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| 1 | Nerve growth factor pretreatment against glutamate-induced hippocampal neuronal injury Action mechanism of phosphatase and tensin homologue deleted on chromosome 10显示文摘BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis. | Yae Hu Jiahui Mao Yan Zhu Ailing Zhou | 2010 | Neural Regeneration Research2010，5，1： | 12 |
| 2 | Toll-like receptor 4-mediated signaling participates in apoptosis of hippocampal neurons显示文摘The phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway is considered important for cell survival and has been shown to mediate various anti-apoptotic biological effects.This study explored the role of the Toll-like receptor 4(TLR4)-mediated PI3K/AKT-glycogen synthase kinase 3β(GSK-3β)signaling pathways in lipopolysaccharide-induced apoptosis in a primary culture of hippocampal neurons.Results demonstrated that the apoptotic ratio of hippocampal neurons stimulated by lipopolysaccharide was significantly higher compared with the control group.Both the expression of P-AKTSer473and P-GSK-3βSer9in hippocampal neurons stimulated by lipopolysaccharide decreased compared with the control,while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased.The level of active Caspase-3 and the ratio of Bax/Bcl-2 in hippocampal neurons treated with TLR4 antibody or the GSK-3βinhibitor,LiCl,decreased before intervention with lipopolysaccharide,but increased after treatment with the AKT inhibitor,LY294002.These findings suggest that the TLR4-PI3K/AKT-GSK3βsignaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons. | Yue He Ailing Zhou Wei Jiang | 2013 | Neural Regeneration Research2013，8，29： | 8 |
| 3 | Hierarchical composite of biomass derived magnetic carbon framework and phytic acid doped polyanilne with prominent electromagnetic wave absorption capacity显示文摘To solve the electromagnetic pollution,herein,a CoFe_(2)O_(4)/C/PANI composite was developed by a green route,which was constructed with spinel of metal oxide,graphitized carbon and conductive polymer composites.Benefiting from the designable interfaces and increased dipoles,the microwave dielectric response capability can be boosted significantly and resulted in the enhanced microwave absorbing performance.As revealed by the reflection loss curve,the minimum reflection loss(RLmin) reached-51.81 dB at 12.4 GHz under a matched thickness of 2.57 mm.At 2.5 mm,the effective absorbing band covered 8.88 GHz,suggesting the desirable wideband feature.In our case,the method of utilization of a novel green way to fabricate multiple-component EM absorber can be a promising candidate for high-performance EM absorber. | Tianqi Hou Zirui Jia Ailing Feng Zehua Zhou Xuehua Liu Hualiang Lv Guanglei Wu | 2021 | Journal of Materials Science & Technology2021，，9： | 8 |
| 4 | Oxymatrine reduces neuroinflammation in rat brain A signaling pathway显示文摘Cerebral neuroinflammation models were established by injecting 10 μg lipopolysaccharide into the hippocampus of male Sprague-Dawley rats. The rats were treated with an intraperitoneal injection of 120, 90, or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection. Twenty-four hours after model induction, the hippocampus was analyzed by real-time quantitative PCR, and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay. The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine. Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine. Additionally, 120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-κB p65 in the nucleus and of phosphorylated IκBα in the cytoplasm of brain cells, as detected by western blot assay. Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-κB signaling pathway. | Jiahui Mao Yae Hu Ailing Zhou Bing Zheng Yi Liu Yueming Du Jia Li Jinyang Lu Pengcheng Zhou | 2012 | Neural Regeneration Research2012，7，30： | 7 |
| 5 | Tuning the intermolecular interaction of A_(2)-A_(1)-D-A_(1)-A_(2) type non-fullerene acceptors by substituent engineering for organic solar cells with ultrahigh V_(OC) of ~1.2 V显示文摘For non-fullerene acceptors(NFAs)with linear A_(2)-A_(1)-D-A_(1)-A_(2) backbone,there are three kinds of possible intermolecular interaction,A_(1)-A_(1),A_(1)-A_(2) and A_(2)-A_(2) stacking.Hence,it is a huge challenge to control this interaction and investigate the effect of intermolecular stacking model on the photovoltaic performance.Here,we adopt a feasible strategy,by utilizing different substituent groups on terminal A2 unit of dicyanomethylene rhodanine(RCN),to modulate this stacking model.According to theoretical calculation results,the molecule BTA3 with ethyl substituent packs via heterogeneous interaction between A_(2) and A_(1) unit in neighboring molecules.Surprisingly,the benzyl group can effectively transform the aggregation of BTA5 into homogeneous packing of A_(2)-A_(2) model,which might be driven by the strong interaction between benzyl and A1(benzotriazole)unit.However,different with benzyl,phenyl end group impedes the intermolecular interaction of BTA4 due to the large steric hindrance.When using a BTA-based D-π-A polymer J52-F as donor according to“Same-A-Strategy”,BTA3-5 could achieve ultrahigh open-circuit voltage(VOC)of 1.17–1.21 V.Finally,BTA5 with benzyl groups realized an improved power conversion efficiency(PCE)of 11.27%,obviously higher than that of BTA3(PCE=9.04%)and BTA4(PCE=5.61%).It is also worth noting that the same trend can be found when using other four classic p-type polymers of P3HT,PTB7,PTB7-Th and PBDB-T.This work not only investigates the intermolecular interaction of A_(2)-A_(1)-D-A_(1)-A_(2) type NFAs for the first time,but also provides a straightforward and universal method to change the interaction model and improve the photovoltaic performance. | Xiaochen Wang Ailing Tang Jing Yang Mengzhen Du Jianfeng Li Gongqiang Li Qiang Guo Erjun Zhou | 2020 | Science China Chemistry2020，63，11： | 5 |
| 6 | A 2-bp insertion(c.6768insCC) in MC1R causes recessive white coat color in Bama miniature pigs显示文摘Coat color is an important characteristic of various breeds of domestic animal species.Variation in farm animal coat color is of considerable interest for concealment,communication and protection against solar radiation(Slominski et al.,2004).It also plays an important role in the regulation of physiological processes(Miyagi and Terai,2013).Bama miniature pigs are a native breed | Qitao Jia Chunwei Cao Hai Tang Ying Zhang Qiantao Zheng Xiao Wang Rui Zhang Xianlong Wang Ailing Luo Hong Wei Anming Meng Qi Zhou Hongmei Wang Jianguo Zhao | 2017 | Journal of Genetics and Genomics2017，44，4： | 5 |
| 7 | Breast cancer-specific serum peptide profiles显示文摘Early detection of breast cancer is paramount to successful clinical therapy. Yet, early-stage breast cancer lacks specific symptoms or biomarkers. With the emerging of the mass spectrometric (MS) -based signatures as biomarkers, we investigated breast cancer-related serum profile pattern through class prediction and independent validation, and used Fourier transfer MS to identify breast cancer signature. We now show a distinctive serum peptide pattern that discriminates breast cancer from healthy controls with 93.2% sensitivity and 95.4% specificity. m/z 5901.70 and 4465.74 of ion fragment of FPA and alpha1-antichymotrypsin are found in the signatures that predominantly discriminate breast cancer from healthy individuals. These novel findings identify an MS-based serum peptide pattern of breast cancer that may have direct clinical utility in future. | WANG Na WEN XinYu WANG Jie LI AiLing LI WeiHua LI Tao Li Yan ZHANG XueMin WANG HongXia YANG SongCheng ZHOU Tao GONG WeiLi TIAN YaPing HE Kun | 2009 | Chinese Science Bulletin2009，54，3： | 4 |
