bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of α

V

β
3 Integrin Activity
Authors: Hedhli Jamila , Czerwinski Andrzej , Schuelke Matthew , Płoska Agata , Sowinski Paweł , Hood Lukas La , Mamer Spencer B. , Cole John A. , Czaplewska Paulina , Banach Maciej , Dobrucki Iwona T. , Kalinowski Leszek , Imoukhuede Princess , Dobrucki Lawrence W.
Published: June 2017

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α
V
β3 integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α
V
β3 activity (a radiolabeled version, 64Cu-NOTA-PEG4-cRGD2, for PET imaging, and a fluorescent version, FITC-PEG4-cRGD2, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis. Both versions of the probe were found to be stable, demonstrated fast receptor association constants, and showed high specificity for α
V
β3 in HUVECs (K
d
 ~ 35 nM). Dynamic PET-CT imaging indicated rapid blood clearance via kidney filtration, and accumulation within α
V
β3-positive infarcted myocardium. 64Cu-NOTA-PEG4-cRGD2 demonstrated a favorable biodistribution, slow washout, and excellent performance with respect to the quality of the PET-CT images obtained. Importantly, the ratio of probe uptake in infarcted heart tissue compared to normal tissue was significantly higher in non-diabetic rats than in diabetic ones. Overall, our probes are promising agents for non-invasive quantitative imaging of α
V
β3 expression, both in vitro and in vivo.
TRPC5-induced autophagy promotes drug resistance in breast carcinoma via CaMKKβ/AMPKα/mTOR pathway
Authors: Zhang Peng , Liu Xiaoyu , Li Hongjuan , Chen Zhen , Yao Xiaoqiang , Jin Jian , Ma Xin
Published: June 2017

Adriamycin is a first-line chemotherapy agent against cancer, but the development of resistance has become a major problem. Although autophagy is considered to be an adaptive survival response in response to chemotherapy and may be associated with chemoresistance, its inducer and the underlying molecular mechanisms remain unclear. Here, we demonstrate that adriamycin up-regulates the both levels of TRPC5 and autophagy, and the increase in autophagy is mediated by TRPC5 in breast cancer cells. Blockade of TRPC5 or autophagy increased the sensitivity to chemotherapy in vitro and in vivo. Notably, we revealed a positive correlation between TRPC5 and the autophagy-associated protein LC3 in paired patients with or without anthracycline-taxane-based chemotherapy. Furthermore, pharmacological inhibition and gene-silencing showed that the cytoprotective autophagy mediated by TRPC5 during adriamycin treatment is dependent on the CaMKKβ/AMPKα/mTOR pathway. Moreover, adriamycin-resistant MCF-7/ADM cells maintained a high basal level of autophagy, and silencing of TRPC5 and inhibition of autophagy counteracted the resistance to adriamycin. Thus, our results revealed a novel role of TRPC5 as an inducer of autophagy, and this suggests a novel mechanism of drug resistance in chemotherapy for breast cancer.
Enhanced Photocatalytic Activity of WS2 Film by Laser Drilling to Produce Porous WS2/WO3 Heterostructure
Authors: Ma Sainan , Zeng Longlui , Tao Lili , Tang Chun Yin , Yuan Huiyu , Long Hui , Cheng Ping Kwong , Chai Yang , Chen Chuansheng , Fung Kin Hung , Zhang Xuming , Lau Shu Ping , Tsang Yuen Hong
Published: June 2017

Methods and mechanisms for improvement of photocatalytic activity, are important and popular research topics for renewable energy production and waste water treatment. Here, we demonstrate a facile laser drilling method for engineering well-aligned pore arrays on magnetron-sputtered WS2 nanofilms with increased active edge sites; the proposed method promotes partial oxidation to fabricate WS2/WO3 heterojunctions that enhance the separation of photogenerated electron-hole pairs. The WS2 film after one, two, and three treatments exhibited photocurrent density of 3.9, 6.2, and 8 μA/cm2, respectively, reaching up to 31 times larger than that of pristine WS2 film along with greatly improved charge recombination kinetics. The unprecedented combinational roles of laser drilling revealed in this study in regards to geometric tailoring, chemical transformation, and heterojunction positioning for WS2-based composite nanomaterials create a foundation for further enhancing the performance of other 2D transition metal dichalcogenides in photocatalysis via laser treatment.
Discordance in HER2 Status in Gastro-esophageal Adenocarcinomas: A Systematic Review and Meta-analysis
Authors: Creemers A. , ter Veer E. , de Waal L. , Lodder P. , Hooijer G. K. J. , van Grieken N. C. T. , Bijlsma M. F. , Meijer S. L. , van Oijen M. G. H. , van Laarhoven H. W. M.
Published: June 2017

Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41–0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5–10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.
Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis
Authors: Ren Yinghui , Li Yan , Yan Jun , Ma Mingkun , Zhou Dongmei , Xue Zhenyi , Zhang Zimu , Liu Hongkun , Yang Huipeng , Jia Long , Zhang Lijuan , Zhang Qi , Mu Shuqin , Zhang Rongxin , Da Yurong
Published: June 2017

Adiponectin (APN), also known as apM1, Acrp30, GBP28 and adipoQ, is a circulating hormone that is predominantly produced by adipose tissue. Many pharmacological studies have demonstrated that this protein possesses potent anti-diabetic, anti-atherogenic and anti-inflammatory properties. Although several studies have demonstrated the antioxidative activity of this protein, the regulatory mechanisms have not yet been defined in skeletal muscles. The aim of the present study was to examine the cytoprotective effects of APN against damage induced by oxidative stress in mouse-derived C2C12 myoblasts. APN attenuated H2O2-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species that were induced by H2O2. Furthermore, treating C2C12 cells with APN significantly induced heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2). APN also suppressed H2O2-induced mitophagy and partially inhibited the colocalization of mitochondria with autophagosomes/lysosomes, correlating with the expression of Pink1 and Parkin and mtDNA. Moreover, APN protected C2C12 myoblasts against oxidative stress-induced apoptosis. Furthermore, APN significantly reduced the mRNA and protein expression levels of Bax. These data suggest that APN has a moderate regulatory role in oxidative stress-induced mitophagy and suppresses apoptosis. These findings demonstrate the antioxidant potential of APN in oxidative stress-associated skeletal muscle diseases.
Genome-wide mapping and characterization of microsatellites in the swamp eel genome
Authors: Li Zhigang , Chen Feng , Huang Chunhua , Zheng Weixin , Yu Chunlai , Cheng Hanhua , Zhou Rongjia
Published: June 2017

We described genome-wide screening and characterization of microsatellites in the swamp eel genome. A total of 99,293 microsatellite loci were identified in the genome with an overall density of 179 microsatellites per megabase of genomic sequences. The dinucleotide microsatellites were the most abundant type representing 71% of the total microsatellite loci and the AC-rich motifs were the most recurrent in all repeat types. Microsatellite frequency decreased as numbers of repeat units increased, which was more obvious in long than short microsatellite motifs. Most of microsatellites were located in non-coding regions, whereas only approximately 1% of the microsatellites were detected in coding regions. Trinucleotide repeats were most abundant microsatellites in the coding regions, which represented amino acid repeats in proteins. There was a chromosome-biased distribution of microsatellites in non-coding regions, with the highest density of 203.95/Mb on chromosome 8 and the least on chromosome 7 (164.06/Mb). The most abundant dinucleotides (AC)n was mainly located on chromosome 8. Notably, genomic mapping showed that there was a chromosome-biased association of genomic distributions between microsatellites and transposon elements. Thus, the novel dataset of microsatellites in swamp eel provides a valuable resource for further studies on QTL-based selection breeding, genetic resource conservation and evolutionary genetics.
Seroconversion to Lutzomyia intermedia LinB-13 as a biomarker for developing cutaneous leishmaniasis
Authors: Carvalho Augusto M. , Fukutani Kiyoshi F. , Sharma Rohit , Curvelo Rebecca P. , Miranda José Carlos , Barral Aldina , Carvalho Edgar M. , Valenzuela Jesus G. , Oliveira Fabiano , de Oliveira Camila I.
Published: June 2017

Sand flies inject saliva while feeding in the vertebrate host and anti-saliva antibodies can be used as biomarkers of exposure to Leishmania vectors. We expressed recombinant salivary proteins from Lutzomyia intermedia, a vector of Leishmania braziliensis, and evaluated the seroreactivity in exposed individuals in search for exposure markers. We found a strong correlation among positive serology to recombinant proteins LinB-13, 26, 15, 21 and to salivary proteins: rLinB-13 was the top performing molecule; IgG4 was the most predominant antibody subclass and antibodies to rLinB-13 did not cross react with Lu. longipalpis salivary proteins. By evaluating a cohort of contacts of CL patients, we confirmed that rLinB-13, an antigen 5-related protein, is a marker of exposure to Lu. intermedia with high degree of accuracy. In a 5-year follow up, we determined that individuals who developed CL presented higher anti-rLinB13 IgG responses, before the appearance of clinical symptoms. They also presented a lower frequency of cellular responses to the parasite (DTH). Our results show that seroconversion to a salivary molecule, rLinB-13, is a marker of risk for CL development caused by Leishmania braziliensis. This highlight the possibility of developing tools based on vector molecules to manage the disease in endemic areas.
Constructing a visible-light-driven photocatalytic membrane by g-C3N4 quantum dots and TiO2 nanotube array for enhanced water treatment
Authors: Zhang Qi , Quan Xie , Wang Hua , Chen Shuo , Su Yan , Li Zhangliang
Published: June 2017

Photocatalytic membranes that driven by visible light are highly desired for water treatment. Here g-C3N4 quantum dots (QDs) assembled into TiO2 nanotube array (TNA) membranes were fabricated for the first time as a visible-light-driven g-C3N4/TNA membrane. Benefiting from the synergistic effect of membrane filtration and photocatalysis, more than 60% of rhodamine B could be removed from water under visible light irradiation. Meanwhile, the g-C3N4/TNA membrane presented an enhanced anti-fouling ability during filtering water containing Escherichia coli under visible light irradiation, and a permeate flux of 2 times higher than that of filtration alone was obtained by integrated process. This study offers a promising strategy for the potential application of the visible-light-driven membranes in water treatment.
A Metric on the Space of kth-order reduced Phylogenetic Networks
Authors: Wang Juan , Guo Maozu
Published: June 2017

Phylogenetic networks can be used to describe the evolutionary history of species which experience a certain number of reticulate events, and represent conflicts in phylogenetic trees that may be due to inadequacies of the evolutionary model used in the construction of the trees. Measuring the dissimilarity between two phylogenetic networks is at the heart of our understanding of the evolutionary history of species. This paper proposes a new metric, i.e. kth-distance, for the space of kth-order reduced phylogenetic networks that can be calculated in polynomial time in the size of the compared networks.
Altered humoral immunity to mycobacterial antigens in Japanese patients affected by inflammatory demyelinating diseases of the central nervous system
Authors: Cossu Davide , Yokoyama Kazumasa , Tomizawa Yuji , Momotani Eiichi , Hattori Nobutaka
Published: June 2017

Mycobacterium avium subsp. paratuberculosis (MAP) and Mycobacterium bovis (BCG) have been associated to several human autoimmune diseases such as multiple sclerosis (MS), but there are conflicting evidence on the issue. The objective of this study is to evaluate their role in Japanese patients affected by inflammatory demyelinating disorders of the central nervous system (IDDs). A total of 97 IDDs subjects including 51 MS and 46 neuromyelitis optica spectrum disorder (NMOSD) patients, and 34 healthy controls (HCs) were tested for the detection of IgG, IgM and IgA against mycobacterial antigens by indirect ELISA. The levels of anti-MAP IgG were higher in MS patients compared to NMOSD patients (AUC = 0.59, p = 0.02) and HCs (AUC = 0.67, p = 0.01), and the anti-MAP antibodies were more prevalent in MS patients treated with interferon-beta (OR = 11.9; p = 0.004). Anti-BCG IgG antibodies were detected in 8% of MS, 32% of NMOSD and 18% of HCs, the difference between MS and NMOSD groups was statistically significant (AUC = 0.66, p = 0.005). Competition experiments showed that nonspecific IgM were elicited by common mycobacterial antigens. Our study provided further evidence for a possible association between MAP and MS, while BCG vaccination seemed to be inversely related to the risk of developing MS.
Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism
Authors: Hadjikhani Nouchine , Åsberg Johnels Jakob , Zürcher Nicole R. , Lassalle Amandine , Guillon Quentin , Hippolyte Loyse , Billstedt Eva , Ward Noreen , Lemonnier Eric , Gillberg Christopher
Published: June 2017

Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway – i.e., the amygdala – has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.
Bloch oscillations sustained by nonlinearity
Authors: Driben R. , Konotop V. V. , Meier T. , Yulin A. V.
Published: June 2017

We demonstrate that nonlinearity may play a constructive role in supporting Bloch oscillations in a model which is discrete, in one dimension and continuous in the orthogonal one. The model can be experimentally realized in several fields of physics such as optics and Bose-Einstein condensates. We demonstrate that designing an optimal relation between the nonlinearity and the linear gradient strength provides extremely long-lived Bloch oscillations with little degradation. Such robust oscillations can be observed for a broad range of parameters and even for moderate nonlinearities and large enough values of linear potential. We also present an approximate analytical description of the wave packet’s evolution featuring a hybrid Bloch oscillating wave-soliton behavior that excellently corresponds to the direct numerical simulations.
Differential transcript profiling alters regulatory gene expression during the development of Gossypium arboreum, G.stocksii and somatic hybrids
Authors: Ke Liping , Luo Binglun , Zhang Liqing , Zhang Mengna , Yu Xiushuang , Sun Jie , Sun Yuqiang
Published: June 2017

Polyploidy or genome doubling (i.e., the presence of two or more diploid parental genome sets within an organism) are very important in higher plants. Of particular interest are the mechanisms in the new microenvironment of the common nucleus, where doubled regulatory networks interact to generate a viable genetic system capable of regulating growth, development and responses to the environment. To determine the effects of whole genome merging and doubling on the global gene expression architecture of a new polyploid, derived from protoplast fusion of the A1A1 genome of Gossypium arboreum and the E1E1 genome of Gossypium stocksii, we monitored gene expression through cDNA-AFLP in the somatic hybrids (G. arboreum + G. stocksii). The genomic expression patterns of the somatic hybrids revealed that changes in expression levels mainly involved regulatory genes (31.8% of the gene expression profiles), and the AA and EE genomes contributed equally to genome-wide expression in the newly formed AAEE genome from additivity and dominance effects. These results provide a novel perspective on polyploid gene regulation and hint at the underlying genetic basis of allopolyploid adaption in the new microenvironmental nucleus.
Transcriptome of Pterospermum kingtungense provides implications on the mechanism underlying its rapid vegetative growth and limestone adaption
Authors: Ren Yandong , Zhu Yanan , Wang Qi , Xiang Hui , Wang Boyi
Published: June 2017

Pterospermum kingtungense C.Y.Wu ex Hsue is a typical tree species living in the relatively adverse limestone habitat. Due to its excellent wood quality and big size, it is an important timber resource which caused its endangered. We firstly provide the data resources by reporting an annotated transcriptome assembly. 203 million unique Illumina RNA-seq reads were produced with totally 50,333 transcripts, among which 48,778 transcripts were annotated. By a global comparison of homology between P. kingtungense and cacao, we identified 9,507 single copy orthologues and 990 P. kingtungense specific genes. GO enrichment analyses indicate that P. kingtungense specific genes are enriched in defense response, implying potential adaptation to limestone environment. As to cell compartment, the genes are enriched in thylakoid component. Consistently, KEGG enrichment indicates that genes are enriched in photosynthesis. In addition, we identified two genes under positive selection in P. kingtungense species. These results suggest that P. kingtungense have strong photosynthetic capacity, which related to vegetation growth. Our work provides the genomic resources of a limestone specific tree with economic importance to local society and suggests possible mechanism on its characteristics on the limestone adaption and excellent wood properties, which will be important for its conservation and sustainable utilization.
Directing solar photons to sustainably meet food, energy, and water needs
Authors: Gençer Emre , Miskin Caleb , Sun Xingshu , Khan M. Ryyan , Bermel Peter , Alam M. Ashraf , Agrawal Rakesh
Published: June 2017

As we approach a “Full Earth” of over ten billion people within the next century, unprecedented demands will be placed on food, energy and water (FEW) supplies. The grand challenge before us is to sustainably meet humanity’s FEW needs using scarcer resources. To overcome this challenge, we propose the utilization of the entire solar spectrum by redirecting solar photons to maximize FEW production from a given land area. We present novel solar spectrum unbundling FEW systems (SUFEWS), which can meet FEW needs locally while reducing the overall environmental impact of meeting these needs. The ability to meet FEW needs locally is critical, as significant population growth is expected in less-developed areas of the world. The proposed system presents a solution to harness the same amount of solar products (crops, electricity, and purified water) that could otherwise require ~60% more land if SUFEWS were not used—a major step for Full Earth preparedness.
Reconfigurable all-dielectric metasurface based on tunable chemical systems in aqueous solution
Authors: Yang Xiaoqing , Zhang Di , Wu Shiyue , Yin Yang , Li Lanshuo , Cao Kaiyuan , Huang Kama
Published: June 2017

Dynamic control transmission and polarization properties of electromagnetic (EM) wave propagation is investigated using chemical reconfigurable all-dielectric metasurface. The metasurface is composed of cross-shaped periodical teflon tubes and inner filled chemical systems (i.e., mixtures and chemical reaction) in aqueous solution. By tuning the complex permittivity of chemical systems, the reconfigurable metasurface can be easily achieved. The transmission properties of different incident polarized waves (i.e., linear and circular polarization) were simulated and experimentally measured for static ethanol solution as volume ratio changed. Both results indicated this metasurface can serve as either tunable FSS (Frequency Selective Surface) or tunable linear-to-circular/cross Polarization Converter at required frequency range. Based on the reconfigurable laws obtained from static solutions, we developed a dynamic dielectric system and researched a typical chemical reaction with time-varying permittivity filled in the tubes experimentally. It provides new ways for realizing automatic reconfiguration of metasurface by chemical reaction system with given variation laws of permittivity.
Bactericidal metabolites from Phellinus noxius HN-1 against Microcystis aeruginosa
Authors: Jin Pengfei , Wang Haonan , Liu Wenbo , Zhang Shujian , Lin Chunhua , Zheng Fucong , Miao Weiguo
Published: June 2017

