bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway
Authors: Kannathasan Thetchinamoorthy , Kuo Wei-Wen , Chen Ming-Cheng , Viswanadha Vijaya Padma , Shen Chia-Yao , Tu Chuan-Chou , Yeh Yu-Lan , Bharath Mahalakshmi , Shibu Marthandam Asokan , Huang Chih-Yang
Published: May 2020

Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, the identification of predictive biomarkers is necessary to effectively generate therapeutic strategies for metastatic human colorectal cancer (CRC). This study aims to identify how cells acquire resistance to anticancer drugs and whether the downregulation of miR-4454 is associated with the progression of CRC. Here, we have shown that the overexpression of miR-4454 in resistant tumors is a crucial precursor for the posttranscriptional repression of GNL3L in human chemoresistant CRC progression, and we used doxycycline induced miR-4454 overexpression that significantly reduced tumor volume in a subcutaneous injection nude mice model. Together, these observations highlight that the downregulation of miR-4454 in resistant clones is prominently responsible for maintaining their resistance against anticancer drug therapy. Our study indicates that the development of miR-4454 as a microRNA-based therapeutic approach to silence GNL3L may remarkably reduce oncogenic cell survival that depends on GNL3L/NF-κB signaling, making miR-4454 a candidate for treating metastatic human CRC.
Electrospun PLGA Fiber Diameter and Alignment of Tendon Biomimetic Fleece Potentiate Tenogenic Differentiation and Immunomodulatory Function of Amniotic Epithelial Stem Cells
Authors: El Khatib Mohammad , Mauro Annunziata , Di Mattia Miriam , Wyrwa Ralf , Schweder Martina , Ancora Massimo , Lazzaro Francesco , Berardinelli Paolo , Valbonetti Luca , Di Giacinto Oriana , Polci Andrea , Cammà Cesare , Schnabelrauch Matthias , Barboni Barbara , Russo Valentina
Published: May 2020

Injured tendons are challenging in their regeneration; thus, tissue engineering represents a promising solution. This research tests the hypothesis that the response of amniotic epithelial stem cells (AECs) can be modulated by fiber diameter size of tendon biomimetic fleeces. Particularly, the effect of electrospun poly(lactide-co-glycolide) (PLGA) fleeces with highly aligned microfibers possessing two different diameter sizes (1.27 and 2.5 µm: ha1- and ha2-PLGA, respectively) was tested on the ability of AECs to differentiate towards the tenogenic lineage by analyzing tendon related markers (Collagen type I: COL1 protein and mRNA Scleraxis: SCX, Tenomodulin: TNMD and COL1 gene expressions) and to modulate their immunomodulatory properties by investigating the pro- (IL-6 and IL-12) and anti- (IL-4 and IL-10) inflammatory cytokines. It was observed that fiber alignment and not fiber size influenced cell morphology determining the morphological change of AECs from cuboidal to fusiform tenocyte-like shape. Instead, fleece mechanical properties, cell proliferation, tenogenic differentiation, and immunomodulation were regulated by changing the ha-PLGA microfiber diameter size. Specifically, higher DNA quantity and better penetration within the fleece were found on ha2-PLGA, while ha1-PLGA fleeces with small fiber diameter size had better mechanical features and were more effective on AECs trans-differentiation towards the tenogenic lineage by significantly translating more efficiently SCX into the downstream effector TNMD. Moreover, the fiber diameter of 1.27 µm induced higher expression of pro-regenerative, anti-inflammatory interleukins mRNA expression (IL-4 and IL-10) with favorable IL-12/IL-10 ratio with respect to the fiber diameter of 2.5 µm. The obtained results demonstrate that fiber diameter is a key factor to be considered when designing tendon biomimetic fleece for tissue repair and provide new insights into the importance of controlling matrix parameters in enhancing cell differentiation and immunomodulation either for the cells functionalized within or for the transplanted host tissue.
Design of a Double-Nozzle Air Spray Gun and Numerical Research in the Interference Spray Flow Field
Authors: Wang Yin-An , Xie Xiao-Peng , Lu Xiao-Hui
Published: May 2020

