International Journal of Molecular Sciences

Bursaphelenchus xylophilus (PWN), a highly destructive invasive forest pest, has expanded northward in China, even colonizing cold regions, implying evolved low-temperature tolerance. To explore its cold adaptation mechanisms, we selected PWN isolates from diverse origins, screened cold-tolerant strains via low-temperature stress assays, and conducted integrative transcriptomic and metabolomic analyses. We also compared invasive and native populations to clarify adaptive pattern differentiation. The results showed that northern Chinese isolates had significantly higher survival rates, with cold tolerance closely linked to lysophosphatidylethanolamine (LysoPE). Silencing the LysoPE-related gene BX02G0260 markedly elevated nematode mortality under low temperatures. Unlike native populations, invasive PWN may have developed a cold adaptation strategy centered on genetic material protection, with xanthosine as a key metabolite. These findings provide critical molecular insights into invasive species’ rapid cold adaptation in novel environments.

Controlled local hyperthermia supports postoperative wound healing in liver surgery by stimulating metabolism, angiogenesis, and immune responses through the induction of heat shock proteins (HSPs) and modulation of Damage-Associated Molecular Patterns (DAMPs). This study evaluates the impact of thermal modulation on immune processes during abdominal wound repair, specifically analyzing the role of HSPs and immune activation pathways. A narrative review of the literature from 2010 to 2025 was conducted to summarize molecular mechanisms regarding temperature, HSP activation, cytokine expression, and DAMPs, excluding studies conducted solely in animal models. The results indicate that precise local hyperthermia in postoperative abdominal wounds activates HSPs as well as inflammasome and Toll-like receptor (TLR) pathways, modulating immune and cytokine responses depending on the type and depth of tissue injury. Consequently, such thermoimmunomodulation stabilizes immune cell functions, optimizes the balance between inflammation and regeneration, and minimizes the risk of postoperative complications to support effective wound healing.

Charcot–Marie–Tooth disease (CMT), caused by dominant loss-of-function mutations in DNM2, encoding the GTPase dynamin-2, impairs motor and sensory function. However, the respective contributions of muscle and nerve pathology, and the therapeutic potential of increasing DNM2 expression, remain unresolved. We evaluated tissue-targeted and systemic approaches to increase DNM2 in a mouse model carrying the common K562E-CMT mutation. Muscle-specific DNM2 overexpression from embryogenesis in Dnm2^K562E/+ mice ameliorated desmin and integrin mislocalization, membrane trafficking defects, mitochondrial abnormalities, and fibrosis in skeletal muscle, resulting in improved locomotor coordination despite persistent muscle atrophy. Conversely, systemic postnatal AAV delivery of human DNM2 increased DNM2 in muscle but failed to transduce nerves and paradoxically worsened the muscle pathology, producing centronuclear myopathy-like features. These findings reveal a primary pathogenic impact of DNM2-CMT mutation within skeletal muscle, independent of nerve involvement. Collectively, they underscore that precise DNM2 dosage is critical for neuromuscular homeostasis and reveal a narrow therapeutic window for safe and effective therapeutic intervention. This paradox, in which efforts to compensate for a loss-of-function neuropathy risk inducing a gain-of-function myopathy, highlights the need for tightly controlled modulation of DNM2 activity in future therapeutic strategies.