Wireless Bioelectronics for In Vivo Pressure Monitoring with Mechanically-Compliant Hydrogel Biointerfaces.

Recent electronics-tissues biointefacing technology has offered unprecedented opportunities for long-term disease diagnosis and treatment. It remains a grand challenge to robustly anchor the pressure sensing bioelectronics onto specific organs, since the periodically-varying stress generated by normal biological processes may pose high risk of interfacial failures. Here, a general yet reliable approach is reported to achieve the robust hydrogel interface between wireless pressure sensor and biological tissues/organs, featuring highly desirable mechanical compliance and swelling resistance, despite the direct contact with biofluids and dynamic conditions. The sensor is operated wirelessly through inductive coupling, characterizing minimal hysteresis, fast response times, excellent stability, and robustness, thus allowing for easy handling and eliminating the necessity for surgical extraction after a functional period. The operation of the wireless sensor has been demonstrated with a custom-made pressure sensing model and in vivo intracranial pressure monitoring in rats. This technology may be advantageous in real-time post-operative monitoring of various biological inner pressures after the reconstructive surgery, thus guaranteeing the timely treatment of lethal diseases.

Biosynthesis of eriodictyol in citrus waster by endowing P450BM3 activity of naringenin hydroxylation.

The flavonoid naringenin is abundantly present in pomelo peels, and the unprocessed naringenin in wastes is not friendly for the environment once discarded directly. Fortunately, the hydroxylated product of eriodictyol from naringenin exhibits remarkable antioxidant and anticancer properties. The P450s was suggested promising for the bioconversion of the flavonoids, but less naturally existed P450s show hydroxylation activity to C3' of the naringenin. By well analyzing the catalytic mechanism and the conformations of the naringenin in P450, we proposed that the intermediate Cmpd I ((porphyrin)Fe = O) is more reasonable as key conformation for the hydrolyzation, and the distance between C3'/C5' of naringenin to the O atom of CmpdI determines the hydroxylating activity for the naringenin. Thus, the "flying kite model" that gradually drags the C-H bond of the substrate to the O atom of CmpdI was put forward for rational design. With ab initio design, we successfully endowed the self-sufficient P450-BM3 hydroxylic activity to naringenin and obtained mutant M5-5, with kcat, Km, and kcat/Km values of 230.45 min-1, 310.48 µM, and 0.742 min-1 µM-1, respectively. Furthermore, the mutant M4186 was screened with kcat/Km of 4.28-fold highly improved than the reported M13. The M4186 also exhibited 62.57% yield of eriodictyol, more suitable for the industrial application. This study provided a theoretical guide for the rational design of P450s to the nonnative compounds. KEY POINTS: •The compound I is proposed as the starting point for the rational design of the P450BM3 •"Flying kite model" is proposed based on the distance between O of Cmpd I and C3'/C5' of naringenin •Mutant M15-5 with 1.6-fold of activity than M13 was obtained by ab initio modification.

Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism.

Umami is one of five basic tastes, the elucidation of its mechanism by the study of the interaction between umami polypeptides and hT1R1 umami receptors is of great significance. However, research on umami peptides targeting human T1R1 receptors is lacking, and the molecular mechanism remains elusive. Here, we successfully established a system to detect umami peptides targeting human T1R1 receptors by fluorescence spectroscopy, Surface Plasmon Resonance (SPR) and computational simulation. The sensory evaluation, calculated Kd value, and experimental affinity results between the four selected umami peptides (GRVSNCAA, KGDEESLA, KGGGGP, and TGDPEK) and glutamate were tested using this system, and all matched well. The maximum Ka value of GRVSNCAA was 479.55 M-1, and the minimum affinity of TGDPEK was 2.67 M-1. Computational simulations showed that the different peptide binding sites in the hT1R1 binding pocket occupied due to conformational changes are important factors for different taste thresholds, and that peptide hydrophobicity plays an important role in regulating affinity. Thus, our study enables rapid screening of high-intensity umami peptides and the development of T1R1 receptor-based umami detection sensors.

Framework nucleic acid programmed combinatorial delivery nanocarriers for parallel and multiplexed analysis.

Herein we report a framework nucleic acid programmed strategy to develop nanocarriers to precisely and independently package multiple homo- and heterogeneous cargos in vitro and in vivo, thereby enabling multiplexed analysis of aptamer-ligand complexes to distinguish normal people and patients with prostate enlargement via simple serum tests, as well as favorable imaging and discrimination of MCF-7, PC-3 and A549 cancer cells and normal QSG-7701 cells.