bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models
Authors: Luo Yong , Azad Abul Kalam , Karanika Styliani , Basourakos Spyridon P. , Zuo Xuemei , Wang Jianxiang , Yang Luan , Yang Guang , Korentzelos Dimitrios , Yin Jianhua , Park Sanghee , Zhang Penglie , Campbell James J. , Schall Thomas J. , Cao Guangwen , Li Likun , Thompson Timothy C.
Published: December 2017

Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4‐2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub‐G1) in VCaP and C4‐2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p‐EGFR (Y1068), p‐AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133‐4 patient‐derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 μm2) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control‐treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors.
RhoA‐stimulated intra‐capillary morphology switch facilitates the arrest of individual circulating tumor cells
Authors: Huang Xi , Yang Yu , Zhao Yuwei , Cao Dan , Ai Xiaolin , Zeng Anqi , Gou Maling , Cai Lulu , Yang Hanshuo , Zhao Chengjian
Published: December 2017

Metastasis is the primary cause of death for most cancer patients. Hematogenous arrest of circulating tumor cells (CTCs) is an essential prerequisite for metastases formation. Using transparent transgenic zebrafish (kdrl:eGFP; Casper), together with resonant laser scanning confocal microscopy, we tracked the fate of CTCs in vivo in the blood circulation for days. We found the intra‐capillary morphology‐switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further genetic and pharmacological inhibition experiments indicated that the RhoA signaling was necessary for ICMS and the arrest of CTCs. At last, we demonstrated that early treatment by a clinically approved RhoA/ROCK inhibitor, Fasudil, could efficiently inhibit the initial arrest of individual CTCs and reduce the incidence of tumor metastasis in both zebrafish and mouse models. These results together indicate that RhoA‐stimulated ICMS represents a mechanism for the arrest of individual CTCs, providing a potential target for future treatments of hematogenous metastatic disease.
Embracing Teachers as a Vital Literacy Resource
Authors: Conley Mark W.
Published: December 2017

The policy reforms over the past 15 years have placed all the responsibility for reading achievement on teachers, with little, if any, support. What many have achieved is declining achievement in comparison with other countries. Moreover, there are increasing teacher shortages, as promising individuals choose other careers and teachers leave the profession. An oft‐repeated reason why teachers leave concerns accountability pressures and poor working conditions. This article reviews what countries that perform at the top of the reading achievement scale measured by PISA are doing in their educational systems. Many of these countries are taking a systemic approach to educational reform focused on equitable access to great schools and excellent teachers. Ensuring that the best students are entering the teaching profession and then supporting teachers throughout their careers are cornerstones of this strategy. Countries could make great strides with literacy achievement by embracing teachers as a vital literacy resource.
Through the Mind's Eye: Using Multimodal Assignments to Build Engagement and Comprehension
Authors: Verlaan Wolfram
Published: December 2017

Most people have struggled with reading in one situation or another, depending on their appreciation for the content, their prior experiences, and the texts. This department column shares ways for educators to help literacy learners unlock their potential with instruction anchored in their skills, knowledge, ways of learning, interests, and attitudes.
Divergent responsiveness of two isoforms of the estrogen receptor to mixtures of contaminants of emerging concern in four vertebrates
Authors: Kohno Satomi , Katsu Yoshinao , Cipoletti Nicholas , Wang Lina C. , Jorgenson Zachary G. , Miyagawa Shinichi , Schoenfuss Heiko L.
Published: December 2017

Contaminants of emerging concern (CECs) are ubiquitous in aquatic environments with well‐established endocrine‐disrupting effects. A data matrix of 559 water samples was queried to identify two commonly occurring CECs mixtures in Great Lakes tributaries. One mixture consisted of eight agricultural CECs (AG), while another contained 11 urban CECs (UB). The known estrogenic compounds bisphenol A, estrone and nonylphenol were present in both mixtures. According to the EPA Tox21 in ToxCast database, AG and UB mixture at an environmentally relevant concentration were estimated to account for 6.5% and 3.4% estrogenicity of the model endocrine disruptor estradiol‐17β, respectively. Two isoforms of the estrogen receptor (Esr1 and ‐2, former Erα and Erβ) cloned from fathead minnow, bluegill sunfish, American alligator and human, responded differently to AG and UB mixtures. Human and bluegill Esr1 were the most sensitive to AG and UB mixtures, respectively. Fathead minnow Esr1 and Esr2b were the least sensitive to 10× AG and UB in estrogen dose equivalents, respectively. Even at environmentally documented concentrations, UB significantly activated bluegill Esr1. Moreover, 100× concentrated UB hyperstimulated fathead minnow Esr1 beyond the maximum induction of estradiol‐17β. These results indicate that efficacious receptors and species differ in their response to CEC mixtures. Furthermore, estrogenicity may be present in some CECs not previously considered estrogenic, or, alternatively, estrogenicity of a mixture may be enhanced through chemical interactions. Our study highlights the need for further studies of CECs utilizing a variety of receptors cloned from diverse species.
Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol‐17β on medaka embryos
Authors: Yamaguchi Akemi , Ishibashi Hiroshi , Kono Susumu , Iida Midori , Uchida Masaya , Arizono Koji , Tominaga Nobuaki
Published: December 2017

