bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Reduction Atmosphere on Structure and Catalytic Performance of PtIn/Mg(Al)O/ZnO for Propane Dehydrogenation
Authors: Zhang Ming , Song Zhen , Guo Mengquan , Li Xiangxiang , Lin Yanjun , Zhang Lihong
Published: April 2020

The effect of reduction atmospheres, H2/N2, C3H8/H2/N2, C3H8 and CO, on the structure and propane direct dehydrogenation performance of PtIn/Mg(Al)O/ZnO catalyst derived from ZnO-supported PtIn-hydrotalcite was studied. The physicochemical properties of the as-prepared and used catalytic system were characterized by various characterization methods. The results show that the dehydrogenation performance, especially the stability of the PtIn/Mg(Al)O/ZnO catalyst, was significantly improved along with the change in reduction atmosphere. The highest catalytic activity (51% of propane conversion and 97% propylene selectivity), resistance toward coke deposition, and stability for more than 30 h were achieved with the H2/N2-reduced catalyst. The optimal dehydrogenation performance and coke resistance are mainly related to the high Pt dispersion and In0/In3+ molar ratio, strong Pt–In interaction and small metal particle size, depending on the nature of the reduction atmospheres. The reconstruction of meixnerite favors the stability and coke resistance to some extent.
Gas-Phase Hydrogenation of Furfural to Furfuryl Alcohol over Cu-ZnO-Al2O3 Catalysts Prepared from Layered Double Hydroxides
Authors: R. Bertolini Guillermo , Jiménez-Gómez Carmen P. , Cecilia Juan Antonio , Maireles-Torres Pedro
Published: April 2020

Several layered double hydroxides (LDHs) with general chemical composition (Cu,Zn)1−xAlx(OH)2(CO3)x/2·mH2O have been synthesized by the co-precipitation method, maintaining a (M2+/M3+) molar ratio of 3, and varying the Cu2+/Zn2+ molar ratio between 0.2 and 6.0. After calcination and reduction steps, Cu/ZnO/Al2O3 catalysts were synthesized. These catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), H2 thermoprogrammed reduction (H2-TPR), N2 adsorption-desorption at −196 °C, N2O titration, X-ray photoelectron miscroscopy (XPS), NH3-thermoprogramed desorption (NH3-TPD) and CO2- thermoprogrammed desorption (CO2-TPD). The characterization data revealed that these catalysts are mainly meso-and macroporous, where Cu, ZnO and Al2O3 are well dispersed. The catalytic results show that these catalysts are active in the gas-phase hydrogenation of furfural, being highly selective to furfuryl alcohol (FOL) and reaching the highest FOL yield for the catalyst with a Cu2+/Zn2+ molar ratio of 1. In an additional study, the influence of the aging time on the synthesis of the LDHs was also evaluated. The catalytic data revealed that the use of shorter aging time in the formation of the LDH has a beneficial effect on the catalytic behavior, since more disordered structures with a higher amount of available Cu sites is obtained, leading to a higher yield towards FOL (71% after 5 h of time-on-stream at 210 °C).
Cell Cycle-Dependent Dynamics of the Golgi-Centrosome Association in Motile Cells
Authors: Frye Keyada , Renda Fioranna , Fomicheva Maria , Zhu Xiaodong , Gong Lisa , Khodjakov Alexey , Kaverina Irina
Published: April 2020

Here, we characterize spatial distribution of the Golgi complex in human cells. In contrast to the prevailing view that the Golgi compactly surrounds the centrosome throughout interphase, we observe characteristic differences in the morphology of Golgi ribbons and their association with the centrosome during various periods of the cell cycle. The compact Golgi complex is typical in G1; during S-phase, Golgi ribbons lose their association with the centrosome and extend along the nuclear envelope to largely encircle the nucleus in G2. Interestingly, pre-mitotic separation of duplicated centrosomes always occurs after dissociation from the Golgi. Shortly before the nuclear envelope breakdown, scattered Golgi ribbons reassociate with the separated centrosomes restoring two compact Golgi complexes. Transitions between the compact and distributed Golgi morphologies are microtubule-dependent. However, they occur even in the absence of centrosomes, which implies that Golgi reorganization is not driven by the centrosomal microtubule asters. Cells with different Golgi morphology exhibit distinct differences in the directional persistence and velocity of migration. These data suggest that changes in the radial distribution of the Golgi around the nucleus define the extent of cell polarization and regulate cell motility in a cell cycle-dependent manner.
Adenosinergic System Involvement in Ischemic Stroke Patients’ Lymphocytes
Authors: Pasquini Silvia , Vincenzi Fabrizio , Casetta Ilaria , Laudisi Michele , Merighi Stefania , Gessi Stefania , Borea Pier Andrea , Varani Katia
Published: April 2020

