bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Intervertebral Disc Changes in Asymptomatic Individuals with Distinct Physical Activity Histories Using Three Different Quantitative MRI Techniques
Authors: Belavy Daniel L. , Brisby Helena , Douglas Benjamin , Hebelka Hanna , Quittner Matthew J. , Owen Patrick J. , Rantalainen Timo , Trudel Guy , Lagerstrand Kerstin M.
Published: June 2020

(1) Background: Assessments of intervertebral disc (IVD) changes, and IVD tissue adaptations due to physical activity, for example, remains challenging. Newer magnetic resonance imaging techniques can quantify detailed features of the IVD, where T2-mapping and T2-weighted (T2w) and Dixon imaging are potential candidates. Yet, their relative utility has not been examined. The performances of these techniques were investigated to characterize IVD differences in asymptomatic individuals with distinct physical activity histories. (2) Methods: In total, 101 participants (54 women) aged 25–35 years with distinct physical activity histories but without histories of spinal disease were included. T11/12 to L5/S1 IVDs were examined with sagittal T2-mapping, T2w and Dixon imaging. (3) Results: T2-mapping differentiated Pfirrmann grade-1 from all other grades (p < 0.001). Most importantly, T2-mapping was able to characterize IVD differences in individuals with different training histories (p < 0.005). Dixon displayed weak correlations with the Pfirrmann scale, but presented significantly higher water content in the IVDs of the long-distance runners (p < 0.005). (4) Conclusions: Findings suggested that T2-mapping best reflects IVD differences in asymptomatic individuals with distinct physical activity histories changes. Dixon characterized new aspects of IVD, probably associated with IVD hypertrophy. This complementary information may help us to better understand the biological function of the disc.
The Impact of Gastric Juice pH on the Intraluminal Therapy for Helicobacter pylori Infection
Authors: Wang Yu-Chio , Chen Yen-Po , Ho Cheng-Yu , Liu Ting-Wen , Chu Cheng-Hsin , Wang Horng-Yuan , Liou Tai-Cherng
Published: June 2020

Background: Helicobacter pylori (H. pylori) can be topically eradicated in stomach lumen on endoscopic examination. The procedures of intraluminal therapy for H. pylori infection (ILTHPI) include the control of intragastric pH, mucolytic irrigation of the gastric mucosal surface, and a single-dose medicament containing antimicrobial agents. Aims: To detect gastric juice pH and evaluate its impact on the success rate of ILTHPI. Methods: We enrolled 324 patients with upper abdominal discomfort for endoscopic examinations. Among them, 13C-urea breath test was positive in 218 patients, where 100 underwent ILTHPI, and negative in 106. All patients had their gastric juice pH detected and set into three ranges, including normal acidity (pH < 4.0), low-level hypoacidity (pH 4.0–5.5), and high-level hypoacidity (pH ≥ 6.0). The impact of gastric juice pH on the success rate of ILTHPI was evaluated. Results: Distribution of pH level showed no significant difference between two groups of H. pylori-infected patients (p = 0.942). The eradication rate of ILTHPI is significantly lower in patients with gastric juice pH below 4 (p < 0.001). Conclusions: Detection of gastric juice pH in ILTHPI is extremely important. Rapid control of stomach pH at or above 4 for patients prior to ILTHPI is strongly recommended. (NCT03124420).
Reliability of Synthetic Brain MRI for Assessment of Ischemic Stroke with Phantom Validation of a Relaxation Time Determination Method
Authors: Li Chia-Wei , Hsu Ai-Ling , Huang Chi-Wen C. , Yang Shih-Hung , Lin Chien-Yuan , Shieh Charng-Chyi , Chan Wing P.
Published: June 2020

The reliability of relaxation time measures in synthetic magnetic resonance images (MRIs) of homemade phantoms were validated, and the diagnostic suitability of synthetic imaging was compared to that of conventional MRIs for detecting ischemic lesions. Phantoms filled with aqueous cupric-sulfate (CuSO4) were designed to mimic spin-lattice (T1) and spin-spin (T2) relaxation properties and were used to compare their accuracies and stabilities between synthetic and conventional scans of various brain tissues. To validate the accuracy of synthetic imaging in ischemic stroke diagnoses, the synthetic and clinical scans of 18 patients with ischemic stroke were compared, and the quantitative contrast-to-noise ratios (CNRs) were measured, using the Friedman test to determine significance in differences. Results using the phantoms showed no significant differences in the interday and intersession synthetic quantitative T1 and T2 values. However, between synthetic and referenced T1 and T2 values, differences were larger for longer relaxation times, showing that image intensities in synthetic scans are relatively inaccurate in the cerebrospinal fluid (CSF). Similarly, CNRs in CSF regions of stroke patients were significantly different on synthetic T2-weighted and T2-fluid-attenuated inversion recovery images. In contrast, differences in stroke lesions were insignificant between the two. Therefore, interday and intersession synthetic T1 and T2 values are highly reliable, and discrepancies in synthetic T1 and T2 relaxation times and image contrasts in CSF regions do not affect stroke lesion diagnoses. Additionally, quantitative relaxation times from synthetic images allow better estimations of ischemic stroke onset time, consequently increasing confidence in synthetic MRIs as diagnostic tools for ischemic stroke.
Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms
Authors: Palmieri Lola-Jade , Dermine Solène , Barré Amélie , Dhooge Marion , Brezault Catherine , Cottereau Anne-Ségolène , Coriat Romain
Published: June 2020

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.
Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry
Authors: Álvarez Karin , Orellana Paulina , De la Fuente Marjorie , Canales Tamara , Pinto Eliana , Heine Claudio , Solar Benjamín , Hurtado Claudia , Møller Pål , Kronberg Udo , Zarate Alejandro José , Dominguez-Valentin Mev , López-Köstner Francisco
Published: June 2020

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.
Genetic Variants as Sudden-Death Risk Markers in Inherited Arrhythmogenic Syndromes: Personalized Genetic Interpretation
Authors: Campuzano Oscar , Sarquella-Brugada Georgia , Arbelo Elena , Cesar Sergi , Jordà Paloma , Pérez-Serra Alexandra , Toro Rocío , Brugada Josep , Brugada Ramon
Published: June 2020

Inherited arrhythmogenic syndromes are the primary cause of unexpected lethal cardiac episodes in young people. It is possible that the first sign of the condition may be sudden death. Inherited arrhythmogenic syndromes are caused by genetic defects that may be analyzed using different technical approaches. A genetic alteration may be used as a marker of risk for families who carry the genetic alterations. Therefore, the early identification of the responsible genetic defect may help the adoption of preventive therapeutic measures focused on reducing the risk of lethal arrhythmias. Here, we describe the use of massive sequencing technologies and the interpretation of genetic analyses in inherited arrhythmogenic syndromes.
Advances in Manufacturing Composite Carbon Nanofiber-Based Aerogels
Authors: Gan Yong X. , Gan Jeremy B.
Published: June 2020

This article provides an overview on manufacturing composite carbon nanofiber-based aerogels through freeze casting technology. As known, freeze casting is a relatively new manufacturing technique for generating highly porous structures. During the process, deep cooling is used first to rapidly solidify a well-dispersed slurry. Then, vacuum drying is conducted to sublimate the solvent. This allows the creation of highly porous materials. Although the freeze casting technique was initially developed for porous ceramics processing, it has found various applications, especially for making aerogels. Aerogels are highly porous materials with extremely high volume of free spaces, which contributes to the characteristics of high porosity, ultralight, large specific surface area, huge interface area, and in addition, super low thermal conductivity. Recently, carbon nanofiber aerogels have been studied to achieve exceptional properties of high stiffness, flame-retardant and thermal-insulating. The freeze casting technology has been reported for preparing carbon nanofiber composite aerogels for energy storage, energy conversion, water purification, catalysis, fire prevention etc. This review deals with freeze casting carbon nanofiber composite materials consisting of functional nanoparticles with exceptional properties. The content of this review article is organized as follows. The first part will introduce the general freeze casting manufacturing technology of aerogels with the emphasis on how to use the technology to make nanoparticle-containing composite carbon nanofiber aerogels. Then, modeling and characterization of the freeze cast particle-containing carbon nanofibers will be presented with an emphasis on modeling the thermal conductivity and electrical conductivity of the carbon nanofiber network aerogels. After that, the applications of the carbon nanofiber aerogels will be described. Examples of energy converters, supercapacitors, secondary battery electrodes, dye absorbents, sensors, and catalysts made from composite carbon nanofiber aerogels will be shown. Finally, the perspectives to future work will be presented.
Development of Hydrophilic PVDF Membrane Using Vapour Induced Phase Separation Method for Produced Water Treatment
Authors: Mat Nawi Normi Izati , Chean Ho Min , Shamsuddin Norazanita , Bilad Muhammad Roil , Narkkun Thanitporn , Faungnawakij Kajornsak , Khan Asim Laeeq
Published: June 2020

During the production of oil and gas, a large amount of oily wastewater is generated, which would pollute the environment if discharged without proper treatment. As one of the most promising treatment options, membrane material used for oily wastewater treatment should possess desirable properties of high hydraulic performance combined with high membrane fouling resistance. This project employs the vapor induced phase separation (VIPS) technique to develop a hydrophilic polyvinylidene fluoride (PVDF) membrane with polyethylene glycol (PEG) as an additive for produced water treatment. Results show that thanks to its slow nonsolvent intake, the VIPS method hinders additive leaching during the cast film immersion. The results also reveal that the exposure of the film to the open air before immersion greatly influences the structure of the developed membranes. By extending the exposure time from 0 to 30 min, the membrane morphology change from typical asymmetric with large macrovoids to the macrovoid-free porous symmetric membrane with a granular structure, which corresponds to 35% increment of steady-state permeability to 189 L·m−2h−1bar−1, while maintaining >90% of oil rejection. It was also found that more PEG content resides in the membrane matrix when the exposure time is extended, contributes to the elevation of surface hydrophilicity, which improves the membrane antifouling properties. Overall results demonstrate the potential of VIPS method for the fabrication of hydrophilic PVDF membrane by helping to preserve hydrophilic additive in the membrane matrices.
Performance Improvement and Biofouling Mitigation in Osmotic Microbial Fuel Cells via In Situ Formation of Silver Nanoparticles on Forward Osmosis Membrane
Authors: Lu Yuqin , Jia Jia , Miao Hengfeng , Ruan Wenquan , Wang Xinhua
Published: June 2020

