bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Diethyl Phthalate Leached from Plastic Products in Municipal Solid Waste Using an Ozone-Based Advanced Oxidation Process
Authors: Mohan Sankaralingam , Mamane Hadas , Avisar Dror , Gozlan Igal , Kaplan Aviv , Dayalan Gokul
Published: December 2019

Plastic products in municipal solid waste result in the extraction of phthalates in leachate that also contains large amounts of organic matter, such as humic substances, ammonia, metals, chlorinated organics, phenolic compounds, and pesticide residues. Phthalate esters are endocrine disruptors, categorized as a priority pollutant by the US Environmental Protection Agency (USEPA). Biological processes are inefficient at degrading phthalates due to their stability and toxic characteristics. In this study, the peroxone (ozone/hydrogen peroxide) process (O3/H2O2), an O3-based advanced oxidation process (AOP), was demonstrated for the removal of diethyl phthalate (DEP) in synthetic leachate simulating solid-waste leachate from an open dump. The impact of the O3 dose during DEP degradation; the formation of ozonation intermediate by-products; and the effects of H2O2 dose, pH, and ultraviolet absorbance at 254 nm (UVC) were determined during ozonation. Removal of 99.9% of an initial 20 mg/L DEP was obtained via 120 min of ozonation (transferred O3 dose = 4971 mg/L) with 40 mg/L H2O2 in a semi-batch O3 system. Degradation mechanisms of DEP along with its intermediate products were also determined for the AOP treatment. Indirect OH radical exposure was determined by using a radical probe compound (pCBA) in the O3 treatment.
The Effect of Stabilisation Agents on the Immunomodulatory Properties of Gold Nanoparticles Obtained by Ultrasonic Spray Pyrolysis
Authors: Bekić Marina , Tomić Sergej , Rudolf Rebeka , Milanović Marijana , Vučević Dragana , Anžel Ivan , Čolić Miodrag
Published: December 2019

Gold nanoparticles (GNPs) have been investigated extensively as drug carriers in tumour immunotherapy in combination with photothermal therapy. For this purpose, GNPs should be stabilised in biological fluids. The goal of this study was to examine how stabilisation agents influence cytotoxicity and immune response in vitro. Spherical GNPs, 20 nm in size, were prepared by ultrasonic spray pyrolysis (USP). Three types of stabilising agents were used: sodium citrate (SC), polyvinyl-pyrrolidone (PVP), and poly-ethylene glycol (PEG). Pristine, non-stabilised GNPs were used as a control. The culture models were mouse L929 cells, B16F10 melanoma cells and human peripheral blood mononuclear cells (PBMNCs), obtained from healthy donors. Control SC- and PEG-GNPs were non-cytotoxic at concentrations (range 1–100 µg/mL), in contrast to PVP-GNPs, which were cytotoxic at higher concentrations. Control GNPs inhibited the production of IFN-ϒ slightly, and augmented the production of IL-10 by PHA-stimulated PBMNC cultures. PEG-GNPs inhibited the production of pro-inflammatory cytokines (IL-1, IL-6, IL-8, TNF-α) and Th1-related cytokines (IFN-ϒ and IL-12p70), and increased the production of Th2 cytokines (IL-4 and IL-5). SC-PEG inhibited the production of IL-8 and IL-17A. In contrast, PVP-GNPs stimulated the production of pro-inflammatory cytokines, Th1 cytokines, and IL-17A, but also IL-10. When uptake of GNPs by monocytes/macrophages in PBMNC cultures was analysed, the ingestion of PEG- GNPs was significantly lower compared to SC- and PVP-GNPs. In conclusion, stabilisation agents modulate biocompatibility and immune response significantly, so their adequate choice for preparation of GNPs is an important factor when considering the use of GNPs for application in vivo.
Analysis of Density, Roughness, and Accuracy of the Atomic Diffusion Additive Manufacturing (ADAM) Process for Metal Parts
Authors: Galati Manuela , Minetola Paolo
Published: December 2019

Atomic Diffusion Additive Manufacturing (ADAM) is a recent layer-wise process patented by Markforged for metals based on material extrusion. ADAM can be classified as an indirect additive manufacturing process in which a filament of metal powder encased in a plastic binder is used. After the fabrication of a green part, the plastic binder is removed by the post-treatments of washing and sintering (frittage). The aim of this work is to provide a preliminary characterisation of the ADAM process using Markforged Metal X, the unique system currently available on the market. Particularly, the density of printed 17-4 PH material is investigated, varying the layer thickness and the sample size. The dimensional accuracy of the ADAM process is evaluated using the ISO IT grades of a reference artefact. Due to the deposition strategy, the final density of the material results in being strongly dependent on the layer thickness and the size of the sample. The density of the material is low if compared to the material processed by powder bed AM processes. The superficial roughness is strongly dependent upon the layer thickness, but higher than that of other metal additive manufacturing processes because of the use of raw material in the filament form. The accuracy of the process achieves the IT13 grade that is comparable to that of traditional processes for the production of semi-finished metal parts.
Facile One-Step Dynamic Hydrothermal Synthesis of Spinel LiMn2O4/Carbon Nanotubes Composite as Cathode Material for Lithium-Ion Batteries
Authors: Shen Chaoqi , Xu Hui , Liu Liu , Hu Heshan , Chen Siyuan , Su Liwei , Wang Lianbang
Published: December 2019

Nano-sized spinel LiMn2O4/carbon nanotubes (LMO/CNTs) composite is facilely synthesized via a one-step dynamic hydrothermal approach. The characterizations and electrochemical measurements reveal that LiMn2O4 particles with narrow size distribution are well dispersed with CNTs in the composite. The LMO/CNTs nanocomposite with 5 wt % CNTs displays a high specific discharge capacity of 114 mAh g−1 at 1C rate, and the retention rate after 180 cycles at room temperature reaches 94.5% in the potential window of 3.3 to 4.3 V vs. Li/Li+. Furthermore, the electrochemical performance of the composite with 5 wt % CNTs at elevated temperature (55 °C) is also impressive, 90% discharging capacity could be maintained after 100 cycles at 1C. Such excellent electrochemical performance of the final product is attributed to the content of CNTs added in the hydrothermal process and small particle size inherited from pretreated MnO2 precursor.
In Vivo Hepatoprotective Effects of a Peptide Fraction from Krill Protein Hydrolysates against Alcohol-Induced Oxidative Damage
Authors: Park Soo Yeon , Fernando Ilekuttige Priyan Shanura , Han Eui Joeng , Kim Min Ju , Jung Kyungsook , Kang Dong-Soo , Ahn Chang-Bum , Ahn Ginnae
Published: December 2019

Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. Alcoholic liver disease is a prevalent cause of death worldwide. The present study explores the hepatoprotective effects of krill peptide hydrolysate fractions against ethanol-induced liver damage in BALB/c mice. Methods: Hydrolysis was carried out by mimicking the gastrointestinal digestion environment and the filtrate was fractionated based on molecular weight (<1 kDa, 1–3 kDa, and >3 kDa). The 1–3 kDa fraction (KPF), which indicated the highest antioxidant effect, was further investigated for its effect on weight and survival rate increase in mice and its influence on serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels were measured, followed by Nrf2 and HO-1 expression. Histopathology studies were conducted to assess hepatic tissue damage. Results: KPF enhanced the weight and survival rate of mice while reducing serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, KPF upregulated SOD, CAT, and GPx in liver tissues, while downregulating tumor necrosis factor α and interleukin-6 mRNA expression. KPF further increased Nrf2 and HO-1 expression and suppressed ethanol-induced apoptotic proteins in the liver. Histopathology of KPF-treated mice showed less hepatic tissue damage compared to ethanol-treated mice. Conclusions: Hydrolysates and bioactive peptides prepared from krill can be employed as functional foods to enhance liver function and health. Further investigations of KPF could lead to the development of functional foods.
Epinecidin-1 Protects against Methicillin Resistant Staphylococcus aureus Infection and Sepsis in Pyemia Pigs
Authors: Huang Han-Ning , Pan Chieh-Yu , Su Bor-Chyuan , Wu Hung-Yi , Chen Jyh-Yih
Published: December 2019

Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This report demonstrates that the antimicrobial peptide (AMP) epinecidin-1 (Epi-1) efficiently protects against MRSA infection in a pyemia pig model. We first found that Epi-1 exhibits bactericidal activity against MRSA. Next, pharmacokinetic analysis revealed that Epi-1 was stable in serum for 4 h after injection, followed by a gradual decrease. This pharmacokinetic profile suggested Epi-1 may bind serum albumin, which was confirmed in vitro. Harmful effects were not observed for doses up to 100 mg/kg body weight in pigs. When Epi-1 was supplied as a curative agent 30 min post-infection, MRSA-induced abnormalities in blood uric acid (UA), blood urea nitrogen (BUN), creatine (CRE), GOT, and GPT levels were restored to normal levels. We further showed that the bactericidal activity of Epi-1 was higher than that of the antibiotic drug vancomycin. Epi-1 significantly decreased MRSA counts in the blood, liver, kidney, heart, and lungs of infected pigs. Elevated levels of serum C reactive protein (CRP), proinflammatory cytokine IL6, IL1β, and TNFα were also attenuated by Epi-1 treatment. Moreover, the MRSA genes, enterotoxin (et)-A, et-B, intrinsic methicillin resistance A (mecA), and methicillin resistance factor A (femA), were significantly reduced or abolished in MRSA-infected pigs after treatment with Epi-1. Hematoxylin and eosin staining of heart, liver, lung, and kidney sections indicated that Epi-1 attenuated MRSA toxicity in infected pigs. A survival study showed that the pyemia pigs infected with MRSA alone died within a week, whereas the pigs post-treated with 2.5 mg/kg Epi-1 were completely protected against death. The present investigation, thus, demonstrates that Epi-1 effectively protects pyemia pigs against pathogenic MRSA without major toxic side effects.
Microstructure and Mechanical Properties of Sintered and Heat-Treated HfNbTaTiZr High Entropy Alloy
Authors: Málek Jaroslav , Zýka Jiří , Lukáč František , Čížek Jakub , Kunčická Lenka , Kocich Radim
Published: December 2019

