Basal-like breast cancer (BLBC) is associated with poor prognosis, high recurrence rates, and limited therapeutic options, largely due to its molecular heterogeneity and complexity, which include epigenetic alterations. This study investigated epigenetic regulatory networks in BLBC by analyzing DNA methylation in distal cis-regulatory regions and its impact on genes, transcription factors (TFs), and microRNAs (miRNAs) expression. Data from TCGA were processed using the ELMER and DESeq2 tools to identify differentially methylated regions and differentially expressed genes, TFs, and miRNAs. The FANMOD algorithm was used to identify the regulatory interactions uncovering the feed-forward loops (FFLs). The analysis identified 110 TF-mediated FFLs, 43 miRNA-mediated FFLs, and five composite FFLs, involving 18 hypermethylated and 32 hypomethylated genes, eight upregulated and nine downregulated TFs, and 21 upregulated and seven downregulated miRNAs. The TF-mediated FFLs major regulators involved the AR, EBF1, FOS, FOXM1, and TEAD4 TFs, while key miRNAs were miR-3662, miR-429, and miR-4434. Enriched pathways involved cAMP, ErbB, FoxO, p53, TGF-beta, Rap1, and Ras signaling. Differences in hallmark gene set categories reflected distinct methylation and miRNA expression profiles. Overall, this integrative analysis mapped the intricate epigenetic landscape of BLBC, emphasizing the role of FFLs as regulatory motifs that integrate DNA methylation, TFs, and miRNAs in orchestrating disease’s development and progression and offering potential targets for future diagnostic and therapeutic strategies.

Background/Objectives: Adrenocortical carcinoma (ACC) is a rare malignancy in which overexpression of steroidogenic factor-1 (SF-1/NR5A1) and aberrant activation of canonical Wnt/β-catenin signaling are important oncogenic events. However, the extent to which these regulatory axes converge or interact at the transcriptional level remains unclear. We investigated their relationship using bulk transcriptomic and regulatory-network approaches. Methods: Regulatory network inference using RTN/ARACNe was applied to the TCGA-ACC cohort. NR5A1 and β-catenin-associated TCF/LEF regulon activities were evaluated in perturbation datasets and tested for associations with CpG island methylator phenotype (CIMP), overall survival, and gene-level interaction effects. Candidate modulators of NR5A1 activity were assessed using the MINDy algorithm. The effects of cBAF inhibition on NR5A1 regulon activity were also evaluated in H295R and CU-ACC1 cells. Results: NR5A1 knockdown repressed steroidogenic pathways, whereas β-catenin knockdown predominantly suppressed Wnt/β-catenin signaling. In TCGA-ACC, NR5A1 regulon activity was associated with CIMP-high status and overall survival. In contrast, β-catenin-related regulons were not significantly associated with CIMP-high status after adjustment for NR5A1 activity, and no significant multiplicative interaction effects were identified. Fewer than 3% of protein-coding genes showed improved fit in models including NR5A1 × TCF/LEF interaction terms, without enrichment for steroidogenic or Wnt/β-catenin-related pathways. CTNNB1 was identified as a statistically significant but low-ranking positive modulator of NR5A1 activity, whereas CTNNBIP1 was a top-decile negative modulator. cBAF inhibition was associated with NR5A1 regulon repression in both cell models. Conclusions: These findings indicate limited detectable global transcriptional convergence between NR5A1 and canonical β-catenin-related regulons in the evaluated bulk transcriptomic frameworks. Potential relationships between these pathways may depend on more localized, chromatin-dependent, protein-level, or context-specific regulatory mechanisms. NR5A1 regulon activity showed more consistent associations with CIMP-high status and clinical outcome than the β-catenin/TCF-LEF regulons in the evaluated TCGA-ACC models. The modulation patterns associated with CTNNB1 and CTNNBIP1, together with the repression of NR5A1 regulon activity following cBAF inhibition, raise the possibility that NR5A1 acts as a context-dependent regulatory node connecting oncogenic signaling and chromatin-remodeling mechanisms in ACC. These findings support further investigation into the role of chromatin-remodeling complexes in sustaining NR5A1-driven transcriptional programs in ACC.

Neuroblastoma is the most common extracranial solid tumor in children, presenting remarkable clinical heterogeneity with survival outcomes ranging from spontaneous regression to aggressive progression. MYCN oncogene amplification and age at diagnosis are established prog-nostic factors that are typically treated as independent covariates in risk stratification, yet their joint influence on the tumor immune microenvironment remains poorly understood. Here we show that stratifying patients by both variables simultaneously reveals six reproducible immune subtypes with distinct transcriptional programs and prognostic significance. Consensus clustering of immunomodulatory gene expression profiles from 149 patients in the TARGET-NBL cohort identified subtypes whose survival trajectories differ significantly within clinical strata defined by MYCN status and age at diagnosis. A linear Support Vector Machine classifier trained on these subtypes, using immunomodulatory gene expression combined with MYCN amplification status and age at diagnosis as predictive features, achieved 97.2% accuracy and a Cohen’s Kappa of 0.963 under 10-fold cross-validation, and generalized to an independent cohort of 493 patients (GSE62564). Kaplan-Meier analysis revealed significant survival differences across subtypes in both cohorts (TARGET-NBL: log-rank p = 0.0018; GSE62564: log-rank p < 0.0001). Single-sample gene set enrichment analysis identified differential activation of proliferative and immune response pathways across subtypes, consistent between both cohorts. These findings suggest that integrating MYCN amplification status and age at diagnosis as joint determinants of immune organization may reveal prognostic heterogeneity that is not fully captured when these factors are considered independently.

Piper regnellii (Miq.) C. DC. var. regnellii, popularly known as "pariparoba", is used for therapeutic purposes. However, the morphological similarity among Piper species can lead to misidentifications, so molecular markers have been used to validate the identification of species and their morphotypes. Among the molecular markers used in plants, the intergenic spacer region trnL-trnF has proven effective in identifying plant species. For this reason, this region was used to evaluate two morphotypes of Piper regnellii var. regnellii. Studies with the trnL-trnF region have shown this region as a good marker for establishing phylogenetic relationships, distinguishing species, and identifying new species. We concluded that the trnL-trnF sequenced region show one indel of difference between the two morphotypes. It would be interesting to analyze these two morphotypes with a more variable region than the one used here, aiming to show intraspecific differences.

Este trabalho teve como objetivo quantificar os metais Cobre e Chumbo presentes na água e no sedimento do lago Aratimbó, localizado na cidade de Umuarama-PR e analisar os indicadores abióticos de temperatura e pH da água. As coletas foram feitas em triplicatas, em três pontos distintos, em dois diferentes dias, sendo o primeiro em tempo seco, anterior a chuva e outro logo após a primeira chuva. As amostras tiveram sua temperatura e pH verificado in locu e a determinação dos metais ocorreu através de Espectrofotometria de Absorção Atômica por chama. Os resultados de pH obtiveram valores satisfatórios em todos os pontos. Em relação à concentração de metais, na água, houve maior concentração de chumbo antes da chuva e uma concentração abaixo do limite apenas para o cobre no ponto 1. No sedimento, a concentração de ambos metais foi maior antes da chuva, exceto no ponto três, onde a concentração foi maior após a chuva. É possível que os maiores valores de concentração para os metais tenham sido superiores no período de seca em virtude do volume aumentado de água após a chuva, com maior diluição dos mesmos, assim como atribuir a contaminação às atividades antropogênicas uma vez que o lago se localiza em região urbana central.Palavras-chave: Contaminação; Metais; Lago Aratimbó.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignant neoplasm with limited therapeutic options and an often poor prognosis. A deeper understanding of its interaction with the immune system is essential for the advancement of personalized treatment strategies, particularly in light of the tumor heterogeneity of hormone production. ACC tumors can be classified into high steroid phenotype (HSP) and low steroid phenotype (LSP) subtypes, which exhibit distinct biological behaviors and immunological microenvironments. However, the composition and prognostic significance of T‐cell and B‐cell receptor (TCR and BCR) repertoires in these subtypes remain largely unknown. In this study, we demonstrate that steroid phenotype is a key determinant of the adaptive immune response and clinical outcomes in ACC. LSP tumors exhibit significantly higher lymphocytic infiltration and greater repertoire diversity, reflecting a more immunogenic tumor microenvironment, despite the significant expression of immune evasion and exhaustion genes. These findings provide new insights into how the hormonal environment shapes the immunobiology of ACC, reveal possible mechanisms of immune escape in cortisol‐producing tumors, and highlight the prognostic relevance of immune repertoire characteristics. Our results support the integration of TCR/BCR profiling with steroid phenotyping to improve risk stratification and inform the design of precision immunotherapeutic strategies for ACC.