bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulation of the Air Cooling System for Scientific Payload Rack on a Space Station
Authors: Lou Yuan-Yuan , Cai Ben-Yuan , Li Yun-Ze , Li Jia-Xin , Li En-Hui
Published: November 2020

The space scientific payload rack is a multifunctional experimental platform, and the requirements of the environmental temperature index are different for diversified experimental modules inside. The air cooling system is an important part of the rack thermal control system. A new type of air cooling system with small size and flexible arrangement is proposed in this paper, that is, micro air ducts with pinhole-sized air vents. The rack physical models of new and traditional air cooling modes are established, respectively. The numerical simulation of the inner air flow is carried out by Ansys Fluent CFD software (Ansys Inc., Canonsburg, PA, USA), which verifies that compared with the traditional method, the temperature field and flow field of the new air cooling method are more uniform, and the heat sources located at the edge of the rack can also be cooled better.
Techno-Economic Feasibility Analysis through Optimization Strategies and Load Shifting in Isolated Hybrid Microgrids with Renewable Energy for the Non-Interconnected Zone (NIZ) of Colombia
Authors: García-Vera Yimy E. , Dufo-López Rodolfo , Bernal-Agustín José L.
Published: November 2020

In developing countries, electrification in remote areas, where access to energy is limited or null, has been one of the biggest challenges in recent years. Isolated microgrids with renewable generation are an efficient alternative for the energy supply in these areas. The objective of this work was to analyse the techno-economic viability of 6 isolated microgrids in different locations in the non-interconnected zone of Colombia, considering different climatic conditions, the availability of renewable resources, the current consumption profile, and a modified profile applying demand-side management. Modelling and simulation were performed considering storage systems based on lithium and lead-acid batteries. The resulting simulations provide the optimal system cost, emissions levels, electricity cost and battery lifetime. This study demonstrates that isolated hybrid microgrids with renewable energy are a feasible alternative to solve access to energy problems, reducing the need for diesel generators and optimizing the use of renewable energies and battery-based storage systems.
Impact of Current Density and Cooling on the Weight Balance of Electrical Propulsion Drives for Aviation
Authors: Hoffmann Jan , Canders Wolf-Rüdiger , Henke Markus
Published: November 2020

Through applying an exemplary design study, the dependencies between current density, temperatures, and weight in an electrical drive system for a small range aircraft with conventional electrical fan or propeller drives are evaluated. This study applies a combined numerical (Finite Element Method FEM) and analytical approach to the machine design, calculation of temperatures, and cooling system design (cooler, pumps, piping). A design scenario was defined using start and climb flight in a warm tropical surrounding as the worst load case. The design has to move between two fixed temperature limits: The maximum allowable temperature in the machine insulation and the ambient temperature. The implemented method facilitates a comparatively fast-medium depth design of the drive system. The derived results show, in fact, a minimum of weight at a certain current density, which is one of the key interests for the designers of the electrical machine. The main influences on this minimum are the temperature drops in the machine, the heat transfer to the cooling fluid, the heat transfer to the cooler wall, and the remaining heat rejection to the ambient. Method and results are transferable to other types of airplanes with different ratings.
Numerical Analysis for Hydrogen Flame Acceleration during a Severe Accident in the APR1400 Containment Using a Multi-Dimensional Hydrogen Analysis System
Authors: Kang Hyung Seok , Kim Jongtae , Hong Seong Wan , Kim Sang Baik
Published: November 2020

Korea Atomic Energy Research Institute (KAERI) established a multi-dimensional hydrogen analysis system to evaluate hydrogen release, distribution, and combustion in the containment of a Nuclear Power Plant (NPP), using MAAP, GASFLOW, and COM3D. In particular, KAERI developed an analysis methodology for a hydrogen flame acceleration, on the basis of the COM3D validation results against measured data of the hydrogen combustion tests in the ENACCEF and THAI facilities. The proposed analysis methodology accurately predicted the peak overpressure with an error range of approximately ±10%, using the Kawanabe model used for a turbulent flame speed in the COM3D. KAERI performed a hydrogen flame acceleration analysis using the multi-dimensional hydrogen analysis system for a severe accident initiated by a station blackout (SBO), under the assumption of 100% metal–water reaction in the Reactor Pressure Vessel (RPV), to evaluate an overpressure buildup in the containment of the Advanced Power Reactor 1400 MWe (APR1400). The magnitude of the overpressure buildup in the APR1400 containment might be used as a criterion to judge whether the containment integrity is maintained or not, when the hydrogen combustion occurs during a severe accident. The COM3D calculation results using the established analysis methodology showed that the calculated peak pressure in the containment was lower than the fracture pressure of the APR1400 containment. This calculation result might have resulted from a large air volume of the containment, a reduced hydrogen concentration owing to passive auto-catalytic recombiners installed in the containment during the hydrogen release from the RPV, and a lot of stem presence during the hydrogen combustion period in the containment. Therefore, we found that the current design of the APR1400 containment maintained its integrity when the flame acceleration occurred during the severe accident initiated by the SBO accident.
An Economic Penalty Scheme for Optimal Parking Lot Utilization with EV Charging Requirements
Authors: Shi Ruifeng , Zhang Jie , Su Hao , Liang Zihang , Lee Kwang Y.
Published: November 2020

In the parking lots of public commercial areas, such as shopping malls, hospitals, and scenic spots, the parking spaces with electric vehicle (EV) charging facilities are often occupied by ordinary cars. How to regulate the parking order in the parking lot is a key issue in the operation and management of the parking facilities. In this paper, a method of assessing parking fees for vehicles parked at the charging facilities is proposed based on an economic penalty strategy, including fixed-penalty and dynamic-penalty strategies. First, a traffic flow model of the parking lot in public area is established. Then, a price and consumption model of parking fees and parking lot utilization is established, along with different penalty strategies. Finally, taking the parking lot of a shopping mall as an example, the penalty strategies are optimized through particle swarm optimization (PSO) algorithm. The simulation results show that the method proposed can help to improve the utilization of EV charging facilities in parking lots and guide the orderly parking and charging of EVs at the same time.
Effect of Different Egg Products on Lipid Oxidation of Biscuits
Authors: Verardo Vito , Messia Maria Cristina , Marconi Emanuele , Caboni Maria Fiorenza
Published: November 2020

Egg products are one of the main ingredients used in bakery industries, and they contain cholesterol. Cholesterol suffers several chemical changes during the food processes, allowing some potentially toxic compounds called cholesterol oxidized products (COPs). Thus, the aim of this work was to study the evolution of lipid oxidation from eggs to egg products, and to evaluate the influence of egg products on COPs formation in biscuits formulated with them. The results confirmed that spray-drying technology improves the cholesterol oxidation 2.6 times compared to pasteurized eggs. Biscuit samples showed a COPs content that is strictly related to the egg products used. Samples formulated with spray-dried eggs noticed lower amounts of COPs compared to those formulated with pasteurized eggs. It is important to stress that COPs composition was different between the two samples, underlining that the kinetic of COPs formation is dependent on the type of egg products.
The Role of Fruit by-Products as Bioactive Compounds for Intestinal Health
Authors: Chaouch Mohamed Aymen , Benvenuti Stefania
Published: November 2020

The fruit processing industry generates large amounts of wastes (pomace, seeds, peels) that causes negative environmental impact with considerable treatment expenses. Nevertheless, various studies demonstrated that these by-products are still rich in bioactive compounds, especially dietary fibres and phenolic compounds, thus leading to significant chemical, physical and biological properties. These characteristics make fruits by-products a good source for new supplements in food products having important effect on intestinal function. Thus, the aim of this review is to evaluate the different bioactive compounds isolated from fruit by-products and to analyse their application in various formulations for the food and nutraceutical industries. In consideration of the biological properties of these compounds, their role in the functioning and action on intestine and gut flora was discussed.
Linking Soil Hydrology and Creep: A Northern Andes Case
Authors: Pertuz-Paz Aleen , Monsalve Gaspar , Loaiza-Úsuga Juan Carlos , Caballero-Acosta José Humberto , Agudelo-Vélez Laura Inés , Sidle Roy C.
Published: November 2020

