bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractional-Order Control Techniques for Renewable Energy and Energy-Storage-Integrated Power Systems: A Review
Authors: Alilou Masoud , Azami Hatef , Oshnoei Arman , Mohammadi-Ivatloo Behnam , Teodorescu Remus
Published: May 2023

The worldwide energy revolution has accelerated the utilization of demand-side manageable energy systems such as wind turbines, photovoltaic panels, electric vehicles, and energy storage systems in order to deal with the growing energy crisis and greenhouse emissions. The control system of renewable energy units and energy storage systems has a high effect on their performance and absolutely on the efficiency of the total power network. Classical controllers are based on integer-order differentiation and integration, while the fractional-order controller has tremendous potential to change the order for better modeling and controlling the system. This paper presents a comprehensive review of the energy system of renewable energy units and energy storage devices. Various papers are evaluated, and their methods and results are presented. Moreover, the mathematical fundamentals of the fractional-order method are mentioned, and the various studies are categorized based on different parameters. Various definitions for fractional-order calculus are also explained using their mathematical formula. Different studies and numerical evaluations present appropriate efficiency and accuracy of the fractional-order techniques for estimating, controlling, and improving the performance of energy systems in various operational conditions so that the average error of the fractional-order methods is considerably lower than other ones.
Bernoulli-Type Spectral Numerical Scheme for Initial and Boundary Value Problems with Variable Order
Authors: Khan Zareen A. , Ahmad Sajjad , Zeb Salman , Alrabaiah Hussam
Published: May 2023

This manuscript is devoted to using Bernoulli polynomials to establish a new spectral method for computing the approximate solutions of initial and boundary value problems of variable-order fractional differential equations. With the help of the aforementioned method, some operational matrices of variable-order integration and differentiation are developed. With the aid of these operational matrices, the considered problems are converted to algebraic-type equations, which can be easily solved using computational software. Various examples are solved by applying the method described above, and their graphical presentation and accuracy performance are provided.
A Plant-Based Animal Fat Analog Produced by an Emulsion Gel of Alginate and Pea Protein
Authors: Teng Chong , Campanella Osvaldo H.
Published: May 2023

As the market for plant-based meat analogs grows, the development of plant-based animal fat analogs has become increasingly important. In this study, we propose an approach by developing a gelled emulsion based on sodium alginate, soybean oil (SO), and pea protein isolate. Formulations containing 15% to 70% (w/w) SO were successfully produced without phase inversion. The addition of more SO resulted in pre-gelled emulsions with a more elastic behavior. After the emulsion was gelled in the presence of calcium, the color of the gelled emulsion changed to light yellow, and the formulation containing 70% SO exhibited a color most similar to actual beef fat trimming. The lightness and yellowness values were greatly influenced by the concentrations of both SO and pea protein. Microscopic images revealed that pea protein formed an interfacial film around the oil droplets, and the oil was more tightly packed at higher oil concentrations. Differential scanning calorimetry showed that lipid crystallization of the gelled SO was influenced by the confinement of the alginate gelation, but the melting behavior was like that of free SO. FTIR spectrum analysis indicated a potential interaction between alginate and pea protein, but the functional groups of SO were unchanged. Under mild heating conditions, gelled SO exhibited an oil loss similar to that observed in actual beef trims. The developed product has the potential to mimic the appearance and slow-rendering melting attribute of real animal fat.
FSF-GA: A Feature Selection Framework for Phenotype Prediction Using Genetic Algorithms
Authors: Mowlaei Mohammad Erfan , Shi Xinghua
Published: May 2023

(1) Background: Phenotype prediction is a pivotal task in genetics in order to identify how genetic factors contribute to phenotypic differences. This field has seen extensive research, with numerous methods proposed for predicting phenotypes. Nevertheless, the intricate relationship between genotypes and complex phenotypes, including common diseases, has resulted in an ongoing challenge to accurately decipher the genetic contribution. (2) Results: In this study, we propose a novel feature selection framework for phenotype prediction utilizing a genetic algorithm (FSF-GA) that effectively reduces the feature space to identify genotypes contributing to phenotype prediction. We provide a comprehensive vignette of our method and conduct extensive experiments using a widely used yeast dataset. (3) Conclusions: Our experimental results show that our proposed FSF-GA method delivers comparable phenotype prediction performance as compared to baseline methods, while providing features selected for predicting phenotypes. These selected feature sets can be used to interpret the underlying genetic architecture that contributes to phenotypic variation.
Expression of Transposable Elements in the Brain of the Drosophila melanogaster Model for Fragile X Syndrome
Authors: De Donno Maria Dolores , Puricella Antonietta , D’Attis Simona , Specchia Valeria , Bozzetti Maria Pia
Published: May 2023

