Biomolecules最新文献

{"title":"<i>Schinus molle</i> Resin Essential Oil as Potent Bioinsecticide Against <i>Tribolium castaneum</i>: Chemical Profile, <i>In Vitro</i> Acetylcholinesterase Inhibition, DFT Calculation and Molecular Docking Analysis.","authors":"Wiem Baccari, Ilyes Saidi, Achref Jebnouni, Safa Teka, Sayda Osman, Awatif Mansoor Alrasheeday, Nuzaiha Mohamed, Mabrouka El Oudi, Hichem Ben Jannet","doi":"10.3390/biom14111464","DOIUrl":"10.3390/biom14111464","url":null,"abstract":"<p><p>Plants offer a bountiful source of natural pest control solutions through their essential oils. This research introduces and analyzes an eco-friendly natural essential oil for red flour beetle control. Therefore, the current study was included to show the chemical profile and the insecticidal efficacy of resin essential oil (REO) and its fractions (F_1-3), resulting from chromatographic separation, from the plant <i>Schinus molle</i> against <i>Tribolium castaneum</i> adults. The trunk bark resin essential oil and its fractions' composition were analyzed by GC-MS. Overall, 33 constituents with 98.3% of the total EO composition were identified. REO and F_1-3 displayed impressive repellent properties at a concentration of 0.12 µL/cm². After 120 min of exposure, repellency ranged from 73.3% to a remarkable 96.7%. They also exhibited noteworthy fumigant properties, with median lethal doses of LD₅₀ = 120.6-160.8 μL/L. The fractions F₁ and F₃ showed the most notable topical toxicity at a concentration of 10%, with LD₅₀ values of 8.6% and 5.6%, respectively. Fractions F₃ and F₂ demonstrated the most effective inhibition of acetylcholinesterase (AChE) activity, providing insight into their insecticidal mechanisms. The in silico molecular docking and DFT studies corroborate the results of in vitro tests performed to identify new insecticide products derived from natural sources.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardio-Lipotoxicity of Epicardial Adipose Tissue.","authors":"Monica L Bodenstab, Ron T Varghese, Gianluca Iacobellis","doi":"10.3390/biom14111465","DOIUrl":"10.3390/biom14111465","url":null,"abstract":"<p><p>Epicardial adipose tissue is a unique visceral adipose tissue depot that plays a crucial role in myocardial metabolism. Epicardial adipose tissue is a major source of energy and free fatty acids for the adjacent myocardium. However, under pathological conditions, epicardial fat can affect the heart through the excessive and abnormal influx of lipids. The cardio-lipotoxicity of the epicardial adipose tissue is complex and involves different pathways, such as increased inflammation, the infiltration of lipid intermediates such as diacylglycerol and ceramides, mitochondrial dysfunction, and oxidative stress, ultimately leading to cardiomyocyte dysfunction and coronary artery ischemia. These changes can contribute to the pathogenesis of various cardio-metabolic diseases including atrial fibrillation, coronary artery disease, heart failure, and obstructive sleep apnea. Hence, the role of the cardio-lipotoxicity of epicardial fat and its clinical implications are discussed in this review.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmalogens in Innate Immune Cells: From Arachidonate Signaling to Ferroptosis.","authors":"Jesús Balsinde, María A Balboa","doi":"10.3390/biom14111461","DOIUrl":"10.3390/biom14111461","url":null,"abstract":"<p><p>Polyunsaturated fatty acids such as arachidonic acid are indispensable components of innate immune signaling. Plasmalogens are glycerophospholipids with a vinyl ether bond in the sn-1 position of the glycerol backbone instead of the more common sn-1 ester bond present in \"classical\" glycerophospholipids. This kind of phospholipid is particularly rich in polyunsaturated fatty acids, especially arachidonic acid. In addition to or independently of the role of plasmalogens as major providers of free arachidonic acid for eicosanoid synthesis, plasmalogens also perform a varied number of functions. Membrane plasmalogen levels may determine parameters of the plasma membrane, such as fluidity and the formation of microdomains that are necessary for efficient signal transduction leading to optimal phagocytosis by macrophages. Also, plasmalogens may be instrumental for the execution of ferroptosis. This is a nonapoptotic form of cell death that is associated with oxidative stress. This review discusses recent data suggesting that, beyond their involvement in the cellular metabolism of arachidonic acid, the cells maintain stable pools of plasmalogens rich in polyunsaturated fatty acids for executing specific responses.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Regulation of Periostin for Osteoarthritic Cartilage Repair Applications.","authors":"Sunny Y Shih, Michael P Grant, Laura M Epure, Muskan Alad, Sophie Lerouge, Olga L Huk, Stephane G Bergeron, David J Zukor, Géraldine Merle, Hee-Jeong Im, John Antoniou, Fackson Mwale","doi":"10.3390/biom14111469","DOIUrl":"10.3390/biom14111469","url":null,"abstract":"<p><p>Emerging evidence indicates periostin (POSTN) is upregulated in patients with OA, and studies have shown that it can induce the activation of inflammatory cytokines and catabolic enzymes, making it a potential therapeutic target. Link N (LN) is a peptide fragment derived from the link protein and has been demonstrated as an anabolic-like factor and anti-catabolic and anti-inflammatory factors both in vitro