bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and Numerical Study of Crater Volume in Wire Electrical Discharge Machining
Authors: Wang Jun , Sánchez José. A. , Izquierdo Borja , Ayesta Izaro
Published: January 2020

Wire Electrical Discharge Machining (WEDM) is a popular non-conventional machining technology widely used in high-added value sectors such as aerospace, biomedicine, and the automotive industry. Even though the technology is now ready to meet the requirements of the most complex components, certain fundamental aspects related to the discharge process and gap conditions are not yet fully explained and understood. Combining single discharge experiments with numerical simulation represents a good approach for obtaining a deeper insight into the fundamentals of the process. In this paper, a fundamental study of the WEDM through single discharge experiments and numerical simulation is presented. WEDM single discharge experiments are described with the aim of identifying the relation between crater dimensions, discharge gap, and part surface roughness. A thermal transient numerical model of the WEDM process is presented, and correlation with actual industrial material removal rates (MRR) is analyzed. Results from single discharge WEDM experiments show that crater volume is as much as 40% lower when discharging on a rough surface than when the discharge occurs on a flat surface. The proposed thermal numerical model can predict actual removal rates of industrial machines with great accuracy for roughing cuts, deviations with experimental values being below 10%. However, lager deviations have been observed for other WEDM conditions, namely trim cuts, thus confirming the need for future research in this direction.
Influence of Ti on the Tensile Properties of the High-Strength Powder Metallurgy High Entropy Alloys
Authors: Moravcik Igor , Gamanov Stepan , Moravcikova-Gouvea Larissa , Kovacova Zuzana , Kitzmantel Michael , Neubauer Erich , Dlouhy Ivo
Published: January 2020

The focus of this study is the evaluation of the influence of Ti concentration on the tensile properties of powder metallurgy high entropy alloys. Three Ni1.5Co1.5CrFeTiX alloys with X = 0.3; 0.5 and 0.7 were produced by mechanical alloying and spark plasma sintering. Additional annealing heat treatment at 1100 °C was utilized to obtain homogenous single-phase face centered cubic (FCC) microstructures, with minor oxide inclusions. The results show that Ti increases the strength of the alloys by increasing the average atomic size misfit i.e., solid solution strengthening. An excellent combination of mechanical properties can be obtained by the proposed method. For instance, annealed Ni1,5Co1,5CrFeTi0.7 alloy possessed the ultimate tensile strength as high as ~1600 MPa at a tensile ductility of ~9%, despite the oxide contamination. The presented results may serve as a guideline for future alloy design of novel, inclusion-tolerant materials for sustainable metallurgy.
Characterization of Ethylene–propylene Composites Filled with Perlite and Vermiculite Minerals: Mechanical, Barrier, and Flammability Properties
Authors: Szadkowski Bolesław , Marzec Anna , Rybiński Przemysław , Żukowski Witold , Zaborski Marian
Published: January 2020

Perlite and vermiculite are naturally occurring minerals, commonly used by industry to obtain highly thermoisolative and/or non-flammable materials. However, there has been little research into the preparation and application of rubber compounds containing these inexpensive mineral fillers. Here, we show the benefits of perlite and vermiculite minerals as fillers for ethylene-propylene rubber (EPM) composites. To obtain more uniform dispersion and improved compatibility between the minerals and the elastomer matrix, 1-allyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (AMIMTFSI) and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIMTFSI) imidazolium ionic liquids (ILs) were added. The mineral fillers were found to be attractive semi-reinforcing fillers, which also act as flame retardants in the elastomer composites. Furthermore, a higher content of vermiculite mineral significantly reduced the air permeability of the composites. The incorporation of ionic liquids into the EPM-filled systems had a considerable effect on the torque increment, crosslink density, and more importantly the flammability of the studied compounds. The application of 2.5 parts per hundred parts of rubber (phr) BMIMTFSI, in particular, reduced the flammability of the EPM composite, as the maximum heat release rate (HRRmax) decreased from 189.7 kW/m2 to 170.2 kW/m2.
In-Situ Surface Modification of Terpinen-4-ol Plasma Polymers for Increased Antibacterial Activity
Authors: Kumar Avishek , Al-Jumaili Ahmed , Bazaka Kateryna , Mulvey Peter , Warner Jeffrey , Jacob Mohan V.
Published: January 2020

Surface modification of thin films is often performed to enhance their properties. In this work, in situ modification of Terpinen-4-ol (T4) plasma polymer is carried out via simultaneous surface functionalization and nanoparticle immobilization. Terpinen-4-ol plasma polymers surface were decorated with a layer of ZnO nanoparticles in an oxygen plasma environment immediately after polymer deposition. A combination of hydrophilic modification and ZnO nanoparticle functionalization of the T4 polymer surface led to an enhancement in antibacterial properties by factor of 3 (from 0.75 to 0.25 CFU.mm−2). In addition, ZnO nanoparticle-modified coatings demonstrated improved UV absorbing characteristics in the region of 300–400 nm by 60% relative to unmodified coatings. The ZnO modified coatings were transparent in the visible region of 400–700 nm. The finding points towards the potential use of ZnO nanoparticle-modified T4 plasma polymers as optically transparent UV absorbing coatings.
Shrinkage and Mechanical Properties of Self-Compacting SFRC With Calcium-Sulfoaluminate Expansive Agent
Authors: Li Changyong , Shang Pengran , Li Fenglan , Feng Meng , Zhao Shunbo
Published: January 2020

