bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Synthesis of Carbon Hybrid Materials Containing Oligothiophene Dyes
Authors: Kamedulski Piotr , Gauden Piotr A. , Lukaszewicz Jerzy P. , Ilnicka Anna
Published: October 2019

This paper shows the first study of the synthesis of hybrid materials consisting of commercial Norit carbons and oligothiophenes. The study presents the influence of surface oxidation on dye deposition as well as changes of pore structure and surface chemistry. The hybrid materials were characterised using Raman spectroscopy, and scanning and transmission electron microscopy (SEM and HR-TEM, respectively). Confocal microscopy was employed to confirm the immobilization of oligomers on the surface of the carbons being investigated. Confocal microscopy measurements were additionally used to indicate whether dye molecules covered the entire surface of the selected commercial Norit samples. Specific surface area and pore structure parameters were determined by low-temperature nitrogen adsorption. Additionally, elemental content and surface chemistry were characterised by means of X-ray photoelectron spectroscopy (XPS) and combustion elemental analysis. Experimental results confirmed that oligothiophene dyes were adsorbed onto the internal part of the investigated pores of the carbon materials. The pores were assumed to have a slit-like shape, a set of 82 local adsorption isotherms was modelled for pores from 0.465 nm to 224 nm. Further, XPS data showed promising qualitative results regarding the surface characteristics and chemical composition of the hybrid materials obtained (sulphur content ranged from 1.40 to 1.45 at%). It was shown that the surface chemistry of activated carbon plays a key role in the dye deposition process. High surface heterogeneity after hydrothermal oxidation did not improve dye adsorption due to specific interactions between surface oxygen moieties and local electric charges in the oligothiophene molecules.
Mechanism Understanding of the Role of Rare Earth Inclusions in the Initial Marine Corrosion Process of Microalloyed Steels
Authors: Tang Meng , Wu Kaiming , Liu Jing , Cheng Lin , Zhang Xian , Chen Yan
Published: October 2019

In this study, the corrosion behavior of rare earth (RE) microalloyed steels was first evaluated through potentiodynamic polarization tests and corrosion weight loss experiments, and then the corrosion morphologies were observed by scanning electron microscope (SEM). After immersion in a NaCl solution, the sulfides (or oxygen sulfides) dissolved preferentially, followed by corrosion at the boundary between the Fe matrix and oxides. Afterwards, the inclusions fell off as a whole, which promoted pitting nucleation. The first principle modeling demonstrated that the work functions of various kinds of inclusions descended in the following order: La2Zr2O7 > LaAlO3 > (La2O3 ≈ Fe ≈ La2O2S) > La2S3, which provided a theoretical explanation to the dissolution behaviors of inclusions. That is, inclusions containing sulfur tend to dissolve preferentially, whereas the oxides do not dissolve easily. Subsequently, the surface current distributions were detected by the scanning vibrating electrode technique (SVET), which provided more microscopic insight into the role of inclusions in the corrosion propagation. Results showed that the active sites of pitting nucleation accelerated the transverse propagation of corrosion. Finally, local corrosion spread to the whole surface as uniform corrosion.
Laser Annealing of P and Al Implanted 4H-SiC Epitaxial Layers
Authors: Calabretta Cristiano , Agati Marta , Zimbone Massimo , Boninelli Simona , Castiello Andrea , Pecora Alessandro , Fortunato Guglielmo , Calcagno Lucia , Torrisi Lorenzo , La Via Francesco
Published: October 2019

This work describes the development of a new method for ion implantation induced crystal damage recovery using multiple XeCl (308 nm) laser pulses with a duration of 30 ns. Experimental activity was carried on single phosphorus (P) as well as double phosphorus and aluminum (Al) implanted 4H-SiC epitaxial layers. Samples were then characterized through micro-Raman spectroscopy, Photoluminescence (PL) and Transmission Electron Microscopy (TEM) and results were compared with those coming from P implanted thermally annealed samples at 1650–1700–1750 °C for 1 h as well as P and Al implanted samples annealed at 1650 °C for 30 min. The activity outcome shows that laser annealing allows to achieve full crystal recovery in the energy density range between 0.50 and 0.60 J/cm2. Moreover, laser treated crystal shows an almost stress-free lattice with respect to thermally annealed samples that are characterized by high point and extended defects concentration. Laser annealing process, instead, allows to strongly reduce carbon vacancy (VC) concentration in the implanted area and to avoid intra-bandgap carrier recombination centres. Implanted area was almost preserved, except for some surface oxidation processes due to oxygen leakage inside the testing chamber. However, the results of this experimental activity gives way to laser annealing process viability for damage recovery and dopant activation inside the implanted area.
Evaluation of Nano-Mechanical Behavior on Flax Fiber Metal Laminates Using an Atomic Force Microscope
Authors: Qu Zehua , Pan Xiaoxia , Hu Xiaoyue , Guo Yichun , Shen Yiou
Published: October 2019

The application of plant fiber-reinforced composite (PFRC) is limited due to its relatively low mechanical properties. The hybridization of a thin metal layer with plant fiber into a fiber metal laminate can largely improve the mechanical performance and the brittle fracture behavior of PFRC. However, both plant fiber and metal have difficulty bonding with the polymer matrix. In this paper, several different surface treatment methods were applied on Al alloy sheets, and the influence of surface treatments on the surface morphology and nano-mechanical properties of Al alloy were studied using an atomic force microscope (AFM). After the preparation of flax fiber–metal laminates (FFMLs) with a vacuum-assisted resin transfer molding (VARTM) technique, the nanomechanical properties of different modified FFMLs were also evaluated with an AFM. It was found that the surface treatment combination of the sulfuric acid-ferric sulfate-based treatment (P2 etching) and the silane coupling agent provided the best adhesion force and modulus for Al alloy sheets at nanoscale resolution, which contributed to the surface energy increasing and strong covalent bonds between metal and polymer matrix. The resulting manufactured FFMLs also exhibited the highest nano-mechanical properties due to the great improvement of interfacial properties between metal and matrix, which was caused by mechanical interlocking mechanism and covalent bonds between metal/fiber and resin. Macromechanical performance, including tensile and flexural properties of these modified FFMLs, was also investigated. Comparison of the modulus at the nanoscale and macroscale showed reasonable agreement, and it revealed the tough interlaminar mechanisms of these types of FFMLs.
Influence of the Presence of Different Alkali Cations and the Amount of Fe(CN)6 Vacancies on CO2 Adsorption on Copper Hexacyanoferrates
Authors: Svensson Gunnar , Grins Jekabs , Eklöf Daniel , Eriksson Lars , Wardecki Darius , Thoral Clara , Bodoignet Loic
Published: October 2019

The CO2 adsorption on various Prussian blue analogue hexacyanoferrates was evaluated by thermogravimetric analysis. Compositions of prepared phases were verified by energy-dispersive X-ray spectroscopy, infra-red spectroscopy and powder X-ray diffraction. The influence of different alkali cations in the cubic Fm3m structures was investigated for nominal compositions A2/3Cu[Fe(CN)6]2/3 with A = vacant, Li, Na, K, Rb, Cs. The Rb and Cs compounds show the highest CO2 adsorption per unit cell, ~3.3 molecules of CO2 at 20 °C and 1 bar, while in terms of mmol/g the Na compound exhibits the highest adsorption capability, ~3.8 mmol/g at 20 °C and 1 bar. The fastest adsorption/desorption is exhibited by the A-cation free compound and the Li compound. The influence of the amount of Fe(CN)6 vacancies were assessed by determining the CO2 adsorption capabilities of Cu[Fe(CN)6]1/2 (Fm3m symmetry, nominally 50% vacancies), KCu[Fe(CN)6]3/4 (Fm3m symmetry, nominally 25% vacancies), and CsCu[Fe(CN)6] (I-4m2 symmetry, nominally 0% vacancies). Higher adsorption was, as expected, shown on compounds with higher vacancy concentrations.
Some Implicativities for Groupoids and BCK-Algebras
Authors: Hwang In Ho , Kim Hee Sik , Neggers Joseph
Published: October 2019

In this paper, we generalize the notion of an implicativity discussed in B C K -algebras, and apply it to some groupoids and B C K -algebras. We obtain some relations among those axioms in the theory of groupoids.
Optimal Control of a PDE Model of an Invasive Species in a River
Authors: Pettit Rebecca , Lenhart Suzanne
Published: October 2019

Managing invasive species in rivers can be assisted by appropriate adjustment of flow rates. Using a partial differential equation (PDE) model representing an invasive population in a river, we investigate controlling the water discharge rate as a management strategy. Our goal is to see how controlling the water discharge rate will affect the invasive population, and more specifically how water discharges may force the invasive population downstream. We complete the analysis of a flow control problem, which seeks to minimize the invasive population upstream while minimizing the cost of this management. Using an optimality system, consisting of our population PDE, an adjoint PDE, and corresponding optimal control characterization, we illustrate some numerical simulations in which parameters are varied to determine how far upstream the invasive population reaches. We also change the river’s cross-sectional area to investigate its impact on the optimal control.
Direct-Acting Oral Anticoagulants and Their Reversal Agents—An Update
Authors: Kustos Stephanie , Fasinu Pius
Published: October 2019

Background: Over the last ten years, a new class of drugs, known as the direct-acting oral anticoagulants (DOACs), have emerged at the forefront of anticoagulation therapy. Like the older generation anticoagulants, DOACs require specific reversal agents in cases of life-threatening bleeding or the need for high-risk surgery. Methods: Published literature was searched, and information extracted to provide an update on DOACS and their reversal agents. Results: The DOACs include the direct thrombin inhibitor—dabigatran, and the factor Xa inhibitors—rivaroxaban, apixaban, edoxaban, and betrixaban. These DOACs all have a rapid onset of action and each has a predictable therapeutic response requiring no monitoring, unlike the older anticoagulants, such as warfarin. Two reversal agents have been approved within the last five years: idarucizumab for the reversal of dabigatran, and andexanet alfa for the reversal of rivaroxaban and apixaban. Additionally, ciraparantag, a potential “universal” reversal agent, is currently under clinical development. Conclusions: A new generation of anticoagulants, the DOACs, and their reversal agents, are gaining prominence in clinical practice, having demonstrated superior efficacy and safety profiles. They are poised to replace traditional anticoagulants including warfarin.
Metabolite Changes in an Estuarine Annelid Following Sublethal Exposure to a Mixture of Zinc and Boscalid
Authors: Sinclair Georgia M. , O’Brien Allyson L. , Keough Michael , de Souza David P. , Dayalan Saravanan , Kanojia Komal , Kouremenos Konstantinos , Tull Dedreia L. , Coleman Rhys A. , Jones Oliver A.H. , Long Sara M.
Published: October 2019

