bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in TRPV1-Mediated Physiological Function in Rats Systemically Treated With Capsaicin on the Neonate
Authors: Jeong Keun-Yeong
Published: April 2020

Capsaicin is the active component of chili peppers and is a hydrophobic, colorless, odorless, and crystalline to waxy compound. The transient receptor potential vanilloid 1 (TRPV1) is the capsaicin receptor channels that are involved in a variety of functions like transduction and transmission of the physiological stimulus. Subcutaneous injection of capsaicin to a newborn rat leads to involuntary lifelong TRPV1 desensitization. Various physiological changes including sensory and homeostatic actions in the body associated with neonatal capsaicin treatment are induced by direct TRPV1 channel targeting. Interesting changes include unique phenomena such as the reduction in pain perception, abnormal body temperature, increase in infection, infectious or neuropathological itching, and irregular circadian core body temperature rhythm. These symptoms are associated with relatively higher fever or loss of sensory c-fiber related to TRPV1 desensitization. The aforementioned outcomes not only provide a warning about the risk of capsaicin exposure in newborns but also indicate the possible occurrence of relatively rare diseases that are difficult to diagnose. Therefore, Therefore, the present review aims to summarize the unique phenomena caused by systemic capsaicin administration in neonatal rats.
Potent Inhibitory Effect of BJ-3105, a 6-Alkoxypyridin-3-ol Derivative, on Murine Colitis Is Mediated by Activating AMPK and Inhibiting NOX
Authors: Gurung Pallavi , Dahal Sadan , Chaudhary Prakash , Guragain Diwakar , Karmacharya Ujjwala , Kim Jung-Ae , Jeong Byeong-Seon
Published: April 2020

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation in the gastrointestinal tract. Biological therapeutics and orally available small molecules like tofacitinib (a JAK inhibitor) have been developed to treat IBD, but half of the patients treated with these drugs fail to achieve sustained remission. In the present study, we compared the therapeutic effects of BJ-3105 (a 6-alkoxypyridin-3-ol derivative) and tofacitinib in IBD. BJ-3105 induced activation of AMP-activated protein kinase (AMPK) in the kinase activity measurement and recovery from cytokine-induced AMPK deactivation in HT-29 human colonic epithelial cells. Similar to tofacitinib and D942 (an AMPK activator), BJ-3105 inhibited IL-6-induced JAK2/STAT3 phosphorylation and TNF-α-stimulated activation of IKK/NF-κB, and consequently, stimulus-induced upregulations of inflammatory cytokines and inflammasome components. In addition, unlike tofacitinib or D942, BJ-3105 inhibited NADPH oxidase (NOX) activation and consequent superoxide production induced by activators (mevalonate and geranylgeranyl pyrophosphate) of the NOX cytosolic component Rac. In mice, oral administration with BJ-3105 ameliorated dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-induced colitis-associated tumor formation (CAT) much more potently than that with tofacitinib. Moreover, BJ-3105 suppressed the more severe form of colitis and CAT formation in mice with AMPK knocked-out in macrophages (AMPKαfl/fl-Lyz2-Cre mice) with much greater efficacy than tofacitinib. Taken together, our findings suggest BJ-3105, which exerted a much better anti-colitis effect than tofacitinib through AMPK activation and NOX inhibition, is a promising candidate for the treatment of IBD.
Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
Authors: Navas Arturo , Jannus Fatin , Fernández Belén , Cepeda Javier , Medina O’Donnell Marta , Díaz-Ruiz Luis , Sánchez-González Cristina , Llopis Juan , Seco José M. , Rufino-Palomares E. , Lupiáñez José Antonio , Gómez-Ruiz Santiago , Quiles José Luis , Battino Maurizio , Choquesillo-Lazarte Duane , Ruiz-Muelle Ana Belén , Fernández Ignacio , Reyes-Zurita Fernando , Rodríguez-Diéguez Antonio
Published: April 2020

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.
Host BAG3 Is Degraded by Pseudorabies Virus pUL56 C-Terminal 181L-185L and Plays a Negative Regulation Role during Viral Lytic Infection
Authors: Lyu Chuang , Li Wei-Dong , Wang Shu-Wen , Peng Jin-Mei , Yang Yong-Bo , Tian Zhi-Jun , Cai Xue-Hui
Published: April 2020

Bcl2-associated athanogene (BAG) 3, which is a chaperone-mediated selective autophagy protein, plays a pivotal role in modulating the life cycle of a wide variety of viruses. Both positive and negative modulations of viruses by BAG3 were reported. However, the effects of BAG3 on pseudorabies virus (PRV) remain unknown. To investigate whether BAG3 could modulate the PRV life cycle during a lytic infection, we first identified PRV protein UL56 (pUL56) as a novel BAG3 interactor by co-immunoprecipitation and co-localization analyses. The overexpression of pUL56 induced a significant degradation of BAG3 at protein level via the lysosome pathway. The C-terminal mutations of 181L/A, 185L/A, or 181L/A-185L/A in pUL56 resulted in a deficiency in pUL56-induced BAG3 degradation. In addition, the pUL56 C-terminal mutants that lost Golgi retention abrogated pUL56-induced BAG3 degradation, which indicates a Golgi retention-dependent manner. Strikingly, BAG3 was not observed to be degraded in either wild-type or UL56-deleted PRV infected cells as compared to mock infected ones, whereas the additional two adjacent BAG3 cleaved products were found in the infected cells in a species-specific manner. Overexpression of BAG3 significantly suppressed PRV proliferation, while knockdown of BAG3 resulted in increased viral yields in HEK293T cells. Thus, these data indicated a negative regulation role of BAG3 during PRV lytic infection. Collectively, our findings revealed a novel molecular mechanism on host protein degradation induced by PRV pUL56. Moreover, we identified BAG3 as a host restricted protein during PRV lytic infection in cells.
Characterization of the TCR β Chain CDR3 Repertoire in Subarachnoid Hemorrhage Patients with Delayed Cerebral Ischemia
Authors: Kim Bong Jun , Youn Dong Hyuk , Kim Youngmi , Jeon Jin Pyeong
Published: April 2020

Little is known of the adaptive immune response to subarachnoid hemorrhage (SAH). This study was the first to investigate whether T cell receptor (TCR) immune repertoire may provide a better understanding of T cell immunology in delayed cerebral ischemia (DCI). We serially collected peripheral blood in five SAH patients with DCI. High-throughput sequencing was used to analyze the TCR β chain (TCRB) complimentary determining regions (CDR) 3 repertoire. We evaluated the compositions and variations of the repertoire between admission and the DCI period, for severe DCI and non-severe DCI patients. Clonality did not differ significantly between admission and DCI. Severe DCI patients had significantly lower clonality than non-severe DCI patients (p value = 0.019). A read frequency of 0.005% ≤ – < 0.05% dominated the clonal expansion in non-severe DCI patients. Regarding repertoire diversity, severe DCI had a higher diversity score on admission than non-severe DCI. The CDR3 lengths were similar between admission and DCI. Among 728 annotated V-J gene pairs, we found that the relative frequencies of two V-J pairs were different at the occurrence of DCI than at admission, with T cells increasing by over 15%. TCRB CDR3 repertoires may serve as biomarkers to identify severe DCI patients.
Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer’s Disease
Authors: Bell Simon M. , De Marco Matteo , Barnes Katy , Shaw Pamela J. , Ferraiuolo Laura , Blackburn Daniel J. , Mortiboys Heather , Venneri Annalena
Published: April 2020

Alzheimer’s disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD.
Influence of Oxygen Diffusion on Thermal Ageing of Cross-Linked Polyethylene Cable Insulation
Authors: Zhang Yuanyuan , Hou Zongke , Wu Kangning , Wang Shihang , Li Jianying , Li Shengtao
Published: April 2020

Thermal ageing of cross-linked polyethylene (XLPE) cable insulation is an important issue threatening the safe operation of power cables. In this paper, thermal ageing of XLPE was carried out at 160 °C in air for 240 h. The influence of oxygen diffusion on thermal ageing of XLPE was investigated by Ultraviolet–visible spectrophotometer (UV–Vis), tensile testing, and Fourier transformed infrared spectroscopy (FTIR). It was observed that the degradation degree not only depended on ageing time but also on sample positions. The thermally aged samples were more oxidized in the surface region, presented a darker color, more carbon atoms appeared in the conjugate cluster, had smaller elongation at break and tensile strength, and a larger carbonyl index. As ageing time increased, the non-uniform oxidation of the XLPE samples became more prominent. The degree of non-uniform oxidation caused by oxygen diffusion was quantitatively studied by first order oxidation kinetic. The calculated results demonstrated that carbonyl index measured by FTIR was more sensitive to non-uniform oxidation with a shape parameter in the range of 1–2. The result shown in this paper is helpful for interpreting and predicting the non-uniform ageing behavior of high voltage XLPE cables.
Strongly Selective Polymer Membranes Modified with Heteroarm Stars for the Ethylene Glycol Dehydration by Pervaporation
Authors: Rostovtseva Valeriia , Pulyalina Alexandra , Rudakova Daria , Vinogradova Ludmila , Polotskaya Galina
Published: April 2020

Hybrid membranes based on poly (2,6-dimethyl-1,4-phenylene oxide) modified with heteroarm stars (HAS) were developed to separate ethylene glycol/water mixtures by pervaporation. The HAS consist of a small branching center fullerene C 60 and twelve arms of different nature, six arms of nonpolar polystyrene and six arms of polar poly-tert-butyl methacrylate. The changes of structure and physical properties with HAS inclusion were systematically studied using SEM, X-ray diffraction analysis, TGA, and contact angle measurements. Mass transfer of ethylene glycol and water through membranes was studied by sorption and pervaporation tests. It was found that the growth of HAS content up to 5 wt% in the membrane leads to an increase in the total flux and a strong increase in the separation factor. To evaluate intrinsic properties of the penetrant–membrane system, permeability and selectivity were calculated. Overall, utilizing star-shaped macromolecules as a filler can be a promising way to improve the separation performance of diffusion membranes.
Mechanical Properties of High Strength Aluminum Alloy EN AW-7075 Additively Manufactured by Directed Energy Deposition
Authors: Langebeck Anika , Bohlen Annika , Rentsch Rüdiger , Vollertsen Frank
Published: April 2020

