Copper overload is a novel way to achieve copper-ion-interference therapy by disrupting copper homeostasis and treating diseases through multiple cell death pathways. However, it is difficult to reach copper overload since excess intracellular copper ions will be pumped out. Herein, copper overload is achieved by both raising cellular uptake and reducing the efflux of copper ions using hydrogen sulfide (H2S)-responsive copper hydroxyphosphate nanoparticles (Cu2(PO4)(OH) NPs). After immersion in an H2S-enriched colon cancer microenvironment, Cu2(PO4)(OH) NPs can transform into copper sulfide NPs with reduced size for higher cell entering, resulting in improved Fenton activity as well as copper ion dissociation. Reactive oxygen species generated by the Fenton reaction not only activate inflammasomes and Caspase-1 proteins, cause the cleavage of gasdermin D to induce pyroptosis, but also affect mitochondrial function and down-regulate copper exporter ATP7A to further reduce the copper excretion. The combination of higher endocytosis and lower exportation leads to maximized copper overload. Together with the efficient copper ions release, mitochondrial tricarboxylic acid cycle can be disrupted and iron-sulfur cluster proteins are downregulated, ultimately triggering cuproptosis. As both pyroptosis and cuproptosis are efficient ways to induce cell death, this study provides a novel way to realize effective tumor-targeted therapy based on H2S-activated copper overload with simple Cu2(PO4)(OH) NPs. 相似文献
Lithium (Li) metal is the most ideal anode material for high‐energy density batteries. However, the high activity of Li metal, the large volume change, and Li dendrite formation during cycling hinder its practical application. Herein, 3D porous Cu synthesized through a simple time‐saving hydrogen bubble dynamic template method is used as a host for the improved performance Li metal anode. Contrary to the planar Cu foil, the synthesized 3D porous structure can reduce the local current density, suppress the mossy/dendritic Li growth, and buffer the volume change in the Li metal anode. Highly stable Coulombic efficiency is achieved at different specific current densities (0.5, 1, and 2 mA cm?2) with a capacity of 1.0 mAh cm?2. Moreover, symmetrical Li|Li‐3D Cu cells show more stable cyclic performance with a lower overpotential even at a high current density of 3 mA cm?2. 相似文献
Recently, truthful spectrum auctions have been extensively studied to improve spectrum utilization. Furthermore, privacy preservation in truthful spectrum auctions has also been taken into account. However, existing work mainly focuses on privacy-preserving homogenous spectrum auctions, while the case of heterogeneous spectrum auctions is ignored. In this paper, we propose PATH, a privacy-preserving auction for single-sided heterogeneous spectrum allocations. Through organically combining three security techniques: homomorphic encryption, secret sharing and garbled circuit, PATH reveals nothing about buyers’ bids and identities beyond the auction outcome to any participant party. Specifically, PATH not only maintains the properties of truthfulness and spectrum reuse of the underlining auction mechanism TAMES, but also implements the first provably secure solution for single-sided heterogeneous spectrum auctions. Finally, experimental results demonstrate that PATH incurs only limited computation and communication overhead, and it is feasible for large-scale applications.
