Darobactin is a ribosomally synthesized and post-translationally modified peptide (RiPP), which possesses potent activity against various Gram-negative bacteria. Darobactin features a highly unique bicyclic scaffold, consisting of an ether crosslink between two Trp residues and a C–C crosslink between a Lys and a Trp. Here we report in vivo and in vitro activity of darobactin synthase DarE. We show DarE is a radical S-adenosylmethionine (rSAM) enzyme and is solely responsible for forming the bicyclic scaffold of darobactin. DarE mainly produced the ether-crosslinked product in vitro, and when the assay was performed in H218O, apparent 18O incorporation was observed into the ether-crosslinked product. These observations suggested an rSAM-dependent process in darobactin biosynthesis, involving a highly unusual oxygen insertion step from a water molecule and subsequent O–H and C–H activations. Genome mining analysis demonstrates the diversity of darobactin-like biosynthetic gene clusters, a subclade of which likely encode monocyclic products with only an ether linkage. We propose the name daropeptide for this growing family of ether-containing RiPPs produced by DarE enzymes.

Metal–organic frameworks (MOFs) have attracted intensive study as solid electrolytes (SEs) in recent years. However, MOF particles work separately in SEs and numerous interfaces hinder a high-efficiency ion transport, which lowers the performance of solid-state batteries (SSBs). Herein, continuous ion-conductive paths were constructed by cross-linked MOF chains. Chains of a newly developed MOF (Zr-BPDC-2SO3H) were grown on bacterial cellulose (BC) nanofibers to provide a continuous ion transport network. The cross-linked MOF chains exhibit a high ionic conductivity of 7.88 × 10–4 S cm–1 at 25 °C, single-ion transport ability (t Li +=0.88), a wide electrochemical window up to 5.10 V, excellent interface compatibility, and the capability for suppressing lithium dendrites. Most importantly, the SSB fabricated with the cross-linked MOF chains shows more than 100% improved specific capacity in comparison to an SSB without this design and stable cycling performance at 3 C. This work provides a splendid strategy for developing high-performance SEs with porous ion conductors.

Metal–organic frameworks (MOFs) have been attracting a great deal of attention as potential solid electrolytes (SEs). However, the interfacial compatibility of MOF-based SEs caused by the physical contact among MOF particles, the polymer binder, and electrodes is not yet fully determined. Herein, a bioinspired design strategy aiming to build ion transport pathways at interfaces was introduced. The MOF-to-MOF transport paths were built via in situ ring opening of epoxide, akin to the protein molecules that transport the ion across the cell walls. After optimization, the obtained SE is endowed with a high ion conductivity of 1.70 × 10–3 S cm–1 at 30 °C, a wide electrochemical window of 4.6 V, a high Li+ transference number of 0.8, and a decreased interface resistance. Consequently, the fabricated quasi-solid metal batteries exhibit higher and more stable cycling performance compared to the performance of those without interface optimization. This strategy for optimizing the interfacial compatibility of MOFs thus exploits a new avenue for developing high-performance SEs for various metal batteries.

High intensity focused ultrasound (HIFU) based thrombolysis has emerged as a promising drug-free treatment approach for ischemic stroke. The large amount of acoustic power required by this approach, however, poses a critical challenge to the future clinical translation. In this study, multi-frequency acoustic waves at MHz range (near 1.5 MHz) were introduced as HIFU excitations to reduce the required power for treatment as well as the treatment time. In vitro bovine blood clots weighing around 150 mg were treated by single-frequency and multi-frequency HIFU. The pulse length was 2 ms for all experiments except the ones where the duty cycle was changed. It was found that dual-frequency thrombolysis efficiency was statistically better than single-frequency under the same acoustic power and excitation condition. When varying the acoustic power but fixing the duty cycle at 5%, it was found that dual-frequency ultrasound can save almost 30% power in order to achieve the same thrombolysis efficiency. In the experiment where the duty cycle was increased from 0.5% to 10%, it was shown that dual-frequency ultrasound can achieve the same thrombolysis efficiency with only half of the duty cycle of single-frequency. Dual-frequency ultrasound could also accelerate the thrombolysis by a factor of 2-4 as demonstrated in this study. No significant differences were found between dual-frequencies with different frequency differences (0.025, 0.05, and 0.1 MHz) and between dual-frequency and triple-frequency. The measured cavitation doses of dual-frequency and triple-frequency excitations were at about the same level but both were significantly higher than that of single-frequency.

High-intensity focused ultrasound (HIFU) is becoming an increasingly important noninvasive surgical tool, despite the challenges in temperature rise control and unwanted heating problems. In this study, experiments and simulations on tissue ablation effectiveness were performed using multi-frequency HIFU with frequency differences of more than 500 kHz (center frequencies are 950 kHz, 1.5 MHz, and 3.3 MHz). In the experiments, the temperature was recorded as chicken breast tissue was heated by single-frequency, dual-frequency, and tri-frequency HIFU configurations at controlled acoustic power and exposure time. 5% to 10% temperature rise differences were observed between single- and multi-frequency modes, indicating that multi-frequency HIFU is more effective at producing faster temperature rises. Cavitation detection tests were conducted to compare the cavitation pressure fields between single- and multi-frequency ultrasound. Moreover, simulations on single-frequency and multi-frequency acoustic fields as well as bio-heating-induced temperature fields were performed. With the comparison between experimental and simulation results, we believe that the more effective tissue ablation using multi-frequency ultrasound is likely attributed to the enhanced cavitation, a promising result for HIFU applications.