bluuebunny/crossref_metadata_2025 huggingface dataset:
Metaverse and Medical Diagnosis: A Blockchain-Based Digital Twinning Approach Based on MobileNetV2 Algorithm for Cervical Vertebral Maturation
Authors: Moztarzadeh Omid , Jamshidi Mohammad (Behdad) , Sargolzaei Saleh , Keikhaee Fatemeh , Jamshidi Alireza , Shadroo Shabnam , Hauer Lukas
Published: April 2023

Advanced mathematical and deep learning (DL) algorithms have recently played a crucial role in diagnosing medical parameters and diseases. One of these areas that need to be more focused on is dentistry. This is why creating digital twins of dental issues in the metaverse is a practical and effective technique to benefit from the immersive characteristics of this technology and adapt the real world of dentistry to the virtual world. These technologies can create virtual facilities and environments for patients, physicians, and researchers to access a variety of medical services. Experiencing an immersive interaction between doctors and patients can be another considerable advantage of these technologies, which can dramatically improve the efficiency of the healthcare system. In addition, offering these amenities through a blockchain system enhances reliability, safety, openness, and the ability to trace data exchange. It also brings about cost savings through improved efficiencies. In this paper, a digital twin of cervical vertebral maturation (CVM), which is a critical factor in a wide range of dental surgery, within a blockchain-based metaverse platform is designed and implemented. A DL method has been used to create an automated diagnosis process for the upcoming CVM images in the proposed platform. This method includes MobileNetV2, a mobile architecture that improves the performance of mobile models in multiple tasks and benchmarks. The proposed technique of digital twinning is simple, fast, and suitable for physicians and medical specialists, as well as for adapting to the Internet of Medical Things (IoMT) due to its low latency and computing costs. One of the important contributions of the current study is to use of DL-based computer vision as a real-time measurement method so that the proposed digital twin does not require additional sensors. Furthermore, a comprehensive conceptual framework for creating digital twins of CVM based on MobileNetV2 within a blockchain ecosystem has been designed and implemented, showing the applicability and suitability of the introduced approach. The high performance of the proposed model on a collected small dataset demonstrates that low-cost deep learning can be used for diagnosis, anomaly detection, better design, and many more applications of the upcoming digital representations. In addition, this study shows how digital twins can be performed and developed for dental issues with the lowest hardware infrastructures, reducing the costs of diagnosis and treatment for patients.
Automatic Segmentation of Teeth, Crown–Bridge Restorations, Dental Implants, Restorative Fillings, Dental Caries, Residual Roots, and Root Canal Fillings on Orthopantomographs: Convenience and Pitfalls
Authors: Gardiyanoğlu Emel , Ünsal Gürkan , Akkaya Nurullah , Aksoy Seçil , Orhan Kaan
Published: April 2023

Background: The aim of our study is to provide successful automatic segmentation of various objects on orthopantomographs (OPGs). Methods: 8138 OPGs obtained from the archives of the Department of Dentomaxillofacial Radiology were included. OPGs were converted into PNGs and transferred to the segmentation tool’s database. All teeth, crown–bridge restorations, dental implants, composite–amalgam fillings, dental caries, residual roots, and root canal fillings were manually segmented by two experts with the manual drawing semantic segmentation technique. Results: The intra-class correlation coefficient (ICC) for both inter- and intra-observers for manual segmentation was excellent (ICC > 0.75). The intra-observer ICC was found to be 0.994, while the inter-observer reliability was 0.989. No significant difference was detected amongst observers (p = 0.947). The calculated DSC and accuracy values across all OPGs were 0.85 and 0.95 for the tooth segmentation, 0.88 and 0.99 for dental caries, 0.87 and 0.99 for dental restorations, 0.93 and 0.99 for crown–bridge restorations, 0.94 and 0.99 for dental implants, 0.78 and 0.99 for root canal fillings, and 0.78 and 0.99 for residual roots, respectively. Conclusions: Thanks to faster and automated diagnoses on 2D as well as 3D dental images, dentists will have higher diagnosis rates in a shorter time even without excluding cases.
Development of SARS-CoV-2 Vaccine: Challenges and Prospects
Authors: Mahboob Tooba , Ismail Amni Adilah , Shah Muhammad Raza , Rahmatullah Mohammed , Paul Alok K. , Pereira Maria de Lourdes , Wiart Christophe , Wilairatana Polrat , Rajagopal Mogana , Dolma Karma G. , Nissapatorn Veeranoot
Published: April 2023

The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2.
Quality-Aware Autonomous Navigation with Dynamic Path Cost for Vision-Based Mapping toward Drone Landing
Authors: Sözer Onuralp , Kumbasar Tufan
Published: April 2023

