bluuebunny/crossref_metadata_2025 huggingface dataset:
Modular Battery Charger for Light Electric Vehicles
Authors: Blinov Andrei , Verbytskyi Ievgen , Zinchenko Denys , Vinnikov Dmitri , Galkin Ilya
Published: February 2020

Rapid developments in energy storage and conversion technologies have led to the proliferation of low- and medium-power electric vehicles. Their regular operation typically requires an on-board battery charger that features small dimensions, high efficiency and power quality. This paper analyses an interleaved step-down single-ended primary-inductor converter (SEPIC) operating in the discontinuous conduction mode (DCM) for charging of battery-powered light electric vehicles such as an electric wheelchair. The required characteristics are achieved thanks to favourable arrangement of the inductors in the circuit: the input inductor is used for power factor correction (PFC) without additional elements, while the other inductor is used to provide galvanic isolation and required voltage conversion ratio. A modular interleaved structure of the converter helps to implement low-profile converter design with standard components, distribute the power losses and improve the performance. An optimal number of converter cells was estimated. The converter uses a simple control algorithm for constant current and constant voltage charging modes. To reduce the energy losses, synchronous rectification along with a common regenerative snubber circuit was implemented. The proposed charger concept was verified with a developed 230 VAC to 29.4 VDC experimental prototype that has proved its effectiveness.
Demand Forecasting for a Mixed-Use Building Using Agent-Schedule Information with a Data-Driven Model
Authors: Li Zihao , Friedrich Daniel , Harrison Gareth P.
Published: February 2020

There is great interest in data-driven modelling for the forecasting of building energy consumption while using machine learning (ML) modelling. However, little research considers classification-based ML models. This paper compares the regression and classification ML models for daily electricity and thermal load modelling in a large, mixed-use, university building. The independent feature variables of the model include outdoor temperature, historical energy consumption data sets, and several types of ‘agent schedules’ that provide proxy information that is based on broad classes of activity undertaken by the building’s inhabitants. The case study compares four different ML models testing three different feature sets with a genetic algorithm (GA) used to optimize the feature sets for those ML models without an embedded feature selection process. The results show that the regression models perform significantly better than classification models for the prediction of electricity demand and slightly better for the prediction of heat demand. The GA feature selection improves the performance of all models and demonstrates that historical heat demand, temperature, and the ‘agent schedules’, which derive from large occupancy fluctuations in the building, are the main factors influencing the heat demand prediction. For electricity demand prediction, feature selection picks almost all ‘agent schedule’ features that are available and the historical electricity demand. Historical heat demand is not picked as a feature for electricity demand prediction by the GA feature selection and vice versa. However, the exclusion of historical heat/electricity demand from the selected features significantly reduces the performance of the demand prediction.
Eggshell-Membrane-Derived Carbon Coated on Li2FeSiO4 Cathode Material for Li-Ion Batteries
Authors: Karuppiah Diwakar , Palanisamy Rajkumar , Ponnaiah Arjunan , Liu Wei-Ren , Huang Chia-Hung , Rengapillai Subadevi , Marimuthu Sivakumar
Published: February 2020

Lithium iron orthosilicate (LFS) cathode can be prepared via the polyol-assisted ball milling method with the incorporation of carbon derived from eggshell membrane (ESM) for improving inherent poor electronic conduction. The powder X-ray diffraction (XRD) pattern confirmed the diffraction peaks without any presence of further impure phase. Overall, 9 wt.% of carbon was loaded on the LFS, which was identified using thermogravimetric analysis. The nature of carbon was described using parameters such as monolayer, and average surface area was 53.5 and 24 m2 g−1 with the aid of Langmuir and Brunauer–Emmett–Teller (BET) surface area respectively. The binding energy was observed at 285.66 eV for C–N owing to the nitrogen content in eggshell membrane, which provides more charge carriers for conduction. Transmission electron microscopy (TEM) images clearly show the carbon coating on the LFS, the porous nature of carbon, and the atom arrangements. From the cyclic voltammetry (CV) curve, the ratio of the anodic to the cathodic peak current was calculated as 1.03, which reveals that the materials possess good reversibility. Due to the reversibility of the redox mechanism, the material exhibits discharge specific capacity of 194 mAh g−1 for the first cycle, with capacity retention and an average coulombic efficiency of 94.7% and 98.5% up to 50 cycles.
Research on Down-Regulation Cost of Flexible Combined Heat Power Plants Participating in Real-Time Deep Down-Regulation Market
Authors: Zhang Yan , Lyu Quan , Li Yang , Zhang Na , Zheng Lijun , Gong Haoyan , Sun Hui
Published: February 2020

