bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Colony Predation Algorithm Optimized Convolutional Neural Networks for Electrocardiogram Signal Classification
Authors: He Xinxin , Shan Weifeng , Zhang Ruilei , Heidari Ali Asghar , Chen Huiling , Zhang Yudong
Published: June 2023

Recently, swarm intelligence algorithms have received much attention because of their flexibility for solving complex problems in the real world. Recently, a new algorithm called the colony predation algorithm (CPA) has been proposed, taking inspiration from the predatory habits of groups in nature. However, CPA suffers from poor exploratory ability and cannot always escape solutions known as local optima. Therefore, to improve the global search capability of CPA, an improved variant (OLCPA) incorporating an orthogonal learning strategy is proposed in this paper. Then, considering the fact that the swarm intelligence algorithm can go beyond the local optimum and find the global optimum solution, a novel OLCPA-CNN model is proposed, which uses the OLCPA algorithm to tune the parameters of the convolutional neural network. To verify the performance of OLCPA, comparison experiments are designed to compare with other traditional metaheuristics and advanced algorithms on IEEE CEC 2017 benchmark functions. The experimental results show that OLCPA ranks first in performance compared to the other algorithms. Additionally, the OLCPA-CNN model achieves high accuracy rates of 97.7% and 97.8% in classifying the MIT-BIH Arrhythmia and European ST-T datasets.
Investigating Influence of Visual Elements of Arcade Buildings and Streetscapes on Place Identity Using Eye-Tracking and Semantic Differential Methods
Authors: Fu Hao , Wang Pohsun , Zhou Junling , Zhang Shuyuan , Li Yan
Published: June 2023

This study explored the overall visual elements of arcade buildings and streetscapes from the perspective of tourists and then evaluated their influence on the identity and emotion of places. The scope of the research was to take the arcade building in the port area of Shantou Small Park in Guangdong, China, and apply the eye-tracking experiment method and semantic difference method. This entailed collecting the eye-tracking data of 16 people, implementing 334 questionnaires for evaluation, verifying the correlation between the visual elements and place identity emotions, and then screening out the visual elements that affect place identity through correlation analysis and multiple linear regression analysis. The results show that plaque text morphological richness (p = 0.045 < 0.05, and the regression coefficient B = 0.146), the color brightness of plaque text (p = 0.031 < 0.01, and the regression coefficient B = 0.171), window morphological richness (p = 0.038 < 0.05, and the regression coefficient B = 0.106), window color brilliance (p = 0.047 < 0.01, and regression coefficient B = 0.094), and plant color brilliance (p = 0.029 < 0.05, and the regression coefficient B = 0.154) are five visual element evaluation factors that have a significant correlation with the identity and emotion of places. Although the fineness of architectural decoration is negatively correlated with place identity, it is not obviously significant. The research results provide reference for the visual control design of arcade buildings.
Survival Trends in Patients with Small Intestinal Neuroendocrine Tumours—A Cohort Study in Central Norway
Authors: Folkestad Oddry , Hauso Øyvind , Mjønes Patricia , Fougner Reidun , Wasmuth Hans H. , Fossmark Reidar
Published: June 2023

Improved surgical resection and oncological treatment, or an earlier diagnosis may increase survival in small intestinal neuroendocrine tumours (SI-NETs), but only few studies have examined survival trends. We aimed to examine the trend in overall survival and associated factors in SI-NET patients. All patients with SI-NETs at a regional hospital from June 2005 to December 2021 (n = 242) were identified, and the cohort was divided in half, constituting a first period (until November 2012) and a second period (from November 2012). Disease and treatment characteristics, including European Neuroendocrine Tumour Society (ENETS) stage, surgery, oncological treatment and survival, were recorded. The majority (n = 205 (84.7%)) were treated surgically and surgery was considered curative in 137 (66.8%) patients. Median survival was longer in the second period (9.0 years 95% CI 6.4–11.7 in the first period vs. median not reached in the second period, p = 0.014), with 5-year survival rates of 63.5% and 83.5%, respectively. ENETS stage and oncological treatment did not differ between the periods, but factors associated with surgical quality, such as lymph node harvest and resection of multiple SI-NETs, were significantly higher in the second period. Age, ENETS stage, time period and tumour resection were independently associated with survival in a multivariate analysis.
Evaluation of RANO Criteria for the Assessment of Tumor Progression for Lower-Grade Gliomas
Authors: Raman Fabio , Mullen Alexander , Byrd Matthew , Bae Sejong , Kim Jinsuh , Sotoudeh Houman , Morón Fanny E. , Fathallah-Shaykh Hassan M.
Published: June 2023

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for lower-grade gliomas (LGGs) define tumor progression as ≥25% change in the T2/FLAIR signal area based on an operator’s discretion of the perpendicular diameter of the largest tumor cross-section. Potential sources of error include acquisition inconsistency of 2D slices, operator selection variabilities in both representative tumor cross-section and measurement line locations, and the inability to quantify infiltrative tumor margins and satellite lesions. Our goal was to assess the accuracy and reproducibility of RANO in LG. Materials and Methods: A total of 651 FLAIR MRIs from 63 participants with LGGs were retrospectively analyzed by three blinded attending physicians and three blinded resident trainees using RANO criteria, 2D visual assessment, and computer-assisted 3D volumetric assessment. Results: RANO product measurements had poor-to-moderate inter-operator reproducibility (r2 = 0.28–0.82; coefficient of variance (CV) = 44–110%; mean percent difference (diff) = 0.4–46.8%) and moderate-to-excellent intra-operator reproducibility (r2 = 0.71–0.88; CV = 31–58%; diff = 0.3–23.9%). When compared to 2D visual ground truth, the accuracy of RANO compared to previous and baseline scans was 66.7% and 65.1%, with an area under the ROC curve (AUC) of 0.67 and 0.66, respectively. When comparing to volumetric ground truth, the accuracy of RANO compared to previous and baseline scans was 21.0% and 56.5%, with an AUC of 0.39 and 0.55, respectively. The median time delay at diagnosis was greater for false negative cases than for false positive cases for the RANO assessment compared to previous (2.05 > 0.50 years, p = 0.003) and baseline scans (1.08 > 0.50 years, p = 0.02). Conclusion: RANO-based assessment of LGGs has moderate reproducibility and poor accuracy when compared to either visual or volumetric ground truths.
Allele-Specific Epigenetic Regulation of FURIN Expression at a Coronary Artery Disease Susceptibility Locus
Authors: Yang Wei , Cao Junjun , McVey David G. , Ye Shu
Published: June 2023

Genome-wide association studies have revealed an association between the genetic variant rs17514846 in the FURIN gene and coronary artery disease. We investigated the mechanism through which rs17514846 modulates FURIN expression. An analysis of isogenic monocytic cell lines showed that the cells of the rs17514846 A/A genotype expressed higher levels of FURIN than cells of the C/C genotype. Pyrosequencing showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine increased FURIN expression. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected DNA-protein complex bands that were altered by an anti-MeCP2 antibody. A chromatin immunoprecipitation assay with the anti-MeCP2 antibody showed an enrichment of the DNA sequence containing the rs17514846 site. siRNA-mediated knockdown of MeCP2 caused an increase in FURIN expression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor. The results of our study suggest that DNA methylation inhibits FURIN expression and that the coronary artery disease-predisposing variant rs17514846 modulates FURIN expression and monocyte migration via an allele-specific effect on DNA methylation.
Emergency MRI in Spine Trauma of Children and Adolescents—A Pictorial Review
Authors: Sirén Aapo , Nyman Mikko , Syvänen Johanna , Mattila Kimmo , Hirvonen Jussi
Published: June 2023

Severe spinal trauma is uncommon in the pediatric population, but due to the potentially devastating consequences of missed injury, it poses a diagnostic challenge in emergency departments. Diagnostic imaging is often needed to exclude or confirm the injury and to assess its extent. Magnetic resonance imaging (MRI) offers an excellent view of both bony and soft tissue structures and their traumatic findings without exposing children to ionizing radiation. Our pictorial review aims to demonstrate the typical traumatic findings, physiological phenomena, and potential pitfalls of emergency MRI in the trauma of the growing spine.
Hydrobiome of Thermal Waters: Potential Use in Dermocosmetics
Authors: Mourelle María Lourdes , Gómez Carmen P. , Legido José L.
Published: June 2023

Over the course of the last 20 years, numerous studies have identified the benefits of thermal waters on different skin conditions. Consequently, several investigations have been carried out on their effects on the skin, which are linked to their chemical composition, and, recently, scientists have turned their attention to the role of the thermal spring’s microbiota, named “hydrobiome”, regarding these therapeutic effects. At the same time, the development of cosmetics based on pre, pro, and postbiotics has reached great relevance and research is increasing every day. This review gathers information on the biological diversity of thermal spring waters and their potential use in obtaining biological compounds, metabolites, or bacterial extracts for use in dermocosmetics as active ingredients. These bioactive compounds are able to improve dermatological diseases such as atopic dermatitis or rosacea and ameliorate pruritus and xerosis; moreover, they can increase protection against UV exposure, strengthen barrier function, maintain good homeostasis of skin defenses, repair damaged skin, promote wound healing, improve skin condition, reduce uneven skin pigmentation, and prevent skin aging. From a future perspective, fruitful cooperation among researchers, hydrologists, thermal spa centers, and cosmetic industries will drive this sector toward a better understanding of the role of the hydrobiome of thermal spring waters on healthy skin and dermatological diseases and consider the inclusion of derivatives of this hydrobiome (in the form of fermenters, lysates, extracts, etc.) in dermocosmetic formulations. Therefore, and being aware of the potential of the hydrobiome in dermatological and skin care applications, the future prospects for the use of bioactive substances derived from it in dermocosmetic formulations are promising.
First-Principles Study of MoS2, WS2, and NbS2 Quantum Dots: Electronic Properties and Hydrogen Evolution Reaction
Authors: Abd-Elkader Omar H. , Abdelsalam Hazem , Sakr Mahmoud A. S. , Shaltout Abdallah A. , Zhang Qinfang
Published: June 2023

