Developing efficient, stable, and low-cost catalysts for oxygen evolution reaction (OER) is highly desired in water splitting and metal−air batteries. Transition metal−organic frameworks (MOFs) have emerged as promising catalysts and have been intensively investigated especially due to their tunable crystalline structure. Unlike traditional strategies of tuning the morphology of well-crystalline MOFs, low-crystalline bimetallic MOFs are constructed via inducing exotic metal ions, and the formation process is revealed by experimental and theoretical methods. The lowcrystalline bimetallic MOFs exhibit rich active sites due to local crystallinity and long-range disorder and deliver a small overpotential of 260 mV at 10 mA cm −2 , a low Tafel slope of 35 mV dec −1 , and a high Faradaic efficiency of 99.5% as oxygen evolution elecctrocatalysts. The work opens up a new avenue for the development of highly efficient earth-abundant catalysts in frontier potential applications.

Background: Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation. Methods: In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg•kg À1 •h À1 , which could be adjusted to an infusion rate of 0.06 to 0.80 mg•kg À1 •h À1 , whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg•kg À1 •h À1 , which could be adjusted to 0.30-4.00 mg•kg À1 •h À1 to achieve À2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. Results: Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug-and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. Conclusions: ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting. Trial registration: ClinicalTrials.gov, NCT04147416.

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Introduction: From previous studies of pharmacodynamic data in mice, rats, beagle dogs and mini pigs, frequently in direct comparison to induction doses of propofol, ciprofol produced a rapid onset of anesthesia/sedation. Methods: A phase 1 study suggested potential clinical advantages of ciprofol as a sedation/ anesthetic agent, with no evidence of drug-related toxicity. However, the sedation effects and safety of ciprofol in intensive care unit (ICU) patients with mechanical ventilation should be further confirmed in a phase 3 study with a larger cohort of patients.

The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients.