bluuebunny/crossref_metadata_2025 huggingface dataset:
The Diagnosability of Wheel Networks with Missing Edges under the Comparison Model
Authors: Feng Wei , Wang Shiying
Published: October 2020

The diagnosability is an essential subject for the reliability of a multiple CPU system. As a celebrated topology structure of interconnection networks, an n-dimensional wheel network CWn has numerous great features. In this paper, we discuss the diagnosability of CWn with missing edges under the comparison model. Both the local diagnosability and the strong local diagnosability feature are studied; this feature depicts the equivalence of the local diagnosability of a node and its degree. We demonstrate that CWn(n≥6) possesses this feature, containing the strong feature even with up to 2n−4 missing edges in it, and the outcome is ideal regarding the amount of missing edges.
Double Cyclic Codes over \({\mathbb{F}_{q}+v\mathbb{F}_{q}}\)
Authors: Deng Tenghui , Yang Jing
Published: October 2020

In this paper, an algebraic structure of a type of double cyclic codes is investigated, which covers some existing codes as special cases. The paper presents generic results about the generating polynomials, minimal generating sets, matrices and dual codes of the proposed codes.
Binary Whale Optimization Algorithm for Dimensionality Reduction
Authors: Hussien Abdelazim G. , Oliva Diego , Houssein Essam H. , Juan Angel A. , Yu Xu
Published: October 2020

Feature selection (FS) was regarded as a global combinatorial optimization problem. FS is used to simplify and enhance the quality of high-dimensional datasets by selecting prominent features and removing irrelevant and redundant data to provide good classification results. FS aims to reduce the dimensionality and improve the classification accuracy that is generally utilized with great importance in different fields such as pattern classification, data analysis, and data mining applications. The main problem is to find the best subset that contains the representative information of all the data. In order to overcome this problem, two binary variants of the whale optimization algorithm (WOA) are proposed, called bWOA-S and bWOA-V. They are used to decrease the complexity and increase the performance of a system by selecting significant features for classification purposes. The first bWOA-S version uses the Sigmoid transfer function to convert WOA values to binary ones, whereas the second bWOA-V version uses a hyperbolic tangent transfer function. Furthermore, the two binary variants introduced here were compared with three famous and well-known optimization algorithms in this domain, such as Particle Swarm Optimizer (PSO), three variants of binary ant lion (bALO1, bALO2, and bALO3), binary Dragonfly Algorithm (bDA) as well as the original WOA, over 24 benchmark datasets from the UCI repository. Eventually, a non-parametric test called Wilcoxon’s rank-sum was carried out at 5% significance to prove the powerfulness and effectiveness of the two proposed algorithms when compared with other algorithms statistically. The qualitative and quantitative results showed that the two introduced variants in the FS domain are able to minimize the selected feature number as well as maximize the accuracy of the classification within an appropriate time.
A Set Based Newton Method for the Averaged Hausdorff Distance for Multi-Objective Reference Set Problems
Authors: Uribe Lourdes , Bogoya Johan M , Vargas Andrés , Lara Adriana , Rudolph Günter , Schütze Oliver
Published: October 2020

Multi-objective optimization problems (MOPs) naturally arise in many applications. Since for such problems one can expect an entire set of optimal solutions, a common task in set based multi-objective optimization is to compute N solutions along the Pareto set/front of a given MOP. In this work, we propose and discuss the set based Newton methods for the performance indicators Generational Distance (GD), Inverted Generational Distance (IGD), and the averaged Hausdorff distance Δp for reference set problems for unconstrained MOPs. The methods hence directly utilize the set based scalarization problems that are induced by these indicators and manipulate all N candidate solutions in each iteration. We demonstrate the applicability of the methods on several benchmark problems, and also show how the reference set approach can be used in a bootstrap manner to compute Pareto front approximations in certain cases.
On Singular Distributions With Statistical Structure
Authors: Popescu Paul , Rovenski Vladimir , Stepanov Sergey
Published: October 2020

In this paper, we extend our previous study regarding a Riemannian manifold endowed with a singular (or regular) distribution, generalizing Bochner’s technique and a statistical structure. Following the construction of an almost Lie algebroid, we define the central concept of the paper: The Weitzenböck type curvature operator on tensors, prove the Bochner–Weitzenböck type formula and obtain some vanishing results about the null space of the Hodge type Laplacian on a distribution.
Heat-Related Illnesses Transported by United States Emergency Medical Services
Authors: Yeargin Susan , Hirschhorn Rebecca , Grundstein Andrew
Published: October 2020

