bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Research and Numerical Analysis of the Elastic Properties of Paper Cell Cores before and after Impregnation
Authors: Słonina Michał , Dziurka Dorota , Smardzewski Jerzy
Published: April 2020

The research hypothesis states that the impregnation of the honeycomb paper core of lightweight sandwich panels with modified starch, sodium silicate and epoxy resin (LiquidWood®) resin has a significant effect on its elastic properties. In this study, a recycled paper was used in three thicknesses, seven types of cell shapes, including two after numerical optimization and three types of impregnating agents. The method of digital image analysis determined the elastic constants of manufactured paper cores, which were subjected to axial compression in two directions. Based on the experimental results, elastic constants of the cores were calculated and compared with the results of numerical calculations. It has been shown that each of the impregnating solutions used improved the stiffness of the paper core. The best results were obtained for LiquidWood® epoxy resin and modified starch. An important parameter of cell geometry affecting their rigidity is the angle of the cell wall φ, as well as the arrangement of the common cell wall in relation to the direction of load. The numerical models developed were positively verified.
Cytotoxic or Not? Disclosing the Toxic Nature of Carbonaceous Nanomaterials through Nano–Bio Interactions
Authors: Czarnecka Joanna , Wiśniewski Marek , Forbot Natalia , Bolibok Paulina , Terzyk Artur P. , Roszek Katarzyna
Published: April 2020

The cytotoxic influence of two different carbonaceous nanomaterials on human mesenchymal stem cells (MSCs) cultured in vitro was compared in the short (1–3 days) and long term (up to 60 days). Amorphous carbon and single-walled carbon nanotubes were chosen and evaluated due to their contrasting physicochemical properties. Both materials, though supposed similarly low-toxic in basic short-term cytotoxicity assays, demonstrated dramatically different properties in the long-term study. The surface chemistry and biomolecule-adsorption capacity turned out to be crucial factors influencing cytotoxicity. We proved that amorphous carbon is able to weakly bind a low-affinity protein coat (so-called soft corona), while carbon nanotubes behaved oppositely. Obtained results from zeta-potential and adsorption measurements for both nanomaterials confirmed that a hard protein corona was present on the single-walled carbon-nanotube surface that aggravated their cytotoxic influence. The long-term exposure of the mesenchymal stem cells to carbon nanotubes, coated by the strongly bound proteins, showed a significant decrease in cell-growth rate, followed by cell senescence and death. These results are of great importance in the light of increasing nanomaterial applications in biomedicine and cell-based therapies. Our better understanding of the puzzling cytotoxicity of carbonaceous nanomaterials, reflecting their surface chemistry and interactions, is helpful in adjusting their properties when tailored for specific applications.
Thermal Frequency Drift of 3D Printed Microwave Components
Authors: Le Sage Gregory Peter
Published: April 2020

Fabrication of microwave slot array antennas and waveguide bandpass and notch filters using 3D printing has significant advantages in terms of speed and cost even for parts with high mechanical complexity. One disadvantage of Stereolithography (SLA) 3D printed, copper plated microwave components is that some SLA resins have a high Coefficient of Thermal Expansion (CTE), quoted in micrometers per meter per degree or 10−6 per degree. Compared to typically used metals such as aluminum (CTE 24 × 10−6·K−1) and copper (CTE 17 × 10−6·K−1), SLA resin can have CTE above 100 × 10−6·K−1. Resonant structures experience significant frequency drift with temperature changes on the order of 10–50 °C. The issue of 3D printed microwave structures changing frequency characteristics significantly with temperature shift has not been addressed or reviewed in current literature. We measured and simulated the effect of temperature change on a slot array, cavity notch filters, and post loaded waveguide bandpass filters. We tested several types of SLA resin, different plating techniques, and also Direct Metal Laser Sintering (DMLS) and Binder Infusion metal 3D printing. Performance as a function of temperature is presented for these alternatives.
Acid and Acid-Alkali Treatment Methods of Al-Chloride Solution Obtained by the Leaching of Coal Fly Ash to Produce Sandy Grade Alumina
Authors: Valeev Dmitry , Shoppert Andrei , Mikhailova Alexandra , Kondratiev Alex
Published: April 2020

Sandy grade alumina is a valuable intermediate material that is mainly produced by the Bayer process and used for manufacturing primary metallic aluminum. Coal fly ash is generated in coal-fired power plants as a by-product of coal combustion that consists of submicron ash particles and is considered to be a potentially hazardous technogenic waste. The present paper demonstrates that the Al-chloride solution obtained by leaching coal fly ash can be further processed to obtain sandy grade alumina, which is essentially suitable for metallic aluminum production. The novel process developed in the present study involves the production of amorphous alumina via the calcination of aluminium chloride hexahydrate obtained by salting-out from acid Al-Cl liquor. Following this, alkaline treatment with further Al2O3 dissolution and recrystallization as Al(OH)3 particles is applied, and a final calcination step is employed to obtain sandy grade alumina with minimum impurities. The process does not require high-pressure equipment and reutilizes the alkaline liquor and gibbsite particles from the Bayer process, which allows the sandy grade alumina production costs to be to significantly reduced. The present article also discusses the main technological parameters of the acid treatment and the amounts of major impurities in the sandy grade alumina obtained by the different (acid and acid-alkali) methods.
Microstructure Evolution of Selective Laser Melted Inconel 718: Influence of High Heating Rates
Authors: Tabaie Seyedmohammad , Rézaï-Aria Farhad , Jahazi Mohammad
Published: April 2020

Inconel 718 (IN718) superalloy samples fabricated by selective laser melting (SLM) were submitted to different heating cycles and their microstructural characteristics were investigated. The selected heating rates, ranging from 10 °C/min to 400 °C/s, represent different regions in the heat-affected zone (HAZ) of welded additively manufactured specimens. A combination of differential thermal analysis (DTA), high-resolution dilatometry, as well as laser confocal and electron microscopy were used to study the precipitation and dissolution of the secondary phases and microstructural features. For this purpose, the microstructure of the additively manufactured specimen was investigated from the bottom, in contact with the support, to the top surface. The results showed that the dissolution of γ″ and δ phases were delayed under high heating rates and shifted to higher temperatures. Microstructural analysis revealed that the Laves phase at the interdendritic regions was decomposed in specific zones near the surface of the samples. It was determined that the thickness and area fraction of these zones were inversely related to the applied heating rate. A possible mechanism based on the influence of heating rate on Nb diffusion in the interdendritic regions and core of the dendrites is proposed to interpret the observed changes in the microstructure.
Metabolomics in Central Sensitivity Syndromes
Authors: Miller Joseph S. , Rodriguez-Saona Luis , Hackshaw Kevin V.
Published: April 2020

Central sensitization syndromes are a collection of frequently painful disorders that contribute to decreased quality of life and increased risk of opiate abuse. Although these disorders cause significant morbidity, they frequently lack reliable diagnostic tests. As such, technologies that can identify key moieties in central sensitization disorders may contribute to the identification of novel therapeutic targets and more precise treatment options. The analysis of small molecules in biological samples through metabolomics has improved greatly and may be the technology needed to identify key moieties in difficult to diagnose diseases. In this review, we discuss the current state of metabolomics as it relates to central sensitization disorders. From initial literature review until Feb 2020, PubMed, Embase, and Scopus were searched for applicable studies. We included cohort studies, case series, and interventional studies of both adults and children affected by central sensitivity syndromes. The majority of metabolomic studies addressing a CSS found significantly altered metabolites that allowed for differentiation of CSS patients from healthy controls. Therefore, the published literature overwhelmingly supports the use of metabolomics in CSS. Further research into these altered metabolites and their respective metabolic pathways may provide more reliable and effective therapeutics for these syndromes.
Evaluation of MDA-MB-468 Cell Culture Media Analysis in Predicting Triple-Negative Breast Cancer Patient Sera Metabolic Profiles
Authors: Wojtowicz Wojciech , Wróbel Anna , Pyziak Karolina , Tarkowski Radosław , Balcerzak Alicja , Bębenek Marek , Młynarz Piotr
Published: April 2020

Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive 1H NMR metabolic characterization of the MDA-MB-468 cell line, a commonly used model of TNBC, followed by an analysis of serum samples obtained from TNBC patients and healthy controls. MDA-MB-468 cells were cultured, and changes in the metabolic composition of the medium were monitored for 72 h. Based on time courses, metabolites were categorized as being consumed, being produced, or showing a mixed behavior. When comparing TNBC and control samples (HC), and by using multivariate and univariate analyses, we identified nine metabolites with differing profiles). The serum of TNBC patients was characterized by higher levels of glucose, glutamine, citrate, and acetoacetate and by lower levels of lactate, alanine, tyrosine, glutamate, and acetone. A comparative analysis between MDA-MB-468 cell culture media and TNBC patients’ serum identified a potential systemic response to the carcinogenesis-associated processes, highlighting that MDA-MB-468 cells footprint does not reflect metabolic changes observed in studied TNBC serum fingerprint.
Challenging a “Cushy” Life: Potential Roles of Thermogenesis and Adipose Tissue Adaptations in Delayed Aging of Ames and Snell Dwarf Mice
Authors: Valencak Teresa G. , Spenlingwimmer Tanja , Nimphy Ricarda , Reinisch Isabel , Hoffman Jessica M. , Prokesch Andreas
Published: April 2020

Laboratory mouse models with genetically altered growth hormone (GH) signaling and subsequent endocrine disruptions, have longer lifespans than control littermates. As such, these mice are commonly examined to determine the role of the somatotropic axis as it relates to healthspan and longevity in mammals. The two most prominent mouse mutants in this context are the genetically dwarf Ames and Snell models which have been studied extensively for over two decades. However, it has only been proposed recently that both white and brown adipose tissue depots may contribute to their delayed aging. Here we review the current state of the field and supplement it with recent data from our labs.
Silicon Multi-Pass Gas Cell for Chip-Scale Gas Analysis by Absorption Spectroscopy
Authors: Fathy Alaa , Sabry Yasser M. , Gnambodoe-Capochichi Martine , Marty Frederic , Khalil Diaa , Bourouina Tarik
Published: April 2020

Semiconductor and micro-electromechanical system (MEMS) technologies have been already proved as strong solutions for producing miniaturized optical spectrometers, light sources and photodetectors. However, the implementation of optical absorption spectroscopy for in-situ gas analysis requires further integration of a gas cell using the same technologies towards full integration of a complete gas analysis system-on-chip. Here, we propose design guidelines and experimental validation of a gas cell fabricated using MEMS technology. The architecture is based on a circular multi-pass gas cell in a miniaturized form. Simulation results based on the proposed modeling scheme helps in determining the optimum dimensions of the gas cell, given the constraints of micro-fabrication. The carbon dioxide spectral signature is successfully measured using the proposed integrated multi-pass gas cell coupled with a MEMS-based spectrometer.
Special Issue: Antimicrobial Resistance in Livestock
Authors: Stanford Kim
Published: April 2020

Antimicrobial resistance threatens the health of both humans and livestock as antimicrobials become continually less effective for controlling infectious disease [...]
Current State of Anthrax Vaccines and Key R&D Gaps Moving Forward
Authors: Clark Adam , Wolfe Daniel N.
Published: April 2020

A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.
From Decompression Melting to Mantle-Wedge Refertilization and Metamorphism: Insights from Peridotites of the Alag Khadny Accretionary Complex (SW Mongolia)
Authors: Gornova Marina , Karimov Anas , Skuzovatov Sergei , Belyaev Vasiliy
Published: April 2020

This study reports on mineral and bulk rock compositions of metaperidotites from the Alag Khadny accretionary complex in SW Mongolia, to reveal their nature and relationships with associated eclogites. The peridotites preserved original porphyroclastic textures and are composed of olivine, orthopyroxene relics, Cr-spinel, interstitial (not residual) clinopyroxene, and secondary chlorite, tremolite, olivine, Cr-magnetite, clinopyroxene, and antigorite. Cr-spinel has Cr# of 0.3–0.5, and primary olivine shows Mg# of 0.90–0.92. The pyroxenes are high-magnesian with low Al2O3 and Cr2O3. The bulk rocks have U-shaped normalized trace-element patterns with enrichment in LILE, L-MREE relative to HREE, and weak Pb–Sr peaks and Nb–Zr–Hf minima. Interstitial clinopyroxene exhibits V- and U-shaped normalized REE patterns with (La/Yb)N > 1 (Yb = 1.2–3 of chondritic values) and enrichment in fluid-mobile elements and Zr. HREE abundances of clinopyroxene can be simulated by 23–26% partial melting of depleted mantle starting at garnet-facies (6–8%) depths, followed by hydrous or anhydrous melting at spinel-facies depths L-MREE characteristics of clinopyroxenes can be simulated by further interaction of harzburgites with an island-arc basaltic melt in a supra-subduction environment. The association of hydrous secondary minerals in the Alag Khadny peridotites suggests their retrograde metamorphism at 1.6–2.0 GPa and 640–720 °C, similar to P–T conditions reported earlier for the spatially associated eclogites. This supports metamorphism of the Alag Khadny peridotites in a mantle wedge, followed by joint exhumation of peridotites and eclogites. Given the findings above and implying the regional geological background, we advocate for a sequential Neoproterozoic evolution the Alag Khadny harzburgites from (1) their formation by decompression partial melting in an Early Neoproterozoic or older spreading center of a mid-ocean or back-arc setting, and (2) refertilization by supra-subduction melts, followed by (3) Late Neoproterozoic–Early Cambrian hydrous-fluid metamorphism and juxtaposition with eclogites.
Detrital Zircon U-Pb Ages in the East China Seas: Implications for Provenance Analysis and Sediment Budgeting
Authors: Huang Xiangtong , Song Jiaze , Yue Wei , Wang Zhongbo , Mei Xi , Li Yalong , Li Fangliang , Lian Ergang , Yang Shouye
Published: April 2020

