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Aim: To explore the neuroprotective effects of ARA290 and the role of β‐common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO). Methods: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO‐induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5‐triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry‐based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot. Results: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR. Conclusion: ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention. [ABSTRACT FROM AUTHOR]

An alcohol dehydrogenase LkADH was successfully engineered to exhibit improved activity and substrate tolerance for the production of (S)‐2‐chloro‐1‐(3,4‐difluorophenyl)ethanol, an important precursor of ticagrelor. Five potential hotspots were identified for enzyme mutagenesis by using natural residue abundance as an indicator to evaluate their potential plasticity. A semi‐rational strategy named "aromatic residue scanning" was applied to randomly mutate these five sites simultaneously by using tyrosine, tryptophan, and phenylalanine as "exploratory residues" to introduce steric hindrance or potential π‐π interactions. The best variant Lk‐S96Y/L199W identified with 17.2‐fold improvement in catalytic efficiency could completely reduce up to 600 g/L (3.1 M) 2‐chloro‐1‐(3,4‐difluorophenyl)ethenone in 12 h with >99.5 % ee, giving the highest space‐time yield ever reported. This study, therefore, offers a strategy for mutating alcohol dehydrogenase to reduce aromatic substrates and provides an efficient variant for the efficient synthesis of (S)‐2‐chloro‐1‐(3,4‐difluorophenyl)ethanol. [ABSTRACT FROM AUTHOR]

Developing luminescent radicals with tunable emission is a challenging task due to the limitation of alternative skeletons. Herein, a series of carbene‐triphenylamine hybrids were prepared by the direct C2‐arylation of N‐heterocyclic carbenes with 4‐bromo‐N,N‐bis(4‐methoxyphenyl)aniline. These hybrids showed multiple redox‐active properties and could be converted to carbon‐centered luminescent radicals with blue‐to‐cyan emissions (λmax: 436–486 nm) or nitrogen‐centered luminescent radicals with orange emissions (λmax: 590–623 nm) through chemical reduction or oxidation, respectively. The radical species were characterized by electron paramagnetic resonance spectroscopy, ultraviolet‐visible spectroscopy, and single‐crystal X‐ray diffractometry analysis. Notably, the corresponding nitrogen‐centered radicals exhibited good stability in atmospheric air, and their thermal decomposition temperatures were determined to be above 200 °C. In addition, spectral and theoretical calculations indicate that all radicals exhibit anti‐Kasha emissions. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. Methods: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. Results: The optimal cut‐off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32‐4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan–Meier curve indicated that patients at high nutritional risk have poorer 365‐days [hazard ratio (HR) = 1.76, 95% CI = 1.30‐2.37, p < 0.001] and 1000‐days (HR = 2.30, 95% CI = 1.87–2.83, p < 0.001) overall survival. Conclusions: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long‐term survival in CSRU patients. More well‐designed clinical trials are needed to verify and update our findings. [ABSTRACT FROM AUTHOR]