bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the Compaction Pressure and Sintering Temperature on the Mechanical Properties of Porous Titanium for Biomedical Applications
Authors: Castillo Sandra M. , Muñoz Sergio , Trueba Paloma , Díaz Eduardo , Torres Yadir
Published: November 2019

In the present work, the use of porous titanium is proposed as a solution to the difference in stiffness between the implant and bone tissue, avoiding the bone resorption. Conventional powder metallurgical technique is an industrially established route for fabrication of this type of material. The results are discussed in terms of the influence of compaction pressure and sintering temperature on the porosity (volumetric fraction, size, and morphology) and the quality of the sintering necks. A very good agreement between the predicted values obtained using a simple 2D finite element model, the experimental uniaxial compression behavior, and the analytical model proposed by Nielsen, has been found for both the Young’s modulus and the yield strength. The porous samples obtained by the loose sintering technique and using temperatures between 1000 °C −1100 °C (about 40% of total porosity) are recommended for achieving a suitable biomechanical behavior for cortical bone partial replacement.
InAs/InAsSb Strained-Layer Superlattice Mid-Wavelength Infrared Detector for High-Temperature Operation
Authors: Ariyawansa Gamini , Duran Joshua , Reyner Charles , Scheihing John
Published: November 2019

This paper reports an InAs/InAsSb strained-layer superlattice (SLS) mid-wavelength infrared detector and a focal plane array particularly suited for high-temperature operation. Utilizing the nBn architecture, the detector structure was grown by molecular beam epitaxy and consists of a 5.5 µm thick n-type SLS as the infrared-absorbing element. Through detailed characterization, it was found that the detector exhibits a cut-off wavelength of 5.5 um, a peak external quantum efficiency (without anti-reflection coating) of 56%, and a dark current of 3.4 × 10−4 A/cm2, which is a factor of 9 times Rule 07, at 160 K temperature. It was also found that the quantum efficiency increases with temperature and reaches ~56% at 140 K, which is probably due to the diffusion length being shorter than the absorber thickness at temperatures below 140 K. A 320 × 256 focal plane array was also fabricated and tested, revealing noise equivalent temperature difference of ~10 mK at 80 K with f/2.3 optics and 3 ms integration time. The overall performance indicates that these SLS detectors have the potential to reach the performance comparable to InSb detectors at temperatures higher than 80 K, enabling high-temperature operation.
Microbially Induced Carbonate Precipitation Using Microorganisms Enriched from Calcareous Materials in Marine Environments and Their Metabolites
Authors: Kim Yumi , Roh Yul
Published: November 2019

Microbially induced Ca-carbonate precipitation (MICP) in general, refers to a process in which the urease secreted by microbes hydrolyzes urea to ammonium and carbon dioxide. The main objectives of this study were to identify the environmental factors (e.g., microbial growth, cell/metabolite presences, and calcium sources) that control Ca-carbonate formation and to investigate the mineralogical characteristics of the Ca-carbonate precipitated using ureolytic microorganisms cultured in marine environments. The two types of carbonate-forming microorganisms (CFMs), mixed cultures hydrolyzing urea, were enriched from calcareous materials in marine environments. The experiments using a CFM, Sporosarcina pasteurii, was also used for comparison. All the microbes were cultured aerobically in D-1 growth media that included urea. To investigate the effect of microbial growth states on Ca-carbonate precipitation, Ca-acetate was injected into the media before (i.e., lag phase) and after (i.e., stationary phase) microbial growth, and into the soluble microbial products (SMP) solution, respectively. XRD, FT-IR, and SEM-EDS analyses were used for mineralogical characterization of the precipitated Ca-carbonates. Results indicated that the Ca-carbonates, vaterite and/or calcite, precipitated under all the experimental conditions. The fastest precipitation of Ca-carbonates occurred in the SMP solution and formed calcite (size = 5–15 μm). When the concentrations of added Ca-acetate were varied from 0 to 0.5 M, the highest amounts of calcite, 22.8 g/L, were produced when 0.3 M Ca-acetate was injected. Therefore, the environmental factors (e.g., microbial growth, cell/metabolite presences, and calcium sources) could have an effect the rate of formation of Ca-carbonate and the types of carbonate minerals formed. Moreover, the use of cell-free SMP solution is expected to be applicable to Ca-carbonate precipitation in an environment where microbial growth is unfavorable.
Determination of Size Distribution of Precipitation Aggregates Using Non-Invasive Microscopy and Semiautomated Image Processing and Analysis
Authors: Quilaqueo Michelle , Gim-Krumm Minghai , Ruby-Figueroa René , Troncoso Elizabeth , Estay Humberto
Published: November 2019

Particle size distribution (PSD) determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes form colloidal or aggregated suspensions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or a cyclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativeness in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used were obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction (Mastersizer). The PSD results obtained with optical microscopy show a bi-modal behavior of the precipitates. However this behavior could be not determined when using the laser diffraction technique. The PSD obtained for the sample tested by microscopy had a mean of 119.7 μm, a median of 147 μm and a 90% distribution reached a particle size of 312.5 μm. These values differ with those obtained by the laser diffraction technique. Our results show significant differences between the methods analyzed, demonstrating that the image processing and analysis obtained by optical microscopy is an excellent and non-invasive alternative to obtain size distributions of aggregates in precipitation processes.
Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application
Authors: Adachi Tatsuo , Nakamura Yoshikazu
Published: November 2019

Aptamers are short, single-stranded oligonucleotides that bind to specific target molecules. The shape-forming feature of single-stranded oligonucleotides provides high affinity and excellent specificity toward targets. Hence, aptamers can be used as analogs of antibodies. In December 2004, the US Food and Drug Administration approved the first aptamer-based therapeutic, pegaptanib (Macugen), targeting vascular endothelial growth factor, for the treatment of age-related macular degeneration. Since then, however, no aptamer medication for public health has appeared. During these relatively silent years, many trials and improvements of aptamer therapeutics have been performed, opening multiple novel directions for the therapeutic application of aptamers. This review summarizes the basic characteristics of aptamers and the chemical modifications available for aptamer therapeutics.
First Study on the Oxidative Stability and Elemental Analysis of Babassu (Attalea speciosa) Edible Oil Produced in Brazil Using a Domestic Extraction Machine
Authors: Melo Elaine , Michels Flavio , Arakaki Daniela , Lima Nayara , Gonçalves Daniel , Cavalheiro Leandro , Oliveira Lincoln , Caires Anderson , Hiane Priscila , Nascimento Valter
Published: November 2019

Interest in edible oil extraction processes is growing interest because the final nutritional quality of the extracted oil depends on the procedure used to obtain ir. In this context, a domestic cold oil press machine is a valuable tool that avoids the use of chemicals during oil extraction, in an environmentally friendly way. Although babassu (Attalea speciosa) oil is economically important in several Brazilian regions due to its nutritional and healthy features, few studies have been conducted on the chemical composition and stability of babassu oils extracted by cold pressing. Babassu oil’s major constituents are saturated fatty acids (~86.42%), with the most prevalent fatty acids being lauric (~47.40%), myristic (15.64%), and oleic (~11.28%) acids, respectively, within the recommended range by Codex Alimentarius, presenting atherogenicity and thrombogenicity indexes favorable for human consumption. Peroxide value, Rancimat, and TGA/DSC results indicated that babassu oil is stable to oxidation. Also, macro- (Na, K, Ca, Mg, P) and micro-elements (Fe, Mn, Cr, Se, Al, and Zn) of babassu oil were determined, revealing levels below the tolerable upper intake level (ULs) for adults. These findings demonstrated that cold-press extraction using a domestic machine yielded a high-quality oil that kept oil chemical composition stable to oxidation with natural antioxidants.
Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice
Authors: Berger Geraint , Arora Nipun , Burkovskiy Ian , Xia Yanfang , Chinnadurai Anu , Westhofen Robert , Hagn Georg , Cox Ashley , Kelly Melanie , Zhou Juan , Lehmann Christian
Published: November 2019

Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.
Changes in Arsenic and Copper Bioavailability and Oxytetracycline Degradation during the Composting Process
Authors: Shehata Ebrahim , Liu Yuanwang , Feng Yao , Cheng Dengmiao , Li Zhaojun
Published: November 2019

This research focuses on the effects of the composting process on oxytetracycline antibiotic degradation and the bioavailability of arsenic and copper. A compost experiment was conducted using cow and pig manure contaminated with oxytetracycline, and copper and arsenic salts. The changes in physicochemical properties, oxytetracycline concentration, and the germination index were measured. Copper and arsenic were estimated by sequential chemical extraction. We also detected the effects of compost properties, oxytetracycline concentration, and heavy metal (loid)s on the germination index through simple regression analysis. The results showed that the composting process positively and significantly affected heavy metal(loid)s bioavailability, oxytetracycline degradation, and the germination index. Oxytetracycline concentration declined in all treatments, and the decline was more evident in cows’ manure. The copper and arsenic bioavailable fraction decreased significantly, while the low bioavailability fraction increased. The germination index increased above 50%, which showed that the compost was free of toxic substances. This result also showed that the compost properties had the most significant impact on the germination index, and their regression had the highest R2 values (0.84 and 0.99) in the cow and pig manure treatments, respectively. In conclusion, the composting process provides an economical method for oxytetracycline degradation and heavy metal(loid)s bioavailability reduction.
Nanostructured and Photochromic Material for Environmental Detection of Metal Ions
Authors: Machado Raphael C. L. , Alexis Frank , De Sousa Frederico B.
Published: November 2019

Compared to conventional spectroscopy or chromatography analysis, chemical sensing based on colorimetric changes offers an alternative to monitor potential metal hazards in aqueous environment through rapid and low-cost colorimetric changes which can be easily interpreted. In this work poly(ethylene glycol) (PEG 2000) was modified with a carboxylic acid spiropyran (SPCOOH) derivate by Steglich esterification (PEGSP2). PEGSP2 was incorporated into a poly(ε-caprolactone) (PCL) polymer matrix by electrospinning technique to produce nanofibers with photochromic properties. Spectroscopic analysis, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to characterize PEGSP2. Drop shape analysis (DSA) and scanning electronic microscopy (SEM) were used to characterize the electrospun (ES) nanofibers morphology. Several metal ions solutions relevant to environmental hazards were prepared to be spotted on the surface of ES nanofibers for photochromatic sensing. Among them, Mg2+, Ca2+, Zn2+, Cd2+, La3+, and Er3+ demonstrated orange fluorescence when exposed to UV light. ES nanofibers also presented higher wettability when compared to a pure PCL polymer matrix, which is critical for sensitivity. Eighteen metals ions could be detected on the electrospun material. Additionally, among all metal ions Fe3+ was the most sensitive one in solution, in a µmol L−1 range.
Graphene Oxide: A Smart (Starting) Material for Natural Methylxanthines Adsorption and Detection
Authors: Petrucci Rita , Chiarotto Isabella , Mattiello Leonardo , Passeri Daniele , Rossi Marco , Zollo Giuseppe , Feroci Marta
Published: November 2019

Natural methylxanthines, caffeine, theophylline and theobromine, are widespread biologically active alkaloids in human nutrition, found mainly in beverages (coffee, tea, cocoa, energy drinks, etc.). Their detection is thus of extreme importance, and many studies are devoted to this topic. During the last decade, graphene oxide (GO) and reduced graphene oxide (RGO) gained popularity as constituents of sensors (chemical, electrochemical and biosensors) for methylxanthines. The main advantages of GO and RGO with respect to graphene are the easiness and cheapness of synthesis, the notable higher solubility in polar solvents (water, among others), and the higher reactivity towards these targets (mainly due to π–π interactions); one of the main disadvantages is the lower electrical conductivity, especially when using them in electrochemical sensors. Nonetheless, their use in sensors is becoming more and more common, with the obtainment of very good results in terms of selectivity and sensitivity (up to 5.4 × 10−10 mol L−1 and 1.8 × 10−9 mol L−1 for caffeine and theophylline, respectively). Moreover, the ability of GO to protect DNA and RNA from enzymatic digestion renders it one of the best candidates for biosensors based on these nucleic acids. This is an up-to-date review of the use of GO and RGO in sensors.
Mechanical Respond and Failure Mode of Large Size Honeycomb Sandwiched Composites under In-Plane Shear Load
Authors: Wang Mo-Nan , Wang Baoqin , Liu Changxi , Zhang Guangxin , Wan Yumin , Zhang Fa
Published: November 2019

The present work focuses on the in-plane shear respond and failure mode of large size honeycomb sandwich composites which consist of plain weave carbon fabric laminate skins and aramid paper core. A special size specimen based on a typical element of aircraft fuselage was designed and manufactured. A modified in-plane shear test method and the corresponding fixture was developed. Three large size specimens were tested. The distributed strain gauges were used to monitor the mechanical response and ultimate bearing capacity. The results show that a linear respond of displacement and strain appears with the increase of the load. The average shear failure load reaches 205.68 kN with the shear failure occurring on the face sheet, and the maximum shear strain monitored on the composite plate is up to 16,115 με. A combination of theoretical analysis and finite element method (FEM) was conducted to predict the shear field distribution and the overall buckling load. The out-of-plane displacement field distribution and in-plane shear strain field distribution under the pure shear loading were revealed. The theoretical analysis method was deduced to obtain the variation rule of the shear buckling load. A good agreement was achieved among the experiment, theoretical analysis, and FEM results. It can be concluded that the theoretical analysis method is relatively conservative, and the FEM is more accurate in case of deformation and strain. The results predicted by h element and p element methods are very close. The results of the study could provide data support for the comprehensive promotion of the design and application of honeycomb sandwich composites.
Improving the Light-Induced Spin Transition Efficiency in Ni(II)-Based Macrocyclic-Ligand Complexes
Authors: Farcaș Alex-Adrian , Bende Attila
Published: November 2019

The structural stability and photoabsorption properties of Ni(II)-based metal-organic complexes with octahedral coordination having different planar ligand ring structures were investigated employing density functional theory (DFT) and its time-dependent extension (TD-DFT) considering the M06 exchange-correlation functional and the Def2-TZVP basis set. The results showed that the molecular composition of different planar cyclic ligand structures had significant influences on the structural stability and photoabsorption properties of metal-organic complexes. Only those planar ligands that contained aromatic rings met the basic criteria (thermal stability, structural reversibility, and appropriate excitation frequency domain) for light-induced excited spin state trapping, but their spin transition efficiencies were very different. While, in all three aromatic cases, the singlet electronic excitations induced charge distribution that could help in the singlet-to-triplet spin transition, and triplet excitations, which could assist in the backward (triplet-to-singlet) spin transition, was found only for one complex.
IR Studies of the Cu Ions in Cu-Faujasites
Authors: Kuterasiński Łukasz , Podobiński Jerzy , Rutkowska-Zbik Dorota , Datka Jerzy
Published: November 2019

The properties of Cu ions in dealuminated faujasite-type zeolites (Si/Al = 31) containing 1, 2, and 5 wt.% of Cu were investigated by IR spectroscopy with CO and NO as probe molecules. Cu was introduced by impregnation into zeolites in both protonic (HFAU) and sodium (NaFAU) forms of zeolite. Four kinds of Cu species were found: Cu+exch., Cu+oxide, Cu2+exch. (square, planar, and square pyramidal), and Cu2+oxide (CuO). The proportions between these four kinds of Cu depended on the amount of Cu and on the form of zeolite to which Cu was introduced (HFAU or NaFAU). Zeolites with 1 wt.% of Cu introduced to HFAU (denoted as Cu(1)HFAU) contained only Cu+exch., whereas other forms of Cu were present in zeolites of higher Cu contents. The concentration of Cu+exch. was determined by quantitative IR studies of CO adsorption. According to the IR results, some Cu ions were situated inside hexagonal prisms and/or cuboctahedra, and were inaccessible to adsorbed molecules. IR studies also evidenced that Cu ions in oxide forms—Cu+oxide and Cu2+oxide (CuO)—were better electron donors than Cu in exchange positions (Cu+exch. and Cu2+exch).
Curdlan (Alcaligenes faecalis) (1→3)-β-d-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways
Authors: Liu Jun , Tang Jiqing , Li Xiuting , Yan Qiaojuan , Ma Junwen , Jiang Zhengqiang
Published: November 2019

Functional oligosaccharides, particularly curdlan (1→3)-β-d-glucan oligosaccharides (GOS), play important roles in modulating host immune responses. However, the molecular mechanisms underlying the immunostimulatory effects of GOS on macrophage polarization are not clear. In this work, GOS (5–1000 µg/mL) were non-toxic to bone marrow-derived macrophages (BMDMs) with improved pinocytic and bactericidal capacities. Incubation with GOS (100 µg/mL) induced M1 phenotype polarization of BMDMs as evidenced by increased CD11c+/CD86+ (10.1%) and M1 gene expression of inducible nitric oxide synthase, interleukin (IL)-1β, and chemokine C-C-motif ligand 2. Accordingly, the secretion of cytokines IL-1β, IL-6, monocyte chemotactic protein-1, and tumor necrosis factor-α, as well as the nitrite release of BMDMs were increased by GOS (100 µg/mL). Expression of mitogen-activated protein kinases (MAPKs) of phosphorylated (p)-c-Jun amino-terminal kinase, p-extracellular signal regulated kinase, and p-p38 in BMDMs were increased by GOS, as well as the p-Stat1. Moreover, nuclear factor-kappa B (NF-κB) p-p65 expression in BMDMs was promoted by GOS while it suppressed IκBα expression. Receptor blocking with anti-CR3 (CD11b/CD18) and anti-toll-like receptor (TLR) 2 antibodies diminished GOS induced M1 phenotype polarization with reduced mRNA expression of M1 genes, decreased cytokine and nitrite releases, and suppressed signaling pathway activation. Thus, CR3 (CD11b/CD18) and TLR2 mediated activation of MAPKs and NF-κB pathways are responsible for GOS induced polarization of BMDMs.
Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats
Authors: Górny Magdalena , Wnuk Agnieszka , Kamińska Adrianna , Kamińska Kinga , Chwatko Grażyna , Bilska-Wilkosz Anna , Iciek Małgorzata , Kajta Małgorzata , Rogóż Zofia , Lorenc-Koci Elżbieta
Published: November 2019

