bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Beneficial and Inhibiting Undesirable Biofilm Formation with Mangrove Extracts
Authors: Glasenapp Yvana , Cattò Cristina , Villa Federica , Saracchi Marco , Cappitelli Francesca , Papenbrock Jutta
Published: July 2019

The extracts of two mangrove species, Bruguiera cylindrica and Laguncularia racemosa, have been analyzed at sub-lethal concentrations for their potential to modulate biofilm cycles (i.e., adhesion, maturation, and detachment) on a bacterium, yeast, and filamentous fungus. Methanolic leaf extracts were also characterized, and MS/MS analysis has been used to identify the major compounds. In this study, we showed the following. (i) Adhesion was reduced up to 85.4% in all the models except for E. coli, where adhesion was promoted up to 5.10-fold. (ii) Both the sum and ratio of extracellular polysaccharides and proteins in mature biofilm were increased up to 2.5-fold and 2.6-fold in comparison to the negative control, respectively. Additionally, a shift toward a major production of exopolysaccharides was found coupled with a major production of both intracellular and extracellular reactive oxygen species. (iii) Lastly, detachment was generally promoted. In general, the L. racemosa extract had a higher bioactivity at lower concentrations than the B. cylindrica extract. Overall, our data showed a reduction in cells/conidia adhesion under B. cylindrica and L. racemosa exposure, followed by an increase of exopolysaccharides during biofilm maturation and a variable effect on biofilm dispersal. In conclusion, extracts either inhibited or enhanced biofilm development, and this effect depended on both the microbial taxon and biofilm formation step.
Elucidation of the Molecular Mechanism Underlying Lippia citriodora(Lim.)-Induced Relaxation and Anti-Depression
Authors: Sabti Mouad , Sasaki Kazunori , Gadhi Chemseddoha , Isoda Hiroko
Published: July 2019

Lippia citriodora ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and Vs in vivo and in vitro, on human neurotypic SH-SY5Y cells.TST was conducted on mice treated orally with VEE (25, 50 and 100 mg/Kg), Vs (2.5 and 5 mg/Kg), Bupropion (20 mg/Kg) and Milli-Q water. Higher dose of VEE-treated mice showed an increase of immobility time compared to control groups, indicating an induction of relaxation. This effect was found to be induced by regulation of genes playing key roles in calcium homeostasis (calcium channels), cyclic AMP (cAMP) production and energy metabolism. On the other hand, low doses of VEE and Vs showed an antidepressant-like effect and was confirmed by serotonin, noradrenalin, dopamine and BDNF expressions. Finally, VEE and Vsenhancedcell viability, mitochondrial activity and calcium uptake in vitro confirming in vivo findings. Our results showed induction of relaxation and antidepressant-like effects depending on the administered dose of VEE and Vs, through modulation of cAMP and calcium.
Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database
Authors: Bolcato Giovanni , Cuzzolin Alberto , Bissaro Maicol , Moro Stefano , Sturlese Mattia
Published: July 2019

The number of entries in the Protein Data Bank (PDB) has doubled in the last decade, and it has increased tenfold in the last twenty years. The availability of an ever-growing number of structures is having a huge impact on the Structure-Based Drug Discovery (SBDD), allowing investigation of new targets and giving the possibility to have multiple structures of the same macromolecule in a complex with different ligands. Such a large resource often implies the choice of the most suitable complex for molecular docking calculation, and this task is complicated by the plethora of possible posing and scoring function algorithms available, which may influence the quality of the outcomes. Here, we report a large benchmark performed on the PDBbind database containing more than four thousand entries and seventeen popular docking protocols. We found that, even in protein families wherein docking protocols generally showed acceptable results, certain ligand-protein complexes are poorly reproduced in the self-docking procedure. Such a trend in certain protein families is more pronounced, and this underlines the importance in identification of a suitable protein–ligand conformation coupled to a well-performing docking protocol.
Alteration of Sphingolipids in Biofluids: Implications for Neurodegenerative Diseases
Authors: Pujol-Lereis Luciana M.
Published: July 2019

Sphingolipids (SL) modulate several cellular processes including cell death, proliferation and autophagy. The conversion of sphingomyelin (SM) to ceramide and the balance between ceramide and sphingosine-1-phosphate (S1P), also known as the SL rheostat, have been associated with oxidative stress and neurodegeneration. Research in the last decade has focused on the possibility of targeting the SL metabolism as a therapeutic option; and SL levels in biofluids, including serum, plasma, and cerebrospinal fluid (CSF), have been measured in several neurodegenerative diseases with the aim of finding a diagnostic or prognostic marker. Previous reviews focused on results from diseases such as Alzheimer’s Disease (AD), evaluated total SL or species levels in human biofluids, post-mortem tissues and/or animal models. However, a comprehensive review of SL alterations comparing results from several neurodegenerative diseases is lacking. The present work compiles data from circulating sphingolipidomic studies and attempts to elucidate a possible connection between certain SL species and neurodegeneration processes. Furthermore, the effects of ceramide species according to their acyl-chain length in cellular pathways such as apoptosis and proliferation are discussed in order to understand the impact of the level alteration in specific species. Finally, enzymatic regulations and the possible influence of insulin resistance in the level alteration of SL are evaluated.
Non-Cytotoxic Agarose/Hydroxyapatite Composite Scaffolds for Drug Release
Authors: Witzler Markus , Ottensmeyer Patrick Frank , Gericke Martin , Heinze Thomas , Tobiasch Edda , Schulze Margit
Published: July 2019

Healing of large bone defects requires implants or scaffolds that provide structural guidance for cell growth, differentiation, and vascularization. In the present work, an agarose-hydroxyapatite composite scaffold was developed that acts not only as a 3D matrix, but also as a release system. Hydroxyapatite (HA) was incorporated into the agarose gels in situ in various ratios by a simple procedure consisting of precipitation, cooling, washing, and drying. The resulting gels were characterized regarding composition, porosity, mechanical properties, and biocompatibility. A pure phase of carbonated HA was identified in the scaffolds, which had pore sizes of up to several hundred micrometers. Mechanical testing revealed elastic moduli of up to 2.8 MPa for lyophilized composites. MTT testing on Lw35human mesenchymal stem cells (hMSCs) and osteosarcoma MG-63 cells proved the biocompatibility of the scaffolds. Furthermore, scaffolds were loaded with model drug compounds for guided hMSC differentiation. Different release kinetic models were evaluated for adenosine 5′-triphosphate (ATP) and suramin, and data showed a sustained release behavior over four days.
Highly Efficient and Stable Removal of Arsenic by Live Cell Fabricated Magnetic Nanoparticles
Authors: Kim Hyo Kyeong , Jeong Sun-Wook , Yang Jung Eun , Choi Yong Jun
Published: July 2019

As concerns about public health and environmental problems regarding contamination by toxic substances increase worldwide, the development of a highly effective and specific treatment method is imperative. Although physicochemical arsenic treatment methods have been developed, microbial in vivo remediation processes using live cell fabricated nanoparticles have not yet been reported. Herein, we report the development of magnetic iron nanoparticles immobilized an extremophilic microorganism, Deinococcus radiodurans R1, capable of removing toxic arsenic species. First, in vivo synthesis of magnetic iron nanoparticles was successfully achieved with the D. radiodurans R1 strain and characterized by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), dynamic light scattering (DLS), zeta-potential, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis. Second, the maximum removal capacity of the magnetic iron nanoparticle-immobilized D. radiodurans R1 strain (DR-FeNPs) for arsenic [As(V)] was evaluated under the optimized conditions. Finally, the removal capacity of DR-FeNPs in the presence of various competitive anions was also investigated to simulate the practical application. More than 98% of As(V) was efficiently removed by DR-FeNPs within 1 h, and the removal efficiency was stably maintained for up to 32 h (98.97%). Furthermore, the possibility of recovery of DR-FeNPs after use was also suggested using magnets as a proof-of-concept.
Identification of Jasmonic Acid Biosynthetic Genes in Sweet Cherry and Expression Analysis in Four Ancient Varieties from Tuscany
Authors: Berni Roberto , Cai Giampiero , Xu Xuan , Hausman Jean-Francois , Guerriero Gea
Published: July 2019

Sweet cherries are non-climacteric fruits whose early development is characterized by high levels of the phytohormone jasmonic acid (JA). Important parameters, such as firmness and susceptibility to cracking, can be affected by pre- and postharvest treatments of sweet cherries with JA. Despite the impact of JA on sweet cherry development and fruit characteristics, there are no studies (to the best of our knowledge) identifying the genes involved in the JA biosynthetic pathway in this species. We herein identify the sweet cherry members of the lipoxygenase family (13-LOX); allene oxide synthase, allene oxide cyclase and 12-oxo-phytodienoic acid reductase 3, as well as genes encoding the transcriptional master regulator MYC2. We analyze their expression pattern in four non-commercial Tuscan varieties (‘Carlotta’, ‘Maggiola’, ‘Morellona’, ‘Crognola’) having different levels of bioactives (namely phenolics). The highest differences are found in two genes encoding 13-LOX in the variety ‘Maggiola’ and one MYC2 isoform in ‘Morellona’. No statistically-significant variations are instead present in the allene oxide synthase, allene oxide cyclase and 12-oxo-phytodienoic acid reductase 3. Our data pave the way to follow-up studies on the JA signaling pathway in these ancient varieties, for example in relation to development and post-harvest storage.
Targeting HIV/HCV Coinfection Using a Machine Learning-Based Multiple Quantitative Structure-Activity Relationships (Multiple QSAR) Method
Authors: Wei Yu , Li Wei , Du Tengfei , Hong Zhangyong , Lin Jianping
Published: July 2019

