Search Results (152)

The Ouarzazate Group in the Anti-Atlas Belt of southern Morocco, part of the West African Craton (WAC), is a significant Proterozoic lithostratigraphic unit formed during the late Ediacaran period. It includes extensive volcanic rocks associated with the early stages of Iapetus Ocean opening. Zircon U-Pb dating and geochemical analyses of the Oued Dar’a Caldera (ODC) volcanic succession in the Saghro Massif reveal two major eruptive cycles corresponding to the lower and upper Ouarzazate Group. The 1st cycle (588–563 Ma) includes pre- and syn-caldera volcanic succession characterized by basaltic andesite to rhyolitic rocks, formed in a volcanic arc setting through lithospheric mantle-derived mafic magmatism and crustal melting. A major caldera-forming eruption occurred approximately 571–562 Ma, with associated rhyolitic dyke swarms indicating a larger caldera extent than previously known. The 2nd cycle (561–543 Ma) features post-caldera bimodal volcanism, with tholeiitic basalts and intraplate felsic magmas, signaling a shift to continental flood basalts and silicic volcanic systems. The entire volcanic activity spans approximately 23–40 million years. This succession is linked to late Ediacaran intracontinental super-eruptions tied to orogenic collapse and continental extension, likely in association with the Central Iapetus Magmatic Province (CIMP), marking a significant transition in the geodynamic evolution of the WAC. Full article

Lycopene exhibits a broad spectrum of biological activities with potential therapeutic applications. Despite its established antioxidant and anti-inflammatory properties, the molecular basis for its pharmacological actions remains incompletely defined. Here we investigated the molecular targets, pharmacodynamic feasibility, and tissue-specific expression of lycopene targets using a computational pharmacology approach combined with affinity and protein–protein interaction (PPI) analyses. Lycopene-associated human protein targets were predicted using a Swiss target screening platform. Molecular docking was used to estimate binding affinities, and concentration-affinity (CA) ratios were calculated based on physiologically relevant plasma concentrations (75–210 nM). PPI networks of lycopene targets were constructed to identify highly connected targets, and tissue expression analysis was assessed for high-affinity targets using protein-level data from the Human Protein Atlas database. Of the 94 predicted targets, 37% were nuclear receptors and 18% were Family A G Protein Coupled Receptors (GPCRs). Among the top 15 high-affinity targets, nuclear receptors and GPCRs comprised 40% and 26.7%, respectively. Twenty targets had affinities < 10 μM, with six key targets (MAP2K2, SCN2A, SLC6A5, SCN3A, TOP2A, and TRIM24) showing submicromolar binding. CA ratio analysis identified MAP2K2, SCN2A, and SLC6A5 as pharmacodynamically feasible targets (CA > 1). PPI analysis revealed 32 targets with high interaction and 9 with significant network connectivity. Seven targets (TRIM24, GRIN1, NTRK1, FGFR1, NTRK3, CHRNB4, and PIK3CD) showed both high affinity and centrality in the interaction network. The expression profiling of submicromolar targets revealed widespread tissue distribution for MAP2K2 and SCN3A, while SCN2A, TOP2A, and TRIM24 showed more restricted expression patterns. This integrative analysis identifies a subset of lycopene targets with both high affinity and pharmacological feasibility, particularly MAP2K2, SCN2A, and TRIM24. Lycopene appears to exert its biological effects through modulation of interconnected signalling networks involving nuclear receptors, GPCRs, and ion channels. These findings support the potential of lycopene as a multi-target therapeutic agent and provide a rationale for future experimental and clinical validation. Full article

The Aghbar-Bou Azzer East mining district (ABED) is located between the Bou Azzer East and Aghbar deposits. It is an area of approximately 7 km long towards ENE–WSW and 2 km wide towards N–S. In this barren area, volcano-sedimentary rocks are attributed to the Ouarzazate group outcrop (Ediacarian age): they are composed of volcanic rocks (ignimbrite, andesite, rhyolite, dacite, etc.) covered by the Adoudou detritic formation in angular unconformity. Given the absence of serpentinite outcrops, exploration investigation in this area has been very limited. This paper aims to use ionic leach geochemistry (on samples of soil) to detect the presence of Co-bearing arsenides above hidden ore deposits in this unexplored area of the Bou Azzer inlier. In addition, a detailed structural analysis allowed the identification of four families of faults and fractures with or without filling. Three directional major fault systems of several kilometers in length and variable orientation in both the Cryogenian basement and the Ediacaran cover have been identified: (i) ENE–WSW, (ii) NE–SW, and (iii) NW–SE. Several geochemical anomalies for Co, As, Ni, Ag, and Cu are aligned along three main directions, including NE–SW, NW–SE, and ENE–WSW. They are particularly well-defined in the western zone but are only minor in the central and eastern zones. Some of these anomalies correlate with the primary structural features observed in the studied area. These trends are consistent with those known under mining exploitation in nearby ore deposits, supporting the potential for similar mineralization in the ABED. Based on structural analysis and ionic leach geochemistry, drilling programs were conducted in the study area, confirming the continuity of serpentinites at depth beneath the Ediacaran cover and the presence of Co–Fe-bearing arsenide ores. This validates the ionic geochemistry technique as a reliable method for exploring buried ore deposits. Full article

Emergent cancer drug resistance and further metastasis can mainly be attributed to altered expression levels and functional activities of multiple genes of cancer cells under chemotherapy. In response to challenge with anticancer drugs, enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) confers drug resistance and enrichment with cancer stem cells. p53 mutations, which gain function in tumor progression, are prevalently extant in ovarian cancers. Via integrated gene expression assessments, we characterized GCS-responsive genes in ovarian cancer cells treated with dactinomycin. NCI/ADR-RES cells dominantly expressed a p53 mutant (7 aa deleted in exon-5) and displayed anti-apoptosis; however, silencing GCS expression rendered these cells sensitive to dactinomycin-induced apoptosis. Microarray analyses of NCI/ADR-RES and its GCS transfected sublines found that elevated GCS expression or ceramide glycosylation was associated with altered expression of 41 genes, notably coding for ABCB1, FGF2, ALDH1A3, apolipoprotein E, laminin 2, chemokine ligands, and IL6, with cellular resistance to induced apoptosis and enrichment with cancer stem cells, promoting cancer progression. These findings were further corroborated through integrated genomic analyses of ovarian cancer from The Cancer Genome Atlas (TCGA) and cancer resistance to platinum-based chemotherapy. Altogether, our present study indicates that altered ceramide glycosylation can modulate expression of these GCS-responsive genes and alter cancer cell attributes under chemotherapy. Full article

The Aït Abdellah copper deposit in the Bou Azzer-El Graara inlier of the Moroccan Anti-Atlas provides key insights into structurally and lithologically controlled mineralization in Precambrian terranes. The deposit is hosted in feldspathic sandstones of the Tiddiline Group, which unconformably overlie the Bou Azzer ophiolite, and is spatially associated with a NE–SW-trending shear zone. This zone is characterized by mylonitic fabrics, calcite veining, and an extensive network of fractures, reflecting a two-stage deformation history involving early ductile shearing followed by brittle faulting and brecciation. These structural features enhanced rock permeability, enabling fluid flow and metal precipitation. Copper mineralization includes primary sulfides such as chalcopyrite, bornite, pyrite, chalcocite, digenite, and covellite, as well as supergene minerals like malachite, azurite, and chrysocolla. Sulfur isotope values (δ³⁴S = +5.9% to +22.8%) indicate a mixed sulfur source, likely derived from both ophiolitic rocks and volcano-sedimentary sequences. Carbon and oxygen isotope data suggest fluid interaction with marine carbonates and meteoric waters, potentially linked to post-Snowball Earth deglaciation processes. Fluid inclusion studies reveal homogenization temperatures ranging from 195 °C to 310 °C and salinities between 5.7 and 23.2 wt.% NaCl equivalent, supporting a model of fluid mixing between magmatic-hydrothermal and volcano-sedimentary sources. The paragenetic evolution of the deposit comprises three stages: (1) early hydrothermal precipitation of quartz, dolomite, sericite, pyrite, and early chalcopyrite and bornite; (2) a main mineralizing stage characterized by fracturing and deposition of bornite, chalcopyrite, and Ag-bearing sulfosalts; and (3) a late supergene phase with oxidation and secondary enrichment. The Aït Abdellah deposit is best classified as a shear zone-hosted copper system with a complex, multistage mineralization history. The integrated analysis of structural features, mineral assemblages, isotopic signatures, and fluid inclusion data reveals a dynamic interplay between deformation processes, hydrothermal alteration, and evolving fluid sources. Full article

Background: Human leukocyte antigen class I (HLA-I) plays a pivotal role in shaping anti-tumour immunity by influencing the functionality of T cells and natural killer (NK) cells within the tumour microenvironment. Methods: Here, we explored the transcriptional landscape of HLA-I molecules across various solid cancer transcriptomes from The Cancer Genome Atlas (TCGA) database and assessed the impact of HLA-I expression on the clinical significance of tumour-infiltrating CD56^dim and CD56^bright NK cells. Results: Our analysis revealed that high HLA-I expression correlated with reduced patient survival in the TCGA lower-grade glioma (LGG) cohort, with this association varying by histopathological subtype. We then estimated the relative abundance of 23 immune and stromal cell signatures in LGG transcriptomes using a cellular deconvolution approach, which revealed that LGG patients with low HLA-I expression and high CD56^dim NK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56^dim NK cell abundance. Furthermore, HLA-I expression was positively correlated with various inhibitory NK cell receptors and negatively correlated with activating NK cell receptors, particularly those within the killer cell lectin-like receptor (KLR) gene family. High co-expression of HLA-E and NKG2A predicted poor survival outcomes in LGG patients, whereas low HLA-E and high NKG2C/E abundance predicted more favourable outcomes, suggesting a potential modulatory role of HLA-I on the tumour-infiltrating cytotoxic CD56^dim NK cell subset. Conclusions: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56^dim NK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC), a challenging and malignant cancer, primarily originates from the exocrine cells of the pancreas. The superfamily of solute carrier (SLC) transporters, consisting of more than 450 proteins divided into 65 families, is integral to various cellular processes and represents a promising target in precision oncology. As therapeutic targets, SLC transporters are explored through an integrative analysis. Materials and Methods: The expression profiles of SLCs were systematically analyzed using mRNA data from The Cancer Genome Atlas (TCGA) and protein data from the Human Protein Atlas (HPA). Survival analysis was examined to evaluate the prognostic significance of SLC transporters for overall survival (OS) and disease-specific survival (DSS). Genetic alterations were examined using cBioPortal, while structural studies were performed with AlphaFold and AlphaMissense to predict functional impacts. Furthermore, Gene Set Enrichment Analysis (GSEA) was carried out to identify oncogenic pathways linked to SLC transporter expression. Results: SLC transporters were significantly upregulated in tumors relative to normal tissues. Higher expression levels of SLC39A10 (HR = 1.89, p = 0.0026), SLC22B5 (HR = 1.84, p = 0.0042), SLC55A2 (HR = 2.15, p = 0.00023), and SLC30A6 (HR = 1.90, p = 0.003) were strongly associated with unfavorable OS, highlighting their connection to poor prognosis in PDAC. GSEA highlighted that these four transporters are significantly involved in key oncogenic pathways, such as epithelial–mesenchymal transition (EMT), TNF-α signaling, and angiogenesis. Conclusions: The study identifies four SLCs as therapeutic targets in PDAC, highlighting their crucial role in essential metabolic pathways. These findings lay the groundwork for developing next-generation metabolic anti-cancer treatment to improve survival for PDAC patients. Full article

UL-16 binding protein 2 (ULBP2), a human NKG2D ligand, has been identified as a poor prognostic factor in several cancers based on recent comprehensive analyses of immune-related genes using the Cancer Genome Atlas datasets. Despite its clinical significance, the functional role of ULBP2 in vivo remains largely unknown. In this study, we investigated the role of ULBP2 in modulating anti-tumor immunity using murine melanoma cell lines engineered to stably express surface-expressed or soluble ULBP2. Subcutaneous transplantation of ULBP2-expressing melanoma cells into syngeneic mice resulted in accelerated tumor growth, mediated by surface-expressed ULBP2, through the suppression of NKG2D-dependent immune responses. In vitro experiments revealed that sustained exposure to tumor-expressed ULBP2 reduced NKG2D expression and cytotoxic activity of splenocytes. In contrast, soluble ULBP2 did not significantly affect tumor growth or immune responses. These findings suggest that surface-expressed ULBP2 plays a pivotal role in tumor immune evasion and highlight its potential as a therapeutic target to enhance anti-tumor immunity. Full article

Modern multi-junction solar cell technology offers a pathway to achieving consistent and high photovoltaic conversion efficiencies through enhanced solar spectrum absorption. Indeed, during the last years, the industries of solar cells have focused on optimizing device structures, utilizing both robust and delicate materials to maximize their performances. This paper presents the modeling and optimization of the electrical and structural properties of high-efficiency InGaP/GaAs double-junction solar cells, specifically without employing an anti-reflective coating. This developed structure has been achieved by introducing a buffer layer in the lower layer and incorporating an upper back surface field layer into the investigated cell structure. Furthermore, the optimization conducted in this paper using Silvaco-Atlas software (version 2018) under the AM1.5G spectrum reveals that the proposed InGaP/GaAs tandem cell configuration exhibits significant performance, reaching conversion efficiency of 41.585%. It can be said that this adapted structure yields a short-circuit current density of 21.65 mA/cm², an open-circuit voltage of 2.319 V, and a filling factor of 84.001%. Whereas this newly optimized structure demonstrates its effectiveness in enhancing solar cell efficiency performance, presenting highly promising results with potential significance for the devices’ optical and electrical properties. Full article

T cells play diverse roles in cancer immunology, acting as tumor suppressors, cytotoxic effectors, enhancers of cytotoxic T lymphocyte responses and immune suppressors; providing memory and surveillance; modulating the tumor microenvironment (TME); or activating innate immune cells. However, cancer cells can disrupt T cell function, leading to T cell exhaustion and a weakened immune response against the tumor. The expression of exhausted T cell (Tex) markers plays a pivotal role in shaping the immune landscape of multiple cancers. Our aim was to systematically investigate the role of known T cell exhaustion (Tex) markers across multiple cancers while exploring their molecular interactions, mutation profiles, and potential implications for immunotherapy. The mRNA expression profile of six Tex markers, LAG-3, PDCD1, TIGIT, HAVCR2, CXCL13, and LAYN was investigated in pan-cancer. Utilizing data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The Cancer Proteome Atlas (TCPA), and other repositories, we characterized the differential expression of the Tex markers, their association with the patients’ survival outcome, and their mutation profile in multiple cancers. Additionally, we analyzed the effects on cancer-related pathways and immune infiltration within the TME, offering valuable insights into mechanisms of cancer immune evasion and progression. Finally, the correlation between their expression and sensitivity to multiple anti-cancer drugs was investigated extensively. Differential expression of all six markers was significantly associated with KIRC and poor prognosis in several cancers. They also played a potential activating role in apoptosis, EMT, and hormone ER pathways, as well as a potential inhibitory role in the DNA damage response and RTK oncogenic pathways. Infiltration of different immune cells was also found to be associated with the expression of the Tex-related genes in most cancer types. These findings underline that the reviving of exhausted T cells can be used to enhance the efficacy of immunotherapy in cancer patients. Full article

Post-collisional volcanism provides valuable insights into mantle dynamics, crustal processes, and mechanisms driving orogen uplift and collapse. This study presents geological, geochemical, and geochronological data for Ediacaran effusive and pyroclastic units from the Taghdout Volcanic Field (TVF) in the Siroua Window, Anti-Atlas Belt. Two eruptive cycles are identified based on volcanological and geochemical signatures. The first cycle comprises a diverse volcanic succession of basalts, basaltic andesites, andesites, dacites, and rhyolitic crystal-rich tuffs and ignimbrites, exhibiting arc calc-alkaline affinities. These mafic magmas were derived from a lithospheric mantle metasomatized by subduction-related fluids and are associated with the gravitational collapse of the Pan-African Orogen. The second cycle is marked by bimodal volcanism, featuring tholeiitic basalts sourced from the asthenospheric mantle and felsic intraplate magmas. These units display volcanological characteristics typical of facies models for continental basaltsuccessions and continental felsic volcanoes. Precise CA-ID-TIMS U-Pb zircon dating constrains the volcanic activity to 575–557 Ma, reflecting an 18-million-year period of lithospheric thinning, delamination, and asthenospheric upwelling. This progression marks the transition from orogen collapse to continental rifting, culminating in the breakup of the Rodinia supercontinent and the opening of the Iapetus Ocean. The TVF exemplifies the dynamic interplay between lithospheric and asthenospheric processes during post-collisional tectonic evolution. Full article

Advanced gastric cancer (AGC) is characterized by poor prognosis and limited responsiveness to immunotherapy. Tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapeutic outcomes. In this study, we developed a novel gene signature associated with M1-like TAMs using data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) to predict prognosis and immunotherapy response. This gene signature was determined as an independent prognostic indicator for AGC, with high-risk patients exhibiting an immunosuppressive tumor immune microenvironment (TIME) and poorer survival outcomes. Furthermore, Interferon regulatory factor 8 (IRF8) was identified as a key gene and validated through in vitro and in vivo experiments. IRF8 overexpression reshaped the suppressive TIME, leading to an increased presence of M1-like TAMs, IFN-γ⁺ CD8⁺ T cells, and Granzyme B⁺ CD8⁺ T cells. Notably, the combination of IRF8 overexpression and anti-PD-1 therapy significantly inhibited tumor growth in syngeneic mouse models. AGC patients with elevated IRF8 expression were found to be more responsive to anti-PD-1 treatment. These findings highlight potential biomarkers for prognostic evaluation and immunotherapy in AGC, offering insights that could guide personalized treatment strategies. Full article

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is frequently upregulated in various cancers, including triple-negative breast cancer (TNBC), and is associated with poor clinical outcomes. Analysis of The Cancer Genome Atlas (TCGA) data confirmed that PTK7 mRNA expression is significantly higher in TNBC tumor tissues compared with adjacent normal tissues and non-TNBC breast cancer subtypes. Kaplan–Meier survival analysis demonstrated a strong correlation between high PTK7 expression and worse relapse-free survival in TNBC patients (HR = 1.46, p = 0.015). In vitro, anti-PTK7 monoclonal antibodies (mAbs) significantly reduced proliferation, wound healing, migration, and invasion in TNBC MDA-MB-231 cells. Ki-67 immunofluorescence assays revealed substantial decreases in cell proliferation following treatment with PTK7 mAbs (32-m, 43-m, 50-m, and 52-m). Moreover, actin polymerization, a critical process in cell migration and invasion, was markedly impaired upon PTK7 mAb treatment. In vivo, PTK7 mAbs significantly reduced tumor volume and weight in a TNBC xenograft mouse model compared with controls. Treated tumors exhibited decreased expression of Ki-67 and vimentin, indicating reduced proliferation and epithelial-to-mesenchymal transition. These findings highlight PTK7 as a promising therapeutic target in TNBC and demonstrate the potent anti-cancer effects of PTK7-neutralizing mAbs both in vitro and in vivo. Further exploration of PTK7-targeted therapies, including humanized mAbs and antibody-drug conjugates, is warranted to advance treatment strategies for PTK7-positive TNBC. Full article

Teucrium polium L. is a plant with various claims of ethnobotanical use, primarily for inflammatory diseases. Chemical studies have already isolated different types of terpenes from the species, and studies have established its pharmacological potential. The present study evaluates the components of T. polium essential oil cultivated in the Algerian Saharan Atlas. GC-MS identified the major components as fenchone (31.25%), 3-carene (15.77%), cis-limonene oxide (9.77%), and myrcene (9.15%). In the in silico prediction, molecules with more than 1% abundance were selected. Regarding Lipinski’s rule, all molecules followed the rule. All molecules were found to be toxic in at least one model, with some molecules being non-genotoxic (6, 8, 10, 11, 12, 13) and others being non-mutagenic (5, 7, 9, 14). Three molecules were selected that showed the best results in pharmacokinetic and toxicity studies: the molecules that did not present carcinogenic potential (7—myrtenal; 9—myrtenol; 14—verbenol). The molecular target was established, and it seems that all three bound to the nuclear factor NF-kappa-B. Based on the docking and molecular dynamics results, these molecules have potential as anti-inflammatory and antitumor therapies, with further in vitro and in vivo studies needed to evaluate their activity and toxicity. Full article

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck squamous cell carcinoma (HNSCC). HNSCC is recognized as the eighth most commonly occurring cancer globally in men. It is essential to distinguish between cancers arising in the head and neck regions due to significant differences in their etiologies, treatment approaches, and prognoses. As the Cancer Genome Atlas (TCGA) dataset is available in HNSCC, the survival analysis prognosis of OSCC patients based on the TCGA dataset for discovering gene expression-based prognostic biomarkers is limited. To address this paucity, we aimed to provide comprehensive evidence by recruiting studies that have reported new biomarkers/signatures to establish a prognostic model to predict the survival of OSCC patients. Using PubMed search, we have identified 34 studies that have been using the least absolute shrinkage and selection operator (LASSO)-based Cox regression analyses to establish signature prognosis that related to different pathways in OSCC from the past 4 years. Our review was focused on summarizing these signatures and implications for targeted therapy using FDA-approved drugs. Furthermore, we conducted an analysis of the LASSO Cox regression gene signatures. Our findings revealed 13 studies that correlated a greater number of regulatory T cells (Tregs) cells in protective gene signatures with increased recurrence-free and overall survival rates. Conversely, two studies displayed an opposing trend in cases of OSCC. We will also explore how the dysregulation of these signatures impacts immune status, promoting tumor immune evasion or, conversely, enhancing immune surveillance. Overall, this review will provide new insight for future anti-cancer therapies based on the potential gene that is associated with poor prognosis in OSCC. Full article