Background and objectives: Heat-related illness (HRI) can have significant morbidity and mortality consequences. Research has predominately focused on HRI in the emergency department, yet health care leading up to hospital arrival can impact patient outcomes. Therefore, the purpose of this study was to describe HRI in the prehospital setting. Materials and Methods: A descriptive epidemiological design was utilized using data from the National Emergency Medical Services (EMS) Information System for the 2017–2018 calendar years. Variables of interest in this study were: patient demographics (age, gender, race), US census division, urbanicity, dispatch timestamp, incident disposition, primary provider impression, and regional temperatures. Results: There were 34,814 HRIs reported. The majority of patients were white (n = 10,878, 55.6%), males (n = 21,818, 62.7%), and in the 25 to 64 age group (n = 18,489, 53.1%). Most HRIs occurred in the South Atlantic US census division (n = 11,732, 33.7%), during the summer (n = 23,873, 68.6%), and in urban areas (n = 27,541, 83.5%). The hottest regions were East South Central, West South Central, and South Atlantic, with peak summer temperatures in excess of 30.0 °C. In the spring and summer, most regions had near normal temperatures within 0.5 °C of the long-term mean. EMS dispatch was called for an HRI predominately between the hours of 11:00 a.m.–6:59 p.m. (n = 26,344, 75.7%), with the majority (27,601, 79.3%) of HRIs considered heat exhaustion and requiring the patient to be treated and transported (n = 24,531, 70.5%). Conclusions: All age groups experienced HRI but particularly those 25 to 64 years old. Targeted education to increase public awareness of HRI in this age group may be needed. Region temperature most likely explains why certain divisions of the US have higher HRI frequency. Afternoons in the summer are when EMS agencies should be prepared for HRI activations. EMS units in high HRI frequency US divisions may need to carry additional treatment interventions for all HRI types.
HPLC-DAD-ESI-QTOF-MS Determination of Bioactive Compounds and Antioxidant Activity Comparison of the Hydroalcoholic and Water Extracts from Two Helichrysum italicum Species
Authors: Kramberger Katja , Barlič-Maganja Darja , Bandelj Dunja , Baruca Arbeiter Alenka , Peeters Kelly , Miklavčič Višnjevec Ana , Jenko Pražnikar Zala
Published: October 2020

Mediterranean plant Helichrysum italicum represents a rich source of versatile bioactive compounds with potential benefits for human health. Despite extensive research on the plant’s active constituents, little attention has yet been paid to characterizing the relationship between its intra-specific genetic diversity and metabolite profile. The study aimed to determine metabolic profile of H. italicum ssp. italicum (HII) and ssp. tyrrhenicum (HIT) cultivated on the experimental plantation in Slovenia and to compare the chemical composition of extracts regarding the solvent extraction process. Extracts were prepared upon conventional extract preparation procedures: maceration with 50% methanol or ethanol and cold or hot water infusion and analyzed using High Performance Liquid Chromatography-Diode Array Detection-Electrospray Ionization-Quadrupole Time-of-Flight-Mass Spectrometry (HPLC-DAD-ESI-QTOF-MS). One hundred compounds were identified in the samples, among them several isomers and derivatives were reported for the first time, while caffeoylquinic acids and pyrones were the most abundant. Semi-quantitative comparison revealed that the extraction procedure had a greater impact on the chemical profile than genetic variability. All HIT extracts showed a higher total phenolic content compared to HII, while the antioxidant potential evaluated by 1,1-diphenyl-2-picrylhydrazil test was not proportionally higher. In addition, hot water extracts proved to be comparably active as alcoholic ones, confirming high commercial potential of Helichrysum italicum as herbal functional beverages.
Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment
Authors: Angeli Andrea , Carta Fabrizio , Nocentini Alessio , Winum Jean-Yves , Zalubovskis Raivis , Akdemir Atilla , Onnis Valentina , Eldehna Wagdy M. , Capasso Clemente , Simone Giuseppina De , Monti Simona Maria , Carradori Simone , Donald William A. , Dedhar Shoukat , Supuran Claudiu T.
Published: October 2020

The tumor microenvironment is crucial for the growth of cancer cells, triggering particular biochemical and physiological changes, which frequently influence the outcome of anticancer therapies. The biochemical rationale behind many of these phenomena resides in the activation of transcription factors such as hypoxia-inducible factor 1 and 2 (HIF-1/2). In turn, the HIF pathway activates a number of genes including those involved in glucose metabolism, angiogenesis, and pH regulation. Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as CA IX and XII, actively participate in these processes and were validated as antitumor/antimetastatic drug targets. Here, we review the field of CA inhibitors (CAIs), which selectively inhibit the cancer-associated CA isoforms. Particular focus was on the identification of lead compounds and various inhibitor classes, and the measurement of CA inhibitory on-/off-target effects. In addition, the preclinical data that resulted in the identification of SLC-0111, a sulfonamide in Phase Ib/II clinical trials for the treatment of hypoxic, advanced solid tumors, are detailed.
Rapid Preparation of a Large Sulfated Metabolite Library for Structure Validation in Human Samples
Authors: Correia Mario S. P. , Lin Weifeng , Aria Arash J. , Jain Abhishek , Globisch Daniel
Published: October 2020

Metabolomics analysis of biological samples is widely applied in medical and natural sciences. Assigning the correct chemical structure in the metabolite identification process is required to draw the correct biological conclusions and still remains a major challenge in this research field. Several metabolite tandem mass spectrometry (MS/MS) fragmentation spectra libraries have been developed that are either based on computational methods or authentic libraries. These libraries are limited due to the high number of structurally diverse metabolites, low commercial availability of these compounds, and the increasing number of newly discovered metabolites. Phase II modification of xenobiotics is a compound class that is underrepresented in these databases despite their importance in diet, drug, or microbiome metabolism. The O-sulfated metabolites have been described as a signature for the co-metabolism of bacteria and their human host. Herein, we have developed a straightforward chemical synthesis method for rapid preparation of sulfated metabolite standards to obtain mass spectrometric fragmentation pattern and retention time information. We report the preparation of 38 O-sulfated alcohols and phenols for the determination of their MS/MS fragmentation pattern and chromatographic properties. Many of these metabolites are regioisomers that cannot be distinguished solely by their fragmentation pattern. We demonstrate that the versatility of this method is comparable to standard chemical synthesis. This comprehensive metabolite library can be applied for co-injection experiments to validate metabolites in different human sample types to explore microbiota-host co-metabolism, xenobiotic, and diet metabolism.
Tularemia Goes West: Epidemiology of an Emerging Infection in Austria
Authors: Seiwald Stefanie , Simeon Anja , Hofer Erwin , Weiss Günter , Bellmann-Weiler Rosa
Published: October 2020

The zoonotic disease tularemia is caused by the Gram-negative bacterium Francisella tularensis, with the two major subspecies tularensis and holarctica being responsible for infections in humans and animals. The F. tularensis subspecies holarctica is less virulent and prevalent in Europe and Asia. Over the last few centuries, few epidemic outbreaks and low numbers of infections have been registered in the eastern part of Austria, specifically in the provinces of Lower Austria, Burgenland, and Styria. The reported infections were mostly associated with hunting hares and the skinning of carcasses. Within the last decade, ticks have been identified as important vectors in Tyrol and served as first evidence for the spread of F. tularensis to Western Austria. In 2018, the pathogen was detected in hares in the provinces of Tyrol, Vorarlberg, and Salzburg. We presume that F. tularensis is now established in most regions of Austria, and that the investigation of potential host and vector animals should be spotlighted by public institutions. Tularemia in humans presents with various clinical manifestations. As glandular, ulceroglandular, and typhoidal forms occur in Austria, this infectious disease should be considered as a differential diagnosis of unknown fever.
Crucial Role of the C-Terminal Domain of Hfq Protein in Genomic Instability
Authors: Parekh Virali J. , Wien Frank , Grange Wilfried , De Long Thomas A. , Arluison Véronique , Sinden Richard R.
Published: October 2020

G-rich DNA repeats that can form G-quadruplex structures are prevalent in bacterial genomes and are frequently associated with regulatory regions of genes involved in virulence, antigenic variation, and antibiotic resistance. These sequences are also inherently mutagenic and can lead to changes affecting cell survival and adaptation. Transcription of the G-quadruplex-forming repeat (G3T)n in E. coli, when mRNA comprised the G-rich strand, promotes G-quadruplex formation in DNA and increases rates of deletion of G-quadruplex-forming sequences. The genomic instability of G-quadruplex repeats may be a source of genetic variability that can influence alterations and evolution of bacteria. The DNA chaperone Hfq is involved in the genetic instability of these G-quadruplex sequences. Inactivation of the hfq gene decreases the genetic instability of G-quadruplex, demonstrating that the genomic instability of this regulatory element can be influenced by the E. coli highly pleiotropic Hfq protein, which is involved in small noncoding RNA regulation pathways, and DNA organization and packaging. We have shown previously that the protein binds to and stabilizes these sequences, increasing rates of their genomic instability. Here, we extend this analysis to characterize the role of the C-terminal domain of Hfq protein in interaction with G-quadruplex structures. This allows to better understand the function of this specific region of the Hfq protein in genomic instability.
In silico Investigation on the Inhibiting Role of Nicotine/Caffeine by Blocking the S Protein of SARS-CoV-2 Versus ACE2 Receptor
Authors: Mohammadi Saeedeh , Heidarizadeh Mohammad , Entesari Mehrnaz , Esmailpour Ayoub , Esmailpour Mohammad , Moradi Rasoul , Sakhaee Nader , Doustkhah Esmail
Published: October 2020

In this paper, we studied the in silico interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. Caffeine and nicotine are interesting structures for interactions because of their similar structure to the candidate antiviral drugs. Our results reveal that caffeine or nicotine in a specific molar ratio to 6LZG shows a very strong interaction and indicate that caffeine is more efficient in the interaction with 6LZG and further blocking of this site against S protein binding. Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2.
Tourmalines as a Tool in Provenance Studies of Terrigenous Material in Extra-Carpathian Albian (Uppermost Lower Cretaceous) Sands of Miechów Synclinorium, Southern Poland
Authors: Kotowski Jakub , Nejbert Krzysztof , Olszewska-Nejbert Danuta
Published: October 2020

