{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies have consistently demonstrated that sperm‐specific phospholipase C‐zeta (PLCζ) is the key physiological trigger of egg activation in mammals. Following gamete fusion, PLCζ is delivered by the sperm into the oocyte where its highly Ca²⁺-sensitive catalytic activity hydrolyzes phosphatidylinositol 4,5-bisphosphate from internal vesicular pools to generate inositol 1,4,5-trisphosphate. This in turn produces repetitive intracellular Ca²⁺ oscillations that are critical for oocyte activation and subsequent embryonic development. Detailed structure–function analyses have revealed that well‐orchestrated domain features—including the four EF-hand motifs, the XY catalytic core with its positively charged linker regions, and the C2 domain—are essential not only for optimal enzymatic activity and sensitivity to basal Ca²⁺ levels but also for spatial regulation through nuclear localization, which helps terminate Ca²⁺ transients at the appropriate cell cycle phase. Moreover, investigations across species and using genetic knockout models have underscored the significance of PLCζ levels and subcellular dynamics (for example, its cleavage into active fragments, species-specific differences in nuclear accumulation, and responsiveness to assisted oocyte activation protocols), as well as the impact of factors such as advanced male age and cytoskeletal integrity on its function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the extensive body of work on PLCζ in fertilization, emerging evidence has identified a distinct role for microRNA‐5683 (miR-5683) in the context of gastric cancer. Analysis of patient data revealed that miR-5683 is markedly downregulated in gastric cancer tissues, and experimental manipulation in gastric cancer cells demonstrated that reduced miR-5683 levels result in enhanced cell proliferation, diminished apoptosis, and increased glycolysis. These oncogenic effects are mediated, at least in part, by the loss of miR-5683–dependent suppression of its direct target, pyruvate dehydrogenase kinase 4 (PDK4), which is associated with poorer overall and disease-free survival. Consequently, restoration of miR-5683 expression may present a promising therapeutic approach to repress tumor progression by counteracting aberrant metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christopher M Saunders, Mark G Larman, John Parrington, et al. 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