bluuebunny/crossref_metadata_2025 huggingface dataset:
Monofloral Honeys as a Potential Source of Natural Antioxidants, Minerals and Medicine
Authors: Mărgăoan Rodica , Topal Erkan , Balkanska Ralitsa , Yücel Banu , Oravecz Titanilla , Cornea-Cipcigan Mihaiela , Vodnar Dan Cristian
Published: June 2021

Background: vegetative diversity is based on different climate and geographical origins. In terms of beekeeping, herbal diversity is strongly correlated to the production of a wide variety of honey. Therefore, based on the existing plant diversity in each country, multiple honey varieties are produced with different health characteristics. While beekeeping potential and consumption preferences are reflected in products’ variety, this leads to an increase in the region’s economy and extensive export. In the last years, monofloral honey has gained interest from consumers and especially in the medicinal field due to the presence of phytochemicals which are directly linked to health benefits, wound healing, antioxidant, anticancer and anti-inflammatory activities. Scope and approach: this review aims to highlight the physicochemical properties, mineral profiles and antioxidant activities of selected monofloral honeys based on their botanical and geographical origin. Moreover, this review focuses on the intercorrelation between monofloral honey’s antioxidant compounds and in vitro and in vivo activities, focusing on the apoptosis and cell proliferation inhibition in various cell lines, with a final usage of honey as a potential therapeutic product in the fight towards reducing tumor growth. Key findings and conclusions: multiple studies have demonstrated that monofloral honeys have different physicochemical structures and bioactive compounds. Useful chemical markers to distinguish between monofloral honeys were evidenced, such as: 2-methoxybenzoic acid and trimethoxybenzoic acid are distinctive to Manuka honey while 4-methoxyphenylacetic acid is characteristic to Kanuka honey. Furthermore, resveratrol, epigallocatechin and pinostrobin are markers distinct to Sage honey, whereas carvacrol and thymol are found in Ziziphus honey. Due to their polyphenolic profile, monofloral honeys have significant antioxidant activity, as well as antidiabetic, antimicrobial and anticancer activities. It was demonstrated that Pine honey decreased the MDA and TBARS levels in liver, kidney, heart and brain tissues, whereas Malicia honey reduced the low-density lipoprotein level. Consumption of Clover, Acacia and Gelam honeys reduced the weight and adiposity, as well as trygliceride levels. Furthermore, the antiproliferative effect of chrysin, a natural flavone in Acacia honey, was demonstrated in human (A375) and murine (B16-F1) melanoma cell lines, whereas caffeic acid, a phenolic compound found in Kelulut honey, proves to be significant candidate in the chemoprevention of colon cancer. Based on these features, the use of hiney in the medicinal field (apitherapy), and the widespread usage of natural product consumption, is gaining interest by each year.
Antioxidant Properties of Ergosterol and Its Role in Yeast Resistance to Oxidation
Authors: Dupont Sebastien , Fleurat-Lessard Paul , Cruz Richtier Gonçalves , Lafarge Céline , Grangeteau Cédric , Yahou Fairouz , Gerbeau-Pissot Patricia , Abrahão Júnior Odonírio , Gervais Patrick , Simon-Plas Françoise , Cayot Philippe , Beney Laurent
Published: June 2021

Although the functions and structural roles of sterols have been the subject of numerous studies, the reasons for the diversity of sterols in the different eukaryotic kingdoms remain unclear. It is thought that the specificity of sterols is linked to unidentified supplementary functions that could enable organisms to be better adapted to their environment. Ergosterol is accumulated by late branching fungi that encounter oxidative perturbations in their interfacial habitats. Here, we investigated the antioxidant properties of ergosterol using in vivo, in vitro, and in silico approaches. The results showed that ergosterol is involved in yeast resistance to tert-butyl hydroperoxide and protects lipids against oxidation in liposomes. A computational study based on quantum chemistry revealed that this protection could be related to its antioxidant properties operating through an electron transfer followed by a proton transfer mechanism. This study demonstrates the antioxidant role of ergosterol and proposes knowledge elements to explain the specific accumulation of this sterol in late branching fungi. Ergosterol, as a natural antioxidant molecule, could also play a role in the incompletely understood beneficial effects of some mushrooms on health.
Integrated Analysis of Transcriptome and Metabolome and Evaluation of Antioxidant Activities in Lavandula pubescens
Authors: Park Chang , Yeo Hyeon , Park Ye , Kim Ye , Park Chanung , Kim Jae , Park Sang
Published: June 2021

