bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Microscopic Pore Characteristics and Mechanisms of Disturbance Damage in Zhanjiang Formation Structural Clay
Authors: Xie Yanhua , Tang Bin , Liu Shuaiyu , Xu Jicheng , Zhang Binghui
Published: November 2024

To investigate the microscopic pore evolution characteristics of Zhanjiang Formation structural clay during the disturbance process, unconfined compressive strength tests, scanning electron microscopy (SEM), and X-ray diffraction (XRD) were conducted on disturbed samples subjected to various disturbance conditions after vibrational disturbance. Based on the evolution characteristics of the microstructure, the microscopic pore characteristics of the disturbance damage of Zhanjiang Formation structural clay were examined. The results indicate the following. (1) The porosity in three-dimensional visualization images of the microstructure reconstructed by ArcGIS 10.1 increases with the disturbance degree, showing a linear growth trend. (2) The correlation analysis between macroscopic mechanics and microscopic pores shows that the unconfined compressive strength of Zhanjiang Formation structural clay is mainly affected by its porosity, with a significant linear negative correlation. Based on this, a reasonable regression model between the microscopic porosity and the unconfined compressive strength has been established. The model can rapidly estimate the unconfined compressive strength from porosity data, facilitating the assessment engineering properties of the soil. (3) The microscopic pore structure of Zhanjiang Formation structural clay exhibits prominent Menger fractal characteristics. The three-dimensional pore fractal dimension has a certain positive correlation with the disturbance degree, and can be utilized to characterize the pore structure and complexity, serving as a significant parameter for the quantitative evaluation of the pore structure characteristics of Zhanjiang Formation structural clay. Consequently, the complexity of the pore structure of the engineering soil can be evaluated by the pore fractal dimension. (4) The impact of disturbance on soil is primarily manifested in the structural changes in secondary clay minerals, transitioning from a relatively intact to a fully adjusted state. During this process, interparticle pores continuously increase, pore structure complexity increases, and interparticle cementation weakens, resulting in the continuous degradation of unconfined compressive strength. This study contributes to a deeper understanding of the disturbance damage characteristics of Zhanjiang Formation structured clays from a microscopic pore perspective, providing a theoretical basis for the engineering construction and operational maintenance in regions with Zhanjiang Formation structural clay.
Strength Retention of Carbon Fiber/Epoxy Vitrimer Composite Material for Primary Structures: Towards Recyclable and Reusable Carbon Fiber Composites
Authors: Nartam Sudhanshu , Rautela Vishal , Budhe Sandip , Paul Jinu , de Barros Silvio
Published: November 2024

Recently, the growth of the recyclability of carbon fiber reinforced polymer (CFRP) composites has been driven by environmental and circular economic aspects. The main aim of this research work is to investigate the strength retention of a bio-based vitrimer composite reinforced with carbon fibers, which offers both recyclability and material reusability. The composite formulation consisted of an epoxy resin composed of diglycidyl ether of bioshpenol A (DGEBA) combined with tricarboxylic acid (citric acid, CA) and cardanol, which was then reinforced with carbon fibers to enhance its performance. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy were performed to analyze the chemical composition and curing behavior of the vitrimer. Mechanical testing under tensile loading at room temperature was carried out on epoxy, vitrimer, and associated carbon fiber reinforced composite materials. The results demonstrated that the DGEBA/CA/cardanol vitrimer exhibited thermomechanical properties comparable to those of an epoxy cured with petroleum-based curing agents. It was observed that the maximum tensile strength of vitrimer is about 50 MPa, which is very close to the range of epoxy resins cured with petroleum-based curing agents. Notably, the ability of the vitrimer composite to be effectively dissolved in a dimethylformamide (DMF) solvent is a significant advantage, as it enables the recovery of the fibers. The recovered carbon fiber retained comparable tensile strength to that of the fresh carbon composites. More than 95% strength was retained after the first recovery, which confirms the use of fibers for primary and secondary applications. These research results open up new avenues for efficient recycling and contribute to the overall sustainability of the composite material at an economic level.
Third-Order Differential Subordination Features of Meromorphic Functions: Erdelyi–Kober Model Integral Operator Application
Authors: Elshazly Ibrahim S. , Halouani Borhen , El-Ashwah Rabha M. , El-Qadeem Alaa H. , Murugusundaramoorthy Gangadharan
Published: November 2024

