Diabetes最新文献

{"title":"A Neuron-Mast Cell Axis Regulates Skin Microcirculation in Diabetes.","authors":"Xinran Li, Dan Yuan, Peng Zhang, Chenglei Luo, Xinyang Xie, Yue Zhang, Zhengqi Wei, Mingyang Wang, Yunqiu Cai, Yi Zeng, Luying Lai, Delu Che, Hao Ling, Shengjun Shi, Hong-Fei Zhang, Fang Wang, Fengxian Li","doi":"10.2337/db23-0862","DOIUrl":"10.2337/db23-0862","url":null,"abstract":"<p><p>Changes in microcirculation lead to the progression of organ pathology in diabetes. Although neuroimmune interactions contribute to a variety of conditions, it is still unclear whether abnormal neural activities affect microcirculation related to diabetes. Using laser speckle contrast imaging, we examined the skin of patients with type 2 diabetes and found that their microvascular perfusion was significantly compromised. This phenomenon was replicated in a high-fat diet-driven murine model of type 2 diabetes-like disease. In this setting, although both macrophages and mast cells were enriched in the skin, only mast cells and associated degranulation were critically required for the microvascular impairment. Sensory neurons exhibited enhanced TRPV1 activities, which triggered mast cells to degranulate and compromise skin microcirculation. Chemical and genetic ablation of TRPV1+ nociceptors robustly improved skin microcirculation status. Substance P (SP) is a neuropeptide and was elevated in the skin and sensory neurons in the context of type 2 diabetes. Exogenous administration of SP resulted in impaired skin microcirculation, whereas neuronal knockdown of SP dramatically prevented mast cell degranulation and consequently improved skin microcirculation. Overall, our findings indicate a neuron-mast cell axis underlying skin microcirculation disturbance in diabetes and shed light on neuroimmune therapeutics for diabetes-related complications.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1728-1741"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon Resistance in Individuals With Obesity and Hepatic Steatosis Can Be Measured Using the GLUSENTIC Test and Index.","authors":"Sasha A S Kjeldsen, Michael M Richter, Nicole J Jensen, Malin S D Nilsson, Niklas Heinz, Janus D Nybing, Frederik H Linden, Erik Høgh-Schmidt, Mikael P Boesen, Thomas L Andersen, Helle H Johannesen, Samuel A J Trammell, Trisha J Grevengoed, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiødt, Andreas Møller, Elias B Rashu, Kirsten Nørgaard, Signe Schmidt, Lise L Gluud, Steen B Haugaard, Jens J Holst, Jørgen Rungby, Nicolai J Wewer Albrechtsen","doi":"10.2337/db23-0858","DOIUrl":"10.2337/db23-0858","url":null,"abstract":"<p><p>Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, which consists of 2 study days: a glucagon injection and measurements of plasma amino acids and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The δ-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (P = 0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (P < 0.0001) but not T1D (P > 0.99). In contrast, glucagon-induced glucose increments were similar in control participants and participants with MASLD (P = 0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1716-1727"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sensory Neuron-Mast Cell Axis Regulation of Skin Microcirculation in Diabetes: Implication for Diabetes-Related Cutaneous Complications.","authors":"Zhenqi Liu","doi":"10.2337/dbi24-0035","DOIUrl":"10.2337/dbi24-0035","url":null,"abstract":"","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":"73 10","pages":"1563-1565"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 Receptor Agonist Treatment Improves Fasting and Postprandial Lipidomic Profiles Independently of Diabetes and Weight Loss.","authors":"Giuseppe Della Pepa, Bárbara G Patrício, Fabrizia Carli, Silvia Sabatini, Brenno Astiarraga, Ele Ferrannini, Stefania Camastra, Amalia Gastaldelli","doi":"10.2337/db23-0972","DOIUrl":"10.2337/db23-0972","url":null,"abstract":"<p><p>Treatment with glucagon-like peptide 1 receptor agonists reduces liver steatosis and cardiometabolic risk (CMR). Few data are available on lipid metabolism, and no information is available on the postprandial lipidomic profile. Thus, we investigated how exenatide treatment changes lipid metabolism and composition during fasting and after a mixed-meal tolerance test (MMTT) in adults with severe obesity without diabetes. Thirty individuals (26 females and 4 males, 30-60 years old, BMI >40 kg/m2, HbA1c 5.76%) were assigned (1:1) to diet with exenatide 10 μg twice daily treatment (n = 15) or without treatment as control (n = 15) for 3 months. Fasting and postprandial lipidomic profile (by liquid chromatography quadrupole time-of-flight mass spectrometry) and fatty acid metabolism (following a 6-h MMTT/tracer study) and composition (by gas chromatography-mass spectrometry) were evaluated before and after treatment. Both groups had slight weight loss (-5.5% vs. -1.9%, exenatide vs. control; P = 0.052). During fasting, exenatide, compared with control, reduced some ceramides (CERs) and lysophosphatidylcholines (LPCs) previously associated with CMR, while relatively increasing unsaturated phospholipid species (phosphatidylcholine [PC], LPC) with protective effects on CMR, although concentrations of total lipid species were unchanged. During MMTT, both groups showed suppressed lipolysis equal to baseline, but exenatide significantly lowered free fatty acid clearance and postprandial triacyclglycerol (TAG) concentrations, particularly saturated TAGs with 44-54 carbons. Exenatide also reduced some postprandial CERs, PCs, and LPCs previously linked to CMR. These changes in lipidomic profile remained statistically significant after adjusting for weight loss. Exenatide improved fasting and postprandial lipidomic profiles associated with CMR mainly by reducing saturated postprandial TAGs and CERs independently of weight loss and diabetes.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1605-1614"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Stress Levels Influence the Ability of Myelin Transcription Factors to Regulate β-Cell Identity and Survival.","authors":"Xin Tong, Mahircan Yagan, Ruiying Hu, Simone Nevills, Teri D Doss, Roland W Stein, Appakalai N Balamurugan, Guoqiang Gu","doi":"10.2337/db23-0528","DOIUrl":"10.2337/db23-0528","url":null,"abstract":"<p><p>A hallmark of type 2 diabetes (T2D) is endocrine islet β-cell failure, which can occur via cell dysfunction, loss of identity, and/or death. How each is induced remains largely unknown. We used mouse β-cells deficient for myelin transcription factors (Myt TFs; including Myt1, -2, and -3) to address this question. We previously reported that inactivating all three Myt genes in pancreatic progenitor cells (MytPancΔ) caused β-cell failure and late-onset diabetes in mice. Their lower expression in human β-cells is correlated with β-cell dysfunction, and single nucleotide polymorphisms in MYT2 and MYT3 are associated with a higher risk of T2D. We now show that these Myt TF-deficient postnatal β-cells also dedifferentiate by reactivating several progenitor markers. Intriguingly, mosaic Myt TF inactivation in only a portion of islet β-cells did not result in overt diabetes, but this created a condition where Myt TF-deficient β-cells remained alive while activating several markers of Ppy-expressing islet cells. By transplanting MytPancΔ islets into the anterior eye chambers of immune-compromised mice, we directly show that glycemic and obesity-related conditions influence cell fate, with euglycemia inducing several Ppy+ cell markers and hyperglycemia and insulin resistance inducing additional cell death. These findings suggest that the observed β-cell defects in T2D depend not only on their inherent genetic/epigenetic defects but also on the metabolic load.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1662-1672"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryopreservation of Stem Cell-Derived β-Like Cells Enriches for Insulin-Producing Cells With Improved Function.","authors":"Jessie M Barra, Austin T Kratz, Roberto Castro-Gutierrez, James Proia, Gurprit Bhardwaj, Edward A Phelps, Holger A Russ","doi":"10.2337/db24-0346","DOIUrl":"10.2337/db24-0346","url":null,"abstract":"<p><p>The generation of stem cell-derived β-like cells (sBCs) holds promise as not only an abundant insulin-producing cell source for replacement therapy of type 1 diabetes (T1D) but also as an invaluable model system for investigating human β-cell development, immunogenicity, and function. Several groups have developed methodology to direct differentiate human pluripotent stem cells into pancreatic cell populations that include glucose-responsive sBCs. Nevertheless, the process of generating sBCs poses substantial experimental challenges. It involves lengthy differentiation periods, there is substantial variability in efficiency, and there are inconsistencies in obtaining functional sBCs. Here, we describe a simple and effective cryopreservation approach for sBC cultures that yields homogeneous sBC clusters that are enriched for insulin-expressing cells while simultaneously depleting proliferative progenitors. Thawed sBCs have enhanced glucose-stimulated insulin release compared with controls in vitro and can effectively engraft and function in vivo. Collectively, this approach alleviates current challenges with inefficient and variable sBC generation while improving their functional state. We anticipate that these findings can inform ongoing clinical application of sBCs for the treatment of patients with T1D and serve as an important resource for the wider diabetes field that will allow for accelerated research discoveries.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1687-1696"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpressed Poldip2 Incurs Retinal Fibrosis via the TGF-β1/SMAD3 Signaling Pathway in Diabetic Retinopathy.","authors":"Zhiyu Ji, Siyu Lin, Siyu Gui, Jie Gao, Fan Cao, Yiming Guan, Qinyu Ni, Keyang Chen, Liming Tao, Jiang Zhengxuan","doi":"10.2337/db23-1036","DOIUrl":"10.2337/db23-1036","url":null,"abstract":"<p><p>Retinal fibrosis is one of the major features of diabetic retinopathy (DR). Our recent research has shown that Poldip2 can affect early DR through oxidative stress, but whether Poldip2 would regulate retinal fibrosis during DR development is still enigmatic. Here, diabetic Sprague-Dawley (SD) rats were induced with streptozotocin (STZ) and treated with adeno-associated virus serotype 9-polymerase-δ interacting protein 2 (Poldip2) shRNA, while human adult retinal pigment epithelial (ARPE-19) cells were treated with high glucose or Poldip2 siRNA. We identified that in STZ-induced DR rats and ARPE-19 cells treated with high glucose, the expression of Poldip2, transforming growth factor-β1 (TGF-β1), phosphorylated-SMAD3/SMAD3, MMP9, COL-1, FN, and CTGF increased while the expression of cadherin decreased. However, deleting Poldip2 inhibited the TGF-β1/SMAD3 signaling pathway and attenuated the above protein expression in vivo and in vitro. Mechanistically, we found that Poldip2 promotes the activation of SMAD3, facilitates its nuclear translocation through interacting with it, and significantly enhances the expression of fibrosis makers. Collectively, Poldip2 was identified is a novel regulator of DR fibrosis and is expected to become a therapeutic target for PDR.