Lavandula pubescens, belonging to the Labiatae family, is a newly discovered strongly aromatic species of lavender that is potentially beneficial for human health. Given the economic importance of lavender species, we sought in this study to characterize the terpenoid biosynthesis of L. pubescens by obtaining transcriptomic and metabolic datasets. Transcriptome analysis of L. pubescens grown aseptically in tissue culture medium yielded 124,233 unigenes with an average length of 470 bp and N50 value of 522 bp from 9,476,122,928 raw reads. In order to provide relevant biological information, the unigenes were annotated using the following public databases: National Center for Biotechnology Information (NCBI) nucleotide (NT) and non-redundant protein (NR), Brassica (BRAD), Arabidopsis Information Resource (TAIR), Clusters of Orthologous Groups (COG), and Gene Ontology (GO). NR annotation results revealed that L. pubescens is genetically closely related to Sesamum indicum. On the basis of the transcriptome data, a total of 14 cDNA clones encoding the terpene biosynthetic genes LpDXS, LpMCT, LpMCS, LpHDR, LpIDI, LpAACT, LpHMGS, LpHMGR, LpMVK, LpPMK, LpMVD, LpGPPS, LpSQS, and LpGGPPS were identified in L. pubescens. These were quantified in the roots, stems, and leaves of L. pubescens using quantitative real-time polymerase chain reaction (qRT-PCR), which revealed that the gene expression levels were higher in the leaves and stems than in the roots, which was found to be consistent with the levels of ursolic and oleanolic acids in the different organs using high-performance liquid chromatography (HPLC). A total of 48 hydrophilic metabolites were identified and quantified in the organs using gas chromatography time-of-flight mass spectrometry (GC-TOFMS). Furthermore, the antioxidant activity of an ethyl acetate extract of L. pubescens leaves was examined using different methods to determine the potential therapeutic properties. A reducing power assay revealed that the absorbance values increased in a concentration-dependent manner, whereas a 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay indicated the strong activity (60.4 ± 0.9%) of the ethyl acetate extract at a concentration of 100 µg/mL, which also showed strong hydrogen peroxide (57.4 ± 2.7%), superoxide radical (62.1 ± 0.7%), and hydroxyl radical (58.6 ± 0.4%) scavenging activities.
Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage
Authors: Wang Baoming , Chan Yik-Lung , Li Gerard , Ho Kin Fai , Anwer Ayad G. , Smith Bradford J. , Guo Hai , Jalaludin Bin , Herbert Cristan , Thomas Paul S. , Liao Jiayan , Chapman David G. , Foster Paul S. , Saad Sonia , Chen Hui , Oliver Brian G.
Published: June 2021

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health.
Improved Modulation Strategy Based on Minimum Energy Storage Principle for Electrolytic-Capacitor-Less Six-Switch Converter
Authors: Tan Qingyang , He Liangzong
Published: June 2021

An improved modulation strategy based on minimum energy storage for DC-link capacitance reduction in a six-switch AC-AC converter is proposed. The proposed modulation strategy enables the energy on the capacitor to accumulate and release twice each in a complete switching cycle, achieving the effect of “fast charging and discharging”. Meanwhile, the inversion and rectification are modulated synchronously. Hence, there is minimum energy stored in the DC-link capacitor. Then, the time average modeling analysis is presented to take insight analysis. When there is the same voltage ripples constraint on the DC side for the conventional and improved modulation strategies, the six-switch converter under the improved modulation strategy has the much less capacitance value of the storage capacitor and even realizes non-electrolytic capacitance. Therefore, improving the system efficiency, power density, and output waveform quality and extending the system life can be achieved. The operation principle and modulation strategy are discussed in detail. Finally, the simulation model and experimental prototype are built to verify effectiveness of the topology and correctness of the proposed six-switch AC-AC converter modulation strategy.
Mechanical and Thermal Properties of Insulating Sustainable Mortars with Ampelodesmos mauritanicus and Pennisetum setaceum Plants as Aggregates
Authors: Badagliacco Dionisio , Sanfilippo Carmelo , Megna Bartolomeo , La Mantia Tommaso , Valenza Antonino
Published: June 2021

The use of natural fibers in cement composites is a widening research field as their application can enhance the mechanical and thermal behavior of cement mortars and limit their carbon footprint. In this paper, two different wild grasses, i.e., Ampelodesmos mauritanicus, also called diss, and Pennisetum setaceum, also known as crimson fountaingrass, are used as a source of natural aggregates for cement mortars. The main purpose is to assess the possibility of using the more invasive crimson fountaingrass in place of diss in cement-based vegetable concrete. The two plant fibers have been characterized by means of scanning electron microscopy (SEM), helium picnometry and thermogravimetric analysis. Moreover, the thermal conductivity of fiber panels has been measured. Mortars samples have been prepared using untreated, boiled and Polyethylene glycol 4000 (PEG) treated fibers. The mechanical characterization has been performed by means of three point bending and compression tests. Thermal conductivity and porosity have been measured to characterize physical modification induced by fibers’ treatments. The results showed better thermal and mechanical properties of diss fiber composites than fountaingrass one and that fiber treatments lead to a reduction of the thermal insulation properties.
10th Anniversary of Applied Sciences Invited Papers in Civil Engineering Section
Authors: OBrien Eugene J.
Published: June 2021

