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A series of cobalt complexes with bis(imino)pyridine derivatives featuring unsymmetrical substitution with bulky groups has been synthesized and characterized. The molecular structures of two representatives have been determined by the single-crystal X-ray diffraction study, revealing distorted tetrahedral geometry with different degrees of steric hindrance imparted by the two inequivalent aryl groups attached to the imine nitrogen atoms. On activation with either MAO or MMAO, these complexes display high activity toward ethylene polymerization, reaching 8.71 × 10

Human catechol-O-methyltransferase (hCOMT) is considered a therapeutic target due to its crucial roles in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs. There are nevertheless few safe and effective COMT inhibitors and there lacks a diversity in structure. To discover novel safe and effective hCOMT inhibitors from herbal products, in this study, 53 herbal products were collected and their inhibitory effects against hCOMT were investigated. Among them, Scutellariae radix (SR) displayed the most potent inhibitory effect on hCOMT with an IC50 value of 0.75 μg mL−1. To further determine specific chemicals as COMT inhibitors, an affinity ultrafiltration coupled with liquid chromatography-mass spectrometry method was developed and successfully applied to identify COMT inhibitors from SR extract. The results demonstrated that scutellarein 2, baicalein 9 and oroxylin A 12 were potent COMT inhibitors, showing a high binding index (>3) and very low IC50 values (32.9 ± 3.43 nM, 37.3 ± 4.32 nM and 18.3 ± 2.96 nM). The results of inhibition kinetics assays and docking simulations showed that compounds 2, 9 and 12 were potent competitive inhibitors against COMT-mediated 3-BTD methylation, and they could stably bind to the active site of COMT. These findings suggested that affinity ultrafiltration allows a rapid identification of natural COMT inhibitors from a complex plant extract matrix. Furthermore, scutellarein 2, baicalein 9 and oroxylin A 12 are potent inhibitors of hCOMT in SR, which could be used as promising lead compounds to develop more efficacious non-nitrocatechol COMT inhibitors for biomedical applications.

DNA cytosine modifications are important epigenetic modifications in gene regulation and pathogenesis. DNA hydrolysis followed by HPLC-MS/MS is the gold standard in DNA modification quantification. In particular, it is the only sensitive and accurate method for low abundance modifications, such as 5-carboxylcytosine (5caC). Here, we report the discovery of the nuclease resistance property of 5caC to snake venom phosphodiesterase I (PDE1), a 3' to 5' exonuclease commonly used in several DNA hydrolysis protocols. We conducted a systematic evaluation of six commonly used hydrolysis protocols and found that all protocols that use PDE1 underestimate the level of 5caC. Finally, we identified the best method for cytosine modification quantification of biological samples, which leads to an over 10-fold higher amount of 5caC being detected compared with other methods. Our results highlight that caution should be taken when choosing a DNA hydrolysis protocol to quantify certain DNA modifications.

Six new ent-kaurane diterpenoids, isodonrubescins A–F (1–6), together with twenty-five known ent-kaurane diterpenoids (7–31), a known ent-atisane diterpenoid (32), and two known ent-abietane diterpenoids (33–34), were isolated from Isodon rubescens. Their structures were established by means of extensive MS and NMR data analysis. Among the all isolates, compound 7 was found in a natural product for the first time, and ent-atisane diterpenoid was discovered from I. rubescens in Hubei Province, P. R. China for the first time. Furthermore, all the isolated compounds were tested for their NO production inhibitory activity in LPS stimulated RAW264.7 cells. Compounds 7–9, 12, 13, 16, and 17 displayed NO production inhibitory activities with IC50 values ranging from 1.36 to 18.25 μM, respectively.

