bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer
Authors: Alasadi Amer , Chen Michael , Swapna G. V. T. , Tao Hanlin , Guo Jingjing , Collantes Juan , Fadhil Noor , Montelione Gaetano T. , Jin Shengkan 
Published: February 2018

AbstractMetabolism of cancer cells is characterized by aerobic glycolysis, or the Warburg effect. Aerobic glycolysis reduces pyruvate flux into mitochondria, preventing a complete oxidation of glucose and shunting glucose to anabolic pathways essential for cell proliferation. Here we tested a new strategy, mitochondrial uncoupling, for its potential of antagonizing the anabolic effect of aerobic glycolysis and for its potential anticancer activities. Mitochondrial uncoupling is a process that facilitates proton influx across the mitochondrial inner membrane without generating ATP, stimulating a futile cycle of acetyl- CoA oxidation. We tested two safe mitochondrial uncouplers, NEN (niclosamide ethanolamine) and oxyclozanide, on their metabolic effects and anti-cancer activities. We used metabolomic NMR to examine the effect of mitochondrial uncoupling on glucose metabolism in colon cancer MC38 cells. We further tested the anti-cancer effect of NEN and oxyclozanide in cultured cell models, APCmin/+ mouse model, and a metastatic colon cancer mouse model. Using a metabolomic NMR approach, we demonstrated that mitochondrial uncoupling promotes pyruvate influx to mitochondria and reduces various anabolic pathway activities. Moreover, mitochondrial uncoupling inhibits cell proliferation and reduces clonogenicity of cultured colon cancer cells. Furthermore, oral treatment with mitochondrial uncouplers reduces intestinal polyp formation in APCmin/+ mice, and diminishes hepatic metastasis of colon cancer cells transplanted intrasplenically. Our data highlight a unique approach for targeting cancer cell metabolism for cancer prevention and treatment, identified two prototype compounds, and shed light on the anti-cancer mechanism of niclosamide.
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410
Authors: Dong Liyang , Pu Yanan , Zhang Lina , Qi Qianqian , Xu Lei , Li Wei , Wei Chuan , Wang Xiaofan , Zhou Sha , Zhu Jifeng , Wang Xuefeng , Liu Feng , Chen Xiaojun , Su Chuan 
Published: February 2018

AbstractAlthough accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor model. Then, we observed that hUCMSC-derived extracellular vesicles (hUCMSC-EVs) contribute to the hUCMSC-promoted LUAD cell growth through a direct effect on LUAD cells. Furthermore, we showed that hUCMSC-EV-mediated LUAD growth is associated with increased proliferation and decreased apoptosis in LUAD cells, concomitant with reduced PTEN expression mediated by the hUCMSC-EV-transmitted miR-410. Our findings provide novel insights into the intercellular communications between cancer cells and MSCs through MSC-EV-miRNA and suggest that modification of hUCMSC-EVs might be an attractive therapeutic option for the clinical application of hUCMSC-EVs that would reduce unwanted side effects.
Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
Authors: Janas Maja M. , Schlegel Mark K. , Harbison Carole E. , Yilmaz Vedat O. , Jiang Yongfeng , Parmar Rubina , Zlatev Ivan , Castoreno Adam , Xu Huilei , Shulga-Morskaya Svetlana , Rajeev Kallanthottathil G. , Manoharan Muthiah , Keirstead Natalie D. , Maier Martin A. , Jadhav Vasant 
Published: February 2018

AbstractSmall interfering RNAs (siRNAs) conjugated to a trivalent N-acetylgalactosamine (GalNAc) ligand are being evaluated in investigational clinical studies for a variety of indications. The typical development candidate selection process includes evaluation of the most active compounds for toxicity in rats at pharmacologically exaggerated doses. The subset of GalNAc-siRNAs that show rat hepatotoxicity is not advanced to clinical development. Potential mechanisms of hepatotoxicity can be associated with the intracellular accumulation of oligonucleotides and their metabolites, RNA interference (RNAi)-mediated hybridization-based off-target effects, and/or perturbation of endogenous RNAi pathways. Here we show that rodent hepatotoxicity observed at supratherapeutic exposures can be largely attributed to RNAi-mediated off-target effects, but not chemical modifications or the perturbation of RNAi pathways. Furthermore, these off-target effects can be mitigated by modulating seed-pairing using a thermally destabilizing chemical modification, which significantly improves the safety profile of a GalNAc-siRNA in rat and may minimize the occurrence of hepatotoxic siRNAs across species.
Expedient syntheses of N-heterocycles via intermolecular amphoteric diamination of allenes
Authors: Ye Zhishi , Adhikari Sarju , Xia Yu , Dai Mingji 
Published: February 2018

AbstractSaturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4-diazocanes, are highly important for therapeutic development, but their syntheses are often tedious. We describe here an amphoteric diamination strategy to unite readily available 1,2-, 1,3- or 1,4-diamine derivatives with electron-deficient allenes via a formal [n + 2] (n = 4, 5, 6) cyclization mode to produce the corresponding 1,4-diazo heterocycles in just one step. This strategy features mild reaction conditions, high functional group tolerance, and scalability (gram scale). The reagents used are cheap and readily available and no transition metal catalysts are needed. More sophisticated products containing trifluoromethyl group or bicyclic ring systems can be accessed via a one-pot procedure as well. Our mechanistic studies support that formation of mono-iodinated or chlorinated diamine intermediates is important for the desired transformation and the commonly proposed chloride-iodide exchange process and a radical N−C bond formation is unlikely when the combination of NCS/KI is used.
Route to high-energy density polymeric nitrogen t-N via He−N compounds
Authors: Li Yinwei , Feng Xiaolei , Liu Hanyu , Hao Jian , Redfern Simon A. T. , Lei Weiwei , Liu Dan , Ma Yanming 
Published: February 2018

AbstractPolymeric nitrogen, stabilized by compressing pure molecular nitrogen, has yet to be recovered to ambient conditions, precluding its application as a high-energy density material. Here we suggest a route for synthesis of a tetragonal polymeric nitrogen, denoted t-N, via He-N compounds at high pressures. Using first-principles calculations with structure searching, we predict a class of nitrides with stoichiometry HeN4 that are energetically stable (relative to a mixture of solid He and N2) above 8.5 GPa. At high pressure, HeN4 comprises a polymeric channel-like nitrogen framework filled with linearly arranged helium atoms. The nitrogen framework persists to ambient pressure on decompression after removal of helium, forming pure polymeric nitrogen, t-N. t-N is dynamically and mechanically stable at ambient pressure with an estimated energy density of ~11.31 kJ/g, marking it out as a remarkable high-energy density material. This expands the known polymeric forms of nitrogen and indicates a route to its synthesis.
Saliva as a medium to detect and measure biomarkers related to pain
Authors: Jasim Hajer , Carlsson Anders , Hedenberg-Magnusson Britt , Ghafouri Bijar , Ernberg Malin 
Published: February 2018

AbstractSaliva is often neglected as a body fluid of diagnostic or prognostic value, even though generally well accepted by the patients. This is due to lack of a standardized collection procedure. The aim of this study was to identify the ideal saliva collection technique and develop new sensitive methods to detect and analyse markers related to pain in healthy pain-free subjects. Plasma and five different saliva collection approached was evaluated during strictly controlled conditions. Levels of nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and brain derived neurotropic factor (BDNF) were determined using novel western blotting based technology. Glutamate and substance P (SP) was determined using commercial available methods. Several new isoforms were found for NGF, CGRP and BDNF in saliva. The isoform pattern showed significant variation in both expression and chemiluminescence levels between different collection methods. New sensitive methods to study pain related markers in saliva were developed in this study. Furthermore, we are first to demonstrate a correlation between the Glutamate concentration in stimulated whole saliva and blood. However, the fundamental conclusion drawn is the importance of consistency in the collection method.
Serum Metabolomics of Activity Energy Expenditure and its Relation to Metabolic Syndrome and Obesity
Authors: Palmnäs Marie S. A. , Kopciuk Karen A. , Shaykhutdinov Rustem A. , Robson Paula J. , Mignault Diane , Rabasa-Lhoret Rémi , Vogel Hans J. , Csizmadi Ilona 
Published: February 2018