This article presents a novel autonomous navigation approach that is capable of increasing map exploration and accuracy while minimizing the distance traveled for autonomous drone landings. For terrain mapping, a probabilistic sparse elevation map is proposed to represent measurement accuracy and enable the increasing of map quality by continuously applying new measurements with Bayes inference. For exploration, the Quality-Aware Best View (QABV) planner is proposed for autonomous navigation with a dual focus: map exploration and quality. Generated paths allow for visiting viewpoints that provide new measurements for exploring the proposed map and increasing its quality. To reduce the distance traveled, we handle the path-cost information in the framework of control theory to dynamically adjust the path cost of visiting a viewpoint. The proposed methods handle the QABV planner as a system to be controlled and regulate the information contribution of the generated paths. As a result, the path cost is increased to reduce the distance traveled or decreased to escape from a low-information area and avoid getting stuck. The usefulness of the proposed mapping and exploration approach is evaluated in detailed simulation studies including a real-world scenario for a packet delivery drone.
Weighted BATS Codes with LDPC Precoding
Authors: Zhang Wenyue , Zhu Min
Published: April 2023

Batched Sparse (BATS) codes are a type of network coding scheme that use a combination of random linear network coding (RLNC) and fountain coding to enhance the reliability and efficiency of data transmission. In order to achieve unequal error protection for different data, researchers have proposed unequal error protection BATS (UEP-BATS) codes. However, current UEP-BATS codes suffer from high error floors in their decoding performance, which restricts their practical applications. To address this issue, we propose a novel UEP-BATS code scheme that employs a precoding stage prior to the weighted BATS code. The proposed precoding stage utilizes a partially regular low-density parity-check (PR-LDPC) code, which helps to mitigate the high error floors in the weighted BATS code We derive the asymptotic performance of the proposed scheme based on density evolution (DE). Additionally, we propose a searching algorithm to optimize precoding degree distribution within the complexity range of the precoding stage. Simulation results show that compared to the conventional weighted BATS codes, our proposed scheme offers superior UEP performance and lower error floor, which verifies the effectiveness of our scheme.
Correction: Zhang et al. Wildlife Object Detection Method Applying Segmentation Gradient Flow and Feature Dimensionality Reduction. Electronics 2023, 12, 377
Authors: Zhang Mingyu , Gao Fei , Yang Wuping , Zhang Haoran
Published: April 2023

In the original publication [...]
FPGA-Flux Proprietary System for Online Detection of Outer Race Faults in Bearings
Authors: Cureño-Osornio Jonathan , Zamudio-Ramirez Israel , Morales-Velazquez Luis , Jaen-Cuellar Arturo Yosimar , Osornio-Rios Roque Alfredo , Antonino-Daviu Jose Alfonso
Published: April 2023

Online fault detection in industrial machinery, such as induction motors or their components (e.g., bearings), continues to be a priority. Most commercial equipment provides general measurements and not a diagnosis. On the other hand, commonly, research works that focus on fault detection are tested offline or over processors that do not comply with an online diagnosis. In this sense, the present work proposes a system based on a proprietary field programmable gate array (FPGA) platform with several developed intellectual property cores (IPcores) and tools. The FPGA platform together with a stray magnetic flux sensor are used for the online detection of faults in the outer race of bearings in induction motors. The integrated parts comprising the monitoring system are the stray magnetic flux triaxial sensor, several developed IPcores, an embedded processor for data processing, and a user interface where the diagnosis is visualized. The system performs the fault diagnosis through a statistical analysis as follows: First, a triaxial sensor measures the stray magnetic flux in the motor’s surroundings (this flux will vary as symptoms of the fault). Second, an embedded processor in an FPGA-based proprietary board drives the developed IPcores in calculating the statistical features. Third, a set of ranges is defined for the statistical features values, and it is used to indicate the condition of the bearing in the motor. Therefore, if the value of a statistical feature belongs to a specific range, the system will return a diagnosis of whether a fault is present and, if so, the severity of the damage in the outer race. The results demonstrate that the values of the root mean square (RMS) and kurtosis, extracted from the stray magnetic field from the motor, provide a reliable diagnostic of the analyzed bearing. The results are provided online and displayed for the user through interfaces developed on the FPGA platform, such as in a liquid crystal display or through serial communication by a Bluetooth module. The platform is based on an FPGA XC6SLX45 Spartan 6 of Xilinx, and the architecture of the modules used are described through hardware description language. This system aims to be an online tool that can help users of induction motors in maintenance tasks and for the early detection of faults related to bearings.
EV-Station-Grid Coordination Optimization Strategy Considering Psychological Preferences
Authors: Wang Chudi , Ma Shaohua , Wang Qiwei , Yan Ning , Dong Yannan , Cai Zhiyuan
Published: April 2023