A manifold variety of additive manufacturing techniques has a significant positive impact on many industry sectors. Large components are often manufactured via directed energy deposition (DED) instead of using powder bed fusion processes (PBF). The advantages of the DED process are a high build-up rate with values up to 300 cm3/h and a nearly limitless build-up volume. In combination with the lightweight material aluminum it is possible to manufacture large lightweight components with geometries adapted to customer requirements in small batches. This contributes the pursuit of higher efficiency of machines through lightweight materials as well as lightweight design. A low-defect additive manufacturing of high strength aluminum EN AW-7075 powder via DED is an important challenge. The laser power has a significant influence on the remaining porosity. By increasing the laser power from 2 kW to 4 kW the porosity in single welding tracks can be lowered from 2.1% to only (0.09 ± 0.07)% (n = 3). However, when manufacturing larger specimens; the remaining porosity is higher than in single tracks; which can be attributed to the oxide skin on the preceding welding tracks. Further investigations regarding the mechanical properties were carried out. In tensile tests an ultimate tensile strength of (222 ± 17) MPa (n = 6) was measured. The DED processed EN AW-7075 shows comparable mechanical properties to PBF processed EN AW-7075.
Numerical Simulation of Buckling and Post-Buckling Behavior of a Central Notched Thin Aluminum Foil with Nonlinearity in Consideration
Authors: Shahmardani Mahdieh , Ståhle Per , Islam Md Shafiqul , Kao-Walter Sharon
Published: April 2020

In thin notched sheets under tensile loading, wrinkling appears on the sheet surface, specifically around the cracked area. This is due to local buckling and compression stresses near the crack surfaces. This study aims to numerically study the buckling behavior of a thin sheet with a central crack under tension. A numerical model of a notched sheet under tensile loading is developed using the finite element method, which considers both material and geometrical nonlinearity. To overcome the convergence problem caused by the small thickness-to-length/width ratio and to stimulate the buckling, an imperfection is defined as a small perturbation in the numerical model. Both elastic and elasto-plastic behavior are applied, and the influence of them is studied on the critical buckling stress and the post-buckling behavior of the notched sheet. Numerical results for both elastic and elasto-plastic behavior reflect that very small perturbations need more energy for the activation of buckling mode, and a higher buckling mode is predominant. The influences of different parameters, including Poisson’s ratio, yield limit, crack length-to-sheet-width ratio, and the sheet aspect ratio are also evaluated with a focus on the critical buckling stress and the buckling mode shape. With increase in Poisson’s ratio. First, the critical buckling stress reduces and then remains constant. A higher yield limit results in increases in the critical buckling stress, and no change in the buckling mode shape while adopting various crack length-to-sheet-width ratios, and the sheet aspect ratio changes the buckling mode shape.
Microstructural Precipitation Evolution and In Vitro Degradation Behavior of a Novel Chill-Cast Zn-Based Absorbable Alloy for Medical Applications
Authors: Ramirez–Ledesma Ana Laura , Roncagliolo–Barrera Paola , Paternoster Carlo , Casati Riccardo , Lopez Hugo , Vedani Maurizio , Mantovani Diego
Published: April 2020

In recent years, increasing interest has been placed in the development of Zn alloys for absorbable biomedical applications. It has been demonstrated that these alloys are potential candidates for endovascular applications. In the present work, a novel Zn-12.5Ag-1Mg alloy was investigated as a potential biomedical absorbable material. As a reference, the exhibited biocompatible properties are compared with those of pure Zn and a Zn-1Mg alloy. All the alloys investigated in this work were cast in a water-cooled Cu-mold (chill casting). Subsequently, the alloys were solution-treated and then extruded. The microstructural evolution at each stage of the alloy processing was resolved by analytical means including optical, scanning, transmission microscopy, and X-ray diffraction. By these means, the various phases belonging to this alloy system were disclosed. In addition, determinations of both corrosion and mechanical properties were carried out in the proposed Zn-12.5Ag-1Mg alloy. In particular, an excellent combination of strength and ductility was found, which is attributed to grain refinement as well as the precipitation of a uniform distribution of refined phases (i.e., AgZn solid solution, ε-AgZn3, and Ag0.15MgZn1.85 intermetallics). All the precipitated intermetallics were embedded in a η-Zn matrix. As for the corrosion degradation in the physiological NaCl solution in the as-extruded condition, the experimental outcome indicates that the Zn-12.5Ag-1Mg alloy exhibits degradation rates far superior to currently reported ones for Zn-based alloys intended for absorbable biomedical applications.
Development of a Disposable Single-Nozzle Printhead for 3D Bioprinting of Continuous Multi-Material Constructs
Authors: Cameron Tiffany , Naseri Emad , MacCallum Ben , Ahmadi Ali
Published: April 2020

Fabricating multi-cell constructs in complex geometries is essential in the field of tissue engineering, and three-dimensional (3D) bioprinting is widely used for this purpose. To enhance the biological and mechanical integrity of the printed constructs, continuous single-nozzle printing is required. In this paper, a novel single-nozzle printhead for 3D bioprinting of multi-material constructs was developed and characterized. The single-nozzle multi-material bioprinting was achieved via a disposable, inexpensive, multi-fuse IV extension set; the printhead can print up to four different biomaterials. The transition distance of the developed printhead was characterized over a range of pressures and needle inner diameters. Finally, the transition distance was decreased by applying a silicon coating to the inner channels of the printhead.
Laser-Induced Microgrooves Improve the Mechanical Responses of Cemented Implant Systems
Authors: Khandaker Morshed , Ait Moussa Abdellah , Sama Desmond Nuyebga , Safavinia Fereshteh , Hazra Susmita , Kalay Onur Can , Karpat Fatih , Clary Erik , Haleem Amgad
Published: April 2020

The impact of a laser-induced microgroove (LIM) architecture on mechanical responses of two cemented implant systems was evaluated. One system consisted of two aluminum alloy rods bonded end-to-end by polymethylmethacrylate cement. The second system consisted of a custom-made, aluminum tibial tray (TT) cemented in an artificial canine tibia. Control specimens for each system were polished smooth at the cement interface. For LIM samples in the rod system, microgrooves were engraved (100 µm depth, 200 µm width, 500 µm spacing) on the apposing surface of one of the two rods. For TT system testing, LIM engraving (100 µm spacing) was confined to the underside and keel of the tray. Morphological analysis of processed implant surfaces revealed success in laser microgrooving procedures. For cemented rods tested under static tension, load to failure was greater for LIM samples (279.0 ± 14.9 N vs. 126.5 ± 4.5 N). Neither non-grooved nor grooved TT samples failed under cyclic compression testing (100,000 cycles at 1 Hz). Compared with control specimens, LIM TT constructs exhibited higher load to failure under static compression and higher strain at the bone interface under cyclic compression. Laser-induced microgrooving has the potential to improve the performance of cemented orthopedic implants.
Broadband Plasmonic Polarization Filter Based on Photonic Crystal Fiber with Dual-Ring Gold Layer
Authors: Chen Nan , Zhang Xuedian , Chang Min , Lu Xinglian , Zhou Jun
Published: April 2020

Polarization filter is a very important optical device with extinction characteristics. Due to the design flexibility of photonic crystal fibers and the high excitation losses of the gold layer, the polarization filter based on the photonic crystal fiber and surface plasmonic resonance effect is widely studied. Considering these, we present a simple and high-performance polarization filter using the finite element method. Numerical simulations show that there is a large difference in energy between the two polarization directions by reasonable adjustment of the structural parameters, the confinement loss in the x-pol direction is less than that in the y-pol direction, which is suitable to realize a broadband polarization filter. When the fiber length is 2 mm, the extinction ratio peak can reach −478 dB, and the bandwidth with the extinction ratio better than −20 dB is 750 nm, which covers communication wavelengths of 1.31 μm and 1.55 μm (1.05–1.8 μm). It also has a low insertion loss of 0.11 dB at 1.31 μm and 0.04 dB at 1.55 μm. In addition, our design has high feasibility in fabrication and better tolerance. The proposed filter with compactness, high extinction ratio, broad bandwidth, and low insertion loss would play an important role in the sensing detection, bio-medical, and telecommunication field.
Modal Coupling Effect in a Novel Nonlinear Micromechanical Resonator
Authors: Lu Kuo , Li Qingsong , Zhou Xin , Song Guoxiong , Wu Kai , Zhuo Ming , Wu Xuezhong , Xiao Dingbang
Published: April 2020

Capacitive micromechanical resonators share electrodes with the same bias voltage, resulting in the occurrence of electrostatic coupling between intrinsic modes. Unlike the traditional mechanical coupling, the electrostatic coupling is determined by the structural electric potential energy, and generally, it only occurs when the coupling modes operate in nonlinear regions. However, previous electrostatic coupling studies mainly focus on the stiffness softening region, with little attention on the opposite stiffness hardening condition. This paper presents a study on the electrostatic modal coupling effect in the stiffness hardening region. A novel capacitive micromechanical resonator with different modal nonlinearities is designed and fabricated. It is demonstrated that activating a cavity mode can shift the fundamental resonance of the manipulated mode by nearly 90 times its mechanical bandwidth. Moreover, the frequency shifting direction is found to be related to the manipulated mode’s nonlinearity, while the frequency hopscotch is determined by the cavity mode’s nonlinearity. The electrostatic coupling has been proven to be an efficient and tunable dynamical coupling with great potential for tuning the frequency in a wide range. The modal coupling theory displayed in this paper is suitable for most capacitive resonators and can be used to improve the resonator’s performance.
Modes of Occurrence and Origin of Minerals in Permian Coals from the Huainan Coalfield, Anhui, China
Authors: Li Yuan , Huang Wenhui , Jiu Bo , Sun Qilong , Che Qingsong
Published: April 2020

Minerals in coal provide useful information for not only paleo-environments of peat accumulation, but also for geological evolution during later diagenesis and/or epigenesis. This paper reports new data on coal quality and the mineralogical and geochemical compositions of 17 unaltered (by intrusion) coal samples collected from the Huainan coalfield, providing new insight into the origins and modes of occurrence of the minerals in coal and their geological evolution. The results showed that the studied coal samples were low rank bituminous coal, with low ash yield (11.92–38.31%, average 24.80%) and high volatile content (25.13–43.43%, average 37.29%). Minerals in the coal mainly included kaolinite and quartz; varying proportions of calcite, siderite, ankerite, and pyrite; and traces of chlorite, zircon, strontianite, apatite, and gorceixite. Typical modes of mineral occurrence could be used to determine the formation stage of minerals. The detrital mineral, occurring as sub-angular to rounded discrete fragments or thin layers intimately admixed with organic matter at particular horizons, was of terrigenous origin, deposited during peat accumulation. Cell infillings, as well as nodule siderites and polycrystalline aggregates of pyrite, precipitated during the syngenetic to early diagenetic stages. Cleat infillings, compressed cell infillings, and fracture infillings precipitated in the epigenetic stage. However, the stage of mineral formation of the pore infilling was difficult to determine. Combined with coal quality, mineralogy, and geochemical analysis, the sedimentary environment of Shanxi Formation was affected by seawater, and Fe-rich hydrothermal fluids filled into the No. 3 coal seam in the epigenetic stage. The sedimentary environment of the No. 8 coal seam had widespread reduction and acid conditions due to basin subsidence, and sulfate-rich hydrothermal fluids may have been formed during the peat deposition stage. In contrast, the peat accumulation environment of the Upper Shihezi Formation was oxidized with a low pH condition. Alkaline fluid then flowed into the No. 13-1 coal seam in the epigenetic stage.
Past Hydrological Conditions in a Fluvial Valley: Records from C-O Isotope Signatures of Holocene Sediments in the Loire River (France)
Authors: Négrel Philippe , Kloppmann Wolfram
Published: April 2020

Multi-proxy indices (grainsize distribution, mineralogy, δ18O, δ13C) in sediments from a meander infill in the Middle Loire alluvial plain of central France are used to highlight some aspects of the basin evolution over the period from 0 to 10,000 years BP. During the Late-Glacial and Holocene period, the lacustrine carbonate substratum of the alluvial plain was incised by the Loire River, creating numerous oxbows and channels related to meander migration. The channel fills consist mainly of fine clayey sediments deposited during flooding of the river, with an almost total absence of coarse-clastic and sandy material, except in the basal part. The record of isotope ratio variations together with the distribution of particle sizes allows the evolution of the river dynamics to be constrained. The strong decrease of carbonate δ13C in the upper part of the record is ascribed to a progressive closure of the meander and, thus, an increasing control of the C-isotope signature by biological activity in a local environment. Variations in carbonate δ18O, rather, reflect paleohydrological/paleoclimatic changes at the basin scale. The isotope record of the river dynamics also agrees with the variations in clay mineralogy.
Aillikites and Alkali Ultramafic Lamprophyres of the Beloziminsky Alkaline Ultrabasic-Carbonatite Massif: Possible Origin and Relations with Ore Deposits
Authors: Ashchepkov Igor , Zhmodik Sergey , Belyanin Dmitry , Kiseleva Olga N. , Medvedev Nikolay , Travin Alexei , Yudin Denis , Karmanov Nikolai S. , Downes Hilary
Published: April 2020

