bluuebunny/crossref_metadata_2025 huggingface dataset:
Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease
Authors: Shah Anuri , Han Pei , Wong Mung-Yee , Chang Raymond Chuen-Chung , Legido-Quigley Cristina
Published: February 2019

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. Methods: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. Results: In plasma, palmitic acid (q = 3.72 × 10−2, FC = 1.81) and stearic acid (q = 3.84 × 10−2, FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10−2) and stearic acid (q = 2.7 × 10−2) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10−2, FC = −11.7), monostearin (q = 3.72 × 10−2, FC = −15.1) and myo-inositol (q = 3.81 × 10−2, FC = −3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. Conclusion: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.
Deep-Learning-Based Polar-Body Detection for Automatic Cell Manipulation
Authors: Wang Yuqing , Liu Yaowei , Sun Mingzhu , Zhao Xin
Published: February 2019

Polar-body detection is an essential and crucial procedure in various automatic cell manipulations. The polar body can only be observed when it is located near the focal plane of the microscope, so we need to detect the polar body during cell rotation in cell manipulations. However, three-dimensional cell rotation by micropipette causes polar-body defocus and cell/polar-body deformation, which have not been discussed in existing image-level polar-body-detection approaches. Moreover, varying sizes of the polar bodies increase the difficulty of polar-body detection. In this paper, we propose a deep-learning-based framework to realize polar-body detection in cell rotation. The detection problem is interpreted as image segmentation, which separates the polar body from the background. Then, we improve U-net, which is a typical convolutional neural network (CNN) for medical-image segmentation, so that the network can be applied to polar-body detection, especially for the detection of defocused polar bodies and polar bodies of different sizes. For CNN training, we also designed a particular image-transformation method to simulate more cell-rotation situations, including cell- and polar-body deformation, so that the deformed polar body in cell rotation would be detected by the proposed method. Experiment results show that our method achieves high detection accuracy of 98.7% on a test dataset of 1000 images, and performs well in cell-rotation processes. This method can be applied to various automatic cell manipulations in the future.
Editorial for Special Issue “New Mineral Species and Their Crystal Structures”
Authors: Galuskina Irina O. , Pekov Igor V.
Published: February 2019

Mineralogy is the oldest and one of the most important sciences of the geological cycle [...]
An Innovative Method for Placement of Gangue Backfilling Material in Steep Underground Coal Mines
Authors: Yin Yanchun , Zhao Tongbin , Zhang Yubao , Tan Yunliang , Qiu Yue , Taheri Abbas , Jing Yuan
Published: February 2019

Using gangue backfilling in underground coal mining not only controls the roof deformation in the gob area but also reduces the amount of mining waste rock. However, due to the limitations of the complicated engineering conditions, backfilling mining in the steep coal seam is not widely applied. In this study, a long-distance backfilling technology with a scraper winch for a steep coal seam was proposed and applied in a flexible shield supporting working face in Datai Mine, Beijing. Aiming at the problem of the decreasing backfilling ratio in field practice, numerical simulation was carried out to research the moving law of gangue in the goaf. The gangue mainly experienced four stages: gangue landslide stage, small-scale subsidence stage, funnel-shaped subsidence stage, and large-scale subsidence stage. The moving area of the gangue could be divided into five areas including a motionless area, a landslide area, a subsidence area, a funnel-shaped subsidence area, and a to-be-backfilled area. With the increase of the inclined length of the working face, the moving time of the gangue increased gradually. Based on the simulation results, the scheme of backfilling and mining in Datai Mine was optimized, for which the inclined length of the working face was shortened, and a higher backfilling ratio was obtained.
The Correlation of Roasting Conditions in Selective Potassium Extraction from K-Feldspar Ore
Authors: Serdengeçti Mete Tayhan , Baştürkcü Hüseyin , Burat Fırat , Kangal Murat Olgaç
Published: February 2019

Feldspar minerals are essential ingredients for the glass and ceramic-glass industries. The potassium element found in certain proportions in the composition of K-feldspar minerals has a fundamental function in the growth of plants. The production of potassium fertilizers is mostly made from the soluble minerals, which are located in lakes. Despite having a huge area of use in the agriculture industry, the reserves of these salts are limited and not evenly distributed in the earth’s crust. Due to the high availability of feldspar reserves in the earth’s crust, the production of potential potassium salts can provide a wide range of social and economic benefits. In this study, potassium extraction from a feldspar ore, which contained microcline, albite, muscovite, and quartz, was studied using chloridizing (CaCl2) roasting followed by leaching. Direct leaching experiments were also performed on the sample by adapting various solvents. To emphasize the importance of roasting before the dissolution process, different parameters such as particle size, roasting temperature, and duration, as well as the feldspar/CaCl2 ratio, were tested. Under the optimum conditions (i.e., −106 microns, 850 Co, 60 minutes, 1:1.5 feldspar:CaCl2), 99% of the potassium was successfully extracted from the ore feed.
Natural Graphite Cuboids
Authors: Korsakov Andrey , Rezvukhina Olga , Jaszczak John , Rezvukhin Dmitriy , Mikhailenko Denis
Published: February 2019