Applied Sciences has achieved a major milestone this year: it is the 10th anniversary of the journal [...]
Product Quality Prediction for Wire Electrical Discharge Machining with Markov Transition Fields and Convolutional Long Short-Term Memory Neural Networks
Authors: Jiang Jehn-Ruey , Yen Cheng-Tai
Published: June 2021

This paper proposes a wire electrical discharge machining (WEDM) product quality prediction method, called MTF-CLSTM, to integrate the Markov transition field (MTF) and the convolutional long short-term memory (CLSTM) neural network. The proposed MTF-CLSTM method can accurately predict WEDM workpiece surface roughness right after manufacturing by collecting and analyzing static machining parameters and dynamic manufacturing conditions. The highly accurate prediction is due to the following two reasons. First, MTF can transform data into images to extract data temporal information and state transition probability information. Second, the CLSTM neural network can extract image spacial features and temporal relationship of data that are separated far apart. In short, MTF-CLSTM predicts WEDM workpiece surface roughness with the MTF model and the CLSTM neural network using static machining parameters and dynamic manufacturing conditions. MTF-CLSTM is compared with 10 related research studies in many aspects. There is only one existing method that is like MTF-CLSTM to predict WEDM workpiece surface roughness by using static machining parameters and dynamic manufacturing conditions. Experiments are conducted to evaluate MTF-CLSTM performance to show that MTF-CLSTM significantly outperforms the existing method in terms of the prediction mean absolute percentage error.
A New Method for Evaluating the Bearing Capacity of the Bridge Pile Socketed in the Soft Rock
Authors: Lu Yao , Li Dejian , Jia Shiwei , Wang Kai
Published: June 2021

Aiming at the rock-socketed pile in the soft rock area, this paper studies the inherent constitutive relationship between the vertical restraint stiffness at the pier bottom and the bearing capacity of the pile foundation. A new method to evaluate the bearing capacity of the pile foundation is proposed. Based on the Rayleigh energy method and the Southwell frequency synthesis method, the analytical expression of the vertical vibration fundamental frequency of the pier was calculated, and the constraint stiffness expression of the pier bottom was derived. By investigating the impact of parameters on the bearing capacity coefficient of the pile foundation, the fitting formula of the bearing capacity coefficient was obtained by multiple linear regression. Then, with this method, the vertical fundamental frequency of the pier was obtained through a field dynamic test to calculate the vertical constraint stiffness and evaluate the bearing capacity of the rock-socketed pile in the soft rock area. This method can overcome the shortcomings of the traditional static load test method, such as the high cost, long cycle, and poor representativeness. Finally, this method’s accuracy was verified by comparing field measurements and finite element simulation results. The results show that the difference between the code design constraint stiffness and the constraint stiffness by the frequency synthesis method was about 0.7%, and the bearing capacity difference between the analytical solution and the numerical simulation was small. The new method is accurate and effective.
Simultaneous SAXS/SANS Method at D22 of ILL: Instrument Upgrade
Authors: Metwalli Ezzeldin , Götz Klaus , Zech Tobias , Bär Christian , Schuldes Isabel , Martel Anne , Porcar Lionel , Unruh Tobias
Published: June 2021

A customized portable SAXS instrument has recently been constructed, installed, and tested at the D22 SANS instrument at ILL. Technical characteristics of this newly established plug-and-play SAXS system have recently been reported (J. Appl. Cryst. 2020, 53, 722). An optimized lead shielding arrangement on the SAXS system and a double energy threshold X-ray detector have been further implemented to substantially suppress the unavoidable high-energy gamma radiation background on the X-ray detector. The performance of the upgraded SAXS instrument has been examined systematically by determining background suppression factors (SFs) at various experimental conditions, including different neutron beam collimation lengths and X-ray sample-to-detector distances (SDDX-ray). Improved signal-to-noise ratio SAXS data enables combined SAXS and SANS measurements for all possible experimental conditions at the D22 instrument. Both SAXS and SANS data from the same sample volume can be fitted simultaneously using a common structural model, allowing unambiguous interpretation of the scattering data. Importantly, advanced in situ/real time investigations are possible, where both the SAXS and the SANS data can reveal time-resolved complementary nanoscale structural information.
A Novel Decision Support System for Long-Term Management of Bridge Networks
Authors: Karaaslan Enes , Bagci Ulas , Catbas Necati
Published: June 2021

