{"title":"Lipopolysaccharide and tyloxapol accelerate the development of atherosclerosis in mice","authors":"Meiyu Jin, Di Zhang, Lianwen Zheng, Yunfei Wei, Siru Yan, Haiyan Qin, Qi Wang, Lilei Zhao, Haihua Feng","doi":"10.1002/lipd.12331","DOIUrl":"10.1002/lipd.12331","url":null,"abstract":"<p>The occurrence of atherosclerosis is closely related to inflammation and lipid metabolism disorder. It has been found that lipopolysaccharide (LPS) could induce inflammation, and tyloxapol (Ty) could induce hyperlipidemia. However, the effects of LPS and Ty on the development and mechanism of atherosclerosis have not been investigated thoroughly. To answer this question, we used assay kits to detect total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) content to evaluate dyslipidemia. We used hematoxylin and eosin staining to evaluate the pathological structure of the aorta and liver, and then used Oil Red O staining to access lipid accumulation in the aortic wall. Subsequently, we used the alanine transaminase (ALT) kit to examine the liver injury. Finally, we used the Western blot experiment to measure proteins that regulate lipid metabolism. We found that the LPS + Ty group could increase the levels of TC, TG, and LDL in the serum and promote lipid accumulation in the aortic wall in mice. Moreover, our study showed that the LPS + Ty group induced pathological changes in hepatocytes and increased ALT content in mice. Significantly, we found that the LPS + Ty group could activate acetyl-CoA carboxylase, sterol regulatory element-binding protein-1c, and inhibit peroxisome proliferator-activated receptors α in mice. Therefore, we suppose that LPS and Ty aggravated the development of atherosclerosis by promoting hyperlipidemia and the disorder of lipid metabolism in mice. These findings are significant for the study of the pathogenesis of atherosclerosis and the selection of animal models.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"83-90"},"PeriodicalIF":1.9,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789568","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}
LipidsPub Date : 2021-12-05DOI: 10.1002/lipd.12330
Yan Liu, Daniel Mihna, Lahoucine Izem, Richard E. Morton
{"title":"Both full length-cholesteryl ester transfer protein and exon 9-deleted cholesteryl ester transfer protein promote triacylglycerol storage in cultured hepatocytes","authors":"Yan Liu, Daniel Mihna, Lahoucine Izem, Richard E. Morton","doi":"10.1002/lipd.12330","DOIUrl":"10.1002/lipd.12330","url":null,"abstract":"<p>We previously reported that overexpression of full-length cholesteryl ester transfer protein (FL-CETP), but not its exon 9-deleted variant (∆E9-CETP), in an adipose cell line reduces their triacylglycerol (TAG) content. This provided mechanistic insight into several in vivo studies where FL-CETP levels are inversely correlated with adiposity. However, increased FL-CETP is also associated with elevated hepatic lipids, suggesting that the effect of CETP on cellular lipid metabolism may be tissue-specific. Here, we directly investigated the role of FL-CETP and ∆E9-CETP in hepatic lipid metabolism. FL- or ∆E9-CETP was overexpressed in HepG2-C3A by adenovirus transduction. Overexpression of either FL or ∆E9-CETP in hepatocytes increased cellular TAG mass by 25% but reduced TAG secretion. This cellular TAG was contained in larger and more numerous lipid droplets. Analysis of TAG synthetic and catabolic pathways showed that this elevated TAG content was due to increased incorporation of fatty acid into TAG (24%), and higher de novo synthesis of fatty acid (50%) and TAG from acetate (40%). siRNA knockdown of CETP had the opposite effect on TAG synthesis and lipogenesis, and decreased cellular TAG. This novel increase in cellular TAG by FL-CETP overexpression was reproduced in Caco-2 intestinal epithelial cells. We conclude that, unlike that seen in adipocyte cells, overexpression of either CETP isoform in lipoprotein-secreting cells promotes the accumulation of TAG. These data suggest that the in vivo correlation between CETP levels and hepatic steatosis can be explained, in part, by a direct effect of CETP on hepatocyte cellular metabolism.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"69-79"},"PeriodicalIF":1.9,"publicationDate":"2021-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060302/pdf/nihms-1773171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10456833","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}
LipidsPub Date : 2021-11-20DOI: 10.1002/lipd.12329
Ahmed S. A. El-Zenary, Khalid M. Gaafar, Reham Abou-Elkhair, Robert G. Elkin, John W. Boney, Kevin J. Harvatine
{"title":"Comparison of Ahiflower oil containing stearidonic acid to a high-alpha-linolenic acid flaxseed oil at two levels on tissue omega-3 enrichment in broilers","authors":"Ahmed S. A. El-Zenary, Khalid M. Gaafar, Reham Abou-Elkhair, Robert G. Elkin, John W. Boney, Kevin J. Harvatine","doi":"10.1002/lipd.12329","DOIUrl":"10.1002/lipd.12329","url":null,"abstract":"Enrichment of broiler meat with very long-chain omega-3 fatty acids (VLCn-3 FA) is of interest because of their beneficial effects on human health. The ability of Ahiflower® (AHI) oil (Buglossoides arvensis), which naturally contains stearidonic acid (SDA), and a high-alpha-linolenic acid (ALA) flaxseed (FLAX) oil to enrich VLCn-3 FA contents in broilers tissues was investigated. Fifty-five Cobb 500 chicks were fed from days 12 to 35 of life either a control (CON) diet that contained 27.9 g/kg soybean oil or AHI or FLAX oils, each individually at 7.5 or 22.5 g/kg of the diet in substitution for soybean oil (all on an as fed basis). Total VLCn-3 FA contents were greater in breast, thigh, liver, adipose tissue, and plasma of all n-3 treatments compared to CON, with the greatest increase observed at the highest level of AHI and FLAX oils (p < 0.001). AHI oil at 7.5 g/kg promoted the most efficient synthesis and deposition of VLCn-3 in broiler tissues measured as deposition of VLCn-3 FA in tissues relative to intake of n3 FA. In conclusion, both ALA and SDA oils increased VLCn-3 FA deposition in tissues, but there were diminishing returns when increasing dietary levels of the oils.","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"57-68"},"PeriodicalIF":1.9,"publicationDate":"2021-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39893632","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}
LipidsPub Date : 2021-11-09DOI: 10.1002/lipd.12326
Rahau S. Shirazi, Mikhail Vyssotski, Kirill Lagutin, Dion Thompson, Christa MacDonald, Vincent Luscombe, Michelle Glass, Kim Parker, Emma K. Gowing, D. Bradley G. Williams, Andrew N. Clarkson
{"title":"Neuroprotective activity of new Δ3-N-acylethanolamines in a focal ischemia stroke model","authors":"Rahau S. Shirazi, Mikhail Vyssotski, Kirill Lagutin, Dion Thompson, Christa MacDonald, Vincent Luscombe, Michelle Glass, Kim Parker, Emma K. Gowing, D. Bradley G. Williams, Andrew N. Clarkson","doi":"10.1002/lipd.12326","DOIUrl":"10.1002/lipd.12326","url":null,"abstract":"<p>N-acylethanolamines (NAE, also called ethanolamides) are significant lipid signaling molecules with anti-inflammatory, pain-relieving, cell-protective, and anticancer properties. Here, we present the use of a hitherto unreported group of Δ3-NAE and also some Δ4- and Δ5-NAE, in in vitro and in vivo assays to gain a better understanding of their structure–bioactivity relationships. We have developed an efficient synthetic method to rapidly produce novel unlabeled and <sup>13</sup>C-labeled Δ3-NAE (NAE-18:5n-3, NAE-18:4n-6) and Δ4-NAE (NAE-22:5n-6). The new NAE with shorter carbon backbone structures confers greater neuroprotection than their longer carbon backbone counterparts, including anandamide (Δ5-NAE-20:4n-6) in a focal ischemia mouse model of stroke. This study highlights structure-dependent protective