With the premise of ensuring workability on a fresh mixture, the volume stability of hardened self-compacting steel fiber reinforced concrete (SFRC) becomes an issue due to the content of cementitious materials increased with the volume fraction of steel fiber. By using the expansive agent to reduce the shrinkage deformation of self-compacting SFRC, the strength reduction of hardened self-compacting SFRC is another issue. To solve these issues, this paper performed an experimental investigation on the workability, shrinkage, and mechanical properties of self-compacting SFRC compared to the self-compacting concrete (SCC) with or without an expansive agent. The calcium-sulfoaluminate expansive agent with content optimized to be 10% mass of binders and the steel fiber with a varying volume fraction from 0.4% to 1.2% were selected as the main parameters. The mix proportion of self-compacting SFRC with expansive agent was designed by the direct absolute volume method, of which the steel fibers are considered to be the distributed coarse aggregates. Results showed that rational high filling and passing ability of fresh self-compacting SFRC was ensured by increasing the binder to coarse-aggregate ratio and the sand ratio in the mix proportions; the autogenous and drying shrinkages of hardened self-compacting SFRC reduced by 22.2% to 3.2% and by 18.5% to 7.3% compared to those of the SCC without expansive agent at a curing age of 180 d, although the expansion effect of expansive agent decreased with the increasing volume fraction of steel fiber; the mechanical properties, including the compressive strength, the splitting tensile strength, and the modulus of elasticity increased with the incorporation of an expansive agent and steel fibers, which met the design requirements.
Mechanical Evaluation of Titanium Plates for Osteoesynthesis High Neck Condylar Fracture of Mandible
Authors: Zieliński Rafał , Kozakiewicz Marcin , Konieczny Bartłomiej , Krasowski Michał , Okulski Jakub
Published: January 2020

Background: In the literature no information about plates for the high-neck mandibular condylar osteosynthesis could be found despite that 30 plate designs have been published. The main course consider the basal condylar or diacapitular fractures. The aim of the study was to test mechanically all available designs (only 4 of 30 was proper) on polyurethane mandibles using an individually designed clamping system. Methods: Forces required for a 1 mm displacement of fixed fracture fragments and incidents of screw loosening were recorded. Results: It has occured that dedicated plates for fixation are much weaker than set of two straight plates (p < 0.0001). General observation is the bigger plate and more screws, the better rigid stable osteosynthesis of mandibular condyle, however, there are limitations in plates design for high-neck fractures resulted in restricted operation field. Conclusion: Double straight plates occured to be the best mechanical fixation for high-neck fractures of the mandibular condyle. Maybe other existing plates could be used but only after prebending or that fracture required novel dedicated plates design.
Metabolomic Insights into Marine Phytoplankton Diversity
Authors: Marcellin-Gros Rémy , Piganeau Gwenaël , Stien Didier
Published: January 2020

The democratization of sequencing technologies fostered a leap in our knowledge of the diversity of marine phytoplanktonic microalgae, revealing many previously unknown species and lineages. The evolutionary history of the diversification of microalgae can be inferred from the analysis of their genome sequences. However, the link between the DNA sequence and the associated phenotype is notoriously difficult to assess, all the more so for marine phytoplanktonic microalgae for which the lab culture and, thus, biological experimentation is very tedious. Here, we explore the potential of a high-throughput untargeted metabolomic approach to explore the phenotypic–genotypic gap in 12 marine microalgae encompassing 1.2 billion years of evolution. We identified species- and lineage-specific metabolites. We also provide evidence of a very good correlation between the molecular divergence, inferred from the DNA sequences, and the metabolomic divergence, inferred from the complete metabolomic profiles. These results provide novel insights into the potential of chemotaxonomy in marine phytoplankton and support the hypothesis of a metabolomic clock, suggesting that DNA and metabolomic profiles co-evolve.
A Green Enzymatic Extraction Optimization and Oxidative Stability of Krill Oil from Euphausia Superba
Authors: Zhou Li , Yang Fu , Zhang Minghao , Liu Jikai
Published: January 2020

Krill oil enriched with polyunsaturated fatty acids is in the form of phospholipid. However, its application as a dietary supplement is limited, because of its rapid deterioration. Thus, this study aims to investigate the oxidative stability of krill oil extracted from Euphausia superba. Under optimal conditions (enzyme concentration 0.16%, enzymolysis time 2.9 h, and enzymolysis temperature of 45 °C) designed by response surface methodology, the extraction yield of krill oil is 86.02%. Five assays, including peroxide value (POV), thiobarbituric acid-reactive substances (TBARS), pH value, and turbidity were used to determine the oxidative stability of krill oil nanoliposomes during storage. Carboxymethyl chitosan (CMCS) nanoliposomes showed a significant reduction in POV and TBARS values, a prevention of pH value decrease and turbidity increase. This study indicated that CMCS nanoliposome can effectively improve the oxidative stability of krill oil during storage. Furthermore, the release profile in vitro illustrated that the controlled release of krill oil carried out by CMCS nanoliposomes is feasible.
Algae Oil Treatment Protects Retinal Ganglion Cells (RGCs) via ERK Signaling Pathway in Experimental Optic Nerve Ischemia
Authors: Huang Tzu-Lun , Wen Yao-Tseng , Ho Yu-Chieh , Wang Jia-Kang , Lin Kuan-Hung , Tsai Rong-Kung
Published: January 2020

Background: We investigated the therapeutic effects and related mechanisms of algae oil (ALG) to protect retinal ganglion cells (RGCs) in a rat model of anterior ischemic optic neuropathy (rAION). Methods: Rats were daily gavaged with ALG after rAION induction for seven days. The therapeutic effects of ALG on rAION were evaluated using flash visual evoked potentials (FVEPs), retrograde labeling of RGCs, TUNEL assay of the retina, and ED1 staining of optic nerves (ONs). The levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, Cl-caspase-3, ciliary neurotrophic factor (CNTF), and p-ERK were analyzed by using western blots. Results: Protection of visual function in FVEPs amplitude was noted, with a better preservation of the P1–N2 amplitude in the ALG-treated group (p = 0.032) than in the rAION group. The density of RGCs was 2.4-fold higher in the ALG-treated group compared to that in the rAION group (p < 0.0001). The number of ED1-positive cells in ONs was significantly reduced 4.1-fold in the ALG-treated group compared to those in the rAION group (p = 0.029). The number of apoptotic RGCs was 3.2-fold lower in number in the ALG-treated group (p = 0.001) than that in the rAION group. The ALG treatment inhibited ERK activation to reduce the levels of iNOS, IL-1β, TNF-α, and Cl-caspase-3 and to increase the level of CNTF in the rAION model. Conclusion: The treatment with ALG after rAION induction inhibits ERK activation to provide both anti-inflammatory and antiapoptotic effects in rAION.
Defining Community-Acquired Pneumonia as a Public Health Threat: Arguments in Favor from Spanish Investigators
Authors: Cillóniz Catia , Menéndez Rosario , García-Vidal Carolina , Péricas Juan Manuel , Torres Antoni
Published: January 2020

Despite advances in its prevention, pneumonia remains associated with high morbidity, mortality, and health costs worldwide. Studies carried out in the last decade have indicated that more patients with community-acquired pneumonia (CAP) now require hospitalization. In addition, pneumonia management poses many challenges, especially due to the increase in the number of elderly patients with multiple comorbidities, antibiotic-resistant pathogens, and the difficulty of rapid diagnosis. In this new call to action, we present a wide-ranging review of the information currently available on CAP and offer some reflections on ways to raise awareness of this disease among the general public. We discuss the burden of CAP and the importance of attaining better, faster microbiological diagnosis and initiating appropriate treatment. We also suggest that closer cooperation between health professionals and the population at large could improve the management of this largely preventable infectious disease that takes many lives each year.
The Potential Role of Astrocytes in Parkinson’s Disease (PD)
Authors: Hindeya Gebreyesus Hiluf , Gebrehiwot Gebremichael Teklu
Published: January 2020

Astrocytes are multi-functional cells, now recognized as critical participants in many brain functions. They play a critical physiological role in the clearance of neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA), and in the regulation of K+ from the space of synaptic clefts. Astrocytes also express the excitatory amino acid transporters (EAATs) and aquaporin-4 (AQP4) water channel, which are involved in both physiological functions and neurodegenerative diseases (ND). Some of the ND are the Alzheimer’s (AD), Huntington’s (HD), Parkinson’s diseases (PD), Cerebral edema, amyotrophic lateral sclerosis (ALS), and epilepsy pathological conditions in specific regions of the CNS. Parkinson’s disease is the second most common age-related neurodegenerative disorder, characterized by degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc). These project to the striatum, forming an important pathway within the basal ganglia. Mostly, PD has no clear etiology, and the mechanism of dopaminergic (DA) neuron loss is not well illustrated. The results of various studies suggest that astrocytes are involved in the pathophysiology of PD. Evidence has shown that the down-regulation of EAAT-2/GLT-1 and AQP4 expression is associated with PD pathogenesis. However, controversial results were reported in different experimental studies about the expression and function of EAAT-2/GLT-1 and AQP4, as well as their colocalization in different brain regions, and their involvement in PD development. Therefore, under neurological disorders, Parkinson’s disease is related to the genetic and phenotypic change of astrocytes’ biology. In this review, the authors summarized recent their research findings, which revealed the involvement of EAAT-2/GLT-1 and AQP4 expression, the physical interaction between EAAT-2/GLT-1 and AQP4 in astrocyte function, and their potential role in the development of PD in SNpc and Subthalamic nucleus (STN) of the basal ganglia nuclei.
A Numerical Study of the Effect of Isotropic Hardening Parameters on Mode I Fatigue Crack Growth
Authors: Borges M. F. , Antunes F. V. , Prates P. A. , Branco R.
Published: January 2020

