Search

Background: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB. Results: In this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated with MYC and the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript, FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data. FAM163A is abnormally transcribed by SEs, playing an important role in NB occurrence and development. Conclusion: GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB. [ABSTRACT FROM AUTHOR]

Different silicon sources caused diverse Al spatial distribution in HZSM-5, and this affected the hierarchical structures and catalytic performance of desilicated zeolites. After being treated with 0.1 M NaOH, HZSM-5 zeolites synthesized with silica sol exhibited relatively widely distributed mesopores and channels, and possessed highly improved propylene selectivity and activity stability. [ABSTRACT FROM AUTHOR]

A cyano-bridged Cu(i) organic framework based on [Cu6(CN)6]n was synthesized, in which cyano anions were generated in situ from the C–C bond cleavage of acetonitrile. The as-synthesized compound displays orange-red luminescence and is further proven to be a promising Fe3+ luminescent sensor with high selectivity and sensitivity. [ABSTRACT FROM AUTHOR]

Antibody therapy against antibiotics resistant Klebsiella pneumoniae infections represents a promising strategy, the success of which depends critically on the ability to identify appropriate antibody targets. Using a target-agnostic strategy, we recently discovered MrkA as a potential antibody target and vaccine antigen. Interestingly, the anti-MrkA monoclonal antibodies isolated through phage display and hybridoma platforms all recognize an overlapping epitope, which opens up important questions including whether monoclonal antibodies targeting different MrkA epitopes can be generated and if they possess different protective profiles. In this study we generated four anti-MrkA antibodies targeting different epitopes through phage library panning against recombinant MrkA protein. These anti-MrkA antibodies elicited strong in vitro and in vivo protections against a multi-drug resistant Klebsiella pneumoniae strain. Furthermore, mutational and epitope analysis suggest that the two cysteine residues may play essential roles in maintaining a MrkA structure that is highly compacted and exposes limited antibody binding/neutralizing epitopes. These results suggest the need for further in-depth understandings of the structure of MrkA, the role of MrkA in the pathogenesis of Klebsiella pneumoniae and the protective mechanism adopted by anti-MrkA antibodies to fully explore the potential of MrkA as an efficient therapeutic target and vaccine antigen. [ABSTRACT FROM AUTHOR]

Nitrogen-doped porous carbons were prepared using a facile method, with low-biotechnology fulvic acid potassium salts as a precursor. The prepared carbons had a high surface area (1623 m g) and good electrochemical properties, making them suitable electrode materials for supercapacitors. Nitrogen-doped porous carbons were tested as an electrode in both 6 M KOH aqueous solution and different concentrations KNO aqueous solution. The nitrogen-doped porous carbons with unique microstructure and nitrogen functionalities exhibited a capacitance of 235 F g in a 6 M KOH aqueous solution. Electrochemical investigation showed that the nitrogen-doped porous carbons exhibited a broad potential operational window in a 2.5 M KNO aqueous solution. Furthermore, a high capacitance retention of 88.1 % was achieved even after 5000 cycles at 1.7 V. Potassium nitrate solutions in a wide range of concentrations were also proven to be promising electrolytes for electrochemical capacitors because they are cheap, noncorrosive, electrochemically stable, and compatible to diverse current collectors. [ABSTRACT FROM AUTHOR]

Objectives: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren’s syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. Methods: BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. Results: Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. Conclusions: Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis. [ABSTRACT FROM AUTHOR]

The series of 2-(benzimidazolyl)-6-(1-aryliminoethyl)pyridylcobalt complexes was investigated by the DFT-QEq method to study the catalytic activity. The net charges on cobalt were evaluated at doublet and quartet states for the geometries, and correlated with the activities of these complex pre-catalysts experimentally observed toward ethylene polymerization. Their activities are consistent with the trend of the effective net charges of cobalt. Based on the presence of methyl-substituent on benzimidazolyl group or not, two families of cobalt complex pre-catalysts show similar tendency according to the substituents on phenyl-imino group. In other words, the substituents of methyl or proton on benzimidazolyl group made significant influence on the net charges of cobalt and their catalytic activities. However, the variation tendency between net charge and activity was similar within each class. Consistent with their iron analogous pre-catalysts, the charge variation of cobalt is in line with the charge values on N3 atom within the complexes. [ABSTRACT FROM AUTHOR]

By using a nitrone as the oxidizing directing group, a mild, practical and efficient rhodium(III)-catalyzed CH functionalization for the synthesis of indole derivatives has been developed. This reaction obviates the need for an external oxidant and shows good functional group tolerance. The employment of a sterically hindered Mes group on the carbon center of the nitrone is crucial to produce indoles in high yield. [ABSTRACT FROM AUTHOR]

Based on the analogous kagomé [Co3(imda)2] layers (imda=imidazole-4,5-dicarboxylate), a family of pillar-layered frameworks with the formula of [Co3(imda)2(L)3] ⋅(L) n ⋅ xH2O ( 1: L=pyrazine, n=0, x=8; 2: L=4,4′-bipyridine, n=1, x=8; 3: L=1,4-di(pyridin-4-yl)benzene, n=1, x=13; 4: L=4,4′-di(pyridin-4-yl)-1,1′-biphenyl, n=1, x=14) have been successfully synthesized by a hydrothermal/solvothermal method. Single-crystal structural analysis shows a significant increase in the interlayer distances synchronized with the extension of the pillar ligands, namely, 7.092(3) ( 1), 10.921(6) ( 2), 14.780(5) ( 3), and 19.165(4) Å ( 4). Despite the wrinkled kagomé layers in complexes 2- 4, comprehensive magnetic characterizations revealed weakening of interlayer magnetic interactions and an increase in the degree of frustration as the pillar ligand becomes longer from 1 to 4; this leads to characteristic magnetic ground states. For compound 4, which has the longest interlayer distance, the interlayer interaction is so weak that the magnetic properties observed within the range of temperature measured would correspond to the frustrated layer. [ABSTRACT FROM AUTHOR]

A novelprocedure for the cascade reaction of the addition of aGrignard reagent to a nitrile with a copper-catalyzed C–N bondcoupling was developed, which afforded various polysubstituted phenanthridinesin moderate to good yields with tolerance for a wide variety of substrates.Experimental data demonstrated that the reaction proceeded more likelythrough a Cu(I/III) catalytic cycle. [ABSTRACT FROM AUTHOR]

A crude extract of earthworms was used as an eco-friendly, environmentally benign, and easily accessible biocatalyst for various organic synthesis including the asymmetric direct aldol and Mannich reactions, Henry and Biginelli reactions, direct three-component aza-Diels-Alder reactions for the synthesis of isoquinuclidines, and domino reactions for the synthesis of coumarins. Most of these reactions have never before seen in nature, and moderate to good enantioselectivities in aldol and Mannich reactions were obtained with this earthworm catalyst. The products can be obtained in preparatively useful yields, and the procedure does not require any additional cofactors or special equipment. This work provides an example of a practical way to use sustainable catalysts from nature. [ABSTRACT FROM AUTHOR]

Abstract: A series new 2H-chromene-3-carboxamides (4a–4i) and S-2H-chromene-3-carbothioates (5j–5t) were synthesized and evaluated as monoamine oxidase A and B inhibitors. Among them, compound 5k (IC50 =0.21μM, IC50 iproniazid =7.65μM) showed the most activity and higher MAO-B selectivity (189.2-fold vs 1-fold) with respect to the MAO-A isoform. The need to clarify at a 3D level some important molecular aspects of discussed SAR, we undertaked a number of docking simulations to better assess. The steric effect was analyzed interms of both posing and scoring by investigating the nature of the binding interactions. The docking results of active compound 5k with hMAO-B complex indicated that conserved residue ILE 199 was important for ligand binding via Sigma–Pi interaction. [Copyright &y& Elsevier]

Abstract: A green chemistry strategy was developed to prepare two barium copper silicate pigments. Chinese purple BaCuSi2O6 and dark blue BaCu2Si2O7 are synthesized through mild hydrothermal treatment in narrow pH range. The compounds are characterized by powder X-ray diffraction techniques, infrared spectroscopy, X-ray photoelectron spectroscopy, energy dispersive spectroscopy, luminance and magnetic measurements. When excited by a visible laser, hydrothermally synthetic BaCuSi2O6 exhibits a broad emission in the near-infrared region with an excited state lifetime 6.4 μs due to the square-planar Cu2+ ions as the chromophores. Magnetic analysis of BaCuSi2O6 indicates the spin gapped antiferromagnetic property due the presence of the Cu–Cu dimers in the structure. BaCu2Si2O7 shows interesting quasi-one-dimensional antiferromagnetic property. [Copyright &y& Elsevier]

The TbIII compound [Tb(tci)(H2O)] n · n(DMF) ( 1) [H3tci = tri(2-carboxythyl)isocyanurate, DMF = N,N′-dimethylformamide] was synthesized by the reaction of terbium oxide, H3tci, and two drops of concentrated nitric acid in the presence of DMF and H2O. Single crystal X-ray analysis reveals that it features a three-dimensional (3D) framework based on infinite -Tb-COO-Tb- chains. The tci ligand in 1 links six different TbIII ions with its two carboxylate groups in μ2-κ1O;κ2O,O′ mode and the third in μ2-κ1O;κ1O′ mode. Thermal analysis reveals that it remains high thermal stability until 390 °C. Luminescence investigation shows that it emits characteristic green light of TbIII ions. [ABSTRACT FROM AUTHOR]

Hexahydropyridazine derivatives are synthesized by the entitled one-pot reaction sequence in high yields and good stereoselectivities. [ABSTRACT FROM AUTHOR]

Abstract: A series new 2H-chromene-3-carboxamide derivatives 4a–4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC50 iproniazid = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi–Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199. [Copyright &y& Elsevier]

5-Hydroxytryptophan (5-HTP), as the precursor of serotonin and melatonin in animals, can regulate mood, sleep, and behavior, which is widely used in pharmaceutical and health products industry. The enzymatic production of 5-hydroxytryptophan (5-HTP) from L-tryptophan (L-Trp) using tryptophan hydroxylase (TPH) show huge potential in application due to its advantages, such as mild reaction conditions, avoidance of protection/deprotection processes, excellent regioselectivity and considerable catalytic efficiency, compared with chemical synthesis and natural extraction. However, the low thermostability of TPH restricted its hydroxylation efficiency toward L-Trp. In this study, we aimed to improve the thermostability of TPH via semi-rational design guided by (folding free energy) ΔΔG fold calculation. After two rounds of evolution, two beneficial mutants M1 (S422V) and M30 (V275L/I412K) were obtained. Thermostability evaluation showed that M1 and M30 possessed 5.66-fold and 6.32-fold half-lives (t 1/2) at 37 °C, and 4.2 °C and 6.0 °C higher melting temperature (T m) than the WT, respectively. The mechanism behind thermostability improvement was elucidated with molecular dynamics simulation. Furthermore, biotransformation of 5-HTP from L-Trp was performed, M1 and M30 displayed 1.80-fold and 2.30-fold than that of WT, respectively. This work provides important insights into the thermostability enhancement of TPH and generate key mutants that could be robust candidates for practical production of 5-HTP. [ABSTRACT FROM AUTHOR]

An enhanced cleanup efficiency hydroxy functionalized-magnetic graphene oxide (EH-Mag-GO) fully covered porous nano-titania as coating has been designed and synthesized. It has been evaluated in PRiME (process, robustness, improvements, matrix effects, ease of use) pass-through cleanup procedure for human plasma prior to analysis of strychnine and brucine by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). Comparing with the magnetic carboxyl-graphene (Mag-CG), EH-Mag-GO is much more effective for the removal of matrix effect resulted from blood phospholipids. Under optimal conditions, the results show higher cleanup efficiency of EH-Mag-GO with recoveries in the range of 89.4%–118%. The limits of quantification (LOQs) for strychnine and brucine are 0.088 μg/L and 0.092 μg/L, respectively. Especially, the EH-Mag-GO is also evaluated for reuse (20 times) without much sacrifice of the cleanup efficiency. Validation results on linearity, specificity, accuracy and precision, as well as on the application to analysis of strychnine and brucine in six cases of suspected semen strychni poisoning demonstrate the applicability to clinical studies. [ABSTRACT FROM AUTHOR]

The title synthesis succeeds in high yields, with high diastereoselectivities and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

The binding ability of calix[3]carbazole ( 1 ) to metal ions has been investigated. It is found that 1 could serve as a non crown ether based, C 3 -symmetrical receptor for Ba 2 + via the marriage of cation–π and cation–dipole interactions. FID assay further illustrates that 1 could selectively interact with Ba 2 + over Pd 2 + . A possible binding mechanism for [1-Ba 2 + ] complex is proposed. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Rhodium(III)-Catalyzed Redox-Neutral C-H Annulation of Arylnitrones and Alkynes for the Synthesis of Indole Derivatives" by Z. Zhou and others, published in the "Advanced Synthesis & Catalysis " in 2015.

A huge number of indolylglycine derivatives (III) bearing a tetrasubstituted carbon center is efficiently synthesized camphorsulfonic acid catalyzed. Friedel--Crafts reaction of indoles (II) to ketimino esters (I). [ABSTRACT FROM AUTHOR]

Highlights: [•] Ni(OH)2·0.75H2O flowerlike architectures are synthesized by a hydrothermal process. [•] NiO flowerlike architectures are obtained by annealing Ni(OH)2·0.75H2O precursors. [•] NiO flowerlike architectures are constructured with ultrathin nanoflakes. [•] NiO flowerlike architectures show excellent adsorbent ability to Malachite green. [•] The adsorption capacity depends on structures of adsorbent and dye molecule. [ABSTRACT FROM AUTHOR]

Abstract: Sr2Fe1−0.5x Mo1−0.5x Ir x O6 ceramics (x=0, 0.02, 0.04, 0.06, and 0.08) have been synthesized and the structures, magnetic and transport properties have been investigated. X-ray diffraction reveals a very low solution limit of x=0.06, which however, results in significantly decreased Fe/Mo ordering degree and thus decreased magnetization value. On the other hand, the Curie temperature (T c) rises from 390K (x=0) to 400K (x=0.02) firstly, and then decreases to 360K and 340K for the compositions with x=0.04 and 0.06, respectively. In addition, the resistivity and magnetoresistance drop drastically with increasing x. The composition with x=0 shows semiconductor transport behavior in the temperature range of 10–400K, whereas the other compositions show a minimum resistivity around 120K. These results are discussed in detail by considering the effects of Ir substitution. [Copyright &y& Elsevier]

Abstract: Uniform spherical flowerlike SnO2 architectures with the diameters of 1.7–2.0μm were synthesized by a hydrothermal reaction of SnCl4 with NaOH and H2O in the presence of polyvinylpyrrolidone (PVP). These flowerlike architectures are assembled from submicron rods with the diameters of 300–600nm. The constituent submicron rods are single crystalline SnO2 with the tetragonal structure, and grow along the direction perpendicular to (101) facet. The spherical flowerlike architectures constructed with SnO2 submicron rods are formed via the oriented attachment process. The response performance of the sensors based on the SnO2 spherical flowerlike architectures toward ethanol and triethylamine is better than that of SnO2 powders and can be further enhanced by improving their crystallinity. The sensor response is 3.65 and 2.97 when the concentration of ethanol and triethylamine is 105 and 45ppm, respectively. [Copyright &y& Elsevier]

A diagram which shows the synthesis of the chemical compound tetrahydropyrroles based on spiropyrazolone through three-component 1,3-dipolar cycloadditions is presented.

An intramolecular coupling of tertiary amines and anilines is developed starting from 2-(N,N-dialkylamino)anilines. [ABSTRACT FROM AUTHOR]

Introducing a bulky group into nitenpyram leads to a series consisting of fourteen novel title derivatives. [ABSTRACT FROM AUTHOR]