Environmental pollutants such as heavy metals and fungicides pose a serious threat to waterways worldwide. Toxicological assessment of such contaminants is usually conducted using single compound exposures, as it is challenging to understand the effect of mixtures on biota using standard ecotoxicological methods; whereas complex chemical mixtures are more probable in ecosystems. This study exposed Simplisetia aequisetis (an estuarine annelid) to sublethal concentrations of a metal (zinc) and a fungicide (boscalid), both singly and as a mixture, for two weeks. Metabolomic analysis via gas and liquid chromatography-mass spectrometry was used to measure the stress response(s) of the organism following exposure. A total of 75 metabolites, including compounds contributing to the tricarboxylic acid cycle, the urea cycle, and a number of other pathways, were identified and quantified. The multiplatform approach identified distinct metabolomic responses to each compound that differed depending on whether the substance was presented singly or as a mixture, indicating a possible antagonistic effect. The study demonstrates that metabolomics is able to elucidate the effects and mode of action of contaminants and can identify possible outcomes faster than standard ecotoxicological endpoints, such as growth and reproduction. Metabolomics therefore has a possible future role in biomonitoring and ecosystem health assessments.
A Frequency Up-Converted Hybrid Energy Harvester Using Transverse Impact-Driven Piezoelectric Bimorph for Human-Limb Motion
Authors: Halim Miah Abdul , Kabir M. Humayun , Cho Hyunok , Park Jae Yeong
Published: October 2019

Energy harvesting from human-body-induced motion is mostly challenging due to the low-frequency, high-amplitude nature of the motion, which makes the use of conventional cantilevered spring-mass oscillators unrealizable. Frequency up-conversion by mechanical impact is an effective way to overcome the challenge. However, direct impact on the transducer element (especially, piezoelectric) increases the risk of damaging it and raises questions on the reliability of the energy harvester. In order to overcome this shortcoming, we proposed a transverse mechanical impact driven frequency up-converted hybrid energy harvester for human-limb motion. It utilizes the integration of both piezoelectric and electromagnetic transducers in a given size that allows more energy to be harvested from a single mechanical motion, which, in turn, further improves the power density. While excited by human-limb motion, a freely-movable non-magnetic sphere exerts transverse impact by periodically sliding over a seismic mass attached to a double-clamped piezoelectric bimorph beam. This allows the beam to vibrate at its resonant frequency and generates power by means of the piezoelectric effect. A magnet attached to the beam also takes part in generating power by inducing voltage in a coil adjacent to it. A mathematical model has been developed and experimentally corroborated. At a periodic limb-motion of 5.2 Hz, maximum 93 µW and 61 µW average powers (overall 8 µW·cm−3 average power density) were generated by the piezoelectric and the electromagnetic transducers, respectively. Moreover, the prototype successfully demonstrated the application of low-power electronics via suitable AC-DC converters.
Differential Distribution and Determinants of Ammonia Oxidizing Archaea Sublineages in the Oxygen Minimum Zone off Costa Rica
Authors: Lu Yanhong , Xia Xiaomin , Cheung Shunyan , Jing Hongmei , Liu Hongbin
Published: October 2019

Ammonia oxidizing archaea (AOA) are microbes that are widely distributed in the ocean that convert ammonia to nitrite for energy acquisition in the presence of oxygen. Recent study has unraveled highly diverse sublineages within the previously defined AOA ecotypes (i.e., water column A (WCA) and water column B (WCB)), although the eco-physiology and environmental determinants of WCB subclades remain largely unclear. In this study, we examined the AOA communities along the water columns (40–3000 m depth) in the Costa Rica Dome (CRD) upwelling region in the eastern tropical North Pacific Ocean. Highly diverse AOA communities that were significantly different from those in oxygenated water layers were observed in the core layer of the oxygen minimum zone (OMZ), where the dissolved oxygen (DO) concentration was < 2μM. Moreover, a number of AOA phylotypes were found to be enriched in the OMZ core. Most of them were negatively correlated with DO and were also detected in other OMZs in the Arabian Sea and Gulf of California, which suggests low oxygen adaptation. This study provided the first insight into the differential niche partitioning and environmental determinants of various subclades within the ecotype WCB. Our results indicated that the ecotype WCB did indeed consist of various sublineages with different eco-physiologies, which should be further explored.
Biomineralization of Monohydrocalcite Induced by the Halophile Halomonas Smyrnensis WMS-3
Authors: Pan Juntong , Zhao Hui , Tucker Maurice , Zhou Jingxuan , Jiang Mengzhen , Wang Yapeng , Zhao Yanyang , Sun Bin , Han Zuozhen , Yan Huaxiao
Published: October 2019

