bluuebunny/crossref_metadata_2025 huggingface dataset:
An Interval Two-Stage Stochastic Programming Model for Flood Resources Allocation under Ecological Benefits as a Constraint Combined with Ecological Compensation Concept
Authors: Qiu Yu , Liu Yuan , Liu Yang , Chen Yingzi , Li Yu
Published: March 2019

The Momoge National Nature Reserve (MNNR) is located at the intersection of Nenjiang and Taoer Rivers in Baicheng City, Jilin Province, where the Taoer River is the main source of water for the nature reserve. However, due to the construction of the water control project in the upper reaches of the Taoer River, the MNNR has been in a state of water shortage for a long time. To guarantee the wetland function of the nature reserve, the government planned to carry out normal and flood water supply from Nenjiang River through the West Water Supply Project of Jilin Province. Therefore, how to improve the utilization of flood resources effectively has become one of the key issues of ecological compensation for the MNNR. In this paper, a flood resources optimal allocation model that is based on the interval two-stage stochastic programming method was constructed, and the corresponding flood resource availability in different flow scenarios of Nenjiang River were included in the total water resources to improve their utilization. The results showed that the proportion of flood resources that were used in the MNNR after optimization was more than 70% under different flow scenarios, among which the proportion of flood resources under a low-flow scenario reached 77%, which was 23% higher than the proposed increase. In addition, the ecological benefits of low, medium, and high flow levels reached the range of 26.30 (106 CNY) to 32.14(106 CNY), 28.21(106 CNY) to 34.49(106 CNY) and 29.41(106 CNY) to 35.94(106 CNY), respectively. According to the results, flood resources significantly reduce the utilization of normal water resources, which can be an effective supplement to the ecological compensation of nature reserves and provide a basis for the distribution of transit flood resources in other regions.
Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli
Authors: Dreschers Stephan , Platen Christopher , Ludwig Andreas , Gille Christian , Köstlin Natascha , Orlikowsky Thorsten W.
Published: March 2019

Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.
Map-Based Cloning, Phylogenetic, and Microsynteny Analyses of ZmMs20 Gene Regulating Male Fertility in Maize
Authors: Wang Yanbo , Liu Dongcheng , Tian Youhui , Wu Suowei , An Xueli , Dong Zhenying , Zhang Simiao , Bao Jianxi , Li Ziwen , Li Jinping , Wan Xiangyuan
Published: March 2019

Genic male sterility (GMS) mutant is a useful germplasm resource for both theory research and production practice. The identification and characterization of GMS genes, and assessment of male-sterility stability of GMS mutant under different genetic backgrounds in Zea may (maize) have (1) deepened our understanding of the molecular mechanisms controlling anther and pollen development, and (2) enabled the development and efficient use of many biotechnology-based male-sterility (BMS) systems for hybrid breeding. Here, we reported a complete GMS mutant (ms20), which displays abnormal anther cuticle and pollen development. Its fertility restorer gene ZmMs20 was found to be a new allele of IPE1 encoding a glucose methanol choline (GMC) oxidoreductase involved in lipid metabolism in anther. Phylogenetic and microsynteny analyses showed that ZmMs20 was conserved among gramineous species, which provide clues for creating GMS materials in other crops. Additionally, among the 17 maize cloned GMS genes, ZmMs20 was found to be similar to the expression patterns of Ms7, Ms26, Ms6021, APV1, and IG1 genes, which will give some clues for deciphering their functional relationships in regulating male fertility. Finally, two functional markers of ZmMs20/ms20 were developed and tested for creating maize ms20 male-sterility lines in 353 genetic backgrounds, and then an artificial maintainer line of ms20 GMS mutation was created by using ZmMs20 gene, ms20 mutant, and BMS system. This work will promote our understanding of functional mechanisms of male fertility and facilitate molecular breeding of ms20 male-sterility lines for hybrid seed production in maize.
Robust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads
Authors: Mangare Caroline , Tischer-Zimmermann Sabine , Riese Sebastian B. , Dragon Anna C. , Prinz Immo , Blasczyk Rainer , Maecker-Kolhoff Britta , Eiz-Vesper Britta
Published: March 2019

Viral infections and reactivations remain a serious obstacle to successful hematopoietic stem cell transplantation (HSCT). When antiviral drug treatment fails, adoptive virus-specific T-cell transfer provides an effective alternative. Assuming that naive T cells (TN) are mainly responsible for GvHD, methods were developed to generate naive T-cell-depleted products while preserving immune memory against viral infections. We compared two major strategies to deplete potentially alloreactive T cells: CD45RA and CD62L depletion and analyzed phenotype and functionality of the resulting CD45RA−/CD62L− naive T-cell-depleted as well as CD45RA+/CD62L+ naive T-cell-enriched fractions in the CMV pp65 and IE1 antigen model. CD45RA depletion resulted in loss of terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA), and CD62L depletion in loss of central memory T cells (TCM). Based on these differences in target cell-dependent and target cell-independent assays, antigen-specific T-cell responses in CD62L-depleted fraction were consistently 3–5 fold higher than those in CD45RA-depleted fraction. Interestingly, we also observed high donor variability in the CD45RA-depleted fraction, resulting in a substantial loss of immune memory. Accordingly, we identified donors with expected response (DER) and unexpected response (DUR). Taken together, our results showed that a naive T-cell depletion method should be chosen individually, based on the immunophenotypic composition of the T-cell populations present.
Biomimetic Membranes with Transmembrane Proteins: State-of-the-Art in Transmembrane Protein Applications
Authors: Ryu Hyunil , Fuwad Ahmed , Yoon Sunhee , Jang Huisoo , Lee Jong Chan , Kim Sun Min , Jeon Tae-Joon
Published: March 2019

In biological cells, membrane proteins are the most crucial component for the maintenance of cell physiology and processes, including ion transportation, cell signaling, cell adhesion, and recognition of signal molecules. Therefore, researchers have proposed a number of membrane platforms to mimic the biological cell environment for transmembrane protein incorporation. The performance and selectivity of these transmembrane proteins based biomimetic platforms are far superior to those of traditional material platforms, but their lack of stability and scalability rule out their commercial presence. This review highlights the development of transmembrane protein-based biomimetic platforms for four major applications, which are biosensors, molecular interaction studies, energy harvesting, and water purification. We summarize the fundamental principles and recent progress in transmembrane protein biomimetic platforms for each application, discuss their limitations, and present future outlooks for industrial implementation.
The Significance of Lactoperoxidase System in Oral Health: Application and Efficacy in Oral Hygiene Products
Authors: Magacz Marcin , Kędziora Karolina , Sapa Jacek , Krzyściak Wirginia
Published: March 2019

Lactoperoxidase (LPO) present in saliva are an important element of the nonspecific immune response involved in maintaining oral health. The main role of this enzyme is to oxidize salivary thiocyanate ions (SCN−) in the presence of hydrogen peroxide (H2O2) to products that exhibit antimicrobial activity. LPO derived from bovine milk has found an application in food, cosmetics, and medical industries due to its structural and functional similarity to the human enzyme. Oral hygiene products enriched with the LPO system constitute an alternative to the classic fluoride caries prophylaxis. This review describes the physiological role of human salivary lactoperoxidase and compares the results of clinical trials and in vitro studies of LPO alone and complex dentifrices enriched with bovine LPO. The role of reactivators and inhibitors of LPO is discussed together with the possibility of using nanoparticles to increase the stabilization and activity of this enzyme.
Characterization of the High-Affinity Drug Ligand Binding Site of Mouse Recombinant TSPO
Authors: Iatmanen-Harbi Soria , Senicourt lucile , Papadopoulos Vassilios , Lequin Olivier , Lacapere Jean-Jacques
Published: March 2019

The optimization of translocator protein (TSPO) ligands for Positron Emission Tomography as well as for the modulation of neurosteroids is a critical necessity for the development of TSPO-based diagnostics and therapeutics of neuropsychiatrics and neurodegenerative disorders. Structural hints on the interaction site and ligand binding mechanism are essential for the development of efficient TSPO ligands. Recently published atomic structures of recombinant mammalian and bacterial TSPO1, bound with either the high-affinity drug ligand PK 11195 or protoporphyrin IX, have revealed the membrane protein topology and the ligand binding pocket. The ligand is surrounded by amino acids from the five transmembrane helices as well as the cytosolic loops. However, the precise mechanism of ligand binding remains unknown. Previous biochemical studies had suggested that ligand selectivity and binding was governed by these loops. We performed site-directed mutagenesis to further test this hypothesis and measured the binding affinities. We show that aromatic residues (Y34 and F100) from the cytosolic loops contribute to PK 11195 access to its binding site. Limited proteolytic digestion, circular dichroism and solution two-dimensional (2-D) NMR using selective amino acid labelling provide information on the intramolecular flexibility and conformational changes in the TSPO structure upon PK 11195 binding. We also discuss the differences in the PK 11195 binding affinities and the primary structure between TSPO (TSPO1) and its paralogous gene product TSPO2.
Medicanes Triggering Chlorophyll Increase
Authors: Kotta Dionysia , Kitsiou Dimitra
Published: March 2019

