bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of GirK Channels in Long-Term Potentiation of Synaptic Inhibition in an In Vivo Mouse Model of Early Amyloid-β Pathology
Authors: Sánchez-Rodríguez Irene , Gruart Agnès , Delgado-García José María , Jiménez-Díaz Lydia , Navarro-López Juan D.
Published: March 2019

Imbalances of excitatory/inhibitory synaptic transmission occur early in the pathogenesis of Alzheimer’s disease (AD), leading to hippocampal hyperexcitability and causing synaptic, network, and cognitive dysfunctions. G-protein-gated potassium (GirK) channels play a key role in the control of neuronal excitability, contributing to inhibitory signaling. Here, we evaluate the relationship between GirK channel activity and inhibitory hippocampal functionality in vivo. In a non-transgenic mouse model of AD, field postsynaptic potentials (fPSPs) from the CA3–CA1 synapse in the dorsal hippocampus were recorded in freely moving mice. Intracerebroventricular (ICV) injections of amyloid-β (Aβ) or GirK channel modulators impaired ionotropic (GABAA-mediated fPSPs) and metabotropic (GirK-mediated fPSPs) inhibitory signaling and disrupted the potentiation of synaptic inhibition. However, the activation of GirK channels prevented Aβ-induced changes in GABAA components. Our data shows, for the first time, the presence of long-term potentiation (LTP) for both the GABAA and GirK-mediated inhibitory postsynaptic responses in vivo. In addition, our results support the importance of an accurate level of GirK-dependent signaling for dorsal hippocampal performance in early amyloid pathology models by controlling the excess of excitation that disrupts synaptic plasticity processes.
Inhibitory Effects of Menadione on Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation via NF-κB Inhibition
Authors: Lee Min Ho , Yang Ji Yeong , Cho Yoonjung , Woo Hyun Jun , Kwon Hye Jin , Kim Do Hyun , Park Min , Moon Cheol , Yeon Min Ji , Kim Hyun Woo , Seo Woo-Duck , Kim Sa-Hyun , Kim Jong-Bae
Published: March 2019

H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori.
Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease
Authors: Er Leay Kiaw , Hsu Lung-An , Juang Jyh-Ming Jimmy , Chiang Fu-Tien , Teng Ming-Sheng , Tzeng I-Shiang , Wu Semon , Lin Jeng-Feng , Ko Yu-Lin
Published: March 2019

Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10−21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan–Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.
Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer
Authors: McDonald Megan E. , Salinas Erin A. , Devor Eric J. , Newtson Andreea M. , Thiel Kristina W. , Goodheart Michael J. , Bender David P. , Smith Brian J. , Leslie Kimberly K. , Gonzalez-Bosquet Jesus
Published: March 2019

Nearly one-third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial treatment with platinum-based therapy. Genomic and clinical characterization of these patients may lead to potential alternative therapies. Here, the objective is to classify non-responders into subsets using clinical and molecular features. Using patients from The Cancer Genome Atlas (TCGA) dataset with platinum-resistant or platinum-refractory HGSC, we performed a genome-wide unsupervised cluster analysis that integrated clinical data, gene copy number variations, gene somatic mutations, and DNA promoter methylation. Pathway enrichment analysis was performed for each cluster to identify the targetable processes. Following the unsupervised cluster analysis, three distinct clusters of non-responders emerged. Cluster 1 had overrepresentation of the stage IV disease and suboptimal debulking, under-expression of miRNAs and mRNAs, hypomethylated DNA, “loss of function” TP53 mutations, and the overexpression of genes in the PDGFR pathway. Cluster 2 had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the HIF-1 signaling pathway. Cluster 3 had more optimally cytoreduced stage III patients, overexpression of miRNAs, mixed methylation patterns, and “gain of function” TP53 mutations. However, the survival for all clusters was similar. Integration of genomic and clinical data from patients that do not respond to chemotherapy has identified different subgroups or clusters. Pathway analysis further identified the potential alternative therapeutic targets for each cluster.
Biological Toxins as the Potential Tools for Bioterrorism
Authors: Janik Edyta , Ceremuga Michal , Saluk-Bijak Joanna , Bijak Michal
Published: March 2019

Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as “Chemicals produced by living organisms that have toxic properties for another organism”. Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD50 < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, Clostridium perfringens toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins.
Urinary Metabolites Altered during the Third Trimester in Pregnancies Complicated by Gestational Diabetes Mellitus: Relationship with Potential Upcoming Metabolic Disorders
Authors: López-Hernández Yamilé , Herrera-Van Oostdam Ana Sofía , Toro-Ortiz Juan Carlos , López Jesús Adrián , Salgado-Bustamante Mariana , Murgu Michael , Torres-Torres Lourdes Mariela
Published: March 2019

Gestational diabetes mellitus (GDM) is a disorder in pregnancy with highest impact in the future life of both mother and newborn. Increasing incidence, economic impact, and potential for severe GDM-related pregnancy complications are some factors that have motivated the deep study of physiopathology, risk factors for developing GDM, and potential biomarkers for its diagnosis. In the present pilot study, we analyzed the urinary metabolome profile of GDM patients in the 3rd trimester of pregnancy, when GDM is already established and the patients are under dietary and pharmacological control. An untargeted metabolomics method based on liquid chromatography–mass spectrometry analysis was developed to identify differentially expressed metabolites in the GDM group. We identified 14 metabolites that are significantly upregulated in the urine of GDM patients, and, more importantly, we identified those related with the steroid hormone biosynthesis and tryptophan (TRP) metabolism pathways, which are associated with GDM pathophysiology. Thus, these metabolites could be screened as potential prognostic biomarkers of type two diabetes mellitus, coronary artery disease and chronic renal failure in future follow-up studies with GDM patients.
AdRAP2.3, a Novel Ethylene Response Factor VII from Actinidia deliciosa, Enhances Waterlogging Resistance in Transgenic Tobacco through Improving Expression Levels of PDC and ADH Genes
Authors: Pan De-Lin , Wang Gang , Wang Tao , Jia Zhan-Hui , Guo Zhong-Ren , Zhang Ji-Yu
Published: March 2019

APETALA2/ethylene-responsive factor superfamily (AP2/ERF) is a transcription factor involved in abiotic stresses, for instance, cold, drought, and low oxygen. In this study, a novel ethylene-responsive transcription factor named AdRAP2.3 was isolated from Actinidia deliciosa ‘Jinkui’. AdRAP2.3 transcription levels in other reproductive organs except for the pistil were higher than those in the vegetative organs (root, stem, and leaf) in kiwi fruit. Plant hormones (Salicylic acid (SA), Methyl-jasmonate acid (MeJA), 1-Aminocyclopropanecarboxylic Acid (ACC), Abscisic acid (ABA)), abiotic stresses (waterlogging, heat, 4 °C and NaCl) and biotic stress (Pseudomonas Syringae pv. Actinidiae, Psa) could induce the expression of AdRAP2.3 gene in kiwi fruit. Overexpression of the AdRAP2.3 gene conferred waterlogging stress tolerance in transgenic tobacco plants. When completely submerged, the survival rate, fresh weight, and dry weight of transgenic tobacco lines were significantly higher than those of wile type (WT). Upon the roots being submerged, transgenic tobacco lines grew aerial roots earlier. Overexpression of AdRAP2.3 in transgenic tobacco improved the pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) enzyme activities, and improved the expression levels of waterlogging mark genes NtPDC, NtADH, NtHB1, NtHB2, NtPCO1, and NtPCO2 in roots under waterlogging treatment. Overall, these results demonstrated that AdRAP2.3 might play an important role in resistance to waterlogging through regulation of PDC and ADH genes in kiwi fruit.
Quality of Life of Women after Giving Birth: Associated Factors Related with the Birth Process
Authors: Martínez-Galiano Juan Miguel , Hernández-Martínez Antonio , Rodríguez-Almagro Julián , Delgado-Rodríguez Miguel
Published: March 2019

The World Health Organization (WHO) considers quality of life a fundamental indicator. The effect of birth on women’s long-term quality of life (QoL) has barely been studied. The purpose of this study was to determine the factors related with the pregnancy, delivery and puerperium, and assess women’s QoL after giving birth. A cross-sectional study with Spanish puerperal women was carried out; it collected data on socio-demographic variables, obstetric variables, newborn data, and several quality of life parameters. An ad hoc online questionnaire, including SF-36 (validated instrument to measure QoL), was used. Crude mean differences (MD) and adjusted mean differences (aMD) were estimated by multiple linear regression. A total of 2990 women participated whose overall QoL lowered with time until three years postpartum (p = 0.045). Caesarean section (aMD = −3.61, 95% confidence interval (CI): −5.07, −2.15), mother admitted to ICU (aMD = −4.81, 95% CI: −9.56, −2.68), newborn hospitalized (aMD = −2.10, 95% CI: −4.31, −0.13) or third/fourth degree perineal tears (aMD = −6.87 95%CI: −9.93, −3.82) were detected as risk factors that affect negatively and significantly on postpartum QoL scores. Women’s postpartum QoL worsens with time. Some determining factors negatively influence postpartum QoL: Caesarean section, a mother´s admission to an intensive care unit (ICU) or a premature newborn.
Effects of Oral Anticoagulant Therapy on Gene Expression in Crosstalk between Osteogenic Progenitor Cells and Endothelial Cells
Authors: Dalle Carbonare Luca , Mottes Monica , Brunelli Anna , Deiana Michela , Cheri Samuele , Suardi Silvia , Valenti Maria Teresa
Published: March 2019

