Clinical factors affecting the long-term survival of breast cancer patients.

OBJECTIVE: The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. METHODS: Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. RESULTS: Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. CONCLUSIONS: Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

Single-cell RNA sequencing of mouse left ventricle reveals cellular diversity and intercommunication.

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10× Genomics). Detailed t-distributed stochastic neighbor embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2, and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits > 2, P < 0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included 5 subtypes, fibroblasts comprising 7 subtypes, and macrophages contained 11 subtypes. The key representative DEGs (P < 0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, and Clec4e and Trem-1 in cluster 3 of macrophages perhaps involved in the occurrence of atherosclerosis, heart failure, and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.

Cytotoxic Effect of Latanoprost on Human Corneal Stromal Cells in vitro and its Possible Mechanisms.

PURPOSE: To investigate the cytotoxic effect of latanoprost on corneal stroma and its underlying cellular and molecular mechanisms using non-transfected human corneal stromal (HCS) cells as an in vitro model. METHODS: After HCS cells were treated with latanoprost at concentrations varying from 50 mg/l (clinical therapeutic dosage) to 0.78125 mg/l, and cell morphology, cell viability, and cell cycle were detected by light microscopy, methyl thiazolyl tetrazolium assay, and flow cytometry (FCM) with propidium iodide (PI) staining, respectively. Meanwhile, alterations in plasma membrane permeability, phosphatidylserine (PS) orientation, DNA integrality, and cell ultrastructure were examined by acridine orange (AO)/ethidium bromide (EB) double staining, FCM with Annexin-V/propidium iodide (PI) staining, DNA electrophoresis, and transmission electron microscopy. Furthermore, caspase activation, mitochondrial transmembrane potential (MTP), and expression of pro-apoptotic regulators were determined by ELISA, FCM with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethybenzimida (JC-1) staining, and Western blot, respectively. RESULTS: Latanoprost above concentrations of 3.125 mg/l can induce dose- and time-dependent morphological abnormality, growth retardation, viability decline, and plasma membrane permeability elevation of HCS cells. Moreover, latanoprost can arrest the cell cycle of these cells at S phase and induce PS externalization, DNA fragmentation, and apoptotic body formation of the cells. Furthermore, latanoprost can induce activation of caspase-3, -8 and -9; disruption of MTP; downregulation of anti-apoptotic Bcl-2; upregulation of pro-apoptotic Bax; and cytoplasmic cytochrome c release. CONCLUSIONS: Latanoprost above and at 3.125 mg/l (1/16 of its clinical therapeutic dosage) has a dose- and time-dependent cytotoxicity to HCS cells by inducing death receptor-mediated mitochondria-dependent apoptosis, which should be used with great caution in clinical situations to avoid undesired damages to HCS cells.

Formation mechanism of fractal structures on wax surfaces with reference to their super -repellency.

Alkylketene dimer (AKD: a kind of wax) spontaneously forms a fractal structure and its surfaces show super water-repellency (the contact angle = 174°). However, the formation mechanism of the fractal surfaces of AKD is still unclear. In this work, surface structures, wettability and phase behaviors of various waxes have been investigated in order to understand the mechanism for spontaneous formation of super water-repellent fractal surfaces. We have found an empirical general rule without any exceptions at least for the wax samples tested. First, the wax must form a meta-stable crystalline phase when solidified from its melt. Then, the super water-repellent fractal surfaces form spontaneously during the phase transition from a meta-stable to a stable crystalline form. The tempering method also supported the above rule for the waxes showing the fractal structure formation on their surfaces.

Studies on the synthesis of (2S,3R)-3-hydroxy-3-methylproline via C2-N bond formation.

A new efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) is reported. During the course of a recent study on the Lewis acid promoted intramolecular opening of an epoxide by a carbamate NH, a highly concerted rearrangement was unexpectedly observed. Further investigations of substrate generality show that delta-carbamate-alpha,beta-epoxide esters commonly underwent similar rearrangements with the aid of Lewis acids. Retrosynthetic analysis of such a C(2)-N disconnection can lead to an efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) in high enantio purity. Stereochemistries were established by a Sharpless asymmetric dihydroxylation and a diastereoselective reductive amination.