bluuebunny/crossref_metadata_2025 huggingface dataset:
Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways
Authors: Poiroux Guillaume , Barre Annick , Simplicien Mathias , Pelofy Sandrine , Segui Bruno , Van Damme Els J. M. , Rougé Pierre , Benoist Hervé
Published: January 2019

Morniga-G, the Gal-specific black mulberry (Morus nigra) lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at the cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat cell line. The lectin, used in a concentration range between 5–20 μg/mL, induced cell death in leukemic Jurkat cells. Microscopic and cytofluorometric analyses indicated that Jurkat cell death was essentially apoptotic, associated with an increase in the ceramide content and a depolarization of the mitochondrial transmembrane potential. This lectin-mediated cell death was inhibited by the pan caspase-inhibitor zVAD. In addition, cleavage of caspases 8, 9, and 3 was observed in Morniga-G-treated Jurkat cells whereas Jurkat cell lines that are deficient in caspase 8–10, caspase 9, or FADD, survived to the lectin-mediated toxicity. Furthermore, in the presence of TRAIL- or DR5-blocking mononoclonal antibodies, Jurkat cells became resistant to Morniga-G, suggesting that the lectin triggers cell death via the TRAIL/DR5 pathway. In silico computer simulations suggest that Morniga-G might facilitate both the DR5 dimerization and the building of TRAIL/DR5 complexes. Finally, upon treatment of Jurkat cells with benzyl-GalNAc, an O-glycosylation inhibitor, a decrease in Tn antigen expression associating with a reduced Morniga-G toxicity, was observed. Taken together, these results suggest that Morniga-G induces the cell death of Tn-positive leukemic cells via concomitant O-glycosylation-, caspase-, and TRAIL/DR5-dependent pathways.
The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice
Authors: Moretti Rita , Caruso Paola
Published: January 2019

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke. The aim of our research is to review the possible role of HHcy in neurodegenerative disease and stroke and to understand its pathogenesis.
Flame Retardant Polypropylene Composites with Low Densities
Authors: Pérez Nerea , Qi Xiao-Lin , Nie Shibin , Acuña Pablo , Chen Ming-Jun , Wang De-Yi
Published: January 2019

Polypropylene (PP) is currently widely used in areas requiring lightweight materials because of its low density. Due to the intrinsic flammability, the application of PP is restricted in many conditions. Aluminum trihydroxide (ATH) is reported as a practical flame retardant for PP, but the addition of ATH often diminishes the lightweight advantage of PP. Therefore, in this work, glass bubbles (GB) and octacedylamine-modified zirconium phosphate (mZrP) are introduced into the PP/ATH composite in order to lower the material density and simultaneously maintain/enhance the flame retardancy. A series of PP composites have been prepared to explore the formulation which can endow the composite with balanced flame retardancy, good mechanical properties, and low density. The morphology, thermal stability, flame retardancy, and mechanical properties of the composites were characterized. The results indicated the addition of GB could reduce the density, but decreased the flame retardancy of PP composites at the same time. To overcome this defect, ATH and mZrP with synergetic effect of flame retardancy were added into the composite. The dosage of each additive was optimized for achieving a balance of flame retardancy, good mechanical properties, and density. With 47 wt % ATH, 10 wt % GB, and 3 wt % mZrP, the peak heat release rate (pHRR) and total smoke production (TSP) of the composite PP-4 were reduced by 91% and 78%, respectively. At the same time, increased impact strength was achieved compared with neat PP and the composite with ATH only. Maintaining the flame retardancy and mechanical properties, the density of composite PP-4 (1.27 g·cm−3) is lower than that with ATH only (PP-1, 1.46 g·cm−3). Through this research, we hope to provide an efficient approach to designing flame retardant polypropylene (PP) composites with low density.
Sol–Gel Synthesis of Silica-Based Materials with Different Percentages of PEG or PCL and High Chlorogenic Acid Content
Authors: Tranquillo Elisabetta , Barrino Federico , Dal Poggetto Giovanni , Blanco Ignazio
Published: January 2019

Implanted biomedical devices can induce adverse responses in the human body, which can cause failure of the implant—referred to as implant failure. Early implant failure is induced numerous factors, most importantly, infection and inflammation. Natural products are, today, one of the main sources of new drug molecules due to the development of pathogenic bacterial strains that possess resistance to more antibiotics used currently in various diseases. The aim of this work is the sol–gel synthesis of antibacterial biomedical implants. In the silica matrix, different percentages (6, 12, 24, 50 wt %) of polyethylene glycol (PEG) or poly(ε-caprolactone) (PCL) were embedded. Subsequently, the ethanol solutions with high amounts of chlorogenic acid (CGA 20 wt %) were slowly added to SiO2/PEG and SiO2/PCL sol. The interactions among different organic and inorganic phases in the hybrid materials was studied by Fourier transform infrared (FTIR) spectroscopy. Furthermore, the materials were soaked in simulated body fluid (SBF) for 21 days and the formation of a hydroxyapatite layer on their surface was evaluated by FTIR and XRD analysis. Finally, Escherichia coli and Pseudomonas aeruginosa were incubated with several hybrids, and the diameter of zone of inhibition was observed to assessment the potential antibacterial properties of the hybrids.
One-Shot Drilling Analysis of Stack CFRP/UNS A92024 Bonding by Adhesive
Authors: Bañon Fermin , Sambruno Alejandro , Fernandez-Vidal Sergio , Fernandez-Vidal Severo Raul
Published: January 2019

The use of adhesive layers can improve the properties and reduce the defects produced in the interfaces. This provides adherence to the structure, adapting the joining surfaces and avoiding spaces between the layers. However, the presence of the adhesive can potentiate the defects caused during drilling. In turn, a loss of adhesive in the interface can occur during machining affecting the final structure. This work has followed a conventional OSD strategy in CFRP and UNS A92024 aluminium sheet stacking with adhesive. A series of dry drilling tests have been developed with different cutting conditions and new noncoated WC-Co helical cutting tools. Analysis of Variance (ANOVA) statistical analyses and surface response models have been applied to determine the mechanical behaviour in the holes. For this purpose, the dimensional deviation, surface quality, and adhesive loss in the interface in relation to the number of holes have been considered. A combination of cutting parameters that minimizes the evaluated defects has been found. Diametric deviations and surface qualities below 2% and 3.5 µm have been measured in the materials that make up the stack with cutting speeds higher than 140 m/min and feed rates between 200 and 250 mm/min. However, the greatest adhesive losses occur at high cutting speeds.
Influence of α-Calcium Sulfate Hemihydrate on Setting, Compressive Strength, and Shrinkage Strain of Cement Mortar
Authors: Lee Bokyeong , Kim Gyuyong , Nam Jeongsoo , Lee Kyehyouk , Kim Gyeongtae , Lee Sangkyu , Shin Kyoungsu , Koyama Tomoyuki
Published: January 2019

This study focused on the quick initial setting time and the expansion strain that occurs during the early aging of α-calcium sulfate hemihydrate (αHH) and examined the setting, compressive strength, and shrinkage strain of αHH-replaced cement mortar. The results show that the initial setting time significantly decreased with an increase in the αHH replacement ratio. Drastic occurrence of ettringite was observed early in the aging of cement mortar when αHH was substituted into the cement; however, the ettringite was not converted to monosulfate with increasing age and thus was not favorable for the development of the compressive strength. When αHH was substituted into cement, using Portland blast-furnace slag cement (PSC) was more advantageous than using ordinary Portland cement (OPC) for the development of the compressive strength. Meanwhile, the expansion of early age αHH can decrease the shrinkage strain of cement mortar. The generation of ettringite is more effective when αHH is substituted into PSC than into OPC and is thus more effective in suppressing the shrinkage strain.
Study of the Microstructure and Crack Evolution Behavior of Al-5Fe-1.5Er Alloy
Authors: Li Ming , Shi Zhiming , Wu Xiufeng , Wang Huhe , Liu Yubao
Published: January 2019

In this work, the microstructure of Al-5Fe-1.5Er alloy was characterized and analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS) techniques. The effect of microstructure on the behavior of crack initiation and propagation was investigated using in situ tensile testing. The results showed that when 1.5 wt.% Er was added in the Al-5Fe alloy, the microstructure consisted of α-Al matrix, Al3Fe, Al4Er, and Al3Fe + Al4Er eutectic phases. The twin structure of Al3Fe phase was observed, and the twin plane was {001}. Moreover, a continuous concave and convex interface structure of Al4Er was observed. Furthermore, Al3Fe was in the form of a sheet with a clear gap inside. In situ tensile tests of the alloy at room temperature showed that the crack initiation mainly occurred in the Al3Fe phase, and that the crack propagation modes included intergranular and trans-granular expansions. The crack trans-granular expansion was due to the strong binding between Al4Er phases and surrounding organization, whereas the continuous concave and convex interface structure of Al4Er provided a significant meshing effect on the matrix and the eutectic structure.
Mechanical Properties and Microstructure of DMLS Ti6Al4V Alloy Dedicated to Biomedical Applications
Authors: Mierzejewska Żaneta Anna , Hudák Radovan , Sidun Jarosław
Published: January 2019

