Search Results (5)

Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3. Using two independent medulloblastoma RNA-sequencing cohorts (MB-PBTA and MTAB-10767), we investigated the expression of ferroptosis-related molecules through multiple approaches, including Weighted Gene Co-Expression Network Analysis (WGCNA), molecular subtype stratification, protein–protein interaction (PPI) networks, and univariable and multivariable overall survival analyses. A prognostic expression score was computed based on a cross-validated ferroptosis signature. In training and validation cohorts, the regulation of the ferroptosis transcriptional program distinguished the four molecular subtypes of medulloblastoma. WGCNA identified nine gene modules in the MB tumor transcriptome; five correlated with molecular subtypes, implicating pathways related to oxidative stress, hypoxia, and trans-synaptic signaling. One module, associated with disease recurrence, included epigenetic regulators and nucleosome organizers. Univariable survival analyses identified a 45-gene ferroptosis prognostic signature associated with nutrient sensing, cysteine and methionine metabolism, and trans-sulfuration within a one-carbon metabolism. The top ten unfavorable ferroptosis genes included CCT3, SNX5, SQOR, G3BP1, CARS1, SLC39A14, FAM98A, FXR1, TFAP2C, and ATF4. Patients with a high ferroptosis score showed a worse prognosis, particularly in the G3 and SHH subtypes. The PPI network highlighted IL6 and CBS as unfavorable hub genes. In a multivariable overall survival model, which included gender, age, and the molecular subtype classification, the ferroptosis expression score was validated as an independent adverse prognostic marker (hazard ratio: 5.8; p-value = 1.04 × 10⁻⁹). This study demonstrates that the regulation of the ferroptosis transcriptional program is linked to medulloblastoma molecular subtypes and patient prognosis. A cross-validated ferroptosis signature was identified in two independent RNA-sequencing cohorts, and the ferroptosis score was confirmed as an independent and adverse prognostic factor in medulloblastoma. Full article

(1) Background: Hepatoblastoma and medulloblastoma are two types of pediatric tumors with embryonic origins. Both tumor types can exhibit genetic alterations that affect the β-catenin and Wnt pathways; (2) Materials and Methods: This study used bioinformatics and integrative analysis of multi-omics data at both the tumor and single-cell levels to investigate two distinct pediatric tumors: medulloblastoma and hepatoblastoma; (3) Results: The cross-transcriptome analysis revealed a commonly regulated expression signature between hepatoblastoma and medulloblastoma tumors. Among the commonly upregulated genes, the transcription factor LEF1 was significantly expressed in both tumor types. In medulloblastoma, LEF1 upregulation is associated with the WNT-subtype. The analysis of LEF1 genome binding occupancy in H1 embryonic stem cells identified 141 LEF1 proximal targets activated in WNT medulloblastoma, 13 of which are involved in Wnt pathway regulation: RNF43, LEF1, NKD1, AXIN2, DKK4, DKK1, LGR6, FGFR2, NXN, TCF7L1, STK3, YAP1, and NFATC4. The ROC curve analysis of the combined expression of these 13 WNT-related LEF1 targets yielded an area under the curve (AUC) of 1.00, indicating 100% specificity and sensitivity for predicting the WNT subtype in the PBTA medulloblastoma cohort. An expression score based on these 13 WNT-LEF1 targets accurately predicted the WNT subtype in two independent medulloblastoma transcriptome cohorts. At the single-cell level, the WNT-LEF1 expression score was exclusively positive in WNT-medulloblastoma tumor cells. This WNT-LEF1-dependent signature was also confirmed as activated in the hepatoblastoma tumor transcriptome. At the single-cell level, the WNT-LEF1 expression score was higher in tumor cells from both human hepatoblastoma samples and a hepatoblastoma patient-derived xenotransplant model; (4) Discussion: This study uncovered a shared transcriptional activation of a LEF1-dependent embryonic program, which orchestrates the regulation of the Wnt signaling pathway in tumor cells from both hepatoblastoma and medulloblastoma. Full article

The packaging nets used for bell peppers act as a form of protection. However, the manufacturing is based on polymers that cause serious environmental problems. The effects of nets made of biodegradable materials, such as poly(lactic) acid (PLA), poly(butylene adipate-co-terephthalate) (PBAT), and cactus stem residues, were evaluated on four different colors of ‘California Wonder’ bell peppers stored over a 25-day storage period under controlled and ambient temperature conditions. Compared to commercial polyethylene nets, the bell peppers kept in the biodegradable nets did not show notable differences with respect to color, weight loss, total soluble solids, and titratable acidity. However, there were significant differences (p < 0.05) in terms of phenol content, carotenoids (orange bell peppers), anthocyanins, and vitamin C, with an overall tendency to show a higher content in those kept in PLA 60%/PBTA 40%/cactus stem flour 3% compared to commercial packaging. In addition, the same net notably reduced the development of bacteria, fungi, and yeasts during the storage of red, orange, and yellow bell peppers. As postharvest packaging for bell peppers, this net could be considered a viable option for the storage of this product. Full article

Building on the debate about global convergence or divergence of practices, this study aims to query the viability of a new strategic action tool specifically geared to the interests of public bus transportation authorities (PBTA) around the globe and explore the degree of homogeneity in their responses as well as the possible drivers of them. To answer its research question, the study first offers a generic business model design for a PBTA, which integrates an extended version of the business model canvas with external environmental factors in order to enhance its sustainability. Subsequently, the importance attributions of international transportation experts to different model components are evaluated by using the Spherical Fuzzy AHP method. The model is developed in three hierarchical layers and evaluated by experts from four continents: America, Asia, Australia, and Europe. The results indicate that the expert opinions tend to converge more on the internal components of the model and diverge on the external components, especially regarding economic and technological factors. A strategic response action set is also designed to facilitate the adoption of the model by PBTA. The study not only extends the research on the strategic management of the public bus transportation domain but also contributes to the convergence and divergence debate by offering a reconciliatory duality perspective. Full article

A series of mixed-metal oxide structures based on the stacking of α-U₃O₈ type pentagonal bipyramid layers have been investigated for symmetry lowering distortions and photocatalytic activity. The family of structures contains the general composition A^m+_((n+1)/m)B_(3n+1)O_(8n+3) (e.g., A = Ag, Bi, Ca, Cu, Ce, Dy, Eu, Gd K, La, Nd, Pb, Pr, Sr, Y; B = Nb, Ta; m = 1–3; n = 1, 1.5, 2), and the edge-shared BO₇ pentagonal pyramid single, double, and/or triple layers are differentiated by the average thickness, (i.e., 1 ≤ n ≤ 2), of the BO₇ layers and the local coordination environment of the “A” site cations. Temperature dependent polymorphism has been investigated for structures containing single layered (n = 1) monovalent (m = 1) “A” site cations (e.g., Ag₂Nb₄O₁₁, Na₂Nb₄O₁₁, and Cu₂Ta₄O₁₁). Furthermore, symmetry lowering distortions were observed for the Pb ion-exchange synthesis of Ag₂Ta₄O₁₁ to yield PbTa₄O₁₁. Several members within the subset of the family have been constructed with optical and electronic properties that are suitable for the conversion of solar energy to chemical fuels via water splitting. Full article