The halophilic bacterium Halomonas smyrnensis from a modern salt lake used in experiments to induce biomineralization has resulted in the precipitation of monohydrocalcite and other carbonate minerals. In this study, a Halomonas smyrnensis WMS-3 (GenBank:MH425323) strain was identified based on 16S rDNA homology comparison, and then cultured in mediums with 3% NaCl concentration to induce monohydrocalcite at different Mg/Ca molar ratios of 0, 2, 5, 7, and 9. The growth curve of WMS-3 bacteria, pH values, NH4+ concentration, HCO3− and CO32− concentration, carbonic anhydrase (CA) activity, and the changes in Ca2+ and Mg2+ ion concentration were determined to further explore the extracellular biomineralization mechanism. Moreover, the nucleation mechanism of monohydrocalcite on extracellular polymeric substances (EPS) was analyzed through studying ultrathin slices of the WMS-3 strain by High resolution transmission electron microscopy (HRTEM), Selected area election diffraction (SAED), Scanning transmission electron microscopy (STEM), and elemental mapping, besides this, amino acids in the EPS were also analyzed. The results show that pH increased to about 9.0 under the influence of ammonia and CA activity. The precipitation ratio (%, the ratio of the mass/volume concentration) of the Ca2+ ion was 64.32%, 62.20%, 60.22%, 59.57%, and 54.42% at Mg/Ca molar ratios of 0, 2, 5, 7, and 9, respectively, on the 21st day of the experiments, and 6.69%, 7.10%, 7.74%, 8.09% for the Mg2+ ion concentration at Mg/Ca molar ratios 2, 5, 7, and 9, respectively. The obtained minerals were calcite, Mg-rich calcite, aragonite, and hydromagnesite, in addition to the monohydrocalcite, as identified by X-ray diffraction (XRD) analyses. Monohydrocalcite had higher crystallinity when the Mg/Ca ratio increased from 7 to 9; thus, the stability of monohydrocalcite increased, also proven by the thermogravimetry (TG), derivative thermogravimetry (DTG) and differential scanning calorimetry (DSC) analyses. The C=O and C–O–C organic functional groups present in/on the minerals analyzed by Fourier transform infrared spectroscopy (FTIR), the various morphologies and the existence of P and S determined by scanning electron microscope-energy dispersive spectrometer (SEM-EDS), the relatively more negative stable carbon isotope values (−16.91‰ to −17.91‰) analyzed by a carbon isotope laser spectrometer, plus the typical surface chemistry by XPS, all support the biogenesis of these mineral precipitates. Moreover, Ca2+ ions were able to enter the bacterial cell to induce intracellular biomineralization. This study is useful to understand the mechanism of biomineralization further and may provide theoretical reference concerning the formation of monohydrocalcite in nature.
The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity
Authors: Tałałaj Urszula , Uścinowicz Paulina , Bruzgo Irena , Surażyński Arkadiusz , Zaręba Ilona , Markowska Agnieszka
Published: October 2019

KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series of novel pentapeptides, analogues of KTTKS with the general formula X-KTTKS-OH(NH2), where X = acetyl, lipoyl, palmitoyl residues, was designed and synthesized. Their effect on amidolytic activity of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein were tested. Cytotoxic tests on fibroblasts, as well as collagen and DNA biosynthesis tests for selected peptides, were also carried out. The test results showed that the most active plasmin inhibitors were palmitoyl peptides, whether in acid or amide form. No biological effects of lysine modification to arginine in the synthesized peptides were found. None of the synthesized peptides was not cytotoxic on fibroblasts, and three of them showed cell growth. These three compounds showed no concentration-activity relationship in the collagen and DNA biosynthesis assays.
PI3K–AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model
Authors: Cao Li-Hua , Qiao Jing-Yi , Huang Hui-Yuan , Fang Xiao-Yan , Zhang Rui , Miao Ming-San , Li Xiu-Min
Published: October 2019

Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K–AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E2), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K–AKT pathway-related proteins.
Unambiguous Characterization of p-Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease
Authors: Paroni Rita , Casati Silvana , Dei Cas Michele , Bignotto Monica , Rubino Federico Maria , Ciuffreda Pierangela
Published: October 2019

p-Cresyl sulfate is one of the bound uremic toxins whose level increases in the sera of patients with the severity of chronic kidney disease and is therefore used as a standard for clinical investigations. Our first attempts to obtain p-cresyl sulfate led exclusively to the product of sulfonation of the aromatic ring instead of sulfation on the OH moiety. Nevertheless, this initial discouraging result allowed us to handle both p-cresyl sulfate and 2-hydroxy-5-methylbenzenesulfonic acid obtained by different synthetic pathways. Interestingly, the comparison between the two isomers pointed out that the two molecules show the same fragmentation pattern and are indistinguishable by mass spectrometry. They cannot be separated on several commercially available columns. The only difference between the two compounds is a 10-fold higher ionization yield under negative ion electrospray ionization. NMR spectral studies definitely confirmed the different molecular structures. We present here an unambiguous biomimetic synthetic route for p-cresyl sulfate and the spectroscopic characterization of both the compounds by nuclear magnetic resonance and mass spectrometry.
6-Shogaol Inhibits Advanced Glycation End-Products-Induced IL-6 and ICAM-1 Expression by Regulating Oxidative Responses in Human Gingival Fibroblasts
Authors: Nonaka Kohei , Bando Mika , Sakamoto Eijiro , Inagaki Yuji , Naruishi Koji , Yumoto Hiromichi , Kido Jun-ichi
Published: October 2019

