bluuebunny/crossref_metadata_2025 huggingface dataset:
Remembering Thomas Becket in Saint-Lô
Authors: Jordan Alyce A.
Published: September 2021

France numbered second only to England in its veneration of the martyred archbishop of Canterbury. Nowhere in France was that veneration more widespread than Normandy, where churches and chapels devoted to Saint Thomas, many embellished with sculptures, paintings, and stained-glass windows, appeared throughout the Middle Ages. A nineteenth-century resurgence of interest in the martyred archbishop of Canterbury gave rise to a new wave of artistic production dedicated to him. A number of these modern commissions appear in the same sites and thus in direct visual dialogue with their medieval counterparts. This essay examines the long legacy of artistic dedications to Saint-Thomas in the town of Saint-Lô. It considers the medieval and modern contexts underpinning the creation of these works and what they reveal about Thomas Becket’s enduring import across nine centuries of Saint-Lô’s history.
Coherence and Entropy of Credit Cycles across the Euro Area Candidate Countries
Authors: Criste Adina , Lupu Iulia , Lupu Radu
Published: September 2021

The pattern of financial cycles in the European Union has direct impacts on financial stability and economic sustainability in view of adoption of the euro. The purpose of the article is to identify the degree of coherence of credit cycles in the countries potentially seeking to adopt the euro with the credit cycle inside the Eurozone. We first estimate the credit cycles in the selected countries and in the euro area (at the aggregate level) and filter the series with the Hodrick–Prescott filter for the period 1999Q1–2020Q4. Based on these values, we compute the indicators that define the credit cycle similarity and synchronicity in the selected countries and a set of entropy measures (block entropy, entropy rate, Bayesian entropy) to show the high degree of heterogeneity, noting that the manifestation of the global financial crisis has changed the credit cycle patterns in some countries. Our novel approach provides analytical tools to cope with euro adoption decisions, showing how the coherence of credit cycles can be increased among European countries and how the national macroprudential policies can be better coordinated, especially in light of changes caused by the pandemic crisis.
Hydrogen as Energy Sources—Basic Concepts
Authors: Badea Nicolae I.
Published: September 2021

This paper covers the hydrogen technologies regarding the role of hydrogen as an energy carrier and the possibilities of its production and use. It is initially presented the modalities and the efficiency of the current technologies of obtaining hydrogen, detailing its obtaining by the electrolysis of the water, the electrochemical efficiency and the specific consumption of electricity as well as the thermodynamics of the electrochemical processes. The following paragraph addresses hydrogen conversion possibilities. This paragraph details the thermodynamic analysis of the fuel cell, the external characteristic of the fuel cell and the types of fuel cell. The last paragraph addresses the possibilities of using the fuel cells for electrical vehicles and cogeneration systems for buildings.In this context, the traditional transport and distribution grid will have to adapt to the new realities as they will need to actively participate in the internal energy market by the transformation of the traditional electricity grid in energy flow, from unidirectional to bidirectional through the production of hydrogen offering the same facilities as the gas grid.
Application of a New Statistical Model for the Description of Solid Fuel Decomposition in the Analysis of Artemisia apiacea Pyrolysis
Authors: Gu Tianbao , Berning Torsten , Yin Chungen
Published: September 2021

Pyrolysis, one of the key thermochemical conversion technologies, is very promising to obtain char, oil and combustible gases from solid fuels. Kinetic modeling is a crucial method for the prediction of the solid conversion rate and analysis of the pyrolysis process. We recently developed a new statistical model for the universal description of solid fuel decomposition, which shows great potential in studying solid fuel pyrolysis. This paper demonstrates three essential applications of this new model in the analysis of Artemisia apiacea pyrolysis, i.e., identification of the conversion rate peak position, determination of the reaction mechanism, and evaluation of the kinetics. The results of the first application show a very good agreement with the experimental data. From the second application, the 3D diffusion-Jander reaction model is considered as the most suitable reaction mechanism for the description of Artemisia stem pyrolysis. The third application evaluates the kinetics of Artemisia stem pyrolysis. The evaluated kinetics vary with the conversion degree and heating rates, in which the activation energies and pre-exponential factors (i.e., lnA vs. Ea) show a linear relationship, regardless of the conversion and heating rates. Moreover, the prediction of the conversion rate using the obtained kinetics shows an excellent fit with the experimental data.
Hierarchical Auto-Ignition and Structure-Reactivity Trends of C2–C4 1-Alkenes
Authors: Sun Wuchuan , Zhang Yingjia , Li Yang , Huang Zuohua
Published: September 2021

