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Gold nanoparticles loaded onto Keggin-type insoluble polyoxometalates (Cs(x)H(3-x)PW(12)O(40)) showed superior catalytic performances for the direct conversion of cellobiose into gluconic acid in water in the presence of O(2). The selectivity of Au/Cs(x)H(3-x)PW(12)O(40) for gluconic acid was significantly higher than those of Au catalysts loaded onto typical metal oxides (e.g., SiO(2), Al(2)O(3), and TiO(2)), carbon nanotubes, and zeolites (H-ZSM-5 and HY). The acidity of polyoxometalates and the mean-size of the Au nanoparticles were the key factors in the catalytic conversion of cellobiose into gluconic acid. The stronger acidity of polyoxometalates not only favored the conversion of cellobiose but also resulted in higher selectivity of gluconic acid by facilitating desorption and inhibiting its further degradation. On the other hand, the smaller Au nanoparticles accelerated the oxidation of glucose (an intermediate) into gluconic acid, thereby leading to increases both in the conversion of cellobiose and in the selectivity of gluconic acid. The Au/Cs(x)H(3-x)PW(12)O(40) system also catalyzed the conversion of cellulose into gluconic acid with good efficiency, but it could not be used repeatedly owing to the leaching of a H(+)-rich hydrophilic moiety over long-term hydrothermal reactions. We have demonstrated that the combination of H(3)PW(12)O(40) and Au/Cs(3.0)PW(12)O(40) afforded excellent yields of gluconic acid (about 85%, 418 K, 11 h), and the deactivation of the recovered H(3)PW(12)O(40)-Au/Cs(3.0)PW(12)O(40) catalyst was not serious during repeated use.

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

Chimeric antigen receptor T-cell (CAR-T) therapy demonstrates impressive efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T therapy–related severe cytokine release syndrome and neurological toxicity limit its clinical application in R/R DLBCL patients with high tumor burden. Here, we conducted a phase II clinical trial testing the efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin lymphoma patients (NCT03196830). Among the enrolled patients, 10 R/R DLBCL patients with high tumor burden were analyzed. Before CAR-T therapy, 4 were treated with intensive combined chemotherapy (C-CAR-cohort), and 6 were exposed to radiotherapy (R-CAR-cohort). Patients in the R-CAR-T-cohort showed a higher overall response rate (100% vs. 25%, P=0.033) and less severe cytokine release syndrome (0% vs. 100%, P=0.0048) and neurotoxicity (0% vs. 75%, P=0.033) incidences than patients in the C-CAR-T-cohort. Furthermore, one case who responded to CAR-T therapy initially and who suffered a relapse shortly was exposed to radiation and achieved complete remission, with an increase in the number of CAR-T copies detected. This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies.

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