An osmotic microbial fuel cell (OsMFC) using a forward osmosis (FO) membrane to replace the proton exchange membrane in a typical MFC achieves superior electricity production and better effluent water quality during municipal wastewater treatment. However, inevitable FO membrane fouling, especially biofouling, has a significantly adverse impact on water flux and thus hinders the stable operation of the OsMFC. Here, we proposed a method for biofouling mitigation of the FO membrane and further improvement in current generation of the OsMFC by applying a silver nanoparticle (AgNP) modified FO membrane. The characteristic tests revealed that the AgNP modified thin film composite (TFC) polyamide FO membrane showed advanced hydrophilicity, more negative zeta potential and better antibacterial property. The biofouling of the FO membrane in OsMFC was effectively alleviated by using the AgNP modified membrane. This phenomenon could be attributed to the changes of TFC–FO membrane properties and the antibacterial property of AgNPs on the membrane surface. An increased hydrophilicity and a more negative zeta potential of the modified membrane enhanced the repulsion between foulants and membrane surface. In addition, AgNPs directly disturbed the functions of microorganisms deposited on the membrane surface. Owing to the biofouling mitigation of the AgNP modified membrane, the water flux and electricity generation of OsMFC were correspondingly improved.
Analysis for Reverse Temperature Dependence of Hydrogen Permeability through Pd-X (X = Y, Ho, Ni) Alloy Membranes Based on Hydrogen Chemical Potential
Authors: Suzuki Asuka , Yukawa Hiroshi
Published: June 2020

It is generally understood that the hydrogen permeability of Pd-Ag alloy membranes declines with decreasing temperature. However, recent studies have revealed that the hydrogen permeability of Pd-Ag alloy membranes inversely increases at a certain temperature range and reaches a peak. The peak behavior reflects the shape of pressure-composition isotherms (PCT curves). In order to elucidate the relationship between the reverse temperature dependence of hydrogen permeability and the PCT curves, the hydrogen permeability of pure Pd and Pd-X (X = Ho, Y, and Ni) alloy membranes were investigated. The pure Pd and Pd-5 mol%Ni alloy membranes, in which the α-α’ phase transition occurs, exhibits more significant peak behaviors than Pd-5 mol%Ho, Pd-5 mol%Y, and Pd-23 mol%Ag alloy membranes, in which the α-α’ phase transition is suppressed. Large differences in hydrogen solubility, at the hydrogen pressures above and below the plateau region or the inflection point, make the peak behaviors more significant. It is revealed that the peak temperature can be roughly predicted by the hydrogen pressure at the plateau regions or the inflection points in the PCT curves.
Casting Blanks Cleanliness Evaluation Based on Ultrasonic Microscopy and Morphological Filtering
Authors: Ding Heng , Qian Qingting , Li Xue , Wang Zhu , Li Min
Published: June 2020

The cleanliness of the casting blanks could seriously affect the quality of downstream products. Recently, ultrasound technology has been introduced to detect the inclusions in metal materials. However, due to the anisotropy of the material crystal, the ultrasonic wave has the characteristics of multiple scattering and refraction in its propagation process. This makes it difficult to evaluate the casting blanks cleanliness effectively, for the inclusion echoes are submerged in the background noise. Therefore, the ultrasonic microscope is innovatively proposed to carry out efficient scanning on the casting blanks. In the meantime, the morphological filtering algorithm has the advantages of fewer parameters and faster calculation speed which can be used to increase the signal-to-noise ratio of ultrasound images and extract the defect features more efficiently. In order to verify the effectiveness of the proposed method, specimens were taken from three strands of continuous caster for detection and analysis. The experimental results show that the second strand has the best quality and the cleanliness is 2.2/mm3, which is obviously better than the other two strands. This method will provide a new technology for the quantitative evaluation of the internal quality of the casting blanks.
Laser Shock Processing and Related Phenomena
Authors: Ocaña José Luis , Grum Janez
Published: June 2020