Fragile X syndrome is a neuro-developmental disease affecting intellectual abilities and social interactions. Drosophila melanogaster represents a consolidated model to study neuronal pathways underlying this syndrome, especially because the model recapitulates complex behavioural phenotypes. Drosophila Fragile X protein, or FMRP, is required for a normal neuronal structure and for correct synaptic differentiation in both the peripheral and central nervous systems, as well as for synaptic connectivity during development of the neuronal circuits. At the molecular level, FMRP has a crucial role in RNA homeostasis, including a role in transposon RNA regulation in the gonads of D. m. Transposons are repetitive sequences regulated at both the transcriptional and post-transcriptional levels to avoid genomic instability. De-regulation of transposons in the brain in response to chromatin relaxation has previously been related to neurodegenerative events in Drosophila models. Here, we demonstrate for the first time that FMRP is required for transposon silencing in larval and adult brains of Drosophila “loss of function” dFmr1 mutants. This study highlights that flies kept in isolation, defined as asocial conditions, experience activation of transposable elements. In all, these results suggest a role for transposons in the pathogenesis of certain neurological alterations in Fragile X as well as in abnormal social behaviors.
Numerical Modeling of an Asteroid Impact on Earth: Matching Field Observations at the Chicxulub Crater Using the Distinct Element Method (DEM)
Authors: Duong Tam N.-M. , Hernawan Billy , Medina-Cetina Zenon , Urrutia Fucugauchi Jaime
Published: May 2023

In recent years, an international consortium of research organizations conducted investigations at the Chicxulub Crater in Yucatan, Mexico, to better understand the crater’s formation mechanisms and the effects produced by the impact of the asteroid that is hypothesized to have caused one of the major life extinctions on Earth. This study aims to reproduce the asteroid’s impact mechanics by matching computer simulations obtained with the use of the distinct element method (DEM) against the latest topographic data observed across the crater footprint. A 2D model was formulated using ITASCA’s PFC2D software to reproduce the asteroid’s impact on Earth. The model ground conditions prior to impact were replicated based on available geological and geophysical field information. Also, the proposed DEM model configuration was designed to reproduce a far-field effect to ascertain the energy dissipation of the asteroid’s impact at the model’s boundaries. Impact conditions of the asteroid were defined based on previous asteroid impact investigations. A parametric analysis including the asteroid’s impact angle and the asteroid’s impact velocity was conducted to assess their influence on the crater formation process. Results of the simulations included the final crater topography and stratigraphy, stress profiles, contact force chains, and velocity fields. Numerical simulations showed that both the asteroid velocity and impact inclination play a major role in the crater formation process, and that the use of DEM provides interesting insights into impact crater formation.
Mental Health in Coronary Heart Disease (CHD) Patients: Findings from the UK Household Longitudinal Study (UKHLS)
Authors: Kang Weixi , Malvaso Antonio
Published: May 2023

Objectives: Mental health conditions in patients with coronary heart disease (CHD) are closely related to clinical outcomes. Thus, this study’s goal is to investigate how CHD affects general and specific aspects of mental health. Methods: We analyzed data from Wave 10 Understanding Society: the UK Household Longitudinal Study (UKHLS), which were collected between 2018 and 2019. After removing people who had missing data, there were 450 participants who indicated that they have CHD, and 6138 age- and sex-matched healthy participants indicated that they were not clinically diagnosed with CHD. Results: The main findings were that participants with CHD had more mental health problems, as shown by the GHQ-12 summary score (t (449) = 6.00, p < 0.001, 95% C.I. [0.20, 0.40], Cohen’s d = 0.30), social dysfunction and anhedonia, (t (449) = 5.79, p < 0.001, 95% C.I. [0.20, 0.40], Cohen’s d = 0.30), depression and anxiety (t (449) = 5.04, p < 0.001, 95% C.I. [0.15, 0.33], Cohen’s d = 0.24), and loss of confidence (t (449) = 4.46, p < 0.001, 95% C.I. [0.11, 0.30], Cohen’s d = 0.21). Conclusion: This study implies that GHQ-12 is a valid assessment of mental health problems in CHD patients, and there is a need to consider how different aspects of mental health are affected by CHD rather than solely focusing on depression or anxiety problems alone in patients with CHD.
Periodontitis in Pregnant Women: A Possible Link to Adverse Pregnancy Outcomes
Authors: Butera Andrea , Maiorani Carolina , Morandini Annalaura , Trombini Julia , Simonini Manuela , Ogliari Chiara , Scribante Andrea
Published: May 2023

Background: Periodontitis develops in 11% of pregnant women, and it is independently linked to severe complications during pregnancy such as preterm birth, low birth weight, and gestational diabetes. Methods: A literature search (Pubmed/MEDLINE, and Scopus) from 2003 to 2023 was conducted to analyze studies focused on periodontitis and adverse pregnancy outcomes. Results: 16 articles have been included. Most of the studies showed adverse outcomes, like preterm birth and the low weight of the unborn child, are among the most frequent consequences (respectively 62.5% and 68.7% of articles); pre-eclampsia is also linked to this condition (12.5% of articles); and perinatal mortality (12.5% of articles). Conclusions: Periodontal disease appears to be associated with adverse events in pregnancy due to the transport of biofilm bacteria into the bloodstream and into placental tissue; what would cause adverse events is the body’s immune response to infection.
Changes and Determinants of Maternal Health Services Utilization in Ethnic Minority Rural Areas in Central China, 1991–2015: An Ecological Systems Theory Perspective
Authors: Zhang Changli , Lu Jun
Published: May 2023

Background: Universal maternal health coverage is a proven, effective strategy for maternal survival. This study aimed to describe the changes and determinants of maternal health service use between 1991 and 2015 in central China. Methods: The study was conducted in Enshi Prefecture. Women were eligible for inclusion if they were rural women who lived in villages, had live births during 1991–2015, could recall their maternal care histories, and had no communication problems. This retrospective study included 470 rural women in 9 villages and collected 770 records. The conceptual framework was designed based on the Society Ecosystem Theory. The determinants included micro-factors (individual characteristics), meso-factors (family factors, community factors, healthcare factors), and macro-factors (government-run maternal and child health programs, abbreviated as MCH programs). Multivariate logistic regressions were applied to analyze the determinants of maternal health service utilization. Results: The utilization of maternal healthcare has improved in Enshi. The hospital birth rate was 98.1% in 2009 and mostly 100% in subsequent years. The prenatal examination rate, the postpartum visit rate, and the continuum of maternal health service (CMHS) rate increased to 73.3%, 67.7%, and 53.4%, respectively, in 2009–2015. The utilization of maternal health services was affected by macro-factors, meso-factors, and micro-factors, with macro-factors being the most notable contributors. Conclusions: Despite the remarkable improvements in antenatal care (ANC) use and hospital birth, gaps in postpartum visits remain. Promoting the integrated continuum of maternal and child healthcare in ethnic minority rural areas requires the joint efforts of the government, health and other sectors, communities, families, and individuals.
Geological Insights on the Calcareous Tufas (Pietra Spugna) Used as Building and Ornamental Stones in the UNESCO Historical Centre of Urbino (Marche Region, Italy)
Authors: Santi Patrizia , Renzulli Alberto , Veneri Francesco , Tonelli Gianluigi , Tramontana Mario , Taussi Marco , Calcagnile Lucio , Quarta Gianluca
Published: May 2023

This study is addressed at the cultural heritage of the UNESCO historical centre of Urbino (Italy) through the focus on a very peculiar building and ornamental carbonate porous (spongy) stone also found in the opus quadratum Roman dry walls. For these rocks, the mathematician and historian Bernardino Baldi (16th century AD) and the mineralogist Francesco Rodolico (middle of the 20th century AD) introduced, respectively, the popular terms of Tufo spugnoso or Pietra Spugna. Physical observations and stable isotope data (δ13C and δ18O) of these rocks allowed, for the first time, their classification as calcareous tufas, thus contributing to the valorization of the stone heritage of the city. This carbonate lithotype was formed by the chemical precipitation of CaCO3, driven by the CO2 degassing of supersaturated calcium-bicarbonate-rich waters, coupled with the passive encrustations of organic material in continental environments. Radiocarbon analyses dated these stones mostly between 9100 and 4700 yr. BP when a maximum growth of these carbonate continental deposits occurred in Mediterranean regions and northern Europe, i.e., during the Holocene Atlantic climatic optimum. Work is still in progress on a perched springline of calcareous tufas found along the Metauro Valley (a few km from Urbino), being good candidates for provenance, at least for those blocks exploited by the Romans and successively reused in the architectural framework of Urbino.
Managing Water Stress in Olive (Olea europaea L.) Orchards Using Reference Equations for Midday Stem Water Potential
Authors: Sánchez-Piñero Marta , Corell Mireia , Moriana Alfonso , Castro-Valdecantos Pedro , Martin-Palomo María-José
Published: May 2023

