Metabolomic-based investigation of Yinlan alleviating hyperlipidemia by inhibiting blood stasis and phlegm turbidity through the PXR-CYP3A4-ABCB1-FXR pathway

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.     

Hydrothermal synthesis, crystal structures and luminescent properties of two new Ln(III)–succinate (Ln=Eu, Tb) complexes exhibiting three dimensional networks

Two new coordination polymers, [Eu₂(L)₃(H₂O)₂]_n 1 and {[Tb₂(L)₃(H₂O)₂]·H₂O}_n 2, (H₂L=succinic acid) have been synthesized by the reaction of H₂L with nitrate salts of Eu(III) or Tb(III) under hydrothermal conditions. The X-ray diffraction analysis reveals that the two complexes are constructed by L bridging the chains of edge-sharing EuO₈(H₂O) or TbO₈(H₂O) polyhedra to form 3D network structure. 1 and 2 possess different topological structures due to the difference in the conformations of L. The solid photoluminescence of 1 and 2 was also investigated in room temperature.     

Local and non-local sources of airborne particulate pollution at Beijing--The ratio of Mg/Al as an element tracer for estimating the contributions of mineral aerosols from outside Beijing

A new element tracer technique has firstly been established to estimate the contributions of mineral aerosols from both inside and outside Beijing. The ratio of Mg/Al in aerosol is a feasible element tracer to distinguish between the sources of inside and outside Beijing. Mineral aerosol, inorganic pollution aerosol mainly as sulfate and nitrate, and organic aerosol are the major components of airborne particulates in Beijing, of which mineral aerosol accounted for 32%―67% of total suspended particles (TSP), 10%―70% of fine particles (PM2.5), and as high as 74% and 90% of TSP and PM2.5, respectively, in dust storm. The sources from outside Beijing contributed 62% (38%―86%) of the total mineral aerosols in TSP, 69% (52%―90%) in PM10, and 76% (59%―93%) in PM2.5 in spring, and 69% (52%―83%), 79% (52%―93%), and 45% (7%―79%) in TSP, PM10, and PM2.5, respectively, in winter, while only ～20% in summer and autumn. The sources from outside Beijing contributed as high as 97% during dust storm and were the dominant source of airborne particulates in Beijing. The contributions from outside Beijing in spring and winter are higher than those in summer, indicating clearly that it was related to the various meteorological factors.     

Synthesis and crystal structures of heterobimetallic Fe-Cd,Fe-Zn,and Fe-In complexes containing hemilabile phosphorus/oxygen and silicon/oxygen bridging ligands

The reactions of K[Fe{Si(OMe)₃}(CO)₃(PY)][PY=Ph₂PCH₂C(O)Ph, Ph₂PCH₂C(O)[(-C₅H₄)FeCp] (Cp=⁵-C₅H₅), Ph₂P(CH₂)₂CN] with CdCl₂·2.5H₂O, ZnX ₂ (X=Cl, I) or InCl₃ afforded Fe-Cd-Fe or Fe-M(-X)₂ M-Fe (M=Cd, Zn, In;X=Cl, I) and Fe-InCl₂ complexes. Some of them contain an unusual and labile -²-SiO alkoxysilyl bridge which may be associated with a bridging mode for the ketophosphine ligand (first such example structurally established), thus providing original results in bimetallic chemistry on the intramolecular coordination of oxygendonor functions ofchemically different hemilabile ligands firmly attached to a neighboring metal center. The structures of the trinuclear complex (3), of the chlorobenzene solvate of the tetranuclear complex (4a·C₆H₅Cl) and of [mer-(OC)₃{(EtO)₃Si} (4e) have been determined by X-ray diffraction. Crystals of 3 are orthorhombic, space groupPbcn, witha=19.010(4),b=11.766(5),c=26.998(7)Å, andZ=4. Crystals of4a·C₆H₅Cl are monoclinic, space groupC2/c witha=22.455(3),b=17.680(2),c=16.627(4)Å, =90.80(4)°, andZ=4. Crystals of4e are monoclinic, space groupC2/c witha=25.392(5),b=18.554(6),c=16.28(1)Å, =120.73(3)°, andZ=4. The structures were solved using direct methods and Fourier difference techniques and refined by blocked full-matrix least squares toR=0.035 (R _w =0.049) for 2719 observed reflections, toR=0.042 (R _w =0.056) for 3082 observed reflections, and toR=0.057 (R _w =0.075) for 1850 observed reflections for3, 4a·C₆H₅Cl and4e, respectively. The Fe-Zn complexes (9a), (9b) and (9c) were prepared and characterized by spectroscopic methods.Part 21 in the Series: Complexes with Functional Phosphines. Part 20: P. Braunstein, S. Coco Cea, A. DeCian, and J. Fischer (1992).Inorg. Chem. 31, 4203.     

