Peptides最新文献

{"title":"Spexin expression in the human bile duct and perihilar cholangiocarcinoma","authors":"Sara Huber ,&nbsp;Theresia Fitzner ,&nbsp;René G. Feichtinger ,&nbsp;Theo Kraus ,&nbsp;Stefanie Gaisbauer ,&nbsp;Sarah Hochmann ,&nbsp;Karl Sotlar ,&nbsp;Barbara Kofler ,&nbsp;Martin Varga","doi":"10.1016/j.peptides.2025.171405","DOIUrl":"10.1016/j.peptides.2025.171405","url":null,"abstract":"<div><div>The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL_1–3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL₂-R and GAL₃-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (<em>p</em> = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171405"},"PeriodicalIF":2.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxyntomodulin - past, present and future","authors":"Jens Juul Holst ,&nbsp;Mette M. Rosenkilde","doi":"10.1016/j.peptides.2025.171393","DOIUrl":"10.1016/j.peptides.2025.171393","url":null,"abstract":"<div><div>Almost since its discovery, glucagon was suspected to be formed in the gastrointestinal tract, and the L-cells were shown to contain glucagon-like immunoreactivity. This was due to the presence of two peptides that both contained the full glucagon sequence:glicentin of 69 amino acids and oxyntomodulin of 37 amino acids. While glicentin is a part of the glucagon precursor, proglucagon, and probably is inactive, oxyntomodulin, a fragment of glicentin, interacts although weakly with the glucagon as well as the GLP-1 receptor. However, in agreement with these activities, oxyntomodulin inhibited appetite and food intake in humans and inspired development of long acting, potent glucagon-GLP-1 co-agonists. Several such co-agonists are currently in clinical development and show promise because they combine GLP-1 like activities with those of glucagon agonism: additive weight loss and a stimulation of hepatic lipid metabolism with unique effectiveness on hepatic steatosis. They may therefore be effective in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171393"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin prevents visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome","authors":"Tsukasa Nozu ,&nbsp;Saori Miyagishi ,&nbsp;Masatomo Ishioh ,&nbsp;Kaoru Takakusaki ,&nbsp;Toshikatsu Okumura","doi":"10.1016/j.peptides.2025.171394","DOIUrl":"10.1016/j.peptides.2025.171394","url":null,"abstract":"<div><div>Visceral hypersensitivity and impaired gut barrier function, accompanied by minor inflammation, are crucial components of the pathophysiology of irritable bowel syndrome (IBS). Research has demonstrated that corticotropin-releasing factor (CRF) and toll-like receptor 4 (TLR4) signaling mutually activate to produce proinflammatory cytokines, which modulate these gastrointestinal changes. Irisin, a myokine, has been shown to inhibit TLR4-proinflammatory cytokine signaling, thereby improving inflammation driven by obesity and metabolic syndrome. Based on this, we hypothesized that irisin could improve visceral hypersensitivity and impaired gut barrier function induced by lipopolysaccharide (LPS) or CRF (IBS rat models), and tested this hypothesis. The visceral pain threshold, triggered by colonic balloon distention, was assessed by electrophysiologically monitoring abdominal muscle contractions in male Sprague-Dawley rats. Colonic permeability was evaluated by measuring the amount of Evans blue dye absorbed within the colonic tissue. Intraperitoneal irisin prevented LPS-induced visceral hypersensitivity and colonic hyperpermeability in a dose-dependent manner. Irisin also prevented CRF-induced gastrointestinal alterations. The beneficial effects of irisin in the LPS model were reversed by compound C, an AMP-activated protein kinase (AMPK) inhibitor; N^G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor; sulpiride or domperidone, a dopamine D₂ receptor antagonist; atropine and intracisternal injection of SB-334867, a selective orexin 1 receptor antagonist. Overall, these findings suggest that irisin improves visceral sensation and colonic barrier function through AMPK, NO and dopamine D₂, cholinergic and brain orexin signaling in IBS model. Thus, irisin may be a promising therapeutic agent for treating IBS.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171394"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of plasma arginine vasopressin during hypertonic saline loading: A comparison of radioimmunoassay and liquid chromatography–tandem mass spectrometry","authors":"Narantsatsral Daramjav ,&nbsp;Junko Takagi ,&nbsp;Fumio Nomura ,&nbsp;Kazuo Otake ,&nbsp;Akiyoshi Takami","doi":"10.1016/j.peptides.2025.171392","DOIUrl":"10.1016/j.peptides.2025.171392","url":null,"abstract":"<div><div>Plasma arginine vasopressin (AVP) measurement is critical for diagnosing central diabetes insipidus (CDI). Conventional radioimmunoassay (RIA) is widely used for AVP quantification, but its limited sensitivity, specificity, and dynamic range have prompted exploration of alternative methods. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a promising technique for AVP measurement, offering potential advantages over RIA. This study aimed to evaluate LC-MS/MS performance for AVP quantification during hypertonic saline loading and compare its diagnostic accuracy with that of RIA in differentiating CDI patients from controls. A total of 335 plasma samples were collected from 77 individuals—23 diagnosed with CDI and 54 controls—during hypertonic saline loading. AVP concentrations were measured using both LC-MS/MS and RIA. Statistical analyses included Wilcoxon tests to compare AVP levels, correlation analysis between LC-MS/MS and RIA, and receiver operating characteristic (ROC) curve analysis to assess diagnostic performance. LC-MS/MS demonstrated a lower detection limit (0.3 pg/mL) and a broader quantification range than RIA. Regression analysis showed a strong correlation between LC-MS/MS and RIA in the control group, but no correlation in the CDI group. ROC analysis indicated that LC-MS/MS provided diagnostic accuracy comparable to RIA for distinguishing CDI patients from controls. Bland-Altman analysis showed the agreement between two methods at the low range of AVP. LC-MS/MS offers equivalent specificity and sensitivity to RIA for AVP measurement, while providing added benefits in time efficiency, cost-effectiveness, and differential diagnosis of CDI. These findings suggest that LC-MS/MS is a viable alternative to RIA for clinical AVP quantification.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171392"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adropin: A cardio-metabolic hormone in the periphery, a neurohormone in the brain?","authors":"Andrew A. Butler ,&nbsp;Peter J. Havel","doi":"10.1016/j.peptides.2025.171391","DOIUrl":"10.1016/j.peptides.2025.171391","url":null,"abstract":"<div><div>Whole-body metabolic homeostasis is regulated by physiological responses across organs and tissues to proteins and peptides (&lt;50 amino acids) released into the interstitial and circulatory spaces. These secreted factors integrate signals of metabolic status at both the cellular and systemic level, regulate the intake and distribution of ingested and stored energy substrates across tissues, and minimize toxicity from excessive excursions in circulating concentrations of energy substrates (for example, glucotoxicity and lipotoxicity). The proteins and peptides that are known to be secreted into circulation that are involved in regulating metabolic processes represent a fraction of the secretome predicted by the Human Proteome Atlas. Many undiscovered leads for targeting new therapies for metabolic diseases may therefore exist. In this review, we discuss the biology of adropin, the peptide encoded by the Energy Homeostasis Associated (<em>ENHO</em>) gene<em>.</em> First described as a feeding-responsive, liver-secreted peptide (“hepatokine”) involved in metabolic homeostasis, &gt; 2 decades of research indicate adropin is a stress-responsive peptide acting across multiple tissues, vascular, and organ systems. Adropin modulates the responses of liver and muscle to insulin and glucagon in regulating glucose homeostasis. Adropin inhibits hepatic glucose production and stimulates glycolysis but also inhibits tissue fibrosis and maintains vascular health in aging and metabolic disease states. Adropin is also highly expressed in the central nervous system where recent data suggest neuroprotective actions. Collectively, these results suggest the potential for targeting adropin in reducing risk of both metabolic (metabolic syndrome/type-2 diabetes) and neurodegenerative diseases in the context of aging and obesity.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171391"},"PeriodicalIF":2.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities","authors":"Clifford J. Bailey ,&nbsp;Peter R. Flatt ,&nbsp;J. Michael Conlon","doi":"10.1016/j.peptides.2025.171380","DOIUrl":"10.1016/j.peptides.2025.171380","url":null,"abstract":"<div><div>Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and ‘real-world’ studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171380"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel regulator of NLRP3 inflammasome: Peptides","authors":"Zhuo Zuo,&nbsp;Yaxing Wang,&nbsp;Yanwei Fang,&nbsp;Mengya Zhao,&nbsp;Zhe Wang,&nbsp;Zhouqi Yang,&nbsp;Bin Jia,&nbsp;Yulong Sun","doi":"10.1016/j.peptides.2025.171381","DOIUrl":"10.1016/j.peptides.2025.171381","url":null,"abstract":"<div><div>The NLRP3 inflammasome plays a crucial role as a critical regulator of the immune response and has been implicated in the pathogenesis of numerous diseases. Peptides, known for their remarkable potency, selectivity, and low toxicity, have been extensively employed in disease treatment. Recent research has unveiled the potential of peptides in modulating the activity of the NLRP3 inflammasome. This review begins by examining the structure of the NLRP3 inflammasome, encompassing NLRP3, ASC, and Caspase-1, along with the three activation pathways: canonical, non-canonical, and alternative. Subsequently, we provide a comprehensive summary of peptide modulators targeting the NLRP3 inflammasome and elucidate their underlying mechanisms. The efficacy of these modulators has been validated through <em>in vitro</em> and <em>in vivo</em> experiments on NLRP3 inflammasome regulation. Furthermore, we conduct sequence alignment of the identified peptides and investigate their binding sites on the NLRP3 protein. This work is a foundational exploration for advancing peptides as potential therapeutic agents for NLRP3-related diseases.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171381"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Oxytocin attenuates cardiac hypertrophy by improving cardiac glucose metabolism and regulating OXTR/JAK2/STAT3 axis” [Peptides 182 (2024) 171323]","authors":"Yuqiao Yang ,&nbsp;Jin Liu ,&nbsp;Lingyan Wang ,&nbsp;Wen Wu,&nbsp;Quan Wang,&nbsp;Yu Zhao,&nbsp;Xi Qian,&nbsp;Zhuoran Wang,&nbsp;Na Fu,&nbsp;Yanqiong Wang,&nbsp;Jinqiao Qian","doi":"10.1016/j.peptides.2025.171365","DOIUrl":"10.1016/j.peptides.2025.171365","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171365"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLF4 regulates FAM3A to promotes angiotensin II-induced proliferation and migration of vascular smooth muscle cells through the PI3K/AKT signaling pathway","authors":"Min Zhang,&nbsp;Rong Lei,&nbsp;Liqiong Wang,&nbsp;Yimin Jiang,&nbsp;Xiaoyan Zhou,&nbsp;Yuquan Wang","doi":"10.1016/j.peptides.2025.171379","DOIUrl":"10.1016/j.peptides.2025.171379","url":null,"abstract":"<div><h3>Background</h3><div>Hypertension, a major cause of cardiovascular disease, is linked to vascular remodeling, which is influenced by phenotypic changes in vascular smooth muscle cells (VSMCs). Studies have shown that KLF4 influences vascular remodeling by promoting VSMC dedifferentiation, increasing proliferation, and enhancing inflammatory responses, while FAM3 may play a key role in VSMC migration and proliferation. Angiotensin II (Ang II) contributes to remodeling, but the mechanisms are unclear.</div></div><div><h3>Methods</h3><div>Ang II was used to stimulate VSMCs in order to evaluate the expression levels of KLF4 and FAM3A. EdU assays, transwell and scratch wound healing assays measured proliferation and migration. KLF4 knockdown and overexpression experiments were performed to examine the effects on FAM3A expression and VSMC behavior. Western blotting was conducted to analyze protein expression levels of KLF4, FAM3A, and PI3K/AKT signaling components. Bioinformatics analysis was used to predict KLF4 binding sites on the FAM3A promoter. Luciferase and CHIP assays confirmed regulation.</div></div><div><h3>Results</h3><div>Ang II stimulation increased VSMC proliferation, migration, and the expression of KLF4 and FAM3A. Knockdown of KLF4 reduced Ang II-induced proliferation and migration of VSMCs, accompanied by decreased FAM3A expression. Conversely, overexpression of KLF4 enhanced FAM3A levels, promoting VSMC proliferation and migration. Bioinformatics, luciferase reporter assays and CHIP assay confirmed that KLF4 directly binds to the FAM3A promoter. FAM3A knockdown inhibited Ang II-induced VSMC proliferation and migration by reducing PI3K/AKT pathway activation, whereas FAM3A overexpression reversed the inhibitory effects of KLF4 knockdown.</div></div><div><h3>Conclusion</h3><div>KLF4 transcriptionally regulates FAM3A, modulating Ang II-induced VSMC proliferation and migration through the PI3K/AKT signaling pathway.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"187 ","pages":"Article 171379"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A murine model of obesity with hyperinsulinemia and hepatic steatosis involving neurosecretory protein GL gene and a low-fat/medium-sucrose diet","authors":"Yuki Narimatsu ,&nbsp;Masaki Kato ,&nbsp;Eiko Iwakoshi-Ukena,&nbsp;Megumi Furumitsu,&nbsp;Kazuyoshi Ukena","doi":"10.1016/j.peptides.2025.171376","DOIUrl":"10.1016/j.peptides.2025.171376","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) featuring hepatic steatosis and insulin dysregulation is becoming a common cause of chronic hepatic diseases. Although the involvement of endocrine disruption in the onset and progression of MASLD is thought to be critical, there are limited effective animal models reflecting hyperinsulinemia and hepatic steatosis. Here, we propose a MASLD mouse model that combines neuropeptide effects and dietary nutrition. We employed chronic overexpression of the gene encoding neurosecretory protein GL (NPGL) in the hypothalamus of ICR mice under a low-fat/medium-sucrose diet (LFMSD). <em>Npgl</em> overexpression promoted fat accumulation in the white adipose tissues in 2 weeks. Basal insulin levels were increased and pancreatic islets expanded following <em>Npgl</em> overexpression. Histological and molecular biological approaches revealed that <em>Npgl</em> overexpression enhanced de novo lipogenesis, leading to hepatic steatosis. Nine-week overexpression of <em>Npgl</em> exacerbated obesity and hyperinsulinemia, resulting in hyperglycemia. Moreover, prolonged <em>Npgl</em> overexpression aggravated fat accumulation in the liver with a change in the lipid metabolic pathway. These findings suggest that <em>Npgl</em> overexpression readily leads to obesity with hyperinsulinemia and hepatic steatosis in ICR mice under an LFMSD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"186 ","pages":"Article 171376"},"PeriodicalIF":2.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}