bluuebunny/crossref_metadata_2025 huggingface dataset:
Mirtazapine Reduces Adipocyte Hypertrophy and Increases Glucose Transporter Expression in Obese Mice
Authors: Wu Ching-Feng , Hou Po-Hsun , Mao Frank Chiahung , Su Yao-Chi , Wu Ching-Yang , Yang Wei-Cheng , Lin Chen-Si , Tsai Hsiao-Pei , Liao Huei-Jyuan , Chang Geng-Ruei
Published: August 2020

Metabolic syndrome is known to engender type 2 diabetes as well as some cardiac, cerebrovascular, and kidney diseases. Mirtazapine—an atypical second-generation antipsychotic drug with less severe side effects than atypical first-generation antipsychotics—may have positive effects on blood glucose levels and obesity. In our executed study, we treated male high-fat diet (HFD)-fed C57BL/6J mice with mirtazapine (10 mg/kg/day mirtazapine) for 4 weeks to understand its antiobesity effects. We noted these mice to exhibit lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression when compared with their counterparts (i.e., HFD-fed control mice). Furthermore, we determined a considerable drop in fatty liver scores and mean fat cell size in the epididymal white adipose tissue in the treated mice, corresponding to AMP-activated protein kinase expression activation. Notably, the treated mice showed lower glucose tolerance and blood glucose levels, but higher glucose transporter 4 expression. Overall, the aforementioned findings signify that mirtazapine could reduce lipid accumulation and thus prevent HFD-induced increase in body weight. In conclusion, mirtazapine may be useful in body weight control and antihyperglycemia therapy.
Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics
Authors: Mishra Nagendra N. , Tran Truc T. , Arias Cesar A. , Seepersaud Ravin , Sullam Paul M. , Bayer Arnold S.
Published: August 2020

Viridans group streptococci (VGS), especially the Streptococcus mitis-oralis subgroup, are pivotal pathogens in a variety of invasive endovascular infections, including “toxic shock” in neutropenic cancer patients and infective endocarditis (IE). Previously, we showed that the serial in vitro passage of S. mitis-oralis strains in sublethal daptomycin (DAP) resulted in rapid, high-level and stable DAP-resistance (DAP-R), which is accompanied by distinct changes in several genotypic and phenotypic signatures: (1) the disappearance of two key membrane phospholipids, phosphatidylglycerol (PG) and cardiolipin (CL); (2) increased membrane fluidity; (3) increased positive surface charge; (4) single nucleotide polymorphisms (SNPs) in two loci involved in CL biosynthesis (pgsA; cdsA); and (5) DAP hyperaccumulation. The current study examined these same metrics following in vitro serial DAP passages of a separate well-characterized S. mitis-oralis bloodstream isolate (SF100). Although some metrics seen in prior DAP post-passage strains were recapitulated with SF100 (e.g., pgsA SNPs, enhanced membrane fluidity), we observed the following major differences (comparing the parental versus post-passage variant): (1) no change in PG content; (2) reduced, but not absent, CL, with enhancement in phosphatidic acid (PA) content; (3) an unusual pattern of CL localization; (4) significantly decreased positive surface charge; (5) no difference in DAP accumulation; and (6) no cdsA SNPs. Thus, S. mitis-oralis strains are not “pre-programmed” phenotypically and/or genotypically to adapt in an identical manner during the evolution of the DAP-R.
The Pathogenic Role of Actinomyces spp. and Related Organisms in Genitourinary Infections: Discoveries in the New, Modern Diagnostic Era
Authors: Gajdács Márió , Urbán Edit
Published: August 2020

Actinomycosis is a chronic, suppurative, granulomatous infectious disease, caused by different species of Actinomyces bacteria. To date, 26 validly published Actinomyces species have been described as part of a normal human microbiota or from human clinical specimens. Due to the rapid spread of new, modern diagnostic procedures, 13 of 26 of these species have been described in this century and the Actinomycetaceae family has undergone several taxonomic revisions, including the introduction of many novel species termed Actinomyces-like organisms (ALOs). There is scarce data available on the role of these novel bacterial species in various infectious processes in human medicine. The aim of this review is to provide a comprehensive overview of Actinomyces and closely related organisms involved in human diseases—with a special focus on newly described species—in particular their role in genitourinary tract infections in females and males.
Oxidative Stress—Part of the Solution or Part of the Problem in the Hypoxic Environment of a Brain Tumor
Authors: Krawczynski Kamil , Godlewski Jakub , Bronisz Agnieszka
Published: August 2020

Rapid growth of brain tumors such as glioblastoma often results in oxygen deprivation and the emergence of hypoxic zones. In consequence, the enrichment of reactive oxygen species occurs, harming nonmalignant cells and leading them toward apoptotic cell death. However, cancer cells survive such exposure and thrive in a hypoxic environment. As the mechanisms responsible for such starkly different outcomes are not sufficiently explained, we aimed to explore what transcriptome rearrangements are used by glioblastoma cells in hypoxic areas. Using metadata analysis of transcriptome in different subregions of the glioblastoma retrieved from the Ivy Glioblastoma Atlas Project, we created the reactive oxygen species-dependent map of the transcriptome. This map was then used for the analysis of differential gene expression in the histologically determined cellular tumors and hypoxic zones. The gene ontology analysis cross-referenced with the clinical data from The Cancer Genome Atlas revealed that the metabolic shift is one of the major prosurvival strategies applied by cancer cells to overcome hypoxia-related cytotoxicity.
Experimental Research on Mechanical Performance of SSRC Columns under Eccentric Compression
Authors: Li Qingfu , Kuang Yihang , Guo Wei , Zhang Yanlong
Published: August 2020

