bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus
Authors: Song Anji , Cho Gwang-Won , Moon Changjong , Park Ilyong , Jang Chul Ho
Published: November 2022

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.
Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives
Authors: Khvostov Mikhail V. , Gladkova Elizaveta D. , Borisov Sergey A. , Fedotova Marina S. , Zhukova Nataliya A. , Marenina Mariya K. , Meshkova Yuliya V. , Luzina Olga A. , Tolstikova Tatiana G. , Salakhutdinov Nariman F.
Published: November 2022

Novel 9-N-alkyltetrahydroberberine derivatives were synthesized, among which, based on the results of OGTT, one compound containing the longest aliphatic substituent was selected for study in mice C57BL/6Ay, which demonstrate obesity, impaired glucose tolerance, and concomitant liver non-alcoholic fatty disease. Administration of this substance at a dose of 15 mg/kg for four weeks improved the insulin sensitivity of mice, which resulted in a decrease in fasting glucose levels and improved the tolerance of mice to OGTT glucose loading. A decrease in the level of lactate in the blood and a decrease in the amount of glucokinase in the liver were also found. The introduction of compound 3c did not have a toxic effect on animals based on biochemical data, histological analysis, and measurements of general parameters such as body weight and feed intake. Thus, the 9-N-heptyltetrahydroberberine derivative showed prominent hypoglycemic effects, which makes it promising to obtain and study other derivatives with longer substituents.
Complementary Experimental Methods to Obtain Thermodynamic Parameters of Protein Ligand Systems
Authors: Mohanakumar Shilpa , Lee Namkyu , Wiegand Simone
Published: November 2022

In recent years, thermophoresis has emerged as a promising tool for quantifying biomolecular interactions. The underlying microscopic physical effect is still not understood, but often attributed to changes in the hydration layer once the binding occurs. To gain deeper insight, we investigate whether non-equilibrium coefficients can be related to equilibrium properties. Therefore, we compare thermophoretic data measured by thermal diffusion forced Rayleigh scattering (TDFRS) (which is a non-equilibrium process) with thermodynamic data obtained by isothermal titration calorimetry (ITC) (which is an equilibrium process). As a reference system, we studied the chelation reaction between ethylenediaminetetraacetic acid (EDTA) and calcium chloride (CaCl2) to relate the thermophoretic behavior quantified by the Soret coefficient ST to the Gibb’s free energy ΔG determined in the ITC experiment using an expression proposed by Eastman. Finally, we have studied the binding of the protein Bovine Carbonic Anhydrase I (BCA I) to two different benzenesulfonamide derivatives: 4-fluorobenzenesulfonamide (4FBS) and pentafluorobenzenesulfonamide (PFBS). For all three systems, we find that the Gibb’s free energies calculated from ST agree with ΔG from the ITC experiment. In addition, we also investigate the influence of fluorescent labeling, which allows measurements in a thermophoretic microfluidic cell. Re-examination of the fluorescently labeled system using ITC showed a strong influence of the dye on the binding behavior.
Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response
Authors: Wu Pei-Liang , Ling Xiao Chun , Kang Eugene Yu-Chuan , Chen Kuan-Jen , Wang Nan-Kai , Liu Laura , Chen Yen-Po , Hwang Yih-Shiou , Lai Chi-Chun , Yang Shun-Fa , Wu Wei-Chi
Published: November 2022

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028–2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023–3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030–2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.
ILCs—Crucial Players in Enteric Infectious Diseases
Authors: Leupold Tamara , Wirtz Stefan
Published: November 2022

Research of the last decade has remarkably increased our understanding of innate lymphoid cells (ILCs). ILCs, in analogy to T helper (Th) cells and their cytokine and transcription factor profile, are categorized into three distinct populations: ILC1s express the transcription factor T-bet and secrete IFNγ, ILC2s depend on the expression of GATA-3 and release IL-5 and IL-13, and ILC3s express RORγt and secrete IL-17 and IL-22. Noteworthy, ILCs maintain a level of plasticity, depending on exposed cytokines and environmental stimuli. Furthermore, ILCs are tissue resident cells primarily localized at common entry points for pathogens such as the gut-associated lymphoid tissue (GALT). They have the unique capacity to initiate rapid responses against pathogens, provoked by changes of the cytokine profile of the respective tissue. Moreover, they regulate tissue inflammation and homeostasis. In case of intracellular pathogens entering the mucosal tissue, ILC1s respond by secreting cytokines (e.g., IFNγ) to limit the pathogen spread. Upon infection with helminths, intestinal epithelial cells produce alarmins (e.g., IL-25) and activate ILC2s to secrete IL-13, which induces differentiation of intestinal stem cells into tuft and goblet cells, important for parasite expulsion. Additionally, during bacterial infection ILC3-derived IL-22 is required for bacterial clearance by regulating antimicrobial gene expression in epithelial cells. Thus, ILCs can limit infectious diseases via secretion of inflammatory mediators and interaction with other cell types. In this review, we will address the role of ILCs during enteric infectious diseases.
Effect of Sex Differences in Silicotic Mice
Authors: Jin Fuyu , Li Yaqian , Wang Xiaojing , Yang Xinyu , Li Tian , Xu Hong , Wei Zhongqiu , Liu Heliang
Published: November 2022

