Exploring the activation mechanism of metabotropic glutamate receptor 2.

Homomeric dimerization of metabotropic glutamate receptors (mGlus) is essential for the modulation of their functions and represents a promising avenue for the development of novel therapeutic approaches to address central nervous system diseases. Yet, the scarcity of detailed molecular and energetic data on mGlu2 impedes our in-depth comprehension of their activation process. Here, we employ computational simulation methods to elucidate the activation process and key events associated with the mGlu2, including a detailed analysis of its conformational transitions, the binding of agonists, Gi protein coupling, and the guanosine diphosphate (GDP) release. Our results demonstrate that the activation of mGlu2 is a stepwise process and several energy barriers need to be overcome. Moreover, we also identify the rate-determining step of the mGlu2's transition from the agonist-bound state to its active state. From the perspective of free-energy analysis, we find that the conformational dynamics of mGlu2's subunit follow coupled rather than discrete, independent actions. Asymmetric dimerization is critical for receptor activation. Our calculation results are consistent with the observation of cross-linking and fluorescent-labeled blot experiments, thus illustrating the reliability of our calculations. Besides, we also identify potential key residues in the Gi protein binding position on mGlu2, mGlu2 dimer's TM6-TM6 interface, and Gi α5 helix by the change of energy barriers after mutation. The implications of our findings could lead to a more comprehensive grasp of class C G protein-coupled receptor activation.

Post-abortion needs-based education via the WeChat platform to lessen fear and encourage effective contraception: a post-abortion care service intervention-controlled trial.

OBJECTIVE: Our study aims to investigate post-abortion needs-based education via the WeChat platform for women who had intended abortion in the first trimester, whether they are using effective contraception or becoming pregnant again. DESIGN: This single hospital intervention-controlled trial used a nearly 1:1 allocation ratio. Women who had intended abortions were randomly assigned to a Wechat group (needs-based education) and a control group (Traditional education). The women's ability to use effective contraception was the main result. Whether they unknowingly became pregnant again was the second result. Another result was patient anxiousness. Before and after education, women filled out questionnaires to assess their contraception methods and anxiety. METHODS: Based on the theoretical framework of contraceptions of IBL (inquiry-based learning), post-abortion women were included in WeChat groups. We use WeChat Group Announcement, regularly sending health education information, one-on-one answers to questions, and consultation methods to explore the possibilities and advantages of WeChat health education for women after abortion. A knowledge paradigm for post-abortion health education was established: From November 2021 until December 2021, 180 women who had an unintended pregnancy and undergone an induced or medical abortion were recruited, their progress was tracked for four months, and the PAC service team monitored the women's speech, discussed and classified the speech entries and summarized the common post-abortion needs in 8 aspects. At least 2 research group members routinely extracted records and categorized the outcomes. RESULTS: Before education, there were no appreciable variations between the two groups regarding sociodemographic characteristics, obstetrical conditions, abortion rates, or methods of contraception (P > 0.05). Following education, the WeChat group had a greater rate of effective contraception (63.0%) than the control group (28.6%), and their SAS score dropped statistically more than that of the control group (P < 0.05). Following the education, there were no unwanted pregnancies in the WeChat group, whereas there were 2 in the traditional PAC group. Only 5 participants in the WeChat group and 32 in the conventional PAC group reported mild anxiety after the education.