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Protein crystallization could be promoted with a low concentration of impurities and inhibited with a high concentration of impurities, and this inhibition can be weakened by an audible sound.

RNA interference is a promising way to treat cancer and the construction of a stable drug delivery system is critically important for its application. Gelatin nanospheres (GNs) comprise a biodegradable drug vehicle with excellent biocompatibility, but there are limited studies on its delivery and role in the stabilization of miRNA and siRNA. Breast cancer is the most diagnosed type of female cancer worldwide. Abnormal miRNA expression is closely related to the occurrence and progression of estrogen receptor-positive (ER+) breast cancer. In this study, miR-4458 was upregulated in ER+ breast cancer and could inhibit MCF-7 cell viability, colony formation, migration, and invasion. Collagen type XI alpha 1 (COL11A1) was identified as a directly interacting protein of miR-4458 and an important component of the extracellular matrix. High COL11A1 expression was positively correlated with poor prognosis, lower overall survival, disease-free survival, and a late tumor-node-metastasis stage. COL11A1 knockdown could inhibit MCF-7 cell migration and invasion. GNs were used to load a miR-4458 mimic or COL11A1 siRNA (si-COL11A1) to achieve sustained and controlled release in xenograft nude mice. Their tumor volume was decreased, tumor cell apoptosis was promoted, and hepatic metastasis was significantly inhibited. Moreover, the DDR2/SRC signaling pathway was inactivated after transfection with the miR-4458 mimic and si-COL11A1. In conclusion, GNs can be potentially used to deliver siRNA or miRNA, and miR-4458 and COL11A1 can be possible targets for ER+ breast cancer treatment.

Liquid-liquid phase separation (LLPS) is a ubiquitous process found in a variety of fields. It is of particular importance in biological sciences since it plays essential and vital roles in a number of physiological and pathological processes in biological systems. After LLPS, the dense droplets can grow in size via incorporating solutes from surrounding environment and in some cases coalescing with other droplets. Interestingly, the size of the dense droplets seems to have an upper limit but the mechanism remains to be explored. Since the droplet size can be essential for biological functioning, it is important to understand the size evolution of the phase separated droplets. Here we propose a physical mechanism with consideration of impurities on the surface of the dense liquid droplets. The theoretical predictions can be used to explain the observations on the size evolution. Based on the coalescence mechanism, we succeeded for the first time performing a challenging task, i.e., growing a single suspended protein crystal via merging phase-separated droplets in a fully non-contact manner. The mechanism observed may be considered as a basic model for researches in much broader fields involving phase separation, such as in biology, materials science, physics, chemistry, and meteorology.