bluuebunny/crossref_metadata_2025 huggingface dataset:
Cynanoside F Controls Skin Inflammation by Suppressing Mitogen-Activated Protein Kinase Activation
Authors: Fleitas Mara Melissa Duarte , Kim Seon Sook , Kim Nam Kyoung , Seo Su Ryeon
Published: September 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and dry skin. Currently, the incidence of AD due to excessive activation of immune cells by various environmental factors is increasing worldwide, and research on inflammatory response inhibitors with fewer side effects is continuously needed. Cynanoside F (CF) is one of the pregnane-type compounds in the root of Cynanchum atratum, an oriental medicinal herb that has been shown to have antioxidant, antitumor, and anti-inflammatory effects. Although CF has been isolated as a component in Cynanchum atratum, the scientific role of CF has not yet been explored. In this study, we evaluated the effect of CF on AD and revealed the mechanism using in vitro and in vivo experimental models. CF significantly reduced lipopolysaccharide (LPS)-induced protein expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), which are important proinflammatory mediators in the RAW264.7 macrophage cell line. CF did not inhibit the nuclear factor-kappa B (NF-κB) signaling activated by LPS but significantly reduced the phosphorylation of mitogen-activated protein kinases (MAPKs), such as p38 MAPK, JNK, and ERK. CF consistently inhibited the activity of the activator protein-1 (AP-1) transcription factor, a downstream molecule of MAPK signaling. In addition, in an experiment using an oxazolone-induced AD mouse model, the CF-treated group showed a marked decrease in epidermal thickness, the number of infiltrated mast cells, and the amount of histamine. The mRNA levels of IL-1β, interleukin-4 (IL-4), and thymic stromal lymphopoietin (TSLP) were consistently lowered in the group treated with CF. Moreover, the phosphorylation of c-Jun and c-Fos protein levels, which are the AP-1 components, were lowered in the skin tissues of CF-treated mice. These results provide the first evidence that CF has an inhibitory effect on AD and suggest the possibility of CF being developed as a potential therapeutic agent for AD.
The Standardization Method and Application of the BIM Model for Interchanges
Authors: Zhai Yiyang , Zhang Chi , Wang Bo , Wang Xue , Liu Kai , Tang Zhongze
Published: September 2022

Research on the standardization of interchange BIM components is required to encourage the use of BIM technology in interchange and quicken the development and improvement of relevant standards and specifications. The depth level of the model, classification, and coding of interchange BIM components, and the design and administration of the component library are the main topics of this work. First, the concept and main research content on the standardization of interchange BIM components were proposed. Second, the common forms of interchange were summarized. The basic components of interchanges include through lanes, ramps, connections, overpass bridges, and traffic safety facilities, and can be divided into 14 second-level components, such as the main line, the minor cross highway, the speed-change lane, etc. On this basis, a method for interchange BIM components classification based on faceted classification and a coding method based on a combination code was proposed. The model depth grading of the BIM component of the interchange was studied, and grading was carried out considering three aspects: the level of detail (LOD), geometric accuracy, and information level. Finally, the process of creating interchange BIM component libraries was proposed. The results showed that the interchange BIM components can adopt a three-level coding method, namely “the overall spatial code–classification code–instance code”, and the LOD, geometric accuracy, and information level of the interchange BIM components can be divided into four levels. Additionally, interchange BIM component libraries can be created using five steps: an overall plan of component resources, standard determination, component creation, component audit, component storage, and application.
Review of Glyphosate-Based Herbicide and Aminomethylphosphonic Acid (AMPA): Environmental and Health Impacts
Authors: Ojelade Babatunde Solomon , Durowoju Olatunde Samod , Adesoye Peter Oluremi , Gibb Stuart W. , Ekosse Georges-Ivo
Published: September 2022

The use of synthetic molecules to achieve specific goals is steadily increasing in the environment, and these molecules adversely impact human health and ecosystem services. Considering the adverse effects, a better understanding of how these molecules behave in the environment and their associated risks is necessary to keep their use acceptably limited. To meet the demands of farmers and combat weed problems, woodlands and farmlands are sprayed with agrochemicals, primarily glyphosate-based herbicides. Farmers increasingly embrace these herbicides containing glyphosate. Glyphosate and aminomethylphosphonic acid (AMPA), a key metabolite of glyphosate, have been reported as toxicological concerns when they become more prevalent in the food chain. The chemical glyphosate has been linked to various health issues in humans and other living organisms, including endocrine disruption, reproductive issues, tumours, non-Hodgkin lymphomas, and liver, heart, and blood problems. Therefore, the current review aims to compile data on glyphosate-based herbicide use in the environment, potential risks to human and ecological health, and various maximum residual limits for crops as suggested by international organizations. As a result, regulatory agencies can advise glyphosate users on safe usage practices and synthesize herbicides more efficiently.
Gas Bubble Photonics: Manipulating Sonoluminescence Light with Fluorescent and Plasmonic Nanoparticles
Authors: Maksymov Ivan S.
Published: September 2022

Oscillations of gas bubbles in liquids irradiated with acoustic pressure waves may result in an intriguing physical phenomenon called sonoluminescence, where a collapsing bubble emits the in a broad optical spectral range. However, the intensity of the so-generated light is typically weak for practical purposes. Recently, it has been demonstrated that nanoparticles can be used to increase the efficiency of sonoluminescence, thereby enabling one to generate light that is intense enough for a number of applications in photonics, biomedicine, and materials science. In this article, we review the latest achievements in the field of nanoparticle-enhanced sonoluminescence and showcase the perspectives of their practical applications.
Marketing Strategies for Cultured Meat: A Review
Authors: Siddiqui Shahida Anusha , Khan Sipper , Murid Misbah , Asif Zarnab , Oboturova Natalya Pavlovna , Nagdalian Andrey Ashotovich , Blinov Andrey Vladimirovich , Ibrahim Salam A. , Jafari Seid Mahdi
Published: September 2022

Environmentally intense and negative consequences relateing to conventional meat production systems have induced some actors to suggest alternative meat sources. Diseases carried by animals, human perception of cruelty to animals, and public health concerns about cardiovascular diseases have provided the basis for the development of cultured meat. The current market is influenced by many factors, including regulators, affordability, religion, and media perception. The existing cultured meat market is also regulated by legislatures, affordability, consumer religion, and the media. Consumer perception is distributed across various aspects, including ethical priorities, nutritional profile of the meat consumed, age-based acceptance, gender differentiation, political orientation, land-based attitude, education status, socioeconomic factors, and familiarity factor with the existing product in the market. Inhibiting barriers reported among consumers—including low naturalness, safety, nutritional concerns, trust, neophobia, economic, and ethical approaches—should be employed as marketing tactics directly to address their respective concerns. Tissue culture, starter cells, printing, and 3D printing are some of the methods currently being used for the production of cultured meat. Similarly, many hybrid technologies are also being used to produce meat-like products to increase consumer familiarity along and market presence. Existing research frameworks have improved the previous mindset of consumers with media coverage, educational frameworks, and the textural attributes of cultured meat. Additional benefits of CUME may include being environmentally friendly with less production of greenhouse gases. However, consumer trust, affordability, improving nutritional status, and widescale adoption are just a few of the parameters that need to be addressed to enhance consumer acceptability of these products. The aim of this article was to analyze the current state of cultured meat and the marketing content challenges and strategies used to advance public acceptance of cultured meat.
Motion Generation for Crane Simulators Using Streamlined Motion Blending Technology
Authors: Zhu Ze , Luo Yangyi , Xiao Hanbin , Li Zhanfeng , Xu Chang , Wang Guoxian
Published: September 2022

For development of a simulator with a motion platform to generate an appropriate motion to reproduce the motion sense for the users, one of the most significant but disregarded complicated tasks is to build up a dynamic virtual motion model to reflect the motion of the simulated object in the corresponding physical world. Recently, a motion generation method based on motion blending technology was developed to alleviate the complication involved. It decomposes the simulated motion into a great number of parameterized motion blocks which are depicted by real motion data acquired from field tests and stored in a database. This paper proposes a streamlined motion blending technology suitable for a container crane simulator to further improve the current motion generation method based on the motion blending technology. Motion components, rather than motion blocks specially marked and stored in a database, are taken as the basic motion unit easily acquired through united analysis of crane dynamics and motion perception characteristics. They are then blended on demand to produce a one-stop model to directly act as the driving command of the motion platform without the need for a subsequent dedicated wash-out procedure. The calculation workload is greatly reduced and finally allows for achievement of higher fidelity of motion perceptions. Experiments are conducted to verify the effectiveness of the proposed streamlined motion blending technology for motion perception generation. Better training effect is found to be achieved due to more realistic simulation effects. The comprehensive training effectiveness index is enhanced from 54% to 82% once a motion simulation system developed using the proposed approach is introduced into the crane simulator.
Numerical Simulation Research on Mechanical Optimization of a Novel Fastener Type Ballastless Track (NFTBT) for Tram
Authors: Zeng Zhiping , He Xiaodong , Huang Xudong , Wang Weidong , Wang Di , Qahtan Ayoub Abdullah Senan , Yuan Weidong , Boumedienne Houdou Saidi
Published: September 2022

