bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-Inspired Dynamic Trust and Congestion-Aware Zone-Based Secured Internet of Drone Things (SIoDT)
Authors: Jghef Yousif Sufyan , Jasim Mohammed Jasim Mohammed , Ghanimi Hayder M. A. , Algarni Abeer D. , Soliman Naglaa F. , El-Shafai Walid , Zeebaree Subhi R. M. , Alkhayyat Ahmed , Abosinnee Ali S. , Abdulsattar Nejood Faisal , Abbas Ali Hashim , Hariz Hussein Muhi , Abbas Fatima Hashim
Published: November 2022

The Internet of Drone Things (IoDT) is a trending research area where drones are used to gather information from ground networks. In order to overcome the drawbacks of the Internet of Vehicles (IoV), such as congestion issues, security issues, and energy consumption, drones were introduced into the IoV, which is termed drone-assisted IoV. Due to the unique characteristics of the IoV, such as dynamic mobility and unsystematic traffic patterns, the performance of the network is reduced in terms of delay, energy consumption, and overhead. Additionally, there is the possibility of the existence of various attackers that disturb the traffic pattern. In order to overcome this drawback, the drone-assisted IoV was developed. In this paper, the bio-inspired dynamic trust and congestion-aware zone-based secured Internet of Drone Things (BDTC-SIoDT) is developed, and it is mainly divided into three sections. These sections are dynamic trust estimation, congestion-aware community construction, and hybrid optimization. Initially, through the dynamic trust estimation process, triple-layer trust establishment is performed, which helps to protect the network from all kinds of threats. Secondly, a congestion-aware community is created to predict congestion and to avoid it. Finally, hybrid optimization is performed with the combination of ant colony optimization (ACO) and gray wolf optimization (GWO). Through this hybrid optimization technique, overhead occurs during the initial stage of transmission, and the time taken by vehicles to leave and join the cluster is reduced. The experimentation is performed using various threats, such as flooding attack, insider attack, wormhole attack, and position falsification attack. To analyze the performance, the parameters that are considered are energy efficiency, packet delivery ratio, routing overhead, end-to-end delay, packet loss, and throughput. The outcome of the proposed BDTC-SIoDT is compared with earlier research works, such as LAKA-IOD, NCAS-IOD, and TPDA-IOV. The proposed BDTC-SIoDT achieves high performance when compared with earlier research works.
Joint Communication and Action Learning in Multi-Target Tracking of UAV Swarms with Deep Reinforcement Learning
Authors: Zhou Wenhong , Li Jie , Zhang Qingjie
Published: November 2022

Communication is the cornerstone of UAV swarms to transmit information and achieve cooperation. However, artificially designed communication protocols usually rely on prior expert knowledge and lack flexibility and adaptability, which may limit the communication ability between UAVs and is not conducive to swarm cooperation. This paper adopts a new data-driven approach to study how reinforcement learning can be utilized to jointly learn the cooperative communication and action policies for UAV swarms. Firstly, the communication policy of a UAV is defined, so that the UAV can autonomously decide the content of the message sent out according to its real-time status. Secondly, neural networks are designed to approximate the communication and action policies of the UAV, and their policy gradient optimization procedures are deduced, respectively. Then, a reinforcement learning algorithm is proposed to jointly learn the communication and action policies of UAV swarms. Numerical simulation results verify that the policies learned by the proposed algorithm are superior to the existing benchmark algorithms in terms of multi-target tracking performance, scalability in different scenarios, and robustness under communication failures.
Demonstration of the Holonomically Controlled Non-Abelian Geometric Phase in a Three-Qubit System of a Nitrogen Vacancy Center
Authors: Bhattacharyya Shaman , Bhattacharyya Somnath
Published: November 2022

The holonomic approach to controlling (nitrogen-vacancy) NV-center qubits provides an elegant way of theoretically devising universal quantum gates that operate on qubits via calculable microwave pulses. There is, however, a lack of simulated results from the theory of holonomic control of quantum registers with more than two qubits describing the transition between the dark states. Considering this, we have been experimenting with the IBM Quantum Experience technology to determine the capabilities of simulating holonomic control of NV-centers for three qubits describing an eight-level system that produces a non-Abelian geometric phase. The tunability of the geometric phase via the detuning frequency is demonstrated through the high fidelity (~85%) of three-qubit off-resonant holonomic gates over the on-resonant ones. The transition between the dark states shows the alignment of the gate’s dark state with the qubit’s initial state hence decoherence of the multi-qubit system is well-controlled through a π/3 rotation.
Configurations of Proto-Cell Aggregates with Anisotropy: Gravity Promotes Complexity in Theoretical Biology
Authors: Flores Juan César
Published: November 2022

This contribution considers proto-cell structures associated with asymmetries, mainly gravity, in the framework of reaction–diffusion. There are equivalent solutions for defined morphogen parameters in the equations that allow for defining proto-tissue complexity and configurational entropy. Using RNA data, improvements to the complexity and entropy due to the Earth’s gravity are presented. The theoretical proto-tissues complexity estimation, as a function of arbitrary surface gravity, is likewise proposed. In this sense, hypothetical aggregates of proto-cells on Mars would have a lower complexity than on Earth, which is equally valid for the Moon. Massive planets, or exoplanets like BD+20594b, could have major proto-tissue complexity and, eventually, rich biodiversity.
Mather β-Function for Ellipses and Rigidity
Authors: Bialy Michael
Published: November 2022

The goal of the first part of this note is to get an explicit formula for rotation number and Mather β-function for ellipse. This is done here with the help of non-standard generating function of billiard problem. In this way the derivation is especially simple. In the second part we discuss application of Mather β-function to rigidity problem.
A Novel Experimental Study on Conductivity Evaluation of Intersected Fractures
Authors: Wang Haitao , Chen Chen , Yao Yiming , Zhao Jingrui , Zeng Qijun , Lu Cong
Published: November 2022

Massive hydraulic fracturing (MHF) is currently the most effective technology used to create fracture networks with sufficient conductivity and maximize the stimulated reservoir volume (SRV) in tight oil and gas reservoirs. The newly initiated fracture networks during MHF usually exhibit complex fracture morphology and contain intersected fractures and fracture branches. The conductivity of these fractures plays a pivotal role in determining long-term productivity. Due to the complex geometry, it is difficult to accurately evaluate intersected fracture conductivity through traditional conductivity measurement methods and devices which are designed for a single primary fracture. Unlike previous studies where fracture conductivity was measured using two rock slabs under single-direction (vertical) loading, we establish a novel conductivity measurement apparatus that can mimic different fracture intersection scenarios under both vertical and transverse loading to facilitate the evaluation of intersected fracture conductivity. Based on this apparatus, a standard conductivity measurement framework for intersected fractures under biaxial compaction conditions is also proposed, and stable and reliable conductivity testing data are obtained. Sensitivity analyses are performed to find out the controlling factors of intersected fracture conductivity and the corresponding conductivity evolution law. Results indicate that the overall intersected fracture conductivity of intersected fractures can be divided into three stages, with closure pressure increasing, videlicet, the conductivity rapid reduction stage at low closure pressure, the conductivity slow reduction stage, and the conductivity stabilization stage. Higher proppant concentration results in higher conductivity. However, the conductivity differences among cases with different proppant concentration are relatively small at high closure pressure (conductivity stabilization stage). The more complex the fracture intersecting pattern is, the higher the conductivity would be. The experimental results can provide guidance for the design of proppant placement procedure for intersected fractures.
Experimentally Validated Coulomb Counting Method for Battery State-of-Charge Estimation under Variable Current Profiles
Authors: Zine Bachir , Bia Haithem , Benmouna Amel , Becherif Mohamed , Iqbal Mehroze
Published: November 2022

Battery state of charge as an effective operational indicator is expected to play a crucial role in the advancement of electric vehicles, improving the battery capacity and energy utilization, avoiding battery overcharging and over-discharging, extending the battery’s useful lifespan, and extending the autonomy of electric vehicles. In context, this article presents a computationally efficient battery state-of-charge estimator based on the Coulomb counting technique with constant and variable discharging current profiles for an actual battery pack in real time. A dedicated experimental bench is developed for validation purposes, where pivotal measurements such as current, voltage, and temperature are initially measured during the charging/discharging cycle. The state of charge thus obtained via these measurements is then compared with the value estimated through the battery generic model. Detailed analysis with conclusive outcomes is finally presented to exhibit the flexible nature of the proposed method in terms of the precise state-of-charge estimation for a variety of batteries, ranging from lead–acid batteries for domestic applications to Li-ion batteries inside electric vehicles.
Experimental and Numerical Investigation on the Dynamics of Impacting Droplet Spreading at Small Weber Numbers
Authors: Wang Ning , Zhang Jiqing , Zhang Zhenyu
Published: November 2022

The dynamic of droplet spreading on a free-slip surface was studied experimentally and numerically, with particularly interest in the impacts under relatively small droplet inertias (We≤30). Our experimental results and numerical predictions of dimensionless droplet maximum spreading diameter βmax agree well with those of Wildeman et al.’s widely-used model at We>30. The “1/2 rule” (i.e., approximately one half of the initial kinetic energy Ek0 finally transferred into surface energy) was found to break down at small Weber numbers (We≤30) and droplet height is non-negligible when the energy conservation approach is employed to estimate βmax. As We increases, surface energy and kinetic energy alternately dominates the energy budget. When the initial kinetic energy is comparable to the initial surface energy, competition between surface energy and kinetic energy finally results in the non-monotonic energy budget. In this case, gas viscous dissipation contributes the majority of the dissipated energy under relatively large Reynolds numbers. A practical model for estimating βmax under small Weber numbers (We≤30) was proposed by accounting for the influence of impact parameters on the energy budget and the droplet height. Good agreement was found between our model predictions and previous experiments.
Thermodynamic, Exergoeconomic and Multi-Objective Analyses of Supercritical N2O-He Recompression Brayton Cycle for a Nuclear Spacecraft Application
Authors: Miao Xinyu , Zhang Haochun , Wang Qi , Sun Wenbo , Xia Yan
Published: November 2022

Detailed thermodynamic, exergoeconomic, and multi-objective analysis are performed for a supercritical recompression Brayton cycle in which the advanced working medium mixture of nitrous oxide and helium (N2O–He) is utilized for power generation. The thermodynamic and exergoeconomic models are propitious based on the standard components’ mass and energy conservation, exergy balance equation, and exergy cost calculation equation. An investigation of the sensitivity parametric is considered for judging the impact of crucial decision variable parameters on the performance of the proposed Brayton cycle. The proposed cycle’s performance is evaluated by systematic analysis of the thermal efficiency (ηth), exergy efficiency (ηex), total cost rate (C.total), levelized cost of electricity (LCOE), and the total heat transfer area (Atotal). Furthermore, multi-objective optimization is adopted from the viewpoint of the first and second laws of exergoeconomics to find the optimum operating parameters and to improve the circular’s exergoeconomic performance. The final results illustrate that the optimization calculation is based on the fact of the exergoeconomics method; the whole system produces electrical power of 0.277 MW with C.total of USD 18.37/h, while the ηth, ηex, Atotal, and LCOE are 49.14%, 67.29%, 165.55 m2 and USD 0.0196/kWh, respectively. It is concluded that the work exergy destruction for the reactor and turbine is higher than that of other components; then, after the multi-objective optimization analysis, the ηth and ηex improved by 2.08% and 5.07%, respectively, and the C.total, Atotal, and LCOE decreased by 13.99%, 0.01%, and 5.13%, respectively.
CO2 Emissions of Electric Scooters Used in Shared Mobility Systems
Authors: Kubik Andrzej
Published: November 2022

The development of the electric mobility market in cities is becoming more and more important every year. With this development, more and more electric scooters are appearing in cities. Currently, the restrictions that result from the upcoming trends are reducing the number of vehicles powered by combustion engines in favor of vehicles equipped with electric motors. Considering the number of electric vehicles, the dominant type is an electric scooter. The aim of this article is to determine the CO2 that is emitted into the atmosphere by using this type of vehicle. The main suppliers of this type of vehicle in cities are shared mobility systems. To recognize the research gap, consisting of the lack of CO2 emissions of an electric scooter type vehicle, studies were carried out on the energy consumption of an electric scooter and CO2 emissions, which were calculated based on the CO2 emission value needed to produce a given energy value kWh. The plan of the research performed was developed on the basis of the D-optimal plan of the experiment, thanks to which the results could be saved in the form of mathematical models based on formulas.
Research on the Optimal Economic Power Dispatching of a Multi-Microgrid Cooperative Operation
Authors: Wang Haipeng , Wu Xuewei , Sun Kai , He Yuling
Published: November 2022

The economic power-dispatching model of a multi-microgrid is comprehensively established in this paper, considering many factors, such as generation cost, discharge cost, power-purchase cost, power sales revenue, and environmental cost. To construct this model, power interactions between the two microgrids and those between the micro- and main grids are considered. Furthermore, the particle swarm optimization (PSO) algorithm is utilized to solve the economic power-dispatching model. To validate the effectiveness of the proposed model as well as the solution algorithm, a practical project case is studied and discussed. In the case study, the impact of multiple scenarios is first analyzed. Then, the system operation economic costs under different scenarios are described in detail. Moreover, according to the optimization power-dispatching results of the multi-microgrid, power interactions between the two microgrids and those between the micro- and main grids are fully discussed.
Study on Biomass Models of Artificial Young Forest in the Northwestern Alpine Region of China
Authors: Mao Chunyan , Yi Lubei , Xu Wenqiang , Dai Li , Bao Anming , Wang Zhengyu , Zheng Xueting
Published: November 2022

The artificial young forest is an important component of ecosystems, and biomass models are important for estimating the carbon storage of ecosystems. However, research on biomass models of the young forest is lacking. In this study, biomass data of 96 saplings of three tree species from the southern foot of the Qilian Mountains were collected. These data, coupled with allometric growth equations and the nonlinear joint estimation method, were used to establish independent, component-additive, and total-control compatible models to estimate the biomass of artificial young wood of Picea crassifolia (Picea crassifolia Kom.), Sabina przewalskii (Sabina przewalskii Kom.), and Pinus tabulaeformis (Pinus tabuliformis Carr.). The distribution characteristics of the biomass components (branch, leaf, trunk, and root biomass) and the goodness of fit of the models were also analyzed. The results showed that (1) the multiple regression models with two independent variables (MRWTIV) were superior to the univariate models for all three tree species. Base diameter was the best-fitting variable of the univariate model for Picea crassifolia and Pinus tabulaeformis, and the addition of base diameter and crown diameter as variables to the MRWTIV can significantly improve model accuracy. Tree height was the best-fitting variable of the univariate model of Sabina przewalskii, and the addition of tree height and crown diameter to the MRWTIV can significantly improve model accuracy; (2) the two independent variable component-additive compatible model was the best-fitting biomass model. The compatible models constructed by the nonlinear joint estimation method were less accurate than the independent models. However, they maintained good compatibility among the biomass components and enabled more robust estimates of regional biomass; and (3) for the young wood of Picea crassifolia, Sabina przewalskii, and Pinus tabulaeformis, the aboveground biomass ratio of each component to total biomass was highest for leaf biomass (26%–68%), followed by branch (10%–46%) and trunk (11%–55%) biomass, and the aboveground biomass was higher than the underground biomass. In conclusion, the optimal biomass model of artificial young forest at the sampling site is a multivariate component-additive compatible biomass model. It can well estimate the biomass of young forest and provide a basis for future research.
Assessment of Variability: Chloroplast Microsatellite DNA, Defoliation, and Regeneration Potential of Old Pine Stands of Different Origins in the Context of Assisted Genotype Migration
Authors: Przybylski Paweł
Published: November 2022

The development of transportation in the 19th century allowed for the transfer of large quantities of pine seeds between significant areas in Europe. This artificial migration usually had negative breeding consequences, so regulations were introduced to protect local gene pools. The current dynamically changing climate contributes to a reconsideration of the assisted migration of genotypes as a factor in the mitigation of breeding risks. However, the assisted migration of genotypes requires extensive research into safe geographic and genetic distances over which we can move gene pools. The analyses presented here demonstrate the differences in chloroplast microsatellite DNA variation (cpSSR) and the implications for the health and regeneration potential of old stands from introduced seeds and local seeds. Analyses of the genetic variation in chloroplast DNA, crown defoliation, and regeneration potential (number of cones and number of seedlings) were performed. The stand grown from introduced seeds (from France) had higher genetic variability than the local populations and differed genetically from the local genotypes (Fst from 4% to 12%). The high genetic variability in the studied period did not affect the lower defoliation of the stand. On the other hand, the stand grown from introduced seeds had a significantly lower yield, and there was no natural regeneration (seedlings) to ensure the transfer of genetic information to the progeny generation. The obtained results confirmed the mechanisms of natural selection acting on pine genotypes that are alien to local ecological conditions.
Influence of Oxygen Concentration on Combustion Kinetics and Gas Products of a Polyurethane–Coal Mixture
Authors: Wang Haiyan , Chen Xiao , Wang Zhuo , Xiang Linchuan
Published: November 2022

Polyurethane materials are often used in mines to fill the geological structural areas for pretreatment and plugging. These areas are primarily high-incidence areas of coal spontaneous combustion (CSC). Polyurethane will promote the spontaneous combustion of the remaining coal because of its superior thermal insulation performance. Previous studies have focused on the effect of polyurethane on the spontaneous combustion of coal in air atmosphere, without considering the variation of oxygen concentration in the mining area. The paper investigates the effect of polyurethane on the spontaneous combustion of coal in the mining area under different oxygen concentration conditions according to the variation law of oxygen concentration in the mining area. Herein, thermogravimetry-Fourier transform infrared spectroscopy (TG-FTIR) coupled methods were used to study the kinetics and gas release laws of a polyurethane–coal mixture. The critical temperature of coal increases with the decrease of oxygen concentration. When the oxygen concentration exceeds 10%, the shift of the thermogravimetric curve to the right is smaller, indicating that the oxygen concentration has less influence on the combustion of a polyurethane–coal mixture. When the oxygen concentration is less than 10%, the shift of the thermogravimetric curve toward a higher temperature is more prominent, indicating that the oxygen concentration has a greater influence on the thermogravimetric curve. Simultaneously, the maximum value of DTG increases with the increasing oxygen concentration. The main gas products of coal pyrolysis are CO2, CH4, and H2O, while those of polyurethane pyrolysis are mainly CO2, CO, CH4, and H2O during the pyrolysis process. The amount of CO2 during the pyrolysis of various proportions of coal and polyurethane is the main difference in the gas products. Coal can promote the pyrolysis of polyurethane to some extent. The characteristic temperature rises and falls as the proportion of polyurethane in the polyurethane–coal mixture changes. In the actual monitoring, small amounts of H2O, CO2, and CO gases appear in the starting phase, then a large increase in the amount of gases can be considered that polyurethane is involved in the relevant combustion reactions, which can avoid misjudgment of the spontaneous combustion of coal in the mining area.
Enrichment of Agar Gel with Antioxidant Pectin from Fireweed: Mechanical and Rheological Properties, Simulated Digestibility, and Oral Processing
Authors: Popov Sergey , Smirnov Vasily , Paderin Nikita , Khramova Daria , Chistiakova Elizaveta , Vityazev Fedor , Golovchenko Victoria
Published: November 2022

The aims of the study were to evaluate the influence of pectin isolated from fireweed (FP) on the mechanical and rheological properties of agar (A) gel, to investigate the release of phenolic compounds (PCs) and pectin from A-FP gels at simulated digestion in vitro, and to evaluate the oral processing and sensory properties of A-FP gels. The hardness of A-FP gels decreased gradually with the increase in the concentration of FP added (0.1, 0.4, and 1.6%). The hardness of A-FP1.6 gel was 41% lower than A gel. Rheological tests found A gel was a strong physical gel (storage modulus (G′) >>loss modulus (G″)), and the addition of FP up to 1.6% did not significantly change its G’. The G″ value decreased in A-FP gels compared to A gel. The release of galacturonic acid (GalA) was 3.4 ± 0.5, 0.5 ± 0.2, 2.4 ± 1.0, and 2.2 ± 0.7 mg/mL after digestion of A-FP1.6 gel in the oral in vivo phase (OP) and subsequent incubation in simulated gastric (SGF), intestinal (SIF), and colonic (SCF) fluids in vitro. The incubation medium after OP, SGF, and SIF digestion of A-FP1.6 contained 24–64 μg GAE/mL of PCs, while SCF contained 144 μg GAE/mL, supposing a predominant release of antioxidant activity from the gel in the colon. Chewing to readiness for swallowing A-FP gel required less time and fewer chews with less activity of the masseter and temporalis muscles. A-FP1.6 gel had a lower likeness score for taste and consistency and a similar score for appearance and aroma when compared with A gel. Thus, A-FP gels were weakened compared to A gel and required less time and muscle activity for oral processing. A-FP gel had antioxidant activity due to the PCs associated with pectin, while A gel had no antioxidant activity.
Development of CRISPR-Mediated Nucleic Acid Detection Technologies and Their Applications in the Livestock Industry
Authors: Zhang Xuying
Published: November 2022

The rapid rate of virus transmission and pathogen mutation and evolution highlight the necessity for innovative approaches to the diagnosis and prevention of infectious diseases. Traditional technologies for pathogen detection, mostly PCR-based, involve costly/advanced equipment and skilled personnel and are therefore not feasible in resource-limited areas. Over the years, many promising methods based on clustered regularly interspaced short palindromic repeats and the associated protein systems (CRISPR/Cas), i.e., orthologues of Cas9, Cas12, Cas13 and Cas14, have been reported for nucleic acid detection. CRISPR/Cas effectors can provide one-tube reaction systems, amplification-free strategies, simultaneous multiplex pathogen detection, visual colorimetric detection, and quantitative identification as alternatives to quantitative PCR (qPCR). This review summarizes the current development of CRISPR/Cas-mediated molecular diagnostics, as well as their design software and readout methods, highlighting technical improvements for integrating CRISPR/Cas technologies into on-site applications. It further highlights recent applications of CRISPR/Cas-based nucleic acid detection in livestock industry, including emerging infectious diseases, authenticity and composition of meat/milk products, as well as sex determination of early embryos.
Bidirectional Association between Major Depressive Disorder and Gastroesophageal Reflux Disease: Mendelian Randomization Study
Authors: Miao Yuyang , Yuan Shuai , Li Ye , Chen Jie , Li Xue , Larsson Susanna C. , Zhang Qiang
Published: November 2022

Background: Observational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined. Aims: A bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease. Methods: For the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r2 ≤ 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p ≤ 5 × 10−8). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively. Results: Genetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19–1.43; p = 1.64 × 10−8) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15–1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05–1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11–1.47; p = 1.0 × 10−3). Conclusions: This Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease.
Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease
Authors: Pellegrini Miguel , Bergonzoni Guendalina , Perrone Federica , Squitieri Ferdinando , Biagioli Marta
Published: November 2022

