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African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKβ via selective autophagy. However, the E3 ubiquitin ligase responsible for IKKβ ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKKβ ubiquitination. Finally, we indicated that the degradation of IKKβ by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKKβ by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF. [ABSTRACT FROM AUTHOR]

For the purpose of measuring µN- and mN-level micro-force, the optical reflection characteristics of a circular thin film are utilized to develop a micro-force sensor and double concentric circle fibres are used to measure the micro-force. This paper focuses on the relation between the output parameters of the system, namely the voltage ratio of the two receiving fibres, and the micro-force, the diameter, the thickness and the materials of the thin film, as well as the displacement between the fibre probe and the film. A measurement platform has been set-up and a large number of experiments have been conducted to determine the relationship between the voltage ratio and the micro-force, the diameter and the thickness of the thin film by using a least square exponential fitting algorithm. Furthermore, the errors between the calculating values from the fitting equation and the experimental values are obtained and analysed, which supports the conclusion that when the micro-force is in the range of 0–10 mN, the equation can be used to measure the micro-force with the resolution of 10 µN in the error range of −1.5%–+2.5%, and an automatic measurement process is realized. [ABSTRACT FROM AUTHOR]

In order to realize the precise measurement of a micro-force in the biomedical domain and industrial fields, a type of spherical film, of about 700 nm thickness and 50 mm diameter, was used as sensing element to detect a nano-Newton (nN) level force. Distortions were observed when nN-level particles were placed on the spherical film or such level forces were applied on the spherical film. From the deformation of spherical film, we can obtain the gravity of the particle or applied force. A dynamic model of the spherical film was constructed using the ANSYS software. Adopting the orthogonal experimental method, we designed effective experimental parameters for numerical calculation and mainly focused on the relations among nN-level force, thickness and diameter of spherical film, and deformation parameters. Then a fitting formula describing the relationship between deformation, the thickness and diameter of the spherical film, and the loaded force was obtained from the experimental data using the least square algorithm. The error analysis of experimental and computational data showed that when controlling the force in the range of 20–160 nN, the detecting error was less than ±3.2%. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), which imposes a substantial economic burden on the global pig industry. When screening for the virus replication-regulating genes in the left variable region of the ASFV genome, we observed a notable reduction in ASFV replication following the deletion of the MGF300-4L gene. However, the role of MGF300-4L in ASFV infection remains unexplored. In this study, we found that MGF300-4L could effectively inhibit the production of proinflammatory cytokines IL-1 β and TNF- α , which are regulated by the NF- κ B signaling pathway. Mechanistically, we demonstrated that MGF300-4L interacts with IKK β and promotes its lysosomal degradation via the chaperone-mediated autophagy. Meanwhile, the interaction between MGF300-4L and I κ B α competitively inhibits the binding of the E3 ligase β -TrCP to I κ B α , thereby inhibiting the ubiquitination-dependent degradation of I κ B α . Remarkably, although ASFV encodes other inhibitors of NF- κ B, the MGF300-4L gene-deleted ASFV (Del4L) showed reduced virulence in pigs, indicating that MGF300-4L plays a critical role in ASFV pathogenicity. Importantly, the attenuation of Del4L was associated with a significant increase in the production of IL-1 β and TNF- α early in the infection of pigs. Our findings provide insights into the functions of MGF300-4L in ASFV pathogenicity, suggesting that MGF300-4L could be a promising target for developing novel strategies and live attenuated vaccines against ASF.

Selective autophagy is a protein clearance mechanism mediated by evolutionarily conserved selective autophagy receptors (SARs), which specifically degrades misfolded, misassembled, or metabolically regulated proteins. SARs help the host to suppress viral infections by degrading viral proteins. However, viruses have evolved sophisticated mechanisms to counteract, evade, or co-opt autophagic processes, thereby facilitating viral replication. Therefore, this review aims to summarize the complex mechanisms of SARs involved in viral infections, specifically focusing on how viruses exploit strategies to regulate selective autophagy. We present an updated understanding of the various critical roles of SARs in viral pathogenesis. Furthermore, newly discovered evasion strategies employed by viruses are discussed and the ubiquitination-autophagy-innate immune regulatory axis is proposed to be a crucial pathway to control viral infections. This review highlights the remarkable flexibility and plasticity of SARs in viral infections., Competing Interests: The authors declare no conflict of interest.

Cell-mediated immune response is an important part of machinery in maintaining the body's homeostasis. After the innate immune system selectively activates the adaptive immune system, the cell-mediated immunity exerts its killing and clearance functions. Therefore, evaluating the level of cell-mediated immune response is crucial in the diagnosis and treatment of cancer, monitoring the immune status after organ transplantation, diagnosing and preventing viral diseases, and evaluating the effectiveness of vaccines and other areas. From the initial overall assessment of the immune effects in vivo to the precise detection of the number and function of multiple immune cells, the evaluation methods of cell-mediated immune response have greatly advanced. However, cell-mediated immune response involves multiple levels in the body, and it's difficult to choose the numerous detection methods available. The article systematically compares the evaluation methods of cell-mediated immune response at four different levels: the organism, the tissue and organ, the immune cells and the immune molecules, with the aim to facilitate the applications of related technologies.