bluuebunny/crossref_metadata_2025 huggingface dataset:
Chair- and V-Shaped of H-bonded Supramolecular Complexes of Azophenyl Nicotinate Derivatives; Mesomorphic and DFT Molecular Geometry Aspects
Authors: Alhaddad Omaima A. , Abu Al-Ola Khulood A. , Hagar Mohamed , Ahmed Hoda A.
Published: April 2020

New geometrical architectures of chair- and V-shaped supramolecular liquid crystalline complexes were molded through 1:1 intermolecular hydrogen bonding interactions between 4-(4-(hexyloxy)phenylazo)methyl)phenyl nicotinate and 4-alkoxybenzoic acids. The length of terminal alkoxy acid chains varied, n = 6 to 16 carbons. The mesomorphic behaviour of these complexes was examined through differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). Fourier-transform infrared spectroscopy (FT-IR) was carried out to confirm the presence of Fermi bands that appeared for the hydrogen bonding formation. Enantiotropic nematic phases were observed and covered all lengths of alkoxy chains. The geometrical structures of the prepared supramolecular complexes geometries were estimated by Density functional theory (DFT) calculations. The supramolecular complexes I/An are projected to exhibit a nonlinear geometry with V-shaped and chair-shaped geometry. The chair-shaped conformers of I/An were found to be more stable than V-shaped isomeric complexes. Moreover, the effect of the change of the mesogenic core on the mesophase thermal stability (TC) has been investigated by a comparative study of the present azo supramolecular H-bonding LCs (SMHBCs) I/An and our previously reported their Schiff base analogue complexes, II/An. The findings of the DFT illustrated the high impact of CH=N as a mesogenic core on the mesomorphic behavior in terms of the competitive lateral and terminal intermolecular interactions as well as the molecular electrostatic potential (MEP).
Feedforward Artificial Neural Network-Based Model for Predicting the Removal of Phenolic Compounds from Water by Using Deep Eutectic Solvent-Functionalized CNTs
Authors: Ibrahim Rusul Khaleel , Fiyadh Seef Saadi , AlSaadi Mohammed Abdulhakim , Hin Lai Sai , Mohd Nuruol Syuhadaa , Ibrahim Shaliza , Afan Haitham Abdulmohsin , Fai Chow Ming , Ahmed Ali Najah , Elshafie Ahmed
Published: April 2020

In the recent decade, deep eutectic solvents (DESs) have occupied a strategic place in green chemistry research. This paper discusses the application of DESs as functionalization agents for multi-walled carbon nanotubes (CNTs) to produce novel adsorbents for the removal of 2,4-dichlorophenol (2,4-DCP) from aqueous solution. Also, it focuses on the application of the feedforward backpropagation neural network (FBPNN) technique to predict the adsorption capacity of DES-functionalized CNTs. The optimum adsorption conditions that are required for the maximum removal of 2,4-DCP were determined by studying the impact of the operational parameters (i.e., the solution pH, adsorbent dosage, and contact time) on the adsorption capacity of the produced adsorbents. Two kinetic models were applied to describe the adsorption rate and mechanism. Based on the correlation coefficient (R2) value, the adsorption kinetic data were well defined by the pseudo second-order model. The precision and efficiency of the FBPNN model was approved by calculating four statistical indicators, with the smallest value of the mean square error being 5.01 × 10−5. Moreover, further accuracy checking was implemented through the sensitivity study of the experimental parameters. The competence of the model for prediction of 2,4-DCP removal was confirmed with an R2 of 0.99.
A New Class of Smart Gadolinium Contrast Agent for Tissue pH Probing Using Magnetic Resonance Imaging
Authors: Mouffouk Fouzi , Serrai Hacene , Bhaduri Sourav , Achten Rik , Seyyedhamzeh Mozhdeh , Husain Ali A. , Alhendal Abdullah , Zourob Mohammed
Published: April 2020

Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so far suffer from inadequate accuracy, due to poor sensitivity at low concentration of the target or nonspecific interactions within the tissue matrix. To overcome these issues, we describe herein the development of a simple, yet reliable, way to estimate pH with high precision using a Gd(III)-DOTA-silyl-based acid-labile group as a pH-sensitive contrast agent with Magnetic Resonance Imaging (MRI). With this method, a change in T 1 weighted image intensity of the newly developed pH-sensitive contrast is directly linked to the proton concentration in the media. As a result, we were able estimate the pH of the target with 95% reliability.
Disordered Residues and Patterns in the Protein Data Bank
Authors: Lobanov Mikhail Yu. , Likhachev Ilya V. , Galzitskaya Oxana V.
Published: April 2020

