bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Soybean-Derived Lunasin in Wheat and Assessment of Its Anti-Proliferative Activity in Colorectal Cancer HT-29 Cells
Authors: Fan Xin , Qin Peiyou , Hao Yuqiong , Guo Huimin , Blecker Christophe , Everaert Nadia , Ren Guixing
Published: December 2020

Lunasin is a soybean-derived peptide that exhibits anticancer bioactivity in different cancer cells and has been identified in different plants. However, recent studies revealed through molecular and chemical analyses that lunasin was absent in wheat and other cereals. In this study, the soybean-derived lunasin was cloned into pCAMBIA3300 and we transferred the expression vector into wheat via an Agrobacterium-mediated transformation. The identification of transgenic wheat was detected by polymerase chain reaction, Western blot analysis, and ultra-performance liquid chromatography with tandem mass spectrometry. An enzyme-linked immunosorbent assay showed that lunasin content in transgenic wheat L32-3, L32-6, and L33-1 was 308.63, 436.78, and 349.07 µg/g, respectively, while lunasin was not detected in wild-type wheat. Lunasin enrichment from transgenic wheat displayed an increased anti-proliferative activity compared with peptide enrichment from wild-type wheat in HT-29 cells. Moreover, the results of a real-time quantitative polymerase chain reaction showed a significant elevation in p21, Bax, and caspase-3 expression, while Bcl-2 was significantly downregulated. In conclusion, soybean-derived lunasin was successfully expressed in wheat via Agrobacterium-mediated transformation and may exert anti-proliferative activity by regulating the apoptosis pathway in HT-29 cells, which provides an effective approach to compensate for the absence of lunasin in wheat.
The Effect of Orally Supplemented Melatonin on Larval Performance and Skeletal Deformities in Farmed Gilthead Seabream (Sparus aurata)
Authors: Mhalhel Kamel , Germanà Antonino , Abbate Francesco , Guerrera Maria Cristina , Levanti Maria , Laurà Rosaria , Montalbano Giuseppe
Published: December 2020

The gilthead seabream larval rearing in continuous light is common in most Mediterranean hatcheries to stimulate larval length growth and increase food consumption. Several studies have shown that continuous light affects larval development and increases the prevalence of skeletal deformities. Melatonin is a crucial pineal neurohormone that displays daily secretion patterns, stimulates cell proliferation and embryonic development in Atlantic salmon and zebrafish, and improves osseointegration in mice and humans. However, no studies have examined the effects of orally supplemented melatonin on skeletal deformities in Sparus aurata larvae. We administered exogenous melatonin to gilthead seabream larvae via enriched rotifers and nauplii of Artemia. Exogenous melatonin induced bone deformities and stimulated parathyroid hormone-related protein-coding gene (PTHrP) mRNA expression. In addition to the melatonin-induced PTHrP high expression level, the recorded non coordinated function of skeletal muscle and bone during growth can be the fountainhead of bone deformities. Both myosin light chain 2 (mlc2) and bone gamma-carboxyglutamate protein-coding gene (bglap) expression levels were significantly affected by melatonin administration in an inverse dose–response manner during the exogenous melatonin administration. This is the first study to report the effect of inducing melatonin bone deformities on Sparus aurata larvae reared under ordinary hatchery conditions.
Extracellular Vesicles from Adipose Tissue Stem Cells in Diabetes and Associated Cardiovascular Disease; Pathobiological Impact and Therapeutic Potential
Authors: Constantin Alina , Filippi Alexandru , Alexandru Nicoleta , Nemecz Miruna , Georgescu Adriana
Published: December 2020

Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. “Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication between cells, transferring their specific bioactive molecules into host target cells”. There is a general consensus on how to define and isolate ADSCs, however, multiple separation and characterization protocols are being used in the present which complicate the results’ integration in a single theory on ADSCs’ and their derived factors’ way of action. Metabolic syndrome and type 2 diabetes mellitus (T2DM) are mainly caused by abnormal adipose tissue size, distribution and metabolism and so ADSCs and their secretory factors such as EVs are currently investigated as therapeutics in these diseases. Moreover, due to their relatively easy isolation and propagation in culture and their differentiation ability, ADSCs are being employed in preclinical studies of implantable devices or prosthetics. This review aims to provide a comprehensive summary of the current knowledge on EVs secreted from ADSCs both as diagnostic biomarkers and therapeutics in diabetes and associated cardiovascular disease, the molecular mechanisms involved, as well as on the use of ADSC differentiation potential in cardiovascular tissue repair and prostheses.
Molecular Targets in Precision Chemoprevention of Colorectal Cancer: An Update from Pre-Clinical to Clinical Trials
Authors: Yarla Nagendra S. , Madka Venkateshwar , Pathuri Gopal , Rao Chinthalapally V.
Published: December 2020

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. The initiation and progression of CRC is a multi-step process that proceeds via precursor lesions to carcinoma, with each stage characterized by its distinct molecular and tissue microenvironment changes. Precursor lesions of CRC, aberrant crypt foci, and adenoma exhibit drastic changes in genetic, transcriptomic, and proteomic profiles compared to normal tissue. The identification of these changes is essential and provides further validation as an initiator or promoter of CRC and, more so, as lesion-specific druggable molecular targets for the precision chemoprevention of CRC. Mutated/dysregulated signaling (adenomatous polyposis coli, β-catenin, epidermal growth factor receptor, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), tumor protein53, Akt, etc.), inflammatory (cyclooxygenase-2, microsomal prostaglandin E synthase-1, inducible nitric oxide synthase, and other pro-inflammatory mediators), and metabolic/growth factor (fatty acid synthase, β-Hydroxy β-methylglutaryl-CoA reductase, and ornithine decarboxylase) related targets are some of the well-characterized molecular targets in the precision chemoprevention of CRC. In this review, we discuss precursor-lesion specific targets of CRC and the current status of pre-clinical studies regarding clinical interventions and combinations for better efficacy and safety toward future precision clinical chemoprevention. In addition, we provide a brief discussion on the usefulness of secondary precision chemopreventive targets for tertiary precision chemoprevention to improve the disease-free and overall survival of advanced stage CRC patients.
Fancy-Shaped Gold–Platinum Nanocauliflowers for Improved Proton Irradiation Effect on Colon Cancer Cells
Authors: Klebowski Bartosz , Depciuch Joanna , Stec Malgorzata , Krzempek Dawid , Komenda Wiktor , Baran Jarek , Parlinska-Wojtan Magdalena
Published: December 2020

Enhancing the effectiveness of colorectal cancer treatment is highly desirable. Radiation-based anticancer therapy—such as proton therapy (PT)—can be used to shrink tumors before subsequent surgical intervention; therefore, improving the effectiveness of this treatment is crucial. The addition of noble metal nanoparticles (NPs), acting as radiosensitizers, increases the PT therapeutic effect. Thus, in this paper, the effect of novel, gold–platinum nanocauliflowers (AuPt NCs) on PT efficiency is determined. For this purpose, crystalline, 66-nm fancy shaped, bimetallic AuPt NCs were synthesized using green chemistry method. Then, physicochemical characterization of the obtained AuPt NCs by transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDS), and UV-Vis spectra measurements was carried out. Fully characterized AuPt NCs were placed into a cell culture of colon cancer cell lines (HCT116, SW480, and SW620) and a normal colon cell line (FHC) and subsequently subjected to proton irradiation with a total dose of 15 Gy. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test, performed after 18-h incubation of the irradiated cell culture with AuPt NCs, showed a significant reduction in cancer cell viability compared to normal cells. Thus, the radio-enhancing features of AuPt NCs indicate their potential application for the improvement in effectiveness of anticancer proton therapy.
Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress
Authors: Ano Yasuhisa , Kitaoka Shiho , Ohya Rena , Kondo Keiji , Furuyashiki Tomoyuki
Published: December 2020

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.
AhR Activation Leads to Alterations in the Gut Microbiome with Consequent Effect on Induction of Myeloid Derived Suppressor Cells in a CXCR2-Dependent Manner
Authors: Neamah Wurood Hantoosh , Busbee Philip Brandon , Alghetaa Hasan , Abdulla Osama A. , Nagarkatti Mitzi , Nagarkatti Prakash
Published: December 2020

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated donor mice into antibiotic-treated mice induced MDSCs and increased regulatory T-cells (Tregs). Injecting TCDD directly into antibiotic-treated mice also induced MDSCs, although to a lesser extent. These data suggested that TCDD-induced dysbiosis plays a critical role in MDSC induction. Interestingly, treatment with TCDD led to induction of MDSCs in the colon and undetectable levels of cysteine. MDSCs suppressed T cell proliferation while reconstitution with cysteine restored this response. Lastly, blocking CXC chemokine receptor 2 (CXCR2) impeded TCDD-mediated MDSC induction. Our data demonstrate that AhR activation by TCDD triggers dysbiosis which, in turn, regulates, at least in part, induction of MDSCs.
How Ah Receptor Ligand Specificity Became Important in Understanding Its Physiological Function
Authors: Murray Iain A. , Perdew Gary H.
Published: December 2020

Increasingly, the aryl hydrocarbon receptor (AHR) is being recognized as a sensor for endogenous and pseudo-endogenous metabolites, and in particular microbiota and host generated tryptophan metabolites. One proposed explanation for this is the role of the AHR in innate immune signaling within barrier tissues in response to the presence of microorganisms. A number of cytokine/chemokine genes exhibit a combinatorial increase in transcription upon toll-like receptors and AHR activation, supporting this concept. The AHR also plays a role in the enhanced differentiation of intestinal and dermal epithelium leading to improved barrier function. Importantly, from an evolutionary perspective many of these tryptophan metabolites exhibit greater activation potential for the human AHR when compared to the rodent AHR. These observations underscore the importance of the AHR in barrier tissues and may lead to pharmacologic therapeutic intervention.
Novel Psychoactive Phenethylamines: Impact on Genetic Material
Authors: Cocchi Veronica , Gasperini Sofia , Hrelia Patrizia , Tirri Micaela , Marti Matteo , Lenzi Monia
Published: December 2020

Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and the popular 3,4-Methylenedioxymethylamphetamine (MDMA). On the basis of cytotoxicity and cytostasis results, we selected the concentrations (6.25–35 µM) to be used in genotoxicity analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by an automated flow cytometric protocol. All substances, except MDMA, resulted genotoxic; therefore, we evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the demonstrated genotoxicity. The obtained results showed a statistically significant increase in ROS levels for all genotoxic phenethylamines confirming this hypothesis. Our results highlight the importance of genotoxicity evaluation for a complete assessment of the risk associated also with NPS exposure. Indeed, the subjects who do not have hazardous behaviors or require hospitalization by using active but still “safe” doses could run into genotoxicity and in the well-known long-term effects associated.
Conserved Imprinted Genes between Intra-Subspecies and Inter-Subspecies Are Involved in Energy Metabolism and Seed Development in Rice
Authors: Yang Lin , Xing Feng , He Qin , Tahir ul Qamar Muhammad , Chen Ling-Ling , Xing Yongzhong
Published: December 2020

Genomic imprinting is an epigenetic phenomenon in which a subset of genes express dependent on the origin of their parents. In plants, it is unclear whether imprinted genes are conserved between subspecies in rice. Here we identified imprinted genes from embryo and endosperm 5–7 days after pollination from three pairs of reciprocal hybrids, including inter-subspecies, japonica intra-subspecies, and indica intra-subspecies reciprocal hybrids. A total of 914 imprinted genes, including 546 in inter-subspecies hybrids, 211 in japonica intra-subspecies hybrids, and 286 in indica intra-subspecies hybrids. In general, the number of maternally expressed genes (MEGs) is more than paternally expressed genes (PEGs). Moreover, imprinted genes tend to be in mini clusters. The number of shared genes by R9N (reciprocal crosses between 9311 and Nipponbare) and R9Z (reciprocal crosses between 9311 and Zhenshan 97), R9N and RZN (reciprocal crosses between Zhonghua11 and Nipponbare), R9Z and RZN was 72, 46, and 16. These genes frequently involved in energy metabolism and seed development. Five imprinted genes (Os01g0151700, Os07g0103100, Os10g0340600, Os11g0679700, and Os12g0632800) are commonly detected in all three pairs of reciprocal hybrids and were validated by RT-PCR sequencing. Gene editing of two imprinted genes revealed that both genes conferred grain filling. Moreover, 15 and 27 imprinted genes with diverse functions in rice were shared with Arabidopsis and maize, respectively. This study provided valuable resources for identification of imprinting genes in rice or even in cereals.
Effects of Fe2+/Fe3+ Binding to Human Frataxin and Its D122Y Variant, as Revealed by Site-Directed Spin Labeling (SDSL) EPR Complemented by Fluorescence and Circular Dichroism Spectroscopies
Authors: Doni Davide , Passerini Leonardo , Audran Gérard , Marque Sylvain R. A. , Schulz Marvin , Santos Javier , Costantini Paola , Bortolus Marco , Carbonera Donatella
Published: December 2020

Frataxin is a highly conserved protein whose deficiency results in the neurodegenerative disease Friederich’s ataxia. Frataxin’s actual physiological function has been debated for a long time without reaching a general agreement; however, it is commonly accepted that the protein is involved in the biosynthetic iron-sulphur cluster (ISC) machinery, and several authors have pointed out that it also participates in iron homeostasis. In this work, we use site-directed spin labeling coupled to electron paramagnetic resonance (SDSL EPR) to add new information on the effects of ferric and ferrous iron binding on the properties of human frataxin in vitro. Using SDSL EPR and relating the results to fluorescence experiments commonly performed to study iron binding to FXN, we produced evidence that ferric iron causes reversible aggregation without preferred interfaces in a concentration-dependent fashion, starting at relatively low concentrations (micromolar range), whereas ferrous iron binds without inducing aggregation. Moreover, our experiments show that the ferrous binding does not lead to changes of protein conformation. The data reported in this study reveal that the currently reported binding stoichiometries should be taken with caution. The use of a spin label resistant to reduction, as well as the comparison of the binding effect of Fe2+ in wild type and in the pathological D122Y variant of frataxin, allowed us to characterize the Fe2+ binding properties of different protein sites and highlight the effect of the D122Y substitution on the surrounding residues. We suggest that both Fe2+ and Fe3+ might play a relevant role in the context of the proposed FXN physiological functions.
Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models
Authors: Almodóvar-Payá Aitana , Villarreal-Salazar Mónica , de Luna Noemí , Nogales-Gadea Gisela , Real-Martínez Alberto , Andreu Antoni L. , Martín Miguel Angel , Arenas Joaquin , Lucia Alejandro , Vissing John , Krag Thomas , Pinós Tomàs
Published: December 2020