The aim of this work was to investigate the microstructure and mechanical properties of samples produced by direct metal laser sintering (DMLS) with varied laser beam speed before and after heat treatment. Optical analysis of as-built samples revealed microstructure built of martensite needles and columnar grains, growing epitaxially towards the built direction. External and internal pores, un-melted or semi-melted powder particles and inclusions in the examined samples were also observed. The strength and Young’s modulus of the DMLS samples before heat treatment was higher than for cast and forged samples; however, the elongation at break for vertical and horizontal orientation was lower than required for biomedical implants. After heat treatment, the hardness of the samples decreased, which is associated with the disappearance of boundary effect and martensite decomposition to lamellar mixture of α and β, and the anisotropic behaviour of the material also disappears. Ultimate tensile strength (UTS) and yield strength(YS) also decreased, while elongation increased. Tensile properties were sensitive to the build orientation, which indicates that DMLS generates anisotropy of material as a result of layered production and elongated β prior grains. It was noticed that inappropriate selection of parameters did not allow properties corresponding to the standards to be obtained due to the high porosity and defects of the microstructure caused by insufficient energy density.
Increasing Uptake of Silica Nanoparticles with Electroporation: From Cellular Characterization to Potential Applications
Authors: Phonesouk Erick , Lechevallier Séverine , Ferrand Audrey , Rols Marie-Pierre , Bezombes Christine , Verelst Marc , Golzio Muriel
Published: January 2019

In the fields of biology and medicine, nanoproducts such as nanoparticles (NPs) are specifically interesting as theranostic tools, since they offer the double capacity to locally deliver active drugs and to image exactly where the product is delivered. Among the many described possibilities, silica nanoparticles (SiNPs) represent a good choice because of their ease of synthesis, the possibility of their vast functionalization, and their good biocompatibility. However, SiNPs’ passive cell internalization by endocytosis only distributes NPs into the cell cytoplasm and is unable to target the nucleus if SiNPs are larger than a few nanometers. In this study, we demonstrate that the cell penetration of SiNPs of 28–30 nm in diameter can be strongly enhanced using a physical method, called electroporation or electropermeabilization (EP). The uptake of fluorescently labelled silica nanoparticles was improved in two different cancer cell lines, namely, HCT-116 (human colon cancer) cells and RL (B-lymphoma) cells. First, we studied cells’ capability for the regular passive uptake of SiNPs in vitro. Then, we set EP parameters in order to induce a more efficient and rapid cell loading, also comprising the nuclear compartment, while preserving the cell viability. In the final approach, we performed in vivo experiments, and evidenced that the labeling was long-lasting, as confirmed by fluorescence imaging of labeled tumors, which enabled a 30-day follow-up. This kind of SiNPs delivery, achieved by EP, could be employed to load extensive amounts of active ingredients into the cell nucleus, and concomitantly allow the monitoring of the long-term fate of nanoparticles.
Preparation and Luminescence Properties of Ba5Si8O21 Long Persistent Phosphors Doped with Rare-Earth Elements
Authors: Silvestri Andrea , Ligabue Maria Laura , Malavasi Gianluca , Lusvardi Gigliola
Published: January 2019

The phosphors of formula Ba5Si8O21:Eu2+,Dy3+ were synthesized and studied in order to improve their properties. Their synthesis conditions were evaluated as a function of precursors, crucible composition, flux agents, dopants and temperatures. The samples were characterised by means of a systematic investigation through elemental, kinetic, mineralogical (both qualitative and quantitative), and morphological analysis. This study allows for a careful evaluation of the parameters that influence the formation and properties of Ba5Si8O21:Eu2+,Dy3+ phosphors. As for the synthesis conditions, the use of Na2SiO3, BaCO3 and NH4Cl as precursors was very important to reduce the temperature and time of synthesis. The reducing atmosphere produced with purified coal was cheaper and gave results similar to the more traditional gas mixture (H2/N2). At the end of this study, a phosphor with improved long persistent phosphorescence (LPP) characteristics was obtained with Ba/Si = 0.7, Eu/Si = 2.8 × 10−3 and Dy/Si = 3.6 × 10−3 following a 6 h-synthesis in a quartz crucible.
Micromechanism of Cold Deformation of Two-Phase Polycrystalline Ti–Al Alloy with Void
Authors: Feng Ruicheng , Wang Maomao , Li Haiyan , Qi Yongnian , Wang Qi , Rui Zhiyuan
Published: January 2019

Cold deformation behavior of polycrystalline metallic material is affected by intrinsic defects such as dislocations, voids, inclusions etc. Existing studies on α 2 ( Ti 3 Al ) + γ ( TiAl ) two-phase Ti–Al alloy cover about deformation behavior mainly on macro scale. This paper focuses on the cold deformation mechanism of two-phase Ti–Al alloy at micro scale, and the role of voids in deformation process. Molecular dynamics simulations were performed to study the evolution of micro structure of material under uniaxial tension. Interaction between spherical nano voids with different size and position was also examined in the simulation. The results show that (1) In elastic stage, deformation of the two-phase is coordinated, but Ti 3 Al is more deformable; (2) In plastic stage, γ phase is the major dislocation source in two-phase alloy; (3) voids detracts the strength of the two-phase alloy, while the position of void affect the degree of this subtraction, voids located at the boundary of α 2 / γ phase have significant detraction to strength.
Control over the Percentage, Shape and Size of the Graphite Particles in Martensitic White Castings Alloyed with Cr, Nb and Mg
Authors: Cofiño-Villar Alberto , Alvarez-Antolin Florentino , Asensio-Lozano Juan , Garcia-Garcia Maria
Published: January 2019