To study the mechanical properties of stainless-steel-reinforced concrete (SSRC) columns under eccentric compression, one ordinary reinforced concrete column and eight SSRC columns were designed for eccentric compression load tests. The eccentricity and reinforcement ratio were considered as the variation parameters. The cracking and failure modes of the SSRC columns were studied. The effects of the variation parameters on the longitudinal strain, concrete strain, lateral displacement, and ultimate load were analyzed. The test results demonstrated that the failure modes of SSRC columns under eccentric compression are similar to those of ordinary reinforced columns. Eccentricity significantly affected the failure modes of the SSRC columns. Under the same eccentricity, the reinforcement ratio had negligible effect on the lateral displacement corresponding to the ultimate load. The mechanical properties of SSRC columns under small eccentric compression were better than expected; however, the ultimate loads under large eccentric compression were proposed. The ultimate load–bending moment curves obtained were consistent with the results of the test and finite element analysis. Based on the experimental results, the force characteristic coefficient was set as 2.7 for calculating the long-term crack width.
Assessment of Landslide Susceptibility Combining Deep Learning with Semi-Supervised Learning in Jiaohe County, Jilin Province, China
Authors: Yao Jingyu , Qin Shengwu , Qiao Shuangshuang , Che Wenchao , Chen Yang , Su Gang , Miao Qiang
Published: August 2020

Accurate and timely landslide susceptibility mapping (LSM) is essential to effectively reduce the risk of landslide. In recent years, deep learning has been successfully applied to landslide susceptibility assessment due to the strong ability of fitting. However, in actual applications, the number of labeled samples is usually not sufficient for the training component. In this paper, a deep neural network model based on semi-supervised learning (SSL-DNN) for landslide susceptibility is proposed, which makes full use of a large number of spatial information (unlabeled data) with limited labeled data in the region to train the mode. Taking Jiaohe County in Jilin Province, China as an example, the landslide inventory from 2000 to 2017 was collected and 12 metrological, geographical, and human explanatory factors were compiled. Meanwhile, supervised models such as deep neural network (DNN), support vector machine (SVM), and logistic regression (LR) were implemented for comparison. Then, the landslide susceptibility was plotted and a series of evaluation tools such as class accuracy, predictive rate curves (AUC), and information gain ratio (IGR) were calculated to compare the prediction of models and factors. Experimental results indicate that the proposed SSL-DNN model (AUC = 0.898) outperformed all the comparison models. Therefore, semi-supervised deep learning could be considered as a potential approach for LSM.
Optical Properties of CaF2 Thin Film Deposited on Borosilicate Glass and Its Electrical Performance in PV Module Applications
Authors: Zahid Muhammad Aleem , Hussain Shahzada Qamar , Cho Young Hyun , Yi Junsin
Published: August 2020

Calcium fluoride (CaF2) is deposited via vacuum thermal evaporation on borosilicate glass to produce an anti-reflection coating for use in solar modules. Macleod’s essential simulation is used to optimize the thickness of the CaF2 coating on the glass. Experimentally, a 120 ± 4 nm-thin CaF2 film on glass shows an average increase of ~4% in transmittance and a decrease of ~3.2% in reflectance, respectively, when compared to that of uncoated glass (Un CG), within the wavelength spectrum of approximately 350 to 1100 nm. The electrical PV performance of CaF2-coated glass (CaF2-CG) was analyzed for conventional and lightweight photovoltaic module applications. An improvement in the short-circuit current (Jsc) from 38.13 to 39.07 mA/cm2 and an increase of 2.40% in the efficiency (η) was obtained when CaF2-CG glass was used instead of Un CG in a conventional module. Furthermore, Jsc enhancement from 35.63 to 36.44 mA/cm2 and η improvement of 2.32% was observed when a very thin CaF2-CG was placed between the polymethyl methacrylate (PMMA) and solar cell in a lightweight module.
Structural, Magnetic and Mechanical Properties of Nd16 (Fe76−xCox)B8 0 ≤ x ≤ 25 Alloys
Authors: Trujillo Hernández Juan Sebastián , Talaat Ahmed , Tabares Jesús , Oyola Lozano Dagoberto , Bustos Rodríguez Humberto , Martínez Sánchez Hugo , Pérez Alcázar German Antonio
Published: August 2020