Ignition delay times of small alkenes are a valuable constraint for the refinement of the core kinetic mechanism of hydrocarbons used in representing combustion properties of real fuels. Moreover, the chemical reactivity comparison of those small alkenes provides a reference in object-oriented fuel design and logical combustion utilization. In this study, the ignition delay times of C2–C4 alkenes (ethylene, propene and 1-butene) were measured behind reflected shock waves first, with a fixed oxygen concentration (XO2 = 6%) and equivalence ratio (φ = 1.0) at various pressures of 1.2, 4.0 and 16.0 atm, in order to facilitate the comparison. Three chemical-based-Arrhenius-type correlations covering a wide range of temperature, pressure, equivalence ratio, and dilution were proposed. The simplified reaction network for pyrolysis and oxidation of 1-alkenes was depicted relying on the reaction classes of alkenes. Nine generally accepted mechanisms were used to simulate the ignition delay times measured by this study as well as literature. All the kinetic models show reasonable structure-reactivity trends for all of the three alkenes, but only NUIGMech 1.1 is capable of representing quantificationally the chemical reactivity at all tested conditions. Generally, ethylene exhibits the highest reactivity while propene presents the lowest at high temperatures. Analyses of sensitivity and flux indicate that the main oxidation pathway of ethylene is chain-branching, which accelerates the accumulation of free radical pools, especially for the Ḣ atom, Ȯ atom and ȮH radical, which results in the highest reactivity of ethylene. For propene and 1-butene, due to the presence of the allylic site, consumption of allylic radicals becomes the decisive step of oxidation and allylic radicals are mostly consumed by the HȮ2 radical. However, there are no such efficient reaction pathways for the formation of HȮ2 radicals during the propene oxidation process, while reaction pathways for HȮ2 formation in 1-butene are efficient. Thus, 1-butene presents higher reactivity compared to propene.
Evaluating the Combined Effect of Climate Change and Urban Microclimate on Buildings’ Heating and Cooling Energy Demand in a Mediterranean City
Authors: Tsoka Stella , Velikou Kondylia , Tolika Konstantia , Tsikaloudaki Aikaterini
Published: September 2021

Climate change has a major impact on the urban built environment, both with respect to the heating and cooling energy requirements, but also regarding the higher probability of confronting extreme events such as heatwaves. In parallel, the ongoing urbanization, the urban microclimate and the formation of the urban heat island effect, compounding the ongoing climate change, is also a considerable determinant of the building’s energy behavior and the outdoor thermal environment. To evaluate the magnitude of the complex phenomenon, the current research investigates the effect of climate change and urban heat island on heating and cooling energy needs of an urban building unit in Thessaloniki, Greece. The study comparatively evaluates different tools for the generation of future weather datasets, considering both statistical and dynamical downscaling methods, with the latter involving the use of a regional climate model. Based on the output of the regional climate model, another future weather dataset is created, considering not only the general climatic conditions, but also the microclimatic parameters of the examined case study area, under the future climate projections. The generated future weather datasets are then used as an input parameter in the dynamic energy performance simulations with EnergyPlus. For all examined weather datasets, the simulation results show a decrease of the heating energy use, an effect that is strongly counterbalanced by the rise of the cooling energy demand. The obtained simulation results also reveal the contribution of the urban warming of the ongoing climate change, demonstrating the need to perform a holistic analysis for the buildings’ energy needs under future climate conditions.
Effects of Nanosecond Repetitively Pulsed Discharges Timing for Aeroengines Ignition at Low Temperature Conditions by Needle-Ring Plasma Actuator
Authors: Mehdi Ghazanfar , Bonuso Sara , De Giorgi Maria Grazia
Published: September 2021

