The FEBS journal最新文献_第9页

d-amino acids: new functional insights. d-氨基酸：新的功能见解。

The FEBS journal Pub Date : 2025-03-27 DOI: 10.1111/febs.70083

Loredano Pollegioni, Natasa Kustrimovic, Luciano Piubelli, Elena Rosini, Valentina Rabattoni, Silvia Sacchi

{"title":"d-amino acids: new functional insights.","authors":"Loredano Pollegioni, Natasa Kustrimovic, Luciano Piubelli, Elena Rosini, Valentina Rabattoni, Silvia Sacchi","doi":"10.1111/febs.70083","DOIUrl":"https://doi.org/10.1111/febs.70083","url":null,"abstract":"The d-enantiomers of amino acids (d-AAs) were initially considered \"unnatural\" molecules. They are primarily of microbial origin, present in low amounts, and without biological functions in eukaryotes. However, over the past few decades, sensitive analytical methods have uncovered the presence of both free and peptide-bound d-AAs in higher organisms. During the same period, the discovery of serine racemase-the enzyme that catalyzes the reversible formation of d-serine from l-serine-in rat brains demonstrated that mammals synthesize d-AAs. Notably, the enzymes responsible for d-AAs catabolism were identified almost 90 years ago. Subsequently, free d-AAs such as d-serine, d-aspartate, d-alanine, and d-cysteine have emerged as a novel and important class of signaling molecules in various organs, including the brain and endocrine system. Their involvement in a wide range of neurological disorders has drawn significant scientific interest. We have focused on novel findings, based on the latest analytical techniques, that have reshaped our understanding of physiological processes across diverse organisms, from plants to humans. Beyond neurotransmission, recent studies have highlighted the versatile roles of d-AAs in cancer, inflammation, immune regulation, kidney disease, and diabetes. Moreover, these studies suggest that the levels of d-AAs in blood and urine could serve as early biomarkers for conditions such as Alzheimer's disease, schizophrenia, and chronic kidney disease. Understanding the role of d-AAs in certain pathological states is helping to identify new therapeutic targets, offering promising opportunities for clinical applications in treating various diseases.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733662","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}

引用次数: 0

The influence of fatty acid metabolism on T cell function in lung cancer. 脂肪酸代谢对肺癌患者T细胞功能的影响。

The FEBS journal Pub Date : 2025-03-25 DOI: 10.1111/febs.70081

Jessica Petiti, Ludovica Arpinati, Alessio Menga, Giovanna Carrà

{"title":"The influence of fatty acid metabolism on T cell function in lung cancer.","authors":"Jessica Petiti, Ludovica Arpinati, Alessio Menga, Giovanna Carrà","doi":"10.1111/febs.70081","DOIUrl":"https://doi.org/10.1111/febs.70081","url":null,"abstract":"The tumor microenvironment (TME) is a complex ecosystem, encompassing a variety of cellular and non-cellular elements surrounding and interacting with cancer cells, overall promoting tumor growth, immune evasion, and therapy resistance. In the context of solid tumors, factors, such as hypoxia, nutritional competition, increased stress responses, glucose demand, and PD-1 signals strongly influence metabolic alterations in the TME, highly contributing to the maintenance of a tumor-supportive and immune-suppressive milieu. Cancer cell-induced metabolic alterations partly result in an increased fatty acid (FA) metabolism within the TME, which strongly favors the recruitment of immune-suppressive M2 macrophages and myeloid-derived suppressor cells, crucial contributors to T-cell exhaustion, tumor exclusion, and decreased effector functions. The drastic pro-tumoral changes induced by the tumor metabolic rewiring result in signaling loops that support tumor progression and metastatic spreading, and negatively impact therapy efficacy. As tumor- and immune metabolism are increasingly gaining attention due to their potential therapeutic implications, we discuss the effects of altered lipid metabolism on tumor progression, immune response, and therapeutic efficacy in the context of lung cancer. In particular, we focus our analysis on the tumor-induced metabolic alterations experienced by T lymphocytes and the possible strategies to overcome immunotherapy resistance by targeting specific metabolic pathways in T cells.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712639","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}

