bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms
Authors: Isacescu Ecaterina , Chiroi Paul , Zanoaga Oana , Nutu Andreea , Budisan Liviuta , Pirlog Radu , Atanasov Atanas G. , Berindan-Neagoe Ioana
Published: February 2023

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols—natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment.
Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides
Authors: Cardozo Giuliana , Mastrogiovanni Mauricio , Zeida Ari , Viera Nicolás , Radi Rafael , Reyes Aníbal M. , Trujillo Madia
Published: February 2023

Human peroxiredoxin 3 (HsPrx3) is a thiol-based peroxidase responsible for the reduction of most hydrogen peroxide and peroxynitrite formed in mitochondria. Mitochondrial disfunction can lead to membrane lipoperoxidation, resulting in the formation of lipid-bound fatty acid hydroperoxides (LFA-OOHs) which can be released to become free fatty acid hydroperoxides (fFA-OOHs). Herein, we report that HsPrx3 is oxidized and hyperoxidized by fFA-OOHs including those derived from arachidonic acid and eicosapentaenoic acid peroxidation at position 15 with remarkably high rate constants of oxidation (>3.5 × 107 M−1s−1) and hyperoxidation (~2 × 107 M−1s−1). The endoperoxide-hydroperoxide PGG2, an intermediate in prostanoid synthesis, oxidized HsPrx3 with a similar rate constant, but was less effective in causing hyperoxidation. Biophysical methodologies suggest that HsPrx3 can bind hydrophobic structures. Indeed, molecular dynamic simulations allowed the identification of a hydrophobic patch near the enzyme active site that can allocate the hydroperoxide group of fFA-OOHs in close proximity to the thiolate in the peroxidatic cysteine. Simulations performed using available and herein reported kinetic data indicate that HsPrx3 should be considered a main target for mitochondrial fFA-OOHs. Finally, kinetic simulation analysis support that mitochondrial fFA-OOHs formation fluxes in the range of nM/s are expected to contribute to HsPrx3 hyperoxidation, a modification that has been detected in vivo under physiological and pathological conditions.
Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability
Authors: Carrageta David F. , Freire-Brito Laís , Guerra-Carvalho Bárbara , Ribeiro João C. , Monteiro Bruno S. , Barros Alberto , Oliveira Pedro F. , Monteiro Mariana P. , Alves Marco G.
Published: February 2023

Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to assess the expression and function of the different homologs (UCP1-6) in human spermatozoa. For this purpose, we screened for the mRNA expression of all UCP homologs. Protein expression and immunolocalization of UCP1, UCP2, and UCP3 were also assessed. Highly motile spermatozoa were isolated from human normozoospermic seminal samples (n = 16) and incubated with genipin, an inhibitor of UCPs (0, 0.5, 5, and 50 µM) for 3 h at 37 °C. Viability and total motility were assessed. Mitochondrial membrane potential and ROS production were evaluated. Media were collected and the metabolic profile and antioxidant potential were analyzed by 1H-NMR and FRAP, respectively. The expression of all UCP homologs (UCP1-6) mRNA by human spermatozoa is herein reported for the first time. UCP1-3 are predominant at the head equatorial segment, whereas UCP1 and UCP2 are also expressed at the spermatozoa midpiece, where mitochondria are located. The inhibition of UCPs by 50 µM genipin, resulting in the UCP3 inhibition, did not compromise sperm cell viability but resulted in irreversible total motility loss that persisted despite washing or incubation with theophylline, a cAMP activator. These effects were associated with decreased mitochondrial membrane potential and lactate production. No differences concerning UCP3 expression, however, were observed in spermatozoa from normozoospermic versus asthenozoospermic men (n = 6). The inhibition of UCPs did not increase ROS production, possibly due to the decreased mitochondrial activity and genipin antioxidant properties. In sum, UCPs are major regulators of human spermatozoa motility and metabolism. The discovery and characterization of UCPs’ role in human spermatozoa can shed new light on spermatozoa ROS-related pathways and bioenergetics physiology.
Multifunctional Profiling of Moringa oleifera Leaf Extracts for Topical Application: A Comparative Study of Different Collection Time
Authors: Baldisserotto Anna , Barbari Riccardo , Tupini Chiara , Buzzi Raissa , Durini Elisa , Lampronti Ilaria , Manfredini Stefano , Baldini Erika , Vertuani Silvia
Published: February 2023

