First-Principles Studies on the Efficient Photoluminescent Iridium(III) Complexes with C^∧NN Ligands

The electronic structures and photophysical properties of several homoleptic iridium complexes IrL3 with C∧NN ligands, including 1 (L = 3,6-diphenylpyridazine), 2 (L = 1,4-diphenylphthalazine), 3 (L = 3-phenyl-5H-indeno[1,2-c]pyridazine), and 4 (L = 3-phenylbenzo[h]cinnoline), are investigated using the density functional method. The comparison between the calculated results of the four complexes shows that the assumed complex 4 may possess higher photoluminescent quantum efficiency than complexes 1–3 and is the potential candidate to be an efficient green-emitting material. The photophysical properties of the assumed complex 3 can be comparable to that of experimentally found complex 1. For 1 and 3, the emission energies are nearly the same, consistent with their similar HOMO–LUMO energy gaps. Their emission characters are also similar and mainly dominated by one ligand. For 4 and the experimentally found complex 2, although they have similar HOMO–LUMO energy gaps, and their luminescent nature is nearly the same and dominated by the three ligands, the emission spectrum of 4 is blue-shifted as compared to that of 2

TSCs display thymus identity.

<p>(a) RNAs were extracted from TSC2, 1307-6.1.7 and mTEC8 cells, and transcripts were detected by RT-PCR for the expression of indicated genes. (b) Immunoblot analysis of CBX4, delta Np63, TAp63 and DNMT3a in extracts of TSC2, mTEC1 and mTEC8 cells. GAPDH was used as a loading control.</p

Established TSC cells express markers of non-hematopoietic stem cells.

<p>(a) Representative spindle-like morphology of TSC clone 2 established from C57BL/6 E14.5 thymus repeated subculture and limiting dilution cloning.(b) Flow cytometric analysis of WT TSC with antibodies to Sca-1, CD29, CD44, CD45, CD73, CD105, CD133, CD80, MHC class I and II.</p

Established Thymic Epithelial Progenitor/Stem Cell-Like Cell Lines Differentiate into Mature Thymic Epithelial Cells and Support T Cell Development

<div><p>Common thymic epithelial progenitor/stem cells (TEPCs) differentiate into cortical and medullary thymic epithelial cells (TECs), which are required for the development and selection of thymocytes. Mature TEC lines have been widely established. However, the establishment of TEPC lines is rarely reported. Here we describe the establishment of thymic epithelial stomal cell lines, named TSCs, from fetal thymus. TSCs express some of the markers present on tissue progenitor/stem cells such as Sca-1. Gene expression profiling verifies the thymic identity of TSCs. RANK stimulation of these cells induces expression of autoimmune regulator (Aire) and Aire-dependent tissue-restricted antigens (TRAs) in TSCs <i>in vitro</i>. TSCs could be differentiated into medullary thymic epithelial cell-like cells with exogenously expressed NF-κB subunits RelB and p52. Importantly, upon transplantation under the kidney capsules of nude mice, TSCs are able to differentiate into mature TEC-like cells that can support some limited development of T cells <i>in vivo</i>. These findings suggest that the TSC lines we established bear some characteristics of TEPC cells and are able to differentiate into functional TEC-like cells <i>in vitro</i> and <i>in vivo</i>. The cloned TEPC-like cell lines may provide useful tools to study the differentiation of mature TEC cells from precursors.</p> </div

TSCs differentiate into Aire-expressing TECs <i>in vitro</i>.

<p>(a) Immunoblot analysis of Aire, delta Np63, DNMT3a, c-Myc, p52 and. RelB in extracts of TSCs stably overexpressed with p52 and RelB for 11 days. (b) Immunofluorescence analysis for UEA-1 and K8 in TSCs stably overexpressed with p52 and RelB for 11 days.</p

TSCs express cell surface markers of TEPCs.

<p>(a) Flow cytometry analysis of WT TSC line with anti-K5, anti-K8, anti-MTS24, anti-MTS10, anti-CDC205, anti-EpCAM1, 3T3 cells as a negative control for anti-CD205 and anti-EpCAM1. (b) Immunostaining of WT TSC line and 1307-6.1.7 cells with anti-K5 (green), anti-K8 (blue), anti-EpCAM1 (green), anti-Aire (red). (c) Immunostaining of WT TSC line with anti-K8 (blue) and anti-pan-cytokeratin (green).</p

TSCs express Aire and tissue-restricted antigens after stimulation.

<p>(a) RT-PCR analysis for the expression of <i>aire</i>, aire-dependent <i>i-fabp</i> and aire-independent <i>crp</i> and <i>col2</i> in non-cloned WT TSC cells and cloned TSC cells (TSC2) treated with agonistic antibody to RANK (50 ng/ml) for 4 days. <i>Tubulin</i> was used as loading control. The data represented three individual experiments with similar results. (b) Quantitative PCR of mRNA expression for <i>aire</i>, <i>spt1</i> and <i>crp</i> in TSC cells treated with agonistic antibody to RANK (50 ng/ml) for 4 days. <i>Tubulin</i> was used as a reference for data normalization. Bar graphs showed means ± standard deviations of at least three independent experiments. * p < 0.05. (c and d) Immunoblot analysis of Aire in extracts of 1307-6.1.7 cell line or TSCs treated with agonistic mAb to RANK and/or agonistic mAb to LTβ receptor, TSA (0.3 µM), AZA (0.3 µM) (LTβ represents mAb to LTβ receptor; RANK represents agonistic antibody to RANK). Tubulin was used as a loading control. Data represent three independent experiments with similar results.</p

TSCs can partially support the T lymphocytes differentiation in vivo.

<p>(a) Flow cytometric analysis of thymocyte subset distribution in thymus-like tumors and corresponding spleens of nude mice 7 weeks after engraftment with re-aggregates containing thymocytes with TSCs or MEFs as defined by CD4, CD8, B220, and CD3. (b) Gross anatomy of kidneys engrafted 7 weeks earlier with MEFs (as negative control), wild type E14.5 thymus (as positive control), re-aggregates of 1×10⁴ TSCs plus MEFs or 2×10⁵ TSCs plus MEFs. (c) Flow cytometric analysis of lymphocyte subset distribution in thymus-like tumors and corresponding spleens of nude mice grafted with re-aggregates containing 1×10⁴ TSCs plus MEFs or 2×10⁵ TSCs plus MEFs as defined by CD4, CD8, B220, and CD3. (d) Frequencies of T cell populations (D3⁺ cells, CD4⁺ cells and CD8⁺ cells) in spleens of nude mice engrafted with TSC cells or MEF cells. * p < 0.05. Data represented the means ± standard deviations of three independent experiments with at least three mice per group. (e) Immunostaining of the reconstituted thymus-like tumor with anti-K8, anti-K14 and UEA-1-biotin. All data represent three individual experiments with similar results.</p

DUCNP@Mn–MOF/FOE as a Highly Selective and Bioavailable Drug Delivery System for Synergistic Combination Cancer Therapy

Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal–organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn–MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn–MOF and the unique optical features of DUCNPs granted the DUCNP@Mn–MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn–MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn–MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn–MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors