bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Moderate Consumption of Different Phenolic-Content Beers on the Human Gut Microbiota Composition: A Randomized Crossover Trial
Authors: Martínez-Montoro José Ignacio , Quesada-Molina Mar , Gutiérrez-Repiso Carolina , Ruiz-Limón Patricia , Subiri-Verdugo Alba , Tinahones Francisco J. , Moreno-Indias Isabel
Published: April 2022

The moderate consumption of beer has been associated with positive effects on health, and these benefits are driven, in part, by the antioxidant properties of phenolic compounds found in this beverage. However, the potential impact of beer polyphenols on the human gut microbiome and their consequences are yet to be elucidated. In this study, our aim was to evaluate the effect of three different phenolic-content beers on the gut microbiome and the potential role of the induced shifts in the antioxidant capacity of beer polyphenols. In total, 20 subjects (10 healthy volunteers and 10 individuals with metabolic syndrome) were randomly assigned in a crossover design to consume each of the different beers (alcohol-free, lager or dark beer) during a 2-week intervention. Significant changes in the relative abundance of Streptococcaceae and Streptococcus were found after beer consumption. An increased abundance of Streptococcaceae and Streptococcus was observed after the consumption of dark beer, with no detected differences between baseline and alcohol-free/lager beer intervention. Moreover, some of the detected differences appeared to be related to the metabolic status. Finally, a decrease in porphyrin metabolism and heme biosynthesis was found after the intervention, especially after the consumption of dark beer. These results show that the antioxidant capacity of beer polyphenols may induce positive shifts in gut microbiota composition, and some of the observed changes may also boost the antioxidant capacity of these compounds.
The Relationship between Cancer and Paraoxonase 1
Authors: Medina-Díaz Irma Martha , Ponce-Ruíz Néstor , Rojas-García Aurora Elizabeth , Zambrano-Zargoza José Francisco , Bernal-Hernández Yael Y. , González-Arias Cyndia Azucena , Barrón-Vivanco Briscia S. , Herrera-Moreno José Francisco
Published: April 2022

Extensive research has been carried out to understand and elucidate the mechanisms of paraoxonase 1 (PON1) in the development of diseases including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. This review focuses on the relationship between PON1 and cancer. The data suggest that PON1, oxidative stress, chronic inflammation, and cancer are closely linked. Certainly, the gene expression of PON1 will remain challenging to study. Therefore, targeting PON1, redox-sensitive pathways, and transcription factors promise prevention and therapy in the development of several diseases, including cancer.
The Role of the Directivity of Various THz Detectors in Multiplexing Systems
Authors: Komorowski Paweł , Siemion Agnieszka , Walczakowski Michał , Zagrajek Przemysław
Published: April 2022

Many modern and future systems, based on the wireless communication at the THz frequencies, could benefit from multichannel transmission. One of the possible approaches is to (de)multiplex several separate signals to and from a single transmission channel using dedicated diffractive optical elements. Proper selection of receivers for such systems is crucial and strongly depends not only on the frequencies used but also on the geometry of the setup. In this article, we present a complex analysis of the applicability of various detectors for the characterization of highly convergent and off-axis beams. Three three-focal-spot diffractive lenses have been designed, optimized and manufactured to verify the influence of parameters such as focal length, focal position shift, deflection angle or radiation frequency on the proper detection and separation of focal spots using different receivers. The reliable characterization of multi-focal-point structures can be performed only with high-acceptance-angle detectors, such as, for example, field-effect transistors equipped with a patch antenna. On the other hand, for the detection of a single demultiplexed signal, a much more directive receiver can be applied, as long as it is placed at a proper angle.
Hemp Cultivation in Soils Polluted by Cd, Pb and Zn in the Mediterranean Area: Sites Characterization and Phytoremediation in Real Scale Settlement
Authors: Canu Marta , Mulè Paolo , Spanu Erminio , Fanni Stefania , Marrone Alessandro , Carboni Gianluca
Published: April 2022

Polluting activities affect, directly or indirectly, large areas of agricultural lands. Metal polluted soils could be managed by phytoremediation using hemp (Cannabis sativa L.). To know the phytoremediation capability of industrial hemp in metal polluted soils under semiarid environments, an experimental project with the support of local farmers was conducted in Sardinia (Italy). This work was carried out in three main steps: (i) identification and selection of the study sites, (ii) field trials, at local farms, both on contaminated and non-polluted sites, (iii) evaluation of heavy metals contents accumulated in the different parts of the plants. Five study sites were chosen. Three of them were severely polluted by heavy metals. Concentrations of Zn and Cd in plants generally were positively correlated with soil content and were different in each part of the plant. The higher values of Zn and Cd were detected in leaves of plants grown in polluted sites (Zn > 950 mg kg−1 and Cd > 6.8 mg kg−1). High values of Pb were also detected in plants grown in non-contaminated soils: this contamination may be due to atmospheric deposition related to polluting sources far to the cultivation.
Blockchain-based Multifactor Authentication for Future 6G Cellular Networks: A Systematic Review
Authors: Asim Jamil , Khan Adnan Shahid , Saqib Rashad Mahmood , Abdullah Johari , Ahmad Zeeshan , Honey Shehla , Afzal Shehroz , Alqahtani Malak S. , Abbas Mohamed
Published: April 2022

There are continued advances in the internet and communication fields regarding the deployment of 5G-based applications. It is expected that by 2030, 6G applications will emerge as a continued evolution of the mobile network. Blockchain technology is one of the leading supporting technologies predicted to provide a secure and unique network to 6G-enabled devices, transactions, and applications. It is anticipated that the 6G mobile networks will be virtualized, have cloud-based systems, and aim to be the foundation for the Internet of Everything. However, along with the development of communication technologies, threats from malicious parties have become more sophisticated, making security a significant concern for the 6G era in the future. Despite enormous efforts by researchers to improve security and authentication protocols, systems still face novel intrusion and attacks. Recently, multifactor authentication techniques (MFA) have been deployed as potential solutions to attacks in blockchains. The 6G applications and the cellular network have specific vulnerabilities that need to be addressed using blockchain-based MFA technologies. The current paper is a systematic review that discusses the three technologies under consideration; then, several studies are reviewed that discuss MFA techniques in general and use blockchains as potential solutions to future security and authentication issues that may arise for 6G applications.
A2BCF: An Automated ABC-Based Feature Selection Algorithm for Classification Models in an Education Application
Authors: Zahedi Leila , Ghareh Mohammadi Farid , Amini Mohammad Hadi
Published: April 2022

Feature selection is an essential step of preprocessing in Machine Learning (ML) algorithms that can significantly impact the performance of ML models. It is considered one of the most crucial phases of automated ML (AutoML). Feature selection aims to find the optimal subset of features and remove the noninformative features from the dataset. Feature selection also reduces the computational time and makes the data more understandable to the learning model. There are various heuristic search strategies to address combinatorial optimization challenges. This paper develops an Automated Artificial Bee Colony-based algorithm for Feature Selection (A2BCF) to solve a classification problem. The application domain evaluating our proposed algorithm is education science, which solves a binary classification problem, namely, undergraduate student success. The modifications made to the original Artificial Bee Colony algorithm make the algorithm a well-performed approach.
Cellular Effects of Silver Nanoparticle Suspensions on Lung Epithelial Cells and Macrophages
Authors: Shimizu Kaori , Kashiwada Shosaku , Horie Masanori
Published: April 2022

Background: Silver nanoparticles (AgNPs) are used in industrial applications as catalysts, sanitary materials, and health supplements. Generally, AgNPs have shown cytotoxicity such as cell membrane damage. However, the mechanisms of their toxicity have not been completely elucidated. Methods: The cellular effects (cell viability, induction of chemokine and cellular oxidative stress) of two AgNP water suspensions (AgNP-A for cosmetic application and AgNP-B for industrial application) on epithelial-like A549 cells and macrophage-like differentiated THP-1 (dTHP-1) cells were examined. Results: AgNPs caused enhancement of IL-8 expression and oxidative stress. The cellular uptake of AgNP-A cells was observed. However, the cellular uptake of AgNP-B into A549 cells was hardly observed. Moreover, the intracellular Ag level was increased by AgNP suspensions exposure. Cell viability was not affected by AgNP suspensions exposure. Conclusions: AgNPs induce chemokine expression and cellular oxidative stress on culture cells. The intracellular Ag level may be important for these cellular effects.
Differential Expression of MicroRNAs in Dark-Cutting Meat from Beef Carcasses
Authors: Riggs Penny K. , Therrien Dustin A. , Vaughn Robert N. , Rotenberry Marissa L. , Davis Brian W. , Herring Andy D. , Riley David G. , Cross H. Russell
Published: April 2022

