bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phenotypic Responses of Vascular Smooth Muscle Cells Exposed to Mechanical Cues
Authors: Jensen Lise Filt , Bentzon Jacob Fog , Albarrán-Juárez Julian
Published: August 2021

During the development of atherosclerosis and other vascular diseases, vascular smooth muscle cells (SMCs) located in the intima and media of blood vessels shift from a contractile state towards other phenotypes that differ substantially from differentiated SMCs. In addition, these cells acquire new functions, such as the production of alternative extracellular matrix (ECM) proteins and signal molecules. A similar shift in cell phenotype is observed when SMCs are removed from their native environment and placed in a culture, presumably due to the absence of the physiological signals that maintain and regulate the SMC phenotype in the vasculature. The far majority of studies describing SMC functions have been performed under standard culture conditions in which cells adhere to a rigid and static plastic plate. While these studies have contributed to discovering key molecular pathways regulating SMCs, they have a significant limitation: the ECM microenvironment and the mechanical forces transmitted through the matrix to SMCs are generally not considered. Here, we review and discuss the recent literature on how the mechanical forces and derived biochemical signals have been shown to modulate the vascular SMC phenotype and provide new perspectives about their importance.
Time-Dependent Serial Changes of Antigen-Presenting Cell Subsets in the Ocular Surface Are Distinct between Corneal Sterile Inflammation and Allosensitization in a Murine Model
Authors: Kim Kyoung-Woo , Lee Hyun-Ju , Kim Hyeon-Ji , Kim Mee-Kum
Published: August 2021

The kinetics of antigen-presenting cells (APCs) vary depending on their resident tissues and the manner of immunization. We investigated the long-term changes in mature APC and T-cell subsets over 4 weeks in the ocular surface in murine models of corneal quiescent or potent sterile inflammation, and allosensitization using partial (PT), syngeneic (Syn), and allogeneic (Allo) corneal transplantation. In PT, CD11bintCD11chiMHCIIhiCD86hi cells increased until 4 weeks with an increase in IFNγhi T cells. In Syn, both CD11bintCD11chiMHCIIhiCD86hi and CD11bhiCD11chiMHCIIhiCD86hi APC subsets increased until 4 weeks with a brief increase in CD69hi T cells at 2 weeks. In Allo, CD11bintCD11chiMHCIIhiCD86hi and CD11bhiCD11chiMHCIIhiCD86hi APC subsets increased until 4 weeks, and an early increase in CD69hi T cells was observed at 2 weeks followed by a late increase in IFNγhi T cells at 4 weeks. The frequency of the IFNγhi T cell subset was positively correlated with the frequency of the CD11bintCD11chiMHCIIhiCD86hi subset, indicating the existence of APC–T cell interaction in the ocular surface. Together, the results indicate that allosensitization in mature APCs leads to T-cell activation in the ocular surface, whereas sterile inflammation merely induces a brief and non-specific T-cell activation in the ocular surface.
A Claudin-Based Molecular Signature Identifies High-Risk, Chemoresistant Colorectal Cancer Patients
Authors: Gowrikumar Saiprasad , Primeaux Mark , Pravoverov Kristina , Wu Chao , Szeglin Bryan C. , Sauvé Charles-Etienne Gabriel , Thapa Ishwor , Bastola Dhundy , Chen Xi Steven , Smith J. Joshua , Singh Amar B. , Dhawan Punita
Published: August 2021