The 650–621 Ma plume which impinged beneath the Siberian craton during the breakup of Rodinia caused the formation of several alkaline carbonatite massifs in craton margins of the Angara rift system. The Beloziminsky alkaline ultramafic carbonatite massif (BZM) in the Urik-Iya graben includes alnöites, phlogopite carbonatites and aillikites. The Yuzhnaya pipe (YuP) ~ 645 Ma and the 640–621 Ma aillikites in BZM, dated by 40Ar/39Ar, contain xenoliths of carbonated sulfide-bearing dunites, xenocrysts of olivines, Cr-diopsides, Cr-phlogopites, Cr-spinels (P ~ 4–2 GPa and T ~ 800–1250 °C) and xenocrysts of augites with elevated HFSE, U, Th. Al-augites and kaersutites fractionated from T ~ 1100–700 °C along the 90 mW/m2 geotherm. Higher T trend for Al-Ti augite, pargasites, Ti-biotites series (0.4–1.5 GPa) relate to intermediate magma chambers near the Moho and in the crust. Silicate xenocrysts show Zr-Hf, Ta-Nb peaks and correspond to carbonate-rich magma fractionation that possibly supplied the massif. Aillikites contain olivines, rare Cr-diopsides and oxides. The serpentinites are barren, fragments of ore-bearing Phl carbonatites contain perovskites, Ta-niobates, zircons, thorites, polymetallic sulphides and Ta-Mn-Nb-rich magnetites, ilmenites and Ta-Nb oxides. The aillikites are divided by bulk rock and trace elements into seven groups with varying HFSE and LILE due to different incorporation of carbonatites and related rocks. Apatites and perovskites reveal remarkably high LREE levels. Aillikites were generated by 1%–0.5% melting of the highly metasomatized mantle with ilmenite, perovskite apatite, sulfides and mica, enriched by subduction-related melts and fluids rich in LILE and HFSE. Additional silicate crystal fractionation increased the trace element concentrations. The carbonate-silicate P-bearing magmas may have produced the concentration of the ore components and HFSE in the essentially carbonatitic melts after liquid immiscibility in the final stage. The mechanical enrichment of aillikites in ore and trace element-bearing minerals was due to mixture with captured solid carbonatites after intrusion in the massif.
In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors Against Leishmania donovani and Trypanosoma brucei
Authors: Phan Trong-Nhat , Baek Kyung-Hwa , Lee Nakyung , Byun Soo Young , Shum David , No Joo Hwan
Published: April 2020

Kinetoplastid parasites, including Leishmania and Trypanosoma spp., are life threatening pathogens with a worldwide distribution. Next-generation therapeutics for treatment are needed as current treatments have limitations, such as toxicity and drug resistance. In this study, we examined the activities of established mammalian target of rapamycin (mTOR)/phosphoinositide 3-kinase (PI3K) inhibitors against these tropical diseases. High-throughput screening of a library of 1742 bioactive compounds against intracellular L. donovani was performed, and seven mTOR/PI3K inhibitors were identified. Dose-dilution assays revealed that these inhibitors had half maximal effective concentration (EC50) values ranging from 0.14 to 13.44 μM for L. donovani amastigotes and from 0.00005 to 8.16 μM for T. brucei. The results of a visceral leishmaniasis mouse model indicated that treatment with Torin2, dactolisib, or NVP-BGT226 resulted in reductions of 35%, 53%, and 54%, respectively, in the numbers of liver parasites. In an acute T. brucei mouse model using NVP-BGT226 parasite numbers were reduced to under the limits of detection by five consecutive days of treatment. Multiple sequence and structural alignment results indicated high similarities between mTOR and kinetoplastid TORs; the inhibitors are predicted to bind in a similar manner. Taken together, these results indicated that the TOR pathways of parasites have potential for the discovery of novel targets and new potent inhibitors.
Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs
Authors: Artasensi Angelica , Pedretti Alessandro , Vistoli Giulio , Fumagalli Laura
Published: April 2020

Diabetes Mellitus (DM) is a multi-factorial chronic health condition that affects a large part of population and according to the World Health Organization (WHO) the number of adults living with diabetes is expected to increase. Since type 2 diabetes mellitus (T2DM) is suffered by the majority of diabetic patients (around 90–95%) and often the mono-target therapy fails in managing blood glucose levels and the other comorbidities, this review focuses on the potential drugs acting on multi-targets involved in the treatment of this type of diabetes. In particular, the review considers the main systems directly involved in T2DM or involved in diabetes comorbidities. Agonists acting on incretin, glucagon systems, as well as on peroxisome proliferation activated receptors are considered. Inhibitors which target either aldose reductase and tyrosine phosphatase 1B or sodium glucose transporters 1 and 2 are taken into account. Moreover, with a view at the multi-target approaches for T2DM some phytocomplexes are also discussed.
MnO2/rGO/CNTs Framework as a Sulfur Host for High-Performance Li-S Batteries
Authors: Dong Wei , Meng Lingqiang , Hong Xiaodong , Liu Sizhe , Shen Ding , Xia Yingkai , Yang Shaobin
Published: April 2020