AbstractModifiable lifestyle factors, including exercise and activity energy expenditure (AEE), may attenuate the unfavorable health effects of obesity, such as risk factors of metabolic syndrome (MetS). However, the underlying mechanisms are not clear. In this study we sought to investigate whether the metabolite profiles of MetS and adiposity assessed by body mass index (BMI) and central obesity are inversely correlated with AEE and physical activity. We studied 35 men and 47 women, aged 30–60 years, using doubly labeled water to derive AEE and the Sedentary Time and Activity Reporting Questionnaire (STAR-Q) to determine the time spent in moderate and vigorous physical activity. Proton nuclear magnetic resonance spectroscopy was used for serum metabolomics analysis. Serine and glycine were found in lower concentrations in participants with more MetS risk factors and greater adiposity. However, serine and glycine concentrations were higher with increasing activity measures. Metabolic pathway analysis and recent literature suggests that the lower serine and glycine concentrations in the overweight/obese state could be a consequence of serine entering de novo sphingolipid synthesis. Taken together, higher levels of AEE and physical activity may play a crucial part in improving metabolic health in men and women with and without MetS risk factors.
Crystal structure of the hydroxylaminopurine resistance protein, YiiM, and its putative molybdenum cofactor-binding catalytic site
Authors: Namgung Byeol , Kim Jee-Hyeon , Song Wan Seok , Yoon Sung-il 
Published: February 2018

AbstractThe molybdenum cofactor (Moco) is a molybdenum-conjugated prosthetic group that is ubiquitously found in plants, animals, and bacteria. Moco is required for the nitrogen-reducing reaction of the Moco sulfurase C-terminal domain (MOSC) family. Despite the biological significance of MOSC proteins in the conversion of prodrugs and resistance against mutagens, their structural features and Moco-mediated catalysis mechanism have not been described in detail. YiiM is a MOSC protein that is involved in reducing mutagenic 6-N-hydroxylaminopurine to nontoxic adenine in bacteria. Here, we report two crystal structures of YiiM: one from Gram-positive Geobacillus stearothermophilus (gsYiiM) and the other from Gram-negative Escherichia coli (ecYiiM). Although gsYiiM and ecYiiM differ in oligomerization state and protein stability, both consist of three structural modules (a β-barrel and two α-helix bundles) and feature a cavity surrounded by the three modules. The cavity is characterized by positive electrostatic potentials and high sequence conservation. Moreover, the ecYiiM cavity houses a phosphate group, which emulates a part of Moco, and contains a highly reactive invariant cysteine residue. We thus propose that the cavity is the catalytic site where Moco binds and the substrate is reduced. Moreover, our comparative structural analysis highlights the common but distinct structural features of MOSC proteins.
The value of hip circumference/heightx ratio for identifying childhood hypertension
Authors: Lu Na , Wang Rui , Ji Meijing , Liu Xiaoli , Qiang Lu , Ma Chunming , Yin Fuzai 
Published: February 2018

AbstractTo investigate the value of hip circumference related indexes for identifying childhood hypertension. In 2011, 1,352 Han children aged 7–12 years were recruited in our study. Hypertension was defined as systolic blood pressure or diastolic blood pressure ≥95th percentile for all three screenings. We set the power value of the hip circumference/heightx ratio (x = 0, 0.8, 1 and 1.5) and studied the association with blood pressure. Hip circumference, hip circumference/height0.8, hip circumference/height and hip circumference/height1.5 all showed a positive correlation with systolic blood pressure and diastolic blood pressure(P < 0.05). Area under the curve (AUC) was used to evaluate the abilities of hip circumference related indexes. Hip circumference/height0.8, hip circumference/height and hip circumference/height1.5 were not superior to hip circumference. The present study demonstrates that hip circumference measurement is a helpful tool to detect the presence of hypertension in Han children 7–12 years old.
Identification of a locus conferring dominant resistance to maize rough dwarf disease in maize
Authors: Li Ronggai , Song Wei , Wang Baoqiang , Wang Jianghao , Zhang Dongmin , Zhang Quanguo , Li Xinghua , Wei Jianfen , Gao Zengyu 
Published: February 2018