This research investigated plant extracts as a source of potential new actives in the nutritional, cosmetic, and pharmaceutical fields. Moringa oleifera, which is extensively known for its nutritional properties, has been investigated in this work by preparation, characterization, and evaluation of the antioxidant (FRAP, DPPH, ORAC, and PCL test), antifungal, photoprotective, and cytotoxicity profile against human melanoma Colo38 cell line of two different extracts (hydroalcoholic and methanolic) and one infusion of dry leaves collected from Paraguay in four distinct harvest times (February, March, April, and May 2017). The outcomes of this study highlight Moringa oleifera as a potential ally to counteract skin aging and oxidative stress, as indicated by the favorable antioxidant profile of the extracts and infusions of Paraguay, which was, in all cases, superior to that provided by the same plant species when collected from Senegal. Moreover, some samples were more efficient in preventing the photodegradation of UVA filter butyl methoxydibenzoylmethane (Avobenzone) compared to commercial filters, thus suggesting an interesting future role as natural additives in sunscreens.
Field Pull-Out Tests of Percussion Driven Earth Anchors (PDEAs)
Authors: Asfaw Natnael Tilahun , Lei Gang , Azizian Mehran , Poudel Arjan , Hoyos Laureano , Yu Xinbao
Published: February 2023

Percussion driven earth anchors (PDEAs) are driven into soils using an installation steel hammer rod. PDEAs are relatively easy to install and have gained wide applications recently. The Texas Department of Transportation (TxDOT) planned to use these anchors for slope stability mitigation along the Clear Fork Trinity River at Interstate Highway 20 (IH-20) in Benbrook, Texas. However, there are no straightforward design and construction guidelines for these systems. In addition, the pull-out capacity and failure mechanisms of PDEAs in clayey soils have not been thoroughly studied. In this study, three PDEAs, Duckbill model 138 II (DB-138 II), were installed and tested on the proposed west channel bank slope to acquire the ultimate pull-out capacity. The anchors were embedded to an average depth of 10 feet into the slope bank, predominantly consisting of sandy lean clay (CL) soil. The slope was graded at an average 2:1 to 2.5:1 configuration. After installation, the anchors were subjected to an upward pull-out force using a hydraulic jack system to measure their pull-out capacity. The pull-out load, displacement, and strains were continuously recorded with a load cell, a linear variable differential transformer (LVDT), and a strain gauge, respectively. Pull-out load versus displacement curves were produced and analyzed to determine the behavior of the anchors. An empirical estimation method was then chosen to estimate pull-out capacity based on undrained shear strengths obtained either from laboratory tests or in situ Texas cone penetration (TCP) data. The comparison between estimated and field-obtained pull-out capacities showed that the pull capacity estimated using TCP data resulted in reasonably good agreement with the field-obtained capacity. The field experiment results help us to understand the relationship between the calculated and actual field pull-out resistance when PDEAs are used in clayey soil slopes.
Improved Procedure for Multi-Focus Image Quality Enhancement Using Image Fusion with Rules of Texture Energy Measures in the Hybrid Wavelet Domain
Authors: Mohan Chinnem Rama , Kiran Siddavaram , Vasudeva
Published: February 2023

Feature extraction is a collection of the necessary detailed information from the given source, which holds the information for further analysis. The quality of the fused image depends on many parameters, particularly its directional selectivity and shift-invariance. On the other hand, the traditional wavelet-based transforms produce ringing distortions and artifacts due to poor directionality and shift invariance. The Dual-Tree Complex Wavelet Transforms (DTCWT) combined with Stationary Wavelet Transform (SWT) as a hybrid wavelet fusion algorithm overcomes the deficiencies of the traditional wavelet-based fusion algorithm and preserves the directional and shift invariance properties. The purpose of SWT is to decompose the given source image into approximate and detailed sub-bands. Further, approximate sub-bands of the given source are decomposed with DTCWT. In this extraction, low-frequency components are considered to implement Texture Energy Measures (TEM), and high-frequency components are considered to implement the absolute-maximum fusion rule. For the detailed sub-bands, the absolute-maximum fusion rule is implemented. The texture energy rules have significantly classified the image and improved the output image’s accuracy after fusion. Finally, inverse SWT is applied to generate an extended fused image. Experimental results are evaluated to show that the proposed approach outperforms approaches reported earlier. This paper proposes a fusion method based on SWT, DTCWT, and TEM to address the inherent defects of both the Parameter Adaptive-Dual Channel Pulse coupled neural network (PA-DCPCNN) and Multiscale Transform-Convolutional Sparse Representation (MST-CSR).
Finite Element Modeling of the Soil-Nailing Process in Nailed-Soil Slopes
Authors: Mohamed Mahmoud H. , Ahmed Mohd , Mallick Javed , AlQadhi Saeed
Published: February 2023

