bluuebunny/crossref_metadata_2025 huggingface dataset:
TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties
Authors: Startek Justyna , Boonen Brett , Talavera Karel , Meseguer Victor
Published: January 2019

Transient Receptor Potential ion channels (TRPs) have been described as polymodal sensors, being responsible for transducing a wide variety of stimuli, and being involved in sensory functions such as chemosensation, thermosensation, mechanosensation, and photosensation. Mechanical and chemical stresses exerted on the membrane can be transduced by specialized proteins into meaningful intracellular biochemical signaling, resulting in physiological changes. Of particular interest are compounds that can change the local physical properties of the membrane, thereby affecting nearby proteins, such as TRP channels, which are highly sensitive to the membrane environment. In this review, we provide an overview of the current knowledge of TRP channel activation as a result of changes in the membrane properties induced by amphipathic structural lipidic components such as cholesterol and diacylglycerol, and by exogenous amphipathic bacterial endotoxins.
Tocotrienols Modulate a Life or Death Decision in Cancers
Authors: Tham Shiau-Ying , Loh Hwei-San , Mai Chun-Wai , Fu Ju-Yen
Published: January 2019

Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
Expanding the Genetic Code for Site-Directed Spin-Labeling
Authors: Braun Theresa , Drescher Malte , Summerer Daniel
Published: January 2019

Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy enables studies of the structure, dynamics, and interactions of proteins in the noncrystalline state. The scope and analytical value of SDSL–EPR experiments crucially depends on the employed labeling strategy, with key aspects being labeling chemoselectivity and biocompatibility, as well as stability and spectroscopic properties of the resulting label. The use of genetically encoded noncanonical amino acids (ncAA) is an emerging strategy for SDSL that holds great promise for providing excellent chemoselectivity and potential for experiments in complex biological environments such as living cells. We here give a focused overview of recent advancements in this field and discuss their potentials and challenges for advancing SDSL–EPR studies.
Role of Semaphorins in Immunopathologies and Rheumatic Diseases
Authors: Garcia Samuel
Published: January 2019

Rheumatic diseases are disorders characterized by joint inflammation, in which other organs are also affected. There are more than two hundred rheumatic diseases, the most studied so far are rheumatoid arthritis, osteoarthritis, spondyloarthritis, systemic lupus erythematosus, and systemic sclerosis. The semaphorin family is a large group of proteins initially described as axon guidance molecules involved in nervous system development. Studies have demonstrated that semaphorins play a role in other processes such as the regulation of immunity, angiogenesis, bone remodeling, apoptosis, and cell migration and invasion. Moreover, semaphorins have been related to the pathogenesis of multiple sclerosis, asthma, Alzheimer, myocarditis, atherosclerosis, fibrotic diseases, osteopetrosis, and cancer. The aim of this review is to summarize current knowledge regarding the role of semaphorins in rheumatic diseases, and discuss their potential applications as therapeutic targets to treat these disorders.
Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma
Authors: Eckert Alexander W. , Horter Susanne , Bethmann Daniel , Kotrba Johanna , Kaune Tom , Rot Swetlana , Bache Matthias , Bilkenroth Udo , Reich Waldemar , Greither Thomas , Wickenhauser Claudia , Vordermark Dirk , Taubert Helge , Kappler Matthias
Published: January 2019

Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.
Semaphorin Signaling in Cancer-Associated Inflammation
Authors: Franzolin Giulia , Tamagnone Luca
Published: January 2019

The inflammatory and immune response elicited by the growth of cancer cells is a major element conditioning the tumor microenvironment, impinging on disease progression and patients’ prognosis. Semaphorin receptors are widely expressed in inflammatory cells, and their ligands are provided by tumor cells, featuring an intense signaling cross-talk at local and systemic levels. Moreover, diverse semaphorins control both cells of the innate and the antigen-specific immunity. Notably, semaphorin signals acting as inhibitors of anti-cancer immune response are often dysregulated in human tumors, and may represent potential therapeutic targets. In this mini-review, we provide a survey of the best known semaphorin regulators of inflammatory and immune cells, and discuss their functional impact in the tumor microenvironment.
In-Cell NMR: Analysis of Protein–Small Molecule Interactions, Metabolic Processes, and Protein Phosphorylation
Authors: Kumar Amit , Kuhn Lars , Balbach Jochen
Published: January 2019