Developing a bridge management strategy at the network level with efficient use of capital is very important for optimal infrastructure remediation. This paper introduces a novel decision support system that considers many aspects of bridge management and successfully implements the investigated methodology in a web-based platform. The proposed decision support system uses advanced prediction models, decision trees, and incremental machine learning algorithms to generate an optimal decision strategy. The system aims to achieve adaptive and flexible decision making while entailing powerful utilization of nondestructive evaluation (NDE) methods. The NDE data integration and visualization allow automatic retrieval of inspection results and overlaying the defects on a 3D bridge model. Furthermore, a deep learning-based damage growth prediction model estimates the future condition of the bridge elements and utilizes this information in the decision-making process. The decision ranking takes into account a wide range of factors including structural safety, serviceability, rehabilitation cost, life cycle cost, and societal and political factors to generate optimal maintenance strategies with multiple decision alternatives. This study aims to bring a complementary solution to currently in-use systems with the utilization of advanced machine-learning models and NDE data integration while still equipped with main bridge management functions of bridge management systems and capable of transferring data to other systems.
Thai Rice Vinegars: Production and Biological Properties
Authors: Taweekasemsombut Samuch , Tinoi Jidapha , Mungkornasawakul Pitchaya , Chandet Nopakarn
Published: June 2021

Four types of traditional Thai rice—polished, black fragrant, glutinous and black glutinous rice—were separately used as raw material for vinegar production. During alcohol fermentation, using enriched baker’s dried yeast (S. cerevisiae) as a starter culture gave the highest ethanol content over 7 days of fermentation. The conversion of ethanol to acetic acid for vinegar production by Acetobacter pasteurianus TISTR 102 was performed for 25 days. The highest amount of acetic acid was detected with glutinous rice fermentation (6.68% w/v). The biological properties of Thai rice vinegars were determined, including the total phenolic content, antioxidant activity, antibacterial activity and cytotoxicity. Black glutinous rice vinegar exhibited the maximum total phenolic content of 133.68 mg GAE/100 mL. This result was related to the antioxidative activity findings, for which black glutinous rice vinegar exhibited the strongest activity against both ABTS•+ and DPPH• radicals. Cytotoxicity against the human colon cancer cell line (HT-29) provided an IC50 value of 74.02 μg/mL and weak activity in a mouse fibroblast normal cell line (L929) with an IC50 value of 171.06 μg/mL. Glutinous rice vinegar was the most effective vinegar for inhibiting pathogenic bacterial growth of both Gram-negative and Gram-positive bacteria. These results suggested that the value of total phenolic content corresponded to the anticancer activity and antioxidant activity results, while antibacterial activity depended on the acidity of rice vinegar.
Are Saliva Tests Important in the Prediction of Carious Disease?
Authors: Ichim Daniela Luminita , Sachelarie Liliana , Calin Gabriela , Burlui Alexandra
Published: June 2021

(1) Background: The appearance and progression of carious lesions represent a complex phenomenon of interactions of microbial factors (the action of bacteria on the tooth), of the factors related to the host, to the diet, and to the time factor. Which hasan influence on the rate of microbismof the oral cavity on the installation of carious disease? (2) Methods: In order to correctly assess the cariogenic risk of an individual, it is recommended to perform twoor more tests based on different principles (microbiological, clinical, epidemiological). The representative data series for the investigation were analyzed statistically and by applying the Pearson correlation test considering the coefficient of determination R for all pairs of data series. (3) Results: Salivary tests played animportant role in establishing control sessions, in carrying out prophylactic caries therapy, and establishing prognosis. The existence of a statistical associationwas confirmed between the prevalence of dental caries and the results of salivary tests for the study group. (4) Conclusions: The results of the saliva tests can be used in oral health promotion.
Recirculated Wave Undulators for Compact FELs
Authors: Curcio Alessandro
Published: June 2021

Particular schemes of Free Electron Lasers (FELs) are designed to exploit wave undulators. We consider a system employing a recirculated electromagnetic undulator provided by a high-power laser in a resonator cavity. The aim is to establish from calculations a set of realizable parameters for such a device. Indeed, novel generation electron accelerators push forward the limits on the accelerating fields, reducing to the sub-meter scale the length over which the electrons can gain enough energy for lasing in the VUV/X-ray region of the electromagnetic spectrum. On the other hand, these innovative technologies do not solve yet the problem associated with the saturation length and therefore of the undulator length, which can be as long as several tens of meters. The option of a FEL based on a wave undulator might provide a valid solution in this respect.
Assessing Hydrological Impact of Forested Area Change: A Remote Sensing Case Study
Authors: Sidău Mugurel Raul , Horváth Csaba , Cheveresan Maria , Șandric Ionuț , Stoica Florin
Published: June 2021

