Calcins represent a class of novel peptide ligands for ryanodine receptors (RyRs), demonstrating therapeutic potential against Ca²⁺ dysregulation-related cardiac diseases. Nevertheless, their biological effects beyond RyR modulation and underlying mechanisms remain unexplored. This study employed Opicalcin1 (OpiCa1), the most bioactive calcin member, revealing that while it reduced cytosolic Ca²⁺ in H9c2 cardiomyocytes, it concurrently diminished cell viability and promoted apoptosis. Transcriptomics and Western blot analyses identified suppression of the negatively regulatory PI3K/Akt pathway as the mechanistic basis. In acute/chronic in vivo studies, high-dose OpiCa1 (≥50 mg/kg i.v.) exhibited minimal impact on body weight, histopathology, and organ indices, while accompanied with subtle alterations in serum indicators, including slight elevations in AST, ALT, and LDH, alongside mild reductions in CK-MB and TBIL-Z. These findings unveil OpiCa1’s modulation on cardiomyocyte viability through PI3K/Akt inhibition with minimal systemic impact, providing new insights into non-RyR-mediated actions of calcins and critical toxicological support for developing calcin-based therapies targeting Ca²⁺-dysregulated cardiac pathologies.

Toxins as naturally occurring hazardous substances, have evolved as a defense mechanism in organisms for survival. The expression of toxins is profoundly influenced by environmental factors, and the investigation of their correlation holds significant implications for understanding toxin-induced harm and developing protective measures. Scorpions are a significant venomous species, and the relationship between the variability in scorpion toxin expression and environmental factors remains unclear. By conducting transcriptome profiling of scorpion samples collected from eight distinct climatic and environmental regions in East Asia, we successfully identified two distinct scorpion species. Furthermore, we found that the divergence in toxin composition, specifically the expression of two recently discovered calcins are closely aligned with the environmental humidity of their respective habitats. These calcins exhibited varying capacities to modulate the binding affinity of [³H]ryanodine to ryanodine receptors, inducing prolonged subconductance states. Our findings demonstrate that the distinct toxin arsenals of these scorpions reflect long-term adaptive evolution to their specific climatic niches. This study underscores the importance of considering ecological factors in understanding the evolutionary diversification of venomous species, providing a theoretical foundation for the rational exploration of natural toxins in traditional Chinese medicine and drug discovery.

Accurate detection of residual jellyfish venom is crucial for species identification and clinical management post-envenomation. We developed a highly specific immunoassay for Nemopilema nomurai venom using polyclonal antibodies (titer: 1:256,000). The established i-ELISA exhibited linear detection (0–20 ng/mL) with low variability (intra-plate CV: 0.77–2.78%; inter-plate CV: 2.25–5.17%). The kit demonstrated remarkable thermal stability (1-year shelf life at 4 °C. It showed significantly higher sensitivity for N. nomurai venom than venoms from Rhopilema esculentum, Chrysaora quinquecirrha, Cyanea melanaster, scorpions, or bees (p < 0.01). Validation in murine/human skin envenomation models and serum from systemically intoxicated mice confirmed the reproducibility and stability of residual toxins. This study developed a highly sensitive, specific, reproducible, and stable i-ELISA for Nemopilema nomurai venom, providing a methodological basis for creating diagnostic kits for marine envenomation.

Introduction: The modification of the marine ecological environment has led to the frequent occurrence of jellyfish blooms, causing global hazards. The budding reproduction of jellyfish polyps is a critical factor in their population size, yet there is limited understanding of the molecular mechanisms involved in this process. This study aims to explore the intrinsic regulatory factors of the budding of jellyfish Aurelia coerulea (A. coerulea) polyps from the perspective of jellyfish biotoxin and to develop new strategies for the management of jellyfish abundance.Methods: The main biological toxins of the A. coerulea polyp were screened through the integrated analysis of transcriptomic and proteomic data. The broad-spectrum metalloproteinase inhibitor, ethylenediaminetetraacetic acid (EDTA), was employed to treat polyps for observing its effect on the budding of A. coerulea polyps. Through conducting the detection of metzincin proteolytic activity, molecular docking and kinetic analysis, as well as transcriptomic analysis and RT-qPCR verification before and after EDTA treatment of the polyp, the key biological toxins and the mechanisms influencing polyp budding were clarified.Results: Four types of the metzincin family of metalloproteinases constituted the main biotoxins in the A. coerulea polyp. Among them, astacins (NAS) were the predominant metzincins of the A. coerulea polyp. We discovered that EDTA significantly inhibited the activity of metzincins and the budding of A. coerulea polyps. EDTA was capable of stably binding to the zinc-binding active sites of the four major types of metzincins in the A. coerulea polyp and could down-regulate the expression levels of key metzincin molecules and enrich multiple pathways related to development.Conclusion: This study elucidates the effects of metzincins on the budding of jellyfish polyps, providing a potential target for mitigating jellyfish blooms.