Spray painting robots equipped with air spray guns have been widely used in the painting industry. In view of the low efficiency of single-nozzle air spray guns when spraying large targets, a new double-nozzle air spray gun structure was designed in this paper based on the Coanda effect of double jets. Firstly, a 3-D physical model of the double-nozzle air spray gun was built in Solidworks, in which unstructured grids were generated for the computational domain by ICEM. Secondly, the spray painting process was numerically modeled with the help of the computational fluid dynamics (CFD) software ANSYS-Fluent 16.0. The two-phase spray flow was calculated by coupling a discrete phase model (DPM) and the Taylor analogy breakup (TAB) method. The TAB model was applied to predict the secondary break-up. The DPM model was applied to predict the droplet trajectories. The geometry of an air spray gun has a significant influence on the spray flow field characteristics. The influence of the air spray gun geometry on the interference spray flow field characteristics and coating film thickness distribution were investigated by changing the values of the distance between the centers of the two paint holes (L) and the angle between the axes of the two paint holes (θ). Numerical results show that the smaller L and θ are, the stronger the interference effect between the two jets, while the more concentrated the paint is in the central region of the target surface, the easier it is for overspray to occur. With increasing L and θ, the interference effect gradually decreased and the extension distance of the coating film along the x-axis gradually increased. However, if L and θ are too large, the interference effect will become too weak and the shape of the coating film will become a concave, with more paint on both side regions and less paint in the central region, which will cause an uneven coating film. From the simulation results, it can be concluded that a more uniform coating film can be obtained when L = 30 mm and θ = 10°. The effective coating width of the double-nozzle air spray gun was increased by 85.7% compared with the single-nozzle air spray gun, which improved the spraying efficiency.
Superfluid Properties of Superconductors with Disorder at the Nanoscale: A Random Impedance Model
Authors: Venditti Giulia , Maccari Ilaria , Grilli Marco , Caprara Sergio
Published: May 2020

Some two-dimensional superconductors like, e.g., LaAlO 3 /SrTiO 3 heterostructures or thin films of transition metal dichalcogenides, display peculiar properties that can be understood in terms of electron inhomogeneity at the nanoscale. In this framework, unusual features of the metal-superconductor transition have been interpreted as due to percolative effects within a network of superconducting regions embedded in a metallic matrix. In this work we use a mean-field-like effective medium approach to investigate the superconducting phase below the critical temperature T c at which the resistivity vanishes. Specifically, we consider the finite frequency impedance of the system to extract the dissipative part of the conductance and the superfluid stiffness in the superconducting state. Intriguing effects arise from the metallic character of the embedding matrix: upon decreasing the temperature below T c proximity effects may rapidly increase the superfluid stiffness. Then, a rather fragile superconducting state, living on a filamentary network just below T c , can be substantially consolidated by additional superconducting regions induced by proximity effect in the interstitial metallic regions. This mean-field prediction should call for further theoretical analyses and trigger experimental investigations of the superconducting properties of the above systems.
Power and Frequency Control in the National Power System of the 370 MW Coal Fired Unit Superstructured with a Gas Turbine
Authors: Bartnik Ryszard , Buryn Zbigniew , Hnydiuk-Stefan Anna , Szega Marcin , Popławski Tomasz
Published: May 2020

A very important task of power units with high power capacity is their participation in the control of the national power system. One of the most important questions posed at work is whether a 370 MW power unit superstructured with a gas turbine in parallel and a heat recovery steam generator be able to take part in the national power system control and if such an upgrade will be economically effective. The analysis was carried out using a proprietary and novel mathematical model. The model takes into account, among others, the influence of the ambient temperature on the parameters of the gas turbine and the changes in thermal steam parameters at its steam extractions as a result of load changes. The results of the analyses showed that it is possible for the modernized unit to participate in the power system control. It can be done only by using a gas turbine with a variable power and a shut off option. The presented results of economic calculations show that at price and cost levels assumed for calculations, the turbine gas superstructure is at the threshold of viability and the investment carries a high degree of risk.
Forecasting Crude Oil Market Crashes Using Machine Learning Technologies
Authors: Zhang Yulian , Hamori Shigeyuki
Published: May 2020

To the best of our knowledge, this study provides new insight into the forecasting of crude oil futures price crashes in America, employing a moving window. One is the fixed-length window and the other is the expanding-length window, which has never been reported in the past. We aimed to investigate if there is any difference when historical data are discarded. As the explanatory variables, we adapted 13 variables to obtain two datasets, 16 explanatory variables for Dataset1 and 121 explanatory variables for Dataset2. We try to observe results from the different-sized sets of explanatory variables. Specifically, we leverage the merits of a series of machine learning techniques, which include random forests, logistic regression, support vector machines, and extreme gradient boosting (XGBoost). Finally, we employ the evaluation metrics that are broadly used to assess the discriminatory power of imbalanced datasets. Our results indicate that we should occasionally discard distant historical data, and that XGBoost outperforms the other employed approaches, achieving a detection rate as high as 86% using the fixed-length moving window for Dataset2.
Energy-Sufficiency for a Just Transition: A Systematic Review
Authors: Burke Matthew J.
Published: May 2020