The mature transgressive Albian quartz sands in the Miechów Synclinorium contain a poor (<1%) heavy mineral suite consisting of tourmaline, rutile, garnet, staurolite, ilmenite, zircon, monazite, kyanite, and gahnite. The other minerals, especially those containing Fe and Ti (e.g., biotite), are subordinate. Over 512 tourmaline grains from seven outcrops in the Miechów Segment were analysed using electron probe microanalysis (EPMA). The majority of grains belong to the alkali tourmaline group in which the X-site is dominated by Na (0.4 to 0.9 apfu). Detrital tourmalines are mainly dravite with a prevalent schorl end-member with average XMg values over 0.6. Apart from Mg and Fe, the other Y-site cations rarely exceed 0.1 apfu. Fluorine content is usually below the detection limit. Their chemical composition suggests that most tourmaline grains were sourced from Al-rich and Al-poor metapelites/metapsammites. The main source rocks for the Albian sands were rocks from low- to medium-grade metamorphism, probably from Al-rich quartz-muscovite schist and/or muscovite rich gneisses. Additional minor source rocks were granites and pegmatites coexisting with them. A comparison of the examined tourmaline to tourmaline from possible source areas indicates that these areas were located in the eastern part of the Bohemian Massif and/or eastern Sudetes.
Emergences of New Technology for Ultrafast Automated Mineral Phase Identification and Quantitative Analysis Using the CORIOSITY Laser-Induced Breakdown Spectroscopy (LIBS) System
Authors: Rifai Kheireddine , Michaud Paradis Marie-Chloé , Swierczek Zofia , Doucet François , Özcan Lütfü , Fayad Alejandro , Li Jing , Vidal François
Published: October 2020

Geochemical and mineralogical characterization studies play an important role in the definition of mineral deposits. Each mineral system has a unique set of minerals with different chemical makeup and physical properties. Platinum-group elements (PGEs), for example, are scarce resources with many applications. The optimization of extraction process efficiency is therefore crucial to prevent resource shortage and increased bulk prices. To improve the mineral liberation process, high throughput sensors must be added alongside the production line as part of fast process analysis implementation. Current analytical methods are either ineffective to assess PGE content, or unusable in the conditions of the processing facilities. This article shows how Laser-induced breakdown spectroscopy (LIBS) technology, developed by ELEMISSION Inc, can circumvent these drawbacks by enabling automated, ultra-fast, and precise quantitative mineral analyses in any working environment. The drill core samples that were used in this study were collected at the Stillwater platinum group element mine in the United States. The data used for the mineralogical database was validated using the TESCAN Integrated Mineral Analyzer (TIMA) instrument.
Clay Minerals in Hydrothermal Systems
Authors: Fulignati Paolo
Published: October 2020

The study of active and fossil hydrothermal systems shows clay minerals to be a fundamental tool for the identification and characterization of hydrothermal alteration facies. The occurrence and composition of hydrothermal alteration facies could provide useful information on the physicochemical conditions of the hydrothermal activity affecting a rock volume. In particular, clay minerals (i.e., smectite group, chlorite, illite, kaoline group, pyrophyllite, biotite) are pivotal for extrapolating important parameters that strongly affect the development of water/rock interaction processes such as the temperature and pH of the hydrothermal environment. This work aims to give a general reference scheme concerning the occurrence of clay minerals in hydrothermal alteration paragenesis, their significance, and the information that can be deduced by their presence and chemical composition, with some examples from active and fossil hydrothermal systems around the world. The main mineralogical geothermometers based on chlorite and illite composition are presented, together with the use of hydrogen and oxygen isotope investigation of clay minerals in hydrothermal systems. These techniques provide a useful tool for the reconstruction of the origin and evolution of fluids involved in hydrothermal alteration. Finally, a list of oxygen and hydrogen fractionation factor equations between the main clay minerals and water is also provided.
Magnolol Enhances the Therapeutic Effects of TRAIL through DR5 Upregulation and Downregulation of c-FLIP and Mcl-1 Proteins in Cancer Cells
Authors: Woo Seon Min , Min Kyoung-jin , Kwon Taeg Kyu
Published: October 2020

