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749 results on '"Shi, Yanhong"'

1. The Apolipoprotein E neutralizing antibody inhibits SARS‐CoV‐2 infection by blocking cellular entry of lipoviral particles

Author

Cui, Qi, Jeyachandran, Arjit Vijey, Garcia, Gustavo, Qin, Chao, Zhou, Yu, Zhang, Mingzi, Wang, Cheng, Sun, Guihua, Liu, Wei, Zhou, Tao, Feng, Lizhao, Palmer, Chance, Li, Zhuo, Aziz, Adam, Gomperts, Brigitte N, Feng, Pinghui, Arumugaswami, Vaithilingaraja, and Shi, Yanhong

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Immunology, Coronaviruses, Infectious Diseases, Emerging Infectious Diseases, Immunization, Lung, Biotechnology, Coronaviruses Therapeutics and Interventions, Prevention, Vaccine Related, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, antiviral therapy for SARS-CoV-2, ApoE, ApoE neutralizing antibody, ApoE receptors, human iPSC-derived astrocytes, LDLR, antiviral therapy for SARS‐CoV‐2, human iPSC‐derived astrocytes
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent for coronavirus disease 2019 (COVID-19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS-CoV-2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS-CoV-2 for infection. Preincubation of SARS-CoV-2 with a neutralizing antibody specific to ApoE led to inhibition of SARS-CoV-2 infection. The ApoE neutralizing antibody efficiently blocked SARS-CoV-2 infection of human iPSC-derived astrocytes and air-liquid interface organoid models in addition to human ACE2-expressing HEK293T cells and Calu-3 lung cells. ApoE mediates SARS-CoV-2 entry through binding to its cellular receptors such as the low density lipoprotein receptor (LDLR). LDLR knockout or ApoE mutations at the receptor binding domain or an ApoE mimetic peptide reduced SARS-CoV-2 infection. Furthermore, we detected strong membrane LDLR expression on SARS-CoV-2 Spike-positive cells in human lung tissues, whereas no or low ACE2 expression was detected. This study provides a new paradigm for SARS-CoV-2 cellular entry through binding of ApoE on the lipoviral particles to host cell receptor(s). Moreover, this study suggests that ApoE neutralizing antibodies are promising antiviral therapies for COVID-19 by blocking entry of both parental virus and variants of concern.

Published
2023

2. Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model

Author

Liu, Zhenqing, Chao, Jianfei, Wang, Cheng, Sun, Guihua, Roeth, Daniel, Liu, Wei, Chen, Xianwei, Li, Li, Tian, E, Feng, Lizhao, Davtyan, Hayk, Blurton-Jones, Mathew, Kalkum, Markus, and Shi, Yanhong

Subjects
Biological Sciences, Genetics, Aging, Brain Disorders, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Neurodegenerative, Stem Cell Research, Neurosciences, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Neurological, Humans, Alleles, Astrocytes, Cell Proliferation, Clusterin, Genetic Predisposition to Disease, Induced Pluripotent Stem Cells, Oligodendrocyte Precursor Cells, Polymorphism, Single Nucleotide, Alzheimer’s disease, CLU, CLU SNP, CP: Neuroscience, CXCL10, astrocytes, iPSCs, inflammatory response, interferon response, myelination, oligodendrocyte progenitor cells, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The C allele of rs11136000 variant in the clusterin (CLU) gene represents the third strongest known genetic risk factor for late-onset Alzheimer's disease. However, whether this single-nucleotide polymorphism (SNP) is functional and what the underlying mechanisms are remain unclear. In this study, the CLU rs11136000 SNP is identified as a functional variant by a small-scale CRISPR-Cas9 screen. Astrocytes derived from isogenic induced pluripotent stem cells (iPSCs) carrying the "C" or "T" allele of the CLU rs11136000 SNP exhibit different CLU expression levels. TAR DNA-binding protein-43 (TDP-43) preferentially binds to the "C" allele to promote CLU expression and exacerbate inflammation. The interferon response and CXCL10 expression are elevated in cytokine-treated C/C astrocytes, leading to inhibition of oligodendrocyte progenitor cell (OPC) proliferation and myelination. Accordingly, elevated CLU and CXCL10 but reduced myelin basic protein (MBP) expression are detected in human brains of C/C carriers. Our study uncovers a mechanism underlying reduced white matter integrity observed in the CLU rs11136000 risk "C" allele carriers.

Published
2023

6. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

Author

Ai, Xinyue, An, Chun, An, Yuhong, Bai, Shiru, Bai, Xueke, Bi, Jingao, Bin, Xiaoling, Bu, Miaomiao, Bu, Peili, Bu, Wei, Cai, Lvping, Cai, Nana, Cai, Shuhui, Cai, Ting, Cai, Wenjing, Cao, Bin, Cao, Bingbing, Cao, Huaping, Cao, Libo, Cao, Xiancun, Chai, Hui, Chai, Yonggui, Chai, Zhiyong, Chang, Chunduo, Chang, Jianbao, Chang, Shuyue, Chang, Yunling, Chao, Huanhuan, Che, Hang, Che, Qianqiu, Chen, Danlin, Chen, Dongsheng, Chen, Faxiu, Chen, Guang, Chen, Hairong, Chen, Hao, Chen, Huahua, Chen, Huijun, Chen, Jiafu, Chen, Jian, Chen, Jiasen, Chen, Jing, Chen, Jinzi, Chen, Junrong, Chen, lichun, Chen, Lijuan, Chen, Liyuan, Chen, Qun, Chen, Run, Chen, Shaoxing, Chen, Song, Chen, Tieshuang, Chen, Xianghong, Chen, Xiaowu, Chen, Xudong, Chen, Xue, Chen, Xunchun, Chen, Yao, Chen, Yongli, Chen, Yuanyue, Chen, Yuhong, Chen, Yuyi, Chen, Zhangying, Chen, Zhidong, Chen, Zuyi, Cheng, Caiming, Cheng, Jianbin, Cheng, Xiaoxia, Chu, Junjie, Cui, Ruifeng, Cui, Xiaolin, Cui, Xuechen, Cui, Yang, Cui, Zhonghua, Dai, Wanhong, Dai, Xing, Ding, Chunxia, Ding, Huihong, Ding, Qiuhong, Ding, Yaozong, Ding, Yingjie, Dong, Jiajia, Dong, Lei, Dong, Qi, Dong, Yumei, Du, Bing, Du, Hong, Du, Jie, Du, Laijing, Du, Meiling, Du, Qiong, Du, Tianmin, Du, Xue, Duan, Ru, Duan, Xiaojing, Duan, Xiaoting, Fan, Dandan, Fan, Xiaohong, Fan, Xin, Fang, Fang, Fang, Jing, Fang, Xibo, Fang, Yang, Feng, Erke, Feng, Hejin, Feng, Ling, Feng, Rui, Feng, Zhaohui, Fu, Hongmei, Fu, Qiuai, Gao, Haofei, Gao, Li, Gao, Lina, Gao, Liwei, Gao, Lu, Gao, Min, Gao, Qian, Gao, Yan, Gao, Yuan, Ge, Jinzhuo, Geng, Hongxu, Geng, Hui, Geng, Leijun, Geng, Lianqing, Gou, Hongyan, Gu, Qin, Guan, Lili, Guan, Shuo, Guan, Wenchi, Guan, Zheng, Guang, Bin, Guo, Anran, Guo, Changhong, Guo, Gaofeng, Guo, Lizhi, Guo, Qing, Guo, Qiue, Guo, Ying, Guo, Zhihua, Han, Aihong, Han, Meihong, Han, Suhui, Han, Xinru, Han, Yajun, Hao, Feng, Hao, Jingmin, Hao, Shiguo, He, Chuanhui, He, Dejian, He, Mengyuan, He, Miaomiao, He, Shaojuan, He, Wenkai, He, Xiaoyu, He, Yuxiang, Hong, Jige, Hou, Chuanxing, Hou, Jing, Hu, Danli, Hu, Jian, Hu, Jun, Hu, Lingai, Hu, Mengying, Hu, Zhiyuan, Huang, Anhui, Huang, Chunxia, Huang, Haolin, Huang, Jianlan, Huang, Sha, Huang, Siqi, Huang, Weijun, Huang, Wenxiu, Huang, Xinghe, Huang, Xinsheng, Huang, Xinxin, Hui, Jiliang, Hui, Lijun, Hui, Zhongsheng, Huo, Fangjie, Ji, Runqing, Jia, Guojiong, Jia, Hao, Jia, Jingjing, Jia, Jingmei, Jia, Xiaoling, Jiang, Hua, Jiang, Jingcheng, Jiang, Qian, Jiang, Xianyan, Jiang, Xiaoyuan, Jiang, Yanxiang, Jiao, Yunhong, Jie, Liying, Jin, Binbin, Jin, Lingjiao, Jin, Renshu, Jin, Rong, Jin, Xiang, Jin, Xianping, Jin, Yongfan, Jin, Zepu, Jin, Zhenan, Jing, Chengrong, Jing, Jiajie, Jing, Ruiling, Kang, Liping, Kang, Yu, Kong, Jianqiong, Kou, Shijie, Kou, Xianli, Kulaxihan, Lai, Jijia, Lei, Lubi, Li, Baoxiang, Li, Bin, Li, Bing, Li, Chaohui, Li, Cheng, Li, Chunmei, Li, Chunyan, Li, Daqing, Li, Deen, Li, Di, Li, Feng, Li, Guanyi, Li, Haiyang, Li, Hongwei, Li, Jia, Li, Jialin, Li, Jianan, Li, Jianguang, Li, Jiaying, Li, Jing, Li, Jinmei, Li, Lala, Li, Li, Li, Lijun, Li, Liping, Li, Lize, Li, Mingju, Li, Minglan, Li, Mingyan, Li, Na, Li, Nan, Li, Nana, Li, Qiang, Li, Qianru, Li, Rui, Li, Ruihong, Li, Shanshan, Li, Shilin, Li, Si, Li, Suwen, Li, Tongshe, Li, Tongying, Li, Wanke, Li, Wei, Li, Wenbo, Li, Wenjuan, Li, Xi, Li, Xiangxia, Li, Xiao, Li, Xiaohui, Li, Xingyan, Li, Xiujuan, Li, Yan, Li, Yanfang, Li, Yang, Li, Yanxia, Li, Yaona, Li, Yichong, Li, Ying, Li, Yuqing, Li, Zheng, Li, Zhengye, Liang, Chuanliang, Liang, Jihua, Liang, Jin, Liang, Ke, Liang, Linju, Liang, Tingchen, Liang, Xia, Liang, Xianfeng, Liang, Yanli, Liang, Zhenye, Lie, Zhenbang, Lin, Qingfei, Lin, Ruifang, Lin, Xiao, Lin, Zhiqiang, Liu, Aijun, Liu, Chao, Liu, Chunxia, Liu, Cong, Liu, Fang, Liu, Guaiyan, Liu, Hongjun, Liu, Jiamin, Liu, Jiangling, Liu, Jianqi, Liu, Jieyun, Liu, Jihong, Liu, Jing, Liu, Jinsha, Liu, Juan, Liu, Junfang, Liu, Liming, Liu, Lin, Liu, Ling, Liu, Lu, Liu, Qiang, Liu, Qiaoling, Liu, Qiaoxia, Liu, Qiuxia, Liu, Shaobo, Liu, Xiaobao, Liu, Xiaocheng, Liu, Xiaoyuan, Liu, Xinbo, Liu, Xu, Liu, Yang, Liu, Yanhu, Liu, Yanming, Liu, Yaqin, Liu, Yong, Liu, Zhihong, Long, Jing, Lu, Futang, Lu, Huamei, Lu, Jiapeng, Lu, Junhong, Lu, Weibin, Lu, Yanrong, Lu, Yuchun, Luan, Tianwei, Luo, Qingwei, Luo, Qun, Luo, Tian, Luo, Xia, Luo, Yongmei, Lv, Jing, Lv, Jinhai, Lv, Lei, Lv, Lili, Lv, Meng, Ma, Aiqing, Ma, Huaimin, Ma, Huihuang, Ma, Jie, Ma, Jinbao, Ma, Li, Ma, Lingzhen, Ma, Nan, Ma, Qiaojuan, Ma, Shumei, Ma, Tengfei, Ma, Xiange, Ma, Xiaowen, Ma, Yuehua, Mai, Lanxian, Mei, Xiao, Meng, Gen, Miao, Ruichao, Miao, Xue, Miao, Xuyan, Min, Tingting, Mo, Shubing, Morigentu, Nan, Tingyan, Ni, Jinyang, Ni, Shuguo, Nie, Yu, Ning, Benxing, Ning, Xiaowei, Niu, Manman, Niu, Qingying, Niu, Wentang, Niu, Xiaoxia, Ou, Fang, Pan, Biyun, Pan, Chengjie, Pan, Congming, Pan, Jieli, Pan, Xiaowen, Pan, Ziying, Pei, Guangzhong, Pei, Lingyu, Pei, Min, Pei, Yanzhen, Peng, Yinyu, Peng, Yuming, Pu, Zhaokun, Qi, Fengjun, Qi, Liwei, Qi, Meiqiong, Qi, Yan, Qian, Jun, Qin, Lei, Qin, Zhonghua, Qing, Lan, Qiu, Lixia, Qiu, Weiyu, Qiu, Xiaoling, Qu, Yueli, Quan, Minghua, Ren, Dingping, Ren, Hong, Ren, Lingzhi, Ren, Tingting, Ren, Wei, Ren, Yihui, Rong, Yufang, Ruan, Jiahui, Shang, Peiqin, Shao, Minyan, Shao, Xuefeng, Shao, Yuling, Shen, Junrong, Shen, Rui, Sheng, Lin, Shi, Jiangjie, Shi, Xun, Shi, Yanhong, Shi, Yeju, Shi, Yujiao, Shu, Bo, Song, Bingchun, Song, Dan, Song, Jinhui, Song, Jinwang, Song, Jinxian, Song, Wei, Song, Xiaoping, Song, Yawen, Su, He, Su, Qinfeng, Su, Shuhong, Su, Xiaozhou, Sun, Chengxiang, Sun, Fangfang, Sun, Gongping, Sun, Jiangnan, Sun, Mengmeng, Sun, Rongrong, Sun, Shuting, Sun, Songtao, Sun, Ying, Sun, Yongmiao, Sun, Yunhong, Sun, Zhiqiang, Suo, Mengying, Tan, Binghu, Tang, Chunyan, Tang, Zhongli, Tao, Yu, Tian, Changming, Tian, Hongmei, Tian, Jian, Tian, Xiaomin, Wan, Huaibin, Wan, Qin, Wan, Rongjun, Wang, Bobin, Wang, Chao, Wang, Chaoqun, Wang, Chengliang, Wang, Di, Wang, Enfang, Wang, Feng, Wang, Gang, Wang, Guangqiang, Wang, Guixiang, Wang, Haifeng, Wang, Haijun, Wang, Haiyang, Wang, Jianfang, Wang, Jianfeng, Wang, Jing, Wang, Junping, Wang, Junying, Wang, Kang, Wang, Lei, Wang, Lin, Wang, Lize, Wang, Meng, Wang, Pan, Wang, Qi, Wang, Qiong, Wang, Qiuli, Wang, Qiuxue, Wang, Ran, Wang, Shaojin, Wang, Shuai, Wang, Tao, Wang, Tiantian, Wang, Tinghui, Wang, Tongyan, Wang, Wanhong, Wang, Wenjuan, Wang, Wenyan, Wang, Wenying, Wang, Wenzhuan, Wang, Xiaofei, Wang, Xiaoyan, Wang, Xitong, Wang, Xu, Wang, Yan, Wang, Yanfang, Wang, Yang, Wang, Yanping, Wang, Yanying, Wang, Yaoxin, Wang, Yingli, Wang, Yiting, Wang, Yue, Wang, Yumei, Wang, Yuzhuo, Wang, Zhenhua, Wang, Zhifang, Wang, Zhimin, Wei, Chunli, Wei, Lixia, Wei, Pei, Wei, Shuying, Wei, Xiqing, Wen, Hong, Wen, Yun, Wu, Chaoqun, Wu, Hairong, Wu, Lihua, Wu, Lingxiang, Wu, Qi, Wu, Shaorong, Wu, Wenting, Wu, Xueyi, Wu, Yongshuan, Wu, Zhihao, Wu, Zhuying, Wu, Zongyin, Wuhanbilige, Xia, Jun, Xia, Yang, Xiang, Jing, Xiao, Heliu, Xiao, Yaying, Xie, Meiling, Xie, Yinyan, Xin, Huiling, Xing, Jing, Xiu, Guoquan, Xu, Baohua, Xu, Chuangze, Xu, En, Xu, Jian, Xu, Shuli, Xu, Wei, Xu, Wen, Xue, Na, Xue, Tingting, Xue, Wei, Yan, Haiyan, Yan, Xiaofang, Yan, Yanqing, Yang, Bo, Yang, Hui, Yang, Huiyu, Yang, Jinhua, Yang, Kun, Yang, Man, Yang, Mengya, Yang, Ning, Yang, Ping, Yang, Xiajiao, Yang, Xiaomo, Yang, Xin, Yang, Xiujuan, Yang, Xuemei, Yang, Xuming, Yang, Yan, Yang, Yanhua, Yang, Yi, Yang, Yuanyuan, Yang, Zhimei, Yang, Zhiming, Yao, Hui, Yao, Lu, Ye, Jinling, Ye, Wenhua, Yi, Mingjiao, Yi, Shaowei, Yi, Wenyi, Yi, Zhimin, Yin, Guangxia, Yin, Guoyuan, Yu, Guibin, Yu, Hairong, Yu, Huaitao, Yu, Lijie, Yu, Lijun, Yu, Nana, Yu, Qin, Yu, Xinli, Yu, Yi, Yuan, Biao, Zeng, Chunmei, Zhai, Na, Zhai, Xiaojuan, Zhan, Hongju, Zhang, Aizhen, Zhang, Baohua, Zhang, Bin, Zhang, Caizhu, Zhang, Chaoying, Zhang, Chengbo, Zhang, Chunlai, Zhang, Churuo, Zhang, Fan, Zhang, Feiqin, Zhang, Ge, Zhang, Haibo, Zhang, Hailin, Zhang, Hanxue, Zhang, Huaixing, Zhang, Hui, Zhang, Huijuan, Zhang, Jinguo, Zhang, Jingyu, Zhang, Jinyun, Zhang, Jisheng, Zhang, Jun, Zhang, Lei, Zhang, Li, Zhang, Liang, Zhang, Lifeng, Zhang, Lina, Zhang, Liping, Zhang, Min, Zhang, Ping, Zhang, Qiang, Zhang, Rufang, Zhang, Ruifen, Zhang, Shengde, Zhang, Siqi, Zhang, Sufang, Zhang, Tingting, Zhang, Wanyue, Zhang, Weiliang, Zhang, Xiaohan, Zhang, Xiaohong, Zhang, Xiaojuan, Zhang, Xin, Zhang, Xue, Zhang, Xuewei, Zhang, Yachen, Zhang, Yang, Zhang, Yanyan, Zhang, Yaojie, Zhang, Yingyu, Zhang, Yuan, Zhang, Yun, Zhang, Yunfeng, Zhang, Zaozhang, Zhang, Zhichao, Zhao, Baihui, Zhao, Dan, Zhao, Fuxian, Zhao, Guizeng, Zhao, Haijie, Zhao, Honglei, Zhao, Huizhen, Zhao, Jindong, Zhao, Juan, Zhao, Liming, Zhao, Ling, Zhao, Lingshan, Zhao, Qingxia, Zhao, Qiuping, Zhao, Wanchen, Zhao, Wangxiu, Zhao, Weiyi, Zhao, Xiaodi, Zhao, Xiaojing, Zhao, Xiaoli, Zhao, Xiaoyan, Zhao, Xiling, Zhao, Yannan, Zhao, Yiyuan, Zheng, Shuzhen, Zheng, Xin, Zhi, Lixia, Zhong, Hui, Zhong, Qing, Zhong, Xin, Zhong, Yunzhi, Zhou, Jianfeng, Zhou, Jihu, Zhou, Ke, Zhou, Liangliang, Zhou, Ling, Zhou, Na, Zhou, Shengcheng, Zhou, Suyun, Zhou, Tao, Zhou, Wanren, Zhou, Weifeng, Zhou, Weijuan, Zhou, Xiaohong, Zhou, Yunke, Zhou, Yuquan, Zhou, Zhaohai, Zhou, Zhiming, Zhu, Bingpo, Zhu, Jifa, Zhu, Jing, Zhu, Mengnan, Zhu, Youcun, Zong, Dafei, Zuo, Hongbo, and Zuo, Zhaokai

Published
2024
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18. Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure

Author

Chen, Xianwei, Sun, Guoqiang, Tian, E, Zhang, Mingzi, Davtyan, Hayk, Beach, Thomas G, Reiman, Eric M, Blurton‐Jones, Mathew, Holtzman, David M, and Shi, Yanhong

Subjects
Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Alzheimer's Disease, Aging, Brain Disorders, Neurodegenerative, Stem Cell Research - Induced Pluripotent Stem Cell, Dementia, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Aetiology, Development of treatments and therapeutic interventions, Neurological, Good Health and Well Being, Alzheimer Disease, Brain, Humans, Induced Pluripotent Stem Cells, Organoids, brain organoids, disease modeling, induced pluripotent stem cells, serum exposure, sporadic Alzheimer's disease
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure. Huge efforts have been made to develop anti-AD drugs in the past decades. However, all drug development programs for disease-modifying therapies have failed. Possible reasons for the high failure rate include incomplete understanding of complex pathophysiology of AD, especially sporadic AD (sAD), and species difference between humans and animal models used in preclinical studies. In this study, sAD is modeled using human induced pluripotent stem cell (hiPSC)-derived 3D brain organoids. Because the blood-brain barrier (BBB) leakage is a well-known risk factor for AD, brain organoids are exposed to human serum to mimic the serum exposure consequence of BBB breakdown in AD patient brains. The serum-exposed brain organoids are able to recapitulate AD-like pathologies, including increased amyloid beta (Aβ) aggregates and phosphorylated microtubule-associated tau protein (p-Tau) level, synaptic loss, and impaired neural network. Serum exposure increases Aβ and p-Tau levels through inducing beta-secretase 1 (BACE) and glycogen synthase kinase-3 alpha / beta (GSK3α/β) levels, respectively. In addition, single-cell transcriptomic analysis of brain organoids reveals that serum exposure reduced synaptic function in both neurons and astrocytes and induced immune response in astrocytes. The human brain organoid-based sAD model established in this study can provide a powerful platform for both mechanistic study and therapeutic development in the future.

Published
2021

22. ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response

Author

Wang, Cheng, Zhang, Mingzi, Garcia, Gustavo, Tian, E, Cui, Qi, Chen, Xianwei, Sun, Guihua, Wang, Jinhui, Arumugaswami, Vaithilingaraja, and Shi, Yanhong

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Stem Cell Research, Dementia, Neurosciences, Stem Cell Research - Induced Pluripotent Stem Cell, Acquired Cognitive Impairment, Aging, Brain Disorders, Infectious Diseases, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Emerging Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Neurological, Good Health and Well Being, Adenosine Monophosphate, Alanine, Animals, Antiviral Agents, Apolipoproteins E, Astrocytes, Brain, COVID-19, Cell Differentiation, Chlorocebus aethiops, Humans, Induced Pluripotent Stem Cells, Nerve Degeneration, Neurites, Neurons, Organoids, Protein Isoforms, SARS-CoV-2, Synapses, Tropism, Vero Cells, Alzheimer's disease, ApoE, SARS-CoV-2 neurotropism, astrocytes, brain organoids, iPSCs, induced pluripotent stem cells, neuron-astrocyte co-culture, neurons, remdesivir, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.

