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Programmed death‐ligand 1 (PD‐L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC‐1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC‐1 is positively correlated with PD‐L1 in human CRC specimens. SRC‐1 deficiency significantly inhibits PD‐L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8+ T cells. Genetic ablation of SRC‐1 in mice also decreases PD‐L1 expression in AOM/DSS‐induced murine CRC. These results suggest that tumor‐derived SRC‐1 promotes CRC immune escape by enhancing PD‐L1 expression. Mechanistically, SRC‐1 activated JAK‐STAT signaling by inhibiting SOCS1 expression and coactivated STAT3 and IRF1 to enhance PD‐L1 transcription as well as stabilized PD‐L1 protein by inhibiting proteasome‐dependent degradation mediated by speckle type POZ protein (SPOP). Pharmacological inhibition of SRC‐1 improved the antitumor effect of PD‐L1 antibody in both subcutaneous graft and AOM/DSS‐induced murine CRC models. Taken together, these findings highlight a crucial role of SRC‐1 in regulating PD‐L1 expression and targeting SRC‐1 in combination with PD‐L1 antibody immunotherapy may be an attractive strategy for CRC treatment. [ABSTRACT FROM AUTHOR]

This paper employs algebraic transformation to describe complex social network learning (SNL) behaviors under continuous expected payoff. Three distinct algorithms are then introduced that factor in uncertainty and heterogeneity. We find that individuals' strategies tend to converge through SNL. We then construct a framework for studying the convergence process in the principal–agent relationship by applying our SNL algorithms to distinct scenarios. Our results show that network topology plays a significant role in changes in the payoffs and the convergence speed of individuals' strategies. We also evaluate the impacts of uncertainty, heterogeneity, agents' output efficiency and risk aversion, and individual's centrality on the effectiveness of SNL. [ABSTRACT FROM AUTHOR]

A fabrication method comprising near‐field holography (NFH) with an electron beam lithography (EBL)‐written phase mask was developed to fabricate soft X‐ray varied‐line‐spacing gratings (VLSGs). An EBL‐written phase mask with an area of 52 mm × 30 mm and a central line density greater than 3000 lines mm−1 was used. The introduction of the EBL‐written phase mask substantially simplified the NFH optics for pattern transfer. The characterization of the groove density distribution and diffraction efficiency of the fabricated VLSGs indicates that the EBL–NFH method is feasible and promising for achieving high‐accuracy groove density distributions with corresponding image properties. Vertical stray light is suppressed in the soft X‐ray spectral range. [ABSTRACT FROM AUTHOR]