Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider
{"title":"Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age","authors":"Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider","doi":"10.1016/j.mce.2025.112508","DOIUrl":"10.1016/j.mce.2025.112508","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of <em>Cyp4a12a</em>, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112508"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga
{"title":"Bisphenol A exposure alters hormonal modulation and responsivity in the prostate of aged female gerbils","authors":"Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga","doi":"10.1016/j.mce.2025.112507","DOIUrl":"10.1016/j.mce.2025.112507","url":null,"abstract":"<div><div>The female prostate is a gland regulated by steroid hormones for homeostasis. Bisphenol A (BPA) is an endocrine disruptor related to the progression of malignant lesions in prostate. The aim of this study was to analyze the hormonal modulation and responsiveness of the prostate of aged female gerbils previously exposed to BPA. Females were exposed to 50 μg/kg/day during pregnancy and lactation, and the prostate was analyzed at 18 months of age. Control groups were included to normalize the analysis. The samples were analyzed using histological and immunohistochemical techniques for the expression of androgen (AR), estrogen (ERα and ERβ), prolactin (PRL), and progesterone (PR) receptors, as well as steroidogenic enzymes (5α-reductase and aromatase) and the proliferation (PHH3) and epigenetic (EZH2) markers. Protein quantification was also performed for the receptors and enzymes described, as well as morphological and morphometric analyses of the gland. The results showed an increase in the epithelial expression of AR and ERα and a decrease in the expression of ERβ in this compartment. In addition, a decrease in epithelial expression was observed for the 5α-reductase and aromatase in the prostate epithelium and an increase in the expression of PHH3 and EZH2. By Western blot analyses, significant differences were observed in the protein quantification of the receptors and enzymes described. Thus, the current study showed the role of BPA in intraprostatic hormonal modulation, through alterations in the expression of hormone receptors and the conversion of enzymes in the female prostate, which can lead to the progression of malignant lesions in this tissue.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112507"},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole
{"title":"Mechanisms of ligand-mediated modulation of mineralocorticoid receptor signaling","authors":"Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole","doi":"10.1016/j.mce.2025.112504","DOIUrl":"10.1016/j.mce.2025.112504","url":null,"abstract":"<div><div>The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism. This review will discuss the current understanding, including recent insights into these interactions, with implications for an emerging array of novel non-steroidal compounds targeting the mineralocorticoid receptor; and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic agents.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112504"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada
{"title":"New perspectives about the article “Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms”","authors":"Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada","doi":"10.1016/j.mce.2025.112495","DOIUrl":"10.1016/j.mce.2025.112495","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112495"},"PeriodicalIF":3.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Understanding metabolic remodeling in shock through metabolomics lenses","authors":"Zoé Demailly , Fabienne Tamion , Emmanuel Besnier , Soumeya Bekri , Abdellah Tebani","doi":"10.1016/j.mce.2025.112491","DOIUrl":"10.1016/j.mce.2025.112491","url":null,"abstract":"<div><div>The management of shock in critical care must transition from a predominantly hemodynamic approach to one that comprehensively addresses the biological intricacies of this complex multisystemic syndrome. A thorough understanding of the metabolic mechanisms involved in shock is pivotal for precise patient phenotyping and accurate risk stratification. Metabolomics, an emerging “-omics” approach, offers a powerful tool for unraveling the molecular underpinnings of shock. By analyzing the metabolic pathways within the cardiovascular system, metabolomics can elucidate the diverse mechanisms leading to circulatory insufficiency. This approach holds significant promise for identifying clinically actionable diagnostic and prognostic biomarkers, which can enhance individualized patient management and potentially prevent the progression to multi-organ failure. Improved insight into the metabolic alterations in shock may pave the way for novel therapeutic strategies and more targeted treatments, ultimately improving patient outcomes in critical care settings. This work provides a comprehensive overview of metabolomic investigations in shock, focusing on septic shock and the main metabolic pathways involved in cardiac and vascular dysfunction.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112491"},"PeriodicalIF":3.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Cristina Miola , Fernanda Yamamoto Ricardo-da-Silva , Pedro Luiz Zonta de Freitas, Marina Vidal-dos-Santos, Luiz Felipe Pinho Moreira, Ana Cristina Breithaupt-Faloppa, Cristiano de Jesus Correia