AbstractMaize rough dwarf disease (MRDD) is a severe viral disease of maize that occurs worldwide, particularly in the summer maize-growing areas in China, resulting in yield losses and quality deterioration in susceptible maize varieties. An effective solution to control MRDD is to use resistance genes to improve the behavior of susceptible genotypes. Here, we employed maize F2 populations derived from a cross between susceptible line S221 and resistant line K36 for the deep sequencing of the two DNA pools containing extremely resistant and susceptible F2 individuals, and used traditional linkage analysis to locate the resistance-related genomic region. The results showed that MRDD resistance in K36 was controlled by a single dominant locus, and an associated region was identified within the genomic interval of 68,396,487 bp and 69,523,478 bp on chromosome 6. Two simple sequence repeat (SSR) markers 6F29R29 and 6F34R34 were tightly linked to the MRDD resistance locus. The findings of the present study improve our understanding of the inheritance patterns of MRDD resistance, and should inform MRDD-resistant maize breeding programs.
Poly(butylene succinate)/bamboo powder blends as solid-phase carbon source and biofilm carrier for denitrifying biofilters treating wastewater from recirculating aquaculture system
Authors: Liu Dezhao , Li Jiawei , Li Changwei , Deng Yale , Zhang Zeqing , Ye Zhangying , Zhu Songming 
Published: February 2018

AbstractIn this study, Poly(butylene succinate)/bamboo powder (PBS/BP) was newly applied and tested for 8 months as the carbon source in two moving bed reactors for nitrate removal in real RAS wastewater (fresh/sea water), with the purposes of simultaneous reducing the cost of PBS packing and effluent DOC. Fast start-ups were obtained in both reactors, in which high denitrification rates were observed (0.68 ± 0.03 and 0.83 ± 0.11 kg $${{\bf{NO}}}_{{\bf{3}}}^{-}$$

NO

3

−

-N m−3 d−1 for fresh and sea water, respectively) with no nitrite and low ammonia accumulation. Reduced DOC concentrations in the effluents were also observed compared to pure PBS. The freezing of PBS/BP showed a further slower release of DOC, which might be beneficial to the life of the PBS/BP for the denitrification process, however, microbial activity, especially in high salinity wastewater, was observed to have declined. Illumina sequencing revealed that the autotrophic genus arcobacter was discovered first time in solid-phase denitrification system with salinity. Redundancy analysis (RDA) was used to reveal the relationships between environmental factors and the microbial community. In overall, PBS/BP blends were proven to be an economically attractive carbon source for nitrate removal in RAS.
Broadband terahertz absorber based on multi-band continuous plasmon resonances in geometrically gradient dielectric-loaded graphene plasmon structure
Authors: Yang Jiawen , Zhu Zhihong , Zhang Jianfa , Guo Chucai , Xu Wei , Liu Ken , Yuan Xiaodong , Qin Shiqiao 
Published: February 2018

AbstractWe propose a broadband terahertz absorber consisting of nonstructured graphene loaded with arrays of elliptic dielectric cylinders. The relative bandwidth for the absorption above 90% reaches about 65%. The working mechanism of broad bandwidth mainly comes from two aspects. One is that the nonstructured graphene loaded with elliptic dielectric cylinders provides multiple discrete graphene plasmon resonances with large relative frequency interval. The other is that, for each discrete resonance, there exists a set of continuous plasmon resonances because the width of the dielectric structure varies continuously and gradiently. The broadband terahertz absorber we demonstrate here, based on geometrically gradient dielectric structures and nonstructured graphene, avoids the graphene processing, which shows great potential applications in related devices.
Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin and its valine ester derivative
Authors: Cai Enbo , Song Xingzhuo , Han Mei , Yang Limin , Zhao Yan , Li Wei , Han Jiahong , Tu Shumei 
Published: February 2018