Linking marine sinks to potential terrestrial sources is one of most intriguing but challenging aspects of sediment source-to-sink studies. In this study, we analyzed 23 zircon samples (3271 filtered best ages) from surface sediments of the east China seas (ECSs) that cover a large portion of the Bohai Sea, Yellow Sea, East China Sea to part of the northeastern South China Sea. The results of U-Pb age distributions exhibit variable signatures in different seas. The Bohai Sea is characterized by 4 age populations at 203–286 Ma, 383–481 Ma, 1830–1940 Ma and 2480–2548 Ma, whereas the southern Yellow Sea and the East China Sea are featured by 5 age populations at 176–223 Ma, 383–481 Ma, 732–830 Ma, 1830–1940 Ma and 2480–2548 Ma. We propose that the presence or absence of the population of 732–830 Ma in the Yangtze Craton (YC) and the North China Craton (NCC) is a possible geochronological signature to distinguish zircon grains derived from the two source regions. Furthermore, on the basis of multidimensional scaling (MDS), U-Pb ages in the sediments of the Bohai Sea, East China Sea and the Taiwan Strait could be correspondently linked to those of the Yellow River, the Yangtze River and Taiwan rivers. The good linkages support the view that U-Pb age distributions of detrital zircons in the margin seas are mainly controlled by fluvial discharges, and ultimately, by the tectonic history of the corresponding source regions. Using a sediment forward mixing model, we obtained the relative sediment contributions and spatial variations of five most important river discharges in the region. The mixing results suggest that the major rivers in the region, i.e., the Yangtze and the Yellow Rivers, are the dominant sediment contributors to the continental margin, and their mixing coefficients could be used to infer relative sediment budgeting. In addition, spatial variations in mixing coefficient in the East China Sea indicate that sediment mixing and partitioning processes in the marine depositional environment have played a part role in propagating the provenance signals as a result of interaction of oceanic currents and tides. The combined method between provenance analysis and mixing modeling provides a feasible way to appreciate sediment budgeting in the geological past.
Protective Effects of Vitamin K Compounds on the Proteomic Profile of Osteoblasts under Oxidative Stress Conditions
Authors: Muszyńska Marta , Ambrożewicz Ewa , Gęgotek Agnieszka , Grynkiewicz Grzegorz , Skrzydlewska Elżbieta
Published: April 2020

Oxidative stress, which accompanies the pathogenesis of many bone diseases, contributes to the reduction of osteoblast activity, resulting in the inhibition of differentiation. This study aimed to assess the effect of vitamins K1 and K2 (MK4 and MK7) on the proteomic profile of human osteoblasts cell line under oxidative conditions induced by hydrogen peroxide (H2O2). The analysis was performed using QExactiveHF mass spectrometer with a nanoelectrospray ionization source. The osteoblast protein exposed to oxidative stress and vitamin K was compared with the proteome of cells exposed only to oxidative stress. Our proteomic analysis identified 1234 proteins changed after 5 days, 967 after 15 days, and 1214 after 20 days of culture. We observed the most frequent changes in the expression of proteins with catalytic activity or protein/DNA binding properties (45% and 40%, respectively). Significant changes were also observed in proteins with transcription/translation regulator activity (2–6%), regulators of molecular functions (5–6%), signal transducers (1–4%), transporters (4–6%), and structural molecules (3–5%). Our results clearly show that vitamins K protect cells from H2O2-induced changes in protein expression, primarily through their effects on transcriptional regulators and transporter proteins. As a result, vitamins K can support the formation, remodeling, and mineralization of bone tissue.
Induced Pluripotent Stem Cell (iPSC)-Based Neurodegenerative Disease Models for Phenotype Recapitulation and Drug Screening
Authors: Chang Chia-Yu , Ting Hsiao-Chien , Liu Ching-Ann , Su Hong-Lin , Chiou Tzyy-Wen , Lin Shinn-Zong , Harn Horng-Jyh , Ho Tsung-Jung
Published: April 2020

Neurodegenerative diseases represent a significant unmet medical need in our aging society. There are no effective treatments for most of these diseases, and we know comparatively little regarding pathogenic mechanisms. Among the challenges faced by those involved in developing therapeutic drugs for neurodegenerative diseases, the syndromes are often complex, and small animal models do not fully recapitulate the unique features of the human nervous system. Human induced pluripotent stem cells (iPSCs) are a novel technology that ideally would permit us to generate neuronal cells from individual patients, thereby eliminating the problem of species-specificity inherent when using animal models. Specific phenotypes of iPSC-derived cells may permit researchers to identify sub-types and to distinguish among unique clusters and groups. Recently, iPSCs were used for drug screening and testing for neurologic disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), spinocerebellar atrophy (SCA), and Zika virus infection. However, there remain many challenges still ahead, including how one might effectively recapitulate sporadic disease phenotypes and the selection of ideal phenotypes and for large-scale drug screening. Fortunately, quite a few novel strategies have been developed that might be combined with an iPSC-based model to solve these challenges, including organoid technology, single-cell RNA sequencing, genome editing, and deep learning artificial intelligence. Here, we will review current applications and potential future directions for iPSC-based neurodegenerative disease models for critical drug screening.
Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice
Authors: Park Ju-Hyoung , Hwang Min Hee , Cho Young-Rak , Hong Seong Su , Kang Jae-Shin , Kim Won Hee , Yang Seung Hwan , Seo Dong-Wan , Oh Joa Sub , Ahn Eun-Kyung
Published: April 2020

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.
Synthetic Kavalactone Analogues with Increased Potency and Selective Anthelmintic Activity against Larvae of Haemonchus contortus In Vitro
Authors: Herath H.M.P. , Taki Aya , Nguyen Nghi , Garcia-Bustos José , Hofmann Andreas , Wang Tao , Ma Guangxu , Chang Bill , Jabbar Abdul , Sleebs Brad , Gasser Robin
Published: April 2020