Published
2021

37. Development and Validation of Deep Learning Model for Intermediate-Stage Hepatocellular Carcinoma Survival with Transarterial Chemoembolization (MC-hccAI 002): a Retrospective, Multicenter, Cohort Study

Author

Chen, Yaying, primary, Shi, Yanhong, additional, Wang, Ruiqi, additional, Wang, Xuewen, additional, Lin, Qin, additional, Huang, Yan, additional, Shao, Erqian, additional, Pan, Yan, additional, Huang, Shanshan, additional, Lu, Linbin, additional, and Chen, Xiong, additional

Published
2024
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41. Induced pluripotent stem cell technology: a decade of progress

Author

Shi, Yanhong, Inoue, Haruhisa, Wu, Joseph C, and Yamanaka, Shinya

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human, Stem Cell Research - Embryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Neurodegenerative, Clinical Trials and Supportive Activities, Bioengineering, Stem Cell Research - Induced Pluripotent Stem Cell, Aging, Clinical Research, Stem Cell Research, Stem Cell Research - Induced Pluripotent Stem Cell - Human, 5.9 Resources and infrastructure (treatment development), Development of treatments and therapeutic interventions, Neurological, Generic health relevance, Good Health and Well Being, Drug Discovery, Drug Therapy, High-Throughput Screening Assays, History, 21st Century, Humans, Induced Pluripotent Stem Cells, Stem Cell Transplantation, Biological Sciences, Medical and Health Sciences, Pharmacology & Pharmacy, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modelling, drug discovery and cell therapy development. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated. In particular, the combination of human iPSC technology with recent developments in gene editing and 3D organoids makes iPSC-based platforms even more powerful in each area of their application, including precision medicine. In this Review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field.