The issue of real-time deep down-regulation ancillary service has received increasing attention in the Northeast of China. Participation of combined heat and power plants with multitype units and flexible heating devices in the market is investigated. This paper establishes a model of feasible operating region and the coal consumption function for the combined heat and power plant. An internal optimal dispatch model and the minimum overall electric power output model for the plant satisfying a given heat load are presented. Furthermore, the models of total cost for down-regulation and average cost for deep down-regulation in two levels are established. These models are validated based on the realistic data of the plant in the Northeast of China. In case studies, the influence factors and change rules of the minimum electric power output, the total cost, and the average cost of plants are analyzed.
Sustainable Solutions for Green Financing and Investment in Renewable Energy Projects
Authors: Taghizadeh-Hesary Farhad , Yoshino Naoyuki
Published: February 2020

The lack of long-term financing, the low rate of return, the existence of various risks, and the lack of capacity of market players are major challenges for the development of green energy projects. This paper aimed to highlight the challenges of green financing and investment in renewable energy projects and to provide practical solutions for filling the green financing gap. Practical solutions include increasing the role of public financial institutions and non-banking financial institutions (pension funds and insurance companies) in long-term green investments, utilizing the spillover tax to increase the rate of return of green projects, developing green credit guarantee schemes to reduce the credit risk, establishing community-based trust funds, and addressing green investment risks via financial and policy de-risking. The paper also provides a practical example of the implementation of the proposed tools.
The Senescence (Stay-Green)—An Important Trait to Exploit Crop Residuals for Bioenergy
Authors: Munaiz Eduardo D. , Martínez Susana , Kumar Arun , Caicedo Marlon , Ordás Bernardo
Published: February 2020

In this review, we present a comprehensive revisit of past research and advances developed on the stay-green (SG) paradigm. The study aims to provide an application-focused review of the SG phenotypes as crop residuals for bioenergy. Little is known about the SG trait as a germplasm enhancer resource for energy storage as a system for alternative energy. Initially described as a single locus recessive trait, SG was shortly after reported as a quantitative trait governed by complex physiological and metabolic networks including chlorophyll efficiency, nitrogen contents, nutrient remobilization and source-sink balance. Together with the fact that phenotyping efforts have improved rapidly in the last decade, new approaches based on sensing technologies have had an impact in SG identification. Since SG is linked to delayed senescence, we present a review of the term senescence applied to crop residuals and bioenergy. Firstly, we discuss the idiosyncrasy of senescence. Secondly, we present biological processes that determine the fate of senescence. Thirdly, we present the genetics underlying SG for crop-trait improvement in different crops. Further, this review explores the potential uses of senescence for bioenergy crops. Finally, we discuss how high-throughput phenotyping methods assist new technologies such as genomic selection in a cost-efficient manner.
Intelligent Thermal Comfort Controlling System for Buildings Based on IoT and AI
Authors: Zhao Yafei , Genovese Paolo Vincenzo , Li Zhixing
Published: February 2020

With the improvement of technologies, people’s demand for intelligent devices of indoor and outdoor living environments keeps increasing. However, the traditional control system only adjusts living parameters mechanically, which cannot better meet the requirements of human comfort intelligently. This article proposes a building intelligent thermal comfort control system based on the Internet of Things and intelligent artificial intelligence. Through the literature review, various algorithms and prediction methods are analyzed and compared. The system can automatically complete a series of operations through IoT hardware devices which are located at multiple locations in the building with key modules. The code is developed and debugged by Python to establish a model for energy consumption prediction with environmental factors such as temperature, humidity, radiant temperature, and air velocity on thermal comfort indicators. By using the simulation experiments, 1700 data sets are used for training. Then, the output PMV predicted values are compared with the real figure. The results show that the performance of this system is superior to traditional control on energy-saving and comfort.
Volatile Changes during Storage of Shelf Stable Apple Juice: Integrating GC-MS Fingerprinting and Chemometrics
Authors: Kebede Biniam , Ting Vivien , Eyres Graham , Oey Indrawati
Published: February 2020

