Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

Maskless Preparation of Spatially-Resolved Plasmonic Nanoparticles on Polydimethylsiloxane via In Situ Fluoride-Assisted Synthesis

Here, a fluoride-assisted route for the controlled in-situ synthesis of metal nanoparticles (NPs) (i.e., AgNPs, AuNPs) on polydimethylsiloxane (PDMS) is reported. The size and coverage of the NPs on the PDMS surface are modulated with time and over space during the synthetic process, leveraging the improved yield (10×) and faster kinetics (100×) of NP formation in the presence of F⁻ ions, compared to fluoride-free approaches. This enables the maskless preparation of both linear and step gradients and patterns of NPs in 1D and 2D on the PDMS surface. As an application in flexible plasmonics/photonics, continuous and step-wise spatial modulations of the plasmonic features of PDMS slabs with 1D and 2D AgNP gradients on the surface are demonstrated. An excellent spatially resolved tuning of key optical parameters, namely, optical density from zero to 5 and extinction ratio up to 100 dB, is achieved with AgNP gradients prepared in AgF solution for 12 minutes; the performance are comparable to those of commercial dielectric/interference filters. When used as a rejection filter in optical fluorescence microscopy, the AgNP-PDMS slabs are able to reject the excitation laser at 405 nm and retain the green fluorescence of microbeads (100 µm) used as test cases.     

Event-triggered variable horizon Supervisory Predictive control of hybrid power plants

The supervision of a hybrid power plant, including solar panels, a gas microturbine and a storage unit operating under varying solar power profiles is considered. The Economic Supervisory Predictive controller assigns the power references to the controlled subsystems of the hybrid cell using a financial criterion. A prediction of the renewable sources power is embedded into the supervisor. Results deteriorate when the solar power is unsteady, owing to the inaccuracy of the predictions for a long-range horizon of 10 s. The receding horizon is switched between an upper and a lower value according to the amplitude of the solar power trend. Theoretical results show the relevance of horizon switching, according to a tradeoff between performance and prediction accuracy. Experimental results, obtained in a Hardware In the Loop (HIL) framework, show the relevance of the variable horizon approach. Power amplifiers allow us to simulate virtual components, such as a gas microturbine, and to blend their powers with that of real devices (storage unit, real solar panels). In this case, fuel savings, reaching 15%, obtained under unsteady operating conditions lead to a better overall performance of the hybrid cell. The overall savings obtained in the experiments amount to 12%.     

Annual and regional variations of aflatoxin B1 levels seen in grains and feed coming from Croatian dairy farms over a 5-year period

The aim of the study was to investigate annual and regional differences in the level of aflatoxin B₁ (AFB₁) in grains and dairy cattle feed. Maize (n = 972), wheat (n = 201), barley (n = 147), oat (n = 136), grain mixtures (n = 168), and dairy cattle feed (n = 325) were sampled from 2009 to 2013 on different farms and in different farm factories situated in four Croatian regions. The samples were analysed for AFB₁ using the validated ELISA immunoassay. AFB₁ was determined in 16.4% of all investigated samples, among which maize was proven to be the most contaminated, with 21.7% of the samples recovered during 2013 harbouring AFB₁ in concentrations over the permissible ones. Levels higher than permitted were observed in 17.9% and 12.3% of grain mixtures and dairy cattle feed, respectively, whereas concentrations of AFB₁ determined in other crops throughout the investigated period met the stipulated requirements. The results revealed the AFB₁ occurrence to be significantly (p < 0.05) dependent on the cultivation region, with the highest levels generally found in maize harvested in 2013 and consequently in grain mixtures and cattle feed that can most likely be associated with climatic conditions as the most critical factor for mould formation, and thus also AFB₁ production.     

In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.     

A unified critical state model for geomaterials with an application to tunnelling

This paper is prepared in honour of Professor E.T. Brown for his outstanding contributions to rock mechanics and geotechnical engineering and also for his personal influence on the first author's research career in geomechanics and geotechnical engineering. As a result, we have picked a topic that reflects two key research areas in which Professor E.T. Brown has made seminal contributions over a long and distinguished career. These two areas are concerned with the application of the critical state concept to modelling geomaterials and the analysis of underground excavation or tunnelling in geomaterials.Partially due to Professor Brown's influence, the first author has also been conducting research in these two areas over many years. In particular, this paper aims to describe briefly the development of a unified critical state model for geomaterials together with an application to cavity contraction problems and tunnelling in soils.     

青年医学工作者科普能力培养新模式

为了培养青年医师运用医学科普语言传播医学知识的能力，向社会提供更优质、可及的健康知识，改善医患关系，促进社会和谐；同时出于向社区、媒体推送一批优秀青年医学科普人才的考虑，本文在总结北京协和医院培养青年医务人员医学科普能力经验的基础上，尝试构建一套适合大型公立医院（尤其是教学医院）培养青年医务人员医学科普能力的新模式——“科普训练营”。本文旨在系统介绍该模式的产生背景、实践经验及初期效果，阐释实施后的重要意义，及实施过程中的挑战与应对策略。