This study is concerned with the class of p-valent meromorphic functions, represented by the series f(ζ)=ζ−p+∑k=1−p∞dkζk, with the domain characterized by 0<|ζ|<1. We apply an Erdelyi–Kober-type integral operator to derive two recurrence relations. From this, we draw specific conclusions on differential subordination and differential superordination. By looking into suitable classes of permitted functions, we obtain various outcomes, including results analogous to sandwich-type theorems. The operator used can provide generalizations of previous operators through specific parameter choices, thus providing more corollaries.
Algal Active Ingredients and Their Involvement in Managing Diabetic Mellitus
Authors: Tong Aijun , Wang Dengwei , Jia Nan , Zheng Ying , Qiu Yusong , Chen Weichao , El-Seed Hesham R. , Zhao Chao
Published: November 2024

Diabetes mellitus (DM) is becoming increasingly prominent, posing a serious threat to human health. Its prevalence is rising every year, and often affects young people. In the past few decades, research on marine algae has been recognized as a major field of drug discovery. Seaweed active substances, including algal polysaccharides, algal polyphenols, algal unsaturated fatty acids, and algal dietary fiber, have unique biological activities. This article reviews the effects and mechanisms of the types, structures, and compositions of seaweed on inhibiting glucose and lipid metabolism disorders, with a focus on the inhibitory effect of active substances on blood glucose reduction. The aim is to provide a basis for the development of seaweed active substance hypoglycemic drugs.
Synthesis, Analytical Characterization, and Human CB1 Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA
Authors: Münster-Müller Sascha , Hansen Steven , Lucas Tobias , Giorgetti Arianna , Mogler Lukas , Fischmann Svenja , Westphal Folker , Auwärter Volker , Pütz Michael , Opatz Till
Published: November 2024

Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB1 receptors (hCB1), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet–visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described. Furthermore, all five derivatives of MDMB-CHMICA were analyzed for their hCB1 binding affinities. Chlorination at position 4 and 5 of the indole core reduced the binding affinity compared to MDMB-CHMICA, while the test compounds chlorinated in positions 2, 6, and 7 largely retained their binding affinities relative to the non-chlorinated parent compound.
Load Modulation Affects Pediatric Lower Limb Joint Moments During a Step-Up Task
Authors: Goyal Vatsala , Gordon Keith E. , Sukal-Moulton Theresa
Published: November 2024

Introduction: Performance in a single step has been suggested to be a sensitive measure of movement quality in pediatric clinical populations. Although there is less information available in children with typical development, researchers have postulated the importance of analyzing the effect of body weight modulation on the initiation of stair ascent, especially during single-limb stance where upright stability is most critical. The purpose of this study was to investigate the effect of load modulation from −20% to +15% of body weight on typical pediatric lower limb joint moments during a step-up task. Methods: Fourteen participants between 5 and 21 years who did not have any neurological or musculoskeletal concerns were recruited to perform multiple step-up trials. Peak extensor support and hip abduction moments were identified during the push-off and pull-up stance phases. Linear regressions were used to determine the relationship between peak moments and load. Mixed-effects models were used to estimate the effect of load on hip, knee, and ankle percent contributions to peak support moments. Results: There was a positive linear relationship between peak support moments and load in both stance phases, where these moments scaled with load. There was no relationship between peak hip abduction moments and load. While the ankle and knee were the primary contributors to the support moments, the hip contributed more than expected in the pull-up phase. Discussion: Clinicians can use these results to contextualize movement differences in pediatric clinical populations, including in those with cerebral palsy, and highlight potential target areas for rehabilitation for populations such as adolescent athletes.
Oxysterols Suppress Release of DNA from Granulocytes into Extracellular Space After Stimulation with Phorbol Myristate Acetate
Authors: Watanabe Yuichi , Obama Takashi , Makiyama Tomohiko , Itabe Hiroyuki
Published: November 2024

Background: Neutrophils eject their DNA strings and cellular proteins into the extracellular space upon treatment with various stimulants. In the present study, we examined the effects of four major oxidized cholesterol metabolites on DNA release from granulocytes. Methods and Results: When oxysterols were added to HL-60-derived granulocytes stimulated with phorbol 12-myristate 13-acetate (PMA), they suppressed the release of DNA and myeloperoxidase from the cells. Among the four oxysterols tested, 7-ketocholesterol was the most effective. Addition of the same concentration of 7-ketocholesterol did not induce any cytotoxic effects, as evaluated based on the release of lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assays. DNA release from human peripheral blood neutrophils after PMA stimulation was also suppressed by 7-ketocholesterol. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to quantify sterol content in the cells. The addition of oxysterols increased the cellular content of the corresponding compounds by more than 10-fold compared to those at baseline. Treatment of HL-60-derived granulocytes with methyl-β-cyclodextrin that removes sterol compounds from the membranes increased DNA release from the cells in a dose-dependent manner. Conclusions: These results suggest that oxysterols have suppressive effects on DNA release from granulocytes stimulated with PMA.
Circadian Alterations in Brain Metabolism Linked to Cognitive Deficits During Hepatic Ischemia-Reperfusion Injury Using [1H-13C]-NMR Metabolomics
Authors: Li Yijing , Liu Yanbo , He Zhigang , Li Zhixiao , Xiang Hongbing
Published: November 2024