“Dark-cutting” meat in beef carcasses can result from conditions such as long-term stress and depleted glycogen stores, but some aspects of the physiological mechanisms that cause dark-cutting phenotypes remain poorly understood. Certain responses to stress factors in fully developed tissues are known to be regulated by specific microRNAs. We investigated microRNA expression in Longissimus lumborum biopsies from carcasses derived from a contemporary group of 78 steers from which a high incidence of dark-cutting meat occurred. Our objective was to identify any potential microRNA signatures that reflect the impact of environmental factors and stresses on genetic signaling networks and result in dark-cutting beef (also known as dark, firm, and dry, or DFD) in some animals. MicroRNA expression was quantified by Illumina NextSeq small RNA sequencing. When RNA extracts from DFD muscle biopsy samples were compared with normal, non-DFD (NON) samples, 29 differentially expressed microRNAs were identified in which expression was at least 20% different in the DFD samples (DFD/NON fold ratio ≤0.8 or ≥1.2). When correction for multiple testing was applied, a single microRNA bta-miR-2422 was identified at a false discovery probability (FDR) of 5.4%. If FDR was relaxed to 30%, additional microRNAs were differentially expressed (bta-miR-10174-5p, bta-miR-1260b, bta-miR-144, bta-miR-142-5p, bta-miR-2285at, bta-miR-2285e, bta-miR-3613a). These microRNAs may play a role in regulating aspects of stress responses that ultimately result in dark-cutting beef carcasses.
Nonuniform Dual-Rate Extended Kalman-Filter-Based Sensor Fusion for Path-Following Control of a Holonomic Mobile Robot with Four Mecanum Wheels
Authors: Pizá Ricardo , Carbonell Rafael , Casanova Vicente , Cuenca Ángel , Salt Llobregat Julián J.
Published: April 2022

This paper presents an extended Kalman-filter-based sensor fusion approach, which enables path-following control of a holonomic mobile robot with four mecanum wheels. Output measurements of the mobile platform may be sensed at different rates: odometry and orientation data can be obtained at a fast rate, whereas position information may be generated at a slower rate. In addition, as a consequence of possible sensor failures or the use of lossy wireless sensor networks, the presence of the measurements may be nonuniform. These issues may degrade the path-following control performance. The consideration of a nonuniform dual-rate extended Kalman filter (NUDREKF) enables us to estimate fast-rate robot states from nonuniform, slow-rate measurements. Providing these estimations to the motion controller, a fast-rate control signal can be generated, reaching a satisfactory path-following behavior. The proposed NUDREKF is stated to represent any possible sampling pattern by means of a diagonal matrix, which is updated at a fast rate from the current, existing measurements. This fact results in a flexible formulation and a straightforward algorithmic implementation. A modified Pure Pursuit path-tracking algorithm is used, where the reference linear velocity is decomposed into Cartesian components, which are parameterized by a variable gain that depends on the distance to the target point. The proposed solution was evaluated using a realistic simulation model, developed with Simscape Multibody (Matlab/Simulink), of the four-mecanum-wheeled mobile platform. This model includes some of the nonlinearities present in a real vehicle, such as dead-zone, saturation, encoder resolution, and wheel sliding, and was validated by comparing real and simulated behavior. Comparison results reveal the superiority of the sensor fusion proposal under the presence of nonuniform, slow-rate measurements.
A Personalized Learning Service Compatible with Moodle E-Learning Management System
Authors: Chang Yi-Chun , Li Jian-Wei , Huang De-Yao
Published: April 2022

Among the numerous learning management platforms, Moodle is free, open-source software supporting expanding and modularized system functions and services to facilitate online courses or online resources and interactive activities. This study enhanced a personalized learning service for the Moodle e-learning management system, which synchronizes the user’s identity according to the user information database of the third-party user management platform system. According to the user’s demand to provide a personalized e-course, including personalized learning process, e-materials, and learning path to improve learning efficiency. This study adopted the pre-test and post-test achievement to compare the benefit of the personalized e-learning platform. Research samples were students in the “programming” course at the Technology University in central Taiwan. The experiment results indicate: (i) The average post-test result after using the proposed platform was higher than the average pre-test result (before using the proposed platform). (ii) The learning effect gap in the post-test between students was less than in the pre-test result. Hence, the proposed personalized e-learning platform was beneficial.
The Virtual Reconstruction of the Aesculapius and Hygeia Statues from the Sanctuary of Isis in Lilybaeum: Methods and Tools for Ancient Sculptures’ Enhancement
Authors: Fazio Leonarda , Lo Brutto Mauro , Gonizzi Barsanti Sara , Malatesta Saverio Giulio
Published: April 2022

Thanks to recent technological developments in 3D surveys, computer graphics and virtual reality, new scenarios have been opened for the documentation and enhancement of ancient sculptures. When not totally preserved, sculptures can be digitally reproduced, modified and visualized to simulate their physical or virtual reconstruction in a non-invasive way for specialists or for dissemination aims. The virtual sculptural reconstruction process starts usually from the 3D survey of real fragments, and then continues by integrating missing parts with 3D modelling techniques by means of source evaluation. Along with primary data sources (reality-based model), secondary data sources (photos, drawings and 3D models of similar sculptures) can be directly used in the reconstruction process. This approach has a double advantage of making the reconstruction activities easier and less arbitrary, contributing to a decrease in the degree of uncertainty for the sculptural reconstruction work, also thanks to many iconographic comparisons to ancient copies. Moreover, virtual reconstruction can be easily visualized alongside a scalable rendering system using open-source Web3D apps and platforms, accessing information, 3D models and descriptions in order to enhance the experience of artworks. Inspecting theoretical and technical approaches, this work aims at establishing how primary and secondary data sources can be effectively used in sculptural reconstruction workflows, and how 3D outputs can be applied to implement digital sculptural heritage exploitation for museums and cultural institutions. The statues of Aesculapius and Hygeia from the sanctuary of Isis in Lilybaeum (Marsala, Italy) were chosen as a case study.
Antioxidant, Antimicrobial and Antibiofilm Properties of Glechoma hederacea Extracts Obtained by Supercritical Fluid Extraction, Using Different Extraction Conditions
Authors: Gwiazdowska Daniela , Uwineza Pascaline Aimee , Frąk Szymon , Juś Krzysztof , Marchwińska Katarzyna , Gwiazdowski Romuald , Waśkiewicz Agnieszka
Published: April 2022