Direct oral anti-coagulants (DOACs) are employed in clinical practice for the prevention and treatment of recurrent venous thromboembolism and for the prevention of stroke in non-valvular atrial fibrillation. DOACs directly and reversibly inhibit activated factor X or thrombin and can interfere with other pathophysiological processes such as inflammation, lipid metabolism, and bone turnover. We aimed to evaluate the possible effects of DOACs on osteogenesis and angiogenesis. We treated 34 patients affected by cardiovascular disorders with DOACs; biochemical and molecular analyses were performed before and after three months of treatment. Circulating progenitors (CPs; CD34−, CD45−, CD14−, CD73+, CD105+), which share typical bone marrow stem cell (MSCs) features, were harvested from peripheral blood of the study subjects to monitor the expression of osteogenesis-related genes RUNX2 and SPARC. Human umbilical vein endothelial cells (HUVECs) were used to probe angiogenesis-related VEGF, CD31, and CD105 gene expression. We performed co-culture experiments using a commercial human mesenchymal stem cells line (hMSCs) obtained from bone marrow and HUVECs. Clinical parameters related to bone metabolism, coagulation, renal and liver function, and the lipid profile were evaluated. Values of the C-terminal telopeptide type I collagen (CTX) increased after the treatment. We found a significant increase in osteogenesis marker gene expression in CPs after three months of anticoagulant therapy. An increase in the RUNX2 expression determinant alone was detected instead in hMSCs co-cultured with HUVECs in the presence of treated patients’ sera. The VEGF, CD31, and CD105 marker genes appeared to be significantly upregulated in HUVECs co-cultured with hMSCs in the presence of treated patients’ sera. Under these conditions, new vessel formation increased as well. Our results highlight an unexpected influence of DOAC therapy on osteogenic commitment and vascular endothelial function promotion.
Spin Cross-Over (SCO) Complex Based on Unsymmetrical Functionalized Triazacyclononane Ligand: Structural Characterization and Magnetic Properties
Authors: Halit Merzouk , Roger Mélissa , Patinec Véronique , Yefsah Said , Gómez-García Carlos J. , Triki Smail
Published: March 2019

The unsymmetrical ligand 1-(2-aminophenyl)-4,7-bis(pyridin-2-ylmethyl)-1,4,7-triazacyclononane (L6) has been prepared and characterized by NMR spectroscopy. The L6 ligand is based on the triazamacrocycle (tacn) ring that is functionalized by two flexible 2-pyridylmethyl and one rigid 2-aminophenyl groups. Reaction of this ligand with Fe(ClO4)2·xH2O led to the complex [Fe(L6)](ClO4)2 (1), which was characterized as the first Fe(II) complex based on the unsymmetrical N-functionalized tacn ligand. The crystal structure revealed a discrete monomeric [FeL6]2+ entity in which the unsymmetrical N-functionalized triazacyclononane molecule (L6) acts as hexadentate ligand. As observed in the few parent examples that are based on the symmetrical N-functionalized tacn ligands, the triazacyclononane ring is facially coordinated and the N-donor atoms of the three functional groups (two pyridine and one aniline groups) are disposed in the same side of the tacn ring, leading to a distorted FeN6 environment. The magnetic studies of 1 revealed the presence of an incomplete spin crossover (SCO) transition above 425 K, whose progress would be prevented by a very exothermic thermal decomposition at ca. 472 K, as shown by thermogravimetric and DSC measurements.
Effect of Oral Ingestion of Low-Molecular Collagen Peptides Derived from Skate (Raja Kenojei) Skin on Body Fat in Overweight Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Tak Young Jin , Kim Yun Jin , Lee Jeong Gyu , Yi Yu-Hyun , Cho Young Hye , Kang Geun Hee , Lee Sang Yeoup
Published: March 2019

Recent animal studies found the potential of a collagen peptide derived from skate skin to have anti-obesity effects through the suppression of fat accumulation and regulation of lipid metabolism. However, no studies have yet been performed in humans. Here, this very first human randomized, placebo-controlled, and double-blinded study was designed to investigate the efficacy and tolerability of skate skin collagen peptides (SCP) for the reduction of body fat in overweight adults. Ninety healthy volunteers (17 men) aged 41.2 ± 10.4 years with a mean body mass index of 25.6 ± 1.9 kg/m2 were assigned to the intervention group (IG), which received 2000 mg of SCP per day or to the control group (CG) given the placebo for 12 weeks and 81 (90%) participants completed the study. Changes in body fat were evaluated using dual energy X-ray absorptiometry as a primary efficacy endpoint. After 12 weeks of the trial, the percentage of body fat and body fat mass (kg) in IG were found to be significantly better than those of subjects in CG (−1.2% vs. 2.7%, p = 0.024 and −1.2 kg vs. 0.3 kg, p = 0.025). Application of SCP was well tolerated and no notable adverse effect was reported from both groups. These results suggest the beneficial potential of SCP in the reduction of body fat in overweight adults.
Optimization of Phlorotannins Extraction from Fucus vesiculosus and Evaluation of Their Potential to Prevent Metabolic Disorders
Authors: Catarino Marcelo D. , Silva Artur M. S. , Mateus Nuno , Cardoso Susana M.
Published: March 2019