AbstractArctigenin (ARG) is a functional active component that has important physiological and pharmacological activities. The anti-tumour and anti-inflammatory activities of ARG show good potential for application and development, but this material has the defect of low water solubility. In this experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics of ARG following oral administration and ARG-V following oral administration in rats were also studied. The Cmax and AUC values of ARG-V showed significant differences compared to ARG. The relative bioavailabilities of three doses of ARG-V compared to ARG were 664.7%, 741.5% and 812.9%. These pharmacokinetic results may be useful for further studies of the bioactive mechanism of ARG and provide a theoretical basic for clinical use.
Device physics of van der Waals heterojunction solar cells
Authors: Furchi Marco M. , Höller Florian , Dobusch Lukas , Polyushkin Dmitry K. , Schuler Simone , Mueller Thomas 
Published: February 2018

AbstractHeterostructures based on atomically thin semiconductors are considered a promising emerging technology for the realization of ultrathin and ultralight photovoltaic solar cells on flexible substrates. Much progress has been made in recent years on a technological level, but a clear picture of the physical processes that govern the photovoltaic response remains elusive. Here, we present a device model that is able to fully reproduce the current–voltage characteristics of type-II van der Waals heterojunctions under optical illumination, including some peculiar behaviors such as exceedingly high ideality factors or bias-dependent photocurrents. While we find the spatial charge transfer across the junction to be very efficient, we also find a considerable accumulation of photogenerated carriers in the active device region due to poor electrical transport properties, giving rise to significant carrier recombination losses. Our results are important to optimize future device architectures and increase power conversion efficiencies of atomically thin solar cells.
Reading Behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users
Authors: Zekveld Adriana A. , Pronk Marieke , Danielsson Henrik , Rönnberg Jerker 
Published: February 2018

Purpose
The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in the TRT. Second, we aimed to assess the relationships between the TRT and the speech reception thresholds (SRTs) estimated in various conditions.

Method
First, we reviewed studies reporting relationships between the TRT and the auditory and/or cognitive factors and formulated specific hypotheses regarding the TRT predictors. These hypotheses were tested using a prediction model applied to a rich data set of 180 hearing aid users. In separate association models, we tested the relationships between the TRT and the various SRTs and subjective hearing difficulties, while taking into account potential confounding variables.

Results
The results of the prediction model indicate that the TRT is predicted by the ability to fill in missing words in incomplete sentences, by lexical access speed, and by working memory capacity. Furthermore, in line with previous studies, a moderate association between higher age, poorer pure-tone hearing acuity, and poorer TRTs was observed. Better TRTs were associated with better SRTs for the correct perception of 50% of Hagerman matrix sentences in a 4-talker babble, as well as with better subjective ratings of speech perception. Age and pure-tone hearing thresholds significantly confounded these associations. The associations of the TRT with SRTs estimated in other conditions and with subjective qualities of hearing were not statistically significant when adjusting for age and pure-tone average.

Conclusions
We conclude that the abilities tapped into by the TRT test include processes relevant for speeded lexical decision making when completing partly masked sentences and that these processes require working memory capacity. Furthermore, the TRT is associated with the SRT of hearing aid users as estimated in a challenging condition that includes informational masking and with experienced difficulties with speech perception in daily-life conditions. The current results underline the value of using the TRT test in studies involving speech perception and aid in the interpretation of findings acquired using the test.
SE adjustment of planar mesh screen by fine‐tuning metal thickness
Authors: Corredores Yonathan , Castel Xavier , Besnier Philippe , Dupeyrat Cyril , Foutrel Patrice 
Published: February 2018

The study presents the thickness effect of mesh metal films printed onto glass substrate on the shielding effectiveness (SE) of such transparent screens. Currently, standards in microelectronic technology use a metal film thickness of between ∼100 nm and few micrometres, depending on the available deposition and implementation techniques. This study demonstrates that the thickness of mesh metal films is a key parameter which needs to be adjusted precisely. A theoretical model based on SE, complex impedance and optical transparency has been developed for this purpose. At microwaves, a relevant selection of the metal thickness values from 0.1 to 2 µm changes the SE at low frequency (from 36 to 40 dB at 2 GHz, respectively) while maintaining it constantly at a higher frequency (close to 20 dB at 18 GHz). The optical transparency of such mesh screens is kept constant over the entire visible light spectrum (78%). Experimental data are in complete agreement with the theoretical values.