Modular Approach to Bio-Based Poly(enol ether)s with Tunable Thermal Properties and Degradability

Biomass-derived polymer materials are emerging as sustainable and low-carbon footprint alternatives to the current petroleum-based commodity plastics. In the past decade, the ring-opening metathesis polymerization (ROMP) technique has been widely used for the polymerization of cyclic olefin monomers derived from biorenewable resources, giving rise to a diverse set of biobased polymer materials. However, most synthetic biobased polymers made by ROMP are nondegradable because of their all-carbon backbones. Herein, we present a modular synthetic strategy to acid-degradable poly(enol ether)s via ring-opening metathesis copolymerization of biorenewable oxanorbornenes and 3,4-dihydropyran (DHP). 1H NMR analysis reveals that the percentage of DHP units in the resulting copolymers gradually increases as the feed ratio of DHP to oxanorbornene increases. The composition of the copolymers plays a pivotal role in governing their thermal properties. Thermogravimetric analysis shows that an increasing percentage of DHP results in a decrease in the decomposition temperatures, suggesting that the incorporation of enol ether groups in the polymer backbone reduces the thermal stability of the copolymers. Moreover, a wide range of glass transition temperatures (16–165 °C) can be achieved by tuning the copolymer composition and the oxanorbornene structure. Critically, all of the poly(enol ether)s developed in this study are degradable under mildly acidic conditions. A higher incorporation of DHP in the copolymer leads to enhanced degradability, as evidenced by smaller final degradation products. Altogether, this study provides a facile approach for synthesizing biorenewable and degradable polymer materials with highly tunable thermal properties desired for their potential industrial applications

Unsymmetric Dendrimers Containing a Single Ureidopyrimidine Unit: Generation-Dependent Dimerization via Hydrogen Bonding

A new series of unsymmetric Newkome-type dendrimers have been prepared and characterized. These dendrimers contain a single ureidopyrimidine residue covalently attached to their apical positions. In low polarity solvents, the first and second generation dendrimers form highly stable dimers via hydrogen bonding of their AADD ureidopyrimidine units, whereas the third generation dendrimer dimerizes to a very low extent

Metabolism of 4-Aminopiperidine Drugs by Cytochrome P450s: Molecular and Quantum Mechanical Insights into Drug Design

4-Aminopiperidines are a variety of therapeutic agents that are extensively metabolized by cytochrome P450s with CYP3A4 as a major isoform catalyzing their N-dealkylation reaction. However, its catalytic mechanism has not been fully elucidated in a molecular interaction level. Here, we applied theoretical approaches including the molecular mechanics-based docking to study the binding patterns and quantum mechanics-based reactivity calculations. They were supported by the experimental human liver microsomal clearance and P450 isoform phenotyping data. Our results herein suggested that the molecular interactions between substrates and CYP3A4 active site residues are essential for the N-dealkylation of 4-aminopiperidines. We also found that the serine 119 residue of CYP3A4 may serve as a key hydrogen-bonding partner to interact with the 4-amino groups of the studied drugs. The reactivity of the side chain α-carbon hydrogens drives the direction of catalysis as well. As a result, structure-based drug design approaches look promising to guide drug discovery programs into the optimized drug metabolism space

Data_Sheet_1_Causal association between depression and intracranial aneurysms: a bidirectional two-sample Mendelian randomization study.pdf

BackgroundAlthough observational studies have suggested a bidirectional relation between depression and intracranial aneurysms (IAs), their causal relations remain unclear. Thus we aimed to assess the causal association between depression and IAs.MethodsWe conducted a bidirectional two-sample Mendelian randomization (MR) study using summary-level data from publicly available genome-wide association studies of depression (n = 500,199), IAs (n = 79,429), unruptured intracranial aneurysm (uIA) (n = 74,004), and subarachnoid hemorrhage (SAH) (n = 77,074). MR analyses included the inverse-variance weighted (IVW) method as the primary analytic, plus weighted-median, simple mode, weighted mode, MR-Egger, and MR PRESSO.ResultsGenetically predicted depression was strongly positively related to IAs (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.19–2.39, p = 0.003), uIA (OR = 1.96, 95% CI 1.06–3.64, p = 0.032), and SAH (OR = 1.73, 95% CI 1.14–2.61, p = 0.009). Reverse MR analyses showed that while genetically predicted uIA was positively related to depression (OR = 1.02, 95% CI 1.00–1.05, p = 0.044), no causal relations were observed for either IAs or SAH for depression.ConclusionOur findings provide evidence of a causal effect of depression on IAs, uIA, and SAH. For the reverse MR analyses, we found a causal impact of uIA on depression, but no causal influence of either IAs or SAH for depression.</p

Description of the parameters of sebnif and their default values.

