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Abstract Gliomas represent a heterogeneous group of uniformly fatal brain tumors. Low and high-grade gliomas have diverse molecular signatures. Despite successful advances in understanding glioma, several genetic, epigenetic, and post-transcriptional alterations leave various targeted therapies ineffective, leading to a poor prognosis for high-grade glioma. Recent advances have revealed the implication of dysregulated alternative splicing (AS) events in glioma development. AS is a process that produces, from a single genomic sequence, several mature messenger RNAs. Splicing of pre-messenger RNAs concerns at least 95% of transcripts and constitutes an important mechanism in gene expression regulation. Dysregulation of this process, through variations in spliceosome components, aberrant splicing factors and RNA-binding protein activity, disproportionate regulation of non-coding RNAs, and abnormal mRNA methylation, can contribute to the disruption of AS. Such disruptions are usually associated with the development of several cancers, including glioma. Consequently, AS constitutes a key regulatory mechanism that could serve as a target for future therapies. In this review, we explore how AS events, spliceosome components, and their regulatory mechanisms play a critical role in glioma development, highlighting their potential as targets for innovative therapeutic strategies against this challenging cancer.

Introduction According to the literature, quitting tobacco before the age of 30 years would mitigate almost all tobacco-related hazards. In this respect, understanding behavioral patterns associated with the process of individual change to a healthier behavior is likely to contribute to tobacco control and avoidance of the related health risks, as well as to promote healthier behaviors, especially during adolescence. Methods This study is a secondary dataset analysis utilizing the 2016 Global Youth Tobacco Survey (GYTS) data for Morocco. Initially, a descriptive analysis is conducted to outline smoking prevalence and related behaviors among Moroccan youth, with a focus on gender differences, employing chi-squared tests for comparison. This is followed by bivariate and multivariate logistic regression analyses, which were adjusted for potential confounders to identify the determinants of intended smoking cessation. Results The survey was based on a sample of 3883 adolescents, of whom 11.07% have already tried smoking cigarettes at least once during childhood and adolescence, and 1.39% are current smokers. As for those close to the surveyed subjects, 22.2% had at least one smoking parent, and 24.1% had friends who smoked. Self-efficacy (AOR=15.54; 95% CI: 3.05–79.03) and noticing health warnings on cigarette packages (AOR=5.41; 95% CI: 2.54–11.52) were found to be important determinants of the intent to quit tobacco. Conclusions This study is a focused analysis of self-efficacy and health warnings as predictors of smoking cessation intent among Moroccan adolescents. The study elucidates the role of self-efficacy and exposure to health warnings in shaping the intent to quit smoking among Moroccan adolescents. These findings provide evidence for developing targeted interventions that support self-efficacy and impactful health warnings to promote healthier choices and reduce tobacco use among young Moroccans.

Abstract This study proposes a promising candidate for organic solar cells through the creation of a novel nano-hybrid system composed of caffeine molecules encapsulated within a semiconducting single-walled carbon nanotube known as NT14 (14,0). The stability and optoelectronic properties of this hybrid system, designated as CA@NT14, were thoroughly investigated. We determined the optimal diameter for the NT14 nanotube using molecular mechanics, Density Functional Theory, spectral moment’s method, and bond polarizability model, finding it to be approximately 1.18 nm. The encapsulation’s impact on the Raman-active modes, specifically the radial breathing mode and tangential mode, was analyzed through Raman spectra calculations, revealing structural stability and charge transfer from CA to NT14. Notably, the NT14’s Fermi level position increased upon encapsulation, indicating charge transfer and a type-II band alignment. The study further examined the bandgap characteristics of the hybrid system, finding that the encapsulation of CA within semiconducting NT14 nanotubes minimally impacts the nanotube’s bandgap, thus retaining its excellent visible light absorption properties. Conversely, encapsulating CA within metallic nanotubes significantly reduces their bandgap, limiting their light absorption range. The nonresonant Raman responses of NT14 pre- and post-encapsulation corroborated the charge transfer between CA and NT14. Future research will focus on computing the electronic transport characteristics, transmission spectra, I-V characteristics, and yield of CA@NT14 using DFT and Non-Equilibrium Green’s Function ( formalism. An experimental study will be conducted to validate these theoretical findings. These results indicate the potential of CA@NT14 hybrids as effective active layers in organic solar cells, highlighting their significance in advancing optoelectronic applications.