Kava extract, an aqueous rhizome emulsion of the plant Piper methysticum, has been used for centuries by Pacific Islanders as a ceremonial beverage, and has been sold as an anxiolytic agent for some decades. Kavalactones are a major constituent of kava extract. In a previous investigation, we had identified three kavalactones that inhibit larval development of Haemonchus contortus in an in vitro-bioassay. In the present study, we synthesized two kavalactones, desmethoxyyangonin and yangonin, as well as 17 analogues thereof, and evaluated their anthelmintic activities using the same bioassay as employed previously. Structure activity relationship (SAR) studies showed that a 4-substituent on the pendant aryl ring was required for activity. In particular, compounds with 4-trifluoromethoxy, 4-difluoromethoxy, 4-phenoxy, and 4-N-morpholine substitutions had anthelmintic activities (IC50 values in the range of 1.9 to 8.9 µM) that were greater than either of the parent natural products—desmethoxyyangonin (IC50 of 37.1 µM) and yangonin (IC50 of 15.0 µM). The synthesized analogues did not exhibit toxicity on HepG2 human hepatoma cells in vitro at concentrations of up to 40 µM. These findings confirm the previously-identified kavalactone scaffold as a promising chemotype for new anthelmintics and provide a basis for a detailed SAR investigation focused on developing a novel anthelmintic agent.
Extraction of Protein from Four Different Seaweeds Using Three Different Physical Pre-Treatment Strategies
Authors: O’ Connor Jack , Meaney Steve , Williams Gwilym A. , Hayes Maria
Published: April 2020

Seaweeds are a rich source of protein and can contain up to 47% on the dry weight basis. It is challenging to extract proteins from the raw biomass of seaweed due to resilient cell-wall complexes. Four species of macroalgae were used in this study-two brown, Fucus vesiculosus and Alaria esculenta, and two red, Palmaria palmata and Chondrus crispus. Three treatments were applied individually to the macroalgal species: (I) high-pressure processing (HPP); (II) laboratory autoclave processing and (III) a classical sonication and salting out method. The protein, ash and lipid contents of the resulting extracts were estimated. Yields of protein recovered ranged from 3.2% for Fucus vesiculosus pre-treated with high pressure processing to 28.9% protein recovered for Chondrus crispus treated with the classical method. The yields of protein recovered using the classical, HPP and autoclave pre-treatments applied to Fucus vesiculosus were 35.1, 23.7% and 24.3%, respectively; yields from Alaria esculenta were 18.2%, 15.0% and 17.1% respectively; yields from Palmaria palmata were 12.5%, 14.9% and 21.5% respectively, and finally, yields from Chondrus crispus were 35.2%, 16.1% and 21.9%, respectively. These results demonstrate that while macroalgal proteins may be extracted using either physical or enzymatic methods, the specific extraction procedure should be tailored to individual species.
Simple Synthesis of 17-β-O-hemisuccinate of Stanozolol for Immunoanalytical Methods
Authors: Casati Silvana , Ottria Roberta , Ciuffreda Pierangela
Published: April 2020

The use of doping in sports is a global problem that affects athletes around the world. Among the different methods developed to detect doping agents in biological samples, there are antibody-based methods that need an appropriate hapten design. Steroids with a hydroxyl group can be converted to the corresponding hemisuccinates. A novel approach to the synthesis of 17β-O-hemisuccinate of the common doping agent stanozolol is described here. Acylation of stanozolol with methyl 4-chloro-4-oxobutyrate/4-dimethylaminopyridine, followed by mild alkaline hydrolysis with methanolic sodium hydroxide at room temperature, gave the simultaneous protection and deprotection of pyrazole-nitrogen atoms. The proposed new synthetic method allows the desired hemisuccinate derivative to be obtained in only two steps, and with a good total yield starting from stanozolol.
Preconditioning of Adipose-Derived Mesenchymal Stem-Like Cells with Eugenol Potentiates Their Migration and Proliferation In Vitro and Therapeutic Abilities in Rat Hepatic Fibrosis
Authors: Fathy Moustafa , Okabe Motonori , M. Othman Eman , Saad Eldien Heba M. , Yoshida Toshiko
Published: April 2020

Mesenchymal stem cells (MSCs) have considerable therapeutic abilities in various disorders, including hepatic fibrosis. They may be affected with different culture conditions. This study investigated, on molecular basics, the effect of pretreatment with eugenol on the characteristics of adipose tissue-derived MSCs (ASCs) in vitro and the implication of eugenol preconditioning on the in vivo therapeutic abilities of ASCs against CCl4-induced hepatic fibrosis in rats. The effect of eugenol on ASCs was assessed using viability, scratch migration and sphere formation assays. Expressions of genes and proteins were estimated by immunofluorescence or qRT-PCR. For the in vivo investigations, rats were divided into four groups: the normal control group, fibrotic (CCl4) group, CCl4+ASCs group and CCl4 + eugenol-preconditioned ASCs (CCl4+E-ASCs) group. Eugenol affected the viability of ASCs in a concentration- and time-dependent manner. Eugenol improved their self-renewal, proliferation and migration abilities and significantly increased their expression of c-Met, reduced expression 1 (Rex1), octamer-binding transcription factor 4 (Oct4) and nanog genes. Furthermore, E-ASCs showed more of a homing ability than ASCs and improved the serum levels of ALT, AST, albumin, total bilirubin and hyaluronic acid more efficient than ASCs in treating CCl4-induced hepatic fibrosis, which was confirmed with histopathology. More interestingly, compared to the CCl4+ASCs group, CCl4+E-ASCs group showed a lower expression of inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), cluster of differentiation 163 (CD163) and tumor necrosis factor-α (TNF-α) genes and higher expression of matrix metalloproteinase (MMP)-9 and MMP-13 genes. This study, for the first time, revealed that eugenol significantly improved the self-renewal, migration and proliferation characteristics of ASCs, in vitro. In addition, we demonstrated that eugenol-preconditioning significantly enhanced the therapeutic abilities of the injected ASCs against CCl4-induced hepatic fibrosis.
Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus
Authors: Papukashvili Dimitri , Rcheulishvili Nino , Deng Yulin
Published: April 2020

Creatine supplementation of the population with type 2 diabetes mellitus (T2DM) combined with an exercise program is known to be a possible therapy adjuvant with hypoglycemic effects. However, excessive administration of creatine leads to the production of methylamine which is deaminated by the enzyme semicarbazide-sensitive amine oxidase (SSAO) and as a result, cytotoxic compounds are produced. SSAO activity and reaction products are increased in the serum of T2DM patients. Creatine supplementation by diabetics will further augment the activity of SSAO. The current review aims to find a feasible way to ameliorate T2DM for patients who exercise and desire to consume creatine. Several natural agents present in food which are involved in the regulation of SSAO activity directly or indirectly are reviewed. Particularly, zinc-α2-glycoprotein (ZAG), zinc (Zn), copper (Cu), histamine/histidine, caffeine, iron (Fe), and vitamin D are discussed. Inhibiting SSAO activity by natural agents might reduce the potential adverse effects of creatine metabolism in population of T2DM.
Rapid Classification and Quantification of Camellia (Camellia oleifera Abel.) Oil Blended with Rapeseed Oil Using FTIR-ATR Spectroscopy
Authors: Han Jianxun , Sun Ruixue , Zeng Xiuying , Zhang Jiukai , Xing Ranran , Sun Chongde , Chen Ying
Published: April 2020

Currently, the authentication of camellia oil (CAO) has become very important due to the possible adulteration of CAO with cheaper vegetable oils such as rapeseed oil (RSO). Therefore, we report a Fourier transform infrared (FTIR) spectroscopic method for detecting the authenticity of CAO and quantifying the blended levels of RSO. In this study, two characteristic spectral bands (1119 cm−1 and 1096 cm−1) were selected and used for monitoring the purity of CAO. In combination with principal component analysis (PCA), linear discriminant analysis (LDA), and partial least squares regression (PLSR) analysis, qualitative and quantitative methods for the detection of camellia oil adulteration were proposed. The results showed that the calculated I1119/I1096 intensity ratio facilitated an initial check for pure CAO and six other edible oils. PCA was used on the optimized spectral region of 1800–650 cm−1. We observed the classification of CAO and RSO as well as discrimination of CAO with RSO adulterants. LDA was utilized to classify CAO from RSO. We could differentiate and classify RSO adulterants up to 1% v/v. In the quantitative PLSR models, the plots of actual values versus predicted values exhibited high linearity. Root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSECV) values of the PLSR models were 1.4518–3.3164% v/v and 1.7196–3.8136% v/v, respectively. This method was successfully applied in the classification and quantification of CAO adulteration with RSO.
Enhanced Lycopene Extraction from Tomato Peels by Optimized Mixed-Polarity Solvent Mixtures
Authors: Zuorro Antonio
Published: April 2020

Mounting evidence from clinical and epidemiological studies suggests that lycopene, the most abundant carotenoid in tomatoes, may be beneficial in the prevention or treatment of some important diseases. Ripe tomato peels are the richest source of lycopene, but the use of conventional solvent extraction methods without pretreatment of the plant material results in very poor recovery. The reason lies in the localization of lycopene in the plant tissue and the low permeability of the latter to solvent molecules. In this paper, a mixture design procedure was used to formulate solvent mixtures allowing the recovery of lycopene from non-pretreated tomato peels. Two ternary systems were investigated: (a) n-hexane–ethanol–acetone and (b) ethyl lactate–ethanol–acetone. Optimization of the ternary mixture composition led to a recovery of over 90% of the lycopene present in the peels. The high extraction efficiency was explained in terms of lycopene affinity combined with the ability to swell the plant material. A tomato oleoresin with high antioxidant activity and a lycopene content of about 13% (w/w) was also produced. Overall, the results indicate that highly effective solvents for direct recovery of lycopene from tomato peels can be easily prepared by a mixture design approach.
Antibacterial Activity of Amidodithiophosphonato Nickel(II) Complexes: An Experimental and Theoretical Approach
Authors: Podda Enrico , Arca Massimiliano , Atzeni Giulia , Coles Simon J. , Ibba Antonella , Isaia Francesco , Lippolis Vito , Orrù Germano , Orton James B. , Pintus Anna , Tuveri Enrica , Aragoni M. Carla
Published: April 2020