Inflammation constitutes an important component of non-alcoholic fatty liver disease. STAT3 is a direct target of inflammatory cytokines, but also mediates glycolipid metabolism in the liver. As a potent inhibitor of STAT3, the effect of Nifuroxazide (Nifu) on glycolipid metabolism in liver has not been reported. In this study, we used palmitic acid (PA)-induced HepG2 cells to examine the expression of inflammatory factors and apoptosis-related proteins and the content of triglyceride (TG), total cholesterol (TC), and glycogen. The expression of hepatic lipogenic proteins (ACCα, SREBP-1c, FAS), gluconeogenesis enzymes (PEPCK, G6Pase, and IRS2), the IL-6/STAT3/SOCS3 inflammatory axis, and the insulin signaling pathway was determined. Our study shows that Nifu significantly improves lipid metabolism disorders in the PA-induced HepG2 cells, whereas, it remarkably reduced intracellular free fatty acid (FFA), TG, and TC content, suppressed lipid synthesis, and increased lipid decomposition. Our results also showed that Nifu significantly improved dysregulated glucose metabolism in the PA-treated HepG2 cells, increased glycogen content, and inhibited gluconeogenesis. Further research indicated that Nifu markedly inhibited activation of the IL-6/STAT3/SOCS3 signaling pathway. Finally, due to anti-inflammatory stress, Nifu enhanced insulin signaling in the PA-induced HepG2 cells. Therefore, Nifu can improve glucose and lipid metabolism in the PA-induced HepG2 cells, which provides new evidence that Nifu has a positive effect on PA-induced cellular hepatic steatosis and improves glucose metabolism in HepG2 cells, providing a new perspective for studying drug treatment of glucose and lipid metabolism disorders.

Human catechol

A family of unsymmetrical 2-(2,4-bis(di(4-methoxyphenyl)methyl)-6-MeC

Benzene dye intermediate (BDI) 4-methoxy-2-nitroaniline (4M2NA) wastewater has caused significant environmental concern due to its strong toxicity and potential carcinogenic effects. Reports concerning the degradation of 4M2NA by advanced oxidation process are limited. In this study, 4M2NA degradation by Fenton oxidation has been studied to obtain more insights into the reaction mechanism involved in the oxidation of 4M2NA. Results showed that when the 4M2NA (100 mg L−1) was completely decomposed, the TOC removal efficiency was only 30.70–31.54%, suggesting that some by-products highly recalcitrant to the Fenton oxidation were produced. UV-Vis spectra analysis based on Gauss peak fitting, HPLC analysis combined with two-dimensional correlation spectroscopy and GC-MS detection were carried out to clarify the degradation mechanism and pathway of 4M2NA. A total of nineteen reaction intermediates were identified and two possible degradation pathways were illustrated. Theoretical TOC calculated based on the concentration of oxalic acid, acetic acid, formic acid, and 4M2NA in the degradation process was nearly 94.41–97.11% of the measured TOC, indicating that the oxalic acid, acetic acid and formic acid were the main products. Finally, the predominant degradation pathway was proposed. These results could provide significant information to better understand the degradation mechanism of 4M2NA.

Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL−1 of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.

We investigated the anti-neuroinflammatory activity and mechanism of glibenclamide, sulfonylurea receptor 1 (Sur1) antagonist, against LPS-induced microglial activation in vitro. BV2 microglia cells were exposed to LPS (100 ng mL−1). iNOS and COX-2 levels, proinflammatory cytokine mRNA expression, and the p38/MAPK signaling pathway were analyzed by RT-PCR and Western blotting. Pretreatment with glibenclamide (2.5, 10, and 40 μM) inhibited the LPS-induced overexpression of iNOS and COX-2 in BV2 microglia cells. Blocking Sur1 reduced intracellular reactive oxygen species (ROS) levels. Glibenclamide dose-dependently (2.5, 10 μM) decreased LPS-induced over-expression of TNF-α, IL-6, and IL-1β, and alleviated the intracellular calcium accumulation in LPS-treated BV2 microglia cells. Moreover, glibenclamide diminished the LPS-induced phosphorylation of p38/MAPK, SB203580, a selective p38/MAPK inhibitor, significantly potentiated glibenclamide-caused inhibition of the expression of iNOS and COX-2 in LPS-exposed BV2 cells. Glibenclamide–Sur1 antagonist exerts anti-inflammatory activity in murine microglia in vitro by inhibiting the p38/MAPK signaling pathways and proinflammatory responses. Glibenclamide may be developed as a novel agent for suppressing inflammatory responses in the central nervous system.