The electronic and catalytic properties of two-dimensional MoS2, WS2, and NbS2 quantum dots are investigated using density functional theory investigations. The stability of the considered structures is confirmed by the positive binding energies and the real vibrational frequencies in the infrared spectra. The ab initio molecular dynamics simulations show that these nanodots are thermally stable at 300 K with negligible changes in the potential energy and metal–S bonds. The pristine nanodots are semiconductors with energy gaps ranging from 2.6 to 3 eV. Edge sulfuration significantly decreases the energy gap of MoS2 and WS2 to 1.85 and 0.75 eV, respectively. The decrease is a result of the evolution of low-energy molecular orbitals by the passivating S-atoms. The energy gap of NbS2 is not affected, which could be due to the spin doublet state. Molecular electrostatic potentials reveal that the edge sulfur/transition metal atoms are electrophilic/nucleophilic sites, while the surface atoms are almost neutral sites. MoS2 quantum dots show an interestingly low change in the hydrogen adsorption free energy ~0.007 eV, which makes them competitive for hydrogen evolution catalysts.
Development of Heuristic Approaches for Last-Mile Delivery TSP with a Truck and Multiple Drones
Authors: Rinaldi Marco , Primatesta Stefano , Bugaj Martin , Rostáš Ján , Guglieri Giorgio
Published: June 2023

Unmanned Aerial Vehicles (UAVs) are gaining momentum in many civil and military sectors. An example is represented by the logistics sector, where UAVs have been proven to be able to improve the efficiency of the process itself, as their cooperation with trucks can decrease the delivery time and reduce fuel consumption. In this paper, we first state a mathematical formulation of the Travelling Salesman Problem (TSP) applied to logistic routing, where a truck cooperates synchronously with multiple UAVs for parcel delivery. Then, we propose, implement, and compare different sub-optimal routing approaches to the formulated mFSTSP (multiple Flying Sidekick Travelling Salesman Problem) since the inherent combinatorial computational complexity of the problem makes it unattractable for commercial Mixed-Integer Linear Programming (MILP) solvers. A local search algorithm, two hybrid genetic algorithms that permutate feasible and infeasible solutions, and an alternative ad-hoc greedy method are evaluated in terms of the total delivery time of the output schedule. For the sake of the evaluation, the savings in terms of delivery time over the well-documented truck-only TSP solution are investigated for each proposed routing solution, and this is repeated for two different scenarios. Monte Carlo simulations corroborate the results.
LERMS: A Low-Latency and Reliable Downlink Packet-Level Encoding Transmission Method in Untrusted 5GA Edge Network
Authors: Guo Zhongfu , Ji Xinsheng , You Wei , Xu Mingyan , Zhao Yu , Cheng Zhimo , Zhou Deqiang , Wang Lingwei
Published: June 2023

The increasing demand for end-to-end low-latency and high-reliability transmissions between edge computing nodes and user elements in 5G Advance edge networks has brought new challenges to the transmission of data. In response, this paper proposes LERMS, a packet-level encoding transmission scheme designed for untrusted 5GA edge networks that may encounter malicious transmission situations such as data tampering, discarding, and eavesdropping. LERMS achieves resiliency against such attacks by using 5GA Protocol data unit (PDU) coded Concurrent Multipath Transfer (CMT) based on Lagrangian interpolation and Raptor’s two-layer coding, which provides redundancy to eliminate the impact of an attacker’s malicious behavior. To mitigate the increased queuing delay resulting from encoding in data blocks, LERMS is queue-aware with variable block length. Its strategy is modeled as a Markov chain and optimized using a matrix method. Numerical results demonstrate that LERMS achieves the optimal trade-off between delay and reliability while providing resiliency against untrusted edge networks.
Effect of Interplay between Parallel and Perpendicular Magnetic and Electric Fields on Partial Discharges
Authors: Florkowski Marek
Published: June 2023

