bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific Protein S-Glutathionylation in the Zebrafish (Danio rerio) Embryo
Authors: Marques Emily S. , Severance Emily G. , Arsenault Paige , Zahn Sarah M. , Timme-Laragy Alicia R.
Published: August 2024

Activation of Nrf2—the master regulator of antioxidative response—at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific Nrf2 cellular localization and the downstream changes in protein S-glutathionylation during critical windows of zebrafish (Danio rerio) development. Wild-type and mutant zebrafish embryos with a loss-of-function mutation in Nrf2a were treated with two canonical activators, sulforaphane (SFN; 40 µM) or tert-butylhydroquinone (tBHQ; 1 µM), for 6 h at either pharyngula, hatching, or the protruding-mouth stage. Nrf2a protein and S-glutathionylation were visualized in situ using immunohistochemistry. At the hatching stage, Nrf2a protein levels were decreased with SFN, but not tBHQ, exposure. Exposure to both activators, however, decreased downstream S-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and S-glutathionylation were identified in the pancreatic islet and liver. Protein S-glutathionylation in Nrf2a mutant fish was increased in the liver by both activators, but not the islets, indicating a tissue-specific and Nrf2a-dependent dysregulation. This work demonstrates that critical windows of exposure and Nrf2a activity may influence redox homeostasis and highlights the importance of considering tissue-specific outcomes and sensitivity in developmental redox biology.
Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus
Authors: Hung Shao-Chi , Chan Te-Fu , Chan Hsiu-Chuan , Wu Chia-Ying , Chan Mei-Lin , Jhuang Jie-Yang , Tan Ji-Qin , Mei Jia-Bin , Law Shi-Hui , Ponnusamy Vinoth Kumar , Chan Hua-Chen , Ke Liang-Yin
Published: August 2024

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.
Resolvin D5 Protects Female Hairless Mouse Skin from Pathological Alterations Caused by UVB Irradiation
Authors: Saito Priscila , Pinto Ingrid C. , Rodrigues Camilla C. A. , de Matos Ricardo L. N. , Vale David L. , Melo Cristina P. B. , Fattori Victor , Saraiva-Santos Telma , Mendes-Pierotti Soraia , Bertozzi Mariana M. , Bracarense Ana P. F. R. L. , Vignoli Josiane A. , Baracat Marcela M. , Georgetti Sandra R. , Verri Waldiceu A. , Casagrande Rubia
Published: August 2024

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action.
Effects of Hyperbaric (Non-Thermal) Sanitization and the Method of Extracting Pomegranate Juice on Its Antioxidant and Antihypertensive Properties
Authors: Campos-Lozada Gieraldin , Hernández-Miranda Jonathan , del Valle-Mondragón Leonardo , Ortiz-Polo Araceli , Betanzos-Cabrera Gabriel , Aguirre-Álvarez Gabriel
Published: August 2024

Pomegranate (Punica granatum L.) is considered a functional food due to its polyphenol content that benefits the body. The type of processing the fruit undergoes is important, as this also influences the concentrations of these compounds. The pomegranate juice was extracted by two methods: manual extraction using a manual juicer through heat treatment in a water bath (Man-P), and extraction through mechanical pressing using Good Nature X-1 equipment and hyperbaric sanitization (Mech-Hyp). Bromatological analyses showed significant differences (p ≤ 0.05) between the two treatments. When subjected to hyperbaric sanitization, the juice showed higher concentrations of moisture, soluble solids, protein, and carbohydrates. In an antioxidant analysis, the ABTS radical showed no significant difference in the treatments, with 96.99% inhibition. For the DPPH radical, the sample with the highest inhibition was Man-P with 98.48%. The determination of phenols showed that there was a higher concentration in juice that underwent pasteurization (104.566 mg GAE/mL). However, the Mech-Hyp treatment exhibited a minor concentration of phenols with 85.70 mg GAE/mL. FTIR spectra revealed that the functional groups were mainly associated with carbohydrates. Regarding ACE inhibition, it was observed that the Man-P and Mech-Hyp juices showed greater inhibition of enzyme in hypertensive patients compared to normotensive patients. This activity can be attributed to the mechanisms of action of antioxidant compounds. Both extraction methods manual and mechanical pressing resulted in increased antioxidant and antihypertensive activity. The antioxidant compounds accompanied by adequate sanitation were decisive in an antimicrobial analysis, since no pathogenic microorganisms were observed in the juices.
Application of Machine Learning in the Identification and Prediction of Maritime Accident Factors
Authors: Maceiras Candela , Cao-Feijóo Genaro , Pérez-Canosa José M. , Orosa José A.
Published: August 2024

