bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Thyroid: Progress and Prospects
Authors: Gorini Francesca , Bianchi Fabrizio , Iervasi Giorgio
Published: September 2020

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide. A number of serious effects on various organs and systems have been reported in humans, and recently emerging evidence on the potential association between the infection and thyroid dysfunction are attracting attention from the scientific community. This editorial critically summarizes the main findings on this topic published so far and defines research lines according to the translational approach from the bench to the bed to epidemiological studies and back again, aimed at patient care and effective public health measures.
Two-Year Scale-Up of Seasonal Malaria Chemoprevention Reduced Malaria Morbidity among Children in the Health District of Koutiala, Mali
Authors: Maiga Hamma , Gaudart Jean , Sagara Issaka , Diarra Modibo , Bamadio Amadou , Djimde Moussa , Coumare Samba , Sangare Boubou , Dicko Yeyia , Tembely Aly , Traore Djibril , Dicko Alassane , Lasry Estrella , Doumbo Ogobara , Djimde Abdoulaye A.
Published: September 2020

Background: Previous controlled studies demonstrated seasonal malaria chemoprevention (SMC) reduces malaria morbidity by >80% in children aged 3–59 months. Here, we assessed malaria morbidity after large-scale SMC implementation during a pilot campaign in the health district of Koutiala, Mali. Methods: Starting in August 2012, children received three rounds of SMC with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ). From July 2013 onward, children received four rounds of SMC. Prevalence of malaria infection, clinical malaria and anemia were assessed during two cross-sectional surveys conducted in August 2012 and June 2014. Investigations involved 20 randomly selected clusters in 2012 against 10 clusters in 2014. Results: Overall, 662 children were included in 2012, and 670 in 2014. Children in 2014 versus those surveyed in 2012 showed reduced proportions of malaria infection (12.4% in 2014 versus 28.7% in 2012 (p = 0.001)), clinical malaria (0.3% versus 4.2%, respectively (p < 0.001)), and anemia (50.1% versus 67.4%, respectively (p = 0.001)). A propensity score approach that accounts for environmental differences showed that SMC conveyed a significant protective effect against malaria infection (IR = 0.01, 95% CI (0.0001; 0.09), clinical malaria (OR = 0.25, 95% CI (0.06; 0.85)), and hemoglobin concentration (β = 1.3, 95% CI (0.69; 1.96)) in 2012 and 2014, respectively. Conclusion: SMC significantly reduced frequency of malaria infection, clinical malaria and anemia two years after SMC scale-up in Koutiala.
Psychological Impact of COVID-19 Confinement and Its Relationship with Meditation
Authors: Jiménez Óliver , Sánchez-Sánchez Laura C. , García-Montes José M.
Published: September 2020

The objective of this study was to evaluate the psychological impact of confinement due to the COVID-19 pandemic, considering any protective factors, such as the practice of meditation or self-compassion, and their relationship with different lifestyles and circumstances of adults residing in Spain. A cross-sectional study was done using an anonymous online survey in which 412 participants filled out the Depression, Anxiety and Stress Scale-2; the Impact of Events Scale; and the Self-Compassion Scale-Short Form, reporting severe symptomatology of posttraumatic stress and mild anxiety and depression. Quality of cohabitation and age were found to be key variables in the psychological impact of confinement. The impact of confinement was more negative for those who reported very poor cohabitation as opposed to very good (F (3, 405) = 30.75, p ≤ 0.001, d = 2.44, r = 0.054) or for those under 35 years of age compared to those over 46 (F (2, 409) = 5.14, p = 0.006, d = 0.36). Practicing meditation was not revealed as a protective factor, but self-compassion was related to better cohabitation during confinement (F (3, 403) = 11.83, p ≤ 0.001, d = 1.05). These results could be relevant in designing psychological interventions to improve coping and mental health in other situations similar to confinement.
Toxoplasma GRA16 Inhibits NF-κB Activation through PP2A-B55 Upregulation in Non-Small-Cell Lung Carcinoma Cells
Authors: Seo Seung-Hwan , Kim Sang-Gyun , Shin Ji-Hun , Ham Do-Won , Shin Eun-Hee
Published: September 2020