The finite element technique has been accepted as a tool for modeling geotechnical complex processes. In this study, finite element (FE) modeling of various stages of the soil-nailing process, i.e., construction stages and overburden pressure stages, is carried out considering different soil parameters, simulating with in-house developed laboratory models. The soil-nailing process built in laboratory models is idealized as a plain strain problem and modeled in PLAXIS software. The laboratory models of the soil-nailing process consist of a Perspex sheet box containing a sandy soil slope, a Perspex sheet facing, steel bars as reinforcement and a steel plate as foundation. The stress–strain relationship of the sand is represented by a Hardening-Soil model. The interface at the soil and nail is described by the Coulomb friction model. The behavior of the soil-nailing process, during the construction stage and under varying overburden pressure and varying soil density, are investigated in terms of displacements of slope and stress conditions in slope soil mass. The slope displacements and stress conditions in slope soil mass are all well presented by the FE modeling and compared with laboratory model test data. The sensitivity analysis of the laboratory models’ dimensions is carried out by three-dimensional modeling of the nailed-soil slope. It can be concluded that the developed finite element model has the potential to simulate the performance of a field nailed-soil slope during construction and working stages and could provide guidance for the construction/maintenance of soil-nailed cut slopes in granular soils/weathered rocks.
Event-Triggered Single-Network ADP for Zero-Sum Game of Unknown Nonlinear Systems with Constrained Input
Authors: Peng Binbin , Cui Xiaohong , Cui Yang , Chen Wenjie
Published: February 2023

In this paper, an event-triggered adaptive dynamic programming (ADP) method is proposed to deal with the H∞ problem with unknown dynamic and constrained input. Firstly, the H∞-constrained problem is regarded as the two-player zero-sum game with the nonquadratic value function. Secondly, we develop the event-triggered Hamilton–Jacobi–Isaacs(HJI) equation, and an event-triggered ADP method is proposed to solve the HJI equation, which is equivalent to solving the Nash saddle point of the zero-sum game. An event-based single-critic neural network (NN) is applied to obtain the optimal value function, which reduces the communication resource and computational cost of algorithm implementation. For the event-triggered control, a triggering condition with the level of disturbance attenuation is developed to limit the number of sampling states, and the condition avoids Zeno behavior by proving the existence of events with minimum triggering interval. It is proved theoretically that the closed-loop system is asymptotically stable, and the critic NN weight error is uniformly ultimately boundedness (UUB). The learning performance of the proposed algorithm is verified by two examples.
Tasks Allocation Based on Fuzzy Rules in Fractional Assembly Line with Redundancy
Authors: Renna Paolo
Published: February 2023

In recent years, assembly line design methodologies have included the possibility of sharing tasks between stations. These approaches increase the throughput, improving the workload balance among the stations. Sharing operations can support the management of assembly lines with task redundancy. The redundancy of the tasks between two consecutive stations improves the robustness of the assembly line to unforeseen events. A control policy that allocates the shared tasks between two adjacent stations is crucial for the performance of the assembly line. This paper proposes a fuzzy approach to distributing the workload of the shared tasks between two consecutive stations. The fuzzy model allows for the distribution of the workload between the stations in a more gradual way. Simulations were conducted to allow for a performance evaluation with a model proposed in the literature. The results show how the fuzzy model improves all the performance measures evaluated; in particular, when the inter-arrival of the raw items is rather stable. In these conditions, the reduction of the average time and its standard deviation is about 50% to 80%, while the reduction of the work in process is about 60% to 90%. These benefits are obtained with a relevant increase of the variations of the average utilization of the stations.
Design Optimization of Stacked Pallet Load Units
Authors: Sawicki Piotr , Sawicka Hanna
Published: February 2023

The article deals with the problem of building stacked pallet load units consisting of at least two stackable pallet load units. Moreover, this article concerns the part of the flow of goods in distribution networks that is prepared at the place of initial assembly in the form of palletized loading units designed for the final receiver. Such a unit does not exceed the limits of permissible weight or height. The article proposes a single-criteria binary programming model in which the goal is to minimize the pallet spaces required to accommodate the constructed units. In addition to the classical parameters of acceptable weight and height of the units, the constraints also take into account the fragility of the goods placed on each unit, filling the top layer of each unit, and its height homogeneity. The model developed was verified on a test dataset, and the savings from the use of optimum construction of the stacked palletized cargo units were demonstrated through the conducted experiments.
Biosignals by In-Shoe Plantar Pressure Sensors on Different Hardness Mats during Running: A Cross-Over Study
Authors: García-Arroyo Jaime , Pacheco-da-Costa Soraya , Molina-Rueda Francisco , Vicente-Campos Davinia , Calvo-Lobo César , Alguacil-Diego Isabel M.
Published: February 2023