The interaction between precipitation and vegetation plays a significant role in the formation of runoff, and it is still a widely discussed issue in hydrology. The difficulty lies in estimating the degree to which a forest influences runoff generation, especially flood peaks, on the one hand, due to the small amount of information regarding the evolution of the forest area and density, and, on the other hand, the correlations between these indicators and the runoff and precipitation values. The analysis focuses on a small basin in the mountain region of Romania, the upper basin of the Ruscova River located in northwestern Romania. In this river basin, there is no significant anthropic influence, other than the intense deforestation and reforestation actions. Using satellite images captured by Landsat missions 5, 7 and 8 for the period 1985–2019, the forest canopy density vegetation index was extracted. Using a gridded precipitation dataset, a hydrological model was calibrated based on three scenarios to assess the impact of forest vegetation on the runoff. Analysis of the results of these models conducted on scenarios allowed us to deduce a simple equation for estimating the influence of forest area on maximum river flows. The analysis showed that even small differences in the forest surface area exert an influence on the peak flow, varying between −5.28% and 8.09%.
Thermal Conductivity in Aged Li-Ion Cells under Various Compression Conditions and State-of-Charge
Authors: Kovachev Georgi , Astner Andrea , Gstrein Gregor , Aiello Luigi , Hemmer Johann , Sinz Wolfgang , Ellersdorfer Christian
Published: June 2021

Thermal conductivity (TC) is a parameter, which significantly influences the spatial temperature gradients of lithium ion batteries in operative or abuse conditions. It affects the dissipation of the generated heat by the cell during normal operation or during thermal runaway propagation from one cell to the next after an external short circuit. Hence, the thermal conductivity is a parameter of great importance, which concurs to assess the safety of a Li-ion battery. In this work, an already validated, non-destructive measurement procedure was adopted for the determination of the evolution of the through-plane thermal conductivity of 41 Ah commercially available Li-ion pouch cells (LiNiMnCoO2-LiMn2O4/Graphite) as function of battery lifetime and state of charge (SOC). Results show a negative parabolic behaviour of the thermal conductivity over the battery SOC-range. In addition, an average decrease of TC in thickness direction of around 4% and 23% was measured for cells cycled at 60 °C with and without compression, respectively. It was shown that pretension force during cycling reduces battery degradation and thus minimises the effect of ageing on the thermal parameter deterioration. Nevertheless, this study highlights the need of adjustment of the battery pack cooling system due to the deterioration of thermal conductivity after certain battery lifetime with the aim of reducing the risk of battery overheating after certain product life.
Correction: Paccha-Herrera et al. Thermal Modeling Approaches for a LiCoO2 Lithium-ion Battery—A Comparative Study with Experimental Validation. Batteries 2020, 6, 40
Authors: Paccha-Herrera Edwin , Calderón-Muñoz Williams R. , Orchard Marcos , Jaramillo Francisco , Medjaher Kamal
Published: June 2021

The authors wish to make the following corrections to their paper [...]
A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors
Authors: Tsoli Marina , Daskalakis Kosmas , Kassi Eva , Kaltsas Gregory , Tsolakis Apostolos V.
Published: June 2021

Pheochromocytomas/Paragangliomas (PPGLs) and adrenocortical tumors are rare neoplasms with significant heterogeneity in their biologic and clinical behavior. Current diagnostic and predictive biomarkers include hormone secretion, as well as histopathological and genetic features. PPGL diagnosis is based on biochemical measurement of catecholamines/metanephrines, while histopathological scoring systems have been proposed to predict the risk of malignancy. Adrenocortical tumors are mostly benign, but some can be malignant. Currently, the stage of disease at diagnosis and tumor grade, appear to be the most powerful prognostic factors. However, recent genomic and proteomic studies have identified new genetic and circulating biomarkers, including genes, immunohistochemical markers and micro-RNAs that display high specificity and sensitivity as diagnostic or prognostic tools. In addition, new molecular classifications have been proposed that divide adrenal tumors in distinct subgroups with different clinical outcomes.
Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?
Authors: Subileau Mariela , Vittet Daniel
Published: June 2021

Lymphatic vessels exert major effects on the maintenance of interstitial fluid homeostasis, immune cell trafficking, lipid absorption, tumor progression and metastasis. Recently, novel functional roles for the lymphatic vasculature have emerged, which can be associated with pathological situations. Among them, lymphatics have been proposed to participate in eye aqueous humor drainage, with potential consequences on intraocular pressure, a main risk factor for progression of glaucoma disease. In this review, after the description of eye fluid dynamics, we provide an update on the data concerning the distribution of ocular lymphatics. Particular attention is given to the results of investigations allowing the three dimensional visualization of the ocular surface vasculature, and to the molecular mechanisms that have been characterized to regulate ocular lymphatic vessel development. The studies concerning the potential role of lymphatics in aqueous humor outflow are reported and discussed. We also considered the novel studies mentioning the existence of an ocular glymphatic system which may have, in connection with lymphatics, important repercussions in retinal clearance and in diseases affecting the eye posterior segment. Some remaining unsolved questions and new directions to explore are proposed to improve the knowledge about both lymphatic and glymphatic system interactions with eye fluid homeostasis.
Modulation of Energy Metabolism and Epigenetic Landscape in Rainbow Trout Fry by a Parental Low Protein/High Carbohydrate Diet
Authors: Callet Thérèse , Li Hongyan , Coste Pascale , Glise Stéphane , Heraud Cécile , Maunas Patrick , Mercier Yvan , Turonnet Nicolas , Zunzunegui Chloé , Panserat Stéphane , Bolliet Valérie , Marandel Lucie
Published: June 2021