Identifying molecular characteristics that are associated with aggressive cancer phenotypes through gene expression profiling can help predict treatment responses and clinical outcomes. Claudins are deregulated in colorectal cancer (CRC). In CRC, increased claudin-1 expression results in epithelial-to-mesenchymal transition and metastasis, while claudin-7 functions as a tumor suppressor. In this study, we have developed a molecular signature based on claudin-1 and claudin-7 associated with poor patient survival and chemoresistance. This signature was validated using an integrated approach including publicly available datasets and CRC samples from patients who either responded or did not respond to standard-of-care treatment, CRC cell lines, and patient-derived rectal and colon tumoroids. Transcriptomic analysis from a patient dataset initially yielded 23 genes that were differentially expressed along with higher claudin-1 and decreased claudin-7. From this analysis, we selected a claudins-associated molecular signature including PIK3CA, SLC6A6, TMEM43, and ASAP-1 based on their importance in CRC. The upregulation of these genes and their protein products was validated using multiple CRC patient datasets, in vitro chemoresistant cell lines, and patient-derived tumoroid models. Additionally, blocking these genes improved 5-FU sensitivity in chemoresistant CRC cells. Our findings propose a new claudin-based molecular signature that associates with poor prognosis as well as characteristics of treatment-resistant CRC including chemoresistance, metastasis, and relapse.
The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type
Authors: Pluta Ryszard , Czuczwar Stanisław J. , Januszewski Sławomir , Jabłoński Mirosław
Published: August 2021

Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer’s disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer’s disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer’s disease-type neurodegeneration.
Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas
Authors: Wróblewska Joanna P. , Dias-Santagata Dora , Ustaszewski Adam , Wu Cheng-Lin , Fujimoto Masakazu , Selim M. Angelica , Biernat Wojciech , Ryś Janusz , Marszalek Andrzej , Hoang Mai P.
Published: August 2021

Background: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. Methods: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989–2020 in several clinical institutions were analyzed. NRAS, KIT, BRAF, IGF2R and SF3B1 mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (BRAF, NRAS, NF1)-negative cases, APC, KIT and KRAS are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. NRAS, KIT, BRAF, IGF2R and SF3B1 mutations are detected in 19% (37/198), 22% (44/197), 12% (25/201), 16% (22/138) and 15% (20/133) of cases, respectively. In univariate analyses, advanced stage (p = 0.016), 65 years or older (p = 0.048) and presence of ulceration (p = 0.027) are significantly correlated with worse overall survival (OS), respectively. NRAS mutation significantly correlates with worse OS (p = 0.028) and worse melanoma-specific survival (MSS) (p = 0.03) for all cases of mucosal melanomas. In multivariate analyses, NRAS mutation remains as an independent predictor of worse OS (p = 0.036) and worse MSS (p = 0.024). Conclusion: NRAS mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated IGF2R in mucosal melanomas remains unclear.
Tunable Bandgaps in Phononic Crystal Microbeams Based on Microstructure, Piezo and Temperature Effects
Authors: Hong Jun , He Zhuangzhuang , Zhang Gongye , Mi Changwen
Published: August 2021

A new model of non-classical phononic crystal (PC) microbeam for the elastic wave bandgap generation is provided, incorporating microstructure, piezomagnetism, piezoelectricity and temperature effects. The wave equation of a general magneto–electro–elastic (MEE) phononic crystal microbeam is derived, which recovers piezoelectric- and piezomagnetic-based counterparts as special cases. The piezomagnetic and piezoelectric materials are periodically combined to construct the PC microbeam and corresponding bandgaps are obtained by using the plane wave expansion (PWE) method. The effects of the piezomagnetism, piezoelectricity, microstructure, geometrical parameters and applied multi-fields (e.g., external electric potential, external magnetic potential, temperature change) on the bandgaps are discussed. The numerical results reveal that the bandgap frequency is raised with the presence of piezo and microstructure effects. In addition, the geometry parameters play an important role on the bandgap. Furthermore, large bandgaps can be realized by adjusting the external electric and magnetic potentials at micron scale, and lower bandgap frequency can be realized through the temperature rise at all length scales.
Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues
Authors: Cortesi Valeria , Manzoni Francesca , Raffaeli Genny , Cavallaro Giacomo , Fattizzo Bruno , Amelio Giacomo Simeone , Gulden Silvia , Amodeo Ilaria , Giannotta Juri Alessandro , Mosca Fabio , Ghirardello Stefano
Published: August 2021

Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).
Robust Stabilization and Synchronization of a Novel Chaotic System with Input Saturation Constraints
Authors: Azar Ahmad Taher , Serrano Fernando E. , Zhu Quanmin , Bettayeb Maamar , Fusco Giuseppe , Na Jing , Zhang Weicun , Kamal Nashwa Ahmad
Published: August 2021

