Cell Chemical Biology最新文献_第8页

Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes 扩大可配体蛋白质组的化学工具：基于多样性合成的光活性立体配体

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.10.005

Daisuke Ogasawara , David B. Konrad , Zher Yin Tan , Kimberly L. Carey , Jessica Luo , Sang Joon Won , Haoxin Li , Trever R. Carter , Kristen E. DeMeester , Evert Njomen , Stuart L. Schreiber , Ramnik J. Xavier , Bruno Melillo , Benjamin F. Cravatt

{"title":"Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes","authors":"Daisuke Ogasawara , David B. Konrad , Zher Yin Tan , Kimberly L. Carey , Jessica Luo , Sang Joon Won , Haoxin Li , Trever R. Carter , Kristen E. DeMeester , Evert Njomen , Stuart L. Schreiber , Ramnik J. Xavier , Bruno Melillo , Benjamin F. Cravatt","doi":"10.1016/j.chembiol.2024.10.005","DOIUrl":"10.1016/j.chembiol.2024.10.005","url":null,"abstract":"<div><div>Chemical proteomics enables the global analysis of small molecule-protein interactions in native biological systems and has emerged as a versatile approach for ligand discovery. The range of small molecules explored by chemical proteomics has, however, remained limited. Here, we describe a diversity-oriented synthesis (DOS)-inspired library of stereochemically defined compounds bearing diazirine and alkyne units for UV light-induced covalent modification and click chemistry enrichment of interacting proteins, respectively. We find that these “photo-stereoprobes” interact in a stereoselective manner with hundreds of proteins from various structural and functional classes in human cells and demonstrate that these interactions can form the basis for high-throughput screening-compatible NanoBRET assays. Integrated phenotypic screening and chemical proteomics identified photo-stereoprobes that modulate autophagy by engaging the mitochondrial serine protease CLPP. Our findings show the utility of DOS-inspired photo-stereoprobes for expanding the ligandable proteome, furnishing target engagement assays, and facilitating the discovery and characterization of bioactive compounds in phenotypic screens.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2138-2155.e32"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates 利用 PD-L1 靶向抗体纳米凝胶共轭物治疗诱导肿瘤中的铁变态反应

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.10.014

Mengdie Wang , Theeraphop Prachyathipsakul , Christi A. Wisniewski , Choua Xiong , Shivam Goel , Hira Lal Goel , Emmet R. Karner , Dimpi Mukhopadhyay , Prachi Gupta , Aniket Majee , S. Thayumanavan , Arthur M. Mercurio

{"title":"Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates","authors":"Mengdie Wang , Theeraphop Prachyathipsakul , Christi A. Wisniewski , Choua Xiong , Shivam Goel , Hira Lal Goel , Emmet R. Karner , Dimpi Mukhopadhyay , Prachi Gupta , Aniket Majee , S. Thayumanavan , Arthur M. Mercurio","doi":"10.1016/j.chembiol.2024.10.014","DOIUrl":"10.1016/j.chembiol.2024.10.014","url":null,"abstract":"<div><div>Although programmed cell death ligand 1 <strong>(</strong>PD-L1) is best known for its role in immune suppression, tumor-intrinsic functions are emerging. Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE). PD-L1 promotes ferroptosis sensitivity because it suppresses SLC7A11 expression and diminishes glutathione levels. Although the use of anti-PD-L1 antibody drug conjugates (ADCs) could be effective for the delivery of ferroptosis inducers to specific tumor populations, the chemistry of most ferroptosis inducers precludes their incorporation in ADCs. To overcome this challenge, we synthesized an antibody nanogel conjugate (ANC) comprised of an anti-PD-L1 antibody conjugated to a nanogel encapsulated with IKE. This ANC targets PD-L1-expressing cells <em>in vitro</em> and <em>in vivo</em> and induces ferroptosis, resulting in tumor suppression. Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2039-2051.e6"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Platelets accelerate lipid peroxidation and induce pathogenic neutrophil extracellular trap release 血小板加速脂质过氧化，诱导致病性中性粒细胞胞外陷阱释放