This paper reports on the influence of a magnetic field on the dynamics of partial discharges (PDs) in two distinct configurations with respect to the mutual orientation of electric fields. The broad application areas include electrical insulation systems of both high-voltage grids and industrial network devices as well as emerging segments such as electric vehicles or more electric aircraft. Traditionally, PD measurements are only carried out in an electric field. In all current-carrying power equipment, magnetic fields are also superimposed onto electric ones, thus influencing partial discharge behavior. It has been observed that the interplay between electric and magnetic fields influences the dynamics of PDs; parallel and perpendicular mutual orientations were specifically investigated. The measurement technique allowed us to quantitively detect the effect of magnetic fields on PDs in a corona point–plane arrangement. The novel element presented in this article is a detection of PD intensity modulated by a magnetic field, with both perpendicular and parallel orientations with respect to electric one, and a quantitative visualization in the form of the time-sequence diagrams. The simulation of electron trajectories in the presence of electric and magnetic fields revealed the elongation of the pathways and differentiation of the charged particle propagation times. The perpendicularly oriented magnetic field led to a twisting effect, whereas the parallel alignment reflected the propagation along a helical trajectory. A slightly stronger PD intensity amplification effect was observed in the case of a parallel alignment of electric versus magnetic fields as compared with the perpendicular orientation. The presented results may contribute to PD measurement methodology in both electric and magnetic fields as well as a better understanding of the underlying physical mechanisms. The observed effect of the modulation of the magnetically based PD dynamics may be relevant for the insulation systems of power equipment.
Simulating Sustainable Forest Management Practices Using Crown Attributes: Insights for Araucaria angustifolia Trees in Southern Brazil
Authors: Finger César Augusto Guimarães , Costa Emanuel Arnoni , Hess André Felipe , Liesenberg Veraldo , Bispo Polyanna da Conceição
Published: June 2023

Araucaria angustifolia (Bertol.) Kuntze, commonly known as Brazilian pine, is a significant tree species in the Brazilian flora that once covered an area of 200,000 km2 in the Southern region. During the 1970s, high-quality timber logs from this conifer became the primary export product of the country. However, the species is endangered due to uncontrolled exploitation and is subject to a harvesting ban. It is crucial, therefore, to explore sustainable cultivation methods for this species, which necessitates urgent research and scientific insights. In this study, we present a simulation of a management strategy for in situ conservation by manipulating growth space and crown size dynamics. Forest inventory data and mixed forest regression equations were employed to describe the horizontal dimensions of average and maximum potential crown growth, resulting in two management scenarios. The results presented in management diagrams show that both approaches required logging numerous trees to ensure adequate space for healthy tree growth and provide soil coverage and forest protection. Therefore, the absence of effective forest management initiatives for Araucaria forests may have further implications for the structure, production, conservation, and overall development. To address these challenges, we propose two hypotheses: firstly, that tree diameter depends on crown dimensions, which are in turn influenced by tree growth space, and, secondly, that crown dimensions serve as a reliable indicator of existing competition and can be utilized to simulate forest management practices. We urge that implementing sustainable forest management initiatives for Araucaria angustifolia at selected locations can contribute to expanding natural forest areas, mitigate deterioration caused by high competition, discourage illegal logging, and prevent overexploitation of their edible seeds, which hinders regeneration. Our results underscore the significant implications of the lack of forest management initiatives in rural properties, potentially resulting in irreversible deterioration. The exact consequences of this deterioration remain unclear, emphasizing the need for further studies to understand its eventual effects on the growth reaction of trees of different diameters, ages, and crown conditions after the liberation of their crowns.
Mechanisms of Plasma Actuators Controlling High-Aspect-Ratio Rectangular Jet Width for Automobile Air Conditioning Systems
Authors: Pham Anh Viet , Inaba Kazuaki
Published: June 2023

High-aspect-ratio (HAR) rectangular jets have attracted attention in automobile air conditioning (A/C) systems and turbulent jet applications owing to their excellent air delivery and mixing and attractive interior design. Active flow control (AFC) of rectangular jets using plasma actuators (PAs) has proven to be a promising technique because the actuator is simple, has low energy consumption, and can create flow features without interference. This research aims to understand the interaction between PAs and flow from a HAR rectangular nozzle using hot-wire anemometry, particle image velocimetry, and theoretical studies. Understanding how PAs affect the flow is beneficial for designing air vents to fit automobile A/C systems and various engineering applications by recreating the flow features with other AFC techniques and actuators. The combination of periodic excitation and vectoring effects transfers the flow’s mean energy to organized structures—known as spanwise vortexes—as large as 6 mm. The interaction between these coherent structures and the dissipative environment compresses the vortexes, resulting in the flow converging on the spanwise–streamwise (X–Z) plane and diverging on the transverse–streamwise (X–Y) plane. HAR rectangular jet flow features controlled by PAs can be predicted for specific cases by calculating the Strouhal number based on PA operating parameters.
The Effect of Sodium Bicarbonate Injection on the Physico-Chemical Quality of Post-Harvest Trout
Authors: Korkmaz Koray
Published: June 2023

The muscle hardness of fish is an important parameter associated with meat quality, and the post-mortem decrease in the pH of fish tissue pH affects its physical properties. We hypothesized that maintaining a high pH in fish tissue after death would prevent protein denaturation and consequent textural deterioration. This study aimed to determine the effectiveness of sodium bicarbonate (SBC) injections in preventing tissue softening caused by low pH after death in trout. We injected varying molar concentrations of SBC in rainbow trout (Oncorhynchus mykiss; 0 M, 0.5 M, 0.75 M, and 1 M) after harvest, and the product quality was assessed at 0, 24, 48, 72, and 96 h of ice storage. Quality was evaluated using proximate analyses for color, pH, water holding capacity (WHC), texture profile, and rigor index. The 0 M group had the lowest pH, and the 0.75 M group had the highest pH at all time points during storage. We observed improved tissue texture during storage in fish treated with 0.75 and 1 M SBC. The texture profile analysis showed higher hardness, frangibility, and stickiness in the tail than in the other regions. These varying results can be explained by significant differences between parts of the fish and sampling point selection. We also observed the highest pH and WHC values in the groups injected with 0.75 and 1 M SBC during storage.
Influence of Parenting Guilt on the Mental Health among Single-Parent Women: Multiple Additive Moderating Effect of Economic Well-Being and Level of Education
Authors: Kim Anna , Jeon Sesong , Park Inah
Published: June 2023