We created a new library of disordered patterns and disordered residues in the Protein Data Bank (PDB). To obtain such datasets, we clustered the PDB and obtained the groups of chains with different identities and marked disordered residues. We elaborated a new procedure for finding disordered patterns and created a new version of the library. This library includes three sets of patterns: unique patterns, patterns consisting of two kinds of amino acids, and homo-repeats. Using this database, the user can: (1) find homologues in the entire Protein Data Bank; (2) perform a statistical analysis of disordered residues in protein structures; (3) search for disordered patterns and homo-repeats; (4) search for disordered regions in different chains of the same protein; (5) download clusters of protein chains with different identity from our database and library of disordered patterns; and (6) observe 3D structure interactively using MView. A new library of disordered patterns will help improve the accuracy of predictions for residues that will be structured or unstructured in a given region.
Full Parametric Study of the Influence of Ionomer Content, Catalyst Loading and Catalyst Type on Oxygen and Ion Transport in PEM Fuel Cell Catalyst Layers
Authors: Alink Robert , Singh Rajveer , Schneider Patrick , Christmann Kläre , Schall Johannes , Keding Roman , Zamel Nada
Published: April 2020

To advance the technology of polymer electrolyte membrane fuel cells, material development is at the forefront of research. This is especially true for membrane electrode assembly, where the structuring of its various layers has proven to be directly linked to performance increase. In this study, we investigate the influence of the various ingredients in the cathode catalyst layer, such as ionomer content, catalyst loading and catalyst type, on the oxygen and ion transport using a full parametric analysis. Using two types of catalysts, 40 wt.% Pt/C and 60 wt.% Pt/C with high surface area carbon, the ionomer/carbon content was varied between 0.29–1.67, while varying the Pt loading in the range of 0.05–0.8 mg cm−2. The optimum ionomer content was found to be dependent on the operating point and condition, as well as catalyst loading and type. The data set provided in this work gives a starting point to further understanding of structured catalyst layers.
Discovery, Design, Synthesis, and Application of Nucleoside/Nucleotides
Authors: Seley-Radtke Katherine
Published: April 2020

For decades, nucleosides and nucleotides have formed the cornerstone of antiviral, antiparasitic and anticancer therapeutics and have been used as tools in exploring nucleic acid structure and function [...]
An Efficient Metal-Free Oxidative Esterification and Amination of Benzyl C–H Bond
Authors: Liu Saiwen , Chen Ru , He Guowen , Zhang Jin
Published: April 2020

An esterification and amination of benzylic C–H bonds was developed by using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) under metal- and iodide-free conditions. Both carboxylic acids and amines could be used as ideal coupling partners for the oxidative coupling reactions with various diarylmethanes. A close to equal amount of coupling reagents was enough to afford the product in good to high yields.
Are Alkynyl Spacers in Ancillary Ligands in Heteroleptic Bis(diimine)copper(I) Dyes Beneficial for Dye Performance in Dye-Sensitized Solar Cells?
Authors: Risi Guglielmo , Becker Mariia , Housecroft Catherine E. , Constable Edwin C.
Published: April 2020

The syntheses of 4,4′-bis(4-dimethylaminophenyl)-6,6′-dimethyl-2,2′-bipyridine (1), 4,4′-bis(4-dimethylaminophenylethynyl)-6,6′-dimethyl-2,2′-bipyridine (2), 4,4′-bis(4-diphenylaminophenyl)-6,6′-dimethyl-2,2′-bipyridine (3), and 4,4′-bis(4-diphenylaminophenylethynyl)-6,6′-dimethyl-2,2′-bipyridine (4) are reported along with the preparations and characterisations of their homoleptic copper(I) complexes [CuL2][PF6] (L = 1–4). The solution absorption spectra of the complexes exhibit ligand-centred absorptions in addition to absorptions in the visible region assigned to a combination of intra-ligand and metal-to-ligand charge-transfer. Heteroleptic [Cu(5)(Lancillary)]+ dyes in which 5 is the anchoring ligand ((6,6′-dimethyl-[2,2′-bipyridine]-4,4′-diyl)bis(4,1-phenylene))bis(phosphonic acid) and Lancillary = 1–4 have been assembled on fluorine-doped tin oxide (FTO)-TiO2 electrodes in dye-sensitized solar cells (DSCs). Performance parameters and external quantum efficiency (EQE) spectra of the DSCs (four fully-masked cells for each dye) reveal that the best performing dyes are [Cu(5)(1)]+ and [Cu(5)(3)]+. The alkynyl spacers are not beneficial, leading to a decrease in the short-circuit current density (JSC), confirmed by lower values of EQEmax. Addition of a co-absorbent (n-decylphosphonic acid) to [Cu(5)(1)]+ lead to no significant enhancement of performance for DSCs sensitized with [Cu(5)(1)]+. Electrochemical impedance spectroscopy (EIS) has been used to investigate the interfaces in DSCs; the analysis shows that more favourable electron injection into TiO2 is observed for sensitizers without the alkynyl spacer and confirms higher JSC values for [Cu(5)(1)]+.
Design, Synthesis and Characterization of a New Series of Fluorescent Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulators
Authors: Fernández-Dueñas Víctor , Qian Mingcheng , Argerich Josep , Amaral Carolina , Risseeuw Martijn D.P. , Van Calenbergh Serge , Ciruela Francisco
Published: April 2020