These days, various national and international research organizations are working on the development of low NOx combustors. The present work describes the experimental and numerical characterization of flow dynamics and combustion characteristics in a rectangular burner. A ring-needle type plasma actuator was developed and driven by a high voltage nanosecond pulsed generator under atmospheric conditions. Smoke flow visualizations and Proper Orthogonal Decomposition (POD) were carried out to identify the relevant flow structures. Electrical characterization of the non-reactive flow was carried out to predict the electrical power and the optimum value of the reduced electric field (EN), which is useful for the implementation of a numerical model for the study of plasma-assisted ignition. A detailed plasma kinetic mechanism integrated with all excited species was considered and validated with experimental studies. Numerical modeling of plasma ignition has been performed by coupling ZDPlasKin with CHEMKIN. Energy and power consumption for methane/air plasma actuation is higher than the air plasma actuation. This could be due to the excitation and ionization of methane that required more energy deposition and power. The mole fraction of O atoms and ozone was higher in the air than the methane/air actuation. However, O atoms were produced in a very short time interval of 10−7 to 10−6 s; in contrast, the concentration of ozone was gradually increased with the time interval and the peak was observed around 10−1 s. Plasma discharges on the methane/air mixture also produced radicals that played a key role to enhance the combustion process. It was noticed that the concentration of H species was high among all radicals with a concentration of nearly 10−1. The concentration peak of CH3 and OH was almost the same in the order of 10−2. Finally, the mixture ignition characteristics under different low inlet temperatures were analyzed for both air and methane/air plasma actuation in the presence of different plasma discharges pulses numbers. Results showed that it is possible to reach flame ignition at inlet temperature lower than the minimum required in the absence of plasma actuation, which means ignition is possible in cold flow, which could be essential to address the re-ignition problems of aeroengines at high altitudes. At Ti = 700 K, the ignition was reached only with plasma discharges; ignition time was in the order of 0.01 s for plasma discharges on methane/air, lower than in case of plasma in air, which permitted ignition at 0.018 s. Besides this, in the methane/air case, 12 pulses were required to achieve successful ignition; however, in air, 19 pulses were needed to ignite.
A Review: Ion Transport of Two-Dimensional Materials in Novel Technologies from Macro to Nanoscopic Perspectives
Authors: Unsuree Nawapong , Phanphak Sorasak , Prajongtat Pongthep , Bunpheng Aritsa , Jitapunkul Kulpavee , Kongputhon Pornpis , Srinoi Pannaree , Iamprasertkun Pawin , Hirunpinyopas Wisit
Published: September 2021

Ion transport is a significant concept that underlies a variety of technologies including membrane technology, energy storages, optical, chemical, and biological sensors and ion-mobility exploration techniques. These applications are based on the concepts of capacitance and ion transport, so a prior understanding of capacitance and ion transport phenomena is crucial. In this review, the principles of capacitance and ion transport are described from a theoretical and practical point of view. The review covers the concepts of Helmholtz capacitance, diffuse layer capacitance and space charge capacitance, which is also referred to as quantum capacitance in low-dimensional materials. These concepts are attributed to applications in the electrochemical technologies such as energy storage and excitable ion sieving in membranes. This review also focuses on the characteristic role of channel heights (from micrometer to angstrom scales) in ion transport. Ion transport technologies can also be used in newer applications including biological sensors and multifunctional microsupercapacitors. This review improves our understanding of ion transport phenomena and demonstrates various applications that is applicable of the continued development in the technologies described.
Effect of Traffic Calming in a Downtown District of Szczecin, Poland
Authors: Sołowczuk Alicja
Published: September 2021

The increasing use of road vehicles has caused a number of transport and environmental issues throughout the world. To cope with them, traffic calming schemes are being increasingly implemented in built-up areas. An example of such schemes are Tempo-30 zones. The traffic calming measures applied as part of this scheme must be carefully planned in terms of location and design details in order to obtain the desired reduction in speed, traffic volume and exhaust emissions and, last but foremost, to increase the safety and facilitate the movement of vulnerable road users. The coexistence and combined effect of these measures and their design details must also be taken into account. The purpose of this study was to investigate whether the applied traffic calming measures had a considerable bearing on the reduction in speed to the desired level, as assumed in the traffic calming plan. Three street sections starting and ending with different intersection types were chosen to examine the synergy of the applied traffic calming measures. The numbers and speeds of vehicles were measured in three day-long continuous surveys. As it was expected, the amount of speed reduction depended on the hourly traffic volume on a one-way street and various other traffic engineering aspects. The obtained results may be used to modify the existing speed profile models and can guide traffic engineers in choosing the most effective traffic calming measures.
The Potential of Cylindrical Piezoelectric Transducers for High-Frequency Acoustic Energy Harvesting
Authors: Salem Shehab , Fraňa Karel , Nová Iva
Published: September 2021