Nuclear factor kappa B (NF-κB) activation is a well-known mechanism by which chemoresistance to anticancer agents is reported. It is well-known that irinotecan as a chemotherapeutic drug against non-small-cell lung carcinoma (NSCLC) has limited anticancer effect due to NF-κB activation. In this study, we propose the novel role of GRA16, a dense granule protein of Toxoplasma gondii, as an anticancer agent to increase the effectiveness of chemotherapy via the inhibition of NF-κB activation. To demonstrate this, H1299 cells were stably transfected with GRA16. The anticancer effects of GRA16 were demonstrated as a reduction in tumor size in a mouse xenograft model. GRA16 directly elevated B55 regulatory subunit of protein phosphatase 2A (PP2A-B55) expression in tumor cells, thereby decreasing GWL protein levels and ENSA phosphorylation. This cascade, in turn, induced PP2A-B55 activation and suppressed AKT/ERK phosphorylation and cyclin B1 levels, suggesting reduced cell survival and arrested cell cycle. Moreover, PP2A-B55 activation and AKT phosphorylation inhibition led to NF-κB inactivation via the reduction in inhibitory kappa B kinase beta (IKKβ) levels, de-phosphorylation of inhibitor of kappa B alpha (IκBα), and reduction in the nuclear transit of NF-κB p65. Furthermore, this molecular mechanism was examined under irinotecan treatment. The PP2A-B55/AKT/NF-κB p65 pathway-mediated anticancer effects were only induced in the presence of GRA16, but not in the presence of irinotecan. Moreover, GRA16 synergistically promoted the anticancer effects of irinotecan via the induction of the sub-G1 phase and reduction of cell proliferation. Collectively, irinotecan and GRA16 co-treatment promotes the anticancer effects of irinotecan via NF-κB inhibition and cell cycle arrest induced by GRA16, subsequently increasing the chemotherapeutic effect of irinotecan to NSCLC cells via NF-κB inhibition.
mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer
Authors: Dolicka Dobrochna , Sobolewski Cyril , Correia de Sousa Marta , Gjorgjieva Monika , Foti Michelangelo
Published: September 2020

AU-rich element-binding proteins (AUBPs) represent important post-transcriptional regulators of gene expression. AUBPs can bind to the AU-rich elements present in the 3’-UTR of more than 8% of all mRNAs and are thereby able to control the stability and/or translation of numerous target mRNAs. The regulation of the stability and the translation of mRNA transcripts by AUBPs are highly complex processes that occur through multiple mechanisms depending on the cell type and the cellular context. While AUBPs have been shown to be involved in inflammatory processes and the development of various cancers, their important role and function in the development of chronic metabolic and inflammatory fatty liver diseases (FLDs), as well as in the progression of these disorders toward cancers such as hepatocellular carcinoma (HCC), has recently started to emerge. Alterations of either the expression or activity of AUBPs are indeed significantly associated with FLDs and HCC, and accumulating evidence indicates that several AUBPs are deeply involved in a significant number of cellular processes governing hepatic metabolic disorders, inflammation, fibrosis, and carcinogenesis. Herein, we discuss our current knowledge of the roles and functions of AUBPs in liver diseases and cancer. The relevance of AUBPs as potential biomarkers for different stages of FLD and HCC, or as therapeutic targets for these diseases, are also highlighted.
Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism
Authors: Lathen Daniel R. , Merrill Collin B. , Rothenfluh Adrian
Published: September 2020

Alcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism, play a role in alcohol responses, and/or contribute to the development of addiction. As a highly tractable and translatable genetic and behavioral model organism, Drosophila melanogaster has proven valuable to uncover important genes and mechanistic pathways that have obvious orthologs in humans and that help explain the complexities of addiction. Vinegar flies exhibit remarkably strong face and mechanistic validity as a model for AUDs, permitting many advancements in the quest to understand human genetic involvement in this disease. These advancements occur via approaches that essentially fall into one of two categories: (1) discovering candidate genes via human genome-wide association studies (GWAS), transcriptomics on post-mortem tissue from AUD patients, or relevant physiological connections, then using reverse genetics in flies to validate candidate genes’ roles and investigate their molecular function in the context of alcohol. (2) Utilizing flies to discover candidate genes through unbiased screens, GWAS, quantitative trait locus analyses, transcriptomics, or single-gene studies, then validating their translational role in human genetic surveys. In this review, we highlight the utility of Drosophila as a model for alcoholism by surveying recent advances in our understanding of human AUDs that resulted from these various approaches. We summarize the genes that are conserved in alcohol-related function between humans and flies. We also provide insight into some advantages and limitations of these approaches. Overall, this review demonstrates how Drosophila have and can be used to answer important genetic questions about alcohol addiction.
Adult Neurogenesis in the Drosophila Brain: The Evidence and the Void
Authors: Li Guiyi , Hidalgo Alicia
Published: September 2020

Establishing the existence and extent of neurogenesis in the adult brain throughout the animals including humans, would transform our understanding of how the brain works, and how to tackle brain damage and disease. Obtaining convincing, indisputable experimental evidence has generally been challenging. Here, we revise the state of this question in the fruit-fly Drosophila. The developmental neuroblasts that make the central nervous system and brain are eliminated, either through apoptosis or cell cycle exit, before the adult fly ecloses. Despite this, there is growing evidence that cell proliferation can take place in the adult brain. This occurs preferentially at, but not restricted to, a critical period. Adult proliferating cells can give rise to both glial cells and neurons. Neuronal activity, injury and genetic manipulation in the adult can increase the incidence of both gliogenesis and neurogenesis, and cell number. Most likely, adult glio- and neuro-genesis promote structural brain plasticity and homeostasis. However, a definitive visualisation of mitosis in the adult brain is still lacking, and the elusive adult progenitor cells are yet to be identified. Resolving these voids is important for the fundamental understanding of any brain. Given its powerful genetics, Drosophila can expedite discovery into mammalian adult neurogenesis in the healthy and diseased brain.
Aryl Hydrocarbon Receptor (AHR) Ligands as Selective AHR Modulators (SAhRMs)
Authors: Safe Stephen , Jin Un-ho , Park Hyejin , Chapkin Robert S. , Jayaraman Arul
Published: September 2020