Graphite cuboids are abundant in ultrahigh-pressure metamorphic rocks and are generally interpreted as products of partial or complete graphitization of pre-existing diamonds. The understanding of the graphite cuboid structure and its formation mechanisms is still very limited compared to nanotubes, cones, and other carbon morphologies. This paper is devoted to the natural occurrences of graphite cuboids in several metamorphic and magmatic rocks, including diamondiferous metamorphic assemblages. The studied cuboids are polycrystalline aggregates composed either of numerous smaller graphite cuboids with smooth surfaces or graphite flakes radiating from a common center. Silicates, oxides, and sulphides are abundant in all the samples studied, testifying that the presence of oxygen, sulfur, or sulphides in natural systems does not prevent the spherulitic growth of graphite. The surface topography and internal morphology of graphite cuboids combined with petrological data suggest that graphite cuboids originated from a magmatic or metamorphic fluid/melt and do not represent products of diamond-graphite transformation processes, even in diamond-bearing rocks.
Active Components, Antioxidant, Inhibition on Metabolic Syndrome Related Enzymes, and Monthly Variations in Mature Leaf Hawk Tea
Authors: Chen Zhuo , Zhang Dan , Guo Jia-Jia , Tao Wei , Gong Rui-Xue , Yao Ling , Zhang Xing-Long , Cao Wei-Guo
Published: February 2019

Hawk tea is a rich and edible resource, traditionally used as a beverage in South China. This drink has many pharmacologic effects, such as acting as an antioxidant and reducing blood sugar and lipids. The objective of this work was to explore the active compound contents, bioactivities and their monthly changes, and optimize the harvest time. In the present study, Hawk tea from each month in 2017 was collected and extracted with 70% (v/v) ethanol. The contents of the total flavonoids and total phenols were determined using the colorimetric method. We determined the contents of seven characteristic active substances—hyperin, isoquercitrin, trifolin, quercitrin, astragalin, quercetin, and kaempferol—using high-performance liquid chromatography. The crude extract was tested for its antioxidant and inhibitory properties on enzymes involved in metabolic syndrome. Specifically, 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing power assay, and the inhibition capacity test on α-glucosidase and lipase were conducted to determine the antioxidant effect in vitro, as well as the reduction of blood sugar and lipids. Monthly variations in activities and components were determined by numeric analysis and comparison. Correlation analysis revealed that antioxidant effects are significantly correlated with the total flavonoids. The hierarchical cluster analysis of bioactivities and their contents indicates that October and November are the best harvesting months, which differs with the habitual collection of Hawk tea.
Study on Speciation of As, Cr, and Sb in Bottled Flavored Drinking Water Samples Using Advanced Analytical Techniques IEC/SEC-HPLC/ICP-DRC-MS and ESI-MS/MS
Authors: Lorenc Wiktor , Markiewicz Barbara , Kruszka Dariusz , Kachlicki Piotr , Barałkiewicz Danuta
Published: February 2019

The main aim of the research was to develop a complementary analytical approach consisting of bespoke speciation analysis and non-targeted speciation analysis of As, Sb, and Cr in flavored bottled drinking water samples using HPLC/ICP-DRC-MS and ESI-MS/MS. The scope of two previously developed analytical procedures, (1) multielemental speciation procedure for AsIII, AsV, CrVI, SbIII, and SbV analysis and (2) arsenic speciation procedure for AsB, AsIII, DMA, MMA, and AsV quantification, was extended to the analysis of a new sample type in terms of bespoke speciation analysis. As for the non-targeted speciation, analysis size exclusion chromatography was used with ICP-MS and a complementary technique, ESI-MS/MS, was used for the organic species of As, Sb, and Cr screening. Full validation of procedures 1 and 2 was conducted. Procedure 1 and 2 were characterized with precision values in the range from 2.5% to 5.5% and from 3.6% to 7.2%, respectively. Obtained recoveries ranged from 97% to 106% and from 99% to 106% for procedures 1 and 2, respectively. Expanded uncertainties calculated for procedures 1 and 2 ranged from 6.1% to 9.4% and from 7.4% to 9.9%, respectively. The applicability of the proposed procedures was tested on bottled drinking water samples. Results for the real samples in procedure 1 were in the range from 0.286 ± 0.027 [μg L−1] to 0.414 ± 0.039 [μg L−1] for AsIII, from 0.900 ± 0.083 [μg L−1] to 3.26 ± 0.30 [μg L−1] for AsV, and from 0.201 ± 0.012 [μg L−1] to 0.524 ± 0.032 [μg L−1] for SbV. CrVI and SbIII were not detected in any sample. As for procedure 2, results were in the range from 0.0541 ± 0.0053 [μg L−1] to 0.554 ± 0.054 [μg L−1] for AsB. Results for AsIII and AsV obtained with procedure 2 were in good accordance with results obtained with procedure 1. DMA and MMA were not detected in any sample.
Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity
Authors: Kozłowska Joanna , Grela Ewa , Baczyńska Dagmara , Grabowiecka Agnieszka , Anioł Mirosław
Published: February 2019