Soil creep is common along the hillslopes of the tropical Andes of Colombia, where very heterogeneous soils develop on old debris flow deposits and are subjected to abundant rainfall with a bimodal annual regime. In particular, the western hillside of the city of Medellín, Colombia, is comprised of a series of debris and earth flow deposits in which landslides and soil creep are common. To explore linkages between soil creep and hydrology, we selected an experimental site in the western hillslope of the Medellín valley to assess the behavior of water within the soil mass, its relationship with rainfall, and its connection with soil displacement. In experimental plots, we systematically measured runoff, percolation, water table levels, and volumetric water content, for a period of almost 2 years; we also conducted several alti-planimetric positioning surveys to estimate relative displacements of the soil surface. Moisture content of the soil remained above field capacity for most of the year (~68% of the time) and active and quasi-permanent lateral subsurface flow occurred within the upper 80 cm of the profile. The shallow flow likely facilitates the downslope movement. Additionally, our results suggest that displacement magnitudes are largest during the wet season of September–October–November, when a highly humid soil experiences changes in water content, so it is during this time that the effects of expansion / contraction of the soil particles (associated to wetting / drying cycles) contribute the most to the movement. This observational study represents a contribution to the understanding of soil creep in tropical hillslopes, where it responds to the wetting / drying cycles, with the particularities of a rainy weather (>1500 mm/year), warm temperatures (~22 °C on average), and a bimodal precipitation seasonality.
Re-assessing the Upper Permian Stratigraphic Succession of the Northern Sydney Basin, Australia, by CA-IDTIMS
Authors: Maravelis Angelos G. , Breckenridge Jake , Ruming Kevin , Holmes Erin , Amelin Yuri , Collins William J.
Published: November 2020

High precision Chemical abrasion-isotope dilution thermal ionisation mass spectrometry (CA-IDTIMS) U-Pb zircon results from tuff marker beds that are interstratified within the Upper Permian deposits of the northern Sydney Basin add constraints on the timing of sediment deposition, and afford a better understanding of the regional stratigraphy. The results indicate a magmatic influence during the deposition of the sediments, with episodic events spanning at least from 255.65 ± 0.08 to 255.08 ± 0.09 Ma. The zircon data suggest that the studied sedimentary rocks and tuffs have accumulated simultaneously over a short time interval, which contrasts with current stratigraphic models that suggest a much greater period of deposition and stratigraphic thickness. Therefore, an updated stratigraphic correlation of the basin is suggested, which combines the presently defined Lambton, Adamstown, and Boolaroo sub-groups into a single Lambton sub-group. This updated correlation framework is stratigraphically and geochronologically constrained and provides a more precise exploration model for the northern Sydney Basin. This case study highlights the valuable contribution of the CA-IDTIMS method in intrabasinal correlations of sedimentary successions, when integrated with a robust sedimentological framework, to minimize the stratigraphic uncertainties.
Do High Psychopaths Care More about Moral Consequences than Low Psychopaths in Chinese Culture? An Exploration Using the CNI Model
Authors: Li Shenglan , Ding Daoqun , Wu Zhihui , Yi Liangliang , Lai Ji , Dang Le
Published: November 2020

