bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor‐Site‐Directed Rational Assembly of Heteroleptic cis‐[Pd2L2L′2] Coordination Cages from Picolyl Ligands
Authors: Zhu Rongmei , Bloch Witold M. , Holstein Julian J. , Mandal Soham , Schäfer Lars V. , Clever Guido H.
Published: June 2018

A donor‐site engineering approach facilitates the formation of heteroleptic [Pd2L2L′2]4+ cage structures through a favored cis‐′in2/out2′ spatial configuration of the methyl groups of 5‐ and 3‐substituted bis‐monodentate picolyl ligands with flat acridone and bent phenothiazine backbones. The heteroleptic cages were confirmed by ESI‐MS and 2D NMR experiments as well as DFT calculations, which pointed toward a cis‐configuration being energetically favored. This was further supported by the synthesis and X‐ray structure of a previously unreported cis‐[Pd(2‐picoline)4]2+ complex. The formation of homoleptic structures, however, was met with considerable steric hindrance at the PdII centers, as observed by the formation of [Pd2L3(solvent)2]4+ and [Pd2L2(solvent)4]4+ species when only one type of acridone‐based ligand was offered. In contrast, bent phenothiazine ligands with outside‐pointing methyl groups showed the ability to form interpenetrated double‐cages, as revealed by X‐ray crystallography. The general route presented herein enables the assembly of uniform cis‐[Pd2L2L′2]4+ coordination cages, thus furthering the possibility to increase structural and functional complexity in supramolecular systems.
Synthesis of Colloidal Metal Nanocrystals: A Comprehensive Review on the Reductants
Authors: Rodrigues Thenner S. , Zhao Ming , Yang Tung‐Han , Gilroy Kyle D. , da Silva Anderson G. M. , Camargo Pedro H. C. , Xia Younan
Published: June 2018

There is a growing interest in controlling the synthesis of colloidal metal nanocrystals and thus tailoring their properties toward various applications. In this context, choosing an appropriate combination of reagents (e.g., salt precursor, reductant, capping agent, and stabilizer) plays a pivotal role in enabling the synthesis of metal nanocrystals with diversified sizes, shapes, and structures. Here we present a comprehensive review that highlights one of the key reagents for the synthesis of metal nanocrystals via chemical reduction: the reductants. We start with a brief introduction to the compounds commonly employed as reductants in the colloidal synthesis of metal nanocrystals by showing their oxidation half‐reactions and the corresponding oxidation potentials. Then we offer specific examples pertaining to the controlled synthesis of metal nanocrystals, followed by some fundamental aspects covering the general mechanisms of metal ion reduction based on the Marcus Theory. Afterwards, we present a case‐by‐case discussion on a wide variety of reductants, including their major properties, reduction mechanisms, and additional effects on the final products. We illustrate these aspects by selecting key examples from the literature and paying close attention to the underlying mechanism in each case. At the end, we conclude by summarizing the highlights of the review and providing some perspectives on future directions.
Monitoring the Effect of Different Metal Centers in Metal–Organic Frameworks and Their Adsorption of Aromatic Molecules using Experimental and Simulation Studies
Authors: Lirio Stephen , Shih Yung‐Han , Hsiao Shu‐Ying , Chen Jian‐Hong , Chen Hsin‐Tsung , Liu Wan‐Ling , Lin Chia‐Her , Huang Hsi‐Ya
Published: June 2018

In this study, the adsorption behavior of different metal centers in analogous M‐1,4‐NDC frameworks (1,4‐NDC=1,4‐naphthalenedicarboxylate) towards guest molecules through simulation studies and experimental studies is reported. Simulation studies showed that the adsorption behavior of analogous M‐1,4‐NDC is affected by the atomic radius of the metal center, which was found to be in agreement with the experimental studies.
N‐Heterocycle‐Fused Pentalenes by a Gold‐Catalyzed Annulation of Diethynyl‐Quinoxalines and ‐Phenazines
Authors: Sekine Kohei , Stuck Fabian , Schulmeister Jürgen , Wurm Thomas , Zetschok Dominik , Rominger Frank , Rudolph Matthias , Hashmi A. Stephen K.
Published: June 2018

The gold‐catalyzed annulation of diethynyl N‐heterocycles for the synthesis of quinoxaline‐/phenazine‐based pentalenes and the study of their optoelectronic properties are described. The inhibition of the gold catalyst by the nitrogen centers in the substrate and the product could be overcome by increasing the reaction temperature to 130 °C, which usually leads to catalyst decomposition in gold catalysis. At 130 °C, 6,7‐di(arylethynyl)quinoxalines in chlorobenzene give the corresponding pentalenes. The annulation of 2,3‐di(arylethynyl)quinoxalines requires an even higher temperature under microwave irradiation. The quinoxaline‐based pentalenes showed lower LUMO levels compared to the corresponding naphthalene‐based pentalenes.
Modelling of cross‐flow microfiltration coupled with bentonite treatment in sugar beet molasses purification
Authors: Djordjević Miljana , Šereš Zita , Došenović Tatjana , Šoronja‐Simović Dragana , Maravić Nikola , Šaranović Žana , Šereš Laslo , Šćiban Marina , Djordjević Marijana
Published: June 2018

