A series of perfluorobutane sulfonate (PFBS)-related substances are produced as the alternatives to corresponding perfluorooctane sulfonate (PFOS). However, there is little reliable information about PFBS available for the whole ecotoxicology compartments. At present, its ecotoxicity of perfluorobutane sulfonate potassium (PFBSK) was selected as a typical PFBS chemical to investigate and evaluate its aquatic, terrestrial, microorganism and sediment toxicity according to the Organization for Economic Cooperation and Development (OECD) guideline under the framework of the REACH regulation. Meanwhile, the ecotoxicology hazard and risk for PFBSK and PFOS were compared comprehensively.
PFBSK did not show acute and chronic aquatic, microorganisms and terrestrial animal toxicity, while exhibited some terrestrial plants toxicity. The ecotoxicology of PFBSK decreased sharply except for terrestrial plants compared with PFOS. Especially, for acute and chronic aquatic ecotoxicity, PFBSK is lower than 100 times those of PFOS.
Although the similar terrestrial plants toxicity level was observed for PFBSK and PFOS, the lower risk of PFBSK was deduced for the reason that there was far less chances to be exposed and retained in the soil and sediment for its high water solubility and low adsorption.
In conclusion, PFBSK showed lower ecotoxicity hazard and risk than those of PFOS. PFBSK could be an environmental friendly alternative to PFOS. 相似文献
The discovery of clinically relevant inhibitors against MurF enzyme has proven to be a challenging task. In order to get further insight into the structural features required for the MurF inhibitory activity, we performed pharmacophore and atom-based three-dimensional quantitative structure–activity relationship studies for novel thiophene-3-carbonitriles based MurF inhibitors. The five-feature pharmacophore model was generated using 48 inhibitors having IC50 values ranging from 0.18 to 663?μm. The best-fitted model showed a higher coefficient of determination (R2?=?0.978), cross-validation coefficient (Q2?=?0.8835) and Pearson coefficient (0.9406) at four component partial least-squares factor. The model was validated with external data set and enrichment study. The effectiveness of the docking protocol was validated by docking the co-crystallized ligand into the catalytic pocket of MurF enzyme. Further, binding free energy calculated by the molecular mechanics generalized Born surface area approach showed that van der Waals and non-polar solvation energy terms are the main contributors to ligand binding in the active site of MurF enzyme. A 10-ns molecular dynamic simulation was performed to confirm the stability of the 3ZM6-ligand complex. Four new molecules are also designed as potent MurF inhibitors. These results provide insights regarding the development of novel MurF inhibitors with better binding affinity. 相似文献
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide. However, there remain many unmet clinical needs, from diagnosis to treatment strategies. The inherent complexity of the molecular characteristics of PDAC has made it difficult to meet these challenges, rendering proteomic profiling of PDAC a critical area of research.
Area covered: In this review, we present recent advances in mass spectrometry (MS) and its current application in proteomic studies on PDAC. In addition, we discuss future directions for research that can efficiently incorporate current MS-based technologies that address key issues of PDAC proteomics.
Expert commentary: Compared with other cancer studies, little progress has been made in PDAC proteomics, perhaps attributed to the difficulty in performing in-depth and large-scale clinical studies on PDAC. However, recent advances in mass spectrometry can advance PDAC proteomics past the fundamental research stage. 相似文献