A poly(vinylidene fluoride) grafted polystyrene (PVDF-g-PS) solvent resistant nanofiltration membrane (SRNF) was designed and prepared. A PVDF porous membrane was firstly prepared by phase inversion in a non-solvent bath. PS was grafted onto the PVDF porous membrane to form a PVDF-g-PS nanofiltration membrane. The influence of grafting degree and concentration of the casting solution on the morphology of the membranes was investigated by Scanning Electron Microscopy (SEM). Separation performance was evaluated by filtering three different dyes: Rose Bengal (RB), Acid Fuchsin (AF) and Bromothymol Blue (BTB) using water, ethanol and IPA as solvents. The RB retentions of the PVDF-g-PS20 membrane in water, ethanol and IPA could reach 92.3%, 91.2% and 90% respectively. The RB retentions in water, ethanol and IPA of the PVDF-g-PS20 membrane were all higher than 90%, both in aqueous and organic solvent systems. All the results showed that the graft porous membrane was very promising for SRNF.

Twenty C-7 modified flavonoids were designed and synthesized. Biological evaluation in vitro indicated that compounds generated by SYBYL-X with high scores also showed good inhibitory activities against TyrRS. Compounds containing the nargenin core exhibit better enzyme inhibitory activities than other flavonoid cores, with (S)-5-hydroxy-4′-hydroxy-7-(2-morpholino-2-oxoethoxy)-2,3-dihydroflavone (b1) being the most active (IC50 = 0.10 ± 0.01 μM) in all assayed compounds. All compounds were also assayed for antimicrobial activities against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and b1 also displayed excellent activity, showing 6-fold more potent than the marketed antibiotic ciprofloxacin. In comparison with Gram-positive organism, all these derivatives exhibited better activity against Gram-negative organism, and did not displayed significant differences between the two assayed Gram-negative strains (E. coli ATCC 8739 and P. aeruginosa ATCC 9027).

Six new

Germanium and phosphorus co-doped carbon nanotubes (Ge–P-CNTs) were prepared by a simple and scalable approach. The morphology and structure of the Ge–P-CNTs was characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The ORR electrocatalytic performances were evaluated by exchange current density, reaction pathway selectivity, on-set potential, kinetic current density and H2O2 yields from rotating ring-disk electrode (RRDE) measurements, indicating that the co-doped GeP2C2, GeP3C and GeP4 + PC3 microstructures in Ge–P-CNTs are crucial to improving the ORR catalytic performance. In fact, the electrochemical performance enhancement results from the synergistic effects by the appropriate proportion of Ge and P atoms. The ORR catalytic synergistic effect has also been verified by calculating the work function based on density functional theory (DFT). Because of these outstanding features, it is expected that the Ge–P-CNTs materials will be a very suitable catalyst for fuel cells and metal–air batteries.

Procalcitonin (PCT) is a potentially specific early marker of bloodstream infection and sepsis. In this work, we report, for the first time, the development of a fluorescence-based immunochromatographic strip test (IST) which employs Eu(DBM)3phen-containing nanoparticles as reporters for the detection of PCT in human serum. Experimental results demonstrate that the developed IST has an excellent ability for rapid (15 min), sensitive (0.05 ng mL−1) and quantitative analysis of PCT, and the assay results are comparable to which of the conventional enzyme-linked immunosorbent assay (ELISA). These results suggest that the developed assay could be utilized for point-of-care detection of PCT.

Treatment of the mixed amidinate-amido-lithium, [PhN(CH2)3NC(Ph)NSiMe3]2Li4·2Et2O, with group IV metal chlorides yields the corresponding compounds 3–5. Their structures were confirmed by X-ray diffraction analysis, showing a distorted octahedral geometry. The catalytic behaviors of compounds 3–5 were investigated in the presence of MAO as a co-catalyst. Compounds 3 and 4 showed high activities for ethylene polymerization.

The novel propeller type compound, 2,4,6-tri(anthracen-9-yl)-1,3,5-triazine (TAT) with C3 symmetry was synthesized by using 9-anthryl lithium with 1,3,5-trichlorotriazine or 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of palladium catalyst in 22–48% yield. Another two propeller-like compounds, 2-(anthracen-9-yl)-4,6-dimethoxy-1,3,5-triazine (3) and 2,4-di(anthracen-9-yl)-6-methoxy-1,3,5-triazine (4) were obtained at the same time. The propeller type structures of TAT, 3 and 4 were confirmed by crystal analysis and theoretical calculations. The intramolecular C–C bond rotations between the anthryl groups and the triazine units in molecules TAT, 3 and 4 were regarded as the key factor to understand their spectroscopic behaviors in fluid medium and rigid solution.

CadR is a metal-binding protein first isolated from rhizobacterium Pseudomonas putida and specifically recognizes Cd2+. Escherichia coli cells surface engineered with CadR shows a high Cd2+ adsorption capacity of 19.5 μmol g−1 cells. The surface engineered E. coli cells also show higher tolerance towards cadmium contamination for up to 100 mM and could potentially be utilized as a bio-remediation treatment of cadmium contamination.

Covalent modifications of lactoferrin (LF) with epigallocatechin gallate (EGCG), chlorogenic acid (CA) and gallic acid (GA) were performed by adopting a free-radical grafting procedure in aqueous media. The resulting LF–polyphenol conjugates were characterized in terms of structural and functional properties. Results showed that the covalent binding amount into the LF molecule of EGCG, CA and GA was 68, 58 and 17 nmol mg−1, respectively. Covalent insertion of polyphenols into the LF molecule was verified by SDS-PAGE and MALDI-TOF-MS analysis, and in particular the molecular weight was increased from 84 011 Da (LF) to 85 906 Da (LF–CA conjugate). The circular dichroism and Fourier transform infrared spectroscopy analyses revealed that the content of α-helix increased and the contents of the remaining structures decreased, while the differential scanning calorimetry data indicated that the thermal stability of LF–polyphenol conjugates was enhanced after the modification. In addition, the antioxidant activity of LF–polyphenol conjugates was 0.23- to 2.10-fold (ABTS˙+ scavenging assay), and 0.04- to 2.19-fold (reducing power assay) higher than that of the control LF. Moreover, the covalent modification obviously changed the solubility and emulsifying properties of LF. The emulsifying properties of the LF–CA conjugate were better than those of the LF–EGCG and LF–GA conjugates.

A fluorescent assay for oxytetracycline (OTC) detection was presented based on an indirectly fluorescein-labelled aptamer probe, which was fabricated through the partial hybridization of an OTC long-chain aptamer with a FAM-labelled short-chain ssDNA (S1). Upon combination of the target OTC and its aptamer, S1 with quenched fluorescein was released from the probe to the graphene sheet freely. Subsequently, it was hybridized with the complementary ssDNA (C1) and escaped from the quencher graphene to the solution, resulting in the restoration of fluorescence. Benefiting from the labelling of S1 instead of the OTC aptamer directly, the restoration of fluorescence was independent of the long-chain aptamer, perfectly avoiding the negative effects of the intrinsically existing secondary structure. Together with the high affinity of the aptamer for its target, this assay exhibited excellent sensitivity and selectivity. The linear response for OTC was found to be 0.01–0.2 μM with a limit of quantitation of 0.01 μM. Furthermore, the feasibility of the developed assay in a fresh water system and a milk sample was verified through the recovery experiments using spiked samples. This achievement based on such an indirect labelling method is also expected to lay a foundation to realize effective analysis of small molecule pollutants in the environment, for which the specific aptamers are long-chain nucleotide sequences.