The consideration of plastic crack tip opening displacement (CTOD, δp), as a crack driving force has given us the opportunity to predict fatigue crack growth (FCG) rate numerically, and, therefore, to develop parametric studies focused on the effect of loading, geometrical, and material parameters. The objective here is to study the effect of the isotropic hardening parameters of the Voce law on FCG, which are the isotropic saturation stress, YSat, and the isotropic saturation rate, CY. The increase of these hardening parameters causes δp to decrease. However, this effect is much more pronounced for YSat than CY. The variation is non-linear, and the rate of variation decreases with the increase of isotropic parameters. The increase of YSat increases the crack closure phenomenon. Finally, the influence of the isotropic parameters is more relevant for pure isotropic hardening than for mixed hardening.
Special Issue on “NMR-Based Metabolomics and Its Applications Volume 2”
Authors: Cesare Marincola Flaminia , Mannina Luisa
Published: January 2020

Over the last decade, the number of scientific publications in the metabolomics area has increased exponentially. The literature includes ~29,000 contributions (articles and reviews) during the period of 2009–2019, revealing metabolomics applications in a wide range of fields, including medical, plant, animal, and food sciences (this bibliographic data were retrieved from the SCOPUS database, searching “metabolomics” in keywords). The high applicability of this approach is due to its ability to qualitatively and quantitatively characterize the chemical profile of all the low molecular weight metabolites (metabolome) present in cells, tissues, organs, and biological fluids as end products of the cellular regulatory pathways. Thus, providing a snapshot of the phenotype of a biological system, metabolomics offers useful contributions to a comprehensive insight into the functional status of human, animal, plant, and microbe organisms. The contributions collected in this Special Issue (12 articles, one review and one technical report) report on the recent technical advances and practical applications of NMR spectroscopy to metabolomics analyses.
Fabrication of Cross-Sinusoidal Anti-Reflection Nanostructure on a Glass Substrate Using Imperfect Glass Imprinting with a Nano-Pin Array Vitreous Carbon Stamp
Authors: Haq Muhammad Refatul , Kim Jun , Yeom Jeong-woo , Ryu Saem , Asgar Md. Ali , Kim Young Kyu , Kim Seok-min
Published: January 2020

Although polymer nanoimprinting on glass substrates has been widely employed for the fabrication of functional anti-reflective (AR) nanostructures, several drawbacks exist with respect to durability and delamination. The direct patterning of glass material is a potential solution for outdoor applications that require AR functional nanostructured glass plates. In this study, a glass imprinting technique was employed for the fabrication of an AR nanostructure on a soda-lime glass substrate using a vitreous carbon (VC) stamp. The VC stamp, which had a high aspect ratio nanopost array with a pitch of 325 nm, diameter of 110 nm, and height of ~220 nm, was fabricated by the carbonization of a replicated Furan precursor from an Si master. During the glass imprinting process using the nanopost array VC stamp, the softened glass material gradually protruded into the spaces between the nanopins owing to viscoelastic behavior, and one can achieve a cross-sinusoidal surface relief under specific imprinting condition, which can be used as an AR nanostructure with a gradually increasing refractive index. The effects of the processing temperature on the surface profile of the glass imprinted parts and the measured transmission spectra were analyzed, and a glass imprinting temperature of 700 °C and pressure of 1 MPa were found to be the optimum condition. The height of the fabricated cross-sinusoidal nanostructure was 80 nm, and the light transmission was increased by ~2% over the entire visible-light range. Furthermore, the measured transmission spectrum observed to be in good agreement with the simulation results.
Biostimulating Gut Microbiome with Bilberry Anthocyanin Combo to Enhance Anti-PD-L1 Efficiency against Murine Colon Cancer
Authors: Liu Xuerun , Wang Luoyang , Jing Nan , Jiang Guoqiang , Liu Zheng
Published: January 2020

Recent advances have revealed the essential role of gut microbiomes in the therapeutic efficiency of immune checkpoint inhibitors (ICIs). Inspired by biostimulation, a method using nutrients to accelerate the growth of soil microorganisms and the recovery of soil microbial consortia, here we propose a bilberry anthocyanin combo containing chitosan and low molecular citrus pectin (LCP), in which LCP–chitosan is used to encapsulate anthocyanins so to enhance its digestive stability and, moreover, modulate the microbiome more favorable for the PD-L1 blockade treatment. Using murine MC38 colon cancer as a model system, we examined the effects of the combo on modulating the gut microbiome and therapeutic efficiency of PD-L1 blockade treatment. It was shown that bilberry anthocyanins enriched the subdominant species, increased both the concentration and the proportion of butyrate in feces and enhanced intratumoral CD8+ T cell infiltrations. The application of the bilberry anthocyanin combo restored the species diversity of gut microbiome decreased by LCP–chitosan and achieved the best control of tumor growth. These preliminary results indicated unprecedented opportunities of probiotics combo in improving the therapeutic efficiency of immune checkpoint inhibitor through manipulating gut microbiome.
Evaluation of the Potential of Biofilm Formation of Bifidobacterium longum subsp. infantis and Lactobacillus reuteri as Competitive Biocontrol Agents Against Pathogenic and Food Spoilage Bacteria
Authors: Speranza Barbara , Liso Arcangelo , Russo Vincenzo , Corbo Maria Rosaria
Published: January 2020