Purpose: Fewer studies are about the influence of psychopath traits on moral judgment and the underlying psychological mechanism in Chinese cultural background. In this paper, we use the creative CNI (Consequences, Norms, Inaction versus action) model to quantify the subject’s reaction to moral dilemmas. Method: In this research, the Chinese version of the Levenson Psychopathic Scale, CNI model materials, and a multinomial model to further analyze the associations among the psychopathy characteristics and utilitarian moral judgment are applied. The CNI model is proposed by Gawronski et al., which can quantify the subjects’ sensitivity to moral consequence, sensitivity to moral norms, and the general preference for inaction or action in moral dilemmas. Result: This study finds that there were significant differences in the utilitarian moral judgment between the groups, t (360) = 3.24, p = 0.001, and Cohen’s d = 0.36. The analysis results of the CNI model show that the high psychopathy group on the N parameter was significantly lower than the group of low psychopathy, ΔG2 (2) = 79.70, p = 0.001. In terms of the C parameter, we found no significant distinctions between the two groups, ΔG2 (2) = 1.356, p = 0.244. For the I parameter, the two groups also have no significant differences, ΔG2 (2) = 0.093, p = 0.76. Conclusion: Persons with high psychopathy traits prefer to make more utilitarian moral judgments and have a weak sensitivity to moral norms (N). The sensitivity to consequences (C) of the two groups is no significant difference. The general preference for inaction versus action (I) also has no significant differences between those two groups. Moreover, the CNI model fits well in Chinese subjects.
The Impact of Teammates’ Online Reputations on Physicians’ Online Appointment Numbers: A Social Interdependency Perspective
Authors: Liu Jingfang , Zhang Xin , Kong Jun , Wu Liangyu
Published: November 2020

Online medical team is an emerging online medical model in which patients can choose a doctor to register and consult. A doctor’s reputation cannot be ignored. It is worth studying how that online reputation affects the focal doctor’s appointment numbers on the online medical team. Based on the online reputation mechanism and social interdependence theory, this study empirically studied the impact of the focal doctor’s own reputation and other teammates’ reputation on his/her appointment numbers. Our data include 31,143 doctors from 6103 online expert teams of Guahao.com. The results indicate that for a leader doctor, his/her appointment numbers are not related to his/her own reputation, and there was an inverted U-shaped relationship with the ordinary doctors’ reputations on the team. For an ordinary doctor, his/her appointment numbers were positively correlated with his/her own reputation and positively correlated with his/her leader’s reputation and there was an inverted U-shaped relationship with the other ordinary doctors’ reputations. The research showed that there is a positive spillover effect on the team leader’s reputation. There are two relationships between team doctors: competition and cooperation. This study provides guidance for the leader to select team members and the ordinary doctor to select a team.
Levels of Ethylene Oxide Biomarker in an Exposed Residential Community
Authors: Szwiec Emily , Friedman Lee , Buchanan Susan
Published: November 2020

The purpose of this study was to examine whether there is a difference in ethylene oxide (EtO) biomarker levels based on residential proximity to facilities emitting EtO, a carcinogen. We recruited residents living near two EtO-emitting facilities and administered a questionnaire on items such as address and length of residency, smoking habits, occupational exposures to EtO, and demographics. We also collected venous blood samples to measure an EtO biomarker, hemoglobin adduct N-2-hydroxyethyl-valine (HbEO), and cotinine, a metabolite of nicotine. Questionnaires and blood samples were collected from 93 participants. The overall geometric HbEO adduct level was 35.0 pmol/gmHb and for nonsmokers it was 29.7 pmol/gmHb. Mean HbEO adduct levels were not significantly associated with sex, age, race, BMI, or education level. HbEO adduct levels for nonsmoking participants who lived in a neighborhood approximately 0.8 km from one of the facilities were significantly higher compared to persons living farther away (p < 0.001). These results suggest that facilities that emit EtO may put nearby communities at risk of cancer and other associated health outcomes.
Mapping Landslide Hazard Risk Using Random Forest Algorithm in Guixi, Jiangxi, China
Authors: Zhang Yang , Wu Weicheng , Qin Yaozu , Lin Ziyu , Zhang Guiliang , Chen Renxiang , Song Yong , Lang Tao , Zhou Xiaoting , Huangfu Wenchao , Ou Penghui , Xie Lifeng , Huang Xiaolan , Peng Shanling , Shao Chongjian
Published: November 2020

Landslide hazards affect the security of human life and property. Mapping the spatial distribution of landslide hazard risk is critical for decision-makers to implement disaster prevention measures. This study aimed to predict and zone landslide hazard risk, using Guixi County in eastern Jiangxi, China, as an example. An integrated dataset composed of 21 geo-information layers, including lithology, rainfall, altitude, slope, distances to faults, roads and rivers, and thickness of the weathering crust, was used to achieve the aim. Non-digital layers were digitized and assigned weights based on their landslide propensity. Landslide locations and non-risk zones (flat areas) were both vectorized as polygons and randomly divided into two groups to create a training set (70%) and a validation set (30%). Using this training set, the Random Forests (RF) algorithm, which is known for its accurate prediction, was applied to the integrated dataset for risk modeling. The results were assessed against the validation set. Overall accuracy of 91.23% and Kappa Coefficient of 0.82 were obtained. The calculated probability for each pixel was consequently graded into different zones for risk mapping. Hence, we conclude that landslide risk zoning using the RF algorithm can serve as a pertinent reference for local government in their disaster prevention and early warning measures.
Role of NEU3 Overexpression in the Prediction of Efficacy of EGFR-Targeted Therapies in Colon Cancer Cell Lines
Authors: Bovio Federica , Epistolio Samantha , Mozzi Alessandra , Monti Eugenio , Fusi Paola , Forcella Matilde , Frattini Milo
Published: November 2020

The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors’ activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future.
Early Transcriptomic Response to OxLDL in Human Retinal Pigment Epithelial Cells
Authors: Koirala Diwa , Beranova-Giorgianni Sarka , Giorgianni Francesco
Published: November 2020

In the sub-retinal pigment epithelium (sub-RPE) space of the aging macula, deposits of oxidized phospholipids, oxidized derivatives of cholesterol and associated oxidized low-density lipoproteins (OxLDL) are considered contributors to the onset and development of age-related macular degeneration (AMD). We investigated the gene expression response of a human-derived RPE cell line exposed for short periods of time to non-cytotoxic levels of OxLDL or LDL. In our cell model, treatment with OxLDL, but not LDL, generated an early gene expression response which affected more than 400 genes. Gene pathway analysis unveiled gene networks involved in the regulation of various cellular functions, including acute response to oxidative stress via up-regulation of antioxidative gene transcripts controlled by nuclear factor erythroid-2 related factor 2 (NRF2), and up-regulation of aryl hydrocarbon receptor-controlled detoxifying gene transcripts. In contrast, circadian rhythm-controlling genes and genes involved in lipid metabolism were strongly down-regulated. Treatment with low-density lipoprotein (LDL) did not induce the regulation of these pathways. These findings show that RPE cells are able to selectively respond to the oxidized forms of LDL via the up-regulation of gene pathways involved in molecular mechanisms that minimize cellular oxidative damage, and the down-regulation of the expression of genes that regulate the intracellular levels of lipids and lipid derivatives. The effect on genes that control the cellular circadian rhythm suggests that OxLDL might also disrupt the circadian clock-dependent phagocytic activity of the RPE. The data reveal a complex cellular response to a highly heterogeneous oxidative stress-causing agent such as OxLDL commonly present in drusen formations.
Meibomian Gland Dysfunction: What Have Animal Models Taught Us?
Authors: Sun Mingxia , Moreno Isabel Y. , Dang Michelle , Coulson-Thomas Vivien J.
Published: November 2020

Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.
Food-Derived Opioid Peptides in Human Health: A Review
Authors: Tyagi Akanksha , Daliri Eric Banan-Mwine , Kwami Ofosu Fred , Yeon Su-Jung , Oh Deog-Hwan
Published: November 2020

World Health Organization data suggest that stress, depression, and anxiety have a noticeable prevalence and are becoming some of the most common causes of disability in the Western world. Stress-related disorders are considered to be a challenge for the healthcare system with their great economic and social impact. The knowledge on these conditions is not very clear among many people, as a high proportion of patients do not respond to the currently available medications for targeting the monoaminergic system. In addition, the use of clinical drugs is also associated with various side effects such as vomiting, dizziness, sedation, nausea, constipation, and many more, which prevents their effective use. Therefore, opioid peptides derived from food sources are becoming one of the safe and natural alternatives because of their production from natural sources such as animals and plant proteins. The requirement for screening and considering dietary proteins as a source of bioactive peptides is highlighted to understand their potential roles in stress-related disorders as a part of a diet or as a drug complementing therapeutic prescription. In this review, we discussed current knowledge on opioid endogenous and exogenous peptides concentrating on their production, purification, and related studies. To fully understand their potential in stress-related conditions, either as a drug or as a therapeutic part of a diet prescription, the need to screen more dietary proteins as a source of novel opioid peptides is emphasized.
From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors
Authors: Guillén-Gómez Elena , Silva Irene , Serra Núria , Caballero Francisco , Leal Jesús , Breda Alberto , San Martín Rody , Pastor-Anglada Marçal , Ballarín José A. , Guirado Lluís , Díaz-Encarnación Montserrat M.
Published: November 2020

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-β1 and other profibrotic markers, as well as CD163, C/EBPβ, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-β1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-β1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA–CREB axis, inducing the macrophage M2 phenotype, TGF-β1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.
Involvement of MicroRNA-1-FAM83A Axis Dysfunction in the Growth and Motility of Lung Cancer Cells
Authors: Liu Pei-Jung , Chen Yu-Hsuan , Tsai Kuo-Wang , Yeah Hui-Ying , Yeh Chung-Yu , Tu Ya-Ting , Yang Chih-Yun
Published: November 2020

Lung cancer is the most prevalent types of cancer and the leading cause of cancer-related deaths worldwide. Among all cancers, lung cancer has the highest incidence, accompanied by a high mortality rate at the advanced stage. Favorable prognostic biomarkers can effectively increase the survival rate in lung cancer. Our results revealed FAM83A (Family with sequence similarity 83, member A) overexpression in lung cancer tissues compared with adjacent normal tissues. Furthermore, high FAM83A expression was closely associated with poor lung cancer survival. Here, through siRNA transfection, we effectively inhibited FAM83A expression in the lung cancer cell lines H1355 and A549. FAM83A knockdown significantly suppressed the proliferation, migration, and invasion ability of these cells. Furthermore, FAM83A knockdown could suppress Epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinase (MAPK)/Choline kinase alpha (CHKA) signaling activation in A549 and H1355. By using a bioinformatics approach, we found that FAM83A overexpression in lung cancer may result from miR-1-3p downregulation. In summary, we identified a novel miR-1-FAM83A axis could partially modulate the EGFR/choline phospholipid metabolism signaling pathway, which suppressed lung cancer growth and motility. Our findings provide new insights for the development of lung cancer therapeutics.
Machine Learning Identifies Robust Matrisome Markers and Regulatory Mechanisms in Cancer
Authors: Kääriäinen Anni , Pesola Vilma , Dittmann Annalena , Kontio Juho , Koivunen Jarkko , Pihlajaniemi Taina , Izzi Valerio
Published: November 2020

The expression and regulation of matrisome genes—the ensemble of extracellular matrix, ECM, ECM-associated proteins and regulators as well as cytokines, chemokines and growth factors—is of paramount importance for many biological processes and signals within the tumor microenvironment. The availability of large and diverse multi-omics data enables mapping and understanding of the regulatory circuitry governing the tumor matrisome to an unprecedented level, though such a volume of information requires robust approaches to data analysis and integration. In this study, we show that combining Pan-Cancer expression data from The Cancer Genome Atlas (TCGA) with genomics, epigenomics and microenvironmental features from TCGA and other sources enables the identification of “landmark” matrisome genes and machine learning-based reconstruction of their regulatory networks in 74 clinical and molecular subtypes of human cancers and approx. 6700 patients. These results, enriched for prognostic genes and cross-validated markers at the protein level, unravel the role of genetic and epigenetic programs in governing the tumor matrisome and allow the prioritization of tumor-specific matrisome genes (and their regulators) for the development of novel therapeutic approaches.
Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types
Authors: Taracha-Wisniewska Agnieszka , Kotarba Grzegorz , Dworkin Sebastian , Wilanowski Tomasz
Published: November 2020

Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.
Sarcopenia: Molecular Pathways and Potential Targets for Intervention
Authors: Pascual-Fernández Jorge , Fernández-Montero Alejandro , Córdova-Martínez Alfredo , Pastor Diego , Martínez-Rodríguez Alejandro , Roche Enrique
Published: November 2020

Aging is associated with sarcopenia. The loss of strength results in decreased muscle mass and motor function. This process accelerates the progressive muscle deterioration observed in older adults, favoring the presence of debilitating pathologies. In addition, sarcopenia leads to a decrease in quality of life, significantly affecting self-sufficiency. Altogether, these results in an increase in economic resources from the National Health Systems devoted to mitigating this problem in the elderly, particularly in developed countries. Different etiological determinants are involved in the progression of the disease, including: neurological factors, endocrine alterations, as well as nutritional and lifestyle changes related to the adoption of more sedentary habits. Molecular and cellular mechanisms have not been clearly characterized, resulting in the absence of an effective treatment for sarcopenia. Nevertheless, physical activity seems to be the sole strategy to delay sarcopenia and its symptoms. The present review intends to bring together the data explaining how physical activity modulates at a molecular and cellular level all factors that predispose or favor the progression of this deteriorating pathology.
TNF Is Partially Required for Cell-Death-Triggered Skin Inflammation upon Acute Loss of cFLIP
Authors: Feoktistova Maria , Makarov Roman , Leverkus Martin , Yazdi Amir S. , Panayotova-Dimitrova Diana
Published: November 2020

cFLIP is required for epidermal integrity and skin inflammation silencing via protection from TNF-induced keratinocyte apoptosis. Here, we generated and analyzed cFLIP epidermal KO mice with additional TNF deficiency. Intriguingly, the ablation of TNF rescued the pathological phenotype of epidermal cFLIP KO from characteristic weight loss and increased mortality. Moreover, the lack of TNF in these animals strongly reduced and delayed the epidermal hyperkeratosis and the increased apoptosis in keratinocytes. Our data demonstrate that TNF signaling in cFLIP-deficient keratinocytes is the critical factor for the regulation of skin inflammation via modulated cytokine and chemokine expression and, thus, the attraction of immune cells. Our data suggest that autocrine TNF loop activation upon cFLIP deletion is dispensable for T cells, but is critical for neutrophil attraction. Our findings provide evidence for a negative regulatory role of cFLIP for TNF-dependent apoptosis and partially for epidermal inflammation. However, alternative signaling pathways may contribute to the development of the dramatic skin disease upon cFLIP deletion. Our data warrant future studies of the regulatory mechanism controlling the development of skin disease upon cFLIP deficiency and the role of cFLIP/TNF in a number of inflammatory skin diseases, including toxic epidermal necrolysis (TEN).
Taurine Attenuates Catabolic Processes Related to the Onset of Sarcopenia
Authors: Barbiera Alessandra , Sorrentino Silvia , Lepore Elisa , Carfì Andrea , Sica Gigliola , Dobrowolny Gabriella , Scicchitano Bianca Maria
Published: November 2020

Sarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles.
Unraveling the Role of Epicardial Adipose Tissue in Coronary Artery Disease: Partners in Crime?
Authors: Conceição Glória , Martins Diana , M. Miranda Isabel , Leite-Moreira Adelino F. , Vitorino Rui , Falcão-Pires Inês
Published: November 2020

The role of epicardial adipose tissue (EAT) in the pathophysiology of coronary artery disease (CAD) remains unclear. The present systematic review aimed at compiling dysregulated proteins/genes from different studies to dissect the potential role of EAT in CAD pathophysiology. Exhaustive literature research was performed using the keywords “epicardial adipose tissue and coronary artery disease”, to highlight a group of proteins that were consistently regulated among all studies. Reactome, a pathway analysis database, was used to clarify the function of the selected proteins and their intertwined association. SignalP/SecretomeP was used to clarify the endocrine function of the selected proteins. Overall, 1886 proteins/genes were identified from 44 eligible studies. The proteins were separated according to the control used in each study (EAT non-CAD or subcutaneous adipose tissue (SAT) CAD) and by their regulation (up- or downregulated). Using a Venn diagram, we selected the proteins that were upregulated and downregulated (identified as 27 and 19, respectively) in EAT CAD for both comparisons. The analysis of these proteins revealed the main pathways altered in the EAT and how they could communicate with the heart, potentially contributing to CAD development. In summary, in this study, the identified dysregulated proteins highlight the importance of inflammatory processes to modulate the local environment and the progression of CAD, by cellular and metabolic adaptations of epicardial fat that facilitate the formation and progression of atherogenesis of coronaries.
Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
Authors: Karousi Paraskevi , Artemaki Pinelopi I. , Sotiropoulou Christina D. , Christodoulou Spyridon , Scorilas Andreas , Kontos Christos K.
Published: November 2020

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.
TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
Authors: Cherezov Roman O. , Vorontsova Julia E. , Simonova Olga B.
Published: November 2020

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.
Hypoxia-Responsive Class III Peroxidases in Maize Roots: Soluble and Membrane-Bound Isoenzymes
Authors: Hofmann Anne , Wienkoop Stefanie , Harder Sönke , Bartlog Fabian , Lüthje Sabine
Published: November 2020

Flooding induces low-oxygen environments (hypoxia or anoxia) that lead to energy disruption and an imbalance of reactive oxygen species (ROS) production and scavenging enzymes in plants. The influence of hypoxia on roots of hydroponically grown maize (Zea mays L.) plants was investigated. Gene expression (RNA Seq and RT-qPCR) and proteome (LC–MS/MS and 2D-PAGE) analyses were used to determine the alterations in soluble and membrane-bound class III peroxidases under hypoxia. Gel-free peroxidase analyses of plasma membrane-bound proteins showed an increased abundance of ZmPrx03, ZmPrx24, ZmPrx81, and ZmPr85 in stressed samples. Furthermore, RT-qPCR analyses of the corresponding peroxidase genes revealed an increased expression. These peroxidases could be separated with 2D-PAGE and identified by mass spectrometry. An increased abundance of ZmPrx03 and ZmPrx85 was determined. Further peroxidases were identified in detergent-insoluble membranes. Co-regulation with a respiratory burst oxidase homolog (Rboh) and key enzymes of the phenylpropanoid pathway indicates a function of the peroxidases in membrane protection, aerenchyma formation, and cell wall remodeling under hypoxia. This hypothesis was supported by the following: (i) an elevated level of hydrogen peroxide and aerenchyma formation; (ii) an increased guaiacol peroxidase activity in membrane fractions of stressed samples, whereas a decrease was observed in soluble fractions; and (iii) alterations in lignified cells, cellulose, and suberin in root cross-sections.
Effect of Intravitreal Bevacizumab Injection before Panretinal Photocoagulation on the Prevention of Macular Edema Aggravation in Proliferative Diabetic Retinopathy
Authors: Choi Wungrak , Kang Hyun Goo , Choi Eun Young , Kim Sung Soo , Koh Hyoung Jun , Kim Min
Published: November 2020

Objective: To investigate the effects of intravitreal bevacizumab (IVB) injection before PRP on the prevention of macular edema (ME) in patients with PDR. Methods: This retrospective observational study included patients diagnosed with PDR treated by PRP with (combination group) or without (PRP alone group) preoperative IVB injection (1.25 mg/0.05 mL). The primary outcome measure was the change in the central macular thickness (CMT), while the secondary outcome measure was the change in visual acuity. Measurements were made before and at one, two, and three months after treatment. Results: In the PRP alone group, the mean baseline CMT of 277.8 μm increased to 290.4 μm at one month (p = 0.201) and 308.8 μm at two months (p = 0.002), followed by a decrease to 271.2 μm at three months (p = 0.437). In the combination group, the values at baseline and one, two, and three months after PRP were 322.9 μm, 295.4 μm (p = 0.002), 330.1 μm (p = 0.906), and 274.5 μm (p = 0.030), respectively. Visual acuity changes were comparable between the two groups at all time points. Conclusion: IVB injection before PRP leads to decreased CMT in comparison to CMT in patients with PRP alone.
Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges
Authors: Schindler Philipp , Heinzow Hauke , Trebicka Jonel , Wildgruber Moritz
Published: November 2020

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.