The aryl hydrocarbon receptor (AhR) was first identified as the intracellular protein that bound and mediated the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and dioxin-like compounds (DLCs). Subsequent studies show that the AhR plays an important role in maintaining cellular homeostasis and in pathophysiology, and there is increasing evidence that the AhR is an important drug target. The AhR binds structurally diverse compounds, including pharmaceuticals, phytochemicals and endogenous biochemicals, some of which may serve as endogenous ligands. Classification of DLCs and non-DLCs based on their persistence (metabolism), toxicities, binding to wild-type/mutant AhR and structural similarities have been reported. This review provides data suggesting that ligands for the AhR are selective AhR modulators (SAhRMs) that exhibit tissue/cell-specific AhR agonist and antagonist activities, and that their functional diversity is similar to selective receptor modulators that target steroid hormone and other nuclear receptors.
Pathological Responses of Cardiac Mitochondria to Burn Trauma
Authors: Wang Meijing , Scott Susan R. , Koniaris Leonidas G. , Zimmers Teresa A.
Published: September 2020

Despite advances in treatment and care, burn trauma remains the fourth most common type of traumatic injury. Burn-induced cardiac failure is a key factor for patient mortality, especially during the initial post-burn period (the first 24 to 48 h). Mitochondria, among the most important subcellular organelles in cardiomyocytes, are a central player in determining the severity of myocardial damage. Defects in mitochondrial function and structure are involved in pathogenesis of numerous myocardial injuries and cardiovascular diseases. In this article, we comprehensively review the current findings on cardiac mitochondrial pathological changes and summarize burn-impaired mitochondrial respiration capacity and energy supply, induced mitochondrial oxidative stress, and increased cell death. The molecular mechanisms underlying these alterations are discussed, along with the possible influence of other biological variables. We hope this review will provide useful information to explore potential therapeutic approaches that target mitochondria for cardiac protection following burn injury.
Minor Ginsenoside Rg2 and Rh1 Attenuates LPS-Induced Acute Liver and Kidney Damages via Downregulating Activation of TLR4-STAT1 and Inflammatory Cytokine Production in Macrophages
Authors: Huynh Diem Thi Ngoc , Baek Naehwan , Sim Sohyun , Myung Chang-Seon , Heo Kyung-Sun
Published: September 2020

Ginsenosides have been reported to have various biological effects, such as immune regulation and anticancer activity. In this study, we investigated the anti-inflammatory role of a combination of Rg2 and Rh1, which are minor ginsenosides, in lipopolysaccharide (LPS)-stimulated inflammation. In vitro experiments were performed using the RAW264.7 cell line, and an in vivo model of inflammation was established using LPS-treated ICR mice. We employed Griess assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction, western blotting, immunofluorescence staining, and hematoxylin and eosin staining to evaluate the effect of Rg2 and Rh1. We found that Rg2 and Rh1 significantly decreased LPS-induced major inflammatory mediator production, inducible-nitric oxide synthase expression, and nitric oxide production in macrophages. Moreover, Rg2 and Rh1 combination treatment inhibited the binding of LPS to toll-like receptor 4 (TLR4) on peritoneal macrophages. Therefore, the combination of ginsenoside Rg2 and Rh1 suppressed inflammation by abolishing the binding of LPS to TLR4, thereby inhibiting the TLR4-mediated signaling pathway. The combined ginsenoside synergistically blocked LPS-mediated PKCδ translocation to the plasma membrane, resulting in p38-STAT1 activation and NF-κB translocation. In addition, mRNA levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IFN-β, were significantly decreased by combined ginsenoside treatment. Notably, the 20 mg/kg ginsenoside treatment significantly reduced LPS-induced acute tissue inflammation levels in vivo, as indicated by the tissue histological damage scores and the levels of biochemical markers for liver and kidney function from mouse serum. These results suggest that the minor ginsenosides Rg2 and Rh1 may play a key role in prevention of LPS-induced acute inflammation and tissue damage.
Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology
Authors: Kyriazi Athina A. , Papiris Efstathios , Kitsos Kalyvianakis Konstantinos , Sakellaris George , Baritaki Stavroula
Published: September 2020

The identification of cancer stem cells (CSCs) as initiators of carcinogenesis has revolutionized the era of cancer research and our perception for the disease treatment options. Additional CSC features, including self-renewal and migratory and invasive capabilities, have further justified these cells as putative diagnostic, prognostic, and therapeutic targets. Given the CSC plasticity, the identification of CSC-related biomarkers has been a serious burden in CSC characterization and therapeutic targeting. Over the past decades, a compelling amount of evidence has demonstrated critical regulatory functions of non-coding RNAs (ncRNAs) on the exclusive features of CSCs. We now know that ncRNAs may interfere with signaling pathways, vital for CSC phenotype maintenance, such as Notch, Wnt, and Hedgehog. Here, we discuss the multifaceted contribution of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as representative ncRNA classes, in sustaining the CSC-like traits, as well as the underlying molecular mechanisms of their action in various CSC types. We further discuss the use of CSC-related ncRNAs as putative biomarkers of high diagnostic, prognostic, and therapeutic value.
Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich’s Ataxia Patients
Authors: Pérez-Luz Sara , Loria Frida , Katsu-Jiménez Yurika , Oberdoerfer Daniel , Yang Oscar-Li , Lim Filip , Muñoz-Blanco José Luis , Díaz-Nido Javier
Published: September 2020