This study proposes to exploit the in vivo metabolism of two probiotics (Bifidobacterium longum subsp. infantis and Lactobacillus reuteri) which, upon adhesion on a solid surface, form a biofilm able to control the growth of pathogenic and food spoilage bacteria. The results showed that pathogenic cell loads were always lower in presence of biofilm (6.5–7 log CFU/cm2) compared to those observed in its absence. For Escherichia coli O157:H7, a significant decrease (>1–2 logarithmic cycles) was recorded; for Listeria monocytogenes, Staphylococcus aureus, and Salmonella enterica, cell load reductions ranged from 0.5 to 1.5 logarithmic cycles. When tested as active packaging, the biofilm was successfully formed on polypropylene, polyvinyl chloride, greaseproof paper, polyethylene and ceramic; the sessile cellular load ranged from 5.77 log CFU/cm2 (grease-proof paper) to 6.94 log CFU/cm2 (polyethylene, PE). To test the potential for controlling the growth of spoilage microorganisms in food, soft cheeses were produced, inoculated with L. monocytogenes and Pseudomonas fluorescens, wrapped in PE pellicles with pre-formed biofim, packed both in air and under vacuum, and stored at 4 and 15 °C: an effective effect of biofilms in slowing the decay of the microbiological quality was recorded.
Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications 2018
Authors: Moura Nuno M. M. , Faustino Maria Amparo F. , Neves Maria Graça P. M. S.
Published: January 2020

Natural and synthetic macrocycles like porphyrins, corroles and phthalocyanines are considered strong candidates to be used in different fields, such as catalysis, sensing, medicine, materials science, or in the development of advanced biomimetic models. All these applications are strongly dependent on the availability of compounds with adequate and specific structural features. This Special Issue has collected 13 contributions which consolidate and expand our knowledge on the application of these macrocycles in different fields accompanied by innovative synthetic methodologies to afford and to functionalize this type of compounds.
Alginate-Mediated Synthesis of Hetero-Shaped Silver Nanoparticles and Their Hydrogen Peroxide Sensing Ability
Authors: Bhagyaraj Sneha , Krupa Igor
Published: January 2020

A new method for the simple synthesis of stable heterostructured biopolymer (sodium alginate)-capped silver nanoparticles (Ag-NPs) based on green chemistry is reported. The as-prepared nanoparticles were characterized using the ultraviolet-visible (UV-Vis) absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) techniques. The results showed that the as-prepared Ag-NPs have a heterostructured morphology with particle size in the range 30 ± 18–60 ± 25 nm, showing a zeta potential of −62 mV. The silver nanoparticle formation was confirmed from UV-Vis spectra showing 424 nm as maximum absorption. The particle size and crystallinity of the as-synthesized nanoparticles were analyzed using TEM and XRD measurements, respectively. FTIR spectra confirmed the presence of alginate as capping agent to stabilize the nanoparticles. The Ag-NPs also showed excellent sensing capability, with a linear response to hydrogen peroxide spanning a wide range of concentrations from 10−1 to 10−7 M, which indicates their high potential for water treatment applications, such as pollution detection and nanofiltration composites.
Preparation of Key Intermediates for the Syntheses of Coenzyme Q10 and Derivatives by Cross-Metathesis Reactions
Authors: Nguyen Trang , Mac Hung , Pham Phong
Published: January 2020

An alternative catalytic strategy for the preparation of benzylmethacrylate esters, key intermediates in the synthesis of coenzyme Q10 and derivatives, was reported. This strategy avoided undesirable stoichiometric reduction/oxidation processes by utilizing the catalytic formation of allylarenes and then cross-metathesis to selectively form E-benzylmethacrylate esters with good yields (58–64%) and complete E-selectivity. The ester intermediates were reduced to common key benzylallylic alcohols (90–92% yield), which were subsequently used in the formal syntheses of coenzyme Q10 and one derivative.
Discovery of Selective SIRT2 Inhibitors as Therapeutic Agents in B-Cell Lymphoma and Other Malignancies
Authors: Chowdhury Sarwat , Sripathy Smitha , Webster Alyssa A. , Park Angela , Lao Uyen , Hsu Joanne H. , Loe Taylor , Bedalov Antonio , Simon Julian A.
Published: January 2020

Genetic ablation as well as pharmacological inhibition of sirtuin 2 (SIRT2), an NAD+-dependent protein deacylase, have therapeutic effects in various cancers and neurodegenerative diseases. Previously, we described the discovery of a dual SIRT1/SIRT2 inhibitor called cambinol (IC50 56 and 59 µM, respectively), which showed cytotoxic activity against cancer cells in vitro and a marked anti-proliferative effect in a Burkitt lymphoma mouse xenograft model. A number of recent studies have shown a protective effect of SIRT1 and SIRT3 in neurodegenerative and metabolic diseases as well as in certain cancers prompting us to initiate a medicinal chemistry effort to develop cambinol-based SIRT2-specific inhibitors devoid of SIRT1 or SIRT3 modulating activity. Here we describe potent cambinol-based SIRT2 inhibitors, several of which show potency of ~600 nM with >300 to >800-fold selectivity over SIRT1 and 3, respectively. In vitro, these inhibitors are found to be toxic to lymphoma and epithelial cancer cell lines. In particular, compounds 55 (IC50 SIRT2 0.25 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) and 56 (IC50 SIRT2 0.78 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) showed apoptotic as well as strong anti-proliferative properties against B-cell lymphoma cells.
Volatile Flavor Compounds in Cheese as Affected by Ruminant Diet
Authors: Ianni Andrea , Bennato Francesca , Martino Camillo , Grotta Lisa , Martino Giuseppe
Published: January 2020

