Science Bulletin最新文献

Peritoneal metastasis (PM) is typically intractable by immunotherapy due to an immunosuppressive microenvironment and the peritoneal-plasma barrier. Sonodynamic therapy (SDT) presents unique advantages of noninvasive in situ treatment and the potential for antitumor immune activation. Building upon SDT technology, the study reports on a novel biodegradable sonosensitizer, CaS₂O₈, characterized by a narrow bandgap, abundant oxygen vacancies and a rapid ultrasound (US) response for abdominal SDT. Such sonosensitizer only produces lethal reactive oxygen species (ROS) after US irradiation, which is nontoxic in a physiological environment. After US irradiation, CaS₂O₈ yields a large amount of sulfate radical (SO₄^-), as well as sonodynamic related ROS (OH, and ¹O₂), which exerts a synergistic effect with Ca²⁺ overload to induce Z-conformation nucleic acid by augmenting oxidative damage. As a result, the PANoptosis is initiated through the ZBP1/RIPK3 pathway in tumor cells. This inflammatory cell death leads to a multi-faceted release of tumor cell contents which serve as an in situ tumor antigen to induce a robust antitumor immune response. Notably, the precision sono-immunotherapy enhances the infiltration of T cells into tumors by transforming an immunosuppressive phenotype into an immunostimulatory one. Therefore, targeting PANoptosis by CaS₂O₈-induced SDT can provide an alternative or additional clinical treatment and prolonged survival outcome for patients with PM.

The Fe-N₄ motif is regarded as a leading non-precious metal catalyst for the oxygen reduction reaction (ORR) with the potential to replace platinum (Pt), yet achieving or surpassing the performance of Pt-based catalysts remains a significant challenge. In this study, we introduce a modification strategy employing homogeneous few-atom Fe₃ cluster to regulate the spin polarization of Fe-N₄. Experimental research and theoretical calculations show that the incorporation of the Fe₃ cluster significantly enhances the adsorption of Fe-N₄ motif toward OH ligands, leading to a structural transformation from a square-planar field (Fe-N₄) to a square-pyramid field structure (Fe(OH) -N₄). This structural transformation reduces the spin polarization of 3d_xz, 3d_yz, and 3d_z² orbitals of Fe-N₄, resulting in a decrease in unpaired electrons within 3d orbitals. As a result, this modulation leads to moderate adsorption/desorption energies of reaction intermediates, thereby facilitating the ORR process. Moreover, the in-situ spectroscopy confirms that the desorption of OH* on Fe₃/Fe(OH) -NC motif is more favorable compared to atomic Fe-NC, indicating a lower energy barrier for ORR. Consequently, the Fe₃/Fe-NC catalyst demonstrates outstanding ORR performance with a half-wave potential of 0.836 V vs. reversible hydrogen electrode (RHE) in 0.1 mol L^-1 HClO₄ solution and 0.936 V vs. RHE in 0.1 mol L^-1 KOH solution, even surpassing commercial Pt/C catalyst. It also exhibits excellent Zn-air battery efficiency. Our study introduces a novel approach to modulating the electronic structure of single atoms catalysts by leveraging the robust interaction between single atoms and atomic clusters.

Designing three-dimensional (3D) catalytic sites in single-atom catalysts (SACs) that mimic thyroid peroxidase (TPO) function for achieving iodotyrosine coupling, although highly desirable for the synthesis of thyroid hormones, poses a great challenge. Herein, we design and synthesize a class of SACs with 3D catalytic centers composed of Cu-N₅ as catalytic sites and BO₂ as binding sites (BO₂/CuN₅C) for mimicking TPO in activating H₂O₂ to facilitate tyrosine iodination and conjugation for producing thyroid hormones. We demonstrate that the as-prepared BO₂/CuN₅C not only provides binding sites for H₂O₂ through hydrogen bond interactions but also possesses catalytic sites to promote an alternative O-O heterolysis process. BO₂/CuN₅C with TPO-like catalytic centers can produce 3,3',5-triiodothyronine and d-thyroxine with 2.4-fold and 11.1-fold improvements relative to those of CuN₅C. Besides, the assessment of 2-mercapto-1-methylimidazole and 6-propyl-2-thiouracil in vitro investigations of antithyroid drugs corresponds well with the European Thyroid Association guidelines and therefore can provide clinical medication guidance to prevent toxic reactions. Overall, this work unlocks an approach to precisely simulate the natural enzyme active site for amino acid coupling and pharmaceutical assessment.