Background: Hepatic ischemia-reperfusion injury (HIRI) is known to affect cognitive functions, with particular concern for its impact on brain metabolic dynamics. Circadian rhythms, as a crucial mechanism for internal time regulation within organisms, significantly influence metabolic processes in the brain. This study aims to explore how HIRI affects hippocampal metabolism and its circadian rhythm differences in mice, and to analyze how these changes are associated with cognitive impairments. Methods: A C57BL/6 male mouse model was used, simulating HIRI through hepatic ischemia-reperfusion surgery, with a sham operation conducted for the control group. Cognitive functions were evaluated using open field tests, Y-maze tests, and novel object recognition tests. Magnetic resonance spectroscopic imaging (MRSI) technology, combined with intravenous injection of [2-13C]-acetate and [1-13C]-glucose, was utilized to analyze metabolic changes in the hippocampus of HIRI mice at different circadian time points (Zeitgeber Time ZT0, 8:00 and ZT12, 20:00). Circadian rhythms regulate behavioral, physiological, and metabolic rhythms through transcriptional feedback loops, with ZT0 at dawn (lights on) and ZT12 at dusk (lights off). Results: HIRI mice exhibited significant cognitive impairments in behavioral tests, particularly in spatial memory and learning abilities. MRSI analysis revealed significant circadian rhythm differences in the concentration of metabolites in the hippocampus, with the enrichment concentrations of lactate, alanine, glutamate, and taurine showing different trends at ZT0 compared to ZT12, highlighting the important influence of circadian rhythms on metabolic dysregulation induced by HIRI. Conclusions: This study highlights the significant impact of HIRI on brain metabolic dynamics in mice, especially in the hippocampal area, and for the first time reveals the differences in these effects within circadian rhythms. These findings not only emphasize the association between HIRI-induced cognitive impairments and changes in brain metabolism but also point out the crucial role of circadian rhythms in this process, offering new metabolic targets and timing considerations for therapeutic strategies against HIRI-related cognitive disorders.
Improvement of Electric Fish Optimization Algorithm for Standstill Label Combined with Levy Flight Strategy
Authors: Luo Wangzhou , Wu Hailong , Peng Jiegang
Published: November 2024

The Electric Fish Optimization (EFO) algorithm is inspired by the predation behavior and communication of weak electric fish. It is a novel meta-heuristic algorithm that attracts researchers because it has few tunable parameters, high robustness, and strong global search capabilities. Nevertheless, when operating in complex environments, the EFO algorithm encounters several challenges including premature convergence, susceptibility to local optima, and issues related to passive electric field localization stagnation. To address these challenges, this study introduces Adaptive Electric Fish Optimization Algorithm Based on Standstill Label and Level Flight (SLLF-EFO). This hybrid approach incorporates the Golden Sine Algorithm and good point set theory to augment the EFO algorithm’s capabilities, employs a variable-step-size Levy flight strategy to efficiently address passive electric field localization stagnation problems, and utilizes a standstill label strategy to mitigate the algorithm’s tendency to fall into local optima during the iterative process. By leveraging multiple solutions to optimize the EFO algorithm, this framework enhances its adaptability in complex environments. Experimental results from benchmark functions reveal that the proposed SLLF-EFO algorithm exhibits improved performance in complex settings, demonstrating enhanced search speed and optimization accuracy. This comprehensive optimization not only enhances the robustness and reliability of the EFO algorithm but also provides valuable insights for its future applications.
In Situ and Label-Free Quantification of Membrane Protein–Ligand Interactions Using Optical Imaging Techniques: A Review
Authors: Huang Caixin , Zhang Jingbo , Liu Zhaoyang , Xu Jiying , Zhao Ying , Zhang Pengfei
Published: November 2024