Harmful algal blooms cause serious problems worldwide due to large quantities of cyanotoxins produced by cyanobacteria in eutrophic water. In this study, a new compound named 2-(3, 4-dihydroxy-2-methoxyphenyl)-1, 3-benzodioxole-5-carbaldehyde (Compound 1), together with one known compound, 3, 4-dihydroxybenzalacetone (DBL), was purified from Phellinus noxius HN-1 (CCTCC M 2016242). Compound 1 and DBL displayed activity against the cyanobacteria Microcystis aeruginosa with a half maximal effective concentration of 21 and 5 μg/mL, respectively. Scanning electron and transmission electron microscopic observations showed that the compounds caused serious damage and significant lysis to M. aeruginosa cells. qRT-PCR assay indicated that compound 1 and DBL exposure up-regulated the expression of gene mcyB and down-regulated the expression of genes ftsZ, psbA1, and glmS in M. aeruginosa. This study provides the first evidence of bactericidal activity of a new compound and DBL. In summary, our results suggest that compound 1 and DBL might be developed as naturally-based biocontrol agents.
Epe1 contributes to activation of AMPK by promoting phosphorylation of AMPK alpha subunit, Ssp2
Authors: Chen Yongyi , Hu Xiaoyue , Guo Chao , Yu Yao , Lu Hong
Published: June 2017

AMP-activated protein kinase (AMPK) is a pivotal cellular energy sensor. It is activated by stresses that cause depletion of energy and initiates adaptive responses by regulating metabolism balance. AMPK forms αβγ heterotrimer. In fission yeast, activation of AMPK mainly depends on the phosphorylation of AMPKα subunit Ssp2 at Thr189 by upstream kinase Ssp1. However, not much is known about the regulation of this process. In this study, we identified Epe1 as a novel positive regulator of AMPK. Epe1, a jmjC-domain-containing protein, is best-known as a negative regulator of heterochromatin spreading. Although the novel role of Epe1 in regulation of AMPK relies on predicted iron- and 2-oxyglutarate-binding residues inside jmjC domain, it seems to be irrelevant to inhibition of heterochromatin spreading. Epe1 is associated with Ssp2 directly and promotes phosphorylation of Ssp2 upon various environmental stresses, including low-glucose, high-sodium, high-pH and oxidative conditions. Similar to Epe1, Jmj1 and Msc1 also contribute to phosphorylation of Ssp2. Deletion of epe1+ impairs downstream events following phosphorylation of Ssp2, including nuclear translocation of Ssp2, sexual differentiation and inhibition of fatty acid synthesis. Our study reveals a novel way in which a jmjC-domain-containing protein regulates adaptive response by directly binding to a principal sensor.
An innovative cell-laden α-TCP/collagen scaffold fabricated using a two-step printing process for potential application in regenerating hard tissues
Authors: Kim Won Jin , Yun Hui-Suk , Kim Geun Hyung
Published: June 2017

Cell-laden scaffolds are widely investigated in tissue engineering because they can provide homogenous cell distribution after long culture periods, and deposit multiple types of cells into a designed region. However, producing a bioceramic 3D cell-laden scaffold is difficult because of the low processability of cell-loaded bioceramics. Therefore, designing a 3D bioceramic cell-laden scaffold is important for ceramic-based tissue regeneration. Here, we propose a new strategy to fabricate an alpha-tricalcium-phosphate (α-TCP)/collagen cell-laden scaffold, using preosteoblasts (MC3T3-E1), in which the volume fraction of the ceramic exceeded 70% and was fabricated using a two-step printing process. To fabricate a multi-layered cell-laden scaffold, we manipulated processing parameters, such as the diameter of the printing nozzle, pneumatic pressure, and volume fraction of α-TCP, to attain a stable processing region. A cell-laden pure collagen scaffold and an α-TCP/collagen scaffold loaded with cells via a simple dipping method were used as controls. Their pore geometry was similar to that of the experimental scaffold. Physical properties and bioactivities showed that the designed scaffold demonstrated significantly higher cellular activities, including metabolic activity and mineralization, compared with those of the controls. Our results indicate that the proposed cell-laden ceramic scaffold can potentially be used for bone regeneration.
Multisensory Perception of Contradictory Information in an Environment of Varying Reliability: Evidence for Conscious Perception and Optimal Causal Inference
Authors: Mahani Mohammad-Ali Nikouei , Sheybani Saber , Bausenhart Karin Maria , Ulrich Rolf , Ahmadabadi Majid Nili
Published: June 2017

Two psychophysical experiments examined multisensory integration of visual-auditory (Experiment 1) and visual-tactile-auditory (Experiment 2) signals. Participants judged the location of these multimodal signals relative to a standard presented at the median plane of the body. A cue conflict was induced by presenting the visual signals with a constant spatial discrepancy to the other modalities. Extending previous studies, the reliability of certain modalities (visual in Experiment 1, visual and tactile in Experiment 2) was varied from trial to trial by presenting signals with either strong or weak location information (e.g., a relatively dense or dispersed dot cloud as visual stimulus). We investigated how participants would adapt to the cue conflict from the contradictory information under these varying reliability conditions and whether participants had insight to their performance. During the course of both experiments, participants switched from an integration strategy to a selection strategy in Experiment 1 and to a calibration strategy in Experiment 2. Simulations of various multisensory perception strategies proposed that optimal causal inference in a varying reliability environment not only depends on the amount of multimodal discrepancy, but also on the relative reliability of stimuli across the reliability conditions.
Association of Interleukin-12A rs568408 with Susceptibility to Asthma in Taiwan
Authors: Shen Te-Chun , Tsai Chia-Wen , Chang Wen-Shin , Wang Shengyu , Chao Che-Yi , Hsiao Chieh-Lun , Chen Wei-Chun , Hsia Te-Chun , Bau Da-Tian
Published: June 2017

Asthma is an inflammatory disease and interleukin 12 (IL-12) may play a regulatory role in allergen-induced inflammation. The aim of this study was to investigate the association of polymorphisms in IL-12A/IL-12B with asthma. The asthma group included 198 adult patients and the control group included 453 individuals without asthma that were frequency-matched by gender and age. The distribution of genotypic and allelic frequencies of IL-12A rs568408 demonstrated significant differences between case and control groups. Specifically, the percentages of AA genotype of IL-12A rs568408 was significantly higher among asthmatic patients in Taiwan than healthy controls, compared to GG genotype. No significant difference was observed among the IL-12A rs2243115 and IL-12B rs3212227 genotypes between case and control groups. In addition, the A allele at IL-12A rs568408 was associated with more severe symptoms (P = 0.0085) among asthmatic patients. These results suggest that IL-12A rs568408 may contribute to the etiology and symptoms severity of asthma, indicating its usefulness as a predictive and diagnostic biomarker of asthma.
Improving Spatiotemporal Breast Cancer Assessment and Prediction in Hangzhou City, China
Authors: Lou Zhaohan , Fei Xufeng , Christakos George , Yan Jianbo , Wu Jiaping
Published: June 2017

Breast cancer (BC) is the main cause of death of female cancer patients in China. Mainstream mapping techniques, like spatiotemporal ordinary kriging (STOK), generate disease incidence maps that improve our understanding of disease distribution. Yet, the implementation of these techniques experiences substantive and technical complications (due mainly to the different characteristics of space and time). A new spatiotemporal projection (STP) technique that is free of the above complications was implemented to model the space-time distribution of BC incidence in Hangzhou city and to estimate incidence values at locations-times for which no BC data exist. For comparison, both the STP and the STOK techniques were used to generate BC incidence maps in Hangzhou. STP performed considerably better than STOK in terms of generating more accurate incidence maps showing a closer similarity to the observed incidence distribution, and providing an improved assessment of the space-time BC correlation structure. In sum, the inter-connections between space, time, BC incidence and spread velocity established by STP allow a more realistic representation of the actual incidence distribution, and generate incidence maps that are more accurate and more informative, at a lower computational cost and involving fewer approximations than the incidence maps produced by mainstream space-time techniques.
Evaluation of intraretinal migration of retinal pigment epithelial cells in age-related macular degeneration using polarimetric imaging
Authors: Miura Masahiro , Makita Shuichi , Sugiyama Satoshi , Hong Young-Joo , Yasuno Yoshiaki , Elsner Ann E. , Tamiya Shigeo , Tsukahara Rintaro , Iwasaki Takuya , Goto Hiroshi
Published: June 2017

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R2 = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED.
The ModA2 Phasevarion of nontypeable Haemophilus influenzae Regulates Resistance to Oxidative Stress and Killing by Human Neutrophils
Authors: Brockman Kenneth L. , Branstool M. Taylor , Atack John M. , Robledo-Avila Frank , Partida-Sanchez Santiago , Jennings Michael P. , Bakaletz Lauren O.
Published: June 2017

Nontypeable Haemophilus influenzae (NTHI) is the causative agent of multiple respiratory tract infections. Several human pathogens, including NTHI, possess a novel genetic system, termed the phasevarion, which mediates a rapid and reversible change in the expression of many genes throughout the chromosome. This occurs by phase variation of a single gene (modA) that encodes a DNA methyltransferase and results in two phenotypically distinct subpopulations, ON and OFF. NTHI encounters many pressures within the various microenvironments of its human host as the disease course evolves from one of asymptomatic nasopharyngeal carriage to overt disease. These include oxidative stresses, which are present throughout the respiratory tract. To persist in the human nasopharynx and as a pathogen throughout the airways, NTHI must be able to mitigate toxic levels of oxidative stress. Here we show that expression of ModA2, modA2 ON status, resulted in increased sensitivity to oxidative stress. Furthermore, the modA2 ON status resulted in decreased resistance to neutrophil-mediated killing, which resulted in selection for the modA2 OFF subpopulation in an ex vivo survival assay. These findings highlight the importance of the ModA2 phasevarion in adaptation to innate host defences and reveal an additional microenvironmental pressure that selected for a specific ModA2 subpopulation.
Topological Phase Transition in Single Crystals of (Cd1−xZnx)3As2
Authors: Lu Hong , Zhang Xiao , Bian Yi , Jia Shuang
Published: June 2017