| 8 | Introduction of a multicenter online database for non-metastatic breast cancer in China显示文摘Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016). | Yaping Yang Jieqiong Liu Min Peng Fengxi Su Xiaoming Xie Zhenzhen Liu Jundong Wu Wei Wei Dongxian Zhou Weiwen Li Ailing Zhang Guosen Su Weixiong Yang Jishang Chen Dekui Ma Yongguang Cai Kai Chen Liling Zhu Qiang Liu Erwei Song | 2020 | Science China(Life Sciences)2020，63，9： | 4 |
| 9 | Effect of Nao Yikang on choline acetyltransferase and caspase-3 brain expression in a rat model of Alzheimer's disease显示文摘BACKGROUND: The main components of the traditional Chinese medicine compound Nao Yikanghave been shown to possibly alleviate neural damage.OBJECTIVE: To observe the effects of Nao Yikang on expression of choline acetyltransferase(ChAT) and caspase-3 in the rat brains of an experimental Alzheimer's disease (AD) model, and toinvestigate the mechanisms of potential neuroprotective effects.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at theDepartment of Pathophysiology, Medical School of Nantong University between November 2006and December 2007.MATERIALS: The main active components of Nao Yikang were as follows: prepared polygonummultiflorum, Rhizoma anemarrhenae, and Rhizoma acori tatarinowii. Nao Yikang granules wereprepared by Nantong Hospital of Traditional Chinese Medicine. Ibotenic acid (IBO) was purchasedfrom Sigma-Aldrich, USA, ChAT goat anti-rat antibody from Chemicon, USA, and cleaved caspase-3rabbit anti-rat (Asp175) (5A1) antibody from Cell Signaling, USA.METHODS: A total of 60 male, Sprague Dawley rats (2 months old) were randomly assigned to 6groups: sham-surgery, model, Nao Yikang 1.73, 3.45, 6.90 g/kg per day, and piracetam, with 10 ratsin each group. Bilateral infusions of 5 μg IBO into the nucleus basalis of Meynert were performedwith Hamilton syringe and stereotaxic apparatus for AD model establishment. For the sham-surgerygroup, rats received 1 μL saline in the identical stereotaxic position. From the second day, NaoYikang groups were administrated 1.73, 3.45, and 6.90 g/kg per day Nao Yikang, respectively, whilethe piracetam group received 0.04 g/mL piracetam, the model group received 0.5% sodiumcarboxymethyl cellulose, and the sham-surgery group received normal saline. Rats wereintragastrically administered 1 mL/100 g daily for 28 consecutive days.MAIN OUTCOME MEASURES: Following treatment of the various solutions for 28 days, Westernblot was utilized to observe ChAT expression in the frontal cortex of AD rats, andimmunohistochemistry was applied to quantify caspase-3-positive cells in the frontal cortex.RESULTS: ChAT protein expression significantly decreased in the model group (P < 0.01), howevercaspase-3 expression was significantly elevated (P < 0.01) compared with the sham-surgery group.Compared with the model group, ChAT protein expression increased in the Nao Yikang 1.73 g/kgper day, 3.45 g/kg per day, 6.90 g/kg per day groups, and the piracetam group (P < 0.05 or P < 0.01)and the number of caspase-3-positive cells decreased in the Nao Yikang 3.45 g/kg per day and6.90 g/kg per day groups (P < 0.01). However, there was no change in the number ofcaspase-3-positive cells in the 3.45 g/kg per day group.CONCLUSION: The traditional Chinese medicine compound Nao Yikangincreased ChAT proteinexpression and suppressed caspase-3 expression in the frontal cortex in a dose-dependent manner. | Jinsong Geng Hengjian Ni Jiancheng Dong Kui Jiang Ailing Zhou Yae Hu | 2009 | Neural Regeneration Research2009，4，12： | 3 |