The work presented in this paper studies the potential of cylindrical piezoelectric transducers for harvesting high-frequency acoustic energy. The cylinder was made of a modified PZT (lead zirconate titanate) and had the shape of a squared cylinder with a side length of 4 cm and a wall thickness of 1 mm. The study used open-circuit measurements to study the relationship between the sound wavelength and the cylinder size and its effect on the performance of energy harvesting. The cylinder was found to give the best performance at a frequency of 20 kHz. In addition to open-circuit measurements, closed-circuit measurements were performed to demonstrate the ability to dissipate energy harvested from 20 kHz sound waves across an electric load. The load was designed in a series of experimental steps that aimed at optimizing an impedance-matched energy harvester. Finally, the cylinder was tested at the optimized load conditions, and it was possible to harvest and store energy with a power of 67.6 μW and harvesting efficiency of 86.1%.
Egg Freshness Evaluation Using Transmission and Reflection of NIR Spectroscopy Coupled Multivariate Analysis
Authors: Wang Fuyun , Lin Hao , Xu Peiting , Bi Xiakun , Sun Li
Published: September 2021

This work presents a novel work for the detection of the freshness of eggs stored at room temperature and refrigerated conditions by the near-infrared (NIR) spectroscopy and multivariate models. The NIR spectroscopy of diffuse transmission and reflection modes was used to compare the quantitative and qualitative investigation of egg freshness. It was found that diffuse transmission is more conducive to the judgment of egg freshness. The linear discriminant analysis model (LDA) for pattern recognition based on the diffuse transmission measurement was employed to analyze egg freshness during storage. NIR diffuse transmission spectroscopy showed great potential for egg storage time discrimination in normal atmospheric conditions. The LDA model discrimination rated up to 91.4% in the prediction set, while only 25.6% of samples were correctly discriminated among eggs in refrigerated storage conditions. Furthermore, NIR spectra, combined with the synergy interval partial least squares (Si-PLS) model, showed excellent ability in egg physical index prediction under normal atmospheric conditions. The root means square error of prediction (RMSEP) values of Haugh unit, yolk index, and weight loss from predictive Si-PLS models were 4.25, 0.031, and 0.005432, respectively.
Semantic-Linked Data Ontologies for Indoor Navigation System in Response to COVID-19
Authors: Alamri Abdullah
Published: September 2021

Indoor navigation has become more important these days due to the current situation worldwide in the aftermath of the outbreak of the COVID-19 pandemic, posing an unparalleled threat amounting to a humanitarian crisis on a global scale. Indoor navigation employs a variety of technologies, including Wi-Fi, Bluetooth, and RFID. Support for these technologies requires accurate information and appropriate processing and modeling to help and direct users of the optimal route to desired destinations and to monitor crowd density in order to maintain social distancing. This research will present a semantic indoor ontology model for indoor navigation and the reduction of human density in indoor space to ensure social distancing and prevent transmission. The proposed system is based on semantic representations of the components of navigation paths which, in turn, enable reasoning functionality. Despite the system’s complexity, the evaluation revealed that it functions well.
Melatonin Suppresses Oral Squamous Cell Carcinomas Migration and Invasion through Blocking FGF19/FGFR 4 Signaling Pathway
Authors: Wang Leilei , Su Yuxiong , Choi Wing Shan
Published: September 2021

Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the anti-cancer effects of melatonin on OSCCs and the underlying mechanisms. A human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin, followed by transwell migration and invasion assays. Relative expression levels of Fibroblast Growth Factor 19 (FGF19) was identified by Cytokine Array and further verified by qPCR and Western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Invasion and migration abilities of SCC-15 cells were suppressed by melatonin, in parallel with the decreased FGF19/FGFR4 expression level. Exogenous hFGF19 eliminated the inhibitory effects of melatonin on SCC-15 cells invasion and migration, while FGF19 knocking-down showed similar inhibitory activities with melatonin. This study proves that melatonin suppresses SCC-15 cells invasion and migration through blocking the FGF19/FGFR4 pathway, which enriches our knowledge on the anticancer effects of melatonin. Blocking the FGF19/FGFR4 pathway by melatonin could be a promising alternative for OSCCs prevention and management, which would facilitate further development of novel strategies to combat OSCCs.
Effect of Exogenous pH on Cell Growth of Breast Cancer Cells
Authors: Lee Sungmun , Shanti Aya
Published: September 2021

Breast cancer is the most common type of cancer in women and the most life-threatening cancer in females worldwide. One key feature of cancer cells, including breast cancer cells, is a reversed pH gradient which causes the extracellular pH of cancer cells to be more acidic than that of normal cells. Growing literature suggests that alkaline therapy could reverse the pH gradient back to normal and treat the cancer; however, evidence remains inconclusive. In this study, we investigated how different exogenous pH levels affected the growth, survival, intracellular reactive oxygen species (ROS) levels and cell cycle of triple-negative breast cancer cells from MDA-MB-231 cancer cell lines. Our results demonstrated that extreme acidic conditions (pH 6.0) and moderate to extreme basic conditions (pH 8.4 and pH 9.2) retarded cellular growth, induced cell death via necrosis and apoptosis, increased ROS levels, and shifted the cell cycle away from the G0/G1 phase. However, slightly acidic conditions (pH 6.7) increased cellular growth, decreased ROS levels, did not cause significant cell death and shifted the cell cycle from the G0/G1 phase to the G2/M phase, thereby explaining why cancer cells favored acidic conditions over neutral ones. Interestingly, our results also showed that cellular pH history did not significantly affect the subsequent growth of cells when the pH of the medium was changed. Based on these results, we suggest that controlling or maintaining an unfavorable pH (such as a slightly alkaline pH) for cancer cells in vivo could retard the growth of cancer cells or potentially treat the cancer.
Zone-Dependent Architecture and Biochemical Composition of Decellularized Porcine Nasal Cartilage Modulate the Activity of Adipose Tissue-Derived Stem Cells in Cartilage Regeneration
Authors: Kuhlmann Constanze , Schenck Thilo L. , Aszodi Attila , Giunta Riccardo E. , Wiggenhauser Paul Severin
Published: September 2021

Previous anatomical studies have shown different functional zones in human nasal septal cartilage (NC). These zones differ in respect to histological architecture and biochemical composition. The aim of this study was to investigate the influence of these zones on the fate of stem cells from a regenerative perspective. Therefore, decellularized porcine septal cartilage was prepared and subjected to histological assessment to demonstrate its equivalence to human cartilage. Decellularized porcine NC (DPNC) exposed distinct surfaces depending on two different histological zones: the outer surface (OS), which is equivalent to the superficial zone, and the inner surface (IS), which is equivalent to the central zone. Human adipose tissue-derived stem cells (ASCs) were isolated from the abdominal fat tissue of five female patients and were seeded on the IS and OS of DPNC, respectively. Cell seeding efficiency (CSE), vitality, proliferation, migration, the production of sulfated glycosaminoglycans (sGAG) and chondrogenic differentiation capacity were evaluated by histological staining (DAPI, Phalloidin, Live-Dead), biochemical assays (alamarBlue®, PicoGreen®, DMMB) and the quantification of gene expression (qPCR). Results show that cell vitality and CSE were not influenced by DPNC zones. ASCs, however, showed a significantly higher proliferation and elevated expression of early chondrogenic differentiation, as well as fibrocartilage markers, on the OS. On the contrary, there was a significantly higher upregulation of hypertrophy marker MMP13 (p < 0.0001) and GAG production (p = 0.0105) on the IS, whereas cell invasion into the three-dimensional DPNC was higher in comparison to the OS. We conclude that the zonal-dependent distinct architecture and composition of NC modulates activities of ASCs seeded on DPNC. These findings might be used for engineering of cartilage substitutes needed in facial reconstructive surgery that yield an equivalent histological and functional structure, such as native NC.
3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors
Authors: Erokhin Kirill S. , Gordeev Evgeniy G. , Samoylenko Dmitriy E. , Rodygin Konstantin S. , Ananikov Valentine P.
Published: September 2021

The development of new drugs is accelerated by rapid access to functionalized and D-labeled molecules with improved activity and pharmacokinetic profiles. Diverse synthetic procedures often involve the usage of gaseous reagents, which can be a difficult task due to the requirement of a dedicated laboratory setup. Here, we developed a special reactor for the on-demand production of gases actively utilized in organic synthesis (C2H2, H2, C2D2, D2, and CO2) that completely eliminates the need for high-pressure equipment and allows for integrating gas generation into advanced laboratory practice. The reactor was developed by computer-aided design and manufactured using a conventional 3D printer with polypropylene and nylon filled with carbon fibers as materials. The implementation of the reactor was demonstrated in representative reactions with acetylene, such as atom-economic nucleophilic addition (conversions of 19–99%) and nickel-catalyzed S-functionalization (yields 74–99%). One of the most important advantages of the reactor is the ability to generate deuterated acetylene (C2D2) and deuterium gas (D2), which was used for highly significant, atom-economic and cost-efficient deuterium labeling of S,O-vinyl derivatives (yield 68–94%). Successful examples of their use in organic synthesis are provided to synthesize building blocks of heteroatom-functionalized and D-labeled biologically active organic molecules.
Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells
Authors: Medapati Manoj Reddy , Bhagirath Anjali Yadav , Singh Nisha , Schroth Robert J. , Bhullar Rajinder P. , Duan Kangmin , Chelikani Prashen
Published: September 2021