Although the effects of running on plantar pressures have been detailed on several surfaces with different hardness, there is a lack of studies assessing the mechanical behavior analysis by in-shoe plantar pressure sensors on different hardness mats during running. The aim of the present study was to determine in-shoe maximum forces and peak plantar pressures on mats with different hardness, such as hard, soft and air chamber mats, during running. A cross-over study was carried out including 36 amateur runners from a sport center. The maximum force and peak pressures of the foot plantar region were analyzed on three different mat hardnesses —soft and hard polyurethane foam mats and air chamber mats—by in-shoe instrumented insoles. Running on soft polyurethane foam mats presented reduced maximum forces in the whole plantar region and mainly peak pressures in the anterior part of the foot plantar region, such as the toes and first to fourth metatarsal heads, compared to hard polyurethane foam and air chamber mats. The peak pressure in the fifth metatarsal head was specifically reduced during running on soft compared to hard polyurethane foam mats, and running on these soft mats decreased calcaneus peak pressures compared to running on air chamber mats. Running on air chamber mats increased peak plantar pressures in the first metatarsal head compared to running on hard polyurethane foam mats. The mechanical behavior of mats of different hardness could be used to adjust the degree of impact on plantar pressures to determine the most appropriate materials and hardness for running.
A Cooperative Automatic Retransmission Request Technique Based on Listening Node Participation Competition
Authors: Chen Guangjiao , Chen Guifen
Published: February 2023

To improve the stability of automatic retransmission requests, a competition control method for automatic retransmission requests of cooperative-based listening nodes is proposed. Because the number of source nodes involved in retransmission communication is reduced, the method reduces the communication energy consumption. Cooperative communication consists of two main parts of work. When the source node sends signals to the surrounding nodes, the relay nodes and other nodes receive the broadcast signals. The signals received by both nodes are the same. A node competition mechanism based on the probability of link disruption as an indicator is designed. The node with higher energy is identified as the node that retransmits the signal. An experiment on the performance comparison of multiple algorithms is organized by simulation. The results show that the proposed new strategy has lower values in BER and BER metrics. This indicates that the proposed method transmits high values of signal quality compared to other dominant methods of retransmitting signals. Because the forwarded signal is successfully transmitted and the source node is no longer involved in the retransmission effort. In cooperative communication, the number of retransmission requests is reduced, and the energy consumed by the system is reduced. Because the improved algorithm achieves low-power communication, the proposed algorithm is practical and innovative in cooperative communication.
Sol-Gel Synthesis of Caffeic Acid Entrapped in Silica/Polyethylene Glycol Based Organic-Inorganic Hybrids: Drug Delivery and Biological Properties
Authors: Vertuccio Luigi , Guadagno Liberata , D’Angelo Antonio , Viola Veronica , Raimondo Marialuigia , Catauro Michelina
Published: February 2023

The failure of medical devices, such as bones prosthesis, is mainly due to inflammatory and infectious phenomena. Entrapping anti-inflammatory and antimicrobial agents inside the biomaterial matrix could avoid these phenomena. In this context, inorganic/organic silica (S)/polyethylene glycol (P)/caffeic acid (A) hybrid systems were synthesized via the sol-gel method with different weight percentages of P and A. Fourier-transform infrared (FT-IR) revealed that caffeic acid undergoes an oxidizing phenomenon in the sol-gel synthesis condition. Additionally, the formation of a hydroxyapatite layer on hybrid surfaces was demonstrated by employing the Kokubo test and analyzing the samples using scanning electron microscopy, X-ray diffraction, and FT-IR. Moreover, further characterization of the antimicrobial activity of the synthesized biomaterials was carried out using the Kirby–Bauer test. Finally, UV-Vis measurement was useful to evaluate the caffeic acid kinetic release in simulated body fluid (SBF) at 37 °C. The kinetic study disclosed that the hybrid materials without polyethylene glycol had faster release rates than the ones obtained without the organic polymer.
Speech Emotion Recognition Based on Two-Stream Deep Learning Model Using Korean Audio Information
Authors: Jo A-Hyeon , Kwak Keun-Chang
Published: February 2023

Identifying a person’s emotions is an important element in communication. In particular, voice is a means of communication for easily and naturally expressing emotions. Speech emotion recognition technology is a crucial component of human–computer interaction (HCI), in which accurately identifying emotions is key. Therefore, this study presents a two-stream-based emotion recognition model based on bidirectional long short-term memory (Bi-LSTM) and convolutional neural networks (CNNs) using a Korean speech emotion database, and the performance is comparatively analyzed. The data used in the experiment were obtained from the Korean speech emotion recognition database built by Chosun University. Two deep learning models, Bi-LSTM and YAMNet, which is a CNN-based transfer learning model, were connected in a two-stream architecture to design an emotion recognition model. Various speech feature extraction methods and deep learning models were compared in terms of performance. Consequently, the speech emotion recognition performance of Bi-LSTM and YAMNet was 90.38% and 94.91%, respectively. However, the performance of the two-stream model was 96%, which was a minimum of 1.09% and up to 5.62% improved compared with a single model.
Condition-Based Maintenance Optimization Method Using Performance Margin
Authors: Li Shuyu , Wen Meilin , Zu Tianpei , Kang Rui
Published: February 2023