| 10 | Role of Toll-like receptor 4 in inflammatory reactions of hippocampal neurons显示文摘Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined. In this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-1β and tumor necrosis factor-α were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B α inhibitor in the cytosol and increased nuclear factor-κB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-κB pathway in hippocampal neurons, which may be both 'passive victims' and 'activators' of neuroinflammation. | Yae Hu Jiahui Mao Yu Zhang Ailing Zhou | 2013 | Neural Regeneration Research2013，8，16： | 3 |
| 11 | Chicory polysaccharides alleviate high-fat diet-induced non-alcoholic fatty liver disease via alteration of lipid metabolism-and inflammation-related gene expression显示文摘Administration of chicory polysaccharides(CP) can modify lipid metabolism, improve dyslipidemia, and reduce liver inflammation, all of which may help alleviate non-alcoholic fatty liver disease(NAFLD). However, the underlying mechanisms remain unclear. This study aimed to gain further understanding of the potential molecular mechanisms that mediate the protective effects of CP against NAFLD via transcriptomic and metabolomic analyses. Hepatic RNA-sequencing analysis demonstrated that long-term intake of CP restored expression of lipid metabolism-related genes Xbp1, Insig2, and Cth in NAFLD rats, thereby inhibiting de novo lipogenesis. Moreover, CP consumption restored expression levels of genes involved in pro-inflammatory responses, such as Irf1. In addition, metabolic data confirmed that CP treatment increased levels of L-palmitoylcarnitine and hexadecanoyl-Co A, implying that CP administration can promote hepatic fatty acid β-oxidation. The present results demonstrate the underlying mechanisms of CP in high-fat dietinduced NAFLD rats and suggest that CP treatment might provide a dietary therapeutic tool for the treatment of NAFLD in humans. | Shengjie Li Yulong Wu Haitao Jiang Feng Zhou Ailing Ben Renlei Wang Chun Hua | 2022 | Food Science and Human Wellness2022，11，4： | 2 |
| 12 | Wide Band Gap Non-Fullerene Small Molecular Acceptors Containing Spirobifluorene and Benzotriazole with Three Different End-Capped Groups for P3HT-Based Organic Solar Cells显示文摘 | Xiaoyu Wen Bo Xiao Ailing Tang Junyi Hu Chunhe Yang Erjun Zhou | 2018 | Chinese Journal of Chemistry2018，36，5： | 2 |
| 13 | Fluorescence enhancement of Tb^(3+) complexes by adding silica-coated silver nanoparticles显示文摘Six kinds of terbium ternary complexes with halo-benzoic acids were synthesized. Their compositions were determined by C, H elemental analyzer and EDTA titration. The infrared spectra, ultraviolet absorption spectra, and fluorescence spectra were also measured to identify the complexes. Elemental analysis showed that the compositions of these complexes were Tb(p-Br BA)3?H2O, Tb(p-Cl BA)3?2H2O, Tb(p-FBA)3?H2O, Tb(o-FBA)3?2H2O, Tb(o-Cl BA)3?H2O, and Tb(o-Br BA)3?H2O, respectively. The monodispersed Ag@Si O2 core-shell nanoparticles with silica thicknesses of 10, 15, and 25 nm were successfully prepared and characterized by transmission-electron microscopy. Fluorescence intensities of the complexes were detected before and after Ag@Si O2 core-shell nanoparticles were added; the enhancement times were related to the silica-shell thickness. The fluorescence enhancement times were largest when the thickness of the silica shell was 25 nm. The mechanism may be attributed to the localized surface-plasmon resonance. Furthermore, the enhancement effect of terbium fluoro-benzoate complexes was the strongest in these complexes. This result may be attributed to the hydrogen bond between the hydroxyl on the surface of the silica shell and the fluorine atom. | Dan Zhou Xuemei Lin Ailing Wang Jingjing Li Yanrong Qu Haibin Chu Yongliang Zhao | 2015 | Science China Chemistry2015，58，6： | 2 |