Magnolol is a biologically active compound, isolated from the Chinese herb Magnolia, that regulates antiproliferative, anticancer, antiangiogenic and antimetastatic activities. We found that magnolol sensitizes TRAIL-induced apoptotic cell death via upregulation of DR5 and downregulation of cellular FLICE-inhibitory protein (c-FLIP) and Mcl-1 in cancer cells, but not in normal cells. Mechanistically, magnolol increased ATF4-dependent DR5 expression at the transcription level, and knockdown of ATF4 markedly inhibited magnolol-induced DR5 upregulation. Silencing DR5 with siRNA prevented combined treatment with magnolol and TRAIL-induced apoptosis and PARP cleavage. Magnolol induced proteasome-mediated Mcl-1 downregulation, while magnolol-induced c-FLIP downregulation was regulated, at least in part, by lysosomal degradation. Our results revealed that magnolol enhanced TRAIL-induced apoptosis via ATF4-dependent DR5 upregulation and downregulation of c-FLIP and Mcl-1 proteins.
Enzyme Stability in Nanoparticle Preparations Part 1: Bovine Serum Albumin Improves Enzyme Function
Authors: Duskey Jason Thomas , da Ros Federica , Ottonelli Ilaria , Zambelli Barbara , Vandelli Maria Angela , Tosi Giovanni , Ruozi Barbara
Published: October 2020

Enzymes have gained attention for their role in numerous disease states, calling for research for their efficient delivery. Loading enzymes into polymeric nanoparticles to improve biodistribution, stability, and targeting in vivo has led the field with promising results, but these enzymes still suffer from a degradation effect during the formulation process that leads to lower kinetics and specific activity leading to a loss of therapeutic potential. Stabilizers, such as bovine serum albumin (BSA), can be beneficial, but the knowledge and understanding of their interaction with enzymes are not fully elucidated. To this end, the interaction of BSA with a model enzyme B-Glu, part of the hydrolase class and linked to Gaucher disease, was analyzed. To quantify the natural interaction of beta-glucosidase (B-Glu,) and BSA in solution, isothermal titration calorimetry (ITC) analysis was performed. Afterwards, polymeric nanoparticles encapsulating these complexes were fully characterized, and the encapsulation efficiency, activity of the encapsulated enzyme, and release kinetics of the enzyme were compared. ITC results showed that a natural binding of 1:1 was seen between B-Glu and BSA. Complex concentrations did not affect nanoparticle characteristics which maintained a size between 250 and 350 nm, but increased loading capacity (from 6% to 30%), enzyme activity, and extended-release kinetics (from less than one day to six days) were observed for particles containing higher B-Glu:BSA ratios. These results highlight the importance of understanding enzyme:stabilizer interactions in various nanoparticle systems to improve not only enzyme activity but also biodistribution and release kinetics for improved therapeutic effects. These results will be critical to fully characterize and compare the effect of stabilizers, such as BSA with other, more relevant therapeutic enzymes for central nervous system (CNS) disease treatments.
Loseolamycins: A Group of New Bioactive Alkylresorcinols Produced after Heterologous Expression of a Type III PKS from Micromonospora endolithica
Authors: Lasch Constanze , Gummerlich Nils , Myronovskyi Maksym , Palusczak Anja , Zapp Josef , Luzhetskyy Andriy
Published: October 2020

Natural products are a valuable source of biologically active compounds with potential applications in medicine and agriculture. Unprecedented scaffold diversity of natural products and biocatalysts from their biosynthetic pathways are of fundamental importance. Heterologous expression and refactoring of natural product biosynthetic pathways are generally regarded as a promising approach to discover new secondary metabolites of microbial origin. Here, we present the identification of a new group of alkylresorcinols after transcriptional activation and heterologous expression of the type III polyketide synthase of Micromonospora endolithica. The most abundant compounds loseolamycins A1 and A2 have been purified and their structures were elucidated by NMR. Loseolamycins contain an unusual branched hydroxylated aliphatic chain which is provided by the host metabolism and is incorporated as a starter fatty acid unit. The isolated loseolamycins show activity against gram-positive bacteria and inhibit the growth of the monocot weed Agrostis stolonifera in a germination assay. The biosynthetic pathway leading to the production of loseolamycins is proposed in this paper.
Bis-Phenoxo-CuII2 Complexes: Formal Aromatic Hydroxylation via Aryl-CuIII Intermediate Species
Authors: Ribas Xavi , Xifra Raül , Fontrodona Xavier
Published: October 2020

Ullmann-type copper-mediated arylC-O bond formation has attracted the attention of the catalysis and organometallic communities, although the mechanism of these copper-catalyzed coupling reactions remains a subject of debate. We have designed well-defined triazamacrocyclic-based aryl-CuIII complexes as an ideal platform to study the C-heteroatom reductive elimination step with all kinds of nucleophiles, and in this work we focus our efforts on the straightforward synthesis of phenols by using H2O as nucleophile. Seven well-defined aryl-CuIII complexes featuring different ring size and different electronic properties have been reacted with water in basic conditions to produce final bis-phenoxo-CuII2 complexes, all of which are characterized by XRD. Mechanistic investigations indicate that the reaction takes place by an initial deprotonation of the NH group coordinated to CuIII center, subsequent reductive elimination with H2O as nucleophile to form phenoxo products, and finally air oxidation of the CuI produced to form the final bis-phenoxo-CuII2 complexes, whose enhanced stability acts as a thermodynamic sink and pushes the reaction forward. Furthermore, the corresponding triazamacrocyclic-CuI complexes react with O2 to undergo 1e− oxidation to CuII and subsequent C-H activation to form aryl-CuIII species, which follow the same fate towards bis-phenoxo-CuII2 complexes. This work further highlights the ability of the triazamacrocyclic-CuIII platform to undergo aryl-OH formation by reductive elimination with basic water, and also shows the facile formation of rare bis-phenoxo-CuII2 complexes.
Conversion of CO2 into Chloropropene Carbonate Catalyzed by Iron (II) Phthalocyanine Hypercrosslinked Porous Organic Polymer
Authors: Maya Eva M. , Valverde-González Antonio , Iglesias Marta
Published: October 2020