In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter’ systems, thus providing safe and effective treatments for a number of central nervous system diseases. The metabotropic glutamate type 5 receptor (mGlu5R) has been shown to possess a druggable allosteric binding domain. Accordingly, novel allosteric ligands are being explored in order to finely regulate glutamate neurotransmission, especially in the brain. However, before testing the activity of these new ligands in the clinic or even in animal disease models, it is common to characterize their ability to bind mGlu5Rs in vitro. Here, we have developed a new series of fluorescent ligands that, when used in a new NanoBRET-based binding assay, will facilitate screening for novel mGlu5R allosteric modulators.
Novel Approach to Automated Flow Titration for the Determination of Fe(III)
Authors: Kozak Joanna , Paluch Justyna , Kozak Marek , Duracz Marta , Wieczorek Marcin , Kościelniak Paweł
Published: April 2020

A novel approach to automated flow titration with spectrophotometric detection for the determination of Fe(III) is presented. The approach is based on the possibility of strict and simultaneous control of the flow rates of sample and titrant streams over time. It consists of creating different but precisely defined concentration gradients of titrant and analyte in each successively formed monosegments, and is based on using the calculated titrant dilution factor. The procedure was verified by complexometric titration of Fe(III) in the form of a complex with sulfosalicylic acid, using EDTA as a titrant. Fe(III) and Fe(II) (after oxidation to Fe(III) with the use of H2O2) were determined with good precision (CV lower than 1.7%, n = 6) and accuracy ( | RE | lower than 3.3%). The approach was applied to determine Fe(III) and Fe(II) in artesian water samples. Results of determinations were consistent with values obtained using the ICP–OES reference method. Using the procedure, it was possible to perform titration in 6 min for a wide range of analyte concentrations, using 2.4 mL of both sample and titrant.
Glycosylated-Chitosan Derivatives: A Systematic Review
Authors: Sacco Pasquale , Cok Michela , Scognamiglio Francesca , Pizzolitto Chiara , Vecchies Federica , Marfoglia Andrea , Marsich Eleonora , Donati Ivan
Published: April 2020

Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this set of engineered polysaccharides finds application in different sectors, spanning from food to the biomedical field. Overcoming chitosan (physical) limitations or grafting biological relevant molecules, to mention a few, represent two cardinal strategies to modify parent biopolymer; thereby, synthetizing high added value polysaccharides. The present review is focused on the introduction of oligosaccharide side chains on the backbone of chitosan. The synthetic aspects and the effect on physical-chemical properties of such modifications are discussed. Finally, examples of potential applications in biomaterials design and drug delivery of these novel modified chitosans are disclosed.
Outlier Profiles of Atomic Structures Derived from X-ray Crystallography and from Cryo-Electron Microscopy
Authors: Chen Lin , He Jing
Published: April 2020

Background: As more protein atomic structures are determined from cryo-electron microscopy (cryo-EM) density maps, validation of such structures is an important task. Methods: We applied a histogram-based outlier score (HBOS) to six sets of cryo-EM atomic structures and five sets of X-ray atomic structures, including one derived from X-ray data with better than 1.5 Å resolution. Cryo-EM data sets contain structures released by December 2016 and those released between 2017 and 2019, derived from resolution ranges 0–4 Å and 4–6 Å respectively. Results: The distribution of HBOS values in five sets of X-ray structures show that HBOS is sensitive distinguishing sets of X-ray structures derived from different resolution ranges-higher than 1.5 Å, 1.5–2.0 Å, 2.0–2.5 Å, 2.5–3.0 Å, and 3.0–3.5 Å. The overall quality of cryo-EM structures is likely improved, as shown in a comparison of cryo-EM structures released before the end of 2016, those between 2017 and 2018, and those between 2018 and 2019. Our investigation shows that leucine (LEU) has a significantly higher rate of HBOS outliers than that of the reference data set (X-ray-1.5) and of other residue types in the cryo-EM data sets. HBOS was able to detect outliers for those residues that are currently marked as green in PDB validation reports. Conclusions: The HBOS profile of a dataset is a potential method to characterize the overall structural quality of the set. Residue LEU deserves special attention since it has a significantly higher HBOS outlier rate in sets of cryo-EM structures and those X-ray structures derived from X-ray data of lower than 2.5 Å resolutions. Most HBOS outlier residues from the EM-0-4-2019 set are located on loops for most types of residues.
Genetic Polymorphism of GSTP-1 Affects Cyclophosphamide Treatment of Autoimmune Diseases
Authors: Hajdinák Péter , Szabó Melinda , Kiss Emese , Veress Lili , Wunderlich Lívius , Szarka András
Published: April 2020