Laser Shock Processing (LSP) is continuously developing as an effective technology for improving the surface and mechanical properties of metallic alloys and is emerging in direct competition with other established technologies, such as shot peening, both in preventive manufacturing treatments and maintenance/repair operations [...]
A Tale of Two Biomarkers: Untargeted 1H NMR Metabolomic Fingerprinting of BHBA and NEFA in Early Lactation Dairy Cows
Authors: Luke Timothy D. W. , Pryce Jennie E. , Wales William J. , Rochfort Simone J.
Published: June 2020

Disorders of energy metabolism, which can result from a failure to adapt to the period of negative energy balance immediately after calving, have significant negative effects on the health, welfare and profitability of dairy cows. The most common biomarkers of energy balance in dairy cows are β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA). While elevated concentrations of these biomarkers are associated with similar negative health and production outcomes, the phenotypic and genetic correlations between them are weak. In this study, we used an untargeted 1H NMR metabolomics approach to investigate the serum metabolomic fingerprints of BHBA and NEFA. Serum samples were collected from 298 cows in early lactation (calibration dataset N = 248, validation N = 50). Metabolomic fingerprinting was done by regressing 1H NMR spectra against BHBA and NEFA concentrations (determined using colorimetric assays) using orthogonal partial least squares regression. Prediction accuracies were high for BHBA models, and moderately high for NEFA models (R2 of external validation of 0.88 and 0.75, respectively). We identified 16 metabolites that were significantly (variable importance of projection score > 1) correlated with the concentration of one or both biomarkers. These metabolites were primarily intermediates of energy, phospholipid, and/or methyl donor metabolism. Of the significant metabolites identified; (1) two (acetate and creatine) were positively correlated with BHBA but negatively correlated with NEFA, (2) nine had similar associations with both BHBA and NEFA, (3) two were correlated with only BHBA concentration, and (4) three were only correlated with NEFA concentration. Overall, our results suggest that BHBA and NEFA are indicative of similar metabolic states in clinically healthy animals, but that several significant metabolic differences exist that help to explain the weak correlations between them. We also identified several metabolites that may be useful intermediate phenotypes in genomic selection for improved metabolic health.
Photosynthetic Co-production of Succinate and Ethylene in a Fast-Growing Cyanobacterium, Synechococcus elongatus PCC 11801
Authors: Sengupta Annesha , Pritam Prem , Jaiswal Damini , Bandyopadhyay Anindita , Pakrasi Himadri B. , Wangikar Pramod P.
Published: June 2020

Cyanobacteria are emerging as hosts for photoautotrophic production of chemicals. Recent studies have attempted to stretch the limits of photosynthetic production, typically focusing on one product at a time, possibly to minimise the additional burden of product separation. Here, we explore the simultaneous production of two products that can be easily separated: ethylene, a gaseous product, and succinate, an organic acid that accumulates in the culture medium. This was achieved by expressing a single copy of the ethylene forming enzyme (efe) under the control of PcpcB, the inducer-free super-strong promoter of phycocyanin β subunit. We chose the recently reported, fast-growing and robust cyanobacterium, Synechococcus elongatus PCC 11801, as the host strain. A stable recombinant strain was constructed using CRISPR-Cpf1 in a first report of markerless genome editing of this cyanobacterium. Under photoautotrophic conditions, the recombinant strain shows specific productivities of 338.26 and 1044.18 μmole/g dry cell weight/h for ethylene and succinate, respectively. These results compare favourably with the reported productivities for individual products in cyanobacteria that are highly engineered. Metabolome profiling and 13C labelling studies indicate carbon flux redistribution and suggest avenues for further improvement. Our results show that S. elongatus PCC 11801 is a promising candidate for metabolic engineering.
Technical Model of Micro Electrical Discharge Machining (EDM) Milling Suitable for Bottom Grooved Micromixer Design Optimization
Authors: Sabotin Izidor , Tristo Gianluca , Valentinčič Joško
Published: June 2020

In this paper, development of a technical model of micro Electrical Discharge Machining in milling configuration (EDM milling) is presented. The input to the model is a parametrically presented feature geometry and the output is a feature machining time. To model key factors influencing feature machining time, an experimental campaign by machining various microgrooves into corrosive resistant steel was executed. The following parameters were investigated: electrode dressing time, material removal rate, electrode wear, electrode wear control time and machining strategy. The technology data and knowledge base were constructed using data obtained experimentally. The model is applicable for groove-like features, commonly applied in bottom grooved micromixers (BGMs), with widths from 40 to 120 µm and depths up to 100 µm. The optimization of a BGM geometry is presented as a case study of the model usage. The mixing performances of various micromixer designs, compliant with micro EDM milling technology, were evaluated using computational fluid dynamics modelling. The results show that slanted groove micromixer is a favourable design to be implemented when micro EDM milling technology is applied. The presented technical model provides an efficient design optimization tool and, thus, aims to be used by a microfluidic design engineer.
Biosignatures in Subsurface Filamentous Fabrics (SFF) from the Deccan Volcanic Province, India
Authors: Götze Jens , Hofmann Beda , Machałowski Tomasz , Tsurkan Mikhail V. , Jesionowski Teofil , Ehrlich Hermann , Kleeberg Reinhard , Ottens Berthold
Published: June 2020

The morphology, chemical, and mineralogical composition of subsurface filamentous fabrics (SFF) from the Deccan Volcanic Province (DVP) were investigated to determine the origin of these spectacular aggregates. SFF occur in a wide variety of morphologies ranging from pseudo-stalactites to irregular fabrics and are classified as SFFIr (irregular) or SFFMa (matted). The SFF samples exhibit a thread-like (or filament-like) center from which mineral precipitation starts to form the final macroscopic morphologies. Detailed investigations revealed organic material (fungal chitin) in the innermost filamentous core, which may have acted as an initial nucleus for the mineralization processes. The morphometric characteristics of certain filamentous fabrics are very similar to those of microbial filaments and the fabrics formed from them but are clearly distinct from similar types of non-biological precipitates (fibrous minerals, speleothems, and “chemical gardens”). These features indicate that the filamentous cores might be products of microbial communities that were active in the basaltic cavities. The SFF cross-sections display similar concentric layers of the mineral succession and reach thicknesses of several centimeters with spectacular lengths up to 100 cm and constant diameters. The typical mineralization sequence points to temporal variation in the chemical composition of the mineralizing fluids from Fe(Mg)-rich (Fe-oxides/-hydroxides, Fe-rich sheet silicates such as celadonite and di-/tri-smectite) to Ca-dominated (Ca-rich zeolites) and finally pure SiO2 (opal-CT, chalcedony, and macro-crystalline quartz). Assuming biological activity at least during the early mineralization processes, circumneutral pH conditions and maximum temperatures of 100–120 °C were supposed. The formation of filamentous cores including Fe-bearing phyllosilicates probably occurred near the surface after cooling of the lava, where the elements necessary for mineral formation (i.e., Si, Mg, Al, Fe) were released during alteration of the volcanic host rocks by percolating fluids.
Synthesis of Nitroxide Diradical Using a New Approach
Authors: Fedyushin Pavel , Rybalova Tatyana , Asanbaeva Nargiz , Bagryanskaya Elena , Dmitriev Alexey , Gritsan Nina , Kazantsev Maxim , Tretyakov Evgeny
Published: June 2020

A new synthetic pathway to diradical organic systems is proposed. The effectiveness of this approach was exemplified by the synthesis of a new nitroxide diradical. An interaction of perfluorobiphenyl with lithium tert-butylamide, followed by oxidation of the thusly formed N4,N4′-di-tert-butyl-2,2′,3,3′,5,5′,6,6′-octafluorobiphenyl-4,4′-diamine with meta-chloroperoxybenzoic acid, led to the polyfluorinated nitroxide diradical, N,N′-(perfluorobiphenyl-4,4′-diyl)bis(N-tert-butyl(oxyl)amine), with a good total yield. The polyfluorinated diradical is stable and can be isolated in free form and completely characterized. The structure of the nitroxide diradical was proved by single-crystal X-ray diffraction analysis. According to the X-ray diffraction data, the diradical is considerably twisted: dihedral angles between the planes of the nitroxide groups and aromatic cycles are 65.1° and 69.5°, and between aromatic cycles 52.6°. Quantum chemical calculations predict well-balanced size of both intramolecular and intermolecular exchange interactions with J from −2.65 to −1.14 cm−1.
Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes
Authors: Dettori Maria Antonietta , Fabbri Davide , Dessì Alessandro , Dallocchio Roberto , Carta Paola , Honisch Claudia , Ruzza Paolo , Farina Donatella , Migheli Rossana , Serra Pier Andrea , Pantaleoni Roberto A. , Fois Xenia , Rocchitta Gaia , Delogu Giovanna
Published: June 2020

The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most of the inhibitors showed an IC50 in a range of 20–423 nM for tyrosinase and 23–2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model Tenebrio molitur.
Continuous Bioinspired Oxidation of Sulfides
Authors: Mangiavacchi Francesca , Crociani Letizia , Sancineto Luca , Marini Francesca , Santi Claudio
Published: June 2020

A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen peroxide as the final oxidant. The scope of the proposed methodology was investigated using aryl alkyl sulfides, aryl vinyl sulfides, and dialkyl sulfides as substrates, evidencing, in general, a good applicability. The scaled-up synthesis of (methylsulfonyl)benzene was also demonstrated, leading to its gram-scale preparation.
The Role of Structural Representation in the Performance of a Deep Neural Network for X-ray Spectroscopy
Authors: Madkhali Marwah M.M. , Rankine Conor D. , Penfold Thomas J.
Published: June 2020