Efforts to achieve an energy transition often neglect to account for the levelling of benefits realizable with higher levels of energy use, despite knowledge of a saturation effect and recognition of increasing harms of use. This research examines energy sufficiency as a maximum quantity of energy associated with improvements in human well-being to inform a recalibration of energy targets among high-energy societies. A systematic review of recent research was performed to identify the point at which increasing levels of energy use no longer correlate with meaningful increases in well-being. For selected studies (n = 18), energy sufficiency values range from 60–221 gigajoules per capita per year with a mean of 132 gigajoules per capita per year for associated measures of well-being. The review finds agreement in a pattern of saturation and provides a range of values for energy sufficiency maximums, suggesting that a relatively modest amount and a diverse quality of energy is needed to support high levels of human well-being. Beyond the conventional emphasis on energy efficiency and renewable energy, energy sufficiency therefore offers a necessary and complementary approach for supporting just and ecological energy transitions.
SiC-Based Bidirectional Multilevel High-Voltage Gain Switched-Capacitor Resonant Converter with Improved Efficiency
Authors: Kawa Adam , Stala Robert
Published: May 2020

This paper presents the research results of the bidirectional multilevel resonant switched capacitor converter (MRSCC). The converter can achieve a high voltage ratio in multilevel topology, which limits the voltage stress on switches and is able to operate with high power efficiency. The converter can be applied as an interconnector between DC voltage systems used for various applications. This paper presents a method that significantly improves the efficiency of the MSRCC through topology modification. Furthermore, the feasibility of the converter was demonstrated with the use of SiC and Si MOSFET switches, together with suitable passive components. It was demonstrated that the proposed modification of the topology makes the converter very efficient in SiC-based ones and can significantly improve the efficiency of Si MOSFET converters. The series of test results of the SiC-based converter is a novel aspect presented in this paper and shows promising achievements of efficiency. The results were obtained from the laboratory setup of 5 kW and 0.5/2 kV MRSCC. To demonstrate the bidirectional operation of the converter, a back-to-back setup (0.5/2/0.5 kV) was used. It also demonstrates that such a high-voltage gain converter can be accurately tested with the use of laboratory equipment with a typical voltage range.
Energy Effects of Retrofitting the Educational Facilities Located in South-Eastern Poland
Authors: Życzyńska Anna , Suchorab Zbigniew , Kočí Jan , Černý Robert
Published: May 2020

One way to decrease the greenhouse gas emissions in the building sector is to improve the building energy performance, which can be mainly achieved by the reduction of energy consumption. In the case of the existing objects, this goal could be achieved by the thermo-modernization of the building partitions and equipment. This article concerns the issue of heat consumption for heating purposes after a comprehensive retrofitting of nine educational buildings (two kindergartens and seven schools) located in south-eastern Poland where both the total efficiency of the heating installation and the thermal insulation of building partitions were improved. The evaluation of the real energy effects was made on the basis of the measurements performed over the 8 year period of operation for each building. The obtained values were compared with the boundary values of the factors that were in force in Poland during the period when all of the buildings were retrofitted. Additionally, they were compared with the results of theoretical calculations included in the energy audits of the example of three objects and an attempt to describe the reasons for the discrepancies was made. All obtained results were discussed with the available literature sources and summarized with the suitable conclusions.
A Review of Pulsed Current Technique for Lithium-ion Batteries
Authors: Huang Xinrong , Li Yuanyuan , Acharya Anirudh Budnar , Sui Xin , Meng Jinhao , Teodorescu Remus , Stroe Daniel-Ioan
Published: May 2020

Lithium-ion (Li-ion) batteries have been competitive in Electric Vehicles (EVs) due to their high energy density and long lifetime. However, there are still issues, which have to be solved, related to the fast-charging capability of EVs. The pulsed current charging technique is expected to improve the lifetime, charging speed, charging/discharging capacity, and the temperature rising of Li-ion batteries. However, the impact of the pulsed current parameters (i.e., frequency, duty cycle, and magnitude) on characteristics of Li-ion batteries has not been fully understood yet. This paper summarizes the existing pulsed current modes, which are positive Pulsed Current Mode (PPC) and its five extended modes, and Negative Pulsed Current (NPC) mode and its three extended modes. An overview of the impact of pulsed current techniques on the performance of Li-ion batteries is presented. Then the main impact factors of the PPC strategy and the NPC strategy are analyzed and discussed. The weight of these impact factors on lifetime, charging speed, charging/discharging capacity, and the temperature rising of batteries is presented, which provides guidance to design advanced charging/discharging strategies as well as to determine future research gaps.
Human Comfort-Based-Home Energy Management for Demand Response Participation
Authors: Park Herie
Published: May 2020

The residential building sector is encouraged to participate in demand response (DR) programs owing to its flexible and effective energy resources during peak hours with the help of a home energy management system (HEMS). Although the HEMS contributes to reducing energy consumption of the building and the participation of occupants in energy saving programs, unwanted interruptions and strict guidance from the system cause inconvenience to the occupants further leading to their limited participation in the DR programs. This paper presents a human comfort-based control approach for home energy management to promote the DR participation of households. Heating and lighting systems were chosen to be controlled by human comfort factors such as thermal comfort and visual comfort. Case studies were conducted to validate the proposed approach. The results showed that the proposed approach could effectively reduce the energy consumption during the DR period and improve the occupants’ comfort.
Demand Response of Residential Houses Equipped with PV-Battery Systems: An Application Study Using Evolutionary Algorithms
Authors: Lezama Fernando , Faia Ricardo , Faria Pedro , Vale Zita
Published: May 2020

Households equipped with distributed energy resources, such as storage units and renewables, open the possibility of self-consumption of on-site generation, sell energy to the grid, or do both according to the context of operation. In this paper, a model for optimizing the energy resources of households by an energy service provider is developed. We consider houses equipped with technologies that support the actual reduction of energy bills and therefore perform demand response actions. A mathematical formulation is developed to obtain the optimal scheduling of household devices that minimizes energy bill and demand response curtailment actions. In addition to the scheduling model, the innovative approach in this paper includes evolutionary algorithms used to solve the problem under two optimization approaches: (a) the non-parallel approach combine the variables of all households at once; (b) the parallel-based approach takes advantage of the independence of variables between households using a multi-population mechanism and independent optimizations. Results show that the parallel-based approach can improve the performance of the tested evolutionary algorithms for larger instances of the problem. Thus, while increasing the size of the problem, namely increasing the number of households, the proposed methodology will be more advantageous. Overall, vortex search overcomes all other tested algorithms (including the well-known differential evolution and particle swarm optimization) achieving around 30% better fitness value in all the cases, demonstrating its effectiveness in solving the proposed problem.
Production of Biodiesel from Castor Oil: A Review
Authors: Osorio-González Carlos S. , Gómez-Falcon Natali , Sandoval-Salas Fabiola , Saini Rahul , Brar Satinder K. , Ramírez Antonio Avalos
Published: May 2020

An attractive alternative to the use of fossil fuels is biodiesel, which can be obtained from a variety of feedstock through different transesterification systems such as ultrasound, microwave, biological, chemical, among others. The efficient and cost-effective biodiesel production depends on several parameters such as free fatty acid content in the feedstock, transesterification reaction efficiency, alcohol:oil ratio, catalysts type, and several parameters during the production process. However, biodiesel production from vegetable oils is under development, causing the final price of biodiesel to be higher than diesel derived from petroleum. An alternative to decrease the production costs will be the use of economical feedstocks and simple production processes. Castor oil is an excellent raw material in terms of price and quality, but especially this non-edible vegetable oil does not have any issues or compromise food security. Recently, the use of castor oil has attracted attention for producing and optimizing biodiesel production, due to high content of ricinoleic fatty acid and the possibility to esterify with only methanol, which assures low production costs. Additionally, biodiesel from castor oil has different advantages over conventional diesel. Some of them are biodegradable, non-toxic, renewable, they can be used alone, low greenhouse gas emission, among others. This review discusses and analyzes different transesterification processes, technologies, as well as different technical aspects during biodiesel production using castor oil as a feedstock.
Alternative Fuels from Forestry Biomass Residue: Torrefaction Process of Horse Chestnuts, Oak Acorns, and Spruce Cones
Authors: Dyjakon Arkadiusz , Noszczyk Tomasz
Published: May 2020