High entropy alloys (HEAs) have attracted researchers’ interest in recent years. The aim of this work was to prepare the HfNbTaTiZr high entropy alloy via the powder metallurgy process and characterize its properties. The powder metallurgy process is a prospective solution for the synthesis of various alloys and has several advantages over arc melting (e.g., no dendritic structure, near net-shape, etc.). Cold isostatic pressing of blended elemental powders and subsequent sintering at 1400 °C for various time periods up to 64 h was used. Certain residual porosity, as well as bcc2 (Nb- and Ta-rich) and hcp (Zr- and Hf-rich) phases, remained in the bcc microstructure after sintering. The bcc2 phase was completely eliminated during annealing (1200 °C/1h) and subsequent water quenching. The hardness values of the sintered specimens ranged from 300 to 400 HV10. The grain coarsening during sintering was significantly limited and the maximum average grain diameter after 64 h of sintering was approximately 60 μm. The compression strength at 800 °C was 370 MPa and decreased to 47 MPa at 1200 °C. Porosity can be removed during the hot deformation process, leading to an increase in hardness to ~450 HV10.
Microstructure, Micro-Indentation, and Scratch Behavior of Cr Films Prepared on Al alloys by Using Magnetron Sputtering
Authors: Ding Yi , Zhang Fanyong , Yan Shu , Li Hongtao , He Jining , Yin Fuxing
Published: December 2019

In this study, closed-field unbalanced magnetron sputtering (CFUMS) was employed to deposit pure Cr films on soft substrate of 2024 Al alloy. The effects of deposition powers and biases on the microstructures and mechanical performance of Cr films were systematically investigated by using X-ray diffraction (XRD), scanning electron microscope (SEM), micro-indentation and scratch test. Results showed that all the Cr films had a strong (110) preferred orientation and anisotropic surface morphology with columnar structures. The size of Cr particles was in the range of 50–350 nm, increasing with larger target power and higher biases. The hardness of Cr films was between 3.3 and 4.8 GPa, which was much higher than the Al alloy substrate (1.44 GPa). The Young’s modulus of Cr film could reach a maximum value of 169 GPa at 2.0 kW/70 V. The critical load increased when increasing the power but decreased with higher bias, achieving a maximum value of 53.83 N at 2.0 kW/10 V. The adhesive failure mechanism of Cr film was mainly attributed to the plastic deformation of softer Al substrate.
Design, Analysis, and Experiment on a Novel Stick-Slip Piezoelectric Actuator with a Lever Mechanism
Authors: Huang Weiqing , Sun Mengxin
Published: December 2019

A piezoelectric actuator using a lever mechanism is designed, fabricated, and tested with the aim of accomplishing long-travel precision linear driving based on the stick-slip principle. The proposed actuator mainly consists of a stator, an adjustment mechanism, a preload mechanism, a base, and a linear guide. The stator design, comprising a piezoelectric stack and a lever mechanism with a long hinge used to increase the displacement of the driving foot, is described. A simplified model of the stator is created. Its design parameters are determined by an analytical model and confirmed using the finite element method. In a series of experiments, a laser displacement sensor is employed to measure the displacement responses of the actuator under the application of different driving signals. The experiment results demonstrate that the velocity of the actuator rises from 0.05 mm/s to 1.8 mm/s with the frequency increasing from 30 Hz to 150 Hz and the voltage increasing from 30 V to 150 V. It is shown that the minimum step distance of the actuator is 0.875 μm. The proposed actuator features large stroke, a simple structure, fast response, and high resolution.
Automatic Detection of Granuloma Necrosis in Pulmonary Tuberculosis Using a Two-Phase Algorithm: 2D-TB
Authors: Kus Pelin , Gurcan Metin N. , Beamer Gillian
Published: December 2019

Granuloma necrosis occurs in hosts susceptible to pathogenic mycobacteria and is a diagnostic visual feature of pulmonary tuberculosis (TB) in humans and in super-susceptible Diversity Outbred (DO) mice infected with Mycobacterium tuberculosis. Currently, no published automated algorithms can detect granuloma necrosis in pulmonary TB. However, such a method could reduce variability, and transform visual patterns into quantitative data for statistical and machine learning analyses. Here, we used histopathological images from super-susceptible DO mice to train, validate, and performance test an algorithm to detect regions of cell-poor necrosis. The algorithm, named 2D-TB, works on 2-dimensional histopathological images in 2 phases. In phase 1, granulomas are detected following background elimination. In phase 2, 2D-TB searches within granulomas for regions of cell-poor necrosis. We used 8 lung sections from 8 different super-susceptible DO mice for training and 10-fold cross validation. We used 13 new lung sections from 10 different super-susceptible DO mice for performance testing. 2D-TB reached 100.0% sensitivity and 91.8% positive prediction value. Compared to an expert pathologist, agreement was 95.5% and there was a statistically significant positive correlation for area detected by 2D-TB and the pathologist. These results show the development, validation, and accurate performance of 2D-TB to detect granuloma necrosis.
Establishing Boundaries: The Relationship That Exists between Intestinal Epithelial Cells and Gut-Dwelling Bacteria
Authors: O’Callaghan Amy A. , Corr Sinéad C.
Published: December 2019

The human gastrointestinal (GI) tract is a highly complex organ in which various dynamic physiological processes are tightly coordinated while interacting with a complex community of microorganisms. Within the GI tract, intestinal epithelial cells (IECs) create a structural interface that separates the intestinal lumen from the underlying lamina propria. In the lumen, gut-dwelling microbes play an essential role in maintaining gut homeostasis and functionality. Whether commensal or pathogenic, their interaction with IECs is inevitable. IECs and myeloid immune cells express an array of pathogen recognition receptors (PRRs) that define the interaction of both pathogenic and beneficial bacteria with the intestinal mucosa and mount appropriate responses including induction of barrier-related factors which enhance the integrity of the epithelial barrier. Indeed, the integrity of this barrier and induction of appropriate immune responses is critical to health status, with defects in this barrier and over-activation of immune cells by invading microbes contributing to development of a range of inflammatory and infectious diseases. This review describes the complexity of the GI tract and its interactions with gut bacteria.
Inhibition–Disruption of Candida glabrata Biofilms: Symmetrical Selenoesters as Potential Anti-Biofilm Agents
Authors: De la Cruz-Claure María L. , Cèspedes-Llave Ariel A. , Ulloa María T. , Benito-Lama Miguel , Domínguez-Álvarez Enrique , Bastida Agatha
Published: December 2019

Candida glabrata is one of the most prevalent pathogenic Candida species in dental plaque on tooth surfaces. Candida biofilms exhibit an enhanced resistance against most antifungal agents. Thus, the development of alternative more potent and effective antimicrobials is required to overcome this resistance. In this study, three novel fluorinated derivatives and nine selenoester compounds were screened as novel antifungal and antibiofilm agents against C. krusei, C. parapsilosis, and C. glabrata (N = 81 dental isolates). C. glabrata strains were susceptible only to fluorinated compounds while C. krusei, C. parapsilosis, and C. glabrata were susceptible to the action of the selenoesters. The evaluated symmetrical selenoester compounds presented very good antifungal activity against all the tested C. glabrata dental isolates (1–4 μg/mL of minimum inhibitory concentration-MIC). The most active compound (Se-5) was able to inhibit and disperse C. glabrata biofilms. These results demonstrated that selenoesters may be novel and promising biocide agents against C. glabrata clinical dental isolates.
Fungal Laccase Production from Lignocellulosic Agricultural Wastes by Solid-State Fermentation: A Review
Authors: Wang Feng , Xu Ling , Zhao Liting , Ding Zhongyang , Ma Haile , Terry Norman
Published: December 2019

Laccases are copper-containing oxidase enzymes found in many fungi. They have received increasing research attention because of their broad substrate specificity and applicability in industrial processes, such as pulp delignification, textile bleaching, phenolic removal, and biosensors. In comparison with traditional submerged fermentation (SF), solid-state fermentation (SSF) is a simpler technique for laccase production and has many advantages, including higher productivity, efficiency, and enzyme stability as well as reduced production costs and environmental pollution. Here, we review recent advances in laccase production technology, with focus on the following areas: (i) Characteristics and advantages of lignocellulosic agricultural wastes used as SSF substrates of laccase production, including detailed suggestions for the selection of lignocellulosic agricultural wastes; (ii) Comparison of fungal laccase production from lignocellulosic substrates by either SSF or SF; (iii) Fungal performance and strain screening in laccase production from lignocellulosic agricultural wastes by SSF; (iv) Applications of laccase production under SSF; and (v) Suggestions and avenues for future studies of laccase production by fungal SSF with lignocellulosic materials and its applications.
Effect of Myclobutanil Pesticide on the Physiological Behavior of Two Newly Isolated Saccharomyces cerevisiae Strains during Very-High-Gravity Alcoholic Fermentation
Authors: Terpou Antonia , Dimopoulou Maria , Belka Aikaterini , Kallithraka Stamatina , Nychas George-John E. , Papanikolaou Seraphim
Published: December 2019

