Life

Objective: We aimed to characterize the somatic mutational landscape of oropharyngeal squamous cell carcinoma (OPSCC) and identify potential genomic drivers of tumor progression and therapeutic resistance using the AACR GENIE database. Study Design: Retrospective genomic analysis was employed. Setting: We used publicly available data from the American Association for Cancer Research (AACR) Project GENIE database accessed via cBioPortal. Methods: We analyzed 412 tumor samples from 401 patients diagnosed with OPSCC. Somatic mutations, clinical variables and tumor characteristics were extracted and analyzed. Statistical comparisons of mutation frequencies across gender and tumor stage (primary vs. metastatic) were conducted. Co-occurrence and mutual exclusivity analyses were performed to identify significant genomic patterns. Results: The most frequently mutated genes included TP53 (30.1%), PIK3CA (26.0%), and KMT2D (21.6%). Gender-specific analyses suggested potential enrichment of TP53 and MET mutations in females and of ZNF750 in males. Distinct mutation patterns were observed between primary and metastatic tumors; primary tumors were enriched for mutations in TP53 and CDKN2A, while metastatic lesions harbored unique alterations in genes like CBLB and BUB1B, suggesting pathways involved in immune evasion and chromosomal instability may drive disease progression. Co-occurrence was noted between PIK3CA and FBXW7, and mutual exclusivity between TP53 and CYLD. Conclusions: This study identifies distinct genomic signatures in OPSCC subgroups, highlighting candidate biomarkers in pathways like PI3K/AKT signaling that warrant further investigation. Validating these markers in prospective trials is a critical next step to translate these findings into personalized therapeutic strategies for OPSCC patients.

Endothelial integrity is essential for cardiovascular health, and circulating endothelial progenitor cells, particularly endothelial colony-forming cells (ECFCs), are key contributors to vascular repair and maintenance. Long non-coding RNAs (lncRNAs) have emerged as novel epigenetic regulators of endothelial physiology and pathology. Building on our previous work identifying the lncRNA KLRK1-AS1 as a positive modulator of ECFC wound healing, we aimed to elucidate its role in endothelial biology. Cord blood-derived ECFCs were subjected to siRNA-mediated silencing of KLRK1-AS1, followed by blinded evaluations of monolayer morphology, barrier stability using ECIS impedance measurements, assessments of proliferation, and spheroid-based angiogenic activity. SiRNA-mediated silencing of KLRK1-AS1 induced detectable alterations in ECFC monolayer morphology (p = 0.047), while proliferation remained unaffected. Notably, KLRK1-AS1 knockdown significantly compromised endothelial barrier integrity, resulting in a 44% reduction in impedance after 48 h (p < 0.001), suggesting weakened intercellular contacts. In contrast, loss of KLRK1-AS1 enhanced angiogenic behaviour, demonstrated by an increased number of sprouts (+62%, p = 0.031). Together, these findings indicate that KLRK1-AS1 supports a quiescent, stable endothelial phenotype, with intact barrier function, while its depletion shifts ECFCs toward a more angiogenic, activated state. Our results identify KLRK1-AS1 as a previously unrecognised regulator of endothelial function.

As human space exploration advances towards establishing sustainable Martian habitats, achieving autonomous food production is a critical requirement. The potato (Solanum tuberosum L.), with its notable environmental resilience and nutritional efficiency, is a prime candidate crop. This study develops a conceptual framework for Martian potato cultivation by systematically analyzing the profound disparities between Martian conditions and plant physiology. We identify and evaluate seven fundamental challenges: atmospheric composition, extreme temperatures, water scarcity, soil properties, nutrient deficiencies, absent microbiota, and radiation/gravity effects. To address these challenges, we propose a phased, testable roadmap comprising four stages: (I) screening and bio-engineering of multi-stress-tolerant potato genotypes; (II) phased domestication via Earth-based analog experiments to define adaptability thresholds; (III) deployment of a controlled cultivation module within a Martian habitat, integrating targeted technological interventions; and (IV) conceptual exploration of extra-habitat agricultural potential. The primary contribution of this work is a structured set of hypotheses and key performance indicators for each stage, translating visionary goals into a defined research agenda to guide future empirical work in extraterrestrial agronomy.