Background: Ultraviolet-C (UV-C) radiation is a high-energy physical mutagen capable of inducing DNA damage and oxidative stress, thereby generating genomic variability in photosynthetic organisms. However, its genome-wide effects in unicellular eukaryotic microalgae remain poorly characterized. This study developed a UV-C mutagenesis protocol in Chlamydomonas reinhardtii and evaluated its genomic and physiological impacts. Methods: Axenic cultures of Chlamydomonas reinhardtii (137c+) were exposed to UV-C (100–280 nm) for 12, 48, and 96 min. Viable colonies were analyzed by Random Amplification of Polymorphic DNA PCR (RAPD-PCR) to assess genetic variability, while chlorophyll content and the expression of stress-responsive genes were measured via spectrophotometry and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR), respectively. Results: UV-C treatment induced extensive genomic polymorphism with heterogeneous clustering patterns independent of exposure time, consistent with stochastic mutagenesis. Several mutants exhibited reduced chlorophyll content, indicating impaired photosynthetic efficiency. In contrast, one genotype (pop18) maintained wild-type chlorophyll levels despite marked genetic divergence, coupled with upregulation of antioxidant, DNA repair, and stress-response genes. Conclusions: Overall, UV-C irradiation represents an effective approach to generate non-directional genomic variability in Chlamydomonas reinhardtii, with evidence that random mutagenesis can drive functional reorganization of stress-response pathways, supporting its application in microalgal strain improvement.

Acute respiratory distress syndrome (ARDS) is a complex and heterogeneous clinical syndrome characterized by diffuse alveolar damage, severe hypoxemia, and a high risk of respiratory complications. Among these, the Macklin effect has emerged as an early radiological sign associated with the subsequent development of barotrauma. Although several genetic and molecular factors have been implicated in ARDS susceptibility and progression, their potential contribution to the biological processes underlying Macklin effect development remains largely unexplored. This review aims to examine current evidence on genetic susceptibility factors, molecular biomarkers, and multi-omics signatures involved in ARDS pathophysiology, with particular attention to mechanisms that may increase alveolar fragility and predispose to the development of the Macklin effect. A narrative review of the literature was conducted, focusing on studies investigating genetic polymorphisms, inflammatory pathways, transcriptomic profiles, proteomic biomarkers, and metabolomic alterations associated with ARDS severity, tissue injury, and pulmonary complications. Available evidence indicates that genetic variants involved in innate immunity, inflammatory signaling, and endothelial barrier regulation, including polymorphisms in TLRs, IL-1B, TNF-α, and S1PR3, contribute to interindividual variability in ARDS susceptibility and clinical outcomes. Multi-omics studies have identified several biomarkers, including TIMP1, MMP8, PTX3, and CCL2, that are consistently associated with dysregulated inflammation, extracellular matrix remodeling, immune cell recruitment, and epithelial-endothelial barrier dysfunction. These mechanisms are biologically plausible contributors to progressive alveolar injury and increased susceptibility to air leak syndromes. In parallel, molecular profiling studies have identified distinct ARDS subphenotypes associated with differences in disease severity, ventilator dependence, and mortality. To date, no genetic or molecular biomarkers have been specifically validated as predictors of Macklin effect development. Nevertheless, the available literature supports the existence of molecular pathways linking inflammation, tissue remodeling, and barrier dysfunction to processes that may facilitate alveolar rupture and air dissection. Further prospective studies integrating molecular profiling, radiological findings, and clinical outcomes are needed to determine whether these candidate biomarkers can improve risk stratification and prediction of barotrauma in patients with ARDS.