In this paper, the robust stabilization and synchronization of a novel chaotic system are presented. First, a novel chaotic system is presented in which this system is realized by implementing a sigmoidal function to generate the chaotic behavior of this analyzed system. A bifurcation analysis is provided in which by varying three parameters of this chaotic system, the respective bifurcations plots are generated and evinced to analyze and verify when this system is in the stability region or in a chaotic regimen. Then, a robust controller is designed to drive the system variables from the chaotic regimen to stability so that these variables reach the equilibrium point in finite time. The robust controller is obtained by selecting an appropriate robust control Lyapunov function to obtain the resulting control law. For synchronization purposes, the novel chaotic system designed in this study is used as a drive and response system, considering that the error variable is implemented in a robust control Lyapunov function to drive this error variable to zero in finite time. In the control law design for stabilization and synchronization purposes, an extra state is provided to ensure that the saturated input sector condition must be mathematically tractable. A numerical experiment and simulation results are evinced, along with the respective discussion and conclusion.
Improved YOLO Based Detection Algorithm for Floating Debris in Waterway
Authors: Lin Feng , Hou Tian , Jin Qiannan , You Aiju
Published: August 2021

Various floating debris in the waterway can be used as one kind of visual index to measure the water quality. The traditional image processing method is difficult to meet the requirements of real-time monitoring of floating debris in the waterway due to the complexity of the environment, such as reflection of sunlight, obstacles of water plants, a large difference between the near and far target scale, and so on. To address these issues, an improved YOLOv5s (FMA-YOLOv5s) algorithm by adding a feature map attention (FMA) layer at the end of the backbone is proposed. The mosaic data augmentation is applied to enhance the detection effect of small targets in training. A data expansion method is introduced to expand the training dataset from 1920 to 4800, which fuses the labeled target objects extracted from the original training dataset and the background images of the clean river surface in the actual scene. The comparisons of accuracy and rapidity of six models of this algorithm are completed. The experiment proves that it meets the standards of real-time object detection.
Dual-Frequency RF Impedance Matching Circuits for Semiconductor Plasma Etch Equipment
Authors: Lee Jeongsu , Hong Sangjeen
Published: August 2021

The change in electrode impedance of semiconductor equipment due to repetitive processes is a major issue that creates process drift. In the current plasma etch chamber with a dual-frequency power system, the high-powered radio frequency (RF) source contributes to the enhancement of the plasma density, and the low-frequency bias power at the bottom electrode is adopted to enhance the injected ion energy in the plasma. The impedance control of the top electrode in dual-frequency capacity coupled plasma limits the impedance matching capability of the RF matching system because it only considers the high-frequency RF source. To control the precise impedance in dual-frequency semiconductor equipment, independent impedance control is required for each frequency. In this study, the impedance corresponding to a specific frequency was independently controlled using L (inductor) and C (capacitor). A 60 MHz stop filter and VVC were used to control 2 MHz impedance at a specific point, and a 2 MHz stop filter and VVC were used to control 60 MHz impedance. In the case of 2 MHz impedance control, the 2 MHz impedance changed from 10.9−j893 to 0.3−j62 and the 60 MHz impedance did not change. When controlling the 60 MHz impedance, the 60 MHz impedance changed from 0.33 + j26.53 to 0.2 + j190 and the 2 MHz impedance did not change. The designed LC circuits cover the impedance of 60 and 2 MHz separately and are verified by the change in the capacitance of the vacuum variable capacitors implemented in the RF impedance matching system.
Evolutionary Multiobjective Optimization with Endmember Priori Strategy for Large-Scale Hyperspectral Sparse Unmixing
Authors: Wang Zhao , Wei Jinxin , Li Jianzhao , Li Peng , Xie Fei
Published: August 2021