Cyclophosphamide is one of the most potent and reliable anti-cancer and immunosuppressive drugs. In our study, 33 individuals with different autoimmune diseases were treated with cyclophosphamide according to standard protocols. The responses to the treatments were determined by measuring the alteration of several typical parameters characterizing the given autoimmune diseases over time. We concluded that about 45% of the patients responded to the treatment. Patients were genotyped for polymorphisms of the CYP3A4, CYP2B6, GSTM1, GSTT1, and GSTP1 genes and disease remission cases were compared to the individual polymorphic genotypes. It was found that the GSTP1 I105V allelic variation significantly associated with the cyclophosphamide treatment-dependent disease-remissions. At the same time the GSH content of the erythrocytes in the patients with I105V allelic variation did not change. It appears that the individuals carrying the Ile105Val SNP in at least one copy had a significantly higher response rate to the treatment. Since this variant of GSTP1 can be characterized by lower conjugation capacity that results in an elongated and higher therapeutic dose of cyclophosphamide, our data suggest that the decreased activity of this variant of GSTP1 can be in the background of the more effective disease treatment.
Heterocyclic Amine Formation in Grilled Chicken Depending on Body Parts and Treatment Conditions
Authors: Pleva Dániel , Lányi Katalin , Monori Kitti Dóra , Laczay Péter
Published: April 2020

Heterocyclic amines (HCAs) carcinogenicity is known since the 1970′s, but the exact way of their formation is still unclear. During these examinations different body parts (breast filet with and without skin, thigh filet without skin and full wing with skin) of chickens from the same Ross 308 strain were analyzed after grilling with the combination of 3-3 temperature and duration levels (150-180-210 °C and 2.5-5-10 min per side). Five different kinds of heterocyclic amines (HAR, NOR, MeIQx, 4,8-DiMeIQx and PhIP) were detected by HLPC-MS/MS. The results obtained from the present study confirm that, in general, the higher the temperature and longer the duration of the grilling the more HCAs will be generated. Grilling of chicken thigh without bones and skin resulted in lower amounts of HCAs generated in comparison to the grilling of chicken breast without skin. The presence of skin on the chicken breast increased the amounts of HCAs formed, especially if grilling was performed at high temperature for longer duration, especially at 210 °C for 10 min. In case of grilling the chicken wings, the amounts of HCAs formed were lower than observed in the breast.
Development of a Liquid Chromatography–High Resolution Mass Spectrometry Method for the Determination of Free Fatty Acids in Milk
Authors: Kokotou Maroula G. , Mantzourani Christiana , Kokotos George
Published: April 2020

The determination of free fatty acids (FFAs) in milk is of importance for quality control, legislative purposes, authentication and product development. We present herein a liquid chromatography–high resolution mass spectrometry method for the direct determination of FFAs in milk. The method involves mild sample preparation, avoids time-consuming derivatization and allows the direct quantification of twenty-two FFAs in a 10-min single run. It was validated and applied in thirteen cow milk and seven goat milk samples. Saturated fatty acids C16:0, C18:0 and unsaturated C18:1 (n-9) were found to be the major components of milk FFAs at concentrations of 33.1 ± 8.2 μg/mL, 16.5 ± 5.3 μg/mL and 14.8 ± 3.8 μg/mL, respectively, in cow milk and at concentrations of 22.8 ± 1.8 μg/mL, 12.7 ± 2.8 μg/mL and 13.3 ± 0.3 μg/mL, respectively, in goat milk. Other saturated and unsaturated FFAs were found in significantly lower quantities. Saturated fatty acids C6:0, C8:0 and C10:0 were found in higher quantities in goat milk than in cow milk. The levels of the important (for human health) odd-chain FFAs C15:0 and C17:0 were estimated in cow and goat milk.
Improved Predictive Tools for Structural Properties of Metal–Organic Frameworks
Authors: Choudhuri Indrani , Truhlar Donald
Published: April 2020

The accurate determination of structural parameters is necessary to understand the electronic and magnetic properties of metal–organic frameworks (MOFs) and is a first step toward accurate calculations of electronic structure and function for separations and catalysis. Theoretical structural determination of metal-organic frameworks is particularly challenging because they involve ionic, covalent, and noncovalent interactions, which must be treated in a balanced fashion. Here, we apply a diverse group of local exchange-correlation functionals (PBE, PBEsol, PBE-D2, PBE-D3, vdW-DF2, SOGGA, MN15-L, revM06-L, SCAN, and revTPSS) to a broad test set of MOFs to seek the most accurate functionals to study various structural aspects of porous solids, in particular to study lattice constants, unit cell volume, two types of pore size characteristics, bond lengths, bond angles, and torsional angles). The recently developed meta functionals revM06-L and SCAN, without adding any molecular mechanics terms, are able to predict more accurate structures than previously recommended functionals, both those without molecular mechanics terms (PBE, PBEsol, vdW-DF2, and revTPSS) and those with them (PBE-D2 and PBE-D3). To provide a broader test, these two functionals are also tested for lattice constants and band gaps of unary, binary, and ternary semiconductors.
Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [18F]AlF-Affibody Conjugates
Authors: Da Pieve Chiara , Makarem Ata , Turnock Stephen , Maczynska Justyna , Smith Graham , Kramer-Marek Gabriela
Published: April 2020

Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide–thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions.
Ionic Liquids and Ohmic Heating in Combination for Pd-Catalyzed Cross-Coupling Reactions: Sustainable Synthesis of Flavonoids
Authors: Silva Vera L. M. , Soengas Raquel G. , Silva Artur M. S.
Published: April 2020

In order to meet the increasing demand for environmentally benign chemical processes, we developed a Suzuki–Miyaura reaction protocol based on the combination of ohmic heating (ΩH) and supported ionic liquid phase catalysis (SILPC) in aqueous media. This methodology was applied to the synthesis of a series of flavonoid derivatives, including isoflavones, styrylisoflavones, and diarylalkenylisoflavones.
Preliminary Study on the Differences in Hydrocarbons Between Phosphine-Susceptible and -Resistant Strains of Rhyzopertha dominica (Fabricius) and Tribolium castaneum (Herbst) Using Direct Immersion Solid-Phase Microextraction Coupled with GC-MS
Authors: Alnajim Ihab , Agarwal Manjree , Liu Tao , Li Beibei , Du Xin , Ren Yonglin
Published: April 2020

Phosphine resistance is a worldwide issue threatening the grain industry. The cuticles of insects are covered with a layer of lipids, which protect insect bodies from the harmful effects of pesticides. The main components of the cuticular lipids are hydrocarbon compounds. In this research, phosphine-resistant and -susceptible strains of two main stored-grain insects, T. castaneum and R. dominica, were tested to determine the possible role of their cuticular hydrocarbons in phosphine resistance. Direct immersion solid-phase microextraction followed by gas chromatography-mass spectrometry (GC-MS) was applied to extract and analyze the cuticular hydrocarbons. The results showed significant differences between the resistant and susceptible strains regarding the cuticular hydrocarbons that were investigated. The resistant insects of both species contained higher amounts than the susceptible insects for the majority of the hydrocarbons, sixteen from cuticular extraction and nineteen from the homogenized body extraction for T. castaneum and eighteen from cuticular extraction and twenty-one from the homogenized body extraction for R. dominica. 3-methylnonacosane and 2-methylheptacosane had the highest significant difference between the susceptible and resistant strains of T. castaneum from the cuticle and the homogenized body, respectively. Unknown5 from the cuticle and 3-methylhentriacontane from the homogenized body recorded the highest significant differences in R. dominica. The higher hydrocarbon content is a key factor in eliminating phosphine from entering resistant insect bodies, acting as a barrier between insects and the surrounding phosphine environment.
Direct Analysis of Psilocin and Muscimol in Urine Samples Using Single Drop Microextraction Technique In-Line with Capillary Electrophoresis
Authors: Poliwoda Anna , Zielińska Katarzyna , Wieczorek Piotr P.
Published: April 2020

The fully automated system of single drop microextraction coupled with capillary electrophoresis (SDME-CE) was developed for in-line preconcentration and determination of muscimol (MUS) and psilocin (PSC) from urine samples. Those two analytes are characteristic active metabolites of Amanita and Psilocybe mushrooms, evoking visual and auditory hallucinations. Study analytes were selectively extracted from the donor phase (urine samples, pH 4) into the organic phase (a drop of octanol layer), and re-extracted to the acidic acceptor (background electrolyte, BGE), consisting of 25 mM phosphate buffer (pH 3). The optimized conditions for the extraction procedure of a 200 µL urine sample allowed us to obtain more than a 170-fold enrichment effect. The calibration curves were linear in the range of 0.05–50 mg L−1, with the correlation coefficients from 0.9911 to 0.9992. The limit of detections was determined by spiking blank urine samples with appropriate standards, i.e., 0.004 mg L−1 for PSC and 0.016 mg L−1 for MUS, respectively. The limits of quantification varied from 0.014 mg L−1 for PSC and 0.045 mg L−1 for MUS. The developed method practically eliminated the sample clean-up step, which was limited only to simple dilution (1:1, v/v) and pH adjustment.
Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant
Authors: Gonçalves Elaine C. D. , Baldasso Gabriela M. , Bicca Maíra A. , Paes Rodrigo S. , Capasso Raffaele , Dutra Rafael C.
Published: April 2020

Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound—Δ9-tetrahydrocannabinol (Δ9-THC)—as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.
Automatic On-Line Purge-and-Trap Sequential Injection Analysis for Trace Ammonium Determination in Untreated Estuarine and Seawater Samples
Authors: Dimitriadou Athina , Anthemidis Aristidis
Published: April 2020

An innovative automatic purge-and-trap (P&T) system coupled with fluorimetric sequential injection (SI), for the on-line separation and preconcentration of volatile compounds, is presented. The truth of concept is demonstrated for the ammonium fluorimetric determination in environmental water samples with complex matrices without any pretreatment. The P&T flow system comprises a thermostated purge-vessel where ammonium is converted into gaseous ammonia and a trap-vessel for ammonia collection. This configuration results in matrix removal as well as analyte preconcentration, avoiding membrane-associated problems. All the main parameters affecting the efficiency of a P&T system were studied and optimized. The proposed method is characterized by a working range of 2.7–150.0 μg L−1 of NH4+, with a detection and quantification limit of 0.80 and 2.66 μg L−1, respectively, for a 10-mL sample consumption. The accuracy of the method was assessed by recovery assays in seawater, estuarine, and lake water samples as well as by the analysis of standard reference material.
Purification, Identification, and Characterization of an Endo-1,4-β-Xylanase from Wheat Malt
Authors: Peng Zhaojun , Jin Yuhong
Published: April 2020

In this study, an endo-1,4-β-xylanase was purified from wheat malt following the procedures of ammonium sulfate precipitation, cation-exchange chromatography, and two-step anion-exchange chromatography. The purified endo-1,4-β-xylanase had a specific activity of 3.94 u/mg, demonstrating a weight average molecular weight (Mw) of approximately 58,000 Da. After LC–MS/MS (Liquid chromatography-tandem mass spectrometry) identification, the purified enzyme had the highest matching degree with a GH10 (Glycoside Hydrolase 10) domain-containing protein from wheat, there were 23 match peptides with a score above the threshold and the prot-cover was 45.5%. The resulting purified enzyme was used to investigate its degradation ability on high viscosity wheat-derived water-extractable arabinoxylan (WEAX). Degradation experiments confirmed that the purified enzyme was a true endo-acting enzyme, which could degrade large WEAX into smaller WEAX. The average degree of polymerization (avDP) and the viscosity of WEAX decreased with the increasing reaction time. The enzyme could degrade a small amount of WEAX into arabinoxylan-oligosaccharides (AXOS) with a degree of polymerization of 2–6, but no monosaccharide was produced. The degradation occurred rapidly in the first 3.5 h and decreased with the further prolongation of reaction time.
Antioxidant Potential of Antiviral Drug Umifenovir
Authors: Proskurnina Elena V. , Izmailov Dmitry Yu. , Sozarukova Madina M. , Zhuravleva Tatiana A. , Leneva Irina A. , Poromov Artem A.
Published: April 2020

Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol®). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM−1 min.−1, for Umifenovir k1 = 300 nM−1min.−1, k2 = 4 nM−1min.−1. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.
Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells
Authors: Huang Haizhi , Chen Allen Y. , Ye Xingqian , Guan Rongfa , Rankin Gary O. , Chen Yi Charlie
Published: April 2020

Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC50 values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.
Modulation of the Autophagy-Lysosomal Pathway in Hepatocellular Carcinoma Using Small Molecules
Authors: Lee Yu Geon , Jeon Tae–Il
Published: April 2020

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer; it is the third most frequent cause of cancer-related death worldwide. In early-stage disease, surgical resection and liver transplantation are considered curative treatments. However, the majority of HCC patients present with advanced-stage disease that is treated using palliative systemic therapy. Since HCC is heterogeneous owing to its multiple etiologies, various risk factors, and inherent resistance to chemotherapy, the development of an effective systemic treatment strategy for HCC remains a considerable challenge. Autophagy is a lysosome-dependent catabolic degradation pathway that is essential for maintaining cellular energy homeostasis. Autophagy dysfunction is closely linked with the pathogenesis of various cancers; therefore, the discovery of small molecules that can modulate autophagy has attracted considerable interest in the development of a systemic treatment strategy for advanced HCC. Here, we reviewed the roles of autophagy in HCC and the recent advances regarding small molecules that target autophagy regulatory mechanisms.
Proapoptotic Activity of Achillea membranacea Essential Oil and Its Major Constituent 1,8-Cineole against A2780 Ovarian Cancer Cells
Authors: Abdalla Ashraf N. , Shaheen Usama , Abdallah Qasem M. A. , Flamini Guido , Bkhaitan Majdi M. , Abdelhady Mohamed I. S. , Ascrizzi Roberta , Bader Ammar
Published: April 2020

Among the hundreds of reported Achillea species, A. membranacea (Labill.) DC. is one of the six that grow in Jordan. Many species of this genus are used in folk medicine to treat a variety of ailments and several biological and pharmacological activities have been ascribed to their essential oil (EO). For this study, the EO obtained from a specimen of A. membranacea grown in Jordan was analyzed by GC-MS. Ninety-six compounds were detected, of which oxygenated monoterpenes was the predominant class (47.9%), followed by non-terpene derivatives (27.9%), while sesquiterpenes represented 14.2% of the total composition. The most abundant compound in the EO was 1,8-cineole (21.7%). The cytotoxic activity of the EO was evaluated against three cancer cell lines (MCF7, A2780 and HT29), and one normal fibroblast cell line (MRC5) by MTT assay. Significant growth inhibition was observed in EO-exposed A2780 and HT29 cells (IC50 = 12.99 and 14.02 μg/mL, respectively), while MCF7 and MRC5 were less susceptible. The EO induced apoptosis and increased the preG1 events in A2780 cells. 1,8-Cineole, the major constituent of the EO, exhibited submicromolar cytotoxicity against A2780 cells, and was 42 times more selective against MRC5 cells. Its cytotoxicity against A2780 cells was comparable with that of doxorubicin, but 1,8-cineole was more selective for MRC5 normal cells. Interestingly, 1,8-cineole enhanced apoptosis in A2780, and caused a remarkable dose-dependent increase in preG1 events. Thus, 1,8-cineole has demonstrated promising cytotoxic and proapoptotic properties.
Polydopamine-Lysophosphatidate-Functionalised Titanium: A Novel Hybrid Surface Finish for Bone Regenerative Applications
Authors: Baldwin Fiona , Craig Tim J. , Shiel Anna I. , Cox Timothy , Lee Kyueui , Mansell Jason P.
Published: April 2020

Aseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £135m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices. In realising the development of a superior titanium (Ti) technology, we took inspiration from the growing interest in reactive polydopamine thin films for biomaterial surface functionalisations. Adopting a “one-pot” approach, we exposed medical-grade titanium to a mildly alkaline solution of dopamine hydrochloride (DHC) supplemented with (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant analogue of lysophosphatidic acid (LPA). Importantly, LPA and selected LPA analogues like FHBP synergistically cooperate with calcitriol to promote human osteoblast formation and maturation. Herein, we provide evidence that simply immersing Ti in aqueous solutions of DHC-FHBP afforded a surface that was superior to FHBP-Ti at enhancing osteoblast maturation. The facile step we have taken to modify Ti and the biological performance of the final surface finish are appealing properties that may attract the attention of implant manufacturers in the future.
Can We Predict the Pressure Induced Phase Transition of Urea? Application of Quantum Molecular Dynamics
Authors: Mazurek Anna , Szeleszczuk Łukasz , Pisklak Dariusz Maciej
Published: April 2020

Crystalline urea undergoes polymorphic phase transition induced by high pressure. Form I, which is the most stable form at normal conditions and Form IV, which is the most stable form at 3.10 GPa, not only crystallize in various crystal systems but also differ significantly in the unit cell dimensions. The aim of this study was to determine if it is possible to predict polymorphic phase transitions by optimizing Form I at high pressure and Form IV at low pressure. To achieve this aim, a large number of periodic density functional theory (DFT) calculations were performed using CASTEP. After geometry optimization of Form IV at 0 GPa Form I was obtained, performing energy minimization of Form I at high pressure did not result in Form IV. However, employing quantum molecular isothermal–isobaric (NPT) dynamics calculations enabled to accurately predict this high-pressure transformation. This study shows the potential of different approaches in predicting the polymorphic phase transition and points to the key factors that are necessary to achieve the success.
A Simple Iron-Catalyst for Alkenylation of Ketones Using Primary Alcohols
Authors: Sk Motahar , Kumar Ashish , Das Jagadish , Banerjee Debasis
Published: April 2020

Herein, we developed a simple iron-catalyzed system for the α-alkenylation of ketones using primary alcohols. Such acceptor-less dehydrogenative coupling (ADC) of alcohols resulted in the synthesis of a series of important α,β-unsaturated functionalized ketones, having aryl, heteroaryl, alkyl, nitro, nitrile and trifluoro-methyl, as well as halogen moieties, with excellent yields and selectivity. Initial mechanistic studies, including deuterium labeling experiments, determination of rate and order of the reaction, and quantitative determination of H2 gas, were performed. The overall transformations produce water and dihydrogen as byproducts.
The Role of Brassica Bioactives on Human Health: Are We Studying It the Right Way?
Authors: Quirante-Moya Sarai , García-Ibañez Paula , Quirante-Moya Francisco , Villaño Débora , Moreno Diego A.
Published: April 2020

Brassica vegetables and their components, the glucosinolates, have been suggested as good candidates as dietary coadjutants to improve health in non-communicable diseases (NCDs). Different preclinical and clinical studies have been performed in the last decade; however, some concerns have been posed on the lack of established and standardized protocols. The different concentration of bioactive compounds used, time of intervention or sample size, and the lack of blinding are some factors that may influence the studies’ outcomes. This review aims to analyze the critical points of the studies performed with Brassica-related biomolecules and propose some bases for future trials in order to avoid biases.
Organic Eluates Derived from Intermediate Restorative Dental Materials
Authors: Vouzara Triantafyllia , Roussou Konstantina , Nikolaidis Alexandros K. , Tolidis Kosmas , Koulaouzidou Elisabeth A.
Published: April 2020

A great number of different types of materials have been used in dentistry as intermediate restoratives. Among them, new resin-based bases have been released in the dental market. The present study focuses on the identification of the organic eluates released from such materials and the study of their surface microstructure in combination with their corresponding elemental composition. For this purpose, the following materials were used:ACTIVA™BioACTIVE-BASE/LINER™, Ketac™Bond Glass Ionomer, SDR™ and Vitrebond™Light Cure Glass Ionomer Liner/Base. Methanolic leachates derived from polymerized materials were analyzed by means of gas chromatography-mass spectrometry (GC-MS). Scanning electron microscopy(SEM) was used for the surface monitoring of suitably prepared specimens. The GC-MS analysis revealed the elution of twenty different substances from the three resin-based materials, while none was eluted from the glass ionomer base. The SEM analysis for Vitrebond™ presented small pits, the one for Ketac™Bond presented elongated cracks, while no voids were present for ACTIVA™BioACTIVE-BASE/LINER™ and SDR™. Moreover, the resin matrix of some dental materials may inhibit elements’ accumulation on the surface layers. Particularly, the detected organic eluents may be related to potential toxic effects.
Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
Authors: Goel Emily , Erwin Megan , Cawthon Claire V. , Schaff Carson , Fedor Nathaniel , Rayl Trevor , Wilson Onree , Christians Uwe , Register Thomas C. , Geary Randolph L. , Saul Justin , Yazdani Saami K.
Published: April 2020

Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.
Metal-Organic Framework-Based Engineered Materials—Fundamentals and Applications
Authors: Rasheed Tahir , Rizwan Komal , Bilal Muhammad , Iqbal Hafiz M. N.
Published: April 2020

Metal-organic frameworks (MOFs) are a fascinating class of porous crystalline materials constructed by organic ligands and inorganic connectors. Owing to their noteworthy catalytic chemistry, and matching or compatible coordination with numerous materials, MOFs offer potential applications in diverse fields such as catalysis, proton conduction, gas storage, drug delivery, sensing, separation and other related biotechnological and biomedical applications. Moreover, their designable structural topologies, high surface area, ultrahigh porosity, and tunable functionalities all make them excellent materials of interests for nanoscale applications. Herein, an effort has been to summarize the current advancement of MOF-based materials (i.e., pristine MOFs, MOF derivatives, or MOF composites) for electrocatalysis, photocatalysis, and biocatalysis. In the first part, we discussed the electrocatalytic behavior of various MOFs, such as oxidation and reduction candidates for different types of chemical reactions. The second section emphasizes on the photocatalytic performance of various MOFs as potential candidates for light-driven reactions, including photocatalytic degradation of various contaminants, CO2 reduction, and water splitting. Applications of MOFs-based porous materials in the biomedical sector, such as drug delivery, sensing and biosensing, antibacterial agents, and biomimetic systems for various biological species is discussed in the third part. Finally, the concluding points, challenges, and future prospects regarding MOFs or MOF-based materials for catalytic applications are also highlighted.