Adenosine modulates many physiological processes through the interaction with adenosine receptors (ARs) named as A1, A2A, A2B, and A3ARs. During ischemic stroke, adenosine mediates neuroprotective and anti-inflammatory effects through ARs activation. One of the dominant pathways generating extracellular adenosine involves the dephosphorylation of ATP by ecto-nucleotidases CD39 and CD73, which efficiently hydrolyze extracellular ATP to adenosine. The aim of the study is to assess the presence of ARs in lymphocytes from ischemic stroke patients compared to healthy subjects and to analyze changes in CD39 and CD73 expression in CD4+ and CD8+ lymphocytes. Saturation binding experiments revealed that A2AARs affinity and density were significantly increased in ischemic stroke patients whilst no differences were found in A1, A2B, and A3ARs. These results were also confirmed in reverse transcription (RT)-polymerase chain reaction (PCR) assays where A2AAR mRNA levels of ischemic stroke patients were higher than in control subjects. In flow cytometry experiments, the percentage of CD73+ cells was significantly decreased in lymphocytes and in T-lymphocyte subclasses CD4+ and CD8+ obtained from ischemic stroke patients in comparison with healthy individuals. These data corroborate the importance of the adenosinergic system in ischemic stroke and could open the way to more targeted therapeutic approaches and biomarker development for ischemic stroke.
Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows
Authors: González-Nieto Daniel , Fernández-Serra Rocío , Pérez-Rigueiro José , Panetsos Fivos , Martinez-Murillo Ricardo , Guinea Gustavo V.
Published: April 2020

Ischemic stroke represents one of the most prevalent pathologies in humans and is a leading cause of death and disability. Anti-thrombolytic therapy with tissue plasminogen activator (t-PA) and surgical thrombectomy are the primary treatments to recanalize occluded vessels and normalize the blood flow in ischemic and peri-ischemic regions. A large majority of stroke patients are refractory to treatment or are not eligible due to the narrow time window of therapeutic efficacy. In recent decades, we have significantly increased our knowledge of the molecular and cellular mechanisms that inexorably lead to progressive damage in infarcted and peri-lesional brain areas. As a result, promising neuroprotective targets have been identified and exploited in several stroke models. However, these considerable advances have been unsuccessful in clinical contexts. This lack of clinical translatability and the emerging use of biomaterials in different biomedical disciplines have contributed to developing a new class of biomaterial-based systems for the better control of drug delivery in cerebral disorders. These systems are based on specific polymer formulations structured in nanoparticles and hydrogels that can be administered through different routes and, in general, bring the concentrations of drugs to therapeutic levels for prolonged times. In this review, we first provide the general context of the molecular and cellular mechanisms impaired by cerebral ischemia, highlighting the role of excitotoxicity, inflammation, oxidative stress, and depolarization waves as the main pathways and targets to promote neuroprotection avoiding neuronal dysfunction. In the second part, we discuss the versatile role played by distinct biomaterials and formats to support the sustained administration of particular compounds to neuroprotect the cerebral tissue at risk of damage.
Adenosine A2A Receptor Antagonists Affects NMDA Glutamate Receptor Function. Potential to Address Neurodegeneration in Alzheimer’s Disease
Authors: Franco Rafael , Rivas-Santisteban Rafael , Casanovas Mireia , Lillo Alejandro , Saura Carlos A. , Navarro Gemma
Published: April 2020

(1) Background. N-methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer’s disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A2A receptor (A2AR), which is a target in neurodegeneration, may affect NMDAR functionality. (2) Methods. Immuno-histo/cytochemical, biophysical, biochemical and signaling assays were performed in a heterologous cell expression system and in primary cultures of neurons and microglia (resting and activated) from control and the APPSw,Ind transgenic mice. (3) Results. On the one hand, NMDA and A2A receptors were able to physically interact forming complexes, mainly in microglia. Furthermore, the amount of complexes was markedly enhanced in activated microglia. On the other hand, the interaction resulted in a novel functional entity that displayed a cross-antagonism, that could be useful to prevent the exacerbation of NMDAR function by using A2AR antagonists. Interestingly, the amount of complexes was markedly higher in the hippocampal cells from the APPSw,Ind than from the control mice. In neurons, the number of complexes was lesser, probably due to NMDAR not interacting with the A2AR. However, the activation of the A2AR receptors resulted in higher NMDAR functionality in neurons, probably by indirect mechanisms. (4) Conclusions. A2AR antagonists such as istradefylline, which is already approved for Parkinson’s disease (Nouriast® in Japan and Nourianz® in the US), have potential to afford neuroprotection in AD in a synergistic-like fashion. i.e., via both neurons and microglia.
Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress
Authors: Ha Tae Won , Jeong Ji Hun , Shin HyeonSeok , Kim Hyun Kyu , Im Jeong Suk , Song Byung Hoo , Hanna Jacob , Oh Jae Sang , Woo Dong-Hun , Han Jaeseok , Lee Man Ryul
Published: April 2020

Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress.
Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation
Authors: McKay Tina B. , Hutcheon Audrey E. K. , Zieske James D. , Ciolino Joseph B.
Published: April 2020

The corneal epithelium mediates the initial response to injury of the ocular surface and secretes a number of profibrotic factors that promote corneal scar development within the stroma. Previous studies have shown that corneal epithelial cells also secrete small extracellular vesicles (EVs) in response to corneal wounding. In this paper, we hypothesized that EVs released from corneal epithelial cells in vitro contain protein cargo that promotes myofibroblast differentiation, the key cell responsible for scar development. We focused on the interplay between corneal epithelial-derived EVs and the stroma to determine if the corneal fibroblast phenotype, contraction, proliferation, or migration were promoted following vesicle uptake by corneal fibroblasts. Our results showed an increase in myofibroblast differentiation based on α-smooth muscle actin expression and elevated contractility following EV treatment compared to controls. Furthermore, we characterized the contents of epithelial cell-derived EVs using proteomic analysis and identified the presence of provisional matrix proteins, fibronectin and thrombospondin-1, as the dominant encapsulated protein cargo secreted by corneal epithelial cells in vitro. Proteins associated with the regulation of protein translation were also abundant in EVs. This paper reveals a novel role and function of EVs secreted by the corneal epithelium that may contribute to corneal scarring.
In Vitro Cytotoxicity Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells
Authors: Pinho Ana Rita , Martins Filipa , Costa M. Elisabete V. , Senos Ana M. R. , da Cruz e Silva Odete A. B. , Pereira Maria de Lourdes , Rebelo Sandra
Published: April 2020

Zinc Oxide Nanoparticles (ZnO NPs) are a type of metal oxide nanoparticle with an extensive use in biomedicine. Several studies have focused on the biosafety of ZnO NPs, since their size and surface area favor entrance and accumulation in the body, which can induce toxic effects. In previous studies, ZnO NPs have been identified as a dose- and time-dependent cytotoxic inducer in testis and male germ cells. However, the consequences for the first cell stage of spermatogenesis, spermatogonia, have never been evaluated. Therefore, the aim of the present work is to evaluate in vitro the cytotoxic effects of ZnO NPs in spermatogonia cells, focusing on changes in cytoskeleton and nucleoskeleton. For that purpose, GC-1 cell line derived from mouse testes was selected as a model of spermatogenesis. These cells were treated with different doses of ZnO NPs for 6 h and 12 h. The impact of GC-1 cells exposure to ZnO NPs on cell viability, cell damage, and cytoskeleton and nucleoskeleton dynamics was assessed. Our results clearly indicate that higher concentrations of ZnO NPs have a cytotoxic effect in GC-1 cells, leading to an increase of intracellular Reactive Oxygen Species (ROS) levels, DNA damage, cytoskeleton and nucleoskeleton dynamics alterations, and consequently cell death. In conclusion, it is here reported for the first time that ZnO NPs induce cytotoxic effects, including changes in cytoskeleton and nucleoskeleton in mouse spermatogonia cells, which may compromise the progression of spermatogenesis in a time- and dose-dependent manner.
The Lysosomotropic Activity of Hydrophobic Weak Base Drugs is Mediated via Their Intercalation into the Lysosomal Membrane
Authors: Stark Michal , Silva Tomás F. D. , Levin Guy , Machuqueiro Miguel , Assaraf Yehuda G.
Published: April 2020

Lipophilic weak base therapeutic agents, termed lysosomotropic drugs (LDs), undergo marked sequestration and concentration within lysosomes, hence altering lysosomal functions. This lysosomal drug entrapment has been described as luminal drug compartmentalization. Consistent with our recent finding that LDs inflict a pH-dependent membrane fluidization, we herein demonstrate that LDs undergo intercalation and concentration within lysosomal membranes. The latter was revealed experimentally and computationally by (a) confocal microscopy of fluorescent compounds and drugs within lysosomal membranes, and (b) molecular dynamics modeling of the pH-dependent membrane insertion and accumulation of an assortment of LDs, including anticancer drugs. Based on the multiple functions of the lysosome as a central nutrient sensory hub and a degradation center, we discuss the molecular mechanisms underlying the alteration of morphology and impairment of lysosomal functions as consequences of LDs’ intercalation into lysosomes. Our findings bear important implications for drug design, drug induced lysosomal damage, diseases and pertaining therapeutics.
RNA Interference Screening Identifies Novel Roles for RhoBTB1 and RhoBTB3 in Membrane Trafficking Events in Mammalian Cells
Authors: Long Maeve , Kranjc Tilen , Mysior Margaritha M. , Simpson Jeremy C.
Published: April 2020

In the endomembrane system of mammalian cells, membrane traffic processes require a high degree of regulation in order to ensure their specificity. The range of molecules that participate in trafficking events is truly vast, and much attention to date has been given to the Rab family of small GTPases. However, in recent years, a role in membrane traffic for members of the Rho GTPase family, in particular Cdc42, has emerged. This prompted us to develop and apply an image-based high-content screen, initially focussing on the Golgi complex, using RNA interference to systematically perturb each of the 21 Rho family members and assess their importance to the overall organisation of this organelle. Analysis of our data revealed previously unreported roles for two atypical Rho family members, RhoBTB1 and RhoBTB3, in membrane traffic events. We find that depletion of RhoBTB3 affects the morphology of the Golgi complex and causes changes in the trafficking speeds of carriers operating at the interface of the Golgi and endoplasmic reticulum. In addition, RhoBTB3 was found to be present on these carriers. Depletion of RhoBTB1 was also found to cause a disturbance to the Golgi architecture, however, this phenotype seems to be linked to endocytosis and retrograde traffic pathways. RhoBTB1 was found to be associated with early endosomal intermediates, and changes in the levels of RhoBTB1 not only caused profound changes to the organisation and distribution of endosomes and lysosomes, but also resulted in defects in the delivery of two different classes of cargo molecules to downstream compartments. Together, our data reveal new roles for these atypical Rho family members in the endomembrane system.
Genome Editing of the SNAI1 Gene in Rhabdomyosarcoma: A Novel Model for Studies of Its Role
Authors: Ulman Aleksandra , Skrzypek Klaudia , Konieczny Paweł , Mussolino Claudio , Cathomen Toni , Majka Marcin
Published: April 2020

Genome editing (GE) tools and RNA interference technology enable the modulation of gene expression in cancer research. While GE mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 or transcription activator-like effector nucleases (TALEN) activity can be used to induce gene knockouts, shRNA interacts with the targeted transcript, resulting in gene knockdown. Here, we compare three different methods for SNAI1 knockout or knockdown in rhabdomyosarcoma (RMS) cells. RMS is the most common sarcoma in children and its development has been previously associated with SNAI1 transcription factor activity. To investigate the role of SNAI1 in RMS development, we compared CRISPR/Cas9, TALEN, and shRNA tools to identify the most efficient tool for the modulation of SNAI1 expression with biological effects. Subsequently, the genome sequence, transcript levels, and protein expression of SNAI1 were evaluated. The modulation of SNAI1 using three different approaches affected the morphology of the cells and modulated the expression of myogenic factors and HDAC1. Our study revealed a similar effectiveness of the tested methods. Nevertheless, the low efficiency of the GE tools was a limiting factor in obtaining biallelic gene knockouts. To conclude, we established and characterized three different models of SNAI1 knockout and knockdown that might be used in further studies investigating the role of SNAI1 in RMS.
Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine
Authors: Alt Eckhard U. , Winnier Glenn , Haenel Alexander , Rothoerl Ralf , Solakoglu Oender , Alt Christopher , Schmitz Christoph
Published: April 2020

It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither ‘fat stem cells’ nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.
A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish
Authors: Solanki Ashish K. , Kondkar Altaf A. , Fogerty Joseph , Su Yanhui , Kim Seok-Hyung , Lipschutz Joshua H. , Nihalani Deepak , Perkins Brian D. , Lobo Glenn P.
Published: April 2020

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is, however, not expressed in systemic tissues, where there is high affinity RBP4 binding and ROL uptake. We tested the hypothesis that the second retinol binding protein 4 receptor 2 (Rbpr2), which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR-generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, which were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatment rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.
P0-Related Protein Accelerates Human Mesenchymal Stromal Cell Migration by Modulating VLA-5 Interactions with Fibronectin
Authors: Roubelakis Maria G. , Tsaknakis Grigorios , Lyu Feng-Juan , Trohatou Ourania , Zannettino Andrew C. W. , Watt Suzanne M.
Published: April 2020