Commercial iron (II) phthalocyanine (FePc) was knitted with biphenyl using a Friedel–Crafts reaction to yield a micro-meso porous organic polymer (FePc-POP) with a specific surface area of 427 m2/g and 5.42% of iron loading. This strategy allowed for the direct synthesis of a heterogeneous catalyst from an iron containing monomer. The catalytic system, formed by the knitted polymer containing FePc and DMAP (4-dimethylamino pyridine) as base, results in an efficient heterogeneous catalyst in the cycloaddition of CO2 to epichlorohydrin to selectively obtain the corresponding cyclic carbonate. Thus, a TON (mmol substrate converted/mmol catalysts used) value of 2700 was reached in 3 h under mild reaction conditions (solvent free, 90 °C, 3 bar of CO2). The catalyst does not exhibit leaching during the reactions, which was attributed to the excellent stability of the metal in the macrocycle.
Mass Spectrometry Imaging of Flavonols and Ellagic Acid Glycosides in Ripe Strawberry Fruit
Authors: Enomoto Hirofumi
Published: October 2020

Flavonols and ellagic acid glycosides are major phenolic compounds in strawberry fruit. They have antioxidant activity, show protective functions against abiotic and biotic stress, and provide health benefits. However, their spatial distribution in ripe fruit has not been understood. Therefore, matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) was performed to investigate their distribution in fruit tissues. Using strawberry extract, five flavonols, namely, three kaempferols and two quercetins, and two ellagic acid glycosides, were tentatively identified by MALDI-tandem MS. To investigate the tentatively identified compounds, MALDI-MSI and tandem MS imaging (MS/MSI) analyses were performed. Kaempferol and quercetin glycosides showed similar distribution patterns. They were mainly found in the epidermis, while ellagic acid glycosides were mainly found in the achene and in the bottom area of the receptacle. These results suggested that the difference in distribution pattern between flavonols and ellagic acid glycosides depends on the difference between their aglycones. Seemingly, flavonols play a role in protective functions in the epidermis, while ellagic acid glycosides play a role in the achene and in the bottom side of the receptacle, respectively. These results demonstrated that MALDI-MSI is useful for distribution analysis of flavonols and ellagic acid glycosides in strawberry fruit.
Nanohydroxyapatite-Mediated Imatinib Delivery for Specific Anticancer Applications
Authors: Sobierajska Paulina , Serwotka-Suszczak Anna , Szymanski Damian , Marycz Krzysztof , Wiglusz Rafal J.
Published: October 2020

In the present study, a nanoapatite-mediated delivery system for imatinib has been proposed. Nanohydroxyapatite (nHAp) was obtained by co-precipitation method, and its physicochemical properties in combination with imatinib (IM) were studied by means of XRPD (X-ray Powder Diffraction), SEM-EDS (Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy), FT-IR (Fourier-Transform Infrared Spectroscopy), absorption spectroscopy as well as DLS (Dynamic Light Scattering) techniques. The obtained hydroxyapatite was defined as nanosized rod-shaped particles with high crystallinity. The amorphous imatinib was obtained by conversion of its crystalline form. The beneficial effects of amorphous pharmaceutical agents have been manifested in the higher dissolution rate in body fluids improving their bioavailability. Imatinib-to-hydroxyapatite interactions on the surface were confirmed by SEM images as well as absorption and FT-IR spectroscopy. The cytotoxicity of the system was tested on NI-1, L929, and D17 cell lines. The effectiveness of imatinib was not affected by nHAp modification. The calculated IC50 values for drug-modified nHAp were similar to those for the drug itself. However, higher cytotoxicity was observed at higher concentrations of imatinib, in comparison with the drug alone.
Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study
Authors: Singh Rajveer , Gautam Anupam , Chandel Shivani , Ghosh Arijit , Dey Dhritiman , Roy Syamal , Ravichandiran Velayutham , Ghosh Dipanjan
Published: October 2020

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.
Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer
Authors: Abdalla Ashraf N. , Qattan Amal , Malki Waleed H. , Shahid Imran , Hossain Mohammad Akbar , Ahmed Muhammad
Published: October 2020

The hormonal luminal-A is the most pre-dominant sub type of breast cancer (BC), and it is associated with a high level of cyclin D1 in Saudi patients. Tamoxifen is the golden therapy for hormonal BC, but resistance of cancer cells to tamoxifen contributes to the recurrence of BC due to many reasons, including high levels of AIB1 and cyclin D1. Overcoming drug resistance could be achieved by exploring alternative targetable therapeutic pathways and new drugs or combinations. The objective of this study was to determine the differentially enriched pathways in 12 samples of Saudi women diagnosed with luminal-A using the PamChip peptide microarray-based kinase activity profiling, and to compare the activity of HAA2020 and dinaciclib with tamoxifen in singles and combinations in the MCF7 luminal-A cell line. Our results of network and pathway analysis of the 12 samples highlighted the importance of VEGFR and CDKs in promoting luminal-A breast cancer. The activation of VEGF signaling via VEGFR-2 leads to activation of PI3K/AKT kinases and an increase of cell survival, and leads to activation of Hsp90, which induces the phosphorylation of FAK1, resulting in cytoskeleton remodeling. PLC-gamma 1 is also activated, leading to FAK-2 and PKC activation. Notably, the G1/S cell cycle phases and phosphorylation processes contribute to the top seven tumorigenesis processes in the 12 samples. Further, the MTT combination of HAA2020 and dinaciclib showed the best combination index (CI), was more clonogenic against MCF7 cells compared to the other combinations, and it also showed the best selectivity index (SI) in normal MRC5 cells. Interestingly, HAA2020 and dinaciclib showed a synergistic apoptotic and G1 cell cycle effect in MCF7 cells, which was supported by their synergistic CDK2, cyclin D1, and PCNA inhibition activities. Additionally, the combination showed VEGFR-2 and Hsp90 inhibition activities in MCF7 cells. The results show the significance of targeting VEGFR-2 and cyclin D1 in Saudi luminal-A breast cancer patients, and the effect of combining HAA2020 and dinaciclib on those targets in the MCF7 model. It also warrants further preclinical and in vivo investigations for the combination of HAA2020 and dinaciclib as a possible future second-line treatment for luminal-A breast cancers.
Effect of Different Enological Tannins on Oxygen Consumption, Phenolic Compounds, Color and Astringency Evolution of Aglianico Wine
Authors: Picariello Luigi , Rinaldi Alessandra , Forino Martino , Errichiello Francesco , Moio Luigi , Gambuti Angelita
Published: October 2020

Background: In the wine industry, in addition to condensed tannins of grape origin, other commercial tannins are commonly used. However, the influence of oxygen uptake related to different tannin additions during the post fermentative phase in wine has not been completely investigated. In this study, we evaluated the influence of four different commercial tannins (namely, condensed tannins, gallotannins, ellagitannins and tea tannins) during four saturation cycles. Method: Wine samples were added with four different tannin classes (30 g/hL) as to have 5 different experimental samples: control, gallotannins (GT), condensed tannins (CT), ellagitannins (ET), and tea tannins (TT). The chemical composition of the four commercially available tannin mixtures was defined by means of NMR and high-resolution mass spectrometry. After the addition of tannins, each wine sample was oxidized by air over four cycles of saturation. During the experiment oxygen consumption rate (OCR), sulfur dioxide consumption, acetaldehyde production, phenolic compounds, chromatic characteristics, astringency measured by the reactivity towards saliva proteins and astringency subqualities were evaluated. Results: The experiment lasted 52 days. The addition of tannins influenced the oxygen consumption on the 1st day of the saturation cycles and, in the case of TT, a higher total consumption of oxygen was also detected. Acetaldehyde increased during the experiment while the native anthocyanins decreased throughout the oxidation process. Conclusion: Wines added with tannins featured improved color intensities with respect to the control; the addition of TT, GT and ET slightly promoted the formation of short polymeric pigments; the astringency, determined before and at the end of the experiment, decreased in all the samples, including the control wine, and mostly in the ET and GT samples.
Improvement of Chemical Composition of Tisochrysis lutea Grown Mixotrophically under Nitrogen Depletion towards Biodiesel Production
Authors: Almutairi Adel W.
Published: October 2020

In the present study, the marine microalga Tisochrysis lutea was cultivated mixotrophically in F2 growth medium with sodium acetate as exogenous carbon source. The medium was composed of different concentrations of nitrogen to determine the impact of nitrogen depletion on cellular growth and chemical composition. Nitrogen depletion led to severely decreased growth and protein content. However, mild nitrogen depletion (0.22 mM NaNO3) led to maximum lipid yield. The fatty acid methyl ester profile also showed increased unsaturation as the nitrogen content decreased. Growth in nitrogen-free medium increased the proportions of mono- and poly-unsaturated fatty acids, while the proportion of saturated fatty acids decreased. Growth under all tested nitrogen levels showed undetectable fatty acids with ≥4 double bonds, indicating these fatty acids had oxidative stability. In addition, all tested nitrogen concentrations led to specific gravity, kinematic viscosity, iodine value, and cetane number that meet the standards for Europe and the U.S.A. However, growth in the presence of nitrogen deficiency enhanced the higher heating value of the resulting biodiesel, a clear advantage from the perspective of energy efficiency. Thus, mixotrophic cultivation of T. lutea with nitrogen limitation provides a promising approach to achieve high lipid productivity and production of high-quality biodiesel.
An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats
Authors: Lee Hye-Jin , Jeong Moses , Na Young-Guk , Kim Sung-Jin , Lee Hong-Ki , Cho Cheong-Weon
Published: October 2020