In our investigation, we concentrated on naringenin (NG)—a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel O-alkyl derivatives of naringenin (7a–11a, 13a, 17a) were obtained. Another chemical modification led to 9 oximes of O-alkyl naringenin derivatives (7b–13b, 16b–17b) that were never described before. The obtained compounds were evaluated for their potential antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The results were reported as the standard minimal inhibitory concentration (MIC) values and compared with naringenin and its known O-alkyl derivatives. Compounds 4a, 10a, 12a, 14a, 4b, 10b, 11b, and 14b were described with MIC of 25 µg/mL or lower. The strongest bacteriostatic activity was observed for 7-O-butylnaringenin (12a) against S. aureus (MIC = 6.25 µg/mL). Moreover, the antitumor effect of flavonoids was examined on human colon cancer cell line HT-29. Twenty-six compounds were characterized as possessing an antiproliferative activity stronger than that of naringenin. The replacement of the carbonyl group with an oxime moiety significantly increased the anticancer properties. The IC50 values below 5 µg/mL were demonstrated for four oxime derivatives (8b, 11b, 13b and 16b).
Mulinane and Azorellane Diterpenoid Biomarkers by GC-MS from a Representative Apiaceae (Umbelliferae) Species of the Andes
Authors: Simoneit Bernd R.T. , Oros Daniel R. , Jaffé Rudolf , Didyk-Peña Alexandra , Areche Carlos , Sepúlveda Beatriz , Didyk Borys M.
Published: February 2019

Extracts of bled resin from Azorella compacta, of the Azorelloideae family from the Andes (>4000 m), were analyzed by gas chromatography-mass spectrometry. The mass spectra of the dominant compounds of the resin and its hydrogenation products were documented. The most abundant compounds were oxygenated diterpenoids, namely mulinadien-20-oic (Δ11,13 and Δ11,14) acids, azorell-13-en-20-oic acid, 13α,14β-dihydroxymulin-11-en-20-oic acid, and azorellanol, with a group of azorellenes and mulinadienes. The mass spectra of the novel diterpenoid hydrocarbons with the azorellane and mulinane skeletons were also presented. This study documents the molecular diversity of these diterpenoid classes, and could be of great utility for future organic geochemical, environmental, archeological, pharmaceutical, and forensic chemistry studies.
Inhibition of Amyloid Beta Aggregation and Deposition of Cistanche tubulosa Aqueous Extract
Authors: Chao Chien-Liang , Huang Hsin-Wen , Huang Hui-Chi , Chao Hsin-Fan , Yu Shuen-Wen , Su Muh-Hwan , Wang Chao-Jih , Lin Hang-Ching
Published: February 2019

Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer’s disease (AD) activity by inhibiting amyloid β peptide (Aβ) aggregation and deposition. However, recent studies considered that the phenylethanoid glycosides may be metabolized by intestinal bacteria, because all analysis results showed that the bioavailability of phenylethanoid glycosides is extremely low. In this study we demonstrate how iron chelation plays a crucial role in the Aβ aggregation and deposition inhibition mechanism of phenylethanoid glycosides of CTE. In addition, we further proved phenylethanoid glycosides (1–3) could reach brain. Active CTE component and action mechanism confirmation will be a great help for product quality control and bioavailability studies in the future. At the same time, we provide a new analysis method useful in determining phenylethanoid glycosides (1–3) in plants, foods, blood, and tissues for chemical fingerprint and pharmacokinetic research.
A Chemiluminescent Method for the Detection of H2O2 and Glucose Based on Intrinsic Peroxidase-Like Activity of WS2 Quantum Dots
Authors: Haddad Irani-nezhad Mahsa , Khataee Alireza , Hassanzadeh Javad , Orooji Yasin
Published: February 2019

Currently, researchers are looking for nanomaterials with peroxidase-like activity to replace natural peroxidase enzymes. For this purpose, WS2 quantum dots (WS2 QDs) were synthesized via a solvothermal method, which improved the mimetic behavior. The resulting WS2 QDs with a size of 1–1.5 nm had a high fluorescence emission, dependent on the excitation wavelength. WS2 QDs with uniform morphology showed a high catalytic effect in destroying H2O2. The peroxidase-like activity of synthesized nanostructures was studied in H2O2 chemical and electrochemical reduction systems. The mimetic effect of WS2 QDs was also shown in an H2O2–rhodamine B (RB) chemiluminescence system. For this aim, a stopped-flow chemiluminescence (CL) detection system was applied. Also, in order to confirm the peroxidase-like effect of quantum dots, colorimetry and electrochemical techniques were used. In the enzymatic reaction of glucose, H2O2 is one of the products which can be determined. Under optimum conditions, H2O2 can be detected in the concentration range of 0–1000 nmol·L−1, with a detection limit of 2.4 nmol·L−1. Using this CL assay, a linear relationship was obtained between the intensity of the CL emission and glucose concentration in the range of 0.01–30 nmol·L−1, with a limit of detection (3S) of 4.2 nmol·L−1.
Fabrication of Cellulose Nanocrystal/Chitosan Hydrogel for Controlled Drug Release
Authors: Xu Qinghua , Ji Yunzhong , Sun Qiucun , Fu Yingjuan , Xu Yongjian , Jin Liqiang
Published: February 2019

