bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination Strategies Involving Immune Checkpoint Inhibitors and Tyrosine Kinase or BRAF Inhibitors in Aggressive Thyroid Cancer
Authors: Ragusa Francesca , Ferrari Silvia Martina , Elia Giusy , Paparo Sabrina Rosaria , Balestri Eugenia , Botrini Chiara , Patrizio Armando , Mazzi Valeria , Guglielmi Giovanni , Foddis Rudy , Spinelli Claudio , Ulisse Salvatore , Antonelli Alessandro , Fallahi Poupak
Published: May 2022

Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and immunotherapy individually have many limitations. Regarding the first one, although it greatly reduces the size of the cancer, clinical responses are generally transient and often lead to cancer relapse after initial treatment. For the second one, although it induces longer-lasting responses in cancer patients than targeted therapy, its response rate is lower. The individual limitations of these two different types of therapies can be overcome by combining them. Here, we discuss MAPK pathway inhibitors, i.e., BRAF and MEK inhibitors, combined with checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Several mutations make tumors resistant to treatments. Therefore, more studies are needed to investigate the patient’s individual tumor mutation burden in order to overcome the problem of resistance to therapy and to develop new combination therapies.
Salinity Tolerance of Halophytic Grass Puccinellia nuttalliana Is Associated with Enhancement of Aquaporin-Mediated Water Transport by Sodium
Authors: Vaziriyeganeh Maryamsadat , Carvajal Micaela , Du Ning , Zwiazek Janusz J.
Published: May 2022

In salt-sensitive plants, root hydraulic conductivity is severely inhibited by NaCl, rapidly leading to the loss of water balance. However, halophytic plants appear to effectively control plant water flow under salinity conditions. In this study, we tested the hypothesis that Na+ is the principal salt factor responsible for the enhancement of aquaporin-mediated water transport in the roots of halophytic grasses, and this enhancement plays a significant role in the maintenance of water balance, gas exchange, and the growth of halophytic plants exposed to salinity. We examined the effects of treatments with 150 mM of NaCl, KCl, and Na2SO4 to separate the factors that affect water relations and, consequently, physiological and growth responses in three related grass species varying in salt tolerance. The grasses included relatively salt-sensitive Poa pratensis, moderately salt-tolerant Poa juncifolia, and the salt-loving halophytic grass Puccinellia nuttalliana. Our study demonstrated that sustained growth, chlorophyll concentrations, gas exchange, and water transport in Puccinellia nuttalliana were associated with the presence of Na in the applied salt treatments. Contrary to the other examined grasses, the root cell hydraulic conductivity in Puccinellia nuttalliana was enhanced by the 150 mM NaCl and 150 mM Na2SO4 treatments. This enhancement was abolished by the 50 µM HgCl2 treatment, demonstrating that Na was the factor responsible for the increase in mercury-sensitive, aquaporin-mediated water transport. The observed increases in root Ca and K concentrations likely played a role in the transcriptional and (or) posttranslational regulation of aquaporins that enhanced root water transport capacity in Puccinellia nuttalliana. The study demonstrates that Na plays a key role in the aquaporin-mediated root water transport of the halophytic grass Puccinellia nuttalliana, contributing to its salinity tolerance.
Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome
Authors: Cheng Hongwei , Charles Ian , James Andrew F. , Abdala Ana P. , Hancox Jules C.
Published: May 2022

Rett syndrome (RTT) is a severe developmental disorder that is strongly linked to mutations in the MECP2 gene. RTT has been associated with sudden unexplained death and ECG QT interval prolongation. There are mixed reports regarding QT prolongation in mouse models of RTT, with some evidence that loss of Mecp2 function enhances cardiac late Na current, INa,Late. The present study was undertaken in order to investigate both ECG and ventricular AP characteristics in the Mecp2Null/Y male murine RTT model and to interrogate both fast INa and INa,Late in myocytes from the model. ECG recordings from 8–10-week-old Mecp2Null/Y male mice revealed prolongation of the QT and rate corrected QT (QTc) intervals and QRS widening compared to wild-type (WT) controls. Action potentials (APs) from Mecp2Null/Y myocytes exhibited longer APD75 and APD90 values, increased triangulation and instability. INa,Late was also significantly larger in Mecp2Null/Y than WT myocytes and was insensitive to the Nav1.8 inhibitor A-803467. Selective recordings of fast INa revealed a decrease in peak current amplitude without significant voltage shifts in activation or inactivation V0.5. Fast INa ‘window current’ was reduced in RTT myocytes; small but significant alterations of inactivation and reactivation time-courses were detected. Effects of two INa,Late inhibitors, ranolazine and GS-6615 (eleclazine), were investigated. Treatment with 30 µM ranolazine produced similar levels of inhibition of INa,Late in WT and Mecp2Null/Y myocytes, but produced ventricular AP prolongation not abbreviation. In contrast, 10 µM GS-6615 both inhibited INa,Late and shortened ventricular AP duration. The observed changes in INa and INa,Late can account for the corresponding ECG changes in this RTT model. GS-6615 merits further investigation as a potential treatment for QT prolongation in RTT.
Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats
Authors: García-Domingo Mónica , García-Pedraza José Ángel , Fernández-González Juan Francisco , López Cristina , Martín María Luisa , Morán Asunción
Published: May 2022

Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine’s (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 μg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 μg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia.
Mechanical Properties of the Modified Denture Base Materials and Polymerization Methods: A Systematic Review
Authors: Khan Aftab Ahmed , Fareed Muhammad Amber , Alshehri Abdulkarim Hussain , Aldegheishem Alhanoof , Alharthi Rasha , Saadaldin Selma A. , Zafar Muhammad Sohail
Published: May 2022

Amidst growing technological advancements, newer denture base materials and polymerization methods have been introduced. During fabrication, certain mechanical properties are vital for the clinical longevity of the denture base. This systematic review aimed to explore the effect of newer denture base materials and/or polymerization methods on the mechanical properties of the denture base. An electronic database search of English peer-reviewed published papers was conducted using related keywords from 1 January 2011, up until 31 December 2021. This systematic review was based on guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search identified 579 papers. However, the inclusion criteria recognized 22 papers for eligibility. The risk of bias was moderate in all studies except in two where it was observed as low. Heat cure polymethyl methacrylate (PMMA) and compression moulding using a water bath is still a widely used base material and polymerization technique, respectively. However, chemically modified PMMA using monomers, oligomers, copolymers and cross-linking agents may have a promising result. Although chemically modified PMMA resin might enhance the mechanical properties of denture base material, no clear inferences can be drawn about the superiority of any polymerization method other than the conventional compression moulding technique.
The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target
Authors: Sophocleous Reece Andrew , Ooi Lezanne , Sluyter Ronald
Published: May 2022

The adenosine 5′-triphosphate-gated P2X4 receptor channel is a promising target in neuroinflammatory disorders, but the ability to effectively target these receptors in models of neuroinflammation has presented a constant challenge. As such, the exact role of P2X4 receptors and their cell signalling mechanisms in human physiology and pathophysiology still requires further elucidation. To this end, research into the molecular mechanisms of P2X4 receptor activation, modulation, and inhibition has continued to gain momentum in an attempt to further describe the role of P2X4 receptors in neuroinflammation and other disease settings. Here we provide an overview of the current understanding of the P2X4 receptor, including its expression and function in cells involved in neuroinflammatory signalling. We discuss the pharmacology of P2X4 receptors and provide an overview of P2X4-targeting molecules, including agonists, positive allosteric modulators, and antagonists. Finally, we discuss the use of P2X4 receptor modulators and antagonists in models of neuroinflammatory cell signalling and disease.
Short-Chain Fatty Acids Augment Differentiation and Function of Human Induced Regulatory T Cells
Authors: Hu Mingjing , Alashkar Alhamwe Bilal , Santner-Nanan Brigitte , Miethe Sarah , Harb Hani , Renz Harald , Potaczek Daniel P. , Nanan Ralph K.
Published: May 2022

Regulatory T cells (Tregs) control immune system activity and inhibit inflammation. While, in mice, short-chain fatty acids (SCFAs) are known to be essential regulators of naturally occurring and in vitro induced Tregs (iTregs), data on their contribution to the development of human iTregs are sparse, with no reports of the successful SCFAs-augmented in vitro generation of fully functional human iTregs. Likewise, markers undoubtedly defining human iTregs are missing. Here, we aimed to generate fully functional human iTregs in vitro using protocols involving SCFAs and to characterize the underlying mechanism. Our target was to identify the potential phenotypic markers best characterizing human iTregs. Naïve non-Treg CD4+ cells were isolated from the peripheral blood of 13 healthy adults and cord blood of 12 healthy term newborns. Cells were subjected to differentiation toward iTregs using a transforming growth factor β (TGF-β)-based protocol, with or without SCFAs (acetate, butyrate, or propionate). Thereafter, they were subjected to flow cytometric phenotyping or a suppression assay. During differentiation, cells were collected for chromatin-immunoprecipitation (ChIP)-based analysis of histone acetylation. The enrichment of the TGF-β-based protocol with butyrate or propionate potentiated the in vitro differentiation of human naïve CD4+ non-Tregs towards iTregs and augmented the suppressive capacity of the latter. These seemed to be at least partly underlain by the effects of SCFAs on the histone acetylation levels in differentiating cells. GITR, ICOS, CD39, PD-1, and PD-L1 were proven to be potential markers of human iTregs. Our results might boost the further development of Treg-based therapies against autoimmune, allergic and other chronic inflammatory disorders.
Characterization of the Cell Wall Component through Thermogravimetric Analysis and Its Relationship with an Expansin-like Protein in Deschampsia antarctica
Authors: Morales-Quintana Luis , Tapia-Valdebenito Daisy , Castro Ricardo I. , Rabert Claudia , Larama Giovanni , Gutiérrez Ana , Ramos Patricio
Published: May 2022

