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

Table_1_Usefulness of continuous glucose monitoring of blood glucose control in patients with diabetes undergoing hemodialysis: A pilot study.docx

BackgroundBlood glucose stability has recently been considered important in the treatment of diabetes. Both hypoglycemia and hyperglycemia can frequently occur in patients with diabetes undergoing hemodialysis. This study aimed to determine the usefulness of continuous glucose monitoring (CGM) for glycemic control and glycemic variability stabilization in patients with diabetes undergoing hemodialysis.Materials and methodsEighteen patients aged ≥18 years with type 1 or 2 diabetes and ≥3 months on hemodialysis at the Eulji Medical Center, Daejeon, Republic of Korea between November 2021 and May 2022 were included. Patients underwent 7 days CGM twice: the baseline study period (T0) and the follow-up study period (T1), at a 12 weeks interval. Physicians modified the treatment strategy according to the T0 results, and then patients conducted T1. As indicators of glycemic control, the mean glucose levels, glycated hemoglobin A1c (HbA1c), and time in range were measured. As indicators of glycemic variability, standard deviation (SD) and % coefficient variation (%CV) were measured.ResultsData from 18 patients were analyzed. The mean glucose levels, HbA1c, SD, and %CV improved in T1 compared to T0 (P ConclusionContinuous glucose monitoring could be a promising tool for individualizing treatment strategies in patients with diabetes undergoing hemodialysis.</p

sj-docx-1-fap-10.1177_09593535231184719 - Supplemental material for Examining ideology and agency within intensive motherhood literature

Supplemental material, sj-docx-1-fap-10.1177_09593535231184719 for Examining ideology and agency within intensive motherhood literature by Maya Autret, Brad van Eeden-Moorefield, Soyoung Lee and Lyndal Khaw in Feminism & Psychology</p

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

DataSheet1_Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects.pdf

AST-001 is an L-isomer of serine that has protective effects on neurological disorders. This study aimed to establish a population pharmacokinetic (PK) model of AST-001 in healthy Korean to further propose a fixed-dose regimen in pediatrics. The model was constructed using 648 plasma concentrations from 24 healthy subjects, including baseline endogenous levels during 24 h and concentrations after a single dose of 10, 20, and 30 g of AST-001. For the simulation, an empirical allometric power model was applied to the apparent clearance and volume of distribution with body weight. The PK characteristics of AST-001 after oral administration were well described by a two-compartment model with zero-order absorption and linear elimination. The endogenous production of AST-001 was well explained by continuous zero-order production at a rate of 0.287 g/h. The simulation results suggested that 2 g, 4 g, 7 g, 10 g, and 14 g twice-daily regimens for the respective groups of 10–14 kg, 15–24 kg, 25–37 kg, 38–51 kg, 52–60 kg were adequate to achieve sufficient exposure to AST-001. The current population PK model well described both observed endogenous production and exogenous administration of AST-001 in healthy subjects. Using the allometric scaling approach, we suggested an optimal fixed-dose regimen with five weight ranges in pediatrics for the upcoming phase 2 trial.</p

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

Hematopoietic lineage- and pluripotent stem cell-regulators.

<p>(A) qPCR analysis for Pu.1 expression in total Lin⁻ cells (left) or sorted Lin⁻Sca-1⁺ cell fraction (right) of <i>Tc1^−/−</i> and wild type mice bone marrow. Data represent mean ± s.d. of 6 male, 8 week-old <i>Tc1</i>^−/− mice, and 6 sex- and age-matched control mice over 3 independent experiments for the total Lin⁻ cell assay, and 10 male, 8 to 9 week-old <i>Tc1</i>^−/− mice, and 10 sex- and age-matched control mice over 2 independent experiments for the sorted-Lin⁻Sca-1⁺ fraction assay, respectively. (B–E) qPCR analysis for Cebpα (B), Gata-1 (C), c-Myc and Ccnd1 (D), and Klf4 (E) expression in Lin⁻ cells. Data represent mean ± s.d. of 6 male, 9 week-old <i>Tc1</i>^−/− mice, and 6 sex- and age-matched control mice over 3 independent experiments. **<i>p</i><0.01; ***<i>p</i><0.001.</p

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

Tc1 expression in bone marrow cells.

<p>(A) Confocal microscopic images of Tc1-positive cells in wild type mice bone marrow. DNA staining is done using Hoechst 33342. Relatively weak cytoplasmic staining (arrows) is present in HSC-like primitive cells (upper panel). Large progenitor cells show strong cytoplasmic staining and faint nuclear staining (arrows) (lower panel). Scale bars represent 10 µm. (B) Representative flow cytometric analysis for Tc1 and Sca-1 in total Lin⁻ bone marrow cells (upper panels), and gated cells according to CD150/CD48 profiles (lower panels).</p