An important consideration when developing a deep neural network (DNN) for the prediction of molecular properties is the representation of the chemical space. Herein we explore the effect of the representation on the performance of our DNN engineered to predict Fe K-edge X-ray absorption near-edge structure (XANES) spectra, and address the question: How important is the choice of representation for the local environment around an arbitrary Fe absorption site? Using two popular representations of chemical space—the Coulomb matrix (CM) and pair-distribution/radial distribution curve (RDC)—we investigate the effect that the choice of representation has on the performance of our DNN. While CM and RDC featurisation are demonstrably robust descriptors, it is possible to obtain a smaller mean squared error (MSE) between the target and estimated XANES spectra when using RDC featurisation, and converge to this state a) faster and b) using fewer data samples. This is advantageous for future extension of our DNN to other X-ray absorption edges, and for reoptimisation of our DNN to reproduce results from higher levels of theory. In the latter case, dataset sizes will be limited more strongly by the resource-intensive nature of the underlying theoretical calculations.
Unsaturated Fatty Acid-Induced Conformational Transitions and Aggregation of the Repeat Domain of Tau
Authors: Barracchia Carlo Giorgio , Tira Roberto , Parolini Francesca , Munari Francesca , Bubacco Luigi , Spyroulias Georgios A. , D’Onofrio Mariapina , Assfalg Michael
Published: June 2020

Background: The intrinsically disordered, amyloidogenic protein Tau associates with diverse classes of molecules, including proteins, nucleic acids, and lipids. Mounting evidence suggests that fatty acid molecules could play a role in the dysfunction of this protein, however, their interaction with Tau remains poorly characterized. Methods: In a bid to elucidate the association of Tau with unsaturated fatty acids at the sub-molecular level, we carried out a variety of solution NMR experiments in combination with circular dichroism and fluorescence measurements. Our study shows that Tau4RD, the highly basic four-repeat domain of Tau, associates strongly with arachidonic and oleic acid assemblies in a high lipid/protein ratio, perturbing their supramolecular states and itself undergoing time-dependent structural adaptation. The structural signatures of Tau4RD/fatty acid aggregates appear similar for arachidonic acid and oleic acid, however, they are distinct from those of another prototypical intrinsically disordered protein, α-synuclein, when bound to these lipids, revealing protein-specific conformational adaptations. Both fatty acid molecules are found to invariably promote the self-aggregation of Tau4RD and of α-synuclein. Conclusions: This study describes the reciprocal influence that Tau4RD and fatty acids exert on their conformational states, contributing to our understanding of fundamental aspects of Tau/lipid co-assembly.
Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Medicinal Fungus Cordyceps with Its Nutraceutical and Therapeutic Potential
Authors: Ashraf Syed Amir , Elkhalifa Abd Elmoneim O. , Siddiqui Arif Jamal , Patel Mitesh , Awadelkareem Amir Mahgoub , Snoussi Mejdi , Ashraf Mohammad Saquib , Adnan Mohd , Hadi Sibte
Published: June 2020

Cordyceps is a rare naturally occurring entomopathogenic fungus usually found at high altitudes on the Himalayan plateau and a well-known medicinal mushroom in traditional Chinese medicine. Cordyceps contains various bioactive components, out of which, cordycepin is considered most vital, due to its utmost therapeutic as well as nutraceutical potential. Moreover, the structure similarity of cordycepin with adenosine makes it an important bioactive component, with difference of only hydroxyl group, lacking in the 3′ position of its ribose moiety. Cordycepin is known for various nutraceutical and therapeutic potential, such as anti-diabetic, anti-hyperlipidemia, anti-fungal, anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anticancer, antiviral, hepato-protective, hypo-sexuality, cardiovascular diseases, antimalarial, anti-osteoporotic, anti-arthritic, cosmeceutical etc. which makes it a most valuable medicinal mushroom for helping in maintaining good health. In this review, effort has been made to bring altogether the possible wide range of cordycepin’s nutraceutical potential along with its pharmacological actions and possible mechanism. Additionally, it also summarizes the details of cordycepin based nutraceuticals predominantly available in the market with expected global value. Moreover, this review will attract the attention of food scientists, nutritionists, pharmaceutical and food industries to improve the use of bioactive molecule cordycepin for nutraceutical purposes with commercialization to aid and promote healthy lifestyle, wellness and wellbeing.
Chiral Aspects of Local Anesthetics
Authors: Čižmáriková Ružena , Čižmárik Jozef , Valentová Jindra , Habala Ladislav , Markuliak Mário
Published: June 2020

Thanks to the progress made in chemical technology (particularly in the methodologies of stereoselective syntheses and analyses) along with regulatory measures, the number of new chiral drugs registered in the form of pure enantiomers has increased over the past decade. In addition, the pharmacological and pharmacokinetic properties of the individual enantiomers of already-introduced racemic drugs are being re-examined. The use of the pure enantiomer of a drug that has been used to date in the form of a racemate is called a “chiral switch”. A re-examination of the properties of the pure enantiomers of racemates has taken place for local anesthetics, which represent a group of drugs which have long been used. Differences in (R) and (S)-enantiomers were found in terms of pharmacodynamic and pharmacokinetic activity as well as in toxicity. Levobupivacaine and robivacaine were introduced into practice as pure (S)-(−)-enantiomers, exhibiting more favorable properties than their (R)-(+)-stereoisomers or racemates. This overview focuses on the influence of chirality on the pharmacological and toxicological activity of local anesthetics as well as on individual HPLC and capillary electrophoresis (CE) methods used for enantioseparation and the pharmacokinetic study of individual local anesthetics with a chiral center.
Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature
Authors: Zou Yupiao , Han Jianlin , Saghyan Ashot S. , Mkrtchyan Anna F. , Konno Hiroyuki , Moriwaki Hiroki , Izawa Kunisuke , Soloshonok Vadim A.
Published: June 2020

Tailor-made amino acids are indispensable structural components of modern medicinal chemistry and drug design. Consequently, stereo-controlled preparation of amino acids is the area of high research activity. Over last decade, application of Ni(II) complexes of Schiff bases derived from glycine and chiral tridentate ligands has emerged as a leading methodology for the synthesis of various structural types of amino acids. This review article summarizes examples of asymmetric synthesis of tailor-made α-amino acids via the corresponding Ni(II) complexes, reported in the literature over the last four years. A general overview of this methodology is provided, with the emphasis given to practicality, scalability, cost-structure and recyclability of the chiral tridentate ligands.
Structural Characterization, DFT Calculation, NCI, Scan-Rate Analysis and Antifungal Activity against Botrytis cinerea of (E)-2-{[(2-Aminopyridin-2-yl)imino]-methyl}-4,6-di-tert-butylphenol (Pyridine Schiff Base)
Authors: Carreño Alexander , Páez-Hernández Dayán , Cantero-López Plinio , Zúñiga César , Nevermann Jan , Ramírez-Osorio Angélica , Gacitúa Manuel , Oyarzún Poldie , Sáez-Cortez Felipe , Polanco Rubén , Otero Carolina , Fuentes Juan A.
Published: June 2020

Botrytis cinerea is a ubiquitous necrotrophic filamentous fungal phytopathogen that lacks host specificity and can affect more than 1000 different plant species. In this work, we explored L1 [(E)-2-{[(2-aminopyridin-2-yl)imino]-methyl}-4,6-di-tert-butylphenol], a pyridine Schiff base harboring an intramolecular bond (IHB), regarding their antifungal activity against Botrytis cinerea. Moreover, we present a full characterization of the L1 by NMR and powder diffraction, as well as UV–vis, in the presence of previously untested different organic solvents. Complementary time-dependent density functional theory (TD-DFT) calculations were performed, and the noncovalent interaction (NCI) index was determined. Moreover, we obtained a scan-rate study on cyclic voltammetry of L1. Finally, we tested the antifungal activity of L1 against two strains of Botrytis cinerea (B05.10, a standard laboratory strain; and A1, a wild type strains isolated from Chilean blueberries). We found that L1 acts as an efficient antifungal agent against Botrytis cinerea at 26 °C, even better than the commercial antifungal agent fenhexamid. Although the antifungal activity was also observed at 4 °C, the effect was less pronounced. These results show the high versatility of this kind of pyridine Schiff bases in biological applications.
Solubility Data of the Bioactive Compound Piperine in (Transcutol + Water) Mixtures: Computational Modeling, Hansen Solubility Parameters and Mixing Thermodynamic Parameters
Authors: Shakeel Faiyaz , Haq Nazrul , Alshehri Sultan
Published: June 2020

The solubility values and thermodynamic parameters of a natural phytomedicine/nutrient piperine (PPN) in Transcutol-HP (THP) + water combinations were determined. The mole fraction solubilities (xe) of PPN in THP + water combinations were recorded at T = 298.2–318.2 K and p = 0.1 MPa by the shake flask method. Hansen solubility parameters (HSPs) of PPN, pure THP, pure water and THP + water mixtures free of PPN were also computed. The xe values of PPN were correlated well with “Apelblat, Van’t Hoff, Yalkowsky–Roseman, Jouyban–Acree and Jouyban–Acree–Van’t Hoff” models with root mean square deviations of < 2.0%. The maximum and minimum xe value of PPN was found in pure THP (9.10 × 10−2 at T = 318.2 K) and pure water (1.03 × 10−5 at T = 298.2 K), respectively. In addition, HSP of PPN was observed more closed with that of pure THP. The thermodynamic parameters of PPN were obtained using the activity coefficient model. The results showed an endothermic dissolution of PPN at m = 0.6–1.0 in comparison to other THP + water combinations studied. In addition, PPN dissolution was recorded as entropy-driven at m = 0.8–1.0 compared with other THP + water mixtures evaluated.
Recent Advances in the Production and Applications of Ellagic Acid and Its Derivatives. A Review
Authors: Evtyugin Dmitry D. , Magina Sandra , Evtuguin Dmitry V.
Published: June 2020