This paper presents the results obtained regarding the control by manufacturers of the percentage, shape, and size of the precipitated graphite in the working layer of duplex work-rolls used in hot strip mill finishing stands. This working layer is manufactured in a martensitic white cast iron alloyed with Cr and Nb to promote the precipitation of M3C and MC carbides, which provide a high wear resistance. The thermal cycling behavior of this layer also has a decisive influence on its service life. In this context, the percentage of graphite and its morphology play a very important role against said thermal cycling. With the aim of studying their effect on the sphericity of graphite, the analyzed industrial manufacturing factors worth highlighting include the liquidus temperature, the %Si, the use of an FeSi inoculant with traces of Lanthanum, inoculation with different amounts of FeB and SiCaMn, and the addition of Mg. At the periphery of the working layer, it was found that the use of the FeSi inoculant with traces of La promoted an increase in the density of counts of graphite, and that inoculation with FeB and the addition of 0.02% Mg diminished the nodularity of the graphite. Furthermore, throughout the entire thickness of the working layer, an increase in the amount of SiCaMn of up to 0.6 kg/T produced an increase in the size of the graphite particles and a marked improvement in their nodularity.
Soft and Stiff Simplex Tensegrity Lattices as Extreme Smart Metamaterials
Authors: Al Sabouni-Zawadzka Anna , Gilewski Wojciech
Published: January 2019

The present paper is dedicated to an evaluation of novel cellular metamaterials based on a tensegrity pattern. The materials are constructed from supercells, each of which consists of a number of simplex modules with different geometrical proportions. Mechanical properties of the metamaterial can be controlled by adjusting the level of self-equilibrated forces or by changing the properties of structural members. A continuum model based on the equivalence of strain energy of the 3D theory of elasticity with a discrete formulation is used to identify the qualitative properties of the considered metamaterials. The model allows the inclusion of nonlinearities related to the equations of equilibrium in actual configuration of the structure with self-equilibrated set of normal forces typical for tensegrities. The lattices are recognised as extreme metamaterials according to the eigensolution of the equivalent elasticity matrices of the continuum model. The six representative deformation modes are defined and discussed: stiff, soft and medium extensional modes and high (double) as well as low shear modes. The lattices are identified as unimode or nearly bimode according to the classification of extreme materials.
Three-Dimensional Porous Ti3C2Tx-NiO Composite Electrodes with Enhanced Electrochemical Performance for Supercapacitors
Authors: Zhang Kaicheng , Ying Guobing , Liu Lu , Ma Fengchen , Su Lin , Zhang Chen , Wu Donghai , Wang Xiang , Zhou Ying
Published: January 2019

Ti3C2Tx and Ti3C2Tx-NiO composites with three-dimensional (3D) porous networks were successfully fabricated via vacuum freeze-drying. The microstructure, absorption, and electrochemical properties of the developed composites were investigated. Nickel oxide (NiO) nanoparticles could be evenly distributed on the three-dimensional network of three-dimensional Ti3C2Tx using solution processing. When employed as electrochemical capacitor electrodes in 1 M environmentally friendly sodium sulfate, Na2SO4, solution, the three-dimensional porous Ti3C2Tx-NiO composite electrodes exhibited considerable volume specific capacitance as compared to three-dimensional porous Ti3C2Tx. The three-dimensional porous Ti3C2Tx-NiO composite delivered a remarkable cycling performance with a capacitance retention of up to 114% over 2500 cycles. The growth trend of the capacitance with NiO content shows that nickel oxide plays a crucial role in the composite electrodes. These results present a roadmap for the development of convenient and economical supercapacitors in consideration with the possibilities of morphological control and the extensibility of the process.
Green Biosynthesis of Silver Nanoparticles Using Eriobotrya japonica (Thunb.) Leaf Extract for Reductive Catalysis
Authors: Yu Chen , Tang Jingchun , Liu Xiaomei , Ren Xinwei , Zhen Meinan , Wang Lan
Published: January 2019

This article reports on silver nanoparticles (AgNPs) that were green-synthesized by using Eriobotrya japonica (Thunb.) leaf extract and their use for the catalytic degradation of reactive dyes. The properties of biogenic AgNPs were characterized using UV-vis absorption spectroscopy, field emission scanning electron microscope (FESEM), X-ray powder diffraction (XRD), transmission electron microscope (TEM), Fourier transforming infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDS), and selected area electron diffraction (SAED) analysis. The UV-vis spectroscopy and X-ray analyses confirmed the formation of AgNPs and showed the strong absorbance around 467 nm with surface plasmon resonance (SPR). The mean diameter of biogenic AgNPs at room (20 °C), moderate (50 °C), and high temperatures (80 °C) were 9.26 ± 2.72, 13.09 ± 3.66, and 17.28 ± 5.78 nm, respectively. The reaction temperature had significant impacts on the sizes of synthesized AgNPs. The higher the synthesis temperature, the larger size and the lower catalysis activity for reductive decomposition of reactive dyes via NaBH4. The results supported a bio-green approach for developing AgNPs with a small size and stable degradation activity of reactive dyes over 92% in 30 min by using Eriobotrya japonica (Thunb.) leaf extract at pH 7, 20 °C, and 1:10 ratio of silver nitrate added to the leaf extract.
Minority Carrier Lifetime Measurements for Contactless Oxidation Process Characterization and Furnace Profiling
Authors: Bscheid Christian , Engst Christian R. , Eisele Ignaz , Kutter Christoph
Published: January 2019

Contactless minority carrier lifetime (lifetime) measurements by means of microwave detected photoconductivity are employed for oxidation process characterization and furnace profiling. Characterization is performed on oxidized float zone substrates with high resistivity and outstanding bulk quality, suggesting that the measured effective lifetime is strongly dominated by interface recombination and therefore reflects the oxide quality. The applied approach requires neither test structures nor time consuming measurements and is therefore of particular interest if high throughput is required. The method is used to investigate the impact of oxidation furnace leakage as well as to analyze the oxidation homogeneity across a horizontal oxidation furnace. For comparison, capacitance-voltage measurements are conducted to characterize the oxide properties. It is found that any type of furnace leakage, which induces fixed oxide charges as well as interface states, has a heavy impact on the measured effective lifetime, especially on the shape of generation rate dependent lifetime curves. Furthermore, a distinct lifetime decrease towards the tube door of the oxidation furnace could be observed. The latter is even detectable in an ideal oxidation process, generating high quality oxides. Besides plain equipment characterization, the presented approach is suitable to optimize the oxidation process itself regarding different parameters like temperature, gas flow, pressure, or process time.
Scalable Extraction of Big Macromolecular Data in Azure Data Lake Environment
Authors: Mrozek Dariusz , Dąbek Tomasz , Małysiak-Mrozek Bożena
Published: January 2019

Calculation of structural features of proteins, nucleic acids, and nucleic acid-protein complexes on the basis of their geometries and studying various interactions within these macromolecules, for which high-resolution structures are stored in Protein Data Bank (PDB), require parsing and extraction of suitable data stored in text files. To perform these operations on large scale in the face of the growing amount of macromolecular data in public repositories, we propose to perform them in the distributed environment of Azure Data Lake and scale the calculations on the Cloud. In this paper, we present dedicated data extractors for PDB files that can be used in various types of calculations performed over protein and nucleic acids structures in the Azure Data Lake. Results of our tests show that the Cloud storage space occupied by the macromolecular data can be successfully reduced by using compression of PDB files without significant loss of data processing efficiency. Moreover, our experiments show that the performed calculations can be significantly accelerated when using large sequential files for storing macromolecular data and by parallelizing the calculations and data extractions that precede them. Finally, the paper shows how all the calculations can be performed in a declarative way in U-SQL scripts for Data Lake Analytics.
Cardiomyocyte Progenitor Cells as a Functional Gene Delivery Vehicle for Long-Term Biological Pacing
Authors: Végh Anna M. D. , Den Haan A. Dénise , Cócera Ortega Lucía , Verkerk Arie O. , Sluijter Joost P. G. , Bakker Diane , Van Amersfoorth Shirley , Van Veen Toon A. B. , Klerk Mischa , Seppen Jurgen , De Bakker Jacques M. T. , Christoffels Vincent M. , Geerts Dirk , Goumans Marie José T. H. , Tan Hanno L. , Boink Gerard J. J.
Published: January 2019

Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (−20 pA/pF at −140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.
Purification and Characterization of A New Cold-Adapted and Thermo-Tolerant Chitosanase from Marine Bacterium Pseudoalteromonas sp. SY39
Authors: Zhou Yu , Chen Xuehong , Li Xiao , Han Yantao , Wang Yanan , Yao Ruyong , Li Shangyong
Published: January 2019

