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The amino acid-stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase-mediated mTORC1 activation. Here, a highly conserved insulin-responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2-AKT1 is localized on lysosomes, and RagD-specific recruitment of mTORC2-AKT1 on lysosomes is identified as an essential step in insulin-AKT1-mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin-induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1-dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross-talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: To evaluate insulin injection knowledge, attitudes, and practices of nurses across China in order to provide reference for the formulation of a national unified standard of insulin injection practice and the targeted implementation of standardized training on insulin injection for nurses. Methods: We enrolled nurses who worked and injected insulin at grassroot hospitals including community health service centers and township clinics, secondary and tertiary care hospitals across China between July 28, 2019 and August 30, 2019. A nurse insulin injection knowledge, attitude, and practice questionnaire was used to evaluate the knowledge, attitude, and practice level of nurses. Results: A total of 223,368 nurses were included in the study. The mean knowledge score was 13.70 ± 3.30 and 35.19% had a poor knowledge score. The mean attitude score was 17.18 ± 2.69 for the study nurses; merely 3.15% had a poor attitude score. The mean practice score of the study population was 83.03 ± 8.16 and only 0.88% had a poor practice score. Pearson correlation analysis showed significant correlation between the knowledge score and the attitude score (r = 0.29; P < 0.001), the knowledge score and the practice score (r = 0.27; P < 0.001), and between the attitude score and the practice score (r = 0.56; P < 0.001). A multivariate analysis revealed that nurses with higher knowledge scores were also more likely to have higher attitude scores and practice scores, and nurses with higher attitude scores were also more likely to have higher practice scores. Conclusion: Chinese nurses have a good attitude and behavior towards insulin injection, while their knowledge of insulin injection is insufficient. It is also revealed that knowledge of insulin injection can directly or indirectly affect insulin injection behavior through attitude, indicating that hospitals should formulate unified insulin injection norms and regularly organize relevant training and assessment so as to improve nurses' knowledge, attitude, and behavior of insulin injection. [ABSTRACT FROM AUTHOR]