The removal of colourants and other non‐sucrose compounds from sugar beet molasses opens the possibility for more acceptable and effective recovery of sucrose, which is the most valuable sugar industry product. In the presented study, the feasibility of the sugar beet molasses purification process, which combines sodium bentonite pre‐treatment and microfiltration with an embedded static mixer, was examined. Molasses pre‐treatment with sodium bentonite consisted of a bentonite suspension addition (7 g/L) under the following conditions: pH 5, temperature 50 °C, and contact time 30 min. Sugar beet molasses separation from bentonite was performed by cross‐flow microfiltration using a 200 nm TiO2 ceramic tubular membrane with static mixer absence or presence and variation in the sugar beet molasses flow rate and dry substance. The molasses purification process efficiency was validated through the permeate flux values as well as colour and turbidity measurements. Higher molasses colour (20–60 %) and turbidity reduction (83.4–99.2 %) was achieved in the experiments with static mixer absence, while static mixer introduction greatly increased the final and especially steady‐state permeate flux.
Study of fluid dynamic conditions in the selected static mixers part III—research of mixture homogeneity
Authors: Stec Magdalena , Synowiec Piotr Maria
Published: June 2018

This paper contains the analysis of mixture homogeneity in two types of static mixers, Koflo and Kenics, based on both experimental and CFD study. The research was also expanded to the recognition of the pipe that was used as a background. The scope of work includes the analysis of the CoV coefficients (as a measure of mixing degree) obtained for the mentioned devices and their comparison. The research showing the impact of such parameters, i.e., pressure drop or L/d ratio on the mentioned mixture homogeneity was also presented. What is more, the axial dispersion model was introduced to describe the devices as non‐ideal reactors. According to this, new relations for the CoV predictions (taking into consideration the turbulence intensity, the deviations from well‐known ideal states, and the mixing elements’ shape) were developed. As a result, it was proven that static mixers are highly efficient devices because the obtained CoVs were at around 2 % in the laminar flow and even less than that in the turbulent regime. When the pipe was used, the satisfactory value of the CoV was obtained when the Reynolds number was increased to 2600.
The intersection of financial toxicity and family building in young adult cancer survivors
Authors: Thom Bridgette , Benedict Catherine , Friedman Danielle N. , Kelvin Joanne F.
Published: June 2018

Financial toxicity and family‐building difficulties may co‐occur in young adult cancer survivors. Herein, the authors describe this intersection and propose steps to alleviate associated distress.
Approach to the Mechanism of Hydrogen Evolution Electrocatalyzed by a Model Co Clathrochelate: A Theoretical Study by Density Functional Theory
Authors: Antuch Manuel , Millet Pierre
Published: June 2018

The hydrogen evolution reaction (HER) has attracted much attention within the scientific community because of increasing demands of modern society for clean and renewable energy sources. Molecular complexes of 3d‐transition metals, such as cobalt, hold potential to replace platinum for the HER in acidic media. Among these, cage complexes such as tris‐glyoximate metal clathrochelates, have demonstrated promising catalytic properties towards the HER. However, it is not clear whether the catalytic activity of this molecule stems from metal‐centered activation of H+, due to a low oxidation state of the metal stabilized by the surrounding organic cage, or if it is the organic cage playing a further cooperative role in bringing protons together. Herein, we report on a density functional theory study of two possible mechanisms for the HER catalyzed by a model Co clathrochelate. To assess the putative ligand involvement in the mechanism, several combinations of single and double protonation sites were investigated. The structural and energetic analysis of relevant intermediates suggests that the electrocatalytic mechanism is not based on the cooperation between the ligand and the metal. Instead, it is mainly due to the activation of H+ by the Co metallocenter. Our calculations further suggest that the last step in the mechanism is a proton coupled electron transfer step.
Clinical Development and Initial Approval of Novel Immune Checkpoint Inhibitors in Oncology: Insights From a Global Regulatory Perspective
Authors: Serrano Philippe , Hartmann Markus , Schmitt Elmar , Franco Pedro , Amexis Georgios , Gross Jan , Mayer‐Nicolai Christine
Published: June 2018

Immune checkpoint inhibitors (ICI) have demonstrated meaningful patterns of clinical efficacy across various cancers. During their development, novel regulatory strategies and clinical design approaches were explored. This metrics‐based narrative review examines submission strategies and clinical evidence expectations of the US, European, and Japanese drug agencies, as well as their impact on approval and overall development times. Also discussed is the role of emerging clinical science and biomarker evaluation to get the first six ICI initially approved.
Bismuth Vanadate with Electrostatically Anchored 3D Carbon Nitride Nano‐networks as Efficient Photoanodes for Water Oxidation
Authors: Luan Peng , Zhang Ying , Zhang Xiaolong , Li Zhijun , Prathapan Ragesh , Bach Udo , Zhang Jie
Published: June 2018

