Additional file 1: of Preparation of Thermoresponsive Polymer Nanogels of Oligo(Ethylene Glycol) Diacrylate-Methacrylic Acid and Their Property Characterization

Figure S1. Illustration of the synthesis of thermoresponsive P(OEGDA-MAA). Figure S2. 1H NMR spectra of the monomers, oligo(ethylene glycol) diacrylate and methacrylic acid, used in the synthesis of thermoresponsive P(OEGDA-MAA). Figure S3. Potentiometric titration of thermoresponsive P(OEGDA-MAA). Figure S4. DLS diameter of P(OEGDA-MAA) hydrogel in water (1 mg/mL) at room temperature. Figure S5. Dependence of light transmittance on increasing temperature for aqueous dispersion of P(OEGDA-MAA) of different concentration (pH 1.0, 150 mM NaCl). The insets are the photos of the hydrogel at concentration of 1.0 mg/mL, taken at 25 and 60 °C, respectively. (PDF 167 kb

Sliding-mode-based robust output regulation and its application in PMSM servo systems

A robust output regulation of a control system aims at disturbance rejection and reference tracking in the presence of uncertainties. Technically, the control design contains two mechanisms: the compensation of nontrivial steady states caused by disturbances and/or reference trajectories and the stabilization of an error system relative to steady states. Feedforward compensation and the internal model (including an approximate integrator) are the two main techniques for the former, while the latter is on a case-by-case basis. This article studies an alternative sliding-mode-based approach that can address the two mechanisms simultaneously, thanks to the new concept of sliding-mode-based output zeroing manifold. This concept bridges the two widely studied areas: robust output regulation and sliding-mode control. The approach is also verified by its application in permanent magnet synchronous motor servo systems.</p

Synthesis of Acylhydroquinones through Visible-Light-Mediated Hydroacylation of Quinones with α‑Keto Acids

A mild and eco-friendly visible-light-induced protocol for the hydroacylation of quinones with α-keto acids has been developed. In the absence of any catalyst or additive, the decarboxylative hydroacylation proceeded smoothly under visible-light irradiation at room temperature. A wide range of quinones and α-keto acids were well-tolerated and afforded hydroacylation products up to 88% isolated yield. The reaction can be scaled up, and the induced groups are useful for further synthetic applications. Preliminarily, mechanistic studies indicated that photoactive quinones absorb visible light to facilitate the transformation

Geochronology and geochemistry of the late Neoproterozoic A-type granitic clasts in the southwestern Tarim Craton: petrogenesis and tectonic implications

<p>Due to sparse data for deciphering the late Neoproterozoic tectonic history, there is still considerable debate on whether long-lasting superplume-related or long-duration subduction-related dynamics dominated the Tarim Craton. In this contribution, our field investigations detail the late Neoproterozoic siliciclastic successions, and we report the first granitic conglomerates with zircon U–Pb ages of 753.9 ± 3.7 Ma in the SW Tarim Craton. Importantly, detrital zircons from the thick Cryogenian sedimentary basin also contain a major zircon population at ca. 750 Ma. Together with seismic data, this suggests a large ca. 750 Ma magmatic event in the SW Tarim Craton. Geochemically, the granitic clasts exhibit A-type granite features with high SiO₂, high alkali but extremely low K, high FeO^T/MgO and Ga/Al, and high high-field strength elements (HFSEs) (i.e. Nb, Hf, and Ta) with significant depletion in Rb, K, Sr, P, Eu, and Ti, and significant negative Eu anomalies (Eu* = 0.13–0.36), showing ferroan granite affinities. Including the detrital zircons, the ca. 750 Ma zircons have a large range of negative εHf(t) values (−19.46 to −1.16). Elemental and zircon Hf isotope data suggest that the granites were derived from Palaeoproterozoic reworked continental crust and are probably related to crustal thinning and extension. By comparison with previous studies, we conclude that Rodinia breakup was diachronous in the outer parts of the supercontinent.</p

Table1_A construction and comprehensive analysis of the immune-related core ceRNA network and infiltrating immune cells in peripheral arterial occlusive disease.DOCX

Background: Peripheral arterial occlusive disease (PAOD) is a peripheral artery disorder that increases with age and often leads to an elevated risk of cardiovascular events. The purposes of this study were to explore the underlying competing endogenous RNA (ceRNA)-related mechanism of PAOD and identify the corresponding immune cell infiltration patterns.Methods: An available gene expression profile (GSE57691 datasets) was downloaded from the GEO database. Differentially expressed (DE) mRNAs and lncRNAs were screened between 9 PAOD and 10 control samples. Then, the lncRNA-miRNA-mRNA ceRNA network was constructed on the basis of the interactions generated from the miRcode, TargetScan, miRDB, and miRTarBase databases. The functional enrichment and protein–protein interaction analyses of mRNAs in the ceRNA network were performed. Immune-related core mRNAs were screened out through the Venn method. The compositional patterns of the 22 types of immune cell fraction in PAOD were estimated through the CIBERSORT algorithm. The final ceRNA network and immune infiltration were validated using clinical tissue samples. Finally, the correlation between immune cells and mRNAs in the final ceRNA network was analyzed.Results: Totally, 67 DE_lncRNAs and 1197 DE_mRNAs were identified, of which 130 DE_mRNAs (91 downregulated and 39 upregulated) were lncRNA-related. The gene ontology enrichment analysis showed that those down- and upregulated genes were involved in dephosphorylation and regulation of translation, respectively. The final immune-related core ceRNA network included one lncRNA (LINC00221), two miRNAs (miR-17-5p and miR-20b-5p), and one mRNA (CREB1). Meanwhile, we found that monocytes and M1 macrophages were the main immune cell subpopulations in PAOD. After verification, these predictions were consistent with experimental results. Moreover, CREB1 was positively correlated with naive B cells (R = 0.55, p = 0.035) and monocytes (R = 0.52, p = 0.049) and negatively correlated with M1 macrophages (R = −0.72, p = 0.004), resting mast cells (R = −0.66, p = 0.009), memory B cells (R = −0.55, p = 0.035), and plasma cells (R = −0.52, p = 0.047).Conclusion: In general, we proposed that the immune-related core ceRNA network (LINC00221, miR-17-5p, miR-20b-5p, and CREB1) and infiltrating immune cells (monocytes and M1 macrophages) could help further explore the molecular mechanisms of PAOD.</p

Synthesis of Fused Metallaaromatics via Intramolecular C–H Activation of Thiophenes

A convenient method to synthesize novel fused ruthena-/osmacycles via intramolecular C–H activation of thiophenes has been developed. Treatment of HCCCH­(OH)­R (R = 2-thienyl) with RuCl₂(PPh₃)₃ or OsCl₂(PPh₃)₃ afforded hydroxyl-coordinated metal vinyl compounds <b>1</b> and <b>4</b>. Reaction of <b>1</b>/<b>4</b> with acid produced metal alkenylcarbene complexes <b>3</b>/<b>5</b>, which can further convert to the corresponding fused metallaaromatics <b>2</b>/<b>7</b> via the C­(sp²)–H activation of the thienyl groups. <b>7</b> is the first example of a metallabenzyne with a fused five-membered ring (thiophene ring). These fused metallaaromatics are thermally stable both in solution and in the solid state in air. The X-ray crystallographic analysis, NMR spectra, and DFT calculations all suggest that these fused metallaaromatics (<b>2</b> and <b>7</b>) show aromatic character

Synthesis of Fused Metallaaromatics via Intramolecular C–H Activation of Thiophenes

A convenient method to synthesize novel fused ruthena-/osmacycles via intramolecular C–H activation of thiophenes has been developed. Treatment of HCCCH­(OH)­R (R = 2-thienyl) with RuCl₂(PPh₃)₃ or OsCl₂(PPh₃)₃ afforded hydroxyl-coordinated metal vinyl compounds <b>1</b> and <b>4</b>. Reaction of <b>1</b>/<b>4</b> with acid produced metal alkenylcarbene complexes <b>3</b>/<b>5</b>, which can further convert to the corresponding fused metallaaromatics <b>2</b>/<b>7</b> via the C­(sp²)–H activation of the thienyl groups. <b>7</b> is the first example of a metallabenzyne with a fused five-membered ring (thiophene ring). These fused metallaaromatics are thermally stable both in solution and in the solid state in air. The X-ray crystallographic analysis, NMR spectra, and DFT calculations all suggest that these fused metallaaromatics (<b>2</b> and <b>7</b>) show aromatic character

Tricyclic GyrB/ParE (TriBE) Inhibitors: A New Class of Broad-Spectrum Dual-Targeting Antibacterial Agents

<div><p>Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.</p> </div

Optimization of inhibitor scaffolds.

<p>For the fragment hit and inhibitor candidates <b>C1</b>, <b>C2</b>, <b>C3</b> and <b>C4,</b> identical cutaway views of solvent accessible surface representations of the active-site pockets of <i>E. faecalis</i> GyrB from the crystal structures of complexes of the inhibitors with the 24 kDa N-terminal fragment of GyrB from <i>E. faecalis</i> GyrB are shown. The bound inhibitors are drawn with green bonds, the conserved ATP-binding aspartate is drawn with blue bonds and the structural water molecule that plays a key role in substrate binding in GyrB and ParE is shown as a red sphere. Potential hydrogen-bonds between the inhibitors, aspartate and water molecule are depicted as dotted lines. Optimization of the pyrrolopyrimidine scaffold led to inhibitors like <b>C1</b> with good enzyme potency but only moderate Gram-negative antibacterial activity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084409#B16" target="_blank">16</a>]. Expansion of the bicyclic pyrrolopyrimidine scaffold to a tricyclic pyrimidoindole scaffold <b>(C2)</b> fills an interior lipophilic pocket and offers superior optimization vectors to improve enzyme potency. Subsequent elaboration of the tricyclic scaffold with a fluorine atom at R₆ and an aminomethyl moiety at R₈ dramatically improved inhibitor potency and ligand efficiency. The 6-fluoro-<i>N-</i>methyl-9<i>H</i>-pyrimido[4,5-<i>b</i>]indol-8-amine scaffold quantitatively fills the lipophilic interior sub-pockets of the GyrB/ParE active-sites and adds a new hydrogen-bond. <b>C3</b> and <b>C4</b> demonstrate sub-nanomolar enzyme potency versus GyrB and ParE enzymes from a broad range of Gram-positive and Gram-negative pathogens; inhibition constants (<i>K</i>_i values) are shown for a representative enzyme panel that includes the full length GyrB and ParE enzymes from <i>E. faecalis</i>, Francisella tularensis, and <i>E. coli</i>. </p

Selectivity of TriBE inhibitors versus eukaryotic ATP-binding proteins.

<p>Inhibitory activities of <b>C3</b> and <b>C4</b> against a panel of divergent human kinases, and human topoisomerase II. All compounds were assayed at 10 μM concentration. Level of inhibition is color-coded as indicated in the inset.</p