Smart Combination of Cyclodextrin Polymer Host–Guest Recognition and Mg²⁺-Assistant Cyclic Cleavage Reaction for Sensitive Electrochemical Assay of Nucleic Acids

A novel enzyme-free electrochemical sensing strategy was proposed for sensitive monitoring of DNA and miRNA by smart combination of the cyclic cleavage reaction of Mg²⁺-dependent DNAzyme and the host–guest inclusion between ferrocene-labeled hairpin probe (H-1) and nitrogen-doped reduced graphene oxide/β-cyclodextrin polymer (NRGO/β-CDP) nanocomposites. The synthesized NRGO/β-CDP nanocomposites with high electrocatalytic activity and recognition capability were modified on the glassy carbon electrode to construct the sensing platform. Upon the hybridization reaction of subunit DNA in the loop region with target sequence, the active DNAzyme was liberated from the caged structure, which bound with H-1 to catalyze its cleavage in the presence of Mg²⁺ and triggered the target recycling amplification for the cleavage of a large number of H-1. Each cleaved H-1 was divided into two single-stranded oligonucleotides, leading to an obvious enhancement of peak current by the molecular recognition of β-CDP on the electrode. Thus, the constructed biosensor showed high sensitivity and selectivity for DNA and miRNA assays, with wide concentration ranges of 0.01–1000 and 0.05–500 pM and low detection limits of 3.2 and 18 fM, respectively. This developed sensing strategy may become a promising nucleic acid detection method in bioassays and clinical diagnosis

Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P‑gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challenge up to now. This study aims to on-demand remotely manipulate RNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein (P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly­[2-(<i>N</i>,<i>N</i>-dimethylaminoethyl)­methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable <i>o</i>-nitrobenzyl ester derivative-caged DOX is loaded into the inner pores of the PMSN. The PMSN is found to be effectively internalized by MDR cancer cells, and the release of the shRNA and DOX is demonstrated to be independently regulated by 405 and 365 nm light irradiations due to selectively cleaved coumarin and <i>o</i>-nitrobenzyl ester, resulting in enhanced drug retention, and finally bring out optimized and significantly improved chemotherapeutic effects both in vitro and in vivo for MDR cancer treatment, which might hold extensive application prospects in MDR cancer treatment in future

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

27 décembre 19431943/12/27 (A44,N15612)

Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples

<p>Interindividual variability in the epigenome has gained tremendous attention for its potential in pathophysiological investigation, disease diagnosis, and evaluation of clinical intervention. DNA methylation is the most studied epigenetic mark in epigenome-wide association studies (EWAS) as it can be detected from limited starting material. Infinium 450K methylation array is the most popular platform for high-throughput profiling of this mark in clinical samples, as it is cost-effective and requires small amounts of DNA. However, this method suffers from low genome coverage and errors introduced by probe cross-hybridization. Whole-genome bisulfite sequencing can overcome these limitations but elevates the costs tremendously. Methyl-Capture Sequencing (MC Seq) is an attractive intermediate solution to increase the methylome coverage in large sample sets. Here we first demonstrate that MC Seq can be employed using DNA amounts comparable to the amounts used for Infinium 450K. Second, to provide guidance when choosing between the 2 platforms for EWAS, we evaluate and compare MC Seq and Infinium 450K in terms of coverage, technical variation, and concordance of methylation calls in clinical samples. Last, since the focus in EWAS is to study interindividual variation, we demonstrate the utility of MC Seq in studying interindividual variation in subjects from different ethnicities.</p

Additional file 3: of Choice of surrogate tissue influences neonatal EWAS findings

Tab-delimited file containing DNA methylation values for 295 cord blood samples, 239,560 CpGs. (TXT 613902 kb

Additional file 1: of Choice of surrogate tissue influences neonatal EWAS findings

Supplementary tables and figures. (PDF 2720 kb

Additional file 2: of Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome

Compressed folder containing a tab-delimited file with methylation values for 987 samples, 174,211 CpGs. (GZ 560574 kb