Phlorotannins are phloroglucinol-based phenolic compounds, occurring particularly in brown macroalgae, that have been recognized for their promising bioactive properties. In this study, the extraction of phlorotannins from Fucus vesiculosus was evaluated with particular emphasis on the influential parameters, including the solvent concentration, solvent-solid ratio, extraction temperature and extraction time, using a single-factor design followed by a Box-Behnken design. The maximum total phlorotannin content, determined using the 2,4-dimethoxybenzaldehyde (DMBA) method, corresponded to 2.92 ± 0.05 mg of phloroglucinol equivalents/g dry seaweed (mg PGE/g DS), and was achieved for extracts carried out with acetone 67% (v/v), a solvent-solid ratio of 70 mL/g and temperature at 25 °C. This crude extract, together with a semi-purified phlorotannin fraction, were further evaluated for their anti-enzymatic capacity against α-glucosidase, α-amylase and pancreatic lipase, both showing promising inhibitory effects, particularly against α-glucosidase for which a greater inhibitory effect was observed compared to the pharmaceutical drug acarbose (IC50 = 4.5 ± 0.8 and 0.82 ± 0.3 μg/mL, respectively, against 206.6 ± 25.1 μg/mL). Additionally, the ultra-high-pressure liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis carried out on the ethyl acetate fraction revealed the presence of fucols, fucophlorethols, fuhalols and several other phlorotannin derivatives. Moreover, possible new phlorotannin compounds, including fucofurodiphlorethol, fucofurotriphlorethol and fucofuropentaphlorethol, have been tentatively identified in this extract. Overall, this study provides evidence that F. vesiculosus phlorotannin-rich extracts hold potential for the management of the activity of α-glucosidase, α-amylase and pancreatic lipase, which are well known to be linked to metabolic disorders such as diabetes and obesity.
The Potential of Magnesium Based Materials in Mandibular Reconstruction
Authors: Prasadh Somasundaram , Ratheesh Vaishnavi , Manakari Vyasaraj , Parande Gururaj , Gupta Manoj , Wong Raymond
Published: March 2019

The future of biomaterial design will rely on development of bioresorbable implant materials that completely and safely degrade in vivo after the tissues grow, without generating harmful degradation products at the targeted anatomic site. Permanent biomaterials such as Ti6Al4V alloy, 316L stainless steel, and Co-based alloys currently used in mandibular reconstruction often result in stress shielding effects due to mismatch in the Young’s modulus values between the bone and the implant, resulting in implant loosening. Also, allergic responses due to metal ion releases necessitates revision surgery to prevent long term exposure of the body to toxic implant contents. Bioresorbable metals are perceived as revolutionary biomaterials that have transformed the nature of metallic biomaterials from bioinert to bioactive and multi-bio functional (anti-bacterial, anti-proliferation, and anti-cancer). In this aspect, magnesium (Mg)-based materials have recently been explored by the biomedical community as potential materials for mandibular reconstruction, as they exhibit favorable mechanical properties, adequate biocompatibility, and degradability. This article reviews the recent progress that has led to advances in developing Mg-based materials for mandibular reconstruction; correlating with the biomechanics of mandible and types of mandibular defects. Mg-based materials are discussed regarding their mechanical properties, corrosion characteristics, and in vivo performance. Finally, the paper summarizes findings from this review, together with a proposed scope for advancing the knowledge in Mg-based materials for mandibular reconstruction.
Microstructural Evaluation and Corrosion Resistance of Semisolid Cast A356 Alloy Processed by Equal Channel Angular Pressing
Authors: Gebril Mohamed Abdelgawad , Omar Mohd Zaidi , Mohamed Intan Fadhlina , Othman Norinsan Kamil
Published: March 2019

As-cast and semisolid casting using a cooling slope A356 alloy were processed by equal channel angular pressing (ECAP) for Si and grain refinement. The ECAP was conducted at room temperature in a mold, with a channel angle of 120°, and this resulted in a significant size reduction of grain and Si particles from 170.5 and 4.22 to 23.12 and 0.71 µm, respectively, after six passes of heat-treated cooling slope casting, using the ECAP process. The hardness increased with ECAP processing, from 61 HV, for the as-cast alloy, to 134 Hv, after six passes of heat-treated cooling slope casting. The corrosion resistance of the alloy improved, from 0.042 to 0.0012 mmy−1, after the ECAP process. In this work both the strength and corrosion resistance of the ECAPed A356 alloys were improved with the application of the cooling slope process than without (i.e., from the as-cast condition).
Effect of Forced Air Cooling on the Microstructures, Tensile Strength, and Hardness Distribution of Dissimilar Friction Stir Welded AA5A06-AA6061 Joints
Authors: Peng Guangjian , Yan Qi , Hu Jiangjiang , Chen Peijian , Chen Zhitong , Zhang Taihua
Published: March 2019