Friedreich’s ataxia is the most common hereditary ataxia for which there is no cure or approved treatment at present. However, therapeutic developments based on the understanding of pathological mechanisms underlying the disease have advanced considerably, with the implementation of cellular models that mimic the disease playing a crucial role. Human olfactory ecto-mesenchymal stem cells represent a novel model that could prove useful due to their accessibility and neurogenic capacity. Here, we isolated and cultured these stem cells from Friedreich´s ataxia patients and healthy donors, characterizing their phenotype and describing disease-specific features such as reduced cell viability, impaired aconitase activity, increased ROS production and the release of cytokines involved in neuroinflammation. Importantly, we observed a positive effect on patient-derived cells, when frataxin levels were restored, confirming the utility of this in vitro model to study the disease. This model will improve our understanding of Friedreich´s ataxia pathogenesis and will help in developing rationally designed therapeutic strategies.
Longitudinal Evaluation of Working Memory in Duchenne Muscular Dystrophy
Authors: Thangarajh Mathula , Elfring Gary L. , Trifillis Panayiota
Published: September 2020

Objective: The developmental maturation of forward and backward digit spans—indices of working memory—in boys with nonsense (nm) Duchenne muscular dystrophy (DMD) (nmDMD) was assessed using prospective, longitudinal data. Methods: Fifty-five boys of the 57 subjects with genetically confirmed nmDMD—who were from the placebo arm of a 48-week-long phase 2b clinical trial—were evaluated. Forward and backward digit spans were obtained every 12 weeks for a total of five assessments in all study subjects. Changes in forward and backward digit spans were evaluated based on age, corticosteroid treatment, and DMD mutation location. Results: Boys with nmDMD had lower mean scores on normalized forward digit span. Normalized forward digit spans were comparable between subjects stratified by age and between corticosteroid-naïve and corticosteroid-treated subjects. When stratified by DMD mutation location, normalized forward digit spans were lower in nmDMD subjects with mutations downstream of DMD exon 30, exon 45, and exon 63, both at baseline evaluation and at follow-up evaluation at 48 weeks. On average, normalized backward digit span scores were stable over 48 weeks in these subjects. Developmental growth modeling showed that subjects with nmDMD mutations upstream of DMD exon 30, upstream of DMD exon 45, and upstream of DMD exon 63 appeared to make better gains in working memory than subjects with mutations downstream of DMD exon 30, downstream of DMD exon 45, and downstream of DMD exon 63. Conclusion: Performance in working memory shows deficits in nmDMD and differed based on nmDMD location. Maturation in cognition was seen over a 48-week period. The developmental trajectory of working memory in this cohort was influenced by DMD mutation location.
The Dimensional Accuracy of Thin-Walled Parts Manufactured by Laser-Powder Bed Fusion Process
Authors: Tomas Josef , Hitzler Leonhard , Köller Marco , von Kobylinski Jonas , Sedlmajer Michael , Werner Ewald , Merkel Markus
Published: September 2020

Laser-Powder Bed Fusion brings new possibilities for the design of parts, e.g., cutter shafts with integrated cooling channels close to the contour. However, there are new challenges to dimensional accuracy in the production of thin-walled components, e.g., heat exchangers. High degrees of dimensional accuracy are necessary for the production of functional components. The aim is to already achieve these during the process, to reduce post-processing costs and time. In this work, thin-walled ring specimens of H13 tool steel are produced and used for the analysis of dimensional accuracy and residual stresses. Two different scanning strategies were evaluated. One is a stripe scan strategy, which was automatically generated and provided by the machine manufacturer, and a (manually designed) sectional scan strategy. The ring segment strategy is designed by manually segmenting the geometry, which results in a longer preparation time. The samples were printed in different diameters and analyzed with respect to the degree of accuracy and residual stresses. The dimensional accuracy of ring specimens could be improved by up to 81% with the introduced sectional strategy compared to the standard approach.
Comparison of the Hybrid Capture II Method with a PCR-Based Screening Method Using a Carboxyfluorescein-Labeled Primer for Detecting Human Papillomavirus in Cervicovaginal Liquid-Based Cytology
Authors: Saiki Yusuke , Gion Yuka , Nishikori Asami , Norimatsu Yoshiaki , Sato Yasuharu
Published: September 2020