Membrane proteins are crucial for various cellular processes and are key targets in pharmacological research. Their interactions with ligands are essential for elucidating cellular mechanisms and advancing drug development. To study these interactions without altering their functional properties in native environments, several advanced optical imaging methods have been developed for in situ and label-free quantification. This review focuses on recent optical imaging techniques such as surface plasmon resonance imaging (SPRi), surface plasmon resonance microscopy (SPRM), edge tracking approaches, and surface light scattering microscopy (SLSM). We explore the operational principles, recent advancements, and the scope of application of these methods. Additionally, we address the current challenges and explore the future potential of these innovative optical imaging strategies in deepening our understanding of biomolecular interactions and facilitating the discovery of new therapeutic agents.
The Impact of Family Wealth on Asset Return: A Moderated Chain Median Model Partially Explaining Wealth Inequality
Authors: Tu Tianye
Published: November 2024

Global wealth is distributed highly unequally, and this issue has worsened in recent years. Such inequality threatens human well-being and fundamental values. In response, this paper aims to explore the wealth inequality phenomenon from the perspective of investment psychology. Recognizing wealth return heterogeneity as a crucial source of inequality, the paper establishes a psychological model focused on two investment skill factors that can partially explain this heterogeneity. The theoretical foundation of this model includes the conservation of resources (COR) theory, prospect theory, and performance determinants theory. In our model, risk preference and asset-holding periods sequentially mediate the relationship between family wealth and asset returns. Moreover, risk preference and the disposition effect are identified as serial mediators in this relationship. Financial literacy also moderates the relationship between the risk preference, asset-holding period, and disposition effect. This proposed model not only provides a richer explanation for wealth return heterogeneity through the lens of investment skill but also extends the application of COR theory to investment psychology, thereby enhancing our understanding of resources. Moreover, it offers a novel explanation for the relationship between risk preference and the deposition effect, enriching prospect theory. Finally, the inclusion of financial literacy’s role broadens the scope of performance determinants theory.
Exploring Factors Affecting Millennial Tourists’ eWOM Behavior: A Lens of BRT Theory
Authors: Song Zibin , Ren Yingying , Li Jie
Published: November 2024

This study employs behavioral reasoning theory (BRT) to investigate factors (i.e., personal values, reasons, and attitudes) affecting existing and future behaviors of Millennial tourists’ electronic word-of-mouth (eWOM). It uses a mixed-methods approach that includes qualitative interviews with 25 tourists to elicit specific reasons for and against eWOM and a survey of 572 Millennial-Chinese tourists to quantitatively validate our BRT structural model. The statistical results from SmartPLS 3.0 show that all hypotheses on direct effects have gained empirical support except for the relationships between the existing behavior and its respective reasons for and against eWOM. These two insignificant direct effects are, however, shown to be fully mediated by global attitudes, respectively. Moreover, gender moderates the relationships between reasons against eWOM and the existing behavior and reasons for eWOM and future behavior, respectively. Most findings regarding the foregoing direct, mediation, and moderation effects are exploratory. In addition, this study contributes significantly to the literature by successfully developing and validating the scale of reasons for and against Millennial tourists’ eWOM within the BRT framework. Destination managers can use this scale of reasons as both a diagnostic tool and a blueprint for eWOM management.
Psychometric Properties of Social Climate in the Classroom Scale for University Students in Chile
Authors: León Camila , Bravo-Sanzana Mónica , Terán-Mendoza Oscar
Published: November 2024

Background: Classroom social climate is a significant phenomenon within educational contexts; however, it has predominantly been studied among high school students, with limited evidence available at the university level and, consequently, in the psychometric properties of measurement instruments. This study aimed to analyze the psychometric properties of the University Classroom Social Climate Scale (ECSA-U) among Chilean students from the La Araucanía region. Method: 422 students participated, responding to the adapted version of the ECSA-U and the Motivation subscale of the Motivation and Learning Strategies Questionnaire. Exploratory structural equation modeling (ESEM), reliability analyses, and correlation analyses were conducted to provide valid evidence for the Chilean University Classroom Social Climate Scale (ECSA-UCL). Results: The scale demonstrated a three-factor structure with good fit indicators, excellent reliability indices, and significant positive associations between the ECSA-UCL and the Motivation Subscale. Conclusions: The ECSA-UCL has proven valid and reliable for measuring the perception of Classroom Social Climate among Chilean university students, making it suitable for use as a measurement tool in studies or interventions that include this variable.
Risk-Based Completion Cost Overrun Ratio Estimation in Construction Projects Using Machine Learning Classification Algorithms: A Case Study
Authors: Turkyilmaz Aynur Hurriyet , Polat Gul
Published: November 2024