Artificial intelligence seems to be a new point of view to classical problems that, in the past, could not be understood in depth, leaving certain gaps in each knowledge area. As an example of this, maritime accidents are one of the most recognised international problems, with clear environmental and human life consequences. From the beginning, statistical studies have shown that not only the typical sampled variables must be considered but the accidents are related to human factors that, at the same time, are related to some variables like fatigue that cannot be easily sampled. In this research work, the use of machine learning algorithms on over 300 maritime accidents is proposed to identify the relationship between human factors and the main variables. The results showed that compliance with the minimum crew members and ship length are the two most relevant variables related to each accident for the Spanish Search and Rescue (SAR) region, as well as the characteristics of the ships. These accidents could be understood as three main groups of accidents related to the general tendency to not meet the minimum number of crew members and its difference in the year of construction of the ship. Finally, it was possible to use neural networks to model accidents with sufficient accuracy (determination factor higher than 0.60), which is particularly interesting in the context of a control system for maritime transport.
Characteristics of Removal of Lead, Cadmium and Chromium from Soil Using Biosorbent and Biochar
Authors: Staroń Paweł , Zawadzka Anita , Radomski Piotr , Chwastowski Jarosław
Published: August 2024

The study proposed the use of aspen wood sawdust and biochar derived from this sawdust for the removal of Pb(II), Cd(II), and Cr(VI) ions from soil in systems containing single metals as well as a mixture of all the studied metals. The effectiveness of the applied sorbents was compared with the sorptive properties of activated carbon. The results showed that all the tested materials reduced the metal content in the soil, and the obtained biochar was able to sorb lead, cadmium, and chromium ions in both studied systems. The influence of the type of sorbent, its dose, process duration, and the impact of metal on the removal efficiency and sorption capacity was analyzed. A statistical analysis of the obtained results was also conducted, determining the influence of process parameters on the removal capabilities of metal ions. The highest Pb, Cd and Cr ion removal efficiencies were obtained in a 36-day process at a sorbent dose of 10%. Aspen sawdust, biochar and activated carbon removed 46%, 50% and 71% of Pb(II), 35%, 43% and 53% of Cd(II) and 15%, 27% and 38% of Cr(VI), respectively. In turn, the highest sorption capacity values were achieved in a 36-day process at a sorbent dose of 2%, obtaining results of 20.2 mg/g, 22.3 mg/g and 23.2 mg/g of Pb(II), 5.1 mg/g, 7.9 mg/g and 11.7 mg/g of Cd(II) and 3.8 mg/g, 5.8 mg/g and 8.5 mg/g of Cr(VI), respectively. It was found that both raw aspen wood sawdust and biochar derived from this wood are effective in removing toxic metal ions from soil, which presents a potential solution to their presence in the natural environment.
A Study on the Propulsion Performance of Hybrid-Driven Underwater Glider Equipped with a Kappel Tip Rake Propeller
Authors: Chen Chen-Wei , Lu Jia-Lin , Chen Xu-Peng , Wang Dong-Jie
Published: August 2024

In order to solve the problem of the lack of maneuverability of the conventional underwater glider, this paper proposes a hybrid-driven underwater glider equipped with a Kappel tip rake propeller, analyzes the propulsion performance of different types of Kappel tip rake propellers in the wake field of the hybrid-driven underwater glider, optimizes the overall propulsion performance of the hybrid-driven underwater glider, and realizes self-propulsion and gliding with high efficiency and low energy consumption. In the research process, the Schnerr–Sauer cavitation model and the cavitation simulation strategy of VOF two-phase flow were adopted, coupled with the SST k-ω and γ transition turbulence model, and the control calculation error was not more than 3%. Based on the hydrodynamic performance study of the Kappel tip rake propeller, the self-propelled simulation was carried out under the working conditions of 6 kn, 5 kn, 4 kn, and 3 kn, and the gliding simulation was carried out under the working conditions of 1 kn, 0.5 kn, and a glide angle of 12°. The propulsion performance of the hybrid-driven underwater glider with different models of Kappel tip rake propellers was analyzed. It was found that the maximum open water propulsion efficiency of the propeller Kap05 had the largest improvement, which was 3.07% higher than that of the reference base propeller. Under the self-propelled condition, the hybrid-driven underwater glider with the propeller Kap05 had the lowest wake fraction, and the propellers Kap04 and Kap05 had the best propulsion performance in the wake field of the hybrid-driven underwater glider. In the gliding condition, the form of the folding paddle can reduce the gliding resistance generated by the propeller by more than 45% and the gliding negative lift by more than 68%. A moderate tip rake can effectively improve the propulsion efficiency of the Kappel tip rake propeller in the wake field of the hybrid-driven underwater glider, reduce energy loss, and improve the overall performance of the hybrid-driven underwater glider.
The Influence of Variable Plasma Welding Parameters on Weld Geometry, Dilution Factor, and Microhardness
Authors: Bazychowska Sylwia , Panasiuk Katarzyna , Starosta Robert
Published: August 2024

Weld surfacing is the process of applying a layer of metal to the surface of metal objects by simultaneously melting the substrate. As a result of this process, the metal content of the padding weld can be as high as several tens of percents. It is a method used to regenerate machine parts and improve the properties of the surface layer, increasing its resistance to abrasion, corrosion, erosion, and cavitation. It also supports the repair and creation of permanent protective coatings in the engineering, automotive, energy, and aerospace industries. This makes it possible to repair damaged parts instead of completely replacing them, saving time and production costs. Plasma surfacing technology is used for components that require high hardness and corrosion resistance under various environmental conditions. Plasma wire surfacing is not sufficiently presented and described in the current literature, which creates problems in determining the appropriate process parameters. The influence of variable plasma surfacing parameters on steel C45 significantly affects surfacing weld geometry, the dilution factor, and microhardness. Higher currents can increase the dilution factor, integrating more base metal into the weld pool, which may alter the chemical composition and mechanical properties of the weld. Variations in surfacing speed and heat input also affect the microhardness of the surfaced joint, with higher heat inputs potentially leading to softer welds due to slower cooling rates. Optimizing these parameters is essential to achieving desired surfacing weld characteristics and ensuring the structural integrity of C45 steel joints. This paper presents the influence of varying plasma surfacing parameters on the surfacing geometry, the dilution factor, and microhardness. The tests were carried out on a Panasonic TM-1400 GIII automated surfacing machine with CastoMag 45554S solid wire as the filler material. Flat bars of C45 steel were prepared, and then the variable parameters of the surfacing process were developed. Tests were carried out to determine the dilution factor, followed by microhardness measurements. The results showed a significant dependence of the effect of the parameters on the surfacing geometry and the dilution factor.
Prevalence of Medical Conditions and Medication Usage: Implications for Oral Health among Older Adults in Rural Victoria
Authors: Mariño Rodrigo , Glenister Kristen , Bourke Lisa , Simmons David
Published: August 2024

(1) Background: A study was undertaken to provide a comprehensive profile of the prevalence and distribution, by selected socio-demographic characteristics, of chronic diseases and health conditions including those that impact the oral health and oral health self-care of independently living older adults in rural areas of the state of Victoria; (2) Methods: The study analyzed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants responded to questionnaires about their medical health history, health service use, and socio-demographics. In total, 572 attended a 2-h health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD = 9.2) years. Participants had a high prevalence of medical conditions; the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, and the potential impact on the oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.
MAPPNet: A Multi-Scale Attention Pyramid Pooling Network for Dental Calculus Segmentation
Authors: Nie Tianyu , Yao Shihong , Wang Di , Wang Conger , Zhao Yishi
Published: August 2024

Dental diseases are among the most prevalent diseases globally, and accurate segmentation of dental calculus images plays a crucial role in periodontal disease diagnosis and treatment planning. However, the current methods are not stable and reliable enough due to the variable morphology of dental calculus and the blurring of the boundaries between the dental edges and the surrounding tissues; therefore, our hope is to propose an accurate and reliable calculus segmentation algorithm to improve the efficiency of clinical detection. We propose a multi-scale attention pyramid pooling network (MAPPNet) to enhance the performance of dental calculus segmentation. The network incorporates a multi-scale fusion strategy in both the encoder and decoder, forming a model with a dual-ended multi-scale structure. This design, in contrast to employing a multi-scale fusion scheme at a single end, enables more effective capturing of features from diverse scales. Furthermore, the attention pyramid pooling module (APPM) reconstructs the features on this map by leveraging a spatial-first and channel-second attention mechanism. APPM enables the network to adaptively adjust the weights of different locations and channels in the feature map, thereby enhancing the perception of important regions and key features. Experimental evaluation of our collected dental calculus segmentation dataset demonstrates the superior performance of MAPPNet, which achieves an intersection-over-union of 81.46% and an accuracy rate of 98.35%. Additionally, on two publicly available datasets, ISIC2018 (skin lesion dataset) and Kvasir-SEG (gastrointestinal polyp segmentation dataset), MAPPNet achieved an intersection-over-union of 76.48% and 91.38%, respectively. These results validate the effectiveness of our proposed network in accurately segmenting lesion regions and achieving high accuracy rates, surpassing many existing segmentation methods.
WCET Analysis Based on Micro-Architecture Modeling for Embedded System Security
Authors: Li Meng , Xiao Kun , Zhou Yong , Huang Dajun
Published: August 2024