Advanced glycation end-products (AGEs) cause diabetes mellitus (DM) complications and accumulate more highly in periodontal tissues of patients with periodontitis and DM. AGEs aggravate periodontitis with DM by increasing the expression of inflammation-related factors in periodontal tissues. 6-Shogaol, a major compound in ginger, has anti-inflammatory and anti-oxidative activities. However, the influence of shogaol on DM-associated periodontitis is not well known. In this study, the effects of 6-shogaol on AGEs-induced oxidative and anti-oxidative responses, and IL-6 and ICAM-1 expression in human gingival fibroblasts (HGFs) were investigated. When HGFs were cultured with 6-shogaol and AGEs, the activities of reactive oxygen species (ROS) and antioxidant enzymes (heme oxygenase-1 [HO-1] and NAD(P)H quinone dehydrogenase 1 [NQO1]), and IL-6 and ICAM-1 expressions were investigated. RAGE expression and phosphorylation of MAPKs and NF-κB were examined by western blotting. 6-Shogaol significantly inhibited AGEs-induced ROS activity, and increased HO-1 and NQO1 levels compared with the AGEs-treated cells. The AGEs-stimulated expression levels of receptor of AGE (RAGE), IL-6 and ICAM-1 and the phosphorylation of p38, ERK and p65 were attenuated by 6-shogaol. These results suggested that 6-shogaol inhibits AGEs-induced inflammatory responses by regulating oxidative and anti-oxidative activities and may have protective effects on periodontitis with DM.
Insulin Hot-Spot Analogs Formed with N-Methylated Amino Acid Residues Inhibit Aggregation of Native Hormone
Authors: Swiontek Monika , Wasko Joanna , Fraczyk Justyna , Galecki Krystian , Kaminski Zbigniew J. , Kolesinska Beata
Published: October 2019

In this study, N-methylated analogs of hot-spots of insulin were designed and synthesized, in the expectation that they would inhibit the aggregation of both insulin hot-spots and the entire hormone. Synthesis of insulin “amyloidogenic” analogs containing N-methylated amino acid residues was performed by microwave-assisted solid phase according to the Fmoc/tert-Bu strategy. As a coupling reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO-) was used. Three independent methods were applied in aggregation studies of the complexes of insulin with its N-methylated peptides. Additionally, circular dichroism (CD) measurements were used to confirm that aggregation processes did not occur in the presence of the N-methylated analogs of hot-spot insulin fragments, and that insulin retains its native conformation. Of the seven N-methylated analogs of the A- and B-chain hot-spots of insulin, six inhibited insulin aggregation (peptides 1 and 3–7). All tested peptides were found to have a lower ability to inhibit the aggregation of insulin hot-spots compared to the capability to inhibit native hormone aggregation.
Aristolochic Acid Affects Upper Tract Urothelial Cancer Behavior through the MAPK Pathway
Authors: Chen I-Hsuan , Luo Hao-Lun , Su Yu-Li , Huang Chun-Chieh , Chiang Po-Hui , Yu Chia-Cheng , Lee Nai-Lun , Lin Jen-Jie , Sung Ming-Tse
Published: October 2019

The prevalence of upper tract urothelial carcinoma (UTUC) in Taiwan is relatively higher than thatin Western countries. Aristolochic acid (AA), which is widely used in traditional Chinese herbology, is now recognized to be one of the carcinogens for UTUC. Numerous UTUC patients have chronic kidney diseases or end-stage renal diseases; however, little literature hasreported on theoncogenic pathway of AA-related UTUC. The aim of our study was to identify the potential target treatment for AA-related UTUC. Here, we established an AA pre-exposure followed bya 3-methylcholanthrene (MCA) stimulus tumorigenic cell model. We not only demonstrated that AA pre-exposure MCA stimulus tumorigenic cells have more behaviors of cell migration and invasion by enhancing the metalloproteinases (MMP) activity, which is compatible with clinical findings of AA-related UTUC, but we also validated that AA pre-exposure MCA stimulus tumorigeniccells could be activated through the mitogen-activated protein kinases (MAPK) pathway. We further dissected the route of the MAPK pathway and found that the p38 and extracellular signal regulated kinases (ERK) sub-pathways might play essential roles in AA pre-exposure urothelial cancer cell lines. This consequence was also corroborated with a tissue study in AA-exposed patients.
A New Alkylation of Aryl Alcohols by Boron Trifluoride Etherate
Authors: Jumbam Ndze Denis , Maganga Yamkela , Masamba Wayiza , Mbunye Nomthandazo I. , Mgoqi Esethu , Mtwa Sphumusa
Published: October 2019

The ethylation of aryl alcohols by an ethyl moiety of boron trifluoride etherate is described. The reaction proceeded cleanly and afforded good yields of the corresponding aryl ethyl ethers. It tolerated the presence of functional groups such as aryl, alkyl, halogens, nitro, nitrile, and amino. However, the presence of amino or nitro groups ortho to a hydroxyl group of an aryl compound drastically reduced the yields of the anticipated products due to the chelation of the aforementioned functional groups with boron trifluoride etherate. A nitrogen atom in the aromatic ring system, as exemplified by hydroxypyridine and 8-hydroxyquinoline, completely inhibited the reaction. Resorcinol, hydroquinone, and aryl alcohols with aldehyde functions decomposed under the reaction conditions.
Nitric Oxide Donor DETA/NO Inhibits the Growth of Endometrial Cancer Cells by Upregulating the Expression of RASSF1 and CDKN1A
Authors: Waheed Sana , Cheng Robert YS , Casablanca Yovanni , Maxwell G. Larry , Wink David A , Syed Viqar
Published: October 2019

