Biochimie最新文献

{"title":"Osmolytes suppress liquid‒liquid phase separation and the aggregation of Tau.","authors":"Jingye Lin, Zongbao Wang, Chenxi Liu, Yiwen Hua, Sen Li","doi":"10.1016/j.biochi.2026.08.019","DOIUrl":"10.1016/j.biochi.2026.08.019","url":null,"abstract":"<p><p>Tau liquid-liquid phase separation (LLPS) is increasingly recognized as an early event that promotes pathological aggregation in Alzheimer's disease and other tauopathies. Osmolytes are natural chemical chaperones that stabilize protein conformations, yet their effects on Tau phase behavior remain poorly understood. Here, we show that sucrose, trehalose, glucose, maltose, and betaine suppress Tau LLPS and dissolve preformed Tau droplets, shifting the equilibrium toward soluble monomers in vitro. Among the five osmolytes, trehalose and glucose exhibited the strongest inhibitory effects on Tau LLPS. They also suppressed the liquid-to-solid phase transition of Tau droplets, as evidenced by reduced Thioflavin T (ThT) fluorescence, inhibition of fibril formation observed by transmission electron microscopy (TEM), and improved condensate dynamics in fluorescence recovery after photobleaching (FRAP) assays performed in okadaic acid-treated cells. These results indicate that osmolytes interfere with multiple stages of Tau phase transition-from initial condensate formation to pathological maturation and fibrillization. Our findings establish osmolytes as effective modulators of Tau phase behavior and provide mechanistic insights into the physicochemical regulation of Tau phase transitions.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876919","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":"Plant phospholipases D: functions, structures, and enzymatic activities.","authors":"Loris Malcles, Assia Mouhand, Abdelkarim Abousalham, Alexandre Noiriel","doi":"10.1016/j.biochi.2026.08.016","DOIUrl":"10.1016/j.biochi.2026.08.016","url":null,"abstract":"<p><p>Phospholipases D (PLDs) (EC 3.1.4.4) are enzymes capable of hydrolyzing the distal phosphodiester bond of phospholipid (PL) substrates. PLD reaction frees phosphatidic acid (PA), a key intermediate in lipid metabolism and an important signaling molecule involved in multiple cellular and physiological processes. Widely distributed across prokaryotes and eukaryotes, PLDs have diversified considerably and fulfill distinct biological functions depending on the organism and physiological context. In plants, increasing evidence highlights their central roles in adaptation to abiotic and biotic stresses, reproductive processes, and developmental regulation, making them particularly relevant in the context of current agronomic and environmental challenges. This review examines the phylogenetic diversity of plant PLDs, with particular emphasis on cereal species, and summarizes recent advances in the characterization of their biological functions. Recent structural data obtained from plant PLDs also provide new insights into structure-function relationships within the PLD superfamily and help refine our understanding of the structural organization and enzymatic properties of plant PLDs.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868371","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":"Electronegativity-based subfractionation of intermediate-density lipoproteins: Comparison with main lipoprotein classes.","authors":"Omer Akyol, Huan-Hsing Chiang, Frances W Ouyang, Jody V Vykoukal, Johannes F Fahrmann, Alan R Burns, Munenori Ishibashi, Chao-Yuh Yang, Chu Huang Chen","doi":"10.1016/j.biochi.2026.08.013","DOIUrl":"10.1016/j.biochi.2026.08.013","url":null,"abstract":"<p><p>Studying the chemical characteristics of intermediate-density lipoprotein (IDL), a transient metabolite and direct precursor to LDL, is crucial for understanding LDL heterogeneity and atherogenic potential. This study aimed to characterize the physicochemical properties and lipidomic composition of distinct IDL subfractions and evaluate their proatherogenic effects. Using ultracentrifugation and anion-exchange chromatography, we fractionated IDL into five increasingly electronegative subpopulations (I1-I5), analogous to LDL, VLDL, and HDL subclasses with high resolution. We then comprehensively characterized these overlooked remnants using TEM, electrophoresis, and exploratory LC-MS lipidomics. Our analysis showed I1 (49.6%) was the least and I5 (6.3%) the most electronegative subfraction. TEM revealed a significant size difference, with I5 particles (averaged 37.9 ± 11.2 nm) being larger than I1 particles (averaged 25.1 ± 4.6 nm; p < 0.05). Furthermore, electrophoretic protein fingerprinting suggested complex remodeling of the putative surface apolipoprotein cargo in highly electronegative particles. Exploratory lipidomic profiling indicated that I5 was enriched in lipid species associated with proatherogenic pathways, including triacylglycerides, lysophosphatidylcholines, and lysophosphatidylethanolamines, whereas I1 particles were enriched in structural phospholipids. These patterns highlight IDL's profound lipidomic heterogeneity. Similarities among V5, I5, and L5 strongly support a shared metabolic continuum, with I5 potentially representing an intermediate transition stage. Crucially, functional assays revealed that the electronegative I5 subfraction possessed potent cytotoxicity in endothelial and monocytic cell models compared to other lipoprotein subfractions and oxLDL, significantly reducing viability and increasing cell death. Given IDL's limited circulation time, the presence of the highly electronegative and lipotoxic I5 subfraction may substantially enhance the overall proatherogenic potential of electronegative lipoproteins.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814921","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":"WITHDRAWN: The hybrid energy metabolism profile of human colorectal cancer cells.","authors":"Rafael Moreno-Sánchez, Emma Verónica Moreno-Saavedra, Emma Saavedra, Jorge Luis Vargas-Navarro, Sara Rodríguez-Enríquez","doi":"10.1016/j.biochi.2026.08.014","DOIUrl":"10.1016/j.biochi.2026.08.014","url":null,"abstract":"<p><p>This article has been withdrawn at the request of the authors, the Editor-in-Chief and publisher for the following reason: subsequently to the pre-proof publication, it came to our attention that the manuscript may contain material or data for which publication was not authorized and that authorship cannot be verified. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802944","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":"Beyond the surface: plasmalogens are dispensable for retinal integrity and fertility in the mouse.","authors":"Ilaria Dorigatti, Viktorija Juric, Michael J Blumer, Denise Kummer, Janik Kokot, Georg Golderer, Fabian Dorninger, Johannes Berger, Markus A Keller, Katrin Watschinger","doi":"10.1016/j.biochi.2026.08.010","DOIUrl":"10.1016/j.biochi.2026.08.010","url":null,"abstract":"<p><p>Ether lipids and their subclass, the plasmalogens, are critical regulators of membrane organization, signaling, and stress responses in multiple tissues. Inborn errors in their anabolism cause severe multi-organ diseases such as Rhizomelic Chondrodysplasia Punctata and related peroxisomal disorders. The Gnpat knockout mouse model, characterized by total ether lipid deficiency, recapitulates key features of this disorder, including dense bilateral cataracts, microphthalmia, and infertility, but the specific contribution of different subclasses, particularly plasmalogens, remains elusive. The recent identification of the Peds1 gene allows dissecting the impact of selective plasmalogen deficiency with retention of plasmanyl lipids, another ether lipid subgroup. Here, we performed the first side-by-side comparison of Gnpat and Peds1 knockout in mice on a matched genetic background (C57BL/6 x CD1). Additionally, we assessed Peds1 knockout on a pure C57BL/6N genetic background. Plasmanyl lipids in Peds1 knockout mice were sufficient to prevent cataract formation on both genetic backgrounds, despite marked shifts in the ocular phospholipidome. Also, fertility and reproductive function were found to be preserved in Peds1 knockout mice. Our data demonstrate that plasmanyl lipids can partially protect against the severe phenotypes observed in mouse models of total ether lipid deficiency; notably, the ocular and reproductive phenotypes were plasmalogen-independent, indicating that loss of the vinyl ether double bond is not the key determinant of all symptoms in human and murine ether lipid deficiency and can at least partly be compensated by plasmanyl lipids.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802937","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":"Mechanistic insights into the neuroprotective effects of monoterpene-rich Eucalyptus citriodora essential oil: integrated in silico and in vitro analysis in 6-OHDA-treated N2a neuronal cells.","authors":"Amel Abidi, Enxhi Shaba, Lorenza Vantaggiato, Oumayma Kouki, Olfa Masmoudi-Kouki, Luca Bini, Cristina Ulivieri, Claudia Landi, Taoufik Ghrairi","doi":"10.1016/j.biochi.2026.08.005","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.08.005","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss driven by mitochondrial dysfunction, oxidative stress, and proteostasis collapse, for which current therapies remain symptomatic. This study investigated the neuroprotective effects of Eucalyptus citriodora essential oil (ECEO) on 6-hydroxydopamine (6-OHDA)-induced toxicity in N2a neuroblastoma cells. GC-MS analysis showed that ECEO was dominated by oxygenated monoterpenes, mainly citronellal (60.7%), isopulegol (16%), and citronellol (5.7%). In silico analysis of these constituents showed favorable ADMET profiles, predicted blood-brain barrier permeability, and non-overlapping multitarget engagement across enzymes, GPCRs and nuclear receptors. At the cellular level, ECEO pretreatment significantly restored cell viability (86.7% of control), reduced LDH release, attenuated ROS and NO, and limited mitochondrial depolarization. Quantitative 2D-gel/MALDI-TOF/TOF proteomics identified 94 differentially abundant proteins, of which 20 showed validated PD-related associations (KEGG, Gene4PD, and DisGeNET databases). ECEO pretreatment modulated 12 of these proteins across mechanistically coherent pathways: (i) reversal of 6-OHDA-induced reprogramming of energy metabolism, by normalizing the glycolytic enzymes PKM and PGK1 and restoring the TCA enzyme SUCLG2; (ii) reinforcement of proteostasis through PSMB4 and PSMA3 induction, VCP upregulation and attenuation of ER stress marker HSPA5/BiP; (iii) preservation of mitochondrial and cytoskeletal integrity through PHB1 induction and bilateral TUBB5 restoration. Overall, our results suggest that ECEO exerts significant neuroprotective effects in a cellular PD model by coordinately modulating energy metabolism, proteostasis, antioxidant defense, and structural integrity. Given its predominance in oxygenated monoterpenes the neuroprotective activity of ECEO may result from the combined contribution of the major constituents supporting further investigation in age-related neurodegeneration.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803001","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":"Impact of sphingomyelin species with different acyl chain lengths on plasma membrane organization.","authors":"Nario Tomishige","doi":"10.1016/j.biochi.2026.08.004","DOIUrl":"10.1016/j.biochi.2026.08.004","url":null,"abstract":"<p><p>The plasma membrane (PM) is characterized by asymmetric bilayer organization in terms of both the chemistry of lipid headgroups and the physical properties of lipid acyl chains. Sphingomyelin (SM), a major outer-leaflet lipid, has long been considered a key partner of cholesterol (Chol) in the formation of ordered membrane domains. However, mammalian cells contain multiple SM species with distinct N-acyl chains, most predominantly C16:0, C24:0, and C24:1, whose structural differences can change membrane packing, Chol distribution, and interleaflet communication. Evidence from model membranes shows that C16:0 SM interacts strongly with Chol and promotes liquid-ordered domain formation. By contrast, C24:0 SM generates thicker, potentially interdigitated bilayers, supports ordered domains with altered Chol association, and may influence coupling between two leaflets. C24:1 SM combines a very-long acyl chain with unsaturation, weakening membrane packing and suppressing macroscopic phase separation in Chol-containing membranes. Asymmetric vesicle studies further indicate that C24 SM can affect Chol transbilayer partitioning, which could have consequences for Chol accessibility and homeostatic signaling. Cellular studies further indicate that remodeling SM species can alter glycosylphosphatidylinositol (GPI)-anchored protein clustering, PM order, Chol-binding probe accessibility, and signaling proteins such as the insulin receptor. Together, current evidence supports a model in which SM species diversity tunes PM organization through coupled effects on lipid packing, Chol behavior, leaflet asymmetry, and protein function. Understanding these mechanisms in living cells remains an important issue for future studies.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708710","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":"Phosphatidylethanolamine as an exclusive substrate for an original phospholipase D from Dechloromonas.","authors":"Zongze Wu, Sébastien Violot, Abdelkarim Abousalham, Alexandre Noiriel","doi":"10.1016/j.biochi.2026.07.014","DOIUrl":"10.1016/j.biochi.2026.07.014","url":null,"abstract":"<p><p>Phospholipases D (PLDs) are lipolytic enzymes that catalyze hydrolysis of the distal phosphodiester bond of various membrane phospholipids (PLs). These enzymes generate invariant phosphatidic acid (PA) and a polar head group whose nature depends on the PL substrate. PA is both a key metabolic intermediate in the synthesis of lipids and a second messenger involved in diverse processes, including cellular signaling, development of cancer in mammals, bacterial pathogenesis, and defense responses in plants. Regarding the diversity of PL nature and composition, all PLDs described so far can act on several PLs. Furthermore, the molecular determinants of PL recognition by PLDs and the preference of one PL over another remain poorly understood. We previously described the biochemical characterization of a PLD, called DaPLD1, from the bacterium Dechloromonas aromatica RCB. This PLD did indeed have a strong preference for phosphatidylethanolamine (PE) over all other PLs but was also able to hydrolyze phosphatidylcholine (PC). Here, we identified a second PLD called DaPLD2, which shares only 38% peptide identity with DaPLD1. We have recombinantly expressed this PLD in Escherichia coli and characterized it biochemically. Unlike DaPLD1, DaPLD2 exhibits an exclusive specificity for PE and is inactive toward other PLs, including PC. DaPLD2 is distant phylogenetically from DaPLD1 but shares common features and key residues found in bacterial PLDs. Altogether, this unique property of DaPLD2 towards PE provides valuable insights into PL metabolism in bacteria and holds potential for development as a tool enzyme to selectively transform PE among other PLs.