Defect Engineering in Composition and Valence Band Center of Y2(YxRu1-x)2O7-δ Pyrochlore Electrocatalysts for Oxygen Evolution Reaction.

Oxygen evolution reaction (OER) takes place in various types of electrochemical devices that are pivotal for the conversion and storage of renewable energy. This paper describes a strategy in the design of solid-state structures of OER electrocatalysts through controlling the cation substitution on the active metal site and consequently valence band center position of site-mixed Y2(YxRu1-x)2O7-δ pyrochlore to achieve high catalytic activity. We found that partially replacing the B-site Ru4+ cation with A-site Y3+ in pyrochlore-structured Y2Ru2O7-δ modifies the oxidation state of B-site Ru from 4+ to 5+, as observed by electron paramagnetic resonance (EPR) spectroscopy but does not continuously increase the oxygen vacancy concentration in these oxygen substoichiometric compositions, as quantified by thermogravimetric analysis (TGA) decomposition studies. We found the increased Ru oxidation state leads to a downshift in valence band center. X-ray photoelectron spectroscopy (XPS) analysis was performed to quantitatively determine the optimal band center to be ∼1.27 eV below the Fermi energy level based on the analysis of the valence band edge of these Ru-based Y2(YxRu1-x)2O7-δ OER electrocatalysts. This work highlights that defect engineering can be a practical, effective approach to the optimization of oxidation state and electronic band center for high OER catalytic performance in a quantitative manner.

Novel cleavable cell-penetrating peptide-drug conjugates: synthesis and characterization.

We report the first drug conjugate with a negatively charged amphipathic cell-penetrating peptide. Furthermore, we compare two different doxorubicin cell-penetrating peptide conjugates, which are both unique in their properties, due to their net charge at physiological pH, namely the positively charged octaarginine and the negatively charged proline-rich amphipathic peptide. These conjugates were prepared exploiting a novel heterobifunctional crosslinker to join the N-terminal cysteine residue of the peptides with the aliphatic ketone of doxorubicin. This small linker contains an activated thiol as well as aminooxy functionality, capable of generating a stable oxime bond with the C-13 carbonyl group of doxorubicin. The disulfide bond formed between the peptide and doxorubicin enables the release of the drug in the cytosol, as confirmed by drug-release studies performed in the presence of glutathione. Additionally, the cytotoxicity as well as the cellular uptake and distribution of this tripartite drug delivery system was investigated in MCF-7 and HT-29 cell lines.

Histologic safety margin in basal cell carcinoma of the eyelid: correlation with recurrence rate.

OBJECTIVE: To examine the correlation between the minimum histologic safety margin (HSM) and recurrence rate of periorbital basal cell carcinomas (BCC). DESIGN: Cohort study. PARTICIPANTS: One hundred one patients with 101 BCCs treated surgically between 1997 and 1999 at the eye hospital in Freiburg were enrolled in this study. Mean follow-up was 7 years (range, 104 days to 9.7 years). METHODS: The tumors' minimum HSM was measured retrospectively in photographs of hematoxylin and eosin-stained paraffin slides using the digital picture analysis system AnalySIS of Soft Imaging System Inc, and/or calculated according to the tumor-free section number. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. MAIN OUTCOME MEASURES: Histologic margins of solid and fibrous BCC and recurrence rate. RESULTS: Seven of the 101 patients experienced tumor recurrence (6.93%) after a mean follow-up of 34.7 months (range, 3-83) according to Kaplan-Meier analysis. The patients were assigned to 1 of 3 groups: (I) those without HSM (n = 11), 3 recurrences (27.27%); (II) those with HSM <0.2 mm (n = 18), 3 recurrences (16.67%); and (III) those with HSM >0.2 mm (n = 72), 1 recurrence (1.39%). The difference in recurrences between those groups with HSM and HSM = 0, as well as between the HSM <0.2 mm-group and HSM >0.2 mm-group were statistically significant (P = 0.01; P = 0.03). CONCLUSIONS: Extremely small HSMs are likely to prevent recurrences. At critical and visually easily accessible tumor sites (e.g., adjacent to the lacrimal puncta) a re-resection in solid BCCs with tumor-positive margins may not be mandatory, provided the surgical site is clinically inspected regularly. This conclusion does not apply to fibrous BCC.

Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy.

A major demand on immunotherapy is the direct interference with specific immune cells in vivo. In contrast to antibody-engineered nanoparticles to control dendritic cells function, targeting of T cells for biomedical applications still remains an obstacle as they disclose reduced endocytic activities. Here, by coupling the cytokine interleukin-2 (IL-2) to the surface of hydroxyethyl starch nanocapsules, we demonstrated a direct and specifc T cell targeting in vitro and in vivo by IL-2 receptor-mediated internalization. For this purpose, defined amounts of azide-functionalized IL-2 were linked to alkyne-functionalized hydroxyethyl starch nanocapsules via copper-free click reactions. In combination with validated quantification of the surface-linked IL-2 with anthracen azide, this method allowed for engineering IL-2-functionalized nanocapsules for an efficient targeting of human and murine T cell populations with various IL-2 receptor affinities. This nanocapsule-mediated technique is a promising strategy for T cell-based immunotherapies and may be translated to other cytokine-related targeting systems.

Functionalized polystyrene nanoparticles trigger human dendritic cell maturation resulting in enhanced CD4+ T cell activation.

Nanoparticles (NP) represent a promising tool for biomedical applications. Here, sulfonate- and phosphonate-functionalized polystyrene NP are analyzed for their interaction with human monocyte-derived dendritic cells (DC). Immature dendritic cells (iDC) display a higher time- and dose-dependent uptake of functionalized polystyrene NP compared to mature dendritic cells (mDC). Notably, NP induce an enhanced maturation of iDC but not of mDC (upregulation of stimulatory molecules and cytokines). NP-triggered maturation results in a significantly enhanced T cell stimulatory capacity (increased CD4(+) T cell proliferation and IFN-γ production), indicating a shift to a pronounced Th1 response. Immunomodulatory properties of NP may be a useful strategy for strengthening the efficacy of NP-based approaches in immunotherapy.