As a maintenance strategy to reduce unexpected failures and enable safe operation, condition-based maintenance (CBM) has been widely used in recent years. The maintenance decision criteria of CBM in the literature mostly originate from statistical failure data or degradation states, few of which can directly and effectively reflect the current state and analyze condition monitoring data, maintenance measures, and reliability together at the same time. In this paper, we introduce the performance margin as a decision criterion of CBM. We propose a condition-based maintenance optimization method using performance margin. Considering a CBM optimization problem for a degrading and periodically inspected component, a newly developed performance margin degradation model is established when three different maintenance measures become involved. Maintenance measure effect factors, maintenance decision vectors, and maintenance measure threshold vectors are developed to update the degradation model. And to build a maintenance optimization model, both cost and loss related to maintenance decision problems and reliability obtained by performance margin have been taken into consideration. Finally, a numerical example is provided to illustrate the proposed optimization method.
Properties of Differential Subordination and Superordination for Multivalent Functions Associated with the Convolution Operators
Authors: Cotîrlă Luminiţa-Ioana , Juma Abdul Rahman S.
Published: February 2023

Using convolution (or Hadamard product), we define the El-Ashwah and Drbuk linear operator, which is a multivalent function in the unit disk U=w:w<1 and w∈₵, and satisfy its specific relationship to derive the subordination, superordination, and sandwich results for this operator by using properties of subordination and superordination concepts.
Two Reliable Computational Techniques for Solving the MRLW Equation
Authors: Al-Khaled Kamel , Jafer Haneen
Published: February 2023

In this paper, a numerical solution of the modified regularized long wave (MRLW) equation is obtained using the Sinc-collocation method. This approach approximates the space dimension of the solution with a cardinal expansion of Sinc functions. First, discretizing the time derivative of the MRLW equation by a classic finite difference formula, while the space derivatives are approximated by a θ—weighted scheme. For comparison purposes, we also find a soliton solution using the Adomian decomposition method (ADM). The Sinc-collocation method was were found to be more accurate and efficient than the ADM schemes. Furthermore, we show that the number of solitons generated can be approximated using the Maxwellian initial condition. The proposed methods’ results, analytical solutions, and numerical methods are compared. Finally, a variety of graphical representations for the obtained solutions makes the dynamics of the MRLW equation visible and provides the mathematical foundation for physical and engineering applications.
On the Estimation of the Binary Response Model
Authors: Amin Muhammad , Akram Muhammad Nauman , Kibria B. M. Golam , Alshanbari Huda M. , Fatima Nahid , Elhassanein Ahmed
Published: February 2023

The binary logistic regression model (LRM) is practical in situations when the response variable (RV) is dichotomous. The maximum likelihood estimator (MLE) is generally considered to estimate the LRM parameters. However, in the presence of multicollinearity (MC), the MLE is not the correct choice due to its inflated standard deviation (SD) and standard errors (SE) of the estimates. To combat MC, commonly used biased estimators, i.e., the Ridge estimators (RE) and Liu estimators (LEs), are preferred. However, most of the time, the traditional LE attains a negative value for its Liu parameter (LP), which is considered to be a major drawback. Therefore, to overcome this issue, we proposed a new adjusted LE for the binary LRM. Owing to numerical evaluation purposes, Monte Carlo simulation (MCS) study is performed under different conditions where bias and mean squared error are the performance criteria. Findings showed the superiority of our proposed estimator in comparison with the other estimation methods due to the existence of high but imperfect multicollinearity, which clearly means that it is consistent when the regressors are multicollinear. Furthermore, the findings demonstrated that whenever there is MC, the MLE is not the best choice. Finally, a real application is being considered to be evidence for the advantage of the intended estimator. The MCS and the application findings pointed out that the considered adjusted LE for the binary logistic regression model is a more efficient estimation method whenever the regressors are highly multicollinear.
Rodent Models of Diabetic Retinopathy as a Useful Research Tool to Study Neurovascular Cross-Talk
Authors: Polewik Karolina , Kosek Maciej , Jamrozik Daniel , Matuszek Iwona , Smędowski Adrian , Lewin-Kowalik Joanna , Pietrucha-Dutczak Marita
Published: February 2023

Diabetes is a group of metabolic diseases leading to dysfunction of various organs, including ocular complications such as diabetic retinopathy (DR). Nowadays, DR treatments involve invasive options and are applied at the sight-threatening stages of DR. It is important to investigate noninvasive or pharmacological methods enabling the disease to be controlled at the early stage or to prevent ocular complications. Animal models are useful in DR laboratory practice, and this review is dedicated to them. The first part describes the characteristics of the most commonly used genetic rodent models in DR research. The second part focuses on the main chemically induced models. The authors pay particular attention to the streptozotocin model. Moreover, this section is enriched with practical aspects and contains the current protocols used in research in the last three years. Both parts include suggestions on which aspect of DR can be tested using a given model and the disadvantages of each model. Although animal models show huge variability, they are still an important and irreplaceable research tool. Note that the choice of a research model should be thoroughly considered and dependent on the aspect of the disease to be analyzed.
Independent Evidence for the Preservation of Endogenous Bone Biochemistry in a Specimen of Tyrannosaurus rex
Authors: Anné Jennifer , Canoville Aurore , Edwards Nicholas P. , Schweitzer Mary H. , Zanno Lindsay E.
Published: February 2023