Mechanisms of silicosis, caused by the inhalation of silica are still unclear, and the effect of sex on silicosis has rarely been reported. The purpose of this study was to investigate whether sex affects the silicotic lesions and the progressive fibrotic responses in silicosis. Our study showed that sex had no significant effect on the area of silicon nodules and the collagen deposition after a one-time bronchial perfusion of silica. Immunohistochemical staining showed that CD68 and the transforming growth factor-β1 (TGF-β1) were positive in male and female silicotic mice. In addition, the western blot results showed that the fibrosis-related factors type I collagen (COL I), α-smooth muscle actin (α-SMA), vimentin, TGF-β1, p-SMAD2/3, inflammatory-related factors interleukin 6 (IL 6), interleukin 1β (IL 1β), and senescence-related factors p16 and p21 were up-regulated in silicotic mice and there was no difference between female or male mice exposed to silica. The expression of TGF-β1, p-SMAD2/3, p16, and p21 were downregulated in the early stage of female silicotic mice, compared to the males. Thus, despite differences in the expression of certain factors, there was no overall difference in the progressive fibrosis between female and male mice in silicosis. These results thus provide a new perspective for studying the pathological development of silicosis.
Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells
Authors: Yoshikawa Hayato , Matsumoto Takahiro , Kitagawa Takahiro , Okayama Masaya , Ohta Tomoe , Yoshida Tatsusada , Watanabe Tetsushi
Published: November 2022

We isolated seven new iridoid glucosides (valerianairidoids I–VII; 1–3, 6, 7, 9, and 12) and six known compounds from the methanol extract of the dried rhizomes and roots of Valeriana fauriei. Chemical and spectroscopic data were used to elucidate the chemical structures of the seven new iridoid glucosides, and their absolute configurations were determined by comparing their electronic circular dichroism (ECD) spectra with those determined experimentally. Aglycones 1a, 6a, and 9a, which were obtained by enzymatic hydrolysis of the isolated iridoid glucosides, exhibited anti-proliferative activities against cancer stem cells (CSCs) established by a sphere-formation assay using human breast cancer (MDA-MB-231) and human astrocytoma (U-251MG) cells. Interestingly, these iridoids selectively showed anti-proliferative activities against CSCs from MDA-MB-231 cells. These results suggest that the iridoids obtained in this study may have potency as a breast cancer treatment and as preventive agent via exterminating CSCs.
The Importance of Immunological Disorders in the Pathogenesis of Lichen Sclerosus in Pediatric Patients: A Systematic Review
Authors: Torres Anna , Zaborek-Łyczba Monika , Łyczba Jakub , Mertowska Paulina , Mertowski Sebastian , Grywalska Ewelina
Published: November 2022

Lichen sclerosus (LS) is defined as a chronic mucocutaneous inflammatory disease with a localization predominantly to the anus and genitals (vulvar sclerosus (VLS)). Pediatric lichen sclerosus (LS) is a chronic inflammatory skin condition with predilection for the anogenital area that if untreated can lead to scarring. Vulvar LS is characterized by two peaks in incidence: it occurs in prepubertal girls and in postmenopausal women. To date, several mechanisms and risk factors have been proposed in the pathogenesis of pediatric vulvar LS; however, the etiology of this condition is still not fully understood and constitutes a challenge for scientists and clinicians. The presented research aimed to systematically review the existing literature on the pathogenesis of pediatric LS and to identify possible underlying autoimmune mechanisms and molecular networks. The clinical presentation of pediatric lichen sclerosus and available treatment modalities are also presented to acquaint a broader audience with this underdiagnosed and undertreated condition. As a result of our review, we discuss several potential mechanisms, molecules, and pathways that have been recognized in this disease. The purpose of our review was also to summarize what we can induce in further studies, which will ultimately help to identify the mechanism responsible for the disease and aid in the development of new, more effective treatment strategies for diagnosis and treatment by clinicians and researchers.
Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 Gene CACNA1D Associated with Familial Sinus Node Dysfunction and Focal Idiopathic Epilepsy
Authors: Rinné Susanne , Stallmeyer Birgit , Pinggera Alexandra , Netter Michael F. , Matschke Lina A. , Dittmann Sven , Kirchhefer Uwe , Neudorf Ulrich , Opp Joachim , Striessnig Jörg , Decher Niels , Schulze-Bahr Eric
Published: November 2022

Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 α1-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3S), whereas a loss of ion channel function was seen in the long (Cav1.3L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3L variant results in sinus node dysfunction.
Novel Antithrombotic Agents in Ischemic Cardiovascular Disease: Progress in the Search for the Optimal Treatment
Authors: Barriuso Ignacio , Worner Fernando , Vilahur Gemma
Published: November 2022

Ischemic cardiovascular diseases have a high incidence and high mortality worldwide. Therapeutic advances in the last decades have reduced cardiovascular mortality, with antithrombotic therapy being the cornerstone of medical treatment. Yet, currently used antithrombotic agents carry an inherent risk of bleeding associated with adverse cardiovascular outcomes and mortality. Advances in understanding the pathophysiology of thrombus formation have led to the discovery of new targets and the development of new anticoagulants and antiplatelet agents aimed at preventing thrombus stabilization and growth while preserving hemostasis. In the following review, we will comment on the key limitation of the currently used antithrombotic regimes in ischemic heart disease and ischemic stroke and provide an in-depth and state-of-the-art overview of the emerging anticoagulant and antiplatelet agents in the pipeline with the potential to improve clinical outcomes.
CPR Quality Assessment in Schoolchildren Training
Authors: Oliveira Katia M. G. , Carmona Maria José C. , Mansur Antonio P. , Takada Julio Y. , Fijačko Nino , Semeraro Federico , Lockey Andrew , Böttiger Bernd W. , Nakagawa Naomi K.
Published: November 2022

Whilst CPR training is widely recommended, quality of performance is infrequently explored. We evaluated whether a checklist can be an adequate tool for chest compression quality assessment in schoolchildren, compared with a real-time software. This observational study (March 2019–2020) included 104 schoolchildren with no previous CPR training (11–17 years old, 66 girls, 84 primary schoolchildren, 20 high schoolchildren). Simultaneous evaluations of CPR quality were performed using an observational checklist and real-time software. High-quality CPR was determined as a combination of 70% correct maneuvers in compression rate (100–120/min), depth (5–6 cm), and complete release, using a real-time software and three positive performance in skills using a checklist. We adjusted a multivariate logistic regression model for age, sex, and BMI. We found moderate to high agreement percentages in quality of CPR performance (rate: 68.3%, depth: 79.8%, and complete release: 91.3%) between a checklist and real-time software. Only 38.5% of schoolchildren (~14 years-old, ~54.4 kg, and ~22.1 kg/m2) showed high-quality CPR. High-quality CPR was more often performed by older schoolchildren (OR = 1.43, 95%IC:1.09–1.86), and sex was not an independent factor (OR = 1.26, 95%IC:0.52–3.07). For high-quality CPR in schoolchildren, a checklist showed moderate to high agreement with real-time software. Better performance was associated with age regardless of sex and BMI.
A Methodology for Shipping Noise Field Calibration and Excess Noise Estimation: The Azores Case Study
Authors: Jesus Sérgio M. , Soares Cristiano , Romagosa Miriam , Cascão Irma , Duarte Ricardo , Zabel Friedrich , Silva Mónica A.
Published: November 2022

Economic globalization and the continuous search for food, energy and raw materials led to an estimated 3 dB/decade increase of ocean noise intensity. Determining the level of anthropogenic noise, the so-called excess noise, and building identifiable meaningful indicators for supporting marine management policies currently requires extensive observation data and computer modeling. For modeling purposes, in this study, anthropogenic noise was reduced to shipping traffic drawn from Automatic Identification System data, and environmental sound was attributed to surface wind only. Data-model comparison allowed introducing a methodology for simple model calibration and estimate excess noise. This methodology was tested on acoustic recordings performed in June 2018 at three locations to the southwest of Faial-Pico Islands in the Azores archipelago. The results show that field-calibrated excess noise sound maps are in line with the shipping distribution in the area, revealing a number of potentially marine life-threatening hotspots. Excess noise addresses the need for a quantifiable measure of ocean noise only and therefore offers a basis for building suitable continuous anthropogenic noise pollution indicators.
Identification and Characterization of a QTL for Growth of Fusarium circinatum on Pine-Based Medium
Authors: Swalarsk-Parry Benedicta S. , Steenkamp Emma T. , van Wyk Stephanie , Santana Quentin C. , van der Nest Magriet A. , Hammerbacher Almuth , Wingfield Brenda D. , De Vos Lieschen
Published: November 2022

Fusarium circinatum is an economically important pathogen of pine and resides in the Fusarium fujikuroi species complex. Here we investigated the molecular processes underlying growth in F. circinatum by exploring the association between growth and the nutritional environment provided by the pine host. For this purpose, we subjected a mapping population consisting of F. circinatum X F. temperatum hybrid progeny to an analysis of growth rate on a pine-tissue derived medium. These data, together with the available genetic linkage map for F. circinatum, were then used to identify Quantitative Trait Loci (QTLs) associated with growth. The single significant QTL identified was then characterized using the available genome sequences for the hybrid progeny’s parental isolates. This revealed that the QTL localized to two non-homologous regions in the F. circinatum and F. temperatum genomes. For one of these, the F. circinatum parent contained a two-gene deletion relative to the F. temperatum parent. For the other region, the two parental isolates encoded different protein products. Analysis of repeats, G+C content, and repeat-induced point (RIP) mutations further suggested a retrotransposon origin for the two-gene deletion in F. circinatum. Nevertheless, subsequent genome and PCR-based analyses showed that both regions were similarly polymorphic within a collection of diverse F. circinatum. However, we observed no clear correlation between the respective polymorphism patterns and growth rate in culture. These findings support the notion that growth is a complex multilocus trait and raise the possibility that the identified QTL contains multiple small-effect QTLs, of which some might be dependent on the genetic backgrounds. This study improved our current knowledge of the genetic determinants of vegetative growth in F. circinatum and provided an important foundation for determining the genes and processes underpinning its ability to colonize its host environment.
Recombinant Expression in Pichia pastoris System of Three Potent Kv1.3 Channel Blockers: Vm24, Anuroctoxin, and Ts6
Authors: Borrego Jesús , Naseem Muhammad Umair , Sehgal Al Nasar Ahmed , Panda Lipsa Rani , Shakeel Kashmala , Gaspar Attila , Nagy Cynthia , Varga Zoltan , Panyi Gyorgy
Published: November 2022

The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia pastoris expression system provides a cost-effective approach to overcoming the limitations of chemical synthesis and E. coli recombinant expression. In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. Using the Pichia system, these toxins could be obtained in sufficient quantities (Vm24 1.6 mg/L, AnTx 46 mg/L, and Ts6 7.5 mg/L) to characterize their biological activity. A comparison was made between the activity of tagged and untagged recombinant peptides. Tagged Vm24 and untagged AnTx are nearly equivalent to native toxins in blocking Kv1.3 (Kd = 4.4 pM and Kd = 0.72 nM, respectively), whereas untagged Ts6 exhibits a 53-fold increase in Kd (Kd = 29.1 nM) as compared to the native peptide. The approach described here provides a method that can be optimized for toxin production to develop more selective and effective Kv1.3 blockers with therapeutic potential.
The Formation of a Polycentric City in Transitional China in a Three-Level Analysis Framework: The Case Study of Hangzhou
Authors: Zhang Liang , Shu Xianfan , Luo Jiaojiao
Published: November 2022

Given cities’ different development backgrounds, the spatial evolution of each city has a path-dependent development track. Understanding the characteristics of urban spatial structure evolution in contemporary China is essential for sustainable urban development. By establishing a theoretical framework comprising a macro-background, planning tool, and resource allocation, this paper takes Hangzhou as an example to analyze the evolutionary process of the polycentric spatial structure and reveal the formation characteristics of its polycentric urban spatial form. The results show that (1) its institutional background and planning tools are the driving forces behind the formation of the polycentric structure in Hangzhou, i.e., the evolution of the polycentric structure mainly relies on planning guidance and government forces rather than being market-driven. (2) Under the government-led mode of polycentric formation, urban elements, such as education, medical care, transportation, and green space, are still concentrated in the main urban center, while subcenters lack the necessary public facilities and are underdeveloped. (3) The spatial distribution of the population and nightlights also shows the trend of diminishing concentric circles with the main center at the core. Therefore, it is impossible to implement polycentric cities by decentralizing the population and industries alone. The comprehensive consideration of capital investment, production services, and the supply of life service facilities is also required. This empirical study can complement empirical evidence in order to verify the validity of polycentrism as a potential solution that can alleviate the sprawl of central urban areas.
Improved Large Covariance Matrix Estimation Based on Efficient Convex Combination and Its Application in Portfolio Optimization
Authors: Zhang Yan , Tao Jiyuan , Yin Zhixiang , Wang Guoqiang
Published: November 2022

The estimation of the covariance matrix is an important topic in the field of multivariate statistical analysis. In this paper, we propose a new estimator, which is a convex combination of the linear shrinkage estimation and the rotation-invariant estimator under the Frobenius norm. We first obtain the optimal parameters by using grid search and cross-validation, and then, we use these optimal parameters to demonstrate the effectiveness and robustness of the proposed estimation in the numerical simulations. Finally, in empirical research, we apply the covariance matrix estimation to the portfolio optimization. Compared to the existing estimators, we show that the proposed estimator has better performance and lower out-of-sample risk in portfolio optimization.
A Robust Optimization Method for Location Selection of Parcel Lockers under Uncertain Demands
Authors: Wang Yang , Zhang Yumeng , Bi Mengyu , Lai Jianhui , Chen Yanyan
Published: November 2022

Parcel lockers have continuously growing in popularity as an alternative mode for last-mile delivery services due to their capability of effectively alleviating the risk of a delivery failure, increasing the possibility of delivery consolidation, and reducing the number of drop-off sites. However, poorly located of parcel lockers be less efficient. When determining the parcel locker location, inadequate consideration of uncertain demands can potentially increase the risk of unsatisfied demands. To remedy this issue, a robust optimization model is proposed in this paper with consideration of the demand uncertainties, including the large and small parcels to be received and sent. Not only can the collection locations be optimally determined, but so can the number of large and small parcel lockers for each location at the same time under various robust levels. Meanwhile, the sites whose demands are covered by one of the collection locations are also determined by the constraints of acceptable walking distance. A series of numerical experiments has been performed to evaluate the proposed model, with the main focus being on the solution robustness. Since the set of non-linear constraints are transformed into the linear counterparts, the robust solution can be obtained by the existing solvers within a reasonable time with moderate computing power. The experimental results also provide useful guidance for the practical application of the method, as slightly more conservative decision making can secure the solution robustness with only a marginal increase in costs.
Design and Analysis of Novel Non-Involute Cylindrical Gears with a Curved Path of Contact
Authors: Jia Chao , He Qingtuo , Xiao Jianming , Dong Hui
Published: November 2022

In this paper, novel non-involute cylindrical gears are designed based on a curved path of contact. Firstly, a parabolic curve is predesigned as the contact path of novel gears. Then, the tooth profiles of the novel gears are calculated using differential geometry and spatial meshing theory. Secondly, the three-dimensional tooth models of the novel non-involute gears are established according to a machining simulation. Thirdly, a simulation model (including misalignment error and longitudinal modification) is established to analyze the performance of the novel non-involute gears. Finally, an example is given, and the results show that the presented novel non-involute gears have greater load-carrying capacity compared with the involute gears. Moreover, whether modified or not, with or without misalignment error, the stresses of the presented novel gears are lower than those of involute gears.
Recurrent Neural Network Models Based on Optimization Methods
Authors: Stanimirović Predrag S. , Mourtas Spyridon D. , Katsikis Vasilios N. , Kazakovtsev Lev A. , Krutikov Vladimir N.
Published: November 2022

Many researchers have addressed problems involving time-varying (TV) general linear matrix equations (GLMEs) because of their importance in science and engineering. This research discusses and solves the topic of solving TV GLME using the zeroing neural network (ZNN) design. Five new ZNN models based on novel error functions arising from gradient-descent and Newton optimization methods are presented and compared to each other and to the standard ZNN design. Pseudoinversion is involved in four proposed ZNN models, while three of them are related to Newton’s optimization method. Heterogeneous numerical examples show that all models successfully solve TV GLMEs, although their effectiveness varies and depends on the input matrix.
Associated Fault Diagnosis of Power Supply Systems Based on Graph Matching: A Knowledge and Data Fusion Approach
Authors: Tao Laifa , Liu Haifei , Zhang Jiqing , Su Xuanyuan , Li Shangyu , Hao Jie , Lu Chen , Suo Mingliang , Wang Chao
Published: November 2022

With the rapid development of more-electric and all-electric aircraft, the role of power supply systems in aircraft is becoming increasingly prominent. However, due to the complex coupling within the power supply system, a fault in one component often leads to parameter abnormalities in multiple components within the system, which are termed associated faults. Compared with conventional faults, the diagnosis of associated faults is difficult because the fault source is hard to trace and the fault mode is difficult to identify accurately. To this end, this paper proposes a graph-matching approach for the associated fault diagnosis of power supply systems based on a deep residual shrinkage network. The core of the proposed approach involves supplementing the incomplete prior fault knowledge with monitoring data to obtain a complete cluster of associated fault graphs. The association graph model of the power supply system is first constructed based on a topology with characteristic signal propagation and the associated measurements of typical components. Furthermore, fault propagation paths are backtracked based on the Warshall algorithm, and abnormal components are set to update and enhance the association relationship, establishing a complete cluster of typical associated fault mode graphs and realizing the organic combination and structured storage of knowledge and data. Finally, a deep residual shrinkage network is used to diagnose the associated faults via graph matching between the current state graph and the historical graph cluster. The comparative experiments conducted on the simulation model of an aircraft power supply system demonstrate that the proposed method can achieve high-precision associated fault diagnosis, even under circumstances where there are an insufficient number of samples and missing parameters.
Double Valorization for a Discard—α-Chitin and Calcium Lactate Production from the Crab Polybius henslowii Using a Deep Eutectic Solvent Approach
Authors: McReynolds Colin , Adrien Amandine , Petitpas Arnaud , Rubatat Laurent , Fernandes Susana C. M.
Published: November 2022

Polybius henslowii, an abundant yet unexploited species of swimming crab, was investigated as a potential source of α-chitin and calcium lactate using deep eutectic solvents (DES) as extracting solvents. Choline chloride–malonic acid (CCMA) and choline chloride–lactic acid (CCLA) were used to obtain high purity α-chitin from ball-milled P. henslowii exoskeleton in 2 h at 120 °C, with yields of 12.05 ± 2.54% and 12.8 ± 1.54%, respectively. The physical and chemical characteristics of the obtained chitins were assessed using CHN elemental analysis, attenuated total reflectance–Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the CCLA solvent was reusable three times with little effect on the extract purity, and calcium lactate was produced at the end of the recycling cycles. The ensuing calcium lactate was also characterized in terms of chemical and physical properties. The obtained chitin is a promising raw material for downstream processing and the double valorization pathway with the obtention of calcium salts may increase the viability of a DES-based approach for the processing of mineralized substrates.
Establishment of the Bacterial Microbiota in a Lab-Reared Model Teleost Fish, the Medaka Oryzias latipes
Authors: Duval Charlotte , Marie Benjamin , Foucault Pierre , Duperron Sébastien
Published: November 2022

Oryzias latipes is an important model organism for physiology, genetics, and developmental studies, and has also emerged as a relevant vertebrate model for aquatic ecotoxicology. Knowledge regarding its associated microbiota on the other hand is still scarce and limited to adults, despite the relevance of the associated microbiome to the host’s biology. This study provides the first insights into the establishment of bacterial microbiota during early developmental stages of laboratory-reared medaka using a 16S-rRNA-sequencing-based approach. Major shifts in community compositions are observed, from a Proteobacteria-dominated community in larvae and juveniles to a more phylum-diverse community towards adulthood, with no obvious difference between female and male specimens. Major bacterial taxa found in adults, including genera Cetobacterium and ZOR0006, establish progressively and are rare during early stages. Dominance shifts are comparable to those documented in another major model teleost, the zebrafish. Results from this study provide a basis for future work investigating the influence of medaka-associated bacteria during host development.
Standardized Pomegranate (Pomella®) and Red Maple (Maplifa®) Extracts and Their Phenolics Protect Type I Collagen by the Inhibition of Matrix Metalloproteinases, Collagenase, and Collagen Cross-Linking
Authors: Li Huifang , Roy Tithi , Boateng Samuel T. , He Hao , Liu Chang , Liu Weixi , Li Dongli , Wu Panpan , Seeram Navindra P. , Chamcheu Jean Christopher , Ma Hang
Published: November 2022

Phenolics enriched pomegranate fruit (Pomella®) and red maple leaf (Maplifa®) extracts and their major phenolic constituents have demonstrated beneficial skin effects through the protection of human skin keratinocytes from oxidative-stress-induced damage. However, their mechanisms of protection of cutaneous collagen are still unclear. Herein, the collagen protective effects of Pomella® and Maplifa®, and their major bioactive phytochemicals, namely, punicalagin (PA) and ginnalin A (GA), respectively, were evaluated using enzymatic assays including collagenase, anti-glycation and cell-based models as well as computational methods. The importance of the modulatory effects was validated at the protein level for type I collagen and matrix metalloproteinases (MMPs) using human-skin-derived keratinocytes. The synergistic collagenase inhibitory effects upon combinations of Pomella® + Maplifa® and PA + GA at a combination ratio of 1:2 and 1:1, respectively, were evaluated using their combination index (CI; a well-established assessment of synergism). Pomella® (50–400 µg/mL), Maplifa® (100–800 µg/mL), PA (50–400 µM), and GA (50–400 µM) dose-dependently inhibited collagenase activity by 26.3–86.3%, 25.7–94.0%, 26.2–94.0%, and 12.0–98.0%, respectively. The CI of the anti-collagenase activity of Pomella® and Maplifa® ranged from 0.53–0.90, while that of PA and GA (12.5/12.5 and 25/25 µM) ranged from 0.66 and 0.69, respectively, suggesting a synergistic inhibitory effect. Interestingly, in the cell-based assays by Western blotting, Pomella® and Maplifa® reduced the protein expression levels of collagen degradation enzymes (MMPs), while simultaneously increasing that of type I collagen in epidermoid carcinoma A431 cells. This is the first report to show that these extracts exert synergistic collagen protective effects. Taken together, these findings provide molecular insights into the usefulness of Pomella® and Maplifa® or their phenolics as bioactive ingredients for skin care products to slow down aging and enhance skin tone.
Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives
Authors: Zhang Lin-Hao , Li Ming-Yue , Wang Da-Yuan , Jin Xue-Jun , Chen Fen-Er , Piao Hu-Ri
Published: November 2022

(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound 6d exhibited the most promising inhibitory activity (IC50 = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that 6d down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound 4f was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds 6d and 4f had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.
Iron Oxide Nanoparticle-Based Ferro-Nanofluids for Advanced Technological Applications
Authors: Imran Mohd , Chaudhary Anis Ahmad , Ahmed Shahzad , Alam Md. Mottahir , Khan Afzal , Zouli Nasser , Hakami Jabir , Rudayni Hassan Ahmad , Khan Salah-Ud-Din
Published: November 2022

Iron oxide nanoparticle (ION)-based ferro-nanofluids (FNs) have been used for different technological applications owing to their excellent magneto-rheological properties. A comprehensive overview of the current advancement of FNs based on IONs for various engineering applications is unquestionably necessary. Hence, in this review article, various important advanced technological applications of ION-based FNs concerning different engineering fields are critically summarized. The chemical engineering applications are mainly focused on mass transfer processes. Similarly, the electrical and electronics engineering applications are mainly focused on magnetic field sensors, FN-based temperature sensors and tilt sensors, microelectromechanical systems (MEMS) and on-chip components, actuators, and cooling for electronic devices and photovoltaic thermal systems. On the other hand, environmental engineering applications encompass water and air purification. Moreover, mechanical engineering or magneto-rheological applications include dampers and sealings. This review article provides up-to-date information related to the technological advancements and emerging trends in ION-based FN research concerning various engineering fields, as well as discusses the challenges and future perspectives.
Isolation, Characterization and Anticancer Activity of Two Bioactive Compounds from Arisaema flavum (Forssk.) Schott
Authors: Nisa Sobia , Bibi Yamin , Masood Saadia , Ali Ashraf , Alam Sadia , Sabir Maimoona , Qayyum Abdul , Ahmed Waqas , Alharthi Sarah , Santali Eman Y. , Alharthy Saif A. , Bawazir Waleed M. , Almashjary Majed N.
Published: November 2022

Medicinal plants play important role in the public health sector worldwide. Natural products from medicinal plants are sources of unlimited opportunities for new drug leads because of their unique chemical diversity. Researchers have focused on exploring herbal products as potential sources for the treatment of cancer, cardiac and infectious diseases. Arisaema flavum (Forssk.) is an important medicinal plant found in the northwest Himalayan regions of Pakistan. It is a poisonous plant and is used as a remedy against snake bites and scorpion stings. In this study, two bioactive compounds were isolated from Arisaema flavum (Forssk.) and their anticancer activity was evaluated against human breast cancer cell line MCF-7 using an MTT assay. The crude extract of Arisaema flavum (Forssk.) was subjected to fractionation using different organic solvents in increasing order of polarity. The fraction indicating maximum activity was then taken for isolation of bioactive compounds using various chromatographic and spectroscopic techniques such as column chromatography, thin-layer chromatography (TLC), gas chromatography–mass spectrometry (GC-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Crude extract of Arisaema flavum (Forssk.), as well as various fractions extracted in different solvents such as n-hexane, chloroform and ethyl acetate, were tested against human breast cancer cell line MCF-7 using an MTT assay. The crude extract exhibited significant dose-dependent anticancer activity with a maximum activity of 78.6% at 500 µg/mL concentration. Two compounds, hexadecanoic acid ethyl ester with molecular formula C18H36O7 and molar mass 284 and 5-Oxo-19 propyl-docosanoic acid methyl ester with molecular formula C26H50O3 and molecular mass 410, were isolated from chloroform fraction. These compounds were tested against the MCF-7cell line for cytotoxic activity and exhibited a significant (p < 0.00l) decrease in cell numbers for MCF-7 cells with IC50 of 25 µM after 48 h of treatment. Results indicated that Arisaema flavum (Forssk.) possesses compounds with cytotoxic activity that can further be exploited to develop anticancer formulations.
Association Complexes of Calix[6]arenes with Amino Acids Explained by Energy-Partitioning Methods
Authors: Masoumifeshani Emran , Chojecki Michał , Rutkowska-Zbik Dorota , Korona Tatiana
Published: November 2022

Intermolecular complexes with calixarenes are intriguing because of multiple possibilities of noncovalent binding for both polar and nonpolar molecules, including docking in the calixarene cavity. In this contribution calix[6]arenes interacting with amino acids are studied with an additional aim to show that tools such as symmetry-adapted perturbation theory (SAPT), functional-group SAPT (F-SAPT), and systematic molecular fragmentation (SMF) methods may provide explanations for different numbers of noncovalent bonds and of their varying strength for various calixarene conformers and guest molecules. The partitioning of the interaction energy provides an easy way to identify hydrogen bonds, including those with unconventional hydrogen acceptors, as well as other noncovalent bonds, and to find repulsive destabilizing interactions between functional groups. Various other features can be explained by energy partitioning, such as the red shift of an IR stretching frequency for some hydroxy groups, which arises from their attraction to the phenyl ring of calixarene. Pairs of hydrogen bonds and other noncovalent bonds of similar magnitude found by F-SAPT explain an increase in the stability of both inclusion and outer complexes.
Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity
Authors: Khramchikhin Andrey V. , Skryl’nikova Mariya A. , Esaulkova Iana L. , Sinegubova Ekaterina O. , Zarubaev Vladimir V. , Gureev Maxim A. , Puzyk Aleksandra M. , Ostrovskii Vladimir A.
Published: November 2022

This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.
The Development of New Methodology for Determination of Vincristine (VCR) in Human Serum Using LC-MS/MS-Based Method for Medical Diagnostics
Authors: Jurowski Kamil , Paprotny Łukasz , Zakrzewski Marcin , Wianowska Dorota , Kasprzyk-Pochopień Joanna , Herman Małgorzata , Madej Katarzyna , Piekoszewski Wojciech , Kubrak Tomasz
Published: November 2022

In this article, we have presented the development and validation of a rapid and sensitive reversed-phase liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the determination of vincristine (VCR) in patient serum samples. Chromatographic separation was achieved on a Kinetex® (Singapore) column using a mobile phase consisting of 25 mM acetic acid and 0.3% formic acid (A) and methanol (B) in a gradient elution mode at a flow rate of 0.3 mL/min. The VCR and internal standard (vinblastine) were monitored using the multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantification (LLOQ) was 0.67 ng/mL, and the upper limit of quantification (ULOQ) was 250 ng/mL for VCR. The calculated values of LOD and LOQ for VCR were 0.075 and 0.228 ng/mL, respectively. The calibration curve was linear over the VCR concentration range of 1.0–250 ng/mL in serum. The intra- and inter-day precision and precision were within the generally accepted criteria for the bioanalytical method (<15%). The method was successfully applied to the analysis of serum samples in clinical practice.