Pyrolyzing soft template-containing poly(ionic liquid) into hierarchical N-doped porous carbon for electroreduction of carbon dioxide

Heteroatom-doped carbon materials have demonstrated great potential in the electrochemical reduction reaction of CO2 (CO2RR) due to their versatile structure and function. However, rational structure control remains one challenge. In this work, we reported a unique carbon precursor of soft template-containing porous poly(ionic liquid) (PIL) that was directly synthesized via free-radical self-polymerization of ionic liquid monomer in a soft template route. Variation of the carbonization temperature in a direct pyrolysis process without any additive yielded a series of carbon materials with facile adjustable textural properties and N species. Significantly, the integration of soft-template in the PIL precursor led to the formation of hierarchical porous carbon material with a higher surface area and larger pore size than that from the template-free precursor. In CO2RR to CO, the champion catalyst gave a Faraday efficiency of 83.0% and a current density of 1.79 mA?cm?2 at ?0.9 V vs. reversible hydrogen electrode (vs. RHE). The abundant graphite N species and hierarchical pore structure, especially the unique hierarchical small-/ultra-micropores were revealed to enable better CO2RR performance

Characterization of Inter- and Intramolecular Interactions of Amyloid Fibrils by AFM-Based Single-Molecule Force Spectroscopy

Amyloids are fibrous protein aggregates defined by shared specific structural features. Abnormal accumulation of amyloid in organs leads to amyloidosis, which results in various neurodegenerative diseases. Atomic force microscopy (AFM) has proven to be an excellent tool investigating amyloids; it has been extensively utilized to characterize its morphology, assembly process, and mechanical properties. This review summarizes studies which applied AFM to detect the inter- and intramolecular interactions of amyloid fibrils and classified the influencing factors of amyloid’s nanomechanics in detail. The characteristics of amyloid fibrils driven by inter- and intramolecular interactions, including various morphologies of amyloid fibrils, self-assembly process, and the aggregating pathway, are described. Successful examples where AFM provided abundant information about inter- and intramolecular interactions of amyloid fibrils in different environments are presented. Direct force measurement of intra- or intermolecular interactions utilizing an AFM-based tool, single-molecular force spectroscopy (SMFS), is introduced. Some mechanical information such as elasticity, adhesiveness, and strength was obtained by stretching amyloid fibrils. This review helps researchers in understanding the mechanism of amyloidogenesis and exploring the properties of amyloid using AFM techniques

Sinomenine Suppresses Development of Hepatocellular Carcinoma Cells via Inhibiting MARCH1 and AMPK/STAT3 Signaling Pathway

Promotion of apoptosis and suppression of proliferation in tumor cells are popular strategies for developing anticancer drugs. Sinomenine (SIN), a plant-derived alkaloid, displays antitumor activity. However, the mechanism of action of SIN against hepatocellular carcinoma (HCC) is unclear. Herein, several molecular technologies, such as Western Blotting, qRT-PCR, flow cytometry, and gene knockdown were applied to explore the role and mechanism of action of SIN in the treatment of HCC. It was found that SIN arrests HCC cell cycle at G0/G1 phase, induces apoptosis, and suppresses proliferation of HCC cells via down-regulating the expression of membrane-associated RING-CH finger protein 1 (MARCH1). Moreover, SIN induces cell death and growth inhibition through AMPK/STAT3 signaling pathway. MARCH1 expression was silenced by siRNA to explore its involvement in the regulation of AMPK/STAT3 signaling pathway. Silencing MARCH1 caused down-regulation of phosphorylation of AMPK, STAT3 and decreased cell viability and function. Our results suggested that SIN inhibits proliferation and promotes apoptosis of HCC cells by MARCH1-mediated AMPK/STAT3 signaling pathway. This study provides new support for SIN as a clinical anticancer drug and illustrates that targeting MARCH1 could be a novel treatment strategy in developing anticancer therapeutics

Determination of banned pigment quinoline yellow in pastries by salting out assisted-high performance liquid chromatography

ObjectiveTo develop an analytical method for fast determination of banned pigment quinoline yellow in pastries by salting out assisted-high performance liquid chromatography.MethodsThe sample was extracted with 40% methanol-sodium chloride-water， precipitated with potassium ferrocyanide-zinc acetate solution， eluted with mobile phase of methanol-0.02 mol/L ammonium acetate solution， separated by X-Bridge C18 column v（150 mm×4.6 mm， 3.5 μm）， and detected with diode -array detector by external standard method.ResultsThe method showed good linearity （r>0.999） in the range of 0.4-40.0 μg/mL. The limit of detection （S/N=3） was 1.25 mg/kg and the limit of quantification （S/N=10） was 5.0 mg/kg. The average recoveries of three different concentrations level at 5.0， 10.0 and 50.0 mg/kg ranged from 89.18% to 110.10%， with relative standard deviation in the range of 2.83%-8.65%.ConclusionThe method was convenient， accurate and reproducible， and it was suitable for qualitative and quantitative analysis of banned pigment quinoline yellow in pastries

A cyclic peptidic serine protease inhibitor:increasing affinity by increasing peptide flexibility

Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase-type plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance analysis, and isothermal titration calorimetry and wild type and engineered variants of murine and human uPA. We demonstrate that Arg6 inserts into the S1 specificity pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending on changes in both P1 - S1 and exosite interactions. Site-directed mutagenesis showed that exosite interactions, while still supporting high affinity binding, differed substantially between different uPA variants. Surprisingly, high affinity binding was facilitated by Ala-substitution of Asp9 of the peptide, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and specificity of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden