Origin of the Activity of Electrochemical Ozone Production over Rutile PbO2 Surfaces.

Ozonation water treatment technology has attracted increasing attention due to its environmental benign and high efficiency. Rutile PbO2 is a promising anode material for electrochemical ozone production (EOP). However, the reaction mechanism underlying ozone production catalyzed by PbO2 was rarely studied and not well-understood, which was in part due to the overlook of the electrochemistry-driven formation of oxygen vacancy (OV) of PbO2. Herein, we unrevealed the origin of the EOP activity of PbO2 starting from the electrochemical surface state analysis using density functional theory (DFT) calculations, activity analysis, and catalytic volcano modeling. Interestingly, we found that under experimental EOP potential (i.e., a potential around 2.2 V vs. reversible hydrogen electrode), OV can still be generated easily on PbO2 surfaces. Our subsequent kinetic and thermodynamic analyses show that these OV sites on PbO2 surfaces are highly active for the EOP reaction through an interesting atomic oxygen (O*)-O2 coupled mechanism. In particular, rutile PbO2(101) with the "in-situ" generated OV exhibited superior EOP activities, outperforming (111) and (110). Finally, by catalytic modeling, we found that PbO2 is close to the theoretical optimum of the reaction, suggesting a superior EOP performance of rutile PbO2. All these analyses are in good agreement with experimental observations.

Fouling evolution of extracellular polymeric substances in forward osmosis based microalgae dewatering.

Membrane fouling was still a challenge for the potential application of forward osmosis (FO) in algae dewatering. In this study, the fouling behaviors of Chlorella vulgaris and Scenedesmus obliquus were compared in the FO membrane filtration process, and the roles of their soluble-extracellular polymeric substances (sEPS) and bound-EPS (bEPS) in fouling performance were investigated. The results showed that fouling behaviors could be divided into two stages including a quickly dropped and later a stable process. The bEPS of both species presented the highest flux decline (about 40.0%) by comparison with their sEPS, cells and broth. This performance was consistent with the largest dissolved organic carbon losses in feed solutions, and the highest interfacial free energy analyzed by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The chemical characterizations of algal foulants further showed that the severe fouling performance was also consistent with a proper ratio of carbohydrates and proteins contents in the cake layer, as well as the higher low molecular weight (LMW) components. Compared with the bEPS, the sEPS was crucial for the membrane fouling of S. obliquus, and an evolution of the membrane fouling structure was found in both species at the later filtration stage. This work clearly revealed the fundamental mechanism of FO membrane fouling caused by real microalgal suspension, and it will improve our understanding of the evolutionary fouling performances of algal EPS.

Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma.

Mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, and anti-tumor and immunoregulatory properties. The limited passage and self-differentiation abilities of MSCs in vitro hinder preclinical studies on them. In this study, we focused on the safety of immortalized mesenchymal stem cells (im-MSCs) and, for the first time, studied the feasibility of im-MSCs as candidates for the treatment of glioma. The im-MSCs were constructed by lentiviral transfection of genes. The proliferative capacity of im-MSCs and the proliferative phenotype of MSCs and MSCs co-cultured with glioma cells (U87) were measured using CCK-8 or EdU assays. After long-term culture, karyotyping of im-MSCs was conducted. The tumorigenicity of engineered MSCs was evaluated using soft agar cloning assays. Next, the engineered cells were injected into the brain of female BALB/c nude mice. Finally, the cell membranes of im-MSCs were labeled with DiO or DiR to detect their ability to be taken up by glioma cells and target in situ gliomas using the IVIS system. Engineered cells retained the immunophenotype of MSC; im-MSCs maintained the ability to differentiate into mesenchymal lineages in vitro; and im-MSCs showed stronger proliferative capacity than unengineered MSCs but without colony formation in soft agar, no tumorigenicity in the brain, and normal chromosomes. MSCs or im-MSCs co-cultured with U87 cells showed enhanced proliferation ability, but did not show malignant characteristics in vitro. Immortalized cells continued to express homing molecules. The cell membranes of im-MSCs were taken up by glioma cells and targeted in situ gliomas in vivo, suggesting that im-MSCs and their plasma membranes can be used as natural drug carriers for targeting gliomas, and providing a safe, adequate, quality-controlled, and continuous source for the treatment of gliomas based on whole-cell or cell membrane carriers.

Ferroptosis Suppressive Genes Correlate with Immunosuppression in Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most lethal primary tumor in the central nervous system. Ferroptosis is a type of programmed iron-dependent cell death. In the present study, we aimed to identify prognostic ferroptosis-related genes and their role in tumor immunity. METHODS: We used differential and survival analysis and The Cancer Genome Atlas (TCGA) GBM RNA sequencing data. We also used systematic bioinformatic methods. RESULTS: Using differential and survival analysis, we found that a ferroptosis suppressor was predominant within ferroptosis-related genes in TCGA GBM RNA sequencing data. By integrating TCGA and gene expression omnibus GBM cohorts, 12 dysregulated ferroptosis suppressors were detected. Among the suppressors, CD44, heat shock protein family B (small) member 1 (HSPB1), and solute carrier family 40 member 1 (SLC40A1) were relevant to overall survival. Using systematic bioinformatic methods, we observed that ferroptosis suppressor expression correlated with immunosuppression, which could be attributed to T-cell exhaustion and cytotoxic T-lymphocyte evasion. Finally, we observed that a potential ferroptosis-inducing drug, acetaminophen, interacted with CD44, HSPB1, and SLC40A1. CONCLUSIONS: The ferroptosis suppressors CD44, HSPB1, and SLC40A1 were significantly associated with prognosis in GBM and correlated with immunosuppression (i.e., T-cell exhaustion and cytotoxic T-lymphocyte evasion). Acetaminophen might have an antitumor function in GBM by regulating CD44, HSPB1, and SLC40A1 to induce ferroptosis. Our results are expected to be of great significance in developing new immunotherapy strategies for GBM.

Dual role of WNT5A in promoting endothelial differentiation of glioma stem cells and angiogenesis of glioma derived endothelial cells.

Glioma is a devastating cancer with a rich vascular network. No anti-angiogenic treatment is available for prolonging the overall survival of glioma patients. Recent studies have demonstrated that the endothelial differentiation of glioma stem cells (GSCs) into glioma-derived endothelial cells (GDECs) may be a novel target for anti-angiogenic therapy in glioma; however, the underlying mechanisms of this process remain unknown. Here, we report that wingless-related integration site (WNT) family member 5A (WNT5A) plays significant roles in GSC endothelial differentiation and GDECs angiogenesis. WNT5A is preferentially secreted by GDECs, and inhibition of WNT5A suppresses angiogenesis and tumorigenesis in GDECs. Silencing of WNT5A in GDECs also disrupts the impact of GDECs on stimulating GSC endothelial differentiation. Frizzled-4 is a receptor that mediates the effect of WNT5A on GSC endothelial differentiation and angiogenesis of GDECs via GSK3ß/ß-catenin/epithelial-mesenchymal transition signalling. The shWNT5A@cRGD-DDD liposomes, targeting WNT5A, exert anti-angiogenic effects in vivo. In this study, we identified that WNT5A has a dual functional role in modulating the endothelial differentiation of GSCs and angiogenesis of GDECs, indicating that WNT5A is a potential target for anti-angiogenesis-based therapeutics in glioma.

Selective exosome exclusion of miR-375 by glioma cells promotes glioma progression by activating the CTGF-EGFR pathway.

BACKGROUND: Exosomes are membrane-bound extracellular vesicles of 40-150 nm in size, that are produced by many cell types, and play an important role in the maintenance of cellular homeostasis. Exosome secretion allows for the selective removal of harmful substances from cells. However, it remains unclear whether this process also takes place in glioma cells. METHODS: Herein, the role of the tumour-suppressor miR-375 was explored in human glioma cells. Immunoblotting and qRT-PCR experiments demonstrated a functional link between miR-375 and its target, connective tissue growth factor (CTGF), which led to the identification of the underlying molecular pathways. The exosomes secreted by glioma cells were extracted by ultracentrifugation and examined by transmission electron microscopy. Exosomal expression of miR-375 was then analysed by qRT-PCR; while the exosome secretion inhibitor, GW4869, was used to examine the biological significance of miR-375 release. Moreover, the dynamics of miR-375 release by glioma cells was investigated using fluorescently labelled exosomes. Finally, exosomal miR-375 release was examined in an orthotopic xenograft model in nude mice. RESULTS: MiR-375 expression was downregulated in gliomas. MiR-375 suppressed glioma proliferation, migration, and invasion by inhibiting the CTGF-epidermal growth factor receptor (EGFR) signalling pathway. MiR-375-containing exosomes were also identified in human peripheral blood samples from glioma patients, and their level correlated with disease progression status. Exosomal miR-375 secretion impacted the CTGF-EGFR pathway activity. Once secreted, exosomal miR-375 was not taken back up by glioma cells. CONCLUSIONS: Exosomal miR-375 secretion allowed for sustained activation of the CTGF-EGFR oncogenic pathway, promoting the proliferation and invasion of glioma cells. These findings enhance our understanding of exosome biology and may inspire development of new glioma therapies.