This paper proposes the electric vehicle (EV)-station-grid coordination optimization strategy considering user preferences, which regulates the charging behaviors of EV users from the user side to ensure the stable and safe operation of the power grid. Firstly, the spatio-temporal prediction model of charging load based on speed-temperature is developed. The model of EV power consumption per unit mileage affected by temperature and EV speed is constructed, and the shortest path algorithm is applied to determine the driving paths of EVs so as to judge the charging demand in combination with the state of charge (SOC) of the battery and to determine the charging periods and locations of the EVs, thus obtaining the spatio-temporal information of the charging load. Secondly, a multi-attribute charging decision model considering user preferences is constructed. Fuzzy clustering and rough set theory are applied to mine user behavior preferences, combined with behavioral economics to describe users’ irrational charging decision-making psychology. Lastly, a real-time charging price model considering voltage fluctuation index and user charging cost is constructed to analyze the impact of price on guiding charging behaviors. The simulation results verify the effectiveness and performance of the collaborative optimization strategy.
Emerging Parameters Extraction Method of PV Modules Based on the Survival Strategies of Flying Foxes Optimization (FFO)
Authors: Aalloul Radouane , Elaissaoui Abdellah , Benlattar Mourad , Adhiri Rhma
Published: April 2023

Nowadays, the world is encountering multiple challenges of energy security, economic recovery, and the effect of global warming. Investing in new fossil fuels only locks in uneconomic practices, sustains existing risks and increases the threats of climate change. In contrast, renewable energies, such as photovoltaic energy, constitute one of the most promising technologies in combating global increase in temperatures. Given its simplicity and low maintenance costs, photovoltaic energy is the most effective alternative to address the issues above. However, the standard test conditions (STCs) of PV modules are, in most cases, different from the real working conditions of a solar module. For instance, high levels of incident irradiation in an arid climate may cause the temperature of a module to rise by many degrees above the STC temperature of 25 °C, lowering the module’s performance. To effectively simulate and control PV systems for a given location, it has become paramount to develop a robust and accurate model that considers how PV modules behave. This study seeks to introduce an emerging metaheuristic optimization algorithm to estimate the unknown parameters of PV modules. The strategies deployed by flying foxes in the event of high temperatures have given birth to the development of a new metaheuristic algorithm called FFO. Contrary to previous methods, this new modeling procedure makes it possible to calculate all the parameters, regardless of temperature or irradiance. Four PV modules, having different technologies, were tested to evaluate the accuracy of the algorithm in question. The effectiveness of FFO is then contrasted with other well-known metaheuristics where single and double diode models are deployed. The results show that the FFO optimizer represents a substantial and compelling substitute for PV module extraction methods.
Experimental Underperformance Detection of a Fixed-Speed Diesel–Electric Generator Based on Exhaust Gas Emissions
Authors: Ghorbanzadeh Milad , Issa Mohamad , Ilinca Adrian
Published: April 2023

Low load is one of the most challenging combustion stages for a fixed-speed diesel electric generator. Due to incomplete combustion during this phase, a significant proportion of contaminants form inside the cylinder. This can lead to numerous chemical and mechanical harms to the diesel engine, resulting in friction, efficiency reduction, increased fuel consumption, and prematurely ending the generator’s life. These phenomena are qualified as underperformance, possibly due to a misfire and/or a low-efficiency value (air fuel–fuel ratio). Therefore, detecting and preventing underperformance and reducing its extended operation is crucial. This paper deals with the performance and emission analysis of a multicylinder fixed-speed diesel engine driving an electric generator (300 kW) fueled with ultra-low sulfur diesel (≤15 mg/kg) to provide energy in an isolated Canadian community. The tests were carried out according to ISO 3046-1:2002 standard in a remote site to identify clues that can prevent prolonged operation in underperformance. Among the tests conducted, emissions such as sulfur (S), carbon dioxide (CO2), nitrogen oxide (NOx), and exhaust gas temperature are considered the best indices for detecting the underperformance of a fixed-speed diesel–electric generator under very-low and low load (0–30%) with the following registered values: 18 ppm for S, 4% for CO2, 150 ppm for NOx, and 210 °C for the temperature.
A Hybrid Deep Neural Network Architecture for Day-Ahead Electricity Forecasting: Post-COVID Paradigm
Authors: Vilaça Neilson Luniere , Costa Marly Guimarães Fernandes , Costa Filho Cicero Ferreira Fernandes
Published: April 2023

Predicting energy demand in adverse scenarios, such as the COVID-19 pandemic, is critical to ensure the supply of electricity and the operation of essential services in metropolitan regions. In this paper, we propose a deep learning model to predict the demand for the next day using the “IEEE DataPort Competition Day-Ahead Electricity Demand Forecasting: Post-COVID Paradigm” database. The best model uses hybrid deep neural network architecture (convolutional network–recurrent network) to extract spatial-temporal features from the input data. A preliminary analysis of the input data was performed, excluding anomalous variables. A sliding window was applied for importing the data into the network input. The input data was normalized, using a higher weight for the demand variable. The proposed model’s performance was better than the models that stood out in the competition, with a mean absolute error of 2361.84 kW. The high similarity between the actual demand curve and the predicted demand curve evidences the efficiency of the application of deep networks compared with the classical methods applied by other authors. In the pandemic scenario, the applied technique proved to be the best strategy to predict demand for the next day.
Development of a Decision Matrix for National Weather Service Red Flag Warnings
Authors: Jakober Sarah , Brown Timothy , Wall Tamara
Published: April 2023

The National Weather Service is responsible for alerting wildland fire management of meteorological conditions that create an environment conducive for extreme fire behavior. This is communicated via Red Flag Warnings (RFWs), which presently lack a national standardized methodology and rarely are explicitly linked to fuel conditions such those as provided by National Fire-Danger Rating System (NFDRS) indicators. The need for a revamped RFW has been expressed recently by both fire management and fire weather meteorologists. A decision matrix approach was developed to determine criteria that consistently and explicitly associates meteorological and fuels information to extreme fire behavior. Extreme fire behavior is defined here as maximum rates of spread (area per day) observed on documented large fires from 1999–2014 utilizing the ICS209 all-hazard dataset. Meteorological conditions occurring with these rates of spread were compared to historical percentiles of relative humidity, wind speed, and the NFDRS Energy Release Component. These percentiles were assigned a numerical score from one through five based on percentile rank. The additive result of all three scores was plotted against rates of spread yielding a two-step decision matrix of RFW categories where, for example, the highest score is the most extreme RFW case. Actual RFW issuances were compared to this matrix method.
Survey Evaluation of Florida’s Freshwater Fisheries Long-Term Monitoring Program
Authors: Bonvechio Kimberly I. , Paudyal Ramesh , Crandall Chelsey , Carlson Andrew K.
Published: April 2023

Natural resource monitoring programs benefit from routine evaluation. Here, Florida’s statewide Freshwater Fisheries Long-Term Monitoring (LTM) program is used to show how stakeholder surveys can be integral to this process. In 2022, an online questionnaire was sent to internal stakeholders, i.e., state agency personnel who collect, enter, or use freshwater fisheries data for fisheries and habitat management purposes. The survey’s primary objective was to evaluate the program at its 15-year mark; secondary objectives were to compare results with a similar survey conducted at the 4-year mark, compare results among respondents based on experience and functional role, and develop recommendations for strategic initiatives to further improve the program. The survey consisted of 43 questions across six sections of program evaluation: demographics; field sampling; data entry, summary, and reporting; management decision support; programmatic views; and additional input. Respondents generally had positive views of the LTM program, but the survey revealed differences among respondents with different functional roles (e.g., fisheries researchers and managers viewed the decisional value, priority, and sample sizes of LTM data more favorably than habitat managers) while highlighting high-priority future initiatives (e.g., database development). Our results demonstrate the utility of stakeholder surveys as an important step in evaluating monitoring programs.
Morphometric Variations of Nile Tilapia (Oreochromis niloticus) (Linnaeus, 1758) Local Strains Collected from Different Fish Farms in South Western Highland Agro-Ecological Zone (SWHAEZ), Uganda: Screening Strains for Aquaculture
Authors: Kwikiriza Gerald , Yegon Mourine J. , Byamugisha Nelson , Beingana Apulnal , Atukwatse Faith , Barekye Alex , Nattabi Juliet K. , Meimberg Harald
Published: April 2023

Despite the global contribution of aquaculture as an important pillar for food and nutritional security, its rapid growth has been hampered by inadequate and poor-quality seed due to inbreeding, hybridization of related stocks, and poor-quality broodstock. Phenotypic and genotypic characterization of Nile tilapia in natural water bodies of Uganda has been studied but research gaps remain on the morphometric characterization of farmed O. niloticus in Uganda, which hinders selective breeding initiatives. This study characterized O. niloticus from various farmers in Uganda’s Southwestern Highland Agro-Ecological Zone using their morphometric traits. In this study, 8 morphometric traits were taken on each of the 258 fish samples collected with at least 30 samples sampled from each pond system in the zone. The morphometric data generated were analyzed using multivariate analysis. In order to delineate the populations from the different ponds, Discriminant Function analysis (DFA) was performed on the dataset and distribution plots generated to test on the purity of the strains. There were significant differences in the morphometric traits among the populations with the Victoria fish population having the highest standard length while the Kyoga population had the highest weight. Morphometric characterization grouped the fish into three clusters, indicative that fish farms in the zone possibly had different sources of fish seed. The condition factor, which is a measure of wellbeing of the fish, showed that all the populations displayed an isometric growth which is indicative of the fish growing in length as it is in weight. The results of this study provide evidence that local O. niloticus from different farms display differences in body shape as a result of using fish seed from different sources. This aspect can be applied in selective breeding programs after establishing the genetic structure of the farmed Nile tilapia stock.
On the Roots of a Family of Polynomials
Authors: Jianu Marilena
Published: April 2023

The aim of this paper is to give a characterization of the set of roots of a special family of polynomials. This family is relevant in reliability theory since it contains the reliability polynomials of the networks created by series-parallel compositions. We prove that the set of roots is bounded, being contained in the two disks of the radius equal to the golden ratio, centered at 0 and at 1. We study the closure of the set of roots and prove that it includes two disks centered at 0 and 1 of a radius slightly greater than 1, as well as the sinusoidal spirals centered at 0 and at 1, respectively. The expression of some limit points is also provided.
Successive Waves of the COVID-19 Pandemic Had an Increasing Impact on Chronic Cardiovascular Patients in a Western Region of Romania
Authors: Tudora Adelina , Lungeanu Diana , Pop-Moldovan Adina , Puschita Maria , Lala Radu I.
Published: April 2023