Lithium-sulfur batteries are very promising next-generation energy storage batteries due to their high theoretical specific capacity. However, the shuttle effect of lithium-sulfur batteries is one of the important bottlenecks that limits its rapid development. Herein, physical and chemical dual adsorption of lithium polysulfides are achieved by designing a novel framework structure consisting of MnO2, reduced graphene oxide (rGO), and carbon nanotubes (CNTs). The framework-structure composite of MnO2/rGO/CNTs is prepared by a simple hydrothermal method. The framework exhibits a uniform and abundant mesoporous structure (concentrating in ~12 nm). MnO2 is an α phase structure and the α-MnO2 also has a significant effect on the adsorption of lithium polysulfides. The rGO and CNTs provide a good physical adsorption interaction and good electronic conductivity for the dissolved polysulfides. As a result, the MnO2/rGO/CNTs/S cathode delivered a high initial capacity of 1201 mAh g−1 at 0.2 C. The average capacities were 916 mAh g−1, 736 mAh g−1, and 547 mAh g−1 at the current densities of 0.5 C, 1 C, and 2 C, respectively. In addition, when tested at 0.5 C, the MnO2/rGO/CNTs/S exhibited a high initial capacity of 1010 mAh g−1 and achieved 780 mAh g−1 after 200 cycles, with a low capacity decay rate of 0.11% per cycle. This framework-structure composite provides a simple way to improve the electrochemical performance of Li-S batteries.
Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA
Authors: Heidari Ali , Ghorbani-Choghamarani Arash , Hajjami Maryam , Hudson Robert H. E.
Published: April 2020

There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4–8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (∆Tm = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences.
Enhancement of A Cationic Surfactant by Capping Nanoparticles: Synthesis, Characterization and Multiple Applications
Authors: Labena A. , Hegazy M. A. , Kamel W. M. , Elkelish Amr , Hozzein Wael N.
Published: April 2020

There is scarce information on cationic surfactants’ biocidal and corrosion inhbibition effects on Slime-Forming Bacteria (SFB) isolated from oil field formation water. Therefore, this work focused on the the synthesis of a cationic surfactant (CS) to increase its features by capping different metal nanoparticles (zinc, ZnNPs-C-CS; manganese, MnNPs-C-CS and tin, SnNPs-C-CS) and used them as biocides and corrosion inhibitors. The cationic surfactant was synthesized and characterized by Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Afterwards, different nanoparticles were synthesized, characterized, and exploited to cap by the CS. The CS and the different nanoparticles capped by the CS were tested for their antimicrobial susceptibility against standard bacterial and yeast strains. The synthesized compounds were further evaluated as anti-biofilms agents against positively-developed bacterial biofilms. Moreover, the CS and the ZnNPs-C-CS, MnNPs-C-CS, and SnNPs-C-CS were assessed as potential biocides against SFB, particularly Pseudomonas sp. (isolated from contaminated formation water), and as corrosion inhibitors against cultivated salinity. The results revealed the great effect of the different CS-capped NPs as broad-spectrum antimicrobial and anti-biofilm agents at lower Minimum Inhibitory Concentrations (MICs), Minimum Bactericidal Concentrations (MBCs), Minimum Fungicidal Concentrations (MFCs) and Minimum Biofilm Inhibitory Concentrations (MBICs), and the activities were reported in order of SnNPs-C-CS > MnNPs-C-CS > ZnNPs-C-CS > CS. Furthermore, the ZnNPs-C-CS, MnNPs-C-CS, and SnNPs-C-CS demonstrated biocidal and corrosion inhibition effects against Pseudomonas sp. at a salinity of 3.5% NaCl, with metal corrosion inhibition efficiencies of 88.6, 94.0 and 96.9%, in comparison to a CS efficiency of 85.7%. In conclusion, the present work provides a newly synthesized cationic surfactant and has enhanced its antimicrobial and its metal corrosion inhibition effects by capping different nanoparticles, and it has been successfully applied against slime-forming bacteria at a salinity of 3.5% NaCl.
Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity
Authors: Delmas Dominique , Xiao Jianbo , Vejux Anne , Aires Virginie
Published: April 2020

Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death—and accumulating cancer cells in a phase of the cell cycle—thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
Fluorescent Submicron-Sized Poly(heptafluoro-n-butyl methacrylate) Particles with Long-Term Stability
Authors: Jarzębski Maciej , Siejak Przemysław , Przeor Monika , Gapiński Jacek , Woźniak Anna , Baranowska Hanna Maria , Pawlicz Jarosław , Baryła-Pankiewicz Elżbieta , Szwajca Anna
Published: April 2020

Fluorescent submicron particles of fluorinated methacrylate (HFMBA) with long-term stability have been synthesized and characterized with regard to their potential applications. Rhodamine B (RBITC) isothiocyanate was used as the fluorescent component. The core–shell structure of the particles effectively protected the dye against bleaching. HFBMA nanoparticle (NP) stability was confirmed after seven years of storage. Only slight differences were found in the polydispersity index (pdi) from 0.002 to 0.010. Particle size measurements were carried out using dynamic light scattering (DLS), nanoparticle tracking (NTA), and fluorescence correlation spectroscopy (FCS). The hydrodynamic diameter evaluated by different methods were in good agreement, respectively: 184–550 nm, 218–579 nm, and 236–508 nm. Particle and core morphology was estimated by using scanning and transmission electron microscopy (SEM and TEM). The ability to recognize particles in 3D as a reference sample in biological media has been confirmed by epifluorescence optical microscopy, confocal laser scanning microscopy, and super-resolution confocal microscopy (STED).
Identification of Transient Receptor Potential Vanilloid 3 Antagonists from Achillea alpina L. and Separation by Liquid-Liquid-Refining Extraction and High-Speed Counter-Current Chromatography
Authors: Sun Shi-Wei , Wang Rong-Rong , Sun Xiao-Ying , Fan Jia-He , Qi Hang , Liu Yang , Qin Guo-Qing , Wang Wei
Published: April 2020