Biomolecules preserved in deep time have potential to shed light on major evolutionary questions, driving the search for new and more rigorous methods to detect them. Despite the increasing body of evidence from a wide variety of new, high resolution/high sensitivity analytical techniques, this research is commonly met with skepticism, as the long standing dogma persists that such preservation in very deep time (>1 Ma) is unlikely. The Late Cretaceous dinosaur Tyrannosaurus rex (MOR 1125) has been shown, through multiple biochemical studies, to preserve original bone chemistry. Here, we provide additional, independent support that deep time bimolecular preservation is possible. We use synchrotron X-ray fluorescence imaging (XRF) and X-ray absorption spectroscopy (XAS) to investigate a section from the femur of this dinosaur, and demonstrate preservation of elements (S, Ca, and Zn) associated with bone remodeling and redeposition. We then compare these data to the bone of an extant dinosaur (bird), as well as a second non-avian dinosaur, Tenontosaurus tilletti (OMNH 34784) that did not preserve any sign of original biochemistry. Our data indicate that MOR 1125 bone cortices have similar bone elemental distributions to that of an extant bird, which supports preservation of original endogenous chemistry in this specimen.
Essential Mineral Elements and Potentially Toxic Elements in Orange-Fleshed Sweet Potato Cultivated in Northern Ethiopia
Authors: Lamaro Gloria Peace , Tsehaye Yemane , Girma Atkilt , Vannini Andrea , Fedeli Riccardo , Loppi Stefano
Published: February 2023

This study investigated the influence of the agro-climatic environment of Northern Ethiopia on the content of essential mineral elements of selected orange-fleshed sweetpotato genotypes, the potential contribution of each genotype’s essential mineral elements to the recommended dietary allowance, and the potential risk to human health from the accumulation of potentially toxic elements in the tuberous roots of the studied genotypes. The results showed consistent interspecific variations in the content of essential mineral elements among the studied orange-fleshed sweetpotato genotypes, as well as important intraspecific differences, which could depend on the variations in soil mineral and organic matter content, rainfall, temperature, as well as interactions between genotype and environment. The investigated genotypes, especially Kulfo, Ininda, Gloria, and Amelia, can provide an amount of several essential mineral elements high enough to meet 100% of the recommended dietary allowance for all age groups ≤8 years. The mean content of potentially toxic elements in tuberous roots and their daily intake values were within the recommended permissible levels; likewise, no health risk was associated with the consumption of these genotypes for Cr, As, and Pb. However, Al, Cd, Cu, Fe, Mn, and Ni is > 1, consumption imposes health risks based on daily accumulation.
A TaqMan® Assay Allows an Accurate Detection and Quantification of Fusarium spp., the Causal Agents of Tomato Wilt and Rot Diseases
Authors: Campos Maria Doroteia , Varanda Carla , Patanita Mariana , Amaro Ribeiro Joana , Campos Catarina , Materatski Patrick , Albuquerque André , Félix Maria do Rosário
Published: February 2023

In tomato plants, Fusarium spp. have been increasingly associated with several wilt and rot diseases that are responsible for severe yield losses. Here, we present a real-time PCR TaqMan® MGB (Minor Groove Binder) assay to detect and discriminate Fusarium spp. from other fungal species that affect tomato plants. The methodology used is based on the selective amplification of the internal transcribed spacer (ITS) region of Fusarium spp. This assay revealed to be highly specific and sensitive for Fusarium species, targeting only the 29 Fusarium isolates from the 45 tested isolates associated to tomato diseases. Sensitivity was assessed with serial dilutions of Fusarium genomic DNA, with the limit of detection of 3.05 pg. An absolute DNA quantification method was also established, based on the determination of the absolute number of target copies. Finally, the effectiveness of the assay was successfully validated with the detection and quantification of Fusarium spp. in potentially infected tomato plants from an experimental field and in control plants grown under controlled conditions. The established methodology allows a reliable, sensitive, and reproducible estimation of Fusarium accumulation in infected tomato plants, gaining new insights for disease control and providing an additional tool in the screening of resistant plants.
The Contribution of the Sheep and the Goat Model to the Study of Ovarian Ageing
Authors: Montenegro Luís , Magalhães Paulo , Guerreiro Adriana Costa , Brandão Catarina , Pinto Anabela , Almeida Henrique , Martins-Bessa Ana , Silva Elisabete
Published: February 2023

Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells has been identified in the ovaries of reproductively aged mice. These cells have been considered hallmarks of ovarian ageing. However, up to date multinucleated giant cells have only been described in the ovaries of the mice. Therefore, the aim of the present work was to evaluate and characterize the presence of such hallmarks of ovarian ageing in the sheep and the goat. In this study, ovaries from juvenile (6 months) and mature animals (18–24 months) were used. The hematoxylin and eosin technique was performed to describe the ovarian morphology and evaluate the ovarian follicle reserve pool. Sudan black B staining and the detection of autofluorescence emission were used to identify and characterize the presence of multinucleated giant cells. Statistical analyses were performed with GraphPad Prism 9.0.0. A decrease in the follicle reserve pool and the presence of multinucleated giant cells, with lipofuscin accumulation and the emission of autofluorescence, were observed in the ovaries of the mature animals of both species. Our results support the interest in the use of the ovine and the caprine model, that share physiological and pathophysiological characteristics with humans, in future studies addressing ovarian ageing.
Distinct Molecular Patterns of Two-Component Signal Transduction Systems in Thermophilic Cyanobacteria as Revealed by Genomic Identification
Authors: Tang Jie , Yao Dan , Zhou Huizhen , Wang Mingcheng , Daroch Maurycy
Published: February 2023

Two-component systems (TCSs) play crucial roles in sensing and responding to environmental signals, facilitating the acclimation of cyanobacteria to hostile niches. To date, there is limited information on the TCSs of thermophilic cyanobacteria. Here, genome-based approaches were used to gain insights into the structure and architecture of the TCS in 17 well-described thermophilic cyanobacteria, namely strains from the genus Leptodesmis, Leptolyngbya, Leptothermofonsia, Thermoleptolyngbya, Thermostichus, and Thermosynechococcus. The results revealed a fascinating complexity and diversity of the TCSs. A distinct composition of TCS genes existed among these thermophilic cyanobacteria. A majority of TCS genes were classified as orphan, followed by the paired and complex cluster. A high proportion of histidine kinases (HKs) were predicted to be cytosolic subcellular localizations. Further analyses suggested diversified domain architectures of HK and response regulators (RRs), putatively in association with various functions. Comparative and evolutionary genomic analyses indicated that the horizontal gene transfer, as well as duplications events, might be involved in the evolutionary history of TCS genes in Thermostichus and Thermosynechococcus strains. A comparative analysis between thermophilic and mesophilic cyanobacteria indicated that one HK cluster and one RR cluster were uniquely shared by all the thermophilic cyanobacteria studied, while two HK clusters and one RR cluster were common to all the filamentous thermophilic cyanobacteria. These results suggested that these thermophile-unique clusters may be related to thermal characters and morphology. Collectively, this study shed light on the TCSs of thermophilic cyanobacteria, which may confer the necessary regulatory flexibility; these findings highlight that the genomes of thermophilic cyanobacteria have a broad potential for acclimations to environmental fluctuations.
Chronic Exposure to Nitric Oxide Induces P53 Mutations and Malignant-like Features in Human Breast Epithelial Cells
Authors: Cheng Robert Y. S. , Burkett Sandra , Ambs Stefan , Moody Terry , Wink David A. , Ridnour Lisa A.
Published: February 2023

The small endogenous signaling molecule nitric oxide (NO) has been linked with chronic inflammation and cancer. The effects of NO are both concentration and temporally dependent; under some conditions, NO protects against damage caused by reactive oxygen species and activates P53 signaling. During chronic inflammation, NO causes DNA damage and inhibits repair proteins. To extend our understanding of the roles of NO during carcinogenesis, we investigated the possible effects of chronic NO exposure on MCF10A breast epithelial cells, as defined by changes in cellular morphology, chromosome/genomic stability, RNA, and protein expression, and altered cell phenotypes. Human MCF10A cells were maintained in varying doses of the NO donor DETANO for three weeks. Distinct patterns of genomic modifications in TP53 and KRAS target genes were detected in NO-treated cells when compared to background mutations. In addition, quantitative real-time PCR demonstrated an increase in the expression of cancer stem cell (CSC) marker CD44 after prolonged exposure to 300 μM DETANO. While similar changes in cell morphology were found in cells exposed to 300–500 μM DETANO, cells cultured in 100 μM DETANO exhibited enhanced motility. In addition, 100 μM NO-treated cells proliferated in serum-free media and selected clonal populations and pooled cells formed colonies in soft agar that were clustered and disorganized. These findings show that chronic exposure to NO generates altered breast epithelial cell phenotypes with malignant characteristics.
Restoring Epigenetic Reprogramming with Diet and Exercise to Improve Health-Related Metabolic Diseases
Authors: Abraham Merlin Jesso , El Sherbini Adham , El-Diasty Mohammad , Askari Sussan , Szewczuk Myron R.
Published: February 2023