This is the first study to reveal potential markers for volatile changes during ambient and accelerated shelf life of pasteurized apple juice. The volatile changes were monitored at 20, 30 and 40 °C using a headspace solid-phase microextraction-gas chromatography-mass spectrometry fingerprinting method. Using modern chemometrics and feature selection, hexanal, trans-2-hexenal, dimethyl sulphide, furfural, ethyl acetate and 1-pentanol were chosen as potential shelf life markers. Volatiles associated with the green, grassy and fresh apple aroma, such as hexanal and trans-2-hexenal, decreased during storage, whereas thermal load and browning associated compounds, like dimethyl sulphide and furfural, increased during storage. Hexanal and trans-2-hexenal can be markers to monitor the change in green-apple like character. Furfural and dimethyl sulphide can be markers of temperature abuse during juice processing and storage. Furfural can also be an indicator for juice browning. The present work effectively identified potential markers to monitor and predict volatile aroma changes of shelf stable apple juice in different storage conditions. Sensory analysis can be conducted in the future to confirm the aroma relevance of selected markers.
Chemopreventive Effect of the Germinated Oat and Its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice
Authors: Damazo-Lima Margarita , Rosas-Pérez Guadalupe , Reynoso-Camacho Rosalía , Pérez-Ramírez Iza F. , Rocha-Guzmán Nuria Elizabeth , de los Ríos Ericka A. , Ramos-Gomez Minerva
Published: February 2020

The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38–50%) and adenocarcinoma (38–63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic β-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process.
Residues of Fluoroquinolone Antibiotics Induce Carbonylation and Reduce In Vitro Digestion of Sarcoplasmic and Myofibrillar Beef Proteins
Authors: Márquez-Lázaro Johana , Méndez-Cuadro Darío , Rodríguez-Cavallo Erika
Published: February 2020

Although the impact of oxidation on human health has been of growing interest, the oxidation of proteins, major component of meat, has received little attention. This paper describes the in vitro effect of five fluoroquinolones (FQs) on carbonylation of sarcoplasmic and myofibrillar proteins of beef when found at concentrations close to the maximum residue limit (MRL). Samples were treated individually with the FQs, determining in each protein fraction the carbonyl index, protein content and oxidized proteins identification, using 2,4-dinitrophenyhydrazine (DNPH) alkaline assay, Western blot and Bradford methods, and mass spectrometry, respectively. Besides, the in vitro effect of these residues on gastric and duodenal digestion of proteins was evaluated. The carbonylation induced by FQs affected both protein fractions being significant with respect to the blank in 73.3% of cases. This damage was correlated with loss of solubility and digestibility, with sarcoplasmic proteins the most affected. Danofloxacin and enrofloxacin were the FQs with greatest oxidant effects, especially affecting glycolysis and glycogen proteins. Our results suggest that these residues induce irreversible oxidative damage on the main beef proteins and could affect their nutritional value.
Synergistic Effects of Mild Heating and Dielectric Barrier Discharge Plasma on the Reduction of Bacillus Cereus in Red Pepper Powder
Authors: Jeon Eun Bi , Choi Man-Seok , Kim Ji Yoon , Park Shin Young
Published: February 2020

The synergistic efficacy of a combined treatment of mild heat (MH) and dielectric barrier discharge (DBD) plasma in Bacillus cereus-contaminated red pepper powder was tested. A cocktail of three strains of B. cereus (NCCP 10623, NCCP 14579, ATCC 11778) was inoculated onto red pepper powder and then treated with MH (60 °C for 5–20 min) and DBD plasma (5–20 min). Treatment with MH and DBD plasma alone for 5–20 min resulted in reductions of 0.23–1.43 and 0.12–0.96 log CFU/g, respectively. Combined treatment with MH and DBD plasma was the most effective at reducing B. cereus counts on red pepper powder, and resulted in log-reductions of ≥6.0 log CFU/g. The largest synergistic values (4.24–4.42 log) against B. cereus in red pepper powder were obtained by the combination of 20 min MH and 5–15 min DBD plasma. The values of Hunter color ‘‘L’’, ‘‘a’’, and ‘‘b’’, were not significantly different from those of the untreated sample and that with the combination of MH (60 °C for 5–20 min) and DBD plasma (5–20 min). Also, no significant (p > 0.05) differences in pH values between samples were observed. Therefore, these results suggest that the combination of MH treatment and DBD plasma can be potentially utilized in the food industry to effectively inactivate B. cereus without incurring quality deterioration of red pepper powder.
Health-Related Quality of Life and Medical Resource Use in Patients with Osteoporosis and Depression: A Cross-Sectional Analysis from the National Health and Nutrition Examination Survey
Authors: Weng Shih-Feng , Hsu Hui-Ru , Weng Yao-Lin , Tien Kai-Jen , Kao Hao-Yun
Published: February 2020