Friction stir welding (FSW) is a promising welding method for welding dissimilar materials without using welding flux. In the present work, 5A06-H112 and 6061-T651 aluminium alloys were successfully welded by friction stir welding with forced air cooling (FAC) and natural cooling (NC). Nanoindentation tests and microstructure characterisations revealed that forced air cooling, which can accelerate the cooling process and suppress the coarsening of grains and the dissolution of precipitate phases, contributes to strengthening and narrowing the weakest area of the joint. The tensile strength of joints with FAC were commonly improved by 10% compared to those with NC. Scanning electron microscopy (SEM) images of the fracture surface elucidated that FSW with FAC tended to increase the number and reduce the size of the dimples. These results demonstrated the advantages of FSW with FAC in welding heat-sensitive materials and provide fresh insight into welding industries.
Characterisation and Comparison of Process Chains for Producing Automotive Structural Parts from 7xxx Aluminium Sheets
Authors: Schuster Philipp A. , Österreicher Johannes A. , Kirov Georg , Sommitsch Christof , Kessler Olaf , Mukeli Ermal
Published: March 2019

Due to their high specific strength, EN AW-7xxx aluminium alloys are promising materials for reducing the weight of automotive structural parts. However, their formability at room temperature is poor due to pronounced natural ageing. Therefore, we investigated hot stamping and W-temper forming for EN AW-7075 and a modified variant of EN AW-7021. For hot stamping of the modified EN AW-7021, a low-temperature stabilisation heat treatment (pre-aging at 80 °C for 1 h) was incorporated into the process chain design to inhibit natural ageing after forming. The process chains were compared with respect to dimensional accuracy, mechanical properties, microstructure, precipitation status (assessed by differential scanning calorimetry) and crashworthiness. It was found that hot stamping is suitable to form failure-free parts with good dimensional accuracy for both alloys while W-temper forming suffers from springback. Within a time-span of 21 days after forming, hardness values of hot stamped and stabilised parts did not increase significantly. Compared to non-stabilised parts, stabilised parts also showed significantly improved folding behaviour in quasi-static compression testing and absorbed approximately 15% more energy.
Influence of Boron Addition on the Microstructure and the Corrosion Resistance of CoCrMo Alloy
Authors: Hernandez-Rodriguez Marco A.L. , Laverde-Cataño Dionisio A. , Lozano Diego , Martinez-Cazares Gabriela , Bedolla-Gil Yaneth
Published: March 2019

Cobalt-based alloys are extensively used in orthopedic applications for joint replacements due to their wear and corrosion resistance. Corrosion, however, is often associated with fatigue failure in these orthopedic devices. In this study, the effect of boron addition on the corrosion behavior of CoCrMo alloys was studied using linear polarization resistance, potentiodynamic polarization curves, electrochemical impedance spectroscopy, and cyclic voltammetry. The samples were analyzed under as-cast and heat treatment conditions after 21 days of immersion in phosphate-buffered saline (PBS) solution at 37 °C. The boron addition increased the particle content, while the heat treatment promoted enlargement and even distribution of the precipitates throughout the structure. The corrosion resistance was improved by both boron and heat treatments. The best performance was observed for a heat-treated alloy having a very small amount of boron, which had an increased resistance to corrosive attack. Such behavior was attributed to the homogenized microstructure achieved by boron and heat treatment that helped to form a stable passive layer of chromium oxide which endured the 21 days of immersion.
Wear and Cavitation Erosion Resistance of an AlMgSc Alloy Produced by DMLS
Authors: Tocci Marialaura , Pola Annalisa , Girelli Luca , Lollio Francesca , Montesano Lorenzo , Gelfi Marcello
Published: March 2019

Pin-on-disk and cavitation tests were performed on an innovative Al-Mg alloy modified with Sc and Zr for additive manufacturing, which was tested in annealed condition. The damaging mechanisms were studied by observations of the morphology of the sample surface after progressive testing. These analyses allowed the identification of an adhesive wear mechanism in the first stages of pin-on-disk test, which evolved into a tribo-oxidative one due to the formation and fragmentation of an oxide layer with increasing testing distance. Regarding cavitation erosion, the AlMgSc alloy was characterized by an incubation period of approximately 1 h before mass loss was measured. Once material removal started, mass loss had a linear behavior as a function of exposure time. No preferential sites for erosion were identified, even though after some minutes of cavitation testing, the boundaries of melting pools can be seen. The comparison with literature data for AlSi10Mg alloy produced by additive manufacturing technology shows that AlMgSc alloy exhibits remarkable wear resistance, while the total mass loss after 8 h of cavitation testing is significantly higher than the value recorded for AlSi10Mg alloy in as-built condition.
Gas Mixing and Final Mixture Composition Control in Simple Geometry Micro-mixers via DSMC Analysis
Authors: Meskos Stavros , Stefanov Stefan , Valougeorgis Dimitris
Published: March 2019