Coordination modes of 2-hydroxynicotinic acid in second- and third-row transition metal complexes

The new Pd(II), Pt(II), Re(V), Mo(VI) and W(VI) complexes of 2-hydroxynicotinic acid (H₂nicO), trans-[PdCl(HnicO)(PPh₃)₂]·0.75CH₃CN (1), K[PdCl(HnicO)₂]·H₂O (2), [Pd(HnicO)₂(bipy)] (3), cis-[PtCl(HnicO)(PPh₃)₂]·0.75CH₃OH·0.5H₂O (4), [PtCl(HnicO)(bipy)] (5), cis-[ReOI₂(HnicO)(PPh₃)] (6), Na₂[Mo₂O₆(HnicO)₂]·5H₂O (7), Na₂[Mo₄O₁₂(HnicO)₂]·2H₂O (8) and Na₂[W₂O₆(HnicO)₂]·5H₂O (9) have been prepared. The crystal structures of 1 and 4, were determined by X-ray diffraction and show the HnicO⁻ ligand coordinated to palladium or platinum through the nitrogen atom only. Infrared, Raman, ¹H and ¹³C{¹H} NMR spectroscopic data for the complexes are presented and are in agreement with the crystallographic results.     

Chiral molecular glass: synthesis and characterization of enantiomerically pure thiophene-based [7]helicene

Synthesis of thiophene-based [7]helicenes, which are functionalized for both design of organic chiral glasses with strong chiroptical properties and for further homologation to higher [n]helicenes, is reported. The key synthetic transformations are kinetic resolution of the intermediate diketone and the annelation step forming the center benzene ring by means of an intramolecular McMurry reaction. Based upon X-ray crystallographic determinations of the absolute configurations for (+)-enantiomers of the diketone and the [7]helicene, stereochemical correlation between the (R) axial chirality of the diketone and the (M) helical chirality of the [7]helicene is established. One such enantiopure trimethylsilyl-substituted [7]helicene possesses enchanced chiroptical properties and forms a chiral molecular glass.     

Rapid biomass analysis

New, rapid, and inexpensive methods that monitor the chemical composition of corn stover and corn stover-derived samples are a key element to enabling the commercialization of processes that convert stover to fuels and chemicals. These new techniques combine near infrared (NIR) spectroscopy and projection to latent structures (PLS) multivariate analysis to allow the compositional analysis of hundreds of samples in 1 d at a cost of about $10 each. The new NIR/PLS rapid analysis methods can also be used to support a variety of research projects that would have been too costly to pursue by traditional methods.     

新型的含硫族元素碳硼烷配体的三(3，5-二甲基-1-吡唑)硼氢钼配合物的合成和分子结构(英)

三齿单核三(3，5-二甲基-1-吡唑)硼氢钼配合物Tp^*Mo(O)Cl₂ (1)(Tp^*=三(3，5-二甲基-1-吡唑)硼氢HB(C₃H(Me₂)N₂)₃)与含硫族元素碳硼烷的锂盐[(THF)₂LiE₂C₂B₁₀H₁₀(THF)]<     

Synthesis and crystal structures of Group 6 metal carbonyl complexes containing S-rich bis(pyrazol-1-yl)methane ligands

The reaction of 3(5)-methylthio-5(3)-phenylpyrazole with dibromomethane under phase-transfer catalytic conditions only affords a new ligand, bis(3-phenyl-5-methylthiopyrazol-1-yl)methane. However, the reaction of 3(5)-methylthio-5(3)-p-methoxyphenylpyrazole or 3(5)-methylthio-5(3)-tert-butylpyrazole with dibromomethane under the same conditions yields three isomers, respectively, indicating that the substituents significantly affect the steric and electronic properties of pyrazole ring during the formation of ligands. Treatment of these potential polydentate ligands with M(CO)₆ (M=Cr, Mo or W) under UV irradiation at room temperature affords (NN)M(CO)₄ derivatives, in which some complexes contain asymmetric substituted bis(pyrazol-1-yl)methane ligands. The X-ray crystal structure analyses indicate that the sulfur atoms in these complexes do not take part in the coordination to the metal centers, and S-rich bis(pyrazol-1-yl)methanes actually act as bidentate chelating ligands by two nitrogen atoms. It is also interesting that in order to reduce the repulsion of methyl groups with carbonyls, the methyl groups in these complexes are oriented away from the metal centers.     

Ab initio study of the ground state and conformational stability of peroxyacetyl nitrate in internal rotation about the peroxide bond

The molecular and electronic structure of the ground state of peroxyacetyl nitrate (PAN) was calculated by the unrestricted Hartree-Fock-Roothaan method with the use of the standard 3–21G and 6–31G basis set. The potential curve of the internal rotation about the peroxide bond of PAN was calculated with the 6–31G basis set. The curve contains two maxima. The ground state of PAN is characterized by a structure in which groups of atoms adjacent to the peroxide bond lie in planes that are perpendicular to each other (the dihedral angle ϱ(COON) is 89.9°). The calculated barriers to rotation are 19.6 and 66.8 kJ mol⁻¹. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 600–604, April, 1998.