Studies have shown that hurricanes and typhoons, apart from being extreme weather phenomena, cause increases in marine chlorophyll-a concentrations and even phytoplankton blooms. Medicanes are the tropical-like Mediterranean cyclones that induce hazardous weather conditions as well. In this study, a couple of medicanes, over the central and eastern parts of the Sea, are examined for the first time in respect to their possible influence on chlorophyll concentrations. The affected area was delineated with the use of numerical model data, while the sea surface temperature and chlorophyll variations were assessed based on satellite-derived data. The results showed that medicanes trigger surface chlorophyll increases; after the cyclones’ passage, the concentrations were higher compared both with those before and with the climatological monthly values over a large part of the affected area. The mechanisms proposed to explain hurricanes’ favorable influence on chlorophyll concentration seem to be valid for medicanes as well. Area averaged chlorophyll concentrations presented analogous increases to the ones reported for hurricanes, though on a smaller scale. Despite the much lower intensity of medicanes compared with hurricanes, the observed increase in surface chlorophyll after their passage points to their favorable influence.
Mucormycosis in Burn Patients
Authors: Devauchelle Pauline , Jeanne Mathieu , Fréalle Emilie
Published: March 2019

Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, and 25 individual cases reports. The prevalence reached 0.04%–0.6%. The median age was 42–48 in the case series and outbreaks, except for the studies from military centers (23.5–32.5) and in individual reports (29.5). The median total body surface area reached 42.5%–65%. Various skin lesions were described, none being pathognomonic: the diagnosis was mainly reached because of extensive necrotic lesions sometimes associated with sepsis. Most patients were treated with systemic amphotericin B or liposomal amphotericin B, and all underwent debridement and/or amputation. Mortality reached 33%–100% in the case series, 29%–62% during outbreaks, and 40% in individual cases. Most patients were diagnosed using histopathology and/or culture. Mucorales qPCR showed detection of circulating DNA 2–24 days before the standard diagnosis. Species included the main clinically relevant mucorales (i.e., Mucor, Rhizopus, Absidia/Lichtheimia, Rhizomucor) but also more uncommon mucorales such as Saksenaea or Apophysomyces. Contact with soil was reported in most individual cases. Bandages were identified as the source of contamination in two nosocomial outbreaks.
Use of Ladle Furnace Slag and Other Industrial By-Products to Encapsulate Chloride in Municipal Solid Waste Incineration Fly Ash
Authors: Wang Ying , Ni Wen , Suraneni Prannoy
Published: March 2019

Municipal solid waste incineration fly ash (MSWIFA) is a hazardous by-product of waste incineration. The objective of this research is to encapsulate the chloride in MSWIFA and to develop a utilizable construction material using MSWIFA, ground granulated blast-furnace slag (GGBFS), ladle furnace slag (LFS), and gypsum. A secondary objective of the work is to explain the hydration and encapsulation mechanisms in this material system using isothermal calorimetry (IC), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and ion chromatography (IC). The predominant hydration products are ettringite, Friedel’s salt, and C-S-H gel, with Friedel’s salt and C-S-H dominating in systems high in LFS and ettringite and C-S-H gel dominating in systems low in LFS. The chloride encapsulation showed a strong correlation with the Friedel’s salt amount; however, some encapsulation was also likely due to physical binding in the C-S-H gel. In a system with 30% MSWIFA (by mass), the optimal amount of LFS for strength and chloride encapsulation is 20%–40% (by mass).
Short-Term Predictors for Weight Correction Success of the First Paediatric Weight Correction Programme in Children’s Clinical University Hospital in Riga
Authors: Gailite Jurgita , Apela Dana , Dzīvīte-Krišāne Iveta , Gardovska Dace
Published: March 2019

Background and objectives: The efficacy of a weight correction programme can be affected by such predictors as the number of contact hours, gender, age, baseline weight, parental weight status, psycho-emotional status, insulin resistance, and socioeconomic status. The aim of this current study was to evaluate the overall efficacy of the Weight Correction Programme at Children’s Clinical University Hospital, and explore the impact of the probable predictors. We evaluated the efficacy depending on gender, age, parental weight status, signs of depression, baseline body mass index z-score (z-BMI), and baseline waist circumference. Materials and Methods: The data were gathered from medical records. The inclusion criteria were as follows: Entered the programme by 13 June 2017, at least five years old, follow-up data available. All the respondents were divided into two age groups: <10 years old and ≥10 years old. Results: The study included 181 respondents. They were 5 to 17 years old on the first day of participation in the Weight Correction Programme. Results indicated that 117 (65%) patients managed to reduce z-BMI and 69 (38%) patients achieved clinically significant reduction of z-BMI. Boys had four times higher odds (odds ratio (OR) = 4,22; CI 1.37–13.05; p = 0.012) to reduce their z-BMI by at least 0.20 units than girls. The respondents of the older age group (≥10 years) had a better chance to reduce z-BMI than the younger ones (OR = 11,51; CI 2.04–64.83; p = 0.006). The odds to reduce z-BMI were lower by 7% for every extra cm of waist circumference (OR = 0.93; CI 0.88–0.99; p = 0.014) for reducing z-BMI. The follow-up time was also a positive predictor, and with every month the odds for clinically significant z-BMI reduction increased by 7% (OR = 1.07; CI 1.00–1.15; p = 0.047). The parental weight status, signs of depression, and baseline z-BMI were not significant predictors. Conclusions: More than half of the patients of the respondents managed to reduce their z-BMI. Female gender, younger age, and larger waist circumference were negative predictors.
Synthesis and Study of Gas Transport Properties of Polymers Based on Macroinitiators and 2,4-Toluene Diisocyanate
Authors: Davletbaeva Ilsiya , Zaripov Ilnaz , Mazilnikov Alexander , Davletbaev Ruslan , Sharifullin Raphael , Atlaskin Artem , Sazanova Tatyana , Vorotyntsev Ilya
Published: March 2019