引用次数: 0

Natural aminosterols inhibit NMDA receptors with low nanomolar potency. 天然氨基甾醇抑制NMDA受体具有低纳摩尔效价。

The FEBS journal Pub Date : 2025-03-24 DOI: 10.1111/febs.70072

Giulia Fani, Elisabetta Coppi, Silvia Errico, Federica Cherchi, Martina Gennari, Denise Barbut, Michele Vendruscolo, Michael Zasloff, Anna Maria Pugliese, Fabrizio Chiti

{"title":"Natural aminosterols inhibit NMDA receptors with low nanomolar potency.","authors":"Giulia Fani, Elisabetta Coppi, Silvia Errico, Federica Cherchi, Martina Gennari, Denise Barbut, Michele Vendruscolo, Michael Zasloff, Anna Maria Pugliese, Fabrizio Chiti","doi":"10.1111/febs.70072","DOIUrl":"https://doi.org/10.1111/febs.70072","url":null,"abstract":"Abnormal functions of N-methyl-D-aspartate receptors (NMDARs) are associated with many brain disorders, making them primary targets for drug discovery. We show that natural aminosterols inhibit the NMDAR-mediated increase of intracellular calcium ions in cultured primary neurons and neuroblastoma cells. Structural comparison with known NMDAR-negative allosteric modulators, such as pregnanolone-sulfate-2 (PAS), raises the hypothesis that aminosterols have the same mechanism of action. Fluorescence resonance energy transfer (FRET) measurements using labeled NMDAR and the labeled aminosterol trodusquemine (TRO) indicate close spatial proximity, likely arising from binding. Other indirect yet plausible mechanisms for NMDAR inhibition by TRO were excluded. Electrophysiological patch clamp measurements on primary neurons indicate that pre-incubated TRO inhibits NMDA-induced ion currents with a IC50 of 5 nm. Inhibition is observed only after cell membrane pre-adsorption, indicating accessibility to NMDAR from the cell membrane and binding to the transmembrane domains (TMDs) and TMD-ligand-binding domain (LBD) linkers, similarly to PAS. The TRO IC50 is 5000-fold higher than that of PAS and 20-16 000 times higher than those of other inhibitors binding to TMD/TMD-LBD regions, identifying aminosterols as promising and potent NMDAR modulators.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694799","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}

引用次数: 0

Mammalian TatD DNase domain containing 1 (TATDN1) is a proteostasis-responsive gene with roles in ventricular structure and neuromuscular function. 哺乳动物 TatD DNase domain containing 1（TATDN1）是一种蛋白稳态响应基因，在心室结构和神经肌肉功能中发挥作用。

The FEBS journal Pub Date : 2025-03-23 DOI: 10.1111/febs.70077

Gisel Barés, Aida Beà, Anna Sancho-Balsells, Juan G Valero, David Aluja, Javier Inserte, Sandra García-Carpi, Elisabet Miró-Casas, Sara Borràs-Pernas, Sara Hernández, Ana Martínez-Val, Jesper V Olsen, Francesc Tebar, Xavier Cañas, Joan X Comella, Patricia Pérez-Galán, Marisol Ruiz-Meana, Albert Giralt, Marta Llovera, Daniel Sanchis

