Inflammasomes are essential complexes of innate immune system, which form the first line of host defense against pathogens. Mounting evidence accumulates that inflammasome signaling is highly correlated with coronavirus disease 2019 (COVID-19). However, there remains a significant gap in our understanding of the regulatory mechanism of inflammasome signaling. Combining mathematical modeling with experimental analysis of NLRP1b inflammasome signaling, we found that only the expression levels of caspase-1 and GSDMD have the potential to individually switch cell death modes. Reduction of caspase-1 or GSDMD switches cell death from pyroptosis to apoptosis. Caspase-1 and GSDMD present different thresholds and exert distinct pathway choices in switching death modes. Pyroptosis switches to apoptosis with an extremely low threshold level of caspase-1, but with a high threshold of GSDMD. Caspase-1-impaired cells employ ASC-caspase-8-dependent pathway for apoptosis, while GSDMD-impaired cells primarily utilize caspase-1-dependent pathway. Additionally, caspase-1 and GSDMD can severally ignite the cooccurrence of pyroptosis and apoptosis. Landscape topography unravels that the cooccurrence is dramatically different in caspase-1- and GSDMD-impaired cells. Besides pyroptosis state and apoptosis state, a potential new “coexisting” state in single cells is proposed when GSDMD acts as the driving force of the landscape. The “seesaw model” is therefore proposed, which can well describe the death states that are controlled by caspase-1 or GSDMD in single cells. Our study sheds new light on NLRP1b inflammasome signaling and uncovers the switching mechanisms among various death modes, providing potential clues to guide the development of more rational control strategies for diseases.

In this work, we investigate gradient coupling effect on oscillation death in a ring of N delay-coupled oscillators. We find that the gradient coupling monotonically reduces the domain of death island in the parameter space of the diffusive coupling and time delay, and thus the death island can be completely eliminated once the gradient coupling strength exceeds a certain threshold, whose value is found to be a constant if N is sufficiently large. For two special cases, a ring with zero gradient coupling and a one-way ring for identical diffusive and gradient couplings, all previous results in the literature are recovered. In particular, for the one-way ring, a size effect of N is discovered, which indicates that under this situation the death can always be eliminated if N is above a critical N(max). All the described results are proved to hold generally in coupled oscillator systems.

Low-frequency signal transmission in one-way coupled bistable systems subject to a high-frequency force is studied. Two cases including the high-frequency force on all sites (case 1) and only on the first site (case 2) are considered. In these two cases, vibrational resonance induced by the high-frequency force can play an active role to effectively improve the signal transmission, and undamped signal transmission can be found in a broad parameter region. The combinative action of injected low-frequency signal, high-frequency driving, and coupling is of importance. Our findings suggest that high-frequency signal could be properly used in low-frequency signal transmission, and especially the implementation of high-frequency force simply on the first site for case 2 is meaningful for its simplicity and high efficiency.