PD-L1/PD-L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK.

Programmed death ligand 1 (PD-L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD-1)/PD-L1 signalling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) are elusive. We previously found that PD-L1 can bind to PD-L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD-L1 binds to PD-L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD-L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD-L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD-L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD-L1 was found to promote epithelial-mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1-86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD-L1 after binding to PD-L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti-PD-L1 antibodies.

MiR-1/GOLPH3/Foxo1 Signaling Pathway Regulates Proliferation of Bladder Cancer.

OBJECTIVE: To investigate role of microRNA-1/Golgi phosphoprotein 3/Foxo1 axis in bladder cancer. METHODS: The expression of Golgi phosphoprotein 3 was determined in both bladder cancer tissues and cell lines using quantitative real-time polymerase chain reaction and Western blotting, respectively. Golgi phosphoprotein 3 was knocked down by small hairpin RNA. MicroRNA-1 was overexpressed or inhibited by microRNA-1 mimic or inhibitor. Cell viability and proliferation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and colony-formation assay. Cell apoptosis and cycle was detected using flow cytometer. The expression of microRNA-1 and Golgi phosphoprotein 3 was determined using quantitative real-time polymerase chain reaction and Western blotting was used to test the expression of Golgi phosphoprotein 3, Foxo1, p-Foxo1, AKT, p-AKT, p27, and CyclinD1. Binding between microRNA-1 and Golgi phosphoprotein 3 was confirmed by Dual-Luciferase Reporter Assay. RESULTS: MicroRNA-1 was downregulated in bladder cancer tissues, while Golgi phosphoprotein 3 was overexpressed in bladder cancer cells and tissues. In both bladder cancer 5637 and T24 cell lines, the cell viability and proliferation were dramatically reduced when Golgi phosphoprotein 3 was knocked down. The inhibition of Golgi phosphoprotein 3 remarkably promoted cell apoptosis and induced cell-cycle arrest, as well as decreased the expression of p-Foxo1, p-AKT, and CyclinD1 and increased the expression of p27. The overexpression of microRNA-1 significantly inhibited cell viability and proliferation, induced G-S cell-cycle arrest, and decreased the expression of Golgi phosphoprotein 3, p-Foxo1, and CyclinD1 and upregulated p27, while inhibition of microRNA-1 led to opposite results. Golgi phosphoprotein 3 was a direct target for microRNA-1. CONCLUSION: Overexpression of microRNA-1 inhibited cell proliferation and induced cell-cycle arrest of bladder cancer cells through targeting Golgi phosphoprotein 3 and regulation of Foxo1.

Effective Removal of Tetracycline Antibiotics from Water using Hybrid Carbon Membranes.

Antibiotic residues in drinking water have become a global problem, especially in developing countries. However, effective purification of water contaminated by antibiotics remains a great challenge. Here, we investigated the removing of tetracycline by carbon nanomaterials with different structures and surface functionalities. The result shows that a membrane of thick graphene oxide (GO) and activated carbon (AC) with a thickness of 15 µm can effectively remove 98.9% of tetracycline hydrochloride (TCH) from water by vacuum filtration. Structural analysis indicated that the AC nanoparticles were uniformly inserted into the GO interstitial sites without any aggregations. Also, GO sheets were loosened by the encapsulated AC nanoparticles, leading to the formation of numerous tiny pores (3-10 nm) that acted as channels for fluid passage, whereas the carbons and chemical groups on the GO surface adsorbed TCH. GO/AC membrane exhibits the best adsorption efficiency among the investigated materials, including pure GO, AC, carbon nanotube (CNT), and CNT/AC and GO/CNT hybrids.

Highly Reproducible Ag NPs/CNT-Intercalated GO Membranes for Enrichment and SERS Detection of Antibiotics.

The increasing pollution of aquatic environments by antibiotics makes it necessary to develop efficient enrichment and sensitive detection methods for environmental antibiotics monitoring. In this work, silver nanoparticles and carbon nanotube-intercalated graphene oxide laminar membranes (Ag NPs/CNT-GO membranes) were successfully prepared for enrichment and surface-enhanced Raman scattering (SERS) detection of antibiotics. The prepared Ag NPs/CNT-GO membranes exhibited a high enrichment ability because of the π-π stacking and electrostatic interactions of GO toward antibiotic molecules, which enhanced the sensitivity of SERS measurements and enabled the antibiotics to be determined at sub-nM concentrations. In addition, the nanochannels created by the intercalation of CNTs into GO layers resulted in an 8-fold enhancement in the water permeance of Ag NPs/CNT-GO membranes compared to that of pure GO membranes. More importantly, the Ag NPs/CNT-GO membranes exhibited high reproducibility and long-term stability. The spot-to-spot variation in SERS intensity was less than 15%, and the SERS performance was maintained for at least 70 days. The Ag NPs/CNT-GO membranes were also used for SERS detection of antibiotics in real samples; the results showed that the characteristic peaks of antibiotics were obviously recognizable. Thus, the sensitive SERS detection of antibiotics based on Ag NPs/CNT-GO offers great potential for practical applications in environmental analysis.