In this study, we demonstrate that the initial morphology of nanoparticles can be transformed into small fragmented nanoparticles, which were densely contacted to each other, during electrochemical CO 2 reduction reaction (CO 2 RR). Cu-based nanoparticles were directly grown on a carbon support by using cysteamine immobilization agent, and the synthesized nanoparticle catalyst showed increasing activity during initial CO 2 RR, doubling Faradaic efficiency of C 2 H 4 production from 27% to 57.3%. The increased C 2 H 4 production activity was related to the morphological transformation over reaction time. Twenty nm cubic Cu 2 O crystalline particles gradually experienced in situ electrochemical fragmentation into 2−4 nm small particles under the negative potential, and the fragmentation was found to be initiated from the surface of the nanocrystal. Compared to Cu@CuO nanoparticle/C or bulk Cu foil, the fragmented Cu-based NP/C catalyst achieved enhanced C 2+ production selectivity, accounting 87% of the total CO 2 RR products, and suppressed H 2 production. In-situ X-ray absorption near edge structure studies showed metallic Cu 0 state was observed under CO 2 RR, but the fragmented nanoparticles were more readily reoxidized at open circuit potential inside of the electrolyte, allowing labile Cu states. The unique morphology, small nanoparticles stacked upon on another, is proposed to promote C−C coupling reaction selectivity from CO 2 RR by suppressing HER.

The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.

Neuroinflammation underlies many diseases of the central nervous system (CNS) and the role of astrocytes in this process is increasingly recognized. Thrombin and the lysophospholipids, LPA and S1P are generated during injury and can activate G‐protein coupled receptors (GPCRs) on astrocytes. We hypothesized that GPCRs that couple to RhoA induce inflammatory gene expression in astrocytes through phospholipase C‐epsilon (PLCε). Using wild‐type (WT) and PLCε (KO) astrocytes, we recently demonstrated that thrombin, LPA, and S1P signal through PLCε to mediate sustained PKD activation and subsequently activation of NFκB to induce expression of inflammatory genes including COX‐2, IL‐1β, and IL‐6 (Dusaban, SS et al. PNAS, 2013). We are currently investigating the molecular mechanism by which PLCε mediates sustained PKD activation and downstream inflammatory responses. Preliminary data using Golgi targeted PKD FRET reporters suggests that PLCε mediates sustained activation of PKD at the Golgi. We also find that disrupting the Golgi with brefeldin A inhibits both PKD activation and COX‐2 expression. We further determined that COX‐2 gene expression was induced through PLCε following in vitro wounding and in vivo cortical stab wound injury. In light of growing evidence for a role of glial cells and S1P receptors in neuroinflammation, we investigated the S1P receptor subtypes coupled to PLCε and its downstream targets. Taking advantage of receptor KO astrocytes and receptor knockdown, we determined that coupling occurs primarily through the S1P3 receptor. Future work is aimed at identifying other GPCRs that signal through PLCε to mediate neuroinflammatory responses. Grant Funding Source: GM 36927

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The protective adaptive response to electrophiles and reactive oxygen species is mediated by enhanced expression of phase II detoxifying genes, including glutathione S-transferases, through activation of antioxidant response element (ARE). The current study was designed to investigate the role of phosphatidylinositol 3-kinase (PI3-kinase)-Akt and mitogen-activated protein (MAP) kinase signaling pathways in the induction of rGSTA2 by tert-butylhydroquinone (t-BHQ). Nuclear ARE complex was activated 1 to 6 h after treatment of H4IIE cells with t-BHQ. The rGSTA2 mRNA level was elevated 6 to 24 h after t-BHQ treatment, which led to the enzyme induction. Activities of PI3-kinase and Akt were increased 10 min through 6 h after t-BHQ treatment, whereas wortmannin or LY294002, PI3-kinase inhibitors, completely abolished ARE binding activity and increases in rGSTA2 mRNA and protein. Extracellular signal-regulated kinase (ERK), p38 MAP kinase, and c-Jun N-terminal kinase (JNK) were all activated by t-BHQ. Treatment with PD98059, an ERK inhibitor, however, increased rGSTA2 mRNA and further enhanced t-BHQ-induced expression of rGSTA2. Neither SB203580 nor overexpression of JNK1 dominant negative mutant altered t-BHQ-inducible rGSTA2 expression. These results demonstrated that t-BHQ activated PI3-kinase and Akt, which was responsible for ARE-mediated rGSTA2 induction, and that ERK might negatively regulate rGSTA2 expression, whereas activation of p38 MAP kinase or of JNK by t-BHQ was not associated with the enzyme induction.

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The origin of the irreversible capacity of O3type NaFeO 2 charged to high voltage is investigated by analyzing the oxidation state of Fe and phase transition of layered NaFeO 2 cathodes for sodium-ion batteries during the charging process. In-situ X-ray absorption spectroscopy results revealed that charge compensation does not occur through the Fe 3+ /Fe 4+ redox reaction during sodium extraction as no significant shift to high energy was observed in the Fe K-edge. These results were reinforced with ex-situ near-edge X-ray absorption spectroscopy, which suggests that oxygen redox activity is responsible for charge compensation. Formation of Fe 3 O 4 product occurs because of oxygen release at high voltage when more than 0.5 Na is extracted from the structure; this is observed by transmission electron microscopy. NaFeO 2 irreversibility is due to the formation of Fe 3 O 4 with oxygen release, which inhibits Na insertion into the structure.