Impaired glutathione (GSH) synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Our research aimed to assess the effects of l-buthionine-(S,R)-sulfoximine (BSO), a GSH synthesis inhibitor, and GBR 12909, a dopamine reuptake inhibitor, administered alone or in combination, to Sprague–Dawley rats during early postnatal development (p5–p16), on the levels of GSH, sulfur amino acids, global DNA methylation, and schizophrenia-like behavior. GSH, methionine (Met), homocysteine (Hcy), and cysteine (Cys) contents were determined in the liver, kidney, and in the prefrontal cortex (PFC) and hippocampus (HIP) of 16-day-old rats. DNA methylation in the PFC and HIP and schizophrenia-like behavior were assessed in adulthood (p90–p93). BSO caused the tissue-dependent decreases in GSH content and alterations in Met, Hcy, and Cys levels in the peripheral tissues and in the PFC and HIP. The changes in these parameters were accompanied by alterations in the global DNA methylation in the studied brain structures. Parallel to changes in the global DNA methylation, deficits in the social behaviors and cognitive functions were observed in adulthood. Only BSO + GBR 12909-treated rats exhibited behavioral alterations resembling positive symptoms in schizophrenia patients. Our results suggest the usefulness of this neurodevelopmental model for research on the pathomechanism of schizophrenia.
Evidence for Effective Inhibitory Actions on Hyperpolarization-Activated Cation Current Caused by Ganoderma Triterpenoids, the Main Active Constitutents of Ganoderma Spores
Authors: Chang Wei-Ting , Gao Zi-Han , Lo Yi-Ching , Wu Sheng-Nan
Published: November 2019

The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 µg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 µg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 µM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.
Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors
Authors: Zhou Yunjiang , Tang Shi , Chen Tingting , Niu Miao-Miao
Published: November 2019

Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in many biological processes and is considered as a potential target for anticancer therapy. Although some PARP-1 inhibitors have been reported, their clinical application in cancer therapy is limited by some shortcomings such as weak affinity, low selectivity and adverse side effects. To identify highly potent and selective PARP-1 inhibitors, an integrated protocol that combines pharmacophore mapping, virtual screening and molecular docking was constructed. It was then used as a screening query to identify potent leads with unknown scaffolds from an in-house database. Finally, four retrieved compounds were selected for biological evaluation. Biological testing indicated that the four compounds showed strong inhibitory activities on the PARP-1 (IC50 < 0.2 μM). MTT assay confirmed that compounds 1–4 inhibited the growth of human lung cancer A549 cells in a dose-dependent manner. The obtained compounds from this study may be potential leads for PARP-1 inhibition in the treatment of cancer.
Bioactive Plant Compounds in Coffee Charcoal (Coffeae carbo) Extract Inhibit Cytokine Release from Activated Human THP-1 Macrophages
Authors: Schiller Laura , Hammoud Mahdi Dima , Jankuhn Steffen , Lipowicz Bartosz , Vissiennon Cica
Published: November 2019

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.
Semi-Synthetic Ingenol Derivative from Euphorbia tirucalli Inhibits Protein Kinase C Isotypes and Promotes Autophagy and S-Phase Arrest on Glioma Cell Lines
Authors: Silva Viviane Aline Oliveira , Rosa Marcela Nunes , Tansini Aline , Martinho Olga , Tanuri Amilcar , Evangelista Adriane Feijó , Cruvinel Carloni Adriana , Lima João Paulo , Pianowski Luiz Francisco , Reis Rui Manuel
Published: November 2019

The identification of signaling pathways that are involved in gliomagenesis is crucial for targeted therapy design. In this study we assessed the biological and therapeutic effect of ingenol-3-dodecanoate (IngC) on glioma. IngC exhibited dose-time-dependent cytotoxic effects on large panel of glioma cell lines (adult, pediatric cancer cells, and primary cultures), as well as, effectively reduced colonies formation. Nevertheless, it was not been able to attenuate cell migration, invasion, and promote apoptotic effects when administered alone. IngC exposure promoted S-phase arrest associated with p21CIP/WAF1 overexpression and regulated a broad range of signaling effectors related to survival and cell cycle regulation. Moreover, IngC led glioma cells to autophagy by LC3B-II accumulation and exhibited increased cytotoxic sensitivity when combined to a specific autophagic inhibitor, bafilomycin A1. In comparison with temozolomide, IngC showed a mean increase of 106-fold in efficacy, with no synergistic effect when they were both combined. When compared with a known compound of the same class, namely ingenol-3-angelate (I3A, Picato®), IngC showed a mean 9.46-fold higher efficacy. Furthermore, IngC acted as a potent inhibitor of protein kinase C (PKC) activity, an emerging therapeutic target in glioma cells, showing differential actions against various PKC isotypes. These findings identify IngC as a promising lead compound for the development of new cancer therapy and they may guide the search for additional PKC inhibitors.
Surface Morphology-Dependent Functionality of Titanium Dioxide–Nickel Oxide Nanocomposite Semiconductors
Authors: Liang Yuan-Chang , Xu Nian-Cih , Chiang Kai-Jen
Published: November 2019

In this study, TiO2–NiO heterostructures were synthesized by combining hydrothermal and chemical bath deposition methods. The post-annealing temperature was varied to control the surface features of the TiO2–NiO heterostructures. TiO2–NiO heterostructures annealed at 350 °C comprised NiO-nanosheet-decorated TiO2 nanostructures (NST), whereas those annealed at 500 °C comprised NiO-nanoparticle-decorated TiO2 nanostructures (NPT). The NPT exhibited higher photodegradation activity than the NST in terms of methylene blue (MB) degradation under irradiation. Structural analyses demonstrated that the NPT had a higher surface adsorption capability for MB dyes and superior light-harvesting ability; thus, they exhibited greater photodegradation ability toward MB dyes. In addition, the NST showed high gas-sensing responses compared with the NPT when exposed to acetone vapor. This result was attributable to the higher number of oxygen-deficient regions on the surfaces of the NST, which increased the amount of surface-chemisorbed oxygen species. This resulted in a relatively large resistance variation for the NST when exposed to acetone vapor.
N-Doped Carbon-Coated ZnS with Sulfur-Vacancy Defect for Enhanced Photocatalytic Activity in the Visible Light Region
Authors: Peng Hao , Liu Daixin , Zheng Xiaogang , Fu Xiaojin
Published: November 2019

In this work, N-doped carbon-coated ZnS with a sulfur-vacancy defect (ZnS@N-C) was performed for the visible-light-driven photodegradation of tetracycline hydrochloride (TCH). The obtained ZnS@N-C exhibited enhanced photocatalytic activity compared with ZnS for TCH removal. Among these ZnS@N-C composites, ZnS@N-C-3 with N-doped content of 3.01% (100 nm) presented the best visible-light photocatalytic activity and superior long-term photocatalytic stability after five cycle times for TCH removal in the visible light region. This may be ascribed to the interface between the N-doped carbon shell and ZnS with a sulfur-vacancy defect for efficient charge transfer and the restrained recombination of charge carriers. Electron spin resonance (ESR) results indicate that the ·O2‒ radical plays a crucial role in the enhanced photocatalytic activity of ZnS@N-C-3.
Oriented Cell Alignment Induced by a Nanostructured Titanium Surface Enhances Expression of Cell Differentiation Markers
Authors: Llopis-Grimalt Maria Antonia , Amengual-Tugores Andreu Miquel , Monjo Marta , Ramis Joana Maria
Published: November 2019

A key factor for dental implant success is a good sealing between the implant surface and both soft (gum) and hard (bone) tissues. Surface nanotopography can modulate cell response through mechanotransduction. The main objective of this research was the development of nanostructured titanium (Ti) surfaces that promote both soft and hard tissue integration with potential application in dental implants. Nanostructured Ti surfaces were developed by electrochemical anodization—nanopores (NPs) and nanonets (NNs)—and characterized by atomic force microscopy, scanning electronic microscopy, and contact angle analysis. In addition, nanoparticle release and apoptosis activation were analyzed on cell culture. NP surfaces showed nanoparticle release, which increased in vitro cell apoptosis. Primary human gingival fibroblasts (hGFs) and human bone marrow mesenchymal stem cells (hBM-MSCs) were used to test cell adhesion, cytotoxicity, metabolic activity, and differentiation markers. Finally, cell orientation on the different surfaces was analyzed using a phalloidin staining. NN surfaces induced an oriented alignment of both cell types, leading in turn to an improved expression of differentiation markers. Our results suggest that NN structuration of Ti surfaces has great potential to be used for dental implant abutments to improve both soft and hard tissue integration.
Nanomaterials towards Biosensing of Alzheimer’s Disease Biomarkers
Authors: Carneiro Pedro , Morais Simone , Pereira Maria Carmo
Published: November 2019

