Catalyst Controlled Divergent C4/C8 Site-Selective C–H Arylation of Isoquinolones

The catalyst-controlled C4/C8 site-selective C–H arylation of isoquinolones using aryliodonium salts as the coupling partners was developed. The C4-selective arylation was successfully achieved via an electrophilic palladation pathway. A completely different selectivity pattern was observed using an Ir­(III) catalytic system, which resulted in C–C bond formation exclusively at the C8 position. The isoquinolone scaffold can be conveniently equipped with various aryl substituents at either the C4 or C8 position

Bilirubin Nanoparticle-Assisted Delivery of a Small Molecule-Drug Conjugate for Targeted Cancer Therapy

Despite growing interest in targeted cancer therapy with small molecule drug conjugates (SMDCs), the short half-life of these conjugates in blood associated with their small size has limited their efficacy in cancer therapy. In this report, we propose a new approach for improving the antitumor efficacy of SMDCs based on nanoparticle-assisted delivery. Ideally, a nanoparticle-based delivery vehicle would prolong the half-life of an SMDC in blood and then release it in response to stimuli in the tumor microenvironment (TME). In this study, PEGylated bilirubin-based nanoparticles (BRNPs) were chosen as an appropriate delivery carrier because of their ability to release drugs in response to TME-associated reactive oxygen species (ROS) through rapid particle disruption. As a model SMDC, ACUPA-SN38 was synthesized by linking the prostate-specific membrane antigen (PSMA)-targeting ligand, ACUPA, to the chemotherapeutic agent, SN38. ACUPA-SN38 was loaded into BRNPs using a film-formation and rehydration method. The resulting ACUPA-SN38@BRNPs exhibited ROS-mediated particle disruption and rapid release of the SMDC, resulting in greater cytotoxicity toward PSMA-overexpressing prostate cancer cells (LNCaP) than toward ROS-unresponsive ACUPA-SN38@Liposomes. In a pharmacokinetic study, the circulation time of ACUPA-SN38@BRNPs in blood was prolonged by approximately 2-fold compared with that of the SMDC-based micellar nanoparticles. Finally, ACUPA-SN38@BRNPs showed greater antitumor efficacy in a PSMA-overexpressing human prostate xenograft tumor model than SN38@BRNPs or the SMDC alone. Collectively, these findings suggest that BRNPs are a viable delivery carrier option for various cancer-targeting SMDCs that suffer from short circulation half-life and limited therapeutic efficacy

Efficient and Stable CsPbBr₃ Quantum-Dot Powders Passivated and Encapsulated with a Mixed Silicon Nitride and Silicon Oxide Inorganic Polymer Matrix

Despite the excellent optical features of fully inorganic cesium lead halide (CsPbX₃) perovskite quantum dots (PeQDs), their unstable nature has limited their use in various optoelectronic devices. To mitigate the instability issues of PeQDs, we demonstrate the roles of dual-silicon nitride and silicon oxide ligands of the polysilazane (PSZ) inorganic polymer to passivate the surface defects and form a barrier layer coated onto green CsPbBr₃ QDs to maintain the high photoluminescence quantum yield (PLQY) and improve the environmental stability. The mixed SiN_<i>x</i>/SiN_<i>x</i>O_<i>y</i>/SiO_<i>y</i> passivated and encapsulated CsPbBr₃/PSZ core/shell composite can be prepared by a simple hydrolysis reaction involving the addition of adding PSZ as a precursor and a slight amount of water into a colloidal CsPbBr₃ QD solution. The degree of the moisture-induced hydrolysis reaction of PSZ can affect the compositional ratio of SiN_<i>x</i>, SiN_<i>x</i>O_<i>y</i>, and SiO_<i>y</i> liganded to the surfaces of the CsPbBr₃ QDs to optimize the PLQY and the stability of CsPbBr₃/PSZ core/shell composite, which shows a high PLQY (∼81.7%) with improved thermal, photo, air, and humidity stability as well under coarse conditions where the performance of CsPbBr₃ QDs typically deteriorate. To evaluate the suitability of the application of the CsPbBr₃/PSZ powder to down-converted white-light-emitting diodes (DC-WLEDs) as the backlight of a liquid crystal display (LCD), we fabricated an on-package type of tricolor-WLED by mixing the as-synthesized green CsPbBr₃/PSZ composite powder with red K₂SiF₆:Mn⁴⁺ phosphor powder and a poly­(methyl methacrylate)-encapsulating binder and coating this mixed paste onto a cup-type blue LED. The fabricated WLED show high luminous efficacy of 138.6 lm/W (EQE = 51.4%) and a wide color gamut of 128% and 111% without and with color filters, respectively, at a correlated color temperature of 6762 K

Destroying Deep Lung Tumor Tissue through Lung-Selective Accumulation and by Activation of Caveolin Uptake Channels Using a Specific Width of Carbon Nanodrug