In this work, the structural, magnetic and mechanical properties of Nd16Fe76−xCoxB8 alloys with a varying Co content of x = 0, 10, 20 and 25 were experimentally investigated by X-ray diffraction (XRD), Mössbauer spectrometry (MS) and vibrating sample magnetometry (VSM) at room temperature (RT), and microhardness tests were performed. The system presented hard Nd2Fe14B and the Nd1.1Fe4B4 phases for samples with x = 0; when the concentration increased to x = 20 and 25, the CoO phase appeared. All MS data showed ferromagnetic behavior (eight sextets: sites 16k1, 16k2, 8j1, 8j2, 4c, 4e, sb) associated with the hard and soft magnetic phases, and one paramagnetic component (doublet: site d) associated with the minority Nd1.1Fe4B4 phase, which was not identified by XRD. All samples were magnetically hard and presented hard magnetic behavior. The increase of Co content in these samples did not improve the hard magnetic properties but increased the critical temperature of the system and decreased the crystallite size of the hard phase. There was a general tendency towards increased microhardness with cobalt content that was attributable to cobalt doping, which reduces the lattice parameters and porosities within the sample, improving its hardness.
Changes in Biochemical and Volatile Flavor Compounds of Shine Muscat at Different Ripening Stages
Authors: Choi Kyeong-Ok , Lee Dong Hoon , Park Seo Jun , Im Dongjun , Hur Youn Young , Kim Su Jin
Published: August 2020

Changes in the biochemistry and flavor of Shine Muscat grapes at different ripening stages (RS) were analyzed to identify factors affecting these characteristics. The yellowness index values were 45.1, 49.4, and 50.2 in the ripening stage 1 (RS1), ripening stage 2 (RS2), and ripening stage 3 (RS3) groups, respectively, representing the different ripening stages. The yellowness of the grape berries tended to increase with ripening due to the gradual breakdown of chlorophylls and the evolution of carotenoids. The total content of monoterpenes, on the other hand, was approximately two-fold higher at RS3 than RS1 and RS2. Moreover, linalool was the most abundant compound contributing to the total content of monoterpenes. The highest correlation was observed between the linalool content and °Brix/acid ratio (r = 0.9981), followed by the monoterpene content and °Brix/acid ratio (r = 0.9933). These findings indicate that changes in the contents of linalool and its oxidized forms may be used as a quality index and an indicator of the timing of harvest for Shine Muscat grapes.
Application of Instantaneous Parameter Characteristic in Active Lamb Wave Based Monitoring of Plate Structural Health
Authors: Xu Baochun , Wang Mulan , Li Peijuan , Cheng Qihua , Sheng Yunlong
Published: August 2020

In the active Lamb wave based monitoring of plate structural health, it is difficult to extract damage information from active Lamb waves based on single sensor collection. Based on the Hilbert–Huang transform (HHT) instantaneous processing method, this paper proposes to study the damage information carried by a single sensor monitoring signal from the instantaneous parameter characteristics of the signal. The instantaneous phase change caused by the phase difference between the damage scattering wave and the direct wave is studied. The change of the marginal spectrum amplitude in the effective range caused by the damage scattering wave is studied in continuous multiple frequency bands. Finally, the damage information extraction based on a single sensor monitoring signal is realized. From the model analysis and experimental results, it is reliable and feasible to realize the active Lamb wave based monitoring of plate structural health according to the instantaneous parameter change characteristics from a single sensor signal.
Modeling the Hydro-Mechanical Coupling Behavior of Unsaturated Geotechnical Materials Based on Non-Equilibrium Thermodynamic Theory
Authors: Yang Guangchang , Liu Yang , Chen Peipei
Published: August 2020

A new hydro-mechanical model for unsaturated geotechnical materials based on the non-equilibrium thermodynamic theory is presented in this paper. Common concepts, such as yield criterion and flow rules, are not involved in the constitutive relationships, and are replaced with the thermodynamic concepts of granular temperature, granular entropy, migration coefficients, and energy functions. The dissipation system and the migration coefficient relationships are theoretically determined, and the constitutive relations of non-elastic deformation and granular temperature are obtained by dissipation relations and thermodynamic identity. Thus, the relationship between dissipation mechanism and macro mechanical behavior can be established by migration coefficients and energy functions. The model can reflect the complex hydro-mechanical coupling behavior of unsaturated geotechnical materials subjected to various mechanical paths. The validity of the model is verified by comparing the modeling results with experimental data, and reasonable agreement is achieved.
Status of Pure Electric Vehicle Power Train Technology and Future Prospects
Authors: Karki Abhisek , Phuyal Sudip , Tuladhar Daniel , Basnet Subarna , Shrestha Bim
Published: August 2020

Electric vehicles (EV) are becoming more common mobility in the transportation sector in recent times. The dependence on oil as the source of energy for passenger vehicles has economic and political implications, and the crisis will take over as the oil reserves of the world diminish. As concerns of oil depletion and security of the oil supply remain as severe as ever, and faced with the consequences of climate change due to greenhouse gas emissions from the tail pipes of vehicles, the world today is increasingly looking at alternatives to traditional road transport technologies. EVs are seen as a promising green technology which could lead to the decarbonization of the passenger vehicle fleet and to independence from oil. There are possibilities of immense environmental benefits as well, as EVs have zero tail pipe emission and therefore are capable of curbing the pollution problems created by vehicle emission in an efficient way so they can extensively reduce the greenhouse gas emissions produced by the transportation sector as pure electric vehicles are the only vehicles with zero-emission potential. However, there are some major barriers for EVs to overcome before totally replacing ICE vehicles in the transportation sector and obtain appreciable market penetration. This review evaluates the technological aspects of the different power train systems of BEV technology and highlights those technological areas where important progress is expected by focusing on reviewing all the useful information and data available on EV architecture, electrical machines, optimization techniques, and its possibilities of future developments as green mobility. The challenges of different electric drive trains’ commercialization are discussed. The major objective is to provide an overall view of the current pure electric vehicle powertrain technology and possibilities of future green vehicle development to assist in future research in this sector.
Spatial-Temporal Pattern Changes of UTCI in the China-Pakistan Economic Corridor in Recent 40 Years
Authors: Zeng Di , Wu Jinkui , Mu Yaqiong , Deng Mingshan , Wei Yanqiang , Sun Weibing
Published: August 2020