The irrigation surface of olive orchards has increased over recent decades. In zones affected, deficit irrigation scheduling is a must. The aim of this work was to study water stress management based on reference equations for midday stem water potential. An experiment was conducted over three seasons in Seville (Spain) from 2020 to 2022. A young hedgerow olive orchard (cv Manzanilla de Sevilla) was irrigated using three different treatments: Control (full irrigated), RDI, and Rainfed, in a completely randomized design (six replications). The midday stem water potential and leaf conductance were measured throughout the three seasons. Stem water potential was more sensitive to water stress than leaf conductance and showed a clearer impact and rehydration. Individual data of stem water potential were grouped according to leaf conductance reduction. The relationship of these stem water potentials and temperature or vapor pressure deficit was significant, linear, and aligned to published baselines. Scattering in these equations increased when the leaf conductance reduction was greater. These reference equations would be useful to define moderate water stress conditions in the most sensitive processes, such as vegetative or fruit growth. Definition of severe water stress conditions would be better established with constant values.
Sector of Employment and Mortality: A Cohort Based on Different Administrative Archives
Authors: Bauleo Lisa , Massari Stefania , Gariazzo Claudio , Michelozzi Paola , Dei Bardi Luca , Zengarini Nicolas , Maio Sara , Stafoggia Massimo , Davoli Marina , Viegi Giovanni , Marinaccio Alessandro , Cesaroni Giulia
Published: May 2023

Administrative data can be precious in connecting information from different sectors. For the first time, we used data from the National Social Insurance Agency (INPS) to investigate the association between the occupational sectors and both non-accidental and accidental mortality. We retrieved information on occupational sectors from 1974 to 2011 for private sector workers included in the 2011 census cohort of Rome. We classified the occupational sectors into 25 categories and analyzed occupational exposure as ever/never have been employed in a sector or as the lifetime prevalent sector. We followed the subjects from the census reference day (9 October 2011) to 31 December 2019. We calculated age-standardized mortality rates for each occupational sector, separately in men and women. We used Cox regression to investigate the association between the occupational sectors and mortality, producing hazard ratios (HRs) and 95% confidence intervals (95%CI). We analyzed 910,559 30+-year-olds (53% males) followed for 7 million person-years. During the follow-up, 59,200 and 2560 died for non-accidental and accidental causes, respectively. Several occupational sectors showed high mortality risks in men in age-adjusted models: food and tobacco production with HR = 1.16 (95%CI: 1.09–8.22), metal processing (HR = 1.66, 95%CI: 1.21–11.8), footwear and wood (HR = 1.19, 95%CI: 1.11–1.28), construction (HR = 1.15, 95%CI: 1.12–1.18), hotels, camping, bars, and restaurants (HR = 1.16, 95%CI: 1.11–1.21) and cleaning (HR = 1.42, 95%CI: 1.33–1.52). In women, the sectors that showed higher mortality than the others were hotels, camping, bars, and restaurants (HR = 1.17, 95%CI: 1.10–1.25) and cleaning services (HR = 1.23, 95%CI: 1.17–1.30). Metal processing and construction sectors showed elevated accidental mortality risks in men. Social Insurance Agency data have the potential to characterize high-risk sectors and identify susceptible groups in the population.
Capabilities, Opportunities, and Motivation: Exploring Fitness Program Experiences of Adults with Intellectual and Developmental Disabilities
Authors: Savage Melissa N. , Colombo-Dougovito Andrew M.
Published: May 2023

Although there are many benefits to regular engagement in physical activity, adults with intellectual and developmental disabilities often do not engage in or near the recommended amount of physical activity. Barriers, such as lack of perceived capability, accessible environments, transportation, social support, and or knowledgeable support staff, may limit participation in physical activity. The present study used qualitative methods to explore the experiences of adults with intellectual and developmental disabilities enrolled in a fitness program. We used field observations and photo-elicited semi-structured interviews to explore what capabilities, opportunities, and motivations facilitate or hinder engagement in fitness classes and their experiences in the program. We used the COM-B model to deductively interpret and analyze the data through thematic analysis. Major themes were identified around types of support and preferences for physical over sedentary activities. Instructor, client, and family support were identified as important in facilitating interest, engagement, and skill. Dependency on others for financial and transportation support was also reported as important for participants to access the fitness program. This study provides valuable insight into the interactions and experiences of adults with intellectual and developmental disabilities, including what keeps them engaged in a fitness program as it relates to capabilities, opportunities, and motivation.
Telemedicine in Adult Congenital Heart Disease: Usefulness of Digital Health Technology in the Assistance of Critical Patients
Authors: Borrelli Nunzia , Grimaldi Nicola , Papaccioli Giovanni , Fusco Flavia , Palma Michela , Sarubbi Berardo
Published: May 2023

The number of adults with congenital heart disease (ACHD) has progressively increased in recent years to surpass that of children. This population growth has produced a new demand for health care. Moreover, the 2019 coronavirus pandemic has caused significant changes and has underlined the need for an overhaul of healthcare delivery. As a result, telemedicine has emerged as a new strategy to support a patient-based model of specialist care. In this review, we would like to highlight the background knowledge and offer an integrated care strategy for the longitudinal assistance of ACHD patients. In particular, the emphasis is on recognizing these patients as a special population with special requirements in order to deliver effective digital healthcare.
The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease
Authors: Alalawi Sulaiman , Albalawi Faizah , Ramji Dipak P.
Published: May 2023

Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.
Dipeptide Nitrile CD34 with Curcumin: A New Improved Combination Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense
Authors: Di Chio Carla , Previti Santo , Totaro Noemi , De Luca Fabiola , Allegra Alessandro , Schirmeister Tanja , Zappalà Maria , Ettari Roberta
Published: May 2023

Rhodesain is the main cysteine protease of Trypanosoma brucei rhodesiense, the parasite causing the acute lethal form of Human African Trypanosomiasis. Starting from the dipeptide nitrile CD24, the further introduction of a fluorine atom in the meta position of the phenyl ring spanning in the P3 site and the switch of the P2 leucine with a phenylalanine led to CD34, a synthetic inhibitor that shows a nanomolar binding affinity towards rhodesain (Ki = 27 nM) and an improved target selectivity with respect to the parent dipeptide nitrile CD24. In the present work, following the Chou and Talalay method, we carried out a combination study of CD34 with curcumin, a nutraceutical obtained from Curcuma longa L. Starting from an affected fraction (fa) of rhodesain inhibition of 0.5 (i.e., the IC50), we observed an initial moderate synergistic action, which became a synergism for fa values ranging from 0.6 to 0.7 (i.e., 60–70% inhibition of the trypanosomal protease). Interestingly, at 80–90% inhibition of rhodesain proteolytic activity, we observed a strong synergism, resulting in 100% enzyme inhibition. Overall, in addition to the improved target selectivity of CD34 with respect to CD24, the combination of CD34 + curcumin resulted in an increased synergistic action with respect to CD24 + curcumin, thus suggesting that it is desirable to use CD34 and curcumin in combination.
Developing Biomarkers for the Skin: Biomarkers for the Diagnosis and Prediction of Treatment Outcomes of Alzheimer’s Disease
Authors: Wu Ching-Ying , Ho Chih-Yi , Yang Yuan-Han
Published: May 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory decline and cognitive impairment. Research on biomarkers can aid in early diagnosis, monitoring disease progression, evaluating treatment efficacy, and advancing fundamental research. We conducted a cross-sectional longitudinal study to see if there is an association between AD patients and age-matched healthy controls for their physiologic skin characteristics, such as pH, hydration, transepidermal water loss (TEWL), elasticity, microcirculation, and ApoE genotyping. The study used the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of the Boxes (CDR-SB) scales as references to quantify the presence of disease, if any. Our findings demonstrate that AD patients have a dominantly neutral pH, greater skin hydration, and less elasticity compared to the control subjects. At baseline, the tortuous capillary percentage negatively correlated with MMSE scores in AD patients. However, AD patients who carry the ApoE E4 allele and exhibit a high percentage of tortuous capillaries and capillary tortuous numbers have shown better treatment outcomes at six months. Therefore, we believe that physiologic skin testing is a rapid and effective way to screen, monitor progression, and ultimately guide the most appropriate treatment for AD patients.
17β-Estradiol Induced Sex Reversal and Gonadal Transcriptome Analysis in the Oriental River Prawn (Macrobrachium nipponense): Mechanisms, Pathways, and Potential Harm
Authors: Cai Pengfei , Yuan Huwei , Gao Zijian , Qiao Hui , Zhang Wenyi , Jiang Sufei , Xiong Yiwei , Gong Yongsheng , Wu Yan , Jin Shubo , Fu Hongtuo
Published: May 2023

Sex reversal induced by 17β-estradiol (E2) has shown the potential possibility for monoculture technology development. The present study aimed to determine whether dietary supplementation with different concentrations of E2 could induce sex reversal in M. nipponense, and select the sex-related genes by performing the gonadal transcriptome analysis of normal male (M), normal female (FM), sex-reversed male prawns (RM), and unreversed male prawns (NRM). Histology, transcriptome analysis, and qPCR were performed to compare differences in gonad development, key metabolic pathways, and genes. Compared with the control, after 40 days, feeding E2 with 200 mg/kg at PL25 (PL: post-larvae developmental stage) resulted in the highest sex ratio (female: male) of 2.22:1. Histological observations demonstrated the co-existence of testis and ovaries in the same prawn. Male prawns from the NRM group exhibited slower testis development without mature sperm. RNA sequencing revealed 3702 differentially expressed genes (DEGs) between M vs. FM, 3111 between M vs. RM, and 4978 between FM vs. NRM. Retinol metabolism and nucleotide excision repair pathways were identified as the key pathways for sex reversal and sperm maturation, respectively. Sperm gelatinase (SG) was not screened in M vs. NRM, corroborating the results of the slice D. In M vs. RM, reproduction-related genes such as cathepsin C (CatC), heat shock protein cognate (HSP), double-sex (Dsx), and gonadotropin-releasing hormone receptor (GnRH) were expressed differently from the other two groups, indicating that these are involved in the process of sex reversal. Exogenous E2 can induce sex reversal, providing valuable evidence for the establishment of monoculture in this species.
Kinetic Intricacies of the Light Emission and Antiradical Influence of Exogenous Bioantioxidants Transformation Products in the Chemiluminescence Bioantioxidant Assay
Authors: Naumov Vladimir V. , Trofimov Aleksei V. , Fedorova Galina F. , Yablonskaya Olga I. , Vasil’ev Rostislav F.
Published: May 2023

