Intrinsic signaling pathways modulate targeted protein degradation.

Targeted protein degradation is a groundbreaking modality in drug discovery; however, the regulatory mechanisms are still not fully understood. Here, we identify cellular signaling pathways that modulate the targeted degradation of the anticancer target BRD4 and related neosubstrates BRD2/3 and CDK9 induced by CRL2- or CRL4 -based PROTACs. The chemicals identified as degradation enhancers include inhibitors of cellular signaling pathways such as poly-ADP ribosylation (PARG inhibitor PDD00017273), unfolded protein response (PERK inhibitor GSK2606414), and protein stabilization (HSP90 inhibitor luminespib).

Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

Aims/introduction: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics.

Materials And Methods: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c).

Wettability evaluation of hydrophilic-hydrophobic nanohybrid silica thin films using picoliter water droplets.

Water wettabilities of hydrophilic-hydrophobic nanohybrid silica thin films were investigated by contact angles of extremely small size water droplets (8 pL-1 nL) and using an antifog analyzer. The nanohybrid silica was prepared via our unique sol-gel process based on tetramethoxysilane (TMOS) and metyltrimethoxysilane (MTMS) with a hydroxyacetone catalyst, in which hydrophilic portion was generated from hydrolysis of microporous silica prepared from TMOS and hydrophobic portion was directly prepared from MTMS. The sizes of these domains were controlled by the growth time of the microporous precursor polymers in solution.

Attainment of the Japanese Society for Dialysis Therapy guidelines for the management of secondary hyperparathyroidism in chronic hemodialysis patients in our clinic.

The treatment according to the Japanese Society for Dialysis Therapy guidelines was performed in 189 patients on maintenance dialysis in our clinic. The mean age of the patients was 64.9 years and the mean dialysis period was 6.