P0-related protein (PZR), a Noonan and LEOPARD syndrome target, is a member of the transmembrane Immunoglobulin superfamily. Its cytoplasmic tail contains two immune-receptor tyrosine-based inhibitory motifs (ITIMs), implicated in adhesion-dependent signaling and regulating cell adhesion and motility. PZR promotes cell migration on the extracellular matrix (ECM) molecule, fibronectin, by interacting with SHP-2 (Src homology-2 domain-containing protein tyrosine phosphatase-2), a molecule essential for skeletal development and often mutated in Noonan and LEOPARD syndrome patients sharing overlapping musculoskeletal abnormalities and cardiac defects. To further explore the role of PZR, we assessed the expression of PZR and its ITIM-less isoform, PZRb, in human bone marrow mesenchymal stromal cells (hBM MSC), and its ability to facilitate adhesion to and spreading and migration on various ECM molecules. Furthermore, using siRNA knockdown, confocal microscopy, and immunoprecipitation assays, we assessed PZR and PZRb interactions with β1 integrins. PZR was the predominant isoform in hBM MSC. Migrating hBM MSCs interacted most effectively with fibronectin and required the association of PZR, but not PZRb, with the integrin, VLA-5(α5β1), leading to modulation of focal adhesion kinase phosphorylation and vinculin levels. This raises the possibility that dysregulation of PZR function may modify hBM MSC migratory behavior, potentially contributing to skeletal abnormalities.
EX-527 Prevents the Progression of High-Fat Diet-Induced Hepatic Steatosis and Fibrosis by Upregulating SIRT4 in Zucker Rats
Authors: Kundu Amit , Dey Prasanta , Park Jae Hyeon , Kim In Su , Kwack Seung Jun , Kim Hyung Sik
Published: April 2020

Sirtuin (SIRT) is known to prevent nonalcoholic fatty liver disease (NAFLD); however, the role of SIRT4 in the progression of hepatic fibrosis remains unknown. We hypothesize that EX-527, a selective SIRT1 inhibitor, can inhibit the progression of high-fat diet (HFD)-induced hepatic fibrosis. We found that SIRT4 expression in the liver of NAFLD patients is significantly lower than that in normal subjects. In this study, EX-527 (5 µg/kg), administered to HFD rats twice a week for ten weeks, reduced the serum levels of triglyceride (TG), total cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and attenuated hepatic fibrosis evidenced by Masson’s trichrome and hepatic fat by oil red-O staining. EX-527 upregulated SIRT2, SIRT3, and SIRT4 expression in the liver of HFD fed rats but downregulated transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression. It decreased proinflammatory cytokine production and hydroxyproline levels in the serum and SMAD4 expression and restored apoptotic protein (Bcl-2, Bax, and cleaved caspase-3) expression. These data propose a critical role for the SIRT4/SMAD4 axis in hepatic fibrogenesis. SIRT4 upregulation has the potential to counter HFD-induced lipid accumulation, inflammation, and fibrogenesis. We demonstrate that EX-527 is a promising candidate in inhibiting the progression of HFD-induced liver fibrosis.
Effects of Mitochondrial-Derived Peptides (MDPs) on Mitochondrial and Cellular Health in AMD
Authors: Nashine Sonali , Kenney M. Cristina
Published: April 2020

Substantive evidence demonstrates the contribution of mitochondrial dysfunction in the etiology and pathogenesis of Age-related Macular Degeneration (AMD). Recently, extensive characterization of Mitochondrial-Derived Peptides (MDPs) has revealed their cytoprotective role in several diseases, including AMD. Here we summarize the varied effects of MDPs on cellular and mitochondrial health, which establish the merit of MDPs as therapeutic targets for AMD. We argue that further research to delve into the mechanisms of action and delivery of MDPs may advance the field of AMD therapy.
Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS
Authors: Illes Peter , Rubini Patrizia , Ulrich Henning , Zhao Yafei , Tang Yong
Published: April 2020

Microglial cells, the resident macrophages of the central nervous system (CNS), exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell-damaging factors, they get transformed into an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species, and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia have a number of important physiological functions in the CNS; for example, they shield small disruptions of the blood–brain barrier by their processes, dynamically interact with synaptic structures, and clear surplus synapses during development. In neurodegenerative illnesses, they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. Therefore, the blockade of this reaction improves the outcome of Alzheimer’s Disease, Parkinson’s Disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, and A3, as targets of endogenous ATP, ADP, or adenosine. ATP is sequentially degraded by the ecto-nucleotidases and 5′-nucleotidase enzymes to the almost inactive inosine as an end product. The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may profoundly interfere with microglial functions and reconstitute the homeostasis of the CNS disturbed by neuroinflammation.
Chemical Solution Deposition of BiFeO3 Films with Layer-by-Layer Control of the Coverage and Composition
Authors: Abramov Alexander , Alikin Denis , Sobol Alexander , Myakishev Dmitry , Slabov Vladislav , Trusov Lev , Safina Violetta , Turygin Anton , Vasiliev Alexander , Shur Vladimir , Kholkin Andrei
Published: April 2020

Chemical solution deposition of BiFeO3 thin films is one of the most commercially available techniques to produce large-scale low-cost coatings for further application in memory devices. In this contribution, we implemented piezoresponse force and conductive atomic force microscopies to study the layer-by-layer sol-gel deposition of BiFeO3 thin films focusing on the local phase distribution, morphology, piezoelectric response, and leakage current. The final properties of resulting thin films are found to be determined not only by the composition of the gel and crystallization step but by the gelation step as well. The drying temperature and treatment duration of the solution are shown to drastically influence the film coverage, which finally determines the morphology of the films and behavior of the crystallization process.
Microstructures and Wear Resistance of CoCrFeNi2V0.5Tix High-Entropy Alloy Coatings Prepared by Laser Cladding
Authors: Li Yaning , Liang Hui , Nie Qiuxin , Qi Zhaoxin , Deng Dewei , Jiang Hui , Cao Zhiqiang
Published: April 2020

CoCrFeNi2V0.5Tix high entropy alloy coatings were synthesized by laser cladding on Ti-6Al-4V (annotated as TC4) substrate. The microstructures, hardness, and wear properties of the coatings were studied in detail. The results showed that these coatings were all composed of body-centered cubic (BCC) solid solution, (Co,Ni)Ti2 phase, and Ti-rich phase. With the increase of Ti content (x in the range of 0–1.0), the hardness of these coatings (about 960 HV) was basically unchanged and stabilized, whereas, when x was increased to 1.25, the correspondent hardness was decreased significantly to about 830 HV. Compared with original substrate, the wear resistance of high-entropy alloy (HEA) coatings was greatly improved. In particular, CoCrFeNi2V0.5Ti0.75 (donated as Ti0.75) exhibited the lowest wear rate, width, and depth of tracks of wear, indicating the best wear resistance. Moreover, the wear mechanisms of Ti0.75 coating were mainly adhesive wear and oxidative wear.
Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT
Authors: Tiralongo Francesco , Palermo Monica , Distefano Giulio , Vancheri Ada , Sambataro Gianluca , Torrisi Sebastiano Emanuele , Galioto Federica , Ferlito Agata , Fazio Giulia , Foti Pietro Valerio , Mauro Letizia Antonella , Vancheri Carlo , Palmucci Stefano , Basile Antonio
Published: April 2020

To evaluate the radiological findings in patients with cryptogenic organizing pneumonia (COP) before steroid treatment and their behavior after therapy, we retrospectively evaluated a total of 22 patients with a diagnosis of COP made by bronchoalveolar lavage (BAL), biopsy or clinical/radiological features, and the patients were followed between 2014 and 2018 at the hospital; the demographic data, symptoms, radiologic findings, diagnostic methods and treatment plans of patients were collected from patients’ hospital records. At least two CT scans of 22 patients (16 female and six men) were evaluated, the first one before starting steroid therapy and the others after therapy. At baseline CT scans, the most common radiological finding was the presence of consolidations (18/22 patients, 81.8%); ground-glass opacities were also very common (15/25, 68.1%). The other findings were as follows: nodules and masses (5/22, 22.7%), atoll sign (4/22, 18.1%), perilobular pattern (3/22, 13.6%) and parenchymal bands (3/22, 13.6%). Two patients had a significant relapse after reducing/interrupting therapy, while three had a complete resolution and are not currently under therapy (maintenance of clinical remission with no oral corticosteroid (OCS)). In High-resolution computed tomography (HRCT) scans after therapy, consolidations were still observable in seven patients (five in new areas of the lung-migratory infiltrates), while most of them disappeared, leaving a residual area of ground glass opacity in two patients. One patient had a residual of the perilobular pattern, with the disappearing of the other findings (consolidations and ground-glass opacities). Two patients developed a fibrosing pattern despite the therapy (9.5%). Cryptogenic organizing pneumonia tends to respond to oral corticosteroid treatment, but some patients may have a null or partial response. We highlight the behavior of this disease after proper therapy.
Pathophysiology of Hip Disorders in Patients with Mucopolysaccharidosis IVA
Authors: Wang Zhigang , Xu Yunlan , Jiang Enze , Wang Jianmin , Tomatsu Shunji , Shen Kaiying
Published: April 2020

