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It also addresses the physiological contribution of endosome maturation mediated by this complex to neuronal polarity and integrity.Autophagy is an important bioprocess throughout the occurrence and development of cancer. However, the role of autophagy-related lncRNAs in pancreatic cancer (PC) remains obscure. In the study, we identified the autophagy-related lncRNAs (ARlncRNAs) and divided the PC patients from The Cancer Genome Atlas into training and validation set. Firstly, we constructed a signature in the training set by the least absolute shrinkage and selection operator penalized cox regression analysis and the multivariate cox regression analysis. Then, we validated the independent prognostic role of the risk signature in both training and validation set with survival analysis, receiver operating characteristic analysis, and Cox regression. The nomogram was established to demonstrate the predictive power of the signature. Moreover, high risk scores were significantly correlated to worse outcomes and severe clinical characteristics. The Pearson's analysis between risk scores with immune cells infiltration, tumor mutation burden, and the expression level of chemotherapy target molecules indicated that the signature could predict efficacy of immunotherapy and targeted therapy. Next, we constructed an lncRNA-miRNA-mRNA regulatory network and identified several potential small molecule drugs in the Connectivity Map (CMap). What's more, quantitative real-time PCR (qRT-PCR) analysis showed that serum LINC01559 could serve as a diagnostic biomarker. In vitro analysis showed inhibition of LINC01559 suppressed PC cell proliferation, migration, and invasion. Additionally, silencing LINC01559 suppressed gemcitabine-induced autophagy and promoted the sensitivity of PC cells to gemcitabine. In conclusion, we identified a novel ARlncRNAs signature with valuable clinical utility for reliable prognostic prediction and personalized treatment of PC patients. And inhibition of LINC01559 might be a novel strategy to overcome chemoresistance.With increasing life expectations, more and more patients suffer from fractures either induced by intensive sports or other bone-related diseases. The balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is the basis for maintaining bone health. Osterix (Osx) has long been known to be an essential transcription factor for the osteoblast differentiation and bone mineralization. Emerging evidence suggests that Osx not only plays an important role in intramembranous bone formation, but also affects endochondral ossification by participating in the terminal cartilage differentiation. Given its essentiality in skeletal development and bone formation, Osx has become a new research hotspot in recent years. In this review, we focus on the progress of Osx's function and its regulation in osteoblast differentiation and bone mass. And the potential role of Osx in developing new therapeutic strategies for osteolytic diseases was discussed.Antenatal corticosteroid therapy (ACT) has been shown to reduce morbidity and mortality rates in preterm delivery, but the fetus is more likely to face the risk of low bone mineralization and low fetal linear growth. However, the mechanism of ACT inducing low bone mineralization remains largely unknown. Pre-osteoclasts, which play an important role in angiogenesis and osteogenesis, are specifically regulating type H vessels (CD31hiEmcnhi) and vessel formation by secreting platelet-derived growth factor-BB (PDGF-BB). We find that the number of pre-osteoclasts and POC-secreted PDGF-BB is dramatically decreased in ACT mice, contributing to the reduction in type H vessels and bone mineralization during the mouse offspring. Quantitative analyses of micro-computed tomography show that the ACT mice have a significant reduction in the mass of trabecular bone relative to the control group. Mononuclear pre-osteoclasts in trabecular bone decreased in ACT mice, which leads to the amount of PDGF-BB reduced and attenuates type H vessel formation. After sorting the Rank+ osteoclast precursors using flow cytometry, we show that the enhancer of zeste homolog 2 (Ezh2) expression is decreased in Rank+ osteoclast precursors in ACT mice. Consistent with the flow data, by using small molecule Ezh2 inhibitor GSK126, we prove that Ezh2 is required for osteoclast differentiation. selleck products Downregulating the expression of Ezh2 in osteoclast precursors would reduce PDGF-BB production. Conditioned medium from osteoclast precursor cultures treated with GSK126 inhibited endothelial tube formation, whereas conditioned medium from vehicle group stimulated endothelial tube formation. These results indicate Ezh2 expression of osteoclast precursors is suppressed after ACT, which reduced the pre-osteoclast number and PDGF-BB secretion, thus inhibiting type H vessel formation and ACT-associated low bone mineralization.The Notch pathway involves evolutionarily conserved signaling regulating the development of the female tract organs such as breast, ovary, cervix, and uterine endometrium. A great number of studies revealed Notch aberrancies in association with their carcinogenesis and disease progression, the management of which is still challenging. The present study is a comprehensive review of the available literature on Notch signaling during the normal development and carcinogenesis of the female tract organs. The review has been enriched with our analyses of the TCGA data including breast, cervical, ovarian, and endometrial carcinomas concerning the effects of Notch signaling at two levels the core components and downstream effectors, hence filling the lack of global overview of Notch-driven carcinogenesis and disease progression. Phenotype heterogeneity regarding Notch signaling was projected in two uniform manifold approximation and projection algorithm dimensions, preceded by the principal component analysis step reducing the data burden. Additionally, overall and disease-free survival analyses were performed with the optimal cutpoint determination by Evaluate Cutpoints software to establish the character of particular Notch components in tumorigenesis. In addition to the review, we demonstrated separate models of the examined cancers of the Notch pathway and its targets, although expression profiles of all normal tissues were much more similar to each other than to its cancerous compartments. Such Notch-driven cancerous differentiation resulted in a case of opposite association with DFS and OS. As a consequence, target genes also show very distinct profiles including genes associated with cell proliferation and differentiation, energy metabolism, or the EMT. In conclusion, the observed Notch associations with the female tract malignancies resulted from differential expression of target genes. This may influence a future analysis to search for new therapeutic targets based on specific Notch pathway profiles.