This paper investigated the spatial and temporal variations of the Universal Thermal Climate Index (UTCI) of the China-Pakistan Economic Corridor (CPEC) from 1979 to 2018. The European Centre for Medium-Range Weather Forecasts Re-Analysis-Interim (ERA-Interim) reanalysis data from the European Centre for Medium-Range Weather Forecasts (ECMWF) is selected for UTCI calculation in the region and analyzed by a linear trend and correlation analysis. The results showed that (1) the UTCI of CPEC is decreased with the increase of latitude and altitude. There is obvious spatial heterogeneity in the seasonal scale and the spatial distribution of different thermal stress categories. (2) UTCI generally exhibited a positive trend of 0.33 °C/10a over the past 40 years, and the seasonal variation characteristics of UTCI show an upward trend in all four seasons, of which spring is the fastest. On the space scale, the growth trend has significant spatial variations. (3) Temperature has a positive correlation with UTCI. The influence of temperature on UTCI is greater than that of wind speed. The results of this study will be helpful for regional planning and also contribute to comprehending the characteristics of the thermal environment in CPEC.
Properties of Arabinogalactan Proteins (AGPs) in Apple (Malus × Domestica) Fruit at Different Stages of Ripening
Authors: Leszczuk Agata , Cybulska Justyna , Skrzypek Tomasz , Zdunek Artur
Published: August 2020

Arabinogalactan proteins (AGPs) are constituents of the cell wall–plasma membrane continuum in fruit tissue. The aim of the study was to characterise AGPs contained in fruit by determination of their chemical structure and morphological properties. The results were obtained from in and ex situ investigations and a comparative analysis of AGPs present in Malus × domestica fruit at different stages of ripening from green fruit through the mature stage to over-ripening during fruit storage. The HPLC and colorimetric methods were used for analyses of the composition of monosaccharides and proteins in AGPs extracted from fruit. We have found that AGPs from fruit mainly consists of carbohydrate chains composed predominantly of arabinose, galactose, glucose, galacturonic acid, and xylose. The protein moiety accounts for 3.15–4.58%, which depends on the various phases of ripening. Taken together, our results show that the structural and morphological properties of AGPs and calcium concentration in AGPs are related to the progress of ripening, which is correlated with proper fruit cell wall assembly. In line with the existing knowledge, our data confirmed the typical carbohydrate composition of AGPs and may be the basis for studies regarding their presumed properties of binding calcium ions.
Histamine Intolerance: The Current State of the Art
Authors: Comas-Basté Oriol , Sánchez-Pérez Sònia , Veciana-Nogués Maria Teresa , Latorre-Moratalla Mariluz , Vidal-Carou María del Carmen
Published: August 2020

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine.
Biotechnological Valorization of Food Marine Wastes: Microbial Productions on Peptones Obtained from Aquaculture By-Products
Authors: Vázquez José Antonio , Durán Ana I. , Menduíña Araceli , Nogueira Margarita
Published: August 2020

Based on a biotechnological strategy, in the present work several peptones are produced from the Alcalase hydrolysis (0.1–0.2% v/w, 56–64 °C, pH 8.27–8.98, 3 h) and thermal processing (105 °C, 60 min) of wastes generated from the industrial processing of turbot, salmon, trout, seabream and seabass. These peptones were included (in the range of 2.6–11 g/L of soluble protein) as main source of organic nitrogen (protein substrates) in low-cost media for the culture of lactic acid bacteria (LAB), marine probiotic bacteria (MPB) and ubiquitous Gram+ bacteria. In most cases, batch fermentations conducted in aquaculture peptone media led to the best growth, metabolic productions and yields. Nevertheless, no significant differences between aquaculture peptones and commercial media were generally observed. Kinetic parameters from a logistic equation and used for cultures modeling were applied with the purpose of comparing the bioproduction outcomes. In economical terms, the validity of the aquaculture peptones as substitutives of the peptones (meat extract, casitone, etc.) from commercial media was also compared. The decreasing of the costs for LAB bioproductions ranged between 3–4 times and the growth costs of MPB and Gram+ bacteria were improved more than 70 and 15 times, respectively, in relation to those found in control commercial media.
C. elegans Models to Study the Propagation of Prions and Prion-Like Proteins
Authors: Sandhof Carl Alexander , Hoppe Simon Oliver , Tittelmeier Jessica , Nussbaum-Krammer Carmen
Published: August 2020