Whether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers. They could be informative not only to follow disease progression and assess treatment efficacy in clinics, but also to aid in the development of new therapeutic approaches. This is especially important for neurological and genetic disorders, where the administration of appropriate treatment during the disease prodromal stage could significantly delay, if not halt, disease progression. In this review we focus on the current status of biomarkers in Huntington’s Disease (HD), a fatal hereditary and degenerative disease condition. First, we revise the sources and type of wet biomarkers currently in use. Then, we explore the feasibility of different RNA types (miRNA, ncRNA, circRNA) as possible biomarker candidates, discussing potential advantages, disadvantages, sources of origin and the ongoing investigations on this topic.
The Etiology of Cholelithiasis in Children and Adolescents—A Literature Review
Authors: Zdanowicz Katarzyna , Daniluk Jaroslaw , Lebensztejn Dariusz Marek , Daniluk Urszula
Published: November 2022

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.
Skeletal Muscle Regeneration in Cardiotoxin-Induced Muscle Injury Models
Authors: Wang Yanjie , Lu Jianqiang , Liu Yujian
Published: November 2022

Skeletal muscle injuries occur frequently in daily life and exercise. Understanding the mechanisms of regeneration is critical for accelerating the repair and regeneration of muscle. Therefore, this article reviews knowledge on the mechanisms of skeletal muscle regeneration after cardiotoxin-induced injury. The process of regeneration is similar in different mouse strains and is inhibited by aging, obesity, and diabetes. Exercise, microcurrent electrical neuromuscular stimulation, and mechanical loading improve regeneration. The mechanisms of regeneration are complex and strain-dependent, and changes in functional proteins involved in the processes of necrotic fiber debris clearance, M1 to M2 macrophage conversion, SC activation, myoblast proliferation, differentiation and fusion, and fibrosis and calcification influence the final outcome of the regenerative activity.
Ligand-Dependent Downregulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Role of miR-128 and miR-195
Authors: Khurana Madan L. , Mani Indra , Kumar Prerna , Ramasamy Chandramohan , Pandey Kailash N.
Published: November 2022

Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in 125I-ANP binding, Guanylyl cyclase (GC) activity of receptor, and intracellular accumulation of cGMP leading to downregulation of NPRA. Treatment with ANP (100 nM) for 12 h led to an 80% decrease in 125I-ANP binding to its receptor, and BNP decreased it by 62%. Neither 100 nM c-ANF (truncated ANF) nor C-type natriuretic peptide (CNP) had any effect. ANP (100 nM) treatment also decreased GC activity by 68% and intracellular accumulation cGMP levels by 45%, while the NPRA antagonist A71915 (1 µM) almost completely blocked ANP-dependent downregulation of NPRA. Treatment with the protein kinase G (PKG) stimulator 8-(4-chlorophenylthio)-cGMP (CPT-cGMP) (1 µM) caused a significant increase in 125I-ANP binding, whereas the PKG inhibitor KT 5823 (1 µM) potentiated the effect of ANP on the downregulation of NPRA. The transfection of miR-128 significantly reduced NPRA protein levels by threefold compared to control cells. These results suggest that ligand-dependent mechanisms play important roles in the downregulation of NPRA in target cells.
Aux/IAA11 Is Required for UV-AB Tolerance and Auxin Sensing in Arabidopsis thaliana
Authors: Mielecki Jakub , Gawroński Piotr , Karpiński Stanisław
Published: November 2022

In order to survive, plants have, over the course of their evolution, developed sophisticated acclimation and defense strategies governed by complex molecular and physiological, and cellular and extracellular, signaling pathways. They are also able to respond to various stimuli in the form of tropisms; for example, phototropism or gravitropism. All of these retrograde and anterograde signaling pathways are controlled and regulated by waves of reactive oxygen species (ROS), electrical signals, calcium, and hormones, e.g., auxins. Auxins are key phytohormones involved in the regulation of plant growth and development. Acclimation responses, which include programmed cell death induction, require precise auxin perception. However, our knowledge of these pathways is limited. The Aux/IAA family of transcriptional corepressors inhibits the growth of the plant under stress conditions, in order to maintain the balance between development and acclimation responses. In this work, we demonstrate the Aux/IAA11 involvement in auxin sensing, survival, and acclimation to UV-AB, and in carrying out photosynthesis under inhibitory conditions. The tested iaa11 mutants were more susceptible to UV-AB, photosynthetic electron transport (PET) inhibitor, and synthetic endogenous auxin. Among the tested conditions, Aux/IAA11 was not repressed by excess light stress, exclusively among its phylogenetic clade. Repression of transcription by Aux/IAA11 could be important for the inhibition of ROS formation or efficiency of ROS scavenging. We also hypothesize that the demonstrated differences in the subcellular localization of the two Aux/IAA11 protein variants might indicate their regulation by alternative splicing. Our results suggest that Aux/IAA11 plays a specific role in chloroplast retrograde signaling, since it is not repressed by high (excess) light stress, exclusively among its phylogenetic clade.
Potential of Vitamin B6 Dioxime Analogues to Act as Cholinesterase Ligands
Authors: Gašo Sokač Dajana , Zandona Antonio , Roca Sunčica , Vikić-Topić Dražen , Lihtar Gabriela , Maraković Nikola , Bušić Valentina , Kovarik Zrinka , Katalinić Maja
Published: November 2022