effects of new NAE following focal ischemia, in which some of the new NAE, administered intranasally, lead to significantly reduced infarct volume and improved recovery of limb use. The relative affinity of the new NAE toward cannabinoid receptors was assessed against anandamide, NAE-22:6n-3 and NAE-20:5n-3, which are known cannabinoid receptor ligands with high-binding constants. Among the newly synthesized NAE, Δ4-NAE-22:5n-6 shows the greatest relative affinity to cannabinoid receptors hCB<sub>1</sub> and hCB<sub>2</sub>, and inhibition of cyclic adenosine monophosphate activity through hCB<sub>2</sub> compared to anandamide.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"17-31"},"PeriodicalIF":1.9,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39709345","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":"Astragalus polysaccharide regulates brown adipocytes differentiation by miR-6911 targeting Prdm16","authors":"Shihe Zhang, Pengkang Song, Xiaoyou Chen, Yu Wang, Xuyang Gao, Lin Liang, Junxing Zhao","doi":"10.1002/lipd.12328","DOIUrl":"10.1002/lipd.12328","url":null,"abstract":"<p>Brown adipose tissue (BAT) is a specialized tissue in mammals related to thermogenesis. The <i>Astragalus</i> polysaccharide (APS) is the major natural active component of <i>Astragalus membranaceus</i>, which has been recognized as one of the most popular herbal medicines worldwide. The role and possible mechanisms of APS on brown adipocytes differentiation is not well defined. Here, we explored the effect of APS on the differentiation of brown adipocytes in C3H10T 1/2 cells. The results showed that APS promoted the differentiation of brown adipocytes and improved insulin sensitivity along with significant increases in the expression of brown adipogenic marker proteins (C/EBPα, C/EBPβ, and PPARγ), thermogenesis marker proteins (UCP1, PRDM16, and PGC-1α), and insulin sensitivity marker protein (GLUT4). Meanwhile, the results showed that the amount of the phosphorylation of insulin receptor substrate 1 (p-IRS1) and phospho-AKT (p-AKT) which are critical factors in the insulin signaling pathway was increased without changing the total amount of IRS and AKT. Furthermore, the results of RNA-seq showed that APS altered the expression profiles of various miRNAs, and among which the expression of miR-6911 as a universal regulatory factor was significantly decreased. Importantly, we found that miR-6911 regulated the differentiation of brown adipocytes by targeting <i>PR domain-containing 16</i> (<i>Prdm16</i>). In addition, after transfection of miR-6911 mimics, compared with the control and inhibitor group, PRDM16 protein expression significantly decreased, which was accompanied by the decrease of PPARγ, UCP1, and PGC-1α. Collectively, our results indicated that APS regulated brown adipocytes differentiation in C3H10T 1/2 cells via miRNA-6911 targeting <i>Prdm16</i>.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"45-55"},"PeriodicalIF":1.9,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39681440","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}
LipidsPub Date : 2021-11-05DOI: 10.1002/lipd.12327
Carina P. Van Nieuwenhove, Andrea del Huerto Moyano, Guido A. Van Nieuwenhove, Verónica Molina, Patricia Luna Pizarro
{"title":"Jacaranda oil administration improves serum biomarkers and bioavailability of bioactive conjugated fatty acids, and alters fatty acid profile of mice tissues","authors":"Carina P. Van Nieuwenhove, Andrea del Huerto Moyano, Guido A. Van Nieuwenhove, Verónica Molina, Patricia Luna Pizarro","doi":"10.1002/lipd.12327","DOIUrl":"10.1002/lipd.12327","url":null,"abstract":"<p>Jacaric acid, a conjugated linolenic acid (CLNA) present in jacaranda oil (JO), is considered a potent anticarcinogenic agent. Several studies have focused on its biological effects, but the metabolism once consumed is not clear yet. The aim of this work was to evaluate the effects of two different daily doses of JO on serum parameters and fatty acid (FA) profile of mice tissues after 4 weeks of feeding. No significant changes on body weight gain, food intake, or tissue weight were determined after 0.7 or 2 ml/kg of JO supplementation compared to control animals. Significantly lower blood low-density lipoproteins-cholesterol (20 mg/dl) and glucose (~147–148 mg/dl) levels were detected in both oil-treated groups compared to control (31.2 and 165 mg/dl, respectively). Moreover, jacaric acid was partially converted into <i>cis</i>9, <i>trans</i>11 conjugated linoleic acid (CLA) and thus further incorporated into tissues. Liver evidenced the highest total conjugated fatty acid content (1.1%–2.2%), followed by epididymal (0.7%–1.9%) and mesenteric (1.4%–1.8%) fat. Lower saturated and higher unsaturated fatty acid content was detected in both oil-treated groups compared to control. Our results support the safety of JO and its potential application with a functional or nutraceutical propose, by increasing human CLNA consumption and further availability of CLA.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"33-44"},"PeriodicalIF":1.9,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39848244","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}
LipidsPub Date : 2021-10-07DOI: 10.1002/lipd.12325
Amal A. Aqul, Charina M. Ramirez, Adam M. Lopez, Dennis K. Burns, Joyce J. Repa, Stephen D. Turley
{"title":"Molecular markers of brain cholesterol homeostasis are unchanged despite a smaller brain mass in a mouse model of cholesteryl ester storage disease","authors":"Amal A. Aqul, Charina M. Ramirez, Adam M. Lopez, Dennis K. Burns, Joyce J. Repa, Stephen D. Turley","doi":"10.1002/lipd.12325","DOIUrl":"10.1002/lipd.12325","url":null,"abstract":"<p>Lysosomal acid lipase (LAL), encoded by the gene <i>LIPA</i>, facilitates the intracellular processing of lipids by hydrolyzing cholesteryl esters and triacylglycerols present in newly internalized lipoproteins. Loss-of-function mutations in <i>LIPA</i> result in cholesteryl ester storage disease (CESD) or Wolman disease when mutations cause complete loss of LAL activity. Although the phenotype of a mouse CESD model has been extensively characterized, there has not been a focus on the brain at different stages of disease progression. In the current studies, whole-brain mass and the concentrations of cholesterol in both the esterified (EC) and unesterified (UC) fractions were measured in <i>Lal</i><sup><i>−/−</i></sup> and matching <i>Lal</i><sup><i>+/+</i></sup> mice (FVB-N strain) at ages ranging from 14 up to 280 days after birth. Compared to <i>Lal</i><sup><i>+/+</i></sup>controls at 50, 68–76, 140–142, and 230–280 days of age, <i>Lal</i><sup><i>−/−</i></sup> mice had brain weights that averaged approximately 6%, 7%, 18%, and 20% less, respectively. Brain EC levels were higher in the <i>Lal</i><sup><i>−/−</i></sup> mice at every age, being elevated 27-fold at 230–280 days. Brain UC concentrations did not show a genotypic difference at any age. The elevated brain EC levels in the <i>Lal</i><sup><i>−/−</i></sup> mice did not reflect EC in residual blood. An mRNA expression analysis for an array of genes involved in the synthesis, catabolism, storage, and transport of cholesterol in the brains of 141-day old mice did not detect any genotypic differences although the relative mRNA levels for several markers of inflammation were moderately elevated in the <i>Lal</i><sup><i>−/−</i></sup> mice. The possible sites of EC accretion in the central nervous system are discussed.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"3-16"},"PeriodicalIF":1.9,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766890/pdf/nihms-1743044.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10805503","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}
LipidsPub Date : 2021-10-04DOI: 10.1002/lipd.12324