Objective: Human papillomaviruses (HPVs) are DNA viruses, of which over 120 types have been identified. The main screening methods for HPV-DNA include the hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays. Liquid-based cytology (LBC) is a high-quality technique developed to improve the diagnostic reliability of traditional Papanicolaou tests (Pap tests). However, relatively few studies have compared the efficacy of PCR and HC-II assays using cervicovaginal LBC specimens. In this study, we conducted a comparative analysis with results derived from the HC-II assay to assess whether a PCR-based assay using a novel carboxyfluorescein (FAM)-labeled primer could be applied to cervicovaginal LBC specimens. Methods and Results: We analyzed 59 specimens diagnosed as atypical squamous cells of undetermined significance (ASCUS) by Pap tests. After extracting DNA from cervicovaginal LBC specimens, we performed PCR using a FAM-labeled consensus primer, and then conducted fragment analysis to confirm the results. The value of the kappa statistic measuring the agreement between the PCR and HC-II results was 0.8557, or “almost perfect agreement.” Conclusion: Our novel HPV-PCR assay can be successfully applied to cervicovaginal LBC specimens for the detection of HPV subtypes.
First-Order Comprehensive Adjoint Method for Computing Operator-Valued Response Sensitivities to Imprecisely Known Parameters, Internal Interfaces and Boundaries of Coupled Nonlinear Systems: II. Application to a Nuclear Reactor Heat Removal Benchmark
Authors: Cacuci Dan Gabriel
Published: September 2020

This work illustrates the application of a comprehensive first-order adjoint sensitivity analysis methodology (1st-CASAM) to a heat conduction and convection analytical benchmark problem which simulates heat removal from a nuclear reactor fuel rod. This analytical benchmark problem can be used to verify the accuracy of numerical solutions provided by software modeling heat transport and fluid flow systems. This illustrative heat transport benchmark shows that collocation methods require one adjoint computation for every collocation point while spectral expansion methods require one adjoint computation for each cardinal function appearing in the respective expansion when recursion relations cannot be developed between the corresponding adjoint functions. However, it is also shown that spectral methods are much more efficient when recursion relations provided by orthogonal polynomials make it possible to develop recursion relations for computing the corresponding adjoint functions. When recursion relations cannot be developed for the adjoint functions, the collocation method is probably more efficient than the spectral expansion method, since the sources for the corresponding adjoint systems are just Dirac delta functions (which makes the respective computation equivalent to the computation of a Green’s function), rather than the more elaborated sources involving high-order Fourier basis functions or orthogonal polynomials. For systems involving many independent variables, it is likely that a hybrid combination of spectral expansions in some independent variables and collocation in the remaining independent variables would provide the most efficient computational outcome.
Effect of Astaxanthin on the Expression and Activity of Aquaporin-3 in Skin in an In-Vitro Study
Authors: Ikarashi Nobutomo , Kon Risako , Nagoya Chika , Ishikura Airi , Sugiyama Yuri , Takahashi Jiro , Sugiyama Kiyoshi
Published: September 2020

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is a red lipophilic pigment with strong antioxidant action. Oral or topical administration of astaxanthin has been reported to improve skin function, including increasing skin moisture. In this study, we examined the mechanism by which astaxanthin improves skin function by focusing on the water channel aquaporin-3 (AQP3), which plays important roles in maintaining skin moisture and function. When astaxanthin was added to PHK16-0b or HaCaT cells, the mRNA expression level of AQP3 increased significantly in a concentration-dependent manner in both cell lines. The AQP3 protein expression level was also confirmed to increase when astaxanthin was added to HaCaT cells. Similarly, when astaxanthin was added to 3D human epidermis model EpiSkin, AQP3 expression increased. Furthermore, when glycerol and astaxanthin were simultaneously added to EpiSkin, glycerol permeability increased significantly compared with that observed for the addition of glycerol alone. We demonstrated that astaxanthin increases AQP3 expression in the skin and enhances AQP3 activity. This result suggests that the increased AQP3 expression in the skin is associated with the increase in skin moisture by astaxanthin. Thus, we consider astaxanthin useful for treating dry skin caused by decreased AQP3 due to factors such as diabetes mellitus and aging.
Effects of Aging on the Microstructure and Properties of 7075 Al Sheets
Authors: Zhao Zhongxin , Wu Ruoqing , Wang Bo , Huang Mingchu , Lei Guopeng , Luo Fenghua
Published: September 2020

The effects of one-step aging and double aging on the properties and microstructures of 7075 Al sheets were studied via mechanical property testing, scanning electron microscopy, and transmission electron microscopy. The results indicated that with continued one-step aging, the tensile and yield strengths of the Al sheets first increased rapidly with an increase in the treatment time to 8 h and then increased slightly with a further increase in the treatment time to 10 h. The tensile and yield strengths became constant after 16 h of treatment. The mechanical strength properties of the Al sheets peaked after 16 h of one-step aging. However, the double aging treatment provided better mechanical properties and working efficiency than the one-step aging treatment. The tensile strength and microhardness resulting from double aging were greater than those resulting from one-step aging by 5.87% and 8.71%, respectively. Herein, we quantified the contribution ofvarious strengthening mechanisms.
Lattice Strain Evolutions in Ni-W Alloys during a Tensile Test Combined with Synchrotron X-ray Diffraction
Authors: Sadat Tarik , Faurie Damien , Thiaudière Dominique , Mocuta Cristian , Tingaud David , Dirras Guy
Published: September 2020

