PD-1/PD-L1 governed cross-talk of exhausted CD8+ T and memory B cells in systemic lupus erythematosus.

BACKGROUND: Indeterminate readout of the quantitative interferon-γ release test (QFT) for Mycobacterium tuberculosis screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling. METHODS: We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy. RESULTS: 104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8+ T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response. CONCLUSION: The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8+ T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE.

Effect of reduced graphene oxide doping on photocatalytic reduction of Cr(VI) and photocatalytic oxidation of tetracycline by ZnAlTi layered double oxides under visible light.

The existence of Cr(VI) and antibiotics in the environment can form the joint contaminant which can be hazardous to the ecosystem. To deal with this, we have explored a plausible method to remove the Cr(VI) and tetracycline (TC) from water by visible light photocatalysis. In this study, a series of reduced graphene oxide@ZnAlTi layered double oxides (rGO@LDO) composites with different doping ratio of rGO were successfully synthesized, which were applied in photocatalytic reduction of Cr(VI) and oxidation of TC. Graphene acts as an electron donor and it can enhance the adsorption of Cr(VI) and TC on the surface of the composites. It's found that the obtained ZnAlTi-LDO composites doped with rGO have higher photo-responsiveness in the visible region. The best-performing rGO@LDO composite (i.e., CGL3) exhibited enhanced visible light-driven photocatalytic Cr(VI) reduction, which was about five times higher than those of ZnAlTi-LDO (without adding hole catcher). The rGO@LDO also showed a satisfactory performance for photocatalytic oxidation of TC with the total organic carbon removal of 80%. However, the doping of rGO did not significantly enhance the removal of TC. The experiment of pH effects demonstrated that acidic pH was favorable to photocatalytic reduction of Cr(VI), while neutral pH was favorable to photocatalytic oxidation of TC. The band structure of ZnAlTi-LDO was first identified, and the EVB and ECB of ZnAlTi-LDO are -2.32 and 0.72 V (vs. RHE). This research provides a feasible method to remove Cr(VI) and tetracycline from water by employing ZnAlTi-LDO doped with rGO as photocatalyst.

Simultaneous and efficient photocatalytic reduction of Cr(VI) and oxidation of trace sulfamethoxazole under LED light by rGO@Cu2O/BiVO4p-n heterojunction composite.

Antibiotics and heavy metals often coexist in polluted environment, and the harm of combined pollution is greater than that of single pollution. In this study, a series of graphene supported p-n heterojunction rGO@Cu2O/BiVO4 composites are synthesized with different Cu2O doping for simultaneous detoxification of Cr(VI) and antibiotics. The obtained photocatalysts (rGO@Cu2O/BiVO4) with proper loading amount of Cu2O shows the a high photocatalytic degradation activity for simultaneously efficient Cr(VI) reduction and sulfamethoxazole (SMZ) oxidation under LED light at neutral pH. The Cr(VI) was completely transformed to Cr(III) rather than simply Cr(VI) adsorbed on the surface of rGO@Cu2O/BiVO4. The photocatalytic activity of composites can be attributed to excellent electrical conductivity of rGO and the p-n heterojunction between Cu2O and BiVO4, which promotes the spatial separation of photogenerated charges at the heterojunction boundary and inhibits of the photogenerated h+ and e- recombination. It's confirmed that h+, O2- and OH are the main reactive species for the photocatalytic SMZ oxidation, and the most important reactive species is h+. Finally, the tentative degradation pathways of SMZ are proposed based on the liquid chromatography-triple quadrupole mass spectrometry analysis. This work provides an effective approach for the treatment of water that contains SMZ and Cr(VI) under LED light.