bluuebunny/crossref_metadata_2025 huggingface dataset:
Gosha-Jinki-Gan Recovers Spermatogenesis in Mice with Busulfan-Induced Aspermatogenesis
Authors: Qu Ning , Kuramasu Miyuki , Hirayanagi Yoshie , Nagahori Kenta , Hayashi Shogo , Ogawa Yuki , Terayama Hayato , Suyama Kaori , Naito Munekazu , Sakabe Kou , Itoh Masahiro
Published: September 2018

Busulfan is an anti-cancer chemotherapeutic drug and is often used as conditioning regimens prior to bone marrow transplant for treatment of chronic myelogenous leukemia. Male infertility, including spermatogenesis disturbance, is known to be one of the side effects of anticancer drugs. While hormone preparations and vitamin preparations are used for spermatogenesis disturbance, their therapeutic effects are low. Some traditional herbal medicines have been administered to improve spermatogenesis. In the present study, we administered Gosha-jinki-gan (TJ107; Tsumura Co., Ltd., Tokyo, Japan) to mice suffering from severe aspermatogenesis after busulfan treatment to determine whether TJ107 can recover spermatogenesis. Male 4-week-old C57BL/6J mice were administered a single intraperitoneal injection of busulfan, and they were then fed a normal diet for 60 days and then a TJ107 diet or TJ107-free normal diet for another 60 days. After busulfan treatment, the weight of the testes and the epididymal sperm count progressively decreased in the normal diet group. On the other hand, in the TJ107 group, these variables dramatically recovered at 120 days. These results suggest that busulfan-induced aspermatogenesis is irreversible if appropriate treatment is not administered. Supplementation of TJ107 can completely recover the injured seminiferous epithelium via normalization of the macrophage migration and reduction of the expressions of Tool-like receptor (TLR) 2 and TLR4, suggesting that TJ107 has a therapeutic effect on busulfan-induced aspermatogenesis.
Effects of Iron Overload and Oxidative Damage on the Musculoskeletal System in the Space Environment: Data from Spaceflights and Ground-Based Simulation Models
Authors: Yang Jiancheng , Zhang Gejing , Dong Dandan , Shang Peng
Published: September 2018

The space environment chiefly includes microgravity and radiation, which seriously threatens the health of astronauts. Bone loss and muscle atrophy are the two most significant changes in mammals after long-term residency in space. In this review, we summarized current understanding of the effects of microgravity and radiation on the musculoskeletal system and discussed the corresponding mechanisms that are related to iron overload and oxidative damage. Furthermore, we enumerated some countermeasures that have a therapeutic potential for bone loss and muscle atrophy through using iron chelators and antioxidants. Future studies for better understanding the mechanism of iron and redox homeostasis imbalance induced by the space environment and developing the countermeasures against iron overload and oxidative damage consequently may facilitate human to travel more safely in space.
PpSARK Regulates Moss Senescence and Salt Tolerance through ABA Related Pathway
Authors: Li Ping , Yang Hong , Liu Gaojing , Ma Wenzhang , Li Chuanhong , Huo Heqiang , He Jianfang , Liu Li
Published: September 2018

Senescence-associated receptor-like kinase (SARK) family members in Arabidopsis, soybean, and rice are known to be positive regulators of leaf senescence. In the meantime, SARKs are extensively involved in stress response. However, their function and underlying molecular mechanism in stress responses in moss are not well known. Here, we investigated functional roles of SARK isolated from Physcomitrella patens (PpSARK) in salt stress response and senescence. PpSARK transcripts significantly accumulated under NaCl and abscisic acid (ABA) treatments, with higher expression in the moss gametophyte stage. Insertional gain-of-function mutants of PpSARK (PpSARKg) were more tolerant to salt stress and ABA than wild type (WT), whereas senescence of mutants was delayed during the protonema stage. Expression of stress-responsive genes in the ABA related pathway, such as PpABI3, PpABI5, PpPP2C, and PpLEA were significantly higher in PpSARKg and WT under salt stress conditions, suggesting that PpSARK might positively regulate salt tolerance via an ABA-related pathway. Endogenous ABA contents also increased 3-fold under salt stress conditions. These results indicate that PpSARK functions as a positive regulator in salt stress responses, while possibly functioning as a negative regulator in senescence in moss.
Evaluation of Toxicity and Neural Uptake In Vitro and In Vivo of Superparamagnetic Iron Oxide Nanoparticles
Authors: Khalid Muhammad Kamran , Asad Muhammad , Henrich-Noack Petra , Sokolov Maxim , Hintz Werner , Grigartzik Lisa , Zhang Enqi , Dityatev Alexander , Van Wachem Berend , Sabel Bernhard A.
Published: September 2018

Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have great potential to be used in different pharmaceutical applications, due to their unique and versatile physical and chemical properties. The aim of this study was to quantify in vitro cytotoxicity of dextran 70,000-coated SPIO-NPs labelled/unlabelled with rhodamine 123, in C6 glioma cells and primary hippocampal neural cells. In addition, we analyzed the in vitro and in vivo cellular uptake of labelled SPIO-NPs. The nanoparticles, with average size of 10–50 nm and polydispersity index of 0.37, were synthesized using Massart’s co-precipitation method. The concentration-dependent cytotoxicity was quantified by using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Intracellular localization of SPIO-NPs was detected by confocal laser microscopy. In vivo confocal neuroimaging (ICON) was performed on male Wistar rats after intravitreal injection followed by ex vivo retina whole mount analysis. When used for in vitro testing concentrations in the range of diagnostic and therapeutic dosages, SPIO-NPs proved to be non-cytotoxic on C6 glioma cells for up to 24 h incubation time. The hippocampal cell culture also did not show impaired viability at low doses after 24 h incubation. Our results indicate that our dextran-coated SPIO-NPs have the potential for in vivo drug delivery applications.
Assembly of ZnO Nanoparticles on SiO2@α-Fe2O3 Nanocomposites for an Efficient Photo-Fenton Reaction
Authors: Uma Kasimayan , Balu Sridharan , Pan Guan-Ting , Yang Thomas C.-K.
Published: September 2018

The SiO2@α-Fe2O3/ZnO metal oxide nanocomposites employed in this study were obtained using the sol-gel method. Their photocatalytic activities were enhanced by photo-Fenton reactions. The metal oxide composite of ZnO and α-Fe2O3 nanoparticles were deposited on the SiO2 nanospheres intended for visible light photocatalysis. Further, the as-synthesized SiO2@α-Fe2O3/ZnO nanocomposites exhibited a robust crystallinity and a high adsorption of dye molecules when compared to SiO2@ZnO and SiO2@α-Fe2O3 nanocomposites, respectively. The experimental results demonstrated a rapid Methylene Blue (MB) degradation among these catalysts within short intervals of time with the addition of α-Fe2O3/ZnO mixed metal oxide catalysts on the SiO2 nanospheres. Finally, a photo-Fenton reaction was implemented to confirm the presence of the hydroxyl (OH) radicals, which are powerful agents used for the degradation of organic pollutants.
A Soft-Switched DC/DC Converter Using Integrated Dual Half-Bridge with High Voltage Gain and Low Voltage Stress for DC Microgrid Applications
Authors: Moradisizkoohi Hadi , Elsayad Nour , Mohammed Osama
Published: September 2018

In this paper, a soft-switched boost converter including an integrated dual half-bridge circuit with high voltage gain and continuous input current is introduced that can be suitable for the applications requiring a wide voltage gain range, such as for the front-end of the inverter in a DC microgrid to integrate renewable energy sources (RES). In the proposed converter, two half-bridge converters are connected in series at the output stage to enhance the voltage gain. Additionally, the balanced voltage multiplier stage is employed at the output to increase the voltage conversion ratio, as well as distribute the voltage stress across semiconductors; hence, switches with smaller on-resistance RDS(on) can be adopted resulting in an improvement in the efficiency. The converter takes advantage of the clamp circuit not only to confine the voltage stress of switches, but also to achieve the soft-switching, which leads to a reduction in the switching loss as well as the cost. The mentioned features make the proposed converter a proper choice for interfacing RES to the DC-link bus of the inverter. The operation modes, steady-state analysis, and design consideration of the proposed topology have been demonstrated in the paper. A 1-kW laboratory prototype was built using gallium nitride (GaN) transistors and silicon carbide (SiC) diodes to confirm the effectiveness of the proposed topology.
Ring Wrinkle Patterns with Continuously Changing Wavelength Produced Using a Controlled-Gradient Light Field
Authors: Li Hongye , Sheng Bin , Wu He , Huang Yuanshen , Zhang Dawei , Zhuang Songlin
Published: September 2018

We report a facile method to prepare gradient wrinkles using a controlled-gradient light field. Because of the gradient distance between the ultraviolet (UV) lamp and polydimethylsiloxane (PDMS) substrate during UV/ozone treatment, the irradiance reaching the substrate continuously changed, which was transferred into the resulting SiOx film with a varying thickness. Therefore, wrinkles with continuously changing wavelength were fabricated using this approach. It was found that the wrinkle wavelength decreased as the distance increased. We fabricated 1-D wrinkle patterns and ring wrinkles with a gradient wavelength. The ring wrinkles were prepared using radial stresses, which were achieved by pulling the center of a freely hanging PDMS film. The resulting wrinkles with changing wavelength can be used in fluid handling systems, biological templates, and optical devices.
Broadband Spectra and Efficient Laser Performance of a Disordered Nd:Sr0.7La0.3Mg0.3Al11.7O19 Crystal
Authors: Zhang Nana , Xu Xiaodong , Pan Yuxin , Liu Jian
Published: September 2018

Here, we demonstrate the broadband spectra and efficient laser performance of a disordered Nd:Sr0.7La0.3Mg0.3Al11.7O19 (Nd:ASL) crystal. The polarized absorption and emission spectra were characterized and calculated with the Judd–Ofelt (J–O) theory, and the results show that this crystal has relatively large σ polarized absorption and emission cross sections, with peak emission cross sections of 4.5 × 10−20 cm2 at 1051 nm and an emission width of 30 nm at 1074 nm, which are favorable for pulsed lasers. The laser-diode-pumped continuous-wave (CW) and passively Q-switched lasers at 1051 nm were realized for the first time to our best knowledge. For CW laser, the maximum output power was 1.95 W with the slope efficiency of 42.6%, and for the passive Q-switching, the maximum output power was 0.73 W with the pulse width of 7.96 ns and peak power of 5.64 W. The results demonstrate that Nd:ASL crystal is a potential candidate for lasers, especially high-peak pulsed lasers such as Q-switching and mode-locking.
A Study of the Effects of Al, Cr, Hf, and Ti Additions on the Microstructure and Oxidation of Nb-24Ti-18Si Silicide Based Alloys
Authors: Nelson Jack , Ghadyani Mohammad , Utton Claire , Tsakiropoulos Panos
Published: September 2018