Published
2017

42. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

Author

Liu, Jiamin, Li, Yan, Ge, Jinzhuo, Yan, Xiaofang, Zhang, Haibo, Zheng, Xin, Lu, Jiapeng, Li, Xi, Gao, Yan, Lei, Lubi, Liu, Jing, Li, Jing, Ai, Xinyue, An, Chun, An, Yuhong, Bai, Shiru, Bai, Xueke, Bi, Jingao, Bin, Xiaoling, Bu, Miaomiao, Bu, Peili, Bu, Wei, Cai, Lvping, Cai, Nana, Cai, Shuhui, Cai, Ting, Cai, Wenjing, Cao, Bin, Cao, Bingbing, Cao, Huaping, Cao, Libo, Cao, Xiancun, Chai, Hui, Chai, Yonggui, Chai, Zhiyong, Chang, Chunduo, Chang, Jianbao, Chang, Shuyue, Chang, Yunling, Chao, Huanhuan, Che, Hang, Che, Qianqiu, Chen, Danlin, Chen, Dongsheng, Chen, Faxiu, Chen, Guang, Chen, Hairong, Chen, Hao, Chen, Huahua, Chen, Huijun, Chen, Jiafu, Chen, Jian, Chen, Jian, Chen, Jiasen, Chen, Jing, Chen, Jinzi, Chen, Junrong, Chen, lichun, Chen, Lijuan, Chen, Liyuan, Chen, Qun, Chen, Run, Chen, Shaoxing, Chen, Song, Chen, Tieshuang, Chen, Xianghong, Chen, Xiaowu, Chen, Xudong, Chen, Xue, Chen, Xunchun, Chen, Yao, Chen, Yongli, Chen, Yuanyue, Chen, Yuhong, Chen, Yuyi, Chen, Zhangying, Chen, Zhidong, Chen, Zuyi, Cheng, Caiming, Cheng, Jianbin, Cheng, Xiaoxia, Chu, Junjie, Cui, Ruifeng, Cui, Xiaolin, Cui, Xuechen, Cui, Yang, Cui, Zhonghua, Dai, Wanhong, Dai, Xing, Ding, Chunxia, Ding, Huihong, Ding, Qiuhong, Ding, Yaozong, Ding, Yingjie, Dong, Jiajia, Dong, Lei, Dong, Qi, Dong, Yumei, Du, Bing, Du, Hong, Du, Jie, Du, Laijing, Du, Meiling, Du, Qiong, Du, Tianmin, Du, Xue, Duan, Ru, Duan, Xiaojing, Duan, Xiaoting, Fan, Dandan, Fan, Xiaohong, Fan, Xin, Fang, Fang, Fang, Jing, Fang, Xibo, Fang, Yang, Feng, Erke, Feng, Hejin, Feng, Ling, Feng, Rui, Feng, Zhaohui, Fu, Hongmei, Fu, Qiuai, Gao, Haofei, Gao, Li, Gao, Lina, Gao, Liwei, Gao, Lu, Gao, Min, Gao, Min, Gao, Qian, Gao, Yan, Gao, Yuan, Ge, Jinzhuo, Geng, Hongxu, Geng, Hui, Geng, Leijun, Geng, Lianqing, Gou, Hongyan, Gu, Qin, Guan, Lili, Guan, Shuo, Guan, Wenchi, Guan, Zheng, Guang, Bin, Guo, Anran, Guo, Changhong, Guo, Gaofeng, Guo, Lizhi, Guo, Qing, Guo, Qiue, Guo, Ying, Guo, Zhihua, Han, Aihong, Han, Meihong, Han, Suhui, 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Li, Bing, Li, Chaohui, Li, Cheng, Li, Chunmei, Li, Chunyan, Li, Daqing, Li, Deen, Li, Di, Li, Feng, Li, Guanyi, Li, Haiyang, Li, Hongwei, Li, Jia, Li, Jialin, Li, Jianan, Li, Jianguang, Li, Jiaying, Li, Jing, Li, Jing, Li, Jinmei, Li, Lala, Li, Li, Li, Lijun, Li, Liping, Li, Lize, Li, Mingju, Li, Minglan, Li, Mingyan, Li, Na, Li, Na, Li, Nan, Li, Nana, Li, Qiang, Li, Qianru, Li, Rui, Li, Ruihong, Li, Shanshan, Li, Shilin, Li, Si, Li, Suwen, Li, Tongshe, Li, Tongying, Li, Wanke, Li, Wei, Li, Wenbo, Li, Wenjuan, Li, Xi, Li, Xiangxia, Li, Xiao, Li, Xiaohui, Li, Xingyan, Li, Xiujuan, Li, Yan, Li, Yanfang, Li, Yang, Li, Yanxia, Li, Yaona, Li, Yichong, Li, Ying, Li, Yuqing, Li, Zheng, Li, Zhengye, Liang, Chuanliang, Liang, Jihua, Liang, Jin, Liang, Ke, Liang, Linju, Liang, Tingchen, Liang, Xia, Liang, Xianfeng, Liang, Yanli, Liang, Zhenye, Lie, Zhenbang, Lin, Qingfei, Lin, Ruifang, Lin, Xiao, Lin, Zhiqiang, Liu, Aijun, Liu, Chao, Liu, Chunxia, Liu, Cong, Liu, Fang, Liu, Fang, Liu, Guaiyan, 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Wei, Chunli, Wei, Lixia, Wei, Pei, Wei, Shuying, Wei, Xiqing, Wen, Hong, Wen, Yun, Wu, Chaoqun, Wu, Hairong, Wu, Lihua, Wu, Lingxiang, Wu, Qi, Wu, Shaorong, Wu, Wenting, Wu, Xueyi, Wu, Yongshuan, Wu, Zhihao, Wu, Zhuying, Wu, Zongyin, Wuhanbilige, Xia, Jun, Xia, Yang, Xiang, Jing, Xiao, Heliu, Xiao, Yaying, Xie, Meiling, Xie, Yinyan, Xin, Huiling, Xing, Jing, Xiu, Guoquan, Xu, Baohua, Xu, Chuangze, Xu, En, Xu, Jian, Xu, Shuli, Xu, Wei, Xu, Wen, Xue, Na, Xue, Tingting, Xue, Wei, Yan, Haiyan, Yan, Xiaofang, Yan, Yanqing, Yang, Bo, Yang, Hui, Yang, Huiyu, Yang, Jinhua, Yang, Kun, Yang, Man, Yang, Mengya, Yang, Ning, Yang, Ping, Yang, Xiajiao, Yang, Xiaomo, Yang, Xin, Yang, Xiujuan, Yang, Xuemei, Yang, Xuming, Yang, Yan, Yang, Yanhua, Yang, Yi, Yang, Yuanyuan, Yang, Zhimei, Yang, Zhiming, Yao, Hui, Yao, Lu, Ye, Jinling, Ye, Wenhua, Yi, Mingjiao, Yi, Shaowei, Yi, Wenyi, Yi, Zhimin, Yin, Guangxia, Yin, Guoyuan, Yu, Guibin, Yu, Hairong, Yu, Huaitao, Yu, Lijie, Yu, Lijun, Yu, Nana, Yu, Qin, Yu, Xinli, Yu, Yi, Yuan, Biao, Zeng, Chunmei, Zhai, Na, Zhai, Xiaojuan, Zhan, Hongju, Zhang, Aizhen, Zhang, Baohua, Zhang, Bin, Zhang, Caizhu, Zhang, Chaoying, Zhang, Chengbo, Zhang, Chunlai, Zhang, Churuo, Zhang, Fan, Zhang, Feiqin, Zhang, Ge, Zhang, Haibo, Zhang, Hailin, Zhang, Hanxue, Zhang, Huaixing, Zhang, Hui, Zhang, Huijuan, Zhang, Jinguo, Zhang, Jingyu, Zhang, Jinyun, Zhang, Jisheng, Zhang, Jun, Zhang, Lei, Zhang, Li, Zhang, Li, Zhang, Liang, Zhang, Lifeng, Zhang, Lina, Zhang, Liping, Zhang, Liping, Zhang, Min, Zhang, Ping, Zhang, Qiang, Zhang, Rufang, Zhang, Ruifen, Zhang, Shengde, Zhang, Siqi, Zhang, Sufang, Zhang, Tingting, Zhang, Wanyue, Zhang, Weiliang, Zhang, Xiaohan, Zhang, Xiaohong, Zhang, Xiaojuan, Zhang, Xin, Zhang, Xin, Zhang, Xue, Zhang, Xuewei, Zhang, Yachen, Zhang, Yang, Zhang, Yanyan, Zhang, Yaojie, Zhang, Yingyu, Zhang, Yuan, Zhang, Yun, Zhang, Yunfeng, Zhang, Zaozhang, Zhang, Zhichao, Zhao, Baihui, Zhao, Dan, Zhao, Fuxian, Zhao, Guizeng, Zhao, Haijie, Zhao, Honglei, Zhao, Huizhen, Zhao, Jindong, Zhao, Juan, Zhao, Liming, Zhao, Ling, Zhao, Lingshan, Zhao, Qingxia, Zhao, Qiuping, Zhao, Wanchen, Zhao, Wangxiu, Zhao, Weiyi, Zhao, Xiaodi, Zhao, Xiaojing, Zhao, Xiaoli, Zhao, Xiaoyan, Zhao, Xiling, Zhao, Yannan, Zhao, Yiyuan, Zheng, Shuzhen, Zheng, Xin, Zhi, Lixia, Zhong, Hui, Zhong, Qing, Zhong, Xin, Zhong, Yunzhi, Zhou, Jianfeng, Zhou, Jihu, Zhou, Ke, Zhou, Liangliang, Zhou, Ling, Zhou, Na, Zhou, Shengcheng, Zhou, Suyun, Zhou, Tao, Zhou, Wanren, Zhou, Weifeng, Zhou, Weijuan, Zhou, Xiaohong, Zhou, Yunke, Zhou, Yuquan, Zhou, Zhaohai, Zhou, Zhiming, Zhu, Bingpo, Zhu, Jifa, Zhu, Jing, Zhu, Mengnan, Zhu, Youcun, Zong, Dafei, Zuo, Hongbo, and Zuo, Zhaokai

