Autophagy最新文献

{"title":"When mitophagy dictates the outcome of cellular infection: the case of <i>Brucella abortus</i>.","authors":"Jérémy Verbeke, Xavier De Bolle, Thierry Arnould","doi":"10.1080/15548627.2023.2246354","DOIUrl":"10.1080/15548627.2023.2246354","url":null,"abstract":"<p><p>Mitochondria are at the basis of various cellular functions ranging from metabolism and redox homeostasis to inflammation and cell death regulation. Mitochondria therefore constitute an attractive target for invading pathogens to fulfil their infectious cycle. This involves the modulation to their advantage of mitochondrial metabolism and dynamics, including the controlled degradation of mitochondria through mitophagy. Mitophagy might for instance be beneficial for bacterial survival as it can clear bactericidal mitochondrial ROS produced by damaged organelle fragments from the intracellular niche. In the case of the bacterial pathogen <i>Brucella abortus</i>, mitophagy induction has another role in the intracellular lifecycle of the bacteria. Indeed, in our study, we showed that <i>B. abortus</i> triggers an iron-dependent BNIP3L-mediated mitophagy response required for proper bacterial egress and infection of neighboring cells. These results highlight the diversity of mitophagy processes that might be crucial for several stages of cellular infection.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3022-3023"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10011809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased apoptosis of gingival epithelium is associated with impaired autophagic flux in medication-related osteonecrosis of the jaw.","authors":"Xian Dong, Yang He, Jingang An, Linhai He, Yi Zheng, Xinyu Wang, Jie Wang, Shuo Chen, Yi Zhang","doi":"10.1080/15548627.2023.2234228","DOIUrl":"10.1080/15548627.2023.2234228","url":null,"abstract":"<p><p>Macroautophagy/autophagy has both negative and positive aspects in the development of many diseases. Yet, its exact role and specific mechanism in the onset of medication-related osteonecrosis of the jaw (MRONJ) is still not fully understood. Retarded gingiva healing is the primary clinical manifestation in patients with MRONJ. In this study, we aimed to explore the relationship between autophagy and apoptosis in MRONJ gingival epithelium and search for a method to prevent this disease. First, we examined clinical samples from patients diagnosed with MRONJ and healthy controls, finding that autophagy-related markers MAP1LC3/LC3 and SQSTM1/p62 synchronously increased, thus suggesting that autophagic flux was suppressed in MRONJ. Moreover, mRNA sequencing analysis and TUNEL assay showed that the process of apoptosis was upregulated in patients and animals with MRONJ, indicating autophagy and apoptosis participate in the development of MRONJ. Furthermore, the level of autophagy and apoptosis in zoledronic acid (ZA)-treated human keratinocytes cell lines (HaCaT cells) was concentration dependent <i>in vitro</i>. In addition, we also found that RAB7 (RAB7, member RAS oncogene family) activator ML098 could rescue MRONJ gingival lesions in mice by activating the autophagic flux and downregulating apoptosis. To sum up, this study demonstrated that autophagic flux is impaired in the gingival epithelium during MRONJ, and the rescued autophagic flux could prevent the occurrence of MRONJ.<b>Abbreviations:</b> ACTB: actin beta; Baf-A1: bafilomycin A₁; CASP3: caspase 3; CASP8: caspase 8; CT: computed tomography; DMSO: dimethyl sulfoxide; GFP: green fluorescent protein; HaCaT cells: human keratinocytes cell lines; H&E: hematoxylin and eosin; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MRONJ: medication-related osteonecrosis of the jaw; PARP: poly(ADP-ribose) polymerase; RAB7: RAB7, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; ZA: zoledronic acid.