Mixed pixels inevitably appear in the hyperspectral image due to the low resolution of the sensor and the mixing of ground objects. Sparse unmixing, as an emerging method to solve the problem of mixed pixels, has received extensive attention in recent years due to its robustness and high efficiency. In theory, sparse unmixing is essentially a multiobjective optimization problem. The sparse endmember term and the reconstruction error term can be regarded as two objectives to optimize simultaneously, and a series of nondominated solutions can be obtained as the final solution. However, the large-scale spectral library poses a challenge due to the high-dimensional number of spectra, it is difficult to accurately extract a few active endmembers and estimate their corresponding abundance from hundreds of spectral features. In order to solve this problem, we propose an evolutionary multiobjective hyperspectral sparse unmixing algorithm with endmember priori strategy (EMSU-EP) to solve the large-scale sparse unmixing problem. The single endmember in the spectral library is used to reconstruct the hyperspectral image, respectively, and the corresponding score of each endmember can be obtained. Then the endmember scores are used as a prior knowledge to guide the generation of the initial population and the new offspring. Finally, a series of nondominated solutions are obtained by the nondominated sorting and the crowding distances calculation. Experiments on two benchmark large-scale simulated data to demonstrate the effectiveness of the proposed algorithm.
Optimization of Thermal Management System with Water and Phase Change Material Cooling for Li-Ion Battery Pack
Authors: Li Quanyi , Cho Jong-Rae , Zhai Jianguang
Published: August 2021

The cooling structure of a battery pack and coupled liquid cooling and phase change material (PCM) were designed in a thermal management system to enhance the cooling performance and extend the service life of lithium-ion battery packs. Numerical simulations were conducted based on the finite volume method. This study focuses on factors such as the layout of the terminal, flow rate of the coolant, different sections of the cooling pipe, position of the cooling pipe, and coupled liquid cooling, and investigates their influences on the operating temperature. The results show that a reasonable terminal layout can reduce heat generation inside the batteries. The appropriate flow rate and position of the cooling pipe effectively reduced the maximum temperature and minimized energy consumption. Then, the PCM was placed between the adjacent batteries near the outlet to enhance the uniformity of the battery pack. The temperature difference was reduced to near 5 K. This study provides a clear direction for improving the cooling performance and extending the service life of battery packs.
The Impact of Incentives on Employees to Change Thermostat Settings—A Field Study
Authors: Zalewska Mariola E.
Published: August 2021

When looking for energy-saving solutions, one should bear in mind the savings that can be obtained through behavioral changes. The article shows that a simple incentive can have a statistically significant impact on employees’ pro-ecological behavior. First, the introduction refers to the general perspective of striving for a global implementation of the Sustainable Developments Goals (SDGs). Additionally, the stakeholders’ point of view is presented, based on reports submitted to the Responsible Business Forum competition (Poland). The two motivating trends are referenced, which include increasing the contribution of powering office buildings to the overall energy demand and increasing the appreciation of behavioral changes as alternatives or complements to technological solutions in pursuit of the SDGs. The following sections of the article present an experiment carried out at one faculty of the University of Warsaw, which consisted of checking the effect of the incentive to lower the temperature in offices after working hours on the actual change in the behavior of the employees. After several weeks of observation of end-of-day thermostat settings in several dozen offices, a statistically significant effect was found. This proves that even simple incentives can lead to pro-ecological behavioral changes.
Flow Field Parametric Interpolation Using a Proper Orthogonal Decomposition: Application to the Variable Valve Timing Effect on a Tumble In-cylinder Miller Engine Mean Flow
Authors: Perceau Marcellin , Guibert Philippe , Guilain Stéphane
Published: August 2021

The current article presents a method to reconstruct the mean velocity field of a cyclic flow for an input parameter value that has not been measured, allowing for the number of tests to be reduced. It is applied to the tumble flow of a gasoline engine following a Miller cycle. New engines often include variable valve timing (VVT) systems to maximize the efficiency of such over-expanded cycles for different operating points. The reconstruction was thus carried out using different offset values of the intake valve lift timing. Experimental data were collected from a transparent engine in an early intake valve closing (EIVC) configuration using particle image velocimetry (PIV). The mean velocity field reconstruction was based on the interpolation of the proper orthogonal decomposition (POD) coefficients. The accuracy of the method was evaluated at different points by comparing the interpolated and the measured flow fields. The accuracy was estimated by calculating the error in the rotation rate of the tumble and the position of its center of rotation. The new mean velocity field set allowed for the position of the tumble’s center of rotation to be closely tracked according to the input parameter and a rotation rate map to be made. Some results on Miller’s cycle could thus be found and the data generated could guide future developments.
Toxic Effect of Ammonium Nitrogen on the Nitrification Process and Acclimatisation of Nitrifying Bacteria to High Concentrations of NH4-N in Wastewater
Authors: Paśmionka Iwona Beata , Bulski Karol , Herbut Piotr , Boligłowa Elżbieta , Vieira Frederico Márcio C. , Bonassa Gabriela , Bortoli Marcelo , Prá Marina Celant de
Published: August 2021