Chitosanases play an important role in chitosan degradation, forming enzymatic degradation products with several biological activities. Although many chitosanases have been discovered and studied, the enzymes with special characteristics are still rather rare. In this study, a new chitosanase, CsnM, with an apparent molecular weight of 28 kDa was purified from the marine bacterium Pseudoalteromonas sp. SY39. CsnM is a cold-adapted enzyme, which shows highest activity at 40 °C and exhibits 30.6% and 49.4% of its maximal activity at 10 and 15 °C, respectively. CsnM is also a thermo-tolerant enzyme that recovers 95.2%, 89.1% and 88.1% of its initial activity after boiling for 5, 10 and 20 min, respectively. Additionally, CsnM is an endo-type chitosanase that yields chitodisaccharide as the main product (69.9% of the total product). It’s cold-adaptation, thermo-tolerance and high chitodisaccharide yield make CsnM a superior candidate for biotechnological application to produce chitooligosaccharides.
A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies
Authors: Borcea Anca-Maria , Marc Gabriel , Ionuț Ioana , Vodnar Dan C. , Vlase Laurian , Gligor Felicia , Pricopie Andreea , Pîrnău Adrian , Tiperciuc Brîndușa , Oniga Ovidiu
Published: January 2019

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.
Vibrational Approach to the Dynamics and Structure of Protein Amyloids
Authors: Li Haoqian , Lantz Richard , Du Deguo
Published: January 2019

Amyloid diseases, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, are linked to a poorly understood progression of protein misfolding and aggregation events that culminate in tissue-selective deposition and human pathology. Elucidation of the mechanistic details of protein aggregation and the structural features of the aggregates is critical for a comprehensive understanding of the mechanisms of protein oligomerization and fibrillization. Vibrational spectroscopies, such as Fourier transform infrared (FTIR) and Raman, are powerful tools that are sensitive to the secondary structure of proteins and have been widely used to investigate protein misfolding and aggregation. We address the application of the vibrational approaches in recent studies of conformational dynamics and structural characteristics of protein oligomers and amyloid fibrils. In particular, introduction of isotope labelled carbonyl into a peptide backbone, and incorporation of the extrinsic unnatural amino acids with vibrational moieties on the side chain, have greatly expanded the ability of vibrational spectroscopy to obtain site-specific structural and dynamic information. The applications of these methods in recent studies of protein aggregation are also reviewed.
Triterpenoids from Cyclocarya paliurus that Enhance Glucose Uptake in 3T3-L1 Adipocytes
Authors: Fang Zhu-Jun , Shen Sheng-Nan , Wang Jia-Min , Wu Yong-Jiang , Zhou Chang-Xin , Mo Jian-Xia , Lin Li-Gen , Gan Li-She
Published: January 2019

Four previously undescribed compounds, including three rarely occurring seco-dammarane triterpenoid glycosides and a pentacyclic triterpenic acid, were isolated from a 70% ethanol extract of the leaves of Cyclocarya paliurus (Juglandaceae), along with eleven known triterpenoids. Their structures were determined by spectroscopic techniques, including 2D NMR and HRESIMS, as well as chemical methods. Among them, several triterpenoids enhanced insulin stimulated glucose uptake in both 3T3-L1 adipocytes and C2C12 myotubes. Furthermore, compound 1 dose-dependently increased glucose uptake through activating AMP-activated protein kinase (AMPK)-p38 pathway. Collectively, triterpenoids from C. paliurus could be developed as insulin sensitizers, which might have therapeutic potential for insulin resistance and hyperglycemia.
Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis
Authors: Amusengeri Arnold , Tastan Bishop Özlem
Published: January 2019

The human heat shock proteins (Hsps), predominantly Hsp72 and Hsp90, have been strongly implicated in various critical stages of oncogenesis and progression of human cancers. While drug development has extensively focused on Hsp90 as a potential anticancer target, much less effort has been put against Hsp72. This work investigated the therapeutic potential of Hsp72 and its constitutive isoform, Hsc70, via in silico-based screening against the South African Natural Compounds Database (SANCDB). A comparative modeling approach was used to obtain nearly full-length 3D structures of the closed conformation of Hsp72 and Hsc70 proteins. Molecular docking of SANCDB compounds identified one potential allosteric modulator, Discorhabdin N, binding to the allosteric β substrate binding domain (SBDβ) back pocket, with good binding affinities in both cases. This allosteric region was identified in one of our previous studies. Subsequent all-atom molecular dynamics simulations and free energy calculations exhibited promising protein–ligand association characteristics, indicative of strong binding qualities. Further, we utilised dynamic residue network analysis (DRN) to highlight protein regions actively involved in cross-domain communication. Most residues identified agreed with known allosteric signal regulators from literature, and were further investigated for the purpose of deducing meaningful insights into the allosteric modulation properties of Discorhabdin N.
Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds
Authors: Karaburun Ahmet Çağrı , Kaya Çavuşoğlu Betül , Acar Çevik Ulviye , Osmaniye Derya , Sağlık Begüm Nurpelin , Levent Serkan , Özkay Yusuf , Atlı Özlem , Koparal Ali Savaş , Kaplancıklı Zafer Asım
Published: January 2019

