After the longest exposure time to serine protease, the drug is even found in the viable epidermis. High-resolution micrographs indicate that the lipophilic drug preferably associates with corneocytes, while signals found in the intercellular lipid compartment were less pronounced. This result is discussed in comparison to previous work obtained from low-molecular-weight lipophilic drugs as well as polymer nanocarriers, which were found to penetrate the intact stratum corneum exclusively via the lipid layers between the corneocytes. Also, the role of the tight junction barrier in the stratum granulosum is briefly discussed with respect to modifications of the skin barrier induced by enhanced serine protease activity, a phenomenon of clinical relevance in a range of inflammatory skin disorders.DNA topoisomerases, essential enzymes to all living organisms, are important targets of certain antibiotics and anticancer drugs. Although efforts have been taken to identify new inhibitors targeting DNA topoisomerases, limited high throughput screening (HTS) studies have been conducted since a widely accessible HTS assay is not available. We report here the establishment of a fluorescence-based, low-cost HTS assay to identify topoisomerase inhibitors. This HTS assay is based on a unique property of T5 exonuclease that can completely digest supercoiled plasmid pAB1 containing an “AT” hairpin structure and spare relaxed pAB1 and has been validated by screening a small library that contains 50 compounds for various topoisomerases. This T5 exonuclease-based HTS assay can also be used to identify DNA intercalators, the major false positives for identifying topoisomerase inhibitors using this HTS assay. Additionally, we found a new compound that potently inhibits human and bacterial DNA topoisomerase I.The Chagan Depression is an important oil and gas exploration tectonic unit in the Yingen-Ejinaqi Basin, north central China. It has been revealed that the Chagan Depression has abundant oil and gas resources, but the study of hydrocarbon kitchens has not been carried out. The Early Cretaceous Bayingebi 2 Formation has the most important source rocks in the Chagan Depression. In this paper, the Bayingebi 2 Formation was selected to study the hydrocarbon kitchen evolution. The thermal maturity evolution of the source rocks and the locations and geological time of the development of hydrocarbon kitchens were revealed. The results show that the maturity of source rocks in the Bayingebi 2 Formation has reached the maximum during the middle depositional period of the Yingen Formation, and the hydrocarbon generation has ceased since the Late Cretaceous. The source rocks of the Bayingebi 2 Formation in the Chagan Depression have two hydrocarbon kitchens, namely, the western subdepression and the eastern subdepression hydrocarbon kitchens. The western subdepression hydrocarbon kitchen was formed in the Suhongtu 1 Formation depositional period and ended in the Yingen Formation depositional period. The location of the hydrocarbon kitchen was relatively stable and developed in the central and southern parts. However, the eastern subdepression hydrocarbon kitchen developed only during the Yingen Formation depositional period and was located in the north subsag of the Hantamiao sag zone. Finally, the evolution of the hydrocarbon kitchen reveals that oil and gas exploration still needs to be carried out around the western subdepression hydrocarbon kitchen and it may be considered to abandon the exploration in the eastern subdepression.New three-dimensional spin crossover (SCO) coordination polymers systematically constructed by the novel building unit [AgI 2(CN)3], FeII(3-Br-5-CH3pyridine)2[AgI 2(CN)3][AgI(CN)2] (1), FeII(3-Br-5-Clpyridine)2[AgI 2(CN)3][AgI(CN)2] (2), and FeII(3,5-Brpyridine)2[AgI 2(CN)3][AgI(CN)2] (3), have been synthesized and characterized. The bismonodentate binuclear [Ag2(CN)3]- and mononuclear [AgI(CN)2]- units and FeII atoms assemble to form a 3D network structure. selleck kinase inhibitor The structures of 1-3 are crystallographically identical, which made up the triply interpenetration combined with complicated intermolecular interactions including Ag···Ag, Ag···X (pyridine substituents) and π-stacking interactions. Magnetic and differential scanning calorimetry studies were performed for 1-3. These compounds display a similar SCO behavior, while the critical temperatures (T c) are shifted by the substituent effect. Due to the identical structures of 1-3, the order of T c clearly corresponds with the Hammett constant.Three growth methods were tested for producing high-transition temperature superconducting Bi2Sr2Ca n-1Cu n O2n+4+δ whiskers, employing different ways to focus a compressive stress and size effect of the precursors. First, thermographic imaging was used to investigate thermal stress from temperature distribution in the precursors during growth annealing. To enhance thermal stress in the precursors, a thermal cycling method and a Ag-paste coating method were proposed and found to significantly accelerate the whisker growth. The use of pulverized precursors also promoted whisker growth, possibly due to contribution from the vapor-liquid-solid growth mechanism. The obtained whiskers revealed the typical composition, diffraction patterns, and superconducting properties of the Bi-2212 phase. The proposed methods were able to stably produce longer whiskers compared to the conventional method. Using the obtained whiskers, electrical transport measurements under high pressure were successfully performed up to around 50 GPa.Nanoparticles made of amphiphilic block copolymers are commonly used in the preparation of nano-sized drug delivery systems. Poly(styrene)-block -poly(acrylic acid) (PS-PAA) copolymers have been proposed for drug delivery purposes; however, the drug loading capacity and cytotoxicity of PS-PAA nanoparticles are still not fully recognized. Herein, we investigated the accumulation of a model hydrophobic drug, curcumin, and its spatial distribution inside the PS-PAA nanoparticles. Experimental methods and atomistic molecular dynamics simulations were used to understand the molecular structure of the PS core and how curcumin molecules interact and organize within the PS matrix. The hydrophobic core of the PS-PAA nanoparticles consists of adhering individually coiled polymeric chains and is compact enough to prevent post-incorporation of curcumin. However, the drug has a good affinity for the PS matrix and can be efficiently enclosed in the PS-PAA nanoparticles at the formation stage. At low concentrations, curcumin is evenly distributed in the PS core, while its aggregates were observed above ca.