The aim of the conducted research was to assess the effectiveness of the nitrification process, at different concentrations of ammonium nitrogen, in biologically treated wastewater in one of the largest municipal and industrial wastewater treatment plants in Poland. The studies also attempted to acclimate nitrifying bacteria to the limited concentration of ammonium nitrogen and determined the efficiency of nitrification under the influence of acclimated activated sludge in the biological wastewater treatment system. The obtained results indicate that the concentration of ammonium nitrogen above 60.00 mg·dm−3 inhibits nitrification, even after increasing the biomass of nitrifiers. The increase in the efficiency of the nitrification process in the tested system can be obtained by using the activated sludge inoculated with nitrifiers. For this purpose, nitrifiers should be preacclimated, at least for a period of time, allowing them to colonize the activated sludge. The acclimated activated sludge allows reducing the amount of ammonium nitrogen in treated sewage by approx. 35.0%. The process of stable nitrification in the biological treatment system was observed nine days after introducing the acclimated activated sludge into the aeration chamber.
Modelling of Reactive and Non-Reactive Multiphase Flows
Authors: Klein Markus , Chakraborty Nilanjan
Published: August 2021

Multiphase flows are found in several industrial processes encompassing power generation, pharmaceutical and chemical industry and agriculture [...]
Clean Label in Bread
Authors: Vargas Maite Cristina Alava , Simsek Senay
Published: August 2021

Bread is considered a staple food worldwide, and therefore there is much interest in research around the topic. The bread industry is usually looking for ways to improve its formulations. Therefore, other ingredients such as dough conditioners, crumb softeners, emulsifiers, and surfactants can be added to enhance bread quality. These ingredients perform functions such as helping standardize processes in the industry, reducing dough-mixing time, increasing water absorption, improving bread quality, and extending its shelf life. Consumers are concerned about the effect of these ingredients on their health, and this has increased the popularity of clean-label bread formulations. A clean label generally indicates that a product is free of chemical additives, has an ingredient list that is easy to understand, has undergone natural or limited processing, and/or is organic and free of additives or preservatives. However, there is no scientific definition of the term “clean label.” Researchers have focused on these clean-label initiatives to replace dough strengtheners and preservatives in bread formulations and give consumers what they perceive as a healthier product.
Chondroitin Sulfate-Based Cryogels for Biomedical Applications
Authors: Demirci Sahin , Sahiner Mehtap , Ari Betul , Sunol Aydin K. , Sahiner Nurettin
Published: August 2021