Abstract

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke.

Published
2024
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44. Effect of Microwave Roasting on Zin--Iron Separaiion of Zin--Containing Metallurgical Dust and Sludge in Iron and Steel Industry.

Author

SHI Yanhong, YU Yuting, LI Qiyong, LI Qiang, LIAO Chinghua, YANG Siwei, and LIN Ruihao

Subjects
*STEEL industry, *IRON industry, *ROASTING (Metallurgy), *DUST, *IRON, *DUST explosions
Abstract

:To promote the resource utiiization of zinccontaining metallurgical dust and sludge in ron and steel industry, the zinccontaining metallurgccal dust and sludge with ron content of 30. 38% and zinc content of 4. 79% was studed by microwave reduction roasting-magnetic separaiion test. The experimental resutts show that t is difficult to reaize the effective separation of zinc and ron in Yin--containing metallurgccal dust and sludge by direct magneto separation wrthout roasting and convenional muffle furnace reduction roasting-magnetic separaion. When the microwave muffle furnace roasiing at 700 C for 15 min. The main phase in the roasted product Is Fe. When the magnetic field intenstty of the roasted product Is 150 mT,the zinc and ron in the zinccontaining metallurgccal dust can achieve better separaion. The concentrate index obtained by magnetic separation:the zinc content Is 2. 73%,the ron content Is 57. 84%, the ron recovery rate ss 88. 67%, tailings index of magneic separaion: the ron content Is 9.54%, the zinc content ss 9. 85 %, the zinc recovery rate Is 61. 72%. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.

Author

Chen, Liang, Kang, Dengfeng, Fang, Leilei, Sun, Mingming, Li, Mingsong, Zhou, Guangxi, Xu, Chunjin, Pang, Zhi, Ye, Yulan, Feng, Baisui, Wu, Huili, Lin, Jian, Ding, Baijing, Liu, Changqin, Shi, Yanhong, and Liu, Zhanju

Subjects
CROHN'S disease, NOMOGRAPHY (Mathematics), INFLAMMATORY bowel diseases, RECEIVER operating characteristic curves, DRUG monitoring
Abstract

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients. Plain language summary: Therapeutic drug monitoring-based nomogram predicts primary endoscopic response in Crohn's disease The present study established a therapeutic drug monitoring-based nomogram, which exhibits an exceptional predictive value, remarkable accuracy, and discrimination. This algorithmic nomogram holds the potential to enhance clinicians' comprehension of the underlying mechanisms contributing to individual patients' failure in achieving expected efficacy. Such approach is crucial for optimizing therapy options and facilitating biologic switching in refractory Crohn's disease. [ABSTRACT FROM AUTHOR]

Published
2024
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