Estimating the completion cost accurately in the early phases of construction projects is critical to their success. However, cost overruns are almost inevitable due to the risks inherent in construction projects. Hence, the completion cost fluctuates throughout the execution phase and requires periodic updates. There is a need for a prompt and user-friendly completion cost estimation model that accounts for fluctuating risk scores and their impacts on the total cost during the execution phase. Machine learning (ML) techniques could address these requirements by providing effective methods for tackling dynamic systems. The proposed approach aims to predict the cost overrun ratio classes of the completion cost according to the changes in the total risk scores at any time of the project. Six classification algorithms were utilized and validated by employing 110 data points from a globally operating construction company. The performances of the algorithms were evaluated with validation and performance indices. The decision tree classifier surpassed other algorithms. Although there are some research limitations, including risk perception, data gathering restrictions, and selecting proper ML algorithms upon data properties, this research improves the planning abilities of construction executives by providing a cost overrun ratio based on changing total risk scores, facilitating swift and simple assessments at any stage of a construction project’s execution.
Evaluation of Steel Slag as a Sustainable Alternative Aggregate for Railway Ballast: A Shakedown Theory-Based Approach
Authors: dos Santos William Wilson , Coelho Lisley Madeira , Monteiro Sergio Neves , Marques Maria Esther Soares , Guimarães Antônio Carlos Rodrigues
Published: November 2024

Recent advancements in railway construction have emphasized environmental sustainability, integrating considerations of environmental impact into the planning and execution of infrastructure projects to reduce costs and mitigate adverse effects. This study investigates the use of steel slag as a sustainable alternative for railway ballast, grounded in shakedown theory. The characterization of the aggregates was performed in accordance with NBR 5564 and AREMA standards, confirming that the material meets most requirements. The mechanical behavior of the ballast was analyzed under cyclic loading conditions, assessing permanent deformation and the material’s ability to achieve stability (shakedown). Triaxial tests with repeated loading simulated real railway conditions, applying vertical stresses up to 600 kPa and confining pressures ranging from 35 to 200 kPa. The results indicate that steel slag aggregates exhibited promising performance, with seven specimens achieving stable deformation levels, characterized by residual deformations of less than 2.5 mm. Notably, these specimens approached deformations on the order of 10−7, indicating stability under cyclic loading. Furthermore, a comparative analysis of shakedown criteria proposed by various authors revealed variations in limits for granular materials, enhancing the understanding of steel slag aggregate behavior. The experimental results were validated through numerical simulations conducted with Systrain software 2.0, which simulated a loading condition of 32.5 tons per axle, confirming the observations with maximum principal stresses ranging from 166 to 184 kPa in the ballast. The analysis showed that steel slag aggregates can withstand stress levels higher than those of granodiorite, reinforcing their viability as a sustainable alternative for railway ballast.
Is Serum Ferritin a Predictor of Blood Transfusions Outcome and Survival in Childhood Lymphomas and Solid Tumors?
Authors: Sawicka-Żukowska Małgorzata , Krętowska-Grunwald Anna , Topczewska Magdalena , Krawczuk-Rybak Maryna , Grubczak Kamil
Published: November 2024

Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific marker of neoplastic growth and transfusion-related iron overload in children with lymphomas and solid tumors. We performed a longitudinal analysis of PRBC transfusions and changes in ferritin concentrations during oncological treatment of 88 children with lymphomas and solid tumors. A ferritin concentration above 500 ng/mL was diagnosed in 14.77% of patients at the moment of admission and 18.18% at the end of treatment. No differences were shown in serum ferritin in the context of tumor type-, sex-, and transfusion-related parameters. Those above the age of 10 demonstrated higher ferritin concentrations compared to subjects younger than 5 years of age. In addition, those over than 10 years old or above 30 kg in weight showed a tendency for better survival. All tested patients demonstrated highly significant correlations between ferritin at the 15th month of treatment or after therapy discontinuation and transfusion-related parameters. Interestingly, ferritin levels were found to lower back to the values before therapy shortly after its discontinuation. Transfusion parameters and ferritin levels had no influence on the survival of the studied cancer patients.
Increased c-MYC Expression Associated with Active IGH Locus Rearrangement: An Emerging Role for c-MYC in Chronic Lymphocytic Leukemia
Authors: Guiyedi Kenza , Parquet Milène , Aoufouchi Said , Chauzeix Jasmine , Rizzo David , Al Jamal Israa , Feuillard Jean , Gachard Nathalie , Peron Sophie
Published: November 2024