Nitric oxide (NO) is implicated in several biological processes, including cancer progression. At low concentrations, it promotes cell survival and tumor progression, and at high concentrations it causes apoptosis and cell death. Until now, the impact of NO donors has not been investigated on human endometrial tumors. Four cancer cell lines were exposed to different concentrations of DETA/NO for 24 to 120 h. The effects of DETA/NO on cell proliferation and invasion were determined utilizing MTS and Boyden chamber assays, respectively. The DETA/NO induced a dose and time-dependent reduction in cell viability by the activation of caspase-3 and cell cycle arrest at the G0/G1 phase that was associated with the attenuated expression of cyclin-D1 and D3. Furthermore, the reduction in the amount of CD133-expressing cancer stem-like cell subpopulation was observed following DETA/NO treatment of cells, which was associated with a decreased expression of stem cell markers and attenuation of cell invasiveness. To understand the mechanisms by which DETA/NO elicits anti-cancer effects, RNA sequencing (RNA-seq) was used to ascertain alterations in the transcriptomes of human endometrial cancer cells. RNA-seq analysis revealed that 14 of the top 21 differentially expressed genes were upregulated and seven were downregulated in endometrial cancer cells with DETA/NO. The genes that were upregulated in all four cell lines with DETA/NO were the tumor suppressors Ras association domain family 1 isoform A (RASSF1) and Cyclin-dependent kinase inhibitor 1A (CDKN1A). The expression patterns of these genes were confirmed by Western blotting. Taken together, the results provide the first evidence in support of the anti-cancer effects of DETA/NO in endometrial cancer.
Evaluation of Chemical Composition of Two Linseed Varieties as Sources of Health-Beneficial Substances
Authors: Tavarini Silvia , Castagna Antonella , Conte Giuseppe , Foschi Lara , Sanmartin Chiara , Incrocci Luca , Ranieri Annamaria , Serra Andrea , Angelini Luciana G.
Published: October 2019

Linseed (Linum usitatissimum L.) is becoming more and more important in the health food market as a functional food, since its seeds and oil represent a rich source of bioactive compounds. Its chemical composition is strongly correlated with, and dependent on, genetic characteristics. The aim of this study was to evaluate the variation in seed yield, oil content, fatty acid composition and secondary metabolite profiles between a low-linolenic linseed variety, belonging to the Solin-type group (Solal), and a high-linolenic traditional one (Bethune), cultivated, both as spring crops, in open field conditions of Central Italy. The achieved results pointed out the different behavior of the two varieties in terms of growth cycle, oil content, and some important yield components, such as capsule number per plant and thousand seed weight. There were also significant differences in seed composition regarding total phenols, total flavonoids, antioxidant activities as well as in carotenoid, tocopherol, and tocotrienol profiles between the two varieties. In particular, Solal was characterized by the greatest contents of oil, phenols, flavonoids, α- and δ- tocotrienol, together with the highest antioxidant activity. Bethune, on the contrary, showed the highest amounts of carotenoids (lutein and β-carotene). These results indicate a clear effect of the genetic characteristics on the biosynthesis of these secondary metabolites and, consequently, on the related antioxidant activity. Our findings suggest that the mutation process, responsible for the selection of the low-linolenic cultivar, is able to modify the biosynthetic pathways of carotenoids and phenolics.
Biodegradable Polymers for Gene Delivery
Authors: Thomas T. J. , Tajmir-Riahi Heidar-Ali , Pillai C. K. S.
Published: October 2019

The cellular transport process of DNA is hampered by cell membrane barriers, and hence, a delivery vehicle is essential for realizing the potential benefits of gene therapy to combat a variety of genetic diseases. Virus-based vehicles are effective, although immunogenicity, toxicity and cancer formation are among the major limitations of this approach. Cationic polymers, such as polyethyleneimine are capable of condensing DNA to nanoparticles and facilitate gene delivery. Lack of biodegradation of polymeric gene delivery vehicles poses significant toxicity because of the accumulation of polymers in the tissue. Many attempts have been made to develop biodegradable polymers for gene delivery by modifying existing polymers and/or using natural biodegradable polymers. This review summarizes mechanistic aspects of gene delivery and the development of biodegradable polymers for gene delivery.
12N-Substituted Matrinol Derivatives Inhibited the Expression of Fibrogenic Genes via Repressing Integrin/FAK/PI3K/Akt Pathway in Hepatic Stellate Cells
Authors: Bao Yunyang , Pang Yudong , Tang Sheng , Niu Tianyun , Guo Zhihao , He Hongwei , Li Yinghong , Song Danqing
Published: October 2019

Twenty new 12N-substituted matrinol derivatives were synthesized and evaluated for their inhibitory effects on collagen α1 (I) (COL1A1) promotor in human hepatic stellate LX-2 cells. The structure-activity relationship (SAR) revealed that introducing a 12N-benzeneaminoacylmethyl substitution might significantly enhance the activity. Compound 8a exhibited the highest inhibitory potency against COL1A1, and its inhibition activity against COL1A1 was further confirmed on both the mRNA and protein levels. It also effectively inhibited the expression of α smooth muscle actin (α-SMA), fibronectin and transforming growth factor β1 (TGFβ1), indicating an extensive inhibitory effect on the expression of fibrogenic genes. The primary mechanism study indicated that it might take action via the Integrin/FAK/PI3K/Akt signaling pathway. The results provided powerful information for further structure optimization, and compound 8a was selected as a novel anti-fibrogenic lead for further investigation.
Fabrication of Robust Hydrogen Evolution Reaction Electrocatalyst Using Ag2Se by Vacuum Evaporation
Authors: Hussain Sajjad , Chae Jinwoong , Akbar Kamran , Vikraman Dhanasekaran , Truong Linh , Naqvi Bilal Abbas , Abbas Yawar , Kim Hyun-Seok , Chun Seung-Hyun , Kim Gunn , Jung Jongwan
Published: October 2019

Much research has been done on reliable and low-cost electrocatalysts for hydrogen generation by water splitting. In this study, we synthesized thin films of silver selenide (Ag2Se) using a simple thermal evaporation route and demonstrated their electrocatalytic hydrogen evolution reaction (HER) activity. The Ag2Se catalysts show improved electrochemical surface area and good HER electrocatalytic behavior (367 mV overpotential @ 10 mA·cm−2, exchange current density: ~1.02 × 10−3 mA·cm−2, and Tafel slope: 53 mV·dec−1) in an acidic medium). The reliability was checked in 0.5 M sulfuric acid over 20 h. Our first-principles calculations show the optimal energy of hydrogen adsorption, which is consistent with experimental results. The works could be further extended for finding a new catalyst by associating the selenide, sulfide or telluride-based materials without complex catalyst synthesis procedures.
The Analysis of Food Intake in Patients with Cirrhosis Waiting for Liver Transplantation: A Neglected Step in the Nutritional Assessment
Authors: Palmese Francesco , Bolondi Ilaria , Giannone Ferdinando Antonino , Zaccherini Giacomo , Tufoni Manuel , Baldassarre Maurizio , Caraceni Paolo
Published: October 2019

Patients with cirrhosis waiting for liver transplantation (LT) frequently present a nutritional disorder, which represents an independent predictor of morbidity and mortality before and after transplantation. Thus, a proper assessment of the food intake by using different methods, such as food records, food frequency questionnaires, and 24 h recall, should be deemed an important step of the nutritional management of these patients. The available published studies indicate that the daily food intake is inadequate in the majority of waitlisted patients. These findings were confirmed by our experience, showing that the daily intake of total calories, proteins and carbohydrates was inadequate in approximately 85–95% of patients, while that of lipids and simple carbohydrates was inadequate in almost 50% of them. These data highlight the need to implement an effective educational program provided by certified nutritionists or dieticians, who should work in close collaboration with the hepatologist to provide a nutritional intervention tailored to the individual patient requirements.
Effect of Intradialytic Exercise on Hyperphosphatemia and Malnutrition
Authors: Salhab Nada , Alrukhaimi Mona , Kooman Jeroen , Fiaccadori Enrico , Aljubori Harith , Rizk Rana , Karavetian Mirey
Published: October 2019

Intradialytic exercise (IDE) is not routinely prescribed in hemodialysis (HD) units despite its potential benefits on patients’ outcomes. This study was the first in the United Arab Emirates to examine the effect of aerobic IDE on hyperphosphatemia, malnutrition, and other health outcomes among HD patients. Participants were chosen from the largest HD unit in Sharjah Emirate for a quasi-experimental intervention with pre and post evaluation. The study lasted for 12 months. Study parameters were collected at baseline, post intervention, and follow-up. The intervention included a moderate-intensity aerobic IDE of 45 min per HD session; intensity was assessed using the Borg Scale. Patients were educated on the importance of exercise. Study outcomes were serum phosphorus (P), malnutrition inflammation score (MIS), quality of life (QOL), and pertinent blood tests. Forty-one eligible consenting HD patients were included in the study. Results at follow-up showed a non-significant reduction in P (p = 0.06) in patients who were hyperphosphatemic at baseline, but not in the sample as whole. MIS did not deteriorate throughout the study (p = 0.97). IDE resulted in a non-significant increase in the QOL visual analogue scale (p = 0.34). To conclude, aerobic IDE for 45 min is safe and could be beneficial, especially for hyperphosphatemic patients.
Plasma Free Amino Acid Responses to Whey Protein and Their Relationships with Gastric Emptying, Blood Glucose- and Appetite-Regulatory Hormones and Energy Intake in Lean Healthy Men
Authors: Elovaris Rachel A. , Hutchison Amy T. , Lange Kylie , Horowitz Michael , Feinle-Bisset Christine , Luscombe-Marsh Natalie D.
Published: October 2019

