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Abstract Despite the extensive developments of flexible capacitive pressure sensors, it is still elusive to simultaneously achieve excellent linearity over a broad pressure range, high sensitivity, and ultrahigh pressure resolution under large pressure preloads. Here, we present a programmable fabrication method for microstructures to integrate an ultrathin ionic layer. The resulting optimized sensor exhibits a sensitivity of 33.7 kPa −1 over a linear range of 1700 kPa, a detection limit of 0.36 Pa, and a pressure resolution of 0.00725% under the pressure of 2000 kPa. Taken together with rapid response/recovery and excellent repeatability, the sensor is applied to subtle pulse detection, interactive robotic hand, and ultrahigh-resolution smart weight scale/chair. The proposed fabrication approaches and design toolkit from this work can also be leveraged to easily tune the pressure sensor performance for varying target applications and open up opportunities to create other iontronic sensors. 

In the eye, the isomerization of all-trans-retinal to 11-cis-retinal is accomplished by a metabolic pathway termed the visual cycle that is critical for vision. RPE65 is the essential trans–cis isomerase of this pathway. Emixustat, a retinoid-mimetic RPE65 inhibitor, was developed as a therapeutic visual cycle modulator and used for the treatment of retinopathies. However, pharmacokinetic liabilities limit its further development including: (1) metabolic deamination of the γ-amino-α-aryl alcohol, which mediates targeted RPE65 inhibition, and (2) unwanted long-lasting RPE65 inhibition. We sought to address these issues by more broadly defining the structure–activity relationships of the RPE65 recognition motif via the synthesis of a family of novel derivatives, which were tested in vitro and in vivo for RPE65 inhibition. We identified a potent secondary amine derivative with resistance to deamination and preserved RPE65 inhibitory activity. Our data provide insights into activity-preserving modifications of the emixustat molecule that can be employed to tune its pharmacological properties. 

Regioselective transformations at similar functional groups are of paramount importance in organic synthesis. Traditional strategies towards regioselective functionalization include serial protection/deprotection and sequential synthesis. Modern organic synthesis emphasizes pathway efficiency and protecting group free routes with a goal of exploiting inherent differences in reactivity. This study reports a method for the regioselective functionalization of anilines over aliphatic amines. Utilizing classic conditions for the Baeyer‐Mills reaction, anilines were shown to react preferentially in the presence of aliphatic amines. Subsequently, this principle of reactivity was extended to other electrophiles and conditions.