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"2899-2911"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy-ER stress crosstalk controls mucus secretion and susceptibility to gut inflammation.","authors":"Maria Naama, Shai Bel","doi":"10.1080/15548627.2023.2228191","DOIUrl":"10.1080/15548627.2023.2228191","url":null,"abstract":"<p><p>Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn produce a thicker and less penetrable mucus barrier. Pharmacological reduction of the ER stress or activation of the unfolded protein response (UPR) in mice, regardless of autophagy activation, lead to excess mucus secretion. This regulation of mucus secretion by ER stress is microbiota-dependent and requires the activity of the intracellular sensor NOD2 (nucleotide-binding oligomerization domain containing 2). Excess mucus production in the colon alters the gut microbiota and protects from chemical- and infection-driven inflammation. Our findings provide new insights into the mechanisms by which autophagy regulates mucus secretion and susceptibility to intestinal inflammation.<b>Abbreviations:</b>BECN1- Beclin 1; ER- endoplasmic reticulum; UPR - unfolded protein response; NOD2 - nucleotide-binding oligomerization domain containing 2; IBD- inflammatory bowel disease; BCL2- B cell leukemia/lymphoma 2; TUDCA- tauroursodeoxycholic acid; ATG16L1- autophagy related 16 like 1; LRRK2- leucine-rich repeat kinase 2.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3014-3016"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of autophagy by chromatin remodeling complex and histone variant.","authors":"Xin Li, Shanshan Wang, Xilan Yu, Shanshan Li","doi":"10.1080/15548627.2023.2200352","DOIUrl":"10.1080/15548627.2023.2200352","url":null,"abstract":"<p><p>Autophagy is a catabolic process to maintain homeostasis, and involved in cell differentiation and development. Autophagy is tightly regulated in response to nutrient availability but the underlying mechanism is not completely understood. Recently, we identified the chromatin remodeling complex INO80 (inositol-requiring mutant 80) and histone variant H2A.Z as new autophagy regulators and uncover how histone deacetylase Rpd3L (reduced potassium dependency 3 large) complex represses autophagy by deacetylating Ino80 and H2A.Z. In particular, Rpd3L complex deacetylates Ino80 at lysine 929, which protects Ino80 from being degraded by autophagy. The stabilized Ino80 then evicts H2A.Z from autophagy-related (ATG) genes, leading to their transcriptional repression. In parallel, Rpd3L complex also deacetylates H2A.Z, which further reduces its association with ATG gene promoters and repress ATG gene transcription. Under nutrient-rich conditions, Rpd3L-mediated deacetylation of Ino80 K929 and H2A.Z is enhanced by the TORC1 complex (target of rapamycin complex 1). Under nitrogen-starvation condition, TORC1 is inactivated, leading to reduced activity of Rpd3L complex and increased acetylation of Ino80 and H2A.Z, which in turn induce the transcription of ATG genes. These results reveal a critical role of chromatin remodelers and histone variants in regulating autophagy in response to nutrient availability.<b>Abbreviations:</b> INO80: inositol-requiring mutant 80; Rpd3: reduced potassium dependency 3; H2A.Z: histone H2A variant; Rpd3L complex: Rpd3 large complex; H4K16: H4 lysine 16; H3R17: H3 arginine 17; H3T11: H3 threonine 11; TORC1 complex: target of rapamycin complex 1; ATG: autophagy-related; SWI/SNF: switch/sucrose non-fermentable; SWR1: Swi2/Snf2-related ATPase complex; RSC: remodel the structure of chromatin; ISWI: imitation switch; CHD1: chromodomain helicase DNA binding protein 1; Arp8: actin-related protein 8; Sds3: suppressor of defective silencing 3; Ume6: unscheduled meiotic gene expression 6.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2824-2826"},"PeriodicalIF":13.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inflammation repressor TNIP1/ABIN-1 is degraded by autophagy following TBK1 phosphorylation of its LIR.","authors":"Nikoline L Rasmussen, Jianwen Zhou, Hallvard Olsvik, Stéphanie Kaeser-Pebernard, Trond Lamark, Joern Dengjel, Terje Johansen","doi":"10.1080/15548627.2023.2185013","DOIUrl":"10.1080/15548627.2023.2185013","url":null,"abstract":"<p><p>The inflammatory repressor TNIP1/ABIN-1 is important for keeping in check inflammatory and cell-death pathways to avoid potentially dangerous sustained activation of these pathways. We have now found that TNIP1 is rapidly degraded by selective macroautophagy/autophagy early (0-4 h) after activation of TLR3 by poly(I:C)-treatment to allow expression of pro-inflammatory genes and proteins. A few hours later (6 h), TNIP1 levels rise again to counteract sustained inflammatory signaling. TBK1-mediated phosphorylation of a TNIP1 LIR motif regulates selective autophagy of TNIP1 by stimulating interaction with Atg8-family proteins. This is a novel level of regulation of TNIP1, whose protein level is crucial for controlling inflammatory signaling.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2819-2820"},"PeriodicalIF":13.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The yeast transcription factor Stb5 acts as a negative regulator of autophagy by modulating cellular metabolism.","authors":"Elizabeth Delorme-Axford, Xin Wen, Daniel J Klionsky","doi":"10.1080/15548627.2023.2228533","DOIUrl":"10.1080/15548627.2023.2228533","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a highly conserved pathway of cellular degradation and recycling that maintains cell health during homeostatic conditions and facilitates survival during stress. Aberrant cellular autophagy contributes to the pathogenesis of human diseases such as cancer, neurodegeneration, and cardiovascular, metabolic and lysosomal storage disorders. Despite decades of research, there remain unanswered questions as to how autophagy modulates cellular metabolism, and, conversely, how cellular metabolism affects autophagy activity. Here, we have identified the yeast metabolic transcription factor Stb5 as a negative regulator of autophagy. Chromosomal deletion of <i>STB5</i> in the yeast <i>Saccharomyces cerevisiae</i> enhances autophagy. Loss of Stb5 results in the upregulation of select <u>a</u>u<u>t</u>opha<u>g</u>y-related (<i>ATG</i>) transcripts under nutrient-replete conditions; however, the Stb5-mediated impact on autophagy occurs primarily through its effect on genes involved in NADPH production and the pentose phosphate pathway. This work provides insight into the intersection of Stb5 as a transcription factor that regulates both cellular metabolic responses and autophagy activity.<b>Abbreviations</b>: bp, base pairs; ChIP, chromatin immunoprecipitation; G6PD, glucose-6-phosphate dehydrogenase; GFP, green fluorescent protein; IDR, intrinsically disordered region; NAD, nicotinamide adenine dinucleotide; NADP⁺, nicotinamide adenine dinucleotide phosphate; NADPH, nicotinamide adenine dinucleotide phosphate (reduced); ORF, open reading frame; PA, protein A; PCR, polymerase chain reaction; PE, phosphatidylethanolamine; PPP, pentose phosphate pathway; prApe1, precursor aminopeptidase I; ROS, reactive oxygen species; RT-qPCR, real-time quantitative PCR; SD, standard deviation; TF, transcription factor; TOR, target of rapamycin; WT, wild-type.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2719-2732"},"PeriodicalIF":14.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ufmylation bridges autophagy and ER homeostasis in plants.","authors":"Baiying Li, Liwen Jiang","doi":"10.1080/15548627.2023.2203985","DOIUrl":"10.1080/15548627.2023.2203985","url":null,"abstract":"<p><p>The autophagic machinery is highly conserved in eukaryotes. Plants, as sessile organisms, are more susceptible to environmental stresses than animals. Autophagy plays a pivotal role in plant stress responses, but the regulation of autophagic flux in plants remains enigmatic with few autophagic receptors identified. We recently characterized an E3 ligase, the ubiquitin-fold modifier 1 (Ufm1) ligase 1 (Ufl1), as well as its small modifier protein Ufm1, as interactors of the core autophagy-related (ATG) proteins. Mutants of these ufmylation system components are hypersensitive to salt stress and trigger the upregulation of endoplasmic reticulum (ER) stress-responsive genes, as well as the accumulation of ER sheets caused by a defect in reticulophagy. Increased expression of Ufl1, Ufm1 and Ufm1-conjugating enzyme 1 (Ufc1) are also triggered by salt stress in plants. This study identified and demonstrated the participation of ufmylation components in maintaining ER homeostasis by regulating reticulophagy under salt stress in plants.<b>Abbreviations</b>: ATG, autophagy-related; ER, endoplasmic reticulum; LIR, LC3-interacting region; ROS, reactive oxygen species; CDK5RAP3/C53, CDK5 regulatory subunit-associated protein 3; Uba5, Ufm1-activating enzyme 5; Ufc1, Ufm1-conjugating enzyme 1; Ufl1, Ufm1 ligase 1; Ufm1, ubiquitin-fold modifier 1; UPR, unfolded protein response.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2830-2831"},"PeriodicalIF":13.