Cryogels attained from natural materials offer exceptional properties in applications such as tissue engineering. Moreover, Halloysite Nanotubes (HNT) at 1:0.5 weight ratio were embedded into CS cryogels to render additional biomedical properties. The hemolysis index of CS cryogel and CS:HNT cryogels was calculated as 0.77 ± 0.41 and 0.81 ± 0.24 and defined as non-hemolytic materials. However, the blood coagulation indices of CS cryogel and CS:HNT cryogels were determined as 76 ± 2% and 68 ± 3%, suggesting a mild blood clotting capability. The maximum% swelling capacity of CS cryogel was measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, at pH 1.0, pH 7.4 and pH 9.0, respectively, which were reduced to 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, for CS:HNT cryogel. It was found that CS cryogels can hydrolytically be degraded 41 ± 1% (by wt) in 16-day incubation, whereas the CS:HNT cryogels degraded by 30 ± 1 wt %. There is no chelation for HNT and 67.5 ± 1% Cu(II) chelation for linear CS was measured. On the other hand, the CS cryogel and CS:HNT cryogel revealed Cu(II) chelating capabilities of 60.1 ± 12.5%, and 43.2 ± 17.5%, respectively, from 0.1 mg/mL Cu(II) ion stock solution. Additionally, at 0.5 mg/mL CS, CS:HNT, and HNT, the Fe(II) chelation capacity of 99.7 ± 0.6, 86.2 ± 4.7% and only 11.9 ± 4.5% were measured, respectively, while no Fe(II) was chelated by linear CS chelated Fe(II). As the adjustable and controllable swelling properties of cryogels are important parameters in biomedical applications, the swelling properties of CS cryogels, at different solution pHs, e.g., at the solution pHs of 1.0, 7.4 and 9.0, were measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, respectively, and the maximum selling% values of CS:HNT cryogels were determined as 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, at the same conditions. Alpha glucosidase enzyme interactions were investigated and found that CS-based cryogels can stimulate this enzyme at any CS formulation.
GIS-Based Spatial and Multi-Criteria Assessment of Riverine Flood Potential: A Case Study of the Nitra River Basin, Slovakia
Authors: Vojtek Matej , Vojteková Jana , Pham Quoc Bao
Published: August 2021

The aim of this study was to identify the areas with different levels of riverine flood potential (RFP) in the Nitra river basin, Slovakia, using multi-criteria evaluation (MCE)-analytical hierarchical process (AHP), geographic information systems (GIS), and seven flood conditioning factors. The RFP in the Nitra river basin had not yet been assessed through MCE-AHP. Therefore, the methodology used can be useful, especially in terms of the preliminary flood risk assessment required by the EU Floods Directive. The results showed that classification techniques of natural breaks (Jenks), equal interval, quantile, and geometric interval classified 32.03%, 29.90%, 41.84%, and 53.52% of the basin, respectively, into high and very high RFP while 87.38%, 87.38%, 96.21%, and 98.73% of flood validation events, respectively, corresponded to high and very high RFP. A single-parameter sensitivity analysis of factor weights was performed in order to derive the effective weights, which were used to calculate the revised riverine flood potential (RRFP). In general, the differences between the RFP and RRFP can be interpreted as an underestimation of the share of high and very high RFP as well as the share of flood events in these classes within the RFP assessment. Therefore, the RRFP is recommended for the assessment of riverine flood potential in the Nitra river basin.
Geospatial Analysis of the Non-Surveyed (Estimated) Coastlines in Inoh’s Map, 1821
Authors: Iwai Yuki , Murayama Yuji
Published: August 2021

The history of modern maps in Japan began with Inoh’s map that was made by surveying the whole of Japan on foot 200 years ago. Inoh’s team investigated coastlines, major roads, and geographical features such as rivers, lakes, temples, forts, village names, etc. The survey was successively conducted ten times from 1800 to 1816. Inoh’s map is known as the first scientific map in Japan using a systematic method. However, the actual survey was conducted only for 75% of the coastlines in Japan and the remaining 25% was drawn by Inoh’s estimation (observation). This study investigated how the non-surveyed (estimated) coastlines were distributed in the map and why the actual survey was not conducted in these non-surveyed coastlines. Using GIS, we overlaid the geometrically corrected Inoh’s map (Digital Inoh’s Map Professional Edition) with the current map published by the Geospatial Information Authority (GSI) of Japan for examining the spatial difference. We found that the non-surveyed coastlines were in places where the practice of actual surveying was topographically difficult because of the limited surveying technology of those days. The analytical result shows that 38.6% of the non-surveyed coastlines were cliffs, 25.7% were rocky beaches, and 6.2% were wetlands and tidal lands (including rice fields and tidal flats).
Evaluation of Loco-Regional Skin Toxicity Induced by an In Situ Forming Depot after a Single Subcutaneous Injection at Different Volumes and Flow Rates in Göttingen Minipigs
Authors: Peloso Charlotte , Trichet Anne-Pascale , Descotes Jacques , Richard Joël , Roberge Christophe , Lopez-Noriega Adolfo
Published: August 2021

The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges.
Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer
Authors: Kantapan Jiraporn , Dechsupa Nathupakorn , Tippanya Damrongsak , Nobnop Wannapha , Chitapanarux Imjai
Published: August 2021

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.
Pleiotrophin Deficiency Induces Browning of Periovarian Adipose Tissue and Protects against High-Fat Diet-Induced Hepatic Steatosis
Authors: Zuccaro Agata , Zapatería Begoña , Sánchez-Alonso María Gracia , Haro María , Limones María , Terrados Gloria , Izquierdo Adriana , Corrales Patricia , Medina-Gómez Gema , Herradón Gonzalo , Sevillano Julio , Ramos-Álvarez María del Pilar
Published: August 2021

(1) Background: Pleiotrophin preserves insulin sensitivity, regulates adipose tissue lipid turnover and plasticity, energy metabolism and thermogenesis. The aim of this study was to determine the role of pleiotrophin in hepatic lipid metabolism and in the metabolic crosstalk between the liver and brown and white adipose tissue (AT) in a high-fat diet-induced (HFD) obesity mice model. (2) Methods: We analyzed circulating variables, lipid metabolism (hepatic lipid content and mRNA expression), brown AT thermogenesis (UCP-1 expression) and periovarian AT browning (brown adipocyte markers mRNA and immunodetection) in Ptn−/− mice either fed with standard-chow diet or with HFD and in their corresponding Ptn+/+ counterparts. (3) Results: HFD-Ptn−/− mice are protected against the development of HFD-induced insulin resistance, had lower liver lipid content and lower expression of the key enzymes involved in triacylglycerides and fatty acid synthesis in liver. HFD-Ptn−/− mice showed higher UCP-1 expression in brown AT. Moreover, Ptn deletion increased the expression of specific markers of brown/beige adipocytes and was associated with the immunodetection of UCP-1 enriched multilocular adipocytes in periovarian AT. (4) Conclusions: Ptn deletion protects against the development of HFD-induced insulin resistance and liver steatosis, by increasing UCP-1 expression in brown AT and promoting periovarian AT browning.
Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview
Authors: Piorecka Kinga , Kurjata Jan , Stanczyk Wlodzimierz A.
Published: August 2021

The development in the area of novel anticancer prodrugs (conjugates and complexes) has attracted growing attention from many research groups. The dangerous side effects of currently used anticancer drugs, including cisplatin and other platinum based drugs, as well their systemic toxicity is a driving force for intensive search and presents a safer way in delivery platform of active molecules. Silicon based nanocarriers play an important role in achieving the goal of synthesis of the more effective prodrugs. It is worth to underline that silicon based platform including silica and silsesquioxane nanocarriers offers higher stability, biocompatibility of such the materials and pro-longed release of active platinum drugs. Silicon nanomaterials themselves are well-known for improving drug delivery, being themselves non-toxic, and versatile, and tailored surface chemistry. This review summarizes the current state-of-the-art within constructs of silicon-containing nano-carriers conjugated and complexed with platinum based drugs. Contrary to a number of other reviews, it stresses the role of nano-chemistry as a primary tool in the development of novel prodrugs.
Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair?
Authors: Evens Lize , Beliën Hanne , D’Haese Sarah , Haesen Sibren , Verboven Maxim , Rummens Jean-Luc , Bronckaers Annelies , Hendrikx Marc , Deluyker Dorien , Bito Virginie
Published: August 2021