The global energy system needs new, environmentally friendly, alternative fuels. Biomass is a good source of energy with global potential. Forestry biomass (especially wood, bark, or trees fruit) can be used in the energy process. However, the direct use of raw biomass in the combustion process (heating or electricity generation) is not recommended due to its unstable and low energetic properties. Raw biomass is characterized by high moisture content, low heating value, and hydrophilic propensities. The initial thermal processing and valorization of biomass improves its properties. One of these processes is torrefaction. In this study, forestry biomass residues such as horse chestnuts, oak acorns, and spruce cones were investigated. The torrefaction process was carried out in temperatures ranging from 200 °C to 320 °C in a non-oxidative atmosphere. The raw and torrefied materials were subjected to a wide range of tests including proximate analysis, fixed carbon content, hydrophobicity, density, and energy yield. The analyses indicated that the torrefaction process improves the fuel properties of horse chestnuts, oak acorns, and spruce cones. The properties of torrefied biomass at 320 °C were very similar to hard coal. In the case of horse chestnuts, an increase in fixed carbon content from 18.1% to 44.7%, and a decrease in volatiles from 82.9% to 59.8% were determined. Additionally, torrefied materials were characterized by their hydrophobic properties. In terms of energy yield, the highest value was achieved for oak acorns torrefied at 280 °C and amounted to 1.25. Moreover, higher heating value for the investigated forestry fruit residues ranged from 24.5 MJ·kg−1 to almost 27.0 MJ·kg−1 (at a torrefaction temperature of 320 °C).
Performance of Hybrid Single Well Enhanced Geothermal System and Solar Energy for Buildings Heating
Authors: He Yujiang , Bu Xianbiao
Published: May 2020

The energy reserves in hot dry rock and hydrothermal systems are abundant in China, however, the developed resources are far below the potential estimates due to immature technology of enhanced geothermal system (EGS) and scattered resources of hydrothermal systems. To circumvent these problems and reduce the thermal resistance of rocks, here a shallow depth enhanced geothermal system (SDEGS) is proposed, which can be implemented by fracturing the hydrothermal system. We find that, the service life for SDEGS is 14 years with heat output of 4521.1 kW. To extend service life, the hybrid SDEGS and solar energy heating system is proposed with 10,000 m2 solar collectors installed to store heat into geothermal reservoir. The service life of the hybrid heating system is 35 years with geothermal heat output of 4653.78 kW. The novelty of the present work is that the hybrid heating system can solve the unstable and discontinuous problems of solar energy without building additional back-up sources or seasonal storage equipment, and the geothermal thermal output can be adjusted easily to meet the demand of building thermal loads varying with outside temperature.
Bulk FDTD Simulation of Distributed Corona Effects and Overvoltage Profiles for HSIL Transmission Line Design
Authors: Leman Jon T. , Olsen Robert G.
Published: May 2020

Power system load growth and transmission corridor constraints are driving industry activity in the area of high surge impedance loading (HSIL). Examples include compact structure design and uprating existing transmission lines. Recent research relating electric field uniformity to transmission line capacity and critical flashover voltage underscored the need for better overvoltage data to quantify insulation margins for HSIL design. To that end, this work extends the finite difference time domain (FDTD) method with distributed corona losses to transmission lines with bundled conductors. The model was adapted for practical use in high-volume statistical transient simulation and applied to an example 500 kV line. Transients included line energization and trapped charge reclosing. Overvoltage profiles and statistical distributions were generated from 9500 simulations obtained by random breaker close timing and variation in line length and altitude. Distributed corona losses reduced 98th percentile line-to-ground switching overvoltages by 4%–14% of nominal. The estimated line-to-ground switching surge flashover probability was 54%–80% lower with corona loss. Corona had less impact on line-to-line overvoltages, but the effects were still notable. Results highlight the importance of considering detailed overvoltage profiles and accounting for corona loss attenuation when seeking to carefully quantify insulation design margins.
Sustainable Management of Acacia auriculiformis Plantations for Wood Production over Four Successive Rotations in South Vietnam
Authors: Huong Vu Dinh , Nambiar E. K. Sadanandan , Hai Nguyen Xuan , Ha Kieu Manh , Dang Nguyen Van
Published: May 2020

Vietnam’s forestry sector is facing rising demands for wood to support national and rural economies, and rural livelihoods. A feasible option to meet this demand is to improve productivity in the current plantation estates, especially in those owned by thousands of small growers. Growers have invested in short-rotation acacia plantations primarily for the woodchip market, but are being urged through government policies and pressured by certification bodies and some NGOs to shift to longer rotations, preferentially, for growing saw logs. In this context, we examined the productivity of an Acacia auriculiformis plantation in South Vietnam, over four successive rotations, spanning 25 years. We show that it is possible to increase and sustain wood production in the long term, by applying simple but integrated management practices, recognizing that the conservation of site resources is critical for sustainability. Practices which depleted site organic matter and nutrients lead to a hidden, but high, cumulative loss of production. Given the site and soil damaging practices prevalent in the country, it is likely that production foregone in those sites may be equivalent to the yield from one in every four or five rotations harvested. With sound management including the conservation of site resources, planting the best germplasm, appropriate stocking and judicious use of herbicide, total wood production and the proportion of saw logs (50–70% of the commercial wood at about 7 years of age) can be increased substantially. At the same time, these practices also can promote understory development and diversity in the stand. Such holistic benefits are possible without extending the rotation length and/or thinning, which are likely to raise the levels of risks for small growers, who are not covered by any insurance. Investments and support for small growers to enable higher productivity and value per unit area in their holdings, through sustainable management, would offer practical and low-risk options for the benefits of growers, processors and ecosystems.
On an Exact Step Length in Gradient-Based Aerodynamic Shape Optimization
Authors: Mohebbi Farzad , Evans Ben
Published: May 2020

This study proposeda novel exact expression for step length (size) in gradient-based aerodynamic shape optimization for an airfoil in steady inviscid transonic flows. The airfoil surfaces were parameterized using Bezier curves. The Bezier curve control points were considered as design variables and the finite-difference method was used to compute the gradient of the objective function (drag-to-lift ratio) with respect to the design variables. An exact explicit expression was derived for the step length in gradient-based shape optimization problems. It was shown that the derived step length was independent of the method used for calculating the gradient (adjoint method, finite-difference method, etc.). The obtained results reveal the accuracy of the derived step length.
Global Landscapes of the Na+/H+ Antiporter (NHX) Family Members Uncover their Potential Roles in Regulating the Rapeseed Resistance to Salt Stress
Authors: Cui Jia-qian , Hua Ying-peng , Zhou Ting , Liu Ying , Huang Jin-yong , Yue Cai-peng
Published: May 2020

Soil salinity is a main abiotic stress in agriculture worldwide. The Na+/H+ antiporters (NHXs) play pivotal roles in intracellular Na+ excretion and vacuolar Na+ compartmentalization, which are important for plant salt stress resistance (SSR). However, few systematic analyses of NHXs has been reported in allotetraploid rapeseed so far. Here, a total of 18 full-length NHX homologs, representing seven subgroups (NHX1-NHX8 without NHX5), were identified in the rapeseed genome (AnAnCnCn). Number variations of BnaNHXs might indicate their significantly differential roles in the regulation of rapeseed SSR. BnaNHXs were phylogenetically divided into three evolutionary clades, and the members in the same subgroups had similar physiochemical characteristics, gene/protein structures, and conserved Na+ transport motifs. Darwin´s evolutionary pressure analysis suggested that BnaNHXs suffered from strong purifying selection. The cis-element analysis revealed the differential transcriptional regulation of NHXs between the model Arabidopsis and B. napus. Differential expression of BnaNHXs under salt stress, different nitrogen forms (ammonium and nitrate), and low phosphate indicated their potential involvement in the regulation of rapeseed SSR. Global landscapes of BnaNHXs will give an integrated understanding of their family evolution and molecular features, which will provide elite gene resources for the genetic improvement of plant SSR through regulating the NHX-mediated Na+ transport.
TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings
Authors: Cumbo Cosimo , Tota Giuseppina , Anelli Luisa , Zagaria Antonella , Specchia Giorgina , Albano Francesco
Published: May 2020

TP53 dysregulation plays a pivotal role in the molecular pathogenesis of myelodysplastic syndromes (MDS), identifying a subgroup of patients with peculiar features. In this review we report the recent biological and clinical findings of TP53-mutated MDS, focusing on the molecular pathways activation and on its impact on the cellular physiology. In MDS, TP53 mutational status is deeply associated with del(5q) syndrome and its dysregulation impacts on cell cycle, DNA repair and apoptosis inducing chromosomal instability and the clonal evolution of disease. TP53 defects influence adversely the MDS clinical outcome and the treatment response rate, thus new therapeutic approaches are being developed for these patients. TP53 allelic state characterization and the mutational burden evaluation can therefore predict prognosis and identify the subgroup of patients eligible for targeted therapy. For these reasons, in the era of precision medicine, the MDS diagnostic workup cannot do without the complete assessment of TP53 mutational profile.
Evading the AAV Immune Response in Mucopolysaccharidoses
Authors: Piechnik Matthew , Sawamoto Kazuki , Ohnishi Hidenori , Kawamoto Norio , Ago Yasuhiko , Tomatsu Shunji
Published: May 2020