The mixing process of two pressure driven steady-state rarefied gas streams flowing between two parallel plates was investigated via DSMC (Direct Simulation Monte Carlo) for different combinations of gases. The distance from the inlet, where the associated relative density difference of each species is minimized and the associated mixture homogeneity is optimized, is the so-called mixing length. In general, gas mixing progressed very rapidly. The type of gas surface interaction was clearly the most important parameter affecting gas mixing. As the reflection became more specular, the mixing length significantly increased. The mixing lengths of the HS (hard sphere) and VHS (variable hard sphere) collision models were higher than those of the VSS (variable soft sphere) model, while the corresponding relative density differences were negligible. In addition, the molecular mass ratio of the two components had a minor effect on the mixing length and a more important effect on the relative density difference. The mixture became less homogenous as the molecular mass ratio reduced. Finally, varying the channel length and/or the wall temperature had a minor effect. Furthermore, it was proposed to control the output mixture composition by adding in the mixing zone, the so-called splitter, separating the downstream flow into two outlet mainstreams. Based on intensive simulation data with the splitter, simple approximate expressions were derived, capable of providing, once the desired outlet mixture composition was specified, the correct position of the splitter, without performing time consuming simulations. The mixing analysis performed and the proposed approach for controlling gas mixing may support corresponding experimental work, as well as the design of gas micro-mixers.
Geological, Mineralogical and Textural Impacts on the Distribution of Environmentally Toxic Trace Elements in Seafloor Massive Sulfide Occurrences
Authors: Fallon Emily , Frische Matthias , Petersen Sven , Brooker Richard , Scott Thomas
Published: March 2019

With mining of seafloor massive sulfides (SMS) coming closer to reality, it is vital that we have a good understanding of the geochemistry of these occurrences and the potential toxicity impact associated with mining them. In this study, SMS samples from seven hydrothermal fields from various tectonic settings were investigated by in-situ microanalysis (electron microprobe (EMPA) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)) to highlight the distribution of potentially-toxic trace elements (Cu, Zn, Pb, Mn, Cd, As, Sb, Co, Ni, Bi, Ag and Hg) within the deposits, their minerals and textures. We demonstrate that a combination of mineralogy, trace element composition and texture characterisation of SMS from various geotectonic settings, when considered along with our current knowledge of oxidation rates and galvanic coupling, can be used to predict potential toxicity of deposit types and individual samples and highlight which may be of environmental concern. Although we cannot quantify toxicity, we observe that arc-related sulfide deposits have a high potential toxicity when compared with deposits from other tectonic settings based on their genetic association of a wide range of potentially toxic metals (As, Sb, Pb, Hg, Ag and Bi) that are incorporated into more reactive sulfosalts, galena and Fe-rich sphalerite. Thus, deposits such as these require special care when considered as mining targets. In contrast, the exclusive concern of ultra-mafic deposits is Cu, present in abundant, albeit less reactive chalcopyrite, but largely barren of other metals such as As, Pb, Sb, Cd and Hg. Whilst geological setting does dictate metal endowment, ultimately mineralogy is the largest control of trace element distribution and subsequent potential toxicity. Deposits containing abundant pyrrhotite (high-temperature deposits) and Fe-rich sphalerite (ubiquitous to all SMS deposits) as well as deposits with abundant colloform textures also pose a higher risk. This type of study can be combined with “bulk lethal toxicity” assessments and used throughout the stages of a mining project to help guide prospecting and legislation, focus exploitation and minimise environmental impact.
Effects of Single and Mixed Energy Sources on Intracellular Nanoparticles Synthesized by Acidithiobacillus ferrooxidans
Authors: Wu Lingbo , Yang Baojun , Wang Xingxing , Wu Baiqiang , He Wanli , Gan Min , Qiu Guanzhou , Wang Jun
Published: March 2019

Effective biosynthesis of magnetite nanoparticles using current technology is challenging. We investigated the synthesis of nanoparticles by Acidithiobacillus ferrooxidans grown on ferrous iron, elemental sulphur, and mixtures of both substrates. A comparison of tests with different doping amounts of elemental sulphur in ferrous-containing medium showed that the addition of 0.25 and 0.5 M elemental sulphur to the medium resulted in an increased delay of microbial growth and ferrous iron oxidation. TEM suggested that the ferrous material was an essential energy source for the synthesis of nanoparticles in cells. TEM results indicated that the different ratios of ferrous and sulphur had no significant effect on the morphology of bacteria and the size of nanoparticles. High-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX), and X-ray absorption near edge structure (XANES) showed that the nanoparticles were composed of magnetite. For the first time, HRTEM and XANES spectra in-situ characterization was conducted to investigate the nanoparticles that were synthesized by A. ferrooxidans. The findings from this study indicated that the different ratios of ferrous and sulphur had no significant effect on size and shape of nanoparticles synthesized by A. ferrooxidans.
Gem-Quality Green Cr-Bearing Andradite (var. Demantoid) from Dobšiná, Slovakia
Authors: Štubňa Ján , Bačík Peter , Fridrichová Jana , Hanus Radek , Illášová Ľudmila , Milovská Stanislava , Škoda Radek , Vaculovič Tomáš , Čerňanský Slavomír
Published: March 2019