Patients with mucopolysaccharidoses IVA (MPS IVA) have a progressive accumulation of the specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS), leading to the degeneration of the cartilage matrix and its connective tissue perturbing the regular microarchitecture of cartilage and successively distorting bone ossification and growth. Impaired cartilage quality and poor bone mineralization lead to serious hip disorders in MPS IVA patients. Although hip dysplasia is seen widely in musculoskeletal abnormality of this disorder, the pathophysiology of the hip bone and cartilage morphology in these patients remains unclear. Until now, no systemic study of the hip joints in MPS IVA has been reported by using the combined images of plain film radiographs (PFR) and Magnetic Resonance Imaging (MRI). This study aimed to assess the bony and cartilaginous features of hip joints and to explore the potentially related factors of femoral head osteonecrosis (FHN) and hip subluxation/dislocation in patients with MPS IVA. Hip joints in MPS IVA patients were retrospectively reviewed, based on the findings of PFR and MRI data from 2014 to 2019. Demographic information was also collected and analyzed with imaging measurements. A total of 19 patients (eight boys and 11 girls) were recruited, and 38 hip joints in these patients were examined. Eleven patients (57.9%) had FHN. FHN patients were statistically compared with those without FHN. Correlations between cartilaginous femoral head coverage (CFHC) and acetabular index (AI), cartilaginous AI (CAI), or neck-shaft angle (NSA) were investigated in patients with hip subluxation or dislocation. The greater cartilaginous coverage of the hips than their osseous inherency was observed. Significant correlation was observed between CFHC and AI (r =−0.351, p = 0.049) or CAI (r =−0.381, p = 0.032). Severe subluxations or dislocations were more likely to be present in those with more dysplastic bony and cartilaginous hips. In conclusion, our study provides the first systemic description of bony and cartilaginous characteristics in the hip morphology of MPS IVA patients. We have demonstrated that plain radiography alone leads to a misunderstanding of hip morphology and that MRI measurements with PFR are an essential tool to evaluate the ‘true’ characterization of hips for MPS IVA patients.
Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients
Authors: Yu Ya-Yen , Chiou Hui-Ling , Tsao Shih-Ming , Huang Chen-Cheng , Lin Chih-Yun , Lee Chia-Yi , Tsao Thomas Chang-Yao , Yang Shun-Fa , Huang Yi-Wen
Published: April 2020

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.
The Warnke Method for the Diagnosis and Improvement of Phonological Competence in Special Needs Children
Authors: Brzdęk Ewa , Brzdęk Janusz
Published: April 2020

Speech, reading, and writing are the basic forms of linguistic communication. Therefore, it is very important to diagnose any problems with them as early and completely as possible, particularly in children with special needs. One of the methods that focuses primarily on the diagnosis and therapy of such learning difficulties is the one developed by Fred Warnke. The diagnostic solutions of the method were motivated by the following assumptions: (a) Automation of hearing, vision, and motor functions can be improved based on the level of brain activity; (b) the development and automation of phonological analysis and synthesis are based on cooperation between the two brain hemispheres. The main purpose of this paper is to present and discuss some research results that show the usefulness of diagnosis of the first stage of the Warnke method, as well as the training determined by it, in improving the phonological memory, language, and reading and writing skills of a group of four Polish children with special needs. The range of automation of each function was estimated on the basis of the values obtained in the diagnoses (initial and final). The final diagnosis showed an improvement in the levels of speech, reading, and writing. Thus, the research has confirmed that the Warnke method diagnosis may help to broaden and complement the standard evaluation methods of phonological competence for Polish children with special needs. The outcomes were so encouraging that we decided to present them to a wider audience.
Prototype of a Low-Cost Electronic Platform for Real Time Greenhouse Environment Monitoring: An Agriculture 4.0 Perspective
Authors: Pisanu Tonino , Garau Salvatore , Ortu Pierluigi , Schirru Luca , Macciò Claudia
Published: April 2020

The Internet of Things has a high impact on upgrade and transformation of the traditional greenhouse agricultural techniques. It is necessary to control the environmental factors for obtaining the optimum growth conditions for the crop and extend the production season to get the optimum yield. These aspects are fundamental for Agriculture 4.0, that uses technology not simply for the sake of innovation but to improve and address the real needs of consumers. In this paper, a prototype of a low-cost electronic platform for real time greenhouse environment monitoring has been designed, developed and built. The prototype has been developed with the purpose of firmware and software prototyping, in order to make the most of device performances. The electronic board is composed by a Main Board, a Green House Core, a Wi-Fi Module, a RS485 Module, an Analog-to-Digital Converter Module and a USB Module. The system permits to collect data by external sensors, elaborate and send them to external devices as laptop, smartphone and internet gateway, using both wired and wireless connection. These data concern to main greenhouse environmental parameters, such as air temperature, humidity, solar radiation, air velocity and CO2 concentration. A Web application has been implemented to allow users a consultation of greenhouse environmental state in a simple and fast way.
Indoor Positioning for Monitoring Older Adults at Home: Wi-Fi and BLE Technologies in Real Scenarios
Authors: Montoliu Raul , Sansano Emilio , Gascó Arturo , Belmonte Oscar , Caballer Antonio
Published: April 2020