This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in which they consumed, on 3 separate occasions, in randomised order, 450-mL drinks containing either 30 g (L) or 70 g (H) of pure whey protein isolate, or control with 0 g of protein (C). Gastric emptying, serum concentrations of AAs, ghrelin, cholecystokinin (CCK), glucagon-like-peptide 1 (GLP-1), insulin, glucagon and blood glucose were measured before and after the drinks over 180 min. Then energy intake was quantified. All AAs were increased, and 7/20 AAs were increased more by H than L. Incremental areas under the curve (iAUC0–180 min) for CCK, GLP-1, insulin and glucagon were correlated positively with iAUCs of 19/20 AAs (p < 0.05). The strongest correlations were with the branched-chain AAs as well as lysine, tyrosine, methionine, tryptophan, and aspartic acid (all R2 > 0.52, p < 0.05). Blood glucose did not correlate with any AA (all p > 0.05). Ghrelin and energy intake correlated inversely, but only weakly, with 15/20 AAs (all R2 < 0.34, p < 0.05). There is a strong relationship between gluco-regulatory hormones with a number of (predominantly essential) AAs. However, the factors mediating the effects of protein on blood glucose and energy intake are likely to be multifactorial.
A New Calcium Oral Controlled-Release System Based on Zeolite for Prevention of Osteoporosis
Authors: Fabiano Angela , Piras Anna Maria , Calderone Vincenzo , Testai Lara , Flori Lorenzo , Puppi Dario , Chiellini Federica , Zambito Ylenia
Published: October 2019

Osteoporosis, a systemic skeleton disease, can be prevented by increasing calcium levels in serum via administration of calcium salts. However, traditional calcium-based formulations have not appeared to be effective, hence the purpose of the present work has been to prepare and test in vitro/vivo a formulation able to gradually release calcium during transit over the GI tract, thus increasing bioavailability and reducing daily dose, and hence, side effects. Calcium controlled-release granules based on zeolite and Precirol® were prepared. In the best case, represented by granules sized 1.2 mm, containing 20% Precirol®, 19% zeolite, 60% calcium (granule), the release lasted ≈6 h. The release is controlled by diffusion of calcium ions through the aqueous channels forming within granules, once these come into contact with physiological fluids. Such a diffusion is hindered by the interaction of calcium ions with the negatively charged surface of the zeolite. Ovariectomy was used to make rats osteopenic. For in vivo studies, rats were divided into the following groups. Sham: not treated; ova: ovariectomized (ova); CaCl2 1.0 g: ova, treated with 1.0 g/die Ca2+; CaCl2 0.5 g: ova, treated with 0.5 g/die Ca2+; granule 1.0 g, or granule 0.5 g: ova, treated with granules equivalent to 1.0 g/die or 0.5 g/die Ca2+ in humans. Ca2+ amounts in femur bone and bone marrow, femur mechanical characteristics, and femur medullary canalicule diameter were measured and the same efficacy rank order was obtained: ova < CaCl2 0.5 g < CaCl2 1.0 g < granule 0.5 g ≈ granule 1.0 g ≈ sham. The results show promise of an effective prevention of osteoporosis, based on a controlled-rate administration of a calcium dose half that administered by the current therapy, with reduced side effects.
Food–Drug Interaction between the Adlay Bran Oil and Drugs in Rats
Authors: Yao Hsien-Tsung , Lin Jia-Hsuan , Liu Yun-Ta , Li Mei-Ling , Chiang Wenchang
Published: October 2019

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline (+28.4%), dextromethorphan (+48.7%), and diltiazem (+46.7%) when co-administered an oral drug cocktail. After 7 days of feeding with an ABO-containing diet, plasma concentrations of theophylline (+45.4%) and chlorzoxazone (+53.6%) were increased after the oral administration of the drug cocktail. The major CYP enzyme activities in the liver and intestinal tract were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food–drug interactions between ABO and co-administered drugs.
Molecular Detection and Antibiotyping of Multidrug-Resistant Salmonella Isolated from Houseflies in a Fish Market
Authors: Sobur Abdus , Hasan Mehedi , Haque Emdadul , Mridul Asmaul Iqbal , Noreddin Ayman , El Zowalaty Mohamed E. , Rahman Tanvir
Published: October 2019

Houseflies (Musca domestica) are well-known mechanical vectors for spreading multidrug-resistant bacteria. Fish sold in open markets are exposed to houseflies. The present study investigated the prevalence and antibiotypes of multidrug-resistant (MDR) Salmonella spp. in houseflies captured from a fish market. Direct interviews with fish vendors and consumers were also performed to draw their perceptions about the role of flies in spreading antibiotic-resistant bacteria. A total of 60 houseflies were captured from a local fish market in Bangladesh. The presence of Salmonella spp. was confirmed using PCR method. Antibiogram was determined by the disk diffusion method, followed by the detection of tetA, tetB, and qnrA resistance genes by PCR. From the interview, it was found that most of the consumers and vendors were not aware of antibiotic resistance, but reported that flies can carry pathogens. Salmonella spp. were identified from the surface of 34 (56.7%) houseflies, of which 31 (91.2%) were found to be MDR. This study revealed 25 antibiotypes among the isolated Salmonella spp. All tested isolates were found to be resistant to tetracycline. tetA and tetB were detected in 100% and 47.1% of the isolates, respectively. Among the 10 isolates phenotypically found resistant to ciprofloxacin, six (60%) were found to be positive for qnrA gene. As far as we know, this is the first study from Bangladesh to report and describe the molecular detection of multidrug-resistant Salmonella spp. in houseflies in a fish market facility. The occurrence of a high level of MDR Salmonella in houseflies in the fish market is of great public health concerns.