Andradite, variety demantoid, is a rare gem mineral. We describe gem-quality garnet crystals from serpentinized harzburgites from Dobšiná, Slovakia which were faceted. Both the andradite samples were transparent, with a vitreous luster and a vivid green color. They were isotropic with refractive indices >1.81. The measured density ranged from 3.82 to 3.84 g·cm−3. Andradite var. demantoid appeared red under Chelsea filter observation. Both samples contained fibrous crystalline inclusions with the typical “horsetail” arrangement. The studied garnet had a strong Fe3+ dominant andradite composition with 1.72–1.85 apfu Fe3+, Cr3+ up to 0.15 apfu, Al3+ 0.03 to 0.04 apfu, V3+ up to 0.006 apfu substituted for Fe3+, Mn2+ up to 0.002 apfu, and Mg up to 0.04 apfu substituted for Ca. Raman spectrum of garnet showed three spectral regions containing relatively strong bands: I—352–371 cm−1, II—816–874 cm−1, and III—493–516 cm−1. The optical absorption spectrum as characterized by an intense band at 438 nm and two broad bands at 587 and 623 nm and last one at 861 nm, which were assigned to Fe3+ and Cr3+. Transmission was observed in the ultraviolet spectral region (<390 nm), near the infrared region (700–800 nm), and around 530 nm in the green region of visible light, resulting in the garnet’s green color.
Novel Phosphorylated Penta-1,4-dien-3-one Derivatives: Design, Synthesis, and Biological Activity
Authors: Chen Lijuan , Guo Tao , Xia Rongjiao , Tang Xu , Chen Ying , Zhang Cheng , Xue Wei
Published: March 2019

A series of novel phosphorylated penta-1,4-dien-3-one derivatives were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and high-resolution mass spectrometry (HRMS). Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compound 3g exhibited substantial antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), with a 50% effective concentration (EC50) value of 8.6 μg/mL, which was significantly superior to bismerthiazol (BT) (58.8 µg/mL) and thiodiazole-copper (TC) (78.7 μg/mL). In addition, compound 3h showed remarkable protective activity against tobacco mosaic virus (TMV), with an EC50 value of 104.2 μg/mL, which was superior to that of ningnanmycin (386.2 μg/mL). Furthermore, the microscale thermophoresis and molecular docking experiments on the interaction of compounds 3h and 3j with TMV coat protein (TMV CP) were also investigated. Compounds 3h and 3j bound to TMV CP with dissociation constants of 0.028 and 0.23 μmol/L, which were better than that of ningnanmycin (0.52 μmol/L). These results suggest that novel phosphorylated penta-1,4-dien-3-one derivatives may be considered as an activator for antibacterial and antiviral agents.
Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin
Authors: Zhou Yuan , Huang Liqun , Ji Shixia , Hou Shi , Luo Liang , Li Conggang , Liu Maili , Liu Yixiang , Jiang Ling
Published: March 2019

The two-component system (TCS) is a significant signal transduction system for bacteria to adapt to complicated and variable environments, and thus has recently been regarded as a novel target for developing antibacterial agents. The natural product luteolin (Lut) can inhibit the autophosphorylation activity of the typical histidine kinase (HK) HK853 from Thermotoga maritime, but the inhibition mechanism is not known. Herein, we report on the binding mechanism of a typical flavone with HK853 by using solution NMR spectroscopy, isothermal titration calorimetry (ITC), and molecular docking. We show that luteolin inhibits the activity of HK853 by occupying the binding pocket of adenosine diphosphate (ADP) through hydrogen bonds and π-π stacking interaction structurally. Our results reveal a detailed mechanism for the inhibition of flavones and observe the conformational and dynamics changes of HK. These results should provide a feasible approach for antibacterial agent design from the view of the histidine kinases.
Comparative Analysis of Chemical Constituents of Moringa oleifera Leaves from China and India by Ultra-Performance Liquid Chromatography Coupled with Quadrupole-Time-Of-Flight Mass Spectrometry
Authors: Lin Hongqiang , Zhu Hailin , Tan Jing , Wang Han , Wang Zhongyao , Li Pingya , Zhao Chunfang , Liu Jinping
Published: March 2019

With the aim to discuss the similarities and differences of phytochemicals in Moringa oleifera leaves collected from China (CML) and India (IML) in mind, comparative ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed in this study. A screening analysis based on a UNIFI platform was first carried out to discuss the similarities. Next, untargeted metabolomic analysis based on multivariate statistical analysis was performed to discover the differences. As a result, a total of 122 components, containing 118 shared constituents, were characterized from CML and IML. The structure types included flavonoids, alkaloids, glyosides, organic acids and organic acid esters, iridoids, lignans, and steroids, etc. For CML, 121 compounds were characterized; among these, 18 potential biomarkers with higher contents enabled differentiation from IML. For IML, 119 compounds were characterized; among these, 12 potential biomarkers with higher contents enabled differentiation from CML. It could be concluded that both CML and IML are rich in phytochemicals and that CML is similar to IML in the kinds of the compounds it contains, except for the significant differences in the contents of some compounds. This comprehensive phytochemical profile study provides a basis for explaining the effect of different growth environments on secondary metabolites and exists as a reference for further research into or applications of CML in China.
Optimization and Formulation of Fucoxanthin-Loaded Microsphere (F-LM) Using Response Surface Methodology (RSM) and Analysis of Its Fucoxanthin Release Profile
Authors: Jaswir Irwandi , Noviendri Dedi , Taher Muhammad , Mohamed Farahidah , Octavianti Fitri , Lestari Widya , Mukti Ali Ghufron , Nirwandar Sapta , Hamad Almansori Bubaker B.
Published: March 2019