Background: Patients with either osteoporosis or depression are prone to develop other diseases and require more medical resources than do the general population. However, there are no studies on health-related quality of life (HRQoL) and medical resource use by osteoporosis patients with comorbid depression. We conducted this study for clarifying it. Methods: This cross-sectional study from 2005 to 2010 (6 years) analyzed 9776 National Health and Nutrition Examination Survey (NHANES) patients > 40 years old. Each patient was assigned to one of four groups: osteoporosis-positive(+) and depression-positive(+) (O+/D+); O+/D−; O−/D+; O−/D−. We used multivariate linear and logistic regression model to analyze the HRQoL and medical resource use between groups. Results: The O+/D+ group reported more unhealthy days of physical health, more unhealthy days of mental health, and more inactive days during a specified 30 days. The adjusted odds ratios (AORs) of O+/D+ patients who had poor general health (7.40, 95% CI = 4.80–11.40), who needed healthcare (3.25, 95% CI = 2.12–5.00), and who had been hospitalized overnight (2.71, 95% CI = 1.89–3.90) were significantly highest. Conclusions: Low HRQoL was significantly more prevalent in D+/O+ patients. We found that depression severity more significantly affected HRQoL than did osteoporosis. However, both diseases significantly increased the risk of high medical resource use.
Supplementation with a Bioactive Melon Concentrate in Humans and Animals: Prevention of Oxidative Damages and Fatigue in the Context of a Moderate or Eccentric Physical Activity
Authors: Saby Marion , Gauthier Audrey , Barial Sandy , Egoumenides Laure , Jover Bernard
Published: February 2020

Exercise is recognized to provide both physical and psychological health benefits. However, oxidative stress can occur and induce muscular damages. SOD B®; M is a melon concentrate, well known to counteract oxidative stress and prevent its side effects. The present study aimed to evaluate the potential of the melon concentrate in the context of both a strong and isolated effort associated with deleterious effects, and a moderate and regular physical activity considered as beneficial. First, a preclinical study was set up on rats to evaluate its potential on the prevention of damages induced by an eccentric exercise. Secondly, the combined effect of the melon concentrate and a regular standardized physical training was studied on the overall physical condition of healthy subjects in a randomized, double-blind, placebo-controlled trial. Repeated measures Analysis of Variance (ANOVA), student’s t test and Mann–Whitney test were used for statistical analyses. Melon concentrate helped to prevent gastrocnemius damages induced by the eccentric exercise. It allowed a reduction of fibrosis by approximately 38% and a reduction of Tumor Necrosis Factor- α (TNF-α) plasma level by 28%. This supplementation also induced a rearrangement of myosin fibers and an increase in PGC-1α plasma level. In the clinical study, melon concentrate was able to decrease oxidative stress and C-Reactive protein (CRP) plasma level. Besides, magnesium (Mg) plasma level was higher in the context of a regular training performed by healthy subjects supplemented with the melon concentrate. Therefore, the melon concentrate allowed a better adaptation to effort linked to PGC-1α activation: a regulator of energy metabolism. The antioxidant properties of the melon concentrate and its ability to mobilize magnesium also suggest that the supplementation could induce a better resistance to fatigue and recovery during regular physical activity.
Genetic Base of Behavioral Disorders in Mucopolysaccharidoses: Transcriptomic Studies
Authors: Pierzynowska Karolina , Gaffke Lidia , Podlacha Magdalena , Węgrzyn Grzegorz
Published: February 2020

Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases caused by mutations leading to defective degradation of glycosaminoglycans (GAGs) and their accumulation in cells. Among 11 known types and subtypes of MPS, neuronopathy occurs in seven (MPS I, II, IIIA, IIIB, IIIC, IIID, VII). Brain dysfunctions, occurring in these seven types/subtypes include various behavioral disorders. Intriguingly, behavioral symptoms are significantly different between patients suffering from various MPS types. Molecular base of such differences remains unknown. Here, we asked if expression of genes considered as connected to behavior (based on Gene Ontology, GO terms) is changed in MPS. Using cell lines of all MPS types, we have performed transcriptomic (RNA-seq) studies and assessed expression of genes involved in behavior. We found significant differences between MPS types in this regard, with the most severe changes in MPS IIIA (the type considered as the behaviorally most severely affected), while the lowest changes in MPS IVA and MPS VI (types in which little or no behavioral disorders are known). Intriguingly, relatively severe changes were found also in MPS IVB (in which, despite no behavioral disorder noted, the same gene is mutated as in GM1 gangliosidosis, a severe neurodegenerative disease) and MPS IX (in which only a few patients were described to date, thus, behavioral problems are not well recognized). More detailed analyses of expression of certain genes allowed us to propose an association of specific changes in the levels of transcripts in specific MPS types to certain behavioral disorders observed in patients. Therefore, this work provides a principle for further studies on the molecular mechanism of behavioral changes occurring in MPS patients.
miR-128a Acts as a Regulator in Cardiac Development by Modulating Differentiation of Cardiac Progenitor Cell Populations
Authors: Hoelscher Sarah C. , Stich Theresia , Diehm Anne , Lahm Harald , Dreßen Martina , Zhang Zhong , Neb Irina , Aherrahrou Zouhair , Erdmann Jeanette , Schunkert Heribert , Santamaria Gianluca , Cuda Giovanni , Gilsbach Ralf , Hein Lutz , Lange Rüdiger , Hassel David , Krane Markus , Doppler Stefanie A.
Published: February 2020