{"title":"Mammalian TatD DNase domain containing 1 (TATDN1) is a proteostasis-responsive gene with roles in ventricular structure and neuromuscular function.","authors":"Gisel Barés, Aida Beà, Anna Sancho-Balsells, Juan G Valero, David Aluja, Javier Inserte, Sandra García-Carpi, Elisabet Miró-Casas, Sara Borràs-Pernas, Sara Hernández, Ana Martínez-Val, Jesper V Olsen, Francesc Tebar, Xavier Cañas, Joan X Comella, Patricia Pérez-Galán, Marisol Ruiz-Meana, Albert Giralt, Marta Llovera, Daniel Sanchis","doi":"10.1111/febs.70077","DOIUrl":"https://doi.org/10.1111/febs.70077","url":null,"abstract":"The characterization of highly conserved but poorly understood genes often reveals unexpected biological roles, advancing our understanding of disease mechanisms. One such gene is Mammalian TatD DNase domain containing 1 (Tatdn1), the mammalian homolog of bacterial Twin-arginine translocation D (TatD), a protein proposed to have roles either in DNA degradation or protein quality control in unicellular organisms. Despite its association with different pathologies, including several cancer types and cardiovascular diseases, the role of TATDN1 in mammals remains unexplored. Here, we demonstrate that Tatdn1 encodes a cytoplasmic protein that does not participate in DNA degradation but is upregulated in cells under proteostasis stress. Tatdn1-deficient mice exhibit dysregulated expression of genes involved in membrane and extracellular protein biology, along with mild dilated cardiomyopathy and impaired motor coordination. These findings identify TATDN1 as a key player in cytosolic processes linked to protein homeostasis, with significant physiological implications for cardiac and neurological function.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695037","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}

引用次数: 0

An adamantane-based ligand as a novel chemical tool for thermosensory TRPM8 channel therapeutic modulation. 以金刚烷为基础的配体是一种新型化学工具，可用于热感 TRPM8 通道的治疗调节。

The FEBS journal Pub Date : 2025-03-23 DOI: 10.1111/febs.70065

Angela Lamberti, Silvio Aprile, David Cabañero, Fabio Travagin, Laura Butron, Gregorio Fernández-Ballester, Gian Cesare Tron, Asia Fernández-Carvajal, Antonio Ferrer-Montiel, Ubaldina Galli

{"title":"An adamantane-based ligand as a novel chemical tool for thermosensory TRPM8 channel therapeutic modulation.","authors":"Angela Lamberti, Silvio Aprile, David Cabañero, Fabio Travagin, Laura Butron, Gregorio Fernández-Ballester, Gian Cesare Tron, Asia Fernández-Carvajal, Antonio Ferrer-Montiel, Ubaldina Galli","doi":"10.1111/febs.70065","DOIUrl":"https://doi.org/10.1111/febs.70065","url":null,"abstract":"Transient receptor potential cation channel subfamily M member 8 (TRPM8) is a nonselective thermosensory cation channel expressed in peripheral nociceptor terminals where it transduces cold temperatures and cooling agents such as menthol. TRPM8 dysfunction has been involved in disabling sensory symptoms, such as cold allodynia. In addition, its widespread expression has signaled this channel as a pivotal therapeutic target for a variety of diseases, from peripheral neuropathies to cancer. Thus, the design and therapeutic validation of TRPM8 antagonists is an important endeavor in biomedicine. To address this, we used the multicomponent Passerini and Ugi reactions to design a novel family of TRPM8 modulators using as a scaffold the adamantane ring that exhibits drug-like qualities. These green chemistry transformations are ideal for the fast synthesis of libraries of medium complexity with minimal or no generation of waste by-products. We report the identification of a family of TRPM8 agonists and antagonists. Among them, 2-((3S,5S,7S)-adamantan-1-ylamino)-2-oxoethyl [1,1'-biphenyl]-2-carboxylate (referred to as compound 23) is a potent and selective antagonist that reduces TRPM8-induced neuronal firing in primary nociceptor cultures. Compound 23 exhibits 10-fold higher potency for human TRPM8 (hTRPM8) than for hTRPV1 and hTRPA1 channels. Notably, local administration of compound 23 significantly attenuated oxaliplatin-induced peripheral cold allodynia by modulating epidermal TRPM8 sensory endings. Thus, α-acyloxy carboxamide 23 appears as a promising therapeutic candidate to topically intervene on TRPM8-mediated peripheral neuropathies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695035","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}

引用次数: 0

The complete absence of cytoplasmic γ-actin results in no discernible phenotype in mice or primary fibroblasts. 细胞质 γ-肌动蛋白的完全缺失不会导致小鼠或原代成纤维细胞出现明显的表型。

