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RELAP5 is one of the most commonly used programs for reactor thermal hydraulic analysis. Due to the early developing time, RELAP5 does not have a friendly graphical user interface and interactive interface, resulting in the lack of human-computer interaction ability. In this work, the visual interactive simulation platform VITARS was developed by Java Script language based on Node.js framework. The origin RELAP5 was reformed then integrated into VITARS, and a bidirectional data communication pipe was established between RELAP5 process and VITARS process. In VITARS, a modeling module was developed, in which all the components in RELAP5 were abstracted into different pictograms and users could complete graphical modular modeling and parameter input for RELAP5 conveniently by stitching these pictograms, thus the use threshold of RELAP5 could be reduced. Due to the data communication pipe, VITARS could send control instructions to RELAP5 for pause, run, snapshot, terminate etc. The calculation results in RELAP5 could be displayed in VITARS as dynamic data meter or dynamic time-data curve in real time, and could be saved in VITARS for future viewing and extraction. In addition, a new signal logic computation system was developed in VITARS, in which more than forty kinds of signal logic computing components were built-in such as logical gate, proportional-integral, time delay integration, and flip-flop. As a data processing center for VITARS, the new signal logic computation system could read the thermal-hydraulic calculation results from RELAP5, user’s operation instruction etc., these data could be processed then distributed to RELAP5 to replace the thermal hydraulic boundary in time dependent component, adjustable equipment parameters or origin control data in the next time step, and could also be distributed to the data display system for real-time display. Therefore, with VITARS, complex proportion integration differentiation control system could be built for RELAP5, and user could adjust valve opening, pump speed and other equipment parameters in real time just like the reactor operators. Moreover, VITARS reserves the interfaces for coupling with other reactor analysis programs. VITARS also has the ability for users to customize the running interface. User could draw any reactor systems as the display background and kinds of graphical components such as dynamic data meter, warning light, reactor shut-down switch could be added. So that VITARS could also be used as a lightweight simulator of nuclear power plants. Model of Ling’ao Nuclear Power Plant was developed and a steady-state simulation was performed in VITARS. The simulation results were compared with that from origin RELAP5 program, which indicates the calculation accuracy of VITARS. VITARS could not only improves the efficiency of RELAP5, but also enhances human-computer interaction capabilities, which could be helpful for reactor safety analysis and operator training work.

Molybdenum nitrogenase catalyzes the reduction of dinitrogen into ammonia, which requires the coordinated transfer of eight electrons to the active site cofactor (FeMoco) through the intermediacy of an [8Fe-7S] cluster (P-cluster), both housed in the molybdenum-iron protein (MoFeP). Previous studies on MoFeP from two different organisms, Azotobacter vinelandii ( Av) and Gluconacetobacter diazotrophicus ( Gd), have established that the P-cluster is conformationally flexible and can undergo substantial structural changes upon two-electron oxidation to the POX state, whereby a backbone amidate and an oxygenic residue (Ser or Tyr) ligate to two of the cluster's Fe centers. This redox-dependent change in coordination has been implicated in the conformationally gated electron transfer in nitrogenase. Here, we have investigated the role of the oxygenic ligand in Av MoFeP, which natively contains a Ser ligand (βSer188) to the P-cluster. Three variants were generated in which (1) the oxygenic ligand was eliminated (βSer188Ala), (2) the P-cluster environment was converted to the one in Gd MoFeP (βPhe99Tyr/βSer188Ala), and (3) two oxygenic ligands were simultaneously included (βPhe99Tyr). Our studies have revealed that the P-cluster can become compositionally labile upon oxidation and reversibly lose one or two Fe centers in the absence of the oxygenic ligand, while still retaining wild-type-like dinitrogen reduction activity. Our findings also suggest that Av and Gd MoFePs evolved with specific preferences for Ser and Tyr ligands, respectively, and that the structural control of these ligands must extend beyond the primary and secondary coordination spheres of the P-cluster. The P-cluster adds to the increasing number of examples of inherently labile Fe-S clusters whose compositional instability may be an obligatory feature to enable redox-linked conformational changes to facilitate multielectron redox reactions.

CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity.

Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicinal plant that is indigenous to the southern regions of China. Previous research has provided evidence of the significant anti-inflammatory, antibacterial, and anticancer properties exhibited by Z. nitidum. The potential therapeutic effects and cardiac toxicity of Z. nitidum remain uncertain. The aim of this research was to investigate the potential therapeutic properties of the four main compounds of Z. nitidum in cardiovascular diseases, their impact on the electrical activity of cardiomyocytes, and the underlying mechanism of their anti-inflammatory effects. We selected the four compounds from Z. nitidum with a high concentration and specific biological activity: nitidine chloride (NC), chelerythrine chloride (CHE), magnoflorine chloride (MAG), and hesperidin (HE). A proteomic analysis was conducted on the myocardial tissues of beagle dogs following the administration of NC to investigate the role of NC in vivo and the associated biological processes. A bioinformatic analysis was used to predict the in vivo biological processes that MAG, CHE, and HE were involved in. Molecular docking was used to simulate the binding between compounds and their targets. The effect of the compounds on ion channels in cardiomyocytes was evaluated through a patch clamp experiment. Organ-on-a-chip (OOC) technology was developed to mimic the physiological conditions of the heart in vivo. Proteomic and bioinformatic analyses demonstrated that the four compounds of Z. nitidum are extensively involved in various cardiovascular-related biological pathways. The findings from the patch clamp experiments indicate that NC, CHE, MAG, and HE elicit a distinct activation or inhibition of the IK1 and ICa-L in cardiomyocytes. Finally, the anti-inflammatory effects of the compounds on cardiomyocytes were verified using OOC technology. NC, CHE, MAG, and HE demonstrate anti-inflammatory effects through their specific interactions with prostaglandin-endoperoxide synthase 2 (PTGS2) and significantly influence ion channels in cardiomyocytes. Our study provides a foundation for utilizing NC, CHE, MAG, and HE in the treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Highly sensitive electronic skin (e‐skin) sensors with considerable operating range offer great possibilities for health care, human–‐machine interfaces, and intelligent robotics. Although subtle microstructures have been used in recent years to improve the sensitivity and sensing range of e‐skin sensors, the trade‐off between these features remains a big challenge to overcome. Here, an asymmetric interlocked gradient elastic modulus (AIGM) structure is designed for the first time to provide sufficient deformation space to the traditional interlocked structure while ensuring high sensitivity, and the gradient elastic modulus further extends the sensing range of the AIGM structure‐based sensors, which exhibit a maximum sensitivity of as high as 9.89 kPa−1 with an ultrawide working range that extends to above 530 kPa at the same time. As a demo, this sensor is integrated into an intelligent adjustable mouse platform for physiological signal monitoring, pressure feedback, and modulus adjustment, providing a viable alternative for hand disease prevention. [ABSTRACT FROM AUTHOR]

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