GSD are a group of disorders characterized by a defect in gene expression of specific enzymes involved in glycogen breakdown or synthesis, commonly resulting in the accumulation of glycogen in various tissues (primarily the liver and skeletal muscle). Several different GSD animal models have been found to naturally present spontaneous mutations and others have been developed and characterized in order to further understand the physiopathology of these diseases and as a useful tool to evaluate potential therapeutic strategies. In the present work we have reviewed a total of 42 different animal models of GSD, including 26 genetically modified mouse models, 15 naturally occurring models (encompassing quails, cats, dogs, sheep, cattle and horses), and one genetically modified zebrafish model. To our knowledge, this is the most complete list of GSD animal models ever reviewed. Importantly, when all these animal models are analyzed together, we can observe some common traits, as well as model specific differences, that would be overlooked if each model was only studied in the context of a given GSD.
Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors
Authors: Szczukowski Łukasz , Krzyżak Edward , Zborowska Adrianna , Zając Patrycja , Potyrak Katarzyna , Peregrym Krzysztof , Wiatrak Benita , Marciniak Aleksandra , Świątek Piotr
Published: December 2020

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.
Mitochondrial Membranes of Human SH-SY5Y Neuroblastoma Cells Express Serotonin 5-HT7 Receptor
Authors: Tempio Alessandra , Niso Mauro , Laera Luna , Trisolini Lucia , Favia Maria , Ciranna Lucia , Marzulli Domenico , Petrosillo Giuseppe , Pierri Ciro Leonardo , Lacivita Enza , Leopoldo Marcello
Published: December 2020

Mitochondria in neurons contribute to energy supply, the regulation of synaptic transmission, Ca2+ homeostasis, neuronal excitability, and stress adaptation. In recent years, several studies have highlighted that the neurotransmitter serotonin (5-HT) plays an important role in mitochondrial biogenesis in cortical neurons, and regulates mitochondrial activity and cellular function in cardiomyocytes. 5-HT exerts its diverse actions by binding to cell surface receptors that are classified into seven distinct families (5-HT1 to 5-HT7). Recently, it was shown that 5-HT3 and 5-HT4 receptors are located on the mitochondrial membrane and participate in the regulation of mitochondrial function. Furthermore, it was observed that activation of brain 5-HT7 receptors rescued mitochondrial dysfunction in female mice from two models of Rett syndrome, a rare neurodevelopmental disorder characterized by severe behavioral and physiological symptoms. Our Western blot analyses performed on cell-lysate and purified mitochondria isolated from neuronal cell line SH-SY5Y showed that 5-HT7 receptors are also expressed into mitochondria. Maximal binding capacity (Bmax) obtained by Scatchard analysis on purified mitochondrial membranes was 0.081 pmol/mg of 5-HT7 receptor protein. Lastly, we evaluated the effect of selective 5-HT7 receptor agonist LP-211 and antagonist (inverse agonist) SB-269970 on mitochondrial respiratory chain (MRC) cytochrome c oxidase activity on mitochondria from SH-SY5Y cells. Our findings provide the first evidence that 5-HT7 receptor is also expressed in mitochondria.
Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide
Authors: Choi Yong-Pyo , Kim Ga Hyun , Kim Song-Hee , Maeng Jongseo , Lee Heesoon , Han Sang-Bae , Kim Ki Ho , Kim Youngsoo
Published: December 2020

Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gene of MITF-M, and functions as a key enzyme in melanin biosynthesis. Tetrahydroquinoline carboxamide (THQC) was previously screened as an antimelanogenic candidate. In the current study, we evaluated the antimelanogenic activity of THQC in vivo and elucidated a possible mechanism. Topical treatment with THQC mitigated ultraviolet B (UVB)-induced skin pigmentation in guinea pig with decreased messenger RNA (mRNA) and protein levels of melanogenic genes such as MITF-M and Tyro. Moreover, THQC inhibited cAMP-induced melanin production in α-melanocyte-stimulating hormone (α-MSH)- or histamine-activated B16-F0 cells, in which it suppressed the expression of the MITF-M gene at the promoter level. As a mechanism, THQC normalized the protein levels of Pax3, a transcriptional activator of the MITF-M gene, in UVB-exposed and pigmented skin, as well as in α-MSH-activated B16-F0 culture. However, THQC did not affect UVB- or α-MSH-induced phosphorylation (activation) of CREB. The results suggest that suppression of the Pax3–MITF-M axis might be a potential strategy in the treatment of skin pigmentary disorders that are at high risk under UVB radiation.
Extracellular RNAs in Bacterial Infections: From Emerging Key Players on Host-Pathogen Interactions to Exploitable Biomarkers and Therapeutic Targets
Authors: Pita Tiago , Feliciano Joana R. , Leitão Jorge H.
Published: December 2020

Non-coding RNAs (ncRNAs) are key regulators of post-transcriptional gene expression in prokaryotic and eukaryotic organisms. These molecules can interact with mRNAs or proteins, affecting a variety of cellular functions. Emerging evidence shows that intra/inter-species and trans-kingdom regulation can also be achieved with exogenous RNAs, which are exported to the extracellular medium, mainly through vesicles. In bacteria, membrane vesicles (MVs) seem to be the more common way of extracellular communication. In several bacterial pathogens, MVs have been described as a delivery system of ncRNAs that upon entry into the host cell, regulate their immune response. The aim of the present work is to review this recently described mode of host-pathogen communication and to foster further research on this topic envisaging their exploitation in the design of novel therapeutic and diagnostic strategies to fight bacterial infections.
Dual Antibacterial Activities and Biofilm Eradication of a Marine Peptide-N6NH2 and Its Analogs against Multidrug-Resistant Aeromonas veronii
Authors: Li Ting , Wang Zhenlong , Han Huihui , Teng Da , Mao Ruoyu , Hao Ya , Yang Na , Wang Xiumin , Wang Jianhua
Published: December 2020

Aeromonas veronii is one of the main pathogens causing various diseases in humans and animals. It is currently difficult to eradicate drug-resistant A. veronii due to the biofilm formation by conventional antibiotic treatments. In this study, a marine peptide-N6NH2 and its analogs were generated by introducing Orn or replacing with D-amino acids, Val and Pro; their enzymic stability and antibacterial/antibiofilm ability against multi-drug resistant (MDR) A. veronii ACCC61732 were detected in vitro and in vivo, respectively. The results showed that DN6NH2 more rapidly killed A. veronii ACCC61732 and had higher stability in trypsin, simulated gastric/intestinal fluid, proteinase K, and mouse serum than the parent peptide-N6NH2. DN6NH2 and other analogs significantly improved the ability of N6NH2 to penetrate the outer membrane of A. veronii ACCC61732. DN6NH2, N6PNH2 and V112N6NH2 protected mice from catheter-associated biofilm infection with MDR A. veronii ACCC61732, superior to N6NH2 and CIP. DN6NH2 had more potent efficacy at a dose of 5 μmol/kg (100% survival) in a mouse peritonitis model than other analogs (50–66.67%) and CIP (83.33%), and it inhibited the bacterial translocation, downregulated pro-inflammatory cytokines, upregulated the anti-inflammatory cytokine, and ameliorated multiple-organ injuries (including the liver, spleen, lung, and kidney). These data suggest that the analogs of N6NH2 may be a candidate for novel antimicrobial and antibiofilm agents against MDR A. veronii infections.
Consuming Parasitized Aphids Alters the Life History and Decreases Predation Rate of Aphid Predator
Authors: Liu Jian-Feng , Wang Xiu-Qin , Beggs Jacqueline R. , Ou Hou-Ding , Yu Xiao-Fei , Shen Xiu-Xian , Yang Mao-Fa
Published: December 2020

Intraguild predation interactions have substantial theoretical and practical implications for the dynamics of natural competitor populations used for biological control. Intraguild predation on parasitized aphids not only has a direct, negative effect on the parasitoid species, but it may indirectly influence the predator’s development, survival, reproduction and predation rates. In this study, we used two-sex life table theory, life table parameters and predation rates of Aphidoletes aphidimyza (Rondani) to compare when its populations fed on aphids (Myzus persicae Sulzer) (Hemiptera: Aphididae) that were either unparasitized or parasitized by Aphidius gifuensis (Ashmead) (Hymenoptera: Braconidae). Our results showed that individuals of A. aphidimyza were capable of completing their development and attaining maturity when they fed on parasitized aphids. Although feeding on parasitized aphids did not influence the survival rates of immature A. aphidimyza, it did significantly slow their development and extended their longevity, thereby reducing the fecundity and predation rates of A. aphidimyza. These findings may be pivotal for better understanding the sustained coexistence of predators with parasitoids in the biological control of aphids.
Functional Analysis of Odorant-Binding Proteins 12 and 17 from Wheat Blossom Midge Sitodiplosis mosellana Géhin (Diptera: Cecidomyiidae)
Authors: Cheng Weining , Zhang Yudong , Yu Jinlin , Liu Wei , Zhu-Salzman Keyan
Published: December 2020