Ni and Ni(W) solid solution of bulk Ni and Ni-W alloys (Ni-10W, Ni-30W, and Ni-50W) (wt%) were mechanically compared through the evolution of their {111} X-ray diffraction peaks during in situ tensile tests on the DiffAbs beamline at the Synchrotron SOLEIL. A significant difference in terms of strain heterogeneities and lattice strain evolution occurred as the plastic activity increased. Such differences are attributed to the number of brittle W clusters and the hardening due to the solid solution compared to the single-phase bulk Ni sample.
The Usefulness of Pine Timber (Pinus sylvestris L.) for the Production of Structural Elements. Part II: Strength Properties of Glued Laminated Timber
Authors: Mirski Radosław , Dziurka Dorota , Chuda-Kowalska Monika , Kawalerczyk Jakub , Kuliński Marcin , Łabęda Karol
Published: September 2020

The paper assessed the feasibility of manufacturing glued structural elements made of pine wood after grading it mechanically in a horizontal arrangement. It was assumed that the pine wood was not free of defects and that the outer lamellas would also be visually inspected. This would result in only rejecting items with large, rotten knots. Beams of the assumed grades GL32c, GL28c and GL24c were made of the examined pine wood. Our study indicated that the expected modulus of elasticity in bending was largely maintained by the designed beam models but that their strength was connected with the quality of the respective lamellas, rather than with their modulus of elasticity. On average, the bending strength of the beams was 44.6 MPa. The cause of their destruction was the individual technical quality of a given item of timber, which was loosely related to its modulus of elasticity, assessed in a bending test. Although the modulus of elasticity of the manufactured beam types differed quite significantly (11.45–14.08 kN/mm2), the bending strength for all types was similar. Significant differences occurred only during a more detailed analysis because lower classes were characterized by a greater variation of the bending strength. In this case, beams with a strength of 24 MPa to 50 MPa appeared.
Finite Element Study on the Shear Capacity of Traditional Joints between Walls Made of AAC Masonry Units
Authors: Kozłowski Marcin , Galman Iwona , Jasiński Radosław
Published: September 2020

This paper presents the development of a numerical model aimed at the simulation of nonlinear behaviour of traditional joints between walls made of autoclaved aerated concrete (AAC) masonry units. Nonlinear behaviour and cracking of AAC and mortar were simulated using the concrete damaged plasticity (CDP) model available in the ABAQUS finite element software. The paper also presents and discusses the results of an experimental campaign involving testing six T-shaped, monosymmetric samples with traditional joints between walls loaded in shear. The results were used to validate the numerical model. The validation confirmed that the model is capable of producing accurate results and predicting the structural behaviour with a reasonably good accuracy in elastic and post-elastic stages. Furthermore, a sensitivity study was conducted, in which the variation of elastic modulus, Poisson’s ratio, tensile strength, compression strength and fracture energy of AAC was investigated. Results showed that the variation of elastic modulus, tensile strength and fracture energy is most critical to the structural behaviour of the model, while variation of the remaining parameters has a negligible effect on the results.
A Solution Concept and Its Axiomatic Results under Non-Transferable-Utility and Multi-Choice Situations
Authors: Hwang Yan-An , Liao Yu-Hsien
Published: September 2020

In real situations, agents might take different energy levels to participate. On the other hand, agents always face an increasing need to focus on non-transferable-utility situations efficiently in their operational processes. Thus, we introduce the replicated core under non-transferable-utility situations, and analyze non-emptiness of the replicated core by means of a balanced result. In order to express the rationality of the replicated core, we also define different reduced games to axiomatize the replicated core.
Simplified LC-MS Method for Analysis of Sterols in Biological Samples
Authors: Skubic Cene , Vovk Irena , Rozman Damjana , Križman Mitja
Published: September 2020

We developed a simple and robust liquid chromatographic/mass spectrometric method (LC-MS) for the quantitative analysis of 10 sterols from the late part of cholesterol synthesis (zymosterol, dehydrolathosterol, 7-dehydrodesmosterol, desmosterol, zymostenol, lathosterol, FFMAS, TMAS, lanosterol, and dihydrolanosterol) from cultured human hepatocytes in a single chromatographic run using a pentafluorophenyl (PFP) stationary phase. The method also avails on a minimized sample preparation procedure in order to obtain a relatively high sample throughput. The method was validated on 10 sterol standards that were detected in a single chromatographic LC-MS run without derivatization. Our developed method can be used in research or clinical applications for disease-related detection of accumulated cholesterol intermediates. Disorders in the late part of cholesterol synthesis lead to severe malformation in human patients. The developed method enables a simple, sensitive, and fast quantification of sterols, without the need of extended knowledge of the LC-MS technique, and represents a new analytical tool in the rising field of cholesterolomics.
Towards the Application of Supramolecular Self-Associating Amphiphiles as Next-Generation Delivery Vehicles
Authors: White Lisa J. , Boles Jessica E. , Hilton Kira L. F. , Ellaby Rebecca J. , Hiscock Jennifer R.
Published: September 2020