MicroRNAs (miRs) appear to be major, yet poorly understood players in regulatory networks guiding cardiogenesis. We sought to identify miRs with unknown functions during cardiogenesis analyzing the miR-profile of multipotent Nkx2.5 enhancer cardiac progenitor cells (NkxCE-CPCs). Besides well-known candidates such as miR-1, we found about 40 miRs that were highly enriched in NkxCE-CPCs, four of which were chosen for further analysis. Knockdown in zebrafish revealed that only miR-128a affected cardiac development and function robustly. For a detailed analysis, loss-of-function and gain-of-function experiments were performed during in vitro differentiations of transgenic murine pluripotent stem cells. MiR-128a knockdown (1) increased Isl1, Sfrp5, and Hcn4 (cardiac transcription factors) but reduced Irx4 at the onset of cardiogenesis, (2) upregulated Isl1-positive CPCs, whereas NkxCE-positive CPCs were downregulated, and (3) increased the expression of the ventricular cardiomyocyte marker Myl2 accompanied by a reduced beating frequency of early cardiomyocytes. Overexpression of miR-128a (4) diminished the expression of Isl1, Sfrp5, Nkx2.5, and Mef2c, but increased Irx4, (5) enhanced NkxCE-positive CPCs, and (6) favored nodal-like cardiomyocytes (Tnnt2+, Myh6+, Shox2+) accompanied by increased beating frequencies. In summary, we demonstrated that miR-128a plays a so-far unknown role in early heart development by affecting the timing of CPC differentiation into various cardiomyocyte subtypes.
Volatile Organic Compounds from Orchids: From Synthesis and Function to Gene Regulation
Authors: Ramya Mummadireddy , Jang Seonghoe , An Hye-Ryun , Lee Su-Young , Park Pil-Man , Park Pue Hee
Published: February 2020

Orchids are one of the most significant plants that have ecologically adapted to every habitat on earth. Orchids show a high level of variation in their floral morphologies, which makes them popular as ornamental plants in the global market. Floral scent and color are key traits for many floricultural crops. Volatile organic compounds (VOCs) play vital roles in pollinator attraction, defense, and interaction with the environment. Recent progress in omics technology has led to the isolation of genes encoding candidate enzymes responsible for the biosynthesis and regulatory circuits of plant VOCs. Uncovering the biosynthetic pathways and regulatory mechanisms underlying the production of floral scents is necessary not only for a better understanding of the function of relevant genes but also for the generation of new cultivars with desirable traits through molecular breeding approaches. However, little is known about the pathways responsible for floral scents in orchids because of their long life cycle as well as the complex and large genome; only partial terpenoid pathways have been reported in orchids. Here, we review the biosynthesis and regulation of floral volatile compounds in orchids. In particular, we focused on the genes responsible for volatile compounds in various tissues and developmental stages in Cymbidium orchids. We also described the emission of orchid floral volatiles and their function in pollination ecology. Taken together, this review will provide a broad scope for the study of orchid floral scents.
High-Cholesterol Diet Decreases the Level of Phosphatidylinositol 4,5-Bisphosphate by Enhancing the Expression of Phospholipase C (PLCβ1) in Rat Brain
Authors: Chun Yoon Sun , Chung Sungkwon
Published: February 2020

Cholesterol is a critical component of eukaryotic membranes, where it contributes to regulating transmembrane signaling, cell–cell interaction, and ion transport. Dysregulation of cholesterol levels in the brain may induce neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease, and Huntington disease. We previously reported that augmenting membrane cholesterol level regulates ion channels by decreasing the level of phosphatidylinositol 4,5-bisphosphate (PIP2), which is closely related to β-amyloid (Aβ) production. In addition, cholesterol enrichment decreased PIP2 levels by increasing the expression of the β1 isoform of phospholipase C (PLC) in cultured cells. In this study, we examined the effect of a high-cholesterol diet on phospholipase C (PLCβ1) expression and PIP2 levels in rat brain. PIP2 levels were decreased in the cerebral cortex in rats on a high-cholesterol diet. Levels of PLCβ1 expression correlated with PIP2 levels. However, cholesterol and PIP2 levels were not correlated, suggesting that PIP2 level is regulated by cholesterol via PLCβ1 expression in the brain. Thus, there exists cross talk between cholesterol and PIP2 that could contribute to the pathogenesis of neurodegenerative diseases.
Quantitative Proteomics to Identify Nuclear RNA-Binding Proteins of Malat1
Authors: Scherer Marian , Levin Michal , Butter Falk , Scheibe Marion
Published: February 2020