Deschampsia antarctica Desv. (Poaceae) is one of the two vascular plants that have colonized the Antarctic Peninsula, which is usually exposed to extreme environmental conditions. To support these conditions, the plant carries out modifications in its morphology and metabolism, such as modifications to the cell wall. Thus, we performed a comparative study of the changes in the physiological properties of the cell-wall-associated polysaccharide contents of aerial and root tissues of the D. antarctica via thermogravimetric analysis (TGA) combined with a computational approach. The result showed that the thermal stability was lower in aerial tissues with respect to the root samples, while the DTG curve describes four maximum peaks of degradation, which occurred between 282 and 358 °C. The carbohydrate polymers present in the cell wall have been depolymerized showing mainly cellulose and hemicellulose fragments. Additionally, a differentially expressed sequence encoding for an expansin-like (DaEXLA2), which is characterized by possessing cell wall remodeling function, was found in D. antarctica. To gain deep insight into a probable mechanism of action of the expansin protein identified, a comparative model of the structure was carried out. DaEXLA2 protein model displayed two domains with an open groove in the center. Finally, using a cell wall polymer component as a ligand, the protein–ligand interaction was evaluated by molecular dynamic (MD) simulation. The MD simulations showed that DaEXLA2 could interact with cellulose and XXXGXXXG polymers. Finally, the cell wall component description provides the basis for a model for understanding the changes in the cell wall polymers in response to extreme environmental conditions.
Neuroinflammation: The Pathogenic Mechanism of Neurological Disorders
Authors: Gorji Ali
Published: May 2022

Neuroinflammation is implicated in the pathophysiology of several neurological diseases [...]
Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy
Authors: Mazzeo Aurora , Porta Massimo , Beltramo Elena
Published: May 2022

The complexity of the retinal structure reflects on the difficulty to describe its composite cell interactions. Microglia is responsible for the immune reaction to inflammatory stimuli during diabetic retinopathy (DR), but most studies still use rodent cells. We characterized a commercially available immortalized human microglial line and tested its susceptibility to inflammation, to study the interactions between the neuro-vascular retinal portions in species-specific models. After checking the expression of microglial markers, we tried lipopolysaccharide (LPS) stimulation and several pro-inflammatory cocktails to select the best combination able to induce a significant M1 (inflammatory) response. We measured M1 induction through the expression of pro- and anti-inflammatory molecules and performed morphologic and functional assays. Marker expression confirmed the human microglial derivation of these cells. Differently from rodents, LPS did not induce a M1 profile. The best pro-inflammatory stimulus was an interleukin-1β + tumor necrosis factor-α + interferon-γ cocktail, which induced morphology changes and increased proliferation, apoptosis, migration, reactive oxygen species, and the expression of inflammatory cytokines and miRNAs. In conclusion, this microglial line proved potentially useful to investigate the cascade of events leading to DR. In perspective, co-culture models involving microvascular cells will help in the understanding of multifaceted interactions of the neurovascular unit.
Keeping Excitation–Inhibition Ratio in Balance
Authors: Kirischuk Sergei
Published: May 2022

Unrelated genetic mutations can lead to convergent manifestations of neurological disorders with similar behavioral phenotypes. Experimental data frequently show a lack of dramatic changes in neuroanatomy, indicating that the key cause of symptoms might arise from impairment in the communication between neurons. A transient imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) synaptic transmission (the E/I balance) during early development is generally considered to underlie the development of several neurological disorders in adults. However, the E/I ratio is a multidimensional variable. Synaptic contacts are highly dynamic and the actual strength of synaptic projections is determined from the balance between synaptogenesis and synaptic elimination. During development, relatively slow postsynaptic receptors are replaced by fast ones that allow for fast stimulus-locked excitation/inhibition. Using the binomial model of synaptic transmission allows for the reassessing of experimental data from different mouse models, showing that a transient E/I shift is frequently counterbalanced by additional pre- and/or postsynaptic changes. Such changes—for instance, the slowing down of postsynaptic currents by means of immature postsynaptic receptors—stabilize the average synaptic strength, but impair the timing of information flow. Compensatory processes and/or astrocytic signaling may represent possible targets for medical treatments of different disorders directed to rescue the proper information processing.
Recombinant Integrin β1 Signal Peptide Blocks Gliosis Induced by Aβ Oligomers
Authors: Ortiz-Sanz Carolina , Llavero Francisco , Zuazo-Ibarra Jone , Balantzategi Uxue , Quintela-López Tania , Wyssenbach Ane , Capetillo-Zarate Estibaliz , Matute Carlos , Alberdi Elena , Zugaza José L.
Published: May 2022

