Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.808.sp3
S. Lee
one their key Herein toxicity is defined as all the pathological changes that from accumulation, mis-localization, and/or oligomerization of disease-associated toxic proteins such as α-synuclein in PD, polyglutamine (polyQ)-containing proteins in polyQ diseases (e.g., HD), and dipeptide repeat proteins and TDP-43 in ALS. Conventional understanding of protein toxicity is that protein toxicity simply reflects the amount of accumulated toxic proteins. For this our challenges done so far against protein toxicity have been based on a simple strategy of reducing the amount of toxic proteins. However, the exact nature of protein toxicity appears to be much more complex than we have conceived, and thus new paradigm for understanding protein toxicity is highly demanded. In this talk, I will present our current efforts to understand exact nature of proteotoxicity in neurodegenerative diseases and potential solutions that can effectively control proteotoxicity, named as protein dynamics-based control of proteotoxicity. I will tell you about our recent study unveiling cellular intrinsic mechanisms regulating nucleocytoplasmic transport of TDP-43 in neurons. Method We used Drosophila as a primary model to study intrinsic regulatory mechanisms underlying nucleocytoplasmic transport of TDP-43. We used various experimental techniques, such as genetic analyses, immunohistochemistry, behavioral analyses, neuronal imaging, and FRAP. Results and discussion Dysregulation of protein localization, often observed in various neurodegenerative diseases, impairs functionality of the protein, alters the pool of its interactors, or both, thereby leading to cellular toxicity. TDP-43, one of well-characterized disease-associated proteins in Lou Gehrig’s disease, are known to translocate from the nucleus to the cytoplasm in the disease condition, which is considered as a hallmark of the disease. Thus, unveiling the regulatory mechanism of intracellular localization of TDP-43 is very important to better understand the pathogenesis of Lou Gehrig’s disease. However, still our understanding on the neuronal intrinsic program regulating the intracellular localization of TDP-43 remains mostly unclear. Interestingly, we observed that the intracellular localization of TDP-43 dynamically changes even in normal condition of a specific neuronal cell type, named Drosophila classIV da sensory neurons, along development. We first identified intracellular Ca2+ level to be critical for the translocation of TDP-43 between the nucleus and the cytoplasm. Additionally, through fluorescence recovery after photobleaching (FRAP) imaging analyses, we found that the nuclear entry of TDP-43 is critically controlled by intracellular Ca2+ level. Further genetic analyses identified Calpain and Importin a3 as mediators of Ca2+-dependent control of TDP-43 translocation in classIV da sensory neurons. Finally, by modulating Ca2+-Calpain-Importing a3 pathway, we could significantly modify the locomotive phenotyp
在这里，毒性被定义为疾病相关毒性蛋白的积累、错误定位和/或寡聚化引起的所有病理变化，如PD中的α-突触核蛋白、多q疾病(如HD)中的含聚谷氨酰胺(polyQ)蛋白、ALS中的二肽重复蛋白和TDP-43。对蛋白质毒性的传统理解是，蛋白质毒性仅仅反映了累积的有毒蛋白质的数量。为此，我们迄今为止针对蛋白质毒性所做的挑战是基于一种简单的策略，即减少有毒蛋白质的数量。然而，蛋白质毒性的确切性质似乎比我们想象的要复杂得多，因此高度需要理解蛋白质毒性的新范式。在这次演讲中，我将介绍我们目前的努力，以了解神经退行性疾病中蛋白质毒性的确切性质，以及可以有效控制蛋白质毒性的潜在解决方案，称为基于蛋白质动力学的蛋白质毒性控制。我将向大家介绍我们最近的研究，揭示了神经元中调节TDP-43核质转运的细胞内在机制。方法以果蝇为主要动物模型，研究TDP-43核质转运的内在调控机制。我们使用了各种实验技术，如遗传分析、免疫组织化学、行为分析、神经元成像和FRAP。在各种神经退行性疾病中经常观察到的蛋白质定位失调，会损害蛋白质的功能，改变其相互作用物的池，或两者兼而有之，从而导致细胞毒性。TDP-43是Lou Gehrig病中特征明确的疾病相关蛋白之一，已知在疾病状态下从细胞核转移到细胞质，这被认为是该疾病的标志。因此，揭示TDP-43在细胞内定位的调控机制，对于更好地了解Lou Gehrig病的发病机制具有重要意义。然而，我们对调控TDP-43细胞内定位的神经元内在程序的理解仍不甚清楚。有趣的是，我们观察到TDP-43的细胞内定位即使在正常情况下也会随着特定神经元类型的发育而动态变化，称为果蝇分类da感觉神经元。我们首先发现细胞内Ca2+水平对于TDP-43在细胞核和细胞质之间的易位至关重要。此外，通过光漂白后荧光恢复(FRAP)成像分析，我们发现TDP-43的核进入受到细胞内Ca2+水平的严格控制。进一步的遗传分析发现Calpain和Importin a3是Ca2+依赖性控制TDP-43易位的介质。最后，通过调节Ca2+- calpain - importa3通路，我们可以显著改变Lou Gehrig病动物模型中显示的运动表型。尽管我们很清楚TDP-43的异常易位与Lou Gehrig病密切相关，但迄今为止，我们对其异常易位在疾病早期是如何开始的了解有限。我们的发现为了解调控TDP-43细胞内定位的神经元内在程序提供了宝贵的线索，该程序的改变可能导致TDP-43致病性易位的启动。这项研究使其他研究人员能够考虑基于蛋白质动力学的蛋白质毒性控制作为对抗神经退行性疾病的新策略，除了他们的传统方法(有毒蛋白质的定量控制)。细胞衰老是指细胞在端粒功能障碍、DNA损伤、致癌基因表达等内源性和外源性刺激下停止增殖的过程(Di Micco et al, 2021)。衰老细胞释放衰老相关分泌表型(senescence associated secretory phenotype, SASP)，将邻近的正常细胞转变为衰老细胞。由于衰老细胞的积累损害了组织的修复和功能，细胞衰老最终导致组织老化和与衰老相关的慢性疾病，包括2型糖尿病。因此，杀死衰老细胞(senolytics)或将衰老细胞逆转为年轻细胞(senomorphics)可以预防或缓解衰老和与衰老相关的疾病(Niedernhofer和Robbins 2018)。最近，先前的研究表明，脂肪组织中衰老细胞的减少可以减轻高脂肪饮食(HFD)喂养的肥胖小鼠的胰岛素抵抗，这表明靶向脂肪组织中的细胞衰老可能是2型糖尿病的潜在治疗方法(Smith et al 2021)。然而，目前尚无临床有效的衰老治疗方法。在我们的研究中，我们旨在寻找一种新的治疗脂肪组织老化和胰岛素抵抗的方法。 方法采用细胞毒性法和衰老相关β -半乳糖苷酶染色法分别检测了2150种临床可用化合物对人真皮成纤维细胞(HDF)的抗衰老或促衰老作用。在发现的10种化合物中，有一种化合物对HDF具有抗衰老或促衰老的作用，其中一种化合物还能延缓人前脂肪细胞和3T3-L1脂肪细胞的衰老。研究了新型抗衰老剂(HT)对高脂饮食喂养的肥胖小鼠和老年小鼠脂肪组织老化和胰岛素敏感性的影响。结果和讨论HT减轻了肥胖小鼠的体重增加和脂肪量，即使它不影响食物摄入量。它减少了肥胖小鼠和老年小鼠的脂肪组织老化，随后减少了大尺寸脂肪细胞、冠状结构的数量和炎症细胞因子的水平。HT改善了血糖控制和胰岛素抵抗。它也减少了体外人体皮下脂肪组织的脂肪组织老化。因此，这些结果表明，我们已经发现了一种新的抗衰老药物，可能是治疗2型糖尿病的潜在药物。目的:由于衰老或病理条件导致的肌肉萎缩，导致生活质量下降，发病率增加，死亡率增加。为了防止肌肉萎缩和无力，许多研究工作都集中在运动模拟物的开发上。在这项研究中，我们通过筛选过氧化物酶体增殖物激活受体γ辅助激活因子α (PGC-1α)诱诱剂确定了吲哚洛芬，并报道了其作为肌肉萎缩药物的潜力。方法采用免疫印迹法观察吲哚洛芬对地塞米松诱导小鼠萎缩及3-磷酸肌醇依赖蛋白激酶-1 (PDK1)缺失C2C12肌管的影响，检测肌球蛋白重链蛋白、合成代谢相关蛋白和氧化代谢相关蛋白的表达水平。用吲哚洛芬(2 mg/kg体重)灌胃治疗年轻、年老和废用性肌萎缩小鼠。评估体重、肌肉重量、握力、等距力和肌肉组织学。通过免疫印迹或免疫染色分析肌肉质量相关蛋白和功能相关蛋白的表达水平。结果在幼龄(3月龄)和老年(22月龄)小鼠中，吲哚洛芬治疗激活了氧化代谢相关酶，导致肌肉质量增加。动物模型和肌肉细胞的机制分析表明，吲哚洛芬治疗诱导AKT/p70S6激酶(S6K)和amp活化蛋白激酶(AMPK)的顺序激活，从而分别促进蛋白质合成和PGC-1α的诱导。结构预测分析发现PDK1是indoprofen的靶点，事实上，短期使用indoprofen可以激活肌肉细胞中的PDK1/AKT/S6K通路。与这一发现一致，PDK1抑制消除了吲哚洛芬诱导的AKT/S6K激活和肥厚反应。结论吲哚洛芬通过顺序激活PDK1/AKT/S6K和AMPK/ pfc -1α来促进骨骼肌质量。综上所述，我们的研究结果表明，吲哚洛芬是一种潜在的药物，可以预防与衰老或肌肉疾病相关的肌肉萎缩和无力。
{"title":"Protein dynamics-based control of proteotoxicity in neurodegenerative diseases","authors":"S. Lee","doi":"10.4017/gt.2022.21.s.808.sp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.808.sp3","url":null,"abstract":"one their key Herein toxicity is defined as all the pathological changes that from accumulation, mis-localization, and/or oligomerization of disease-associated toxic proteins such as α-synuclein in PD, polyglutamine (polyQ)-containing proteins in polyQ diseases (e.g., HD), and dipeptide repeat proteins and TDP-43 in ALS. Conventional understanding of protein toxicity is that protein toxicity simply reflects the amount of accumulated toxic proteins. For this our challenges done so far against protein toxicity have been based on a simple strategy of reducing the amount of toxic proteins. However, the exact nature of protein toxicity appears to be much more complex than we have conceived, and thus new paradigm for understanding protein toxicity is highly demanded. In this talk, I will present our current efforts to understand exact nature of proteotoxicity in neurodegenerative diseases and potential solutions that can effectively control proteotoxicity, named as protein dynamics-based control of proteotoxicity. I will tell you about our recent study unveiling cellular intrinsic mechanisms regulating nucleocytoplasmic transport of TDP-43 in neurons. Method We used Drosophila as a primary model to study intrinsic regulatory mechanisms underlying nucleocytoplasmic transport of TDP-43. We used various experimental techniques, such as genetic analyses, immunohistochemistry, behavioral analyses, neuronal imaging, and FRAP. Results and discussion Dysregulation of protein localization, often observed in various neurodegenerative diseases, impairs functionality of the protein, alters the pool of its interactors, or both, thereby leading to cellular toxicity. TDP-43, one of well-characterized disease-associated proteins in Lou Gehrig’s disease, are known to translocate from the nucleus to the cytoplasm in the disease condition, which is considered as a hallmark of the disease. Thus, unveiling the regulatory mechanism of intracellular localization of TDP-43 is very important to better understand the pathogenesis of Lou Gehrig’s disease. However, still our understanding on the neuronal intrinsic program regulating the intracellular localization of TDP-43 remains mostly unclear. Interestingly, we observed that the intracellular localization of TDP-43 dynamically changes even in normal condition of a specific neuronal cell type, named Drosophila classIV da sensory neurons, along development. We first identified intracellular Ca2+ level to be critical for the translocation of TDP-43 between the nucleus and the cytoplasm. Additionally, through fluorescence recovery after photobleaching (FRAP) imaging analyses, we found that the nuclear entry of TDP-43 is critically controlled by intracellular Ca2+ level. Further genetic analyses identified Calpain and Importin a3 as mediators of Ca2+-dependent control of TDP-43 translocation in classIV da sensory neurons. Finally, by modulating Ca2+-Calpain-Importing a3 pathway, we could significantly modify the locomotive phenotyp","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48929666","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.530.2.sp1
C. Huisman, H. Kort
{"title":"Available technology applications to support sleep for people with dementia and their informal caregiver","authors":"C. Huisman, H. Kort","doi":"10.4017/gt.2022.21.s.530.2.sp1","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.530.2.sp1","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49494876","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.575.opp4
G. Mois, S. Shende, R. Mudar, D. Myers, W. A. Rogers
), user friendly (e.g., large fonts, labeled buttons), supportive of social interactions (e.g., diverse engaging event content), and supportive of users’ privacy (e.g., HIPPA Compliant). They identified potential benefits of using the platform for staff applications such as trainings and administrative tasks (e.g., review and edit documents). Most challenges noted by participants were related to the introduction of a new platform: motivating people to adopt something new and potential staff burden to replace the platform they are currently using. Our research provides key insights pertaining to the potential benefits and concerns of implementing of a video conferencing platform to HCBOs. Our findings informed the design features needed to support delivery of social engagement programs by HCBOs. Furthermore, these insights informed development of a dashboard aimed to help organize and assist with the delivery of social engagement interventions.