The reactions of 2,4-bis(4-methoxyphenyl)-1,3-dithio-2,4-diphosphetane-2,4-disulfide (Lawesson’s Reagent, LR) with benzylamine (BzNH2) and 4-phenylbutylamine (PhBuNH2) yield benzylammonium P-(4-methoxyphenyl)-N-benzyl-amidodithiophosphonate (BzNH3)(BzNH-adtp) and 4-phenylbutylammonium P-(4-methoxyphenyl)-N-(4-phenylbutyl)-amidodithiophosphonate (PhBuNH3)(PhBuNH-adtp). The relevant nickel complexes [Ni(BzNH-adtp)2] and [Ni(PhBuNH-adtp)2] and the corresponding hydrolysed derivatives (BzNH3)2[Ni(dtp)2] and (PhBuNH3)2[Ni(dtp)2] were prepared and fully characterized. The antimicrobial activity of the aforementioned amidodithiophosphonates against a set of Gram-positive and Gram-negative pathogen bacteria was evaluated, and [Ni(BzNH-adtp)2] and [Ni(PhBuNH-adtp)2] showed antiproliferative activity towards Staphylococcus aureus and Staphylococcus haemolyticus strains. density functional theory (DFT) calculations were performed to shed some light on the activity of reported compounds related to their tendency towards P–N bond cleavage.
Complexes of Cobalt(II) Iodide with Pyridine and Redox Active 1,2-Bis(arylimino)acenaphthene: Synthesis, Structure, Electrochemical, and Single Ion Magnet Properties
Authors: Yambulatov Dmitriy S. , Nikolaevskii Stanislav A. , Kiskin Mikhail A. , Magdesieva Tatiana V. , Levitskiy Oleg A. , Korchagin Denis V. , Efimov Nikolay N. , Vasil’ev Pavel N. , Goloveshkin Alexander S. , Sidorov Alexey A. , Eremenko Igor L.
Published: April 2020

Complexes [(dpp-BIAN)0CoIII2]·MeCN (I) and [(Py)2CoI2] (II) were synthesized by the reaction between cobalt(II) iodide and 1,2-bis(2,6-diisopropylphenylimino)acenaphthene (dpp-BIAN) or pyridine (Py), respectively. The molecular structures of the complexes were determined by X-ray diffraction. The Co(II) ions in both compounds are in a distorted tetrahedral environment (CoN2I2). The electrochemical behavior of complex I was studied by cyclic voltammetry. Magnetochemical measurements revealed that when an external magnetic field is applied, both compounds exhibit the properties of field-induced single ion magnets.
Coupling of Bioreaction and Separation via Novel Thermosensitive Ionic Liquids Applied in the Baker’s Yeast-Catalyzed Reduction of Ethyl 2-oxo-4-phenylbutyrate
Authors: Yang Yuexi , Shi Yugang , Feng Lifang , Tian Shiyi
Published: April 2020

The use of baker’s yeast to reduce ethyl 2-oxo-4-phenylbutyrate (EOPB) in conventional biphasic systems is hindered by low productivities due to mass transfer resistance between the biocatalyst and the substrate partitioned into two different phases. To overcome the limitation, a new reaction-separation coupling process (RSCP) was configured in this study, based on the novel thermosensitive ionic liquids (ILs) with polyoxyethylene-tail. The solubility of ILs in common solvents was investigated to configure the unique thermosensitive ionic liquids–solvent biphasic system (TIBS) in which the reduction was performed. [(CH3)2N(C2H5)(CH2CH2O)2H][PF6] (c2) in 1,2-dimethoxyethane possesses the thermosensitive function of homogeneous at lower temperatures and phase separating at higher temperatures. The phase transformation temperature (PTT) of the mixed system of c2/1,2-dimethoxyethane (v/v, 5:18) was about 33 °C. The bioreaction takes place in a “homogeneous” liquid phase at 30 °C. At the end of each reduction run, the system temperature is increased upon to the PTT, while c2 is separated from 1,2-dimethoxyethane with turning the system into two phases. The enantiomeric excesses (e.e.) of ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-EHPB) increased about 25~30% and the yield of ethyl-2-hydroxy-4-phenylbutyrate (EHPB) increased 35% in TIBS, compared with the reduction in 1,2-dimethoxyethane. It is expected that the TIBS established in this study could provide many future opportunities in the biocatalysis.
Differential Proliferation Effect of the Newly Synthesized Valine, Tyrosine and Tryptophan–Naphthoquinones in Immortal and Tumorigenic Cervical Cell Lines
Authors: Córdova-Rivas Sergio , Araujo-Huitrado Jorge Gustavo , Rivera-Avalos Ernesto , Escalante-García Ismailia L. , Durón-Torres Sergio M. , López-Hernández Yamilé , Hernández-López Hiram , López Lluvia , de Loera Denisse , López Jesús Adrián
Published: April 2020