Myocardial infarction (MI) occurs when the coronary blood supply is interrupted. As a consequence, cardiomyocytes are irreversibly damaged and lost. Unfortunately, current therapies for MI are unable to prevent progression towards heart failure. As the renewal rate of cardiomyocytes is minimal, the optimal treatment should achieve effective cardiac regeneration, possibly with stem cells transplantation. In that context, our research group identified the cardiac atrial appendage stem cells (CASCs) as a new cellular therapy. However, CASCs are transplanted into a hostile environment, with elevated levels of advanced glycation end products (AGEs), which may affect their regenerative potential. In this study, we hypothesize that pyridoxamine (PM), a vitamin B6 derivative, could further enhance the regenerative capacities of CASCs transplanted after MI by reducing AGEs’ formation. Methods and Results: MI was induced in rats by ligation of the left anterior descending artery. Animals were assigned to either no therapy (MI), CASCs transplantation (MI + CASCs), or CASCs transplantation supplemented with PM treatment (MI + CASCs + PM). Four weeks post-surgery, global cardiac function and infarct size were improved upon CASCs transplantation. Interstitial collagen deposition, evaluated on cryosections, was decreased in the MI animals transplanted with CASCs. Contractile properties of resident left ventricular cardiomyocytes were assessed by unloaded cell shortening. CASCs transplantation prevented cardiomyocyte shortening deterioration. Even if PM significantly reduced cardiac levels of AGEs, cardiac outcome was not further improved. Conclusion: Limiting AGEs’ formation with PM during an ischemic injury in vivo did not further enhance the improved cardiac phenotype obtained with CASCs transplantation. Whether AGEs play an important deleterious role in the setting of stem cell therapy after MI warrants further examination.
Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation
Authors: Wada Yoshihisa , Umeno Reina , Nagasu Hajime , Kondo Megumi , Tokuyama Atsuyuki , Kadoya Hiroyuki , Kidokoro Kengo , Taniguchi Shun’ichiro , Takahashi Masafumi , Sasaki Tamaki , Kashihara Naoki
Published: August 2021

Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), eNOS knockout (eNOS KO), and ASC knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target.
Overview of Ferroptosis and Synthetic Lethality Strategies
Authors: Kinowaki Yuko , Taguchi Towako , Onishi Iichiroh , Kirimura Susumu , Kitagawa Masanobu , Yamamoto Kouhei
Published: August 2021

Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery.
Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish
Authors: Martínez-Pena Inés , Hurtado Pablo , Carmona-Ule Nuria , Abuín Carmen , Dávila-Ibáñez Ana Belén , Sánchez Laura , Abal Miguel , Chaachou Anas , Hernández-Losa Javier , Cajal Santiago Ramón y , López-López Rafael , Piñeiro Roberto
Published: August 2021

Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.
The Phosphonate Derivative of C60 Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
Authors: Kostyuk Svetlana V. , Proskurnina Elena V. , Ershova Elizaveta S. , Kameneva Larisa V. , Malinovskaya Elena M. , Savinova Ekaterina A. , Sergeeva Vasilina A. , Umriukhin Pavel E. , Dolgikh Olga A. , Khakina Ekaterina A. , Kraevaya Olga A. , Troshin Pavel A. , Kutsev Sergey I. , Veiko Natalia N.
Published: August 2021

Inductors of myogenic stem cell differentiation attract attention, as they can be used to treat myodystrophies and post-traumatic injuries. Functionalization of fullerenes makes it possible to obtain water-soluble derivatives with targeted biochemical activity. This study examined the effects of the phosphonate C60 fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs). Uptake of the phosphonate C60 fullerene derivatives in human MSCs, intracellular ROS visualization, superoxide scavenging potential, and the expression of myogenic, adipogenic, and osteogenic differentiation genes were studied. The prolonged MSC incubation (within 7–14 days) with the C60 pentaphoshonate potassium salt promoted their differentiation towards the myogenic lineage. The transcription factors and gene expressions determining myogenic differentiation (MYOD1, MYOG, MYF5, and MRF4) increased, while the expression of osteogenic differentiation factors (BMP2, BMP4, RUNX2, SPP1, and OCN) and adipogenic differentiation factors (CEBPB, LPL, and AP2 (FABP4)) was reduced or did not change. The stimulation of autophagy may be one of the factors contributing to the increased expression of myogenic differentiation genes in MSCs. Autophagy may be caused by intracellular alkalosis and/or short-term intracellular oxidative stress.
S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation
Authors: Mosca Laura , Pagano Martina , Borzacchiello Luigi , Mele Luigi , Russo Annapina , Russo Giulia , Cacciapuoti Giovanna , Porcelli Marina
Published: August 2021

Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.