Nuclear magnetic resonance (NMR) spectroscopy enables the non-invasive observation of biochemical processes, in living cells, at comparably high spectral and temporal resolution. Preferably, means of increasing the detection limit of this powerful analytical method need to be applied when observing cellular processes under physiological conditions, due to the low sensitivity inherent to the technique. In this review, a brief introduction to in-cell NMR, protein–small molecule interactions, posttranslational phosphorylation, and hyperpolarization NMR methods, used for the study of metabolites in cellulo, are presented. Recent examples of method development in all three fields are conceptually highlighted, and an outlook into future perspectives of this emerging area of NMR research is given.
Analytical Methods for Detection of Plant Metabolomes Changes in Response to Biotic and Abiotic Stresses
Authors: Piasecka Anna , Kachlicki Piotr , Stobiecki Maciej
Published: January 2019

Abiotic and biotic stresses are the main reasons of substantial crop yield losses worldwide. Research devoted to reveal mechanisms of plant reactions during their interactions with the environment are conducted on the level of genome, transcriptome, proteome, and metabolome. Data obtained during these studies would permit to define biochemical and physiological mechanisms of plant resistance or susceptibility to affecting factors/stresses. Metabolomics based on mass spectrometric techniques is an important part of research conducted in the direction of breeding new varieties of crop plants tolerant to the affecting stresses and possessing good agronomical features. Studies of this kind are carried out on model, crop and resurrection plants. Metabolites profiling yields large sets of data and due to this fact numerous advanced statistical and bioinformatic methods permitting to obtain qualitative and quantitative evaluation of the results have been developed. Moreover, advanced integration of metabolomics data with these obtained on other omics levels: genome, transcriptome and proteome should be carried out. Such a holistic approach would bring us closer to understanding biochemical and physiological processes of the cell and whole plant interacting with the environment and further apply these observations in successful breeding of stress tolerant or resistant crop plants.
Relation of the pdxB-usg-truA-dedA Operon and the truA Gene to the Intracellular Survival of Salmonella enterica Serovar Typhimurium
Authors: Yang Xiaowen , Wang Jiawei , Feng Ziyan , Zhang Xiangjian , Wang Xiangguo , Wu Qingmin
Published: January 2019

Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red recombination system was used to construct gene deletion strains and to investigate whether the identified operon was related to intracellular survival. The pdxB-usg-truA-dedA operon enhanced the intracellular survival of S. enterica by resisting the oxidative environment and the usg and truA gene expression was induced by H2O2. Moreover, the genes in this operon (except for dedA) contributed to virulence in mice. These findings indicate that the pdxB-usg-truA-dedA operon functions in resistance to oxidative environments during intracellular survival and is required for in vivo S. enterica virulence. This study provides insight toward a better understand of the characteristics of intracellular pathogens and explores the gene modules involved in their intracellular survival.
Oxazole-Bridged Combretastatin A-4 Derivatives with Tethered Hydroxamic Acids: Structure–Activity Relations of New Inhibitors of HDAC and/or Tubulin Function
Authors: Schmitt Florian , Gosch Lisa Chiara , Dittmer Alexandra , Rothemund Matthias , Mueller Thomas , Schobert Rainer , Biersack Bernhard , Volkamer Andrea , Höpfner Michael
Published: January 2019

New inhibitors of tubulin polymerization and/or histone deacetylase (HDAC) activity were synthesized by attaching alkyl tethered hydroxamic acid appendages of varying length to oxazole-bridged combretastatin A-4 analogous caps. While their antiproliferative and microtubule disrupting effect was most pronounced for derivatives with short spacers, HDAC inhibition was strongest for those with longer spacers. These findings were further supported by computational methods such as structure-based docking experiments exploring the target interactions of the derivatives with varying linkers. For instance, compounds featuring short four-atom spacers between cap and hydroxamic acid inhibited the growth of various cancer cell lines and human endothelial hybrid cells with IC50 values in the low nanomolar range. In line with their ability to inhibit the microtubule assembly, four- and five-atom spacered hydroxamic acids caused an accumulation of 518A2 melanoma cells in G2/M phase, whereas a compound featuring a six-atom spacer and performing best in HDAC inhibition, induced a G1 arrest in these cells. All these beneficial anticancer activities together with their selectivity for cancer cells over non-malignant cells, point out the great potential of these novel pleiotropic HDAC and tubulin inhibitors as drug candidates for cancer therapy.
Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Differentiation in the Presence of Vitamin D3
Authors: Mammoli Fabiana , Castiglioni Sara , Parenti Sandra , Cappadone Concettina , Farruggia Giovanna , Iotti Stefano , Davalli Pierpaola , Maier Jeanette A.M. , Grande Alexis , Frassineti Chiara
Published: January 2019

Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.
Network-Based Assessment of Adverse Drug Reaction Risk in Polypharmacy Using High-Throughput Screening Data
Authors: de Anda-Jáuregui Guillermo , Guo Kai , Hur Junguk
Published: January 2019

The risk of adverse drug reactions increases in a polypharmacology setting. High-throughput drug screening with transcriptomics applied to human cells has shown that drugs have effects on several molecular pathways, and these affected pathways may be predictive proxy for adverse drug reactions. Depending on the way that different drugs may contribute to adverse drug reactions, different options may exist in the clinical setting. Here, we formulate a network framework to integrate the relationships between drugs, biological functions, and adverse drug reactions based on the high-throughput drug perturbation data from the Library of Integrated Network-Based Cellular Signatures (LINCS) project. We present network-based parameters that indicate whether a given reaction may be related to the effect of a single drug or to the combination of several drugs, as well as the relative risk of adverse drug reaction manifestation given a certain drug combination.
Interactions between Host PPARs and Gut Microbiota in Health and Disease
Authors: Hasan Arif Ul , Rahman Asadur , Kobori Hiroyuki
Published: January 2019

The human gastrointestinal tract is inhabited by many types of microbiota, including bacteria, viruses, and fungi. Dysregulations of their microenvironment are associated with various health problems, not only limited to gastrointestinal disorders, such as inflammatory bowel disease, but to impacts beyond the intestine. For example, intestinal microbiota can affect the liver in non-alcoholic fatty liver disease, visceral adipose tissue during adipogenesis, and the heart in atherosclerosis. The factors contributing to these pathogeneses involve the gut microbiota and the effector organs of the host, and everything in between. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are pivotal for the modulation of many of the pathogeneses mentioned above. It is, therefore, conceivable that, in the process of host-microbiota interactions, PPARs play important roles. In this review, we focus on the interactions between host PPARs in different organs and gut microbiota and their impacts on maintaining health and various diseases.
Modulation of the Endocannabinoid System Following Central Nervous System Injury
Authors: Zhou Juan , Noori Haneen , Burkovskiy Ian , Lafreniere J. Daniel , Kelly Melanie E. M. , Lehmann Christian
Published: January 2019

Central nervous system (CNS) injury, such as stroke or trauma, is known to increase susceptibility to various infections that adversely affect patient outcomes (CNS injury-induced immunodepression—CIDS). The endocannabinoid system (ECS) has been shown to have immunoregulatory properties. Therefore, the ECS might represent a druggable target to overcome CIDS. Evidence suggests that cannabinoid type 2 receptor (CB2R) activation can be protective during the early pro-inflammatory phase after CNS injury, as it limits neuro-inflammation and, therefore, attenuates CIDS severity. In the later phase post CNS injury, CB2R inhibition is suggested as a promising pharmacologic strategy to restore immune function in order to prevent infection.
The Effect of the Thermosensitive Biodegradable PLGA–PEG–PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement
Authors: Vojtova Lucy , Michlovska Lenka , Valova Kristyna , Zboncak Marek , Trunec Martin , Castkova Klara , Krticka Milan , Pavlinakova Veronika , Polacek Petr , Dzurov Matej , Lukasova Vera , Rampichova Michala , Suchy Tomas , Sedlacek Radek , Ginebra Maria-Pau , Montufar Edgar B.
Published: January 2019

The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA–PEG–PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA–PEG–PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA–PEG–PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.
Expression Pattern and Function Analysis of AtPPRT1, a Novel Negative Regulator in ABA and Drought Stress Responses in Arabidopsis
Authors: Pei Linsen , Peng Lu , Wan Xia , Xiong Jie , Liu Zhibin , Li Xufeng , Yang Yi , Wang Jianmei
Published: January 2019

Abscisic acid (ABA) plays a fundamental role in plant growth and development, as well as in the responses to abiotic stresses. Previous studies have revealed that many components in ABA and drought stress signaling pathways are ubiquitinated by E3 ligases. In this study, AtPPRT1, a putative C3HC4 zinc-finger ubiquitin E3 ligase, was explored for its role in abiotic stress response in Arabidopsis thaliana. The expression of AtPPRT1 was induced by ABA. In addition, the β-glucuronidase (GUS) gene driven by the AtPPRT1 promoter was more active in the root hair zone and root tips of primary and major lateral roots of young seedlings in the presence of ABA. The assays for seed germination, stomatal aperture, root length, and water deficit demonstrated that the AtPPRT1-overexpressing Arabidopsis was insensitive to ABA and sensitive to drought stress compared with wild-type (WT) plants. The analysis by quantitative real-time PCR (qRT-PCR) revealed that the expression of three stress-inducible genes (AtRAB18, AtERD10, and AtKIN1) were upregulated in the atpprt1 mutant and downregulated in AtPPRT1-overexpressing plants, while two ABA hydrolysis genes (AtCYP707A1 and AtCYP707A3) were downregulated in the atpprt1 mutant and upregulated in AtPPRT1-overexpressing plants in the presence of ABA. AtPPRT1 was localized in the mitochondria. Our findings indicate that AtPPRT1 plays a negative role in ABA and drought stress responses.
Predictive Modeling of Machining Temperatures with Force–Temperature Correlation Using Cutting Mechanics and Constitutive Relation
Authors: Ning Jinqiang , Liang Steven Y.
Published: January 2019

