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Rpn13 is a substrate receptor of the 26S proteasome and an anti-cancer drug target. Here, the authors identify and characterize XL5, a lead compound that binds to the N-terminal Pru domain of human Rpn13 (hRpn13), solve the NMR structure of XL5-ligated hRpn13 Pru and develop XL5-PROTACs that preferentially target an identified hRpn13 Pru fragment present in multiple myeloma cells.

Abstract This prospective randomized clinical trial aimed to evaluate the effect of low-level laser therapy on tooth movement during Class II intermaxillary elastics treatment. Forty-two patients with Class II malocclusion were included, and their maxillary quadrants were allocated into two groups: treatment with an active diode laser and a placebo group. In each group, the time taken to obtain Class I occlusion after 6 months, rate of movement, total displacement of the maxillary canine to Class I occlusion and pain were recorded. The time to reach Class I occlusion in the active laser group (2.46 ± 2.1 months) was not significantly different from that in the placebo group (2.48 ± 2.0 months) (p = 0.938). Interestingly, the total distance of movement on the active laser side (2.27 ± 1.5 mm) was significantly greater than that on the placebo side (1.64 ± 1.3 mm) (p = 0.009). The pain levels on days 1, 2 and 3 were not significantly different between the laser and placebo sections. The rate of distance change toward Class I occlusion in the laser group (1.1 ± 0.7 mm/month) was significantly higher than that in the placebo group (0.74 ± 0.6 mm/month) (p = 0.037). Low-level laser therapy (970 nm) did not reduce the time needed to obtain Class I occlusion, but a significant acceleration in tooth movement was observed in the irradiated group. Trial registration: NCT02181439. Registered 04 July 2014— https://www.clinicaltrials.gov/ct2/results?term=cinelaser .