Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells.

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.

Selective Adsorption of Sr(II) from Aqueous Solution by Na3FePO4CO3: Experimental and DFT Studies.

The efficient segregation of radioactive nuclides from low-level radioactive liquid waste (LLRW) is paramount for nuclear emergency protocols and waste minimization. Here, we synthesized Na3FePO4CO3 (NFPC) via a one-pot hydrothermal method and applied it for the first time to the selective separation of Sr2+ from simulated LLRW. Static adsorption experimental results indicated that the distribution coefficient Kd remained above 5000 mL·g-1, even when the concentration of interfering ions was more than 40 times that of Sr2+. Furthermore, the removal efficiency of Sr2+ showed no significant change within the pH range of 4 to 9. The adsorption of Sr2+ fitted the pseudo-second-order kinetic model and the Langmuir isotherm model, with an equilibrium time of 36 min and a maximum adsorption capacity of 99.6 mg·g-1. Notably, the adsorption capacity was observed to increment marginally with an elevation in temperature. Characterization analyses and density functional theory (DFT) calculations elucidated the adsorption mechanism, demonstrating that Sr2+ initially engaged in an ion exchange reaction with Na+. Subsequently, Sr2+ coordinated with four oxygen atoms on the NFPC (100) facet, establishing a robust Sr-O bond via orbital hybridization.