Elevated temperature in the machining process is detrimental to cutting tools—a result of the effect of thermal softening and material diffusion. Material diffusion also deteriorates the quality of the machined part. Measuring or predicting machining temperatures is important for the optimization of the machining process, but experimental temperature measurement is difficult and inconvenient because of the complex contact phenomena between tools and workpieces, and because of restricted accessibility during the machining process. This paper presents an original analytical model for fast prediction of machining temperatures at two deformation zones in orthogonal cutting, namely the primary shear zone and the tool–chip interface. Temperatures were predicted based on a correlation between force and temperature using the mechanics of the cutting process and material constitutive relation. Minimization of the differences between calculated material flow stresses using a mechanics model and a constitutive model yielded an estimate of machining temperatures. Experimental forces, cutting condition parameters, and constitutive model constants were inputs, while machining forces were easily measurable by a piezoelectric dynamometer. Machining temperatures of AISI 1045 steel were predicted under various cutting conditions to demonstrate the predictive capability of each presented model. Close agreements were observed by verifying them against documented values in the literature. The influence of model inputs and computational efficiency were further investigated. The presented model has high computational efficiency that allows real-time prediction and low experimental complexity, considering the easily measurable input variables.
Optimal Design of Sandwich Composite Cradle for Computed Tomography Instrument by Analyzing the Structural Performance and X-ray Transmission Rate
Authors: Lee Sang Jin , Chung II Sup
Published: January 2019

Carbon fiber-reinforced composite has an excellent X-ray transmission rate as well as specific modulus and strength. The major components of medical devices, X-ray systems, and computed tomography (CT) equipment that require superior X-ray transmission performance also require structural performance for deformation. Therefore, medical components consist of a sandwich composite structure with carbon fiber composites applied as a face material. The X-ray transmission ratios of face material and foam material were measured according to thickness, and the relation equation for thickness and X-ray transmission rate was derived. The X-ray transmission rate for the sandwich composite structure consisting of face and core material was measured and the relationship between the X-ray transmission rate and the dimension for thickness of sandwich cradle was derived. Using the optimization process, the thicknesses of face and core materials for sandwich cradles were determined to minimize the cost of used materials. They also met the criteria that the deflection should not be more than 20 mm, and the X-ray transmission rate of the cradle should be equal to or greater than that of aluminum at 1.5 mm thickness. The sequence pattern of face material was proposed through structural analysis. The face material of the sandwich cradle was manufactured by a resin infusion and vacuum bagging method, followed by inserting the core between the cured faces. Next, the sandwich cradle assembly was completed and re-cured. The sandwich cradle met the criteria that the deflection at the end was 19.04 mm and the X-ray transmission was 78.7% greater than the X-ray transmission of 1.5 mm aluminum.
Analysis of the Behavior of SMA Mixtures with Different Fillers Through the Semicircular Bend (SCB) Fracture Test
Authors: Limón-Covarrubias Pedro , Avalos Cueva David , Valdés Vidal Gonzalo , Reyes Ortiz Oscar Javier , Adame Hernández Rey Omar , Galaviz González José Roberto
Published: January 2019

In most cases, stone mastic asphalt (SMA) mixtures placed in thin layers and subjected to stress develop early cracks (potentially resulting from being improperly affixed to the underlying layer, placed over previously cracked asphalt pavement, or placed over Portland cement concrete slabs). However, the filler used in SMA production is very influential on the performance of the mix. Fillers used in this type of mixture have a low plastic index or are inert (calcium carbonate or lime), so it is important to understand the effect of each material on the possible fissuring and cracking process of the SMA mixture. The objective of this study is to present an evaluation of the behavior of SMA asphalt mixtures with different types of filler and at different temperatures using the semicircular bend (SCB) fracture energy test. This research compares results between fracture energy and different types of filler in SMA asphalt mixtures at temperatures ranging from −10 to 25 °C.
Influence of Cellulose Nanoparticles on Rheological Behavior of Oil Well Cement-Water Slurries
Authors: Tang Zhengjie , Huang Runzhou , Mei Changtong , Sun Xiuxuan , Zhou Dingguo , Zhang Xiuqiang , Wu Qinglin
Published: January 2019