In this study, we report a photoanode consisting of a polymeric/inorganic nanojunction between novel nanostructured 3D C3N4 nano‐networks and BiVO4 substrate. This nanojunction is formed such that 3D C3N4 nano‐networks with a positively charged surface are efficiently anchored on the BiVO4 photoanode with a negatively charged surface. This electrostatic self‐assembly can initiate and contribute to an intimate contact at the interfaces, leading to an enhanced photoelectrochemical activity and stability compared with that fabricated by non‐electrostatic assembly. The C3N4 nano‐network/BiVO4 photoanode achieved a remarkable photocurrent density of 4.87 mA cm−2 for water oxidation at 1.23 V (vs. reversible hydrogen electrode) after depositing FeOOH/NiOOH as oxygen‐evolution co‐catalyst, which is among the highest photocurrent densities reported so far for BiVO4‐based photoanodes.
Shape Engineering of Biomass‐Derived Nanoparticles from Hollow Spheres to Bowls through Solvent‐Induced Buckling
Authors: Chen Chunhong , Li Xuefeng , Deng Jiang , Wang Zhe , Wang Yong
Published: June 2018

The realization of asymmetric hollow carbonaceous nanostructures remains a great challenge, especially when biomass is chosen as the carbon resource through hydrothermal carbonization (HTC). Herein, a simple and straightforward solvent‐induced buckling strategy is demonstrated for the synthesis of asymmetric spherical and bowl‐like carbonaceous nanomaterials. The formation of the bowl‐like morphology was attributed to the buckling of the spherical shells induced by the dissolution of the oligomers. The bowl‐like particles prepared through this solvent‐driven approach demonstrated a well‐controlled morphology and a uniform particle size of approximately 360 nm. The obtained nanospheres and nanobowls were loaded with CoS2 nanoparticles to act as heterogeneous catalysts for the selective hydrogenation of aromatic nitro compounds. As expected, the CoS2/nanobowls catalyst showed good tolerance to a wide scope of reducible groups and afforded both high activity and selectivity in almost all the tested substrates.
New perspectives on the Luoquan Glaciation (Ediacaran‐Cambrian) of North China
Authors: Le Heron Daniel Paul , Vandyk Thomas Matthew , Wu Guanghui , Li Meng
Published: June 2018

The Luoquan Formation provides a record of the Ediacaran‐Cambrian glaciation in the North China Craton. The sedimentary record is well expressed in the Henan Province along the central China orogen, and includes a rich archive of striated pavements, diamictites, and dropstone‐bearing laminites. A reappraisal of the sedimentological evolution of the Luoquan Formation notes the following features. First, striated pavements with crosscutting striations do not necessarily record multiple phases of glacial (re)advance, but more likely originate through the development of sticky spots in a palaeo‐ice stream setting. The development of obstacles, basal adfreezing, or porosity variations in the subglacial substrate resulted in curvilinear and bifurcating striae, which can superficially be mistaken for crosscutting striae in isolated sections. Second, “massive” diamictites as previously described are in fact commonly weakly stratified, and there is a continuum from dropstone‐bearing rhythmically bedded shales and siltstones, through stratified diamictites to massive diamictites. This continuum is believed indicative of deposition by rain out from debris rich ice for those diamictites with less pronounced stratification, in contrast to the mass flow hypothesis previously suggested. Third, the presence of large‐scale, recumbent folds with associated thrusts is described at the type section. The suite of large‐scale deformation structures, measuring >30 m in amplitude, is sealed by undeformed diamictites. The deformation structures are interpreted to reflect soft‐sediment deformation produced through ice bulldozing. Integrating these observations, it is proposed that the Luoquan Formation was deposited in a large proglacial lake setting, with a range of ice contact to ice distal environments recognized.
Chemical Behaviour of CaAg2 under Ethylene Epoxidation Conditions
Authors: Antonyshyn Iryna , Sichevych Olga , Rasim Karsten , Ormeci Alim , Burkhardt Ulrich , Titlbach Sven , Schunk Stephan Andreas , Armbrüster Marc , Grin Yuri
Published: June 2018

The binary compound CaAg2 is examined as a catalyst for the ethylene epoxidation reaction. During the induction phase, conversion and selectivity increase and then remain stable for several hundred hours. The presence of ethyl chloride as a promoter is crucial. The pristine CaAg2 reacts with the gaseous reactants and forms a porous microstructure of calcium‐containing oxidation products on the surface, in which particles of elemental silver are embedded. The microstructure is remarkably stable, and in particular, prevents further sintering of the silver particles.
The production and release of microcystin related to phytoplankton biodiversity and water salinity in two cyanobacteria blooming lakes
Authors: Jia Junmei , Chen Qiuwen , Wang Min , Zhang Jianyun , Yi Qitao , Hu Liuming
Published: June 2018