Nowadays, block copolymers hold great promise for the design of novel membranes to be applied for the membrane gas separation. In this regard, microporous block copolymers based on a macroinitiator with an anionic nature, such as potassium-substituted block copolymers of propylene oxide and ethylene oxide (PPEG) and 2,4-toluene diisocyanate (TDI), were obtained and investigated as effective gas separation membranes. The key element of the macromolecular structure that determines the supramolecular organization of the studied polymers is the coplanar blocks of polyisocyanates with an acetal nature (O-polyisocyanate). In the present research, the influence of the content of peripheral polyoxyethylene (POE) blocks in PPEG on the supramolecular structure processes and gas transport characteristics of the obtained polymers based on PPEG and TDI was investigated. According to the study of polymers if the POE block content is 15 wt %, the polyoxypropylene segments are located in the internal cavity of voids formed by O-polyisocyanate blocks. When the POE block content is 30 wt %, the flexible chain component forms its own microphase outside the segregation zone of the rigid O-polyisocyanate blocks. The permeability for polar molecules, such as ammonia or hydrogen sulfide, significantly exceeds the permeability values obtained for non-polar molecules He, N2 and CH4. A relatively high permeability is also observed for carbon dioxide. At the same time, the content of POE blocks has a small effect on the permeability for all studied gases. The diffusion coefficient increases with an increase in the POE block content in PPEG for all studied gases.
Using Expert Driven Machine Learning to Enhance Dynamic Metabolomics Data Analysis
Authors: Beirnaert Charlie , Peeters Laura , Meysman Pieter , Bittremieux Wout , Foubert Kenn , Custers Deborah , Van der Auwera Anastasia , Cuykx Matthias , Pieters Luc , Covaci Adrian , Laukens Kris
Published: March 2019

Data analysis for metabolomics is undergoing rapid progress thanks to the proliferation of novel tools and the standardization of existing workflows. As untargeted metabolomics datasets and experiments continue to increase in size and complexity, standardized workflows are often not sufficiently sophisticated. In addition, the ground truth for untargeted metabolomics experiments is intrinsically unknown and the performance of tools is difficult to evaluate. Here, the problem of dynamic multi-class metabolomics experiments was investigated using a simulated dataset with a known ground truth. This simulated dataset was used to evaluate the performance of tinderesting, a new and intuitive tool based on gathering expert knowledge to be used in machine learning. The results were compared to EDGE, a statistical method for time series data. This paper presents three novel outcomes. The first is a way to simulate dynamic metabolomics data with a known ground truth based on ordinary differential equations. This method is made available through the MetaboLouise R package. Second, the EDGE tool, originally developed for genomics data analysis, is highly performant in analyzing dynamic case vs. control metabolomics data. Third, the tinderesting method is introduced to analyse more complex dynamic metabolomics experiments. This tool consists of a Shiny app for collecting expert knowledge, which in turn is used to train a machine learning model to emulate the decision process of the expert. This approach does not replace traditional data analysis workflows for metabolomics, but can provide additional information, improved performance or easier interpretation of results. The advantage is that the tool is agnostic to the complexity of the experiment, and thus is easier to use in advanced setups. All code for the presented analysis, MetaboLouise and tinderesting are freely available.
Serrated Chips Formation in Micro Orthogonal Cutting of Ti6Al4V Alloys with Equiaxial and Martensitic Microstructures
Authors: Zhao ZeJia , To Suet , Zhuang ZhuoXuan
Published: March 2019

The formation of serrated chips is an important feature during machining of difficult-to-cut materials, such as titanium alloy, nickel based alloy, and some steels. In this study, Ti6Al4V alloys with equiaxial and acicular martensitic microstructures were adopted to analyze the effects of material structures on the formation of serrated chips in straight line micro orthogonal machining. The martensitic alloy was obtained using highly efficient electropulsing treatment (EPT) followed by water quenching. The results showed that serrated chips could be formed on both Ti6Al4V alloys, however the chip features varied with material microstructures. The number of chip segments per unit length of the alloy with martensite was more than that of the equiaxial alloy due to poor ductility. Besides, the average cutting and thrust forces were about 8.41 and 4.53 N, respectively, for the equiaxed Ti6Al4V alloys, which were consistently lower than those with a martensitic structure. The high cutting force of martensitic alloy is because of the large yield stress required to overcome plastic deformation, and this force is also significantly affected by the orientations of the martensite. Power spectral density (PSD) analyses indicated that the characteristic frequency of cutting force variation of the equiaxed alloy ranged from 100 to 200 Hz, while it ranged from 200 to 400 Hz for workpieces with martensites, which was supposedly due to the formation of serrated chips during the machining process.
Antioxidative and Cardioprotective Effects of Schisandra chinensis Bee Pollen Extract on Isoprenaline-Induced Myocardial Infarction in Rats
Authors: Shen Zhenhuang , Geng Qianqian , Huang Haibo , Yao Hong , Du Tianyu , Chen Lifu , Wu Zhenhong , Miao Xiaoqing , Shi Peiying
Published: March 2019

Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated from S. chinensis bee pollen for the first time. This study could provide a scientific basis for using Schisandra chinensis bee pollen as a functional food for the prevention of MI.
A Comparative Study on the Effects of Different Parts of Panax ginseng on the Immune Activity of Cyclophosphamide-Induced Immunosuppressed Mice
Authors: Chen Li-xue , Qi Yu-li , Qi Zeng , Gao Kun , Gong Rui-ze , Shao Zi-jun , Liu Song-xin , Li Shan-shan , Sun Yin-shi
Published: March 2019

The objective of the present study was to compare the effects of the immunological activity of various parts (root/stem/leaf/flower/seed) of five-year-old ginseng on the immune system of immunosuppressive mice. Immunosuppression was induced by cyclophosphamide (CTX) in the mouse model, whereas levamisole hydrochloride tablet (LTH) was used for the positive control group. We found that ginseng root (GRT), ginseng leaf (GLF), and ginseng flower (GFR) could relieve immunosuppression by increased viability of NK cells, enhanced immune organ index, improved cell-mediated immune response, increased content of CD4+ and ratio of CD4+/CD8+, and recovery of macrophage function, including carbon clearance, phagocytic rate, and phagocytic index, in immunodeficient mice. However, ginseng stem (GSM) and ginseng seed (GSD) could only enhance the thymus indices, carbon clearance, splenocyte proliferation, NK cell activities, and the level of IL-4 in immunosuppressed mice. In CTX-injected mice, GRT and GFR remarkably increased the protein expression of Nrf2, HO-1, NQO1, SOD1, SOD2, and CAT in the spleen. As expected, oral administration of GRT and GFR markedly enhanced the production of cytokines, such as IL-1β, IL-4, IL-6, IFN-γ, and TNF-α, compared with the CTX-induced immunosuppressed mice, and GRT and GFR did this relatively better than GSM, GLF, and GSD. This study provides a theoretical basis for further study on different parts of ginseng.
Determination of Optical Purity of Lactic Acid-Based Chiral Liquid Crystals and Corresponding Building Blocks by Chiral High-Performance Liquid Chromatography and Supercritical Fluid Chromatography
Authors: Poryvai Anna , Vojtylová-Jurkovičová Terezia , Šmahel Michal , Kolderová Natalie , Tomášková Petra , Sýkora David , Kohout Michal
Published: March 2019

Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid state to isotropic liquid. Molecules of LCs in a mesophase still maintain the anisotropy of solid crystals, while simultaneously exhibiting the fluidity of liquids, which gives the system the ability to react immediately to external stimuli such as electric or magnetic fields, light, mechanical stress, pressure and, of course, temperature. For the proper function of LC-based devices, not only chemical, but also optical purity of materials is strongly desirable, since any impurity could be detrimental to the self-assembly of the molecules. Therefore, in this study we aimed to verify synthetic methods published in the literature, which are used nowadays to prepare chiral building blocks based on lactic acid, for their enantioselectivity. Moreover, we have focused on the development of an analytical chiral separation method for target liquid crystalline materials. Using a chiral polysaccharide-based column operated in liquid chromatography mode, we show that not all published methods of LC synthesis are enantioselective, which could lead to significant differences in the properties of the resulting materials. We show that high-performance liquid chromatography with UV detection and supercritical fluid chromatography with UV and mass spectrometry detection enable full control over the chemical and optical purity of the target LCs and the corresponding chiral building blocks. For the first time, we utilise supercritical fluid chromatography with mass detection for the direct chiral analysis of liquid crystalline materials and impurities formed during the synthesis.
Identification of Bis-Cyclic Guanidines as Antiplasmodial Compounds from Positional Scanning Mixture-Based Libraries
Authors: Perry David L. , Roberts Bracken F. , Debevec Ginamarie , Michaels Heather A. , Chakrabarti Debopam , Nefzi Adel
Published: March 2019

