Machine Learning Molecular Dynamics Shows Anomalous Entropic Effect on Catalysis through Surface Pre-melting of Nanoclusters.

Due to the superior catalytic activity and efficient utilization of noble metals, nanocatalysts are extensively used in the modern industrial production of chemicals. The surface structures of these materials are significantly influenced by reactive adsorbates, leading to dynamic behavior under experimental conditions. The dynamic nature poses significant challenges in studying the structure-activity relations of catalysts. Herein, we unveil an anomalous entropic effect on catalysis via surface pre-melting of nanoclusters through machine learning accelerated molecular dynamics and free energy calculation. We find that due to the pre-melting of shell atoms, there exists a non-linear variation in the catalytic activity of the nanoclusters with temperature. Consequently, two notable changes in catalyst activity occur at the respective temperatures of melting for the shell and core atoms. We further study the nanoclusters with surface point defects, i.e. vacancy and ad-atom, and observe significant decrease in the surface melting temperatures of the nanoclusters, enabling the reaction to take place under more favorable and milder conditions. These findings not only provide novel insights into dynamic catalysis of nanoclusters but also offer new understanding of the role of point defects in catalytic processes.

Structural dynamics of Ru clusters during nitrogen dissociation in ammonia synthesis.

The dynamic evolution of catalyst structures greatly influences the reactivity, especially sub-nanometer clusters, exhibiting complex configurational fluctuation. In the present work, we study the structural dynamics of a Ru19 cluster during the dissociation of N2 and calculate the reaction free energies using ab initio molecular dynamics (AIMD). Our AIMD calculation predicts a peak-shaped reaction entropy curve due to the adsorption-induced phase transition of the Ru19 cluster. The low melting points of sub-nanometer clusters make it possible to activate N2 at low temperatures. This work demonstrates that the dynamic changes of cluster structures have a non-negligible effect on reaction free energy and offer an opportunity for achieving ammonia synthesis under mild conditions.

Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/ß-catenin Signal Pathway through Downregulating LncRNA ROR.

BACKGROUND: Cancer stem cells could influence tumor recurrence and metastasis. OBJECTIVE: To develop a new effective treatment modality targeting breast cancer stem cells (BCSCs) and to explore the role of Apatinib in BCSCs. METHODS: BCSCs were isolated from MDA-MB-231 cells by the immune magnetic beads method. BCSCs were treated with Apatinib, lentiviral plasmids (lncRNA ROR), and iCRT-3 (Wnt pathway inhibitors). Viability, colony numbers, sphere numbers, apoptosis, migration, invasion of BCSCs were detected by MTT, colony formation, tumorsphere, flow cytometry, wound-healing, transwell assays, respectively. The expressions of markers (ABCG2, CD44, CD90, and CD24), epithelial-mesenchymal transition (EMT)-related molecules (Ecadherin, N-cadherin, Vimentin, MMP-2, MMP-9), and Wnt/ß-catenin pathway-related proteins (Wnt3a, Wnt5a, ß-catenin) in breast cancer stem cells were determined by performing Western blot and qRT-PCR analysis. RESULTS: Apatinib decreased the viability and colony numbers of BCSCs in a concentration-dependent manner, and it also reduced sphere numbers, suppressed migration, invasion and lncRNA ROR expression, and induced apoptosis of BCSCs. However, these results were partially reversed by lncRNA ROR overexpression. Apatinib suppressed stem property, EMT process, and Wnt/ß-catenin pathway in BCSCs, which was partially reversed by lncRNA ROR overexpression. Moreover, lncRNA ROR overexpression increased the colony and sphere numbers and promoted the cell viability, apoptosis inhibition, migration, and invasion of BCSCs, but these effects were partially reversed by iCRT-3. LncRNA ROR overexpression increased the stem property, EMT process, and Wnt/ß-catenin pathway, which were partially counteracted by iCRT-3. CONCLUSION: Apatinib inhibited stem property and malignant biological behaviors of BCSCs by blocking the Wnt/ß-catenin signal pathway through down-regulating lncRNA ROR.

The Biogenesis and Functions of circRNAs and Their Roles in Breast Cancer.

Recent statistics show that breast cancer is among the most frequent cancers in clinical practice. It is also the second-leading cause of cancer-related deaths among women worldwide. CircRNAs are a new class of endogenous regulatory RNA molecules whose 5' end and 3' end are connected together to form a covalently closed single-stranded loop by back-splicing. CircRNAs present the advantages of disease-specific expression and excellent expression stability, and they can modulate gene expression at posttranscriptional and transcriptional levels. CircRNAs are abnormally expressed in multiple cancers, such as breast cancer, and drive the initiation and progression of cancer. In this review, we describe current knowledge about the functions of circRNAs and generalize their roles in various aspects of breast cancer, including cell proliferation, cell cycle, apoptosis, invasion and metastasis, autophagy, angiogenesis, drug resistance, and tumor immunity, and their prognostic and diagnostic value. This may add to a better understanding of the functions and roles of circRNAs in breast cancer, which may become new diagnostic and predictive biomarkers of breast cancer.

Diallyl trisulfide regulates cell apoptosis and invasion in human osteosarcoma U2OS cells through regulating PI3K/AKT/GSK3ß signaling pathway.

AIMS: To investigate the effects and the mechanisms of action of Diallyl trisulfide (DATS) on the proliferation and metastasis of human osteosarcoma (OS) U2OS. METHODS: U2OS cells were treated by different concentrations of DATS at different time points. Cell proliferations were measured by MTT assay. DATS induced cell cycle distribution and apoptosis were evaluated by flow cytometry (FCM) with Annexin-V. Cell migration and invasion were detected by wound healing assay and transwell assay. The effects of DATS in U2OS cell growth and metastasis were also detected in a mouse OS xenograft model. RESULTS: A time- and concentration-dependent cytotoxic effect of DATS was observed in U2OS cells. FCM with PI staining and Annexin-V -FITC indicated that DATS induces apoptosis and a G0/G1 cell cycle arrest of U2OS cells at all concentrations from 25 µmol/l to 100 µmol/l. DATS also inhibits the migration and invasion of U2OS cells. Western blot showed that the expression levels of p-AKT, p-GSK3ß, Bcl-2, Vimentin and ß-catenin were decreased, while the expression levels of Bad, Bax and E-cadherin were significantly increased in DATS treated U2OS cells. Analysis using a mouse xenograft model indicated that xenografts of DATS treatment group had a significant decrease in tumor volume and weight compared to the control group. Lung metastasis models in mice demonstrated that treatment of DATS inhibits lung metastasis of OS in vivo. CONCLUSIONS: These data suggested that DATS inhibits OS development and progression through the regulation of PI3K/AKT/GSK3ß signaling pathways, accompanied by downregulation of Bcl-2, Vimentin and ß-catenin, as well as upregulation of Bad, Bax and E-cadherin. Therefore, our data demonstrated that DATS exerted its anticancer effects by inhibiting cell proliferation, migration and invasion in vitro and in vivo. These results provide evidence for the use of the natural product DATS either alone or in combination with standard therapy for OS.