Three years since the COVID-19 pandemic started, there is still little information about patients with chronic medical conditions, such as cardiovascular diseases (CVDs), who become infected with SARS-CoV-2. A retrospective analysis was performed to evaluate the impact of the COVID-19 pandemic on patients with cardiovascular comorbidities hospitalized with positive RT-PCR results for SARS-CoV-2 during the highest peaks of the first three pandemic waves: April 2020, October 2020, and November 2021. The primary outcome was in-hospital mortality; the secondary outcomes were length of hospitalization and required mechanical ventilation to assess the disease severity. Data were extracted from the hospital electronic database system: 680 eligible cases were identified out of 2919 patients. Mortality was the highest in wave 3 (31.9%) compared to the previous waves (13.6% and 25.8%). Hospitalization was also significantly longer in wave 3 (11.58 ± 5.34 vs. 8.94 ± 4.74 and 10.19 ± 5.06; p < 0.001), and so was the need for mechanical ventilation (21.7% vs. 8.2% and 9%; p < 0.001). Older age and male gender were confirmed as highly significant predictors of unfavorable outcomes. Ischemic heart disease worsened the odds of patients’ survival irrespective of the three pandemic waves (Breslow–Day test, p = 0.387), with a marginally significant Mantel–Haenszel common estimate for risk: OR = 1.604, 95% (0.996; 2.586). The significantly worse outcomes in wave 3 could have been influenced by a combination of factors: the low percentage of vaccinations in Romanian population, the more virulent delta strain, and pandemic attrition in the care provided to these patients with chronic CVDs.
Lauric Acid Overcomes Hypoxia-Induced Gemcitabine Chemoresistance in Pancreatic Ductal Adenocarcinoma
Authors: Takagi Tadataka , Fujiwara-Tani Rina , Mori Shiori , Kishi Shingo , Nishiguchi Yukiko , Sasaki Takamitsu , Ogata Ruiko , Ikemoto Ayaka , Sasaki Rika , Ohmori Hitoshi , Luo Yi , Bhawal Ujjal Kumar , Sho Masayuki , Kuniyasu Hiroki
Published: April 2023

Although gemcitabine (GEM) is widely used in chemotherapy for pancreatic ductal adenocarcinoma (PDA), drug resistance restricts its clinical effectiveness. To examine the mechanism of GEM resistance, we established two GEM-resistant cell lines from human PDA cells by continuous treatment with GEM and CoCl2-induced chemical hypoxia. One resistant cell line possessed reduced energy production and decreased mitochondrial reactive oxygen species levels, while the other resistant cell line possessed increased stemness. In both cell lines, ethidium bromide-stained mitochondrial DNA levels decreased, suggesting mitochondrial DNA damage. Inhibition of hypoxia-inducible factor-1α in both cell lines did not restore the GEM sensitivity. In contrast, treatment of both cell types with lauric acid (LAA), a medium-chain fatty acid, restored GEM sensitivity. These results suggest that decreased energy production, decreased mitochondrial reactive oxygen species levels, and increased stemness associated with mitochondrial damage caused by GEM lead to GEM resistance, and that hypoxia may promote this process. Furthermore, forced activation of oxidative phosphorylation by LAA could be a tool to overcome GEM resistance. Clinical verification of the effectiveness of LAA in GEM resistance is necessary in the future.
Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage
Authors: Schiano Concetta , Balbi Carolina , de Nigris Filomena , Napoli Claudio
Published: April 2023

Both progression from the early pathogenic events to clinically manifest cardiovascular diseases (CVD) and cancer impact the integrity of the vascular system. Pathological vascular modifications are affected by interplay between endothelial cells and their microenvironment. Soluble factors, extracellular matrix molecules and extracellular vesicles (EVs) are emerging determinants of this network that trigger specific signals in target cells. EVs have gained attention as package of molecules with epigenetic reversible activity causing functional vascular changes, but their mechanisms are not well understood. Valuable insights have been provided by recent clinical studies, including the investigation of EVs as potential biomarkers of these diseases. In this paper, we review the role and the mechanism of exosomal epigenetic molecules during the vascular remodeling in coronary heart disease as well as in cancer-associated neoangiogenesis.
JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells
Authors: Ku Jin Mo , Kim Min Jeong , Choi Yu-Jeong , Lee Seo Yeon , Im Ji-Yeong , Jo Yong-Kyu , Yoon Sanghoon , Kim Ji-Hyun , Cha Jie Won , Shin Yong Cheol , Ko Seong-Gyu
Published: April 2023