Ellagitannins (ETs), characterized by their diversity and chemical complexity, belong to the class of hydrolysable tannins that, via hydrolysis under acidic or alkaline conditions, can yield ellagic acid (EA). They are mostly found as a part of extractives in angiosperms. As known antioxidants and chelators, EA and EA derivatives are drawing an increasing interest towards extensive technical and biomedical applications. The latter ones include possible antibacterial, antifungal, antiviral, anti-inflammatory, hepato- and cardioprotective, chemopreventive, neuroprotective, anti-diabetic, gastroprotective, antihyperlipidemic, and antidepressant-like activities, among others. EA’s synthesis and production challenges prompt further research on new methods and alternative sources. Conventional and prospective methods and raw materials for the production of EA and its derivatives are reviewed. Among the potential sources of EA, the residues and industrial streams of the pulp industry have been highlighted and considered as an alluring alternative in terms of commercial exploitation.
Influence of Terpene Type on the Release from an O/W Nanoemulsion: Experimental and Theoretical Studies
Authors: Miastkowska Małgorzata , Śliwa Paweł
Published: June 2020

The interaction between a drug molecule and its carrier’s components is an important factor which influences the drug release profile. For this purpose, molecular dynamics (MD) may be the in silico tool which can help to understand the mechanism of drug loading/release. The aim of this work is to explain the effect of interactions between different types of terpenes, namely perillyl alcohol, forskolin, ursolic acid, and the nanoemulsion droplet core, on the release by means of experimental and theoretical studies. The basic nanoemulsion was composed of caprylic/capric triglyceride as the oil phase, polysorbate 80 as the emulsifier, and water. The in vitro release tests from a terpene-loaded nanoemulsion were carried out to determine the release profiles. The behavior of terpenoids in the nanoemulsion was also theoretically investigated using the molecular dynamics method. The forskolin-loaded nanoemulsion showed the highest percentage of drug release (almost 80% w/w) in contrast to ursolic acid and perillyl alcohol-loaded nanoemulsions (about 53% w/w and 19% w/w, respectively). The results confirmed that the kinetic model of release was terpene-type dependent. The zero-order model was the best to describe the ursolic acid release profile, while the forskolin and the perillyl alcohol followed a first-order and Higuchi model, respectively. Molecular dynamics simulations, especially energetical analysis, confirmed that the driving force of terpenes diffusion from nanoemulsion interior was their interaction energy with a surfactant.
Preparation, Characterization, and In Vitro Sustained Release Profile of Resveratrol-Loaded Silica Aerogel
Authors: Qin Lili , He Yiwei , Zhao Xinyu , Zhang Ting , Qin Yao , Du Ai
Published: June 2020

Silica aerogel, a kind of nanoporous material, is regarded as a desired drug carrier for its low toxicity, high specific surface area, and excellent biocompatibility. Using silica aerogel in a drug carrier may be an appropriate method to improve the performance of pure resveratrol. In this study, resveratrol-loaded silica aerogel (RSA) as a drug delivery system was prepared by the sol-gel method. Before gelling, resveratrol was added into the hydrolyzed tetraethyl orthosilicate (TEOS) ethanol solution then dispersed by stir and ultrasound. The results showed that RSA has a high loading rate of 19% with low cost and excellent biocompatibility. The SEM images showed that silica aerogel wraps up outside the resveratrol. Sustained releasing effect could be observed in RSA after 1 h, while pure resveratrol did not display this. The release of RSA lasted for over 6 h, and the release amount reached over 90% and 80% in either simulated gastric fluid (pH = 2.0) or phosphate-buffered saline (pH = 7.4) at 37 °C. Preliminary in vitro toxicity test revealed RSA to be biocompatible and stable; and when coupled with the anti-inflammatory effects of resveratrol, showed good potential for osteoarthritis treatment.
Oxidation-Induced Detachment of Ruthenoarene Units and Oxygen Insertion in Bis-Pd(II) Hexaphyrin π-Ruthenium Complexes
Authors: Nakai Akito , Tanaka Takayuki , Osuka Atsuhiro
Published: June 2020

Two types of new bis-Pd(II) hexaphyrin π-ruthenium complexes are reported. A double-decker bis-Pd(II) hexaphyrin π-ruthenium complex 4 was obtained by oxidation-induced detachment of a ruthenoarene unit from the triple-decker complex 3 and oxygen-inserted triple-decker bis-Pd(II) hexaphyrin π-ruthenium complex 6 was obtained upon treatment of bis-Pd(II) [26]hexaphyrin 5 with [RuCl2(p-cymene)]2 under aerobic conditions. Although π-metal complexation of porphyrinoids often results in decreased global aromaticity due to the enhancement of local 6π aromatic segments, distinct aromatic characters were indicated for 4 and 6 by 1H-NMR spectral and theoretical calculations. These results are accounted for in terms of possible resonance contributors of hexaphyrin di- and tetraanion ligands. Thus, π-metal coordination has been shown to be effective for modulation of the overall aromaticity.