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.003

Madoka Ono , Masayasu Toyomoto , Momono Yamauchi , Masatoshi Hagiwara

{"title":"Platelets accelerate lipid peroxidation and induce pathogenic neutrophil extracellular trap release","authors":"Madoka Ono , Masayasu Toyomoto , Momono Yamauchi , Masatoshi Hagiwara","doi":"10.1016/j.chembiol.2024.11.003","DOIUrl":"10.1016/j.chembiol.2024.11.003","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs), an important host defense mechanism, are assembled after the release of decondensed chromatin and other nuclear components by a process termed NETosis. However, excessive NET release destroys surrounding tissues, leading to conditions such as sepsis where platelets are implicated in the pathogenic switch of NETosis. Here, we show that platelets trigger iron accumulation and promote lipid peroxide production in neutrophils co-stimulated with lipopolysaccharide and platelets <em>in vitro</em>, resulting in the induction of NETosis. We also screened for compounds that inhibit lipid peroxidation, identified 8-methyl-<em>N</em>-geranyl-6-nonamide (capsaicin), and assessed its potential in suppressing platelet-mediated pathogenic NETosis. Capsaicin inhibited lipopolysaccharide/platelet-induced cellular lipid peroxidation and suppressed NETosis <em>in vitro</em>. Furthermore, capsaicin attenuated NETosis in a mouse model of lipopolysaccharide-induced lung inflammation. Our findings provide an original therapeutic strategy to target lipid peroxidation and pave the way for drug development for a wide range of NETosis-related diseases.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2085-2095.e4"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas 从假单胞菌中发现非典型 C16-三萜类化合物并进行生物合成

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.09.002

Xu-Hua Mo , Qing-Yin Pu , Tilo Lübken , Gui-Hong Yu , Mert Malay , Paul M. D’Agostino , Tobias A.M. Gulder

{"title":"Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas","authors":"Xu-Hua Mo , Qing-Yin Pu , Tilo Lübken , Gui-Hong Yu , Mert Malay , Paul M. D’Agostino , Tobias A.M. Gulder","doi":"10.1016/j.chembiol.2024.09.002","DOIUrl":"10.1016/j.chembiol.2024.09.002","url":null,"abstract":"<div><div>Biosynthesis of sodorifen with a unique C<sub>16</sub>-bicyclo[3.2.1]octene framework requires an <em>S</em>-adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the <em>sodCD</em> genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, <em>pcch</em> and <em>pcau</em>, from <em>Pseudomonas</em> sp. are heterologously expressed in <em>Escherichia coli</em>, leading to the discovery of two C<sub>16</sub> terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the <em>pcch</em>, <em>pcau</em>, and <em>sod</em> pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C<sub>16</sub>-terpenoids.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2128-2137.e4"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of two repurposed drugs targeting GSDMD oligomerization interface I to block pyroptosis 鉴定两种以 GSDMD 寡聚界面 I 为靶点的再利用药物，以阻断焦细胞增多症

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.10.002

Yingchao Hu , Honghui Li , Xiangyu Zhang , Yuxian Song , Jun Liu , Jie Pu , Shuang Wen , Hongyang Xu , Hongliang Xin , Bingwei Wang , Shuo Yang

{"title":"Identification of two repurposed drugs targeting GSDMD oligomerization interface I to block pyroptosis","authors":"Yingchao Hu , Honghui Li , Xiangyu Zhang , Yuxian Song , Jun Liu , Jie Pu , Shuang Wen , Hongyang Xu , Hongliang Xin , Bingwei Wang , Shuo Yang","doi":"10.1016/j.chembiol.2024.10.002","DOIUrl":"10.1016/j.chembiol.2024.10.002","url":null,"abstract":"<div><div>As an executor of pyroptosis, gasdermin D (GSDMD) plays a critical role in inflammatory diseases and cancer. Thus, GSDMD is currently being widely explored as a drug target. Existing inhibitors targeting GSDMD, such as necrosulfonamide, disulfiram, and fumarate, primarily prevent pyroptosis by modifying human/mouse C191/C192 in the N-terminal fragment of GSDMD. However, cysteine modification can prevent the function of important proteins or enzymes, thereby leading to adverse reactions. Here, we chose an alternative key intervention site for GSDMD activation, which is located at the oligomerization interface I of its pore-forming structure. Through high-throughput virtual and experimental screening and in combination with efficacy and pharmacological validation, we have identified two safe, specific “repurposed drugs” that potently suppress GSDMD-mediated pyroptosis. Moreover, the candidates exhibited synergistic therapeutic effects of “1 + 1>2” in murine sepsis and tumorigenesis models. These recently identified GSDMD inhibitors hold great promise for clinical translation in the development of anti-inflammatory and anti-cancer immunotherapies.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2024-2038.e7"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FAAHcilitating recovery in malnourished kids 促进营养不良儿童的康复

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.007

Franciscus Chandra , Elaine Y. Hsiao

引用次数: 0

Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics 对生物膜结构和成熟的洞察使体外多糖靶向治疗的临床策略得到改善

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.005

J. Sebastian Temme , Zibin Tan , Mi Li , Mo Yang , Alexander Wlodawer , Xuefei Huang , John S. Schneekloth Jr. , Jeffrey C. Gildersleeve

{"title":"Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics","authors":"J. Sebastian Temme , Zibin Tan , Mi Li , Mo Yang , Alexander Wlodawer , Xuefei Huang , John S. Schneekloth Jr. , Jeffrey C. Gildersleeve","doi":"10.1016/j.chembiol.2024.11.005","DOIUrl":"10.1016/j.chembiol.2024.11.005","url":null,"abstract":"<div><div>Polysaccharide intercellular adhesin (PIA), an exopolysaccharide composed of poly-N-acetyl glucosamine (PNAG), is an essential component in many pathogenic biofilms. Partial deacetylation of PNAG is required for biofilm formation, but limited structural knowledge hinders therapeutic development. Employing a new monoclonal antibody (TG10) that selectively binds highly deacetylated PNAG and an antibody (F598) in clinical trials that binds highly acetylated PNAG, we demonstrate that PIA within the biofilm contains distinct regions of highly acetylated and deacetylated exopolysaccharide, contrary to the previous model invoking stochastic deacetylation throughout the biofilm. This discovery led us to hypothesize that targeting both forms of PNAG would enhance efficacy. Remarkably, TG10 and F598 synergistically increased <em>in vitro</em> and <em>in vivo</em> activity, providing 90% survival in a lethal <em>Staphylococcus aureus</em> challenge murine model. Our advanced model deepens the conceptual understanding of PIA architecture and maturation and reveals improved design strategies for PIA-targeting therapeutics, vaccines, and diagnostic agents.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2096-2111.e7"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancer reprogramming underlies therapeutic utility of a SMARCA2 degrader in SMARCA4 mutant cancer 增强子重编程是SMARCA2降解剂在SMARCA4突变癌症中发挥治疗作用的基础

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.09.004

Sasikumar Kotagiri , Nicholas Blazanin , Yuanxin Xi , Yanyan Han , Md Qudratullah , Xiaobing Liang , Yawen Wang , Poonam Pandey , Hira Mazhar , Truong Nguyen Lam , Anand Kamal Singh , Jing Wang , Yonathan Lissanu

{"title":"Enhancer reprogramming underlies therapeutic utility of a SMARCA2 degrader in SMARCA4 mutant cancer","authors":"Sasikumar Kotagiri , Nicholas Blazanin , Yuanxin Xi , Yanyan Han , Md Qudratullah , Xiaobing Liang , Yawen Wang , Poonam Pandey , Hira Mazhar , Truong Nguyen Lam , Anand Kamal Singh , Jing Wang , Yonathan Lissanu","doi":"10.1016/j.chembiol.2024.09.004","DOIUrl":"10.1016/j.chembiol.2024.09.004","url":null,"abstract":"<div><div>Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including <em>SMARCA4</em> and <em>ARID1A</em> in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog <em>SMARCA2</em> is synthetic lethal to <em>SMARCA4</em> suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in <em>SMARCA4</em>-mutant cells with loss of chromatin accessibility at enhancers of genes involved in cell proliferation. Furthermore, we identified YAP/TEADas key partners to SMARCA2 in driving growth of <em>SMARCA4</em>-mutant cells. Finally, we show that YD23 has potent tumor growth inhibitory activity in <em>SMARCA4</em>-mutant xenografts. These findings provide the mechanistic basis for development of SMARCA2 degraders as synthetic lethal therapeutics against <em>SMARCA4</em>-mutant lung cancers.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2069-2084.e9"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383742","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}

引用次数: 0

D-aring to explore: New approaches to gasdermin D targeting D-正在探索：gasdermin D靶向的新方法

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.006

Lei Wang , Wen Zhou

引用次数: 0

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia 发现一种μ-阿片受体调节剂，与吗啡烷拮抗剂联合使用可产生镇痛效果

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-11-21 DOI: 10.1016/j.chembiol.2024.06.013

Yi-Han Huang , Shu-Yu Lin , Li-Chin Ou , Wei-Cheng Huang , Po-Kuan Chao , Yung-Chiao Chang , Hsiao-Fu Chang , Pin-Tse Lee , Teng-Kuang Yeh , Yu-Hsien Kuo , Ya-Wen Tien , Jing-Hua Xi , Pao-Luh Tao , Pin-Yuan Chen , Jian-Ying Chuang , Chuan Shih , Chiung-Tong Chen , Chun-Wei Tung , Horace H. Loh , Shau-Hua Ueng , Shiu-Hwa Yeh

{"title":"Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia","authors":"Yi-Han Huang , Shu-Yu Lin , Li-Chin Ou , Wei-Cheng Huang , Po-Kuan Chao , Yung-Chiao Chang , Hsiao-Fu Chang , Pin-Tse Lee , Teng-Kuang Yeh , Yu-Hsien Kuo , Ya-Wen Tien , Jing-Hua Xi , Pao-Luh Tao , Pin-Yuan Chen , Jian-Ying Chuang , Chuan Shih , Chiung-Tong Chen , Chun-Wei Tung , Horace H. Loh , Shau-Hua Ueng , Shiu-Hwa Yeh","doi":"10.1016/j.chembiol.2024.06.013","DOIUrl":"10.1016/j.chembiol.2024.06.013","url":null,"abstract":"<div><div><span>Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (</span><strong>BPRMU191</strong>), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of <strong>BPRMU191</strong><span><span> and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including </span>gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining </span><strong>BPRMU191</strong> and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 11","pages":"Pages 1885-1898.e10"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0