Glial cells participate actively in the early cognitive decline in Alzheimer’s disease (AD) pathology. In fact, recent studies have found molecular and functional abnormalities in astrocytes and microglia in both animal models and brains of patients suffering from this pathology. In this regard, reactive gliosis intimately associated with amyloid plaques has become a pathological hallmark of AD. A recent study from our laboratory reports that astrocyte reactivity is caused by a direct interaction between amyloid beta (Aβ) oligomers and integrin β1. Here, we have generated four recombinant peptides including the extracellular domain of integrin β1, and evaluated their capacity both to bind in vitro to Aβ oligomers and to prevent in vivo Aβ oligomer-induced gliosis and endoplasmic reticulum stress. We have identified the minimal region of integrin β1 that binds to Aβ oligomers. This region is called signal peptide and corresponds to the first 20 amino acids of the integrin β1 N-terminal domain. This recombinant integrin β1 signal peptide prevented Aβ oligomer-induced ROS generation in primary astrocyte cultures. Furthermore, we carried out intrahippocampal injection in adult mice of recombinant integrin β1 signal peptide combined with or without Aβ oligomers and we evaluated by immunohistochemistry both astrogliosis and microgliosis as well as endoplasmic reticulum stress. The results show that recombinant integrin β1 signal peptide precluded both astrogliosis and microgliosis and endoplasmic reticulum stress mediated by Aβ oligomers in vivo. We have developed a molecular tool that blocks the activation of the molecular cascade that mediates gliosis via Aβ oligomer/integrin β1 signaling.
Increase of Circulating Monocyte–Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage
Authors: Mariscal Anaís , Zamora Carlos , Díaz-Torné César , Ortiz Mᵃ Àngels , Agustín Juan José de , Reina Delia , Estrada Paula , Moya Patricia , Corominas Héctor , Vidal Sílvia
Published: May 2022

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.
Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells
Authors: Nir Dana , Ribarski-Chorev Ivana , Shimoni Chen , Strauss Carmit , Frank Jan , Schlesinger Sharon
Published: May 2022

Mesenchymal stem cells (MSC) have many roles that are important for the body’s proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues. Heat shock impairs MSC capacity by inducing the generation of reactive oxygen species and mitochondrial dysfunction, which, in turn, send the cells into a state of premature senescence. Here, we pre-exposed MSC to melatonin, resveratrol, or curcumin, which are natural antioxidative compounds, and tested the protective effects of these substances from oxidative stress and aging. Our data showed that pre-exposure of MSC to antioxidants decreased reactive oxygen species while mitochondrial damage remained high. Additionally, although the proliferation of the cells was slow, antioxidants protected the cells from premature senescence, and subsequent cytokine release was prevented. We conclude that while elevated temperatures directly cause mitochondrial damage, senescence is induced by elevated ROS levels. We suggest that heat shock alters cell and tissue homeostasis by several independent mechanisms; however, reducing tissue senescence will reduce damage and provide a pathway to overcome physiological challenges in animals.
N-Terminal Peptide of PGLYRP1/Tag7 Is a Novel Ligand for TREM-1 Receptor
Authors: Sharapova Tatiana N. , Ivanova Olga K. , Romanova Elena A. , Sashchenko Lidia P. , Yashin Denis V.
Published: May 2022

An investigation of innate immunity receptors sheds light on the mechanisms of inflammation and associated immune reactions. One of the key immune regulators is the TREM-1 receptor, which is involved in both inflammation and antitumor immune response. In this article, we have obtained a new ligand for the TREM-1 receptor. The peptide, named N3, is a part of the innate immune protein PGLYRP1/Tag7. It is responsible for activating the TREM-1 signaling pathway. Here, we have demonstrated that the N3 peptide acts like other TREM-1 receptor ligands: its binding results in a mild inflammation response and appearance of cytotoxic lymphocytes. We have shown that cytotoxic populations of lymphocytes in N3 peptide-treated PBMCs are similar to those treated with Tag7 or Hsp70. We also determined the part of the N3 peptide responsible for binding to TREM-1. The resulting peptide (N9) consists of nine amino acids and can be considered as a potential peptide that blocks TREM-1 signaling.
Establishment of a Landscape of UPL5-Ubiquitinated on Multiple Subcellular Components of Leaf Senescence Cell in Arabidopsis
Authors: Lan Wei , Zheng Shuai , Yang Ping , Qiu Yuhao , Xu Yun , Miao Ying
Published: May 2022

Catabolism of macromolecules is a major event in senescent cells, especially involving proteolysis of organelles and abnormally aggregated proteins, circulation of nutrients, and precise control of intracellular environmental balance. Proteasomes are distributed in the nucleus and cytoplasm; however, proteasomes in organelles are limited. In this study, multi-omics proteomic analyses of ubiquitinated proteins enriched by using antibody against “di-Gly-Lys” via a free labeling were used to investigate the global changes of protein levels and ubiquitination modification levels of upl5 mutant relative to wild-type plant; subcellular localization analysis of UPL5 was found to be located in the nucleus, cytoplasm, and plastid within the cell; and the direct lysine site patterns of UPL5 were screened by the H89R substitution in the tagged ubiquitinated assay. It suggests that UPL5 acting as a candidate of organelle E3 ligase either in the nucleus or cytoplasm or plastid modifies numerous targets related to nuclear transcription and plastid photosynthesis involving in Ca2+ and hormone signaling pathway in plant senescence and in response to (a)biotic stress protection.
Inhibitory Effects of Saururus chinensis Extract on Receptor for Advanced Glycation End-Products-Dependent Inflammation and Diabetes-Induced Dysregulation of Vasodilation
Authors: Hayashi Kenjiro , Sato Koichi , Ochi Seishi , Kawano Shuhei , Munesue Seiichi , Harashima Ai , Oshima Yu , Kimura Kumi , Kyoi Takashi , Yamamoto Yasuhiko
Published: May 2022

Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) are implicated in inflammatory reactions and vascular complications in diabetes. Signaling pathways downstream of RAGE are involved in NF-κB activation. In this study, we examined whether ethanol extracts of Saururus chinensis (Lour.) Baill. (SE) could affect RAGE signaling and vascular relaxation in streptozotocin (STZ)-induced diabetic rats. Treatment with SE inhibited AGEs-modified bovine serum albumin (AGEs-BSA)-elicited activation of NF-κB and could compete with AGEs-BSA binding to RAGE in a dose-dependent manner. Tumor necrosis factor-α (TNF-α) secretion induced by lipopolysaccharide (LPS)—a RAGE ligand—was also reduced by SE treatment in wild-type Ager+/+ mice as well as in cultured peritoneal macrophages from Ager+/+ mice but not in Ager−/− mice. SE administration significantly ameliorated diabetes-related dysregulation of acetylcholine-mediated vascular relaxation in STZ-induced diabetic rats. These results suggest that SE would inhibit RAGE signaling and would be useful for the improvement of vascular endothelial dysfunction in diabetes.
Reviewing the Applications of Neural Networks in Supply Chain: Exploring Research Propositions for Future Directions
Authors: Meidute-Kavaliauskiene Ieva , Taşkın Kamil , Ghorbani Shahryar , Činčikaitė Renata , Kačenauskaitė Roberta
Published: May 2022

Supply chains have received significant attention in recent years. Neural networks (NN) are a technique available in artificial intelligence (AI) which has many supporters due to their diverse applications because they can be used to move towards complete harmony. NN, an emerging AI technique, have a strong appeal for a wide range of applications to overcome many issues associated with supply chains. This study aims to provide a comprehensive view of NN applications in supply chain management (SCM), working as a reference for future research directions for SCM researchers and application insight for SCM practitioners. This study generally introduces NNs and has explained the use of this method in five features identified by supply chain area, including optimization, forecasting, modeling and simulation, clustering, decision support, and the possibility of using NNs in supply chain management. The results showed that NN applications in SCM were still in a developmental stage since there were not enough high-yielding authors to form a strong group force in the research of NN applications in SCM.
The Correlation between Volatile Compounds Emitted from Sitophilus granarius (L.) and Its Electrophysiological and Behavioral Responses
Authors: Cai Lijun , Macfadyen Sarina , Hua Baozhen , Xu Wei , Ren Yonglin
Published: May 2022

The granary weevil Sitophilus granarius (L.) is one of the most serious primary insect pests of stored products. When S. granarius present in grains, various volatile organic compounds are released as chemical signals which can be used to detect the insects. In this study, volatile chemical compounds released from S. granarius were analyzed using the headspace solid phase micro-extraction (HS-SPME) coupled with gas chromatography (GC)–mass spectrometry (MS) techniques. Two key compounds, 3-hydroxy-2-butanone and 1-pentadecene, were identified from mixed gender of S. granarius adults at high density. Moreover, both male and female adults showed dose-dependent electroantennography (EAG) responses to 3-hydroxy-2-butanone. In behavioral assays, S. granarius was attracted to 3-hydroxy-2-butanone at 0.001 µg/10 µL but repelled at 10 µg/10 µL or higher. S. granarius was consistently repelled by 1-pentadecene at concentrations at 0.001 and 1000 µg/10 µL. 3-hydroxy-2-butanone and 1-pentadecene have considerable potential to offer in the development of new approaches for the monitoring and management of this destructive stored grain insect pest.
Utilization of Pomelo (Citrus maxima) Peel Waste into Bioactive Essential Oils: Chemical Composition and Insecticidal Properties
Authors: Visakh Naduvilthara U. , Pathrose Berin , Narayanankutty Arunaksharan , Alfarhan Ahmed , Ramesh Varsha
Published: May 2022