The screening of more than 30 million compounds derived from 81 small molecule libraries built on 81 distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one of the most active and selective antiplasmodial libraries. The screening of the positional scanning library TPI-1955 arranged on four sets of sublibraries (26 + 26 + 26 + 40), totaling 120 samples for testing provided information about the most important groups of each variable position in the TPI-1955 library containing 738,192 unique compounds. The parallel synthesis of the individual compounds derived from the deconvolution of the positional scanning library led to the identification of active selective antiplasmodial pyrrolidine bis-cyclic guanidines.
Facile Assembling of Novel 2,3,6,7,9-pentaazabicyclo- [3.3.1]nona-3,7-diene Derivatives under Microwave and Ultrasound Platforms
Authors: Al-Matar Hamad M. , Dawood Kamal M. , Tohamy Wael M. , Shalaby Mona A.
Published: March 2019

Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and microwave irradiating conditions in ethanol solvent. The structures of the isolated products were fully characterized by spectral and analytical data as well as X-ray single crystal of selected examples.
Cytinus hypocistis (L.) L. subsp. macranthus Wettst.: Nutritional Characterization
Authors: Silva Ana Rita , Fernandes Ângela , García Pablo A. , Barros Lillian , Ferreira Isabel C.F.R.
Published: March 2019

The habit of eating wild plants in Europe is often associated with times of famine; an example of such is the nectar of Cytinus hypocistis (L.) L., a parasitic plant. To the authors’ best knowledge, there are no studies on its nutritional and chemical composition; thus, the whole C. hypocistis (L.) L. subsp. macranthus Wettst. plant (CH) and its nectar (NCH) were nutritionally and chemically characterized. The proximate composition of CH and NCH were very similar in terms of energy, ash, and carbohydrate content. Protein and fat were approximately 2-fold higher in NCH, and crude fiber was 4.6-fold higher in CH compared to NCH. Fructose, glucose, sucrose, and trehalose were the free sugars present in both samples. Oxalic, malic, and citric acids were the identified organic acids in both samples, with citric acid as the most abundant molecule. For both samples, polyunsaturated and saturated fatty acids (PUFA and SFA, respectively) predominate over monounsaturated fatty acids (MUFA) due to the significant contribution of linoleic and palmitic acids, respectively. However, unsaturated fatty acids (UFA) prevail over SFA in CH and NCH. Therefore, CH proved to be an excellent source of nutritional compounds, which supports its use during past periods of scarcity.
Analysis of Enantiomers in Products of Food Interest
Authors: Fanali Chiara , D’Orazio Giovanni , Gentili Alessandra , Fanali Salvatore
Published: March 2019

The separation of enantiomers has been started in the past and continues to be a topic of great interest in various fields of research, mainly because these compounds could be involved in biological processes such as, for example, those related to human health. Great attention has been devoted to studies for the analysis of enantiomers present in food products in order to assess authenticity and safety. The separation of these compounds can be carried out utilizing analytical techniques such as gas chromatography, high-performance liquid chromatography, supercritical fluid chromatography, and other methods. The separation is performed mainly employing chromatographic columns containing particles modified with chiral selectors (CS). Among the CS used, modified polysaccharides, glycopeptide antibiotics, and cyclodextrins are currently applied.
Cocaine-Induced Reinstatement of Cocaine Seeking Provokes Changes in the Endocannabinoid and N-Acylethanolamine Levels in Rat Brain Structures
Authors: Bystrowska Beata , Frankowska Małgorzata , Smaga Irena , Niedzielska-Andres Ewa , Pomierny-Chamioło Lucyna , Filip Małgorzata
Published: March 2019

There is strong support for the role of the endocannabinoid system and the noncannabinoid lipid signaling molecules, N-acylethanolamines (NAEs), in cocaine reward and withdrawal. In the latest study, we investigated the changes in the levels of the above molecules and expression of cannabinoid receptors (CB1 and CB2) in several brain regions during cocaine-induced reinstatement in rats. By using intravenous cocaine self-administration and extinction procedures linked with yoked triad controls, we found that a priming dose of cocaine (10 mg/kg, i.p.) evoked an increase of the anadamide (AEA) level in the hippocampus and prefrontal cortex only in animals that had previously self-administered cocaine. In the same animals, the level of 2-arachidonoylglycerol (2-AG) increased in the hippocampus and nucleus accumbens. Moreover, the drug-induced relapse resulted in a potent increase in NAEs levels in the cortical areas and striatum and, at the same time, a decrease in the tissue levels of oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) was noted in the nucleus accumbens, cerebellum, and/or hippocampus. At the level of cannabinoid receptors, a priming dose of cocaine evoked either upregulation of the CB1 and CB2 receptors in the prefrontal cortex and lateral septal nuclei or downregulation of the CB1 receptors in the ventral tegmental area. In the medial globus pallidus we observed the upregulation of the CB2 receptor only after yoked chronic cocaine treatment. Our findings support that in the rat brain, the endocannabinoid system and NAEs are involved in cocaine induced-reinstatement where these molecules changed in a region-specific manner and may represent brain molecular signatures for the development of new treatments for cocaine addiction.
Phytochemical Diversity in Rhizomes of Three Reynoutria Species and their Antioxidant Activity Correlations Elucidated by LC-ESI-MS/MS Analysis
Authors: Nawrot-Hadzik Izabela , Ślusarczyk Sylwester , Granica Sebastian , Hadzik Jakub , Matkowski Adam
Published: March 2019

