This issue of the Biomedical Journal highlights regulatory mechanisms that shape aging, disease progression, and biological complexity across molecular, cellular, and systems levels. A central theme is plasminogen activator inhibitor-1 (PAI-1) as a multifunctional regulator linking fibrinolysis, cellular senescence, stem cell dynamics, fibrosis, and tumor biology. Contributions examine structure-guided development of small-molecule PAI-1 inhibitors and their therapeutic potential across thrombotic disease, chronic myeloid leukemia, systemic sclerosis, lung cancer, and skin cancer, emphasizing controlled modulation of PAI-1 activity to preserve physiological balance while overcoming disease-associated dysregulation. Beyond protease signaling, several studies address regulatory layers governing cellular state and adaptability. Epitranscriptomic remodeling via N6-methyladenosine (m6A) emerges as a key mechanism in protozoan parasites and host-pathogen interactions, including parasite-driven reprogramming of host leukocytes. In cancer biology, ferroptosis susceptibility is shown to be regulated through SLC7A11-associated protein interactions, linking redox homeostasis, cell survival, and tumor progression in hepatocellular carcinoma. Exosome-mediated intercellular communication is further examined as a mechanism regulating tissue repair, inflammation, and systemic crosstalk, including gut microbiota-dependent effects on bone homeostasis. Methodological advances further underscore the importance of precision and interpretability in modern biomedical research. These include accessible platforms for reproducible single-cell RNA sequencing analysis, robot-assisted quantification of acupuncture mechanics underlying analgesic responses, and interpretable deep-learning frameworks combining classification and segmentation in medical imaging. Quantitative three-dimensional imaging approaches are also applied to craniofacial surgery, where cone-beam computed tomography-based analyses identify determinants of lip cant and facial midline correction following bimaxillary surgery. A conceptual synthesis places living systems and learning systems within shared theoretical frameworks, highlighting the convergence of physics, information theory, and artificial intelligence in understanding biological organization.
Aila Akosua Kattner (Thu,) studied this question.