Extensive research has been conducted concerning the determination and characterization of volatile compounds contributing to aroma and flavor in cheese. Considerable knowledge has been accumulated on the understanding of the mechanisms through which these compounds are formed during ripening, as well as on the optimization of the methodological approaches which lead to their detection. More recently, particular attention has been given to the aromatic properties of milk and cheeses obtained from lactating dairy ruminants fed experimental diets, characterized, for instance, by the addition of trace elements, natural supplements, or agricultural by-products rich in bioactive compounds. The purpose of this review is to summarize the major families of volatile compounds most commonly found in these types of dairy products at various ripening stages, describing in greater detail the role of animal diet in influencing the synthesis mechanisms most commonly responsible for cheese flavor determination. A large number of volatile compounds, including carboxylic acids, lactones, ketones, alcohols, and aldehydes, can be detected in cheese. The relative percentage of each compound depends on the biochemical processes that occur during ripening, and these are mainly mediated by endogenous enzymes and factors of bacterial origin whose function can be strongly influenced by the bioactive compounds taken by animals with the diet and released in milk through the mammary gland. Further evaluations on the interactions between volatile compounds and cheese matrix would be necessary in order to improve the knowledge on the synthesis mechanisms of such compounds; in addition to this, more should be done with respect to the determination of synergistic effects of flavor compounds, correlating such compounds to the aroma of dairy products.
Extraction of Galphimines from Galphimia glauca with Supercritical Carbon Dioxide
Authors: Verónico Sánchez Francisco Javier , Elizalde Solis Octavio , Zamilpa Alejandro , García Morales Ricardo , Pérez García Ma. Dolores , Jiménez Ferrer Jesús E. , Tortoriello Jaime
Published: January 2020

The anti-depressive and anxiolytic effect of galphimine B (isolated from Galphimia glauca) has been demonstrated by researchers. Therefore, it is necessary to explore extraction techniques that produce materials with adequate quality for pharmaceutical applications. In this work, supercritical extractions of galphimines from Galphimia glauca were performed in the presence of carbon dioxide. Pressure, temperature, particle diameter, and flow rate effects were examined to explore the conditions with the highest yield and the concentration profile of galphimines in the studied interval. The identification of the nor-seco triterpenoids and galphimine B and E was carried out by HPLC analyses. The mathematical modeling of the extraction curves was attained by the approaches proposed by Sovová and Papamichail et al. According to results, the highest yield 2.22% was obtained at 323.15 K, 326 μm, 3 L/min, and 33.75 MPa. Meanwhile, the content of galphimine B in the extract was, on average, 19.5 mg·g−1.
Hepatotoxicity Modeling Using Counter-Propagation Artificial Neural Networks: Handling an Imbalanced Classification Problem
Authors: Bajželj Benjamin , Drgan Viktor
Published: January 2020

Drug-induced liver injury is a major concern in the drug development process. Expensive and time-consuming in vitro and in vivo studies do not reflect the complexity of the phenomenon. Complementary to wet lab methods are in silico approaches, which present a cost-efficient method for toxicity prediction. The aim of our study was to explore the capabilities of counter-propagation artificial neural networks (CPANNs) for the classification of an imbalanced dataset related to idiosyncratic drug-induced liver injury and to develop a model for prediction of the hepatotoxic potential of drugs. Genetic algorithm optimization of CPANN models was used to build models for the classification of drugs into hepatotoxic and non-hepatotoxic class using molecular descriptors. For the classification of an imbalanced dataset, we modified the classical CPANN training algorithm by integrating random subsampling into the training procedure of CPANN to improve the classification ability of CPANN. According to the number of models accepted by internal validation and according to the prediction statistics on the external set, we concluded that using an imbalanced set with balanced subsampling in each learning epoch is a better approach compared to using a fixed balanced set in the case of the counter-propagation artificial neural network learning methodology.
Simple Syntheses of New Pegylated Trehalose Derivatives as a Chemical Tool for Potential Evaluation of Cryoprotectant Effects on Cell Membrane
Authors: Pomeisl Karel , Richter Jan , Golan Martin , Kratochvílová Irena
Published: January 2020

In our work, we developed the synthesis of new polyfunctional pegylated trehalose derivatives and evaluated their cryoprotective effect using flow cytometry. We showed that new compounds (modified trehaloses) bound to appropriate extracellular polymeric cryoprotectants could be helpful as a chemical tool for the evaluation of their potential toxic cell membrane influences. Our aim was to form a chemical tool for the evaluation of cryoprotectant cell membrane influences, which are still not easily predicted during the freezing/thawing process. We combined two basic cryoprotectants: polyethyleneglycols (PEGs) and trehalose in the new chemical compounds—pegylated trehalose hybrids. If PEG and trehalose are chemically bound and trehalose is adsorbed on the cell surface PEGs molecules which are, due to the chemical bonding with trehalose, close to the cell surface, can remove the cell surface hydration layer which destabilizes the cell membrane. This was confirmed by the comparison of new material, PEG, trehalose, and their mixture cryoprotective capabilities.
Bioactives from Agri-Food Wastes: Present Insights and Future Challenges
Authors: Ben-Othman Sana , Jõudu Ivi , Bhat Rajeev
Published: January 2020