The subject matter of the reported work refers to studying the interactions followed by the excited-state generation, which are chemical models of oxidative processes leading to a weak light emission emerging from living cells, and to explore the possibilities of using them as tools for evaluating the activity of oxygen-metabolism modulators, most prominently, natural bioantioxidants of biomedical value in particular. Methodologically, major attention is paid to analyzing the shapes of the time profiles of the light emission derived from a model sensory system in the presence of lipid samples of vegetable and animal (fish) origin rich in bioantioxidants. As a result, a modified reaction mechanism involving 12 elementary steps is proposed to rationalize the light-emission kinetics in the presence of natural bioantioxidants. We conclude that free radicals formed from bioantioxidants and their dimerization products contribute significantly to the general antiradical activity of lipid samples, which should be taken into account in developing efficient bioantioxidant assays for biomedical applications and while establishing the mechanisms of bioantioxidant effects on metabolic processes in vivo.
Infantile Neurodegeneration Results from Mutants of 17β-Hydroxysteroid Dehydrogenase Type 10 Rather Than Aβ-Binding Alcohol Dehydrogenase
Authors: He Xue-Ying , Dobkin Carl , Brown William Ted , Yang Song-Yu
Published: May 2023

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10), a homo-tetrameric multifunctional protein with 1044 residues encoded by the HSD17B10 gene, is necessary for brain cognitive function. Missense mutations result in infantile neurodegeneration, an inborn error in isoleucine metabolism. A 5-methylcytosine hotspot underlying a 388-T transition leads to the HSD10 (p.R130C) mutant to be responsible for approximately half of all cases suffering with this mitochondrial disease. Fewer females suffer with this disease due to X-inactivation. The binding capability of this dehydrogenase to Aβ-peptide may play a role in Alzheimer’s disease, but it appears unrelated to infantile neurodegeneration. Research on this enzyme was complicated by reports of a purported Aβ-peptide-binding alcohol dehydrogenase (ABAD), formerly referred to as endoplasmic-reticulum-associated Aβ-binding protein (ERAB). Reports concerning both ABAD and ERAB in the literature reflect features inconsistent with the known functions of 17β-HSD10. It is clarified here that ERAB is reportedly a longer subunit of 17β-HSD10 (262 residues). 17β-HSD10 exhibits L-3-hydroxyacyl-CoA dehydrogenase activity and is thus also referred to in the literature as short-chain 3-hydorxyacyl-CoA dehydrogenase or type II 3-hydorxyacyl-CoA dehydrogenase. However, 17β-HSD10 is not involved in ketone body metabolism, as reported in the literature for ABAD. Reports in the literature referring to ABAD (i.e., 17β-HSD10) as a generalized alcohol dehydrogenase, relying on data underlying ABAD’s activities, were found to be unreproducible. Furthermore, the rediscovery of ABAD/ERAB’s mitochondrial localization did not cite any published research on 17β-HSD10. Clarification of the purported ABAD/ERAB function derived from these reports on ABAD/ERAB may invigorate this research field and encourage new approaches to the understanding and treatment of HSD17B10-gene-related disorders. We establish here that infantile neurodegeneration is caused by mutants of 17β-HSD10 but not ABAD, and so we conclude that ABAD represents a misnomer employed in high-impact journals.
Abemaciclib, Palbociclib, and Ribociclib in Real-World Data: A Direct Comparison of First-Line Treatment for Endocrine-Receptor-Positive Metastatic Breast Cancer
Authors: Cejuela Mónica , Gil-Torralvo Ana , Castilla M. Ángeles , Domínguez-Cejudo M. Ángeles , Falcón Alejandro , Benavent Marta , Molina-Pinelo Sonia , Ruiz-Borrego Manuel , Salvador Bofill Javier
Published: May 2023

By the end of 2020, there were more than 8 million women alive who had received a breast cancer diagnosis in the previous 5 years, making it the most prevalent neoplasia in the world. About 70% of breast-cancer cases present positivity for estrogen and/or progesterone receptors and a lack of HER-2 overexpression. Endocrine therapy has traditionally been the standard of care for ER-positive and HER-2-negative metastatic breast cancer. In the last 8 years, the advent of CDK4/6 inhibitors has shown that adding them to endocrine therapy doubles PFS. As a result, this combination has become the gold standard in this setting. Three CDK4/6 inhibitors have been approved by the EMA and the FDA: abemaciclib, palbociclib, and ribociclib. They all have the same indications, and it is at each physician’s discretion to choose one or the other. The aim of our study was to perform a comparative efficacy analysis of the three CDK4/6i using real-world data. We selected patients diagnosed with endocrine-receptor-positive and HER2-negative breast cancer who were treated with all three CDK4/6i as first-line therapy at a reference center. After 42 months of retrospective follow up, abemaciclib was associated with a significant benefit in terms of progression-free survival in endocrine-resistant patients and in the population without visceral involvement. In our real-world cohort, we found no other statistically significant differences among the three CDK4/6 inhibitors.
Protein–DNA Interactions Regulate Human Papillomavirus DNA Replication, Transcription, and Oncogenesis
Authors: Evande Roxanne , Rana Anshul , Biswas-Fiss Esther E. , Biswas Subhasis B.
Published: May 2023

Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being “high-risk” types that have been clinically linked to cervical and other types of cancer. “Low-risk” types of HPV cause less severe conditions, such as genital warts. Over the past few decades, numerous studies have shed light on how HPV induces carcinogenesis. The HPV genome is a circular double-stranded DNA molecule that is approximately 8 kilobases in size. Replication of this genome is strictly regulated and requires two virus-encoded proteins, E1 and E2. E1 is a DNA helicase that is necessary for replisome assembly and replication of the HPV genome. On the other hand, E2 is responsible for initiating DNA replication and regulating the transcription of HPV-encoded genes, most importantly the E6 and E7 oncogenes. This article explores the genetic characteristics of high-risk HPV types, the roles of HPV-encoded proteins in HPV DNA replication, the regulation of transcription of E6 and E7 oncogenes, and the development of oncogenesis.
Natural Gallic Acid and Methyl Gallate Induces Apoptosis in Hela Cells through Regulation of Intrinsic and Extrinsic Protein Expression
Authors: Abdullah Hasmah , Ismail Ilyana , Suppian Rapeah , Zakaria Nor Munirah
Published: May 2023

Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC50) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC50 values. The IC50 concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC50 value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.
The Influence of Early Onset Preeclampsia on Perinatal Red Blood Cell Characteristics of Neonates
Authors: Sandor Barbara , Csiszar Beata , Galos Gergely , Funke Simone , Kevey Dora Kinga , Meggyes Matyas , Szereday Laszlo , Toth Kalman
Published: May 2023

Preeclampsia is the leading cause of complicated neonatal adaptation. The present investigation aimed to study the hemorheological factors during the early perinatal period (cord blood, 24 and 72 h after delivery) in newborns of early-onset preeclamptic mothers (n = 13) and healthy neonates (n = 17). Hematocrit, plasma, and whole blood viscosity (WBV), red blood cell (RBC) aggregation, and deformability were investigated. There were no significant differences in hematocrit. WBV was significantly lower in preterm neonates at birth than in the term 24 and 72 h samples. Plasma viscosity was significantly lower in preterm neonates’ cord blood than in healthy controls. RBC aggregation parameters were significantly lower in preterm newborns’ cord blood than in term neonates’ cord blood 24 and 72 h samples. RBC elongation indices were significantly lower in the term group than in preterm neonates 72 h’ sample at the high and middle shear stress range. Changes in the hemorheological parameters, especially RBC aggregation properties, refer to better microcirculation of preterm neonates at birth, which could be an adaptation mechanism to the impaired uteroplacental microcirculation in preeclampsia.
Inflammasome Activity in the Skeletal Muscle and Heart of Rodent Models for Duchenne Muscular Dystrophy
Authors: Onódi Zsófia , Szabó Petra Lujza , Kucsera Dániel , Pokreisz Péter , Dostal Christopher , Hilber Karlheinz , Oudit Gavin Y. , Podesser Bruno K. , Ferdinandy Péter , Varga Zoltán V. , Kiss Attila
Published: May 2023

Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of cardiac and skeletal muscle dysfunction are still not well characterized. Our objective was to characterize the inflammasomes in myocardial and skeletal muscle in rodent models of DMD. Gastrocnemius and heart samples were collected from mdx mice and DMDmdx rats (3 and 9–10 months). Inflammasome sensors and effectors were assessed by immunoblotting. Histology was used to assess leukocyte infiltration and fibrosis. In gastrocnemius, a tendency towards elevation of gasdermin D irrespective of the age of the animal was observed. The adaptor protein was elevated in the mdx mouse skeletal muscle and heart. Increased cleavage of the cytokines was observed in the skeletal muscle of the DMDmdx rats. Sensor or cytokine expression was not changed in the tissue samples of the mdx mice. In conclusion, inflammatory responses are distinct between the skeletal muscle and heart in relevant models of DMD. Inflammation tends to decrease over time, supporting the clinical observations that the efficacy of anti-inflammatory therapies might be more prominent in the early stage.
Role of Senescent Astrocytes in Health and Disease
Authors: Meldolesi Jacopo
Published: May 2023