The rhizome of Reynoutria japonica is a well-known traditional herb (Hu zhang) used in East Asia to treat various inflammatory diseases, infections, skin diseases, scald, and hyperlipidemia. It is also one of the richest natural sources of resveratrol. Although, it has been recently included in the European Pharmacopoeia, in Europe it is still an untapped resource. Some of the therapeutic effects are likely to be influenced by its antioxidant properties and this in turn is frequently associated with a high stilbene content. However, compounds other than stilbenes may add to the total antioxidant capacity. Hence, the aim of this research was to examine rhizomes of R. japonica and the less studied but morphologically similar species, R. sachalinensis and R. x bohemica for their phytochemical composition and antioxidant activity and to clarify the relationship between the antioxidant activity and the components by statistical methods. HPLC/UV/ESI-MS studies of three Reynoutria species revealed 171 compounds, comprising stilbenes, carbohydrates, procyanidins, flavan-3-ols, anthraquinones, phenylpropanoids, lignin oligomers, hydroxycinnamic acids, naphthalenes and their derivatives. Our studies confirmed the presence of procyanidins with high degree of polymerization, up to decamers, in the rhizomes of R. japonica and provides new data on the presence of these compounds in other Reynoutria species. A procyanidin trimer digallate was described for the first time in, the studied plants. Moreover, we tentatively identified dianthrone glycosides new for these species and previously unrecorded phenylpropanoid disaccharide esters and hydroxycinnamic acid derivatives. Furthermore, compounds tentatively annotated as lignin oligomers were observed for the first time in the studied species. The rhizomes of all Reynoutria species exhibited strong antioxidant activity. Statistical analysis demonstrated that proanthocyanidins should be considered as important contributors to the total antioxidant capacity.
Compact Integration of TiO2 Nanoparticles into the Cross-Points of 3D Vertically Stacked Ag Nanowires for Plasmon-Enhanced Photocatalysis
Authors: Linh Vo Thi Nhat , Xiao Xiaofei , Jung Ho Sang , Giannini Vincenzo , Maier Stefan A. , Kim Dong-Ho , Lee Yong-Ill , Park Sung-Gyu
Published: March 2019

The compact integration of semiconductor TiO2 nanoparticles (NPs) into the 3D crossed region of stacked plasmonic Ag nanowires (NWs) enhanced the photocatalytic activities through synergistic effects between the strong localized surface plasmon resonance (LSPR) excitation at the 3D cross-points of the Ag NWs and the efficient hot electron transfer at the interface between the Ag NWs and the TiO2 NPs. This paper explored new hybrid nanostructures based on the selective assembly of TiO2 NPs onto 3D cross-points of vertically stacked Ag NWs. The assembled TiO2 NPs directly contacted the 3D Ag NWs; therefore, charge separation occurred efficiently at the interface between the Ag NWs and the TiO2 NPs. The composite nanomaterials exhibited high extinction across the ultraviolet-visible range, rendering the nanomaterials high-performance photocatalysts across the full (ultraviolet-visible) and the visible spectral regions. Theoretical simulations clearly revealed that the local plasmonic field was highly enhanced at the 3D crossed regions of the vertically stacked Ag NWs. A Raman spectroscopic analysis of probe dye molecules under photodegradation conditions clearly revealed that the nanogap in the 3D crossed region was crucial for facilitating plasmon-enhanced photocatalysis and plasmon-enhanced spectroscopy.
Interaction between Persistent Organic Pollutants and ZnO NPs in Synthetic and Natural Waters
Authors: Khan Rizwan , Inam Muhammad Ali , Khan Sarfaraz , Park Du Ri , Yeom Ick Tae
Published: March 2019

The use of zinc oxide nanoparticles (ZnO NPs) and polybrominated diphenyl ethers (PBDPEs) in different products and applications leads to the likelihood of their co-occurrence in the aquatic system, making it important to study the effect of PBDPEs on the fate and transport of ZnO NPs. In this study, we determine the influence of PBDPEs (BDPE-47 and BDPE-209) on the colloidal stability and physicochemical properties of ZnO NPs in different aqueous matrices. The results indicated the shift in ζ potential of ZnO NP from positive to negative in the presence of both PBDPEs in all tested waters; however, the effect on the NPs surface potential was specific to each water considered. The lower concentration of the PBDPEs (e.g., 0.5 mg/L) significantly reduced the ζ potential and hydrodynamic diameter (HDD) of ZnO NP, even in the presence of high content of dissolved organic matter (DOM) in both freshwater and industrial wastewater. Moreover, both BDPE-47 and BDPE-209 impede the agglomeration of ZnO NP in simple and natural media, even in the presence of monovalent and polyvalent cations. However, the effect of BDPE-47 on the ζ potential, HDD, and agglomeration of ZnO NP was more pronounced than that of BDPE-209 in all tested waters. The results of Fourier transform infrared (FT-IR) and X-ray Photon Spectroscopy (XPS) further confirm the adsorption of PBDPEs onto ZnO NP surface via aromatic ether groups and Br elements. The findings of this study will facilitate a better understanding of the interaction behavior between the ZnO NPs and PBDPEs, which can reduce the exposure risk of aquatic organisms to both pollutants.
Localization of 99mTc-GRP Analogs in GRPR-Expressing Tumors: Effects of Peptide Length and Neprilysin Inhibition on Biological Responses
Authors: Kaloudi Aikaterini , Lymperis Emmanouil , Kanellopoulos Panagiotis , Waser Beatrice , de Jong Marion , Krenning Eric P. , Reubi Jean Claude , Nock Berthold A. , Maina Theodosia
Published: March 2019

The overexpression of gastrin-releasing peptide receptors (GRPRs) in frequently occurring human tumors has provided the opportunity to use bombesin (BBN) analogs as radionuclide carriers to cancer sites for diagnostic and therapeutic purposes. We have been alternatively exploring human GRP motifs of higher GRPR selectivity compared to frog BBN sequences aiming to improve pharmacokinetic profiles. In the present study, we compared two differently truncated human endogenous GRP motifs: GRP(14–27) and GRP(18–27). An acyclic tetraamine was coupled at the N-terminus to allow for stable binding of the SPECT radionuclide 99mTc. Their biological profiles were compared in PC-3 cells and in mice without or with coinjection of phosphoramidon (PA) to induce transient neprilysin (NEP) inhibition in vivo. The two 99mTc-N4-GRP(14/18–27) radioligands displayed similar biological behavior in mice. Coinjection of PA exerted a profound effect on in vivo stability and translated into notably improved radiolabel localization in PC-3 experimental tumors. Hence, this study has shown that promising 99mTc-radiotracers for SPECT imaging may indeed derive from human GRP sequences. Radiotracer bioavailability was found to be of major significance. It could be improved during in situ NEP inhibition resulting in drastically enhanced uptake in GRPR-expressing lesions.
In Vitro Enhanced Skin Permeation and Retention of Imiquimod Loaded in β-Cyclodextrin Nanosponge Hydrogel
Authors: Argenziano Monica , Haimhoffer Adam , Bastiancich Chiara , Jicsinszky László , Caldera Fabrizio , Trotta Francesco , Scutera Sara , Alotto Daniela , Fumagalli Mara , Musso Tiziana , Castagnoli Carlotta , Cavalli Roberta
Published: March 2019

Imiquimod (IMQ) is an immune response modifier clinically used for the treatment of various topical diseases. However, its poor aqueous solubility and skin penetration capability make the topical delivery of IMQ a challenging task. This work aims at developing a nanomedicine-based topical formulation, carrying IMQ to control the scarring process for the treatment of aberrant wounds. For this purpose, IMQ was loaded in β-cyclodextrin-based nanosponges and dispersed in a hydrogel suitable for dermal application. The formulation was characterized in vitro and compared with IMQ inclusion complexes, with (2-hydroxy)propyl β-cyclodextrin(HPβCD) and carboxymethyl β-cyclodextrin (CMβCD) showing enhanced penetration properties. The hydrogel containing IMQ-loaded nanosponges could act as a drug reservoir and guarantee the sustained release of IMQ through the skin. A greater inhibitory effect on fibroblast proliferation was observed for IMQ loaded in nanosponges compared to the other formulations.
Accelerating Biologics Manufacturing by Upstream Process Modelling
Authors: Kornecki Martin , Strube Jochen
Published: March 2019

Intensified and accelerated development processes are being demanded by the market, as innovative biopharmaceuticals such as virus-like particles, exosomes, cell and gene therapy, as well as recombinant proteins and peptides will possess no available platform approach. Therefore, methods that are able to accelerate this development are preferred. Especially, physicochemical rigorous process models, based on all relevant effects of fluid dynamics, phase equilibrium, and mass transfer, can be predictive, if the model is verified and distinctly quantitatively validated. In this approach, a macroscopic kinetic model based on Monod kinetics for mammalian cell cultivation is developed and verified according to a general valid model validation workflow. The macroscopic model is verified and validated on the basis of four decision criteria (plausibility, sensitivity, accuracy and precision as well as equality). The process model workflow is subjected to a case study, comprising a Chinese hamster ovary fed-batch cultivation for the production of a monoclonal antibody. By performing the workflow, it was found that, based on design of experiments and Monte Carlo simulation, the maximum growth rate µmax exhibited the greatest influence on model variables such as viable cell concentration XV and product concentration. In addition, partial least squares regressions statistically evaluate the correlations between a higher µmax and a higher cell and product concentration, as well as a higher substrate consumption.