This study explored how the core problems (e.g., parenting, economy, and education level) of single-parent women affect their mental health. Although parenting guilt, economic well-being, and level of education are important variables that affect the mental health of single parents, there is no study that examines the interaction effect between them together. Therefore, this study examined the moderating effects of economic well-being and level of education on the relationship between parenting guilt and mental health in 419 single-parent women. In addition, it was verified whether there was a multiple additive modulation effect when they were put in at the same time. As a result, the higher the parenting guilt and the lower the economic well-being, the higher the level of mental health pain, but the level of education had no statistical significance. However, the interaction term between parenting guilt and education level had statistical significance, while the interaction term between parenting guilt and economic well-being did not produce significant results. These findings suggest the importance of education for single-parent women’s mental health as well as the need to establish policies that allow them to have sufficient time and room for child rearing.
Effectiveness of Health Promotion Interventions in Primary Schools—A Mixed Methods Literature Review
Authors: Zurc Joca , Laaksonen Camilla
Published: June 2023

School-based health promotion interventions (HPIs) are commonly used in schools, but scientific evidence about the structures of effective interventions is lacking. Therefore, we conducted a mixed methods systematic literature review to recognize the HPI structures related to their effectiveness. Based on the inclusion criteria, 49 articles were selected for the literature review. The articles, published in 2011–2022, described 46 different school-based interventions conducted in 20 different countries. The average duration of the interventions was 12 months, and they were implemented mostly with an RCT study design (61.2%) and by targeting children (69.4%). Three main groups of interventions were identified and explained: (1) extensive and long-term interventions; (2) school policy-changing interventions; and (3) highly effective interventions. Effective school-based HPIs included multiple target groups, multiple providers with external experts, and an efficient duration and timing of follow-ups. The implications for educational research and school practice are presented. Evidence on the effectiveness of health-related interventions is still lacking and needs to be addressed in further studies.
Selection of a Proper Maturity Index for the Mechanical Harvesting of ‘Mihong’ Peach Fruit
Authors: Jayasooriya L. Sugandhi Hirushika , Shin Mi Hee , Wijethunga W. M. Upeksha Darshani , Lee Seul Ki , Cho Jung Gun , Jang Si Hyeong , Kim Jin Gook
Published: June 2023

Peaches are one of the most popular fruits around the globe. Selecting the optimum harvesting maturity for peaches is crucial in assuring high-quality fruits. This study is a model for determining the ideal harvest time for a robot harvester. Our study was carried out over two years on ‘Mihong’ peaches during days after full bloom (DAFB) 71 to 90 in 2021 and DAFB 64 to 84 in 2022 to select the optimal maturity index through a quality survey. The fruit size, soluble solids content (SSC), titratable acidity (TA), firmness, peel color (L*, a*, b*, chroma, and hue), and ethylene production were investigated. Fruit size showed the regular double sigmoid curve, and SSC increased while firmness and TA decreased with time. The samples left in storage conditions in 2022 showed a massive change in SSC and firmness after DAFB 74, implying the optimum harvesting stage. Interestingly, color values manifest the same consequence with a*, b*, and hue by reaching a plateau with apex side color values after DAFB 74, indicating the desired maturity. Overall, the results show that color values are an outstanding non-destructive alternative to typical destructive measurements for determining the exact time to harvest ‘Mihong’ peaches.
A Comparison of Objectively Measured Free-Living Physical Behaviour in Adults with and without Lower Limb Amputation
Authors: Deans Sarah , Kirk Alison , McGarry Anthony , Rowe David A. , Dall Philippa M.
Published: June 2023

Objectively monitored free-living physical behaviours of adults with and without lower limb amputation (LLA) were compared. Methods: 57 adults with LLA wore an activPAL3™ for 8 days. A comparison data set (n = 57) matched on gender, age and employment status was used. Variables included: time sitting; standing; stepping; sit-to-stand transitions; step count and cadence. Comparisons were made between adults with and without LLA and between gender, level and cause of amputation. Results: Participants with LLA due to trauma versus circulatory causes were less sedentary and more active; however, no difference in physical behaviour was recorded across gender or level of amputation. Participants with LLA spent more time sitting (p < 0.001), less time standing and stepping (p < 0.001) and had a lower step count (p < 0.001). Participants with LLA took more steps in cadence bands less than 100 steps·min−1 and fewer steps in cadence bands greater than 100 steps·min−1 compared to participants without LLA. Conclusions: People with LLA were less active and more sedentary than people without LLA and participated in less activity at a moderate or higher intensity when matched on age, gender and employment. Interventions are needed to promote active lifestyles in this population.
Microvascular Skeletal-Muscle Crosstalk in Health and Disease
Authors: Pepe Gerald J. , Albrecht Eugene D.
Published: June 2023