Glechoma hederacea var. longituba is a herbaceous plant from the Lamiaceae family, used in herbal medicine. In this work, we aimed to assess the total phenolic content, antioxidant, antimicrobial and antibiofilm activity of extracts obtained from G. hederacea via supercritical dioxide extraction with methanol as a co-solvent under different extraction conditions. The results showed that the activity of the obtained SC-CO2 extracts is strongly dependent on the extraction temperature. Significantly higher total polyphenol content, as well as antioxidant and antimicrobial activity towards bacteria and yeasts, was observed in the extract obtained at 40 °C, compared to extracts obtained at 50 °C and 60 °C; however, antifungal activity against filamentous fungi was not dependent on the extraction conditions. Antimicrobial activity also depended on the microorganism type. Higher sensitivity was exhibited by Gram-positive bacteria than by Gram-negative bacteria, with S. aureus and P. aeruginosa being the most sensitive species among each group. The most susceptible fungi were Candida albicans and Sclerotinia sclerotiorum. The antibiofilm activity was differentiated and depended on the extraction conditions, the microorganism and the method of biofilm treatment. All tested extracts inhibited biofilm formation, with the extract obtained at 40 °C showing the highest value, whereas only extract obtained at 60 °C efficiently removed mature biofilm.
Influence of Rutin, Sinapic Acid, and Naringenin on Binding of Tyrosine Kinase Inhibitor Erlotinib to Bovine Serum Albumin Using Analytical Techniques Along with Computational Approach
Authors: Wani Tanveer A. , Bakheit Ahmed H. , Zargar Seema , Khayyat Arwa Ishaq A. , Al-Majed Abdulrahman A.
Published: April 2022

Flavonoid-containing food supplements are widely used as antioxidants, and the continuous use of these supplements with other drugs can lead to clinically significant interactions between these and other drugs. The medications in systemic circulation are mainly transported by serum albumin, a major transport protein. This study evaluated the interactions of rutin (RUT), naringenin (NAR), and sinapic acid (SIN) with the most abundant transport protein, bovine serum albumin (BSA), and the anticancer drug, the tyrosine kinase inhibitor Erlotinib (ETB), using various analytical methods. Interaction between multiple types of ligands with the transport proteins and competition between themselves can lead to the bound ETB’s displacement from the BSA-binding site, leading to elevated ETB concentrations in the systemic circulation. These elevated drug fractions can lead to adverse events and lower tolerance, and increased resistance to the therapeutic regimen of ETB. The experimental and computational methods, including molecular-docking studies, were used to understand the molecular interactions. The results suggested that the complexes formed were utterly different in the binary and the ternary system. Furthermore, comparing the ternary systems amongst themselves, the spectra differed from each other. They thus inferred that complexes formed between BSA-ETB in the presence of each RUT, NAR, and SIN separately were also different, with the highest value of the reduction in the binding energy in RUT, followed by SIN and then NAR. Thus, we conclude that a competitive binding between the ETB and these flavonoids might influence the ETB pharmacokinetics in cancer patients by increasing ETB tolerance or resistance.
Analysis of the Refraction Effect in Ultrasound Breast Tomography
Authors: Opieliński Krzysztof J. , Bułkowski Mariusz , Gabryel Andrzej , Wiktorowicz Andrzej
Published: April 2022

Ultrasound breast tomography (UBT) is a promising quantitative imaging method. It allows for precise analysis of ultrasound velocity distribution, which is related to tissue density and elasticity, enabling cancer detection. Only a few centers around the world have a prototype of the device for in vivo breast ultrasound tomography imaging. The quality of images reconstructed from measurements of ultrasound pulse transit times is adversely affected by the refraction of beam rays on the breast immersed in water. Refraction can be reduced using waveform tomography, ray-tracing, and ray-linking methods. However, this requires the acquisition of a pre-reconstructed pattern and is limited by extreme computational costs. In this study, the effect of refraction on transit time measurements of ultrasound passing through the female breast was analyzed under immersion conditions in water. It was found that the refraction causes the highest measurement errors in the area of the water/breast interface, and these can be reduced by adjusting the water temperature and changing the breast geometry. The results allow us to improve the quality of breast images reconstructed using an efficient transformation algorithm that assumes rectilinear ultrasound propagation paths between transmitters and receivers. In vivo breast studies were performed on the developed hybrid UBT scanner.
Modeling Several Optical Components Using Scalar Diffraction Theory
Authors: Hamam Habib
Published: April 2022