Herein, we propose using a nanosecond pulsed electric field (nsPEF) technique to assess teratogenicity and embryonic developmental toxicity of estradiol‐17β (E2) and predict the molecular mechanisms of teratogenicity and embryonic developmental defects caused by E2 on medaka (Oryzias latipes). The 5 hour post‐fertilization embryos were exposed to co‐treatment with 10 μm E2 and nsPEF for 2 hours and then continuously cultured under non‐E2 and nsPEF conditions until hatching. Results documented that the time to hatching of embryos was significantly delayed in comparison to the control group and that typical abnormal embryo development, such as the delay of blood vessel formation, was observed. For DNA microarray analysis, 6 day post‐fertilization embryos that had been continuously cultured under the non‐E2 and nsPEF condition after 2 hour co‐treatments were used. DNA microarray analysis identified 542 upregulated genes and one downregulated gene in the 6 day post‐fertilization embryos. Furthermore, bioinformatic analyses using differentially expressed genes revealed that E2 exposure affected various gene ontology terms, such as response to hormone stimulus. The network analysis also documented that the estrogen receptor α in the mitogen‐activated protein kinase signaling pathway may be involved in regulating several transcription factors, such as FOX, AKT1 and epidermal growth factor receptor. These results suggest that our nsPEF technique is a powerful tool for assessing teratogenicity and embryonic developmental toxicity of E2 and predict their molecular mechanisms in medaka embryos.
Optimized perfusion‐based CUBIC protocol for the efficient whole‐body clearing and imaging of rat organs
Authors: Matryba Paweł , Bozycki Lukasz , Pawłowska Monika , Kaczmarek Leszek , Stefaniuk Marzena
Published: December 2017

Whole‐organ and whole‐body optical tissue clearing methods allowing imaging in 3 dimensions are an area of profound research interest. Originally developed to study nervous tissue, they have been successfully applied to all murine organs, yet clearing and imaging of rat peripheral organs is less advanced. Here, a modification of CUBIC clearing protocol is presented. It provides a rapid and simple approach to clear the entire adult rat organism and thus all organs within as little as 4 days. Upgraded perfusion‐based rat CUBIC protocol preserves both anatomical structure of organs and signal from proteinaceous fluorophores, and furthermore is compatible with antibody staining. Finally, it enables also volumetric cells analyses and is tailored for staining of calcium deposits within unsectioned soft tissues.
Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study
Authors: Underbjerg Line , Sikjaer Tanja , Rejnmark Lars
Published: December 2017

Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca2+tw) was 1.17 mmol/L (interquartile range [IQR], 1.14 to 1.21 mmol/L) and the calcium-phosphate (CaxPtw) product was 2.80 mmol2/L2 (IQR, 2.51 to 3.03 mmol2/L2). High phosphatetw levels were associated with increased mortality and risk of any infections, including infections in the upper airways. A high CaxPtw product was associated with an increased mortality and risk of renal disease. Compared to levels around the lower part of the reference interval, lower Ca2+tw levels were associated with an increased risk of cardiovascular diseases. Mortality and risk of infections, cardiovascular diseases, and renal diseases increased with number of episodes of hypercalcemia and with increased disease duration. Treatment with a relatively high dose of active vitamin D was associated with a decreased mortality and risk of renal diseases and infections. In conclusion, risk of complications in HypoPT is closely associated with disturbances in calcium-phosphate homeostasis. © 2018 American Society for Bone and Mineral Research.
Isolation and characterization of an anti‐leishmanial disintegrin from Cerastes cerastes venom
Authors: Allane Dihia , Oussedik‐Oumehdi Habiba , Harrat Zoubir , Seve Michel , Laraba‐Djebari Fatima
Published: December 2017

Investigating new antimicrobial and antiparasitic components from Viperidae venoms represents an alternative therapeutic strategy. In this study, we report the characterization of a disintegrin isolated from Cerastes cerastes venom, exhibiting antiparasitic activity on Leishmania infantum promastigotes. Indeed, isolated disintegrin, referred to Disintegrin_Cc, induced 84.75% of parasiticidal activity and deep morphological alterations on the parasites. SDS‐PAGE analysis indicated that this disintegrin was homogenous. This dimeric disintegrin of 14,193.97 Da contains an RGD domain and four intramolecular disulfide bridges. It presents a high percentage of identity with other related snake disintegrins. Predicted 3D structure indicated that this peptide shares partial homology with well‐known active antimicrobial peptides. Disintegrin_Cc inhibited 80% of arachidonic acid‐induced platelet aggregation. The obtained results suggest that the isolated molecule plays a dual role as a disintegrin and as an anti‐leishmanial compound. This component could be useful as a drug in the treatment of leishmaniasis.
AP1 mediates uPA/uPAR induced FUT4 expression and trophoblast invasion
Authors: Zheng Qin , Yang Yu , Cui Xinyuan , Zhang Dandan , Liu Shuai , Yan Qiu
Published: December 2017

Trophoblast invasion is crucial for embryo implantation and successful pregnancy. Urokinase‐type plasminogen activator (uPA)/urokinase‐type plasminogen activator receptor (uPAR) are expressed on trophoblasts and involved in trophoblast invasion. The transcription factor activator protein 1 (AP1) (c‐Fos and cJun) and fucosyltransferase IV (FUT4) have been found to be involved in this process. However, the relationship of uPA/uPAR, AP1 and FUT4 is unclear. The current study aimed to investigate the role of AP1 in uPA/uPAR induced FUT4 expression and trophoblast invasion. We found that p‐c‐Fos and p‐c‐Jun were decreased in abortion patients compared to that in normal pregnant women. Employing human trophoblastic cells, we then demonstrated that uPA/uPAR induced the expression of p‐c‐Fos and p‐c‐Jun. Applying an electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), we further proved that transcription factor AP1 bound to FUT4 promoter that could increase FUT4 transcriptional activity, further promoting trophoblast cell migration and invasion through JNK MAPK signaling pathway. Taken together, these results suggest that uPA/uPAR induces FUT4 expression, and trophoblast cell invasion mediated by AP1 transcription factor (c‐Fos and c‐Jun). Our findings provide novel insights into the relationship between AP1 and abortion.
Theoretical insights into the 1D‐charge transport properties in a series of hexaazatrinaphthylene‐based discotic molecules
Authors: An Beibei , Wen Keke , Feng Songyan , Pan Xiao , Wu Wenpeng , Guo Xugeng , Zhang Jinglai
Published: December 2017

Discotic liquid crystal (DLC) materials have attracted considerable attention mainly due to their high charge carrier mobilities in quasi‐one‐dimensional columns. In this article, five hexaazatrinaphthylene‐based DLC molecules were investigated theoretically, and their frontier molecular orbital energy levels, crystal structures, and electron/hole drift mobilities were calculated by combination of density functional theory (DFT) and semiclassical Marcus charge transfer theory. The systems studied in this work include three experimentally reported molecules (1, 2, and 3) and two theoretically designed molecules (4 and 5). Compared with the 1–3 compounds, 4 and 5 have three more extended benzene rings in the π‐conjugated core. The present results show that the orders of the frontier molecular orbital energy levels and electron drift mobilities agree very well with the experiment. For 4 and 5, the electron/hole reorganization energies are lower than those of compounds 1–3. Furthermore, the calculated electron/hole transfer integral of 5 is the largest among all the five systems, leading to the highest electron and hole mobilities. In addition, the hydrophobicity and solubility were also evaluated by DFT, indicating that compound 5 has good hydrophobicity and good solubility in trichloromethane. As a result, it is expected that compound 5 can be a potential charge transport material in electronic and optoelectronic devices. © 2017 Wiley Periodicals, Inc.
Performance of range‐separated hybrid exchange–correlation functionals for the calculation of magnetic exchange coupling constants of organic diradicals
Authors: Shil Suranjan , Herrmann Carmen
Published: December 2017

The prediction of magnetic behavior is important for the design of new magnetic materials. Kohn–Sham density functional theory is popular for this purpose, although one should be careful about choosing the right exchange–correlation functional. Here, we perform a statistical analysis to test different range‐separated hybrid density functionals for the calculation of magnetic exchange coupling constants J of fourteen organic diradicals. Our analysis suggests that in absolute terms the MN12SX functional performs best among the series of twelve functionals studied here (including the popular B3LYP), followed by N12SX functionals along with Scuseria's HSE series of functionals. LC‐
PBE was found to be the least accurate, which is in contrast with its good performance for calculating J for transition metal complexes. The HSE family of functionals and B3LYP are the only functionals to reproduce the qualitative trends of the coupling constants correctly for the ferromagnetically coupled diradicals under study. © 2017 Wiley Periodicals, Inc.
Group divisible ‐packings with any minimum leave
Authors: Gao Yufeng , Chang Yanxun , Feng Tao
Published: December 2017

A decomposition of , the complete n‐partite equipartite graph with a subgraph L (called the leave) removed, into edge disjoint copies of a graph G is called a maximum group divisible packing of with G if L contains as few edges as possible. We examine all possible minimum leaves for maximum group divisible ‐packings. Necessary and sufficient conditions are established for their existences.
Novel insights into FAS defects underlying autoimmune lymphoproliferative syndrome revealed by studies in consanguineous patients
Authors: Ben-Mustapha Imen , Agrebi Nourhen , Barbouche Mohamed-Ridha
Published: December 2017