Seven pyridoxal dioxime quaternary salts (1–7) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal monooxime with substituted 2-bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43–76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes (Ki = 100–400 µM). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon-inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).
CS12192, a Novel JAK3/JAK1/TBK1 Inhibitor, Synergistically Enhances the Anti-Inflammation Effect of Methotrexate in a Rat Model of Rheumatoid Arthritis
Authors: Fang Zhengyu , Hu Yiping , Dai Jiajing , He Lianhua , He Juan , Xu Bihua , Han Xinle , Zhong Fubo , Lan Huiyao , Wang Qingwen
Published: November 2022

Rheumatoid arthritis (RA) is a common disease worldwide and is treated commonly with methotrexate (MTX). CS12192 is a novel JAK3 inhibitor discovered by Chipscreen Biosciences for the treatment of autoimmune diseases. In the present study, we examined the therapeutic effect of CS12192 against RA and explored if the combinational therapy of CS12192 and MTX produced a synergistic effect against RA in rat collagen-induced arthritis (CIA). Arthritis was induced in male Sprague-Dawley rats by two intradermal injections of bovine type II collagen (CII) and treated with MTX, CS12192, or the combination of CS12192 and MTX daily for two weeks. Effects of different treatments on arthritis score, X-ray score, pathology, and expression of inflammatory cytokines and biomarkers were examined. We found that treatment with either CS12192 or MTX produced a comparable therapeutic effect on CIA including: (1) significantly lowering the arthritis score, X-ray score, serum levels of rheumatic factor (RF), C-reactive protein (CRP), and anti-nuclear antibodies (ANA); (2) largely alleviating histopathological damage, reducing infiltration of Th17 cells while promoting Treg cells; (3) inhibiting the expression of inflammatory cytokines and chemokines such as IL-1β, TNF-α, IL-6, CCL2, and CXCL1. All these inhibitory effects were further improved by the combinational therapy with MTX and CS12192. Of importance, the combinational treatment also resulted in a marked switching of the Th17 to Treg and the M1 to M2 immune responses in synovial tissues of CIA. Thus, when compared to the monotherapy, the combination treatment with CS12192 and MTX produces a better therapeutic effect against CIA with a greater suppressive effect on T cells and macrophage-mediated joint inflammation.
Diversity-Oriented Synthesis of a Molecular Library of Immunomodulatory α-Galactosylceramides with Fluorous-Tag-Assisted Purification and Evaluation of Their Bioactivities in Regard to IL-2 Secretion
Authors: Chen Yeng-Nan , Hung Jung-Tung , Jan Fan-Dan , Su Yung-Yu , Hwu Jih-Ru , Yu Alice L. , Adak Avijit K. , Lin Chun-Cheng
Published: November 2022

Structural variants of α-galactosylceramide (α-GalCer) that stimulate invariant natural killer T (iNKT) cells constitute an emerging class of immunomodulatory agents in development for numerous biological applications. Variations in lipid chain length and/or fatty acids in these glycoceramides selectively trigger specific pro-inflammatory responses. Studies that would link a specific function to a structurally distinct α-GalCer rely heavily on the availability of homogeneous and pure materials. To address this need, we report herein a general route to the diversification of the ceramide portion of α-GalCer glycolipids. Our convergent synthesis commences from common building blocks and relies on the Julia–Kocienski olefination as a key step. A cleavable fluorous tag is introduced at the non-reducing end of the sugar that facilitates quick purification of products by standard fluorous solid-phase extraction. The strategy enabled the rapid generation of a focused library of 61 α-GalCer analogs by efficiently assembling various lipids and fatty acids. Furthermore, when compared against parent α-GalCer in murine cells, many of these glycolipid variants were found to have iNKT cell stimulating activity similar to or greater than KRN7000. ELISA assaying indicated that glycolipids carrying short fatty N-acyl chains (1fc and 1ga), an unsubstituted (1fh and 1fi) or CF3-substituted phenyl ring at the lipid tail, and a flexible, shorter fatty acyl chain with an aromatic ring (1ge, 1gf, and 1gg) strongly affected the activation of iNKT cells by the glycolipid-loaded antigen-presenting molecule, CD1d. This indicates that the method may benefit the design of structural modifications to potent iNKT cell-binding glycolipids.
Localization of the Neuropeptide Arginine Vasotocin and Its Receptor in the Osmoregulatory Organs of Black Porgy, Acanthopagrus schlegelii: Gills, Kidneys, and Intestines
Authors: Nagarajan Ganesan , Adimoolam Aruna , Alkhamis Yousef Ahmed , Mathew Roshmon Thomas , Chang Ching-Fong
Published: November 2022

The neurohypophysial hormone arginine vasotocin (avt) and its receptor (avtr) regulates ions in the osmoregulatory organs of euryhaline black porgy (Acanthopagrus schlegelii). The localization of avt and avtr transcripts in the osmoregulatory organs has yet to be demonstrated. Thus, in the present study, we performed an in situ hybridization analysis to determine the localization of avt and avtr in the gills, kidneys, and intestines of the black porgy. The avt and avtr transcripts were identified in the filament and lamellae region of the gills in the black porgy. However, the basal membrane of the filament contained more avt and avtr transcripts. Fluorescence double tagging analysis revealed that avt and avtr mRNAs were partially co-localized with α-Nka-ir cells in the gill filament. The proximal tubules, distal tubules, and collecting duct of the kidney all had positive hybridization signals for the avt and avtr transcripts. Unlike the α-Nka immunoreactive cells, the avt and avtr transcripts were found on the basolateral surface of the distal convoluted tubule and in the entire cells of the proximal convoluted tubules of the black porgy kidney. In the intestine, the avt and avtr transcripts were found in the basolateral membrane of the enterocytes. Collectively, this study provides a summary of evidence suggesting that the neuropeptides avt and avtr with α-Nka-ir cells may have functions in the gills, kidneys, and intestines via ionocytes.
The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma
Authors: Paajanen Juuso , Bueno Raphael , De Rienzo Assunta
Published: November 2022

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.
Characteristics of BRCA2 Mutated Prostate Cancer at Presentation
Authors: Han Hyunho , Park Cheol Keun , Cho Nam Hoon , Lee Jongsoo , Jang Won Sik , Ham Won Sik , Choi Young Deuk , Cho Kang Su
Published: November 2022

Genetic alterations of DNA repair genes, particularly BRCA2 in patients with prostate cancer, are associated with aggressive behavior of the disease. It has reached consensus that somatic and germline tests are necessary when treating advanced prostate cancer patients. Yet, it is unclear whether the mutations are associated with any presenting clinical features. We assessed the incidences and characteristics of BRCA2 mutated cancers by targeted sequencing in 126 sets of advanced prostate cancer tissue sequencing data. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA2 alterations of clinical significance by AMP/ASCO/CAP criteria were found in 19 of 126 samples (15.1%). The BRCA2 mutated cancer did not differ in the distributions of TNM stage, Gleason grade group or histological subtype compared to BRCA2 wild-type cancers. Yet, they had higher tumor mutation burden, and higher frequency of ATM and BRCA1 mutations (44% vs. 10%, p = 0.002 and 21% vs. 4%, p = 0.018, respectively). Of the metastatic subgroup (M1, n = 34), mean PSA was significantly lower in BRCA2 mutated cancers than wild-type (p = 0.018). In the non-metastatic subgroup (M0, n = 64), PSA was not significantly different (p = 0.425). A similar trend was noted in multiple metastatic prostate cancer public datasets. We conclude that BRCA2 mutated metastatic prostate cancers may present in an advanced stage with relatively low PSA.
Advances in Intraoperative Flow Cytometry
Authors: D’Amato Figueiredo Marcos V. , Alexiou George A. , Vartholomatos George , Rehder Roberta
Published: November 2022

Flow cytometry is the gold-standard laser-based technique to measure and analyze fluorescence levels of immunostaining and DNA content in individual cells. It provides a valuable tool to assess cells in the G0/G1, S, and G2/M phases, and those with polyploidy, which holds prognostic significance. Frozen section analysis is the standard intraoperative assessment for tumor margin evaluation and tumor resection. Here, we present flow cytometry as a promising technique for intraoperative tumor analysis in different pathologies, including brain tumors, leptomeningeal dissemination, breast cancer, head and neck cancer, pancreatic tumor, and hepatic cancer. Flow cytometry is a valuable tool that can provide substantial information on tumor analysis and, consequently, maximize cancer treatment and expedite patients’ survival.