The wastes generated during the post-harvest handling of various agricultural commodities is rather under-utlilized. The peels of citrus fruits are often discarded as waste. Citrus peels are rich in essential oils and exhibit toxicity towards various insect species. The essential oils are also an eco-friendly option for insect pest management. The Citrus maxima peel essential oil (CMEO), a waste product, characterized it, and evaluated its potential for insect pest management. The major terpenoids present in CMEO are Limonene and α-Pinene. The CMEO displayed potentials in controlling the insect pests via contact and fumigant toxicity. Moreover, CMEO showed significant larvicidal activities against Culex tritaeniorhynchus and Aedes aegypti species of mosquitoes; however, Armigeres subalbatus was more resistant. The biological safety of the essential oil was also tested against the stored seeds, where no significant inhibition of seed germination was noticed compared to the control. Utilizing a waste product such as citrus peel for pest management can achieve the dual objective of waste utilization and eco-friendly pest management. Overall, the CMEO is therefore found to be a bioactive essential oil extracted from the wastes of pomelo (C. maxima).
Transient Liquid Phase Bonding of Al-6063 to Steel Alloy UNS S32304
Authors: Saleh Mohamed I. , Roven Hans J. , Khan Tahir I. , Iveland Terje
Published: May 2022

Transient liquid phase (TLP) bonding of 6063 aluminum alloy (Al-6063) and duplex alloy 2304 stainless steel (UNS S32304) was performed using copper foil as an interlayer between the base metals. A compression load was applied normal to the specimens. Metallurgical examination of the produced joints showed three distinct regions including a reaction zone, diffusion affected zone, and the base metals. The diffusion of copper into aluminum resulted in an Al–Cu eutectic structure. However, the oxide layer on the aluminum surface controlled the dissolution behavior of copper and the extent of its wettability with the base metals. Although voids and intermetallic compounds were detected at the interfaces of the processed joints, a defect free joint was produced at 570 °C. In addition, the results from corrosion tests showed that the use of copper as an interlayer decreased the corrosion resistance of the joints. However, increase in thickness of the joining reaction zone with increasing bonding temperature was observed to increase corrosion resistance.
Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida glabrata
Authors: Healey Kelley R. , Perlin David S.
Published: May 2022

Candida glabrata has thoroughly adapted to successfully colonize human mucosal membranes and survive in vivo pressures. prior to and during antifungal treatment. Out of all the medically relevant Candida species, C. glabrata has emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole + echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic to C. glabrata, since stable genetic resistance depends on mutation of drug target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription factor, PDR1, which controls expression of major drug transporters, such as CDR1 (azole resistance). However, another hallmark of C. glabrata is the ability to withstand drug pressure both in vitro and in vivo prior to stable “genetic escape”. Additionally, these resistance events can arise within individual patients, which underscores the importance of understanding how this fungus is adapting to its environment and to drug exposure in vivo. Here, we explore the evolution of echinocandin resistance as a multistep model that includes general cell stress, drug adaptation (tolerance), and genetic escape. The extensive genetic diversity reported in C. glabrata is highlighted.
Toolbox for Genetic Transformation of Non-Conventional Saccharomycotina Yeasts: High Efficiency Transformation of Yeasts Belonging to the Schwanniomyces Genus
Authors: Matanović Angela , Arambašić Kristian , Žunar Bojan , Štafa Anamarija , Svetec Miklenić Marina , Šantek Božidar , Svetec Ivan-Krešimir
Published: May 2022

Non-conventional yeasts are increasingly being investigated and used as producers in biotechnological processes which often offer advantages in comparison to traditional and well-established systems. Most biotechnologically interesting non-conventional yeasts belong to the Saccharomycotina subphylum, including those already in use (Pichia pastoris, Yarrowia lypolitica, etc.), as well as those that are promising but as yet insufficiently characterized. Moreover, for many of these yeasts the basic tools of genetic engineering needed for strain construction, including a procedure for efficient genetic transformation, heterologous protein expression and precise genetic modification, are lacking. The first aim of this study was to construct a set of integrative and replicative plasmids which can be used in various yeasts across the Saccharomycotina subphylum. Additionally, we demonstrate here that the electroporation procedure we developed earlier for transformation of B. bruxellensis can be applied in various yeasts which, together with the constructed plasmids, makes a solid starting point when approaching a transformation of yeasts form the Saccharomycotina subphylum. To provide a proof of principle, we successfully transformed three species from the Schwanniomyces genus (S. polymorphus var. polymorphus, S. polymorphus var. africanus and S. pseudopolymorphus) with high efficiencies (up to 8 × 103 in case of illegitimate integration of non-homologous linear DNA and up to 4.7 × 105 in case of replicative plasmid). For the latter two species this is the first reported genetic transformation. Moreover, we found that a plasmid carrying replication origin from Scheffersomyces stipitis can be used as a replicative plasmid for these three Schwanniomyces species.
GDPR-Compliant Social Network Link Prediction in a Graph DBMS: The Case of Know-How Development at Beekeeper
Authors: Korányi Rita , Mancera José A. , Kaufmann Michael
Published: May 2022

The amount of available information in the digital world contains massive amounts of data, far more than people can consume. Beekeeper AG provides a GDPR-compliant platform for frontline employees, who typically do not have permanent access to digital information. Finding relevant information to perform their job requires efficient filtering principles to reduce the time spent on searching, thus saving work hours. However, with GDPR, it is not always possible to observe user identification and content. Therefore, this paper proposes link prediction in a graph structure as an alternative to presenting the information based on GDPR data. In this study, the research of user interaction data in a graph database was compared with graph machine learning algorithms for extracting and predicting network patterns among the users. The results showed that although the accuracy of the models was below expectations, the know-how developed during the process could generate valuable technical and business insights for Beekeeper AG.
(E)-4-(2-(7-Bromo-[1,2,5]thiadiazolo[3,4-c]pyridin-4-yl)vinyl)-N,N-diphenylaniline
Authors: Chmovzh Timofey N. , Rakitin Oleg A.
Published: May 2022

(Diphenylamino)phenylethenyl group-containing chromophores are widely employed to design effective materials with useful electronic properties. In this communication, (E)-4-(2-(7-Bromo-[1,2,5]thiadiazolo[3,4-c]pyridin-4-yl)vinyl)-N,N-diphenylaniline was regioselectively obtained by the Heck reaction of 4,7-dibromo-[1,2,5]thiadiazolo[3,4-c]pyridine with N,N-diphenyl-4-vinylaniline. The structure of the newly synthesized compound was established by means of elemental analysis, high resolution mass-spectrometry, 1H, 13C, NOESY NMR, IR and UV spectroscopy and mass-spectrometry.
Human Gingival Fibroblast Adhesion and Proliferation on Hydroxyapatite-Coated Zirconia Abutment Surfaces
Authors: Bunz Oskar , Steegmann Marie-Christine , Benz Korbinian , Testrich Holger , Quade Antje , Naumova Ella A. , Arnold Wolfgang H. , Fricke Katja , Piwowarczyk Andree , Dittmar Thomas
Published: May 2022

Applying antibacterial coatings to dental implant materials seems reasonable but can have negative influences on desired cell adhesion and healing. In this study, zirconia abutment specimens interacting with gingival tissue were used. The aim was to compare the influence of machined or coated zirconia surfaces on the adhesion and proliferation of human gingival fibroblasts (HGF-1). Surface modifications were performed using atmospheric plasma coating with hydroxyapatite, zinc, and copper. Zirconia specimens were divided into four groups: hydroxyapatite, hydroxyapatite with zinc oxide (ZnO), hydroxyapatite with copper (Cu), and an untreated machined surface. After the characterization of the surface conditions, the morphology of adhered HGF-1 was determined by fluorescence staining and subjected to statistical evaluation. The visual analysis of cell morphology by SEM showed flat, polygonal, and largely adherent fibroblast cells in the untreated group, while round to partially flat cells were recorded in the groups with hydroxyapatite, hydroxyapatite + ZnO, and hydroxyapatite + Cu. The cell membranes in the hydroxyapatite + ZnO and hydroxyapatite + Cu groups appeared porous. The results show that HGF-1 adhere and proliferate well on machined zirconia, while plasma coating with hydroxyapatite or hydroxyapatite mixtures does not lead to increased adhesion or proliferation.
Early Age Shrinkage and Mechanical Effect of Ultra-High-Performance Concrete Composite Deck: A Case Study with In Situ Test and Numerical Simulation
Authors: Ma Zhiguo , Li Yue , Cao Zhensheng , Zhang Shaoqiang , Hou Shengjun , Liu Jilin , Ruan Xin
Published: May 2022

For the Honghe Bridge project located in Yunnan Province, Southwest China, a steel/ultrahigh-performance concrete (UHPC) composite deck is used in the suspension bridge with a 700 m main span, and the steel stud connectors are used in the 50 mm–thick UHPC layer. To investigate the shrinkage behavior of UHPC and the relevant influence, the in situ time-dependent strain is measured continuously, and within the 20-day curing time, the material behavior is summarized based on test results. This paper proposes a prediction model for UHPC shrinkage which is refined from the widely used B3 model for normal concrete material, and the parameter values are modified and optimized by experimental comparison. Combining the numerical model and the finite element analysis model of the composite deck, the detailed mechanical state in structural parts is studied. For the practical construction, the simulation results indicate that the small thickness of UHPC above the stud and weak bond strength can influence the eventual structural performance greatly. In the discussion of stress distribution at different locations of the deck, the potential crack on the edge and the corner of the UHPC–steel interface and the mechanical damage on the stud connector around are also indicated.
Efficacy of Surgical/Wound Washes against Bacteria: Effect of Different In Vitro Models
Authors: Parvin Farhana , Vickery Karen , Deva Anand K. , Hu Honghua
Published: May 2022

Topical antiseptics are often used to treat chronic wounds with biofilm infections and during salvage of biofilm contaminated implants, but their antibacterial efficacy is frequently only tested against non-aggregated planktonic or free-swimming organisms. This study evaluated the antibacterial and antibiofilm efficacy of four commercial surgical washes Bactisure, TorrenTX, minimally invasive lavage (MIS), and Betadine against six bacterial species: Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli, which are commonly isolated from surgical site infections and chronic wound infections using different in vitro models. We determined minimum planktonic inhibitory and eradication concentration and minimum 1-day-old biofilm inhibition and eradication concentration of antiseptics in 96-well plates format with 24 h contact time. We also tested the efficacy of antiseptics at in-use concentration and contact time in the presence of biological soil against 3-day-old biofilm grown on coupons with shear in a bioreactor, such that the results are more applicable to the clinical biofilm situations. In the 96-well plate model, the minimum concentration required to inhibit or kill planktonic and biofilm bacteria was lower for Bactisure and TorrenTX than for MIS and Betadine. However, Betadine and Bactisure showed better antibiofilm efficacy than TorrenTX and MIS in the 3-day-old biofilm bioreactor model at in-use concentration. The minimal concentration of surgical washes required to inhibit or kill planktonic bacterial cells and biofilms varies, suggesting the need for the development and use of biofilm-based assays to assess antimicrobial therapies, such as topical antiseptics and their effective concentrations. The antibiofilm efficacy of surgical washes against different bacterial species also varies, highlighting the importance of testing against various bacterial species to achieve a thorough understanding of their efficacy.
Effects of Elevated Temperature on the Residual Behavior of Concrete Containing Marble Dust and Foundry Sand
Authors: Tiwary Aditya Kumar , Singh Sandeep , Kumar Raman , Chohan Jasgurpreet Singh , Sharma Shubham , Singh Jujhar , Li Changhe , Ilyas R. A. , Asyraf M. R. M. , Malik Mohammad Abdul
Published: May 2022

Concrete is a composite material that is commonly used in the construction industry. It will certainly be exposed to fires of varying intensities when used in buildings and industries. The major goal of this article was to look into the influence of mineral additions such as foundry sand and marble dust on the residual characteristics of concrete. To examine the behavior of residual characteristics of concrete after fire exposure, marble dust was substituted for cement and fine sand was substituted for foundry sand in varying amounts ranging from 0% to 20%. It aided in the better disposal of waste material so that it might be used as an addition. The purpose of the experiment was to see how increased temperatures affected residual properties of concrete, including flexural strength, compressive strength, tensile strength, static as well as dynamic elastic modulus, water absorption, mass loss, and ultrasonic pulse velocity. At temperatures of 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C, the typical fire exposure behavior of concrete was investigated. The effects of two cooling techniques, annealing and quenching, on the residual properties of concrete after exposure to high temperatures were investigated in this study. Replacement of up to 10% of the cement with marble dust and fine sand with foundry sand when concrete is exposed to temperatures up to 400 °C does not influence the behavior of concrete. At temperatures above 400 °C, however, the breakdown of concrete, which includes marble dust and foundry sand, causes a rapid deterioration in the residual properties of concrete, primarily for replacement of more than 10%.
Study on Autolytic Mechanism and Self-Healing Properties of Autolytic Clinker Microsphere in Alkaline Environment
Authors: Li Jun , Li Wenting , Jiang Zhengwu
Published: May 2022

In this study, the autolytic clinker microsphere with clinker as core and polyvinyl pyrrolidone (PVP) as coating film was prepared. Pretreatment of clinker with silane coupling agent was firstly processed during the preparation. To investigate the autolytic mechanism, the microstructures of the autolytic clinker microsphere at different curing ages were observed using environmental scanning electron microscopy (ESEM), equipped with an energy dispersive spectrometer (EDS). The autolytic stages were also identified based on the microstructural evolution. The influence of pretreatment degree on autolytic behavior was also studied by measurements of micro-morphology and isothermal calorimetry. Experimental results indicated that the compressive strength recovery of specimens was increased by 15–19% due to the addition of autolytic clinker microspheres. The recovery of compressive strength was also improved with the increase of pH value. The improvements in compressive strength recovery of specimens with microspheres were in the range of 15–19%, 15–31%, 25–36%, and 29–50% with the pH value of 7, 8, 10, and 12, respectively. It was also found that inner damage of cement-based matrix had greater recovery when pre-cracked specimens were cured in alkaline environments.
High Densification of Tungsten via Hot Pressing at 1300 °C in Carbon Presence
Authors: Popov Oleksii , Vishnyakov Vladimir
Published: May 2022

A reactive sintering technique with a small addition of carbon (up to 1.9 wt.%) has been used for tungsten powder consolidation. The process allowed procurement of the nonporous and fully densified material at 1300 °C and 30 MPa in 12 min. The SEM and EDX analysis showed that the milling of 5 μm tungsten powder with 0.6, 1.3, and 1.9 wt.% of carbon in a planetary mill led to the formation of the nanostructured mix, which appears to be W-C nanopowder surrounding tungsten grains. X-Ray Diffractometry data indicated tungsten hemicarbide (W2C) nucleation during the hot pressing of the milled powders. The exothermic reaction 2W + C → W2C occurs during the sintering process and promotes charge densification. The Vickers hardness and indentation toughness of W-1.3 wt.%C composition reached 5.7 GPa and 12.6 MPa∙m1/2, respectively. High toughness and high material densification allow proposing the W-WC2 for use as a plasma-facing material in fusion applications.