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly associated with autoimmune manifestations primarily directed against blood cells. Herein, we review the heterogeneous ALPS molecular bases and discuss recent findings revealed by the study of consanguineous patients. Indeed, this peculiar genetic background favored the identification of a novel form of AR ALPS-FAS associated with normal or residual protein expression, expanding the spectrum of ALPS types. In addition, rare mutational mechanisms underlying the splicing defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein expression. These findings will help decipher critical regions required for the tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS molecular bases in endogamous populations helps to better classify the disease subgroups and to unravel the Fas pathway functioning.
The evolutionary characteristics and structural biology of Gallus toll‐like receptor 21
Authors: Wu Hongping , Wang Hai , Jiang Wuqi , Lian Zhengxing
Published: December 2017

Toll‐like receptors (TLRs) are an important part of the innate immune system, acting as a first line of defense against many invading pathogens. The ligand known to bind Gallus toll‐like receptor 21 (gTLR21) is the unmethylated cytosine phosphate guanine dideoxy nucleotide motif; however, the evolutionary characteristics and structural biology of gTLR21 are poorly elaborated. Our results suggest that gTLR21 is phylogenetically and evolutionarily related to the TLR11 family and is perhaps a close ortholog of the Mus TLR13. Structural biology of homology modeling of the gTLR21 ectodomain structure suggests that it has no Z‐loop like that seen in Mus TLR9. The cytosolic toll‐IL‐1 receptor region of gTLR21 contains a central 4‐stranded parallel β‐sheet (βA‐βD) surrounded by 5 α‐helices (αA‐αE) on both sides, a highly conserved structure also seen in other TLRs. Molecular docking analysis reveals that the gTLR21 ectodomain has the potential to distinguish between different ligands. Homodimer analysis results also suggest that Phe842 and Pro844 of the BB loop and Cys876 of the αC helix in gTLR21 are conserved in other cytosolic toll‐IL‐1 receptor domains of other TLRs and may contribute to the docking of homodimers. Our study on the evolutionary characteristics and structural biology of gTLR21 reveals that the molecule may have a broader role to play in innate immune system; however, further experimental validation is required to confirm our findings.
Microvascular perfusion of the placenta, developing fetal liver, and lungs assessed with intravoxel incoherent motion imaging
Authors: Jakab András , Tuura Ruth L. , Kottke Raimund , Ochsenbein‐Kölble Nicole , Natalucci Giancarlo , Nguyen Thi Dao , Kellenberger Christian , Scheer Ianina
Published: December 2017

Background

In utero intravoxel incoherent motion magnetic resonance imaging (IVIM‐MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus.

Purpose

To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM‐MRI.

Study Type

Retrospective, cross‐sectional study.

Subjects

Fifty‐five datasets from 33 singleton pregnancies were acquired (17–36 gestational weeks).

Field Strength/Sequence

In utero diffusion‐weighted echo‐planar imaging at 1.5T and 3.0T with b‐factors ranging from 0 to 900 s/mm2 in 16 steps.

Assessment

Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free‐form nonlinear deformation algorithm was used to correct for the frame‐by‐frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound‐based assessment of the umbilical artery resistance index.

Statistical Tests

Pearson product‐moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age‐related changes were assessed using linear regression analysis (LR).

Results

Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = –0.457). The f of the liver decreased sharply during gestation (LR, R = –0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = –0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver.

Data Conclusion

Gestational age‐associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature.

Level of Evidence: 2

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2017.
Impact of the equatorial Pacific and South Atlantic SST anomalies on extremes in austral summer precipitation over Grande river basin in Southeast Brazil
Authors: Bernardino Beatriz S. , Vasconcellos Fernanda C. , Nunes Ana M. B.
Published: December 2017

Grande river basin (GRB) is located in Southeast Brazil, and is socio‐economic important for water supply and electricity generation from its hydroelectric plant reservoirs affected by the inter‐annual variability of precipitation. Dry and rainy summers are selected using rainfall data from the National Water Agency (Agência Nacional de Águas–ANA) in Brazil to assess the influence of the equatorial Pacific and South Atlantic sea surface temperature (SST) anomalies, and to depict the intensity and positioning of large‐scale circulation patterns that might affect the precipitation extremes in summer over GRB. The European Centre for Medium‐Range Weather Forecasts global reanalysis provides the meteorological variables to construct the composites of the years of extremes (dry and rainy) in summer precipitation, as well as the preceding springs. The results show that extreme dry summers in GRB are characterized by neutral to negative SST anomalies in the equatorial Pacific and positive anomalies in the subtropical South Atlantic near Brazilian coastline. Rainy extremes are associated with El Niño conditions in Niño 1 + 2, Niño 3 and 3.4 regions during summer and preceding spring. Extreme rainy summers display negative anomalies of SST in the subtropical South Atlantic, coinciding with the northerly South Atlantic Convergence Zone positioning. In GRB, anomalous rainy springs are mostly followed by anomalous dry summers. Large‐scale atmospheric circulation anomalies in the preceding springs to summer precipitation extremes in GRB show characteristic features that might be proven useful in seasonal predictions of hydro‐meteorological extremes.
Milk adulteration with acidified rennet whey: a limitation for caseinomacropeptide detection by high‐performance liquid chromatography
Authors: de Pádua Alves Érika , de Alcântara Anna Laura D'Amico , Guimarães Anselmo José Klaechim , de Santana Elsa Helena Walter , Botaro Bruno Garcia , Fagnani Rafael
Published: December 2017