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10184195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM16-mediated lysophagy suppresses high-glucose-accumulated neuronal Aβ.","authors":"Chang Woo Chae, Jee Hyeon Yoon, Jae Ryong Lim, Ji Yong Park, Ji Hyeon Cho, Young Hyun Jung, Gee Euhn Choi, Hyun Jik Lee, Ho Jae Han","doi":"10.1080/15548627.2023.2229659","DOIUrl":"10.1080/15548627.2023.2229659","url":null,"abstract":"<p><strong>Abbreviations: </strong>Aβ: amyloid β; AD: Alzheimer disease; AMPK: 5' adenosine monophosphate-activated protein kinase; CTSB: cathepsin B; CTSD: cathepsin D; DM: diabetes mellitus; ESCRT: endosomal sorting complex required for transport; FBXO27: F-box protein 27; iPSC-NDs: induced pluripotent stem cell-derived neuronal differentiated cells; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; LRSAM1: leucine rich repeat and sterile alpha motif containing 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; p-MAPT/tau: phosphorylated microtubule associated protein tau; ROS: reactive oxygen species; STZ: streptozotocin; TFE3: transcription factor E3; TFEB: transcription factor EB; TRIM16: tripartite motif containing 16; UBE2QL1: ubiquitin conjugating enzyme E2 Q family like 1; VCP: valosin containing protein.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2752-2768"},"PeriodicalIF":14.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of programmed mitophagy in germline mitochondrial DNA quality control.","authors":"Jonathan M Palozzi, Thomas R Hurd","doi":"10.1080/15548627.2023.2182595","DOIUrl":"10.1080/15548627.2023.2182595","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) is prone to the accumulation of mutations. To prevent harmful mtDNA mutations from being passed on to the next generation, the female germline, through which mtDNA is exclusively inherited, has evolved extensive mtDNA quality control. To dissect the molecular underpinnings of this process, we recently performed a large RNAi screen in Drosophila and uncovered a programmed germline mitophagy (PGM) that is essential for mtDNA quality control. We found that PGM begins as germ cells enter meiosis, induced, at least in part, by the inhibition of the mTor (mechanistic Target of rapamycin) complex 1 (mTorC1). Interestingly, PGM requires the general macroautophagy/autophagy machinery and the mitophagy adaptor BNIP3, but not the canonical mitophagy genes Pink1 and park (parkin), even though they are critical for germline mtDNA quality control. We also identified the RNA-binding protein Atx2 as a major regulator of PGM. This work is the first to identify and implicate a programmed mitophagy event in germline mtDNA quality control, and it highlights the utility of the Drosophila ovary for studying developmentally regulated mitophagy and autophagy <i>in vivo</i>.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2817-2818"},"PeriodicalIF":13.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The YAP1-TEAD axis promotes autophagy against intracellular <i>Staphylococcus aureus in vitro</i>.","authors":"Robin Caire, Nicola Pordone, Paul O Verhoeven","doi":"10.1080/15548627.2023.2179771","DOIUrl":"10.1080/15548627.2023.2179771","url":null,"abstract":"<p><p>Previously considered as an exclusive extracellular bacterium, <i>Staphylococcus aureus</i> has been shown to be able to invade many cells <i>in vitro</i> and in humans. Once inside the host cell, both cytosolic and endosome-associated <i>S. aureus</i> strongly induce macroautophagy/autophagy. Whether autophagy fosters <i>S. aureus</i> intracellular survival or clearance remains unclear. The YAP1-TEAD axis regulates the expression of target genes controlling the cell fate (<i>e.g</i>., proliferation, migration, cell cycle …). Growing evidence indicates that YAP1-TEAD also regulates autophagy and lysosomal pathways. Recently we showed that the YAP1-TEAD axis promotes autophagy and lysosome biogenesis to restrict <i>S. aureus</i> intracellular replication. We also discovered that the C3 exoenzyme-like EDIN-B toxin produced by the pathogenic <i>S. aureus</i> ST80 strain inhibits YAP1 nuclear translocation resulting in a strong increase of intracellular <i>S. aureus</i> burden.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"19 10","pages":"2811-2813"},"PeriodicalIF":13.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}