This paper presents our experience on a real case of applying an indoor localization system for monitoring older adults in their own homes. Since the system is designed to be used by real users, there are many situations that cannot be controlled by system developers and can be a source of errors. This paper presents some of the problems that arise when real non-expert users use localization systems and discusses some strategies to deal with such situations. Two technologies were tested to provide indoor localization: Wi-Fi and Bluetooth Low Energy. The results shown in the paper suggest that the Bluetooth Low Energy based one is preferable in the proposed task.
Design of a Low-Order FIR Filter for a High-Frequency Square-Wave Voltage Injection Method of the PMLSM Used in Maglev Train
Authors: Zhao He , Zhang Liwei , Liu Jie , Zhang Chao , Cai Jiao , Shen Lu
Published: April 2020

In position sensorless control based on a high-frequency pulsating voltage injection method, filters are used to complete the extraction of high-frequency response signals for position observation. A finite impulse response (FIR) filter has the advantages of good stability and linear phase. However, the FIR filter designed by using traditional methods has a high order which will cause a large time delay. This paper proposes a low-order FIR filter design method for a high-frequency signal injection method in the permanent magnet linear synchronous motor. Based on the frequency characteristics of the current signal, the requirement that the FIR filter needs to meet were analyzed. According to the amplitude–frequency characteristic of the FIR filter, these requirements were converted into constraint equations. By solving these equations, the coefficient of the FIR filter could be obtained. The simulation and experiment results showed the effectiveness of this low-order FIR filter.
Image Classification with Convolutional Neural Networks Using Gulf of Maine Humpback Whale Catalog
Authors: Gómez Blas Nuria , de Mingo López Luis Fernando , Arteta Albert Alberto , Martínez Llamas Javier
Published: April 2020

While whale cataloging provides the opportunity to demonstrate the potential of bio preservation as sustainable development, it is essential to have automatic identification models. This paper presents a study and implementation of a convolutional neural network to identify and recognize humpback whale specimens by processing their tails patterns. This work collects datasets of composed images of whale tails, then trains a neural network by analyzing and pre-processing images with TensorFlow and Keras frameworks. This paper focuses on an identification problem, that is, since it is an identification challenge, each whale is a separate class and whales were photographed multiple times and one attempts to identify a whale class in the testing set. Other possible alternatives with lower cost are also introduced and are the subject of discussion in this paper. This paper reports about a network that is not necessarily the best one in terms of accuracy, but this work tries to minimize resources using an image downsampling and a small architecture, interesting for embedded system.
Enabling ISO 26262 Compliance with Accelerated Diagnostic Coverage Assessment
Authors: Ferlini Frederico , Seman Laio Oriel , Bezerra Eduardo Augusto
Published: April 2020

Modern vehicles are integrating a growing number of electronics to provide a safer experience for the driver. Therefore, safety is a non-negotiable requirement that must be considered through the vehicle development process. The ISO 26262 standard provides guidance to ensure that such requirements are implemented. Fault injection is highly recommended for the functional verification of safety mechanisms or to evaluate their diagnostic coverage capability. An exhaustive analysis is not required, but evidence of best effort through the diagnostic coverage assessment needs to be provided when performing quantitative evaluation of hardware architectural metrics. These metrics support that the automotive safety integrity level—ranging from A (lowest) to D (strictest) levels—was obeyed. In this context, this paper proposed a verification solution in order to build an approach that can accelerate the diagnostic coverage assessment via fault injection in the semiconductor level (i.e., hardware description language). The proposed solution does not require any modification of the design model to enable acceleration. Small parts of the OpenRISC architecture (namely a carry adder, the Tick Timer peripheral, and the exception block) were used to illustrate the methodology.
Revisit of Password-Authenticated Key Exchange Protocol for Healthcare Support Wireless Communication
Authors: Kim Mijin , Moon Jongho , Won Dongho , Park Namje
Published: April 2020

Wireless communication is essential for the infrastructure of a healthcare system. This bidirectional communication is used for data collection and to control message delivery. Wireless communication is applied in industries as well as in our daily lives, e.g., smart cities; however, highly reliable communication may be more difficult in environments with low power consumption, many interferences, or IoT wireless network issues due to resource limitations. In order to solve these problems, we investigated the existing three-party password-authenticated key exchange (3PAKE) and developed an enhanced protocol. Currently, Lu et al. presented a 3PAKE protocol to improve the security flaws found in Farash and Attari’s protocol. This work revisits the protocol proposed by Lu et al. and demonstrates that, in addition to other security weaknesses, the protocol does not provide user anonymity which is an important issue for healthcare environment, and is not secure against insider attacks that may cause impersonation attacks. We propose a secure biometric-based efficient password-authenticated key exchange (SBAKE) protocol in order to remove the incidences of these threats, and present an analysis regarding the security and efficiency of the SBAKE protocol for practical deployment.