BACKGROUND

High‐performance liquid chromatography (HPLC) is widely employed to determine the caseinomacropeptide (CMP) index and to detect milk tampering with rennet whey. Prior to HPLC analysis, CMP is subject to a trichloracetic acid isolation, causing further soluble proteins in the sample to precipitate. On this basis, we aimed to determine whether rennet whey acidification could adversely affect the HPLC sensitivity with respect to detecting this peptide.

RESULTS

As hypothesized, the CMP index from milk with added acidified rennet whey was, on average, half that quantified from milk with added rennet whey. Moreover, the quantum satis of acidified whey added to milk sufficient to demonstrate a HPLC CMP > 30 mg L–1 was 94% greater than that required for this threshold to be reached with rennet whey.

CONCLUSION

Milk tampering with acidified rennet whey may limit the analytical sensitivity of the reversed‐phase HPLC employed for the screening of CMP and, ultimately, disguise the fraudulent addition of whey to milk. © 2017 Society of Chemical Industry
Volatile changes in Hawaiian noni fruit, Morinda citrifolia L., during ripening and fermentation
Authors: Wall Marisa M , Miller Samuel , Siderhurst Matthew S
Published: December 2017

BACKGROUND

Noni fruit (Morinda citrifolia L., Rubiaceae) has been used in traditional medicine throughout the tropics and subtropics and is now attracting interest in western medicine. Fermented noni juice is of particular interest for its promising antitumor activity. The present study collected and analyzed volatiles released at nine time intervals by noni fruit during ripening and fermentation using headspace autosampling coupled to gas chromatography–mass spectrometry.

RESULTS

Twenty‐three noni volatiles were identified and relatively quantified. In addition to volatiles previously identified in noni, four novel volatile 3‐methyl‐2/3‐butenyl esters were identified via the synthesis of reference compounds. Principle component analysis (PCA) and canonical discriminant analysis (CDA) were used to facilitate multidimensional pattern recognition. PCA showed that ripening noni fruit cluster into three groups, pre‐ripe, fully ripe (translucent) and fermented, based on released volatiles. CDA could 83.8% correctly classify noni samples when all ripeness stages were analyzed and 100% when samples were classified into the three PCA groupings.

CONCLUSION

The results of the present study confirm the identities of 3‐methyl‐2/3‐butenyl esters, both novel and previously identified, through the synthesis of reference compounds. These esters constitute a large percentage of the volatiles released by fully ripe and fermented noni and likely produced from the decomposition of noniosides, a group of unique glucosides present in the fruit. © 2017 Society of Chemical Industry
Comparative analysis of volatile compound profiles of propolis from different provenances
Authors: Mohtar Lina G , Rodríguez Sergio A , Nazareno Mónica A
Published: December 2017

BACKGROUND

Propolis is a complex mixture that honey bees produce from the exudates of various plants and presents many medicinal properties. Its chemical composition varies according to the phytogeography characteristics of each region, among others. The aim of this study was to identify and characterize the volatile organic compounds (VOCs) present in Venezuelan propolis and compare with reference samples such as Brazilian and Argentinian propolis.

RESULTS

A total of 90 VOCs were identified in a series of propolis samples using both solid‐phase microextraction and dynamic headspace (DHS), both coupled to a gas chromatograph–electron ionization mass spectrometer. In the case of Venezuelan propolis, sesquiterpenes, esters, aromatic compounds, and aliphatic hydrocarbons were identified. Limonene was found only in Venezuelan samples, this being the first time it has been identified in samples from this country. In the case of green propolis, β‐caryophyllene and nerolidol were the major compounds. As for the Argentinian samples, prenyl acetate, benzyl acetate, and 2‐phenylethyl acetate were detected only in these samples.