Sustainable utilization of agri-food wastes and by-products for producing value-added products (for cosmetic, pharmaceutical or food industrial applications) provides an opportunity for earning additional income for the dependent industrial sector. Besides, effective valorisation of wastes/by-products can efficiently help in reducing environmental stress by decreasing unwarranted pollution. The major focus of this review is to provide comprehensive information on valorisation of agri-food wastes and by-products with focus laid on bioactive compounds and bioactivity. The review covers the bioactives identified from wastes and by-products of plants (fruits, exotic fruits, vegetables and seeds), animals (dairy and meat) and marine (fish, shellfish seaweeds) resources. Further, insights on the present status and future challenges of sustainably utilizing agri-food wastes/by-products for value addition will be highlighted.
Understanding the Solution Behavior of Epinephrine in the Presence of Toxic Cations: A Thermodynamic Investigation in Different Experimental Conditions
Authors: Crea Francesco , De Stefano Concetta , Irto Anna , Lando Gabriele , Materazzi Stefano , Milea Demetrio , Pettignano Alberto , Sammartano Silvio
Published: January 2020

The interactions of epinephrine ((R)-(−)-3,4-dihydroxy-α-(methylaminomethyl)benzyl alcohol; Eph−) with different toxic cations (methylmercury(II): CH3Hg+; dimethyltin(IV): (CH3)2Sn2+; dioxouranium(VI): UO22+) were studied in NaClaq at different ionic strengths and at T = 298.15 K (T = 310.15 K for (CH3)2Sn2+). The enthalpy changes for the protonation of epinephrine and its complex formation with UO22+ were also determined using isoperibolic titration calorimetry: ΔHHL = −39 ± 1 kJ mol−1, ΔHH2L = −67 ± 1 kJ mol−1 (overall reaction), ΔHML = −26 ± 4 kJ mol−1, and ΔHM2L2(OH)2 = 39 ± 2 kJ mol−1. The results were that UO22+ complexation by Eph− was an entropy-driven process. The dependence on the ionic strength of protonation and the complex formation constants was modeled using the extended Debye–Hückel, specific ion interaction theory (SIT), and Pitzer approaches. The sequestering ability of adrenaline toward the investigated cations was evaluated using the calculation of pL0.5 parameters. The sequestering ability trend resulted in the following: UO22+ >> (CH3)2Sn2+ > CH3Hg+. For example, at I = 0.15 mol dm−3 and pH = 7.4 (pH = 9.5 for CH3Hg+), pL0.5 = 7.68, 5.64, and 2.40 for UO22+, (CH3)2Sn2+, and CH3Hg+, respectively. Here, the pH is with respect to ionic strength in terms of sequestration.
A Non-Targeted Capillary Electrophoresis-Mass Spectrometry Strategy to Study Metabolic Differences in an In Vitro Model of High-Glucose Induced Changes in Human Proximal Tubular HK-2 Cells
Authors: Bernardo-Bermejo Samuel , Sánchez-López Elena , Castro-Puyana María , Benito-Martínez Selma , Lucio-Cazaña Francisco Javier , Marina María Luisa
Published: January 2020

Diabetic nephropathy is characterized by the chronic loss of kidney function due to high glucose renal levels. HK-2 proximal tubular cells are good candidates to study this disease. The aim of this work was to study an in vitro model of high glucose-induced metabolic alterations in HK-2 cells to contribute to the pathogenesis of this diabetic complication. An untargeted metabolomics strategy based on CE-MS was developed to find metabolites affected under high glucose conditions. Intracellular and extracellular fluids from HK-2 cells treated with 25 mM glucose (high glucose group), with 5.5 mM glucose (normal glucose group), and with 5.5 mM glucose and 19.5 mM mannitol (osmotic control group) were analyzed. The main changes induced by high glucose were found in the extracellular medium where increased levels of four amino acids were detected. Three of them (alanine, proline, and glutamic acid) were exported from HK-2 cells to the extracellular medium. Other affected metabolites include Amadori products and cysteine, which are more likely cause and consequence, respectively, of the oxidative stress induced by high glucose in HK-2 cells. The developed CE-MS platform provides valuable insight into high glucose-induced metabolic alterations in proximal tubular cells and allows identifying discriminative molecules of diabetic nephropathy.
Binaphthyl-Based Macrocycles as Optical Sensors for Aromatic Diphenols
Authors: Piacentini Stefano , Caricato Marco , Pacini Aurora , Nitti Andrea , Pasini Dario
Published: January 2020

The synthesis of several rigid, homochiral organic macrocycles possessing, respectively, average molecular D2 and D3 symmetries, is described. They have been obtained from aromatic dicarboxylic acids, in combination with an axially-chiral, suitable dibenzylic alcohol, derived from 1,1′-binaphthyl-2,2′-diol (BINOL) using one-pot esterification reactions in good isolated yields. NMR and circular dichroism (CD) spectroscopies detect the structural and shape variability in the scaffolds, reflected both in terms of the changes in chemical shifts and the shape of selected proton resonances, and in terms of the variation of the CD signature related to the dihedral angle defined by the binaphthyl units embedded in the rigid cyclic skeleton. The D2 cyclic adducts are able to form stable complexes with aromatic diphenols, with binding strengths that are dependent on small variations in the spacing units, and therefore on the shapes of the internal cavities of the cyclic structures.
The Role of Salicylic Acid in Plants Exposed to Heavy Metals
Authors: Sharma Anket , Sidhu Gagan Preet Singh , Araniti Fabrizio , Bali Aditi Shreeya , Shahzad Babar , Tripathi Durgesh Kumar , Brestic Marian , Skalicky Milan , Landi Marco
Published: January 2020