This review examines the pivotal role of c-MYC in Chronic Lymphocytic Leukemia (CLL), focusing on how its overexpression leads to increased genetic instability, thereby accelerating disease progression. MYC, a major oncogene, encodes a transcription factor that regulates essential cellular processes, including cell cycle control, proliferation, and apoptosis. In CLL cases enriched with unmutated immunoglobulin heavy chain variable (IGHV) genes, MYC is significantly overexpressed and associated with active rearrangements in the IGH immunoglobulin heavy chain locus. This overexpression results in substantial DNA damage, including double-strand breaks, chromosomal translocations, and an increase in abnormal repair events. Consequently, c-MYC plays a dual role in CLL: it promotes aggressive cell proliferation while concurrently driving genomic instability through its involvement in genetic recombination. This dynamic contributes not only to CLL progression but also to the overall aggressiveness of the disease. Additionally, the review suggests that c-MYC’s influence on genetic rearrangements makes it an attractive target for therapeutic strategies aimed at mitigating CLL malignancy. These findings underscore c-MYC’s critical importance in advancing CLL progression, highlighting the need for further research to explore its potential as a target in future treatment approaches.
Correction: Huang et al. Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer. Cells 2021, 10, 2524
Authors: Huang Wei-Chieh , Chi Hsiang-Cheng , Tung Shiao-Lin , Chen Po-Ming , Shih Ya-Chi , Huang Yi-Ching , Chu Pei-Yi
Published: November 2024

In the original publication [...]
An Investigation of RNA Methylations with Biophysical Approaches in a Cervical Cancer Cell Model
Authors: Sağlam Buket , Akkuş Onur , Akçaöz-Alasar Azime , Ceylan Çağatay , Güler Günnur , Akgül Bünyamin
Published: November 2024

RNA methylation adds a second layer of genetic information that dictates the post-transcriptional fate of RNAs. Although various methods exist that enable the analysis of RNA methylation in a site-specific or transcriptome-wide manner, whether biophysical approaches can be employed to such analyses is unexplored. In this study, Fourier-transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are employed to examine the methylation status of both synthetic and cellular RNAs. The results show that FT-IR spectroscopy is perfectly capable of quantitatively distinguishing synthetic m6A-methylated RNAs from un-methylated ones. Subsequently, FT-IR spectroscopy is successfully employed to assess the changes in the extent of total RNA methylation upon the knockdown of the m6A writer, METTL3, in HeLa cells. In addition, the same approach is shown to accurately detect reduction in total RNA methylation upon the treatment of HeLa cells with tumor necrosis factor alpha (TNF-α). It is also demonstrated that m1A and m6A methylation induce quite a distinct secondary structure on RNAs, as evident from CD spectra. These results strongly suggest that both FT-IR and CD spectroscopy methods can be exploited to uncover biophysical properties impinged on RNAs by methyl moieties, providing a fast, convenient and cheap alternative to the existing methods.
Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes
Authors: Mossetti Laura , Hervás-Herrero Irene , Gil-Juliá María , Navarro Gomez-Lechon Ana , Pacheco-Rendón Rosa María , Rivera-Egea Rocío , Garrido-Puchalt Nicolás
Published: November 2024

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).
Neonatal Presentation of Severe Hemophilia A: An Original Case Report and a Literature Review
Authors: Alboreto Erika , Pezzotta Federico , Vinci Francesco , Calandrino Andrea , Banov Laura , Mongelli Federica , Massirio Paolo , Buratti Silvia , Moscatelli Andrea , Ramenghi Luca Antonio
Published: November 2024