Yeasts are able to act as biosorbents, as their cell wall includes several components capable of binding organic xenobiotic compounds that can potentially be removed during various fermentation processes. In the present investigation, two novel Saccharomyces cerevisiae strains (LMBF-Y 16 and LMBF-Y-18), previously isolated from grapes, were studied regarding their physiological behavior (dry cell weight—DCW production, substrate uptake, and ethanol and glycerol biosynthesis) during fermentations of grape must, in some cases enriched with commercial glucose and fructose (initial total sugar concentration approximately 150 and 250 g/L, respectively). Myclobutanil (a chiral triazole fungicide broadly used as a protective agent of vine) was also added to the culture media at various concentrations in order to assess the ability of the yeasts to simultaneously perform alcoholic fermentations and detoxify the medium (i.e., to remove the fungicide). In the first set of experiments and for both tested strains, trials were carried out in either 250 mL or 2.0 L agitated shake flasks in either synthetic glucose-based experiments or grape musts. Since the results obtained in the trials where the cultures were placed in 2.0 L flasks with grape musts as substrates were superior in terms of both DCW and ethanol production, these experimental conditions were selected for the subsequent studies. Both strains showed high fermentative efficiency, producing high amounts of DCW (9.5–10.5 g/L) in parallel with high ethanol production, which in some cases achieved values very close to the maximum theoretical ethanol production yield (≈0.49 g of ethanol per g of sugar). When using grape must with initial total sugars at approximately 250 g/L (very high gravity fermentation media, close to winemaking conditions), significantly high ethanol quantities (i.e., ranging between 105 and 123 g/L) were produced. Myclobutanil addition slightly negatively affected sugar conversion into ethanol; however, in all cases, ethanol production was very satisfactory. A non-negligible myclobutanil removal during fermentation, which ranged between 5%–27%, as a result of the adsorptive or degradative capacity of the yeast was also reported. The presence of myclobutanil had no effect on DCW production and resulted in no significant differences in the biosynthesis of glycerol. Therefore, these newly isolated yeast strains could be excellent candidates for simultaneous high ethanol production and parallel pesticide removal in a general biorefinery concept demonstrating many environmental benefits.
Surface-Enhanced IR-Absorption Microscopy of Staphylococcus aureus Bacteria on Bactericidal Nanostructured Si Surfaces
Authors: Kudryashov Sergey I. , Nastulyavichus Alena A. , Tolordava Eteri R. , Kirichenko Alexey N. , Saraeva Irina N. , Rudenko Andrey A. , Romanova Yulia M. , Panarin Andrey Yu. , Ionin Andrey A. , Itina Tatiana E.
Published: December 2019

Surface-enhanced IR absorption (SEIRA) microscopy was used to reveal main chemical and physical interactions between Staphylococcus aureus bacteria and different laser-nanostructured bactericidal Si surfaces via simultaneous chemical enhancement of the corresponding IR-absorption in the intact functional chemical groups. A cleaner, less passivated surface of Si nanoripples, laser-patterned in water, exhibits much stronger enhancement of SEIRA signals compared to the bare Si wafer, the surface coating of oxidized Si nanoparticles and oxidized/carbonized Si (nano) ripples, laser-patterned in air and water. Additional very strong bands emerge in the SEIRA spectra on the clean Si nanoripples, indicating the potential chemical modifications in the bacterial membrane and nucleic acids during the bactericidal effect.
Fingerprint Analysis of Cnidium monnieri (L.) Cusson by High-Speed Counter-Current Chromatography
Authors: Wu Xiaoxue , Gao Xuemin , Zhu Xuan , Zhang Shuyi , Liu Xinmei , Yang Huayu , Song Hua , Chen Qing
Published: December 2019

Cnidium monnieri (L.) Cusson is a popular Traditional Chinese Medicine (TCM) with a variety of bioactivities. However, there are some problems that have affected the development of Cnidium monnieri (L.) Cusson. At present, many methods have been reported for the analysis of coumarins in Cnidium monnieri (L.) Cusson. However, the quality control of coumarins in Cnidium monnieri (L.) Cusson by high-speed counter-current chromatography (HSCCC) has not been reported. In this study, analytical high-speed counter-current chromatography (HSCCC) was successfully used for fingerprint of Cnidium monnieri (L.) Cusson with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water at 4:6:6.5:3.5 (v/v). The UV wavelength was set at 254 nm. Six coumarin compounds with high biological activity were selected as indicator compounds for the quality control. The HSCCC fingerprint of the Cnidium monnieri (L.) Cusson was successfully established and there were some differences according to the results of the fingerprint analysis. The present results demonstrate that HSCCC is an established and efficient technique for the fingerprint analysis of Cnidium monnieri (L.) Cusson and can be used to control the quality of Cnidium monnieri (L.) Cusson. In brief, HSCCC is a useful technology for the fingerprint analytical method for TCM.
Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line
Authors: M. Franco Yollanda E. , Y. Okubo Marcia , D. Torre Adriana , P. Paiva Paula , N. Rosa Marcela , O. Silva Viviane A. , M. Reis Rui , T. G. Ruiz Ana L. , M. Imamura Paulo , de Carvalho João E. , B. Longato Giovanna
Published: December 2019

Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.
Wavelength-Conversion-Material-Mediated Semiconductor Wafer Bonding for Smart Optoelectronic Interconnects
Authors: Kishibe Kodai , Hirata Soichiro , Inoue Ryoichi , Yamashita Tatsushi , Tanabe Katsuaki
Published: December 2019

A new concept of semiconductor wafer bonding, mediated by optical wavelength conversion materials, is proposed and demonstrated. The fabrication scheme provides simultaneous bond formation and interfacial function generation, leading to efficient device production. Wavelength-converting functionalized semiconductor interfacial engineering is realized by utilizing an adhesive viscous organic matrix with embedded fluorescent particles. The bonding is carried out in ambient air at room temperature and therefore provides a cost advantage with regard to device manufacturing. Distinct wavelength conversion, from ultraviolet into visible, and high mechanical stabilities and electrical conductivities in the bonded interfaces are verified, demonstrating their versatility for practical applications. This bonding and interfacial scheme can improve the performance and structural flexibility of optoelectronic devices, such as solar cells, by allowing the spectral light incidence suitable for each photovoltaic material, and photonic integrated circuits, by delivering the respective preferred frequencies to the optical amplifier, modulator, waveguide, and detector materials.
High-Efficiency and Broadband Near-Infrared Bi-Functional Metasurface Based on Rotary Different-Size Silicon Nanobricks
Authors: Wang Wei , Guo Chong , Tang Jingluo , Zhao Zehan , Wang Jicheng , Sun Jinghua , Shen Fei , Guo Kai , Guo Zhongyi
Published: December 2019

Several novel spin-dependent bi-functional metasurfaces consisting of different-sized rotary silicon nanobricks have been proposed and numerically investigated based on the Pancharatnam–Berry phase and structural phase simultaneously. Here, a transmission mechanism is strictly deduced, which can avoid crosstalk from the multiplexed bi-functional metasurface. Four kinds of high-efficiency bi-functional devices have been designed successfully at infrared wavelengths, including a spin-dependent bi-functional beam deflector, a spin-dependent bi-functional metalens, a bi-functional metasurface with spin-dependent focusing and deflection function, and a spin-dependent bi-functional vortex phase plate. All of the results demonstrate the superior performances of our designed devices. Our work opens up new doors toward building novel spin-dependent bi-functional metasurfaces, and promotes the development of bi-functional devices and spin-controlled photonics.
Applications of Nanomaterials in Leishmaniasis: A Focus on Recent Advances and Challenges
Authors: Saleem Kiran , Khursheed Zainab , Hano Christophe , Anjum Iram , Anjum Sumaira
Published: December 2019

Leishmaniasis is a widely distributed protozoan vector-born disease affecting almost 350 million people. Initially, chemotherapeutic drugs were employed for leishmania treatment but they had toxic side effects. Various nanotechnology-based techniques and products have emerged as anti-leishmanial drugs, including liposomes, lipid nano-capsules, metal and metallic oxide nanoparticles, polymeric nanoparticles, nanotubes and nanovaccines, due to their unique properties, such as bioavailability, lowered toxicity, targeted drug delivery, and biodegradability. Many new studies have emerged with nanoparticles serving as promising therapeutic agent for anti-leishmanial disease treatment. Liposomal Amphotericin B (AmB) is one of the successful nano-based drugs with high efficacy and negligible toxicity. A new nanovaccine concept has been studied as a carrier for targeted delivery. This review discusses different nanotechnology-based techniques, materials, and their efficacies in leishmaniasis treatment and their futuristic improvements.
Ag Nanostructures with Spikes on Adhesive Tape as a Flexible Sers-Active Substrate for In Situ Trace Detection of Pesticides on Fruit Skin
Authors: Sitjar Jaya , Liao Jiunn-Der , Lee Han , Pan Li Peng , Liu Bernard Haochih , Fu Wei-en , Chen Guo Dung
Published: December 2019

Nanostructures with spikes (NSPs) have been a subject of several surface-enhanced Raman scattering (SERS) applications owing to their significant Raman signal enhancement brought about by the combined effects of interspike coupling and the accumulated induction on the tips of spikes. Thus, NSPs offer great potential as a SERS-active substrate for relevant applications that require a high density of enhanced “hot spots”. In this study, Ag NSPs were synthesized in varying degrees of agglomeration and were thereafter deposited onto a transparent adhesive tape as a flexible substrate for SERS applications, specifically, in the detection of trace amounts of pesticides. These flexible substrates were referred to as Ag NSPs/tape and optimized with an enhancement factor (EF) of ca. 1.7 × 107. A strong resulting signal enhancement could be attributed to an optimal degree of agglomeration and, consequently, the distances among/between spikes. Long spikes on the synthesized core of Ag NSPs tend to be loosely spaced, which are suitable in detecting relatively large molecules that could access the spaces among the spikes where “hot spots” are generally formed. Since one side of the transparent tape is adhesive, the paste-and-peel off method was successful in obtaining phosmet and carbaryl residues from apple peels as reflected in the acquired SERS spectra. In situ trace detection of the pesticides at low concentrations down to 10−7 M could be demonstrated. In situ trace detection of mixed pesticides was possible as the characteristic peaks of both pesticides were observed in equimolar mixtures of the analytes at 10−2 to 10−4 M. This study is, thus, premised upon applying for in situ trace detection on e.g., fruit skin.
Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study
Authors: Arija Victoria , Hernández-Martínez Carmen , Tous Mónica , Canals Josefa , Guxens Mónica , Fernández-Barrés Silvia , Ibarluzea Jesús , Babarro Izaro , Soler-Blasco Raquel , Llop Sabrina , Vioque Jesús , Sunyer Jordi , Julvez Jordi
Published: December 2019