Herein, we present a series of supramolecular self-associating amphiphilic (SSA) salts and establish the potential for these molecular constructs to act as next-generation solution-state molecular delivery vehicles. We characterise the self-association of these SSAs, both alone and when co-formulated with a variety of drug(like) competitive guest species. Single crystal X-ray diffraction studies enable the observation of hydrogen-bonded self-association events in the solid state, whilst high resolution mass spectrometry confirms the presence of anionic SSA dimers in the gas-phase. These same anionic SSA dimeric species are also identified within a competitive organic solvent environment (DMSO-d6/0.5% H2O). However, extended self-associated aggregates are observed to form under aqueous conditions (H2O/5.0% EtOH) in both the absence and presence of these competitive guest species. Finally, through the completion of these studies, we present a framework to support others in the characterisation of such systems.
Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases
Authors: Showalter Hollis D.
Published: September 2020

Nitroimidazole drugs have a long history as therapeutic agents to treat bacterial and parasitic diseases. The discovery in 1989 of a bicyclic nitroimidazole lead, displaying in vitro and in vivo antitubercular activity, spurred intensive exploration of this and related scaffolds, which led to the regulatory approval of pretomanid and delamanid as a new class of tuberculosis drugs. Much of the discovery work related to this took place over a 20-year period ending in 2010, which is covered in a number of cited reviews. This review highlights subsequent research published over the 2011–August 2020 timeframe, and captures detailed structure–activity relationship studies and synthetic strategies directed towards uncovering newer generation drugs for both tuberculosis and selected neglected tropical diseases. Additionally, this review presents in silico calculations relating to the drug-like properties of lead compounds and clinical agents, as well as chemical development and manufacturing processes toward providing bulk drug supplies.
Effect of Microwave Heating on the Acrylamide Formation in Foods
Authors: Michalak Joanna , Czarnowska-Kujawska Marta , Klepacka Joanna , Gujska Elżbieta
Published: September 2020

Acrylamide (AA) is a neurotoxic and carcinogenic substance that has recently been discovered in food. One of the factors affecting its formation is the heat treatment method. This review discusses the microwave heating as one of the methods of thermal food processing and the influence of microwave radiation on the acrylamide formation in food. In addition, conventional and microwave heating were compared, especially the way they affect the AA formation in food. Available studies demonstrate differences in the mechanisms of microwave and conventional heating. These differences may be beneficial or detrimental depending on different processes. The published studies showed that microwave heating at a high power level can cause greater AA formation in products than conventional food heat treatment. The higher content of acrylamide in microwave-heated foods may be due to differences in its formation during microwave heating and conventional methods. At the same time, short exposure to microwaves (during blanching and thawing) at low power may even limit the formation of acrylamide during the final heat treatment. Considering the possible harmful effects of microwave heating on food quality (e.g., intensive formation of acrylamide), further research in this direction should be carried out.
Probing the Y2 Receptor on Transmembrane, Intra- and Extra-Cellular Sites for EPR Measurements
Authors: Laugwitz Jeannette M. , Haeri Haleh H. , Kaiser Anette , Krug Ulrike , Hinderberger Dariush , Beck-Sickinger Annette G. , Schmidt Peter
Published: September 2020

The function of G protein-coupled receptors is intrinsically linked to their conformational dynamics. In conjugation with site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy provides powerful tools to study the highly dynamic conformational states of these proteins. Here, we explored positions for nitroxide spin labeling coupled to single cysteines, introduced at transmembrane, intra- and extra-cellular sites of the human neuropeptide Y2 receptor. Receptor mutants were functionally analyzed in cell culture system, expressed in Escherichia coli fermentation with yields of up to 10 mg of purified protein per liter expression medium and functionally reconstituted into a lipid bicelle environment. Successful spin labeling was confirmed by a fluorescence assay and continuous wave EPR measurements. EPR spectra revealed mobile and immobile populations, indicating multiple dynamic conformational states of the receptor. We found that the singly mutated positions by MTSL ((1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl) methyl methanesulfonothioate) have a water exposed immobilized conformation as their main conformation, while in case of the IDSL (bis(1-oxyl-2,2,5,5-tetramethyl-3-imidazolin-4-yl) disulfide) labeled positions, the main conformation are mainly of hydrophobic nature. Further, double cysteine mutants were generated and examined for potential applications of distance measurements by double electron–electron resonance (DEER) pulsed EPR technique on the receptor.
Sephadex® LH-20, Isolation, and Purification of Flavonoids from Plant Species: A Comprehensive Review
Authors: Mottaghipisheh Javad , Iriti Marcello
Published: September 2020

Flavonoids are considered one of the most diverse phenolic compounds possessing several valuable health benefits. The present study aimed at gathering all correlated reports, in which Sephadex® LH-20 (SLH) has been utilized as the final step to isolate or purify of flavonoid derivatives among all plant families. Overall, 189 flavonoids have been documented, while the majority were identified from the Asteraceae, Moraceae, and Poaceae families. Application of SLH has led to isolate 79 flavonols, 63 flavones, and 18 flavanones. Homoisoflavanoids, and proanthocyanidins have only been isolated from the Asparagaceae and Lauraceae families, respectively, while the Asteraceae was the richest in flavones possessing 22 derivatives. Six flavones, four flavonols, three homoisoflavonoids, one flavanone, a flavanol, and an isoflavanol have been isolated as the new secondary metabolites. This technique has been able to isolate quercetin from 19 plant species, along with its 31 derivatives. Pure methanol and in combination with water, chloroform, and dichloromethane have generally been used as eluents. This comprehensive review provides significant information regarding to remarkably use of SLH in isolation and purification of flavonoids from all the plant families; thus, it might be considered an appreciable guideline for further phytochemical investigation of these compounds.
One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
Authors: Bais Jessica , Benedetti Fabio , Berti Federico , Cerminara Iole , Drioli Sara , Funicello Maria , Regini Giorgia , Vidali Mattia , Felluga Fulvia
Published: September 2020