Performance of hardened oil well cement (OWC) is largely determined by the rheological properties of the cement slurries. This work was carried out to investigate the effect of water- to-cement ratio (WCR) and cellulose nanoparticles (CNPs), including cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs), on rheology performance of OWC-based slurries using a Couette rotational viscometer coupled with rheological models. The yield stress and viscosity of neat OWC slurries had a decreasing trend with the increase of WCRs. The suspension became increased unstable with the increase of WCRs. The properties of CNPs, including rheological behaviors, surface properties and morphology, determine the rheological performance of CNP-OWC slurries. In comparison with CNC-OWC slurries, the gel strength, yield stress and viscosity of CNF-OWC slurries were higher as CNFs were more likely to form an entangled network. The gel strength, yield stress and viscosity of CNP-OWC slurries increased with reduced CNF size through regrinding and the proportion of CNFs in the mixture of CNFs and CNCs, respectively.
On Gibbs Energy for the Metastable bcc_A2 Phase with a Thermal Vacancy in Metals and Alloys
Authors: Tang Ying , Zhang Lijun
Published: January 2019

An approach was proposed to obtain a reasonable thermodynamic description of a thermal vacancy in the metastable disordered body centered cubic (bcc_A2) phase, which had been consistently ignored in previous thermodynamic assessments. The present approach was first applied to obtain the thermodynamic descriptions for pure metastable bcc Ni and Zn, and then in the binary Ni-Zn system. The thermodynamic descriptions for both the metastable disordered bcc_A2 phase and the stable ordered bcc_B2 β phases in the Ni-Zn binary system were updated based on the corresponding experimental equilibria. With these updated thermodynamic descriptions, several drawbacks, including the multiple solutions for thermal vacancy concentrations and the artificial phase boundaries in previous assessments, can be avoided. Moreover, the calculated phase boundaries and invariant reactions related to the β phase agree well with the experimental data.
q-Rung Orthopair Fuzzy Competition Graphs with Application in the Soil Ecosystem
Authors: Habib Amna , Akram Muhammad , Farooq Adeel
Published: January 2019

The q-rung orthopair fuzzy set is a powerful tool for depicting fuzziness and uncertainty, as compared to the Pythagorean fuzzy model. The aim of this paper is to present q-rung orthopair fuzzy competition graphs (q-ROFCGs) and their generalizations, including q-rung orthopair fuzzy k-competition graphs, p-competition q-rung orthopair fuzzy graphs and m-step q-rung orthopair fuzzy competition graphs with several important properties. The study proposes the novel concepts of q-rung orthopair fuzzy cliques and triangulated q-rung orthopair fuzzy graphs with real-life characterizations. In particular, the present work evolves the notion of competition number and m-step competition number of q-rung picture fuzzy graphs with algorithms and explores their bounds in connection with the size of the smallest q-rung orthopair fuzzy edge clique cover. In addition, an application is illustrated in the soil ecosystem with an algorithm to highlight the contributions of this research article in practical applications.
Potent Cytotoxic Analogs of Amphidinolides from the Atlantic Octocoral Stragulum bicolor
Authors: Nuzzo Genoveffa , Gomes Bruno de Araújo , Gallo Carmela , Amodeo Pietro , Sansone Clementina , Pessoa Otília D. L. , Manzo Emiliano , Vitale Rosa Maria , Ianora Adrianna , Santos Evelyne A. , Costa-Lotufo Leticia V. , Fontana Angelo
Published: January 2019

Amphidinolides are cytotoxic macrolides produced by symbiotic unicellular microalgae of the genus Amphidinium. Here we describe the identification of four related molecules belonging to this macrolide family isolated from the invertebrate Stragulum bicolor. The new molecules, named amphidinolide PX1-PX3 and stragulin A (1–4), show an unprecedented carbon skeleton whose complete stereochemistry has been determined by spectroscopic and computational methods. Differences in the structures of these molecules modulate their biological activity in a panel of tumor cell lines, but the opened derivative stragulin (4) shows a very potent and specific cytotoxic activity (IC50 0.18 µM) against the aggressive human melanoma cell A2058.
Molecular Networking Reveals Two Distinct Chemotypes in Pyrroloiminoquinone-Producing Tsitsikamma favus Sponges
Authors: Kalinski Jarmo-Charles J. , Waterworth Samantha C. , Siwe Noundou Xavier , Jiwaji Meesbah , Parker-Nance Shirley , Krause Rui W. M. , McPhail Kerry L. , Dorrington Rosemary A.
Published: January 2019