Susana P. Alves, Payam Vahmani, Cletos Mapiye, Tim A. McAllister, Rui J. B. Bessa, Michael E. R. Dugan
{"title":"Trans-10 18:1 in ruminant meats: A review","authors":"Susana P. Alves, Payam Vahmani, Cletos Mapiye, Tim A. McAllister, Rui J. B. Bessa, Michael E. R. Dugan","doi":"10.1002/lipd.12324","DOIUrl":"10.1002/lipd.12324","url":null,"abstract":"<p><i>Trans</i> (<i>t</i>) fatty acids (TFA) from partially hydrogenated vegetable oils (i.e., industrial <i>trans</i>) have been phased out of foods in many countries due to their promotion of cardiovascular disease. This leaves ruminant-derived foods as the main source of TFA. Unlike industrial TFA where catalytic hydrogenation yields a broad distribution of isomers, ruminant TFA are enzymatically derived and can result in enrichment of specific isomers. Comparisons between industrial and ruminant TFA have often exonerated ruminant TFA due to their lack or at times positive effects on health. At extremes, however, ruminant-sourced foods can have either high levels of <i>t</i>10- or <i>t</i>11-18:1, and when considering enriched sources, <i>t</i>10-18:1 has properties similar to industrial TFA, whereas <i>t</i>11-18:1 can be converted to an isomer of conjugated linoleic acid (<i>cis</i>(<i>c</i>)9,<i>t</i>11-conjugated linoleic acid), both of which have potential positive health effects. Increased <i>t</i>10-18:1 in meat-producing ruminants has not been associated with negative effects on live animal production or meat quality. As such, reducing <i>t</i>10-18:1 has not been of immediate concern to ruminant meat producers, as there have been no economic consequences for its enrichment; nevertheless at high levels, it can compromise the nutritional quality of beef and lamb. In anticipation that regulations regarding TFA may focus more on <i>t</i>10-18:1 in beef and lamb, the present review will cover its production, analysis, biological effects, strategies for manipulation, and regulatory policy.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"56 6","pages":"539-562"},"PeriodicalIF":1.9,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39485671","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":"2-Arachidonoyl glycerol potently induces cholecystokinin secretion in murine enteroendocrine STC-1 cells via cannabinoid receptor CB1","authors":"Keita Ochiai, Rina Hirooka, Masayoshi Sakaino, Shigeo Takeuchi, Tohru Hira","doi":"10.1002/lipd.12323","DOIUrl":"10.1002/lipd.12323","url":null,"abstract":"<p>Cholecystokinin (CCK) is a peptide hormone secreted from enteroendocrine cells and regulates the exocrine pancreas, gastric motility, and appetite. Dietary triacylglycerols are hydrolyzed to fatty acids (FA) and 2-monoacylglycerols (2-MAG) in the small intestine. Although it is well known that FA stimulate CCK secretion, whether 2-MAG have the CCK-releasing activity remains unclear. We examined the CCK-releasing activity of four commercially available 2-MAG in a murine CCK-producing cell line, STC-1, and the molecular mechanism underlying 2-MAG-induced CCK secretion. CCK released from the cells was measured using ELISA. Among four 2-MAG (2-palmitoyl, 2-oleoyl, 2-linoleoyl, and 2-arachidonoyl monoacylglycerols) examined, 2-arachidonoyl glycerol (2-AG) potently stimulated CCK secretion in a dose-dependent manner. Structurally related compounds, such as 2-arachidonoyl glycerol ether and 1-arachidonoyl glycerol, did not stimulate CCK secretion. Both arachidonic acid and 2-AG stimulated CCK secretion at 100 μM, but only 2-AG did at 50 μM. 2-AG-induced CCK secretion but not arachidonic acid-induced CCK secretion was attenuated by treatment with a cannabinoid receptor 1 (CB1) antagonist. These results indicate that a specific 2-MAG, 2-AG, directly stimulates CCK secretion via CB1.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"56 6","pages":"603-611"},"PeriodicalIF":1.9,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39425083","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}