CONCLUSIONS

Possible chemical markers of natural sources such as limonene were detected using DHS extraction. Several compounds have also been identified for the first time in Venezuelan propolis. Cluster analysis allowed the relating of the propolis VOCs profile to their provenance. © 2017 Society of Chemical Industry
Review of pentosidine and pyrraline in food and chemical models: formation, potential risks and determination
Authors: Li He , Yu Shu‐Juan
Published: December 2017

Pyrraline and pentosidine are advanced Maillard reaction products derived from the reaction of glucose with the lysine amino group on proteins. They have been implicated in uremia, diabetes, and related complications, including inflammation, retinopathy, and nephropathy. This review focuses on the formation mechanism, human potential risks, and detections of pentosidine and pyrraline and lays the foundation for further study of pentosidine and pyrraline. © 2017 Society of Chemical Industry
Determination and dissipation of afidopyropen and its metabolite in wheat and soil using QuEChERS–UHPLC–MS/MS
Authors: Chen Yajie , Guo Mingcheng , Liu Xingang , Xu Jun , Dong Fengshou , Wu Xiaohu , Li Baotong , Zheng Yongquan
Published: December 2017

The dissipations of afidopyropen and its metabolite in wheat plant and soil were determined using a quick, easy, cheap, effective, rugged, and safe method with ultra‐high performance liquid chromatography and tandem mass spectrometry under a field ecosystem. The limits of quantification were estimated for both target compounds as 0.001 mg/kg. The recoveries of afidopyropen and its metabolite ranged from 94 to 114% (soil), 90 to 109% (wheat seed) and 81 to 91% (wheat straw) at levels of 0.001, 0.01, 0.1, and 2.0 mg/kg with relative standard deviations ≤7%. The results of the residual dynamics experiments showed that afidopyropen dissipated rapidly in wheat plant and soil. Its metabolite initially showed a tendency of rapid increase followed by a decrease in wheat plant but could not be detected in soil. The data showed that the first + first‐order model was more suitable for describing the decline of afidopyropen in wheat and soil. The half‐lives of afidopyropen in wheat plant and soil were 1.65 and 1.21 days, respectively.
Characterization and application of a lanthanide‐based metal–organic framework in the development and validation of a matrix solid‐phase dispersion procedure for pesticide extraction on peppers (Capsicum annuum L.) with gas chromatography–mass spectrometry
Authors: Santos Barreto Alysson , de Cássia da Silva Andrade Paula , Meira Farias Jéssica , Menezes Filho Adalberto , Fernandes de Sá Gilberto , Alves Júnior Severino
Published: December 2017

The metal–organic framework [(La0.9Sm0.1)2(DPA)3(H2O)3]∞ was synthetized and characterized by X‐ray diffractometry, differential thermogravimetric analysis, and infrared spectroscopy. The material was tested for the development and validation of a matrix solid‐phase dispersion procedure for extraction of atrazine, bifenthrin, bromuconazole, clofentezine, fenbuconazole, flumetralin, procymidone, and pirimicarb, from peppers, with analysis using gas chromatography with mass spectrometry in the selected ion monitoring mode. The method developed was linear over the range tested (50.0–1000.0 μg/kg for procymidone and 200.0–1000.0 μg/kg for all other pesticides), with correlation coefficients ranging from 0.9930 to 0.9992. Experiments were carried out at 250.0, 500.0, and 1000.0 μg/kg fortification levels, and resulted in recoveries in the range of 52.7–135.0%, with coefficient of variation values between 5.2 and 5.4%, respectively, for [(La0.9Sm0.1)2(DPA)3(H2O)3]∞ sorbent. Detection and quantification limits ranged from 16.0 to 67.0 μg/kg and from 50.0 to 200.0 μg/kg, respectively, for the different pesticides studied. The results were compared with literature data. The developed and validated method was applied to real samples. The analysis detected the presence of residues of pesticides procymidone, fenbuconazole, flumetralin, clofentezine, atrazine, and bifenthrin.
Hypercrosslinked particles for the extraction of sweeteners using dispersive solid‐phase extraction from environmental samples
Authors: Lakade Sameer S. , Zhou Qing , Li Aimin , Borrull Francesc , Fontanals Núria , Marcé Rosa M.
Published: December 2017

This work presents a new extraction material, namely, Q‐100, based on hypercrosslinked magnetic particles, which was tested in dispersive solid‐phase extraction for a group of sweeteners from environmental samples. The hypercrosslinked Q‐100 magnetic particles had the advantage of suitable pore size distribution and high surface area, and showed good retention behavior toward sweeteners. Different dispersive solid‐phase extraction parameters such as amount of magnetic particles or extraction time were optimized. Under optimum conditions, Q‐100 showed suitable apparent recovery, ranging in the case of river water sample from 21 to 88% for all the sweeteners, except for alitame (12%). The validated method based on dispersive solid‐phase extraction using Q‐100 followed by liquid chromatography with tandem mass spectrometry provided good linearity and limits of quantification between 0.01 and 0.1 μg/L. The method was applied to analyze samples from river water and effluent wastewater, and four sweeteners (acesulfame, saccharin, cyclamate, and sucralose) were found in both types of sample.
Ultra‐performance convergence chromatography method for the determination of four chromones and quality control of Saposhnikovia divaricata (Turcz.) Schischk.
Authors: Kim Hyo Seon , Choi Goya , Lee A. Yeong
Published: December 2017