The wheat blossom midge Sitodiplosis mosellana, one of the most disastrous wheat pests, depends highly on olfactory cues to track suitable plants. To better understand the olfactory recognition mechanisms involved in host selection, in the present study we cloned two S. mosellana adult antenna-specific odorant binding protein (OBP) genes, SmosOBP12 and SmosOBP17, and evaluated bacterially expressed recombinant proteins for their selectivity and sensitivity for host wheat volatiles using the fluorescence-based ligand binding assay. The results showed that both SmosOBPs effectively bound alcohol, ester, ketone, and terpenoid compounds. Particularly, SmosOBP12 had significantly higher affinities (Ki < 10.5 μM) than SmosOBP17 (Ki2 > 0.1 μM) to 3-hexanol, 1-octen-3-ol, D-panthenol, 3-carene, (Z)-3-hexenylacetate, hexyl acetate, methyl salicylate, heptyl acetate, and ethyl heptanoate. Consistently, S. mosellana females were attracted to all these chemicals in a behavioral assay using Y-tube olfactometer. SmosOBP12 also bound aldehyde, but neither bound alkanes. Notably, SmosOBP12 exhibited strong affinity to ocimene (Ki = 8.2 μM) that repelled S. mosellana. SmosOBP17, however, was insensitive to this compound. Taken together, our results indicate that SmosOBP12 may play a greater role than SmosOBP17 in perceiving these biologically active plant volatiles.
Testing Seven Hypotheses to Determine What Explains the Current Planthopper (Fulgoridae) Geographical and Species Richness Patterns in China
Authors: Zhao Zheng-Xue , Yang Lin , Long Jian-Kun , Chang Zhi-Min , Zhou Zheng-Xiang , Zhi Yan , Yang Liang-Jing , Li Hong-Xing , Sui Yong-Jin , Gong Nian , Wang Xiao-Ya , Chen Xiang-Sheng
Published: December 2020

Although many hypotheses have been proposed to understand the mechanisms underlying large-scale richness patterns, the environmental determinants are still poorly understood, particularly in insects. Here, we tested the relative contributions of seven hypotheses previously proposed to explain planthopper richness patterns in China. The richness patterns were visualized at a 1° × 1° grid size, using 14,722 distribution records for 1335 planthoppers. We used ordinary least squares and spatial error simultaneous autoregressive models to examine the relationships between richness and single environmental variables and employed model averaging to assess the environmental variable relative roles. Species richness was unevenly distributed, with high species numbers occurring in the central and southern mountainous areas. The mean annual temperature change since the Last Glacial Maximum was the most important factor for richness patterns, followed by mean annual temperature and net primary productivity. Therefore, historical climate stability, ambient energy, and productivity hypotheses were supported strongly, but orogenic processes and geological isolation may also play a vital role.
The Effect of Grinding Wheel Contact Stiffness on Plunge Grinding Cycle
Authors: Hashimoto Fukuo , Iwashita Hiroto
Published: December 2020

This paper presents the effect of grinding wheel contact stiffness on the plunge grinding cycle. First, it proposes a novel model of the generalized plunge grinding system. The model is applicable to all plunge grinding operations including cylindrical, centerless, shoe-centerless, internal, and shoe-internal grinding. The analysis of the model explicitly describes transient behaviors during the ramp infeed and the spark-out in the plunge grinding cycle. Clarification is provided regarding the premise that the system stiffness is composed of machine stiffness and wheel contact stiffness, and these stiffnesses significantly affect productivity and grinding accuracy. The elastic deflection of the grinding wheel is accurately measured and formulas for representing the deflection nature under various contact loads are derived. The deflection model allows us to find the non-linear contact stiffness with respect to the normal load. The contact stiffnesses of four kinds of grinding wheels with different grades and bond materials are presented. Both cylindrical grinding and centerless grinding tests are carried out, and it is experimentally revealed that the time constant at ramp infeed and spark-out is significantly prolonged by reducing the grinding force. It is verified that a simulation of the grinding tests using the proposed model can accurately predict critical parameters like forces and machine deflection during plunge grinding operations. Finally, this paper provides a guideline for grinding cycle design in order to achieve the required productivity and grinding accuracy.
Experience in Multiple Sclerosis Patients with COVID-19 and Disease-Modifying Therapies: A Review of 873 Published Cases
Authors: Möhn Nora , Konen Franz F. , Pul Refik , Kleinschnitz Christoph , Prüss Harald , Witte Torsten , Stangel Martin , Skripuletz Thomas
Published: December 2020

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many physicians asked themselves what risk their patients, especially those with chronic diseases, were exposed to. We present an overview of all patients with multiple sclerosis (MS) and SARS-CoV-2 infection published in the literature so far. In total, there are publications on 873 SARS-CoV-2 positive MS patients and information on the outcome can be given for 700 patients. With regard to the different disease modifying therapies (DMTs), by far the most cases were described under anti-CD20 treatment (n = 317). The mortality rate of all MS patients was 4% and a further 3% required invasive or non-invasive ventilation. When looking at the severe and fatal cases, it is particularly noticeable that patients without DMTs, with previous cardiovascular diseases, or with a severe degree of disability are at risk. Immunosuppressive therapy itself does not appear to be a substantial risk factor. Rather, it is reasonable to assume that the therapies could be protective, either directly, by mitigating the cytokine storm, or indirectly, by reducing the disease activity of MS.
Evaluation of Optimization Parameters of Semi-Solid Metal 6063 Aluminum Alloy from Friction Stir Welding Process Using Factorial Design Analysis
Authors: Meengam Chaiyoot , Sillapasa Kittima
Published: December 2020