{"title":"The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats","authors":"Elizabeth Cristina Miola , Fernanda Yamamoto Ricardo-da-Silva , Pedro Luiz Zonta de Freitas, Marina Vidal-dos-Santos, Luiz Felipe Pinho Moreira, Ana Cristina Breithaupt-Faloppa, Cristiano de Jesus Correia","doi":"10.1016/j.mce.2025.112488","DOIUrl":"10.1016/j.mce.2025.112488","url":null,"abstract":"<div><div>Among transplantable organs, the intestine is one of the most challenging organs to transplant. While there is considerable research on the effects of brain death (BD), little is known about the specific intestinal changes that occur, particularly in females. Here we investigated the role of female sex hormones in the BD-induced intestinal inflammation, using an ovariectomy (OVx) model for sex hormones depletion. Wistar rats (female) were divided into four experimental groups: Control non-OVx – non-manipulated; Control-OVx –ovariectomized; BD non-OVx – animals submitted to BD (6h); BD-OVx –ovariectomized animals submitted to BD. OVx was performed 10 days before BD induction. non-OVx groups were chosen during proestrus phase (heat period). Inflammatory mediators and white blood cell count were quantified in the blood. Intestine tissue was sampled for histopathological analysis, myeloperoxidase (MPO) activity, Evans blue dye extravasation assay and immunohistochemistry. Results show higher intestinal injury in BD-OVx than BD non-OVx animals, presenting reduced crypt depth and increased serum inflammatory mediators. Independently from the previous hormonal status, BD increased intestinal inflammation, with higher leukocyte infiltration, MPO activity, ICAM-1 expression, and higher serum MIP-1α. In summary, BD modulates intestinal inflammation by increasing leukocyte mobilization. Whereas OVx, and its consequences on the female hormonal profile, influences homeostasis and BD-induced inflammation, increasing inflammatory mediators and altering intestinal morphology.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112488"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jithine J. Rajeswari, Geneece N.Y. Gilbert, Enezi Khalid, Mathilakath M. Vijayan
{"title":"Brain monoamine changes modulate the corticotropin-releasing hormone receptor 1-mediated behavioural response to acute thermal stress in zebrafish larvae","authors":"Jithine J. Rajeswari, Geneece N.Y. Gilbert, Enezi Khalid, Mathilakath M. Vijayan","doi":"10.1016/j.mce.2025.112494","DOIUrl":"10.1016/j.mce.2025.112494","url":null,"abstract":"<div><div>While central monoamines play a role in regulating stress-related locomotory activity, the modulation of monoamines by the corticosteroid stress axis in shaping acute behavioural responses are unclear. We investigated whether the corticotropin-releasing hormone receptor 1 (Crhr1) modulation of stress-related behavioral response involves monoamine regulation by subjecting Crhr1 knockout (<em>crhr1</em><sup><em>−/−</em></sup>) zebrafish (<em>Danio rerio</em>) to an acute thermal stressor (TS: +5 °C above ambient for 60 min). The TS-induced cortisol response and hyper locomotory activity in the WT larvae was abolished in fish lacking Crhr1. However, both genotypes induced a heat shock protein response to the TS. The <em>crhr1</em><sup><em>−/−</em></sup> larvae showed a region-specific difference in the distribution of serotonin (5-HT)- and tyrosine hydroxylase-positive cells in the brain. This corresponded with increases in whole-body transcript abundance of dopamine beta-hydroxylase, tryptophan hydroxylase 2, and solute carrier family 6-member 4a. Cotreatment with either epinephrine or 5-HT, but not cortisol, was able to rescue the TS-mediated hypo locomotory activity and thigmotaxis seen in the <em>crhr1</em><sup><em>−/−</em></sup> larvae. Together, these results indicate that Crhr1 is essential not only for mediating the TS-induced hyperactivity but also for maintaining the basal locomotory activity and anxiogenic response during stress. The latter response depends on the central monoamine regulation by Crhr1 in zebrafish larvae.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112494"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica D. Pereira , Fernanda M.V. Magalhães , Fabiana M.S. Tameirão , Frederico M. Soriani , Karina T. de O. S. Jorge , Fernando M. Reis , Ana Lúcia Cândido , Fábio V. Comim , Karina B. Gomes
{"title":"The possible regulatory role of miRNA-30c-5p, miRNA-545-3p and miRNA-125a-5p in women with polycystic ovary syndrome: A case-control study and signaling pathways","authors":"Jessica D. Pereira , Fernanda M.V. Magalhães , Fabiana M.S. Tameirão , Frederico M. Soriani , Karina T. de O. S. Jorge , Fernando M. Reis , Ana Lúcia Cândido , Fábio V. Comim , Karina B. Gomes","doi":"10.1016/j.mce.2025.112492","DOIUrl":"10.1016/j.mce.2025.112492","url":null,"abstract":"<div><h3>Introduction</h3><div>Polycystic Ovary Syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. MicroRNA (miRNAs) are small non-coding RNAs related to the control of gene expression in biological fluids. Our study analyzed the expression of miRNAs related to inflammation in individuals with PCOS compared to controls.</div></div><div><h3>Methods</h3><div>Twenty patients with PCOS and 20 controls, matched by body mass index and age, were included in the study. The miRNAs evaluated were miRNA-30c-5p; miRNA-545-3p and miRNA-125a-5p.</div></div><div><h3>Results</h3><div>The expression of the miRNAs was similar between the two groups. A positive correlation was observed between the expression of miRNA-125a-5p and LDLc levels only in the PCOS group. Subsequent analysis of biological pathways showed that miRNA-125a -5p is significantly involved in the regulation of SREBP/SREBF pathways of cholesterol biosynthesis, glycolysis, insulin receptor signaling, oxidative stress-induced senescence and estrogen-dependent gene expression.</div></div><div><h3>Conclusion</h3><div>The results suggest that the miRNA-125a-5p shows a potential implication to the regulation of lipid biosynthesis and LDL-c levels in PCOS women.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112492"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyao Li , Qian Liu , Lingling Wang , Tiao Bu , Xiwen Yang , Sheng Gao , Damin Yun , Fei Sun
{"title":"PPM1G dephosphorylates α-catenin to maintain the integrity of adherens junctions and regulates apoptosis in Sertoli cells","authors":"Xinyao Li , Qian Liu , Lingling Wang , Tiao Bu , Xiwen Yang , Sheng Gao , Damin Yun , Fei Sun","doi":"10.1016/j.mce.2025.112493","DOIUrl":"10.1016/j.mce.2025.112493","url":null,"abstract":"<div><div>Protein phosphatase, Mg2+/Mn2+ dependent, 1G (PPM1G) regulates protein function via dephosphorylation. PPM1G participates in the assembly of adherens junctions by dephosphorylating α-catenin. Here, we demonstrated through siRNA transfection and intratesticular injection that PPM1G is critical for maintaining blood-testis barrier function and regulating Sertoli cell apoptosis. We observed that upon knocking down Ppm1g in rat testes, the function of the blood testis barrier was compromised, and the localization of α-catenin and β-catenin became aberrant. Further investigation in rat Sertoli cells revealed that after Ppm1g knockdown, the level of phosphorylated α-catenin increased, and it failed to properly aggregate at the cell membrane; instead, it was mislocalized to the cytoplasm. The actin to which catenin is attached also exhibited a disordered arrangement in the absence of PPM1G. Additionally, through RNA sequencing and bioinformatics analysis, we identified genes associated with Sertoli cell dysfunction induced by Ppm1g knockdown and identified a set of genes involved in regulating intercellular junctions. Subsequent validation revealed that after Ppm1g knockdown, the expression of the junction-related protein JAM2 was reduced, and Sertoli cells underwent apoptosis. Overall, we identified a gene, Ppm1g, which may be involved in maintaining the normal function of the blood-testis barrier and influencing the survival of Sertoli cells by regulating apoptotic pathways.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112493"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhu , Ming Zong , Ling Hu , Juan Wan , Liyao Zong , Jixiong Xu
{"title":"USP7 deficiency promotes diabetic wound healing by repressing GATA3-mediated pro-inflammatory macrophage polarization","authors":"Yan Zhu , Ming Zong , Ling Hu , Juan Wan , Liyao Zong , Jixiong Xu","doi":"10.1016/j.mce.2025.112489","DOIUrl":"10.1016/j.mce.2025.112489","url":null,"abstract":"<div><h3>Background</h3><div>The polarization of inflammatory macrophages is an important factor contributing to delay wound healing in diabetic foot ulcers (DFU). In this study, the role of ubiquitin-specific protease 7 (USP7) in regulating macrophage polarization during DFU progression was investigated.</div></div><div><h3>Methods</h3><div>Gene and protein expression levels were assessed using qRT-PCR and western blot. In vitro and in vivo diabetes mellitus (DM) models were established by HG treatment and STZ injection, respectively. HUVEC viability, migration, and angiogenesis were detected by CCK8 assay, wound healing assay, and tube formation assay, respectively. Flow cytometry was employed to analyze the levels of macrophage polarization markers. Co-IP assay was performed to analyze the interaction between USP7 and GATA3.</div></div><div><h3>Results</h3><div>Our results demonstrated that USP7 was overexpressed in ulcer margin tissues of DFU patients, wound tissues of DFU mice, and HG-treated macrophages. Functionally, USP7 deficiency inhibited macrophage M1 polarization and promoted wound healing in DFU mice. In vitro, USP7 knockdown promoted HUVEC proliferation, migration, and angiogenesis by inducing M2 macrophage polarization and inhibiting M1 macrophage polarization under HG condition. Mechanistically, USP7 could stabilize GATA3 protein in macrophages by deubiquitinating GATA3. Moreover, the effects of USP7 knockdown on HUVEC function and macrophage polarization under HG condition were partially reversed by GATA3 overexpression.</div></div><div><h3>Conclusion</h3><div>USP7 silencing enhanced wound healing in DFU by inhibiting M1 macrophage polarization and promoting M2 macrophage polarization through mediating GATA3 deubiquitylation.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112489"},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}