USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase

Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow–derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I

Multi-Objective Optimization of the Basic and Regenerative ORC Integrated with Working Fluid Selection

A multi-objective optimization based on the non-dominated sorting genetic algorithm (NSGA-II) is carried out in the present work for the basic organic Rankine cycle (BORC) and regenerative ORC (RORC) systems. The selection of working fluids is integrated into multi-objective optimization by parameterizing the pure working fluids into a two-dimensional array. Two sets of decision indicators, exergy efficiency vs. thermal efficiency and exergy efficiency vs. levelized energy cost (LEC), are adopted and examined. Five decision variables including the turbine inlet temperature, vapor superheat degree, the evaporator and condenser pinch temperature differences, and the mass fraction of the mixture are optimized. It is found that the turbine inlet temperature is the most effective factor for both the BORC and RORC systems. Compared to the reverse variation of exergy efficiency and thermal efficiency, only a weak conflict exists between the exergy efficiency and LEC which tends to make the binary objective optimization be a single objective optimization. The RORC provides higher thermal efficiency than BORC at the same exergy efficiency while the LEC of RORC also becomes higher because the bare module cost of buying one more heat exchange is higher than the cost reduction due to the reduced heat transfer area. Under the heat source temperature of 423.15 K, the final obtained exergy and thermal efficiencies are 45.6% and 16.6% for BORC, and 38.6% and 20.7% for RORC, respectively

Dynamic Modeling and Comparison Study of Control Strategies of a Small-Scale Organic Rankine Cycle

The control strategy is crucial for the effective and safe operation of the ORC system. A transient model of the ORC system was developed in the present work and validated by the experimental data of a 4 kW ORC prototype. Then, the effect of heat source temperature on the dynamic response and operation characteristics of the ORC system were analyzed. Five control strategies were compared: the constant working fluid mass flow rate mode, constant vapor superheat mode, constant vapor temperature mode, constant evaporation pressure mode and constant output power load mode. Under the constraint that the working fluid at the expander inlet should be superheated, we found that the constant vapor superheat mode enabled the safe operation with the largest range of heat source temperature, while the other four modes were only available for a certain temperature range. Apart from the constant output power mode, the constant evaporation pressure mode can also provide a relatively stable performance for the ORC unit. The variation of the thermal efficiency was limited when the heat source temperature was higher than 125 °C, except for the constant vapor temperature mode. Considering the high performance and stable operation of the ORC system, it is necessary to have different operation modes combined in the control strategy according to the specific working scenarios