The ubiquitin system is important for drug discovery, and the discovery of selective small-molecule inhibitors of deubiquitinating enzymes (DUBs) remains an active yet extremely challenging task. With a few exceptions, previously developed inhibitors have been found to bind the evolutionarily conserved catalytic centers of DUBs, resulting in poor selectivity. The small molecule IU1 was the first-ever specific inhibitor identified and exhibited surprisingly excellent selectivity for USP14 over other DUBs. However, the molecular mechanism for this selectivity was elusive. Herein, we report the high-resolution co-crystal structures of the catalytic domain of USP14 bound to IU1 and three IU1 derivatives. All the structures of these complexes indicate that IU1 and its analogs bind to a previously unknown steric binding site in USP14, thus blocking the access of the C-terminus of ubiquitin to the active site of USP14 and abrogating USP14 activity. Importantly, this steric site in USP14 is very unique, as suggested by structural alignments of USP14 with several known DUB X-ray structures. These results, in conjunction with biochemical characterization, indicate a coherent steric blockade mechanism for USP14 inhibition by compounds of the IU series. In light of the recent report of steric blockade of USP7 by FT671, this work suggests a potential generally applicable allosteric mechanism for the regulation of DUBs via steric blockade, as showcased by our discovery of IU1-248 which is 10-fold more potent than IU1.

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In this work, a hybrid structure consisting of a multicomponent germanate glass microsphere containing bismuth as a gain medium is proposed and presented. The bismuth-doped germanate glass microspheres were fabricated from a glass fiber tip with no precipitation of the bismuth metal. Coupling with a fiber taper, the bismuth-doped microsphere single-mode laser was observed to lase at around 1305.8 nm using 808 nm excitation. The low threshold of absorbed pump power at 215 μW makes this microlaser appealing for various applications, including tunable lasers for a range of purposes in telecommunication, biomedical, and optical information processing.

Monitoring the dynamic humidity requires sensors with fast response and anti-electromagnetic interference, especially for human respiration. Here, an ultrafast fiber-optic breath sensor based on the humidity-sensitive characteristics of gelatin film is proposed and experimentally demonstrated. The sensor consists of a microknot resonator superimposed on a Mach−Zehnder (MZ) interferometer produced by a tapered single-mode fiber, which has an ultrafast response (84 ms) and recovery time (29 ms) and a large dynamic transmission range. The humidity in dynamic ambient causes changes in the refractive index of gelatin coating, which could trigger spectral intensity transients that can be explicitly distinguished between the two states. The sensing principle is analyzed using the traditional transfer-matrix analysis method. The influence of coating thickness on the sensor's trigger threshold is further investigated. Experiments on monitoring breath patterns indicate that the proposed breath sensor has high repeatability, reliability, and validity, which enable many other potential applications such as food processing, health monitoring, and other biomedical applications.

A novel temperature sensor based on a Teflon capillary encapsulated 2 × 2 optical microfiber coupler (OMC) filled with refractive index matching liquids is described. The sealed capillary and the filling liquid are demonstrated to enhance the temperature sensing performance, achieving a high temperature sensitivity of 5.3 nm/°C. To the best of our knowledge, the temperature sensor described in this article exhibits the highest sensitivity among the OMC structure based fiber optic temperature sensors. Experimental results also show that it has good repeatability along with a fast response time of 243 ms. 21(11), 461-462 (1985). 21. R. X. Gao, Q. Wang, F. Zhao, B. Meng, and S. L. Qu, "Optimal design and fabrication of SMS fiber temperature sensor for liquid," Opt. Commun. 283(16), 3149-3152 (2010). 22. Y. Chen, Q. Han, T. Liu, and X. Lü, "Self-temperature-compensative refractometer based on singlemodemultimode-singlemode fiber structure," Sens. Actuators B Chem. 212, 107-111 (2015).