In this work, a novel nanocomposite hydrogel based on cellulose nanocrystal (CNC) and chitosan (CS) was fabricated and applied as a carrier for the controlled delivery of theophylline. CNC was firstly periodate-oxidized to obtain dialdehyde nanocellulose (DACNC). Then, chitosan was crosslinked using DACNC as both the matrix and crosslinker in different weight ratios, to fabricate CNC/CS composites. The prepared composites were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction pattern (XRD), scanning electron microscopy (SEM), zeta potential measurement and swelling ratio tests. FT-IR results confirmed the successful reaction between the free amino groups on chitosan and the aldehyde groups on DACNC. With the increase of chitosan percentage in the hydrogel, the isoelectric point was shifted towards an alkaline pH, which was probably caused by the higher content of free amino groups. The swelling ratio of the composite also increased, which may have been due to the decrease of crosslinking density. Because the swelling ratio of the drug-loaded hydrogels differed under varied pH values, the cumulative drug release percentage of the composite hydrogel was achieved to approximately 85% and 23% in the gastric (pH 1.5) and intestinal (pH 7.4) fluids, respectively. Therefore, CNC/CS hydrogel has application potential as a theophylline carrier.
Selected Organometallic Compounds for Third Order Nonlinear Optical Application
Authors: Popczyk Anna , Aamoum Aouatif , Migalska-Zalas Anna , Płóciennik Przemyslaw , Zawadzka Anna , Mysliwiec Jaroslaw , Sahraoui Bouchta
Published: February 2019

In this paper, we present the third harmonic generation response of Znq2 (Bis-(8-hydroxyquinolinato)zinc), Cuq2 (8-Hydroxyquinoline copper(II)), and Alq3 (Tris-(8-hydroxyquinoline)aluminum) organometallic compounds. An experiment was conducted for s and p polarizations of incident beam, using the Maker fringes technique. The third order nonlinear susceptibility χ(3) was estimated using the Kubodera and Kobayashi comparative model, on the grounds that presented compounds exhibit high linear absorption of the generated third harmonic wavelength (355 nm). These complexes were deposited as thin films using the physical vapor deposition (PVD) method. Investigated complexes vary in terms of the coordination center and number of quinoline ligands, which visibly influence their nonlinear response. The global hybrid B3LYP functional with the basis set 6-31G(d) was used in computing the linear and non-linear optical properties. The computed γtot value (8765.36 × 10−36 esu for Cuq2) is superior to that of methylene blue (γ = 32.00 × 10−36 esu). The calculated theoretical values were found to be in good agreement with the experimental results.
Antibacterial Silicon Oxide Thin Films Doped with Zinc and Copper Grown by Atmospheric Pressure Plasma Chemical Vapor Deposition
Authors: Jäger Elisabeth , Schmidt Jürgen , Pfuch Andreas , Spange Sebastian , Beier Oliver , Jäger Nikolaus , Jantschner Oliver , Daniel Rostislav , Mitterer Christian
Published: February 2019

Zn-doped and Cu-doped SiOx films were synthesized by atmospheric pressure plasma chemical vapor deposition to study their antibacterial efficiency against Gram-negative Escherichia coli and their cytotoxic effect on the growth of mouse cells. Zn-rich and Cu-rich particles with diameters up to several microns were found to be homogeneously distributed within the SiOx films. For both doping elements, bacteria are killed within the first three hours after exposure to the film surface. In contrast, mouse cells grow well on the surfaces of both film types, with a slight inhibition present only after the first day of exposure. The obtained results indicate that the films show a high potential for use as effective antibacterial surfaces for medical applications.
Oil-in-Water Emulsions Stabilized by Cellulose Nanofibrils—The Effects of Ionic Strength and pH
Authors: Aaen Ragnhild , Brodin Fredrik Wernersson , Simon Sébastien , Heggset Ellinor Bævre , Syverud Kristin
Published: February 2019

Pickering o/w emulsions prepared with 40 wt % rapeseed oil were stabilized with the use of low charged enzymatically treated cellulose nanofibrils (CNFs) and highly charged 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized CNFs. The emulsion-forming abilities and storage stability of the two qualities were tested in the presence of NaCl and acetic acid, at concentrations relevant to food applications. Food emulsions may be an important future application area for CNFs due to their availability and excellent viscosifying abilities. The emulsion characterization was carried out by visual inspection, light microscopy, viscosity measurements, dynamic light scattering and mild centrifugation, which showed that stable emulsions could be obtained for both CNF qualities in the absence of salt and acid. In addition, the enzymatically stabilized CNFs were able to stabilize emulsions in the presence of acid and NaCl, with little change in the appearance or droplet size distribution over one month of storage at room temperature. The work showed that enzymatically treated CNFs could be suitable for use in food systems where NaCl and acid are present, while the more highly charged TEMPO-CNFs might be more suited for other applications, where they can contribute to a high emulsion viscosity even at low concentrations.
Complementarity of Matrix- and Nanostructure-Assisted Laser Desorption/Ionization Approaches
Authors: Pomastowski Pawel , Buszewski Boguslaw
Published: February 2019