It is now recognized that parental diets could highly affect offspring metabolism and growth. Studies in fish are, however, lacking. In particular, the effect of a parental diet high in carbohydrate (HC) and low in protein (LP) on progeny has never been examined in higher trophic level teleost fish. Thus, two-year old male and female rainbow trout (Oncorhynchus mykiss) were fed either a control diet (0% carbohydrate and 63.89% protein) or a diet containing 35% carbohydrate and 42.96% protein (HC/LP) for a complete reproductive cycle for females and over a 5-month period for males. Cross-fertilizations were then carried out. To evaluate the effect of the parental diet on their offspring, different phenotypic and metabolic traits were recorded for offspring before their first feeding and again three weeks later. When considering the paternal and maternal HC/LP nutrition independently, fry phenotypes and transcriptomes were only slightly affected. The combination of the maternal and paternal HC/LP diets altered the energy metabolism and mitochondrial dynamics of their progeny, demonstrating the existence of a synergistic effect. The global DNA methylation of whole fry was also highly affected by the HC/LP parental diet, indicating that it could be one of the fundamental mechanisms responsible for the effects of nutritional programming.
Effects of Diethylstilbestrol on Zebrafish Gonad Development and Endocrine Disruption Mechanism
Authors: Liu Xuan , Xie Xianyi , Liu Hongling
Published: June 2021

Environmental estrogen is a substance that functions as an endocrine hormone in organisms and can cause endocrine system disruption. A typical environmental estrogen, diethylstilbestrol (DES), can affect normal sexual function and organism development. However, even though the effects of different exposure stages of DES on the endocrine system and gonadal development of zebrafish juveniles are unknown, sex determination is strongly influenced by endocrine-disrupting chemicals (EDCs). From 10–90 days post fertilization (dpf), juvenile zebrafish were exposed to DES (100 and 1000 ng/L) in three different stages (initial development stage (IDS), 10–25 dpf; gonadal differentiation stage (GDS), 25–45 dpf and gonadal maturity stage (GMS), 45–60 dpf). Compared with that of IDS and GMS, the growth indicators (body length, body weight, and others) decreased significantly at GDS, and the proportion of zebrafish females exposed to 100 ng/L DES was significantly higher (by 59.65%) than that of the control; in addition, the zebrafish were biased towards female differentiation. The GDS is a critical period for sex differentiation. Our results show that exposure to environmental estrogen during the critical gonadal differentiation period not only affects the development of zebrafish, but also affects the population development.
Atelocollagen-Embedded Chondrocyte Precursors as a Treatment for Grade-4 Cartilage Defects of the Femoral Condyle: A Case Series with up to 9-Year Follow-Up
Authors: Liu Hwa-Chang , Liu Tzu-Shang Thomas , Liu Yen-Liang , Wang Jyh-Horng , Chang Chih-Hung , Shih Tiffany Ting-Fang , Lin Feng-Huei
Published: June 2021

We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. Neotissues made of CPs were implanted into cartilage defects with an average cell density of 4.9 ± 2.1 × 106 cells/cm2 through arthrotomy. The knee function was evaluated with the International Knee Documentation Committee (IKDC) subjective knee form. Patients’ knee functions significantly improved by the 28th week (IKDC score = 68.3 ± 12.1), relative to the initial functionality before the CP therapy (IKDC score = 46.1 ± 16.4, p-value = 0.0014). Nine of these twelve patients maintained good knee functions for 9 years post-implantation (IKDC score = 69.8 ± 12.3) at levels higher than the pre-implantation values (p-value = 0.0018). Patients were evaluated with MRI and arthroscopy, and the defective sites exhibited a smooth surface without a gap between the implant and host tissue. This study demonstrates that autologous CPs successfully engraft into the host tissue and result in the re-formation of hyaline-like cartilage, thereby improving the impaired knee functions. Most importantly, no adverse event was reported during this long-term follow-up period.
Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers
Authors: Scola Letizia , Giarratana Rosa Maria , Marinello Vincenzo , Cancila Valeria , Pisano Calogera , Ruvolo Giovanni , Frati Giacomo , Lio Domenico , Balistreri Carmela Rita
Published: June 2021

Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>C and IL-1B rs16944C>T SNPs. In addition, the combined rs1800795C/rs16944T genotype showed a synergic effect on TAAA pathogenesis and outcome. The combined rs1800795C/rs16944T genotype was significantly associated with: (a) higher serum levels of both cytokines and MMP-9 and -2; (b) a significant CD3+CD4+CD8+ CD68+CD20+ cell infiltration in aorta aneurysm tissues; (c) a significant shorter telomere length and alterations in telomerase activity. Finally, it significantly correlated with TAAA aorta tissue alterations, including elastic fragmentation, medial cell apoptosis, cystic medial changes, and MMP-9 levels. Conclusions: the combined rs1800795C/rs16944T genotype appears to modulate TAAA risk, pathogenesis, and outcome, and consequently can represent a potential predictive and prognostic TAAA biomarker for individual management, implementation of innovative treatments, and selection of the more proper surgical timing and approaches.
Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets
Authors: Custodia Antía , Aramburu-Núñez Marta , Correa-Paz Clara , Posado-Fernández Adrián , Gómez-Larrauri Ana , Castillo José , Gómez-Muñoz Antonio , Sobrino Tomás , Ouro Alberto
Published: June 2021

Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease.
The Study of the Aorta Metallomics in the Context of Atherosclerosis
Authors: Kuzan Aleksandra , Wujczyk Marta , Wiglusz Rafal J.
Published: June 2021

Atherosclerosis is a multifactorial disease, for which the etiology is so complex that we are currently unable to prevent it and effectively lower the statistics on mortality from cardiovascular diseases. Parallel to modern analyses in molecular biology and biochemistry, we want to carry out analyses at the level of micro- and macroelements in order to discover the interdependencies between elements during atherogenesis. In this work, we used the Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) to determine the content of calcium, magnesium, iron, copper, chromium, zinc, manganese, cadmium, lead, and zinc in the aorta sections of people who died a sudden death. We also estimated the content of metalloenzymes MMP-9, NOS-3, and SOD-2 using the immunohistochemical method. It was observed that with the age of the patient, the calcium content of the artery increased, while the content of copper and iron decreased. Very high correlations (correlation coefficient above 0.8) were observed for pairs of parameters in women: Mn–Ca, Fe–Cu, and Ca–Cd, and in men: Mn–Zn. The degree of atherosclerosis negatively correlated with magnesium and with cadmium. Chromium inhibited absorption of essential trace elements such as Cu and Fe due to its content being above the quantification threshold only if Cu and Fe were lower. Moreover, we discussed how to design research for the future in order to learn more about the pathomechanism of atherosclerosis and the effect of taking dietary supplements on the prevalence of cardiovascular diseases.
HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity
Authors: Bonizzi Arianna , Piuri Gabriele , Corsi Fabio , Cazzola Roberta , Mazzucchelli Serena
Published: June 2021

High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the risk for cardiovascular disease, plasma HDL cholesterol levels do not predict the functionality and composition of HDLs. The importance of defining both the amount of cholesterol transported and lipoprotein functionality has recently been highlighted. Indeed, different clinical conditions such as obesity, diabetes mellitus type 2 (T2DM), and cardiovascular disease (CVD) can alter the HDL functionality, converting normal HDLs into dysfunctional ones, undergoing structural changes, and exhibiting proinflammatory, pro-oxidant, prothrombotic, and proapoptotic properties. The aim of the current review is to summarize the actual knowledge concerning the physical–chemical alteration of HDLs related to their functions, which have been found to be relevant in several pathological conditions associated with systemic inflammation and oxidative stress.
Mandible Biomechanics and Continuously Erupting Teeth: A New Defect Model for Studying Load-Bearing Biomaterials
Authors: Baskin Jonathan Z. , White Brandon M. , Vasanji Amit , Love Thomas E. , Eppell Steven J.
Published: June 2021

Animals with elodont dentition and unfused mandible symphyses are hypothesized to have symmetric incisor morphology. Since these animals maintain their teeth by gnawing, they may provide physiologic feedback on mechanical function when unilateral mandible defects are created that manifest as ipsilateral changes in tooth structure. This defect model would potentially generate important information on the functional/mechanical properties of implants. Rats’ and rabbits’ mandibles and teeth are analyzed with µCT at baseline and post-intervention (n = 8 for each). Baseline incisors were compared. In a unilateral mandible pilot study, defects—ranging from critical size defect to complete ramus osteotomies—were created to assess effect on dentition (rats, n = 7; rabbits, n = 6). Within 90% confidence intervals, animals showed no baseline left/right differences in their incisors. There are apparent dental changes associated with unilateral defect type and location. Thus, at baseline, animals exhibit statistically significant incisor symmetry and there is an apparent relationship between mandible defect and incisor growth. The baseline symmetry proven here sets the stage to study the degree to which hemi-mandible destabilizing procedures result in measurable & reproducible disruption of dental asymmetry. In a validated model, an implant designed to function under load that prevents incisor asymmetry would provide supporting evidence that the implant has clinically useful load-bearing function.
Centromedian–Parafascicular and Somatosensory Thalamic Deep Brain Stimulation for Treatment of Chronic Neuropathic Pain: A Contemporary Series of 40 Patients
Authors: Abdallat Mahmoud , Saryyeva Assel , Blahak Christian , Wolf Marc E. , Weigel Ralf , Loher Thomas J. , Runge Joachim , Heissler Hans E. , Kinfe Thomas M. , Krauss Joachim K.
Published: June 2021

