Simultaneous occurrence of extralobar pulmonary sequestration, esophageal duplication, and bronchogenic cysts in a Chinese child: a rare case report.

The occurrence of simultaneous extralobar pulmonary sequestration, esophageal duplication, and bronchogenic cysts is relatively low. We report the case of a 9-month-old Chinese child who had a right lung cyst, detected in utero and was closely monitored until birth. At age 9 months, contrast-enhanced computed tomography revealed right mediastinal extralobar pulmonary sequestration and two cysts. The patient did not exhibit any abnormalities. However, the parents were concerned about the disease. Following positive psychological counseling to the parents, surgery was the strong desire. Subsequently, successful thoracoscopic surgery was performed, excising the three lesions. No postoperative complications occurred. Postoperative pathology confirmed extralobar pulmonary sequestration syndrome combined with esophageal duplication and bronchogenic cysts. The patient was followed-up at 1 and 12 months postoperatively and recovered well with no abnormal space occupation. In such cases, preoperative imaging examinations should be carefully performed, and intraoperative exploration should correspond to that before surgery to avoid lesion omission.

The association of metabolic dysfunction-associated steatotic liver disease (MASLD) with the risk of myocardial infarction: a systematic review and meta-analysis.

Objective While studies have documented how metabolic dysfunction-associated steatotic liver disease (MASLD) can contribute to cardiovascular disease (CVD), whether MASLD is associated with myocardial infarction (MI) remains debateable. Herein, we systematically reviewed published articles and performed a meta-analysis to determine the relationship between MASLD and MI risk.Methods PubMed, MEDLINE, Embase, Web of Science, CNKI, CBM, VIP, and WanFang databases were searched, and the DerSimonian Laird method was used to obtain hazard ratios (HRs) for binary variables to assess the correlation between MASLD and MI risk. Subgroup analyses for the study region, MASLD diagnosis, quality score, study design, and follow-up time were conducted simultaneously for the selected studies retrieved from the time of database establishment to March 2022. All study procedures were independently conducted by two investigators.Results The final analysis included seven articles, including eight prospective and two retrospective cohort studies. The MI risk was higher among MASLD patients than among non-MASLD patients (HR = 1.26; 95% CI: 1.08-1.47, p = 0.003). The results of the subgroup analysis of the study region revealed an association of MASLD with MI risk among Americans and Asians, but not in Europeans. Subgroup analyses of MASLD diagnosis showed that ultrasonography and other (fatty liver index[FLI] and computed tomography [CT)]) diagnostic methods, but not international classification of disease (ICD), increased the risk of MI. Subgroup analysis of the study design demonstrated a stronger relationship between MASLD and MI in retrospective studies but not in prospective studies. Subgroup analysis based on the follow-up duration revealed the association of MASLD with MI risk in cases with < 3 years of follow-up but not with ≥3 years of follow-up.Conclusion MASLD increases the risk of MI, independent of traditional risk factors.

mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo.

BACKGROUND: Metabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood. METHODS: Pregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos. RESULTS: We showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts. CONCLUSIONS: These results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

Initial experience of thoracoscopic segmentectomy of basal segment through the inferior pulmonary ligament approach in treating congenital lung malformations in children.

PURPOSE: This study aimed to evaluate the feasibility and limitations of thoracoscopic segmentectomy of the basal segment (S10). METHODS: Clinical data of 15 children with congenital lung malformations (CLM) who underwent thoracoscopic segmentectomy of S10 via the inferior pulmonary ligament approach from January to October 2022 were retrospectively analyzed. The demographics, clinical presentation, intraoperative time, blood loss, postoperative events, and follow-up duration were assessed. RESULTS: There were 15 patients in this group (nine males and six females). Age ranges from 4.3 to 96.0 months (median, 7.7 months). Fourteen patients underwent S10 segmentectomy, with one undergoing right S10 segmentectomy and right S6 partial wedge resection. The surgical time was 57-125 min (median, 80 min), intraoperative bleeding volume (5-20 ml; median, 10 ml), postoperative drainage tube indwelling (2-4 d; median, 3 d), and postoperative hospitalization time (4-7 d; median, 5 d). No intraoperative conversions, surgical mortalities, or major complications were observed among these patients. Subcutaneous emphysema appeared in three patients; however, it disappeared following conservative observation without pneumothorax or bronchopleural fistula occurrence. CONCLUSIONS: Thoracoscopic segmentectomy of S10 via the inferior pulmonary ligament approach is technically feasible for treating CLM; however, this surgical approach may have certain limitations for CLM with large cysts.

Melatonin ameliorates simulated-microgravity-induced mitochondrial dysfunction and lipid metabolism dysregulation in hepatocytes.

