Comparison of chimney technique and single-branched stent graft in a cohort of patients with type B aortic dissections: a retrospective cohort study.

Background: Single-branched stent grafts and the chimney technique are widely used in the treatment of type B aortic dissection (TBAD). The main objective of this study was to compare the outcomes of single-branched stent grafts and the chimney technique in the treatment of TBAD.

Methods: From January 2019 to December 2021, the retrospective cohort study contained a cohort of 91 patients with TBAD undergoing thoracic endovascular aortic repair (TEVAR) using single-branched stent grafts and the chimney technique.

Effectiveness of acceptance and commitment therapy in people with type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Acceptance and commitment therapy (ACT) is a psychotherapy technique, which promotes psychological flexibility and enables patients to change behaviors based on value-directed goals. However, the beneficial effects of ACT on glycemic control, self-care behaviors, acceptance of diabetes, self-efficacy, and psychological burden are still unclear among patients with type 2 diabetes mellitus (T2DM).

Aims: This study aimed to systematically synthesize scientific evidence to determine the effectiveness of ACT among patients with T2DM on glycemic control, self-care behaviors, acceptance of diabetes, self-efficacy, and psychological burden and identify the optimal characteristics of effective interventions.

Focus on Radiation Protection Improves Both Correct Behavior and Procedural Performance During Simulation-Based Training - A Randomized Comparison.

Background: To explore whether simulation-based endovascular training with focus on radiation safety could improve correct behavior without jeopardizing the learning of procedural skills.

Methods: Twenty-four residents without previous endovascular experience completed 10 clinical scenarios on a virtual-reality endovascular simulator with software for peripheral endovascular interventions. Participants were randomized to receive feedback (n = 12) or not (n = 12) on radiation protection (RP) performance after each case.

Discovery of Proline-Based p300/CBP Inhibitors Using DNA-Encoded Library Technology in Combination with High-Throughput Screening.

E1A binding protein (p300) and CREB binding protein (CBP) are two highly homologous and multidomain histone acetyltransferases. These two proteins are involved in many cellular processes by acting as coactivators of a large number of transcription factors. Dysregulation of p300/CBP has been found in a variety of cancers and other diseases, and inhibition has been shown to decrease Myc expression.

Selection Method of DNA-Encoded Chemical Library for Irreversible Covalent Binders.

Compounds acting through irreversible covalent interactions with therapeutic targets represent an important mechanism of drug action. Here I describe a selection method for DNA-encoded libraries to discover irreversible covalent binders to target proteins. This method offers an enabling tool in drug discovery for therapeutic targets that may be undruggable for reversible inhibition.

Label-free LC-MS based assay to characterize small molecule compound binding to cells.

Study of small molecule binding to live cells provides important information on the characterization of ligands pharmacologically. Here we developed and validated a label-free, liquid chromatography-mass spectrometry (LC-MS) based cell binding assay, using centrifugation to separate binders from non-binders. This assay was applied to various target classes, with particular emphasis on those for which protein-based binding assay can be difficult to achieve.

Orthogonality catastrophe and quantum speed limit for spin chain at finite temperature.

We present an interesting relationship between the orthogonality catastrophe (OC) and the quantum speed limit (QSL) for a spin chain with uniform nearest neighbour couplings perturbed by an impurity spin. We thoroughly study the catastrophic QSL that specifies a bound on the evolution time between the initial and final states and in this respect, link it to the emerging OC effect. It is found that the speed of state evolution subtle but fundamental, and the bound characterized by QSL shows the same behaviours as the OC effect in the thermodynamic limit.

The development of highly potent and selective small molecule correctors of Z α-antitrypsin misfolding.

α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors.

Development of a small molecule that corrects misfolding and increases secretion of Z α -antitrypsin.

Severe α -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α -antitrypsin. The lead compound blocks Z α -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α -antitrypsin threefold in an iPSC model of disease.

Predictors of primary patency after percutaneous balloon angioplasty for stenosis of Brescia-Cimino hemodialysis arteriovenous fistula.

Objective: Percutaneous transluminal balloon angioplasty (PTA) is recommended as the first choice to treat stenosis of Brescia-Cimino arteriovenous fistulas (B-C AVFs). The ability to predict which B-C AVFs are at risk for recurrent stenosis post-PTA would allow closer monitoring of patients, and possibly result in surgical intervention rather than repeat PTA. The purpose of this study was to identify predictive factors of primary patency after PTA in B-C AVFs.

DNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors.

We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane , had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead .

Oxidative Degradation of Dimethyl Phthalate (DMP) by the Fe(VI)/HO Process.

This study investigates the degradation of dimethyl phthalate (DMP) with hydrogen peroxide and ferrate (Fe(VI)) under various reaction conditions. The results showed that the optimum conditions for dimethyl phthalate removal from water were as follows: (a) pH 7.0 and (b) the original molar ratio of [Fe(VI)]/[HO]/[DMP] equal to 10:2:1.

DNA-Encoded Macrocyclic Peptide Library.