Discovery of novel anticandidal agents with clarified mechanisms of action, could be a rationalist approach against diverse pathogenic fungal strains due to the rise of resistance to existing drugs. In support to this hypothesis, in this paper, a series of benzimidazole-oxadiazole compounds were synthesized and subjected to antifungal activity evaluation. In vitro activity assays indicated that some of the compounds exhibited moderate to potent antifungal activities against tested Candida species when compared positive control amphotericin B and ketoconazole. The most active compounds 4h and 4p were evaluated in terms of inhibitory activity upon ergosterol biosynthesis by an LC-MS-MS method and it was determined that they inhibited ergosterol synthesis concentration dependently. Docking studies examining interactions between most active compounds and lanosterol 14-α-demethylase also supported the in vitro results.
Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer
Authors: Miyata Yasuyoshi , Shida Yohei , Hakariya Tomoaki , Sakai Hideki
Published: January 2019

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.
Correction: Cho, K.H., et al. Blood Pressure Lowering Effect of Cuban Policosanol Is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats. Molecules 2018, 23, 1080
Authors: Cho Kyung-Hyun , Yadav Dhananjay , Kim Suk-Jeong , Kim Jae-Ryong
Published: January 2019

The authors wish to make the following correction to their paper [...]
An Unusual Benzoisoquinoline-9-one Derivative and Other Related Compounds with Antiproliferative Activity from Hawaiian Endophytic Fungus Peyronellaea sp. FT431
Authors: Li Chunshun , Sarotti Ariel M. , Wu Xiaohua , Yang Baojun , Turkson James , Chen Yongfei , Liu Qingsong , Cao Shugeng
Published: January 2019

A new polyketide containing the benzoisoquinoline-9-one moiety, peyronetide A (1), and three other new derivatives peyronetides B–D (2–4), as well as one known compound (5) were purified from the cultured broth of the endophytic fungus Peyronellaea sp. FT431, which was isolated from the Hawaiian indigenous plant, Verbena sp. The structures of the new compounds were determined through the analysis of HRMS and NMR spectroscopic data. Compounds 1, 2, and 5 showed cytotoxic activities against TK-10 (human kidney adenocarcinoma cells), cisplatin sensitive A2780S (human ovarian carcinoma cells), and cisplatin resistant A2780CisR cell lines, with IC50 values between 6.7 to 29.2 μM.
Separation of Five Iridoid Glycosides from Lonicerae Japonicae Flos Using High-Speed Counter-Current Chromatography and Their Anti-Inflammatory and Antibacterial Activities
Authors: Yang Ran , Fang Lei , Li Jia , Zhao Zhenhua , Zhang Hua , Zhang Yongqing
Published: January 2019

A high-speed counter-current chromatography (HSCCC) method, using a two-phase solvent system composed of ethyl acetate/n-butanol/methanol/water (5:1:1:5, v/v/v/v), was successfully established to separate the five iridoid glucosides 7-O-ethyl sweroside (1), secologanin dimethylacetal (2), adinoside F (3), (7R)-secologain n-butyl methyl acetal (4) and adinoside G (5) from Lonicerae Japonicae Flos. Their purities were 96.8%, 98.5%, 93.3%, 98.0% and 99.9%, respectively. All the iridoid glucosides were identified by HR-ESI-MS, 1D and 2D NMR. Compounds 3 and 5 are new iridoid glucosides. The anti-inflammatory tests showed that compounds 1–5 all expressed moderate inhibitory effects on β-glucuronidase release in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF) with IC50 values ranging from 4.52 to 6.50 µM, while the antibacterial assays demonstrated that all the compounds displayed mild inhibitory activities against Staphylococcus aureus ATCC 25923 with MIC values ranging from 13.7 to 26.0 µg/mL.
Small Multitarget Molecules Incorporating the Enone Moiety
Authors: Liargkova Thalia , Eleftheriadis Nikolaos , Dekker Frank , Voulgari Efstathia , Avgoustakis Constantinos , Sagnou Marina , Mavroidi Barbara , Pelecanou Maria , Hadjipavlou-Litina Dimitra
Published: January 2019

Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 µM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 Å) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.
Synthesis and Spectroscopic Identification of Certain Imidazole-Semicarbazone Conjugates Bearing Benzodioxole Moieties: New Antifungal Agents
Authors: Al-Wabli Reem I. , Al-Ghamdi Alwah R. , Ghabbour Hazem A. , Al-Agamy Mohamed H. , Attia Mohamed I.
Published: January 2019