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.
Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols
Authors: Yang Bingyan , Dong Yixin , Wang Fei , Zhang Yu
Published: October 2020

Polyphenols are micronutrients that are widely present in human daily diets. Numerous studies have demonstrated their potential as antioxidants and anti-inflammatory agents, and for cancer prevention, heart protection and the treatment of neurodegenerative diseases. However, due to their vulnerability to environmental conditions and low bioavailability, their application in the food and medical fields is greatly limited. Nanoformulations, as excellent drug delivery systems, can overcome these limitations and maximize the pharmacological effects of polyphenols. In this review, we summarize the biological activities of polyphenols, together with systems for their delivery, including phospholipid complexes, lipid-based nanoparticles, protein-based nanoparticles, niosomes, polymers, micelles, emulsions and metal nanoparticles. The application of polyphenol nanoparticles in food and medicine is also discussed. Although loading into nanoparticles solves the main limitation to application of polyphenolic compounds, there are some concerns about their toxicological safety after entry into the human body. It is therefore necessary to conduct toxicity studies and residue analysis on the carrier.
Biomedical Science to Tackle the COVID-19 Pandemic: Current Status and Future Perspectives
Authors: Zamora-Ledezma Camilo , C. David F. Clavijo , Medina Ernesto , Sinche Federico , Santiago Vispo Nelson , Dahoumane Si Amar , Alexis Frank
Published: October 2020

The coronavirus infectious disease (COVID-19) pandemic emerged at the end of 2019, and was caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in an unprecedented health and economic crisis worldwide. One key aspect, compared to other recent pandemics, is the level of urgency, which has started a race for finding adequate answers. Solutions for efficient prevention approaches, rapid, reliable, and high throughput diagnostics, monitoring, and safe therapies are needed. Research across the world has been directed to fight against COVID-19. Biomedical science has been presented as a possible area for combating the SARS-CoV-2 virus due to the unique challenges raised by the pandemic, as reported by epidemiologists, immunologists, and medical doctors, including COVID-19’s survival, symptoms, protein surface composition, and infection mechanisms. While the current knowledge about the SARS-CoV-2 virus is still limited, various (old and new) biomedical approaches have been developed and tested. Here, we review the current status and future perspectives of biomedical science in the context of COVID-19, including nanotechnology, prevention through vaccine engineering, diagnostic, monitoring, and therapy. This review is aimed at discussing the current impact of biomedical science in healthcare for the management of COVID-19, as well as some challenges to be addressed.
Antibody-Targeted Imaging of Gastric Cancer
Authors: Mandleywala Komal , Shmuel Shayla , Pereira Patricia M. R. , Lewis Jason S.
Published: October 2020

The specificity of antibodies for antigens overexpressed or uniquely expressed in tumor cells makes them ideal candidates in the development of bioconjugates for tumor imaging. Molecular imaging can aid clinicians in the diagnosis of gastric tumors and in selecting patients for therapies targeting receptors with a heterogeneous intratumoral or intertumoral expression. Antibodies labeled with an imaging radiometal can be used to detect primary tumors and metastases using whole-body positron emission tomography (PET) or single photon emission computed tomography (SPECT), both during diagnosis and monitoring disease response. Conjugated with fluorescent dyes, antibodies can image tumors by targeted optical imaging. This review provides an overview of the most recent advances in the use of antibodies labeled with radiometals or conjugated with fluorescent dyes for gastric cancer imaging.
In Silico Molecular Study of Tryptophan Bitterness
Authors: Di Pizio Antonella , Nicoli Alessandro
Published: October 2020

Tryptophan is an essential amino acid, required for the production of serotonin. It is the most bitter amino acid and its bitterness was found to be mediated by the bitter taste receptor TAS2R4. Di-tryptophan has a different selectivity profile and was found to activate three bitter taste receptors, whereas tri-tryptophan activated five TAS2Rs. In this work, the selectivity/promiscuity profiles of the mono-to-tri-tryptophans were explored using molecular modeling simulations to provide new insights into the molecular recognition of the bitter tryptophan. Tryptophan epitopes were found in all five peptide-sensitive TAS2Rs and the best tryptophan epitope was identified and characterized at the core of the orthosteric binding site of TAS2R4.