Alzheimer’s disease (AD) is an incurable and highly debilitating condition characterized by the progressive degeneration and/or death of nerve cells, which leads to manifestation of disabilities in cognitive functioning. In recent years, the development of biosensors for determination of AD’s main biomarkers has made remarkable progress, particularly based on the tremendous advances in nanoscience and nanotechnology. The unique and outstanding properties of nanomaterials (such as graphene, carbon nanotubes, gold, silver and magnetic nanoparticles, polymers and quantum dots) have been contributing to enhance the electrochemical and optical behavior of transducers while offering a suitable matrix for the immobilization of biological recognition elements. Therefore, optical and electrochemical immuno- and DNA-biosensors with higher sensitivity, selectivity and longer stability have been reported. Nevertheless, strategies based on the detection of multiple analytes still need to be improved, as they will play a crucial role in minimizing misdiagnosis. This review aims to provide insights into the conjugation of nanomaterials with different transducers highlighting their crucial role in the construction of biosensors for detection of AD main biomarkers.
Natural Antibacterial Reagents (Centella, Propolis, and Hinokitiol) Loaded into Poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] Composite Nanofibers for Biomedical Applications
Authors: Rebia Rina Afiani , binti Sadon Nurul Shaheera , Tanaka Toshihisa
Published: November 2019

Centella asiatica, propolis, and hinokitiol, as natural antibacterial reagents, were integrated into the poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] (PHBH) polymer to produce antibacterial wound dressings, using electrospinning process. The results showed that the fiber diameters and surface morphology of PHBH composite nanofibers were influenced by the addition of ethanol–centella (EC), methanol–centella (MC), ethanol–propolis (EP), and ethanol–hinokitiol (EH) at various ratios compared to pristine PHBH nanofibers. From FT-IR, the nanofibrous samples with higher contents of natural antibacterial substances showed the peaks of carboxylic acid, aromatic ring, and tropolone carbon ring from centella, propolis, and hinokitiol, respectively. Furthermore, the tensile strength of neat PHBH nanofibers was increased from 8.00 ± 0.71 MPa up to 16.35 ± 1.78 MPa by loading of propolis (EP) 7% into PHBH. X-ray analysis explained that the loading of propolis (EP) was also able to increase the crystallinity in PHBH composite nanofibers from 47.0% to 54.5%. The antibacterial results demonstrated that PHBH composite nanofibers containing natural antibacterial products were potent inhibitors against the growth of Escherichia coli and Staphylococcus aureus, amongst them hinokitiol and propolis proved to be the most effective. Additionally, the release studies displayed that centella and hinokitiol had faster release from PHBH composite nanofibers in comparison to propolis.
Self-Propelled Janus Microdimer Swimmers under a Rotating Magnetic Field
Authors: Yu Shimin , Ma Ningze , Yu Hao , Sun Haoran , Chang Xiaocong , Wu Zhiguang , Deng Jiaxuan , Zhao Shuqi , Wang Wuyi , Zhang Guangyu , Zhang Weiwei , Zhao Qingsong , Li Tianlong
Published: November 2019

Recent strides in micro- and nanofabrication technology have enabled researchers to design and develop new micro- and nanorobots for biomedicine and environmental monitoring. Due to its non-invasive remote actuation and convenient navigation abilities, magnetic propulsion has been widely used in micro- and nanoscale robotic systems. In this article, a highly efficient Janus microdimer swimmer propelled by a rotating uniform magnetic field was investigated experimentally and numerically. The velocity of the Janus microdimer swimmer can be modulated by adjusting the magnetic field frequency with a maximum speed of 133 μm·s−1 (≈13.3 body length s−1) at the frequency of 32 Hz. Fast and accurate navigation of these Janus microdimer swimmers in complex environments and near obstacles was also demonstrated. This efficient propulsion behavior of the new Janus microdimer swimmer holds considerable promise for diverse future practical applications ranging from nanoscale manipulation and assembly to nanomedicine.
The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-κB Activation
Authors: Carpi Sara , Scoditti Egeria , Massaro Marika , Polini Beatrice , Manera Clementina , Digiacomo Maria , Esposito Salsano Jasmine , Poli Giulio , Tuccinardi Tiziano , Doccini Stefano , Santorelli Filippo Maria , Carluccio Maria Annunziata , Macchia Marco , Wabitsch Martin , De Caterina Raffaele , Nieri Paola
Published: November 2019