{"title":"Supporting home- and community-based organization activities through a customized videoconferencing platform","authors":"G. Mois, S. Shende, R. Mudar, D. Myers, W. A. Rogers","doi":"10.4017/gt.2022.21.s.575.opp4","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.575.opp4","url":null,"abstract":"), user friendly (e.g., large fonts, labeled buttons), supportive of social interactions (e.g., diverse engaging event content), and supportive of users’ privacy (e.g., HIPPA Compliant). They identified potential benefits of using the platform for staff applications such as trainings and administrative tasks (e.g., review and edit documents). Most challenges noted by participants were related to the introduction of a new platform: motivating people to adopt something new and potential staff burden to replace the platform they are currently using. Our research provides key insights pertaining to the potential benefits and concerns of implementing of a video conferencing platform to HCBOs. Our findings informed the design features needed to support delivery of social engagement programs by HCBOs. Furthermore, these insights informed development of a dashboard aimed to help organize and assist with the delivery of social engagement interventions.","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45576969","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.673.opp4
T. Yamaguchi, Y. Saito, F. Nakamura, C. Maeda
{"title":"Can a communication robot contribute to the good relationship between the elderly with dementia and the staff?","authors":"T. Yamaguchi, Y. Saito, F. Nakamura, C. Maeda","doi":"10.4017/gt.2022.21.s.673.opp4","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.673.opp4","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42592986","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.536.opp3
J. Je, W. Choi
{"title":"Potential negative effects of neuromuscular electrical stimulation: Does it affect static balance and proprioception?","authors":"J. Je, W. Choi","doi":"10.4017/gt.2022.21.s.536.opp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.536.opp3","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48258811","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.527.5.sp3
W. Choi, S. Lee, K. Lim
{"title":"Biomechanical effects of a mechanical lift on the risk of low back injury during transfers from bed to wheelchair","authors":"W. Choi, S. Lee, K. Lim","doi":"10.4017/gt.2022.21.s.527.5.sp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.527.5.sp3","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47864083","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.506.opp3
J. Park, S. Kim, W. Choi
{"title":"Muscle activation pattern to distinguish balance recovery from falls at loss of balance","authors":"J. Park, S. Kim, W. Choi","doi":"10.4017/gt.2022.21.s.506.opp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.506.opp3","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43903701","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.822.3.sp3
S. Wang, D. Kang, Y. Um, Nak-Young Kim, H. Lim
{"title":"Plasma oligomeric beta-amyloid is associated with cerebral beta-amyloid deposition in cognitively normal older adults","authors":"S. Wang, D. Kang, Y. Um, Nak-Young Kim, H. Lim","doi":"10.4017/gt.2022.21.s.822.3.sp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.822.3.sp3","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44301213","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.527.3.sp3
K. Park, H. Ryu, J. Kim, J. Lee, Y. Lee
{"title":"Analysis of social value for nursing robots with the estimates of demand functions","authors":"K. Park, H. Ryu, J. Kim, J. Lee, Y. Lee","doi":"10.4017/gt.2022.21.s.527.3.sp3","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.527.3.sp3","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43498483","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}
Pub Date : 2022-10-23DOI: 10.4017/gt.2022.21.s.524.pp1
C. M. B. Ho, Jirka Hana, S. Park
{"title":"IoT based health monitoring system - Recent trends and directions","authors":"C. M. B. Ho, Jirka Hana, S. Park","doi":"10.4017/gt.2022.21.s.524.pp1","DOIUrl":"https://doi.org/10.4017/gt.2022.21.s.524.pp1","url":null,"abstract":"","PeriodicalId":38859,"journal":{"name":"Gerontechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44501515","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}
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