Single crystals of (Cd1−xZnx)3As2 were synthesized from high-temperature solutions and characterized in terms of their structural and electrical properties. Based on the measurements of resistivity and Hall signals, we revealed a chemical-doping-controlled transition from a three-dimensional Dirac semimetal to a semiconductor with a critical point xc ~ 0.38. We observed structural transitions from a body-center tetragonal phase to a primitive tetragonal phase then back to a body-center tetragonal phase in the solid solutions as well, which are irrelevant to the topological phase transition. This continuously tunable system controlled by chemical doping provides a platform for investigating the topological quantum phase transition of three-dimensional Dirac electrons.
Global gene expression defines faded whorl specification of double flower domestication in Camellia
Authors: Li Xinlei , Li Jiyuan , Fan Zhengqi , Liu Zhongchi , Tanaka Takayuki , Yin Hengfu
Published: June 2017

Double flowers in cultivated camellias are divergent in floral patterns which present a rich resource for demonstrating molecular modifications influenced by the human demands. Despite the key principle of ABCE model in whorl specification, the underlying mechanism of fine-tuning double flower formation remains largely unclear. Here a comprehensive comparative transcriptomics interrogation of gene expression among floral organs of wild type and “formal double” and “anemone double” is presented. Through a combination of transcriptome, small RNA and “degradome” sequencing, we studied the regulatory gene expression network underlying the double flower formation. We obtained the differentially expressed genes between whorls in wild and cultivated Camellia. We showed that the formation of double flowers tends to demolish gene expression canalization of key functions; the faded whorl specification mechanism was fundamental under the diverse patterns of double flowers. Furthermore, we identified conserved miRNA-targets regulations in the control of double flowers, and we found that miR172-AP2, miR156-SPLs were critical regulatory nodes contributing to the diversity of double flower forms. This work highlights the hierarchical patterning of global gene expression in floral development, and supports the roles of “faded ABC model” mechanism and miRNA-targets regulations underlying the double flower domestication.
Assessment of local treatment modalities for FIGO stage IB-IIB cervical cancer: A propensity-score matched analysis based on SEER database
Authors: Song Xing , Han Yang , Shao Yingjie , Gu Wendong , Pei Honglei , Jiang Jingting
Published: June 2017

The aim of this study was to investigate the impact of local treatment modalities on the survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer, including cancer-directed surgery (CDS) alone and CDS combined with radiotherapy (RT). A total of 8,357 patients with cervical cancer between 1988 and 2013 were included in the final study cohort, including 4,298 (51.4%) patients who underwent CDS alone and 4,059 (48.6%) patients who received combination therapy. Univariate and multivariate analyses showed that local treatment modalities were prognostic factors for cause-specific survival (CSS). Patients who received combination therapy had worse CSS (HR = 1.38; 95% CI = 1.20–1.59; P < 0.001). Subgroup analyses showed the prognostic effect of local treatment modalities was significantly influenced by FIGO stage. In the propensity-score matched (PSM) dataset, CDS was associated with better CSS (P < 0.001) for patients with IB-IIA cervical cancer; nevertheless, no differences were observed in CSS (P = 0.639) for patients with IIB cervical cancer. In conclusion, radical surgery was the preferred treatment for patients with IB-IIA cervical cancer, and there was no difference between radical surgery alone and combination therapy for patients with IIB cervical cancer.
Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine
Authors: Xie Ze-Min , Wang Xing-Ming , Xu Ning , Wang Jing , Pan Wei , Tang Xiao-Hui , Zhou Zhi-Qiang , Hashimoto Kenji , Yang Jian-Jun
Published: June 2017

Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, IL-6) as well as imbalance of pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and sham-operated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype. Interestingly, higher serum levels of IL-1β and IL-6 in the rat with depression-like phenotype were normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine’s antidepressant actions.
Unique copper and reduced graphene oxide nanocomposite toward the efficient electrochemical reduction of carbon dioxide
Authors: Hossain M. Nur , Wen Jiali , Chen Aicheng
Published: June 2017

The electrochemical reduction of CO2 to useful chemicals and fuels has garnered a keen and broad interest. Herein, we report a unique nanocomposite consisting of Cu nanoparticles (NPs) and reduced graphene oxide (rGO) supported on a Cu substrate with a high catalytic activity for CO2 reduction. The nanocomposite was optimized in terms of the composition of Cu NPs and rGO as well as the overall amount. A gas chromatograph was employed to analyze the gaseous products, whereas a chemical oxygen demand (COD) method was proposed and utilized to quantify the overall liquid products. The optimized nanocomposite could effectively reduce CO2 to CO, HCOOH and CH4 with a Faradaic efficiency (FE) of 76.6% at −0.4 V (vs. RHE) in a CO2 saturated NaHCO3 solution. The remarkable catalytic activity, high FE, and excellent stability make this Cu-rGO nanocomposite promising for the electrochemical reduction of CO2 to value-added products to address the pressing environmental and energy challenges.
Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
Authors: Gao Shangfeng , Jin Lei , Liu Guangping , Wang Peng , Sun Zonghan , Cao Yujia , Shi Hengliang , Liu Xuejiao , Shi Qiong , Zhou Xiuping , Yu Rutong
Published: June 2017