As an organ system, skeletal muscle is essential for the generation of energy that underpins muscle contraction, plays a critical role in controlling energy balance and insulin-dependent glucose homeostasis, as well as vascular well-being, and regenerates following injury. To achieve homeostasis, there is requirement for “cross-talk” between the myogenic and vascular components and their regulatory factors that comprise skeletal muscle. Accordingly, this review will describe the following: [a] the embryonic cell-signaling events important in establishing vascular and myogenic cell-lineage, the cross-talk between endothelial cells (EC) and myogenic precursors underpinning the development of muscle, its vasculature and the satellite-stem-cell (SC) pool, and the EC–SC cross-talk that maintains SC quiescence and localizes ECs to SCs and angio-myogenesis postnatally; [b] the vascular–myocyte cross-talk and the actions of insulin on vasodilation and capillary surface area important for the uptake of glucose/insulin by myofibers and vascular homeostasis, the microvascular-myocyte dysfunction that characterizes the development of insulin resistance, diabetes and hypertension, and the actions of estrogen on muscle vasodilation and growth in adults; [c] the role of estrogen in utero on the development of fetal skeletal-muscle microvascularization and myofiber hypertrophy required for metabolic/vascular homeostasis after birth; [d] the EC–SC interactions that underpin myofiber vascular regeneration post-injury; and [e] the role of the skeletal-muscle vasculature in Duchenne muscular dystrophy.
The Role of Oxytocin in Early-Life-Stress-Related Neuropsychiatric Disorders
Authors: Jin Yue , Song Da , Yan Yan , Quan Zhenzhen , Qing Hong
Published: June 2023

Early-life stress during critical periods of brain development can have long-term effects on physical and mental health. Oxytocin is a critical social regulator and anti-inflammatory hormone that modulates stress-related functions and social behaviors and alleviates diseases. Oxytocin-related neural systems show high plasticity in early postpartum and adolescent periods. Early-life stress can influence the oxytocin system long term by altering the expression and signaling of oxytocin receptors. Deficits in social behavior, emotional control, and stress responses may result, thus increasing the risk of anxiety, depression, and other stress-related neuropsychiatric diseases. Oxytocin is regarded as an important target for the treatment of stress-related neuropsychiatric disorders. Here, we describe the history of oxytocin and its role in neural circuits and related behaviors. We then review abnormalities in the oxytocin system in early-life stress and the functions of oxytocin in treating stress-related neuropsychiatric disorders.
Proteome Landscape during Ripening of Solid Endosperm from Two Different Coconut Cultivars Reveals Contrasting Carbohydrate and Fatty Acid Metabolic Pathway Modulation
Authors: Félix Jean Wildort , Granados-Alegría María Inés , Gómez-Tah Rufino , Tzec-Simá Miguel , Ruíz-May Eliel , Canto-Canché Blondy , Zamora-Briseño Jesús Alejandro , Bojórquez-Velázquez Esaú , Oropeza-Salín Carlos , Islas-Flores Ignacio
Published: June 2023

Cocos nucifera L. is a crop grown in the humid tropics. It is grouped into two classes of varieties: dwarf and tall; regardless of the variety, the endosperm of the coconut accumulates carbohydrates in the early stages of maturation and fatty acids in the later stages, although the biochemical factors that determine such behavior remain unknown. We used tandem mass tagging with synchronous precursor selection (TMT-SPS-MS3) to analyze the proteomes of solid endosperms from Yucatan green dwarf (YGD) and Mexican pacific tall (MPT) coconut cultivars. The analysis was conducted at immature, intermediate, and mature development stages to better understand the regulation of carbohydrate and lipid metabolisms. Proteomic analyses showed 244 proteins in YGD and 347 in MPT; from these, 155 proteins were shared between both cultivars. Furthermore, the proteomes related to glycolysis, photosynthesis, and gluconeogenesis, and those associated with the biosynthesis and elongation of fatty acids, were up-accumulated in the solid endosperm of MPT, while in YGD, they were down-accumulated. These results support that carbohydrate and fatty acid metabolisms differ among the developmental stages of the solid endosperm and between the dwarf and tall cultivars. This is the first proteomics study comparing different stages of maturity in two contrasting coconut cultivars and may help in understanding the maturity process in other palms.
In Vitro and In Vivo Biocompatibility Assessment of a Thermosensitive Injectable Chitosan-Based Hydrogel for Musculoskeletal Tissue Engineering
Authors: Canciani Barbara , Semeraro Francesca , Herrera Millar Valentina Rafaela , Gervaso Francesca , Polini Alessandro , Stanzione Antonella , Peretti Giuseppe Michele , Di Giancamillo Alessia , Mangiavini Laura
Published: June 2023