Human immunodeficiency virus type-1 and hepatitis C virus (HIV/HCV) coinfection occurs when a patient is simultaneously infected with both human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV), which is common today in certain populations. However, the treatment of coinfection is a challenge because of the special considerations needed to ensure hepatic safety and avoid drug–drug interactions. Multitarget inhibitors with less toxicity may provide a promising therapeutic strategy for HIV/HCV coinfection. However, the identification of one molecule that acts on multiple targets simultaneously by experimental evaluation is costly and time-consuming. In silico target prediction tools provide more opportunities for the development of multitarget inhibitors. In this study, by combining Naïve Bayes (NB) and support vector machine (SVM) algorithms with two types of molecular fingerprints, MACCS and extended connectivity fingerprints 6 (ECFP6), 60 classification models were constructed to predict compounds that were active against 11 HIV-1 targets and four HCV targets based on a multiple quantitative structure–activity relationships (multiple QSAR) method. Five-fold cross-validation and test set validation were performed to measure the performance of the 60 classification models. Our results show that the 60 multiple QSAR models appeared to have high classification accuracy in terms of the area under the ROC curve (AUC) values, which ranged from 0.83 to 1 with a mean value of 0.97 for the HIV-1 models and from 0.84 to 1 with a mean value of 0.96 for the HCV models. Furthermore, the 60 models were used to comprehensively predict the potential targets of an additional 46 compounds, including 27 approved HIV-1 drugs, 10 approved HCV drugs and nine selected compounds known to be active against one or more targets of HIV-1 or HCV. Finally, 20 hits, including seven approved HIV-1 drugs, four approved HCV drugs, and nine other compounds, were predicted to be HIV/HCV coinfection multitarget inhibitors. The reported bioactivity data confirmed that seven out of nine compounds actually interacted with HIV-1 and HCV targets simultaneously with diverse binding affinities. The remaining predicted hits and chemical-protein interaction pairs with the potential ability to suppress HIV/HCV coinfection are worthy of further experimental investigation. This investigation shows that the multiple QSAR method is useful in predicting chemical-protein interactions for the discovery of multitarget inhibitors and provides a unique strategy for the treatment of HIV/HCV coinfection.
The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders
Authors: Jo-Watanabe Airi , Okuno Toshiaki , Yokomizo Takehiko
Published: July 2019

Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes the biology of LTs and their receptors, recent developments in the area of anti-LT strategies (in settings such as ongoing clinical studies), and prospects for future therapeutic applications.
Study on the Softening Mechanism and Control of Red-Bed Soft Rock under Seawater Conditions
Authors: Liu Zhen , He Xinfu , Fan Jin , Zhou Cuiying
Published: July 2019

Red-bed soft rock easily softens and disintegrates when it comes into contact with water, which is the main factor restricting the application of soft rock as an engineering filler. Therefore, research on the influence of seawater on soft rock softening has great significance for the application of soft rock in marine engineering. To examine the softening mechanism of soft rock under seawater conditions, two kinds of soft rock softening experiments, as well as ion inhibition tests of soft rock softening, were performed under seawater and pure water conditions, and the results were compared. The variation in the soft rock composition, the deformation and failure characteristics of soft rock under the influence of sea water, and the variation in main cations in the softening process of soft rock are examined successively; the influences of different ions on soft rock softening are further analysed. Based on the analyses, the softening mechanism and control method of soft rock under sea water conditions are expounded. The study showed that soft rock softening was inhibited by seawater, which decreased the softening degree of soft rock. The main cations in seawater had an inhibitory effect on soft rock softening, and the order of inhibition was Ca2+ > Mg2+ > Na+. According to the inhibitory effect of ions on soft rock softening, we propose that seawater or calcium salt should be added to reduce the softening of soft rock in soft rock engineering and improve the mechanical strength of soft rock; in addition, soft rock can be considered a raw material in marine engineering. The experimental results have great significance for studies of the disintegration mechanism and inhibitory rules of soft rock under the influence of seawater and provide a theoretical basis for the application of soft rock in marine engineering, such as in artificial reef engineering and coastal dike engineering.
Experimental Study for Wave-Induced Pore-Water Pressures in a Porous Seabed around a Mono-Pile
Authors: Wang Shaohua , Wang Pandi , Zhai Hualing , Zhang Qibo , Chen Linya , Duan Lunliang , Liu Yifei , Jeng Dong-Sheng
Published: July 2019

In this paper, the results of a series of experiments on wave-induced pore-water pressures around a mono-pile are presented. Unlike the previous study, in which the mono-pile was fully buried, the mono-pile in this study was installed at 0.6 m below the seabed surface. In this study, we focus on the pore-water pressures around the mono-pile and beneath the pile. The experimental results lead to the following conclusions: (1) the seabed response is more pronounced near the surface (in the region above 30 cm deep), and the rate of pore pressure attenuation gradually slows down. For the region below 0.3 m, the response is much smaller; (2) in general, along the surface of the pile, pore pressures increase as the wave height and wave period increase; (3) the spatial distribution of pore pressure near the pile will vary with different wave periods, while the wave height only has a significant effect on the amplitude; and (4) At z = −0.15 m, the pore pressure in front of the pile is the largest, while at the point 0.1 m below the bottom of the pile, the largest pore pressure occurs behind the pile.
“Arguments That Could Possibly Be Urged”: Modal Verbs and Tentativeness in the Coruña Corpus
Authors: Moskowich Isabel , Crespo Begoña
Published: July 2019