We previously showed that microwave assisted synthesis is the best method for the synthesis of naphthoquinone amino acid and chloride-naphthoquinone amino acid derivatives by a complete evaluation of reaction conditions such as stoichiometry, bases, and pH influence. Following the same strategy, we synthesized chloride and non-chloride tyrosine, valine, and tryptophan-naphthoquinones achieving 85–95%, 80–92%, and 91–95% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone amino acid derivatives mainly display one redox reaction process. Overall, chloride naphthoquinone amino acid derivatives exhibited redox potential values (E1/2) more positive than non-chloride compounds. The six newly synthesized compounds were tested in HPV positive and negative as well as in immortal and tumorigenic cell lines to observe the effects in different cellular context simulating precancerous and cancerous status. A dose-response was achieved to determine the IC50 of six newly synthesized compounds in SiHa (Tumorigenic and HPV16 positive), CaLo (Tumorigenic and HPV18 positive), C33-A (Tumorigenic and HPV negative) and HaCaT (Keratinocytes immortal HPV negative) cell lines. Non-chloride tryptophan-naphthoquinone (3c) and chloride tyrosine-naphthoquine (4a) effects were more potent in tumorigenic SiHa, CaLo, and C33-A cells with respect to non-tumorigenic HaCaT cells. Interestingly, there seems to be a differential effect in non-chloride and chloride naphthoquinone amino acid derivatives in tumorigenic versus non tumorigenic cells. Considering all naphthoquinone amino acid derivatives that our group synthesized, it seems that hydrophobic and aromatic amino acids have the greatest effect on cell proliferation inhibition. These results show promising compounds for cervical cancer treatment.
5-Hydroxyindole-Based EZH2 Inhibitors Assembled via TCCA-Catalyzed Condensation and Nenitzescu Reactions
Authors: Du Fangyu , Zhou Qifan , Sun Wenjiao , Yang Cheng , Wu Chunfu , Wang Lihui , Chen Guoliang
Published: April 2020

5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L–04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 μM). These findings revealed that compound L–04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with β-diketones or β-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.
Substituent Effects on NMR Spectroscopy of 2,2-Dimethylchroman-4-one Derivatives: Experimental and Theoretical Studies
Authors: Iguchi Daniela , Ravelli Davide , Erra-Balsells Rosa , Bonesi Sergio M.
Published: April 2020

The attribution of 1H and 13C NMR signals of a library of 5-, 6- and 7-substituted 2,2-dimethylchroman-4-one derivatives is reported. Substituent effects were interpreted in terms of the Hammett equation, showing a good correlation for carbons para- to the substituent group, not for the meta- ones. Similarly, the Lynch correlation shows the additivity of the substituent chemical shifts in the case of both H and C nuclei, again with the exception of the carbons in the meta- position. Density Functional Theory (DFT)-predicted 1H and 13C chemical shifts correspond closely with experimentally observed values, with some exceptions for C NMR data; however, the correlation is valid only for the aromatic moiety and cannot be extended to the heterocyclic ring of the chroman-4-one scaffold.
Naphthoquinones as Covalent Reversible Inhibitors of Cysteine Proteases—Studies on Inhibition Mechanism and Kinetics
Authors: Klein Philipp , Barthels Fabian , Johe Patrick , Wagner Annika , Tenzer Stefan , Distler Ute , Le Thien Anh , Schmid Paul , Engel Volker , Engels Bernd , Hellmich Ute A. , Opatz Till , Schirmeister Tanja
Published: April 2020

The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.
Isolation and Identification of Lignans and Other Phenolic Constituents from the Stem Bark of Albizia julibrissin Durazz and Evaluation of Their Nitric Oxide Inhibitory Activity
Authors: Li Wei , Yang Hye Jin
Published: April 2020

A dibenzylbutane-type lignan (16), along with eight furofuran-type (1–8), five furan-type (9–13), two dibenzylbutane-type (14 and 15), two bibenztetrahydronaphthalene-type lignans (17 and 18), two neolignans (19 and 20), and six phenolic derivatives (21–26) were isolated from an MeOH extract of the stem bark of Albizia julibrissin Durazz. The chemical structures of the obtained compounds were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. Of the evaluated compounds, 14 were isolated from A. julibrissin and the Fabaceae family for the first time. Anti-inflammatory effects of the isolated analogs were investigated in terms of the inhibition of the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells. Ten compounds (10–12, 14, and 17–22) displayed significant dose-dependent inhibitory effects against the NO production, with IC50 values ranging from 5.4 to 19.2 µM. Moreover, eight compounds (1–4, 9, 13, 15, and 16) exhibited moderate inhibitory activities, with IC50 values ranging from 21.0 to 62.5 µM.
Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation
Authors: Ahmad Syed Sayeed , Sinha Meetali , Ahmad Khurshid , Khalid Mohammad , Choi Inho
Published: April 2020

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.