Lung cancer is one of the most common malignant tumors and a leading cause of cancer-related death in the worldwide. Various anticancer drugs, such as cisplatin and pemetrexed, have been developed for lung cancer treatment but due their drug resistance and side effects, novel treatments need to be developed. In this study, the efficacy of the natural drug JI017, which is known to have few side effects, was tested in lung cancer cells. JI017 inhibited A549, H460, and H1299 cell proliferation. JI017 induced apoptosis, regulated apoptotic molecules, and inhibited colony formation. Additionally, JI017 increased intracellular ROS generation. JI017 downregulated PI3K, AKT, and mTOR expression. JI017 increased the cytosolic accumulation of LC3. We found that JI017 promoted apoptosis through ROS-induced autophagy. Additionally, the xenograft tumor size was smaller in JI017-treated mice. We found that JI017 treatment increased MDA concentrations, decreased Ki-67 protein levels, and increased cleaved caspase-3 and LC3 levels in vivo. JI017 decreased cell proliferation and increased apoptosis by inducing autophagy signaling in H460 and H1299 lung cancer cells. Targeting JI017 and autophagy signaling could be useful in lung cancer treatment.
Monitoring Cultured Rat Hepatocytes Using RNA-Seq In Vitro
Authors: Hou Yung-Te , Wu Chia-Chun , Wang Wen-Ting , Yang Wen-Tse , Liao Ying-Hsiu , Chen Chien-Yu
Published: April 2023

Compared to other techniques, RNA sequencing (RNA-Seq) has the advantage of having details of the expression abundance of all transcripts in a single run. In this study, we used RNA-Seq to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. Hepatocytes, including mature hepatocytes and small hepatocytes, were analyzed in vitro using RNA-Seq and quantitative polymerase chain reaction (qPCR). The results demonstrated that the gene expression profiles measured by RNA-Seq showed a similar trend to the expression profiles measured by qPCR, and can be used to infer the success of in vitro hepatocyte cultures. The results of the differential analysis, which compared mature hepatocytes against small hepatocytes, revealed 836 downregulated and 137 upregulated genes. In addition, the success of the hepatocyte cultures could be explained by the gene list screened from the adopted gene enrichment test. In summary, we demonstrated that RNA-Seq could become an effective method for monitoring the whole transcriptome of hepatocyte cultures and provide a more comprehensive list of factors related to the differentiation of small hepatocytes into mature hepatocytes. This monitoring system not only shows high potential in medical applications but may also be a novel method for the clinical diagnosis of liver-related diseases.
Modulation of the 5-Lipoxygenase Pathway by Chalcogen-Containing Inhibitors of Leukotriene A4 Hydrolase
Authors: Teder Tarvi , König Stefanie , Singh Rajkumar , Samuelsson Bengt , Werz Oliver , Garscha Ulrike , Haeggström Jesper Z.
Published: April 2023

The 5-lipoxygenase (5-LOX) pathway gives rise to bioactive inflammatory lipid mediators, such as leukotrienes (LTs). 5-LOX carries out the oxygenation of arachidonic acid to the 5-hydroperoxy derivative and then to the leukotriene A4 epoxide which is converted to a chemotactic leukotriene B4 (LTB4) by leukotriene A4 hydrolase (LTA4H). In addition, LTA4H possesses aminopeptidase activity to cleave the N-terminal proline of a pro-inflammatory tripeptide, prolyl-glycyl-proline (PGP). Based on the structural characteristics of LTA4H, it is possible to selectively inhibit the epoxide hydrolase activity while sparing the inactivating, peptidolytic, cleavage of PGP. In the current study, chalcogen-containing compounds, 4-(4-benzylphenyl) thiazol-2-amine (ARM1) and its selenazole (TTSe) and oxazole (TTO) derivatives were characterized regarding their inhibitory and binding properties. All three compounds selectively inhibit the epoxide hydrolase activity of LTA4H at low micromolar concentrations, while sparing the aminopeptidase activity. These inhibitors also block the 5-LOX activity in leukocytes and have distinct inhibition constants with recombinant 5-LOX. Furthermore, high-resolution structures of LTA4H with inhibitors were determined and potential binding sites to 5-LOX were proposed. In conclusion, we present chalcogen-containing inhibitors which differentially target essential steps in the biosynthetic route for LTB4 and can potentially be used as modulators of inflammatory response by the 5-LOX pathway.
The Role of Platelets in Infective Endocarditis
Authors: Braï Mustapha Abdeljalil , Hannachi Nadji , El Gueddari Nabila , Baudoin Jean-Pierre , Dahmani Abderrhamane , Lepidi Hubert , Habib Gilbert , Camoin-Jau Laurence
Published: April 2023

Over the last decade, the incidence of infective endocarditis (IE) has increased, with a change in the frequency of causative bacteria. Early evidence has substantially demonstrated the crucial role of bacterial interaction with human platelets, with no clear mechanistic characterization in the pathogenesis of IE. The pathogenesis of endocarditis is so complex and atypical that it is still unclear how and why certain bacterial species will induce the formation of vegetation. In this review, we will analyze the key role of platelets in the physiopathology of endocarditis and in the formation of vegetation, depending on the bacterial species. We provide a comprehensive outline of the involvement of platelets in the host immune response, investigate the latest developments in platelet therapy, and discuss prospective research avenues for solving the mechanistic enigma of bacteria–platelet interaction for preventive and curative medicine.
GSK-3β Allosteric Inhibition: A Dead End or a New Pharmacological Frontier?
Authors: Balboni Beatrice , Masi Mirco , Rocchia Walter , Girotto Stefania , Cavalli Andrea
Published: April 2023