The long non-coding RNA Malat1 has been implicated in several human cancers, while the mechanism of action is not completely understood. As RNAs in cells function together with RNA-binding proteins (RBPs), the composition of their RBP complex can shed light on their functionality. We here performed quantitative interactomics of 14 non-overlapping fragments covering the full length of Malat1 to identify possible nuclear interacting proteins. Overall, we identified 35 candidates including 14 already known binders, which are able to interact with Malat1 in the nucleus. Furthermore, the use of fragments along the full-length RNA allowed us to reveal two hotspots for protein binding, one in the 5′-region and one in the 3′-region of Malat1. Our results provide confirmation on previous RNA-protein interaction studies and suggest new candidates for functional investigations.
Is Sleep Disruption a Cause or Consequence of Alzheimer’s Disease? Reviewing Its Possible Role as a Biomarker
Authors: Lloret Maria-Angeles , Cervera-Ferri Ana , Nepomuceno Mariana , Monllor Paloma , Esteve Daniel , Lloret Ana
Published: February 2020

In recent years, the idea that sleep is critical for cognitive processing has gained strength. Alzheimer’s disease (AD) is the most common form of dementia worldwide and presents a high prevalence of sleep disturbances. However, it is difficult to establish causal relations, since a vicious circle emerges between different aspects of the disease. Nowadays, we know that sleep is crucial to consolidate memory and to remove the excess of beta-amyloid and hyperphosphorilated tau accumulated in AD patients’ brains. In this review, we discuss how sleep disturbances often precede in years some pathological traits, as well as cognitive decline, in AD. We describe the relevance of sleep to memory consolidation, focusing on changes in sleep patterns in AD in contrast to normal aging. We also analyze whether sleep alterations could be useful biomarkers to predict the risk of developing AD and we compile some sleep-related proposed biomarkers. The relevance of the analysis of the sleep microstructure is highlighted to detect specific oscillatory patterns that could be useful as AD biomarkers.
BDNF as a Promising Therapeutic Agent in Parkinson’s Disease
Authors: Palasz Ewelina , Wysocka Adrianna , Gasiorowska Anna , Chalimoniuk Malgorzata , Niewiadomski Wiktor , Niewiadomska Grazyna
Published: February 2020

Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient’s brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.
Microbial Degradation of Plastic in Aqueous Solutions Demonstrated by CO2 Evolution and Quantification
Authors: Rose Ruth-Sarah , Richardson Katherine H. , Latvanen Elmeri Johannes , Hanson China A. , Resmini Marina , Sanders Ian A.
Published: February 2020

The environmental accumulation of plastics worldwide is a consequence of the durability of the material. Alternative polymers, marketed as biodegradable, present a potential solution to mitigate their ecological damage. However, understanding of biodegradability has been hindered by a lack of reproducible testing methods. We developed a novel method to evaluate the biodegradability of plastic samples based on the monitoring of bacterial respiration in aqueous media via the quantification of CO2 produced, where the only carbon source available is from the polymer. Rhodococcus rhodochrous and Alcanivorax borkumensis were used as model organisms for soil and marine systems, respectively. Our results demonstrate that this approach is reproducible and can be used with a variety of plastics, allowing comparison of the relative biodegradability of the different materials. In the case of low-density polyethylene, the study demonstrated a clear correlation between the molecular weight of the sample and CO2 released, taken as a measure of biodegradability.
Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases
Authors: Sunzini Flavia , De Stefano Susanna , Chimenti Maria Sole , Melino Sonia
Published: February 2020

The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H2S) were recently demonstrated in the context of different inflammatory diseases. In particular, H2S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H2S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H2S, more evidence is needed to understand the pathophysiology and the potential of H2S as a therapeutic agent. Within this review, we provide an overview on H2S biological effects, on its role in immune-mediated inflammatory diseases, on H2S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.
Tissue Distribution and Receptor Activation by Somapacitan, a Long Acting Growth Hormone Derivative
Authors: Petersen Maj , Gandhi Prafull S. , Buchardt Jens , Alanentalo Tomas , Fels Johannes Josef , Johansen Nils Langeland , Helding-Kvist Peter , Vad Knud , Thygesen Peter
Published: February 2020

Somapacitan is a long-acting, once-weekly, albumin-binding growth hormone (GH) derivative. The reversible albumin-binding properties leads to prolonged circulation half-life. Here, we investigated and compared somapacitan with human GH on downstream receptor signaling in primary hepatocytes and hepatocellular models and using isothermal titration calorimetry to characterize receptor binding of somapacitan in the presence or absence of human serum albumin (HSA). With non-invasive fluorescence imaging we quantitatively visualize and compare the temporal distribution and examine the tissue-specific growth hormone receptor (GHR) activation at distribution sites. We found that signaling kinetics were slightly more rapid and intense for GH compared with somapacitan. Receptor binding isotherms were characterized by a high and a low affinity interaction site with or without HSA. Using in vivo optical imaging we found prolonged systemically biodistribution of somapacitan compared with GH, which correlated with plasma pharmacokinetics. Ex vivo mouse organ analysis revealed that the temporal fluorescent intensity in livers dosed with somapacitan was significantly increased compared with GH-dosed livers and correlated with the degree of downstream GHR activation. Finally, we show that fluorescent-labeled analogs distributed to the hypertrophic zone in the epiphysis of proximal tibia of hypophysectomized rats and that somapacitan and GH activate the GHR signaling in epiphyseal tissues.
Beyond PSA: The Role of Prostate Health Index (phi)
Authors: Ferro Matteo , De Cobelli Ottavio , Lucarelli Giuseppe , Porreca Angelo , Busetto Gian Maria , Cantiello Francesco , Damiano Rocco , Autorino Riccardo , Musi Gennaro , Vartolomei Mihai Dorin , Muto Matteo , Terracciano Daniela
Published: February 2020

Background: Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly including indolent cancer. Availability of different therapeutic strategies which have a very different impact on the patient’s quality of life suggested a strong need for tools able to identify clinically significant cancer at diagnosis. Multi-parametric magnetic resonance showed very good performance in pre-biopsy diagnosis. However, it is an expensive tool and requires an experienced radiologist. In this context, a simple blood-based test is worth investigating. In this context, researchers focused their attention on the development of a laboratory test able to minimize overdiagnosis without losing the identification of aggressive tumors. Results: Recent literature data on PCa biomarkers revealed a clear tendency towards the use of panels of biomarkers or a combination of biomarkers and clinical variables. Phi, the 4Kscore, and Stockholm3 as circulating biomarkers and the Mi-prostate score, Exo DX Prostate, and Select MD-X as urinary biomarker-based tests have been developed. In this scenario, phi is worthy of attention as a noninvasive test significantly associated with aggressive PCa. Conclusions: Literature data showed that phi had good diagnostic performance to identify clinically significant (cs) PCa, suggesting that it could be a useful tool for personalized treatment decision-making. In this review, phi potentialities, limitations, and comparisons with other blood- and urinary-based tests were explored.
Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line
Authors: Hámori Lilla , Kudlik Gyöngyi , Szebényi Kornélia , Kucsma Nóra , Szeder Bálint , Póti Ádám , Uher Ferenc , Várady György , Szüts Dávid , Tóvári József , Füredi András , Szakács Gergely
Published: February 2020

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. By the age of 80, the estimated risk for breast cancer for women with germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study the pathogenesis and therapy of triple negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated triple-negative breast cancers including increased motility, high proliferation rate, genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib, veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against 11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal compartment in therapy resistance and metastasis formation. In summary, we have established CST cells as a new model recapitulating major characteristics of BRCA1-negative breast cancers.
T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives
Authors: Banfi Giuseppe , Diani Marco , Pigatto Paolo D. , Reali Eva
Published: February 2020

Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.
MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer
Authors: Lai Xing-Ning , Li Jun , Tang Li-Bo , Chen Wen-Tong , Zhang Lei , Xiong Li-Xia
Published: February 2020

Lung cancer is one of the most malignant cancers around the world, with high morbidity and mortality. Metastasis is the leading cause of lung cancer deaths and treatment failure. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), two groups of small non-coding RNAs (nc-RNAs), are confirmed to be lung cancer oncogenes or suppressors. Transforming growth factor-β (TGF-β) critically regulates lung cancer metastasis. In this review, we summarize the dual roles of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer epithelial-mesenchymal transition (EMT), invasion, migration, stemness, and metastasis. In addition, lncRNAs, competing endogenous RNAs (ceRNAs), and circular RNAs (circRNAs) can act as miRNA sponges to suppress miRNAs, thereby mediating TGF-β signaling-regulated lung cancer invasion, migration, and metastasis. Through this review, we hope to cast light on the regulatory mechanisms of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer metastasis and provide new insights for lung cancer treatment.
Protective Effect of l-Hexaguluroic Acid Hexasodium Salt on UVA-Induced Photo-Aging in HaCaT Cells
Authors: Li Qiong , Bai Donghui , Qin Ling , Shao Meng , Liu Xi , Zhang Shuai , Yan Chengxiu , Yu Guangli , Hao Jiejie
Published: February 2020

This study aimed to show the α-l-Hexaguluroic acid hexasodium salt (G6) protective effect against UVA-induced photoaging of human keratinocyte cells. We found that G6 localized to the mitochondria and improved mitochondrial functions. G6 increased respiratory chain complex activities, which led to increased cellular ATP content and NAD+/NADH ratio. Thus, G6 alleviated the oxidative stress state in UVA-irradiated cells. Moreover, G6 can regulate the SIRT1/pGC-1α pathway, which enhanced the cells’ viability and mitochondria energy metabolism. Notably, the anti-photoaging potential of G6 was directly associated with the increased level of MMP and SIRT1, which was followed by the upregulation of pGC-1α, D-LOOP, and Mt-TFA, and with the transcriptional activation of NRF1/NRF2. Taking all of the results together, we conclude that G6 could protect HaCaT cells from UVA-induced photo-aging via the regulation of mitochondria energy metabolism and its downstream signaling pathways.
The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel
Authors: Langan Ewan A. , Recke Andreas , Bokor-Billmann Therezia , Billmann Franck , Kahle Birgit K. , Zillikens Detlef
Published: February 2020

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)—also known as acne inversa—a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.
In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis
Authors: Siculella Luisa , Giannotti Laura , Testini Mariangela , Gnoni Gabriele V. , Damiano Fabrizio
Published: February 2020

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease in which excessive amount of lipids is accumulated as droplets in hepatocytes. Recently, cumulative evidences suggested that a sustained de novo lipogenesis can play an important role in NAFLD. Dysregulated expression of lipogenic genes, including ATP-citrate lyase (ACLY), has been found in liver diseases associated with lipid accumulation. ACLY is a ubiquitous cytosolic enzyme positioned at the intersection of nutrients catabolism and cholesterol and fatty acid biosyntheses. In the present study, the molecular mechanism of ACLY expression in a cell model of steatosis has been reported. We identified an internal ribosome entry site (IRES) in the 5′ untranslated region of the ACLY mRNA, that can support an efficient mRNA translation through a Cap-independent mechanism. In steatotic HepG2 cells, ACLY expression was up-regulated through IRES-mediated translation. Since it has been demonstrated that lipid accumulation in cells induces endoplasmic reticulum (ER) stress, the involvement of this cellular pathway in the translational regulation of ACLY has been also evaluated. Our results showed that ACLY expression was increased in ER-stressed cells, through IRES-mediated translation of ACLY mRNA. A potential role of the Cap-independent translation of ACLY in NAFLD has been discussed.
Conversion of Glycosylated Platycoside E to Deapiose-Xylosylated Platycodin D by Cytolase PCL5
Authors: Shin Kyung-Chul , Kim Dae Wook , Woo Hyun Sim , Oh Deok-Kun , Kim Yeong-Su
Published: February 2020

Platycosides, the saponins abundant in Platycodi radix (the root of Platycodon grandiflorum), have diverse pharmacological activities and have been used as food supplements. Since deglycosylated saponins exhibit higher biological activity than glycosylated saponins, efforts are on to enzymatically convert glycosylated platycosides to deglycosylated platycosides; however, the lack of diversity and specificities of these enzymes has limited the kinds of platycosides that can be deglycosylated. In the present study, we examined the enzymatic conversion of platycosides and showed that Cytolase PCL5 completely converted platycoside E and polygalacin D3 into deapiose-xylosylated platycodin D and deapiose-xylosylated polygalacin D, respectively, which were identified by LC-MS analysis. The platycoside substrates were hydrolyzed through the following novel hydrolytic pathways: platycoside E → platycodin D3 → platycodin D → deapiosylated platycodin D → deapiose-xylosylated platycodin D; and polygalacin D3 → polygalacin D → deapiosylated polygalacin D → deapiose-xylosylated polygalacin D. Our results show that cytolast PCL5 may have a potential role in the development of biologically active platycosides that may be used for their diverse pharmacological activities.