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。     

Do Intermittent Renewables Threaten the Electricity Supply Security?

Around the globe, intermittent renewable energies in the form of wind and solar power are on the rise. Their subsidization can be seen as a market intervention, which may deter optimal investment. Thus, this study tests the effect of renewable energies on investment in conventional electricity generation technologies. We estimate a dynamic investment model for 14 European economies for the period 2004–2016 and find a non-negligible negative impact of intermittent renewables on investment in peak-load capacity (mainly gas), while base-load (particularly coal) plants are unaffected. However, the production flexibility of gas-fired plants represents a particularly vital function to balance the supply intermittency of wind and solar. Thus, dispatchable conventional power plants are still necessary to back the system under scarcity events, such as unfavorable weather conditions during high electricity demand. Policymakers should be aware of the adverse effects of RES on investment in peak-load plants and may consider a redesign of the current system, for example by introducing capacity markets.     

超临界CFB机组汽动给水泵油中进水分析

白马循环流化床示范电站600MW超临界CFB机组自投运以来,A、B汽动给水泵组经常出现润滑油质偏差现象,主要原因为油中含水过大造成。通过对给水泵相关系统进行全面的分析研究,指出了润滑油进水的原因是,给水泵轴承和密封水采用的呼吸器易堵塞造成回油室为较大负压状态。给水泵转速变化时,低压密封水室压力轻微波动,微正压的水进入微负压的回油室,造成油中微量带水。经过分析研究提出改进建议,运行后取得了较好效果,汽动给水泵组的油中含水量大幅降低,保证了机组安全稳定运行。     

Seeing is believing? When scanning electron microscopy (SEM) meets clinical dentistry: The replica technique.

In restorative dentistry, the in situ replication of intra‐oral situations, is based on a non‐invasive and non‐destructive scanning electron microscopy (SEM) evaluation method. The technique is suitable for investigation restorative materials and dental hard‐ and soft‐tissues, and its interfaces. Surface characteristics, integrity of interfaces (margins), or fracture analysis (chipping, cracks, etc.) with reliable resolution and under high magnification (from ×50 to ×5,000). Overall the current study aims to share detailed and reproducible information about the replica technique. Specific goals are: (a) to describe detailed each step involved in producing a replica of an intra‐oral situation, (b) to validate an integrated workflow based on a rational sequence from visual examination, to macrophotography and SEM analysis using the replica technique; (c) to present three clinical cases documented using the technique. A compilation of three clinical situations/cases were analyzed here by means the replica technique showing a wide range of possibilities that can be reached and explored with the described technique. This guidance document will contribute to a more accurate use of the replica technique and help researchers and clinicians to understand and identify issues related to restorative procedures under high magnification.