The FEBS journal Pub Date : 2025-03-20 DOI: 10.1111/febs.70075

Lauren J Sundby, Katelin M Hawbaker, Jacob Powers, William M Southern, Erynn E Johnson, Xiaobai Patrinostro, Benjamin J Perrin, James M Ervasti

引用次数: 0

Estrogen in the brain - neuroestrogens can regulate appetite and influence body weight. 脑神经中的雌激素可以调节食欲和影响体重。

The FEBS journal Pub Date : 2025-03-20 DOI: 10.1111/febs.70078

Tram Thi-Ngoc Nguyen, Yoshiaki Kanemoto, Tomohiro Kurokawa, Shigeaki Kato

引用次数: 0

The N6-methyladenosine reader IGF2BP3 promotes bladder cancer progression through enhancing HSP90AB1 expression. n6 -甲基腺苷解读子IGF2BP3通过增强HSP90AB1的表达促进膀胱癌的进展。

The FEBS journal Pub Date : 2025-03-19 DOI: 10.1111/febs.70068

Xiaoqing Chen, Wenli Diao, Xinyue Guo, Wenmin Cao, Yang Yang, Tianlei Xie, Wei Chen, Lin Yang, Qing Zhang, Meng Ding, Hongqian Guo

{"title":"The N6-methyladenosine reader IGF2BP3 promotes bladder cancer progression through enhancing HSP90AB1 expression.","authors":"Xiaoqing Chen, Wenli Diao, Xinyue Guo, Wenmin Cao, Yang Yang, Tianlei Xie, Wei Chen, Lin Yang, Qing Zhang, Meng Ding, Hongqian Guo","doi":"10.1111/febs.70068","DOIUrl":"https://doi.org/10.1111/febs.70068","url":null,"abstract":"N6-methyladenosine (m6A) is the most abundant RNA modification in mammalian cells, and has emerged as an important player in tumour development through post-transcriptional gene regulation. In this study, we found that the m6A reader protein IGF2BP3 was the most upregulated m6A modifier in bladder cancer through the proteomic analysis of 17 pairs of human bladder cancer tissues and adjacent normal bladder tissues, for which the expression was also positively correlated with higher tumour stage and poorer prognosis. In vitro and in vivo assays demonstrated the powerful oncogenic function of IGF2BP3 in bladder cancer. Further combined analyses of RNA-sequencing, m6A-sequencing, and RIP (RNA Binding Protein Immunoprecipitation)-sequencing, as well as site-directed mutagenesis assays and RIP-qPCR identified m6A-tagged HSP90AB1 mRNA as a direct target of IGF2BP3. Mechanistically, through in vitro and in vivo assays, as well as clinical sample analysis, we demonstrated that IGF2BP3 modulated the expression of HSP90AB1 in an m6A modification-dependent manner, thus activating the PI3K/AKT-signaling pathway, and promoting the development of bladder cancer. Collectively, our study highlights the critical role of the IGF2BP3-HSP90AB1-signaling axis in bladder cancer progression, which may serve as a promising therapeutic approach for bladder cancer.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660184","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}

引用次数: 0

Tudor staphylococcal nuclease (Tudor-SN) regulates activation of quiescent hepatic stellate cells. Tudor葡萄球菌核酸酶（Tudor- sn）调节静止的肝星状细胞的激活。

The FEBS journal Pub Date : 2025-03-17 DOI: 10.1111/febs.70073

Baoxin Qian, Yan Zhao, Xinxin Zhang, Chunyan Zhao, Xiaoteng Cui, Fengmei Wang, Xiang Jing, Lin Ge, Zhi Yao, Xingjie Gao, Jie Yang