For many decades after their discovery, astrocytes, the abundant glial cells of the brain, were believed to work as a glue, supporting the structure and metabolic functions of neurons. A revolution that started over 30 years ago revealed many additional functions of these cells, including neurogenesis, gliosecretion, glutamate homeostasis, assembly and function of synapses, neuronal metabolism with energy production, and others. These properties have been confirmed, limited however, to proliferating astrocytes. During their aging or following severe brain stress lesions, proliferating astrocytes are converted into their no-longer-proliferating, senescent forms, similar in their morphology but profoundly modified in their functions. The changed specificity of senescent astrocytes is largely due to their altered gene expression. The ensuing effects include downregulation of many properties typical of proliferating astrocytes, and upregulation of many others, concerned with neuroinflammation, release of pro-inflammatory cytokines, dysfunction of synapses, etc., specific to their senescence program. The ensuing decrease in neuronal support and protection by astrocytes induces the development, in vulnerable brain regions, of neuronal toxicity together with cognitive decline. Similar changes, ultimately reinforced by astrocyte aging, are also induced by traumatic events and molecules involved in dynamic processes. Senescent astrocytes play critical roles in the development of many severe brain diseases. The first demonstration, obtained for Alzheimer’s disease less than 10 years ago, contributed to the elimination of the previously predominant neuro-centric amyloid hypothesis. The initial astrocyte effects, operating a considerable time before the appearance of known Alzheimer’s symptoms evolve with the severity of the disease up to their proliferation during the final outcome. Involvement of astrocytes in other neurodegenerative diseases and cancer is now intensely investigated.
GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process
Authors: Maudsley Stuart , Schrauwen Claudia , Harputluoğlu İrem , Walter Deborah , Leysen Hanne , McDonald Patricia
Published: May 2023

G protein-coupled receptors (GPCRs) play a significant role in controlling biological paradigms such as aging and aging-related disease. We have previously identified receptor signaling systems that are specifically associated with controlling molecular pathologies associated with the aging process. Here, we have identified a pseudo-orphan GPCR, G protein-coupled receptor 19 (GPR19), that is sensitive to many molecular aspects of the aging process. Through an in-depth molecular investigation process that involved proteomic, molecular biological, and advanced informatic experimentation, this study found that the functionality of GPR19 is specifically linked to sensory, protective, and remedial signaling systems associated with aging-related pathology. This study suggests that the activity of this receptor may play a role in mitigating the effects of aging-related pathology by promoting protective and remedial signaling systems. GPR19 expression variation demonstrates variability in the molecular activity in this larger process. At low expression levels in HEK293 cells, GPR19 expression regulates signaling paradigms linked with stress responses and metabolic responses to these. At higher expression levels, GPR19 expression co-regulates systems involved in sensing and repairing DNA damage, while at the highest levels of GPR19 expression, a functional link to processes of cellular senescence is seen. In this manner, GPR19 may function as a coordinator of aging-associated metabolic dysfunction, stress response, DNA integrity management, and eventual senescence.
Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as Novel Potential Anticancer Agents: Apoptosis, Oxidative Stress, and Cell Cycle Analysis
Authors: Bukowski Karol , Marciniak Beata , Kciuk Mateusz , Mujwar Somdutt , Mojzych Mariusz , Kontek Renata
Published: May 2023

The current study continues the evaluation of the anticancer potential of three de novo synthesized pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides—MM129, MM130, and MM131—against human cancer cells of HeLa, HCT 116, PC-3, and BxPC-3 lines. The pro-apoptotic activity of the investigated sulfonamides was shown by observations of changes in the mitochondrial transmembrane potential of the tested cells, externalization of phosphatidylserine on the cellular membrane surface, and cell morphology in microscopic imaging. The computational studies have shown that MM129 exhibited the lowest binding energy values when docked against CDK enzymes. In addition, the highest stability was shown for complexes formed between MM129 and CDK5/8 enzymes. All examined compounds induced cell cycle arrest in the G0/G1 phase in the BxPC-3 and PC-3 cells and simultaneously caused the accumulation of cells in the S phase in the HCT 116 cells. In addition, the increase in the subG1 fraction was observed in PC-3 and HeLa cells. The application of a fluorescent H2DCFDA probe revealed the high pro-oxidative properties of the tested triazine derivatives, especially MM131. In conclusion, the obtained results suggest that MM129, MM130, and MM131 exhibited strong pro-apoptotic properties towards investigated cells, mainly against the HeLa and HCT 116 cell lines, and high pro-oxidative potential as well. Moreover, it is suggested that the anticancer activity of the tested compounds may be associated with their ability to inhibit CDK enzymes activities.