A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC50 in the range 100 nM–50 μM.
Analysis of Phenolic Components and Related Biological Activities of 35 Apple (Malus pumila Mill.) Cultivars
Authors: Liang Xiao , Zhu Tailin , Yang Sijia , Li Xin , Song Bo , Wang Yue , Lin Qiong , Cao Jinping
Published: September 2020

Apple (Malus pumila Mill.) is a popular fruit with high economic values and various biological activities that are beneficial to human health. In this study, 35 apple cultivars were collected and were evaluated for their basic quality indexes, phenolic compositions, antioxidant activity, anti-tumour, and anti-diabetic activities. The compositions of phenolics were detected by using high-performance liquid chromatography (HPLC) and high-resolution mass spectroscopy (HRMS) assays. The antioxidant activities of peel and pulp extracts from 35 apple cultivars were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and ferric reducing antioxidant power (FRAP) assay. Results showed that the contents of phenolic acids and proanthocyanidins showed significant correlations with the antioxidant activities. Phenolic-rich extracts significantly inhibited HepG2 cell proliferation, with the inhibition activity varied significantly between cultivars. ‘Gold Delicious’ pulp extract, ‘Xiboliyabaidian’ peel and pulp extracts showed protective effects on H2O2-induced injury of human umbilical vein endothelial cells (HUVEC). ‘Red Fuji’ peel extract, ‘Xiboliyabaidian’ peel and pulp extracts, as well as ‘Gold Delicious’ peel extract, significantly increased glucose consumption of HepG2 cells, in a dose-dependent manner. This research may provide theoretical guidance for further nutritional investigation of the apple resources.
Rheological, Microstructural and Thermal Properties of Magnetic Poly(Ethylene Oxide)/Iron Oxide Nanocomposite Hydrogels Synthesized Using a One-Step Gamma-Irradiation Method
Authors: Marić Ivan , Šijaković Vujičić Nataša , Pustak Anđela , Gotić Marijan , Štefanić Goran , Grenèche Jean-Marc , Dražić Goran , Jurkin Tanja
Published: September 2020

Magnetic polymer gels are a new promising class of nanocomposite gels. In this work, magnetic PEO/iron oxide nanocomposite hydrogels were synthesized using the one-step γ-irradiation method starting from poly(ethylene oxide) (PEO) and iron(III) precursor alkaline aqueous suspensions followed by simultaneous crosslinking of PEO chains and reduction of Fe(III) precursor. γ-irradiation dose and concentrations of Fe3+, 2-propanol and PEO in the initial suspensions were varied and optimized. With 2-propanol and at high doses magnetic gels with embedded magnetite nanoparticles were obtained, as confirmed by XRD, SEM and Mössbauer spectrometry. The quantitative determination of γ-irradiation generated Fe2+ was performed using the 1,10-phenanthroline method. The maximal Fe2+ molar fraction of 0.55 was achieved at 300 kGy, pH = 12 and initial 5% of Fe3+. The DSC and rheological measurements confirmed the formation of a well-structured network. The thermal and rheological properties of gels depended on the dose, PEO concentration and initial Fe3+ content (amount of nanoparticles synthesized inside gels). More amorphous and stronger gels were formed at higher dose and higher nanoparticle content. The properties of synthesized gels were determined by the presence of magnetic iron oxide nanoparticles, which acted as reinforcing agents and additional crosslinkers of PEO chains thus facilitating the one-step gel formation.
A Smart Multi-Plane Detector Design for Ultrafast Electron Beam X-ray Computed Tomography
Authors: Bieberle André , Windisch Dominic , Iskander Kerolos , Bieberle Martina , Hampel Uwe
Published: September 2020

In this paper, a smart detector design for novel multi-plane ultrafast electron beam X-ray computed tomography is presented. The concept is based on multi-plane electron beam scanning on a transparent X-ray target and elongated cuboid-shape scintillation detectors for radiation detection over an extended axial scanning range. The optical part of the scintillation detector acts as both an X-ray sensitive scintillator with a fast time response and a light guide. With that, we reduce detector complexity, number of detector elements, overall power consumption, and detector costs. We investigated the performance of this new multi-plane detector design with an evaluation detector setup that is made of cerium doped lutetium yttrium oxyorthosilicate (LYSO:Ce) as scintillation material and an avalanche photodiode (APD) array. Thereby, we assessed two design variants: A monolithic LYSO bar detector and a sandwich detector made of multiple LYSO crystals and glass light-guides. Both types reveal excellent linear detector responses, long-term stabilities, and comparable signal qualities.