MedComm最新文献

{"title":"Remodeling tumor-associated macrophage for anti-cancer effects by rational design of irreversible inhibition of mitogen-activated protein kinase-activated protein kinase 2","authors":"Danyi Wang,&nbsp;Deqiao Sun,&nbsp;Xiaoyan Wang,&nbsp;Xia Peng,&nbsp;Yinchun Ji,&nbsp;Lu Tang,&nbsp;Qichang He,&nbsp;Danqi Chen,&nbsp;Ye Yang,&nbsp;Xuan Zhou,&nbsp;Bing Xiong,&nbsp;Jing Ai","doi":"10.1002/mco2.634","DOIUrl":"10.1002/mco2.634","url":null,"abstract":"<p>Mitogen-activated protein kinase-activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti-cancer therapies. The limitations of ATP-competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance. Investigating MK2's kinase domain led to the identification of a unique cysteine residue, enabling the creation of targeted covalent inhibitors. Compound <b>11</b> was developed, demonstrating robust MK2 inhibition (IC₅₀= 2.3 nM) and high selectivity. It binds irreversibly to MK2, achieving prolonged signal suppression and reducing pathological inflammatory cytokines in macrophages. Furthermore, compound <b>11</b> or MK2 knockdown can inhibit the tumor-promoting macrophage M2 phenotype in vitro and in vivo. In macrophage-rich tumor model, compound <b>11</b> notably slowed growth in a dose-dependent manner. These findings support MK2 as a promising anticancer target, especially relevant in cancers fueled by inflammation or dominated by macrophages, and provide compound <b>11</b> serving as an invaluable chemical tool for exploring MK2's functions.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases","authors":"Lan-Ting Feng,&nbsp;Zhi-Nan Chen,&nbsp;Huijie Bian","doi":"10.1002/mco2.649","DOIUrl":"10.1002/mco2.649","url":null,"abstract":"<p>Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell–cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell–cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposome-based in situ antigen-modification strategy for “universal” T-cell-receptor engineered T cell in cancer immunotherapy","authors":"Qin Wang,&nbsp;Rui Peng,&nbsp;Haoyue Qi,&nbsp;Ruihan Xu,&nbsp;Wanmin Liu,&nbsp;Fanyan Meng,&nbsp;Shiyao Du,&nbsp;Lixia Yu,&nbsp;Jia Wei,&nbsp;Fangcen Liu,&nbsp;Rutian Li","doi":"10.1002/mco2.618","DOIUrl":"10.1002/mco2.618","url":null,"abstract":"<p>T-cell receptor (TCR) engineered T-cell therapy, unlike chimeric antigen receptor T-cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR-T-cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges. Thus, we aimed to establish a novel “universal” TCR-T “artificial antigen expression” technique that involves the delivery of the antigen to tumor cells using DSPE-PEG-NY-ESO-1^157-165 liposomes (NY-ESO-1 Lips) to express TCR-T-cell-specific recognition targets. In vitro as well as in vivo studies revealed that they could accumulate efficiently in the tumor area and deliver target antigens to activate the tumor-specific cytotoxic T-cell immune response. NY-ESO-1 TCR-T therapy, when used in combination, dramatically curbed tumor progression and extended the longevity of mice. Additionally, PD-1 blockage enhanced the therapeutic effect of the aforementioned therapy. In conclusion, NY-ESO-1 Lips “cursed” tumor cells by enabling antigenic target expression on their surface. This innovative technique presents a groundbreaking approach for the widespread utilization of TCR-T in solid tumor treatment.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene editing therapy for cardiovascular diseases","authors":"Xinyu Wu,&nbsp;Jie Yang,&nbsp;Jiayao Zhang,&nbsp;Yuning Song","doi":"10.1002/mco2.639","DOIUrl":"https://doi.org/10.1002/mco2.639","url":null,"abstract":"<p>The development of gene editing tools has been a significant area of research in the life sciences for nearly 30 years. These tools have been widely utilized in disease detection and mechanism research. In the new century, they have shown potential in addressing various scientific challenges and saving lives through gene editing therapies, particularly in combating cardiovascular disease (CVD). The rapid advancement of gene editing therapies has provided optimism for CVD patients. The progress of gene editing therapy for CVDs is a comprehensive reflection of the practical implementation of gene editing technology in both clinical and basic research settings, as well as the steady advancement of research and treatment of CVDs. This article provides an overview of the commonly utilized DNA-targeted gene editing tools developed thus far, with a specific focus on the application of these tools, particularly the clustered regularly interspaced short palindromic repeat/CRISPR-associated genes (Cas) (CRISPR/Cas) system, in CVD gene editing therapy. It also delves into the challenges and limitations of current gene editing therapies, while summarizing ongoing research and clinical trials related to CVD. The aim is to facilitate further exploration by relevant researchers by summarizing the successful applications of gene editing tools in the field of CVD.