Compound systems are generally treated by geometrical optics, for instance, through the Gauss’ formalism. The objective is to simplify the process of image formation. However, this formalism does not include the wave characteristics of light and boundary effects. The treatment of diffraction is not straightforward. Thus, the extension of this formalism towards the scalar theory of diffraction is very desired. This work offers this extension and emphasizes its importance. Compound systems, including the human eye, are then modeled by Fresnel theory. For illustration, a lens-based model of the Fresnel transform is used to treat the human eye system.
Crypto-Preservation and the Ghost of Andy Warhol
Authors: Ippolito Jon
Published: April 2022

For its enthusiasts, the blockchain is an archivist’s dream come true: an immutable historical record that is publicly accessible and immune from censorship. Distributed file systems such as IPFS aim to store creative works in a redundant, networked fashion outside the control of any single cloud provider. Projects designed to work with blockchains such as Filecoin and Arweave propose a dedicated cryptocurrency as financial incentive to support the cost of governing and sustaining this “permaweb”. As dreamy as this picture sounds, many of these promises depend on technologies that have yet to be sufficiently developed or adopted. Rather than forecast the future, we can separate the hype from the reality in the present day by examining a real-life example, namely the 2021 auction of Andy Warhol’s digital art with NFTs. This essay focuses less on blockchain’s general promise as a preservation medium and more on the particular case of the digital Warhols, which both in form and spirit would seem a perfect application of NFTs to preserve historically important works of digital art. Which promises of the crypto-dream of permanent access to digital heritage ring true for this case study, and which are overblown?
Theoretical Foundation of the Relationship between Three Definitions of Effective Density and Particle Size
Authors: Peng Long , Liu Yonglin
Published: April 2022

Effective density (ρe) is universally used in atmospheric science as an alternative measure of the density (ρ) of aerosol particles, and its definitions can be expressed in terms of the particle mass (mp), ρ, mobility diameter (Dm), vacuum aerodynamic diameter (Dva), and dynamic shape factor (χ), as ρeI = 6mp/(π∙Dm3), ρeII = ρ/χ, and ρeIII = Dva/Dm. However, the theoretical foundation of these three definitions of ρe is still poorly understood before their application. Here, we explore the relationship between ρe and aerosol size through theoretical calculation. This study finds, for the first time, that ρeI and ρeIII inherently decrease with increasing size for aspherical particles with a fixed ρ and χ. We further elucidate that these inherent decreasing tendencies are governed by χ, and the ratio of the Cunningham Slip Correction Factor of the volume-equivalent diameter to that of the mobility diameter (Cc(Dve)/Cc(Dm)), but not by ρ. Taking the variable χ into consideration, the relationships of ρeI and ρeIII to particle size become more complicated, which suggests that the values of ρeI and ρeIII have little indication of the size-resolved physicochemical properties of particles. On the contrary, ρeII is independent on size for fixed χ and ρ, which indicates that the change in ρeII with size can better indicate the change in morphology and the transformation of the chemical compositions of particles. Our new insights into the essence of three ρes provide an accurate and crucial theoretical foundation for their application.
“On-Line” Heating Emissions Based on WRF Meteorology—Application and Evaluation of a Modeling System over Greece
Authors: Liora Natalia , Kontos Serafim , Parliari Daphne , Akritidis Dimitris , Poupkou Anastasia , Papanastasiou Dimitris K. , Melas Dimitrios
Published: April 2022

The main objective of the present study is the development of an “on-line” heating emissions modeling system based on simulated meteorological data and its integration with air quality modeling systems in order to improve their accuracy. The WRF-CAMx air quality modeling system is applied over Greece for the cold period of 2015 (January–April, October–December) for two emissions scenarios: using the (a) “on-line” heating emissions based on WRF meteorology and (b) “static” heating emissions based on static temporal profiles. The monthly variation in total “on-line” heating emissions followed the temporal pattern of the air temperature over Greece, leading to the highest heating emissions in January and February, while higher differences in emissions between winter and spring/autumn months were identified in comparison with the static ones. The overall evaluation of the WRF-CAMx modeling system using the “on-line” heating emissions revealed satisfactory model performance for the mean daily air quality levels. The comparison between the simulated and observed mean monthly concentrations revealed an improvement in the pattern of mean monthly concentrations for the “on-line” scenario. Higher values of the index of agreement and correlation for the mean daily values were also identified for the “on-line” scenario in most monitoring sites.
Modeling COVID-19 Incidence by the Renewal Equation after Removal of Administrative Bias and Noise
Authors: Alvarez Luis , Morel Jean-David , Morel Jean-Michel
Published: April 2022