The humoral immune response elicited by adeno-associated virus (AAV)-mediated gene therapy for the treatment of mucopolysaccharidoses (MPS) poses a significant challenge to achieving therapeutic levels of transgene expression. Antibodies targeting the AAV capsid as well as the transgene product diminish the production of glycosaminoglycan (GAG)-degrading enzymes essential for the treatment of MPS. Patients who have antibodies against AAV capsid increase in number with age, serotype, and racial background and are excluded from the clinical trials at present. In addition, patients who have undergone AAV gene therapy are often excluded from the additional AAV gene therapy with the same serotype, since their acquired immune response (antibody) against AAV will limit further efficacy of treatment. Several methods are being developed to overcome this immune response, such as novel serotype design, antibody reduction by plasmapheresis and immunosuppression, and antibody evasion using empty capsids and enveloped AAV vectors. In this review, we examine the mechanisms of the anti-AAV humoral immune response and evaluate the strengths and weaknesses of current evasion strategies in order to provide an evidence-based recommendation on evading the immune response for future AAV-mediated gene therapies for MPS.
Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration
Authors: Chen Chen-Mei , Wu Meng-Ling , Ho Yen-Chun , Gung Pei-Yu , Tsai Ming-Hsien , Orekhov Alexander N. , Sobenin Igor A. , Lin Pinpin , Yet Shaw-Fang
Published: May 2020

Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with β-catenin, leading to reduced and diffused staining of VE-cadherin and β-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.
The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain
Authors: Kummer Kai K. , Mitrić Miodrag , Kalpachidou Theodora , Kress Michaela
Published: May 2020

Chronic pain patients frequently develop and suffer from mental comorbidities such as depressive mood, impaired cognition, and other significant constraints of daily life, which can only insufficiently be overcome by medication. The emotional and cognitive components of pain are processed by the medial prefrontal cortex, which comprises the anterior cingulate cortex, the prelimbic, and the infralimbic cortex. All three subregions are significantly affected by chronic pain: magnetic resonance imaging has revealed gray matter loss in all these areas in chronic pain conditions. While the anterior cingulate cortex appears hyperactive, prelimbic, and infralimbic regions show reduced activity. The medial prefrontal cortex receives ascending, nociceptive input, but also exerts important top-down control of pain sensation: its projections are the main cortical input of the periaqueductal gray, which is part of the descending inhibitory pain control system at the spinal level. A multitude of neurotransmitter systems contributes to the fine-tuning of the local circuitry, of which cholinergic and GABAergic signaling are particularly emerging as relevant components of affective pain processing within the prefrontal cortex. Accordingly, factors such as distraction, positive mood, and anticipation of pain relief such as placebo can ameliorate pain by affecting mPFC function, making this cortical area a promising target region for medical as well as psychosocial interventions for pain therapy.
Injectable Biomaterials for Dental Tissue Regeneration
Authors: Haugen Håvard Jostein , Basu Poulami , Sukul Mousumi , Mano João F , Reseland Janne Elin
Published: May 2020

Injectable biomaterials scaffolds play a pivotal role for dental tissue regeneration, as such materials are highly applicable in the dental field, particularly when compared to pre-formed scaffolds. The defects in the maxilla-oral area are normally small, confined and sometimes hard to access. This narrative review describes different types of biomaterials for dental tissue regeneration, and also discusses the potential use of nanofibers for dental tissues. Various studies suggest that tissue engineering approaches involving the use of injectable biomaterials have the potential of restoring not only dental tissue function but also their biological purposes.
Bioresorbable Polymeric Scaffold in Cardiovascular Applications
Authors: Toong Daniel Wee Yee , Toh Han Wei , Ng Jaryl Chen Koon , Wong Philip En Hou , Leo Hwa Liang , Venkatraman Subramanian , Tan Lay Poh , Ang Hui Ying , Huang Yingying
Published: May 2020

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6–8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript.
Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes
Authors: Shin Jung-Won , Lee Hyun-Sun , Na Jung-Im , Huh Chang-Hun , Park Kyung-Chan , Choi Hye-Ryung
Published: May 2020

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol’s effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.
Heterobasidion annosum Induces Apoptosis in DLD-1 Cells and Decreases Colon Cancer Growth in In Vivo Model
Authors: Sadowska Anna , Zapora Ewa , Sawicka Diana , Niemirowicz-Laskowska Katarzyna , Surażyński Arkadiusz , Sułkowska-Ziaja Katarzyna , Kała Katarzyna , Stocki Marcin , Wołkowycki Marek , Bakier Sławomir , Pawlik Anna , Jaszek Magdalena , Muszyńska Bożena , Car Halina
Published: May 2020

Application of substances from medicinal mushrooms is one of the interesting approaches to improve cancer therapy. In this study, we commenced a new attempt in the field of Heterobasidion annosum (Fr.) Bref. sensu lato to further extend our knowledge on this basidiomycete fungus. For this purpose, analysis of the active substances of Heterobasidion annosum methanolic extract and also its influence on colorectal cancer in terms of in vitro and in vivo experiments were performed. In vivo studies on mice were conducted to verify its acute toxicity and to further affirm its anticancer potential. Results indicated that all the most common substances of best known medicinal mushrooms that are also responsible for their biological activity are present in tested extracts. In vitro tests showed a high hemocompatibility and a significant decrease in viability and proliferation of DLD-1 cells in a concentration-dependent manner of Heterobasidion annosum extract. The studies performed on xenograft model of mice showed lower tendency of tumor growth in the group of mice receiving Heterobasidion annosum extract as well as mild or moderate toxicity. Obtained results suggest beneficial potential of Heterobasidion annosum against colon cancer as cytotoxic agent or as adjuvant anticancer therapy.
Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone
Authors: Yang Yujie , Chan William K.
Published: May 2020

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation of autophagy by short-term nutrition deprivation reduces its levels. Treatment of chloroquine retards the degradation of AHR and triggers physical interaction between AHR and LC3B. Knockdown of LC3B suppresses the chloroquine-mediated increase of AHR. Down-regulation of p23 promotes AHR degradation via autophagy with no change of the autophagy-related gene expression. Although most data in this study were derived from HeLa cells, human lung (A549), liver (Hep3B), and breast (T-47D and MDA-MB-468) cells also exhibit AHR levels sensitive to chloroquine treatment and AHR–p62/LC3 interactions. Here we provide evidence supporting that AHR undergoes the p62/LC3-mediated selective autophagy in HeLa cells.
Mitochondrial Dynamics and Microglia as New Targets in Metabolism Regulation
Authors: Chiurazzi Martina , Di Maro Martina , Cozzolino Mauro , Colantuoni Antonio
Published: May 2020

Energy homeostasis regulation is essential for the maintenance of life. Neuronal hypothalamic populations are involved in the regulation of energy balance. In order play this role, they require energy: mitochondria, indeed, have a key role in ensuring a constant energy supply to neurons. Mitochondria are cellular organelles that are involved in dynamic processes; their dysfunction has been associated with many diseases, such as obesity and type 2 diabetes, indicating their importance in cellular metabolism and bioenergetics. Food intake excess can induce mitochondrial dysfunction with consequent production of reactive oxygen species (ROS) and oxidative stress. Several studies have shown the involvement of mitochondrial dynamics in the modulation of releasing agouti-related protein (AgRP) and proopiomelanocortin (POMC) neuronal activity, although the mechanisms are still unclear. However, recent studies have shown that changes in mitochondrial metabolism, such as in inflammation, can contribute also to the activation of the microglial system in several diseases, especially degenerative diseases. This review is aimed to summarize the link between mitochondrial dynamics and hypothalamic neurons in the regulation of glucose and energy homeostasis. Furthermore, we focus on the importance of microglia activation in the pathogenesis of many diseases, such as obesity, and on the relationship with mitochondrial dynamics, although this process is still largely unknown.
P53: A Guardian of Immunity Becomes Its Saboteur through Mutation
Authors: Agupitan Arjelle Decasa , Neeson Paul , Williams Scott , Howitt Jason , Haupt Sue , Haupt Ygal
Published: May 2020

Awareness of the importance of immunity in controlling cancer development triggered research into the impact of its key oncogenic drivers on the immune response, as well as their value as targets for immunotherapy. At the heart of tumour suppression is p53, which was discovered in the context of viral infection and now emerges as a significant player in normal and cancer immunity. Wild-type p53 (wt p53) plays fundamental roles in cancer immunity and inflammation. Mutations in p53 not only cripple wt p53 immune functions but also sinisterly subvert the immune function through its neomorphic gain-of-functions (GOFs). The prevalence of mutant p53 across different types of human cancers, which are associated with inflammatory and immune dysfunction, further implicates mutant p53 in modulating cancer immunity, thereby promoting tumorigenesis, metastasis and invasion. In this review, we discuss several mutant p53 immune GOFs in the context of the established roles of wt p53 in regulating and responding to tumour-associated inflammation, and regulating innate and adaptive immunity. We discuss the capacity of mutant p53 to alter the tumour milieu to support immune dysfunction, modulate toll-like receptor (TLR) signalling pathways to disrupt innate immunity and subvert cell-mediated immunity in favour of immune privilege and survival. Furthermore, we expose the potential and challenges associated with mutant p53 as a cancer immunotherapy target and underscore existing therapies that may benefit from inquiry into cancer p53 status.