In Nb-silicide based alloys Al, Cr, Hf, and Ti additions are crucial for achieving balance of properties. It is not known how the simultaneous addition of Hf with Al and Ti, or Hf with Al, Cr, and Ti affects macrosegregation, and how the alloying affects hardness, Young’s modulus and bulk alloy oxidation, and contamination of the solid solution Nbss and the Nb5Si3 compound by oxygen. Two alloys with nominal compositions (at.%) Nb-24Ti-18Si-5Al-5Hf (alloy NbSiTiHf-5Al) and Nb-24Ti-18Si-5Al-5Cr-5Hf (alloy NbSiTiHf-5Al-5Cr) were studied in the as-cast and heat-treated conditions and after isothermal oxidation at 800 and 1200 °C and were compared with similar alloys without Hf. In both alloys there was macrosegregation of Si and Ti, which was more severe in NbSiTiHf-5Al. Both alloys formed Nbss+βNb5Si3 eutectic. The Nbss was stable and its Al and Cr concentrations increased with increasing Ti concentration. In both conditions the βNb5Si3 was observed in the alloys NbSiTiHf-5Al and NbSiTiHf-5Al-5Cr, and the γNb5Si3 only in the alloy NbSiTiHf-5Al. In both heat-treated alloys, separate Hf-rich Nb5Si3 grains were formed. The Si and Al concentrations in Nb5Si3 respectively decreased and increased with increasing Ti concentration. Al and Cr had a stronger hardening effect in the Nbss than Al, Cr, and Hf. Al, Cr, and Ti had a stronger negative effect on the Young’s modulus of the Nbss compared with Al, Cr, Hf, and Ti. When Nb was substituted by Ti, Cr, and Hf, and Si by Al in the βNb5Si3, the Young’s modulus was reduced compared with the unalloyed silicide. At 800 °C both alloys did not exhibit catastrophic pest-oxidation after 100 h. The Nbss and Nb5Si3 were contaminated by oxygen in both alloys, the former more severely. At 1200 °C the scales spalled-off, more severely in the alloy NbSiTiHf-5Al, where substrate that was heavily contaminated by oxygen below the scale also spalled-off. In both alloys the contamination of Nb5Si3 and Nbss by oxygen was more severe compared with 800 °C, but the silicides were not contaminated by oxygen in their bulk. The Nbss was not contaminated by oxygen only in the bulk of the alloy NbSiTiHf-5Al-5Cr.
A Novel Strategy for Creating Tissue-Engineered Biomimetic Blood Vessels Using 3D Bioprinting Technology
Authors: Xu Yuanyuan , Hu Yingying , Liu Changyong , Yao Hongyi , Liu Boxun , Mi Shengli
Published: September 2018

In this work, a novel strategy was developed to fabricate prevascularized cell-layer blood vessels in thick tissues and small-diameter blood vessel substitutes using three-dimensional (3D) bioprinting technology. These thick vascularized tissues were comprised of cells, a decellularized extracellular matrix (dECM), and a vasculature of multilevel sizes and multibranch architectures. Pluronic F127 (PF 127) was used as a sacrificial material for the formation of the vasculature through a multi-nozzle 3D bioprinting system. After printing, Pluronic F127 was removed to obtain multilevel hollow channels for the attachment of human umbilical vein endothelial cells (HUVECs). To reconstruct functional small-diameter blood vessel substitutes, a supporting scaffold (SE1700) with a double-layer circular structure was first bioprinted. Human aortic vascular smooth muscle cells (HA-VSMCs), HUVECs, and human dermal fibroblasts–neonatal (HDF-n) were separately used to form the media, intima, and adventitia through perfusion into the corresponding location of the supporting scaffold. In particular, the dECM was used as the matrix of the small-diameter blood vessel substitutes. After culture in vitro for 48 h, fluorescent images revealed that cells maintained their viability and that the samples maintained structural integrity. In addition, we analyzed the mechanical properties of the printed scaffold and found that its elastic modulus approximated that of the natural aorta. These findings demonstrate the feasibility of fabricating different kinds of vessels to imitate the structure and function of the human vascular system using 3D bioprinting technology.
SrCe0.9Sm0.1O3-α Compounded with NaCl-KCl as a Composite Electrolyte for Intermediate Temperature Fuel Cell
Authors: Shi Ruijuan , Chen Wei , Hu Wenli , Liu Junlong , Wang Hongtao
Published: September 2018

SrCeO3 and SrCe0.9Sm0.1O3-α were synthesized using a high-temperature solid-state reaction method using Sm2O3, SrCO3, CeO2 as precursors, then the SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte was fabricated by compounding SrCe0.9Sm0.1O3-α with NaCl-KCl and sintering it at a lower temperature (750 °C) than that of a single SrCeO3 material (1540 °C). The phase and microstructure of the samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The conductivities of the samples were measured in dry nitrogen atmosphere using electrochemical analyzer. The conductivities of the SrCeO3, SrCe0.9Sm0.1O3-α and SrCe0.9Sm0.1O3-α-NaCl-KCl at 700 °C were 2.09 × 10−5 S·cm−1, 1.82 × 10−3 S·cm−1 and 1.43 × 10−1 S·cm−1 respectively. The conductivities of SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte are four orders of magnitude higher than those of SrCeO3 and two orders of magnitude higher than those of SrCe0.9Sm0.1O3-α. The result of logσ ~ logpO2 plot indicates that SrCe0.9Sm0.1O3-α-NaCl-KCl is almost a pure ionic conductor. The electrolyte resistance and the polarization resistance of the H2/O2 fuel cell based on SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte under open-circuit condition were 1.0 Ω·cm2 and 0.2 Ω·cm2 respectively. Further, the obtained maximum power density at 700 °C was 182 mW·cm−2.
Use of the Wilshire Equations to Correlate and Extrapolate Creep Data of HR6W and Sanicro 25
Authors: Cedro Vito , Garcia Christian , Render Mark
Published: September 2018