The sanitary crisis of the past two years has focused the public’s attention on quantitative indicators of the spread of the COVID-19 pandemic. The daily reproduction number Rt, defined by the average number of new infections caused by a single infected individual at time t, is one of the best metrics for estimating the epidemic trend. In this paper, we provide a complete observation model for sampled epidemiological incidence signals obtained through periodic administrative measurements. The model is governed by the classic renewal equation using an empirical reproduction kernel, and subject to two perturbations: a time-varying gain with a weekly period and a white observation noise. We estimate this noise model and its parameters by extending a variational inversion of the model recovering its main driving variable Rt. Using Rt, a restored incidence curve, corrected of the weekly and festive day bias, can be deduced through the renewal equation. We verify experimentally on many countries that, once the weekly and festive days bias have been corrected, the difference between the incidence curve and its expected value is well approximated by an exponential distributed white noise multiplied by a power of the magnitude of the restored incidence curve.
Ischemia In Vivo Induces Cardiolipin Oxidation in Rat Kidney Mitochondria
Authors: Strazdauskas Arvydas , Trumbeckaite Sonata , Jakstas Valdas , Kamarauskaite Justina , Ivanauskas Liudas , Baniene Rasa
Published: April 2022

Cardiolipin is a mitochondrial phospholipid that plays a significant role in mitochondrial bioenergetics. Cardiolipin is oxidized under conditions like oxidative stress that occurs during ischemia/reperfusion; however, it is known that even during ischemia, many reactive oxygen species are generated. Our aim was to analyze the effect of in vivo ischemia on cardiolipin oxidation. Adult male Wistar rats were anesthetized; then, their abdomens were opened, and microvascular clips were placed on renal arteries for 30, 40 or 60 min, causing ischemia. After ischemia, kidneys were harvested, mitochondria were isolated, and lipids were extracted for chromatographic and mass spectrometric analysis of tetralinoleoyl cardiolipin and its oxidation products. Chromatographic and mass spectrometric analysis revealed a 47%, 68% and 74% decrease in tetralinoleoyl cardiolipin after 30 min, 40 min and 60 min of renal ischemia, respectively (p < 0.05). Eight different cardiolipin oxidation products with up to eight additional oxygens were identified in rat kidney mitochondria. A total of 40 min of ischemia caused an average of a 6.9-fold increase in all oxidized cardiolipin forms. We present evidence that renal ischemia in vivo alone induces tetralinoleoyl cardiolipin oxidation and depletion in rat kidney mitochondria.
Extracellular Vesicles Derived from SIPA1high Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9
Authors: Feng Lingyun , Weng Jun , Yao Chenguang , Wang Ruyuan , Wang Ning , Zhang Yilei , Tanaka Yoshimasa , Su Li
Published: April 2022

Tumour cell metastasis can be genetically regulated by proteins contained in cancer cell-derived extracellular vesicles (EVs) released to the tumour microenvironment. Here, we found that the number of infiltrated macrophages was positively correlated with the expression of signal-induced proliferation-associated 1 (SIPA1) in invasive breast ductal carcinoma tissues and MDA-MB-231 xenograft tumours. EVs derived from MDA-MB-231 cells (231-EVs) significantly enhanced macrophage migration, compared with that from SIPA1-knockdown MDA-MB-231 cells (231/si-EVs) both in vitro and in vivo. We revealed that SIPA1 promoted the transcription of MYH9, which encodes myosin-9, and up-regulated the expression level of myosin-9 in breast cancer cells and their EVs. We also found that blocking myosin-9 by either down-regulating SIPA1 expression or blebbistatin treatment led to the suppression of macrophage infiltration. Survival analysis showed that breast cancer patients with high expression of SIPA1 and MYH9 molecules had worse relapse-free survival (p = 0.028). In summary, SIPA1high breast cancer can enhance macrophage infiltration through EVs enriched with myosin-9, which might aggravate the malignancy of breast cancer.
Reduction in the Dietary VA Status Prevents Type 2 Diabetes and Obesity in Zucker Diabetic Fatty Rats
Authors: Wang Tiannan , Tang Xia , Hu Xinge , Wang Jing , Chen Guoxun
Published: April 2022