This paper complements previous research into the late Modern English scientific writing uses of the adverbs possibly and perhaps as manifestations of either subjectivity or intersubjectivity, as presented in the Coruña Corpus of English Scientific Writing. In order to have a better understanding of the uses of these adverbs as markers of tentativeness, we will explore their syntagmatic relations with modal verbs. It is widely assumed that scientific discourse has an objective nature, although it has been questioned by its use of hedging and other expressions of stance. In the present study, we will assess how modal verbs accompanying these stance adverbs modulate the expression of tentativeness. The use of stance adverbs shows authorial presence and a covert interaction with the reader. The paper examines different degrees of hesitancy depending on the type of modal verb accompanying these adverbs. The analysis has been carried out on four subcorpora of the Coruña Corpus of English Scientific Writing. Our findings will be presented from a more general to a more detailed account for each of the forms under investigation and interpreted taking into account the variables ‘date of publication’ and ‘genre’ for the text, and ‘sex’ for the author.
Effect of Layer Charge Characteristics on the Distribution Characteristics of H2O and Ca2+ in Ca-Montmorillonites Interlayer Space: Molecular Dynamics Simulation
Authors: Qiu Jun , Li Guoqing , Liu Dongliang , Jiang Shan , Wang Guifang , Chen Ping , Zhu Xiangnan , Cao Xiaoqiang , Lyu Xianjun
Published: July 2019

The charge characteristics of montmorillonite have significant effects on its hydration and application performances. In this study, a molecular dynamics simulation method was used to study the influence of the charge position and charge density of montmorillonite on the distribution of H2O and Ca2+ in layers. The results showed that when the layer charge is mainly derived from the substitution among ions in the tetrahedron, a large number of Hw and Ot are combined into a hydrogen bond in the interlayer, thus the water molecules are more compactly arranged and the diffusion of water molecules among the layers is reduced. In addition, the Ca2+ are diffused to the sides by a concentrated distribution in the central axis of the layer. As the charge density of the montmorillonite increases, the polarity of the Si–O surface increases, which lesds to the deterioration of the diffusibility of the water molecules and the structure of the water molecules in the interlayers is more stable. The increase in the layer charge density lesds to the expansion of the isomorphic substitution range of the crystal structure, which results in a more dispersed distribution of Ca2+ among the layers under the action of electrostatic attraction between the substituted negative sites and the Ca2+.
Softening Effect on Fracture Stress of Pure Copper Processed by Asynchronous Foil Rolling
Authors: Chen Jingqi , Hu Xianlei , Liu Xianghua
Published: July 2019

In order to study the size effect on the mechanical property of micro-scale metal, pure copper strips with thicknesses in the range of 20 µm to 600 µm were obtained through the asynchronous foil rolling technology. Progressive mechanical property tests indicated that the pure copper experiences softening effect at a micro-scale when the thickness is below 80 µm, which is contrary to the traditional work hardening theory. The related mechanisms were analyzed and discussed through the observation of microstructure and fracture morphology. The decrease of fracture stress with the decrease of thickness can be attributed to the decreased interfacial energy and dislocation density, which contributes to the release of the cumulative distortion energy and the tendency to soften. In addition, the distribution of misorientation angle and changed Taylor factor with the decrease of thickness are other important factors. The fracture morphology indicated a reduction in the number of micro-voids and the nature of fracture transformed from dimpled pattern to knife edge rupture with thickness. The traditional Hall-Petch relationship is no longer applicable due to the softening effect. A modified Hall-Petch relation considering the distribution of misorientation angle and Taylor factor was established, which provided a better relationship between flow stress and grain size.
Engineering of Chitosan-Hydroxyapatite-Magnetite Hierarchical Scaffolds for Guided Bone Growth
Authors: Pistone Alessandro , Iannazzo Daniela , Celesti Consuelo , Piperopoulos Elpida , Ashok Deepu , Cembran Arianna , Tricoli Antonio , Nisbet David
Published: July 2019