In the present study, a chlorogenic acid (CA)–lactoferrin (LF) conjugate prepared via alkali treatment was glycoslated with glucose (Glc) or polydextrose (PD) by the Maillard reaction. Formation of the covalent CA–LF–Glc/PD ternary conjugates was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and fluorescence analyses. The results showed that the grafting ratio between the CA–LF conjugate and Glc/PD was 40.50% for the CA–LF–Glc ternary conjugate and 11.72% for the CA–LF–PD ternary conjugate. Conjugating CA and Glc/PD onto LF changed the conformation of the protein, leading to a reduction in the α-helix content and an increase in the unordered structure. The thermal stability of the CA–LF conjugate was remarkably improved by the Maillard-type conjugation. According to AFM and DLS results, the ternary conjugates showed coarser structures and bigger particle sizes than their mixtures. The reducing power was increased from 206.91 μmol Trolox g−1 of CA–LF conjugate to 255.76 and 273.25 μmol Trolox g−1 sample, respectively, in CA–LF–Glc and CA–LF–PD ternary conjugates, indicating the glycosylation was an effective way to improve the antioxidant activity of the CA–LF conjugate. Moreover, the ternary conjugates were employed to encapsulate β-carotene as a model biologically active macromolecule, and they could enhance the physicochemical stability of β-carotene emulsions. This work presented a simple and general approach to the preparation of polyphenol–protein–polysaccharide conjugates that could be potentially employed as food-grade biomacromolecules in the food and pharmaceutical industries.

Novel assembly ultrathin PbBiO2Br nanosheets were synthesized by a facile solvothermal method. Structural characterizations indicate that the quaternary oxyhalide compound with a thickness of 8–9 nm can assemble into a hierarchical architecture. The e−–h+ pairs can separate efficiently in such a 2D structure, so that ultrathin PbBiO2Br nanosheets exhibit superior photocatalytic activity towards the degradation of organic contaminants under visible light.

A mild and convenient method for the condensation of ethyl diazoacetate (EDA) with aldehydes catalyzed by tert-BuOK under solvent-free conditions was developed. The corresponding α-diazo-β-hydroxy esters were further converted into β-ketoesters through palladium-catalyzed 1,2-hydrogen migration under neat conditions. The two-step transformation exemplifies a simple method for the efficient and green synthesis of β-ketoesters.

Pyramid-like GaN nanorods have been epitaxially grown on a [001]-oriented sapphire substrate. The as-synthesized GaN nanorods exhibited decent crystal quality and a strong luminescence in UV range.

The reaction of a Et2O solution of LiN(Cy)SiMe3 (Cy = cyclohexyl) with PhCN in the presence of the Lewis-base donor tetrahydrofuran (THF) or Me2N(CH2)2NMe2 (TMEDA) gave the THF- or TMEDA-solvated unsymmetrical aliphatic lithium benzamidinato compound [{PhC(NCy)(NSiMe3)}Li(THF)]2 (1) or [{PhC(NCy)(NSiMe3)}Li(TMEDA)] (2). Treatment of LiN(Cy)SiMe3 with PhCN in diethyl ether, and further with CuCl, MgBr2(THF)2 or ZrCl4 at a ratio of 1:1, 2:1 and 3:1 allowed the formation of novel metal complexes [{PhC(NCy)(NSiMe3)}Cu]2 (3), [{PhC(NCy)(NSiMe3)}2Mg(OEt2)] (4) and [{PhC(NCy)(NSiMe3)}3ZrCl] (5), respectively. The X-ray structures of complexes 1–4 are presented. Complex 5/MAO system allows the moderate polymerization of ethylene.