Computational Insight into Biotransformation Profiles of Organophosphorus Flame Retardants to Their Diester Metabolites by Cytochrome P450

Biotransformation of organophosphorus flame retardants (OPFRs) mediated by cytochrome P450 enzymes (CYPs) has a potential correlation with their toxicological effects on humans. In this work, we employed five typical OPFRs including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri(2-chloroethyl) phosphate (TCEP), triethyl phosphate (TEP), and 2-ethylhexyl diphenyl phosphate (EHDPHP), and performed density functional theory (DFT) calculations to clarify the CYP-catalyzed biotransformation of five OPFRs to their diester metabolites. The DFT results show that the reaction mechanism consists of Cα-hydroxylation and O-dealkylation steps, and the biotransformation activities of five OPFRs may follow the order of TCEP ≈ TEP ≈ EHDPHP > TCIPP > TDCIPP. We further performed molecular dynamics (MD) simulations to unravel the binding interactions of five OPFRs in the CYP3A4 isoform. Binding mode analyses demonstrate that CYP3A4-mediated metabolism of TDCIPP, TCIPP, TCEP, and TEP can produce the diester metabolites, while EHDPHP metabolism may generate para-hydroxyEHDPHP as the primary metabolite. Moreover, the EHDPHP and TDCIPP have higher binding potential to CYP3A4 than TCIPP, TCEP, and TEP. This work reports the biotransformation profiles and binding features of five OPFRs in CYP, which can provide meaningful clues for the further studies of the metabolic fates of OPFRs and toxicological effects associated with the relevant metabolites.     

Preparation of nano-hydroxyapatite/poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) biocomposite microspheres

Nano-hydroxyapatite (HA)/poly(l-lactide) (PLLA) composite microspheres with relatively uniform size distribution were prepared by a solid-in-oil-in-water (s/o/w) emusion solvent evaporation method. The encapsulation of the HA nanopaticles in microshperes was significantly improved by grafting PLLA on the surface of the HA nanoparticles (p-HA) during emulsion process. This procedure gave a possibility to obtain p-HA/PLLA composite microspheres with uniform morphology and the encapsulated p-HA nanoparticle loading reached up to 40 wt% (33 wt% of pure HA) in the p-HA/PLLA composite microspheres. The microstructure of composite microspheres from core-shell to single phase changed with the variation of p-HA to PLLA ratios. p-HA/PLLA composite microspheres with the diameter range of 2–3 μm were obtained. The entrapment efficiency of p-HA in microspheres could high up to 90 wt% and that of HA was only 13 wt%. Surface and bulk characterizations of the composite microspheres were performed by measurements such as wide angle X-ray diffraction (WAXD), thermal gravimetric analysis (TGA), environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM).     

求解中国农业困局：国际视野中的农业规模经营与农业竞争力

近年来中国粮食生产出现的“高产量、高库存、高进口”现象,是由于农均耕地面积过小引起的规模经营不足。这背后,是户籍制度造成的城市化滞后以及针对外来人口的公共服务不平等。同时,政府大力补贴农业和农村,提高了农民向城市转移的机会成本,导致土地流转率不足,进一步阻碍规模经营。通过国际比较,我们认为规模化农场有利于提高农业竞争力,而小农经济现代化的成本较高。研究还发现,在世界范围内,农业劳动力转移适应农业产出比重下降的国家拥有更大的农均在（可）耕地,它对农均粮食净出口存在显著正效应。反事实分析说明,若中国2011年的农业就业比重能和产出比重相适应（即消除城乡间劳动力流动障碍）,则下一年粮食净输入将下降约89%。     