The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.
A Compact Broadband Antenna with Dual-Resonance for Implantable Devices
Authors: Li Rongqiang , Li Bo , Du Guohong , Sun Xiaofeng , Sun Haoran
Published: January 2019

A compact broadband implantable patch antenna is designed for the field of biotelemetry and experimentally demonstrated using the Medical Device Radiocommunications Service (MedRadio) band (401–406 MHz). The proposed antenna can obtain a broad impedance bandwidth by exciting dual-resonant frequencies, and has a compact structure using bent metal radiating strips and a short strategy. The total volume of the proposed antenna, including substrate and superstrate, is about 479 mm3 (23 × 16.4 × 1.27 mm3). The measured bandwidth is 52 MHz (382–434 MHz) at a return loss of −10 dB. The resonance, radiation and specific absorption rate (SAR) performance of the antenna are examined and characterized.
In Situ X-Ray CT Investigations of Meso-Damage Evolution of Cemented Waste Rock-Tailings Backfill (CWRTB) during Triaxial Deformation
Authors: Wang Yu , Wang Huajian , Zhou Xiaolong , Yi Xuefeng , Xiao Yonggang , Wei Xiaoming
Published: January 2019

This work presents an experimental study that focused on the meso-damage evolution of cemented waste rock-tailing backfill (CWRTB) under triaxial compression using the in situ X-ray computed tomography (CT) technique. Although numerous investigations have studied the magnitude of the strength of CWRTB material, the mesoscopic damage evolution mechanisms under triaxial deformation are still poorly understood. Artificial CWRTB samples with a waste rock proportion of 30% were prepared by mixing tailings, waste rock, cement, and water. A specific self-developed loading device was used to match the CT machine to real-time CT scanning for the CWRTB sample. A series of 2D CT images were obtained by performing CT imaging at five key points throughout the test and from three positions in the sample. The CT values, for the purpose of meso-damage evolution in CWRTB, were identified. The results showed that the axial stress–strain curve presented strain hardening characteristics. The CT data revealed the inhomogeneous damage field inside the CWRTB sample and the most severely damaged regions that were usually located at the waste block-tailings paste interfaces. The changes in CT values for the different regions of interest (ROI) revealed the complicated interactions between the waste blocks and the tailings paste matrix. The meso-structural changes, formation of the localized bands, and the associated stress dilatancy phenomenon were strongly influenced by the interactions between the waste blocks and tailing paste.
Preparation and Characterization of Protocatechuic Acid Sulfates
Authors: Gutierrez-Zetina Sofia M. , Gonzalez-Manzano Susana , Perez-Alonso Jose J. , Gonzalez-Paramas Ana M. , Santos-Buelga Celestino
Published: January 2019

Protocatechuic acid (3,4-dihydroxybenzoic acid; PCA) is a phenolic acid present in plants as a secondary metabolite and is also produced in the human organism as a metabolite from the degradation of polyphenols by the intestinal microbiota, particularly of flavonoids. However, PCA, like most polyphenols, is biotransformed in the human body to different conjugates as sulfates, which are found circulating in blood and could be involved in the bioactivity of the original compound. This paper describes a simple process for the preparation of PCA monosulfates with satisfactory yields. Two compounds were obtained that were identified as PCA-3-sulfate and PCA-4-sulfate by mass spectrometry and 1H and 13C nuclear magnetic resonance using one- and two-dimensional techniques (heteronuclear single-quantum coherence and heteronuclear multiple-bond correlation). Differential MS fragmentation behavior and UV spectra were observed for each compound, which could be used for their identification in samples of unknown composition. The described procedure can be used for the preparation of these polyphenol metabolites in view of their use in in vivo and in vitro studies, as well as standards for their analysis in biological fluids, to contribute to the elucidation of biological effects of dietary polyphenols.
Comparison of the Fungistatic Activity of Selected Essential Oils Relative to Fusarium graminearum Isolates
Authors: Krzyśko-Łupicka Teresa , Walkowiak Weronika , Białoń Marietta
Published: January 2019

The aim of the study was to determine the chemical composition of lemon, rosewood, geranium and rosemary oils, and compare their effect on the sensitivity of Fusarium graminearum ZALF 24 and Fusarium graminearum ZALF 339 isolated from infected cereals. The tested oils were added to Potato Dextrose Agar (PDA) medium at concentrations of 0.125%, 0.25%, 0.5%, 1.0% and 2.0%. The activity of the oils on inhibition of the linear growth of mycelium was evaluated by measuring the growth of fungal colonies (growth index), while the fungistatic activity was evaluated on the basis of the percentage growth inhibition of a fungal colony and calculated according to Abbott’s formula. The sensitivity of the test strains was variable and depended on the type and concentration of the tested oils. Geranium and rosewood oils in all of the concentrations completely inhibited the growth of the used isolates. In contrast, lemon oil relative to F. graminearum ZALF 339 showed the highest activity at a concentration of 1.0% and rosemary oil, 0.5%. The highest activity against F. graminearum ZALF 24 was shown by the oils of rosemary and lemon at concentrations from 1.0% to 2.0%. The susceptibility of Fusarium graminearum isolates was differentiated and depended on the type and concentration of tested oils.
Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses
Authors: Hanif Muhammad , Kanwal Fariha , Rafiq Muhammad , Hassan Mubashir , Mustaqeem Muhammad , Seo Sung-Yum , Zhang Yunlong , Lu Changrui , Chen Ting , Saleem Muhammad
Published: January 2019

The present study focuses on the design and synthesis of a cage-like organic skeleton containing two triazole rings jointed via imine linkage. These molecules can act as urease inhibitors. The in-vitro urease inhibition screening results showed that the combination of the two triazole skeleton in the cage-like morphology exhibited comparable urease inhibition activity to that of the reference thiourea while the metallic complexation, especially with copper, nickel, and palladium, showed excellent activity results with IC50 values of 0.94 ± 0.13, 3.71 ± 0.61, and 7.64 ± 1.21 (3a–c), and 1.20 ± 0.52, 3.93 ± 0.45, and 12.87 ± 2.11 µM (4a–c). However, the rest of compounds among the targeted series exhibited a low to moderate enzyme inhibition potential. To better understand the compounds’ underlying mechanisms of the inhibitory effect (3a and 4a) and their most active metal complexes (3b and 4b), we performed an enzymatic kinetic analysis using the Lineweaver–Burk plot in the presence of different concentrations of inhibitors to represent the non-competitive inhibition nature of the compounds, 3a, 4a, and 4b, while mixed type inhibition was represented by the compound, 3b. Moreover, molecular docking confirmed the binding interactive behavior of 3a within the active site of the target protein.
Chiral Derivatives of Xanthones with Antimicrobial Activity
Authors: Araújo Joana , Fernandes Carla , Pinto Madalena , Tiritan Maria Elizabeth
Published: January 2019

According to the World Health Organization, the exacerbated use of antibiotics worldwide is increasing multi-resistant infections, especially in the last decade. Xanthones are a class of compounds receiving great interest in drug discovery and development that can be found as natural products or obtained by synthesis. Many derivatives of xanthones are chiral and associated with relevant biological activities, including antimicrobial. The aim of this review is to compile information about chiral derivatives of xanthones from natural sources and their synthesized examples with antimicrobial activity.
A Microbial Transformation Model for Simulating Mammal Metabolism of Artemisinin
Authors: Ma Yue , Sun Peng , Zhao Yifan , Wang Kun , Chang Xiaoqiang , Bai Yue , Zhang Dong , Yang Lan
Published: January 2019

Artemisinin (ART) is a highly effective antimalarial agent isolated from the traditional Chinese herb Qinghao. Metabolism of ART and its derivatives in the body is one of the most pressing issues for pharmaceutical scientists. Herein, an efficient in vitro microorganism model for simulation of metabolism of ART in vivo was developed employing Cunninghamella elegans. Metabolites in the microbial transformation system and plasma of mice pre-administrated ART orally were analyzed by ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-quadrupole time-of-flight (Q-TOF)-mass spectrometry (MSE) combined with UNIFI software. Thirty-two metabolites were identified in vitro and 23 were identified in vivo. After comparison, 16 products were found to be common to both models including monohydroxylated ART, dihydroxylated ART, deoxyartemisinin, hydroxylated deoxyartemisinin, hydroxylated dihydroartemisinin (DHA), and hydroxylated deoxy-DHA. These results revealed that C. elegans CICC 40250 functioned as an appropriate model to mimic ART metabolism in vivo. Moreover, an overall description of metabolites of ART from C. elegans CICC 40250 has been provided. Notably, DHA was detected and identified as a metabolite of ART in mouse plasma for the first time.
CNF-Functionalization as Versatile Tool for Tuning Activity in Cellulose-Derived Product Hydrogenation
Authors: Jouve Andrea , Cattaneo Stefano , Capelli Sofia , Stucchi Marta , Evangelisti Claudio , Villa Alberto , Prati Laura
Published: January 2019