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type-I-interferon-responsive microglia: participates in cerebral development and disease","authors":"Hua Guo,&nbsp;Liyan Miao,&nbsp;Fangfang Zhou","doi":"10.1002/mco2.629","DOIUrl":"https://doi.org/10.1002/mco2.629","url":null,"abstract":"<p>A recent study conducted by Escoubas et al. published in <i>Cell</i> identified a population of type I interferon (IFN-I)-responsive microglia (IRMs) in the developing murine cortex.<span>¹</span> The study demonstrated a physiological role for IFN-I-driven whole neuronal microglial phagocytosis in brain development and function.</p><p>Microglia, specialized macrophages residing in the brain parenchyma, play a crucial role in the clearance of cellular debris, phagocytosis of invading pathogens, and modulation of neural circuit development. Microglia exhibit heterogeneity and spatial localization in both structure and function. Dysfunctions within distinct subsets of microglia are closely associated with the onset and progression of various diseases, yet the underlying mechanisms remain incompletely elucidated. Continuous advancements in sequencing technology and spatial omics have provided powerful tools for unraveling distinct microglial states. For example, A recent study employed single-nucleus RNA sequencing and spatial transcriptomics to analyze the dorsolateral prefrontal cortex of female cynomolgus macaques exhibiting depression-like behavior in response to social stress, revealing that changes in gene expression, mostly in microglia, are associated with depression-like behavior.<span>²</span></p><p>In order to further investigate the characteristics of microglia subtypes and their roles in neural circuits, the author performed single-cell RNA sequencing on mouse cortical recovery phase cells. Interestingly, the sequencing results revealed a significant increase in the number of microglia expressing high levels of IFN-I response genes. These findings suggest that IRMs play a crucial role in neural circuit remodeling. The authors simultaneously employed multiple independent clustering markers to validate interferon-induced transmembrane protein 3 (IFITM3) as a specific marker for identifying IRMs.<span>¹</span> Subsequently, Escoubas et al. utilized IFITM3 to demonstrate the conservation of IFN-I responsive microglia during cortical development, which transiently appear and persist in various pathological conditions such as neurodegenerative diseases, brain tumors, and viral infections. This provides a novel avenue for investigating the mechanistic involvement of microglia in various disease traits; however, further validation is required to ascertain the specific mode of action.</p><p>The cerebral cortex is a layer of gray matter on the outer surface of the brain and comprises six primary layers, denoted L1–L6, each exhibiting distinct cellular composition and functions. During the investigation of the form and positioning of IRMs, the author observed that IRMs' morphology differed from the typical ramified structure seen in the majority of cortical microglia. Specifically, the subtype located at L4 displayed an elongated shape and had the potential migration towards L5.<span>³</span> L4/ L5 p","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital heart disease: types, pathophysiology, diagnosis, and treatment options","authors":"Xiao Meng,&nbsp;Ming Song,&nbsp;Kai Zhang,&nbsp;Weida Lu,&nbsp;Yunyi Li,&nbsp;Cheng Zhang,&nbsp;Yun Zhang","doi":"10.1002/mco2.631","DOIUrl":"https://doi.org/10.1002/mco2.631","url":null,"abstract":"<p>Congenital heart disease (CHD) is a structural abnormality of the heart and/or great vessels and patients with CHD are at an increased risks of various morbidities throughout their lives and reduced long-term survival. Eventually, CHD may result in various complications including heart failure, arrhythmias, stroke, pneumonia, and sudden death. Unfortunately, the exact etiology and pathophysiology of some CHD remain unclear. Although the quality of life and prognosis of patients with CHD have significantly improved following technological advancement, the influence of CHD is lifelong, especially in patients with complicated CHD. Thus, the management of CHD remains a challenge due to its high prevalence. Finally, there are some disagreements on CHD among international guidelines. In this review, we provide an update of the pathophysiology, diagnosis, and treatment in most common type of CHD, including patent foramen ovale, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, coarctation of the aorta, transposition of the great arteries, congenitally corrected transposition of the great arteries, coronary anomalies, left and right ventricular outflow tract obstruction, tetralogy of Fallot and Ebstein anomaly. In particular, we focus on what is known and what is unknown in these areas, aiming to improve the current understanding of various types of CHD.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 vaccine: recent advancements and future prospects","authors":"Li Xu,&nbsp;Min Li,&nbsp;Wu He","doi":"10.1002/mco2.646","DOIUrl":"https://doi.org/10.1002/mco2.646","url":null,"abstract":"<p>Nowadays, although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has been handled with long-term management globally, the virus strains keep continuous evolution in an uncertain direction. The newly emerged JN.1 dominated the globally circulating variants in a short time and resulted in increasing hospitalizations. Up to 2024, variant vaccines with the composition of XBB sub-lineage were available due to the coordinated efforts of developers and regulatory agencies. The development of updated vaccines is still needed and the regular availability of coronavirus disease 2019 (COVID-19) vaccines should be timely guaranteed. The current landscape of COVID-19 vaccines and the strategies for accelerating vaccine development and approval are reviewed. Proposals to enhance variants monitoring and the establishment of the strain recommendation mechanism are made. This review provides suggestions about platform technology designation and application, real-world data leveraging and modification to regulatory pathways both for the post-pandemic era of SARS-CoV-2 and for the future unknown pathogen pandemic.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptome dissecting the microenvironment remodeled by PD1 blockade combined with photodynamic therapy in a mouse model of oral carcinogenesis","authors":"Yunmei Dong,&nbsp;Kan Zeng,&nbsp;Ruixue Ai,&nbsp;Chengli Zhang,&nbsp;Fei Mao,&nbsp;Hongxia Dan,&nbsp;Xin Zeng,&nbsp;Ning Ji,&nbsp;Jing Li,&nbsp;Xin Jin,&nbsp;Qianming Chen,&nbsp;Yu Zhou,&nbsp;Taiwen Li","doi":"10.1002/mco2.636","DOIUrl":"10.1002/mco2.636","url":null,"abstract":"<p>Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4-nitroquinoline 1-oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single-cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor-promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor-promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment-associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermal growth factor receptor‑targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study","authors":"Peng Zhang,&nbsp;Xinxin Zhang,&nbsp;Jinyi Lang,&nbsp;Shaoxiong Wu,&nbsp;Yan Sun,&nbsp;Peiguo Wang,&nbsp;Sufang Qiu,&nbsp;Xiaodong Huang,&nbsp;Guoxin Ren,&nbsp;Kun Liu,&nbsp;Xiaojing Du,&nbsp;Shaowen Xiao,&nbsp;Zhongqiu Wang,&nbsp;Youliang Weng,&nbsp;Ye Zhang,&nbsp;Hang Zhou,&nbsp;Wenyong Tu,&nbsp;Chenping Zhang,&nbsp;Junlin Yi","doi":"10.1002/mco2.608","DOIUrl":"10.1002/mco2.608","url":null,"abstract":"<p>Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, <i>p</i> = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, <i>p</i> = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered CARD11–PIK3R3 T-cell therapies as weapons of cancer mass destruction","authors":"Wanlu Zhang,&nbsp;Min Wu,&nbsp;Yongye Huang","doi":"10.1002/mco2.628","DOIUrl":"10.1002/mco2.628","url":null,"abstract":"<p>Garcia et al. discover a novel immunotherapy approach by engineering naturally occurring mutations in therapeutic T cells to strongly elevate anti-tumor activity. The authors identify a gene fusion, CARD11–PIK3R3, to increase activator protein 1 and nuclear factor–κB signaling, interleukin-2 production, and tumor death in vitro and in vivo\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}