创新导向减税与就业结构升级—基于研发费用加计扣除的检验

创新在中国经济社会发展中的作用愈发突出,如何促进高技能劳动力向创新主体部门集聚,值得深入探索。基于2018年企业所得税研发费用加计扣除比例提升冲击,利用A股上市公司2016−2019年数据,本文研究了创新导向减税对就业结构的影响。研究发现,加计扣除比例提升显著提高了企业雇佣劳动力中研究生所占比例,促进了企业创新人力资本积累。异质性分析显示,政策在非公有制企业、主板上市企业中效果更明显。对企业各层次雇佣规模的评估表明,雇佣总量及研究生、本科生雇佣数均有所提高,同时本科以下学历人员并未明显减少,这意味着政策未产生明显的挤出效应,高技能劳动力雇佣的增加并不以低技能劳动力的减少为代价。综合来看,政策不但能促进企业加大研发投入,还有助于提高全要素生产率和盈利水平。本文结论为通过实施结构性减税,推动创新驱动发展提供了经验支撑。     

Enzymatic Synthesis of a Diastereomer of Neoabyssomicin Derivative Using the Diels-Alderase AbyU

Main observation and conclusion The enzyme AbyU catalyses a Diels-Alder (DA) reaction during abyssomicin C biosynthesis.In this study,AbyU is shown to convert t...     

Enantioselective Organocatalytic Aza-Michael Additions of Phthalimide Derivatives to α,β-Unsaturated Aldehydes

Phthalimide derivatives as nitrogen nucleophiles with α,β‐unsaturated aldehydes for asymmetric aza‐Michael additions have been reported. The reactions proceed smoothly to afford corresponding Michael adducts in good yields (up to 98%) and enantioselectivities (up to 95% ee).     

Computational studies on 3,5,7,10,12,14,15,16-octanitro-3,5,7,10,12,14,15,16-octaaza-pentacyclo[7.5.1.12,8.04,13.06,11]hexadecane as potential high-energy-density compound

The B3LYP/6-31G(d) method of density functional theory was used to study molecular geometry, electronic structure, infrared spectrum, and thermodynamic properties. Detonation properties were evaluated using Kamlet–Jacobs equations based on the calculated density and heat of formation. Thermal stability of 3,5,7,10,12,14,15,16-octanitro-3,5,7,10,12,14,15,16-octaaza-pentacyclo[7.5.1.1^2,8.0^4,13.0^6,11]hexadecane (cage-HMX) was investigated by calculating the bond dissociation energy at unrestricted B3LYP/6-31G(d) level. The calculated results show that the first step of pyrolysis is the rupture of the N–NO₂ bond. The crystal structure obtained by molecular mechanics belongs to P2₁ space group, with lattice parameters a = 8.866 Å, b = 11.527 Å, c = 13.011 Å, Z = 4, and ρ = 2.219 g cm^?3. Both the detonation velocity of 9.79 km s^?1 and the detonation pressure of 45.45 GPa are better than those of CL-20. According to the quantitative standard of energetics and stability as a high-energy-density compound, cage-HMX essentially satisfies this requirement. These results provide basic information for molecular design of novel HEDCs.     

Imide‐functionalized naphthodithiophene based donor‐acceptor conjugated polymers for solar cells

Donor‐acceptor conjugated polymers containing a new imide‐functionalized naphthodithiophene (INDT) as the acceptor unit and a 2,2'‐bithiophene with varied substituents as the donor unit have been synthesized. The bandgaps of these polymers depend strongly on the dihedral angle of the 2,2'‐bithiophene unit. The 3,3'‐dialkoxy substitution (polymers PDOR / PBOR ) leads to near planar bithiophene conformation due to the well‐known S–O short contact, while the 3,3'‐dialkyl substitution (polymer PDR ) results in significant twisting due to the steric effect. Consequently PDOR / PBOR shows the lowest bandgap of 1.82/1.85 eV while PDR has a bandgap of 2.38 eV. Bulk‐heterojunction solar cells of the polymer/fullerene blends have been fabricated. Preliminary results show that PBOR gives the best device performance with power conversion efficiencies as high as 2.45% in air without any thermal annealing treatment, indicating the promising potential of INDT‐containing conjugated polymers for efficient solar cells. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3818–3828