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1742-1755"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141539099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.","authors":"Magnus F G Grøndahl, Andreas H Lange, Malte P Suppli, Jonatan I Bagger, Mira Thing, Lise L Gluud, Dea H Kofod, Mads Hornum, Gerrit van Hall, Samuel A J Trammell, Trisha J Grevengoed, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Mikkel B Christensen, Asger B Lund, Filip K Knop","doi":"10.2337/db24-0305","DOIUrl":"10.2337/db24-0305","url":null,"abstract":"<p><p>It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1641-1647"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of STAT1 Signaling in Human Pancreatic β-Cells by the Lysine Deacetylase HDAC6: A New Therapeutic Opportunity in Type 1 Diabetes?","authors":"Kaiyven Afi Leslie, Christiana Lekka, Sarah J Richardson, Mark A Russell, Noel G Morgan","doi":"10.2337/db24-0008","DOIUrl":"10.2337/db24-0008","url":null,"abstract":"<p><p>Type 1 diabetes arises from the selective destruction of pancreatic β-cells by autoimmune mechanisms, and intracellular pathways driven by Janus kinase (JAK)-mediated phosphorylation of STAT isoforms (especially STAT1 and STAT2) are implicated as mediators of β-cell demise. Despite this, the molecular mechanisms that regulate JAK-STAT signaling in β-cells during the autoimmune attack remain only partially disclosed, and the factors acting to antagonize proinflammatory STAT1 signaling are uncertain. We have recently implicated signal regulatory protein α (SIRPα) in promoting β-cell viability in the face of ongoing islet autoimmunity and have now revealed that this protein controls the availability of a cytosolic lysine deacetylase, HDAC6, whose activity regulates the phosphorylation and activation of STAT1. We provide evidence that STAT1 serves as a substrate for HDAC6 in β-cells and that sequestration of HDAC6 by SIRPα in response to anti-inflammatory cytokines (e.g., IL-13) leads to increased STAT1 acetylation. This then impairs the ability of STAT1 to promote gene transcription in response to proinflammatory cytokines, including interferon-γ. We further found that SIRPα is lost from the β-cells of subjects with recent-onset type 1 diabetes under conditions when HDAC6 is retained and STAT1 levels are increased. On this basis, we report a previously unrecognized role for cytokine-induced regulation of STAT1 acetylation in the control of β-cell viability and propose that targeted inhibition of HDAC6 activity may represent a novel therapeutic modality to promote β-cell viability in the face of active islet autoimmunity.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1473-1485"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for β-Cell Function During Aging.","authors":"Jose A Ortiz, Nadiah Ghazalli, Kassandra Lopez, Jeffrey Rawson, Erika M McCown, Eunjin Oh, Jose M Irimia, Kevin Jou, Jacob Mares, Min-Hsuan Chen, Xiwei Wu, Heather N Zook, Janine C Quijano, Neslihan Erdem, Anahy Lizarraga, Fouad Kandeel, Patrick T Fueger, Debbie C Thurmond, Hsun Teresa Ku","doi":"10.2337/db23-0490","DOIUrl":"10.2337/db23-0490","url":null,"abstract":"<p><p>Exocrine-to-endocrine cross talk in the pancreas is crucial to maintain β-cell function. However, the molecular mechanisms underlying this cross talk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of β-cells in vitro, but its physiological role in vivo in the pancreas is unknown. Also, it remains unclear which pancreatic cell type expresses Tff2 protein. We therefore created a mouse model with a conditional knockout of Tff2 in the murine pancreas. We find that the Tff2 protein is preferentially expressed in acinar but not ductal or endocrine cells. Tff2 deficiency in the pancreas reduces β-cell mass on embryonic day 16.5. However, homozygous mutant mice are born without a reduction of β-cells and with acinar Tff3 compensation by day 7. When mice are aged to 1 year, both male and female homozygous and male heterozygous mutants develop impaired glucose tolerance without affected insulin sensitivity. Perifusion analysis reveals that the second phase of glucose-stimulated insulin secretion from islets is reduced in aged homozygous mutant compared with controls. Collectively, these results demonstrate a previously unknown role of Tff2 as an exocrine acinar cell-derived protein required for maintaining functional endocrine β-cells in mice.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1447-1461"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}