Bioassay-guided fractionation of the ethanol extract of whole herbs of Achillea alpina led to the isolation of isochlorogenic acids A and B as transient receptor potential vanilloid 3 (TRPV3) channel antagonists by using a calcium fluorescent assay. The structures were identified by spectroscopic analysis and the inhibitory activities of isochlorogenic acids A and B were confirmed by whole-cell patch clamp recordings of human embryonic kidney 293 (HEK293) cells expressing human TRPV3. Molecular docking results revealed that these two compounds reside in the same active pocket of human TRPV3 channel protein with lower binding energy than the agonist 2-aminoethoxydiphenyl borate (2-APB). High-speed counter-current chromatography (HSCCC) coupled with a liquid-liquid extraction approach was successfully established for the separation of isochlorogenic acids A and B from the whole herbs of A. alpina. Ethyl acetate and n-hexane-ethyl acetate-water (3:3:4 and 1:5:4, v/v/v) were selected as liquid-liquid extraction solvent systems to remove high- and low-polarity impurities in the mixture. Sixty g of ethanol extract was refined by solvent partition to yield 1.7 g of the enriched fraction, of which 480 mg in turn obtained 52.5 mg of isochlorogenic acid B (purity 98.3%) and 37.6 mg isochlorogenic acid A (purity 96.2%) after HSCCC with n-hexane-ethyl acetate-water containing 1% acetic acid (1:4:8, v/v/v).
Eicosanoids in Nonalcoholic Fatty Liver Disease (NAFLD) Progression. Do Serum Eicosanoids Profile Correspond with Liver Eicosanoids Content during NAFLD Development and Progression?
Authors: Maciejewska Dominika , Drozd Arleta , Skonieczna-Żydecka Karolina , Skórka-Majewicz Marta , Dec Karolina , Jakubczyk Karolina , Pilutin Anna , Stachowska Ewa
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) is becoming a major public health problem worldwide. The study aimed to evaluate the concentration of eicosanoids in serum and liver tissue during steatosis progression and to assess whether eicosanoid change scores may predict liver tissue remodeling. Thirty six eight-week-old male Sprague Dawley rats were enrolled and sacrificed at different stages of NAFLD. Eicosanoid concentrations, namely lipoxin A4, hydroxyeicosatetraenoic acids (HETE), hydroxyloctadecadienoic acids (HODE), protectin DX, Maresine1, leucotriene B4, prostaglandin E2, and resolvin D1 measurement in serum and liver tissue with Agilent Technologies 1260 liquid chromatography were evaluated. For the liver and serum concentrations of 9-HODE and 13-HODE, the correlations were found to be strong and positive (r > 0.7, p < 0.05). Along with NAFLD progression, HODE concentration significantly increased, and change scores were more abundant in the liver. The moderate positive correlation between liver and serum (r = 0.52, p < 0.05) was also observed for resolvin E1. The eicosanoid concentration decreased during NAFLD progression, but mostly in serum. There were significant correlations between HETE concentrations in liver and serum, but their associations were relatively low and changes the most in liver tissue. Eicosanoids profile, predominantly 9-HODE and 13-HODE, may serve as a potential biomarker for NAFLD development.
Phenolic Profile of Croton urucurana Baill. Leaves, Stems and Bark: Pairwise Influence of Drying Temperature and Extraction Solvent
Authors: Lopes Alves Jáliston Júlio , Dias Maria Inês , Barreira João C. M. , Barros Lillian , Resende Osvaldo , Ribeiro Aguiar Ana Carolina , Ferreira Isabel C. F. R.
Published: April 2020

Cerrado biome represents an area with great biodiversity. Some of its plants have significant ethnopharmacological uses, with specific purposes. Croton urucurana Baill., for instance, was previously acknowledged for its anti-hemorrhagic, anti-inflammatory, antiseptic, healing, and potentially antifungal and entomopathogenic actions. Nevertheless, the compounds supporting these empirical applications are still unknown. Accordingly, this work was designed to achieve a complete characterization of the phenolic profile of different botanical tissues obtained from C. urucurana, and also to verify how different operational conditions (different drying temperatures and extraction conditions) affect that profile. All samples were further characterized by HPLC–DAD–ESI/MSn, and results were compared by advanced chemometric tools. In general, the drying temperatures that maximize the extraction yield of specific individual phenolic compounds were established. Likewise, it was possible to verify that samples extracted with the hydroethanolic solution allowed higher phenolic yields, either in individual compounds (except (epi)catechin-di-O-gallate) or total phenolics. The identification of the best operational conditions and phenolic profiles associated with each C. urucurana botanical part contributes to enabling their use in food or pharmaceutical-related applications.