To ensure the timely execution of hard real-time applications, scheduling analysis techniques must consider safe upper bounds on the possible execution durations of tasks or runnables, which are referred to as Worst-Case Execution Times (WCET). Bounding WCET requires not only program path analysis but also modeling the impact of micro-architectural features present in modern processors. In this paper, we model the ARMv8 ISA and micro-architecture including instruction cache, branch predictor, instruction prefetching strategies, out-of-order pipeline. We also consider the complex interactions between these features (e.g., cache misses caused by branch predictions and branch misses caused by instruction pipelines) and estimate the WCET of the program using the Implicit Path Enumeration Technique (IPET) static WCET analysis method. We compare the estimated WCET of benchmarks with the observed WCET on two ARMv8 boards. The ratio of estimated to observed WCET values for all benchmarks is greater than 1, demonstrating the security of the analysis.
Research on Vehicle-Road Intelligent Capacity Redistribution and Cost Sharing in the Context of Collaborative Intelligence
Authors: Zhu Guangyu , Zhao Fuquan , Song Haokun , Zhang Wang , Liu Zongwei
Published: August 2024

The vehicle-road collaborative intelligence approach has become an industry consensus. It can efficiently tackle the technical hurdles and reduce the performance requirements and costs of on-board perception and computing devices. There is a need for in-depth quantitative studies to optimize the allocation of vehicle-road intelligent capabilities for collaborative intelligence. However, current research tends to focus more on qualitative analysis, and there is little research on the redistribution of vehicle and roadside intelligent capabilities. In this paper, we present a model for distributing perception and computing capabilities between vehicle-side and roadside, ensuring to meet the needs of various autonomous driving levels. Meanwhile, the collaborative intelligence approach will also introduce the costs of intelligent infrastructure deployment, energy, and maintenance. Different roads have varying scene characteristics and usage intensities. It is necessary to conduct a cost-effectiveness analysis of the intelligent deployment of different road types. A vehicle-road cost allocation model is developed based on the lifecycle traveled distance of vehicles and the lifecycle traffic flow of various roads to evaluate the function-cost effectiveness. Our study presents several vehicle-road intelligent schemes that meet the needs of various autonomous driving levels and selects Beijing for case analysis. The results indicate that primary intelligent infrastructure can reduce the lifecycle cost of the vehicle-side intelligent scheme for intermediate autonomous driving from ¥65,301 to ¥37,703, and advanced intelligent infrastructure can reduce the lifecycle cost for advanced autonomous driving from ¥126,938 to ¥42,180. Considering the distributed cost of vehicle-side and roadside, urban roads in Beijing have higher function-cost effectiveness compared to highways, especially urban expressways, which are expected to generate 43.3 times the vehicle-function-cost benefits after the advanced intelligent upgrades. The corresponding research findings can serve as a reference for city managers to make decisions on intelligent road deployment.
Preparation and Properties of Waterborne Polyurethane and SBS Composite-Modified Emulsified Asphalt
Authors: Chen Ruiqi , Xu Wen , Chen Yixing
Published: August 2024

To address the issue of insufficient durability of traditional modified emulsified asphalt in the application of cold mix and cold paving anti-skid wear layers, this study utilizes cationic waterborne polyurethane (PU+) for composite modification to enhance adhesion and performance across a range of temperatures. Initially, composite-modified emulsified asphalt samples were prepared with varying dosages of PU+ according to a gradient method. Routine performance tests were conducted on the evaporated residues for analysis. Advanced rheological tests, including temperature sweep (TS), frequency sweep (FS), linear amplitude sweep (LAS), and multi-stress creep recovery (MSCR) tests, were performed using a dynamic shear rheometer (DSR). Surface free energy (SFE) tests were conducted with a fully automated surface tension meter (STM). A comprehensive evaluation of the high-temperature rheological properties, fatigue properties, adhesion properties, and water damage resistance of the modified emulsified asphalt residues was carried out. Chemical changes before and after modification were characterized using Fourier transform infrared spectroscopy (FTIR), and the distribution of polymers in the evaporated residue was observed using fluorescence microscopy (FM). The results demonstrated that cationic waterborne polyurethane significantly enhanced the fatigue and adhesion properties of SBS-modified emulsified asphalt, but it also weakened the water damage resistance of asphalt. MSCR tests revealed that the addition of cationic waterborne polyurethane might reduce the elastic recovery performance of modified asphalt, thereby weakening its resistance to rutting. Among the samples, the modified asphalt with a PU+ content of 6% exhibited good high-temperature shear resistance and elastic recovery performance, demonstrating the best anti-rutting performance.
Industrial Image Anomaly Detection via Self-Supervised Learning with Feature Enhancement Assistance
Authors: Wu Bin , Wang Xiaoqi
Published: August 2024

