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.     

Organic mesh template-based laminated object manufacturing to fabricate ceramics with regular micron scaled pore structures

A new aqueous slurry-based laminated object manufacturing process for porous ceramics is proposed: firstly, an organic mesh sheet is pre-paved as a pore-forming template before slurry layer scraping; secondly, the 2D pattern is built with laser outline cutting of the dried mesh–ceramic composite layer; finally, the pore structure is formed after degreasing and sintering. Alumina parts with porosities of 51.5 %, round hole diameters of 80 ± 5 μm were fabricated using 70 wt. % solid content slurry and 100 mesh nylon net. Using an organic mesh as the framework and template not only reduces the risk of damage of the green body but also ensures the regularity, uniformity and connectivity of the micron scaled pore network. The layer-by-layer drying method avoids the delamination phenomenon and improves the paving density. The new method can realize the flexible design of the pore structure by using various organic mesh templates.     

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.     

Emergency egress for the elderly in care home fire situations

Practitioners are continuing to develop egress modelling software for the design of the built environment. These models require data about human behaviour and factors for calibration, validation and verification. This study aims to address the specific data and knowledge gap: emergency egress of the elderly. Such data are difficult to collect given privacy and consent concerns, with strong relationships generally being required between residences and researchers. Through the observation of nine fire drills at six Canadian long-term care (LTC) and retirement homes, specific evacuation actions and behaviour were observed for 37 staff members and information about the evacuation of 56 residents was collected. These drills demonstrated that emergency egress in LTC and retirement homes is highly staff dependent with 72% of residents recorded requiring full assistance at all stages of movement in evacuation, and that the type of announced/unannounced drill and level of resident care will affect the type of data collected. The development of travel speed and pre-movement is discussed subject to limitation with qualitative behavioural insights of residents that were observed. This study provides valuable methodological discussion on how to conduct behavioural studies in similar highly restricted research environments. Specific attention is given to understanding the considerations that must be made when using fire drills as data sources, and the impact that these can have on using such data for modelling. This study may inform the initial setup and programming of evacuation models from an actions and behavioural perspectives of staff members and residents.     

用于厚屏蔽小探测器的蒙特卡罗模拟减方差方法研究

反应堆屏蔽计算中经常出现厚屏蔽、小探测器问题，常规蒙特卡罗方法难以有效解决。基于自动重要抽样（AIS）方法，本文提出了小探测器自动重要抽样(SDAIS)方法，并针对小探测器问题，优化了AIS方法的虚粒子赌分裂算法。该方法在自主开发的蒙特卡罗屏蔽程序MCShield上进行了实现。使用NUREG/CR-6115 PWR基准题验证该方法的正确性和计算效率。结果表明，SDAIS方法可有效地解决厚屏蔽小探测器问题，相比AIS方法及传统的重要性方法，计算效率提升1~2个量级。     

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%.     

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.