AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy.

BACKGROUND: Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma. METHODS: The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry. RESULTS: Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion. CONCLUSIONS: This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

An in situ assembled WO3-TiO2 vertical heterojunction for enhanced Z-scheme photocatalytic activity.

The face-to-face contact of a vertical heterojunction is beneficial to charge interaction in photocatalysis. However, constructing a vertical heterojunction with uncompromised redox ability still remains a challenge. Herein, we report the successful synthesis of a WO3-TiO2 vertical heterojunction via establishing an internal electric field across the interface. Experimental investigation and computational simulations reveal that strong electric coupling occurs at the WO3-TiO2 interface forming an internal electric field. The internal electric field induces a Z-scheme charge-carrier transfer through the heterojunction under light irradiation, which leads to effective charge separation and maintains high reaction potentials of charge-carriers. The improved photocatalytic activity of the WO3-TiO2 heterojunction is proved by enhanced generation of reactive oxygen species and accelerated Escherichia coli (E. coli) disinfection. This study provides new insights into understanding and designing Z-scheme heterogeneous photocatalysts.

Self-Assembled Ruddlesden-Popper/Perovskite Hybrid with Lattice-Oxygen Activation as a Superior Oxygen Evolution Electrocatalyst.

The oxygen evolution reaction (OER) is pivotal in multiple gas-involved energy conversion technologies, such as water splitting, rechargeable metal-air batteries, and CO2 /N2 electrolysis. Emerging anion-redox chemistry provides exciting opportunities for boosting catalytic activity, and thus mastering lattice-oxygen activation of metal oxides and identifying the origins are crucial for the development of advanced catalysts. Here, a strategy to activate surface lattice-oxygen sites for OER catalysis via constructing a Ruddlesden-Popper/perovskite hybrid, which is prepared by a facile one-pot self-assembly method, is developed. As a proof-of-concept, the unique hybrid catalyst (RP/P-LSCF) consists of a dominated Ruddlesden-Popper phase LaSr3 Co1.5 Fe1.5 O10-δ (RP-LSCF) and second perovskite phase La0.25 Sr0.75 Co0.5 Fe0.5 O3-δ (P-LSCF), displaying exceptional OER activity. The RP/P-LSCF achieves 10 mA cm-2 at a low overpotential of only 324 mV in 0.1 m KOH, surpassing the benchmark RuO2 and various state-of-the-art metal oxides ever reported for OER, while showing significantly higher activity and stability than single RP-LSCF oxide. The high catalytic performance for RP/P-LSCF is attributed to the strong metal-oxygen covalency and high oxygen-ion diffusion rate resulting from the phase mixture, which likely triggers the surface lattice-oxygen activation to participate in OER. The success of Ruddlesden-Popper/perovskite hybrid construction creates a new direction to design advanced catalysts for various energy applications.

Super-Exchange Interaction Induced Overall Optimization in Ferromagnetic Perovskite Oxides Enables Ultrafast Water Oxidation.

Oxygen evolution reaction (OER) is crucial in many renewable electrochemical technologies including regenerative fuel cells, rechargeable metal-air batteries, and water splitting. It is found that abundant active sites with favorable electronic structure and high electrical conductivity play a dominant role in achieving high electrocatalytic efficiency of perovskites, thus efficient strategies need to be designed to generate multiple beneficial factors for OER. Here, highlighted is an unusual super-exchange effect in ferromagnetic perovskite oxide to optimize active sites and enhance electrical conductivity. A systematic exploration about the composition-dependent OER activity in SrCo1 x Rux O3- δ (denoted as SCRx) (x = 0.0-1.0) perovskite is displayed with special attention on the role of super-exchange interaction between high spin (HS) Co3+ and Ru5+ ions. Induced by the unique Co3+ -O-Ru5+ super-exchange interactions, the SCR0.1 is endowed with abundant OER active species including Co3+ /Co4+ , Ru5+ , and O2 2- /O- , high electrical conductivity, and metal-oxygen covalency. Benefiting from these advantageous factors for OER electrocatalysis, the optimized SCR0.1 catalyst exhibits a remarkable activity with a low overpotential of 360 mV at 10 mA cm-2 , which exceeds the benchmark RuO2 and most well-known perovskite oxides reported so far, while maintaining excellent durability. This work provides a new pathway in developing perovskite catalysts for efficient catalysis.

Improved catalytic combustion of methane using CuO nanobelts with predominantly (001) surfaces.

Through computational calculations, CuO(001) has been identified as an active surface for methane oxidation. Experimental validation with CuO nanobelts comprised of predominantly (001) surfaces has been performed and it is confirmed that the performance of such nanobelts is much higher than normal nanoparticles and nanowires. First principle calculations further clarified that two-coordinated oxygen plays a key role for methane adsorption and oxidation.