Musculoskeletal impairments, especially cartilage and meniscus lesions, are some of the major contributors to disabilities. Thus, novel tissue engineering strategies are being developed to overcome these issues. In this study, the aim was to investigate the biocompatibility, in vitro and in vivo, of a thermosensitive, injectable chitosan-based hydrogel loaded with three different primary mesenchymal stromal cells. The cell types were human adipose-derived mesenchymal stromal cells (hASCs), human bone marrow stem cells (hBMSCs), and neonatal porcine infrapatellar fat-derived cells (IFPCs). For the in vitro study, the cells were encapsulated in sol-phase hydrogel, and then, analyzed via live/dead assay at 1, 4, 7, and 14 days to compare their capacity to survive in the hydrogel. To assess biocompatibility in vivo, cellularized scaffolds were subcutaneously implanted in the dorsal pouches of nude mice and analyzed at 4 and 12 weeks. Our data showed that all the different cell types survived (the live cell percentages were between 60 and 80 at all time points in vitro) and proliferated in the hydrogel (from very few at 4 weeks to up to 30% at 12 weeks in vivo); moreover, the cell-laden hydrogels did not trigger an immune response in vivo. Hence, our hydrogel formulation showed a favorable profile in terms of safety and biocompatibility, and it may be applied in tissue engineering strategies for cartilage and meniscus repair.
Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells
Authors: Masri Samer , Carré Laure , Jaulin Nicolas , Vandamme Céline , Couzinié Célia , Guy-Duché Aurélien , Dupont Jean-Baptiste , Pereira Allwyn , Charpentier Eric , David Laurent , Gernoux Gwladys , Guilbaud Mickaël , Adjali Oumeya
Published: June 2023

Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.
Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells
Authors: Kleszcz Robert , Frąckowiak Mikołaj , Dorna Dawid , Paluszczak Jarosław
Published: June 2023

The Wnt/β-catenin, EGFR, and PI3K pathways frequently undergo upregulation in head and neck squamous carcinoma (HNSCC) cells. Moreover, the Wnt/β-catenin pathway together with Hedgehog (Hh) signaling regulate the activity of cancer stem cells (CSCs). The aim of this study was to investigate the effects of the combinatorial use of the Wnt/β-catenin and Hh pathway inhibitors on viability, cell cycle progression, apoptosis induction, cell migration, and expression of CSC markers in tongue (CAL 27) and hypopharynx (FaDu) cancer cells. Co-inhibition of Wnt signaling with EGFR or PI3K pathways was additionally tested. The cells were treated with selective inhibitors of signaling pathways: Wnt/β-catenin (PRI-724), Hh (vismodegib), EGFR (erlotinib), and PI3K (HS-173). Cell viability was evaluated by the resazurin assay. Cell cycle progression and apoptosis induction were tested by flow cytometric analysis after staining with propidium iodide and Annexin V, respectively. Cell migration was detected by the scratch assay and CSC marker expression by the R-T PCR method. Mixtures of PRI-724 and vismodegib affected cell cycle distribution, greatly reduced cell migration, and downregulated the transcript level of CSC markers, especially POU5F1 encoding OCT4. Combinations of PRI-724 with erlotinib or HS-173 were more potent in inducing apoptosis.
Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait
Authors: Trucas Marcello , Burattini Sabrina , Porcu Susanna , Simbula Michela , Ristaldi Maria Serafina , Kowalik Marta Anna , Serra Maria Pina , Gobbi Pietro , Battistelli Michela , Perra Andrea , Quartu Marina
Published: June 2023

Sickle cell disease (SCD) is caused by the homozygous beta-globin gene mutation that can lead to ischemic multi-organ damage and consequently reduce life expectancy. On the other hand, sickle cell trait (SCT), the heterozygous beta-globin gene mutation, is still considered a benign condition. Although the mechanisms are not well understood, clinical evidence has recently shown that specific pathological symptoms can also be recognized in SCT carriers. So far, there are still scant data regarding the morphological modifications referable to possible multi-organ damage in the SCT condition. Therefore, after genotypic and hematological characterization, by conventional light microscopy and transmission electron microscopy (TEM), we investigated the presence of tissue alterations in 13 heterozygous Townes mice, one of the best-known animal models that, up to now, was used only for the study of the homozygous condition. We found that endothelial alterations, as among which the thickening of vessel basal lamina, are ubiquitous in the lung, liver, kidney, and spleen of SCT carrier mice. The lung shows the most significant alterations, with a distortion of the general tissue architecture, while the heart is the least affected. Collectively, our findings contribute novel data to the histopathological modifications at microscopic and ultrastructural levels, underlying the heterozygous beta-globin gene mutation, and indicate the translational suitability of the Townes model to characterize the features of multiple organ involvement in the SCT carriers.
Zebrafish as an Animal Model in Cannabinoid Research
Authors: Lachowicz Joanna , Szopa Aleksandra , Ignatiuk Katarzyna , Świąder Katarzyna , Serefko Anna
Published: June 2023

Cannabinoids are active substances present in plants of the Cannabis genus. Both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved several medicinal products containing natural cannabinoids or their synthetic derivatives for the treatment of drug-resistant epilepsy, nausea and vomiting associated with cancer chemotherapy, anorexia in AIDS patients, and the alleviation of symptoms in patients with multiple sclerosis. In fact, cannabinoids constitute a broad group of molecules with a possible therapeutic potential that could be used in the management of much more diseases than mentioned above; therefore, multiple preclinical and clinical studies on cannabinoids have been carried out in recent years. Danio rerio (zebrafish) is an animal model that has gained more attention lately due to its numerous advantages, including easy and fast reproduction, the significant similarity of the zebrafish genome to the human one, simplicity of genetic modifications, and body transparency during the early stages of development. A number of studies have confirmed the usefulness of this model in toxicological research, experiments related to the impact of early life exposure to xenobiotics, modeling various diseases, and screening tests to detect active substances with promising biological activity. The present paper focuses on the current knowledge of the endocannabinoid system in the zebrafish model, and it summarizes the results and observations from studies investigating the pharmacological effects of natural and synthetic cannabinoids that were carried out in Danio rerio. The presented data support the notion that the zebrafish model is a suitable animal model for use in cannabinoid research.
Therapeutic Effects of Long-Term Administration of Tranilast in an Animal Model for the Treatment of Fibroids
Authors: Chuang Tsai-Der , Munoz Leslie , Quintanilla Derek , Boos Drake , Khorram Omid
Published: June 2023

Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-β3 and Masson’s trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-β3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids.
Improving Soluble Expression of SARS-CoV-2 Spike Priming Protease TMPRSS2 with an Artificial Fusing Protein
Authors: Ye Xiao , Ling Xue , Wu Min , Bai Guijie , Yuan Meng , Rao Lang
Published: June 2023

SARS-CoV-2 relies on the recognition of the spike protein by the host cell receptor ACE2 for cellular entry. In this process, transmembrane serine protease 2 (TMPRSS2) plays a pivotal role, as it acts as the principal priming agent catalyzing spike protein cleavage to initiate the fusion of the cell membrane with the virus. Thus, TMPRSS2 is an ideal pharmacological target for COVID-19 therapy development, and the effective production of high–quality TMPRSS2 protein is essential for basic and pharmacological research. Unfortunately, as a mammalian–originated protein, TMPRSS2 could not be solubly expressed in the prokaryotic system. In this study, we applied different protein engineering methods and found that an artificial protein XXA derived from an antifreeze protein can effectively promote the proper folding of TMPRSS2, leading to a significant improvement in the yield of its soluble form. Our study also showed that the fused XXA protein did not influence the enzymatic catalytic activity; instead, it greatly enhanced TMPRSS2′s thermostability. Therefore, our strategy for increasing TMPRSS2 expression would be beneficial for the large–scale production of this stable enzyme, which would accelerate aniti–SARS-CoV-2 therapeutics development.
The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis
Authors: Wang Tsz Ki , Xu Shaoting , Fan Yuanjian , Wu Jing , Wang Zilin , Chen Yue , Zhang Yunjian
Published: June 2023

Histone deacetylase inhibitor (HDACi) is a drug mainly used to treat hematological tumors and breast cancer, but its inhibitory effect on breast cancer falls short of expectations. Grape seed proanthocyanidin extract (GSPE) with abundant proanthocyanidins (PAs) has been explored for its inhibition of HDAC activity in vitro and in vivo. To enhance HDACi’s effectiveness, we investigated the potential of PA to synergistically enhance HDACi chidamide (Chi), and determined the underlying mechanism. We evaluated the half-inhibitory concentration (IC50) of PA and Chi using the cell counting kit 8 (CCK8), and analyzed drugs’ synergistic effect with fixed-ratio combination using the software Compusyn. Breast cancer cell’s phenotypes, including short-term and long-term proliferation, migration, invasion, apoptosis, and reactive oxygen species (ROS) levels, were assessed via CCK8, clone-formation assay, wound-healing test, Transwell Matrigel invasion assay, and flow-cytometry. Protein–protein interaction analysis (PPI) and KEGG pathway analysis were used to determine the underlying mechanism of synergy. PA + Chi synergistically inhibited cell growth in T47D and MDA-MB-231 breast cancer cell lines. Short-term and long-term proliferation were significantly inhibited, while cell apoptosis was promoted. Ten signaling pathways were identified to account for the synergistic effect after RNA sequencing. Their synergism may be closely related to the steroid biosynthesis and extracellular matrix (ECM) receptor interaction pathways. PA + Chi can synergistically inhibit breast cancer cell growth and proliferation, and promote apoptosis. These effects may be related to steroid biosynthesis or the ECM receptor pathway.