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.
Human Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review
Authors: Meessen Emma C.E. , Warmbrunn Moritz V. , Nieuwdorp Max , Soeters Maarten R.
Published: December 2019

The importance of the postprandial state has been acknowledged, since hyperglycemia and hyperlipidemia are linked with several chronic systemic low-grade inflammation conditions. Humans spend more than 16 h per day in the postprandial state and the postprandial state is acknowledged as a complex interplay between nutrients, hormones and diet-derived metabolites. The purpose of this review is to provide insight into the physiology of the postprandial inflammatory response, the role of different nutrients, the pro-inflammatory effects of metabolic endotoxemia and the anti-inflammatory effects of bile acids. Moreover, we discuss nutritional strategies that may be linked to the described pathways to modulate the inflammatory component of the postprandial response.
Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study
Authors: Yuan Shuai , Bäck Magnus , Bruzelius Maria , Mason Amy M. , Burgess Stephen , Larsson Susanna
Published: December 2019

Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes ?5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.
Metabolism and Pharmacokinetic Study of the Boron-Containing Prodrug of Belinostat (ZL277), a Pan HDAC Inhibitor with Enhanced Bioavailability
Authors: Zhang Changde , Guo Shanchun , Zhong Qiu , Zhang Qiang , Hossain Ahamed , Zheng Shilong , Wang Guangdi
Published: December 2019

ZL277 is a prodrug of belinostat with enhanced bioavailability and efficacy as a pan histone deacetylase (HDAC) inhibitor. In this study, we investigated the metabolism and pharmacokinetics of ZL277 in liver S9 fractions, liver microsomes, liver cytosol, and in mice. Metabolic products were identified and quantified by a combination of liquid chromatography and tandem mass spectrometry. The in vitro metabolic profile of ZL277 includes ZL277-B(OH)2-452, the major oxidative metabolite ZL277-OH-424, the active ingredient belinostat, belinostat amide, belinostat acid, and methylated belinostat in liver S9 fractions. Both ZL277-OH-424 and belinostat underwent further glucuronidation in liver microsome, whereas only ZL277-OH-424, but not belinostat, underwent some level of sulfation in rat liver cytosols. These metabolites were examined in plasma and in a breast tumor model in vivo. They were also examined in urine and feces from mice treated with ZL277. The pharmacokinetic study of ZL277 showed the parameters of active drug belinostat with a half-life (t1/2) of 10.7 h, an area under curve value (AUC) of 1506.9 ng/mL*h, and a maximum plasma concentration (Cmax) of 172 ng/mL, reached 3 h after a single dose of 10 mg/kg. The hydrolysis product of the prodrug, ZL277-B(OH)2-452 showed an AUC of 8306 ng/mL*h and Cmax of 931 ng/mL 3 h after drug administration.
Comparison of In Vitro and In Vivo Results Using the GastroDuo and the Salivary Tracer Technique: Immediate Release Dosage Forms under Fasting Conditions
Authors: Sager Maximilian , Schick Philipp , Mischek Magdalena , Schulze Christian , Hasan Mahmoud , Kromrey Marie-Luise , Benameur Hassan , Wendler Martin , Tzvetkov Mladen Vassilev , Weitschies Werner , Koziolek Mirko
Published: December 2019

The fasted state administration of immediate release (IR) dosage forms is often regarded as uncritical since physiological aspects seem to play a minor role for disintegration and drug release. However, recent in vivo studies in humans have highlighted that fasted state conditions are in fact highly dynamic. It was therefore the aim of this study to investigate the disintegration and drug release behavior of four different IR formulations of the probe drug caffeine under physiologically relevant conditions with the aid of the GastroDuo. One film-coated tablet and three different capsule formulations based on capsule shells either made from hard gelatin or hydroxypropylmethyl cellulose (HPMC) were tested in six different test programs. To evaluate the relevance of the data generated, the four IR formulations were also studied in a four-way cross-over study in 14 healthy volunteers by using the salivary tracer technique (STT). It could be shown that the IR formulations behaved differently in the in vitro test programs. Thereby, the simulated parameters affected the disintegration and dissolution behavior of the four IR formulations in different ways. Whereas drug release from the tablet started early and was barely affected by temperature, pH or motility, the different capsule formulations showed a longer lag time and were sensitive to specific parameters. However, once drug release was initiated, it typically progressed with a higher rate for the capsules compared to the tablet. Interestingly, the results obtained with the STT were not always in line with the in vitro data. This observation was due to the fact that the probability of the different test programs was not equal and that certain scenarios were rather unlikely to occur under the controlled and standardized conditions of clinical studies. Nonetheless, the in vitro data are still valuable as they allowed to discriminate between different formulations.
Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products
Authors: Ruiz-Picazo Alejandro , Colón-Useche Sarin , Perez-Amorós Blanca , González-Álvarez Marta , Molina-Martínez Irene , González-Álvarez Isabel , García-Arieta Alfredo , Bermejo Marival
Published: December 2019

The purpose of this work is to explore the predictive ability of the biopharmaceutics classification system (BCS) biowaiver based on the dissolution methods for two pravastatin test products, where one of them showed bioequivalence (BE) while the other test failed (non-bioequivalence, or NBE), and to explore the reasons for the BE failure. Experimental solubility and permeability data confirmed that pravastatin is a BCS class III compound. The permeability experiments confirmed that the NBE formulation significantly increased pravastatin permeability, and could explain its higher absorption rate and higher Cmax. This finding highlights the relevance of requiring similar excipients for BCS class III drugs. The BCS-based biowaiver dissolution tests at pH 1.2, 4.5, and 6.8, with the paddle apparatus at 50 rpm in 900 mL media, were not able to detect differences in pravastatin products, although the NBE formulation exhibited a more rapid dissolution at earlier sampling times. Dissolution tests conducted in 500 mL did not achieve complete dissolution, and both formulations were dissimilar because the amount dissolved at 15 min was less than 85%. The difference was less than 10% at pH 1.2 and 4.5, while at pH 6.8 f2, results reflected the Cmax rank order.
Sugar and Polymer Excipients Enhance Uptake and Splice-Switching Activity of Peptide-Dendrimer/Lipid/Oligonucleotide Formulations
Authors: Saher Osama , Lehto Taavi , Gissberg Olof , Gupta Dhanu , Gustafsson Oskar , Andaloussi Samir EL , Darbre Tamis , Lundin Karin E. , Smith C. I. Edvard , Zain Rula
Published: December 2019

Non-viral transfection vectors are commonly used for oligonucleotide (ON) delivery but face many challenges before reaching the desired compartments inside cells. With the support of additional compounds, it might be more feasible for a vector to endure the barriers and achieve efficient delivery. In this report, we screened 18 different excipients and evaluated their effect on the performance of peptide dendrimer/lipid vector to deliver single-stranded, splice-switching ONs under serum conditions. Transfection efficiency was monitored in four different reporter cell lines by measuring splice-switching activity on RNA and protein levels. All reporter cell lines used had a mutated human β-globin intron 2 sequence interrupting the luciferase gene, which led to an aberrant splicing of luciferase pre-mRNA and subsidence of luciferase protein translation. In the HeLa Luc/705 reporter cell line (a cervical cancer cell line), the lead excipients (Polyvinyl derivatives) potentiated the splice-switching activity up to 95-fold, compared to untreated cells with no detected cytotoxicity. Physical characterization revealed that lead excipients decreased the particle size and the zeta potential of the formulations. In vivo biodistribution studies emphasized the influence of formulations as well as the type of excipients on biodistribution profiles of the ON. Subsequently, we suggest that the highlighted impact of tested excipients would potentially assist in formulation development to deliver ON therapeutics in pre-clinical and clinical settings.
Exogenous Dopamine Application Promotes Alkali Tolerance of Apple Seedlings
Authors: Jiao Xueyi , Li Yuxing , Zhang Xiuzhi , Liu Chenlu , Liang Wei , Li Chao , Ma Fengwang , Li Cuiying
Published: December 2019

Arid and semiarid apple producing areas suffer from severe alkalinity of soil, which strongly affects the yield and quality of apples. Dopamine (DA) is involved in metabolic activities in response to abiotic stress in plants. To detect the effects of exogenous DA application on the adaption of apple (Malus hupehensis) seedlings to alkali stress and as a protection from oxidative stress, 0.1 mM DA was identified as the most suitable concentration by hydroponic culture. Further experimentation showed that the growth and photosynthesis of apple seedlings were significantly inhibited under alkali stress, and more reactive oxygen species accumulated, compared with control. However, exogenous DA application suppressed the loss of the plant height, root length, chlorophyll levels, and photosynthetic capacity of apple seedlings that were caused by alkali stress. In the leaves of alkali stressed seedlings, the catalase, superoxide dismutase, and peroxidase activities were lower and hydrogen peroxide and malondialdehyde levels were higher than in the untreated plants. The presence of DA significantly alleviated such effects of alkali stress. In addition, exogenous DA application increased the antioxidant capacity of apple seedlings under alkali stress by increasing the level of chlorogenic acid. These results are significant for improving the alkali tolerance of apple in apple-producing areas with alkalized soil.