In vitro model to assess the adsorption of oral veterinary drugs to mycotoxin binders in a feed- and aflatoxin B1-containing buffered matrix

Mycotoxin binders are feed additives which are mixed in the feed to adsorb mycotoxins and thereby reducing their toxic effects on animals. Interactions with orally administered veterinary medicinal products, such as antimicrobials or coccidiostats, have been reported previously. This paper describes an in vitro model to screen the interaction between mycotoxin binders and veterinary drugs with respect to the non-specific binding of drugs. It is designed as a static setup using a single concentration of drug and binder in a feed-containing or a feed-plus-mycotoxin-containing matrix, buffered at different pH values. The model was applied to two frequently used antimicrobials in veterinary medicine, doxycycline (DOX) and tylosin (TYL), one major mycotoxin, aflatoxin B1 (AFB1), and four mycotoxin binders. Proportions of feed, DOX or TYL, AFB1, and binder are equivalent to the in vivo situation for broiler chickens, while pH and volume of the buffer are representative of the gastrointestinal tract of chickens. A substantial binding of DOX (~ 88%) and TYL (~ 66%) to the feed-matrix was observed. For the mycotoxin binders, similar results were obtained for DOX and TYL; more specifically up to an inclusion rate of 20 g binder/kg feed, no significant binding was demonstrated, determined as the free concentration of DOX and TYL. A single exception was noticed for TYL and one specific bentonite-based mycotoxin binder, for which no significant interaction could be demonstrated up to 10 g binder/kg but there was an effect at 20 g/kg. In all cases, there was no competition between the tested drugs DOX or TYL and the mycotoxin AFB1 for binding to the bentonite-based mycotoxin binder.     

釉面分相对无铅CuO-MnO2系金属光泽釉的影响

以钙系生料釉为基础,引入结晶剂CuO、MnO₂制备无铅CuO-MnO₂系金属光泽釉;结合XRD、SEM-EDS进行物相组成定性分析和显微结构表征,系统探究外加TiO₂、V₂O₅以及玻璃粉对金属光泽釉釉面分相的影响。研究表明:一定量的TiO₂、V₂O₅引入能有效促进釉面的分相,将玻璃粉部分替换基础釉中的钾长石能使得釉熔体的高温粘度降低,并进一步加剧釉面分相,促进CuMn₂O₄铜锰尖晶石在釉层表面的析出和富集;当TiO₂引入量为2%,V₂O₅引入量为1%,玻璃粉引入量为25%(同为质量分数)时,金属光泽釉釉面效果最佳。     

综放工作面风量及采空区漏风定量检测

通过对中煤塔山煤矿30509综放工作面采空区漏风及有害气体分析的研究，总结了通过定量连续释放SF₆示踪气体，来检测工作面风量与采空区漏风的方法，测定了沿工作面采空区的漏风分布及漏风流线的深度。采用定时测量法，确定了30509工作面随工作面不断推进，与对应地表发生了导通现象；采用定量测量法，确定了内部漏风量和外部漏风量较大，对综采工作面采空区自然发火存在较大风险，同时提出了防范措施，为减少综放工作面采空区漏风、防止自然发火的发生提供了参考。     

Study on the Adaptability of Alkanolamide (LDEA) Lowering Oil/Water Interfacial Tension to Different Crude Oils

In order to investigate the high interfacial activity and fair oil phase adaptability of alkanolamide, “1:1” type lauric acid diethanolamide impurities (LDEA) were synthesized and purified by the column chromatography method to obtain dodecanoic acid diethanolamide (C₁₂DEA), ester mixture, etc. The exact structures of these compounds were further confirmed by IR, gas chromatogrph with mass spectroscopy (GC–MS), and NMR. The influence of each component on the interfacial tension of oil/water (IFT) was studied by systematic quantitative analysis. The results showed that (i) the strength of each system to reduce oil/water IFT is C₁₂DEA /DEA ≈ LDEA > C₁₂DEA/DEA/ESTER > C₁₂DEA/NaOH > C₁₂DEA > C₁₂DEA/ESTER > DEA. This indicates that LDEA contributes to the reduction of the oil/water IFT and the enhanced adaptability of crude oil in this order: DEA > > ESTER; (ii) when the IFT of the LDEA/DEA system reached an ultralow value, the minimum content of DEA in the system was 1%, and the maximum ester content was less than 5% when the LDEA/DEA/ESTER system reached the ultralow IFT; (iii) the possible mechanism of effect of LDEA components on the IFT and oil phase adaptability was proposed as the synergistic process among the hydrogen bonding, alkali effect, and interface self-assembly of molecules in the interfacial layer. The contribution of these three factors were hydrogen bonding > alkali effect > interface self-assembly.     

Interaction of Cucurbit[7]uril with Oxime K027, Atropine,and Paraoxon: Risky or Advantageous Delivery System?

Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood–brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC—pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.     

Methods and Applications of In Silico Aptamer Design and Modeling

Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.     

Visualizations of Mercury Methylation and Dynamic Transformations by In Vivo Imaging

Visualization of Hg(II) and MeHg in their native contexts is significant for examining mercury poisoning, while it is challenging because of indistinguishable fluorescent (FL) signals during FL imaging. Herein, visualizations of mercury methylation and dynamic transformations of Hg(II) and MeHg are achieved in living biological systems. Well distinguishable FL responses (blue emission for Hg(II), yellow emission for MeHg) are obtained by a double‐response FL probe (DPAHB) without any interference. As demonstrated by experimental and computational studies, the distinguishable signals are attributed to selective binding with DPAHB and different inhibition of excited‐state proton transfer. Through control tests for live‐dead markers, mercury methylation is demonstrated to be employed in living biological systems. Therefore, the methylation and dynamic transformations of both ions are monitored in zebrafish by imaging, and these results are confirmed by traditional high‐performance liquid chromatography‐based methods. The methylation of Hg(II) to MeHg, dynamic transformations and final accumulations of both species in zebrafish tissues are visualized successfully. This method is also convenient for fast evaluation of detoxification reagents. This is the first visualization of in vivo mercury methylation and dynamic transformation of both species and is effective for studying pathological processes in their native contexts.     

综采工作面过上覆煤柱技术研究

近距离上层煤开采过后留有许多残余煤柱,这些煤柱往往导致下层煤开采过程中出现强烈的矿压显现情况。针对综采工作面过上覆采空区煤柱矿压显现剧烈的问题,以山西上榆泉煤矿工作面地质条件为基础,对相邻43303工作面回采过程中的矿压显现情况进行了总结分析,确定上层煤煤柱与本层煤顶板形成的次生顶板结构是造成工作面来压强度增大的主要原因,并从43302工作面过上覆煤柱前、中、后三个阶段,制定了改变采高、调斜、顶板预裂以及加快工作面推进速度等技术措施。根据现场实践效果,采用该措施能够减弱工作面矿压显现强度,改善工作面片帮、冒顶等情况,实现对工作面降压的目的,具有良好的应用效果。