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Aim: Acute skin failure (ASF) can happen in critically ill patients. Therefore, adequate knowledge and skills regarding ASF are essential to manage this disorder. The aim of this work was to investigate the nurses' knowledge, attitude, and practice (KAP) regarding ASF patients and to analyze its influencing factors in the intensive care unit. Methods: A multicenter cross‐sectional study was performed in 10 tertiary hospitals in March 2022. Eligible nurses received a survey with a self‐designed questionnaire about their KAP regarding ASF, which included three dimensions and a maximum score of 120. A higher score corresponded to better KAP. Results: A total of 255 nurses participated in this study. The mean KAP score was 75.6 ± 16.9. The mean scores of the knowledge, attitude, and practice dimensions were 26.2 ± 10.6, 38.2 ± 6.1, and 11.3 ± 4.3, respectively. The dimensions were ranked according to score (from low to high) as follows: knowledge (2.6 ± 1.1), practice (2.8 ± 1.1), and attitude (3.8 ± 0.6). Multivariate linear regression analysis showed that more training sessions and an advanced professional title were associated with higher KAP scores. Conclusions: The overall KAP score on ASF was low in nurses. Nurses had a positive attitude towards ASF, but their knowledge and practice required significant improvement. Those who had received more training and held a more advanced professional title exhibited higher KAP scores regarding ASF. Therefore, nurse managers should establish a relevant knowledge training system, strengthen relevant training, and improve nursing practices for ASF in order to achieve a high level of KAP in nurses who treat ASF patients. [ABSTRACT FROM AUTHOR]

The histamine H4 receptor (H4R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H4R remains elusive. Here, we report four cryo-EM structures of H4R/Gi complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D943.32 and a π-π network determine the orientation of the positively charged group of ligands, while E1825.46, located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H4R ligand binding allows us to identify mutants at E1825.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and Gi engagement, we establish a framework for understanding H4R signaling and provide a rational basis for designing novel antihistamines targeting H4R.The histamine H4 receptor (H4R) plays key roles in immune cell function. Here, the authors report structures of H4R-Gi complex with various ligands bound, revealing distinct ligand binding modes and a basis for rational design of novel antihistamines targeting H4R. [ABSTRACT FROM AUTHOR]

The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS 2 , plays crucial roles in the regulation of immune responses and holds promise for the treatment of autoimmune diseases. Here, we report the cryoelectron microscopy (cryo-EM) structure of LysoPS-bound P2Y10 in complex with an engineered G 13 heterotrimeric protein. The structure and a mutagenesis study highlight the predominant role of a comprehensive polar network in facilitating the binding and activation of the receptor by LysoPS. This interaction pattern is preserved in GPR174, but not in GPR34. Moreover, our structural study unveils the essential interactions that underlie the Gα 13 engagement of P2Y10 and identifies key determinants for Gα 12 -vs.-Gα 13 -coupling selectivity, whose mutations selectively disrupt Gα 12 engagement while preserving the intact coupling of Gα 13 . The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα 12/ 13 coupling specificity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G q , G s , G i , and G 12 . The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G 12 coupling. A comparison of G q , G s , G i , and G 12 engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)