In view of the problems present in the construction process of the embedded track structure of modern tram, we have designed a Novel Fastener Type Ballastless Track (NFTBT) for tram. To optimize the size of the NFTBT’s structure, the finite element model of the NFTBT’s structure in the tram running stage is built, the mechanical characteristics of the NFTBT’s structure are calculated, and the geometric parameters of the NFTBT’s structure are systematically studied. The research results are as follows: (1) As the size of the track slab increases, the displacement differences of the middle part of the NFTBT are similar, and the size of the track slab has little effect on the displacement. (2) The stress difference of the NFTBT’s structure under the different distances between the centers of the adjacent grouting holes’ conditions is small. Although a larger distance between the centers of the adjacent grouting holes can reduce the number of grouting holes in the track slab, the distance should not be too large to reduce the peak stress at the bottom of the NFTBT. (3) When the distance between the adjacent fasteners of the NFTBT changes within a certain range, the rail is greatly affected by the uneven settlement of the subgrade, and the track irregularity will be aggravated. (4) The NFTBT does not require the implementation of cable passages at intervals, which facilitates the passage and fixation of the cables in the tram operation section and can reduce the difficulty of adjusting the geometry of the track structure, thus accelerating the construction progress.
Perlite as a Biocarrier for Augmentation of Biogas-Producing Reactors from Olive (Olea europaea) Waste
Authors: Ivankovic Tomislav , Kontek Mislav , Mihalic Valentino , Ressler Antonia , Jurisic Vanja
Published: September 2022

Biogas is mainly produced by anaerobic digestion (AD), and in the EU, the widely used substrate for AD is maize silage. Due to a rise in silage prices, the intention is to gradually replace maize with lignocellulose biomass. In the Mediterranean area, the olive industry produces large amounts of lignocellulose wastes, namely olive cake and pruned biomass. Still, due to its high lignin content, it is resistant to biodegradation. This issue could be resolved by adding targeted microorganisms that enhance the substrate’s primary degradation, and the cells’ attachment to suitable biocarriers could boost the augmentation process. A microbial consortium customized for biodegradation of olive cake and pruned biomass was isolated, propagated and immobilized onto the biocarrier, perlite, a naturally occurring aluminosilicate material. The perlite proved to be a suitable biocarrier with numbers of immobilized bacteria as high as 2.1 ± 0.9 × 1011 and 3.4 ± 0.6 × 1010 CFU g−1 when preparation was performed in aerobic and anaerobic conditions, respectively. Bioaugmentation of AD reactors significantly increased the biogas yield, but only if olive cake, not the pruned biomass, was used as a substrate.
Double Dead-Time Signal Injection Strategy for Stator Resistance Estimation of Induction Machines
Authors: Lazcano Urtzi , Poza Javier , Garramiola Fernando , Rivera Christian A. , Iturbe Ion
Published: September 2022

A sensorless online temperature estimator is presented in this paper, which estimates the temperature using a novel signal injection strategy. This allows to eliminate the temperature sensors in the machine, as well as their faults, increasing the system reliability. A double dead-time DC signal is injected in the machine, adding a controlled offset in the control drive through the inverter. The proposed strategy eliminates the effect of the dead-time in the injected signal, which is an important drawback in DC injection strategies for resistance estimation. Furthermore, additional hardware is not needed. The strategy has been implemented in an inverter-fed railway traction induction machine. The proposed algorithm has been validated in a real test-bench.
BIM in Structural Project: Interoperability Analyses and Data Management
Authors: Gomes Augusto M. , Azevedo Gonçalo , Sampaio Alcínia Zita , Lite Alberto Sánchez
Published: September 2022

Building Information Modelling (BIM) is a methodology supported on technological evolution achievements, and consists of a set of processes and tools that allows the creation of a digital three-dimensional model. The model centralizes information, in an organized database, facilitating the data access and the exchange between the collaborators and enterprises along all life cycle of a building. The study is focused on the application of BIM within the framework of a structural design, identifying the benefits and limitations verified in the process and indicating strategies allowing to improve the quality of the project and construction. A structural BIM model of a study case was created; using BIM based platforms, followed by its transfer to the calculation software, where the structural analysis and design were carried out. After, using the structural BIM model complemented with the reinforcements, several applications and tasks were performed, namely, the coordination and collaboration procedures, detection of conflicts analyses, production of dynamic drawings, budget estimation and environmental impact simulation of the structural framework concerning the CO2 emission. In the structural domain, the interoperability is the main problem that must be understood and the present study contributes to clarify the recurrent limitations. The research also presents the capacity of BIM methodology of using the database of the BIM model to achieve several types of tasks that normally are associated to the structural design. The study demonstrates the significant improvement in the quality of the structural design and the wide applicability of the BIM model, when compared with the current traditional sequential and fragmented process.
The Biological Processes of Chloride Ions Removal from the Environment
Authors: Sobiecka Elżbieta
Published: September 2022

Chlorine is one of the macronutrients commonly found in nature. The natural cycle of this element can be destabilized by human activities and causes negative effects in the environment. To come back into a natural balance, various biological processes of water and soil remediation have been investigated. The purpose of the presented research focused on two chlorine conversion processes: (1) anaerobic dechlorination of polychlorinated biphenyls (PCBs) found in transformer oil provided by consortia of microorganisms originating from a wastewater sedimentation tank and (2) chloride elimination from aquatic environments by commercial mixtures of microorganisms in aerobic conditions. Dechlorination allowed the conversion PCB molecules to less-toxic compounds and significantly influenced contamination in the range of 15 to 76%. In the second process, the decrease in chloride ions did not exceed 14%. Both the consortia of microorganisms and biological commercial mixtures used in this study were able to decrease the chloride ion concentration in the investigated aquatic solution.
Special Issue “Emerging Artificial Intelligence (AI) Technologies for Learning”
Authors: Milani Alfredo , Santucci Valentino , Caraffini Fabio
Published: September 2022

The future of education lies in the ability to develop technologies which integrate seamless artificial intelligence (AI) components into the educational process, in order to deliver a personalized service which is dynamically tailored to the learner’s characteristics, abilities, and needs [...]
Individual Environmental Risk Assessment and Management in Industry 4.0: An IoT-Based Model
Authors: Lemos Janaína , Gaspar Pedro D. , Lima Tânia M.
Published: September 2022

This paper addresses the design of a system to facilitate individual environmental risk assessment and long-term risk management in the Industry 4.0 work context. The solution is based on IoT to provide data related to workers’ exposure to hazardous agents (dust, noise, ultraviolet radiation, poor lighting, and inappropriate temperature and humidity) through a simple interface for employees and employers. The system includes a monitoring device and a server and performs employee registration, receives secure messages from the monitoring devices, shows information about the workers’ exposure, and triggers alarms when the measures reach or exceed the limits established by applicable legislation and/or standards. The system was tested in a controlled environment, and the results are presented in this work. Our solution is still under development, and in future stages, it will include a smartphone app for employees to check their exposures and the use of artificial intelligence on the server, which is expected to enable long-term planning by companies based on the analysis of employees’ health history and their exposures to hazardous agents.
Are Atmospheric Situations Now More Favourable for Heavy Rainfall in the Spanish Mediterranean? Analysis of Episodes in the Alicante Province (1981–2020)
Authors: Sánchez-Almodóvar Esther , Martin-Vide Javier , Olcina-Cantos Jorge , Lemus-Canovas Marc
Published: September 2022

Intense rainfall (≥100 mm/24 h) constitutes the most frequent atmospheric hazard on Spain’s Mediterranean coast; this phenomenon causes serious damage to property and kills or injures inhabitants. The Intergovernmental Panel on Climate Change, in its latest report in 2022, indicates that in the current climate change scenario, these episodes will become more frequent, hence the importance of analysing and characterising them. The present paper analysed intense rainfall episodes in the central sector of the Spanish Mediterranean coast (province of Alicante) in the 1981–2020 period. A total of 129 episodes were identified which have affected different areas of this province. The rainfall events were analysed by means of three synoptic classification methods subjective/manual and objective/automatic in order to assess the strengths and weaknesses of the two modalities. The main objective was to identify the most favourable atmospheric situations triggering intense rainfall in the study area. The period with the highest propensity for these episodes to develop was identified, as well as the geographical areas most affected in the study period. Autumn concentrates the biggest amount of intense rainfall episodes throughout the year. Herein, we attempt to demonstrate the relationship between atmospheric situation, accumulated rainfall volume, geographical area affected, and the most favourable period of the year for the development of these events. The main results of the synoptic analysis of extreme events show the coincidence, in the three classification methods used, that the existence of instability in the middle and upper layers of the atmosphere (DANA and troughs) and humid and warm E and NE surface flows are decisive. In addition, the warming recorded in the waters of the western Mediterranean in recent decades is related to extreme events.
Winter Orographic Precipitation and ENSO in Sapporo, Japan
Authors: Yatagai Akiyo , Kinoshita Chisato
Published: September 2022

The effect of global climate change on the distribution of snow water is a great concern. Thus, it is important to clarify the characteristics of winter precipitation variability, including mountain precipitation, together with climate indices. In this study, regional snowfall characteristics were investigated with the daily gridded precipitation over Sapporo City (located on the Japan Sea side of Hokkaido in northern Japan), which was quantified by the APHRODITE method and by adding local precipitation observation data. We found places of showing large interannual variability that is different from that of daily precipitation variability. Applying an EOF analysis to the daily grid precipitation, we defined four local precipitation types. The occurrence of each precipitation type and associated atmospheric circulation was analyzed, and the results revealed that (except for the Super El Niño winter of 1997/1998) more snow fell in the southwestern mountains and inland areas during El Niño winters, and more snow fell in the northeastern plains and along the sea during La Niña winters. Continued development and evaluation of the precise data that incorporate local precipitation network is needed.
A Study on Cryptocurrency Log-Return Price Prediction Using Multivariate Time-Series Model
Authors: Sung Sang-Ha , Kim Jong-Min , Park Byung-Kwon , Kim Sangjin
Published: September 2022

Cryptocurrencies are highly volatile investment assets and are difficult to predict. In this study, various cryptocurrency data are used as features to predict the log-return price of major cryptocurrencies. The original contribution of this study is the selection of the most influential major features for each cryptocurrency using the volatility features of cryptocurrency, derived from the autoregressive conditional heteroskedasticity (ARCH) and generalized autoregressive conditional heteroskedasticity (GARCH) models, along with the closing price of the cryptocurrency. In addition, we sought to predict the log-return price of cryptocurrencies by implementing various types of time-series model. Based on the selected major features, the log-return price of cryptocurrency was predicted through the autoregressive integrated moving average (ARIMA) time-series prediction model and the artificial neural network-based time-series prediction model. As a result of log-return price prediction, the neural-network-based time-series prediction models showed superior predictive power compared to the traditional time-series prediction model.
Li-ion Electrode Microstructure Evolution during Drying and Calendering
Authors: Nikpour Mojdeh , Liu Baichuan , Minson Paul , Hillman Zachary , Mazzeo Brian , Wheeler Dean
Published: September 2022

The drying process of electrodes might seem to be a simple operation, but it has profound effects on the microstructure. Some unexpected changes can happen depending on the drying conditions. In prior work, we developed the multiphase-smoothed-particle (MPSP) model, which predicted a relative increase in the carbon additive and binder adjacent to the current collector during drying. This motivated us to undertake the present experimental investigation of the relationship between the drying rate and microstructure and transport properties for a typical anode and cathode. Specifically, the drying rate was controlled by means of temperature for both an NMC532 cathode and graphite anode. The material distribution was analyzed using a combination of cross-section SEM images and the energy-dispersive X-ray spectroscopy elemental maps. The binder concentration gradients were developed in both the in- and through-plane directions. The through-plane gradient is evident at a temperature higher than 150 °C, whereas the in-plane variations resulted at all drying temperatures. The measurements identified an optimum temperature (80 °C) that results in high electronic conductivity and low ionic resistivity due to a more uniform binder distribution. Trends in transport properties are not significantly altered by calendering, which highlights the importance of the drying rate itself on the assembled cell properties.
Temperature Dependence of Hard Carbon Performance in Sodium Half-Cells with 1 M NaClO4 in EC/DEC Electrolyte
Authors: Liu Bowen , Hector Andrew L. , Razmus Weronika O. , Wills Richard G. A.
Published: September 2022

In recent years, sodium-ion batteries (SIBs) have attracted much attention as an alternative to lithium-ion batteries. Hard carbon (HC) is a well-studied anode material for SIBs; however, the performance as a function of temperature is less established. To investigate temperature dependence of the performance of HC, sodium half-cells with a common NaClO4-based electrolyte were tested at temperatures from 10 to 80 °C. Capacity after 20 cycles at 100 mA g−1 current varied from 90 mA h g−1 at 10 °C to 270 mA h g−1 at 60 °C. Increased temperature significantly improves the HC rate capability, with 120 mA h g−1 capacity found at 60 °C with 500 mA g−1 current. Stability was high at moderate temperature with 220 mA h g−1 capacity remaining after 200 cycles at 40 °C with a current of 100 mA g−1.
Effect of Methyl Jasmonate and Methyl Jasmonate Plus Urea Foliar Applications on Wine Phenolic, Aromatic and Nitrogen Composition
Authors: González-Lázaro Miriam , Sáenz de Urturi Itziar , Murillo-Peña Rebeca , Marín-San Román Sandra , Pérez-Álvarez Eva P. , Rubio-Bretón Pilar , Garde-Cerdán Teresa
Published: September 2022

Foliar application has been studied to enhance grape composition and, therefore, wine quality. This work examined, for first time, the effects of foliar applications of methyl jasmonate (MeJ) and methyl jasmonate plus urea (MeJ+Ur) to Tempranillo vineyard on wine phenolic, aromatic and nitrogen composition over two vintages (2019 and 2020). A reduction in alcoholic degree was observed in MeJ and MeJ+Ur wines. The effect of foliar treatments was season-dependent. MeJ and MeJ+Ur wines were characterized, in the first vintage, by a higher content of total acylated anthocyanins, but a low content of total esters, alcohols and acids when compared with control wines. MeJ+Ur wines presented a higher total amino acids content than control and MeJ wines. However, in the second vintage, MeJ and MeJ+Ur wines presented an increase in some non-acylated anthocyanins, but only MeJ+Ur treatment increased the total content of flavonols, flavanols, hydroxycinnamic acids, stilbenes and total amino acids when compared with control wines. MeJ wines presented a low content of esters and acids, whereas MeJ+Ur did not show differences with control wines. Overall, the effect of MeJ+Ur foliar treatment was greater than the effect of MeJ application in order to improve the wine chemical composition.
DLLμE/GC-MS as a Powerful Analytical Approach to Establish the Volatilomic Composition of Different Whiskeys
Authors: Perestrelo Rosa , Caldeira Michael , Rodrigues Freddy , Pereira Jorge A. M. , Câmara José S.
Published: September 2022