Bitter-taste receptors (T2Rs) have emerged as key players in host–pathogen interactions and important modulators of oral innate immunity. Previously, we reported that T2R14 is expressed in gingival epithelial cells (GECs) and interacts with competence stimulating peptides (CSPs) secreted by the cariogenic Streptococcus mutans. The underlying mechanisms of the innate immune responses and physiological effects of T2R14 on Gram-positive bacteria are not well characterized. In this study, we examined the role of T2R14 in internalization and growth inhibitory effects on Gram-positive bacteria, namely Staphylococcus aureus and S. mutans. We utilized CRISPR-Cas9 T2R14 knockdown (KD) GECs as the study model to address these key physiological mechanisms. Our data reveal that the internalization of S. aureus is significantly decreased, while the internalization of S. mutans remains unaffected upon knockdown of T2R14 in GECs. Surprisingly, GECs primed with S. mutans CSP-1 resulted in an inhibition of growth for S. aureus, but not for S. mutans. The GECs infected with S. aureus induced T2R14-dependent human β-defensin-2 (hBD-2) secretion; however, S. mutans–infected GECs did not induce hBD-2 secretion, but induced T2R14 dependent IL-8 secretion. Interestingly, our results show that T2R14 KD affects the cytoskeletal reorganization in GECs, thereby inhibiting S. aureus internalization. Our study highlights the distinct mechanisms and a direct role of T2R14 in influencing physiological responses to Gram-positive bacteria in the oral cavity.
Effects of Dielectric Barrier Ambient Air Plasma on Two Brassicaceae Seeds: Arabidopsis thaliana and Camelina sativa
Authors: Bafoil Maxime , Yousfi Mohammed , Dunand Christophe , Merbahi Nofel
Published: September 2021

We investigated low-temperature plasma effects on two Brassicaceae seeds (A. thaliana and C. sativa) using dielectric barrier discharge in air. Comparisons of plasma treatments on seeds showed distinct responses on germination rate and speed. Optimal treatment time giving optimal germination is 15 min for A. thaliana with 85% increase compared to control after 48 h of germination and 1 min for C. sativa with 75% increase compared to control after 32 h of germination. Such germination increases are associated with morphological changes shown by SEM of seed surface. For better understanding at the biochemical level, seed surfaces were analyzed using gas chromatography-mass spectrometry which underlined changes of lipidic composition. For both treated seeds, there is a decrease of saturated (palmitic and stearic) fatty acids while treated C. sativa showed a decrease of unsaturated (oleic and linoleic) acids and treated A. thaliana an increase of unsaturated ones. Such lipid changes, specifically a decrease of hydrophobic saturated fatty acids, are coherent with the other analyses (SEM, water uptake and contact angle). Moreover, an increase in A. thaliana of unsaturated acids (very reactive) probably neutralizes plasma RONS effects thus needing longer plasma exposure time (15 min) to reach optimal germination. For C. sativa, 1 min is enough because unsaturated linoleic acid becomes lower in treated C. sativa (1.2 × 107) compared to treated A. thaliana (3.7 × 107).
Oral Semaglutide, the First Ingestible Glucagon-Like Peptide-1 Receptor Agonist: Could It Be a Magic Bullet for Type 2 Diabetes?
Authors: Kim Hwi Seung , Jung Chang Hee
Published: September 2021