Ultra‐performance convergence chromatography is an environmentally friendly analytical technique that employs dramatically reduced amounts of organic solvents compared to conventional chromatographic methods. In this study, a rapid, sensitive, and environmentally friendly method based on ultra‐performance convergence chromatography was developed for the quantification of four major chromones present in the roots of Saposhnikovia divaricata (Turcz.) Schischk. Using this method, the analysis time was significantly shortened compared to conventional high‐performance liquid chromatography techniques. In addition, the influence of cosolvent type, cosolvent ratio, column temperature, system pressure, and flow rate on the peak resolution was investigated. The proposed method was validated in terms of its limits of detection, limits of quantitation, linearity, precision, and accuracy. More specifically, the limits of detection of the four chromones ranged from 0.006 to 0.033 μg/mL, while the limits of quantitation ranged from 0.019 to 0.101 μg/mL. Our method also exhibited a good regression (r2 > 0.999), excellent precision (RSD < 0.60%), and acceptable recoveries (99.48–102.89%). Finally, the quantities of these four chromones present in 20 commercial samples from Korea and China were successfully evaluated using the developed method, indicating that the proposed method is suitable for the rapid and accurate quality control of Saposhnikovia divaricata.
A study of reciprocating seals with a new mixed‐lubrication model based on inverse lubrication theory
Authors: Li Xueli , Suo Shuangfu , Guo Fei , Wu Changgui , Jia Xiaohong
Published: December 2017

A mixed‐lubrication numerical model for hydraulic seals by the inverse‐hydrodynamic‐lubrication method is presented in this paper for the first time. The hydrodynamic effect on the seal inlet is taken into account as well as the asperity contact pressures. The coupling relationship between the fluid pressure, asperity contact pressure, and static contact pressure is provided by finite‐element analysis. The reverse pumping rate and friction force are calculated from the model under different fluid‐pressure and rod‐velocity conditions. All calculation results agree well with the experimental results, which are measured by the bench test as developed by the authors. By this new model, the average relative error between calculation results and experimental results is 10.5% under all test conditions, compared with 62.6% of the results by full‐film lubrication model.
Normothermic machine perfusion of donor livers without the need for human blood products
Authors: Matton Alix P. M. , Burlage Laura C. , van Rijn Rianne , de Vries Yvonne , Karangwa Shanice A. , Nijsten Maarten W. , Gouw Annette S. H. , Wiersema‐Buist Janneke , Adelmeijer Jelle , Westerkamp Andrie C. , Lisman Ton , Porte Robert J.
Published: December 2017

Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin‐based oxygen carrier (HBOC)‐201. Twenty‐four livers declined for transplantation were transported by using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure‐controlled portal and arterial perfusion. A total of 12 livers were perfused using a solution based on RBCs and FFPs (historical cohort), 6 livers with HBOC‐201 and FFPs, and another 6 livers with HBOC‐201 and gelofusine, a gelatin‐based colloid solution. Compared with RBC + FFP perfused livers, livers perfused with HBOC‐201 had significantly higher hepatic adenosine triphosphate content, cumulative bile production, and portal and arterial flows. Biliary secretion of bicarbonate, bilirubin, bile salts, and phospholipids was similar in all 3 groups. The alanine aminotransferase concentration in perfusate was lower in the HBOC‐201–perfused groups. In conclusion, NMP of human donor livers can be performed effectively using HBOC‐201 and gelofusine, eliminating the need for human blood products. Perfusing livers with HBOC‐201 is at least similar to perfusion with RBCs and FFP. Some of the biomarkers of liver function and injury even suggest a possible superiority of an HBOC‐201–based perfusion solution and opens a perspective for further optimization of machine perfusion techniques. Liver Transplantation 24 528–538 2018 AASLD.
Encapsulating Hydrophilic Solution by PU‐PMF Double‐Component Capsule Based on Water‐In‐Oil‐In‐Oil Emulsion Template
Authors: Zheng Ting , Pilla Srikanth
Published: December 2017

This study demonstrates an effective method to encapsulate a hydrophilic payload through the use of polyurethane‐poly(melamine‐formaldehyde) (PU‐PMF) dual‐component capsules based upon the water‐in‐oil‐in‐oil (W/O/O) emulsion template. This emulsion has a middle oil layer that hosts the PU (outer shell) forming reaction while the internal PMF skeleton, fabricated concurrently by polymer precipitation in the aqueous dispersive phase, provides additional mechanical support. The resultant capsules exhibit dense and spherical shape, low permeability, and diameter of ≈50 µm. Remarkably, interfacial tension is the driving factor in the formation of the W/O/O template. This microencapsulation system and the methods used for its fabrication have a great technical potential for use in industrial applications.
Inhibition of autophagy potentiates the anti‐metastasis effect of phenethyl isothiocyanate through JAK2/STAT3 pathway in lung cancer cells
Authors: Wang Huimin , Wang Limin , Cao Limin , Zhang Qicheng , Song Qianqian , Meng Zhaowei , Wu Xiang , Xu Ke
Published: December 2017

Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti‐tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3‐II, and the expression of Beclin‐1. Inhibition of autophagy by 3‐MA and chloroquine (CQ) or knock down of Beclin‐1 enhanced PEITC‐caused metastasis inhibition. JAK2/STAT3 pathway was suppressed by PEITC, and further inhibited by 3‐MA and CQ or Beclin‐1 knock down, as a result of decreased expression of p‐JAK2 and p‐STAT3. Blocking JAK2/STAT3 pathway by inhibitor AG490 and Stattic suppressed cell migration and decreased the expression of MMP2, MMP9, Twist, and c‐Myc. Further in vivo study showed that PEITC inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3 pathway, and inhibitor CQ enhanced this effect. Taken together, our results demonstrate that PEITC inhibits metastasis potential of lung cancer cells, and induces autophagy. The autophagy induced by PEITC preserves metastasis potential of lung cancer cells, via activation of JAK2/STAT3 pathway. Inhibition of autophagy enhanced the inhibitory effect of PEITC on metastasis potential of lung cancer cells. Our finding suggests that targeting autophagy could be a promising strategy for anti‐metastasis therapies.
The tau positron‐emission tomography tracer AV‐1451 binds with similar affinities to tau fibrils and monoamine oxidases
Authors: Vermeiren Céline , Motte Philippe , Viot Delphine , Mairet‐Coello Georges , Courade Jean‐Philippe , Citron Martin , Mercier Joël , Hannestad Jonas , Gillard Michel
Published: December 2017

Background: Lilly/Avid's AV‐1451 is one of the most advanced tau PET tracers in the clinic. Although results obtained in Alzheimer's disease patients are compelling, discrimination of tracer uptake in healthy individuals and patients with supranuclear palsy (PSP) is less clear as there is substantial overlap of signal in multiple brain regions. Moreover, accurate quantification of [18F]AV‐1451 uptake in Alzheimer's disease may not be possible.

Objectives: The aim of the present study was to characterize the in vitro binding of AV‐1451 to understand and identify potential off‐target binding that could explain the poor discrimination observed in PSP patients.

Methods: [3H]AV‐1451 and AV‐1451 were characterized in in vitro binding assays using recombinant and native proteins/tissues from postmortem samples of controls and Alzheimer's disease and PSP patients.

Results: [3H]AV‐1451 binds to multiple sites with nanomolar affinities in brain homogenates and to tau fibrils isolated from Alzheimer's disease or PSP patients. [3H]AV‐1451 also binds with similarly high affinities in brain homogenates devoid of tau pathology. This unexpected binding was demonstrated to be because of nanomolar affinities of [3H]AV‐1451 for monoamine oxidase A and B enzymes.

Conclusions: High affinity of AV‐1451 for monoamine oxidase proteins may limit its utility as a tau PET tracer in PSP and Alzheimer's disease because of high levels of monoamine oxidase expression in brain regions also affected by tau deposition, especially if monoamine oxidase levels change over time or with a treatment intervention. © 2017 International Parkinson and Movement Disorder Society
Hypoxia‐inducible factor‐1 (HIF‐1) inhibitors from the last decade (2007 to 2016): A “structure–activity relationship” perspective
Authors: Bhattarai Deepak , Xu Xuezhen , Lee Kyeong
Published: December 2017

Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia‐inducible factor (HIF‐1) protein leads to angiogenesis, metastasis, apoptosis resistance, and many other pro‐tumorigenic responses in cancer development. HIF‐1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia‐sensitive, a target‐specific HIF‐1 inhibitor may be a better clinical candidate in cancer drug discovery. Though no HIF‐1 inhibitor is clinically available to date, a lot of effort has been applied during the last decade in search of potent HIF‐1 inhibitors. In this review, we will summarize the structure–activity relationship of ten different chemotypes reported to be HIF‐1 inhibitors in the last decade (2007–2016), their mechanisms of action for HIF‐1 inhibition, progress in the way of target‐specific inhibitors, and problems associated with current inhibitors. It is anticipated that the results of these research on the medicinal chemistry of HIF‐1 inhibitors will provide decent information in the design and development of future inhibitors.
Global exponential convergence in a delayed almost periodic Nicholson's blowflies model with discontinuous harvesting
Authors: Duan Lian , Fang Xianwen , Huang Chuangxia
Published: December 2017

This paper is concerned with a delayed Nicholson's blowflies model with discontinuous harvesting, which is described by an almost periodic nonsmooth dynamical system. Under some reasonable assumptions on the discontinuous harvesting function, by using the Filippov regulation techniques and the theory of dichotomy, together with the Halanay inequality, we establish some new criteria on the existence of positive almost periodic solution and its convergence. An example with numerical simulation is also presented to support the theoretical results.