Effect of radiation fractionation on IDO1 via the NF-κB/COX2 axis in non-small cell lung cancer.

Radiotherapy (RT) is the mainstay treatment modality for lung cancer. We recently reported that conventionally fractionated radiotherapy (CRT) with daily fractionation of 2Gy significantly increased the activity of indoleamine 2,3-dioxygenase (IDO1), a known immune checkpoint, which predicted poorer long-term survival in patients with non-small cell lung cancer (NSCLC), while stereotactic body radiotherapy (SBRT) using fractionation size of 10Gy did not increase IDO1 activity and had better survival. Here we hypothesized that the hypofractionated SBRT kind of dose fraction stimulates host antitumor immunity via downregulating IDO1 in which CRT could not. We tested this hypothesis in vitro and in vivo using 10Gyx1 and 2Gyx8 fractionations in the laboratory. The results demonstrated that, although there was an initial downregulation after RT, the expression of IDO1 was ultimately upregulated by both fractionation regimens. The 10Gyx1 regimen had minimum upregulation, while the 2Gyx8 regimen significantly increased in IDO1 expression which was positively correlated with the elevated expressions of p-NF-κB and COX2. Pharmacological inhibition of COX2 abolished RT-induced IDO1 expression. Furthermore, the IDO1 inhibitor, D-1-methyl-tryptophan (D-1MT), exerted RT-related tumor-killing effects in the NSCLC cell lines and mouse models. These findings suggest that, in addition to being an immune suppressor, IDO1 may serve as an adaptive resistance factor in RT. Furthermore, an unappreciated mechanism may exist, where a larger fraction size might be superior to conventional sizes in cancer treatment. This study may provide a rationale for future research in using IDO1 as a biomarker to personalize RT dose fractionation and COX2 inhibitor to decrease radiation immune suppression from CRT.

Defects engineering simultaneously enhances activity and recyclability of MOFs in selective hydrogenation of biomass.

The development of synthetic methodologies towards enhanced performance in biomass conversion is desirable due to the growing energy demand. Here we design two types of Ru impregnated MIL-100-Cr defect engineered metal-organic frameworks (Ru@DEMOFs) by incorporating defective ligands (DLs), aiming at highly efficient catalysts for biomass hydrogenation. Our results show that Ru@DEMOFs simultaneously exhibit boosted recyclability, selectivity and activity with the turnover frequency being about 10 times higher than the reported values of polymer supported Ru towards D-glucose hydrogenation. This work provides in-depth insights into (i) the evolution of various defects in the cationic framework upon DLs incorporation and Ru impregnation, (ii) the special effect of each type of defects on the electron density of Ru nanoparticles and activation of reactants, and (iii) the respective role of defects, confined Ru particles and metal single active sites in the catalytic performance of Ru@DEMOFs for D-glucose selective hydrogenation as well as their synergistic catalytic mechanism.

Single-Metallic Thermoresponsive Coordination Network as a Dual-Parametric Luminescent Thermometer.

The single-metallic coordination networks (CNs), simultaneously exhibiting temperature-dependent lifetime (TDLT) and emission band shift (TDEBS), are desirable for application in luminescent thermometers with high accuracy and reliability in a large temperature range. Nonetheless, up to date, there are no reports on such kinds of materials due to the lack of in-depth understanding of the origin of TDLT and TDEBS at a molecule level, being critical for exploiting a universal approach to design a dual-parametric CN phosphorescent thermometer (CN-PT). Herein, we have constructed a thermoresponsive CN [Cu2(L1)Br2]∞ (IAM21-1, L1 = N1,N6-di(pyridin-3-yl)adipamide) via a flexible-ligand-implanted strategy. The TDLT and TDEBS properties of IAM21-1 enable it to be applied as a single-metallic dual-parametric CN-PT in 50-500 K, which is the widest temperature range reported so far. The combination of structure analysis and DFT calculations demonstrates that the redshift of the emission band upon the decreasing temperature originates from the reversible skeleton-shrinkage-triggered narrower band gap. This work has unveiled the origin of TDLT and TDEBS properties and proposed an efficient strategy for designing dual-parametric CN-PTs.