DNA-encoded library technology (ELT) is a cutting-edge enabling technology platform for drug discovery. Here we describe how to design and synthesize a macrocyclic DNA-encoded library; how to perform selection, sequencing, and data analysis to identify potential active peptides; and how to synthesize off-DNA peptides to confirm activity. This approach provides an effective tool for pharmaceutical research based on peptides.

Development of a Selection Method for Discovering Irreversible (Covalent) Binders from a DNA-Encoded Library.

DNA-encoded libraries (DELs) have been broadly applied to identify chemical probes for target validation and lead discovery. To date, the main application of the DEL platform has been the identification of reversible ligands using multiple rounds of affinity selection. Irreversible (covalent) inhibition offers a unique mechanism of action for drug discovery research.

MiR-140-3p is Involved in In-Stent Restenosis by Targeting C-Myb and BCL-2 in Peripheral Artery Disease.

Aim: In-Stent Restenosis (ISR) is the major reason for recurrent ischemia and amputation after endovascular treatment of Peripheral Artery Disease (PAD). Our previous study demonstrated that miR-140-3p is significantly down-regulated in PAD arteries. However, expression and function of miR-140-3p in ISR of human PAD are currently unclear.

Design and Application of a DNA-Encoded Macrocyclic Peptide Library.

A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 10 members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein.

Encoded library technology screening of hepatitis C virus NS4B yields a small-molecule compound series with in vitro replicon activity.

To identify novel antivirals to the hepatitis C virus (HCV) NS4B protein, we utilized encoded library technology (ELT), which enables purified proteins not amenable to standard biochemical screening methods to be tested against large combinatorial libraries in a short period of time. We tested NS4B against several DNA-encoded combinatorial libraries (DEL) and identified a single DEL feature that was subsequently progressed to off-DNA synthesis. The most active of the initial synthesized compounds had 50% inhibitory concentrations (IC50s) of 50 to 130 nM in a NS4B radioligand binding assay and 300 to 500 nM in an HCV replicon assay.

Involvement of MicroRNA-133a in the Development of Arteriosclerosis Obliterans of the Lower Extremities via RhoA Targeting.

Aim: RhoA is a critical factor in regulating the proliferation and migration of arterial smooth muscle cells (ASMCs) in patients with arteriosclerosis obliterans (ASO). RhoA is modulated by microRNA-133a (miR-133a) in cardiac myocytes and bronchial smooth muscle cells. However, the relationship between miR-133a and RhoA with respect to the onset of ASO in the lower extremities is uncertain.

Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.

Review article: high-throughput affinity-based technologies for small-molecule drug discovery.

High-throughput affinity-based technologies are rapidly growing in use as primary screening methods in drug discovery. In this review, their principles and applications are described and their impact on small-molecule drug discovery is evaluated. In general, these technologies can be divided into 2 groups: those that detect binding interactions by measuring changes to the protein target and those that detect bound compounds.

Use of cryopreserved transiently transfected cells in high-throughput pregnane X receptor transactivation assay.

Cryopreserved, transiently transfected HepG2 cells were compared to freshly transfected HepG2 cells for use in a pregnane X receptor (PXR) transactivation assay. Assay performance was similar for both cell preparations; however, cryopreserved cells demonstrated less interassay variation. Validation with drugs of different PXR activation potencies and efficacies demonstrated an excellent correlation (r(2) > 0.

Ethyl 2-[1-(4-chloro-phen-yl)-2,5-dioxo-1,2,3,5-tetra-hydro-imidazo[1',2':1,2]pyrimidino[5,4-b][1]benzofuran-3-yl]acetate.

The asymmetric unit of the title compound, C(22)H(16)ClN(3)O(5), consists of two crystallographically independent mol-ecules. The fused rings of the imidazo[1,2-a]benzo[4,5]furo[3,2-d]pyrimidine system are nearly coplanar and the chlorophenyl rings are twisted with respect to the two pyrimidinone ring systems by 71.00 (2) and 62.

3-(4-Chloro-phen-yl)-2-(diisopropyl-amino)-1-benzofuro[3,2-d]pyrimidin-4(3H)-one.

In the mol-ecule of the title compound, C(22)H(22)ClN(3)O(2), the three fused rings of the benzofuro[3,2-d]pyrimidine system are almost coplanar. This ring system is oriented with respect to the substituted benzene ring at a dihedral angle of 79.05 (3)°.

Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions.

The human transcription factor pregnane X receptor (hPXR) is a key regulator of enzyme expression, especially cytochrome P450 3A4 (CYP3A4). Due to the prominence of CYP3A4 in the elimination of many drugs, the development of high throughput in vitro models to predict the effect of drugs on CYP3A4 expression have increased. To better interpret and predict potential drug-drug interactions due to CYP3A4 enzyme induction, we evaluated 170 xenobiotics in a hPXR transactivation assay and compared these results to known clinical drug-drug interactions.

Correlation of high-throughput pregnane X receptor (PXR) transactivation and binding assays.

Pregnane X receptor (PXR) transactivation and binding assays have been developed into high-throughput assays, which are robust and reproducible (Z' > 0.5). For most compounds, there was a good correlation between the results of the transactivation and binding assays.