Most kinase inhibitors are designed to bind to highly homologous ATP-binding sites, which leads to promiscuity and possible off-target effects. Allostery is an alternative approach to pursuing selectivity. However, allostery is difficult to exploit due to the wide variety of underlying mechanisms and the potential involvement of long-range conformational effects that are difficult to pinpoint. GSK-3β is involved in several pathologies. This critical target has an ATP-binding site that is highly homologous with the orthosteric sites of other kinases. Unsurprisingly, there is also great similarity between the ATP-binding sites of GSK-3β and its isomer, which is not redundant and thus would benefit from selective inhibition. Allostery would also allow for a moderate and tunable inhibition, which is ideal for GSK-3β, because this target is involved in multiple pathways, some of which must be preserved. However, despite considerable research efforts, only one allosteric GSK-3β inhibitor has reached the clinic. Moreover, unlike other kinases, there are no X-ray structures of GSK-3β in complex with allosteric inhibitors in the PDB data bank. This review aims to summarize the state of the art in allosteric GSK-3β inhibitor investigations, highlighting the aspects that make this target challenging for an allosteric approach.
Endocannabinoid System Components of the Female Mouse Reproductive Tract Are Modulated during Reproductive Aging
Authors: Rossi Gianna , Di Nisio Valentina , Chiominto Alessandro , Cecconi Sandra , Maccarrone Mauro
Published: April 2023

The endocannabinoid (eCB) system has gained ground as a key modulator of several female fertility-related processes, under physiological/pathological conditions. Nevertheless, its modulation during reproductive aging remains unclear. This study aimed to investigate the expression levels of the main receptors (cannabinoid receptor 1,CB1; cannabinoid receptor 2, CB2; G-protein coupled receptor, GPR55; and transient receptor potential vanilloid type 1 channel, TRPV1) and metabolic enzymes (N-acylphosphatidylethanolamine phospholipase D, NAPE-PLD; fatty acid amide hydrolase, FAAH; monoacylglycerol lipase, MAGL; and diacylglycerol lipase, DAGL-α and -β) of this system in the ovaries, oviducts, and uteri of mice at prepubertal, adult, late reproductive, and post-reproductive stages through quantitative ELISA and immunohistochemistry. The ELISA showed that among the receptors, TRPV1 had the highest expression and significantly increased during aging. Among the enzymes, NAPE-PLD, FAAH, and DAGL-β were the most expressed in these organs at all ages, and increased age-dependently. Immunohistochemistry revealed that, regardless of age, NAPE-PLD and FAAH were mainly found in the epithelial cells facing the lumen of the oviduct and uteri. Moreover, in ovaries, NAPE-PLD was predominant in the granulosa cells, while FAAH was sparse in the stromal compartment. Of note, the age-dependent increase in TRPV1 and DAGL-β could be indicative of increased inflammation, while that of NAPE-PLD and FAAH could suggest the need to tightly control the levels of the eCB anandamide at late reproductive age. These findings offer new insights into the role of the eCB system in female reproduction, with potential for therapeutic exploitation.
Effect of Substitution Degree and Homogeneity on Cyclodextrin-Ligand Complex Stability: Comparison of Fenbufen and Fenoprofen Using CD and NMR Spectroscopy
Authors: Kraszni Márta , Ágh Ferenc , Horváth Dániel , Mirzahosseini Arash , Horváth Péter
Published: April 2023

The stability of host–guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution while isomer purity has a smaller effect on the magnitude of stability constants. A significant difference was found in the case of DIMEB50 when compared to DIMEB80/DIMEB95, while the latter two are similar. In the fenbufen–fenoprofen comparison, fenbufen, with its linear axis, gives a more stable complex, while fenoprofen shows lower constants and poorly defined trends.
Mitochondrial DNA Supplementation of Oocytes Has Downstream Effects on the Transcriptional Profiles of Sus scrofa Adult Tissues with High mtDNA Copy Number
Authors: Okada Takashi , Penn Alexander , St. John Justin C.
Published: April 2023

