Chemical proteomics reveals ligustilide targets SMAD3, inhibiting collagen synthesis in aortic endothelial cells

Atherosclerosis is a persistent inflammatory state,while vascular endothelial fibrosis is one of the primary causes of atherosclerosis development.Although ligustilide(Lig) was shown to exert obvious antiatherogenic effects in previous studies,its precise mechanism has not been deeply discussed.In this paper,we designed a Lig-derived photoaffinity labelling(PAL) probe to identify potential therapeutic targets of Lig via chemical proteomics approach.Mothers against decapentaplegic homologue 3(SMAD3),a signal transmitter of transforming growth factor-β(TGF-β) which promotes the development of vascular fibrosis,was identified as a potential target of Lig.Lig suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and TGF-β receptor 1,thereby inhibiting the collagen synthesis process.Hence,developing a novel SMAD3 inhibitor may present a promising therapeutic option for preventing vascular fibrosis.     

Elucidation of the Structure of Lignin–Carbohydrate Complexes in Ginkgo CW-DHP by 13C-2H Dual Isotope Tracer

To elucidate the chemical linkages between lignin and carbohydrates in ginkgo cell walls, ¹³C-²H-enriched cell wall-dehydrogenation polymers (CW-DHP) were selectively prepared with cambial tissue from Ginkgo biloba L. by feeding D-glucose-[6-²H₂], coniferin-[α-¹³C], and phenylalanine ammonia-lyase (PAL) inhibitor. The abundant detection of ¹³C and ²H confirmed that D-glucose-[6-²H₂] and coniferin-[α-¹³C] were involved in the normal metabolism of ginkgo cambial cells that had been effectively labelled with dual isotopes. In the ginkgo CW-DHP, ketal and ether linkages were formed between the C-α of lignin side chains and carbohydrates, as revealed by solid state CP/MAS ¹³C-NMR differential spectroscopy. Furthermore, the DMSO/TBAH ionic liquids system was used to fractionate the ball-milled CW-DHP into three lignin-carbohydrate complex (LCC) fractions: glucan–lignin complex (GL), glucomannan–lignin complex (GML), and xylan–lignin complex (XL). The XRD determination indicated that the cellulose type I of the GL was converted into cellulose type II during the separation process. The molecular weight was in the order of Ac-GL > Ac-GML > XL. The ¹³C-NMR and ¹H-NMR differential spectroscopy of ¹³C-²H-enriched GL fraction indicated that lignin was linked with cellulose C-6 by benzyl ether linkages. It was also found that there were benzyl ether linkages between the lignin side chain C-α and glucomannan C-6 in the ¹³C-²H-enriched GML fraction. The formation of ketal linkages between the C-α of lignin and xylan was confirmed in the ¹³C-²H-enriched XL fraction.     

Novel long alkyl side chain benzo[a]phenoxazinium chlorides: synthesis, photophysical behaviour and DNA interaction

Several fluorescent benzo[a]phenoxazinium chlorides possessing a propyl-, octyl-, decyl-, dodecyl- or tetradecylamino at the 5-position of the heterocyclic moiety were efficiently synthesised. The absorption and emission maxima of all compounds lie in the range 627-638 nm and 654-678 nm, respectively, with good fluorescence quantum yields. Studies of their photophysical properties in ethanol allowed for the estimation of the acid-base dissociation constant, K_a, revealing an enhancement with the increase in the alkyl side-chain length. It is in the aqueous medium only that the acid form is observed as coexisting with H-aggregates. The solubility markedly decreased when the chain length increased. The residual ethanol (0.2% v/v) used to facilitate the solubilisation of the benzo[a]phenoxazinium dyes allow for the existence of the basic form in an aqueous solution, possibly through preferential solvation. Photophysical studies in the presence of DNA revealed that the compounds with an alkyl side chain of up to eight carbon atoms could intercalate between DNA nucleotides. Moreover, other forms of DNA binding were found to be operative, involving also the basic form of benzo[a]phenoxazinium dyes.     

Eco-friendly synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles using alumina-sulfuric acid as a heterogeneous reusable catalyst

A cost-effective and eco-friendly synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles has been developed through the condensation of different aldehydes with o-phenylenediamine using alumina-sulfuric acid as a recyclable heterogeneous solid acid catalyst. Morphological properties of the catalyst have been investigated. Effect of different solvents and comparison of alumina-sulfuric acid with different acid catalysts have also been studied. A plausible mechanistic pathway has been proposed on the basis of the isotope labelling experiments where catalytic behaviour of alumina-sulfuric acid has been explained.     

Raman spectroscopy of n‐pentyl methyl ether and deuterium labelled analogues

The Raman spectra of n‐pentyl methyl ether, C₅H₁₁OCH₃, and six selectively deuteriated analogues are reported and discussed. Correlations between the observed ν(sp³CH) stretching and bending bands and the position of the deuterium atoms in the alkyl chain are developed and refined. Similar progress is possible in associating specific skeletal vibrations with bands in the Raman spectra. The relevance of this study to improving the assignment of bands in the Raman spectra of larger systems of biological interest is highlighted. Copyright © 2010 John Wiley & Sons, Ltd.     

On (d,1)-total numbers of graphs

A (d,1)-total labelling of a graph G assigns integers to the vertices and edges of G such that adjacent vertices receive distinct labels, adjacent edges receive distinct labels, and a vertex and its incident edges receive labels that differ in absolute value by at least d. The span of a (d,1)-total labelling is the maximum difference between two labels. The (d,1)-total number, denoted , is defined to be the least span among all (d,1)-total labellings of G. We prove new upper bounds for , compute some for complete bipartite graphs K_m,n, and completely determine all for d=1,2,3. We also propose a conjecture on an upper bound for in terms of the chromatic number and the chromatic index of G.     

Edge irregular total labellings for graphs of linear size

As an edge variant of the well-known irregularity strength of a graph G=(V,E) we investigate edge irregular total labellings, i.e. functions f:V∪E→{1,2,…,k} such that f(u)+f(uv)+f(v)≠f(u^′)+f(u^′v^′)+f(v^′) for every pair of different edges uv,u^′v^′∈E. The smallest possible k is the total edge irregularity strength of G. Confirming a conjecture by Ivan?o and Jendrol’ for a large class of graphs we prove that the natural lower bound is tight for every graph of order n, size m and maximum degree Δ with m>111000Δ. This also implies that the probability that a random graph from G(n,p(n)) satisfies the Ivan?o-Jendrol’ Conjecture tends to 1 as n→∞ for all functions p∈[0,1]^N. Furthermore, we prove that is an upper bound for every graph G of order n and size m≥3 whose edges are not all incident to a single vertex.     

Edge colouring by total labellings

We introduce the concept of an edge-colouring total k-labelling. This is a labelling of the vertices and the edges of a graph G with labels 1,2,…,k such that the weights of the edges define a proper edge colouring of G. Here the weight of an edge is the sum of its label and the labels of its two endvertices. We define to be the smallest integer k for which G has an edge-colouring total k-labelling. This parameter has natural upper and lower bounds in terms of the maximum degree Δ of . We improve the upper bound by 1 for every graph and prove . Moreover, we investigate some special classes of graphs.     

关于图的具有标号型约束条件的正常全着色

数学的拓扑图可以自然地表示编码关系结构,也叫做拓扑图编码,这种关系结构在许多领域里得到应用.本文将图的全着色和图的边魔幻标号结合产生特殊的全着色,边魔幻tcn-纯全着色和均匀魔幻tcn-纯全着色.研究了树的边魔幻tcn-纯全着色,均匀魔幻tcn-纯全着色,以及具有极值性质的边魔幻全着色数,确定了特殊全着色在树上的精确着...     

Novel formal synthesis of stereospecifically C-6 deuterated d-glucose employing configurationally stable alkoxymethyllithiums

The synthesis and testing of configurational stability of chirally monodeuterated PMB- and THP-substituted oxymethyllithiums are described. Macroscopically they are configurationally stable up to −35 °C, the limit of their chemical stability, and microscopically even up to 0 °C. Furthermore, THP-protected oxy-[D₁]methyllithium has been applied in the formal synthesis of (6R)-[6-D₁]-d-glucose (four steps, 40% yield), an example of its use as a homochiral hydroxymethyl synthon.