The main difficulty with current anticancer nanotherapeutics comes from the low efficiency of tumor targeting. Although many strategies have been investigated, including cancer-specific antibody conjugation, lung tumors remain one of the invulnerable types of cancer that must be overcome in the near future. Meanwhile, despite their advantageous physiochemical properties, carbon nanotube structures are not considered safe medical drug delivery agents, but are considered a hazardous source that may cause pulmonary toxicity. However, high-aspect-ratio (width vs. length) nanostructures can be used as very efficient drug delivery agents due to their lung tissue accumulation property. Furthermore, selection of a specific width of the carbon nanostructures can activate additional caveolin uptake channels in cancer cells, thereby maximizing internalization of the nanodrug. The present study aimed to evaluate the therapeutic potential of carbon nanotube-based nanodrugs having various widths (10–30 nm, 60–100 nm, and 125–150 nm) as a delivery agent to treat lung tumors. The results of the present study provided evidence that both lung tissue accumulation (passive targeting) and caveolin-assisted uptake (active targeting) can simultaneously contribute to the destruction of lung tumor tissues of carbon nanotube

Additional file 1: of Systematic identification of an integrative network module during senescence from time-series gene expression

The experimental results with MSC senescence dataset (DOC 708 kb

Study of Perovskite QD Down-Converted LEDs and Six-Color White LEDs for Future Displays with Excellent Color Performance

A narrow-emitting red, green, and blue (RGB) perovskite quantum dot (PeQD)-based tricolored display system can widen the color gamut over the National Television System Committee (NTSC) to 120%, but this value is misleading with regard to the color perception of cyan and yellow reproduced in the narrow RGB spectra. We propose that a PeQD-based six-color display system can reproduce true-to-life spectral distributions with high fidelity, widen the color gamut, and close the cyan and yellow gap in the RGB tricolored display by adding cyan (Cy), yellowish green (Yg), and orange colors (Or). In this study, we demonstrated pure-colored CsPbX₃ (X = Cl, Br, I, or their halide mixtures; Cl/Br and Br/I) PeQD-based monochromatic down-converted light-emitting diodes (DC-LED) for the first time, and we incorporated PeQDs with UV-curable binders and long-wavelength-pass-dichroic filters (LPDFs). CsPbX₃ PeQD-based pure Cy-, G-, Yg-, Or-, R-emitting monochromatic DC-LED provide luminous efficacy (LE) values of 81, 184, 79, 80, and 35 lm/W, respectively, at 20 mA. We also confirmed the suitability and the possibility of access to future color-by-blue backlights for field-sequential-color liquid crystal displays, using six-color multipackage white LEDs, as well as future six-colored light-emitting devices with high vision and color performance. The fabricated six-color multipackage white LEDs exhibited an appropriate LE (62 lm/W at total 120 mA), excellent color qualities (color rendering index (CRI) = 96, special CRI for red (<i>R</i>₉) = 97) at a correlated color temperature (CCT) of 6500 K, and a wide color gamut covering the NTSC up to 145% in the 1931 Commission International de l’Eclairage (CIE) color coordinates space

TC1(C8orf4) Regulates Hematopoietic Stem/Progenitor Cells and Hematopoiesis

<div><p>Hematopoiesis is a complex process requiring multiple regulators for hematopoietic stem/progenitor cells (HSPC) and differentiation to multi-lineage blood cells. TC1(C8orf4) is implicated in cancers, hematological malignancies and inflammatory activation. Here, we report that Tc1 regulates hematopoiesis in mice. Myeloid and lymphoid cells are increased markedly in peripheral blood of <i>Tc1</i>–deleted mice compared to wild type controls. Red blood cells are small-sized but increased in number. The bone marrow of <i>Tc1</i>^−/− mice is normocellular histologically. However, Lin⁻Sca-1⁺c-Kit⁺ (LSK) cells are expanded in <i>Tc1</i>^−/− mice compared to wild type controls. The expanded population mostly consists of CD150⁻CD48⁺ cells, suggesting the expansion of lineage-restricted hematopoietic progenitor cells. Colony forming units (CFU) are increased in <i>Tc1</i>^−/− mice bone marrow cells compared to controls. In wild type mice bone marrow, Tc1 is expressed in a limited population of HSPC but not in differentiated cells. Major myeloid transcriptional regulators such as Pu.1 and Cebpα are not up-regulated in <i>Tc1</i>^−/− mice bone marrow. Our findings indicate that TC1 is a novel hematopoietic regulator. The mechanisms of TC1-dependent HSPC regulation and lineage determination are unknown.</p></div

Additional file 1 of Lupeol alleviates atopic dermatitis-like skin inflammation in 2,4-dinitrochlorobenzene/Dermatophagoides farinae extract-induced mice

Supplementary Material

Additional file 2: of Systematic identification of an integrative network module during senescence from time-series gene expression

List of the identified common network information (XLSX 30 kb

<i>Tc1</i>-targeting strategy.

<p>Restriction maps of wild type allele, targeting construct and targeted allele. The probe used for Southern blot analysis is indicated. The top line represents the structure and partial restriction map from wild-type allele of <i>Tc1</i>. The middle and low lines depict the targeting construct and predicted structure of targeted allele, respectively.</p