which challenges the commonly-held view of the poor room-temperature plasticity of magnesium alloys. An ultrafine-grained magnesium-lithium (Mg-8 wt.%Li) alloy produced by severe plastic deformation demonstrated 440% elongation at room temperature (0.35 Tm) with a strain-rate sensitivity of 0.37. These unique properties were associated with enhanced grain-boundary sliding, which was approximately 60% of the total elongation. This enhancement originates from fast grain-boundary diffusion caused by the Li segregation along the grain boundaries and the formation of Li-rich interphases. This discovery introduces a new approach for controlling the room-temperature superplasticity by engineering grain-boundary composition and diffusion, which is of importance in metal forming technology without heating.
Three-Dimensional Anisotropic Metamaterials as Triaxial Optical Inclinometers
Authors: Agarwal Kriti , Liu Chao , Joung Daeha , Park Hyeong-Ryeol , Oh Sang-Hyun , Cho Jeong-Hyun
Published: May 2017

Split-ring resonators (SRRs) present an attractive avenue for the development of micro/nano scale inclinometers for applications like medical microbots, military hardware, and nanosatellite systems. However, the 180° isotropy of their two-dimensional structure presents a major hurdle. In this paper, we present the design of a three-dimensional (3D) anisotropic SRR functioning as a microscale inclinometer enabling it to remotely sense rotations from 0° to 360° along all three axes (X, Y, and Z), by employing the geometric property of a 3D structure. The completely polymeric composition of the cubic structure renders it transparent to the Terahertz (THz) light, providing a transmission response of the tilted SRRs patterned on its surface that is free of any distortion, coupling, and does not converge to a single point for two different angular positions. Fabrication, simulation, and measurement data have been presented to demonstrate the superior performance of the 3D micro devices.
Integrated fiber optical receiver reducing the gap to the quantum limit
Authors: Zimmermann Horst , Steindl Bernhard , Hofbauer Michael , Enne Reinhard
Published: May 2017

Experimental results of a single-photon avalanche diode (SPAD) based optical fiber receiver integrated in 0.35 µm PIN-photodiode CMOS technology are presented. To cope with the parasitic effects of SPADs an array of four receivers is implemented. The SPADs consist of a multiplication zone and a separate thick absorption zone to achieve a high photon detection probability (PDP). In addition cascoded quenchers allow to use a quenching voltage of twice the usual supply voltage, i.e. 6.6 V instead of 3.3 V, in order to increase the PDP further. Measurements result in sensitivities of −55.7 dBm at a data rate of 50 Mbit/s and −51.6 dBm at 100 Mbit/s for a wavelength of 635 nm and a bit-error ratio of 2 × 10−3, which is sufficient to perform error correction. These sensitivities are better than those of linear-mode APD receivers integrated in the same CMOS technology. These results are a major advance towards direct detection optical receivers working close to the quantum limit.
Socio-economic inequalities in C-reactive protein and fibrinogen across the adult age span: Findings from Understanding Society
Authors: Davillas Apostolos , Benzeval Michaela , Kumari Meena
Published: May 2017

Systemic inflammation has been proposed as a physiological process linking socio-economic position (SEP) to health. We examined how SEP inequalities in inflammation –assessed using C-reactive protein (CRP) and fibrinogen– varied across the adult age span. Current (household income) and distal (education) markers of SEP were used. Data from 7,943 participants (aged 25+) of Understanding Society (wave 2, 1/2010-3/2012) were employed. We found that SEP inequalities in inflammation followed heterogeneous patterns by age, which differed by the inflammatory marker examined rather than by SEP measures. SEP inequalities in CRP emerged in 30s, increased up to mid-50s or early 60 s when they peaked and then decreased with age. SEP inequalities in fibrinogen decreased with age. Body mass index (BMI), smoking, physical activity and healthy diet explained part, but not all, of the SEP inequalities in inflammation; in general, BMI exerted the largest attenuation. Cumulative advantage theories and those considering age as a leveler for the accumulation of health and economic advantages across the life-span should be dynamically integrated to better understand the observed heterogeneity in SEP differences in health across the lifespan. The attenuating roles of health-related lifestyle indicators suggest that targeting health promotion policies may help reduce SEP inequalities in health.
Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response
Authors: Zinkova Alzbeta , Brynychova Iva , Svacina Alexander , Jirkovska Marie , Korabecna Marie
Published: May 2017

Circulating cell-free DNA (cfDNA) may be involved in immune response regulation. We studied the variations in abundance of telomeric sequences in plasma and serum in young healthy volunteers and the ability of cfDNA contained in these samples to co-activate the TNF-α m RNA expression in monocytes. We performed qPCR to determine relative telomere length (T/S ratios) in plasma, serum and whole blood of 36 volunteers. Using paired samples of plasma and serum and DNase treatment, we analysed the contribution of cfDNA to the co-activation of TNF-α mRNA expression in THP1 monocytic cell line. We found significant differences between paired plasma and serum samples in relative T/S ratios (median 1.38 ± 1.1 vs. 0.86 ± 0.25, respectively) and in total amounts of cfDNA and in estimated total amounts of telomeres which were significantly higher in serum than in plasma. TNF-α mRNA expression in THP1 cells increased significantly after DNase treatment of all samples used for stimulation. The highest TNF-α mRNA expressions were observed after stimulation with DNase treated serum samples. Our results suggest that the different content of telomeric sequences in plasma and serum may contribute to the tuning of immune response. Further studies of this interesting phenomenon are needed.
Enhanced thermal conductivity of epoxy composites filled with silicon carbide nanowires
Authors: Shen Dianyu , Zhan Zhaolin , Liu Zhiduo , Cao Yong , Zhou Li , Liu Yuanli , Dai Wen , Nishimura Kazuhito , Li Chaoyang , Lin Cheng-Te , Jiang Nan , Yu Jinhong
Published: May 2017

In this study, we report a facile approach to fabricate epoxy composite incorporated with silicon carbide nanowires (SiC NWs). The thermal conductivity of epoxy/SiC NWs composites was thoroughly investigated. The thermal conductivity of epoxy/SiC NWs composites with 3.0 wt% filler reached 0.449 Wm−1 K−1, approximately a 106% enhancement as compared to neat epoxy. In contrast, the same mass fraction of silicon carbide micron particles (SiC MPs) incorporated into epoxy matrix showed less improvement on thermal conduction properties. This is attributed to the formation of effective heat conduction pathways among SiC NWs as well as a strong interaction between the nanowires and epoxy matrix. In addition, the thermal properties of epoxy/SiC NWs composites were also improved. These results demonstrate that we developed a novel approach to enhance the thermal conductivity of the polymer composites which meet the requirement for the rapid development of the electronic devices.
Nicotine delivery from the refill liquid to the aerosol via high-power e-cigarette device
Authors: Prévôt Nathalie , de Oliveira Fabien , Perinel-Ragey Sophie , Basset Thierry , Vergnon Jean-Michel , Pourchez Jérémie
Published: May 2017

To offer an enhanced and well-controlled nicotine delivery from the refill liquid to the aerosol is a key point to adequately satisfy nicotine cravings using electronic nicotine delivery systems (ENDS). A recent high-power ENDS, exhibiting higher aerosol nicotine delivery than older technologies, was used. The particle size distribution was measured using a cascade impactor. The effects of the refill liquid composition on the nicotine content of each size-fraction in the submicron range were investigated. Nicotine was quantified by liquid chromatography coupled with tandem mass spectrometry. Particle size distribution of the airborne refill liquid and the aerosol nicotine demonstrated that the nicotine is equally distributed in droplets regardless of their size. Results also proved that the nicotine concentration in aerosol was significantly lower compared to un-puffed refill liquid. A part of the nicotine may be left in the ENDS upon depletion, and consequently a portion of the nicotine may not be transferred to the user. Thus, new generation high-power ENDS associated with propylene glycol/vegetable glycerin (PG/VG) based solvent were very efficient to generate carrier-droplets containing nicotine molecules with a constant concentration. Findings highlighted that a portion of the nicotine in the refill liquid may not be transferred to the user.
Characterization and application studies of ProxyPhos, a chemosensor for the detection of proximally phosphorylated peptides and proteins in aqueous solutions
Authors: Kraskouskaya D. , Cabral A. D. , Fong R. , Bancerz M. , Toutah K. , Rosa D. , Gardiner J. E. , de Araujo E. D. , Duodu E. , Armstrong D. , Fekl U. , Gunning P. T.
Published: May 2017

Optimization of ProxyPhos peptide and protein assay conditions along with sample applications are presented.
The effect of water on methane oxidation over Pd/Al2O3 under lean, stoichiometric and rich conditions
Authors: Mihai Oana , Smedler Gudmund , Nylén Ulf , Olofsson Marcus , Olsson Louise
Published: May 2017

Methane conversion during cooling ramp: water inhibits methane conversion more severely in high oxygen concentration.
SERS-active metal–organic frameworks with embedded gold nanoparticles
Authors: Cao Xiaolin , Hong Sihui , Jiang Zejun , She Yongxin , Wang Shanshan , Zhang Chan , Li Hui , Jin Fen , Jin Maojun , Wang Jing
Published: May 2017

Surface-enhanced Raman scattering (SERS) has been widely used in the detection of targets and strongly depends on the interaction and the distance between the targets and nanoparticles.
Enzyme mediated assembly of gold nanoparticles for ultrasensitive colorimetric detection of hepatitis C virus antibody
Authors: Cheng Yu-Hong , Tang Hao , Jiang Jian-Hui
Published: May 2017

A novel enzyme mediated AuNP assembly based colorimetric method for ultrasensitive detection of hepatitis C virus antibody.
A square-planar nickel dithiolate complex as an efficient molecular catalyst for the electro- and photoreduction of protons
Authors: Luo Geng-Geng , Wang Yong-Heng , Wang Jiang-Hai , Wu Ji-Huai , Wu Rui-Bo
Published: May 2017

A square-planar nickel cis-dithiolate complex is shown to be an active catalyst for both electro- and photoreduction of protons.
Uniform distribution of post-synthetic linker exchange in metal–organic frameworks revealed by Rutherford backscattering spectrometry
Authors: Fluch Ulrike , Paneta Valentina , Primetzhofer Daniel , Ott Sascha
Published: May 2017

Rutherford backscattering spectrometry (RBS) has been used for the first time to study post-synthetic linker exchange (PSE) in metal organic frameworks.
Copper-catalyzed construction of eight-membered rings via oxidative ring expansion and intermolecular cyclization sequencing of indoles with amidines: efficient synthesis of benzo[1,3,5]triazocin-6(5H)-ones
Authors: Cao Wen-Bin , Chu Xue-Qiang , Zhou Yu , Yin Ling , Xu Xiao-Ping , Ji Shun-Jun
Published: May 2017

Novel and efficient synthesis of eight-membered nitrogen heterocycles in one pot by copper-catalyzed oxidative ring expansion and intermolecular cyclization sequencing of indoles with amidines has been described.
Naphtho[b]-fused BODIPYs: one pot Suzuki–Miyaura–Knoevenagel synthesis and photophysical properties
Authors: Zhou Zhikuan , Zhou Jianping , Gai Lizhi , Yuan Aihua , Shen Zhen
Published: May 2017

The facile one-pot synthesis of naphtho[b]-fused BODIPYs and their photophysical properties are reported.
Investigation of a new “N2S2O2” chelating agent with high Po(iv) affinity
Authors: Younes Ali , Montavon Gilles , Gouin Sébastien G. , André-Joyaux Emy , Peumery Roxane , Chalopin Thibaut , Alliot Cyrille , Mokili Marcel , Champion Julie , Deniaud David
Published: May 2017

A water-soluble complexing agent for 210-polonium decorporation was designed and synthesised with a high conditional stability constant.
Catalytic asymmetric [2+2] cycloaddition between quinones and fulvenes and a subsequent stereoselective isomerization to 2,3-dihydrobenzofurans
Authors: Zheng Haifeng , Xu Chaoran , Wang Yan , Kang Tengfei , Liu Xiaohua , Lin Lili , Feng Xiaoming
Published: May 2017