A hallmark common to many age-related neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), is that patients develop proteinaceous deposits in their central nervous system (CNS). The progressive spreading of these inclusions from initially affected sites to interconnected brain areas is reminiscent of the behavior of bona fide prions in transmissible spongiform encephalopathies (TSEs), hence the term prion-like proteins has been coined. Despite intensive research, the exact mechanisms that facilitate the spreading of protein aggregation between cells, and the associated loss of neurons, remain poorly understood. As population demographics in many countries continue to shift to higher life expectancy, the incidence of neurodegenerative diseases is also rising. This represents a major challenge for healthcare systems and patients’ families, since patients require extensive support over several years and there is still no therapy to cure or stop these diseases. The model organism Caenorhabditis elegans offers unique opportunities to accelerate research and drug development due to its genetic amenability, its transparency, and the high degree of conservation of molecular pathways. Here, we will review how recent studies that utilize this soil dwelling nematode have proceeded to investigate the propagation and intercellular transmission of prions and prion-like proteins and discuss their relevance by comparing their findings to observations in other model systems and patients.
Age Differences in the Efficiency of Filtering and Ignoring Distraction in Visual Working Memory
Authors: Maniglia Mariana R. , Souza Alessandra S.
Published: August 2020

Healthy aging is associated with decline in the ability to maintain visual information in working memory (WM). We examined whether this decline can be explained by decreases in the ability to filter distraction during encoding or to ignore distraction during memory maintenance. Distraction consisted of irrelevant objects (Exp. 1) or irrelevant features of an object (Exp. 2). In Experiment 1, participants completed a spatial WM task requiring remembering locations on a grid. During encoding or during maintenance, irrelevant distractor positions were presented. In Experiment 2, participants encoded either single-feature (colors or orientations) or multifeature objects (colored triangles) and later reproduced one of these features using a continuous scale. In multifeature blocks, a precue appeared before encoding or a retrocue appeared during memory maintenance indicating with 100% certainty to the to-be-tested feature, thereby enabling filtering and ignoring of the irrelevant (not-cued) feature, respectively. There were no age-related deficits in the efficiency of filtering and ignoring distractor objects (Exp. 1) and of filtering irrelevant features (Exp. 2). Both younger and older adults could not ignore irrelevant features when cued with a retrocue. Overall, our results provide no evidence for an aging deficit in using attention to manage visual WM.
Emerging Cancer Epigenetic Mechanisms Regulated by All-Trans Retinoic Acid
Authors: Rossetti Stefano , Sacchi Nicoletta
Published: August 2020

All-trans retinoic acid (RA), which is the dietary bioactive derivative obtained from animal (retinol) and plant sources (beta-carotene), is a physiological lipid signal of both embryonic and postembryonic development. During pregnancy, either RA deficiency or an excessive RA intake is teratogenic. Too low or too high RA affects not only prenatal, but also postnatal, developmental processes such as myelopoiesis and mammary gland morphogenesis. In this review, we mostly focus on emerging RA-regulated epigenetic mechanisms involving RA receptor alpha (RARA) and Annexin A8 (ANXA8), which is a member of the Annexin family, as well as ANXA8 regulatory microRNAs (miRNAs). The first cancer showing ANXA8 upregulation was reported in acute promyelocytic leukemia (APL), which induces the differentiation arrest of promyelocytes due to defective RA signaling caused by RARA fusion genes as the PML-RARA gene. Over the years, ANXA8 has also been found to be upregulated in other cancers, even in the absence of RARA fusion genes. Mechanistic studies on human mammary cells and mammary glands of mice showed that ANXA8 upregulation is caused by genetic mutations affecting RARA functions. Although not all of the underlying mechanisms of ANXA8 upregulation have been elucidated, the interdependence of RA-RARA and ANXA8 seems to play a relevant role in some normal and tumorigenic settings.
Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach
Authors: Nouri Zeinab , Fakhri Sajad , Nouri Keyvan , Wallace Carly E. , Farzaei Mohammad Hosein , Bishayee Anupam
Published: August 2020

Multiple dysregulated signaling pathways are implicated in the pathogenesis of cancer. The conventional therapies used in cancer prevention/treatment suffer from low efficacy, considerable toxicity, and high cost. Hence, the discovery and development of novel multi-targeted agents to attenuate the dysregulated signaling in cancer is of great importance. In recent decades, phytochemicals from dietary and medicinal plants have been successfully introduced as alternative anticancer agents due to their ability to modulate numerous oncogenic and oncosuppressive signaling pathways. Rutin (also known as rutoside, quercetin-3-O-rutinoside and sophorin) is an active plant-derived flavonoid that is widely distributed in various vegetables, fruits, and medicinal plants, including asparagus, buckwheat, apricots, apples, cherries, grapes, grapefruit, plums, oranges, and tea. Rutin has been shown to target various inflammatory, apoptotic, autophagic, and angiogenic signaling mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukins, light chain 3/Beclin, B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, caspases, and vascular endothelial growth factor. A comprehensive and critical analysis of the anticancer potential of rutin and associated molecular targets amongst various cancer types has not been performed previously. Accordingly, the purpose of this review is to present an up-to-date and critical evaluation of multiple cellular and molecular mechanisms through which the anticancer effects of rutin are known to be exerted. The current challenges and limitations as well as future directions of research are also discussed.
Anti-Metastasis Fascin Inhibitors Decrease the Growth of Specific Subtypes of Cancers
Authors: Wang Yufeng , Zhang J. Jillian , Huang Xin-Yun
Published: August 2020

