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Chimeric antigen receptor (CAR)‐T cell therapy is a transformative treatment against advanced malignancies. Unfortunately, once administrated in vivo, CAR‐T cells become out of artificial control, and fierce response to CAR‐T therapy may cause severe adverse events, represented by cytokine‐release syndrome and on‐target/off‐tumor effects. Here, a nanomodified switch strategy is developed, leading to sustained and precise “on‐tumor only” activation of CAR‐T cells. Here, original gelatinase‐responsive nanoparticles (NPs) are used to selectively deliver the heterodimerizing switch, which is the key component of switchable CAR with separated activation modules. The “NanoSwitch” is tumor‐specific, thus inactivated switchable CAR‐T cells do little harm to normal cells, even if the normal cells express the target of CAR‐T. Owing to the sustained‐release effect of NPs, the CAR‐T cells are activated smoothly, avoiding sudden release of cytokine. These data introduce NanoSwitch as a universal and applicable solution to safety problems of CAR‐T therapy regardless of the target. Here, nanoparticles based on gelatinase‐responsive strategy are used to construct “NanoSwitch” to control the activation process of chimeric antigen receptor (CAR)‐T cells, leading to on‐site activation of CAR‐T cells at the tumor region in a precise and sustainable way. This platform has promising potential to prevent the main obstacles in the CAR‐T therapy for solid tumors including cytokine‐release syndrome and on‐target/off‐tumor toxicity.

Cancer Immunotherapy In article number 2205044, Baorui Liu, Rutian Li, and co‐workers constructed gelatinase‐responsive NanoSwitch to control the activation process of CAR‐T cells, leading to on‐site activation of CAR‐T cells at the tumor region in a sustainable way. This platform has promising potential to prevent the main obstacles in the CAR‐T therapy for solid tumors including cytokine‐release syndrome and on‐target/off‐tumor toxicity.

The underground rivers and karst fracture networks develop in the Guizhou area. The bedrock predominantly comprises muddy sandstone with pronounced karst geomorphology, significantly compromising the bearing capacity of bridge pile foundations. To elucidate the impact of karst development on drilled shaft performance, two test piles from a highway project in Liupanshui City were subjected to experimental analysis, investigating the correlation between karst features and pile foundation bearing behavior. The axial force distribution pattern, lateral frictional resistance ( f s ) transfer mechanism, and tip resistance characteristics were systematically analyzed by in situ self‐equilibrium static load tests. The test data indicate that during O‐cell loading, significant relative displacement develops between upper and lower pile segments. The peak axial force consistently localizes at the O‐cell interface cross‐section. The attenuation rate is relatively fast downwards along the pile body, and the rate of upward decay starts fast and then becomes relatively flat. The f s exhibits nonlinear decay with diminishing pile‐soil relative displacement gradient, attaining its minimum magnitude within the pile tip region. The comparative analysis reveals that although the reaction force–displacement curve at the pile end of the lower pile section has similar nonlinear characteristics to the static load test. There are significant differences in the stress field distribution characteristics of the soil around the pile. In the self‐balancing method test, the soil around the pile shows an asymmetric stress distribution pattern.

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol’s therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.