and in vivo. This study aims to determine if LN can regulate POSTN expression and function in OA cartilage. Articular cartilage was recovered from donors undergoing total knee replacements to isolate chondrocytes and prepare osteochondral explants. Cells and explants were treated with POSTN and LN (1 and 100 μg) and measured for changes in POSTN expression and various matrix proteins, catabolic and proinflammatory factors, and signaling. To determine the effects of POSTN expression in vivo, a rabbit OA model was used. Immunoprecipitation and in silico modeling were used to determine peptide/POSTN interactions. Western blotting, PCR, and immunohistochemistry demonstrated that LN decreased POSTN expression both in vitro and in vivo. LN was also able to directly inhibit POSTN signaling in OA chondrocytes. In silico docking suggested the direct interaction of LN with POSTN at residues responsible for its oligomerization. Immunoprecipitation experiments confirmed the direct interaction of LN with POSTN and the destabilization of its oligomerization. This study demonstrates the ability of a peptide, LN, to suppress the overexpression and function of POSTN in OA cartilage.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Genetic Relationship Between Type 2 Diabetes and Cardiovascular Disease: A Large-Scale Genetic Association and Polygenic Risk Score Study.","authors":"Ziwei Yao, Xiaomai Zhang, Liufei Deng, Jiayu Zhang, Yalu Wen, Deqiang Zheng, Long Liu","doi":"10.3390/biom14111467","DOIUrl":"10.3390/biom14111467","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is often comorbid with cardiovascular diseases (CVDs). The direction of causation between T2D and CVD is difficult to determine; however, there may be a common underlying pathway attributable to shared genetic factors. We aimed to determine whether there is a shared genetic susceptibility to T2D and CVD. This study utilizes large-scale datasets from the UK Biobank (UKB) and DIAGRAM consortium to investigate the genetic association between T2D and CVD through phenotypic association analyses, linkage disequilibrium score (LDSC) analysis, and polygenic risk score (PRS) analysis. LDSC analysis demonstrates significant genetic associations between T2D and various CVD subtypes, including angina, heart failure (HF), myocardial infarction (MI), peripheral vascular disease (PVD), and stroke. Although the genetic association between T2D and atrial fibrillation (AF) was not significant, individuals in the high-T2D PRS group had a significantly increased risk of CVD. These findings suggest a common genetic basis and suggest that genetic susceptibility to T2D may be a potential predictor of CVD risk.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activins and Inhibins in Cardiovascular Pathophysiology.","authors":"Wenyi Tang, Zhilin Gu, Jiuqi Guo, Mingzhi Lin, Hongqian Tao, Dalin Jia, Pengyu Jia","doi":"10.3390/biom14111462","DOIUrl":"10.3390/biom14111462","url":null,"abstract":"<p><p>Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through the classical TGFβ SMAD signaling pathway, but studies suggest that they also act through other pathways, with their specific signaling being complex and context-dependent. Recent research has identified significant roles for activins and inhibins in the cardiovascular system. Their actions in other systems and their signaling pathways show strong correlations with the development and progression of cardiovascular diseases, indicating potential broader roles in the cardiovascular system. This review summarizes the progress in research on the biological functions and mechanisms of activins and inhibins and their signaling pathways in cardiovascular diseases, offering new insights for the prevention and treatment of cardiovascular diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke.","authors":"Zhen Li, Xinyi He, Qi Fang, Xulong Yin","doi":"10.3390/biom14111463","DOIUrl":"10.3390/biom14111463","url":null,"abstract":"<p><p>Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO's aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe-TMAO pathway.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl Paraben Affects Porcine Oocyte Maturation Through Mitochondrial Dysfunction.","authors":"Huimei Huang, Chuman Huang, Yinghua Li, Xingwei Liang, Namhyung Kim, Yongnan Xu","doi":"10.3390/biom14111466","DOIUrl":"10.3390/biom14111466","url":null,"abstract":"<p><p>Parabens are widely used in various industries, which are including chemical, pharmaceutical, food, cosmetic, and plastic processing industries. Among these, methyl paraben (MP) serves as an antimicrobial preservative in processed foods, pharmaceuticals, and cosmetics, and it is particularly detected in baby care products. Studies indicate that MP functions as an endocrine-disrupting compound with estrogenic properties, negatively affecting mitochondrial bioenergetics and antioxidant activity in testicular germ cells. However, limited information exists regarding studies on the effects of MP in oocytes. The aim of this study was to investigate the specific mechanism and the toxic effects of MP during oocyte maturation cultured in vitro using a porcine oocyte model. The results indicated that MP (50 μM) inhibited oocyte expansion, significantly reducing the expression of expansion-related genes <i>MAPK1</i> and <i>ERK1</i>, and decreased the first polar body extrusion significantly as well. ATP levels decreased, reactive