The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.

Case report: Ileocecal preservation for multiple small intestinal duplications.

Small-intestinal duplication is a rare congenital developmental anomaly that is mainly single; multiple small-intestinal duplications are rare. Most malformations are located in the ileocecal region. The primary surgical treatment is complete resection of the malformations and adjacent intestinal ducts. However, the ileocecal junction plays an important role in children, and it is difficult to preserve it; multiple intestinal repairs increase the risk of postoperative intestinal fistula, which is a challenge for pediatric surgeons. Herein, we report a case of ileocecal preservation surgery for the treatment of multiple small intestinal duplication malformations near the ileocecal area. The child underwent laparoscopically assisted cyst excision and multiple intestinal repairs and had good postoperative recovery and follow-up.

Case report: Joint diagnosis and treatment of intrathoracic gastric duplication with a gastric communication in a child by laparoscopy and gastroscopy.

Intrathoracic gastric duplication has rarely been reported. A 5-year-old child with gastric duplication located in the left thorax was diagnosed and treated successfully using laparoscopy combined with gastroscopy. Preoperative computed tomography, upper gastrointestinal contrast study, ultrasound, and other imaging methods were insufficient for accurate diagnosis in this case. Laparoscopy combined with gastroscopy is more suitable for the diagnosis and treatment of gastric duplication.

Case report: Emergency treatment of late-presenting congenital diaphragmatic hernia with tension gastrothorax in three Chinese children.

Background: Congenital diaphragmatic hernia (CDH) is a scarce birth defect. It is called late-presenting CDH when symptoms are found after 1 month of life. The clinical manifestations of late-presenting CDH are diverse, among which the most fatal is the cardiac arrest caused by tension gastrothorax. The disease is rare, can easily lead to death owing to improper emergency treatment. This report illustrates the emergency treatment of late-presenting CDH with tension gastrothorax in three Chinese children. Case reports and management: Three children presented to emergency room with a sudden dyspnea, diagnosed accurately by x-ray or computed tomography. In case 1, the gastric tube could not be inserted at the first attempt, and the child cried incessantly. Cardiac arrest occurred when the gastric tube was re-inserted. After cardiopulmonary resuscitation and placement of a thoracic drainage tube, a large amount of gas and stomach contents were drained. Laparoscopic surgery was performed. The patient died of sepsis. In case 2, the gastric tube could not be inserted at the first attempt; consequently, emergency surgery was considered instead of retrying. After the patient was anesthetized, a gastric tube was successfully placed. Subsequently, a large amount of gas and gastric contents was drained, and thoracoscopic surgery was performed. The patient recovered evenly. In case 3, the gastric tube was successfully inserted at the first attempt; however, the vital signs were unstable due to poor drainage of the gastric tube. We injected 20 ml of iohexol into the stomach tube for angiography and dynamic chest film monitoring. After adjusting the position of the stomach tube, the stomach collapsed completely. Thoracoscopic surgery was performed. The patient recovered evenly. Conclusion: Early diagnosis is essential for children with late-presenting CDH complicated by tension gastrothorax. Fully collapsing the stomach is a key step in emergency treatment. In addition, gastric tube insertion is the first choice. In children with difficulty in gastric tube placement at the first attempt, the gastric tube can be placed under anesthesia, and emergency surgery performed simultaneously. Endoscopic surgery can be the first choice in cases of complete stomach collapse.

Targeting the chemerin/CMKLR1 axis by small molecule antagonist α-NETA mitigates endometriosis progression.

Endometriosis is a common gynecological disease, characterized by the presence of endometrial-like lesions outside the uterus. This debilitating disease causes chronic pelvic pain and infertility with limited therapeutics. Chemerin is a secretory protein that acts on CMKLR1 (Chemokine-Like Receptor 1) to execute functions vital for immunity, adiposity, and metabolism. Abnormal chemerin/CMKLR1 axis underlies the pathological mechanisms of certain diseases including cancer and inflammatory diseases, but its role in endometriosis remains unknown. Herein, our results showed that chemerin and CMKLR1 are up-regulated in endometriotic lesions by analyzing the human endometriosis database and murine model. Knockdown of chemerin or CMKLR1 by shRNA led to mesenchymal-epithelial transition (MET) along with compromised viability, migration, and invasion of hEM15A cells. Most importantly, 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA), a small molecule antagonist for CMKLR1, was evidenced to exhibit profound anti-endometriosis effects (anti-growth, anti-mesenchymal features, anti-angiogenesis, and anti-inflammation) in vitro and in vivo. Mechanistically, α-NETA exhibited a dual inhibition effect on PI3K/Akt and MAPK/ERK signaling pathways in hEM15A cells and murine endometriotic grafts. This study highlights that the chemerin/CMKLR1 signaling axis is critical for endometriosis progression, and targeting this axis by α-NETA may provide new options for therapeutic intervention.