Sodium-glucose co-transporter inhibitors (SGLTis) are the latest class of anti-hyperglycemic agents. In addition to inhibiting the absorption of glucose by the kidney causing glycosuria, these drugs also demonstrate cardio-renal benefits in diabetic subjects. miR-30 family, one of the most abundant microRNAs in the heart, has recently been linked to a setting of cardiovascular diseases and has been proposed as novel biomarkers in kidney dysfunctions as well; their expression is consistently dysregulated in a variety of cardio-renal dysfunctions. The mechanistic involvement and the potential interplay between miR-30 and SGLT2i effects have yet to be thoroughly elucidated. Recent research has stressed the relevance of this cluster of microRNAs as modulators of several pathological processes in the heart and kidneys, raising the possibility of these small ncRNAs playing a central role in various cardiovascular complications, notably, endothelial dysfunction and pathological remodeling. Here, we review current evidence supporting the pleiotropic effects of SGLT2is in cardiovascular and renal outcomes and investigate the link and the coordinated implication of the miR-30 family in endothelial dysfunction and cardiac remodeling. We also discuss the emerging role of circulating miR-30 as non-invasive biomarkers and attractive therapeutic targets for cardiovascular diseases and kidney diseases. Clinical evidence, as well as metabolic, cellular, and molecular aspects, are comprehensively covered.

This study investigates the application of wave functions to explore various solutions of the Klein-Gordon and Schrödinger equations within the framework of Lovelock gravity. We also present the derived Smarr formula from the topological density. The Klein-Gordon solution leads to the Wheeler-de Witt Hamiltonian and quasinormal modes, and we demonstrate the connection between the potential and the black hole temperature within the Schwarzschild limit. Additionally, we discuss different solutions of the Schrödinger equation, with one solution highlighting the influence of the Airy solution on the wave function's evolution over time.

Snake venom is a cocktail and rich source of various bioactive compounds that have been extensively studied for their potential as pharmaceutical agents due to their diverse chemical structures and wide range of biological activities. In light of the emergency and the re-emergence of viral infectious diseases that threaten human health and economic systems, exploring new fertile and rich fields such as snake venom is an attractive path for anti-viral drug discovery, especially in the lack of effective vaccines. Although 85 % of reported antiviral molecules belong to the phospholipase A2 (PLA2) family, other protein families including L-amino acid oxidases (LAAO), disintegrins, metalloproteases (SVMPs), and cathelicidins have also shown antiviral activity. Thus, in this review, we have highlighted the antiviral properties of compounds derived from snake venom and their mechanisms of action against virus classes like HIV, Coronaviridae, Flaviviridae, and Paramyxoviridae. Although the initial research emphasis has been on Retroviridae (HIV) and Flaviviridae viruses, it is crucial to extend the exploration of the potential of these compounds to other viruses. The utilization of snake venom-derived compounds as antivirals shows significant promise for the development of novel therapeutics to address viral infections. However, a more in-depth investigation is necessary to fully assess the potential of these compounds against other viruses and unveil the mechanisms underlying their action.

The emergence of predatory journals is a global threat for scientific integrity, particularly in under-resourced settings such as low- and middle-income countries (LMICs). A bilingual course on predatory publishing using a distance education approach was developed for Moroccan researchers as a response to the imperative need for training on research ethics to implement good scientific practices. A cross-sectional survey-based study was conducted to evaluate outcomes after delivering two education sessions in both French and English. Before this course, 40% of participants indicated that they don't verify journal quality before manuscript submission and most of them consider Scopus indexing and the impact factor as the best criteria for journal publication. Approximately 50% of surveyees did not have previous information on predatory journals before the webinar. Pressure to publish by supervisors, institutions of affiliation, or funding agencies, was noticed in 43.4% of participants. After the webinar course was delivered, remarkably, the proportion of participants with knowledge on predatory publishing was meaningfully increased from 48.9% to 81%. Importantly, 83.7% of participants indicated that they are motivated to share their new knowledge on predatory publishing with their colleagues. Moreover, the majority of respondents (73.8%) reported that publishing their research in predatory journals may damage their career and professional future. Promisingly, nearly a half or more of participants recommended the use of training based on distance education, surveillance of researchers by their mentors and affiliations, and social networks to increase awareness on predatory publishing. Almost all participants were satisfied with the content of the webinar. Trainers and research institutions in LMICs should benefit from the advent of distance education using webinar platforms to increase awareness on the issue of predatory publishing in their settings.

Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and proinflammatory cytokine production via caspase-11 and gasdermin D (GSDMD). Here, we show that NAD+ treatment protected mice toward bacterial and lipopolysaccharide (LPS)-induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD+ administration impeded systemic IL-1β and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-β/STAT-1 signaling machinery. More importantly, NAD+ administration not only improved casp-11 KO (knockout) survival but rendered wild type (WT) mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD+ blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.

MicroRNA-10b (miR-10b) is an essential glioma driver and one of the top candidates for targeted therapies for glioblastoma and other cancers. This unique miRNA controls glioma cell cycle and viability via an array of established conventional and unconventional mechanisms. Previously reported CRISPR-Cas9-mediated miR-10b gene editing of glioma cells in vitro and established orthotopic glioblastoma in mouse models demonstrated the efficacy of this approach and its promise for therapy development. However, therapeutic gene editing in patients’ brain tumors may be hampered, among other factors, by the imperfect delivery and distribution of targeting vectors. Here, we demonstrate that miR-10b gene editing in glioma cells triggers a potent bystander effect that leads to the selective cell death of the unedited glioma cells without affecting the normal neuroglial cells. The effect is mediated by the secreted miR-10b targets phosphoglycerate kinase 1 (PGK1) and insulin-like growth factor binding protein 2 (IGFBP2) that block cell-cycle progression and induce glioma cell death. These findings further support the feasibility of therapeutic miR-10b editing without the need to target every cell of the tumor.

Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is activated. Major opsonization mediators during infections are immunoglobulins (Igs), the function of which is mediated through Fc receptors (FcRs). However, in addition to their role in adaptive immunity, FcRs have been shown to play a role in innate immunity by interacting directly with bacteria in the absence of their natural ligands (Igs). Additionally, it has been hypothesized that during the early phase of bacterial infection, FcRs play a protective role via innate immune functions mediated through direct recognition of bacteria, and as the infection progresses to later phases, FcRs exhibit their established function as receptors in adaptive immunity. This review provides detailed insight into the potential role of FcRs as innate immune mediators of the host defense against bacterial infection independent of opsonins.

Introduction: Zoonotic transition of Influenza A viruses is the cause of epidemics with high rates of morbidity and mortality. Predicting which viral strains are likely to transition from their genetic sequence could help in the prevention and response against these zoonotic strains. We hypothesized that features predictive of viral hosts could be leveraged to identify biomarkers of zoonotic viral transition.Methods: We trained deep learning models to predict viral hosts based on the virus mRNA or protein sequences. Our multi-host dataset contained 848,630 unique nucleotide sequences obtained from the NCBI Influenza Virus and Influenza Research Databases. Each sequence, representing one gene from one viral strain, was classified into one of the three host categories: Avian, Human, and Swine. Trained models were analyzed using various neural network interpretation methods to identify interesting candidates for zoonotic transition biomarkers.Results: Using mRNA sequences as input led to higher prediction accuracies than amino acids, suggesting that the codon sequence contains information relevant to viral hosts that is lost during protein translation. UMAP visualization of the latent space of our classifiers showed that viral sequences clustered according to their host of origin. Interestingly, sequences from pandemic zoonotic viral strains localized at the margins between hosts, while zoonotic sequences incapable of Human-to-Human transmission localized with non-zoonotic viruses from the same host. In addition, host prediction for pandemic zoonotic sequences had low prediction accuracy, which was not the case for the other zoonotic strains. This supports our hypothesis that ambiguously predicted viral sequences bear features associated with cross-species infectivity. Finally, we compared misclassified sequences to well-classified ones to extract interesting candidates for zoonotic transition biomarkers. While features varied significantly between pairs of species and viral genes, several codons were conserved in Swine-to-Human and Avian-to-Human misclassified sequences, and in particular in the NA, HA, and NP genes, suggesting their importance for zoonosis in Humans.Discussion: Analysis of viral sequences using neural network interpretation approaches revealed important genetic differences between zoonotic viruses with pandemic potential, compared to non-zoonotic viral strains or zoonotic viruses incapable of Human-to-Human transmission.

