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Circular RNAs (circRNAs) belong to a unique class of endogenously expressed non-protein-coding RNAs with a distinct circularized structure, characterized by the absence of 5′-cap and 3′-polyadenylate ends. They are generally formed through back-splicing from pre-mRNAs. They serve as regulators of transcription and splicing, and act as sponges for microRNAs (miRNAs) and RNA-binding proteins, thereby modulating the expression of target genes. As a result, they exert a substantial impact on a diverse array of cellular and biological processes, including cell proliferation, migration, inflammation, and oxidative stress. Asthma and COPD are chronic airway conditions that currently have no cure. In recent years, emerging evidence suggests that altered expression of circRNAs in airway, bronchial and immune cells is involved in asthma and COPD pathogenesis. Studies exploring circRNA dysregulation in asthma have showcased their involvement in regulating the proliferation, migration, and inflammation of airway smooth muscle and bronchial epithelial cells, as well as impacting goblet cell metaplasia, Th2 cell differentiation, and macrophage activation, primarily through interactions with miRNAs. Similarly, in COPD, circRNAs have shown altered expression patterns in the blood and lungs of patients, and these changes have been linked to modulating inflammation, oxidative stress, and airway remodeling in preclinical models. Furthermore, certain circRNAs have demonstrated promising potential as diagnostic and prognostic biomarkers for both asthma and COPD. This review delves into the current understanding of the function and molecular mechanisms of circRNAs in asthma and COPD, along with exploring their potential as biomarkers in these respiratory conditions.

Long non-coding RNAs (lncRNAs) are endogenously expressed RNAs longer than 200 nt that are not translated into proteins. In general, lncRNAs bind to mRNA, miRNA, DNA, and proteins and regulate gene expression at various cellular and molecular levels, including epigenetics, transcription, post-transcription, translation, and post-translation. LncRNAs play important roles in many biological processes, such as cell proliferation, apoptosis, cell metabolism, angiogenesis, migration, endothelial dysfunction, endothelial-mesenchymal transition, regulation of cell cycle, and cellular differentiation, and have become an important topic of study in genetic research in health and disease due to their close link with the development of various diseases. The exceptional stability, conservation, and abundance of lncRNAs in body fluids, have made them potential biomarkers for a wide range of diseases. LncRNA MALAT1 is one of the best-studied lncRNAs in the pathogenesis of various diseases, including cancers and cardiovascular diseases. A growing body of evidence suggests that aberrant expression of MALAT1 plays a key role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary diseases (COPD), Coronavirus Disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), lung cancers, and pulmonary hypertension through different mechanisms. Here we discuss the roles and molecular mechanisms of MALAT1 in the pathogenesis of these lung diseases.

Small nucleolar RNAs (snoRNAs) are non-coding RNA molecules that range from 60 to 300 nucleotides in length and are primarily located in the nucleoli of cells. They play a critical role in modifying ribosomal RNA and can also regulate alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression can affect numerous cellular processes, including cell proliferation, apoptosis, angiogenesis, fibrosis, and inflammation, making them a promising target for diagnostics and treatment of various human pathologies. Recent evidence suggests that abnormal snoRNA expression is strongly associated with the development and progression of several lung diseases, such as lung cancer, asthma, chronic obstructive pulmonary disease, and pulmonary hypertension, as well as COVID-19. While few studies have shown a causal relationship between snoRNA expression and disease onset, this research field presents exciting opportunities for identifying new biomarkers and therapeutic targets in lung disease. This review discusses the emerging role and molecular mechanisms of snoRNAs in the pathogenesis of lung diseases, focusing on research opportunities, clinical studies, biomarkers, and therapeutic potential.

This article introduces Islamic apocalyptic jurisprudence (theories of final law that will govern humanity in the End Times) to academic study. Section 1 considers why the topic has remained unexamined and suggests a basic taxonomy. Section 2 exposes the apocalyptic jurisprudence of two case studies, representing the "reversionist" and "progressivist" poles of Sunni discourses: the Islamic State of Iraq and Syria ("ISIS"), and Dāwūd and his "Awaited Mahdī" movement in Egypt. Section 3 considers two further case studies, representing the "revanchist" and "idealist" orientations in Shi'i discourses: the Islamic Republic of Iran, and al-Ṣadr, a theorist of the Iraqi Ṣadrist movement. Throughout, the following aspects of the final legal system are considered: sources of law; conflicts between Islamic, Jewish, Christian, and international laws; the jurist's role; changes to classical Islamic legal theory, including qiyas and ijtihad; the legitimacy of legal schools; and new positive laws, policies, and rules of evidence. [ABSTRACT FROM AUTHOR]

Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs modify BMPR2 signaling, we used a siRNA-mediated high-throughput screening of 22,124 murine genes in mouse myoblastoma reporter cells using ID1 expression as readout for BMPR2 signaling. We further experimentally validated the top hit, PTPN1 (PTP1B), in healthy human pulmonary arterial endothelial cells (PAECs) either silenced by siRNA or exposed to hypoxia and confirmed its relevance to PAH by measuring PTPN1 levels in blood and PAECs collected from PAH patients. We identified PTPN1 as a novel regulator of BMPR2 signaling in PAECs, which is downregulated in the blood of PAH patients, and documented that downregulation of PTPN1 is linked to endothelial dysfunction in PAECs. These findings point to a potential involvement for PTPN1 in PAH and will aid in our understanding of the molecular mechanisms involved in the disease.

This article introduces a hybrid BE-FE method for solving the EEG forward problem, leveraging the strengths of both the Boundary Element Method (BEM) and Finite Element Method (FEM). FEM accurately models complex and anisotropic tissue properties for realistic head geometries, while BEM excels in handling isotropic tissue regions and dipolar sources efficiently. The proposed hybrid method divides regions into homogeneous boundary element (BE) regions that include sources and heterogeneous anisotropic finite element (FE) regions. So, BEM models the brain, including dipole sources, and FEM models other head layers. Validation includes inhomogeneous isotropic/anisotropic three- and four-layer spherical head models, and a four-layer MRI-based realistic head model. Results for six dipole eccentricities and two orientations are computed using BEM, FEM, and hybrid BE-FE method. Statistical analysis, comparing error criteria of RDM and MAG, reveals notable improvements using the hybrid FE-BE method. In the spherical head model, the hybrid BEFE method compared with FEM demonstrates enhancements of at least 1.05 and 38.31% in RDM and MAG criteria, respectively. Notably, in the anisotropic four-layer head model, improvements reach a maximum of 88.3% for RDM and 93.27% for MAG over FEM. Moreover, in the anisotropic four-layer realistic head model, the proposed hybrid method exhibits 55.4% improvement in RDM and 89.3% improvement in MAG compared to FEM. These findings underscore the proposed method is a promising approach for solving the realistic EEG forward problems, advancing neuroimaging techniques and enhancing understanding of brain function. [ABSTRACT FROM AUTHOR]

Lung diseases, such as asthma, chronic obstructive pulmonary diseases (COPD), and cystic fibrosis (CF), are among the leading causes of mortality and morbidity globally. They contribute to substantial economic burdens on society and individuals. Currently, only a few treatments are available to slow the development and progression of these diseases. Thus, there is an urgent unmet need to develop effective therapies to improve quality of life and limit healthcare costs. An increasing body of clinical and experimental evidence suggests that altered zinc and its regulatory protein levels in the systemic circulation and in the lungs are associated with these disease’s development and progression. Zinc plays a crucial role in human enzyme activity, making it an essential trace element. As a cofactor in metalloenzymes and metalloproteins, zinc involves a wide range of biological processes, such as gene transcription, translation, phagocytosis, and immunoglobulin and cytokine production in both health and disease. Zinc has gained considerable interest in these lung diseases because of its anti-inflammatory, antioxidant, immune, and metabolic modulatory properties. Here we highlight the role and mechanisms of zinc in the pathogenesis of asthma, COPD, CF, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, and pulmonary hypertension.

The importance of the research lies in physical fitness as an important component in soccer and the problem of the research lies in differences in training programs from one place to another and not benefiting from great countries experiences. The research aimed at making a comparative study on the effect of a training program used for a certain period of time as well as identifying differences between pre and post-tests. The researchers hypothesized significant statistical differences in test results in favor of posttests. The researcher used the experimental method for 45 days on Russian players aged (14- 15) years old. The researcher concluded significant statistical differences in posttests.

The video assistant referee technology (VAR) is one of the most important modern electronic technologies used in the management of football matches at the international level, which has been adopted internationally in the most important world championships. The aim of the research is to identify cases of using video assistive judgment technology in the Spanish League and for the teams that won the first three places for the season (2019-2020). The researcher used the descriptive approach. The research sample was the Spanish League matches for the season (2019-2020) (Real Madrid, Barcelona, and Atletico Madrid). The researchers concluded that the assistive video referee technology has a great impact in determining the results of matches in a fair manner and without relying on the assessment of the personal situation by the referee, and that all teams benefit from the assistive video referee technology and that no differentiation occurs between teams because of its use. And the introduction of video assistant refereeing technology in the Iraqi league will have a positive impact on the accuracy of arbitration decisions

ABSTRACT Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa. This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. IMPORTANCE Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.

Maternal iron deficiency occurs in 40–50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma. A low iron diet during pregnancy further increases these major disease features in offspring with experimental asthma. Importantly, a low iron diet increases neutrophilic inflammation, which is indicative of more severe disease, in asthma. Together, our data demonstrate that lower dietary iron and systemic deficiency during pregnancy can lead to physiological, immunological and anatomical changes in the lungs and airways of offspring that predispose to greater susceptibility to respiratory disease. These findings suggest that correcting iron deficiency in pregnancy using iron supplements may play an important role in preventing or reducing the severity of respiratory disease in offspring. They also highlight the utility of experimental models for understanding how iron status in pregnancy affects disease outcomes in offspring and provide a means for testing the efficacy of different iron supplements for preventing disease.

Arteriovenous malformations are a vascular anomaly typically present at birth, characterized by an abnormal connection between an artery and a vein (bypassing the capillaries). These high flow lesions can vary in size and location. Therapeutic approaches are limited, and AVMs can cause significant morbidity and mortality. Here, we describe our current understanding of the pathogenesis of arteriovenous malformations based on preclinical and clinical findings. We discuss past and present accomplishments and challenges in the field and identify research gaps that need to be filled for the successful development of therapeutic strategies in the future.

Pulmonary arterial hypertension (PAH) is a debilitating condition of the pulmonary circulatory system that occurs in patients of all ages and if untreated, eventually leads to right heart failure and death. Despite existing medical treatment options that improve survival and quality of life, the disease remains incurable. Thus, there is an urgent need to develop novel therapies to treat this disease. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in pulmonary vascular remodeling and PAH. LncRNAs are implicated in pulmonary arterial endothelial dysfunction by modulating endothelial cell proliferation, angiogenesis, endothelial mesenchymal transition, and metabolism. LncRNAs are also involved in inducing different pulmonary arterial vascular smooth muscle cell phenotypes, such as cell proliferation, apoptosis, migration, regulation of the phenotypic switching, and cell cycle. LncRNAs are essential regulators of gene expression that affect various diseases at the chromatin, transcriptional, post-translational, and even post-translational levels. Here, we focus on the role of LncRNAs and their molecular mechanisms in the pathogenesis of PAH. We also discuss the current research challenge and potential biomarker and therapeutic potentials of lncRNAs in PAH.

Pulmonary Arterial Hypertension (PAH) is a disease of the pulmonary arteries, that is characterized by progressive narrowing of the pulmonary arterial lumen and increased pulmonary vascular resistance, ultimately leading to right ventricular dysfunction, heart failure and premature death. Current treatments mainly target pulmonary vasodilation and leave the progressive vascular remodeling unchecked resulting in persistent high morbidity and mortality in PAH even with treatment. Therefore, novel therapeutic strategies are urgently needed. Loss of function mutations of the Bone Morphogenetic Protein Receptor 2 (BMPR2) are the most common genetic factor in hereditary forms of PAH, suggesting that the BMPR2 pathway is fundamentally important in the pathogenesis. Dysfunctional BMPR2 signaling recapitulates the cellular abnormalities in PAH as well as the pathobiology in experimental pulmonary hypertension (PH). Approaches to restore BMPR2 signaling by increasing the expression of BMPR2 or its downstream signaling targets are currently actively explored as novel ways to prevent and improve experimental PH as well as PAH in patients. Here, we summarize existing as well as novel potential treatment strategies for PAH that activate the BMPR2 receptor pharmaceutically or genetically, increase the receptor availability at the cell surface, or reconstitute downstream BMPR2 signaling.