Inflammation of the adipose tissue plays an important role in the development of several chronic diseases associated with obesity. Polyphenols of extra virgin olive oil (EVOO), such as the secoiridoids oleocanthal (OC) and oleacein (OA), have many nutraceutical proprieties. However, their roles in obesity-associated adipocyte inflammation, the NF-κB pathway and related sub-networks have not been fully elucidated. Here, we investigated impact of OC and OA on the activation of NF-κB and the expression of molecules associated with inflammatory and dysmetabolic responses. To this aim, fully differentiated Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were pre-treated with OC or OA before stimulation with TNF-α. EVOO polyphenols significantly reduced the expression of genes implicated in adipocyte inflammation (IL-1β, COX-2), angiogenesis (VEGF/KDR, MMP-2), oxidative stress (NADPH oxidase), antioxidant enzymes (SOD and GPX), leukocytes chemotaxis and infiltration (MCP-1, CXCL-10, MCS-F), and improved the expression of the anti-inflammatory/metabolic effector PPARγ. Accordingly, miR-155-5p, miR-34a-5p and let-7c-5p, tightly connected with the NF-κB pathway, were deregulated by TNF-α in both cells and exosomes. The miRNA modulation and NF-κB activation by TNF-α was significantly counteracted by EVOO polyphenols. Computational studies suggested a potential direct interaction between OC and NF-κB at the basis of its activity. This study demonstrates that OC and OA counteract adipocyte inflammation attenuating NF-κB activation. Therefore, these compounds could be novel dietary tools for the prevention of inflammatory diseases associated with obesity.
Home Cooking and Child Obesity in Japan: Results from the A-CHILD Study
Authors: Tani Yukako , Fujiwara Takeo , Doi Satomi , Isumi Aya
Published: November 2019

This study aimed to investigate the association between the frequency of home cooking and obesity among children in Japan. We used cross-sectional data from the Adachi Child Health Impact of Living Difficulty study, a population-based sample targeting all fourth-grade students aged 9 to 10 in Adachi City, Tokyo, Japan. Frequency of home cooking was assessed by a questionnaire for 4258 caregivers and classified as high (almost every day), medium (4–5 days/week), or low (≤3 days/week). School health checkup data on height and weight were used to calculate body mass index z-scores. Overall, 2.4% and 10.8% of children were exposed to low and medium frequencies of home cooking, respectively. After adjusting for confounding factors, children with a low frequency of home cooking were 2.27 times (95% confidence interval: 1.16–4.45) more likely to be obese, compared with those with a high frequency of home cooking. After adjustment for children’s obesity-related eating behaviors (frequency of vegetable and breakfast intake and snacking habits) as potential mediating factors, the relative risk ratio of obesity became statistically non-significant (1.90; 95% confidence interval: 0.95–3.82). A low frequency of home cooking is associated with obesity among children in Japan, and this link may be explained by unhealthy eating behaviors.
Thirst and Drinking Paradigms: Evolution from Single Factor Effects to Brainwide Dynamic Networks
Authors: Armstrong Lawrence E. , Kavouras Stavros A.
Published: November 2019

The motivation to seek and consume water is an essential component of human fluid–electrolyte homeostasis, optimal function, and health. This review describes the evolution of concepts regarding thirst and drinking behavior, made possible by magnetic resonance imaging, animal models, and novel laboratory techniques. The earliest thirst paradigms focused on single factors such as dry mouth and loss of water from tissues. By the end of the 19th century, physiologists proposed a thirst center in the brain that was verified in animals 60 years later. During the early- and mid-1900s, the influences of gastric distention, neuroendocrine responses, circulatory properties (i.e., blood pressure, volume, concentration), and the distinct effects of intracellular dehydration and extracellular hypovolemia were recognized. The majority of these studies relied on animal models and laboratory methods such as microinjection or lesioning/oblation of specific brain loci. Following a quarter century (1994–2019) of human brain imaging, current research focuses on networks of networks, with thirst and satiety conceived as hemispheric waves of neuronal activations that traverse the brain in milliseconds. Novel technologies such as chemogenetics, optogenetics, and neuropixel microelectrode arrays reveal the dynamic complexity of human thirst, as well as the roles of motivation and learning in drinking behavior.
The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-Ay Mice
Authors: Chen Liping , Takatani Naoki , Beppu Fumiaki , Miyashita Kazuo , Hosokawa Masashi
Published: November 2019

n-3 Polyunsaturated fatty acid binding phospholipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-Ay mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-Ay mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic lipid content was markedly alleviated depending on the neutral lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a functional lipid for reducing serum and liver lipids and is able to supply n-3 PUFAs to KK-Ay mice.