Abstract Background miRNAs are regulatory transcripts established as repressors of mRNA stability and translation that have been functionally implicated in carcinogenesis. miR-10b is one of the key onco-miRs associated with multiple forms of cancer. Malignant gliomas exhibit particularly striking dependence on miR-10b. However, despite the therapeutic potential of miR-10b targeting, this miRNA’s poorly investigated and largely unconventional properties hamper the clinical translation. Methods We utilized Covalent Ligation of Endogenous Argonaute-bound RNAs and their high-throughput RNA sequencing to identify miR-10b interactome and a combination of biochemical and imaging approaches for target validation. They included Crosslinking and RNA immunoprecipitation with spliceosomal proteins, a combination of miRNA FISH with protein immunofluorescence in glioma cells and patient-derived tumors, native Northern blotting, and the transcriptome-wide analysis of alternative splicing. Results We demonstrate that miR-10b binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of the direct binding between miR-10b and U6, in situ imaging of miR-10b and U6 co-localization in glioma cells and tumors, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in global splicing alterations, exemplified by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability. Conclusions We identified U6 snRNA, the key RNA component of the spliceosome, as the top miR-10b target in glioblastoma. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.

Women’s breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)/MCF-7 and triple-negative breast cancer (TNBC)/MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 μM

This study proposes a promising candidate for organic solar cells through the creation of a novel nano-hybrid system composed of caffeine molecules encapsulated within a semiconducting single-walled carbon nanotube known as NT14 (14,0). The stability and optoelectronic properties of this hybrid system, designated as CA@NT14, were thoroughly investigated. We determined the optimal diameter for the NT14 nanotube using molecular mechanics, Density Functional Theory, spectral moment's method, and bond polarizability model, finding it to be approximately 1.18 nm. The encapsulation's impact on the Raman-active modes, specifically the radial breathing mode and tangential mode, was analyzed through Raman spectra calculations, revealing structural stability and charge transfer from CA to NT14. Notably, the NT14's Fermi level position increased upon encapsulation, indicating charge transfer and a type-II band alignment. The study further examined the bandgap characteristics of the hybrid system, finding that the encapsulation of CA within semiconducting NT14 nanotubes minimally impacts the nanotube's bandgap, thus retaining its excellent visible light absorption properties. Conversely, encapsulating CA within metallic nanotubes significantly reduces their bandgap, limiting their light absorption range. The nonresonant Raman responses of NT14 pre- and post-encapsulation corroborated the charge transfer between CA and NT14. Future research will focus on computing the electronic transport characteristics, transmission spectra, I-V characteristics, and yield of CA@NT14 using DFT and Non-Equilibrium Green's Function (formalism. An experimental study will be conducted to validate these theoretical findings. These results indicate the potential of CA@NT14 hybrids as effective active layers in organic solar cells, highlighting their significance in advancing optoelectronic applications. [ABSTRACT FROM AUTHOR]

Natural compounds are endowed with a broad spectrum of biological activities, including protection against Toxins. Most of them are known for their antioxidant and radical scavenging activities. However, the synergistic combination of these natural molecules is not well studied. Therefore, the present study aims first to investigate the effect of four potent natural molecules [rosmarinic acid (Ros-A), ellagic acid (Ella-A), curcumin (Cur), and syringic acid (Syr-A)] on H2O2 -induced cell cytotoxicity and oxidative stress on the human monocytes (THP-1) and then to evaluate their combined action effect. Optimal combinations of these molecules were predicted using an augmented mixture design approach. In the first, as preliminary antioxidant activities screening, two in vitro assays were adopted to assess the single radicals scavenging activity of these natural compounds, DPPH• and ABTS• + tests. Based on the results obtained, the multitude of optimal formulas proposed by the mixture design study led to choosing four potent compositions (comp) in addition to ellagic acid, proposed as the most efficient when applied alone. The different molecules and mixtures were used to assess their cytoprotective effect on THP-1 cells in the presence and absence of H2O2. The most potent Comp-4, as well as the molecules forming this mixture, were exploited in a second experiment, aiming to understand the effect on oxidative stress via antioxidant enzyme activities analysis in the H2O2-induced oxidative stress in the THP-1 cell line. Interestingly, the natural molecules used for THP-1 cells treatment exhibited a significant increase in the antioxidant defense and glyoxalase system as well as suppression of ROS generation evaluated as MDA content. These results indicate that the natural compounds tested here, especially the synergistic effect of Cur and Ros-A (Comp-4), could serve as cytoprotective and immunostimulant agents against H2O2-induced cytotoxicity THP-1 cells, which makes them interesting for further investigations on the molecular mechanisms in preclinical animal models.

Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans’ foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells’ metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy.

We present in this paper the stability of SWCNT hybrid systems with Py molecules. vdW type interactions are therefore the main interaction mechanism between encapsulated molecules and nanotubes, and the simplest model to describe these interactions is the Lennard-Jones potential. We have therefore performed energy minimization calculations on hybrid SWCNTs in a very wide range of diameters and of all chirality using the Lennard-Jones potential. The structure of the carbon nanotube is obtained from the winding of graphene on itself to form a hollow cylinder described by the pair of integers (n, m) entirely determining its structural characteristics, while the optimization of the geometry of the Py molecule is obtained by SIESTA using the exchange–correlation functional LDA. After minimisation, an approach that combines density functional theory, molecular mechanics, bond polarizability model, and spectral moment's method has been used to compute Raman spectra. Two types of vibration modes of SWCNTs attract our attention. Initially, the modifications of the modes of Py after encapsulation will be analyzed. In the following discussion, we examine how the vibrational properties of single-walled carbon nanotubes (SWCNTs) are affected by encapsulation, specifically in relation to the RBM and tangential modes. Our analysis of the Raman active modes supports the notion that the structural integrity of the SWCNTs remains intact and indicates the occurrence of a charge transfer between the Py molecules and SWCNTs. This charge transfer depends on the geometric position of Py in the SWCNT. [ABSTRACT FROM AUTHOR]

This research discusses incorporating a single magnesium porphyrin molecule into a semiconducting single‐walled carbon nanotube (SWCNT) for solar cell applications. Using density functional theory (DFT), the study examines the optical and electronic properties of the isolated magnesium porphyrin molecule and two configurations of the hybrid system. Results show structural stability due to charge transfer between the molecule and the nanotube. Different exchange‐correlation functionals (GGA and HSE06) yield varied bandgap results, affecting light absorption. Integration of the molecule into the SWCNT reduces the bandgap. Encapsulation of the molecule influences absorption and stability under irradiation. These encapsulated systems exhibit type II heterojunction characteristics, making them promising for organic solar cells based on SWCNTs, offering potential for highly efficient solar cells. [ABSTRACT FROM AUTHOR]

Graphene is an ideal material for hot-electron bolometers due to its low heat capacity and weak electron-phonon coupling. Nanostructuring graphene with quantum-dot constrictions yields detectors of electromagnetic radiation with extraordinarily high intrinsic responsivity, higher than 1×109 V W−1 at 3 K. The sensing mechanism is bolometric in nature: the quantum confinement gap causes a strong dependence of the electrical resistance on the electron temperature. Here, we show that this quantum confinement gap does not impose a limitation on the photon energy for light detection and these quantum-dot bolometers work in a very broad spectral range, from terahertz through telecom to ultraviolet radiation, with responsivity independent of wavelength. We also measure the power dependence of the response. Although the responsivity decreases with increasing power, it stays higher than 1×108 V W−1 in a wide range of absorbed power, from 1 pW to 0.4 nW.