To find the connections between microcystins and the phytoplankton community, coupled with environmental factors, we investigated 2 cyanobacteria blooming lakes, Lake Taihu (at the center of the Yangtze River Delta, eastern China) and Lake Yanghe (near Qinhuangdao City, northern China). Two years of data, including water quality and the amounts of phytoplankton, microcystins, and the congeners in both algal cells and water, were collected from the 2 lakes during 2013 and 2014. The results showed that both the microcystin quota and release percentage were positively correlated with biodiversity of phytoplankton and the Chlorophyta to phytoplankton ratio, but were negatively correlated with cyanobacteria abundance and the cyanobacteria to phytoplankton ratio; both the microcystin quota and release percentage were closely related to the intensity of competition between cyanobacteria and other phytoplankton; meanwhile, microcystins played a role in the competition between cyanobacteria and other phytoplankton. Salinity had a significantly negative relationship with both cellular and total microcystins, but a significantly positive relationship with the microcystin releasing percentage, indicating that an increase in salinity inhibited the production of microcystins but promoted their release into the aquatic environment. In addition, the average number of microcystins in Lake Yanghe was several times higher than the provisional guideline value adopted by the World Health Organization, indicating a possible health risk to local people. Environ Toxicol Chem 2018;37:2312–2322. © 2018 SETAC.
13q deletion is linked to an adverse phenotype and poor prognosis in prostate cancer
Authors: Kluth Martina , Scherzai Sekander , Büschek Franziska , Fraune Christoph , Möller Katharina , Höflmayer Doris , Minner Sarah , Göbel Cosima , Möller‐Koop Christina , Hinsch Andrea , Neubauer Emily , Tsourlakis Maria Christina , Sauter Guido , Heinzer Hans , Graefen Markus , Wilczak Waldemar , Luebke Andreas M , Burandt Eike , Steurer Stefan , Schlomm Thorsten , Simon Ronald
Published: June 2018

Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow‐up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate‐specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG‐positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.
Real‐time strategy video game experience and structural connectivity – A diffusion tensor imaging study
Authors: Kowalczyk Natalia , Shi Feng , Magnuski Mikolaj , Skorko Maciek , Dobrowolski Pawel , Kossowski Bartosz , Marchewka Artur , Bielecki Maksymilian , Kossut Malgorzata , Brzezicka Aneta
Published: June 2018

Experienced video game players exhibit superior performance in visuospatial cognition when compared to non‐players. However, very little is known about the relation between video game experience and structural brain plasticity. To address this issue, a direct comparison of the white matter brain structure in RTS (real time strategy) video game players (VGPs) and non‐players (NVGPs) was performed. We hypothesized that RTS experience can enhance connectivity within and between occipital and parietal regions, as these regions are likely to be involved in the spatial and visual abilities that are trained while playing RTS games. The possible influence of long‐term RTS game play experience on brain structural connections was investigated using diffusion tensor imaging (DTI) and a region of interest (ROI) approach in order to describe the experience‐related plasticity of white matter. Our results revealed significantly more total white matter connections between occipital and parietal areas and within occipital areas in RTS players compared to NVGPs. Additionally, the RTS group had an altered topological organization of their structural network, expressed in local efficiency within the occipito‐parietal subnetwork. Furthermore, the positive association between network metrics and time spent playing RTS games suggests a close relationship between extensive, long‐term RTS game play and neuroplastic changes. These results indicate that long‐term and extensive RTS game experience induces alterations along axons that link structures of the occipito‐parietal loop involved in spatial and visual processing.
Thalamic white matter in multiple sclerosis: A combined diffusion‐tensor imaging and quantitative susceptibility mapping study
Authors: Bergsland Niels , Schweser Ferdinand , Dwyer Michael G. , Weinstock‐Guttman Bianca , Benedict Ralph H. B. , Zivadinov Robert
Published: June 2018

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty‐five MS patients and 17 demographically‐matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility. Participants underwent cognitive evaluation with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Tract‐based spatial statistics identified thalamic WM. Non‐parametric combination (NPC) analysis was used to perform joint inference on fractional anisotropy (FA), mean diffusivity (MD) and magnetic susceptibility measures. The association of surrounding WM lesions and thalamic WM pathology was investigated with lesion probability mapping. Compared to HCs, the greatest extent of thalamic WM damage was reflected by the combination of increased MD and decreased magnetic susceptibility (63.0% of thalamic WM, peak p = .001). Controlling for thalamic volume resulted in decreased FA and magnetic susceptibility (34.1%, peak p = .004) as showing the greatest extent. In MS patients, the most widespread association with information processing speed was found with the combination of MD and magnetic susceptibility (67.6%, peak p = .0005), although this was not evident after controlling for thalamic volume. For memory measures, MD alone yielded the most widespread associations (45.9%, peak p = .012 or 76.7%, peak p = .001), even after considering thalamic volume, albeit with smaller percentages. White matter lesions were related to decreased FA (peak p = .0063) and increased MD (peak p = .007), but not magnetic susceptibility, of thalamic WM. Our study highlights the complex nature of thalamic pathology in MS.
High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts
Authors: Lipton Allan , Leitzel Kim , Ali Suhail M. , Polimera Hyma V. , Nagabhairu Vinod , Marks Eric , Richardson Angelique E. , Krecko Laura , Ali Ayesha , Koestler Wolfgang , Esteva Francisco J. , Leeming Diana J. , Karsdal Morten A. , Willumsen Nicholas
Published: June 2018

Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)‐mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. ELISAs were used to measure C1M (MMP‐generated type I collagen fragment), C3M (MMP‐generated type III collagen fragment), C4M (MMP‐generated type IV collagen fragment), and PRO‐C3 (pro‐peptide of type III collagen) in pretreatment serum from a phase 3 randomized clinical trial of second‐line hormone therapy (HR+, n = 148), and a first‐line trastuzumab‐treated cohort (HER2+, n = 55). All sites of metastases were included. The collagen fragments were evaluated by Cox‐regression analysis for their association with time‐to‐progression (TTP) and overall survival (OS). In the HR+ cohort, higher C1M and C3M levels (75th percentile cut‐off) were associated with shorter TTP; all fragments were associated with shorter OS. In the HER2+ cohort, higher levels of all fragments were associated with shorter TTP; higher PRO‐C3 was associated with shorter OS. In multivariate analysis of the HR+ trial for OS, higher levels of all fragments were significant for reduced OS when added separately (C1M HR = 2.1, p < 0.001; C3M HR = 1.8, p = 0.028; C4M HR = 1.8, p = 0.018; PRO‐C3 HR = 1.8, p = 0.017); none other clinical covariates were significant. In conclusion, collagen fragments quantified in pretreatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC.
Mycotoxin zearalenone induced gonadal impairment and altered gene expression in the hypothalamic–pituitary–gonadal axis of adult female zebrafish (Danio rerio)
Authors: Muthulakshmi Sellamani , Hamideh Pourmohammadi Fallah , Habibi Hamid R. , Maharajan Kannan , Kadirvelu Krishna , Mudili Venkataramana
Published: June 2018

In the present study, we aimed to assess the adverse effects of zearalenone (ZEA) at environmentally relevant concentrations (0.5, 1, 5 and 10 μg l−1) on hypothalamic–pituitary–gonadal axis associated reproductive function using zebrafish model. ZEA was exposed to female zebrafish for 21 days to assess growth indices such as condition factor, hepatosomatic index, gonadosomatic index and caspase 3 activity. Further, expression of estrogen receptor (ER) α and CYP19a1b genes in the brain, ERα and vitellogenin (Vtg) genes in the liver and follicle‐stimulating hormone receptor, luteinizing hormone receptor, ERα, steroidogenic acute regulatory protein, 3β‐hydroxysteroid dehydrogenase (HSD), 17‐βHSD and CYP19a1 genes in the ovary were also investigated. Our results showed that there were no significant changes in the condition factor and hepatosomatic index, whereas a significant (P < .05) reduction in the gonadosomatic index, increase in caspase 3 activities and Vtg expression was observed at higher concentration. However, no significant changes were observed at lower treatment levels. Further, we also observed significant (P < .05) upregulation in ERα, Vtg, luteinizing hormone receptor, steroidogenic acute regulatory protein, 3β‐HSD, 17β‐HSD, CYP19a1 and CYP19a1b genes in treatment groups with higher levels of ZEA. Moreover, in histopathological examination, we observed oocyte atresia and oocyte membrane detachment in ovaries at the highest concentration. In conclusion, the present study revealed the negative impact of ZEA on zebrafish reproductive system by involvement of the hypothalamic–pituitary–gonadal axis‐associated reproductive function.
Bone Turnover Markers Are Not Associated With Hip Fracture Risk: A Case-Control Study in the Women's Health Initiative
Authors: Crandall Carolyn J , Vasan Sowmya , LaCroix Andrea , LeBoff Meryl S , Cauley Jane A , Robbins John A , Jackson Rebecca D , Bauer Douglas C
Published: June 2018

Current guidelines recommend that serum C-terminal telopeptide of type I collagen (CTX) and serum procollagen type 1 aminoterminal propeptide (PINP), measured by standardized assays, be used as reference markers in observational and interventional studies. However, there are limited data to determine whether serum CTX and PINP are associated with hip fracture risk among postmenopausal women. We determined the associations of serum CTX and serum PINP with hip fracture risk among postmenopausal women aged 50 to 79 years at baseline. We performed a prospective case-control study (400 cases, 400 controls) nested in the Women's Health Initiative Observational Study, which enrolled participants at 40 US clinical centers. Cases were women with incident hip fracture not taking osteoporosis medication; hip fractures were confirmed using medical records. Untreated controls were matched by age, race/ethnicity, and date of blood sampling. Serum CTX and serum PINP were analyzed on 12-hour fasting blood samples. The main outcome measure was incident hip fracture risk (mean follow-up 7.13 years). After adjustment for body mass index, smoking, frequency of falls, history of fracture, calcium and vitamin D intake, and other relevant covariates, neither serum CTX level nor serum PINP level was statistically significantly associated with hip fracture risk (CTX ptrend = 0.22, PINP ptrend = 0.53). Our results do not support the utility of serum CTX level or PINP level to predict hip fracture risk in women in this age group. These results will inform future guidelines regarding the potential utility of these markers in fracture prediction. © 2018 American Society for Bone and Mineral Research.
Retracted: MicroRNA‐183 induces epithelial‐mesenchymal transition and promotes endometrial cancer cell migration and invasion in by targeting CPEB1
Authors: Xiong Hanzhen , Chen Ruichao , Liu Shaoyan , Lin Qiongyan , Chen Hui , Jiang Qingping
Published: June 2018

The aim of this study is to evaluate the ability of microRNA‐183 (miR‐183) to influence epithelial‐mesenchymal transition (EMT) and cell proliferation, migration, invasion, and apoptosis in endometrial cancer (EC) by targeting cytoplasmic polyadenylation element binding protein 1(CPEB1). EC tissues with matched nonmalignant tissues were collected from 208 EC patients. Ishikawa and RL95‐2 cells were selected for cell experiments in vitro and each kind of cells were grouped into blank, negative control (NC), miR‐183 mimic, miR‐183 inhibitor, CPEB1 overexpression, and miR‐183 mimic + CPEB1 overexpression groups. Expressions of miR‐183, CPEB1, E‐cadherin, and Vimentin were determined by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blotting. Cell viability, colony formation ability, migration, invasion, and apoptosis were assessed by MTT assay, clone formation assay, scratch test, Transwell assay, and flow cytometry. In vivo tumorigenesis of Ishikawa cells was evaluated by tumor formation in nude mice. The miR‐183 expression was higher, but the CPEB1 expression was lower in EC tissues than in adjacent nonmalignant tissues. CPEB1 was confirmed as the target of miR‐183 by dual‐luciferase reporter assay. The miR‐183 mimic group had increased cell viability, colony formation ability, cell invasion and migration, tumor volume and weight in nude mice, but decreased cell apoptosis when compared with the blank group. The expression of E‐cadherin was down‐regulate, but expression of Vimentin was up‐regulate in the miR‐183 mimic group in comparison with the blank group. In terms of a comparison between the blank group and CPEB1 overexpression group, the CPEB1 overexpression group had suppressed cell viability, colony formation ability, cell invasion and migration, tumor volume and weight, but increased cell apoptosis. The expression of E‐cadherin was up‐regulated, but the expression of Vimentin was down‐regulated in the CPEB1 overexpression group in comparison with the blank group. The miR‐183 mimic + CPEB1 overexpression group had higher miR‐183 expression than the blank group. These findings indicate that miR‐183 induces EMT, inhibits apoptosis, and promotes cell proliferation, migration, invasion, and in vivo tumorigenesis in EC by targeting CPEB1.
microRNA‐30d mediated breast cancer invasion, migration, and EMT by targeting KLF11 and activating STAT3 pathway
Authors: Han Mingli , Wang Yimeng , Guo Guangcheng , Li Lin , Dou Dongwei , Ge Xin , Lv Pengwei , Wang Fang , Gu Yuanting
Published: June 2018

miR‐30d has been shown to play pivotal roles in cancer development, and has the potential to act as a diagnostic biomarker and therapeutic target in breast cancer. However, the specific function and molecular mechanism of miR‐30d in breast cancer cell growth and metastasis is still unknown. The present study seeks to shed light on the potential contribution of the MiR‐30d‐KLF‐11‐STAT3 pathway in breast cancer. The results revealed that miR‐30d levels were markedly increased in the breast cancer cell lines BT474, MDA‐MB‐231, HCC197, and MDA‐MB‐468 compared with the non‐tumor mammary gland MCF10A cell line. Furthermore, the miR‐30d mimic increased BT474 and MDA‐MB‐231 breast cancer cell survival, inhibited apoptosis and increased Bcl‐2 expression, whilst inhibited Bax protein levels. miR‐30d mimics promote BT474 and MDA‐MB‐231 cell migration, invasion, and mediate the EMT phenotype. However, miR‐30d inhibitors reverse all of the effects of miR‐30d mimics on breast cancer cell biology. Also, we observed that KLF‐11 is a direct target of miR‐30d and KLF‐11 and pSTAT3 expression are determined by miR‐30d. Finally, the results suggest that miR‐30d plays essential roles in breast cancer cells in a manner that is dependent on the levels of KLF‐1 and pSTAT3. In summary, miR‐30d appears to be a novel diagnostic biomarker and treatment target in breast cancer.
EndophilinA2 protects against angiotensin II‐induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes
Authors: Liu Yun , Shen Huan‐Jia , Wang Xin‐Qiu‐Yue , Liu Hai‐Qi , Zheng Ling‐Yun , Luo Jian‐Dong
Published: June 2018

Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin‐mediated endocytosis and clathrin‐independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)‐induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1‐R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT‐PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1‐R.The expression levels of EndoA2, which inhibits AT1‐R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1‐R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co‐localization of AT1‐R with GRP‐78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1‐R transport from the cytoplasm to the membrane to suppress signal transduction.
miR‐423‐5p inhibits myoblast proliferation and differentiation by targeting Sufu
Authors: Ge Jing , Zhu Jiayu , Xia Bo , Cao Haigang , Peng Ying , Li Xiao , Yu Taiyong , Chu Guiyan , Yang Gongshe , Shi Xine
Published: June 2018

Myoblast proliferation and terminal differentiation are the key steps of myogenesis. MicroRNAs are a class of small noncoding RNAs that play important roles in gene expression regulation. They negatively regulate gene expression by causing messenger RNA translational repression or target messenger RNA degradation. Here, we found that microRNA‐423‐5p (miR‐423‐5p) is highly expressed in both slow and fast muscles. Our gain‐of‐function study indicated that miR‐423‐5p actually plays a negative role in regulating myoblast proliferation and differentiation. We also found that miR‐423‐5p is able to inhibit the expression of suppressor of fused homolog to inactivate the expression of the marker genes in myoblast proliferation and differentiation. Taken together, our findings indicated miR‐423‐5p as a potential inhibitor of myogenesis by targeting suppressor of fused homolog in myoblast, and it also contributes to a better understanding of the microRNAs‐target gene regulatory network in different types of porcine muscle types and may benefit the practice of improving the meat quality in animal husbandry.
Isolation and in vitro culture of ovarian stem cells in Chinese soft‐shell turtle (Pelodiscus sinensis)
Authors: Xu Hongyan , Zhu Xinping , Li Wei , Tang Zhoukai , Zhao Yanyan , Wu Xuling
Published: June 2018

Gonadal cell lines provide valuable tools for studying gametogenesis, sex differentiation, and manipulating germ cells in reproductive biology. Female germline stem cells have been characterized and isolated from ovaries of mammalian species, including mice and human, but there has been very few studies on female germline stem cells in reptiles. Here, we described an ovarian stem cell–like line isolated and cultured from the Chinese soft‐shell turtle (Pelodiscus sinensis), designated as PSO1. The cells showed high alkaline phosphatase activity with a normal diploid karyotype. As shown by reverse transcription‐polymerase chain reaction, the cells were positive for the expression of germ cell–specific genes, vasa and dazl, as well as a stem cell marker, nanog, but negative for the expression of the folliculogenesis‐specific gene, figla. Likewise, through fluorescent immunostaining analyses, both the Dazl and Vasa proteins were detected abundantly in the cytoplasm of perinuclear region, whereas Nanog and PCNA were dominantly observed in the nuclei in PSO1 cells. Moreover, PSO1 cells transfected with pCS2:h2b‐egfp could properly express the fusion protein in the nuclei. Taken together, the findings suggested that the germline stem cells exist in the ovary of juvenile Chinese soft‐shell turtle and these cells can be isolated for a long‐term in vitro culture under experimental conditions. This study has provided a valuable basis for further investigations on the molecular mechanisms whereby the germline stem cells develop and differentiate into gametes in turtles. Also, it has paved the way for studies on oogenesis in turtles, even in the other reptiles.
High vulnerability of the heart and liver to 3‐hydroxypalmitic acid–induced disruption of mitochondrial functions in intact cell systems
Authors: Cecatto Cristiane , Wajner Alessandro , Vargas Carmen Regla , Wajner Simone Magagnin , Amaral Alexandre Umpierrez , Wajner Moacir
Published: June 2018

Patients affected by long‐chain 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) deficiency predominantly present severe liver and cardiac dysfunction, as well as neurological symptoms during metabolic crises, whose pathogenesis is still poorly known. In this study, we demonstrate for the first time that pathological concentrations of 3‐hydroxypalmitic acid (3HPA), the long‐chain hydroxyl fatty acid (LCHFA) that most accumulates in LCHAD deficiency, significantly decreased adenosine triphosphate‐linked and uncoupled mitochondrial respiration in intact cell systems consisting of heart fibers, cardiomyocytes, and hepatocytes, but less intense in diced forebrain. 3HPA also significantly reduced mitochondrial Ca2+ retention capacity and membrane potential in Ca2+‐loaded mitochondria more markedly in the heart and the liver, with mild or no effects in the brain, supporting a higher susceptibility of the heart and the liver to the toxic effects of this fatty acid. It is postulated that disruption of mitochondrial energy and Ca2+ homeostasis caused by the accumulation of LCHFA may contribute toward the severe cardiac and hepatic clinical manifestations observed in the affected patients.
In vitro and in silico analyses of Vicia faba L. on Peroxisome proliferator–activated receptor gamma
Authors: Prabhu D. Sathya , Rajeswari V. Devi
Published: June 2018

The agonists of peroxisome proliferator–activated receptor gamma (PPARγ) from natural victual products were used as antidiabetic agents. Faba bean (Vicia faba L.) is a consequential legume that was known to possess potential antidiabetic activity, whose mechanism of action was unknown. The current study was focused to ascertain gene expression of the nuclear receptor PPARγ by Faba bean pod extract in rat cell lines (RINm5F).The real‐time polymerase chain reaction analysis demonstrated that Faba bean pod extract in concentrations of 160 µg/mL have shown 4.97‐fold stimulation compared with control. The cells treated with 320 µg/mL has shown 5.89‐fold upregulation, respectively. Furthermore, in silico docking analysis was carried out against PPARγ, using the bioactive compounds identified from Faba bean pod extracts, which were known reported compounds from the literature. The results suggest that gene expression of PPARγ was inhibited by the constituents in Faba bean. In silico analysis prognosticates, butein has a high binding energy (−8.6 kcal/mol) with an atomic contact energy of −214.10, followed by Apigenin and Quercetin against PPARγ. Similarly, the percentage of interaction was high for butein, followed by Apigenin and Quercetin than other compounds comparatively. Hence, the results conclude inhibition of PPARγ by the bioactive compounds from Faba bean, which may provide insights into developing future therapeutic molecules for diabetes mellitus.
Advances in the computational and molecular understanding of the prostate cancer cell nucleus
Authors: Carleton Neil M. , Lee George , Madabhushi Anant , Veltri Robert W.
Published: June 2018

Nuclear alterations are a hallmark of many types of cancers, including prostate cancer (PCa). Recent evidence shows that subvisual changes, ones that may not be visually perceptible to a pathologist, to the nucleus and its ultrastructural components can precede visual histopathological recognition of cancer. Alterations to nuclear features, such as nuclear size and shape, texture, and spatial architecture, reflect the complex molecular‐level changes that occur during oncogenesis. Quantitative nuclear morphometry, a field that uses computational approaches to identify and quantify malignancy‐induced nuclear changes, can enable a detailed and objective analysis of the PCa cell nucleus. Recent advances in machine learning–based approaches can now automatically mine data related to these changes to aid in the diagnosis, decision making, and prediction of PCa prognoses. In this review, we use PCa as a case study to connect the molecular‐level mechanisms that underlie these nuclear changes to the machine learning computational approaches, bridging the gap between the clinical and computational understanding of PCa. First, we will discuss recent developments to our understanding of the molecular events that drive nuclear alterations in the context of PCa: the role of the nuclear matrix and lamina in size and shape changes, the role of 3‐dimensional chromatin organization and epigenetic modifications in textural changes, and the role of the tumor microenvironment in altering nuclear spatial topology. We will then discuss the advances in the applications of machine learning algorithms to automatically segment nuclei in prostate histopathological images, extract nuclear features to aid in diagnostic decision making, and predict potential outcomes, such as biochemical recurrence and survival. Finally, we will discuss the challenges and opportunities associated with translation of the quantitative nuclear morphometry methodology into the clinical space. Ultimately, accurate identification and quantification of nuclear alterations can contribute to the field of nucleomics and has applications for computationally driven precision oncologic patient care.
miR‐96 regulates migration and invasion of bladder cancer through epithelial‐mesenchymal transition in response to transforming growth factor‐β1
Authors: He Chunfeng , Zhang Qingchuan , Gu Renze , Lou Yujiao , Liu Wei
Published: June 2018

Bladder cancer (BC) is one of the most frequent urological malignancies, and its molecular mechanism still remains unclear. Recent studies have revealed that MicroRNA (miRNAs) acted as oncogenes or tumor suppressors in a variety of cancers. MiRNA‐96 has been reported to play a significant role in the development and progression of many cancers. In the current study, we found that transforming growth factor (TGF)‐β1 played a significant role in the progression that miR‐96 conducted. And TGF‐β1 could also regulate the expression of FOXQ1, which is the target gene of miR‐96. Furthermore, miR‐96 induced epithelial‐mesenchymal transition in BC cells, which is driven by TGF‐β1. In conclusion, our data revealed that miR‐96 regulates the progression and epithelial‐mesenchymal transition, which is driven by TGF‐β1 in BC cells; it may provide a new thought for the therapy of BC.
Functional comparison of high and low molecular weight basic fibroblast growth factors
Authors: Motozawa Keiko , Motoyoshi Mitsuru , Saiki Akari , Sasaki Hideto , Shimizu Noriyoshi , Asano Masatake
Published: June 2018

Acid‐electrolyzed functional water (FW) is obtained through the electrolysis of sodium chloride solution. Stimulation of the human fibroblastic cell line HeLa by FW led to the augmented secretion of basic fibroblast growth factor (bFGF). Immunoprecipitation followed by Western blot analysis revealed that both high and low molecular weight isoforms of bFGF were secreted in response to FW treatment. To explore intracellular bFGF localization, a cell fractionation assay was performed. Despite the presence of nuclear localization signals within the N‐terminal portion of these proteins, the high molecular weight isoforms (34, 24, 22.5, and 21 kDa) were localized in the cytoplasm. FW stimulation drastically reduced the amount of intracytoplasmically localized isoforms, and the 34‐kDa isoform was found to localize in a DNase‐sensitive fraction, suggesting a weak nuclear attachment. By contrast, the 24‐kDa isoform remained in the nucleus even after FW stimulation. Functional differences between the 34‐ and 18‐kDa isoforms were examined further. Chinese hamster ovary cells were transfected with expression plasmids for each isoform. By treating each transfectant with FW, both isoforms were secreted successfully into the culture supernatants. Stimulation of HeLa cells with these supernatants resulted in the augmented secretion of vascular endothelial growth factor (VEGF). To further confirm the functionality of these isoforms, an in vitro transcription/translation reaction was performed; both of the isoforms induced VEGF secretion from HeLa cells. Taken together, these results indicate that the high molecular weight 34‐kDa isoform and low molecular weight 18‐kDa mature bFGF isoform have identical roles in VEGF induction.