Advanced power plant alloys must endure high temperatures and pressures for durations at which creep data are often not available, necessitating the extrapolation of creep life. Many methods have been proposed to extrapolate creep life, and one of recent significance is a set of equations known as the Wilshire equations. With this method, multiple approaches can be used to determine creep activation energy, increase the goodness of fit of available experimental data, and improve the confidence level of calculating long-term creep strength at times well beyond the available experimental data. In this article, the Wilshire equation is used to extrapolate the creep life of HR6W and Sanicro 25, and different methods to determine creep activation energy, region splitting, the use of short-duration test data, and the omission of very-short-term data are investigated to determine their effect on correlation and calculations. It was found that using a known value of the activation energy of lattice self-diffusion, rather than calculating Q C * from each data set, is both the simplest and most viable method to determine Q C * . Region-splitting improved rupture time calculations for both alloys. Extrapolating creep life from short-term data for these alloys was found to be reasonable.
TiO2-KH550 Nanoparticle-Reinforced PVA/xylan Composite Films with Multifunctional Properties
Authors: Liu Xinxin , Chen Xiaofeng , Ren Junli , Zhang Chunhui
Published: September 2018

In order to improve the strength of polyvinyl alcohol (PVA)/xylan composite films and endow them with ultraviolet (UV) shielding ability, TiO2-KH550 nanoparticles was synthesized and added into the PVA/xylan matrix. The TiO2-KH550 nanoparticle dispersed well in the 0.04% sodium hexametaphosphate (SHMP) solution under ultrasonic and stirring treatments. Investigations on the properties of the films showed that TiO2-KH550 had the positive impact on improving the strength, moisture, and oxygen barrier properties of the composite films. The maximum tensile strength (27.3 MPa), the minimum water vapor permeability (2.75 × 10−11 g·m−1·s−1·Pa−1), and oxygen permeability (4.013 cm3·m−2·24 h−1·0.1MPa−1) were obtained under the addition of 1.5% TiO2-KH550. The tensile strength of TiO2-KH550 reinforced composite film was increased by 70% than that of the pure PVA/xylan composite film, and the water vapor and oxygen permeability were decreased by 31% and 41%, respectively. Moreover, the UV transmittance of the film at the wavelength of 400 nm was almost zero when adding ≈1.5~2.5% (weight ratio, based on the total weight of PVA and xylan) of TiO2-KH550, which indicated the PVA/xylan composite films were endowed with an excellent UV light shielding ability.
Force Prediction for Incremental Forming of Polymer Sheets
Authors: Medina-Sanchez Gustavo , Garcia-Collado Alberto , Carou Diego , Dorado-Vicente Rubén
Published: September 2018

Incremental sheet forming (ISF) is gaining attention as a low cost prototyping and small batch production solution to obtain 3D components. In ISF, the forming force is key to define an adequate setup, avoiding damage and reducing wear, as well as to determine the energy consumption and the final shape of the part. Although there are several analytical, experimental and numerical approaches to estimate the axial forming force for metal sheets, further efforts must be done to extend the study to polymers. This work presents two procedures for predicting axial force in Single Point Incremental Forming (SPIF) of polymer sheets. Particularly, a numerical model based on the Finite Element Model (FEM), which considers a hyperelastic-plastic constitutive equation, and a simple semi-analytical model that extends the known specific energy concept used in machining. A set of experimental tests was used to validate the numerical model, and to determine the specific energy for two polymer sheets of polycarbonate (PC) and polyvinyl chloride (PVC). The approaches provide results in good agreement with additional real examples. Moreover, the numerical model is useful for accurately predicting temperature and thickness.
Implementing and Visualizing ISO 22400 Key Performance Indicators for Monitoring Discrete Manufacturing Systems
Authors: Ramis Ferrer Borja , Muhammad Usman , Mohammed Wael M. , Martínez Lastra José L.
Published: September 2018