Salicylic acid (SA) is a very simple phenolic compound (a C7H6O3 compound composed of an aromatic ring, one carboxylic and a hydroxyl group) and this simplicity contrasts with its high versatility and the involvement of SA in several plant processes either in optimal conditions or in plants facing environmental cues, including heavy metal (HM) stress. Nowadays, a huge body of evidence has unveiled that SA plays a pivotal role as plant growth regulator and influences intra- and inter-plant communication attributable to its methyl ester form, methyl salicylate, which is highly volatile. Under stress, including HM stress, SA interacts with other plant hormones (e.g., auxins, abscisic acid, gibberellin) and promotes the stimulation of antioxidant compounds and enzymes thereby alerting HM-treated plants and helping in counteracting HM stress. The present literature survey reviews recent literature concerning the roles of SA in plants suffering from HM stress with the aim of providing a comprehensive picture about SA and HM, in order to orientate the direction of future research on this topic.
Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties
Authors: Assirey Eman , Alsaggaf Azhaar , Naqvi Arshi , Moussa Ziad , Okasha Rawda M. , Afifi Tarek H. , Abd-El-Aziz Alaa S.
Published: January 2020

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.
Analysis of Binding Interactions of Ramipril and Quercetin on Human Serum Albumin: A Novel Method in Affinity Evaluation
Authors: Vaneková Zuzana , Hubčík Lukáš , Toca-Herrera José Luis , Furtműller Paul Georg , Mučaji Pavel , Nagy Milan
Published: January 2020

The aim of this study was to analyze the binding interactions between a common antihypertensive drug (ramipril, R) and the widely distributed plant flavonoid quercetin (Q), in the presence of human serum albumin (HSA). From the observed fluorescence spectra of the (HSA + R) system we can assume that ramipril is also one of the Site 3 ligands—similar to fusidic acid—the binding of which has been proven by RTG crystallography. Our claim is supported by near-UV CD spectroscopy, microscale themophoresis and molecular modeling. The presence of R slightly inhibited the subsequent binding of Q to HSA and, on the contrary, the pre-incubation of HSA with Q caused a stronger binding of R, most likely due to allosteric interactions. At high concentrations, R is also able to displace Q from its binding site. The dissociation constant KD for the binding of R is more than hundredfold larger than for Q, which means that R is a very weak binder to HSA. The knowledge of qualitative and quantitative parameters of R, as well as the methods used in this study, are important for future research into HSA binding. This study shows the importance of implementing other methods for KD determination. Microscale thermophoresis has proved to be a novel, practical and accurate method for KD determination on HSA, especially in cases when fluorescence spectroscopy is unable to produce usable results.
Advances in Synthesis of π-Extended Benzosilole Derivatives and Their Analogs
Authors: Dang Tuan Thanh , Nguyen Hue Minh Thi , Nguyen Hien , Dung Tran Ngoc , Nguyen Minh Tho , Dehaen Wim
Published: January 2020

Benzosiloles and their π-extended derivatives are present in many important advanced materials due to their excellent physical properties. Especially, they have found many potential applications in the development of novel electronic materials such as OLEDs, semiconductors and solar cells. In this review, we have summarized several main approaches to construct (di)benzosilole derivatives and (benzo)siloles fused to aromatic five- and six-membered heterocycles.
A Novel Approach to Enhance Mechanical and Thermal Properties of SLA 3D Printed Structure by Incorporation of Metal–Metal Oxide Nanoparticles
Authors: Mubarak Suhail , Dhamodharan Duraisami , B. Kale Manoj , Divakaran Nidhin , Senthil T. , P. Sathiyanathan , Wu Lixin , Wang Jianlei
Published: January 2020

Silver (Ag) ornamented TiO2 semiconducting nanoparticles were synthesized through the sol-gel process to be utilized as nanofillers with photo resin to enhance the mechanical and thermal properties of stereolithography 3D printed objects. The as-prepared Ag-TiO2 nanoparticles (Ag-TNP) were typified and qualified by XRD, XPS, Raman, and FESEM; TEM analysis dissected the morphologies. The enhancement in the tensile and flexural strengths of SLR/Ag-TNP nanocomposites was noted as 60.8% and 71.8%, respectively, at the loading content of 1.0% w/w Ag-TNP within the SLR (stereolithography resin) matrix. Similarly, the thermal conductivity and thermal stability were observed as higher for SLR/Ag-TNP nanocomposites, equated to neat SLR. The nanoindentation investigation shows an excerpt hike in reduced modulus and hardness by the inclusion of Ag-TNP. The resulted thermal analysis discloses that the introduction of Ag-TNP can appreciably augment the glass transition temperature (Tg), and residual char yield of SLR nanocomposites remarkably. Hence, the significant incorporation of as-prepared Ag-TNP can act as effective nanofillers to enhance the thermal and mechanical properties of photo resin.