The gastrointestinal tract secretes gut hormones in response to food consumption, and some of these stimulate insulin secretion. Glucagon-like peptide-1 (GLP-1) is an incretin peptide hormone released from the lower digestive tract that stimulates insulin secretion, suppresses glucagon secretion, and decreases hunger. GLP-1 receptor agonist (GLP-1RA) mimics the action of endogenous GLP-1, consequently reversing hyperglycemia and causing weight reduction, demonstrating its efficacy as an antidiabetic and antiobesity agent. Previously restricted to injection only, the invention of the absorption enhancer sodium N-(8-[2-hydroxybenzoyl]amino) caprylate resulted in the development of oral semaglutide, the first ingestible GLP-1RA. Oral semaglutide demonstrated its efficacy in glycemic management and body weight loss with a low risk of hypoglycemia as a monotherapy and in combination with other hypoglycemic medications in its clinical trial programs named Peptide Innovation for Early Diabetes Treatment. Consistent with other injectable GLP-1RAs, gastrointestinal side effects were often reported. Additionally, cardiovascular safety was established by demonstrating that oral semaglutide was not inferior to a placebo in terms of cardiovascular outcomes. Thus, oral semaglutide represents a novel treatment option that is particularly well-suited for patients with type 2 diabetes and/or obesity.
Synchrotron-Based Fourier-Transform Infrared Micro-Spectroscopy (SR-FTIRM) Fingerprint of the Small Anionic Molecule Cobaltabis(dicarbollide) Uptake in Glioma Stem Cells
Authors: Nuez-Martínez Miquel , Pedrosa Leire , Martinez-Rovira Immaculada , Yousef Ibraheem , Diao Diouldé , Teixidor Francesc , Stanzani Elisabetta , Martínez-Soler Fina , Tortosa Avelina , Sierra Àngels , Gonzalez José Juan , Viñas Clara
Published: September 2021

The anionic cobaltabis (dicarbollide) [3,3′-Co(1,2-C2B9H11)2]−, [o-COSAN]−, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]− could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic ν(B-H) frequency in the infrared range 2.600–2.500 cm−1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]−, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]− translocates GIC cells’ membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells.
An Overview of Near Infrared Spectroscopy and Its Applications in the Detection of Genetically Modified Organisms
Authors: Sohn Soo-In , Pandian Subramani , Oh Young-Ju , Zaukuu John-Lewis Zinia , Kang Hyeon-Jung , Ryu Tae-Hun , Cho Woo-Suk , Cho Youn-Sung , Shin Eun-Kyoung , Cho Byoung-Kwan
Published: September 2021

Near-infrared spectroscopy (NIRS) has become a more popular approach for quantitative and qualitative analysis of feeds, foods and medicine in conjunction with an arsenal of chemometric tools. This was the foundation for the increased importance of NIRS in other fields, like genetics and transgenic monitoring. A considerable number of studies have utilized NIRS for the effective identification and discrimination of plants and foods, especially for the identification of genetically modified crops. Few previous reviews have elaborated on the applications of NIRS in agriculture and food, but there is no comprehensive review that compares the use of NIRS in the detection of genetically modified organisms (GMOs). This is particularly important because, in comparison to previous technologies such as PCR and ELISA, NIRS offers several advantages, such as speed (eliminating time-consuming procedures), non-destructive/non-invasive analysis, and is inexpensive in terms of cost and maintenance. More importantly, this technique has the potential to measure multiple quality components in GMOs with reliable accuracy. In this review, we brief about the fundamentals and versatile applications of NIRS for the effective identification of GMOs in the agricultural and food systems.
Influence of Human Jaw Periosteal Cells Seeded β-Tricalcium Phosphate Scaffolds on Blood Coagulation
Authors: Weber Marbod , Umrath Felix , Steinle Heidrun , Schmitt Lukas-Frank , Yu Lin Tzu , Schlensak Christian , Wendel Hans-Peter , Reinert Siegmar , Alexander Dorothea , Avci-Adali Meltem
Published: September 2021

Tissue engineering offers auspicious opportunities in oral and maxillofacial surgery to heal bone defects. For this purpose, the combination of cells with stability-providing scaffolds is required. Jaw periosteal cells (JPCs) are well suited for regenerative therapies, as they are easily accessible and show strong osteogenic potential. In this study, we analyzed the influence of uncoated and polylactic-co-glycolic acid (PLGA)-coated β-tricalcium phosphate (β-TCP) scaffolds on JPC colonization and subsequent osteogenic differentiation. Furthermore, interaction with the human blood was investigated. This study demonstrated that PLGA-coated and uncoated β-TCP scaffolds can be colonized with JPCs and further differentiated into osteogenic cells. On day 15, after cell seeding, JPCs with and without osteogenic differentiation were incubated with fresh human whole blood under dynamic conditions. The activation of coagulation, complement system, inflammation, and blood cells were analyzed using ELISA and scanning electron microscopy (SEM). JPC-seeded scaffolds showed a dense cell layer and osteogenic differentiation capacity on both PLGA-coated and uncoated β-TCP scaffolds. SEM analyses showed no relevant blood cell attachment and ELISA results revealed no significant increase in most of the analyzed cell activation markers (β-thromboglobulin, Sc5B-9, polymorphonuclear (PMN)-elastase). However, a notable increase in thrombin-antithrombin III (TAT) complex levels, as well as fibrin fiber accumulation on JPC-seeded β-TCP scaffolds, was detected compared to the scaffolds without JPCs. Thus, this study demonstrated that besides the scaffold material the cells colonizing the scaffolds can also influence hemostasis, which can influence the regeneration of bone tissue.
Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts
Authors: Erario María de los Ángeles , Croce Eduardo , Moviglia Brandolino Maria Teresita , Moviglia Gustavo , Grangeat Aníbal M.
Published: September 2021

Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results in the majority of spinal diseases, it is not yet fully accepted within the medical community. Perhaps it is partly due to the fact that, sometimes, indications are not appropriately made. The objective of our work is to explain the mechanisms of action of ozone therapy on the extruded disc herniation. Indeed, these mechanisms are quite different from those exerted by ozone on the protruded disc herniation and on the degenerative disc disease because the inflammatory response is very different between the various cases. Extruded disc herniation occurs when the nucleus squeezes through a weakness or tear in the annulus. Host immune system considers the nucleus material to be a foreign invader, which triggers an immune response and inflammation. We think ozone therapy modulates this immune response, activating macrophages, which produce phagocytosis of extruded nucleus pulposus. Ozone would also facilitate the passage from the M1 to M2 phase of macrophages, going from an inflammatory phase to a reparative phase. Further studies are needed to verify the switch of macrophages.
Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
Authors: Koma Ayaka , Asai Shunichi , Minemura Chikashi , Oshima Sachi , Kinoshita Takashi , Kikkawa Naoko , Koshizuka Keiichi , Moriya Shogo , Kasamatsu Atsushi , Hanazawa Toyoyuki , Uzawa Katsuhiro , Seki Naohiko
Published: September 2021

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.
Beyond G-Quadruplexes—The Effect of Junction with Additional Structural Motifs on Aptamers Properties
Authors: Kotkowiak Weronika , Pasternak Anna
Published: September 2021

G-quadruplexes constitute an important type of nucleic acid structure, which can be found in living cells and applied by cell machinery as pivotal regulatory elements. Importantly, robust development of SELEX technology and modern, nucleic acid-based therapeutic strategies targeted towards various molecules have also revealed a large group of potent aptamers whose structures are grounded in G-quadruplexes. In this review, we analyze further extension of tetraplexes by additional structural elements and investigate whether G-quadruplex junctions with duplex, hairpin, triplex, or second G-quadruplex motifs are favorable for aptamers stability and biological activity. Furthermore, we indicate the specific and pivotal role of the G-quadruplex domain and the additional structural elements in interactions with target molecules. Finally, we consider the potency of G-quadruplex junctions in future applications and indicate the emerging research area that is still waiting for development to obtain highly specific and effective nucleic acid-based molecular tools.
Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer
Authors: Tanaka Mai , Siemann Dietmar W.
Published: September 2021

Many signaling pathways are dysregulated in cancer cells and the host tumor microenvironment. Aberrant receptor tyrosine kinase (RTK) pathways promote cancer development, progression, and metastasis. Hence, numerous therapeutic interventions targeting RTKs have been actively pursued. Axl is an RTK that belongs to the Tyro3, Axl, MerTK (TAM) subfamily. Axl binds to a high affinity ligand growth arrest specific 6 (Gas6) that belongs to the vitamin K-dependent family of proteins. The Gas6/Axl signaling pathway has been implicated to promote progression, metastasis, immune evasion, and therapeutic resistance in many cancer types. Therapeutic agents targeting Gas6 and Axl have been developed, and promising results have been observed in both preclinical and clinical settings when such agents are used alone or in combination therapy. This review examines the current state of therapeutics targeting the Gas6/Axl pathway in cancer and discusses Gas6- and Axl-targeting agents that have been evaluated preclinically and clinically.
Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease: Rationale, Clinical Results and Perspectives
Authors: Buscail Etienne , Le Cosquer Guillaume , Gross Fabian , Lebrin Marine , Bugarel Laetitia , Deraison Céline , Vergnolle Nathalie , Bournet Barbara , Gilletta Cyrielle , Buscail Louis
Published: September 2021

Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.
Functional Changes of T-Cell Subsets with Age and CMV Infection
Authors: Hassouneh Fakhri , Goldeck David , Pera Alejandra , van Heemst Diana , Slagboom P. Eline , Pawelec Graham , Solana Rafael
Published: September 2021

Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.