The employment of tools and techniques for monitoring and supervising the performance of industrial systems has become essential for enterprises that seek to be more competitive in today’s market. The main reason is the need for validating tasks that are executed by systems, such as industrial machines, which are involved in production processes. The early detection of malfunctions and/or improvable system values permits the anticipation to critical issues that may delay or even disallow productivity. Advances on Information and Communication Technologies (ICT)-based technologies allows the collection of data on system runtime. In fact, the data is not only collected but formatted and integrated in computer nodes. Then, the formatted data can be further processed and analyzed. This article focuses on the utilization of standard Key Performance Indicators (KPIs), which are a set of parameters that permit the evaluation of the performance of systems. More precisely, the presented research work demonstrates the implementation and visualization of a set of KPIs defined in the ISO 22400 standard-Automation systems and integration, for manufacturing operations management. The approach is validated within a discrete manufacturing web-based interface that is currently used for monitoring and controlling an assembly line at runtime. The selected ISO 22400 KPIs are described within an ontology, which the description is done according to the data models included in the KPI Markup Language (KPIML), which is an XML implementation developed by the Manufacturing Enterprise Solutions Association (MESA) international organization.
α-Glucosidase Inhibitors: Diphenyl Ethers and Phenolic Bisabolane Sesquiterpenoids from the Mangrove Endophytic Fungus Aspergillus flavus QQSG-3
Authors: Wu Yingnan , Chen Yan , Huang Xishan , Pan Yahong , Liu Zhaoming , Yan Tao , Cao Wenhao , She Zhigang
Published: September 2018

Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane sesquiterpenoids (3–6), together with five known related derivatives, were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 obtained from a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, China. The structures of compounds 1–6 were determined by analyzing NMR and HRESIMS data. The absolute configurations of 5 and 6 were assigned by comparing their experimental ECD spectra with those reported for similar compounds in the literature. All isolates were evaluated for their α-glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11 showed strong inhibitory effects with IC50 values in the range of 1.5–4.5 μM.
Transcriptomic Profiling and Gene Disruption Revealed that Two Genes Related to PUFAs/DHA Biosynthesis May be Essential for Cell Growth of Aurantiochytrium sp.
Authors: Liang Yuanmei , Liu Ying , Tang Jie , Ma Jiong , Cheng Jay , Daroch Maurycy
Published: September 2018

Aurantiochytrium sp. PKU#SW7 is a thraustochytrid strain that was found to exhibit high potential for docosahexaenoic acid (DHA, C22:6n-3) production. In this work, the transcriptome of Aurantiochytrium sp. PKU#SW7 was analyzed for the study of genes involved in basic metabolic functions and especially in the mechanisms of DHA biosynthesis. Sequence annotation and functional analysis revealed that the strain contains components of fatty acid synthesis (FAS) and polyketide synthase (PKS) pathways. Fatty acid desaturases and elongases were identified as components of FAS pathway, whilst key components of PKS pathway were also found in the cDNA library. The relative contribution of the two pathways to the synthesis of DHA was unknown, as both pathways appeared to be lacking full complement of genes for standalone synthesis of DHA. Further analysis of two putative genes encoding the very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase and dehydrase/isomerase involved in FAS and PKS pathways, respectively, revealed that under various salinity conditions, their relative expression levels changed corresponding to the variation of DHA content in Aurantiochytrium sp. Independent knock outs of these genes in Aurantiochytrium sp. resulted in poor cell growth, probably due to little or no intracellular DHA accumulation. Hence, it can be speculated that both genes are engaged in DHA biosynthesis and DHA in Aurantiochytrium sp. could be produced by jointed actions of both FAS and PKS systems.
Naamines and Naamidines as Novel Agents against a Plant Virus and Phytopathogenic Fungi
Authors: Guo Pengbin , Li Gang , Liu Yuxiu , Lu Aidang , Wang Ziwen , Wang Qingmin
Published: September 2018

Naamines, naamidines and various derivatives of these marine natural products were synthesized and characterized by means of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The activities of these alkaloids against a plant virus and phytopathogenic fungi were evaluated for the first time. A benzyloxy naamine derivative 15d displayed excellent in vivo activity against tobacco mosaic virus at 500 μg/mL (inactivation activity, 46%; curative activity, 49%; and protective activity, 41%); its activities were higher than the corresponding activities of the commercial plant virucide ribavirin (32%, 35%, and 34%, respectively), making it a promising new lead compound for antiviral research. In vitro assays revealed that the test compounds exhibited very good antifungal activity against 14 kinds of phytopathogenic fungi. Again, the benzyloxy naamine derivative 15d exhibited broad-spectrum fungicidal activity, emerging as a new lead compound for fungicidal research. Additional in vivo assays indicated that many of the compounds displayed inhibitory effects >30%.
High-Frequency Occurrence of Surfactin Monomethyl Isoforms in the Ferment Broth of a Bacillus subtilis Strain Revealed by Ion Trap Mass Spectrometry
Authors: Kecskeméti Anita , Bartal Attila , Bóka Bettina , Kredics László , Manczinger László , Shine Kadaikunnan , Alharby Naiyf S. , Khaled Jamal M. , Varga Mónika , Vágvölgyi Csaba , Szekeres András
Published: September 2018

Surfactins are cyclic lipopeptides consisting of a β-hydroxy fatty acid of various chain length and a peptide ring of seven amino acids linked together by a lactone bridge, forming the cyclic structure of the peptide chain. These compounds are produced mainly by Bacillus species and possess numerous biological effects such as antimicrobial (antiviral, antibacterial, and antifungal) activities. A mixture of surfactins extracted from Bacillus subtilis strain SZMC 6179J was examined by HPLC-ESI-IT-MS technique, enhancing their separation to reveal novel lipopeptide varieties with higher masses and to characterize their structures. During the MS2 spectra analyses of their sodiated molecular ions [M + Na]+, a previously rarely encountered group of surfactins was detected and two novel types of the group were discovered containing methyl esterified aspartic acid residue in their fifth amino acid position. The relative amounts of these monomethyl isoforms exceeded 35% of the produced surfactin in total. In the m/z value of 1114, all the detected isoforms possessed aspartic acid 4-methyl ester residue in their fifth amino acid position (C17-[Lxx4, AME5], C18-[AME5]), offering an opportunity to separate a pure fraction of the compound and to study its biological activities in the future.
Who Needs Neighbors? PKS8 Is a Stand-Alone Gene in Fusarium graminearum Responsible for Production of Gibepyrones and Prolipyrone B
Authors: Westphal Klaus Ringsborg , Muurmann Asmus Toftkær , Paulsen Iben Engell , Nørgaard Kim Tanja Hejselbak , Overgaard Marie Lund , Dall Sebastian Mølvang , Aalborg Trine , Wimmer Reinhard , Sørensen Jens Laurids , Sondergaard Teis Esben
Published: September 2018

Genome sequencing of the genus Fusarium has revealed a great capacity for discovery of new natural products of potential economical and therapeutic importance. Several of these are unknown. In this study, we investigated the product of the PKS8 gene in Fusarium graminearum, which was recently linked to gibepyrones in F. fujikuroi. Genomic analyses showed that PKS8 constitutes a stand-alone gene in F. graminearum and related species. Overexpression of PKS8 resulted in production of gibepyrones A, B, D, G and prolipyrone B, which could not be detected in the wild type strain. Our results suggest that PKS8 produces the entry compound gibepyrone A, which is subsequently oxidized by one or several non-clustering cytochrome P450 monooxygenases ending with prolipyrone B.
Pomolic Acid Ameliorates Fibroblast Activation and Renal Interstitial Fibrosis through Inhibition of SMAD-STAT Signaling Pathways
Authors: Park Ji-Hyun , Jang Kyung Mi , An Hyun Jin , Kim Jung-Yeon , Gwon Mi-Gyeong , Gu Hyemin , Park Byoungduck , Park Kwan-Kyu
Published: September 2018

Fibrosis is a common pathological feature in most kinds of chronic kidney disease. Transforming growth factor β1 (TGF-β1) signaling is the master pathway regulating kidney fibrosis pathogenesis, in which mothers against decapentaplegic homolog 3 (SMAD3) with signal transducer and activator of transcription 3 (STAT3) act as the integrator of various pro-fibrosis signals. We examine the effects of pomolic acid (PA) on mice with unilateral ureteral obstruction (UUO) and TGF-β1 stimulated kidney fibroblast cells. UUO mice were observed severe tubular atrophy, and tubulointerstitial fibrosis and extracellular matrix (ECM) deposition at seven days postoperatively. However, PA-treated UUO mice demonstrated only moderate injury, minimal fibrosis, and larger reductions in the expression of ECM protein and epithelial-mesenchymal transition (EMT) progress. PA inhibited the SMAD-STAT phosphorylation in UUO mice. PA effects were also confirmed in TGF-β1 stimulated kidney fibroblast cells. In this study, we first demonstrated that PA ameliorates fibroblast activation and renal interstitial fibrosis. Our results indicate that PA may be useful as a potential candidate in the prevention of chronic kidney disease.
Antinociceptive Effects of Cardamonin in Mice: Possible Involvement of TRPV1, Glutamate, and Opioid Receptors
Authors: Ping Chung Pui , Tengku Mohamad Tengku Azam Shah , Akhtar Muhammad Nadeem , Perimal Enoch Kumar , Akira Ahmad , Israf Ali Daud Ahmad , Sulaiman Mohd Roslan
Published: September 2018

Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV1, glutamate, and opioid receptors.
Design and Synthesis of Novel Dehydroepiandrosterone Analogues as Potent Antiproliferative Agents
Authors: Huang Xing , Shen Qing-Kun , Zhang Hong-Jian , Li Jia-Li , Tian Yu-Shun , Quan Zhe-Shan
Published: September 2018

The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hela, HepG-2, BEL7402, MCF-7, and HCT116. Several of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound was (E)-3-hydroxy-16-((1-(4-iodophenyl)-1H-1,2,3-triazole-4-yl)methylene)-10,13-dimet-hyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14)-one (compound 2n), which showed considerably high antiproliferative activity in the HepG-2 cell line, with an IC50 value of 9.10 µM, and considerably high activity against the MCF-7 cell line, with an IC50 value of 9.18 µM. Flow cytometry assays demonstrated that compound 2n exerted antiproliferative effects by arresting cells in the G2 phase of the cell cycle and inducing apoptosis.
Obesity in Inflammatory Bowel Disease: Gains in Adiposity despite High Prevalence of Myopenia and Osteopenia
Authors: Bryant Robert Venning , Schultz Christopher G. , Ooi Soong , Goess Charlotte , Costello Samuel Paul , Vincent Andrew D. , Schoeman Scott N. , Lim Amanda , Bartholomeusz Francis Dylan , Travis Simon P.L. , Andrews Jane Mary
Published: September 2018

Background: Rising rates of obesity have been reported in patients with inflammatory bowel disease (IBD); however, prospective data is lacking. The aim of this study is to prospectively evaluate body composition in adults with IBD over 24 months. Methods: Whole body dual energy X-ray absorptiometry (DXA) data was performed at 0 months, 12 months, and 24 months. Bone mineral density (BMD), fat mass index (FMI (kg)/height (m2)), appendicular skeletal muscle index (ASMI (kg)/height (m2)), visceral adipose tissue and the visceral adipose height index (VHI, VAT area (cm3)/height (m2)), and clinical and anthropometric assessments were performed at each time point. Multivariable linear mixed effects regression analyses were performed. Results: Initially, 154 participants were assessed at baseline (70% Crohn’s disease, 55% male, median age 31 years), of whom 129 underwent repeated DXA at 12 months, and 110 underwent repeated DXA at 24 months. Amongst those undergoing repeated DXA, their body mass index (BMI) significantly increased over time, such that by 24 months, 62% of patients were overweight or obese (annual change BMI β = 0.43, 95%CI = [0.18, 0.67], p = 0.0006). Gains in BMI related to increases in both FMI and VHI (β = 0.33, 95%CI = [0.14, 0.53], p = 0.0007; β = 0.08, 95%CI = [0.02, 0.13], p = 0.001; respectively), whereas ASMI decreased (β = −0.07, 95%CI = [−0.12, −0.01], p = 0.01) with a concordant rise in rates of myopenia (OR = 3.1 95%CI = [1.2, 7.7]; p = 0.01). Rates of osteopenia and osteoporosis were high (37%), but remained unchanged over time (p = 0.23). Conclusion: Increasing rates of obesity in patients with IBD coincide with decreases in lean muscle mass over time, while high rates of osteopenia remain stable. These previously undocumented issues warrant attention in routine care to prevent avoidable morbidity.
Metabolaid® Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation
Authors: Lee Young-Sil , Yang Won-Kyung , Kim Hwa Yeon , Min Bokkee , Caturla Nuria , Jones Jonathan , Park Yang-Chun , Lee Young-Cheol , Kim Seung-Hyung
Published: September 2018

Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional medicine formulations to treat asthma and diabetes in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese medicine in the form of a tea to treat hypertension and inflammation. In the present study, we examined the synergistic effects of a formula of Metabolaid® (MetA), a combination of lemon verbena and hibiscus-flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced obese mice. The results showed that MetA decreased body weight, white adipose tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles, glucose levels, glucose tolerance, and cold-induced thermogenesis were significantly improved. Appetite-regulating hormones adiponectin and leptin were significantly increased and decreased, respectively, while the inflammatory-related factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated by MetA. Adipogenesis-activating gene expression was decreased, while increased thermogenesis-inducing genes were upregulated in the WAT, correlating with increased phosphorylation of AMPK and fatty-acid oxidation in the liver. Taken together, these results suggest that MetA decreased obesity and its complications in HFD mice. Therefore, this formula may be a candidate for the prevention and treatment of obesity and its complications.
Cross-Cultural Adaptation, Validity, and Reproducibility of the Mediterranean Islands Study Food Frequency Questionnaire in the Elderly Population Living in the Spanish Mediterranean
Authors: Zaragoza-Martí Ana , Ferrer-Cascales Rosario , Hurtado-Sánchez José Antonio , Laguna-Pérez Ana , Cabañero-Martínez María José
Published: September 2018

The objective of this study was to perform cross-cultural adaptation of the Mediterranean Islands Study Food Frequency Questionnaire (MEDIS-FFQ) and to evaluate its reproducibility and validity in a population over 60 years of age in the Spanish Mediterranean. Three hundred forty-one people completed the food frequency questionnaire (FFQ), which was administered twice (FFQ1 and FFQ2) with nine 24-h dietary recalls (24-HDRs) over a nine-month period to assess its reproducibility and validity. Cross-cultural translation and adaptation were performed according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines and included direct translation, back-translation, and a pilot comprehension test. Reproducibility was evaluated with Pearson’s and interclass correlation coefficients. Validity was estimated using correlations between the FFQ food groups and the 24-HDR mean. The levels of agreement and misclassification were expressed as the proportions of individuals classified by comparing the estimated information from the FFQ2 and the 24-HDR. Reproducibility correlation coefficients ranged from r = 0.44 to r = 0.90. Validity indices ranged from 0.71 to 0.99. More than 80% of the subjects were classified in the same quartile on both instruments. The kappa statistic showed a moderate to high level of agreement (0.70–0.95) between the two instruments. In conclusion, the MEDIS-FFQ showed good reproducibility and validity in estimating the nutrient intake of the elderly population in the Spanish Mediterranean.
Glucose and Fat Tolerance Tests Induce Differential Responses in Plasma Choline Metabolites in Healthy Subjects
Authors: Obeid Rima , Awwad Hussain , Knell Astrid , Hübner Ulrich , Geisel Jürgen
Published: September 2018

Plasma choline shows associations with plasma glucose and lipids. We studied changes of choline metabolites after oral glucose tolerance test (OGTT) and fat tolerance test (OFTT). Eighteen healthy subjects (mean age 54.3 years; BMI 26.8 kg/m2) underwent 2 tests. First, OFTT (80 g fat) was applied and blood was collected at baseline and 4 h after OFTT. Seven days later, 75 g glucose was applied and blood was collected at baseline and 2 h after OGTT. Plasma concentrations of choline, betaine, trimethylamine N-oxide (TMAO), dimethylglycine, S-adenosylmethionine (SAM), lipids and glucose were measured. After OFTT, plasma choline declined (10.6 to 9.2 µmol/L; p = 0.004), betaine declined (33.4 to 31.7 µmol/L; p = 0.003), TMAO slightly increased (4.1 to 5.6 µmol/L; p = 0.105), glucose declined (5.39 to 4.98 mmol/L; p < 0.001), and triglycerides increased (1.27 to 2.53 mmol/L; p < 0.001). After OGTT, plasma choline increased (10.1 to 11.1 µmol/L; p < 0.001), TMAO declined (4.0 to 3.5 µmol/L; p = 0.029), dimethylglycine declined (2.0 to 1.7 µmol/L; p = 0.005), SAM declined (103 to 96 nmol/L; p = 0.041), but betaine, glucose, and SAM were unchanged. In conclusion, OFTT lowered plasma betaine and choline and caused heterogeneous changes in plasma TMAO. OGTT reduced the flow of methyl groups and plasma TMAO.
Soybean Bioactive Peptides and Their Functional Properties
Authors: Chatterjee Cynthia , Gleddie Stephen , Xiao Chao-Wu
Published: September 2018