The volatilomic fingerprint of nine different whiskeys was established using a rapid and sensitive analytical approach based on dispersive liquid–liquid microextraction (DLLμE) followed by gas chromatography mass spectrometry detection (GC-MS) and gas chromatography with flame ionization detection (GC-FID). The influence of the extractor solvent on the extraction efficiency of volatile compounds (VOCs) was evaluated by DLLμE/GC-MS. The highest amounts of VOCs were obtained using 5 mL of sample, dichloromethane as the extractor solvent, and acetone as the disperser solvent. The proposed method showed no matrix effect, good linearity (R2 ≥ 0.993) in the assessed concentration range, recovery (ranging from 70 to 99%, precision (RSD ≤ 15%) and sensitivity (low limits of detection and quantification). A total of 37 VOCs belonging to different biosynthetic pathways including alcohols, esters, acids, carbonyl compounds, furanic compounds and volatile phenols were identified and quantified using DLLμE/GC-MS and DLLμE/GC-FID, respectively. Alcohols (3-methylbutan-1-ol, propan-1-ol), esters (ethyl decanoate, ethyl octanoate, ethyl hexanoate), and acids (decanoic acid, octanoic acid, hexanoic acid) were the most abundant chemical families. The multivariate statistical analysis allowed for the discrimination of whiskeys based on their volatilomic fingerprint, namely octanoic acid, 2-furfural, ethyl octanoate, ethyl hexanoate, acetic acid, ethyl dodecanoate, butan-1-ol, and ethyl decanoate.
Nanomaterials in Scaffolds for Periodontal Tissue Engineering: Frontiers and Prospects
Authors: Chen Siyang , Huang Xin
Published: September 2022

The regeneration of periodontium represents important challenges to controlling infection and achieving functional regeneration. It has been recognized that tissue engineering plays a vital role in the treatment of periodontal defects, profiting from scaffolds that create the right microenvironment and deliver signaling molecules. Attributable to the excellent physicochemical and antibacterial properties, nanomaterials show great potential in stimulating tissue regeneration in tissue engineering. This article reviewed the up-to-date development of nanomaterials in scaffolds for periodontal tissue engineering. The paper also represented the merits and defects of different materials, among which the biocompatibility, antibacterial properties, and regeneration ability were discussed in detail. To optimize the project of choosing materials and furthermore lay the foundation for constructing a series of periodontal tissue engineering scaffolds, various nanomaterials and their applications in periodontal regeneration were introduced.
Inhibition of CYP2C8 by Acyl Glucuronides of Gemfibrozil and Clopidogrel: Pharmacological Significance, Progress and Challenges
Authors: Shah Manish B.
Published: September 2022

The lipid-regulating drug gemfibrozil is a useful medication for reducing high cholesterol and triglycerides in the blood. In addition to oxidation, it undergoes extensive glucuronidation to produce gemfibrozil acyl glucuronide, which is a known mechanism-based inactivator of cytochrome P450 (CYP) 2C8. Such selective and time-dependent inhibition results in clinically important drug–drug interactions (DDI) with the drugs metabolized by CYP2C8. Similarly, the acyl glucuronide of clopidogrel, a widely used antiplatelet agent, is a potent time-dependent inhibitor of CYP2C8 that demonstrated significant DDI with the substrates of CYP2C8. Current progress in atomic-level understanding mostly involves studying how different drugs bind and undergo oxidation in the active site of CYPs. It is not clear how an acyl glucuronide metabolite of the drug gemfibrozil or clopidogrel interacts in the active site of CYP2C8 and selectively inhibit the enzyme. This mini-review summarizes the current knowledge on some of the important clinical DDI caused by gemfibrozil and clopidogrel due to the inhibition of CYP2C8 by acyl glucuronide metabolites of these drugs. Importantly, it examines recent developments and potential applications of structural biology tools to elucidate the binding and orientation of gemfibrozil acyl glucuronide and clopidogrel acyl glucuronide in the active site near heme that contributes to the inhibition and inactivation of CYP2C8.
Polyphenolic Compounds Inhibit Osteoclast Differentiation While Reducing Autophagy through Limiting ROS and the Mitochondrial Membrane Potential
Authors: Laha Dipranjan , Sarkar Jaganmay , Maity Jyotirindra , Pramanik Asmita , Howlader Md Sariful Islam , Barthels Derek , Das Hiranmoy
Published: September 2022

Polyphenolic compounds are a diverse group of natural compounds that interact with various cellular proteins responsible for cell survival, differentiation, and apoptosis. However, it is yet to be established how these compounds interact in myeloid cells during their differentiation and the molecular and intracellular mechanisms involved. Osteoclasts are multinucleated cells that originate from myeloid cells. They resorb cartilage and bone, maintain bone homeostasis, and can cause pathogenesis. Autophagy is a cellular mechanism that is responsible for the degradation of damaged proteins and organelles within cells and helps maintain intracellular homeostasis. Imbalances in autophagy cause various pathological disorders. The current study investigated the role of several polyphenolic compounds, including tannic acid (TA), gallic acid (GA), and ellagic acid (EA) in the regulation of osteoclast differentiation of myeloid cells. We demonstrated that polyphenolic compounds inhibit osteoclast differentiation in a dose-dependent manner. Quantitative real-time PCR, immunocytochemistry, and western blotting revealed that osteoclast markers, such as NFATc1, Cathepsin K, and TRAP were inhibited after the addition of polyphenolic compounds during osteoclast differentiation. In our investigation into the molecular mechanisms, we found that the addition of polyphenolic compounds reduced the number of autophagic vesicles and the levels of LC3B, BECN1, ATG5, and ATG7 molecules through the inactivation of Akt, thus inhibiting the autophagy process. In addition, we found that by decreasing intracellular calcium and decreasing ROS levels, along with decreasing mitochondrial membrane potential, polyphenolic compounds inhibit osteoclast differentiation. Together, this study provides evidence that polyphenolic compounds inhibit osteoclast differentiation by reducing ROS production, autophagy, intracellular Ca2+ level, and mitochondrial membrane potentials.
miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion
Authors: Ranković Branislava , Boštjančič Emanuela , Zidar Nina , Žlajpah Margareta , Jeruc Jera
Published: September 2022

Serosal invasion is an independent negative prognostic factor in certain cancers, including CRC. However, the mechanisms behind serosal invasion are poorly understood. We therefore assumed that epithelial-mesenchymal transition (EMT) might be involved. Our study included 34 patients with CRC, 3 stage pT2, 14 stage pT3 and 17 showing serosal invasion (stage pT4a according to TNM staging system). RNA isolated from formalin-fixed paraffin-embedded tissue samples was analysed for expression of the miR-200 family and their target genes CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2 using real-time PCR. We found upregulation of miR-200b and ONECUT2 in CRC pT3 and pT4a compared to normal mucosa, and downregulation of CDKN1B in CRC pT3. Moreover, we observed, downregulation of miR-200b, PTPN13 and ZEB2 in CRC with serosal invasion (pT4a) compared to pT3. Our results suggest the involvement of partial EMT in serosal invasion of CRC. In addition, PTPN13 seems to be one of the important regulators involved in serosal invasion, and ONECUT2 in tumour growth.
Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis
Authors: Graßhoff Hanna , Fourlakis Konstantinos , Comdühr Sara , Riemekasten Gabriela
Published: September 2022

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies represent potentially promising targets for therapeutic approaches including B-cell-targeting therapies, as well as strategies for unselective and selective removal of autoantibodies. In this review, we present mechanisms of the innate immune system leading to the generation of autoantibodies, alterations of the B-cell compartment in SSc, autoantibodies as biomarkers and autoantibody-mediated pathologies in SSc as well as potential therapeutic approaches to target these.
Immunotherapy in Head and Neck Cancer When, How, and Why?
Authors: Pereira Daniela , Martins Diana , Mendes Fernando
Published: September 2022

Head and neck cancer (HNC) is one of the most common cancers worldwide. Alcohol and tobacco consumption, besides viral infections, are the main risk factors associated with this cancer. When diagnosed in advanced stages, HNC patients present a higher probability of recurrence or metastasising. The complexity of therapeutic options and post-treatment surveillance is associated with poor prognosis and reduced overall survival (OS). This review aims to explore immunotherapy (immune checkpoint inhibitors (ICI), therapeutic vaccines, and oncolytic viruses) in HNC patients’ treatment, and to explore when, how, and why patients can benefit from it. The monotherapy with ICI or in combination with chemotherapy (QT) shows the most promising results. Compared to standard therapy, ICI are able to increase OS and patients’ quality of life. QT in combination with ICI demonstrates significant response rates and considerable long-term clinical benefits. However, the toxicity associated with this approach is still a hurdle to overcome. In parallel, the therapeutic vaccines directed to the Human Papilloma Virus are also efficient in increasing the antitumour response, inducing cellular and humoral immunity. Although these results demonstrate clinical benefits compared to standard therapy, it is also important to unravel the resistance mechanisms in order to predict the clinical benefit of immunotherapy.
Effectiveness and Safety of Immunosuppressants and Biological Therapy for Chronic Spontaneous Urticaria: A Network Meta-Analysis
Authors: Lin Wen-Kuang , Lin Shwu-Jiuan , Lee Woan-Ruoh , Lin Chia-Chieh , Lin Weei-Chin , Chang Hua-Ching , Cheng Chi-Tsun , Hsu Jason C.
Published: September 2022

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect quantitative analyses. Omalizumab demonstrated better efficacy in DLQI and UAS7 outcomes compared to a placebo, and UAS7 assessments also demonstrated better outcomes compared to cyclosporine. Alongside this, omalizumab demonstrated relatively lower incidences of safety concerns compared to the other immunosuppressants. Cyclosporin was also associated with higher odds of adverse events than other treatment options. Our findings indicate that omalizumab resulted in greater improvements in terms of the DLQI and UAS7 with good tolerability in CSU patients compared to the other immunosuppressants.
NFkB Pathway and Hodgkin Lymphoma
Authors: Jardin Fabrice
Published: September 2022