Fucoxanthin has interesting anticancer activity, but is insoluble in water, hindering its use as a drug. Microencapsulation is used as a technique for improving drug delivery. This study aimed to formulate fucoxanthin-loaded microspheres (F-LM) for anticancer treatment of H1299 cancer cell lines and optimize particle size (PS) and encapsulation efficiency (EE). Using response surface methodology (RSM), a face centered central composite design (FCCCD) was designed with three factors: Polyvinylalcohol (PVA), poly(d,l-lactic-co-glycolic acid) (PLGA), and fucoxanthin concentration. F-LM was produced using a modified double-emulsion solvent evaporation method. The F-LM were characterized for release profile, release kinetics, and degradation pattern. Optimal F-LM PS and EE of 9.18 µm and 33.09%, respectively, with good surface morphology, were achieved from a 0.5% (w/v) PVA, 6.0% (w/v) PLGA, 200 µg/mL fucoxanthin formulation at a homogenization speed of 20,500 rpm. PVA concentration was the most significant factor (p < 0.05) affecting PS. Meanwhile, EE was significantly affected by interaction between the three factors: PVA, PLGA, and fucoxanthin. In vitro release curve showed fucoxanthin had a high burst release (38.3%) at the first hour, followed by a sustained release stage reaching (79.1%) within 2 months. Release kinetics followed a diffusion pattern predominantly controlled by the Higuchi model. Biodegradability studies based on surface morphology changes on the surface of the F-LM, show that morphology changed within the first hour, and F-LM completely degraded within 2 months. RSM under FCCCD design improved the difference between the lowest and highest responses, with good correlation between observed and predicted values for PS and EE of F-LM.
Structure–Activity Prediction of ACE Inhibitory/Bitter Dipeptides—A Chemometric Approach Based on Stepwise Regression
Authors: Hrynkiewicz Monika , Iwaniak Anna , Bucholska Justyna , Minkiewicz Piotr , Darewicz Małgorzata
Published: March 2019

Forward and backward stepwise regression (FR and BR, respectively) was applied for the structure–bioactivity prediction of angiotensin converting enzyme (ACE)-inhibitory/bitter-tasting dipeptides. The datasets used in this study consisted of 28 sequences and numerical variables reflecting dipeptides’ physicochemical nature. The data were acquired from the BIOPEP-UWM, Biological Magnetic Resonance Databank, ProtScale, and AAindex databases. The calculations were computed using STATISTICA®13.1. FR/BR models differed in R2 (0.91/0.76, respectively). The impact of C-atC(−) and N-Molw(+) on the dual function of dipeptides was observed. Positive (+) and negative (−) correlations with log IC50 are presented in parens. Moreover, C-Bur(+), N-atH(+), and N-Pol(−) were also found to be important in the FR model. The additional statistical significance of N-bul(−), N-Bur(−), and N-Hdr(+) was reported in the BR model. These attributes reflected the composition of the dipeptides. We report that the “ideal” bitter ACE inhibitor should be composed of P, Y, F (C-end) and G, V, I, L (N-end). Functions: log Rcaf. = f (observed log IC50) and log Rcaf. = f (predicted log IC50) revealed no direct relationships between ACE inhibition and the bitterness of the dipeptides. It probably resulted from some structural discrepancies between the ACE inhibitory/bitter peptides and/or the measure of activity describing one of the two bioactivities. Our protocol can be applicable for the structure–bioactivity prediction of other bioactivities peptides.
Inhibitory Effects of (−)-Epigallocatechin-3-gallate on Esophageal Cancer
Authors: Wang Liu-Xiang , Shi Yun-Long , Zhang Long-Jie , Wang Kai-Rong , Xiang Li-Ping , Cai Zhuo-Yu , Lu Jian-Liang , Ye Jian-Hui , Liang Yue-Rong , Zheng Xin-Qiang
Published: March 2019

There is epidemiological evidence showing that drinking green tea can lower the risk of esophageal cancer (EC). The effect is mainly attributed to tea polyphenols and their most abundant component, (−)-epigallocatechin-3-gallate (EGCG). The possible mechanisms of tumorigenesis inhibition of EGCG include its suppressive effects on cancer cell proliferation, angiogenesis, DNA methylation, metastasis and oxidant stress. EGCG modulates multiple signal transduction and metabolic signaling pathways involving in EC. A synergistic effect was also observed when EGCG was used in combination with other treatment methods.