Bioabsorbable materials have received increasing attention as innovative systems for the development of osteoconductive biomaterials for bone tissue engineering. In this paper, chitosan-based composites were synthesized adding hydroxyapatite and/or magnetite in a chitosan matrix by in situ precipitation technique. Composites were characterized by optical and electron microscopy, thermogravimetric analyses (TGA), x-ray diffraction (XRD), and in vitro cell culture studies. Hydroxyapatite and magnetite were found to be homogeneously dispersed in the chitosan matrix and the composites showed superior biocompatibility and the ability to support cell attachment and proliferation; in particular, the chitosan/hydroxyapatite/magnetite composite (CS/HA/MGN) demonstrated superior bioactivity with respect to pure chitosan (CS) and to the chitosan/hydroxyapatite (CS/HA) scaffolds.
Effects of Stress on Phase Transformations in Grinding by FE Modeling and Experimental Approaches
Authors: Xiu Shichao , Deng Yansheng , Kong Xiangna
Published: July 2019

In the grinding process, the materials within the surface layer may undergo phase transformation and finally form a strengthened layer. It is of great significance to model the phase transformation and predict the characteristics of the strengthened layer accurately. The phase transformations occur under the varying temperature and high stress–strain in grinding, so the effects of stress on the transformations are inescapable. This paper focuses on revealing the effects of stress on phase transformations in grinding. For this purpose, a thermal–mechanical–metallurgical direct coupling finite element (FE) model of grinding was established in Abaqus. The coupling interactions such as the latent heat, the volume change strain caused by phase transformation, and the stress-induced phase transformation were considered in the modeling procedure. Grinding experiments were carried out and proved the model could accurately predict the microstructure distribution and thickness of the strengthened layer. Further, the evolution of the phase transformation was discussed, and the effects of stress on the transformations were revealed.
Marked Enhancement of Roll-Off Frequency in FeCoN Synthetic Antiferromagnetic Films Deposited by Oblique Incidence
Authors: Zhang Luran , Gao Dandan , Liu Huan , Xie Jiyang , Hu Wanbiao
Published: July 2019

A series of FeCoN films were successfully deposited on glass substrates in a magnetron sputtering system. Using oblique incidence method and FeCoN/Ru/FeCoN synthetic antiferromagnetic (SAF) structure, two additional anisotropies energy were introduced: oblique incidence anisotropy and exchange anisotropy energy, which marked enhancement of the effective magnetic anisotropy (Hk). The increment of Hk results in a significant improvement in the roll-off frequency of these films. The roll-off frequency of FeCoN/Ru/FeCoN films with SAF structure can reach up to 8.6 GHz. A feasible approach to conveniently controlling Hk of soft magnetic thin films by using oblique deposition and SAF structure can further improve their properties for the potential applications in the high frequency region.
Statistical Tests for Extreme Precipitation Volumes
Authors: Korolev Victor , Gorshenin Andrey , Belyaev Konstatin
Published: July 2019

The analysis of the real observations of precipitation based on the novel statistical approach using the negative binomial distribution as a model for describing the random duration of a wet period is considered and discussed. The study shows that this distribution fits very well to the real observations and generalized standard methods used in meteorology to detect an extreme volume of precipitation. It also provides a theoretical base for the determination of asymptotic approximations to the distributions of the maximum daily precipitation volume within a wet period, as well as the total precipitation volume over a wet period. The paper demonstrates that the relation of the unique precipitation volume, having the gamma distribution, divided by the total precipitation volume taken over the wet period is given by the Snedecor–Fisher or beta distributions. It allows us to construct statistical tests to determine the extreme precipitations. Within this approach, it is possible to introduce the notions of relatively and absolutely extreme precipitation volumes. An alternative method to determine an extreme daily precipitation volume based on a certain quantile of the tempered Snedecor–Fisher distribution is also suggested. The results of the application of these methods to real data are presented.
Functions of Minimal Norm with the Given Set of Fourier Coefficients
Authors: Ivanshin Pyotr
Published: July 2019

We prove the existence and uniqueness of the solution of the problem of the minimum norm function ∥ · ∥ ∞ with a given set of initial coefficients of the trigonometric Fourier series c j , j = 0 , 1 , … , 2 n . Then, we prove the existence and uniqueness of the solution of the nonnegative function problem with a given set of coefficients of the trigonometric Fourier series c j , j = 1 , … , 2 n for the norm ∥ · ∥ 1 .
Existence of Positive Solutions to Singular Boundary Value Problems Involving φ-Laplacian
Authors: Jeong Jeongmi , Kim Chan-Gyun
Published: July 2019

This paper is concerned with the existence of positive solutions to singular Dirichlet boundary value problems involving φ -Laplacian. For non-negative nonlinearity f = f ( t , s ) satisfying f ( t , 0 ) ≢ 0 , the existence of an unbounded solution component is shown. By investigating the shape of the component depending on the behavior of f at ∞ , the existence, nonexistence and multiplicity of positive solutions are studied.
Mycousfurans A and B, Antibacterial Usnic Acid Congeners from the Fungus Mycosphaerella sp., Isolated from a Marine Sediment
Authors: Lee Jihye , Lee Jusung , Kim Geum Jin , Yang Inho , Wang Weihong , Nam Joo-Won , Choi Hyukjae , Nam Sang-Jip , Kang Heonjoong
Published: July 2019