A chiral Lewis acid catalyzed enantioselective [2+2] cycloaddition between quinones and fulvenes was reported for the first time. The method afforded a series of [6,4,5]-tricyclic cyclobutane derivatives in good yields with excellent regio- and stereoselectivities. Furthermore, the [2+2] adducts could be easily converted into formal [3+2] adducts efficiently and stereoselectively.
Direct N-acylation of sulfoximines with carboxylic acids catalyzed by the B3NO2 heterocycle
Authors: Noda Hidetoshi , Asada Yasuko , Shibasaki Masakatsu , Kumagai Naoya
Published: May 2017

Dehydrative coupling of sulfoximines and carboxylic acids is rendered catalytic by a heterocyclic catalyst featuring the B3NO2 ring system.
Stereospecific control of the helical orientation of indolocarbazole–pyridine hybrid foldamers by rational modification of terminal chiral appendages
Authors: Kim Junyoung , Jeon Hae-Geun , Kang Philjae , Jeong Kyu-Sung
Published: May 2017

The helical handedness excess of an indolocarbazole–pyridine hybrid oligomer capable of folding into a stable helical structure was achieved up to 96% by rational modification of terminal chiral residues.
A segmented flow platform for on-demand medicinal chemistry and compound synthesis in oscillating droplets
Authors: Hwang Ye-Jin , Coley Connor W. , Abolhasani Milad , Marzinzik Andreas L. , Koch Guido , Spanka Carsten , Lehmann Hansjoerg , Jensen Klavs F.
Published: May 2017

An automated flow chemistry platform performs single/multi-phase and single/multi-step chemistries in 14 μL droplets with online analysis and product collection.
Magnesia-stabilised zirconia solid electrolyte assisted electrochemical investigation of iron ions in a SiO2–CaO–MgO–Al2O3molten slag at 1723 K
Authors: Gao Yunming , Yang Chuanghuang , Zhang Canlei , Qin Qingwei , Chen George Z.
Published: May 2017

Electrochemical investigation of iron ions in molten slags at ultrahigh temperatures using a unique cell constructed from a solid electrolyte tube.
Investigation of the relationship between the cycle performance and the electronic structure in LiAlxMn2−xO4 (x = 0 and 0.2) using soft X-ray spectroscopy
Authors: Asakura Daisuke , Nanba Yusuke , Makinose Yuki , Matsuda Hirofumi , Hosono Eiji
Published: May 2017

We found that the charge-transfer effect from the O 2p to Mn 3d orbitals is closely connected with the cycle performances for LiMn2O4 cathode.
Modeling of diameter-dependent Fe and Co ultrathin nanowires from first-principles calculations
Authors: Kansara Shivam , Gupta Sanjeev K. , Sonvane Yogesh , Lukačević Igor
Published: May 2017

We present the electronic, magnetic, thermoelectric and optical properties of ferromagnetic metal nanowires (NWs) made of iron (Fe) and cobalt (Co) atoms with different diameter using a first principles approach.
Azaporphyrin phosphorus(v) complexes: synthesis, structure, and modification of optical properties
Authors: Furuyama Taniyuki , Kobayashi Nagao
Published: May 2017

Azaporphyrinoids, such as phthalocyanines (Pcs), tetraazaporphyrins (TAPs), and tetrabenzotriazacorroles (TBCs), are some of the most well-known and successful artificial dyes and pigments in modern material chemistry.
Novel structural phases and the electrical properties of Si3B under high pressure
Authors: Wang Jingjing , Sun Guoliang , Kong Panlong , Sun Weiguo , Lu Cheng , Peng Feng , Kuang Xiaoyu
Published: May 2017

Enthalpy curves relative to the P3̄1m phase of Si3B as a function of pressure ranging from 0 to 160 GPa.
Can time-dependent density functional theory predict intersystem crossing in organic chromophores? A case study on benzo(bis)-X-diazole based donor–acceptor–donor type molecules
Authors: Tam Teck Lip Dexter , Lin Ting Ting , Chua Ming Hui
Published: May 2017

Here we utilized new diagnostic tools in time-dependent density functional theory to explain the trend of intersystem crossing in benzo(bis)-X-diazole based donor–acceptor–donor type molecules.