The emerging roles of GPR158 in the regulation of the endocrine system.

G protein-coupled receptor 158 (GPR158) is a member of class C G protein-coupled receptors (GPCRs) and is highly expressed in the central nervous system (CNS) while lowly expressed in peripheral tissues. Previous studies have mainly focused on its functions in the CNS, such as regulating emotions, memory, and cognitive functions, whereas studies on its role in the non-nervous system are limited. It has been recently reported that GPR158 is directly involved in adrenal regulation, suggesting its role in peripheral tissues. Moreover, GPR158 is a stable dimer coupled to the regulator of G protein signaling protein 7 (RGS7) that forms the GPR158-RGS7-Gß5 complex. Given that the RGS7-Gß5 complex is implicated in endocrine functions, we speculate that GPR158 might be an active component of the endocrine system. Herein, we reviewed the relevant literature on GPR158, including its molecular structure, regulatory molecules, expression, and functions, and highlighted its roles in endocrine regulation. These findings not only enhance our understanding of GPR158 from an endocrine perspective but also provide valuable insights into drug exploration targeting GPR158 and their applicability in endocrine disorders.

Modified thoracoscopic wedge resection of limited peripheral lesions in S10 for children with congenital pulmonary airway malformation: Initial single-center experience.

Objective: The present study aimed to evaluate the safety and feasibility of modified thoracoscopic wedge resection of limited peripheral lesions in the posterior basal segment (S10) in children with congenital pulmonary airway malformation (CPAM). Materials and methods: We retrospectively analyzed the clinical data of children with CPAM who underwent thoracoscopic modified wedge resection at our institution from November 2020 to February 2022. The surgical method was as follows: we marked the external boundary of the lesion with an electric hook, dissected and retained the segmental vein between the lesion and normal lung tissue as the internal boundary, cut the arteries, veins, and bronchus entering the lesion, and cut and sealed the lung tissue between the internal and external boundaries with LigaSure™ to complete the modified wedge resection. Results: A total of 16 patients were included, aged 3.8-70.0 months and weighing 6.5-21.0 kg. The intraoperative course was uneventful in all patients. The median operation time and intraoperative bleeding volume were 74 min (50-110 min) and 5 mL (5-15 mL), respectively. The median postoperative drainage tube indwelling time was 3 days (2-4 days), and the median postoperative hospital stay was 6 days (4-8 days). Pathological diagnosis included two cases of type 1, 10 cases of type 2, and four cases of type 3 CPAM. There were no cases of intraoperative conversion, surgical mortality, or major complications. However, subcutaneous emphysema occurred in two children, which spontaneously resolved without pneumothorax orbronchopleural fistula development. All patients were followed up for a median period of 10 months (3-18 months), and there were no cases of hemoptysis or residual lesions on chest computed tomography. Conclusion: Modified thoracoscopic wedge resection via the inferior pulmonary ligament approach is safe and feasible for children with CPAM with limited peripheral lesions in S10.

Surgical removal of bilateral lung metastases from Wilms tumor via subxiphoid approach video-assisted thoracic surgery: a case report.

Background: Lung is the most common site of metastasis in pediatric patients with Wilms tumor (WT). For such patients, neoadjuvant chemotherapy before nephrectomy is recommended now. A considerable proportion of metastases will shrink in size after the chemotherapy. However, there are still some of them that are not sensitive to chemotherapy and require subsequent surgical resection. For pediatric patients with bilateral lung metastases from WT which are not sensitive to chemotherapy, the simultaneous surgical removal of bilateral lung tumors via one-stage surgery is problematic. These children typically require 2 separate surgeries to remove the bilateral lung metastases and improve their 5-year event-free survival (EFS) rate. There is no precedent in pediatric thoracic surgery for one-stage, bilateral, lung wedge resection via subxiphoid approach video-assisted thoracic surgery (SA-VATS). Case Description: In this article, we report on a successful SA-VATS performed on an 8-year-old boy whereby all of the bilateral lung metastases were completely resected. The operation was performed through 3 incisions under the xiphoid process and costal arch. No complications occurred after surgery. The patient's intraoperative blood loss was approximately 20 mL. Drainage tubes were indwelled in both pleural cavities which were removed on post-operative day (POD) 5 and POD 6. There was no recurrence at follow-up of about 4 months. Conclusions: This case presents a new option for thoracoscopic surgery which is safe and less invasive for patients with bilateral lung metastases from WT. Similar patients may benefit from the shorter time frame between the operation and other postoperative treatment.

Case Report: An extremely rare case of double extralobar pulmonary sequestration with anomalous supplying arteries originating from the abdominal aorta in the left thoracic cavity.

To the best of our knowledge, double or multiple extralobar pulmonary sequestrations (PSs) with anomalous arterial supply in the ipsilateral thoracic cavity have rarely been reported before. PS can be divided into two types: intralobar sequestration (ILS) and extralobar sequestration (ELS). We encountered a 5-month-old infant with double ELS in the left thoracic cavity that was incidentally detected during thoracoscopic surgery. Surgical exploration revealed two separate, well-circumscribed abnormal masses in the left thoracic cavity, and the patient was successfully treated using thoracoscopic surgery. Postoperative pathology confirmed that both masses were PS tissues. Accurate preoperative diagnosis using CT alone may be inadequate in this type of case. Therefore, thoracoscopy may be more suitable for diagnosing and treating unusual ELS.

Chemerin: A Functional Adipokine in Reproductive Health and Diseases.

As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications.

An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis.

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant-like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice.

Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene-Col6a5-and the major differentially enriched signaling pathway-lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes.

Simulated Microgravity Potentiates Hematopoietic Differentiation of Human Pluripotent Stem Cells and Supports Formation of 3D Hematopoietic Cluster.

Microgravity has been shown to induces many changes in proliferation, differentiation and growth behavior of stem cells. Little is known about the effect of microgravity on hematopoietic differentiation of pluripotent stem cells (PSCs). In this study, we used the random position machine (RPM) to investigate whether simulated microgravity (SMG) allows the induction of hematopoietic stem/progenitor cell (HSPC) derived from human embryonic stem cells (hESCs) in vitro. The results showed that SMG facilitates hESCs differentiate to HSPC with more efficient induction of CD34+CD31+ hemogenic endothelium progenitors (HEPs) on day 4 and CD34+CD43+ HSPC on day 7, and these cells shows an increased generation of functional hematopoietic cells in colony-forming unit assay when compared with normal gravity (NG) conditions. Additionally, we found that SMG significantly increased the total number of cells on day 4 and day 7 which formed more 3D cell clusters. Transcriptome analysis of cells identified thousands of differentially expressed genes (DEGs) between NG and SMG. DEGs down-regulated were enriched in the axonogenesis, positive regulation of cell adhesion, cell adhesion molecule and axon guidance, while SMG resulted in the up-regulation of genes were functionally associated with DNA replication, cell cycle, PI3K-Akt signaling pathway and tumorigenesis. Interestingly, some key gene terms were enriched in SMG, like hypoxia and ECM receptor interaction. Moreover, HSPC obtained from SMG culture conditions had a robust ability of proliferation in vitro. The proliferated cells also had the ability to form erythroid, granulocyte and monocyte/macrophage colonies, and can be induced to generate macrophages and megakaryocytes. In summary, our data has shown a potent impact of microgravity on hematopoietic differentiation of hPSCs for the first time and reveals an underlying mechanism for the effect of SMG on hematopoiesis development.

Placenta-Derived Osteoprotegerin Is Required for Glucose Homeostasis in Gestational Diabetes Mellitus.

Osteoprotegerin (OPG) is involved in various biological processes, including bone remodeling, vascular calcification and pancreatic ß-cell function. Although some clinical studies have shown an increase in serum OPG level during pregnancy, the role of OPG in gestational diabetes mellitus (GDM) is largely unknown. Therefore, we explored the effect of OPG in metabolic homeostasis during pregnancy. We initially evaluated serum OPG levels using ELISA and western blotting techniques on samples from GDM patients. We also assessed OPG expression levels in maternal mice. We then used blastocysts transduced with lentiviruses capable of trophoblast-specific transgene expression to establish placenta-specific OPG knockdown or overexpression mouse models for functional and mechanistic investigation after embryo transplantation. We found that OPG expression was positively associated with GDM in clinical samples, and OPG levels were significantly increased in GDM patient sera and term placenta. Serum OPG was significantly increased in maternal compared to non-pregnant mice, and expression levels of OPG were the highest in placenta compared with other organs, including bone, liver and pancreas. OPG was also significantly increased in pregnant mice fed a high-fat diet (HFD). Placenta-specific OPG knockdown induced glucose intolerance, decreased ß-cell proliferation and decreased serum insulin levels, whereas placenta-specific OPG overexpression promoted glucose tolerance and enhanced ß-cell proliferation, which increased serum insulin production and decreased fetal weight in HFD-feeding pregnant mice. Placenta-derived OPG (pl-OPG) regulated glucose homeostasis during pregnancy via enhancement of ß-cell proliferation, which suggests a potential therapeutic application of OPG for GDM.