Photoregulation of Gene Expression with Ligand-Modified Caged siRNAs through Host/Guest Interaction

Small interfering RNA (siRNA) can effectively silence target genes through Argonate 2 (Ago2)-induced RNA interference (RNAi). It is very important to control siRNA activity in both spatial and temporal modes. Among different masking strategies, photocaging can be used to regulate gene expression through light irradiation with spatiotemporal and dose-dependent resolution. Many different caging strategies and caging groups have been reported for light-activated siRNA gene silencing. Herein, we describe a novel caging strategy that increases the blocking effect of RISC complex formation/process through host/guest (including ligand/receptor) interactions, thereby enhancing the inhibition of caged siRNA activity until light activation. This strategy can be used as a general approach to design caged siRNAs for the photomodulation of gene silencing of exogenous and endogenous genes.     

云南磷肥工业副产氟资源综合利用途径初探

根据云南磷肥工业发展情况 ,提出对磷肥工业副产氟资源综合利用的设想 ,并介绍目前国内已有的一些氟资源综合利用的工艺技术     

微波消解-ICP-AES法测定菜油中P、S

采用微波加热,在高温高压下酸消解样品,运用电感耦合等离子体原子发射光谱法(ICP-AES)同时测定菜油中P、S。本法选用紫外区谱线P178.221nm、S180.669nm,避免了基体中存在的Fe、Zn、Al、Cu、Mn、Ca等元素的光谱干扰。实验通过用纯氮吹扫光谱仪光路的方法消减空气中氧对紫外线的吸收,获得了足够的灵敏度。该方法简便、快速,稳定可靠,P、S检出限分别为0.067、0.078μg/ml,RSD为1.35%～5.05%,回收率为89.0%～100.9%。     

The bioconversion of tunisian phosphorite usingAspergillus niger

It is well known that the production of phosphoric fertilizers by traditional methods is connected with certain environmental problems, particularly related to use of acids during the decomposition of natural phosphates. A basic problem is also the fact that only 15 – 20% of the phosphorus contained in superphosphates is assimilated by plants.The development of methods to process natural phosphates without acid precipitation has potential advantages and in this respect biotechnological processing of natural phosphates in order to obtain organo-mineral fertilizers is very promising. The possibility of bioconverting the phosphorus of natural phosphates by usingAspergillus niger fungi through their deep incubation has been investigated. The investigations aim to achieve a high degree of P₂O₅ extraction from the phosphates with conversion from a non-utilizable to a utilizable form. The influence of the fungal strain, the kind of nutritive medium and the time of incubation of the process of biological mobilization of the phosphate rock is examined.It was established that the time of incubation, the kind of micro-organisms of theAspergillus niger group, as well as the kind of nutritive medium, influence significantly the process of bioconversion and the conversion of phosphorus from non-utilizable to water-soluble and utilizable for plants form. A maximum degree 90% of phosphorus extraction in the form of water-soluble and citrate-soluble has been reached for 10-day incubation. Physicochemical examinations have been carried out and they have proved that, as a result of the produced organic acids, a process of decomposition of the initial Tunisian phosphorite takes place.     

Enantioselective extraction of mandelic acid enantiomers based on chiral ligand exchange

Based on the chiral ligand exchange, the distribution behavior of mandelic acid enantiomers, and the partition of Cu^2 at different pH values were studied in a water/alcohol two-phase system containing Cu^2 and N-ndodecyl-L-proline(A). The influences of the solvent sort, the pH value, the concentrations of Cu^2 and chiral ligand on the partition coefficient(K) and separation factor(α) were discussed. The experimental results show that the A formed has more stable ternary complex with D-mandelic acid enantiomer than with L-mandelic acid enantiomer. There is an important influence of the pH value on K and a. When the pH values are less than 3.5, the formation of binary complexes is thermodynamically unfavourable. K and a become maximum when pH values are above 3.5 and the molar ratio of the chiral ligand to Cu^2 is 2:1.     

Synthesis,Characterization and Luminescent Properties of Complexes of Rare Earth Nitrates with Tris{2-[N-(pyridine-methanoyl)amino]ethyl} amine

Duringthelastdecade ,thedesignandsynthesisoftripodalligandsandtheirmetalcomplexeshaveattractedconsiderableattentionduetotheirpotentialusesaslumi nescentprobesinmedicineandbiochemistry[1～ 7] ,ascatalysts[8] andelectrochemicalmaterials[9] .However ,thecomplexesofrareearthmetalwithtripodalligandshavefewreported[10 ] .Asanextensionofourstudiesoncomplexesofmetalwithtripodalligands ,anewtripodalligand (tris { 2 [N (pyridine methanoyl)amino]ethyl}amine ,L)anditscomplexeswithrareearthnitratesweresyn…     

CAST的工作原理与设计计算

详细论述了循环式活性污泥法(CAST)的工作原理，对该工艺的设计计算作了探讨，提出了设计方法，并提供了有关计算公式和操作时间分配。     

Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength

Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R₁/R₂ side-groups as phenyls or R₁–phenyl/R₂–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved K_s, IC₅₀ and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (K_s and IC₅₀ of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.     

Accurate Receptor-Ligand Binding Free Energies from Fast QM Conformational Chemical Space Sampling

Small molecule receptor-binding is dominated by weak, non-covalent interactions such as van-der-Waals hydrogen bonding or electrostatics. Calculating these non-covalent ligand-receptor interactions is a challenge to computational means in terms of accuracy and efficacy since the ligand may bind in a number of thermally accessible conformations. The conformational rotamer ensemble sampling tool (CREST) uses an iterative scheme to efficiently sample the conformational space and calculates energies using the semi-empirical ‘Geometry, Frequency, Noncovalent, eXtended Tight Binding’ (GFN2-xTB) method. This combined approach is applied to blind predictions of the modes and free energies of binding for a set of 10 drug molecule ligands to the cucurbit[n]urils CB[8] receptor from the recent ‘Statistical Assessment of the Modeling of Proteins and Ligands’ (SAMPL) challenge including morphine, hydromorphine, cocaine, fentanyl, and ketamine. For each system, the conformational space was sufficiently sampled for the free ligand and the ligand-receptor complexes using the quantum chemical Hamiltonian. A multitude of structures makes up the final conformer-rotamer ensemble, for which then free energies of binding are calculated. For those large and complex molecules, the results are in good agreement with experimental values with a mean error of 3 kcal/mol. The GFN2-xTB energies of binding are validated by advanced density functional theory calculations and found to be in good agreement. The efficacy of the automated QM sampling workflow allows the extension towards other complex molecular interaction scenarios.