Fascin is an actin-bundling protein that is critical for filopodial formation and other cellular cytoskeletal structures. An elevated expression of fascin has been observed in tumor cells and is correlated with a shorter survival of cancer patients. Given its roles in tumor cell migration and invasion, we have developed small-molecule fascin inhibitors to prevent and delay tumor metastasis. Here we report the characterization of a new fascin inhibitor in mice. In addition to its inhibitory effects on tumor metastasis, we also report that fascin inhibitors can decrease the growth of specific subtypes of cancers, including epidermal growth factor receptor (EGFR)-high triple-negative breast cancer, and activated B-cell subtypes of diffuse large B-cell lymphoma. Hence, fascin inhibitors can be used to not only inhibit tumor metastasis, but also decrease the tumor growth of specific cancer types.
Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition
Authors: Gaballa Rofaida , Ali Hamdy E. A. , Mahmoud Mohamed O. , Rhim Johng S. , Ali Hamed I. , Salem Heba F. , Saleem Mohammad , Kandeil Mohamed A. , Ambs Stefan , Abd Elmageed Zakaria Y.
Published: August 2020

Although integrin alpha 2 subunit (ITGA2) mediates cancer progression and metastasis, its transfer by exosomes has not been investigated in prostate cancer (PCa). We aimed to determine the role of exosomal ITGA2 derived from castration-resistant PCa (CRPC) cells in promoting aggressive phenotypes in androgen receptor (AR)-positive cells. Exosomes were co-incubated with recipient cells and tested for different cellular assays. ITGA2 was enriched in exosomes derived from CRPC cells. Co-culture of AR-positive cells with CRPC-derived exosomes increased their proliferation, migration, and invasion by promoting epithelial-mesenchymal transition, which was reversed via ITGA2 knockdown or inhibition of exosomal uptake by methyl-β-cyclodextrin (MβCD). Ectopic expression of ITGA2 reproduced the effect of exosomal ITGA2 in PCa cells. ITGA2 transferred by exosomes exerted its effect within a shorter time compared to that triggered by its endogenous expression. The difference of ITGA2 protein expression in localized tumors and those with lymph node metastatic tissues was indistinguishable. Nevertheless, its abundance was higher in circulating exosomes collected from PCa patients when compared with normal subjects. Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.
No Difference in Overall Survival and Non-Breast Cancer Deaths after Partial Breast Radiotherapy Compared to Whole Breast Radiotherapy—A Meta-Analysis of Randomized Trials
Authors: Haussmann Jan , Budach Wilfried , Corradini Stefanie , Krug David , Tamaskovics Balint , Bölke Edwin , Djiepmo-Njanang Freddy-Joel , Simiantonakis Ioannis , Kammers Kai , Matuschek Christiane
Published: August 2020

Purpose/objective: Adjuvant radiotherapy after breast conserving surgery is the standard approach in early stage breast cancer. However, the extent of breast tissue that has to be targeted with radiation has not been determined yet. Traditionally, the whole breast was covered by two opposing tangential beams. Several randomized trials have tested partial breast irradiation (PBI) compared to whole breast irradiation (WBI) using different radiation techniques. There is evidence from randomized trials that PBI might result in lower mortality rates compared to WBI. We aimed to reassess this question using current data from randomized trials. Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect sizes for overall survival (OS), breast cancer-specific survival (BCSS), and non-breast cancer death (NBCD) as investigated endpoints. Analysis of subgroups using different radiation techniques was intended. We used hazard ratios (HR) and risk differences (RD) to estimate pooled effect sizes. Statistical analysis was performed using the inverse variance heterogeneity model. Results: We identified eleven studies randomizing between PBI and WBI. We did not find significant differences in OS (n = 14,070; HR = 1.02; CI-95%: 0.89–1.16; p = 0.810, and n = 15,203; RD = −0.001; CI-95%: −0.008–0.006; p = 0.785) and BCSS (n = 15,203; RD = 0.001; CI-95%: −0.002–0.005; p = 0.463). PBI also did not result in a significant decrease of NBCD (n = 15,203; RD = −0.003; CI-95%: −0.010–0.003; p = 0.349). A subgroup analysis by radiation technique also did not point to any detectable differences. Conclusion: In contrast to a previous assessment of mortality, we could not find a detrimental effect of WBI on OS or NBCD. A longer follow-up might be necessary to fully assess the long-term mortality effects of PBI compared to WBI.
Trends in Bone Metastasis Modeling
Authors: Laranga Roberta , Duchi Serena , Ibrahim Toni , Guerrieri Ania Naila , Donati Davide Maria , Lucarelli Enrico
Published: August 2020

Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different kinds of cells that coexist in a coordinated balance. Due to the complexity of bone, it is impossible to capture the intricate interactions between cells under either physiological or pathological conditions. Hence, a variety of in vivo and in vitro approaches have been developed. Various models of tumor–bone diseases are routinely used to provide valuable information on the relationship between metastatic cancer cells and the bone tissue. Ideally, when modeling the metastasis of human cancers to bone, models would replicate the intra-tumor heterogeneity, as well as the genetic and phenotypic changes that occur with human cancers; such models would be scalable and reproducible to allow high-throughput investigation. Despite the continuous progress, there is still a lack of solid, amenable, and affordable models that are able to fully recapitulate the biological processes happening in vivo, permitting a correct interpretation of results. In the last decades, researchers have demonstrated that three-dimensional (3D) methods could be an innovative approach that lies between bi-dimensional (2D) models and animal models. Scientific evidence supports that the tumor microenvironment can be better reproduced in a 3D system than a 2D cell culture, and the 3D systems can be scaled up for drug screening in the same way as the 2D systems thanks to the current technologies developed. However, 3D models cannot completely recapitulate the inter- and intra-tumor heterogeneity found in patients. In contrast, ex vivo cultures of fragments of bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Moreover, ex vivo bone organ cultures could be a better model to resemble the human pathogenic metastasis condition and useful tools to predict in vivo response to therapies. The aim of our review is to provide an overview of the current trends in bone metastasis modeling. By showing the existing in vitro and ex vivo systems, we aspire to contribute to broaden the knowledge on bone metastasis models and make these tools more appealing for further translational studies.
Efficient Chemo-Enzymatic Flow Synthesis of High Value Amides and Esters
Authors: Annunziata Francesca , Letizia Contente Martina , Betti Daniele , Pinna Cecilia , Molinari Francesco , Tamborini Lucia , Pinto Andrea
Published: August 2020

A flow-based chemo-enzymatic synthesis of selected APIs (i.e., butacaine, procaine and procainamide) has been developed. A bioreactor made of MsAcT, a versatile acyltransferase from Mycobacterium smegmatis, immobilised on glyoxyl–garose, was exploited to efficiently prepare amide and ester intermediates in gram scale. Immobilised MsAcT was employed in pure organic solvent, demonstrating high stability and reusability. In-line purification of the key intermediates using polymer-bound sulphonyl chloride was added after the bioreactor, enhancing the automation of the process. A final hydrogenation step using the H-Cube reactor was further carried out to obtain the selected APIs in excellent yields (>99%), making the process fast, safe and easily handled.
Curcumin Doped SiO2/TiO2 Nanocomposites for Enhanced Photocatalytic Reduction of Cr (VI) under Visible Light
Authors: Yan Zhiying , He Zijuan , Li Mi , Zhang Lin , Luo Yao , He Jiao , Chen Yongjuan , Wang Jiaqiang
Published: August 2020

In order to further improve the photocatalytic performance of the SiO2/TiO2 composite under visible light irradiation, curcumin-doped SiO2/TiO2 nanocomposites were synthesized via directly incorporating it into the structure of SiO2/TiO2 during the synthesis using an inexpensive and readily available natural pigment (curcumin) as doping agent. The physicochemical properties of SiO2/TiO2 nanocomposites were characterized in detail by X-ray diffraction, transmission electron microscopy, Fourier transform-infrared spectroscopy, N2 adsorption–desorption isotherms, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. The results indicate that all SiO2/TiO2 nanocomposites exhibited an anatase phase with a typical mesoporous structure. It was found that the dope of curcumin in the SiO2/TiO2 composite could decrease the crystal size, slightly improve the specific surface areas, significantly enhance the visible light absorption, and effectively narrow the band gap energy from 3.04 to 10(eV). Compared with bare SiO2/TiO2, the curcumin-doped SiO2/TiO2 resulted in enhanced photocatalytic reduction activity for Cr(VI) under visible light irradiation, and the CTS (12) sample with the appropriate content of curcumin of 12 wt % shows the photocatalytic yield reaching 100% within 2.5 hours, which is larger than CT (12) without silica. This could be attributed to the curcumin doping and the synergetic effects of SiO2 and TiO2 in SiO2/TiO2 nanocomposites.
Efficient Oxidation of Methyl Glycolate to Methyl Glyoxylate Using a Fusion Enzyme of Glycolate Oxidase, Catalase and Hemoglobin
Authors: Ying Xiangxian , Wang Can , Shao Shuai , Wang Qizhou , Zhou Xueting , Bai Yanbing , Chen Liang , Lu Chenze , Zhao Man , Wang Zhao
Published: August 2020

Possessing aldehyde and carboxyl groups, glyoxylic acid and its ester derivatives serve as platform chemicals for the synthesis of vanillin, (R)-pantolactone, antibiotics or agrochemicals. Methyl glycolate is one of the by-products in the coal-to-glycol industry, and we attempted its value-added use through enzymatic oxidation of methyl glycolate to methyl glyoxylate. The cascade catalysis of glycolate oxidase from Spinacia oleracea (SoGOX), catalase from Helicobacter pylori (HpCAT) and hemoglobin from Vitreoscilla stercoraria (VsHGB) was firstly constructed, despite poor catalytic performance. To enable efficient oxidation of methyl glycolate, eight fusion enzymes of SoGOX, HpCAT and VsHGB were constructed by varying the orientation and the linker length. The fusion enzyme VsHGB-GSG-SoGOX-GGGGS-HpCAT was proved to be best, which reaction yield was 2.9 times higher than that of separated enzymes. The enzyme SoGOX was further subjected to directed evolution and site-saturation mutagenesis. The reaction yield of the resulting variant M267T/S362G was 1.9 times higher than that of the wild type. Then, the double substitution M267T/S362G was integrated with fusion expression to give the fusion enzyme VsHGB-GSG-SoGOXmut-GGGGS-HpCAT, which crude enzyme was used as biocatalyst. The use of crude enzyme virtually eliminated side reactions and simplified the preparation of biocatalysts. Under the optimized conditions, the crude enzyme VsHGB-GSG-SoGOXmut-GGGGS-HpCAT catalyzed the oxidation of 200 mM methyl glycolate for 6 h, giving a yield of 95.3%. The development of efficient fusion enzyme and the use of its crude enzyme paved the way for preparative scale application on enzymatic oxidation of methyl glycolate to methyl glyoxylate.
Highlights on Genomics Applications for Lysosomal Storage Diseases
Authors: La Cognata Valentina , Guarnaccia Maria , Polizzi Agata , Ruggieri Martino , Cavallaro Sebastiano
Published: August 2020

Lysosomal storage diseases (LSDs) are a heterogeneous group of rare multisystem genetic disorders occurring mostly in infancy and childhood, characterized by a gradual accumulation of non-degraded substrates inside the lysosome. Although the cellular pathogenesis of LSDs is complex and still not fully understood, the approval of disease-specific therapies and the rapid emergence of novel diagnostic methods led to the implementation of extensive national newborn screening (NBS) programs in several countries. In the near future, this will help the development of standardized workflows aimed to more timely diagnose these conditions. Hereby, we report an overview of LSD diagnostic process and treatment strategies, provide an update on the worldwide NBS programs, and discuss the opportunities and challenges arising from genomics applications in screening, diagnosis, and research.
RF/DC Magnetron Sputtering Deposition of Thin Layers for Solar Cell Fabrication
Authors: Gulkowski Slawomir , Krawczak Ewelina
Published: August 2020

Thin film Cu(In,Ga)Se2 (CIGS)-based solar cells with relatively high efficiency and low material usage might become a promising alternative for crystalline silicon technology. The most challenging task nowadays is to decrease the PV module fabrication costs by application of easily scalable industrial process. One of the possible solutions is the usage of magnetron sputtering system for deposition of all structures applied in CIGS-based photovoltaic device. The main object of these studies was fabrication and characterization of thin films deposited by sputtering technique. Structural and electrical properties of the sputtered films were analyzed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray Powder Diffraction (XRD), and four-point probe resistivity measurements. The presented findings revealed technological parameters for which sheet resistance of molybdenum (Mo) back contact decreased up to 0.3 Ω/□ and to even 0.08 Ω/□ in case of aluminum layer. EDS analysis provided evidence for the appropriate stoichiometry of CIGS absorber (with CGI and GGI equal to 0.96 and 0.2, respectively). XRD characterization confirmed high-quality chalcopyrite polycrystalline structure of Cu(In,Ga)Se2 film fabricated at relatively low substrate temperature of 400 °C. Characteristic XRD peaks of hexagonal-oriented structures of sputtered CdS and i-ZnO layers were noticed.
Broadband Asymmetric Propagation in Pillared Meta-Plates
Authors: Chen Lin , Wang Wei , Nie Guohua , Jin Yabin , Torrent Daniel , Djafari-Rouhani Bahram
Published: August 2020

The asymmetric propagation of mechanical energy across interfaces is a challenging problem with a wide range of applications. In this work, we present a novel structure presenting the asymmetric propagation of elastic waves in thin plates in a broadband range. The structure consists of a combination of symmetrically and asymmetrically distributed pillars, so that the former decouple the different Lamb modes and the latter mix all of them. We show that a combination in tandem with these two structures can realize an efficient broadband asymmetric propagation at the subwavelength range and achieve a transmission difference larger than 200 dB between forward and backward directions. The proposed pillared meta-plate brings a new way for subwavelength and broadband wave manipulation in the fields of wave isolation, sensing and communication, among others.
Recognition and Characterization of Forest Plant Communities through Remote-Sensing NDVI Time Series
Authors: Pesaresi Simone , Mancini Adriano , Casavecchia Simona
Published: August 2020

Phytosociology is a reference method to classify vegetation that relies on field data. Its classification in hierarchical vegetation units, from plant associations to class level, hierarchically reflects the floristic similarity between different sites on different spatial scales. The development of remotely sensed multispectral platforms as satellites enormously contributes to the detection and mapping of vegetation on all scales. However, the integration between phytosociology and remotely sensed data is rather difficult and little practiced despite being a goal for the modern science of vegetation. In this study, we demonstrate how normalized difference vegetation index (NDVI) time series with functional principal component analysis (FPCA) could support the analyses of phytosociologists. The approach supports the recognition and characterization of forest plant communities identified on the ground by the phytosociological approach by using NDVI time series that encode phenological behaviors. The methodology was evaluated in two study areas of central Italy, and it could characterize and discriminate six different forest plant associations that have similar dominant tree species but distinct specific composition: three dominated by black hornbeam (Ostrya carpinifolia) and three dominated by holm oak (Quercus ilex). The methodology was also able to optimize the ground data collection of unexplored areas (from a phytosociological point of view) by using a phenoclustering approach. The obtained results confirmed that by using remote sensing, it is possible to separate and distinguish plant communities in an objective/instrumental way, thus overcoming the subjectivity intrinsic to the phytosociological method. In particular, FPCA functional components (NDVI seasonalities) were significantly correlated with vegetation abundance data variation (Mantel r = 0.76, p < 0.001).