In recent years, matrix-assisted laser desorption/ionization (MALDI) has become the main tool for the study of biological macromolecules, such as protein nano-machines, especially in the determination of their molecular masses, structure, and post-translational modifications. A key role in the classical process of desorption and ionization of the sample is played by a matrix, usually a low-molecular weight weak organic acid. Unfortunately, the interpretation of mass spectra in the mass range of below m/z 500 is difficult, and hence the analysis of low molecular weight compounds in a matrix-assisted system is an analytical challenge. Replacing the classical matrix with nanomaterials, e.g., silver nanoparticles, allows improvement of the selectivity and sensitivity of spectrometric measurement of biologically important small molecules. Nowadays, the nanostructure-assisted laser desorption/ionization (NALDI) approach complements the classic MALDI in the field of modern bioanalytics. In particular, the aim of this work is to review the recent advances in MALDI and NALDI approaches.
Overview of Human Intervention Studies Evaluating the Impact of the Mediterranean Diet on Markers of DNA Damage
Authors: Del Bo' Cristian , Marino Mirko , Martini Daniela , Tucci Massimiliano , Ciappellano Salvatore , Riso Patrizia , Porrini Marisa
Published: February 2019

The Mediterranean diet (MD) is characterized by high consumption of fruits, vegetables, cereals, potatoes, poultry, beans, nuts, lean fish, dairy products, small quantities of red meat, moderate alcohol consumption, and olive oil. Most of these foods are rich sources of bioactive compounds which may play a role in the protection of oxidative stress including DNA damage. The present review provides a summary of the evidence deriving from human intervention studies aimed at evaluating the impact of Mediterranean diet on markers of DNA damage, DNA repair, and telomere length. The few results available show a general protective effect of MD alone, or in combination with bioactive-rich foods, on DNA damage. In particular, the studies reported a reduction in the levels of 8-hydroxy-2′–deoxyguanosine and a modulation of DNA repair gene expression and telomere length. In conclusion, despite the limited literature available, the results obtained seem to support the beneficial effects of MD dietary pattern in the protection against DNA damage susceptibility. However, further well-controlled interventions are desirable in order to confirm the results obtained and provide evidence-based conclusions.
HM-Chromanone Isolated from Portulaca Oleracea L. Protects INS-1 Pancreatic β Cells against Glucotoxicity-Induced Apoptosis
Authors: Park Jae Eun , Seo Youngwan , Han Ji Sook
Published: February 2019

In this study, we investigated whether (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone, a homoisoflavonoid compound isolated from Portulaca oleracea L., protects INS-1 pancreatic β cells against glucotoxicity-induced apoptosis. Treatment with high glucose (30 mM) induced apoptosis in INS-1 pancreatic β cells; however, the level of cell viability was significantly increased by treatment with (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone. Treatment with 10–20 µM of (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone dose-dependently increased cell viability and significantly decreased the intracellular level of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide levels in INS-1 pancreatic β cells pretreated with high glucose. These effects were associated with increased anti-apoptotic Bcl-2 protein expression, while reducing pro-apoptotic Bax, cytochrome C, and caspase 9 protein expression. Treatment with (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone reduced the apoptosis previously induced by high-level glucose-treatment, according to annexin V/propidium iodide staining. These results demonstrate that (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone may be useful as a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.
Helicobacter pylori-induced DNA Methylation as an Epigenetic Modulator of Gastric Cancer: Recent Outcomes and Future Direction
Authors: Muhammad Jibran Sualeh , Eladl Mohamed Ahmed , Khoder Ghalia
Published: February 2019

Gastric cancer is ranked fifth in cancer list and has the third highest mortality rate. Helicobacter pylori is a class I carcinogen and a predominant etiological factor of gastric cancer. H. pylori infection may induce carcinogenesis via epigenetic alterations in the promoter region of various genes. H. pylori is known to induce hypermethylation-silencing of several tumor suppressor genes in H. pylori-infected cancerous and H. pylori-infected non-cancerous gastric mucosae. This article presents a review of the published literature mainly from the last year 15 years. The topic focuses on H. pylori-induced DNA methylation linked to gastric cancer development. The authors have used MeSH terms “Helicobacter pylori” with “epigenetic,” “DNA methylation,” in combination with “gastric inflammation”, gastritis” and “gastric cancer” to search SCOPUS, PubMed, Ovid, and Web of Science databases. The success of epigenetic drugs such as de-methylating agents in the treatment of certain cancers has led towards new prospects that similar approaches could also be applied against gastric cancer. However, it is very important to understand the role of all the genes that have already been linked to H. pylori-induced DNA methylation in order to in order to evaluate the potential benefits of epigenetic drugs.
Inflammation and Depression: A Nervous Plea for Psychiatry to Not Become Immune to Interpretation
Authors: Konsman Jan Pieter
Published: February 2019