The semi-solid-metal 6063 aluminum alloy was developed for the automotive industry. The objective of this research was to optimize parameters in friction stir welding process that can provide the highest tensile strength. The ANOVA factorial design was used to analyze rotation speed, welding speed, and tool geometry at different factor levels of experimentation. The results showed that the optimized tensile strength was 120.7 MPa from the cylindrical tool, rotation speed was from 1300 to 2100 rpm, and welding speed less than 75 mm/min in the coefficient of determination R2 was 95.09%, as can be considered from the regression equation. The examination of the stir-zone and thermal mechanical affected zone using SEM and EDX showed that the new recrystallization of the microstructure causes fine grain in the stir-zone, coarse grain in advancing-side thermal mechanical affected zone, and equiaxed grain in the retracting-side thermal-mechanical affect zone. The intermetallic compounds of β-Al5FeSi phase transformation phase were formed to three types, i.e., β″-Al5Fe, Mg2Si, and Al8Fe2Si phase were observed. Moreover, in the stir-zone and thermal-mechanical-affected zone, defects were found such as flash defects, void or cavity defects, crack defects, lack of penetration defects, tunnel defects, kissing bond defects, and dendrite formation defects affecting weldability.
Influence of Microstructure and Chemical Composition on Microhardness and Wear Properties of Laser Borided Monel 400
Authors: Kukliński Mateusz , Bartkowska Aneta , Przestacki Damian , Kinal Grzegorz
Published: December 2020

In this study, wear properties of Monel 400 after laser alloying with boron are described. Surfaces were prepared by covering them with boron paste layers of two different thicknesses (100 µm and 200 μm) and re-melting using diode laser. Laser beam power density was equal to 178.3 kW/cm2. Two laser beam scanning velocities were chosen for the process: 5 m/min and 50 m/min. Surfaces alloyed with boron were investigated in terms of wear resistance, and the surface of untreated Monel 400 was examined for comparison. Wear tests were performed using counterspecimen made from steel 100Cr6 and water as a lubricant. Both quantitative and qualitative analysis of surfaces after wear test are described in this paper. Additionally, microstructures and properties of obtained laser alloyed surfaces are presented. It was found that the wear resistance increased from four to tens of times, depending on parameters of the laser boriding process. The wear mechanism was mainly adhesive for surfaces alloyed with initial boron layer 100 µm thick and evolves to abrasive with increasing boron content and laser beam scanning velocity. Iron particles detached from counterspecimens were detected on each borided surface after the wear test, and it was found that the harder the surface the less built-ups are present. Moreover, adhered iron particles oxidized during the wear test.
Floor Vibration Experiment and Serviceability Test of iFLASH System
Authors: Lee Jong Ho , Park Min Jae , Yoon Sung Won
Published: December 2020

Studies on novel composite structures that can decrease floor height and improve constructional efficiency in order to increase spatial efficiency and lease revenue have been actively conducted. An innovative fire-proof, lightweight, absorbed, shallow, and hybrid (iFLASH) system was developed to solve construction site issues, such as improving constructability, reducing construction time, and attaining structural efficiency by reducing the weight of the building structure. This system can shorten the construction duration and decrease the floor height and structural weight, owing to features such as a low thickness and light weight. However, studies on the vibration characteristics of this new floor system have not been performed yet. As the general thickness of the iFLASH system ranges from 25 to 30 mm, it must have a sufficient floor vibration performance in order to be utilized. To evaluate the floor vibration performance of the iFLASH system, an experiment was performed in two buildings where the system was applied. This paper presents the results of the dynamic characteristics and serviceability testing as basic data for the vibration characteristics of the iFLASH system.
The Effects of Oxygen Functional Groups on Graphene Oxide on the Efficient Adsorption of Radioactive Iodine
Authors: Zhang Qian , Gao Yangyang , Xu Zhanglian , Wang Sheng , Kobayashi Hisayoshi , Wang Jie
Published: December 2020

Oxygen-containing functional groups tend to induce a strong interaction between solid adsorbents and iodine molecules, yet have not been systematically investigated. Herein, on the basis of a series of nitric acid-treated graphene oxide (GO) with different contents of oxygen functional groups for iodine adsorption, it was found that the iodine uptake capacity is proportionate to the oxygen content and the diversities of oxygen-containing groups. The density functional theory (DFT) calculation results also suggest that oxygen-containing groups result in strong interactions between iodine molecules and the adsorbents through a covalent bond-forming process, among which -OH groups possess a higher adsorption energy averagely. Such theoretical and experimental work deepens our understanding of the effects of oxygen functional groups on iodine adsorption and provides novel ideas for future design and synthesis of high-performance solid adsorbents for radioactive iodine.
Effects of Different Surface Native Pre-Oxides on the Hot Corrosion Properties of Nickel-Based Single Crystal Superalloys
Authors: Chen Zehao , Li Shusuo , Wu Mengmeng , Pei Yanling , Gong Shengkai , Zhang Heng
Published: December 2020