Soy consumption has been associated with many potential health benefits in reducing chronic diseases such as obesity, cardiovascular disease, insulin-resistance/type II diabetes, certain type of cancers, and immune disorders. These physiological functions have been attributed to soy proteins either as intact soy protein or more commonly as functional or bioactive peptides derived from soybean processing. These findings have led to the approval of a health claim in the USA regarding the ability of soy proteins in reducing the risk for coronary heart disease and the acceptance of a health claim in Canada that soy protein can help lower cholesterol levels. Using different approaches, many soy bioactive peptides that have a variety of physiological functions such as hypolipidemic, anti-hypertensive, and anti-cancer properties, and anti-inflammatory, antioxidant, and immunomodulatory effects have been identified. Some soy peptides like lunasin and soymorphins possess more than one of these properties and play a role in the prevention of multiple chronic diseases. Overall, progress has been made in understanding the functional and bioactive components of soy. However, more studies are required to further identify their target organs, and elucidate their biological mechanisms of action in order to be potentially used as functional foods or even therapeutics for the prevention or treatment of chronic diseases.
Contaminants in Grain—A Major Risk for Whole Grain Safety?
Authors: Thielecke Frank , Nugent Anne P
Published: September 2018

Grains are the main energy and carbohydrate sources for human nutrition globally. Governmental and non-governmental authorities recommend whole grains as a healthy food choice. The role of contaminants in (whole) grains and how to mitigate any potential risk following their consumption has not been reported. With this narrative review, we shed light on the potential human health risk from contaminants in whole grains and elaborate strategies to mitigate such risk. We found that grains represent a significant source of food-borne contaminants, the main ones being; mycotoxins including (A) aflatoxin B1; (B) ochratoxin A; (C) fumonisin B1; (D) deoxynivalenol; (E) zearalenone; toxic metals like arsenic, cadmium and lead; as well as process contaminants such as acrylamide. Whole grains usually contain more contaminants than refined products. However, whole grains also provide more nutrients that may reduce the impact of these contaminants. Strict regulatory thresholds aim to minimize the risk of contaminants to public health. The consumer can further impact on the mitigation of any risk by eating a healthy diet filled with nutrient-dense foods such as whole grains and probiotics. The risk posed by contaminants from whole grains do not outweigh the known nutritional benefits of whole grain consumption.
Do Aspects of Protein Intake Vary Across the Week in Healthy Community-Dwelling Older Adults?—An enable Study
Authors: Gingrich Anne , Rennekamp Rachel , Brandl Beate , Skurk Thomas , Hauner Hans , Sieber Cornel C. , Volkert Dorothee , Kiesswetter Eva
Published: September 2018

Various aspects of protein intake are thought to be crucial for the prevention of sarcopenia in older adults. Information about the day-to-day variation in these aspects is lacking. Our objective was to examine whether daily protein intake, protein distribution across meals, number of meals providing adequate protein, and protein sources vary across the week in healthy community-dwelling older adults. In 140 persons (51% women) that were aged 75–85 years, protein intake was assessed by seven-day food records. On average across the week, protein intake (median [IQR]) was 0.93 [0.79–1.10] g/kg body weight (BW) and the coefficient of variation across the three main meals was 0.50 [0.40–0.61]. The number of meals per day providing ≥0.4 g protein/kg BW was 0.57 [0.43–1.00] and 60.0 [52.4–65.2]% of protein intake was animal-based. According to Friedman’s test, differences throughout the week were observed in women for daily protein intake (p = 0.038; Sunday: 0.99 [0.78–1.31] vs. Tuesday: 0.79 [0.68–1.12] g/kg BW) and number of meals with adequate protein (p = 0.019; ≥1 daily meal: Sunday: 69.4% vs. Tuesday: 41.7%). On Sunday, protein intake was most in agreement with suggestions to prevent sarcopenia. In men, protein intake did not differ throughout the week.
Challenges in Nanofluidics—Beyond Navier–Stokes at the Molecular Scale
Authors: Daivis Peter J. , Todd Billy D.
Published: September 2018

The fluid dynamics of macroscopic and microscopic systems is well developed and has been extensively validated. Its extraordinary success makes it tempting to apply Navier–Stokes fluid dynamics without modification to systems of ever decreasing dimensions as studies of nanofluidics become more prevalent. However, this can result in serious error. In this paper, we discuss several ways in which nanoconfined fluid flow differs from macroscopic flow. We give particular attention to several topics that have recently received attention in the literature: slip, spin angular momentum coupling, nonlocal stress response and density inhomogeneity. In principle, all of these effects can now be accurately modelled using validated theories. Although the basic principles are now fairly well understood, much work remains to be done in their application.