During the last three decades the extent of life-threatening fungal infections has increased remarkably worldwide. Synthesis and structure elucidation of certain imidazole-semicarbazone conjugates 5a–o are reported. Single crystal X-ray analysis of compound 5e unequivocally confirmed its assigned chemical structure and the (E)-configuration of its imine double bond. Compound 5e crystallized in the triclinic system, P-1, a = 6.3561 (3) Å, b = 12.5095 (8) Å, c = 14.5411 (9) Å, α = 67.073 (4)°, β = 79.989 (4)°, γ =84.370 (4)°, V = 1048.05 (11) Å3, Z = 2. In addition, DIZ and MIC assays were used to examine the in vitro antifungal activity of the title conjugates 5a–o against four fungal strains. Compound 5e, bearing a 4-ethoxyphenyl fragment, showed the best MIC value (0.304 µmol/mL) against both C. tropicalis and C. parapsilosis species, while compounds 5c (MIC = 0.311 µmol/mL), 5k, and 5l (MIC = 0.287 µmol/mL) exhibited the best anti-C. albicans activity.
Effect of Planarity of Aromatic Rings Appended to o-Carborane on Photophysical Properties: A Series of o-Carboranyl Compounds Based on 2-Phenylpyridine- and 2-(Benzo[b]thiophen-2-yl)pyridine
Authors: Jin Hyomin , Kim Seonah , Bae Hye Jin , Lee Ji Hye , Hwang Hyonseok , Park Myung Hwan , Lee Kang Mun
Published: January 2019

Herein, we investigated the effect of ring planarity by fully characterizing four pyridine-based o-carboranyl compounds. o-Carborane was introduced to the C4 position of the pyridine rings of 2-phenylpyridine and 2-(benzo[b]thiophen-2-yl)pyridine (CB1 and CB2, respectively), and the compounds were subsequently borylated to obtain the corresponding C∧N-chelated compounds CB1B and CB2B. Single-crystal X-ray diffraction analysis of the molecular structures of CB2 and CB2B confirmed that o-carborane is appended to the aryl moiety. In photoluminescence experiments, CB2, but not CB1, showed an intense emission, assignable to intramolecular charge transfer (ICT) transition between the aryl and o-carborane moieties, in both solution and film states. On the other hand, in both solution and film states, CB1B and CB2B demonstrated a strong emission, originating from π-π * transition in the aryl groups, that tailed off to 650 nm owing to the ICT transition. All intramolecular electronic transitions in these o-carboranyl compounds were verified by theoretical calculations. These results distinctly suggest that the planarity of the aryl groups have a decisive effect on the efficiency of the radiative decay due to the ICT transition.
Self-Assembly of Short Elastin-like Amphiphilic Peptides: Effects of Temperature, Molecular Hydrophobicity and Charge Distribution
Authors: Cao Meiwen , Shen Yang , Wang Yu , Wang Xiaoling , Li Dongxiang
Published: January 2019

A novel type of self-assembling peptides has been developed by introducing the basic elastomeric β-turn units of elastin protein into the amphiphilic peptide molecules. The self-assembly behaviors of such peptides are affected by the overall molecular hydrophobicity, charge distribution and temperature. The molecules with higher hydrophobicity exhibit better self-assembling capability to form long fibrillar nanostructures. For some peptides, the temperature increase can not only promote the self-assembly process but also change the self-assembly routes. The self-assembly of the peptides with two charges centralized on one terminal show higher dependence on temperature than the peptides with two charges distributed separately on the two terminals. The study probes into the self-assembly behaviors of short elastin-like peptides and is of great help for developing novel self-assembling peptides with thermo sensitivity.
Spectroscopic and Structural Study of Some Oligosilanylalkyne Complexes of Cobalt, Molybdenum and Nickel
Authors: Zirngast Michaela , Marschner Christoph , Baumgartner Judith
Published: January 2019

Metal induced stabilization of α-carbocations is well known for cobalt- and molybdenum complexed propargyl cations. The same principle also allows access to reactivity enhancement of metal coordinated halo- and hydrosilylalkynes. In a previous study, we have shown that coordination of oligosilanylalkynes to the dicobalthexacarbonyl fragment induces striking reactivity to the oligosilanyl part. The current paper extends this set of oligosilanylalkyne complexes to a number of new dicobalthexacarbonyl complexes but also to 1,2-bis(cyclopentadienyl)tetracarbonyldimolybdenum and (dippe)Ni complexes. NMR-Spectroscopic and crystallographic analysis of the obtained complexes clearly show that the dimetallic cobalt and molybdenum complexes cause rehybridization of the alkyne carbon atoms to sp3, while in the nickel complexes one π-bond of the alkyne is retained. For the dicobalt and dimolybdenum complexes, strongly deshielded 29Si NMR resonances of the attached silicon atoms indicate enhanced reactivity, whereas the 29Si NMR shifts of the respective nickel complexes are similar to that of respective vinylsilanes.