Industrial anomaly detection is constrained by the scarcity of anomaly samples, limiting the applicability of supervised learning methods. Many studies have focused on anomaly detection by generating anomaly images and adopting self-supervised learning approaches. Leveraging pre-trained networks on ImageNet has been explored to assist in this training process. However, achieving accurate anomaly detection remains time-consuming due to the network’s depth and parameter count not being reduced. In this paper, we propose a self-supervised learning method based on Feature Enhancement Patch Distribution Modeling (FEPDM), which generates simulated anomalies. Unlike direct training on the original feature extraction network, our approach utilizes a pre-trained network to extract multi-scale features. By aggregating these multi-scale features, we are able to train at the feature level, thereby adapting more efficiently to various network structures and reducing domain bias with respect to natural image classification. Additionally, it significantly reduces the number of parameters in the training process. Introducing this approach not only enhances the model’s generalization ability but also significantly improves the efficiency of anomaly detection. The method was evaluated on MVTec AD and BTAD datasets, and (image-level, pixel-level) AUROC scores of (95.7%, 96.2%), (93.4%, 97.6%) were obtained, respectively. The experimental results have convincingly demonstrated the efficacy of our method in tackling the scarcity of abnormal samples in industrial scenarios, while simultaneously highlighting its broad generalizability.
Detection of Novel Objects without Fine-Tuning in Assembly Scenarios by Class-Agnostic Object Detection and Object Re-Identification
Authors: Eisenbach Markus , Franke Henning , Franze Erik , Köhler Mona , Aganian Dustin , Seichter Daniel , Gross Horst-Michael
Published: August 2024

Object detection is a crucial capability of autonomous agents for human–robot collaboration, as it facilitates the identification of the current processing state. In industrial scenarios, it is uncommon to have comprehensive knowledge of all the objects involved in a given task. Furthermore, training during deployment is not a viable option. Consequently, there is a need for a detector that is able to adapt to novel objects during deployment without the necessity of retraining or fine-tuning on novel data. To achieve this, we propose to exploit the ability of discriminative embeddings learned by an object re-identification model to generalize to unknown categories described by a few shots. To do so, we extract object crops with a class-agnostic detector and then compare the object features with the prototypes of the novel objects. Moreover, we demonstrate that the embedding is also effective for predicting regions of interest, which narrows the search space of the class-agnostic detector and, consequently, increases processing speed. The effectiveness of our approach is evaluated in an assembly scenario, wherein the majority of objects belong to categories distinct from those present in the training datasets. Our experiments demonstrate that, in this scenario, our approach outperforms the current best few-shot object-detection approach DE-ViT, which also does not perform fine-tuning on novel data, in terms of both detection capability and inference speed.
Differential Geometry and Its Application, 2nd Edition
Authors: Stanković Mića S.
Published: August 2024

With this Editorial, we present a Special Issue of Axioms entitled ‘Differential Geometry and Its Application, 2nd edition’ [...]
Rare Earth Element Content in Hair Samples of Children Living in the Vicinity of the Kola Peninsula Mining Site and Nervous System Diseases
Authors: Belisheva Natalia K. , Drogobuzhskaya Svetlana V.
Published: August 2024

The aim of this study is to assess the rare earth element (REE) content in hair samples of children living in Lovozero village, near an REE mining site, and the possible effects of REEs on the prevalence of nervous system diseases in Lovozersky District (Murmansk region, Kola Peninsula). Fifty-three school-age children were recruited for the analysis of REE content in hair samples. REE (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) content was estimated by means of inductively coupled plasma mass spectrometry (ICP-MS). The analysis of REE content in the hair of children living in Russia, Kazakhstan, and China indicated REE intake from the environment. The possible contribution of REEs to nervous system disorders is supported by the link between the REE content in hair samples of children living near REE mining areas (China) and the manifestation of cognitive disorders in these children. It is also found that the prevalence of nervous system diseases in children aged 15–17 years is higher in Lovozersky District compared to the other districts of the Murmansk region. In this paper, the possible contribution of REEs to the prevalence of episodic paroxysmal disorders (G40–G47), cerebral palsy (G80–G83), and epilepsy and status epilepticus (G40–G41) is discussed.
Neutralizing Oxidized Phosphatidylcholine Reduces Airway Inflammation and Hyperreactivity in a Murine Model of Allergic Asthma
Authors: Vaghasiya Jignesh , Jha Aruni , Basu Sujata , Bagan Alaina , Jengsuksavat Siwon K. , Ravandi Amir , Pascoe Christopher D. , Halayko Andrew J.
Published: August 2024

Oxidative stress is associated with asthma pathobiology. We reported that oxidized phosphatidylcholines (OxPCs) are mediators of oxidative stress and accumulate in the lung in response to allergen challenge. The current study begins to unravel mechanisms for OxPC accumulation in the lung, providing the first insights about how OxPCs underpin allergic airway pathophysiology, and pre-clinical testing of selective neutralization of OxPCs in a murine model of allergic asthma. We hypothesized that intranasal delivery of E06, a natural IgM antibody that neutralizes the biological activity of OxPCs, can ameliorate allergen-induced airway inflammation and airway hyperresponsiveness. Adult BALB/c mice were intranasally (i.n.) challenged with house dust mite (HDM) (25 μg/mouse, 2 weeks). Some animals also received E06 monoclonal antibody (mAb) (10 µg) i.n. 1 hr before each HDM challenge. HDM challenge reduced mRNA for anti-oxidant genes (SOD1, SOD2, HO-1, and NFE2L2) in the lung by several orders of magnitude (p < 0.05). Concomitantly, total immune cell number in bronchoalveolar lavage fluid (BALF) increased significantly (p < 0.001). E06 mAb treatment prevented allergen-induced BALF immune cell number by 43% (p < 0.01). This included a significant blockade of eosinophils (by 48%, p < 0.001), neutrophils (by 80%, p < 0.001), macrophages (by 80%, p < 0.05), and CD4 (by 30%, p < 0.05) and CD8 (by 42%, p < 0.01) lymphocytes. E06 effects correlated with a significant reduction in TNF (by 64%, p < 0.001) and IL-1β (by 75%, p < 0.05) and a trend to diminish accumulation of other cytokines (e.g., IL-4, -10, and -33, and IFN-γ). E06 mAb treatment also inhibited HDM exposure-induced increases in total respiratory resistance and small airway resistance by 24% and 26%, respectively. In conclusion, prophylactic treatment with an OxPC-neutralizing antibody significantly limits allergen-induced airway inflammation and airway hyperresponsiveness, suggesting that OxPCs are important mediators of oxidative stress-associated allergic lung pathophysiology.
Assembly, Activation, and Helicase Actions of MCM2-7: Transition from Inactive MCM2-7 Double Hexamers to Active Replication Forks
Authors: You Zhiying , Masai Hisao
Published: August 2024

In this review, we summarize the processes of the assembly of multi-protein replisomes at the origins of replication. Replication licensing, the loading of inactive minichromosome maintenance double hexamers (dhMCM2-7) during the G1 phase, is followed by origin firing triggered by two serine–threonine kinases, Cdc7 (DDK) and CDK, leading to the assembly and activation of Cdc45/MCM2-7/GINS (CMG) helicases at the entry into the S phase and the formation of replisomes for bidirectional DNA synthesis. Biochemical and structural analyses of the recruitment of initiation or firing factors to the dhMCM2-7 for the formation of an active helicase and those of origin melting and DNA unwinding support the steric exclusion unwinding model of the CMG helicase.
Rotational Thromboelastometric Profile in Early Sepsis: A Prospective Cohort Study
Authors: Czempik Piotr F. , Wiórek Agnieszka
Published: August 2024

Background: Coagulation abnormalities are common in sepsis patients and are associated with increased mortality. This study aimed to assess the hemostatic profile of sepsis patients using rotational thromboelastometry (ROTEM) and to find the ROTEM parameters best predicting short-term mortality. Methods: We conducted a prospective analysis of consecutive sepsis patients hospitalized in the intensive care unit. The inclusion criteria were diagnosis of sepsis or septic shock and pro-calcitonin concentration >0.5 ng mL−1. Clinical, standard laboratory, and ROTEM analyses were performed. Results: The study group comprised 38 (49%) males and 40 (51%) females. Median Sequential Organ Failure Assessment (SOFA) score was 8 (interquartile range IQR 5–11) points. The most common primary sites of infection were pneumonia (n = 27/35%), intra-abdominal (n = 27/35%), urinary tract infection (n=20/26%), and others (n = 4/6%). The following parameters evaluating fibrinogen function were outside the reference range: clotting time (CT), clot amplitude (A) at 10 and 20 min, and maximal clot firmness (MCF). Out of 78 patients, 28 (36%) died in the intensive care unit. Significant differences between survivors and non-survivors of sepsis were present for the ROTEM parameters assessing fibrinolytic activity. Conclusions: ROTEM in the early phase of sepsis reveals increased coagulation mediated through the function of fibrinogen. Non-survivors showed slightly lower fibrinolytic activity than survivors; however, it was still within test reference values. The highest predicting value was obtained by a model incorporating, among others, extrinsic coagulation pathway fibrinolytic parameters.
Molecular Hydrogen and Extracorporeal Gas Exchange: A Match Made in Heaven? An In Vitro Pilot Study
Authors: Mouzakis Foivos Leonidas , Hima Flutura , Kashefi Ali , Greven Johannes , Rink Lothar , van der Vorst Emiel P. C. , Jankowski Joachim , Mottaghy Khosrow , Spillner Jan
Published: August 2024

Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC treatments themselves are also responsible for sustaining or promoting inflammation. On these grounds, an in vitro study was designed to investigate the therapeutic potential of molecular hydrogen (H2) against pro-inflammatory agents in ECC settings. Five miniature ECMO circuits and a small vial (Control) were primed with heparinized blood from healthy adult donors (n = 7). Three of the ECMO systems were injected with lipopolysaccharide (LPS), out of which one was additionally treated with an H2 gas mixture. After 6 h, samples were drawn for the assessment of specific biomarkers (MCP-1, MPO, MDA-a, TRX1, and IL-6). Preliminary results indicate a progressive oxidative and inflammatory response between the six systems. Circulation has triggered inflammation and blood trauma, but the staggering influence of LPS in this outcome is indisputable. Accordingly, hydrogen’s remedial potential becomes immediately apparent as biomarker concentrations tend to be lower in the H2-handled circuit. Future research should have distinct objectives (e.g., dosage/duration/cycle of hydrogen administration) in order to ascertain the optimal protocol for patient treatment.
Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment
Authors: Mima Yoshihito , Ohtsuka Tsutomu , Ebato Ippei , Nakata Yukihiro , Tsujita Akihiro , Nakazato Yoshimasa , Norimatsu Yuta
Published: August 2024

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body’s immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1–PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1–PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.
Insulin Resistance, a Risk Factor for Alzheimer’s Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach
Authors: Affuso Flora , Micillo Filomena , Fazio Serafino
Published: August 2024

Peripheral insulin resistance (IR) is a well-documented, independent risk factor for the development of type 2 diabetes, cardiovascular disease, cancer and cellular senescence. Recently, the brain has also been identified as an insulin-responsive region, where insulin acts as regulator of the brain metabolism. Despite the clear link between IR and the brain, the exact mechanisms underlying this relationship remain unclear. Therapeutic intervention in patients showing symptoms of neurodegenerative diseases has produced little or no results. It has been demonstrated that insulin resistance plays a significant role in the pathogenesis of neurodegenerative diseases, particularly cognitive decline. Peripheral and brain IR may represent a modifiable state that could be used to prevent major brain disorders. In this review, we will analyse the scientific literature supporting IR as a risk factor for Alzheimer’s disease and suggest some therapeutic strategies to provide a new proposal for the prevention of brain IR and its consequences.
The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell
Authors: Maqoud Fatima , Simone Laura , Tricarico Domenico , Camerino Giulia Maria , Antonacci Marina , Nicchia Grazia Paola
Published: August 2024

K+ channels do play a role in cell shape changes observed during cell proliferation and apoptosis. Research suggested that the dynamics of the aggregation of Aquaporin-4 (AQP4) into AQP4-OAP isoforms can trigger cell shape changes in malignant glioma cells. Here, we investigated the relationship between AQP4 and some K+ channels in the malignant glioma U87 line. The U87 cells transfected with the human M1-AQP4 and M23-AQP4 isoforms were investigated for morphology, the gene expression of KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, and Cyclin genes by RT-PCR, recording the whole-cell K+ ion currents by patch-clamp experiments. AQP4 aggregation into OAPs increases the plasma membrane functional expression of the Kir6.2 and SUR2 subunits of the KATP channels and of the KCNMA1 of the BK channels in U87 cells leading to a large increase in inward and outward K+ ion currents. These changes were associated with changes in morphology, with a decrease in cell volume in the U87 cells and an increase in the ER density. These U87 cells accumulate in the mitotic and G2 cell cycle. The KATP channel blocker zoledronic acid reduced cell proliferation in both M23 AQP4-OAP and M1 AQP4-tetramer-transfected cells, leading to early and late apoptosis, respectively. The BK channel sustains the efflux of K+ ions associated with the M23 AQP4-OAP expression in the U87 cells, but it is downregulated in the M1 AQP4-tetramer cells. The KATP channels are effective in the M1 AQP4-tetramer and M23 AQP4-OAP cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramer cell phenotypes inhibiting KATP channels and inducing early apoptosis.
Characterization of ZnWO4, MgWO4, and CaWO4 Ceramics Synthesized in the Field of a Powerful Radiation Flux
Authors: Alpyssova Gulnur , Lisitsyn Viktor , Bakiyeva Zhanara , Chakin Ivan , Kaneva Ekaterina , Afanasyev Dmitriy , Tussupbekova Ainura , Vaganov Vitalii , Tulegenova Aida T. , Tuleuov Serik
Published: August 2024

This paper presents the results of a study on the morphology, structure, and luminescent properties of ceramics synthesized in the radiation field of MeWO4 compositions (where Me is Mg, Ca, and Zn). The synthesis of ceramics was carried out by the direct action of the electron flux on an initial mixture of powders of the given stoichiometric composition. WO3, ZnO, MgO, and CaO powders with particle sizes in the range of 1–50 microns were used for the synthesis of the samples. It was found that the yield of the radiation synthesis reaction (the ratio of the mass of the sample and the charge used), when treated with an electron flux with an energy of 1.4 MeV and a flux power density of 15–18 kW/cm2, was in the range of 75–99%. The synthesis of all compositions was carried out under the same radiation treatment modes, although the melting temperatures of the starting materials varied significantly and ranged from 1473 °C (WO3) to 2825 °C (MgO). The study of the ceramic structure showed that under the radiation effect of powerful radiation fluxes on the charge, a crystalline phase of the appropriate composition formed, regardless of the synthesis modes. The results of XRD studies show that during the radiation treatment of the charge, ceramics are formed mainly with the crystalline phases ZnWO4, MgWO4, and CaWO4. These resulting MeWO4 ceramics can be used for the same purposes as crystals. Photoluminescence (PL) and cathodoluminescence (CL) were studied under excitation using stationary ultraviolet radiation and nanosecond pulses of electron flux. In general, the PL and CL of synthesized ceramic samples ZnWO4, MgWO4, and CaWO4 showed that their luminescent properties are similar to those of luminescence in corresponding crystalline materials. This indicates the formation of a crystalline phase in synthesized ceramic samples.
Simultaneous Detection of Serotonin and 17β-Estradiol Using rGO/SPCE Modified with Cu(II) Complex: A Novel Approach for PMDD Diagnosis
Authors: Núñez Claudia , Nelson Ronald , Tabilo Gerald , Pefaur Paulina , Castillo Rodrigo , Mestra Alifhers
Published: August 2024

Approximately 4% of women of reproductive age are estimated to suffer from premenstrual dysphoric disorder (PMDD), a condition likely underdiagnosed due to various biases, suggesting that actual prevalence may be higher. Addressing this, a novel electrochemical sensor was developed using a screen-printed electrode of reduced graphene oxide modified with a Cu(II) triazole complex, Cu(LNO2)2/rGO/SPCE. This sensor aims to determine levels of serotonin and 17β-estradiol rapidly, and simultaneously, key analytes implicated in PMDD. The method demonstrated high sensitivity for both analytes, achieving sensitivity levels of 0.064 μA/μmol L−1 for serotonin and 0.055 μA/μmol L−1 for 17β-estradiol, with a linear detection range of 2 to 42 μmol L−1. Detection limits were 42 nmol L−1 for serotonin and 53 nmol L−1 for estrogen. The sensor also exhibited high stability and selectivity against common interferents found in biological fluids. It was successfully used to measure serotonin and 17β-estradiol in human serum and urine, with recovery percentages within the expected ranges. This demonstrates that the sensor proposed in this work holds significant potential to contribute not only to the accurate diagnosis of such disorders but also to their treatment. We hope that this research will pave the way for the development of devices that have a positive impact on the quality of life of women suffering from multisystem diseases caused by hormonal malfunctions.
Chiral Trapped-Headspace GC-QMS-IMS: Boosting Untargeted Benchtop Volatilomics to the Next Level
Authors: Bodenbender Lukas , Rohn Sascha , Sauer Simeon , Jungen Markus , Weller Philipp
Published: August 2024

In the field of quality analysis of food and flavoring products, gas chromatography–quadrupole mass spectrometry–ion mobility spectrometry (GC-QMS-IMS) is a powerful technique for the simultaneous detection of volatile organic compounds (VOCs) by both QMS and IMS. GC is an established technique for the separation of complex VOC-rich food products. While subsequent detection by IMS features soft ionization of fragile compounds (e.g., terpenes) with characteristic drift times, MS provides analytes’ m/z values for database substance identification. A limitation of the prominently used static-headspace-based GC-QMS-IMS systems is the substantially higher sensitivity of IMS in comparison to full-scan QMS. The present study describes a new prototypic trapped-headspace (THS)-GC-QMS-IMS setup using mango purees. This approach ultimately allows the combination of soft ionization with m/z values obtained from database-searchable electron ionization (EI) spectra. The new setup features aligned retention times for IMS and MS and sufficient signal intensities for QMS and IMS. The results demonstrate that THS-GC-QMS-IMS allows for the classification of mango purees from different cultivars and that it could be a promising alternative method for authenticity control of food, flavors, and beverages.