A study is carried out on the effect of different surface native pre-oxides on hot corrosion of single crystal nickel-based superalloy at 900 °C. The effect of different oxides formed by different superalloys through pre-oxidation on hot corrosion is verified by normal hot corrosion and tube sealing experiments. The relationship between different surface oxides and the effect of different surface oxides layer on the hot corrosion properties of alloys are studied. In summary, the stable and dense surface pre-Al2O3 layer which can be obtained by pre-oxidation has an obvious positive effect on the improvement of superalloy hot corrosion resistance in reaction. In addition, the internal sulfides are analyzed in depth, and the relationship between Cr, Mo, O and S is discussed in detail.
The Effect of Different Thermal Treatment on the Allotropic fcc↔hcp Transformation and Compression Behavior of Polycrystalline Cobalt
Authors: Knapek Michal , Minárik Peter , Dobroň Patrik , Šmilauerová Jana , Celis Mayerling Martinez , Hug Eric , Chmelík František
Published: December 2020

Pure polycrystalline cobalt is systematically thermally treated in order to assess the effect of the microstructure on the compression behavior. Isothermal annealing of the as-drawn material leads to recrystallization and grain growth dependent on the annealing temperature (600–1100 ∘C). Consequently, the yield strength decreases and the fracture strain increases as a function of rising grain size; the content of the residual fcc phase is ~6–11%. Subsequent thermal cycling around the transition temperature is applied to further modify the microstructure, especially in terms of the fcc phase content. With the increasing number of cycles, the grain size further increases and the fraction of the fcc phase significantly drops. At the same time, the values of both the yield strength and fracture strain somewhat decrease. An atypical decrease in the fracture strain as a function of grain size is explained in terms of decreasing fcc phase content; the stress-induced fcc→hcp transformation can accommodate a significant amount of plastic strain. Besides controlling basic material parameters (e.g., grain size and texture), adjusting the content of the fcc phase can thus provide an effective means of mechanical performance optimization with respect to particular applications.
Review on Learning and Extracting Graph Features for Link Prediction
Authors: Mutlu Ece C. , Oghaz Toktam , Rajabi Amirarsalan , Garibay Ivan
Published: December 2020

Link prediction in complex networks has attracted considerable attention from interdisciplinary research communities, due to its ubiquitous applications in biological networks, social networks, transportation networks, telecommunication networks, and, recently, knowledge graphs. Numerous studies utilized link prediction approaches in order sto find missing links or predict the likelihood of future links as well as employed for reconstruction networks, recommender systems, privacy control, etc. This work presents an extensive review of state-of-art methods and algorithms proposed on this subject and categorizes them into four main categories: similarity-based methods, probabilistic methods, relational models, and learning-based methods. Additionally, a collection of network data sets has been presented in this paper, which can be used in order to study link prediction. We conclude this study with a discussion of recent developments and future research directions.
Pervaporative Dehydration of Methanol Using PVA/Nanoclay Mixed Matrix Membranes: Experiments and Modeling
Authors: Selim Asmaa , Toth András Jozsef , Fozer Daniel , Szanyi Agnes , Mizsey Péter
Published: December 2020

Encouraged by the industrial problem of removing water from methanol solutions, a simple exfoliation method is applied to prepare polyvinyl alcohol (PVA)/laponite nanoclay mixed matrix membranes (MMMs). The membranes are used for the pervaporative dehydration of the methanol-water solution. The influence of the nanoclay content on the pervaporation performance is investigated. The results show that the PVA10 membrane containing 10 wt% Laponite loading exhibits excellent separation efficiency; therefore, all the experimental work is continued using the same membrane. Additionally, the effects of feed concentration and temperature on methanol dehydration performance are thoroughly investigated. The temperatures are ranging from 40–70 °C and the water feed concentrations from 1–15 wt% water. A maximum separation factor of 1120 can be observed at 40 °C and the feed water concentration of 1 wt%. Remarkably, two solution–diffusion models, the Rautenbach (Model I) and modified method by Valentínyi et al. (Model II), are used and compared to evaluate and describe the pervaporation performance of the mixed matrix membrane. Model II proves to be more appropriate for the modeling of pervaporative dehydration of methanol than Model I. This work demonstrates that PVA/nanoclay mixed matrix membranes prepared can efficiently remove water from methanol aqueous solution with pervaporation and the whole process can be accurately modeled with Model II.