The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients. We thus established lentivirus-mediated RASD1-overexpressing glioma cells and found that overexpressing RASD1 had no significant effects on glioma cell proliferation. However, the overexpression of RASD1 inhibited glioma cell migration and invasion. In the intracranial glioma xenograft model, the overexpression of RASD1 significantly reduced the number of tumor cells invading into the surrounding tissues without affecting the tumor size. An intracellular signaling array revealed that the phosphorylation of both AKT and the S6 ribosomal protein significantly decreased with RASD1 overexpression in glioma cells. Interestingly, RASD1 protein levels were significantly higher in grade II and grade III astrocytoma tissues than in nontumorous brain tissues. These findings suggest that the upregulation of RASD1 in glioma tissues may play an inhibitory role in tumor expansion, possibly through inactivating the AKT/mTOR signaling pathway.
Influence of W substitution on crystal structure, phase evolution and microwave dielectric properties of (Na0.5Bi0.5)MoO4 ceramics with low sintering temperature
Authors: Pang Li-Xia , Zhou Di , Qi Ze-Ming , Yue Zhen-Xing
Published: June 2017

In this work, the (Na0.5Bi0.5)(Mo1−xWx)O4 (x = 0.0, 0.5 and 1.0) ceramics were prepared via solid state reaction method. All the samples can be well densified at sintering temperature about ~720 °C. Dense and homogeneous microstructure with grain size lying between 2~8 μm can be observed from scanning electron microscopy (SEM). Microwave dielectric permittivity of the (Na0.5Bi0.5)(Mo0.5W0.5)O4 ceramic was found to be temperature-independent in a wide range between 25~120 °C with a temperature coefficient of frequency (TCF) ~−6 ppm/°C, a permittivity ~28.9, and Qf values 12,000~14,000 GHz. Crystal structure was refined using Rietveld method and lattice parameters are a = b = 5.281 (5) Å and c = 11.550 (6) Å with a space group I 41/a (88). The (Na0.5Bi0.5)(Mo1−xWx)O4 ceramics might be good candidate for low temperature co-fired ceramics (LTCC) technology.
Induction of sirtuin-1 signaling by resveratrol induces human chondrosarcoma cell apoptosis and exhibits antitumor activity
Authors: Chao Sung-Chuan , Chen Ying-Ju , Huang Kuo-How , Kuo Kuan-Lin , Yang Ting-Hua , Huang Kuo-Yuan , Wang Ching-Chia , Tang Chih-Hsin , Yang Rong-Sen , Liu Shing-Hwa
Published: June 2017

Chondrosarcoma is a malignant primary bone tumor. Sirtuin-1 (SIRT1), which is a member of sirtuin family, plays a dual role either in cancer promotion or suppression. There is no report about the role of SIRT1 in the human chondrosarcoma cells. Resveratrol is a potent activator of SIRT1. However, its effects on chondrosarcoma have not been extensively studied. Here, we investigated the role of SIRT1 induction by resveratrol in human chondrosarcoma cell growth and tumor progression. Resveratrol significantly decreased cell viability and induced cell apoptosis in human chondrosarcoma cells in a dose-dependent manner. The protein expression and activity of SIRT1 were activated after treatment with resveratrol. Resveratrol significantly inhibited NF-κB signaling by deacetylating the p65 subunit of NF-κB complex, which could be reversed by siRNA-SIRT1 transfection or deacetylation inhibitor MS-275. Resveratrol induced-apoptosis involved a caspase-3-mediated mechanism. Both siRNA-SIRT1 transfection and MS-275 significantly inhibited the resveratrol-induced caspase-3 cleavage and activity in human chondrosarcoma cells. Moreover, in vivo chondrosarcoma xenograft study revealed a dramatic reduction in tumor volume and the increased SIRT1 and cleaved caspase-3 expressions in tumors by resveratrol treatment. These results suggest that resveratrol induces chondrosarcoma cell apoptosis via a SIRT1-activated NF-κB deacetylation and exhibits anti-chondrosarcoma activity in vivo.
Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy
Authors: Veith Lothar , Vennemann Antje , Breitenstein Daniel , Engelhard Carsten , Wiemann Martin , Hagenhoff Birgit
Published: June 2017

We demonstrate the suitability of the ToF-SIMS technique for the detection of SiO2 nanoparticles in lung tissue sections by a comparison to fluorescence microscopy.
Probing the binding mechanism of polybrominated diphenyl ethers with transthyretin by multi-spectroscopic and molecular dynamics simulations
Authors: Xu Jie , Yi Zhongsheng , Wei Yuchen , Yang Wu , Yang Lulu , Nie Jinfang
Published: June 2017

The physical and chemical properties of polybrominated diphenyl ethers (PBDEs) are important for modeling their transport.