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650096","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":"Mechanistic determinants of fatty acid chain length in fatty acid synthase: The case of dairy fat.","authors":"Bar Sutker, Roni Tadmor-Levi, Maggie Levy, Nurit Argov-Argaman","doi":"10.1016/j.biochi.2026.07.012","DOIUrl":"10.1016/j.biochi.2026.07.012","url":null,"abstract":"<p><p>Lipid chemical and structural properties are responsible for the technological, health and rheological properties of dairy products. Inability to properly mimic those compositional properties will result in lower product quality as well as lower public acceptance. These properties stem from a unique composition of dairy fatty acids which are enriched with short- and medium-chain fatty acids with a carbon chain length of up to 14 atoms, a trait shared among dairy ruminants such as bovine, caprine and ovine, but different from most non-ruminant species. These fatty acids are produced in the mammary gland epithelial cells, by the fatty acid synthase (FASN) multienzyme. While de novo synthesis of fatty acids is highly conserved throughout evolution, and the same sequential elongation and condensation of acetyl-CoA and malonyl-CoA units follow the same mechanistic steps, still the products vary between organisms and tissues. Here we address the fundamental question of ruminant dairy fat production and discuss the general and specific properties of mammalian and ruminant FASN and their potential contribution to the production of short- and medium-chain fatty acids in ruminant milk fat. Current knowledge regarding each catalytic activity of the FASN multi-enzyme is reviewed with special emphasis on consequences to fatty acid profile produced by ruminant FASN. To identify ruminant specific FASN properties with potential to attribute to dairy fat composition, FASN protein sequence was analyzed and compared among 13 ruminant and non-ruminant mammalian species. Unravelling these distinctive properties will expand our understanding of this fundamental question in lipid metabolism and shed light on the evolution of the high diversity of mammalian milk, and specifically on dairy ruminant milk fat.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581616","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":"Maternal dietary n-3 PUFA deficiency leads to sex-specific alterations in placental and cerebral fatty acid profiles and in oxylipin profiles in the developing mouse brain.","authors":"Flore Marchaland, Maud Martinat, Mathieu Di Miceli, Stéphane Grégoire, Moïra Rossitto, Lydie Morel, Agnès Aubert, Alexandra Séré, Jean-Christophe Delpech, Corinne Joffre, Niyazi Acar, Richard P Bazinet, Sophie Layé","doi":"10.1016/j.biochi.2026.07.010","DOIUrl":"10.1016/j.biochi.2026.07.010","url":null,"abstract":"<p><p>Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), are essential for optimal neurodevelopment through their effect on neuronal proliferation, neurite outgrowth and synaptogenesis. Emerging evidence highlights that brain PUFAs are metabolized in oxylipins, the bioactive oxidized PUFA metabolites known to regulate inflammatory processes. Recent data highlighted that both PUFA and oxylipin profiles are modulated in the brains of adult male mice by dietary PUFA content. However, little is known on the impact of maternal dietary n-3 PUFA intake during the perinatal period and the neurodevelopmental profile of brain fatty acids and associated oxylipins in mouse offspring, and whether these effects differ between sexes. To address this question, we first measured fatty acid levels in the placenta and embryonic brain of male and female mice at embryonic day (E)17.5 of mothers fed an n-3 PUFA-sufficient diet (based on canola oil, rich in the n-3 precursor alpha-linolenic acid) or an n-3 PUFA-deficient diet (based on sunflower oil, rich in the n-6 precursor linoleic acid) in n-3 PUFAs starting at E0. Then, fatty acids and oxylipins were measured at different post-natal stages, in the brain at postnatal day (P)0 and P7, and in the hippocampus at P14 and P21, in both male and female mouse offspring. Our results show that maternal n-3 PUFA dietary deficiency alters fatty acid profiles as early as E17.5 in both the placenta and the brain. Furthermore, dietary intervention affects both fatty acid and oxylipin profiles throughout postnatal brain development, with notable sex-specific differences. These findings highlight the importance of maternal n-3 PUFA intake during the perinatal period for establishing and maintaining PUFA and oxylipin profiles in the developing brain.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551744","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}