Introduction: The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Methods: Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian–parafascicular (CM–Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). Results: The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM–Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3–180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM–Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Conclusion: Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain.
Osteoconductive Properties of a Volume-Stable Collagen Matrix in Rat Calvaria Defects: A Pilot Study
Authors: Alccayhuaman Karol Alí Apaza , Tangl Stefan , Blouin Stéphane , Hartmann Markus A. , Heimel Patrick , Kuchler Ulrike , Lee Jung-Seok , Gruber Reinhard
Published: June 2021

Volume-stable collagen matrices (VSCM) are conductive for the connective tissue upon soft tissue augmentation. Considering that collagen has osteoconductive properties, we have investigated the possibility that the VSCM also consolidates with the newly formed bone. To this end, we covered nine rat calvaria circular defects with a VSCM. After four weeks, histology, histomorphometry, quantitative backscattered electron imaging, and microcomputed tomography were performed. We report that the overall pattern of mineralization inside the VSCM was heterogeneous. Histology revealed, apart from the characteristic woven bone formation, areas of round-shaped hypertrophic chondrocyte-like cells surrounded by a mineralized extracellular matrix. Quantitative backscattered electron imaging confirmed the heterogenous mineralization occurring within the VSCM. Histomorphometry found new bone to be 0.7 mm2 (0.01 min; 2.4 max), similar to the chondrogenic mineralized extracellular matrix with 0.7 mm2 (0.0 min; 4.2 max). Microcomputed tomography showed the overall mineralized tissue in the defect to be 1.6 mm3 (min 0.0; max 13.3). These findings suggest that in a rat cranial defect, VSCM has a limited and heterogeneous capacity to support intramembranous bone formation but may allow the formation of bone via the endochondral route.
Lumbar Interbody Fusion Conducted on a Porcine Model with a Bioresorbable Ceramic/Biopolymer Hybrid Implant Enriched with Hyperstable Fibroblast Growth Factor 2
Authors: Krticka Milan , Planka Ladislav , Vojtova Lucy , Nekuda Vladimir , Stastny Premysl , Sedlacek Radek , Brinek Adam , Kavkova Michaela , Gopfert Eduard , Hedvicakova Vera , Rampichova Michala , Kren Leos , Liskova Kvetoslava , Ira Daniel , Dorazilová Jana , Suchy Tomas , Zikmund Tomas , Kaiser Jozef , Stary David , Faldyna Martin , Trunec Martin
Published: June 2021

Many growth factors have been studied as additives accelerating lumbar fusion rates in different animal models. However, their low hydrolytic and thermal stability both in vitro and in vivo limits their workability and use. In the proposed work, a stabilized vasculogenic and prohealing fibroblast growth factor-2 (FGF2-STAB®) exhibiting a functional half-life in vitro at 37 °C more than 20 days was applied for lumbar fusion in combination with a bioresorbable scaffold on porcine models. An experimental animal study was designed to investigate the intervertebral fusion efficiency and safety of a bioresorbable ceramic/biopolymer hybrid implant enriched with FGF2-STAB® in comparison with a tricortical bone autograft used as a gold standard. Twenty-four experimental pigs underwent L2/3 discectomy with implantation of either the tricortical iliac crest bone autograft or the bioresorbable hybrid implant (BHI) followed by lateral intervertebral fixation. The quality of spinal fusion was assessed by micro-computed tomography (micro-CT), biomechanical testing, and histological examination at both 8 and 16 weeks after the surgery. While 8 weeks after implantation, micro-CT analysis demonstrated similar fusion quality in both groups, in contrast, spines with BHI involving inorganic hydroxyapatite and tricalcium phosphate along with organic collagen, oxidized cellulose, and FGF2- STAB® showed a significant increase in a fusion quality in comparison to the autograft group 16 weeks post-surgery (p = 0.023). Biomechanical testing revealed significantly higher stiffness of spines treated with the bioresorbable hybrid implant group compared to the autograft group (p < 0.05). Whilst histomorphological evaluation showed significant progression of new bone formation in the BHI group besides non-union and fibrocartilage tissue formed in the autograft group. Significant osteoinductive effects of BHI based on bioceramics, collagen, oxidized cellulose, and FGF2-STAB® could improve outcomes in spinal fusion surgery and bone tissue regeneration.