Introduction: We report the case of a neonate diagnosed with severe hemophilia A (HA) and conduct a literature review of cases of severe HA presenting at the neonatal age to help define the clinical diagnostic findings and existing differences between the sporadic and familial onset of this condition. Report of a Case: A 6-day-old newborn presented with worsening pallor, inappetence, and hyporeactivity for 48 h. The diagnosis was severe hemophilia A (HA), leading to an unfavorable outcome. A literature review focusing on case reports and series focusing on the clinical expression of HA in neonates was conducted, documenting clinical presentation, family history, and outcomes. Literature review: Forty patients were included. HA was observed in five cases (12.5%) of very preterm births (≤32 weeks) and in four cases (10%) of moderately or late preterm births. Seventeen patients (43%) had a family history, with inheritance being sporadic (21 newborns, 53%) or acquired (2 cases, 4%). Clinical onset typically occurred within the first week of life (approximately 8 out of 10 cases), while only three cases (7.5%) had onset after the first month. Inherited cases presented with hemorrhagic states (nine cases), hypovolemic shock (five cases), or intracranial hypertension (two cases). Sporadic cases showed localized bleeding (11 cases), hypovolemic shock (5 cases), or neurological symptoms like seizures and anisocoria (5 cases). Acquired cases included severe intracranial hemorrhage in one case. Conclusions: Neonatal HA can manifest with severe symptoms and rapid progression, making early diagnosis crucial. Non-specific signs and the absence of coagulophaty disorders in family history can delay diagnosis. Symptoms like prolonged bleeding, cutaneous hematomas, or intracranial bleeding necessitate ruling out major coagulopathy, and neurological signs require immediate imaging to exclude intracranial bleeding.
Effect of Soy Isoflavone on Prostate Cancer Cell Apoptosis Through Inhibition of STAT3, ERK, and AKT
Authors: Lee Yoon-Jin , Lee Changyeol , Choi Dongsic , Lee Yeji , Lee Sang-Han
Published: November 2024

Genistein, an isoflavone found in soybeans, exhibits antioxidant, anti-inflammatory, and anticancer properties. This study explored the molecular mechanisms behind genistein’s anticancer effects in prostate cancer DU145 cells. In this study, genistein decreased cell viability, increased annexin V-PE(+) cells, and enhanced the sub-G0/G1 peak by flow cytometric analysis. Increased reactive oxygen species increased mitochondrial depolarization indicating mitochondrial dysfunction and inhibition of ATP formation were also observed in genistein-treated DU145 cells. Genistein upregulated p53 at the mRNA and protein levels and increased caspase-3/7 activity along with the cleavage of Bax, procaspase-3, and PARP. With the increasing genistein concentrations, the percentage of cells in the sub-G0/G1 peak and G2/M phase increased, which was inhibited by treatment with the pan-caspase inhibitor Z-VAD together with 100 μM genistein, which had little toxicity to normal prostate epithelial HPrEC cells. Genistein treatment simultaneously inhibited the activation of STAT3 and other closely related oncogenic kinases such as AKT and ERK and p38 and decreased VEGF expression. Taken together, these results suggest that genistein inhibits the growth of DU145 cells and induces apoptosis by inhibiting STAT3, AKT, ERK, and p38 which provides a molecular basis for the anticancer activity of genistein and suggests its potential as a valuable therapeutic candidate for prostate cancer.
From Genomic Exploration to Personalized Treatment: Next-Generation Sequencing in Oncology
Authors: Vashisht Vishakha , Vashisht Ashutosh , Mondal Ashis K. , Woodall Jana , Kolhe Ravindra
Published: November 2024

Next-generation sequencing (NGS) has revolutionized personalized oncology care by providing exceptional insights into the complex genomic landscape. NGS offers comprehensive cancer profiling, which enables clinicians and researchers to better understand the molecular basis of cancer and to tailor treatment strategies accordingly. Targeted therapies based on genomic alterations identified through NGS have shown promise in improving patient outcomes across various cancer types, circumventing resistance mechanisms and enhancing treatment efficacy. Moreover, NGS facilitates the identification of predictive biomarkers and prognostic indicators, aiding in patient stratification and personalized treatment approaches. By uncovering driver mutations and actionable alterations, NGS empowers clinicians to make informed decisions regarding treatment selection and patient management. However, the full potential of NGS in personalized oncology can only be realized through bioinformatics analyses. Bioinformatics plays a crucial role in processing raw sequencing data, identifying clinically relevant variants, and interpreting complex genomic landscapes. This comprehensive review investigates the diverse NGS techniques, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and single-cell RNA sequencing (sc-RNA-Seq), elucidating their roles in understanding the complex genomic/transcriptomic landscape of cancer. Furthermore, the review explores the integration of NGS data with bioinformatics tools to facilitate personalized oncology approaches, from understanding tumor heterogeneity to identifying driver mutations and predicting therapeutic responses. Challenges and future directions in NGS-based cancer research are also discussed, underscoring the transformative impact of these technologies on cancer diagnosis, management, and treatment strategies.
The Role of Cacao Powder in Enhancing Skin Moisture and Reducing Wrinkles: A 12-Week Clinical Trial and In Vitro Study
Authors: Lee Sang Gyu , Nguyen Ngoc Ha , Lee Young In , Jung Inhee , Kim In Ah , Jang Hyunsook , Shin Hoyeon , Lee Ju Hee
Published: November 2024