Mycousfurans (1 and 2), two new usnic acid congeners, along with (−)-mycousnine (3), (−)-placodiolic acid (4), and (+)-usnic acid (5), were isolated using high-performance liquid chromatography-ultraviolet (HPLC-UV)-guided fractionation of extracts of Mycosphaerella sp. isolated from a marine sediment. The planar structures of 1 and 2 were elucidated using 1D and 2D NMR spectra. The relative configurations of the stereogenic carbons of 1 and 2 were established via analysis of their nuclear Overhauser spectroscopy (NOESY) spectra, and their absolute configurations were determined using a comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1 and 2 were found to have antibacterial activity, showing moderate activity against Kocuria rhizophila and Staphylococcus aureus.
Engineering Synthetic Microbial Communities through a Selective Biofilm Cultivation Device for the Production of Fermented Beverages
Authors: Ly Sokny , Bajoul Kakahi F. , Mith Hasika , Phat Chanvorleak , Fifani Barbara , Kenne Tierry , Fauconnier Marie-Laure , Delvigne Frank
Published: July 2019

Production of Cambodian rice wine involves complex microbial consortia. Indeed, previous studies focused on traditional microbial starters used for this product revealed that three microbial strains with complementary metabolic activities are required for an effective fermentation, i.e., filamentous fungi (Rhizopus oryzae), yeast (Saccharomyces cerevisiae), and lactic acid bacteria (Lactobacillus plantarum). Modulating the ratio between these three key players led to significant differences, not only in terms of ethanol and organic acid production, but also on the profile of volatile compounds, in comparison with natural communities. However, we observed that using an equal ratio of spores/cells of the three microbial strains during inoculation led to flavor profile and ethanol yield close to that obtained through the use of natural communities. Compartmentalization of metabolic tasks through the use of a biofilm cultivation device allows further improvement of the whole fermentation process, notably by increasing the amount of key components of the aroma profile of the fermented beverage (i.e., mainly phenylethyl alcohol, isobutyl alcohol, isoamyl alcohol, and 2-methyl-butanol) and reducing the amount of off-flavor compounds. This study is a step forward in our understanding of interkingdom microbial interactions with strong application potential in food biotechnology.
Chitosan-Based Bioactive Hemostatic Agents with Antibacterial Properties—Synthesis and Characterization
Authors: Radwan-Pragłowska Julia , Piątkowski Marek , Deineka Volodymyr , Janus Łukasz , Korniienko Viktoriia , Husak Evgenia , Holubnycha Viktoria , Liubchak Iryna , Zhurba Vyacheslav , Sierakowska Aleksandra , Pogorielov Maksym , Bogdał Dariusz
Published: July 2019

Massive blood loss is responsible for numerous causes of death. Hemorrhage may occur on the battlefield, at home or during surgery. Commercially available biomaterials may be insufficient to deal with excessive bleeding. Therefore novel, highly efficient hemostatic agents must be developed. The aim of the following research was to obtain a new type of biocompatible chitosan-based hemostatic agents with increased hemostatic properties. The biomaterials were obtained in a quick and efficient manner under microwave radiation using l-aspartic and l-glutamic acid as crosslinking agents with no use of acetic acid. Ready products were investigated over their chemical structure by FT-IR method which confirmed a crosslinking process through the formation of amide bonds. Their high porosity above 90% and low density (below 0.08 g/cm3) were confirmed. The aerogels were also studied over their water vapor permeability and antioxidant activity. Prepared biomaterials were biodegradable in the presence of human lysozyme. All of the samples had excellent hemostatic properties in contact with human blood due to the platelet activation confirmed by blood clotting tests. The SEM microphotographs showed the adherence of blood cells to the biomaterials’ surface. Moreover, they were biocompatible with human dermal fibroblasts (HDFs). The biomaterials also had superior antibacterial properties against both Staphylococcus aureus and Escherichia coli. The obtained results showed that proposed chitosan-based hemostatic agents have great potential as a hemostatic product and may be applied under sterile, as well as contaminated conditions, by both medicals and individuals.
Role of Post-Exposure Time in Co(II) Sorption of Higher Concentrations on Electron Irradiated Sheep Wool
Authors: Braniša Jana , Jomová Klaudia , Kovalčíková Renáta , Hybler Peter , Porubská Mária
Published: July 2019

Sorption of Co(II) was investigated on natural as well as accelerated electron beam modified sheep wool involving low and high concentrations up to 200 mmol·dm−3. The sorption experiments confirmed the dependence of the sorption capacity not only on sorbate concentration and absorbed dose of energy, but also on post-exposure time. Post-exposure heating to accelerate transformation of the wool structure was of no effect on the sorption comparing with a simple storage for a period of 100 days. Under all tested conditions, the sorption maximum was measured for Co(II) concentration of 125 mmol·dm−3 and that was assigned to form a Co(II) complex with keratin. This assumption was tested on visible spectra of mixed solutions of Arginine and Co(II) to be a simplified model of Co(II) interaction with keratin. The sorption decrease is associated with generation of cross links between macro-chains through ligands of the Co-complex. The nodal points are a hindrance to diffusion of next ions into the fibers. Also, pH variations of aqueous extracts from the wool samples depending on absorbed dose and post-exposure time indicate complexity of the structural transformation being specific for each dose applied.
Molecular Structure and Antioxidant Properties of Alkali Metal Salts of Rosmarinic Acid. Experimental and DFT Studies
Authors: Świsłocka Renata , Regulska Ewa , Karpińska Joanna , Świderski Grzegorz , Lewandowski Włodzimierz
Published: July 2019

The molecular structure of alkali metal rosmarinates was studied in comparison to rosmarinic acid using FT-IR, FT-Raman, 1H and 13C NMR spectroscopy, as well as density functional theory (DFT) calculations. The B3LYP/6-311+G(d,p) method was used to calculate optimized geometrical structures of studied compounds, atomic charges, dipole moments, energies, as well as the wavenumbers and intensities of the bands in vibrational and NMR spectra. Theoretical parameters were compared to experimental data. Antioxidant activity was determined using two spectrophotometric methods: (i) Assessing the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable radical and (ii) assay of antioxidant power of ferric ions reducing (FRAP). The linear correlations were found between HOMO–LUMO (highest occupied molecular orbital–lowest unoccupied molecular orbital) energy gap and the reducing power expressed as FRAP (R = 0.77) as well as between IC50 values (the ability of quenching DPPH radicals) and Δνas-s(COO) in IR spectra (differences between asymmetric and symmetric stretching vibrations bands) (R = 0.99). Photochemical properties of studied compounds were also evaluated. The influence of alkali metal on the electronic system of the rosmarinic acid molecule was discussed.
Predicting and Testing Bioavailability of Magnesium Supplements
Authors: Blancquaert Laura , Vervaet Chris , Derave Wim
Published: July 2019

Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.
Faster Gastric Emptying Is Unrelated to Feeding Success in Preterm Infants: Randomized Controlled Trial
Authors: Baldassarre Maria Elisabetta , Di Mauro Antonio , Montagna Osvaldo , Fanelli Margherita , Capozza Manuela , Wampler Jennifer L. , Cooper Timothy , Laforgia Nicola
Published: July 2019

Objectives: To evaluate the relationship between gastric emptying (GE) time and days to achievement of full enteral feeding (≥140 mL/kg/day) in preterm infants randomly assigned to receive one of two marketed study formulas for the first 14 feeding days: intact protein premature formula (IPF) or extensively hydrolyzed protein (EHF) formula. Methods: In this triple-blind, controlled, prospective, clinical trial, we report GE time (time to half-emptying, t1/2) by real-time ultrasonography on Study Day 14, in preterm infants receiving IPF or EHF formula. The association between GE time and achievement of full enteral feeding was evaluated by Pearson correlation. Per-protocol populations for analysis included participants who (1) completed the study (overall) and (2) who received ≥ 75% study formula intake (mL/kg/day). Results: Median GE time at Day 14 was significantly faster for the EHF vs. IPF group overall and in participants who received ≥ 75% study formula intake (p ≤ 0.018). However, we demonstrated GE time had no correlation with the achievement of full enteral feeding (r = 0.08; p = 0.547). Conclusion: Feeding IP premature formula vs. EH formula was associated with shorter time to full enteral feeding. However, faster GE time did not predict feeding success and may not be a clinically relevant surrogate for assessing feeding tolerance.
Neuroprotective Effect of Schisandra Chinensis on Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonian Syndrome in C57BL/6 Mice
Authors: Li Chi-Lin , Tsuang Yang-Hwei , Tsai Tung-Hu
Published: July 2019

Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a well-known botanical medicine and nutritional supplement that has been shown to have potential effects on neurodegeneration. To investigate the potential neuroprotective effect of S. chinensis fruit extract, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce behavioral disorders and dopaminergic neuronal damage in mice, and biochemical indicators were examined. Male C57BL/6 mice were used to establish the MPTP-induced parkinsonian syndrome model. Open field and rotarod tests were performed to evaluate the overall manifestation of motor deficits and rodent motor coordination. The mice were divided into 8 groups as follows: normal control; MPTP alone (25 mg/kg, i.p.); S. chinensis extract pretreatment (0.5, 1.5, 5 g/kg, p.o.); and S. chinensis extract treatment (0.5, 1.5, 5 g/kg, p.o.). Liquid chromatography coupled to electrochemical detection was used to monitor neurochemicals in the striatum. Tyrosine hydroxylase content was measured by immunohistochemistry, and biochemical antioxidative indicators were used to evaluate the potential neuroprotective effects of S. chinensis fruit extract. The results demonstrated that treatment with S. chinensis fruit extract ameliorated MPTP-induced deficits in behavior, exercise balance, dopamine level, dopaminergic neurons, and tyrosine hydroxylase-positive cells in the striatum of mice. Among the pretreated and treatment groups, a high dose of S. chinensis fruit extract was the most effective treatment. In conclusion, S. chinensis fruit extract is a potential herbal drug candidate for the amelioration and prevention of Parkinson’s disease.
Development of a Paper-Based Sensor Compatible with a Mobile Phone for the Detection of Common Iron Formulas Used in Fortified Foods within Resource-Limited Settings
Authors: Waller Anna W. , Toc Marco , Rigsby Dylan J. , Gaytán-Martínez Marcela , Andrade Juan E.
Published: July 2019

A lack of quality control tools limits the enforcement of fortification policies. In alignment with the World Health Organization’s ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable), a paper-based assay that interfaces with a smartphone application for the quantification of iron fortificants is presented. The assay is based on the Ferrozine colorimetric method. The reaction started after deposition of the 5 µL aqueous sample and drying. After developing color, pixel intensity values were obtained using a smartphone camera and image processing software or a mobile application, Nu3px. From these values, the actual iron concentration from ferrous sulfate and ferrous fumarate was calculated. The limits of detection, quantification, linearity, range, and errors (systematic and random) were ascertained. The paper-based values from real samples (wheat flour, nixtamalized corn flour, and infant formula) were compared against atomic emission spectroscopy. The comparison of several concentrations of atomic iron between the spectrophotometric and paper-based assays showed a strong positive linear correlation (y = 47.01x + 126.18; R2 = 0.9932). The dynamic range (5.0–100 µg/mL) and limit of detection (3.691 µg/mL) of the paper-based assay are relevant for fortified food matrices. Random and systematic errors were 15.9% and + 8.65 µg/g food, respectively. The concept can be applied to limited-resource settings to measure iron in fortified foods.
Food Intolerances
Authors: Tuck Caroline J , Biesiekierski Jessica R , Schmid-Grendelmeier Peter , Pohl Daniel
Published: July 2019

Food intolerances are estimated to affect up to 20% of the population but complete understanding of diagnosis and management is complicated, given presentation and non-immunological mechanisms associated vary greatly. This review aims to provide a scientific update on common food intolerances resulting in gastrointestinal and/or extra-intestinal symptoms. FODMAP sensitivity has strong evidence supporting its mechanisms of increased osmotic activity and fermentation with the resulting distention leading to symptoms in those with visceral hypersensitivity. For many of the other food intolerances reviewed including non-coeliac gluten/wheat sensitivity, food additives and bioactive food chemicals, the findings show that there is a shortage of reproducible well-designed double-blind, placebo-controlled studies, making understanding of the mechanisms, diagnosis and management difficult. Enzyme deficiencies have been proposed to result in other food sensitivities including low amine oxidase activity resulting in histamine intolerance and sucrase-isomaltase deficiency resulting in reduced tolerance to sugars and starch. Lack of reliable diagnostic biomarkers for all food intolerances result in an inability to target specific foods in the individual. As such, a trial-and-error approach is used, whereby suspected food constituents are reduced for a short-period and then re-challenged to assess response. Future studies should aim to identify biomarkers to predict response to dietary therapies.
Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats
Authors: Na Young-Guk , Byeon Jin-Ju , Huh Hyun Wook , Kim Min-Ki , Shin Young G. , Lee Hong-Ki , Cho Cheong-Weon
Published: July 2019

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy.
Vitamin E-Loaded PLA- and PLGA-Based Core-Shell Nanoparticles: Synthesis, Structure Optimization and Controlled Drug Release
Authors: Varga Norbert , Turcsányi Árpád , Hornok Viktória , Csapó Edit
Published: July 2019

The (±)-α-Tocopherol (TP) with vitamin E activity has been encapsulated into biocompatible poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) carriers, which results in the formation of well-defined nanosized (d ~200–220 nm) core-shell structured particles (NPs) with 15–19% of drug loading (DL%). The optimal ratios of the polymer carriers, the TP active drug as well as the applied Pluronic F127 (PLUR) non-ionic stabilizing surfactant, have been determined to obtain NPs with a TP core and a polymer shell with high encapsulation efficiency (EE%) (69%). The size and the structure of the prepared core-shell NPs as well as the interaction of the carriers and the PLUR with the TP molecules have been determined by transmission electron microscopy (TEM), dynamic light scattering (DLS), infrared spectroscopy (FT-IR) and turbidity studies, respectively. Moreover, the dissolution of the TP from the polymer NPs has been investigated by spectrophotometric measurements. It was clearly confirmed that increase in the EE% from ca. 70% (PLA/TP) to ca. 88% (PLGA65/TP) results in the controlled release of the hydrophobic TP molecules (7 h, PLA/TP: 34%; PLGA75/TP: 25%; PLGA65/TP: 18%). By replacing the PLA carrier to PLGA, ca. 15% more active substance can be encapsulated in the core (PLA/TP: 65%; PLGA65/TP: 80%).