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Abstract Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS–STING-mediated signalling and tumour suppression^1–3. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA)^4–10. Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation. We demonstrate that binding of the MRE11–RAD50–NBN complex to nucleosome fragments is necessary to displace cGAS from acidic-patch-mediated sequestration, which enables its mobilization and activation by dsDNA. MRE11 is therefore essential for cGAS activation in response to oncogenic stress, cytosolic dsDNA and ionizing radiation. Furthermore, MRE11-dependent cGAS activation promotes ZBP1–RIPK3–MLKL-mediated necroptosis, which is essential to suppress oncogenic proliferation and breast tumorigenesis. Notably, downregulation ofZBP1in human triple-negative breast cancer is associated with increased genome instability, immune suppression and poor patient prognosis. These findings establish MRE11 as a crucial mediator that links DNA damage and cGAS activation, resulting in tumour suppression through ZBP1-dependent necroptosis. 

The underwater acoustic (UWA) channel is a complex and stochastic process with large spatial and temporal dynamics. This work studies the adaptation of the communication strategy to the channel dynamics. Specifically, a set of communication strategies are considered, including frequency shift keying (FSK), single-carrier communication, and multicarrier communication. Based on the channel condition, a reinforcement learning (RL) algorithm, the Depth Determined Strategy Gradient (DDPG) method along with a Gumbel-softmax scheme is employed for intelligent and adaptive switching among those communication strategies. The adaptive switching is performed on a transmission block-by-block basis, with the goal of maximizing a long-term system performance. The reward function is defined based on the energy efficiency and the spectral efficiency of the communication strategies. Simulation results reveal that the proposed method outperforms a random selection method in time-varying channels.