<p>Description of the parameters of sebnif and their default values.</p

Redox Active, Hybrid Dendrimers Containing Fréchet- and Newkome-Type Blocks

A new series of dendrimers was prepared by covalently attaching a Newkome dendron, a Fréchet dendron, and a redox active, aminoferrocene group to a central triazine core. Growth of the Newkome dendron has a more pronounced effect on the half-wave potential for the one-electron oxidation of the ferrocene residue than growth of the Fréchet dendron. All dendrimers show reversible or quasireversible voltammetric behavior at scan rates in the range 0.10−2.0 V s-1

Sebnif: An Integrated Bioinformatics Pipeline for the Identification of Novel Large Intergenic Noncoding RNAs (lincRNAs) - Application in Human Skeletal Muscle Cells

<div><p><i>Ab initio</i> assembly of transcriptome sequencing data has been widely used to identify large intergenic non-coding RNAs (lincRNAs), a novel class of gene regulators involved in many biological processes. To differentiate real lincRNA transcripts from thousands of assembly artifacts, a series of filtering steps such as filters of transcript length, expression level and coding potential, need to be applied. However, an easy-to-use and publicly available bioinformatics pipeline that integrates these filters is not yet available. Hence, we implemented sebnif, an integrative bioinformatics pipeline to facilitate the discovery of <i>bona fide</i> novel lincRNAs that are suitable for further functional characterization. Specifically, sebnif is the only pipeline that implements an algorithm for identifying high-quality single-exonic lincRNAs that were often omitted in many studies. To demonstrate the usage of sebnif, we applied it on a real biological RNA-seq dataset from Human Skeletal Muscle Cells (HSkMC) and built a novel lincRNA catalog containing 917 highly reliable lincRNAs. Sebnif is available at <a href="http://sunlab.lihs.cuhk.edu.hk/sebnif/" target="_blank">http://sunlab.lihs.cuhk.edu.hk/sebnif/</a>.</p></div

Efficient Electronic Communication between Two Identical Ferrocene Centers in a Hydrogen-Bonded Dimer

A novel ferrocene derivative that contains a donor−donor−acceptor−acceptor (DDAA) hydrogen bonding motif forms highly stable, noncovalent dimers in chloroform and dichloromethane solutions. Its voltammetric behavior and the observation of an intervalence charge-transfer band reveal that the two equivalent ferrocene centers in the hydrogen-bonded dimer exhibit a surprisingly efficient level of electronic communication

Snapshots of sebnif web server.

<p>(A) The data upload page. All the parameters of sebnif could be specified by the users through this page. (B) The result page showing the report of novel lincRNAs identified in Human Skeletal Muscle Cells. The final list of novel lincRNAs in standard GFF format and the iSeeRNA noncoding score for each transcript can be downloaded directly; statistic numbers during the filtering steps and the FRFE Profile and STGE Profile generated by FRFE and STGE algorithms were also provided for users to evaluate the quality of the data.</p

A Simple Method Based on NMR Spectroscopy and Ultramicroelectrode Voltammetry for the Determination of the Number of Electrons in Faradaic Processes

A new, convenient method to determine the number of electrons (n) involved in a faradaic process was demonstrated using a series of four compounds containing two, three, four, and eight equivalent ferrocene centers. The method takes advantage of pulse gradient stimulated echo (PGSE) NMR spectroscopy to determine the diffusion coefficient (Do) of the electroactive species. The value of n is subsequently determined from the steady-state limiting current (iL) measured on a disk ultramicroelectrode