Carbon nanofibers (CNFs) have been functionalized by introducing O, N, and P containing groups in order to investigate the effect of support functionalization in Ru catalysed hydroxymethyl furfural (HMF) and levulinic acid (LA) hydrogenation. In the case of HMF, despite the fact that no effect on selectivity was observed (all the catalysts produced selectively gamma-valerolactone (GVL)), the functionalization strongly affected the activity of the reaction. O-containing and N-containing supports presented a higher activity compared to the bare support. On the contrary, in HMF hydrogenation, functionalization of the support did not have a beneficial effect on the activity of a Ru-catalysed reaction with respect to bare support and only CNFs-O behaved similarly to bare CNFs. In fact, when CNFs-N or CNFs-P were used as the supports, a lower activity was observed, as well as a change in selectivity in which the production of ethers (from the reaction with the solvent) greatly increased.
Effectiveness of Prenyl Group on Flavonoids from Epimedium koreanum Nakai on Bacterial Neuraminidase Inhibition
Authors: Choi Hong Min , Kim Jeong Yoon , Li Zuo Peng , Jenis Janar , Ban Yeong Jun , Baiseitova Aizhamal , Park Ki Hun
Published: January 2019

In this study, the inhibitory potential of bacterial neuraminidase (NA) was observed on the leaves of Epimedium koreanum Nakai, which is a popular ingredient in traditional herbal medicine. This study attempted to isolate the relevant, responsible metabolites and elucidate their inhibition mechanism. The methanol extraction process yielded eight flavonoids (1–8), of which compounds 7 and 8 were new compounds named koreanoside F and koreanoside G, respectively. All the compounds (1–8) showed a significant inhibition to bacterial NA with IC50 values of 0.17–106.3 µM. In particular, the prenyl group on the flavonoids played a critical role in bacterial NA inhibition. Epimedokoreanin B (compound 1, IC50 = 0.17 µM) with two prenyl groups on C8 and C5′ of luteolin was 500 times more effective than luteolin (IC50 = 85.6 µM). A similar trend was observed on compound 2 (IC50 = 0.68 µM) versus dihydrokaempferol (IC50 = 500.4 µM) and compound 3 (IC50 = 12.6 µM) versus apigenin (IC50 = 107.5 µM). Kinetic parameters (Km, Vmax, and Kik/Kiv) evaluated that all the compounds apart from compound 5 showed noncompetitive inhibition. Compound 5 was proven to be a mixed type inhibitor. In an enzyme binding affinity experiment using fluorescence, affinity constants (KSV) were tightly related to inhibitory activities.
Influence of Oxygen-Containing Sulfur Flavor Molecules on the Stability of β-Carotene under UVA Irradiation
Authors: Zhang Gong-Liang , Wu Hong-Yan , Liang Ying , Song Jie , Gan Wei-Qi , Hou Hong-Man
Published: January 2019

The influence of 11 kinds of oxygen-containing sulfur flavor molecules was examined on β-carotene stability under UVA irradiation in ethanol system. Both the effects of sulfides on dynamic degradation of β-carotene and the relation between structure and effect were investigated. The oxidation products of β-carotene accelerated by sulfides under UVA irradiation were also identified. The results indicated that the disulfides had more obvious accelerative effects on the photodegradation of β-carotene than mono sulfides. The degradation of β-carotene after methyl (2-methyl-3-furyl) disulfide (MMFDS), methyl furfuryl disulfide (MFDS) and bis(2-methyl-3-furyl) disulfide (BMFDS) exposure followed first-order kinetics. Furan-containing sulfides such as MMFDS and BMFDS showed more pronounced accelerative effects than their corresponding isomers. The oxidation products were identified as 13-cis-β-carotene, 9,13-di-cis-β-carotene and all-trans-5,6-epoxy-β-carotene. These results suggest that both the sulfur atom numbers and the furan group in oxygen-containing sulfides play a critical role in the photooxidation of β-carotene.
Molecular Modeling in Drug Design
Authors: Wade Rebecca C. , Salo-Ahen Outi M. H.
Published: January 2019

This Special Issue contains thirteen articles that provide a vivid snapshot of the state-of-the-art of molecular modeling in drug design, illustrating recent advances and critically discussing important challenges [...]