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The silk gland is characterized by high protein synthesis. However, the molecular mechanisms controlling silk gland growth and silk protein synthesis remain undetermined. Here we demonstrated that CRISPR/Cas9-based knockdown of let-7 or the whole cluster promoted endoreduplication and enlargement of the silk gland, accompanied by changing silk yield, whereas transgenic overexpression of let-7 led to atrophy and degeneration of the silk gland. Mechanistically, let-7 controls cell growth in the silk gland through coordinating nutrient metabolism processes and energy signalling pathways. Transgenic overexpression of pyruvate carboxylase, a novel target of let-7, resulted in enlargement of the silk glands, which is consistent with the abnormal phenotype of the let-7 knockdown. Overall, our data reveal a previously unknown miRNA-mediated regulation of silk gland growth and physiology and shed light on involvement of let-7 as a critical stabilizer and booster in carbohydrate metabolism, which may have important implications for understanding of the molecular mechanism and physiological function of specialized organs in other species.

Biomimetic design will significantly improve growth and regeneration of dural cells and tissue for better repairing effects and fewer complications in repairing the native dura. This study designed a novel composite, biomimetic substitute based on the characteristics of native dura extracellular matrix.This substitute is expected to rapidly induce cell adhesion, migration, and fast regeneration of neotissue. The material characteristics (contact angle, surface charge, and zeta potential were evaluated), in vitro biological characteristics (cell stretch, connections between cells, cell proliferation) and in vivo tissue regeneration capability of this substitute were evaluated, compared to those of collagen dura substitute, the mostly used dura substitute. The results showed that the surface properties of this composite substitute were more biomimetic to native extracellular matrix than collagen substitute did, together with better cytocompatibility, tissue ingrowth, and neoangiogenesis. This composite substitute further demonstrated in clinical case study its ideal repair effect with no CSF leakage or other adverse reactions.In conclusion, the new biomimetic composite substitute provides alternative substitute for dura repairing.