Activity

reactions, achieving hydrocyanation of conjugated alkenes in high enantioselectivity. These developments showcase the generality of our electrocatalytic strategy in the context of alkene functionalization reactions. We anticipate that electrocatalysis will play an increasingly important role in the ongoing renaissance of synthetic organic electrochemistry.We designed and synthesized 131I-labeled dendrimers modified with the LyP-1 peptide as a multifunctional platform for single-photon emission computed tomography (SPECT) imaging, radionuclide therapy, and antimetastasis therapy of cancer. The multifunctional platform was constructed by modifying amine-terminated generation 5 poly(amidoamine) dendrimers with 33.1 LyP-1 peptide and 9.2 3-(4′-hydroxyphenyl)propionic acid-OSu (HPAO), followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I via the HPAO moieties. The LyP-1-modified dendrimers showed favorable cytocompatibility in the studied concentration range of 0.1-10 μM for 24 h and could be labeled by 131I with satisfactory radiochemical purity (>99%) and stability (>90% even at 16 h). The 131I-labeled LyP-1-modified dendrimers were capable of being utilized as a diagnostic probe for SPECT imaging and as a therapeutic agent for radionuclide therapy and antimetastasis of cancer cells in vitro and in a subcutaneous tumor model in vivo. #link# Based on analyses of the tumor microenvironment, the antitumor and antimetastasis effects could be because of the reduced levels of the molecular markers associated with proliferation and metastasis, improved local hypoxia, and increased apoptosis rate. The developed 131I-labeled dendrimeric nanodevice may hold great promise to be used as a nanotheranostic platform for cancer diagnosis and therapy.Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate “caged” versions of these neuromodulators (CyHQ-O-DA and CyHQ-sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ-O-DA mediated the light activation of dopamine-1 (D1) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ-O-DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.Mesoporous silica nanoparticles (MSNs) have seen a fast development as drug delivery carriers thanks to their tunable porosity and high loading capacity. The employ of MSNs in biomedical applications requires a good understanding of their degradation behavior both to control drug release and to assess possible toxicity issues on human health. In this work, we study mesoporous silica degradation in biologically relevant conditions through in situ ellipsometry on model mesoporous nanoparticle or continuous thin films, in buffer solution and in media containing proteins. In order to shed light on the structure/dissolution relationship, we performed dissolution experiments far from soluble silicate species saturation. Via a complete decorrelation of dissolution and diffusion contributions, we proved unambiguously that surface area of silica vectors is the main parameter influencing dissolution kinetics, while thermal treatment and open mesoporous network architecture have a minor impact. As a logical consequence of our dissolution model, we proved that the dissolution lag-time can be promoted by selective blocking of the mesopores that limits the access to the mesoporous internal surface. This study was broadened by studying the impact of the organosilanes in the silica structure, of the presence of residual structuring agents, and of the chemical composition of the dissolution medium. The presence of albumin at blood concentration was found affecting drastically the dissolution kinetics of the mesoporous structure, acting as a diffusion barrier. Globally, we could identify the main factors affecting mesoporous silica materials degradation and proved that we can tune their structure and composition for adjusting dissolution kinetics in order to achieve efficient drug delivery.Yin Yang 1 is a human transcription factor that controls a number of genes and takes part in the regulation of cell cycle, proliferation, differentiation, and neuronal development. selleck chemicals is composed of an N-terminal intrinsically disordered fragment and a C-terminal domain responsible for binding to DNA, composed of four zinc fingers. Recently, various alterations in the Yin Yang 1’s DNA binding domain were linked with an unexplained intellectual disability named Gabriele-de Vries syndrome. In this paper, a repetitively occurring substitution of aspartate-380 for tyrosine was analyzed to assess its impact on Yin Yang 1’s structure and DNA binding. The substitution was found to affect Yin Yang 1’s secondary and tertiary structure to a limited extent and to impair the specificity of its interaction with DNA.BACKGROUND Long-term data are scarce regarding the efficacy of extended repair for acute type A aortic dissection (ATAAD) using frozen elephant trunk and total arch replacement (FET + TAR) technique. We seek to evaluate our single-center experience with the FET + TAR technique in patients with ATAAD, focusing on early and long-term survival and reoperation. METHODS The early and long-term outcomes of FET + TAR were analyzed for 518 patients with ATAAD operated on between April 2003 and December 2012. Mean age 46.2 ± 10.5 years and 426 were male (82.2%). Malperfusion occurred in 66 (12.7%) and Marfan syndrome (MFS) in 51 (9.8%). Bentall procedure was performed in 153 (29.5%), aortic cusp resuspension in 82 (15.8%), root remodeling (uni- or bi-Yacoub) in 19 (3.7%), ascending aortic replacement in 22 (4.2%) and extra-anatomic bypass in 15 patients (2.9%). The times of cardiopulmonary bypass time (CPB), cross-clamp and selective antegrade cerebral perfusion were 201 ± 50, 112 ± 34, and 26 ± 10 minutes, respectively.