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Brown hares (Lepus europaeus) and mountain hares (Lepus timidus) frequently hybridize in regions where their range overlaps, producing fertile offspring and enabling gene flow between the species. Despite this, no hybrid species has emerged, suggesting that hybrid backcrosses may incur fitness costs. One potential mechanism for such costs involves the interactions between mitochondrial and nuclear gene products, where incompatibilities between species-specific alleles may reinforce species barriers and lead to hybrid breakdown. However, direct experimental evidence for this hypothesis remains limited. In this study, we used fibroblasts derived from skin biopsies of wild-caught hares to generate cytoplasmic hybrid (cybrid) cell lines, wherein mitochondria and mtDNA from one species were transferred to mitochondria-depleted cells of the other species, creating novel mitonuclear gene combinations while preserving the original diploid nuclear background. Employing a range of techniques - including transcriptomics, metabolomics, microscopy, and respirometry - we explored the consequences of mitochondrial transfer between these hare species. Our results reveal that in the studied species mitonuclear incompatibilities exhibit strong effects on cellular fitness but are limited to specific genotypes. We propose mechanisms of cellular-level incompatibility and their potential consequences for interspecific hybrids, offering new insights into the complexity of mitonuclear interactions., Competing Interests: Declaration of competing interest The authors of this work have no interests to declare., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Mirin, a chemical inhibitor of MRE11, has been recently reported to suppress immune response triggered by mitochondrial DNA (mtDNA) breakage and release during replication stalling. We show that while Mirin reduces mitochondrial replication fork breakage in mitochondrial 3´-exonuclease MGME1 deficient cells, this effect occurs independently of MRE11. We also discovered that Mirin directly inhibits cellular immune responses, as shown by its suppression of STAT1 phosphorylation in Poly (I:C)-treated cells. Furthermore, Mirin also altered mtDNA supercoiling and accumulation of hemicatenated replication termination intermediates-hallmarks of topoisomerase dysfunction-while mitigating topological changes induced by the overexpression of mitochondrial TOP3A, including TOP3A-dependent strand breakage at the noncoding region of mtDNA. Although Mirin does not seem to inhibit TOP3A activity in vitro, our findings demonstrate its MRE11-independent effects in cells and give insight into the mechanisms of the maintenance of mtDNA integrity., Competing Interests: Conflicts of Interests: The authors declare no financial conflict of interest.

Peripheral artery disease (PAD) is a major public health concern worldwide, associated with high risk of mortality and morbidity related to cardiovascular and adverse limb events. Despite significant advances in both medical and interventional therapies, PAD often remains under-diagnosed, and the prognosis of patients can be difficult to predict. Artificial intelligence (AI) has brought a wide range of opportunities to improve the management of cardiovascular diseases, from advanced imaging analysis to machine-learning (ML)-based predictive models, and medical data management using natural language processing (NLP). The aim of this review is to summarize and discuss current techniques based on AI that have been proposed for the diagnosis and the evaluation of the prognosis in patients with PAD. The review focused on clinical studies that proposed AI-methods for the detection and the classification of PAD as well as studies that used AI-models to predict outcomes of patients. Through evaluation of study design, we discuss model choices including variability in dataset inputs, model complexity, interpretability, and challenges linked to performance metrics used. In the light of the results, we discuss potential interest for clinical decision support and highlight future directions for research and clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.