{"title":"Tudor staphylococcal nuclease (Tudor-SN) regulates activation of quiescent hepatic stellate cells.","authors":"Baoxin Qian, Yan Zhao, Xinxin Zhang, Chunyan Zhao, Xiaoteng Cui, Fengmei Wang, Xiang Jing, Lin Ge, Zhi Yao, Xingjie Gao, Jie Yang","doi":"10.1111/febs.70073","DOIUrl":"https://doi.org/10.1111/febs.70073","url":null,"abstract":"Several liver diseases have been associated with the Tudor staphylococcal nuclease (Tudor-SN) protein. Our previous results demonstrated that, in comparison to wild-type (WT) mice, systemic overexpression of Tudor-SN in transgenic (Tg) mice (Tudor-SN-Tg) ameliorates obesity-induced insulin resistance and hepatic steatosis. In this study, we observed an inverse correlation in the expression levels of Tudor-SN and profibrogenic factors, such as alpha-smooth muscle actin (α-SMA) and collagen alpha-1(I) chain (COL1A1), in liver tissue samples between Tudor-SN-Tg and WT mice. The correlation was further validated in hepatic fibrotic tissues from patients with cirrhosis and fibrosis. Utilizing a carbon tetrachloride (CCl4)-induced hepatic fibrosis model, we observed that Tudor-SN attenuated hepatic fibrosis in mice. Tudor-SN was abundantly expressed in hepatic stellate cells (HSCs). In the Tudor-SN-Tg group, primary HSCs showed stellate-like morphology as well as reduced in vitro proliferation and chemotactic ability compared to the WT group. Pseudotime series analysis of HSCs further showed the role of Tudor-SN during the dynamic evolution of HSC activation. Reduced Tudor-SN expression facilitated the in vitro activation of LX-2 cells. Furthermore, primary HSC cells from WT and Tudor-SN knockout (KO) mice were isolated for RNA-sequencing analysis. The findings suggested that Tudor-SN may regulate the activation of primary HSCs by influencing lipid metabolism, translation initiation, immune response, and the extracellular matrix. In summary, we identified Tudor-SN as a newly identified regulator involved in the transition of quiescent HSCs to activated states, shedding light on the antifibrotic impact of Tudor-SN expression in the development of hepatic fibrosis.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652840","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}

引用次数: 0

Enhancing therapeutic efficacy through degradation of endogenous extracellular matrix in primary breast tumor spheroids. 通过降解内源性细胞外基质提高原发性乳腺肿瘤球状体的治疗效果。

The FEBS journal Pub Date : 2025-03-17 DOI: 10.1111/febs.70069

Alessandra Lo Cicero, Simona Campora, Gabriele Lo Buglio, Paolo Cinà, Margot Lo Pinto, Simone Dario Scilabra, Giulio Ghersi

{"title":"Enhancing therapeutic efficacy through degradation of endogenous extracellular matrix in primary breast tumor spheroids.","authors":"Alessandra Lo Cicero, Simona Campora, Gabriele Lo Buglio, Paolo Cinà, Margot Lo Pinto, Simone Dario Scilabra, Giulio Ghersi","doi":"10.1111/febs.70069","DOIUrl":"https://doi.org/10.1111/febs.70069","url":null,"abstract":"Solid tumors have a complex extracellular matrix (ECM) that significantly affects tumor behavior and response to therapy. Understanding the ECM's role is crucial for advancing cancer research and treatment. This study established an in vitro model using primary cells isolated from a rat breast tumor to generate three-dimensional spheroids. Monolayer cells and spheroid cultures exhibited different protein expression patterns, with primary tumor spheroids presenting an increased level of ECM-related proteins and a more complex extracellular environment. Furthermore, spheroids produce endogenous collagen type I matrix, which is the main component of the tumoral ECM. This matrix is arranged predominantly around the 3D structure, mimicking the conditions of solid tumors. Treatments with recombinant collagenases class II (acting on the linear collagen region) and class I (acting on the 3D-helix region) completely degrade collagen within the spheroid structure. Collagenase pretreatment enhances the accessibility of the anticancer drug doxorubicin to penetrate the core of spheroids and sensitize them to doxorubicin-induced cytotoxicity. Our findings highlight the importance of overcoming drug resistance in breast cancer by targeting the ECM and proposing a novel strategy for improving therapeutic outcomes in solid tumors. By employing a three-dimensional spheroid model, with an endogenous ECM, we can offer more relevant insights into tumor biology and treatment responses.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652812","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}

引用次数: 0