The possibility that inflammation plays a causal role in major depression is an important claim in the emerging field of immunopsychiatry and has generated hope for new treatments. The aims of the present review are first to provide some historical background and to consider the evidence in favor of the claim that inflammation is causally involved in major depression. The second part discusses some of the possibilities allowed for by the use of broad ‘umbrella’ concepts, such as inflammation and stress, in terms of proposing new working hypotheses and potential mechanisms. The third part reviews proposed biomarkers of inflammation and depression and the final part addresses how elements discussed in the preceding sections are used in immunopsychiatry. The ‘umbrella’ concepts of inflammation and stress, as well as insufficiently-met criteria based inferences and reverse inferences are being used to some extent in immunopsychiatry. The field is therefore encouraged to specify concepts and constructs, as well as to consider potential alternative interpretations and explanations for findings obtained. The hope is that pointing out some of the potential problems will allow for a clearer picture of immunopsychiatry’s current strengths and limitations and help the field mature.
Multivariate Statistical Optimization of Tablet Formulations Incorporating High Doses of a Dry Herbal Extract
Authors: Oh Euichaul , Kim Uijung , Lee Beom-Jin , Moon Cheol
Published: February 2019

The development of oral tablet formulation for herbal medicines has been restricted by large drug loadings and the poor physicochemical and mechanical properties of dry herbal extracts (DHEs). Herein, statistical experimental designs were applied to herbal tablet formulation development and optimization using Wuzi Yanzong dry extract (WYE). The tablet disintegration time and hardness were identified as the critical quality attributes (CQAs) of the product. The tablet formulation was designed to achieve a high drug loading (50% or higher of WYE), shorter tablet disintegration time (less than 30 minutes), and suitable hardness (6.0 to 7.5 kp). A D-optimal mixture design was used to evaluate the effects of excipients on CQAs to minimize the risk compression failure and improve the tabletability in formulations containing WYE at 50% and 65% by weight. A partial least squares model was used to elucidate the multivariate relationships between a large number of formulation variables and product CQAs, and determine the maximum possible WYE loading. From overlaid plots of the effects of formulation variables on CQAs, it was found that a maximum WYE loading of 67% in tablet formulation satisfied the acceptance criteria of CQAs. In conclusion, this study shows that multivariate statistical tools are useful for developing tablet formulations containing high doses of herbal extracts and establishing control strategies that ensure product quality.
Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating
Authors: Chen Lu , Yang Guobao , Chu Xiaoyang , Gao Chunhong , Wang Yuli , Gong Wei , Li Zhiping , Yang Yang , Yang Meiyan , Gao Chunsheng
Published: February 2019

Phase-separated films of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be utilized to tailor drug release from coated pellets. In the present study, the effects of HPC levels and the pH, type, ionic strength and osmolarity of the media on the release profiles of soluble metoprolol succinates from the EC/HPC-coated pellets were investigated, and the differences in drug-release kinetics in multiple media were further elucidated through the HPC leaching and swelling kinetics of the pellets, morphology (SEM) and water uptake of the free films and the interaction between the coating polymers and the media compositions. Interestingly, the drug release rate from the pellets in different media was not in agreement with the drug solubility which have a positive correlation with the drug dissolution rate based on Noyes–Whitney equation law. In particular, the drug release rate in acetate buffer at pH 4.5 was faster than that in other media despite the solubility of drug was relatively lower, regardless of the HPC levels. It may be attributed to the mutual effect between the EC and acetate buffer, which improved the permeability of the film. In contrast, the release of drug in HCl solution was dependent on the HPC levels. Increasing the levels of HPC increased the effects of hydrogen ions on the polymer of HPC, which resulted in a lower viscosity and strength of the gel, forming the larger size of pores in polymer films, thus increasing the drug diffused from the coating film. Further findings in phosphate buffer showed a reduction in the drug release compared to that in other media, which was only sensitive to the osmolarity rather than the HPC level and pH of the buffer. Additionally, a mathematical theory was used to better explain and understand the experimentally measured different drug release patterns. In summary, the study revealed that the effects of the media overcompensated that of the drug solubility to some extent for controlled-release of the coating polymers, and the drug release mechanism in multiple media depend on EC and HPC rather than on HPC alone, which may have a potential to facilitate the optimization of ideally film-coated formulations.
Hydrolyzable Additive-Based Silicone Elastomers: A New Approach for Antifouling Coatings
Authors: Gevaux Laure , Lejars Marlène , Margaillan André , Briand Jean-François , Bunet Robert , Bressy Christine
Published: February 2019

Fouling Release Coatings are marine antifouling coatings based on silicone elastomers. Contrary to commonly used biocide-based antifouling coatings, they do not release biocides into the marine environment, however, they suffer from poor antifouling efficacy during idle periods. To improve their antifouling performances in static conditions, various amounts of hydrolyzable polymers were incorporated within a silicone matrix. These hydrolyzable polymers were chosen for the well-known hydrolytic degradation mechanism of their main chain, e.g. poly(ε-caprolactone) (PCL), or of their ester pending groups, e.g. poly(bis(trimethylsilyloxy)methylsilyl methacrylate) (PMATM2). The degradation kinetics of such hydrolyzable silicone coatings were assessed by mass loss measurements during immersion in deionized water. Coatings containing PMATM2 exhibited a maximum mass loss after 12 weeks, whereas PCL-based coatings showed no significant mass loss after 24 weeks. Dynamic contact angle measurements revealed the modifications of the coatings surface chemistry with an amphiphilic behavior after water exposure. The attachment of macrofoulers on these coatings were evaluated by field tests in the Mediterranean Sea, demonstrating the short or long-term antifouling effect of these hydrolyzable polymers embedded in the silicone matrix. The settlement of A. amphitrite barnacles on the different coatings indicated inhospitable behaviors towards larval barnacles for coatings with at least 15 wt % of additives.
Chemical Modification and Foam Processing of Polylactide (PLA)
Authors: Standau Tobias , Zhao Chunjing , Murillo Castellón Svenja , Bonten Christian , Altstädt Volker
Published: February 2019

Polylactide (PLA) is known as one of the most promising biopolymers as it is derived from renewable feedstock and can be biodegraded. During the last two decades, it moved more and more into the focus of scientific research and industrial use. It is even considered as a suitable replacement for standard petroleum-based polymers, such as polystyrene (PS), which can be found in a wide range of applications—amongst others in foams for packaging and insulation applications—but cause strong environmental issues. PLA has comparable mechanical properties to PS. However, the lack of melt strength is often referred to as a drawback for most foaming processes. One way to overcome this issue is the incorporation of chemical modifiers which can induce chain extension, branching, or cross-linking. As such, a wide variety of substances were studied in the literature. This work should give an overview of the most commonly used chemical modifiers and their effects on rheological, thermal, and foaming behavior. Therefore, this review article summarizes the research conducted on neat and chemically modified PLA foamed with the conventional foaming methods (i.e., batch foaming, foam extrusion, foam injection molding, and bead foaming).
K0.5Na0.5NbO3-SrTiO3/PVDF Polymer Composite Film with Low Remnant Polarization and High Discharge Energy Storage Density
Authors: Chen Chuntian , Wang Lei , Liu Xinmei , Yang Wenlong , Lin Jiaqi , Chen Gaoru , Yang Xinrui
Published: February 2019

A high recoverable energy storage density polymer composite film has been designed in which the ferroelectric-paraelectric 0.85 (K0.5Na0.5NbO3)-0.15SrTiO3 (abbreviated as KNN-ST) solid solution particles were introduced into polyvinylidene fluoride (PVDF) polymer as functional fillers. The effects of the polarization properties of K0.5Na0.5NbO3 (KNN) and KNN-ST particles on the energy storage performances of KNN-ST/PVDF film were systemically studied. And the introduction of SrTiO3 (ST) was effective in reducing the remnant polarization of the particles, improving the dielectric properties and recoverable energy storage density of the KNN-ST/PVDF films. Compared to KNN/PVDF films, the dielectric permittivity of composite films was enhanced from 17 to 38 upon the introduction of ST. A recoverable energy storage density of 1.34 J/cm3 was achieved, which is 202.60% larger than that of the KNN/PVDF composite films. The interface between the particles and the polymer matrix was considered to the enhanced dielectric permittivity of the films. And the reduced remnant polarization of the composites was regarded as the improving high recoverable energy storage density. The results demonstrated that combing ferroelectric- paraelectric particles with polymers might be a key method for composites with excellent dielectric permittivity, high energy storage density, and energy efficiency.
Hyperbranched Polycaprolactone through RAFT Polymerization of 2-Methylene-1,3-dioxepane
Authors: Xu Ping , Huang Xiaofei , Pan Xiangqiang , Li Na , Zhu Jian , Zhu Xiulin
Published: February 2019

Hyperbranched polycaprolactone with controlled structure was synthesized by reversible addition-fragmentation chain transfer radical ring-opening polymerization along with self-condensed vinyl polymerization (SCVP) of 2-methylene-1,3-dioxepane (MDO). Vinyl 2-[(ethoxycarbonothioyl) sulfanyl] propanoate (ECTVP) was used as polymerizable chain transfer agent. Living polymerization behavior was proved via pseudo linear kinetics, the molecular weight of polymers increasing with conversion and successful chain extension. The structure of polymers was characterized by 1H NMR spectroscopy, tripe detection gel permeation chromatography, and differential scanning calorimetry. The polymer composition was shown to be able to tune to vary the amount of ester repeat units in the polymer backbone, and hence determine the degree of branching. As expected, the degree of crystallinity was lower and the rate of degradation was faster in cases of increasing the number of branches.
Modeling of Miniemulsion Polymerization of Styrene with Macro-RAFT Agents to Theoretically Compare Slow Fragmentation, Ideal Exchange and Cross-Termination Cases
Authors: Devlaminck Dries J.G. , Van Steenberge Paul H.M. , Reyniers Marie-Françoise , D’hooge Dagmar R.
Published: February 2019

A 5-dimensional Smith-Ewart based model is developed to understand differences for reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerization with theoretical agents mimicking cases of slow fragmentation, cross-termination, and ideal exchange while accounting for chain length and monomer conversion dependencies due to diffusional limitations. The focus is on styrene as a monomer, a water soluble initiator, and a macro-RAFT agent to avoid exit/entry of the RAFT leaving group radical. It is shown that with a too low RAFT fragmentation rate coefficient it is generally not afforded to consider zero-one kinetics (for the related intermediate radical type) and that with significant RAFT cross-termination the dead polymer product is dominantly originating from the RAFT intermediate radical. To allow the identification of the nature of the RAFT retardation it is recommended to experimentally investigate in the future the impact of the average particle size (dp) on both the monomer conversion profile and the average polymer properties for a sufficiently broad dp range, ideally including the bulk limit. With decreasing particle size both a slow RAFT fragmentation and a fast RAFT cross-termination result in a stronger segregation and thus rate acceleration. The particle size dependency is different, allowing further differentiation based on the variation of the dispersity and end-group functionality. Significant RAFT cross-termination is specifically associated with a strong dispersity increase at higher average particle sizes. Only with an ideal exchange it is afforded in the modeling to avoid the explicit calculation of the RAFT intermediate concentration evolution.
Synthesis of an Aqueous Self-Matting Acrylic Resin with Low Gloss and High Transparency via Controlling Surface Morphology
Authors: Yong Qiwen , Liang Caizhen
Published: February 2019

This paper reports on a novel, film-forming acrylic polymer resin that exhibits low-gloss surface and high transparency via controlling film morphology at sub-micron roughness levels. Such microstructure is controlled by means of the copolymerization process increasing the allyl methacrylate (AMA) crosslinker content from 0 to 0.4 wt %. This acrylic resin makes it possible to avoid high loadings of matting agents, while also having good abrasion resistance and soft-touch feeling. Gloss levels of as low as 4 units at 60° incident angle and light transmittance of up to 85% have been achieved. The chemical structure of the aqueous acrylic resin was characterized by ATR-FTIR and NMR spectroscopy. The film morphology and surface roughness were measured by SEM and AFM analysis. The emulsion particle morphology and glass transition temperature were obtained by TEM and DSC, respectively. The effects of the crosslinker content on the light transmittance, glass transition temperature, and thermal degradation stability were also discussed in detail. The characterization results conclude that an acrylic polymer with interesting optical properties and high thermal stability can be obtained, which is desirable for leather applications.
Purification of Flavonoids from Mulberry Leaves via High-Speed Counter-Current Chromatography
Authors: Zhang Pian , Zhu Kang-Ling , Zhang Jun , Li Yan , Zhang Heng , Wang Yan
Published: February 2019

In order to obtain high-purity flavonoid products, the extracts from mulberry leaves were separated and purified via high-speed counter-current chromatography (HSCCC). Moreover, the product was detected via high-performance liquid chromatography (HPLC). The characteristic absorption wavelength of the rutin standard for HSCCC detection and HPLC analysis at 257 nm was tested by ultraviolet scanning analysis. The effect of solvent systems and mobile phase flow rate on the separation efficiency were then researched. Finally, the solvent system of V(ethyl acetate):V(n-butanol):V(water) = 4:1:5 was selected as the operating system for HSCCC. This work theoretically analyzed the impact of the molecular structure and polarity of flavonoids on the choice of solvent systems. The results showed that the mobile phase flow rate had a great influence on the separation efficiency. Furthermore, the separation efficiency increased as the mobile phase flow rate decreased. When the mobile phase flow rate was 5 mL/min, the peak time for flavonoids was 140 min, the retention of the stationary phase was 56.4%, and the purity of the product reached 93.8%. The results of this study greatly improved the purity of flavonoids in mulberry leaf and provided a strong support for the separation and purification of mulberry leaf extract.
Accelerating Biologics Manufacturing by Modeling or: Is Approval under the QbD and PAT Approaches Demanded by Authorities Acceptable without a Digital-Twin?
Authors: Zobel-Roos Steffen , Schmidt Axel , Mestmäcker Fabian , Mouellef Mourad , Huter Maximilian , Uhlenbrock Lukas , Kornecki Martin , Lohmann Lara , Ditz Reinhard , Strube Jochen
Published: February 2019

Innovative biologics, including cell therapeutics, virus-like particles, exosomes, recombinant proteins, and peptides, seem likely to substitute monoclonal antibodies as the main therapeutic entities in manufacturing over the next decades. This molecular variety causes a growing need for a general change of methods as well as mindset in the process development stage, as there are no platform processes available such as those for monoclonal antibodies. Moreover, market competitiveness demands hyper-intensified processes, including accelerated decisions toward batch or continuous operation of dedicated modular plant concepts. This indicates gaps in process comprehension, when operation windows need to be run at the edges of optimization. In this editorial, the authors review and assess potential methods and begin discussing possible solutions throughout the workflow, from process development through piloting to manufacturing operation from their point of view and experience. Especially, the state-of-the-art for modeling in red biotechnology is assessed, clarifying differences and applications of statistical, rigorous physical-chemical based models as well as cost modeling. “Digital-twins” are described and efforts vs. benefits for new applications exemplified, including the regulation-demanded QbD (quality by design) and PAT (process analytical technology) approaches towards digitalization or industry 4.0 based on advanced process control strategies. Finally, an analysis of the obstacles and possible solutions for any successful and efficient industrialization of innovative methods from process development, through piloting to manufacturing, results in some recommendations. A central question therefore requires attention: Considering that QbD and PAT have been required by authorities since 2004, can any biologic manufacturing process be approved by the regulatory agencies without being modeled by a “digital-twin” as part of the filing documentation?