DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length. Consistently, DNA-sequence was shown to control cGAS activation. Structural analyses revealed that a conserved cGAS residue (mouse R222 or human R236) contributed to the DNA-flexibility detection. And the residue substitution neutralised the flexibility-controlled DNA-potential to activate cGAS, and relaxed the DNA-length specificity of cGAS. Moreover, low dose radiation was shown to mount cGAS-mediated acute immune surveillance (AIS) via repairable (reusable) DNAs in hrs. Loss of cGAS-mediated AIS decreased the regression of local and abscopal tumours in the context of focal radiation and immune checkpoint blockade. Our results build a direct link between immunosurveillance and DNA mechanical feature.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause and limited to the lungs. Schisandrae chinensis fructus (Wuweizi, Schisandra) is commonly used traditional Chinese medicines (TCM) for the treatment of pulmonary fibrosis, bronchitis, and other lung diseases in China. In this study, we investigated the therapeutic effect of Schisandra on IPF which is induced by bleomycin (BLM) in rats and the inhibition of alternatively activated macrophage (M2) polarization. Bleomycin-induced pulmonary fibrosis was used as a model for IPF, and rats were given drug interventions for 7 and 28 days to evaluate the role of Schisandra in the early oxidative phase and late fibrotic phases of BLM-induced pulmonary injury. The data showed that Schisandra exerted protective effects on BLM-induced pulmonary injury in two phases, which were improving inflammatory cell infiltration and severe damages of lung architectures and decreasing markers of M2 subtype. In order to prove the inhibitory effect of Schisandra on M2 polarization, in vitro experiments, we found that Schisandra downregulated the M2 ratio, which confirmed that the polarization of M2 was suppressed. Moreover, Schisandra blocked TGF-β1 signaling in AMs by reducing the levels of Smad3 and Smad4; meanwhile, the upregulation of Smad7 by Schisandra also promoted the effect of inhibition on the TGF-β1/Smad pathway. These results demonstrate that suppression of M2 polarization by Schisandra is associated with the development of IPF in rats.

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Phase separation (PS) is a fundamental principle in diverse life processes including immunosurveillance. Despite numerous studies on PS, little is known about its dissolution. Here, it is shown that oleic acid (OA) dissolves the cyclic GMP–AMP synthase (cGAS)–deoxyribonucleic acid (DNA) PS and inhibits immune surveillance of DNA. As solvent components control PS and metabolites are abundant cellular components, it is speculated that some metabolite(s) may dissolve PS. Metabolite‐screening reveals that the cGAS–DNA condensates formed via PS are markedly dissolved by long‐chain fatty acids, including OA. OA revokes intracellular cGAS–PS and DNA‐induced activation. OA attenuates cGAS‐mediated antiviral and anticancer immunosurveillance. These results link metabolism and immunity by dissolving PS, which may be targeted for therapeutic interventions.

COPD is one of the most prevalent and deadliest diseases in the world today, and in 2019 it was the third leading cause of death in the world. Primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages. For this reason, assessing the status of tracheal ventilation is crucial. To this end, for early detection and early treatment, a biological sound measurement system had been developed that measures vascular and respiratory sounds simultaneously. The system obtains the biological sound by attaching the biological sound sensor on the head. That quantitative assessment of the patient's degree of illness through changes in their tracheal sounds before and after exercise. In this study, the aim is to use wavelet analysis to isolate the noise generated during daily action for extracting the respiratory sound, including stepping conduction noise, short-time friction noise, and the measured vascular sound. Since the original signal-to-noise ratio is too small, the result evaluates the system's effectiveness by comparing the noise-free signal with the absolute noise. As a result, the amplitude and duration of noise are effectively reduced without artifacts. The signal is improved by about 30 dB on average. So, the proposed system is expected to be applied to telemedicine.