We hypothesized that the vitamin A (VA) status regulates type 2 diabetes (T2D) development in Zucker diabetic fatty (ZDF) rats. Zucker Lean and ZDF rats at weaning were fed a VA deficient with basal fat (VAD-BF, no VA and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg retinyl palmitate (RP)/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high fat (VAD-HF, 60% fat energy), VAM-HF or VAS-HF diet for 8 weeks, including an oral glucose tolerance test (OGTT) at week 7.5. The hepatic mRNA and proteins levels were determined using real-time PCR and Western blot, respectively. The VAD-BF/HF and VAM-BF/HF diets prevented peripheral hyperglycemia and attenuated obesity in ZDF rats, which occurred in the presence of the VAS-BF/HF diets. This lowered VA status reduced venous blood hyperglycemia, hyperinsulinemia and hyperlipidemia, and improved OGTT and homeostasis model assessment for insulin resistance results in ZDF rats. The expression levels of key hepatic genes for glucose and fat metabolism were regulated by VA status and dietary fat contents. An interaction between VA and HF condition was also observed. We conclude that the reduction in the dietary VA status in both BF and HF conditions prevents T2D and obesity in ZDF rats.
Cellular Distribution of Brain Aquaporins and Their Contribution to Cerebrospinal Fluid Homeostasis and Hydrocephalus
Authors: Trillo-Contreras José Luis , Ramírez-Lorca Reposo , Villadiego Javier , Echevarría Miriam
Published: April 2022

Brain aquaporins facilitate the movement of water between the four water compartments: blood, cerebrospinal fluid, interstitial fluid, and intracellular fluid. This work analyzes the expression of the four most abundant aquaporins (AQPs) (AQP1, AQP4, AQP9, and AQP11) in the brains of mice and discuss their contribution to hydrocephalus. We analyzed available data from single-cell RNA sequencing of the central nervous system of mice to describe the expression of aquaporins and compare their distribution with that based on qPCR, western blot, and immunohistochemistry assays. Expression of AQP1 in the apical cell membrane of choroid plexus epithelial cells and of AQP4 in ependymal cells, glia limitans, and astrocyte processes in the pericapillary end foot is consistent with the involvement of both proteins in cerebrospinal fluid homeostasis. The expression of both aquaporins compensates for experimentally induced hydrocephalus in the animals. Recent data demonstrate that hypoxia in aged animals alters AQP4 expression in the choroidal plexus and cortex, increasing the ventricle size and intraventricular pressure. Cerebral distensibility is reduced in parallel with a reduction in cerebrospinal fluid drainage and cognitive deterioration. We propose that aged mice chronically exposed to hypoxia represent an excellent experimental model for studying the pathophysiological characteristics of idiopathic normal pressure hydrocephalus and roles for AQPs in such disease.
Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM)
Authors: Lapuente Juan Pedro , Blázquez-Martínez Alejandro , Marco-Brualla Joaquín , Gómez Gonzalo , Desportes Paula , Sanz Jara , Fernández Pablo , García-Gil Mario , Bermejo Fernando , San Martín Juan V. , Algaba Alicia , De Gregorio Juan Carlos , Lapuente Daniel , De Gregorio Almudena , Lapuente Belén , Andrés María de la Viñas , Anel Alberto
Published: April 2022

Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.
Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus
Authors: Kaneto Hideaki , Kimura Tomohiko , Shimoda Masashi , Obata Atsushi , Sanada Junpei , Fushimi Yoshiro , Matsuoka Taka-aki , Kaku Kohei
Published: April 2022

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in β-cells are closely associated with β-cell failure in type 2 diabetes mellitus. Additionally, since incretin receptor expression is reduced in the advanced stage of diabetes mellitus, incretin-based medicines show more favorable effects against β-cell failure, especially in the early stage of diabetes mellitus compared to the advanced stage. On the other hand, many subjects have recently suffered from life-threatening coronavirus infection, and coronavirus infection has brought about a new and persistent pandemic. Additionally, the spread of coronavirus infection has led to various limitations on the activities of daily life and has restricted economic development worldwide. It has been reported recently that SARS-CoV-2 directly infects β-cells through neuropilin-1, leading to apoptotic β-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic β-cell failure, which is often observed in type 2 diabetes mellitus. Finally, we are hopeful that coronavirus infection will decline and normal daily life will soon resume all over the world.
Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy
Authors: Gianferrari Giulia , Martinelli Ilaria , Zucchi Elisabetta , Simonini Cecilia , Fini Nicola , Vinceti Marco , Ferro Salvatore , Gessani Annalisa , Canali Elena , Valzania Franco , Sette Elisabetta , Pugliatti Maura , Tugnoli Valeria , Zinno Lucia , Stano Salvatore , Santangelo Mario , De Pasqua Silvia , Terlizzi Emilio , Guidetti Donata , Medici Doriana , Salvi Fabrizio , Liguori Rocco , Vacchiano Veria , Casmiro Mario , Querzani Pietro , Currò Dossi Marco , Patuelli Alberto , Morresi Simonetta , Longoni Marco , De Massis Patrizia , Rinaldi Rita , Borghi Annamaria ,   ERRALS GROUP, Amedei Amedeo , Mandrioli Jessica
Published: April 2022

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.
Application of Real and Virtual Radial Arm Maze Task in Human
Authors: Palombi Tommaso , Mandolesi Laura , Alivernini Fabio , Chirico Andrea , Lucidi Fabio
Published: April 2022

Virtual Reality (VR) emerges as a promising technology capable of creating different scenarios in which the body, environment, and brain are closely related, proving enhancements in the diagnosis and treatment of several spatial memory deficits. In recent years, human spatial navigation has increasingly been studied in interactive virtual environments. However, navigational tasks are still not completely adapted in immersive 3D VR systems. We stipulate that an immersive Radial Arm Maze (RAM) is an excellent instrument, allowing the participants to be physically active within the maze exactly as in the walking RAM version in reality modality. RAM is a behavioral ecological task that allows the analyses of different facets of spatial memory, distinguishing declarative components from procedural ones. In addition to describing the characteristics of RAM, we will also analyze studies in which RAM has been used in virtual modality to provide suggestions into RAM building in immersive modality.
Interactive Effects of Admixtures on the Compressive Strength Development of Portland Cement Mortars
Authors: Jia Jinqing , Wang Yimu
Published: April 2022

The interaction effects of four chlorine-free admixtures such as calcium formate (CF), triethanolamine, (TEA), triisopropanolamine (TIPA), and sodium sulfate (SS) on the compressive strength development of Portland cement mortars were investigated based on the design of experiment (DoE). The results showed that both the addition of CF and SS contributed significantly to the strength of cement mortars at early curing age. However, the interaction of CF and SS could hinder their respective positive effect on the strength of cement at 1 d. At later curing ages, CF was still beneficial in improving the late strength of cement, but SS had a negative effect on the strength of cement at 28 d. A negative effect of TIPA on the strength of cement was found at 3 d. However, the positive interactive effect of TIPA and CF was sufficient to offset the negative effect of TIPA on the strength of mortars at 3 d if the dosage of CF exceeded 2%. In addition, TEA had a positive influence on 7 d strength until a turning point was reached and the optimum dosage of TEA was approximately 0.013%.
Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?
Authors: Aran Andrea , Garrigós Laia , Curigliano Giuseppe , Cortés Javier , Martí Mercè
Published: April 2022

T cells play a vital role in the anti-tumoural response, and the presence of tumour-infiltrating lymphocytes has shown to be directly correlated with a good prognosis in several cancer types. Nevertheless, some patients presenting tumour-infiltrating lymphocytes do not have favourable outcomes. The TCR determines the specificities of T cells, so the analysis of the TCR repertoire has been recently considered to be a potential biomarker for patients’ progression and response to therapies with immune checkpoint inhibitors. The TCR repertoire is one of the multiple elements comprising the immune system and is conditioned by several factors, including tissue type, tumour mutational burden, and patients’ immunogenetics. Its study is crucial to understanding the anti-tumoural response, how to beneficially modulate the immune response with current or new treatments, and how to better predict the prognosis. Here, we present a critical review including essential studies on TCR repertoire conducted in patients with cancer with the aim to draw the current conclusions and try to elucidate whether it is better to encounter higher clonality with few TCRs at higher frequencies, or higher diversity with many different TCRs at lower frequencies.
Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma
Authors: Timmins Matthew A. , Ringshausen Ingo
Published: April 2022

Transforming growth factor-beta (TGFB) is a critical regulator of normal haematopoiesis. Dysregulation of the TGFB pathway is associated with numerous haematological malignancies including myelofibrosis, acute myeloid leukaemia, and lymphoid disorders. TGFB has classically been seen as a negative regulator of proliferation in haematopoiesis whilst stimulating differentiation and apoptosis, as required to maintain homeostasis. Tumours frequently develop intrinsic resistant mechanisms to homeostatic TGFB signalling to antagonise its tumour-suppressive functions. Furthermore, elevated levels of TGFB enhance pathogenesis through modulation of the immune system and tumour microenvironment. Here, we review recent advances in the understanding of TGFB signalling in B-cell malignancies with a focus on the tumour microenvironment. Malignant B-cells harbour subtype-specific alterations in TGFB signalling elements including downregulation of surface receptors, modulation of SMAD signalling proteins, as well as genetic and epigenetic aberrations. Microenvironmental TGFB generates a protumoural niche reprogramming stromal, natural killer (NK), and T-cells. Increasingly, evidence points to complex bi-directional cross-talk between cells of the microenvironment and malignant B-cells. A greater understanding of intercellular communication and the context-specific nature of TGFB signalling may provide further insight into disease pathogenesis and future therapeutic strategies.