Skin aging is driven by a combination of internal and external mechanisms, with ultraviolet (UV) radiation being a prominent external factor contributing to photoaging. Photoaging manifests through several signs, including decreased skin hydration, diminished elasticity, coarse wrinkles, and dyspigmentation. Cacao beans, known for their flavonoids and polyphenols, offer potential anti-aging benefits. To explore this, we conducted a study using both in vitro experiments and clinical trials. Our results demonstrated that cacao powder significantly improved skin hydration and moisture retention in both experimental settings. Specifically, in UVB-damaged human dermal fibroblasts (HDFs) and H2O2-treated keratinocytes (KCs), cacao powder displayed notable antioxidant properties. Furthermore, cacao powder enhanced the activity of antioxidant enzymes and promoted the production of hyaluronic acid in KCs, contributing to better skin hydration. It also effectively inhibited the expression of matrix metalloproteinase-1, an enzyme associated with wrinkle formation, and stimulated collagen synthesis in HDFs. Clinical trials conducted on participants with aged skin revealed a significant improvement in skin hydration and a reduction in skin wrinkles after 12 weeks of cacao powder consumption, supporting the in vitro findings. These results suggest that cacao powder holds promise as a natural ingredient for improving skin hydration and reducing wrinkles, underscoring its potential in anti-aging skincare.
Gene Delivery via Octadecylamine-Based Nanoparticles for iPSC Generation from CCD1072-SK Fibroblast Cells
Authors: Varlı Hanife Sevgi , Akkurt Yıldırım Meryem , Kızılbey Kadriye , Türkoğlu Nelisa
Published: November 2024

This study presents a novel biotechnological approach using octadecylamine-based solid lipid nanoparticles (OCTNPs) for the first-time reprogramming of human CCD1072-SK fibroblast cells into induced pluripotent stem cells (iPSCs). OCTNPs, with an average size of 178.9 nm and a positive zeta potential of 22.8 mV, were synthesized, thoroughly characterized, and utilized as a non-viral vector to efficiently deliver reprogramming factors, achieving a remarkable transfection efficiency of 82.0%. iPSCs were characterized through immunofluorescence, flow cytometry, and RT-qPCR, confirming the expression of key pluripotency markers such as OCT4, SOX2, and KLF4, with alkaline phosphatase activity further validating their pluripotent state. Following this comprehensive characterization, the iPSCs were successfully differentiated into cardiomyocyte-like cells using 5-azacytidine. Our research highlights the innovative application of OCTNPs as a safe and effective alternative to viral vectors, addressing key limitations of iPSC reprogramming. The novel application of OCTNPs for efficient gene delivery demonstrates a powerful tool for advancing stem cell technologies, minimizing risks associated with viral vectors. These findings pave the way for further innovations in biotechnological applications, particularly in tissue engineering and personalized medicine.
Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis
Authors: Demyashkin Grigory , Koryakin Sergey , Parshenkov Mikhail , Skovorodko Polina , Vadyukhin Matvey , Uruskhanova Zhanna , Stepanova Yulia , Shchekin Vladimir , Mirontsev Artem , Rostovskaya Vera , Ivanov Sergey , Shegay Petr , Kaprin Andrei
Published: November 2024

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function.
The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
Authors: Antar Ryan Michael , Fawaz Christopher , Gonzalez Diego , Xu Vincent Eric , Drouaud Arthur Pierre , Krastein Jason , Pio Faozia , Murdock Andeulazia , Youssef Kirolos , Sobol Stanislav , Whalen Michael J.
Published: November 2024

The genetic landscape of urologic cancers has evolved with the identification of actionable mutations that impact diagnosis, prognosis, and therapeutic strategies. This narrative review consolidates existing literature on genetic mutations across key urologic cancers, including bladder, renal, prostate, upper tract urothelial, testicular, and penile. The review highlights mutations in DNA damage repair genes, such as BRCA1/2 and PTEN, as well as pathway alterations like FGFR and PD-L1 overexpression. These mutations influence tumor behavior and therapeutic outcomes, emphasizing the need for precision oncology approaches. Molecular profiling, through tools like next-generation sequencing, has revolutionized patient care by enabling targeted treatment strategies, especially in cancers with distinct molecular subtypes such as luminal or basal bladder cancer and clear cell renal carcinoma. Emerging therapies, including FGFR inhibitors and immune checkpoint blockade, offer new treatment avenues, although resistance mechanisms remain a challenge. We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes.