Biao Wang

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 + T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB , enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 ( GLUT1 ), hexokinase 1 ( HK1 ), lactate dehydrogenase A ( LDHA ), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8 + T cells and the proportion of interferon‐γ + CD8 + T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.

In the relentless pursuit of quantum computational advantage, we present a significant advancement with the development of Zuchongzhi 3.0. This superconducting quantum computer prototype, comprising 105 qubits, achieves high operational fidelities, with single-qubit gates, two-qubit gates, and readout fidelity at 99.90%, 99.62%, and 99.13%, respectively. Our experiments with an 83-qubit, 32-cycle random circuit sampling on the Zuchongzhi 3.0 highlight its superior performance, achieving 1×10^{6} samples in just a few hundred seconds. This task is estimated to be infeasible on the most powerful classical supercomputers, Frontier, which would require approximately 5.9×10^{9} yr to replicate the task. This leap in processing power places the classical simulation cost 6 orders of magnitude beyond Google's SYC-67 and SYC-70 experiments [Morvan et al., Nature 634, 328 (2024)10.1038/s41586-024-07998-6], firmly establishing a new benchmark in quantum computational advantage. Our work not only advances the frontiers of quantum computing but also lays the groundwork for a new era where quantum processors play an essential role in tackling sophisticated real-world challenges.

In this study, the effects of Mg on the formation of He bubbles and diffusion behavior of He atoms in 3C-SiC were investigated by irradiation and annealing experiment as well as the first-principles calculations. TEM results indicated that two damage bands were formed in the He&Mg irradiated SiC. During annealing, Mg could prevent He atoms from diffusing to the surface, resulting in the formation of He bubbles in the deeper areas far from the Mg-implanted regions, which is helpful to avoid the surface blisters. First-principles calculations were then performed to explore the effects of Mg on the He behavior in SiC. The solution energy, binding energy charge density, bond length, and crystal orbital Hamiltonian population of these elements were calculated to identify their states. The results suggested that the binding capacity between He and Mg was weak, and Mg could increase the diffusion energy barrier of He. AIMD simulation showed that Mg could make He in a high-energy unstable state, and force He atom to move toward the vacancy away from Mg, which explains the experimental results.