Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Objective:To analyze the clinical outcomes and cost-effectiveness ratio of the patients with ovarian reserve dysfunction in three different ovulation induction protocols during in vitro fertilization-embryo transfer (IVF-ET), and to explore a cost-effective ovulation induction protocol. Methods:A retrospective analysis was made on the low prognosis in IVF-ET of elderly patients with low ovarian reserve function (according to POSEIDON criteria, group 4) in Reproductive Center of Ningbo Women & Children Hospital during January 2017 to October 2018. According to the different ovarian stimulation protocols used, they were divided into three groups: antagonist group (group A, 169 cycles), micro-stimulation group (group B, 57 cycles), and progestin-primed ovarian stimulation (PPOS) group (group C, 59 cycles). The clinical outcome and cost-effectiveness of three ovulation-promoting protocols were analyzed.Results:In group A, compared with group B and group C, both the number of obtained eggs [4.46±1.45, 2.42±1.12, 3.28±1.62, respectively in the three groups ( P=0.013, P=0.021)] and the cumulative clinical pregnancy rate were higher (35.50%, 21.43%, 23.73%, respectively in the three groups)( P=0.012, 0.021). In group A, the rate of cycle cancellation was the lowest in the three groups (0.95%, 21.05%, 15.24%, respectively). In group A, the average cost of each egg acquisition was the lowest [(3817±1450) yuan, (5868±1820) yuan, (4484±1678) yuan, respectively in the three groups)]( P=0.001, P=0.012, P=0.017), and the cost of each available embryo was the lowest too [(7276±2329) yuan, (7978±2560) yuan, (7466±2175) yuan, respectively in the three groups)]( P=0.001, P=0.021, P=0.033).The cost per clinical pregnancy was lower in group A than in group B and group C [(47 957±22 388) yuan, (67 450±35 210) yuan, (61 984±33 463) yuan, respectively in the three groups)]( P=0.012, P=0.021). Conclusion:For patients aged over 35 years with poor ovarian reserve before stimulation, antagonist protocol was superior to micro-stimulation and PPOS, considering the clinical outcome and cost-effectiveness ratio, and it was an ideal ovary stimulation protocol.

Objective:To analyze the clinical outcomes and cost-effectiveness ratio of the patients with ovarian reserve dysfunction in three different ovulation induction protocols during in vitro fertilization-embryo transfer (IVF-ET), and to explore a cost-effective ovulation induction protocol. Methods:A retrospective analysis was made on the low prognosis in IVF-ET of elderly patients with low ovarian reserve function (according to POSEIDON criteria, group 4) in Reproductive Center of Ningbo Women & Children Hospital during January 2017 to October 2018. According to the different ovarian stimulation protocols used, they were divided into three groups: antagonist group (group A, 169 cycles), micro-stimulation group (group B, 57 cycles), and progestin-primed ovarian stimulation (PPOS) group (group C, 59 cycles). The clinical outcome and cost-effectiveness of three ovulation-promoting protocols were analyzed.Results:In group A, compared with group B and group C, both the number of obtained eggs [4.46±1.45, 2.42±1.12, 3.28±1.62, respectively in the three groups ( P=0.013, P=0.021)] and the cumulative clinical pregnancy rate were higher (35.50%, 21.43%, 23.73%, respectively in the three groups)( P=0.012, 0.021). In group A, the rate of cycle cancellation was the lowest in the three groups (0.95%, 21.05%, 15.24%, respectively). In group A, the average cost of each egg acquisition was the lowest [(3817±1450) yuan, (5868±1820) yuan, (4484±1678) yuan, respectively in the three groups)]( P=0.001, P=0.012, P=0.017), and the cost of each available embryo was the lowest too [(7276±2329) yuan, (7978±2560) yuan, (7466±2175) yuan, respectively in the three groups)]( P=0.001, P=0.021, P=0.033).The cost per clinical pregnancy was lower in group A than in group B and group C [(47 957±22 388) yuan, (67 450±35 210) yuan, (61 984±33 463) yuan, respectively in the three groups)]( P=0.012, P=0.021). Conclusion:For patients aged over 35 years with poor ovarian reserve before stimulation, antagonist protocol was superior to micro-stimulation and PPOS, considering the clinical outcome and cost-effectiveness ratio, and it was an ideal ovary stimulation protocol.