摘要：The aim of this research is to identify the relationship between the concept of creativity and *** characters depicted in the short stories by the Russian writer AntonČechov,Ward no.6 and The Black Monk,and the historical figure of King Ludwig II of Bavaria will be given particular *** paper aims to show how inČechov’s characters Efymič,Dmitričand Kovrin,the concept of madness plays a negative function,as the protagonists of the abovenamed tales are unable to be *** psychic discomfort leads to pathology by means of hallucinosis and events that,although they induce and promote a function of mental equilibrium in the individual,they do not lead to *** latter constitutes a peculiar,fundamental and present aspect of Ludwig in the poetic,literary and artistic spheres,which specifically led to the realisation of his castles in Bavaria,products of his particular creativity and today admired by visitors from all over the world.

摘要：A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine （TCM） products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

摘要：The coronary artery calcification score and pericardial fat volume have recently been reported to be strongly associated with the severity and presence of coronary atherosclerosis. However, no studies have explored the outcome of phased progression of atherosclerosis by non-contrast computed tomography in asymptomatic people in China. The population-based cohort study in outcome of phased progression of atherosclerosis in China （PERSUADE）, an observational, longitudinal and prospective cohort study in a target population of healthy sub- jects based in Jidong Oilfield （China）, prospectively analyzes the outcome of phased progression of atherosclerosis by non-contrast computed tomography in healthy population. The results of this study are expected to be of value for utilizing noninvasive imaging combine with tradi- tional cardiovascular risk factors to create a risk stratification and find pertinent biomarkers associated with the outcome of phased progres- sion of atherosclerosis in healthy people, thereby could help to establish a more personalized treatment of clinical practice.

摘要：Background:The nanotechnology boom and the ability to manufacture novel nanomaterials have led to increased production and use of engineered nanoparticles(ENPs).However,the increased use of various ENPs inevitably results in their release in or the contamination of the environment,which poses significant threats to human *** recent years,extraordinary economic and societal benefits of nanoproducts as well as their potential risks have been observed and widely *** estimate whether ENPs are safe from the onset of their manufacturing to their disposal,evaluation of the toxicological effects of ENPs on human exposure,especially on more sensitive and vulnerable sectors of the population(infants and children)is *** sources:Papers were obtained from PubMed,Web of Science,and Google *** search words included:"nanoparticles","infants","children","exposure","toxicity",and all relevant ***:A brief overview was conducted to 1)characterize potential exposure routes of ENPs for infants and children;2)describe the vulnerability and particular needs of infants and children about ENPs exposure;3)investigate the current knowledge about the potential health hazards of ENPs;and 4)provide suggestions for future research and regulations in ENP ***:As the manufacturing and use of ENPs become more widespread,directed and focused studies are necessary to measure actual exposure levels and to determine adverse health consequences in infants and children.

摘要：Purpose:Wearable devices are commonly used to measure physical ***,it remains unclear the effect of wearing these devices on health *** aim was to provide evidence related to wearing physical activity trackers and health ***:A quantitative comparison study design was used comparing participants who wore physical activity tracking devices(n=108)and those who did not(n=112).A paper-based Physical health Knowledge survey designed for the purpose of this research was used for data collection in ***:A difference between participants who wore physical activity tracking devices and those that did not was identified in relation to activity levels and physical health *** devices are suggested as an opportunity for nurses to engage people in physical activity with the potential to improve their health ***:Nurses are well placed in the healthcare landscape to work with patients who own an activity tracker device concerning increasing activity *** information the patient has from the device can also form the basis of health discussions between nurses and the people in their care.

摘要：Fragment-based drug discovery （FBDD） has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad （Asp228 and Asp32） of D-site amyloid precursor protein cleaving enzyme 1 （BACE1）. A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 pM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/$2＇ pockets well.

摘要：Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer *** of this pathway by MEK inhibition is an efficient therapeutic approach of *** the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK *** acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.

摘要：Currently,cell culture models play a key role in determining cell behavior under various ***,the accurate simulation of cellular behavior that imitates the body’s conditions remains a ***,to overcome this obstacle,three-dimensional cell culture models have been *** tissues/organs-on-chips(TOOCs)are new devices that have provided the opportunity to culture cells in a medium that is almost similar to the physiological conditions of the *** can be designed in simple or complex models,which are mostly fabricated by soft *** novel structures have been developed to mimic the conditions of various tissues and organs;however,microfluidic models for oral and dental tissues have not yet been widely *** application of TOOCs for oral tissues/organs can provide the opportunity to study cell interactions with biomaterials used in ***,TOOCs can provide the opportunity to study the cellular interactions and developmental stages of oral tissues/organs more *** review of the current advances in the field of TOOC development for oral tissues provides a comprehensive understanding of this burgeoning concept,shows the progress and applications of these novel models in the imitation of oral tissues/organs thus far,and reveals the limitations that TOOCs ***,it suggests further perspectives for future applications.

摘要：Metabolites play important roles in numerous cell biology processes,such as cell proliferation,differentiation,stress response,and cell death[1].Recently,lactate and lactate-derived lysine residue lactylation(Kla)have emerged as newly discovered epigenetic modifications that play critical roles in various physiological and pathological *** the history of lactate research,we can categorize the studies into three mile stones(Fig.S1 online).

摘要：A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linked *** inhibitory activities were assayed against recombinant human ST3Gal I and ST6Gal I by using the Schmidt’s HPLC-based *** synthetic compound 15 g showed moderate inhibitory *** findings implied that carbamate might serve as a bioisosteric replacement for a phosphate group in sialyltransferase inhibitor design to improve the membrane permeability.