Epigenetic reprogramming predicts the long-term functional health effects of health-related metabolic disease. This epigenetic reprogramming is activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The epigenetic and environmental changes involve a roadmap of epigenetic networking, such as dietary components and exercise on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, which are paramount to establishing youthful cell type and health. Nutrition and exercise are among the most well-known environmental epigenetic factors influencing the proper developmental and functional lifestyle, with potential beneficial or detrimental effects on health status. The diet and exercise strategies applied from conception could represent an innovative epigenetic target for preventing and treating human diseases. Here, we describe the potential role of diet and exercise as therapeutic epigenetic strategies for health and diseases, highlighting putative future perspectives in this field.
Therapeutic Oral Application of Carvacrol Alleviates Acute Campylobacteriosis in Mice Harboring a Human Gut Microbiota
Authors: Foote Minnja S. , Du Ke , Mousavi Soraya , Bereswill Stefan , Heimesaat Markus M.
Published: February 2023

Human Campylobacter jejuni infections are rising globally. Since antibiotics are usually not indicated in acute campylobacteriosis, antibiotic-independent intervention measures are desirable. The phenolic compound carvacrol constitutes a promising candidate molecule given its antimicrobial and immune-modulatory features. To test the disease-alleviating effects of oral carvacrol treatment in acute murine campylobacteriosis, IL-10−/− mice harboring a human gut microbiota were perorally infected with C. jejuni and treated with carvacrol via the drinking water. Whereas C. jejuni stably established in the gastrointestinal tract of mice from the placebo cohort, carvacrol treatment resulted in lower pathogen loads in the small intestines on day 6 post infection. When compared to placebo, carvacrol ameliorated pathogen-induced symptoms including bloody diarrhea that was accompanied by less distinct histopathological and apoptotic cell responses in the colon. Furthermore, innate and adaptive immune cell numbers were lower in the colon of carvacrol- versus placebo-treated mice. Notably, carvacrol application dampened C. jejuni-induced secretion of pro-inflammatory mediators in intestinal, extra-intestinal and systemic organs to naive levels and furthermore, resulted in distinct shifts in the fecal microbiota composition. In conclusion, our preclinical placebo-controlled intervention study provides evidence that therapeutic carvacrol application constitutes a promising option to alleviate campylobacteriosis in the infected vertebrate host.
The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer
Authors: Sun Aiqin , Chen Yifei , Tian Xianyan , Lin Qiong
Published: February 2023

Colorectal cancer (CRC) is estimated to rank as the second reason for cancer-related deaths, and the prognosis of CRC patients remains unsatisfactory. Numerous studies on gastrointestinal cell biology have shown that the E3 ligase-mediated ubiquitination exerts key functions in the pathogenesis of CRC. The homologous to E6-associated protein C-terminus (HECT) family E3 ligases are a major group of E3 enzymes, featured with the presence of a catalytic HECT domain, which participate in multiple cellular processes; thus, alterations in HECT E3 ligases in function or expression are closely related to the occurrence and development of many human malignancies, including—but not limited to—CRC. In this review, we summarize the potential role of HECT E3 ligases in colorectal carcinogenesis and the related underlying molecular mechanism to expand our understanding of their pathological functions. Exploiting specific inhibitors targeting HECT E3 ligases could be a potential therapeutic strategy for CRC therapy in the future.
Enamel Structure Defects in Kdf1 Missense Mutation Knock-in Mice
Authors: Li Pei , Zeng Binghui , Xie Weihong , Xiao Xue , Lin Ling , Yu Dongsheng , Zhao Wei
Published: February 2023

The Keratinocyte differentiation factor 1 (KDF1) is reported to take part in tooth formation in humans, but the dental phenotype of Kdf1 mutant mice has not been understood. Additionally, the role of the KDF1 gene in dental hard tissue development is rarely known. In this study, we constructed a Kdf1 missense mutation knock-in mouse model through CRISPR/Cas9 gene-editing technology. Enamel samples from wildtypes (WT) and Kdf1 homozygous mutants (HO) were examined using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), an atomic force microscope (AFM) and Raman microspectroscopy. The results showed that a novel Kdf1 missense mutation (c. 908G>C, p.R303P) knock-in mice model was constructed successfully. The enamel of HO mice incisors appeared chalky and defective, exposing the rough interior of the inner enamel and dentin. Micro-CT showed that HO mice had lower volume and mineral density in their tooth enamel. In addition, declined thickness was found in the unerupted enamel layer of incisors in the HO mice. Using SEM and AFM, it was found that enamel prisms in HO mice enamel were abnormally and variously shaped with loose decussating crystal arrangement, meanwhile the enamel rods were partially fused and collapsed, accompanied by large gaps. Furthermore, misshapen nanofibrous apatites were disorderly combined with each other. Raman microspectroscopy revealed a compromised degree of order within the crystals in the enamel after the Kdf1 mutation. To conclude, we identified enamel structure defects in the Kdf1 missense mutation knock-in mice, which displayed fragmentary appearance, abnormally shaped prism structure, decreased mineral density, altered crystal ordering degree and chemical composition of the enamel layer. This may support the potential role of the KDF1 gene in the natural development of enamel.