Oocytes can be supplemented with extra copies of mitochondrial DNA (mtDNA) to enhance developmental outcome. Pigs generated through supplementation with mtDNA derived from either sister (autologous) or third-party (heterologous) oocytes have been shown to exhibit only minor differences in growth, physiological and biochemical assessments, and health and well-being do not appear affected. However, it remains to be determined whether changes in gene expression identified during preimplantation development persisted and affected the gene expression of adult tissues indicative of high mtDNA copy number. It is also unknown if autologous and heterologous mtDNA supplementation resulted in different patterns of gene expression. Our transcriptome analyses revealed that genes involved in immune response and glyoxylate metabolism were commonly affected in brain, heart and liver tissues by mtDNA supplementation. The source of mtDNA influenced the expression of genes associated with oxidative phosphorylation (OXPHOS), suggesting a link between the use of third-party mtDNA and OXPHOS. We observed a significant difference in parental allele-specific imprinted gene expression in mtDNA-supplemented-derived pigs, with shifts to biallelic expression with no effect on expression levels. Overall, mtDNA supplementation influences the expression of genes in important biological processes in adult tissues. Consequently, it is important to determine the effect of these changes on animal development and health.
Recent Advances in Antimicrobial Peptide Hydrogels
Authors: Copling Aryanna , Akantibila Maxwell , Kumaresan Raaha , Fleischer Gilbert , Cortes Dennise , Tripathi Rahul S. , Carabetta Valerie J. , Vega Sebastián L.
Published: April 2023

Advances in the number and type of available biomaterials have improved medical devices such as catheters, stents, pacemakers, prosthetic joints, and orthopedic devices. The introduction of a foreign material into the body comes with a risk of microbial colonization and subsequent infection. Infections of surgically implanted devices often lead to device failure, which leads to increased patient morbidity and mortality. The overuse and improper use of antimicrobials has led to an alarming rise and spread of drug-resistant infections. To overcome the problem of drug-resistant infections, novel antimicrobial biomaterials are increasingly being researched and developed. Hydrogels are a class of 3D biomaterials consisting of a hydrated polymer network with tunable functionality. As hydrogels are customizable, many different antimicrobial agents, such as inorganic molecules, metals, and antibiotics have been incorporated or tethered to them. Due to the increased prevalence of antibiotic resistance, antimicrobial peptides (AMPs) are being increasingly explored as alternative agents. AMP-tethered hydrogels are being increasingly examined for antimicrobial properties and practical applications, such as wound-healing. Here, we provide a recent update, from the last 5 years of innovations and discoveries made in the development of photopolymerizable, self-assembling, and AMP-releasing hydrogels.
G-QINDER Tool: Bioinformatically Predicted Formation of Different Four-Stranded DNA Motifs from (GT)n and (GA)n Repeats
Authors: Trizna Lukáš , Osif Branislav , Víglaský Viktor
Published: April 2023

The recently introduced semi-orthogonal system of nucleic acid imaging offers a greatly improved method of identifying DNA sequences that are capable of adopting noncanonical structures. This paper uses our newly developed G-QINDER tool to identify specific repeat sequences that adopt unique structural motifs in DNA: TG and AG repeats. The structures were found to adopt a left-handed G-quadruplex form under extreme crowding conditions and a unique tetrahelical motif under certain other conditions. The tetrahelical structure likely consists of stacked AGAG-tetrads but, unlike G-quadruplexes, their stability does not appear to be dependent on the type of monovalent cation present. The occurrence of TG and AG repeats in genomes is not rare, and they are also found frequently in the regulatory regions of nucleic acids, so it is reasonable to assume that putative structural motifs, like other noncanonical forms, could play an important regulatory role in cells. This hypothesis is supported by the structural stability of the AGAG motif; its unfolding can occur even at physiological temperatures since the melting temperature is primarily dependent on the number of AG repeats in the sequence.
50 Hz Magnetic Field Exposure Inhibited Spontaneous Movement of Zebrafish Larvae through ROS-Mediated syn2a Expression
Authors: Guo Yixin , Fu Yiti , Sun Wenjun
Published: April 2023

Extremely low frequency electromagnetic field (ELF-EMF) exists widely in public and occupational environments. However, its potential adverse effects and the underlying mechanism on nervous system, especially behavior are still poorly understood. In this study, zebrafish embryos (including a transfected synapsin IIa (syn2a) overexpression plasmid) at 3 h post-fertilization (hpf) were exposed to a 50-Hz magnetic field (MF) with a series of intensities (100, 200, 400 and 800 μT, respectively) for 1 h or 24 h every day for 5 days. Results showed that, although MF exposure did not affect the basic development parameters including hatching rate, mortality and malformation rate, yet MF at 200 μT could significantly induce spontaneous movement (SM) hypoactivity in zebrafish larvae. Histological examination presented morphological abnormalities of the brain such as condensed cell nucleus and cytoplasm, increased intercellular space. Moreover, exposure to MF at 200 μT inhibited syn2a transcription and expression, and increased reactive oxygen species (ROS) level as well. Overexpression of syn2a could effectively rescue MF-induced SM hypoactivity in zebrafish. Pretreatment with N-acetyl-L-cysteine (NAC) could not only recover syn2a protein expression which was weakened by MF exposure, but also abolish MF-induced SM hypoactivity. However, syn2a overexpression did not affect MF-increased ROS. Taken together, the findings suggested that exposure to a 50-Hz MF inhibited spontaneous movement of zebrafish larvae via ROS-mediated syn2a expression in a nonlinear manner.