oxygen species (ROS) levels remained unchanged, and glutathione (GSH) levels decreased significantly, resulting in an elevated ROS/GSH ratio. The expression of antioxidant genes <i>SOD1</i> and <i>GPX</i> was significantly decreased. Additionally, a significant decrease in levels of mitochondrial production and biosynthesis protein PGC1α+β, whereas levels of antioxidant-related protein Nrf2 and related gene expression were significantly increased. Autophagy protein LC3B and gene expression significantly decreased, and apoptosis assay indicated a significant increase in levels of caspase3 protein and apoptosis-related genes. These results demonstrated the negative effect of MP on oocyte maturation. In conclusion, our findings indicate that MP disrupts redox balance and induces mitochondrial dysfunction during meiosis in porcine oocytes, resulting in the inhibition of meiotic progression. The present study reveals the mechanism underlying the effects of methyl para-hydroxybenzoate on oocyte maturation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Sensitivity C-Reactive Protein Levels in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Alcohol-Associated Liver Disease (MetALD), and Alcoholic Liver Disease (ALD) with Metabolic Dysfunction.","authors":"Seong-Uk Baek, Jin-Ha Yoon","doi":"10.3390/biom14111468","DOIUrl":"10.3390/biom14111468","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a recently introduced term for steatotic liver disease (SLD). Although the inflammatory process is central to the pathogenesis of SLD, research investigating the differences in systemic inflammation across various SLD subtypes as well as sex differences is limited. This population-based, cross-sectional study investigated the association between SLD subtypes and high-sensitivity C-reactive protein (hs-CRP) levels among Korean adults (N = 20,141; mean age: 50.8 ± 16.7 years). The participants were classified into five groups that included no SLD, MASLD, metabolic alcohol-associated liver disease (MetALD), alcoholic liver disease with metabolic dysfunction (ALD with MD), and other SLDs. The median (Q1, Q3) value of the hs-CRP level was 0.54 mg/L (0.33, 1.04). Among men, compared to levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 41.9% (95% confidence interval [CI]: 35.1-49.1%), 46.8% (95% CI: 35.0-59.6%), and 51.8% (95% CI: 30.0-77.2%) increases in hs-CRP levels, respectively. The association between SLD subtypes and hs-CRP levels was stronger among women, and compared to the levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 81.5% (95% CI: 73.6-89.8%), 84.3% (95% CI: 58.1-114.8%), and 98.2% (95% CI: 38.0-184.8%) increases in hs-CRP levels, respectively. In conclusion, our findings indicate a varying profile of systemic inflammation across SLD subtypes, with more pronounced increases in hs-CRP levels in women with SLDs.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin II Induces Vascular Endothelial Dysfunction by Promoting Lipid Peroxidation-Mediated Ferroptosis via CD36.","authors":"Qian Zhou, Ying Zhang, Wei Shi, Lu Lu, Jianglan Wei, Jinhan Wang, Hu Zhang, Yuepu Pu, Lihong Yin","doi":"10.3390/biom14111456","DOIUrl":"10.3390/biom14111456","url":null,"abstract":"<p><p>Angiotensin II (Ang II) is an effective vasoconstriction peptide, a major effector molecule of the renin-angiotensin-aldosterone system (RAAS) and one of the important causes of endothelial dysfunction. Ferroptosis is considered to be involved in the occurrence and development of cardiovascular diseases. This study is dedicated to exploring the role and mechanism of Ang II-induced ferroptosis in HUVECs and to finding molecular targets for vascular endothelial injury and dysfunction during the progression of hypertension. In this study, we found that with the increase in exposure concentration, the intracellular ROS content and apoptosis rate increased significantly, the NO release decreased significantly in the medium- and high-concentration groups and the ET-1 content in the high-concentration group increased significantly. The expression of ZO-1 protein was significantly decreased in the high-concentration group. The expression of p-eNOS, VE-cadherin and Occludin protein showed a dose-dependent downward trend, while the ICAM-1 protein showed an upward trend. Ang II caused lipid metabolism disorders in HUVECs, and the PL-PUFAs associated with ferroptosis were significantly increased. In addition, Ang II promoted a significant increase in intracellular free Fe²⁺ content and MDA and a significant decrease in GSH content. Furthermore, the expression of GPX4, SLC7A11 and SLC3A2 was down-regulated, the expression of ACSL4, LPCAT3 and ALOX15 was up-regulated, and the ratio of p-cPLA2/cPLA2 was increased. After the intervention of ferroptosis inhibitor Fer-1, the injury and dysfunction of HUVECs induced by Ang II were significantly rescued. Immunofluorescence results showed that the expression of CD36 showed a significant increasing trend and was localized in the cytoplasm. Over-expression of CD36 promoted Ang II-induced ferroptosis and endothelial dysfunction. In conclusion, Ang II induces the injury of HUVECs, decreases vascular diastole and endothelial barrier-related molecules, and increases vascular constriction and adhesion-related molecules, which may be related to CD36 and its mediated lipid peroxidation and ferroptosis signals.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}