The tumor cells that drive classical Hodgkin lymphoma (cHL), namely, Hodgkin and Reed-Sternberg (HRS) cells, display hallmark features that include their rareness in contrast with an extensive and rich reactive microenvironment, their loss of B-cell phenotype markers, their immune escape capacity, and the activation of several key biological pathways, including the constitutive activation of the NFkB pathway. Both canonical and alternative pathways are deregulated by genetic alterations of their components or regulators, EBV infection and interaction with the microenvironment through multiple receptors, including CD30, CD40, BAFF, RANK and BCMA. Therefore, NFkB target genes are involved in apoptosis, cell proliferation, JAK/STAT pathway activation, B-cell marker expression loss, cellular interaction and a positive NFkB feedback loop. Targeting this complex pathway directly (NIK inhibitors) or indirectly (PIM, BTK or NOTCH) remains a challenge with potential therapeutic relevance. Nodular predominant HL (NLPHL), a distinct and rare HL subtype, shows a strong NFkB activity signature because of mechanisms that differ from those observed in cHL, which is discussed in this review.
Alterations of the Composition and Neurometabolic Profile of Human Gut Microbiota in Major Depressive Disorder
Authors: Kovtun Alexey S. , Averina Olga V. , Angelova Irina Y. , Yunes Roman A. , Zorkina Yana A. , Morozova Anna Y. , Pavlichenko Alexey V. , Syunyakov Timur S. , Karpenko Olga A. , Kostyuk George P. , Danilenko Valery N.
Published: September 2022

Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut–brain axis. In previous studies of GM in MDD patients, 16S rRNA sequencing was used, which provided information about composition but not about function. In our study, we analyzed whole metagenome sequencing data to assess changes in both the composition and functional profile of GM. We looked at the GM of 36 MDD patients, compared with that of 38 healthy volunteers. Comparative taxonomic analysis showed decreased abundances of Faecalibacterium prausnitzii, Roseburia hominis, and Roseburia intestinalis, and elevated abundances of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients. We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients. These genes produced signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of this species in the GM of MDD patients. These results show the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD, and should be confirmed in future metabolomic studies.
Histostar-Functionalized Covalent Organic Framework for Electrochemical Detection of Exosomes
Authors: Lin Yuxin , Nie Beibei , Qu Xinyu , Wang Minghui , Yang Jie , Li Genxi
Published: September 2022

Covalent organic frameworks (COFs) are gaining growing interest owing to their various structures and versatility. Since their specific physical–chemical characteristics endow them great usage potentiality in biosensing, we herein have synthesized spherical COFs with regular shape and good dispersion, which are further used for the design of a novel nanoprobe by modifying Histostar on the surface of the COFs. Moreover, we have applied a nanoprobe for the fabrication of an electrochemical biosensor to detect exosomes. Since Histostar is a special polymer, conjugated with many secondary antibodies (IgG), and HRP can increase the availability of HRP at the antigenic site, the biosensor can have a strong signal amplification ability. Meanwhile, since COFs with high porosity can be loaded with a huge amount of Histostar, the sensitivity of the biosensor can be further improved. With such a design, the proposed biosensor can achieve a low exosomes detection limit of 318 particles/µL, and a wide linear detection range from 103 particles/µL to 108 particles/µL. So, this work may offer a promising platform for the ultrasensitive detection of exosomes.
Structural Color Controllable Humidity Response Chiral Nematic Cellulose Nanocrystalline Film
Authors: Duan Ran , Lu Mengli , Tang Ruiqi , Guo Yuanyuan , Zhao Dongyu
Published: September 2022

Through self-assembly, environmentally friendly cellulose nanocrystals (CNCs) can form films with a photonic crystal structure whose pitch size can be adjusted in a variety of ways at the fabrication stage. Moreover, the films exhibit response performance to multiple stimuli, which offers extensive applications. Poly(ethylene glycol) (PEG) and CNCs combine to form a smaller chiral nematic domain that develops a solid film with a uniform spiral structure when slowly dried. By changing the composition of CNCs and PEG, flexible and flat photonic composite films with uniform structural colors from blue to red are prepared. Benefiting from the change in pitch size by insertion and detachment of water molecules into the chiral nematic structure, CNCs films and CNC-PEG composite films exhibit a reversible structural color change in response to different humidity. In addition, the chiral nematic films formed by the combination of glycerol and CNCs have a reversible stimulation response to hydrochloric acid gas. Similarly, adjusting the ratio of glycerol can control the pitch size of the films and, thus, the reflective color. In summary, the pitch size of the photonic crystal structure of the films can be precisely tuned by regulating the additive ratio, and the two prepared films have reversible responses to humidity and hydrochloric acid gas, respectively. The CNC-based films show promise in the application of colorimetric biosensors.