| 14 | 增温和放牧对高寒草甸凋落物分解及其养分释放的影响不依赖于凋落物品质显示文摘在放牧生态系统中,增温、放牧和调落物品质共同决定着凋落物分解和养分释放。然而,在以往的研究中这些因子的效应通常被单独地研究。在本研究中,我们在青藏高原高寒草甸开展了一个昼夜非对称增温和中度放牧两因子的调落物分解试验。从每个处理中收集了调落物样品,这些调落物一部分放在它们的来源处理小区,另一部分放在其他处理小区以此来探究增温、放牧以及调落物品质对调落物分解和养分释放的影响。研究结果表明,增温而不是放牧显著增加了调落物质量的损失、单位面积全碳、全氮以及全磷含量的损失,这主要是因为增温增加了落物生物量和分解速率。然而,尽管同时增温放牧处理也加快了调落物分解速率,但由于降低了调落物生物量,所以增温放牧处理并没有显著影响单位面积的凋落物碳和养分释放量。相比木质素含量和碳氮比而言,季节性土壤平均温度能够更好地预测调落物分解速率。增温和放牧对调落物分解存在交互作用,但它们和调落物品质对调落物的影响均不存在交互作用。单位面积的总氮释放的温度敏感性要高于总磷。因此,我们的结果表明,增温对调落物分解以及养分释放的影响要显著大于调落物品质变化对其分解的影响。在高寒草甸,氮释放的增加可能会间接导致土壤磷有效性的缺乏。 | Bowen Li Wangwang Lv Jianping Sun Lirong Zhang Lili Jiang Yang Zhou Peipei Liu Huan Hong Qi Wang Wang A Suren Zhang Lu Xia Zongsong Wang Tsechoe Dorji Ailing Su Caiyun Luo Zhenhua Zhang Shiping Wang | 2022 | Journal of Plant Ecology2022，15，5： | 1 |
| 15 | A Recyclable Electrochemical Allylation in Water显示文摘 | Zhenggen Zha Ailing Hui Yuqing Zhou etc | 2005 | ORGANIC LETTERS2005，7，10： | 1 |
| 16 | Gradually modulating the three parts of D-π-A type polymers for high-performance organic solar cells显示文摘Organic solar cells(OSCs)have received great attention for the prominent advantage of low-cost,light-weight and potential for fabricating flexible and semi-transparent device via roll-to-roll printing toward making better use of inexhaustible renewable clean energy during the past years[1-4]. | Jialing Zhou Peiqing Cong Lie Chen Bao Zhanga Yanfang Geng Ailing Tang Erjun Zhou | 2021 | Journal of Energy Chemistry2021，30，11： | 1 |
| 17 | Targeted delivery of large fusion protein into hippocampal neurons by systemic administration显示文摘 | Lixin Xiang Rumei Zhou Ailing Fu Xingran Xu Yuqi Huang Changhua Hu | 2011 | Journal of Drug Targeting2011，，8： | 1 |
| 18 | Extreme temperature increases the severity of intracerebral hemorrhage: An analysis based on the cold region of China显示文摘Objective:The purpose of this study was to find a suitable model to evaluate the relationship between temperature and intracerebral hemorrhage(ICH)and explore the effects of cold spells and heat waves on the clinicopathological parameters of ICH patients.Methods:We conducted a retrospective study based on the ICH admission in the First Affiliated Hospital of Harbin Medical University from 2015 to 2020(N=11124).The relationship between different seasons and the number of patients with ICH was explored.Poisson Akaike information criterion(AIC)was used to select the optimal model for temperature and ICH.Binary logistic regression analysis was used to investigate the association between extreme temperatures and clinicopathological features.Results:Hospital admissions for patients with ICH showed monthly changes.The optimal cold spell was defined as the daily average temperature<3rd percentile,lasting for five days,while the optimal heat wave was defined as the daily average temperature>97th percentile,lasting for three days.Based on the generalized extreme weather model,cold climate significantly increased the risk of hematoma volume expansion(OR 1.003;95%CI:1.000-1.005,P=0.047).In the optimal model,the occurrence of cold spells and heat waves increased the risk of midline shift in both conditions(OR 1.067;95%CI:1.021-1.115,P=0.004;OR 1.077;95%CI:1.030-1.127,P=0.001).Conclusion:Our study shows that seasonal cold spells and heat waves are essential factors affecting ICH severity,and targeted preventive measures should be taken to minimize the pathological impacts. | Xun Xu Chunyang Liu Rui Liu Qiuyi Jiang Enzhou Lu Chao Yuan Yanchao Liang Huan Xiang Boxian Zhao Xin Chen Ailing Lian Qi Zhou Guang Yang | 2022 | Frigid Zone Medicine2022，2，3： | 1 |
| 19 | Comparative Study of Ship-in-a-Bottle and Anchored Heterogenized Mn Complexes显示文摘 | Yang Guoyu Sun Ailing Zhou Wenfeng Zhu Hailin Jiang Denggao | 2007 | Catalysis Letters (-)2007，，3： | 1 |
| 20 | A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants显示文摘The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years.The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants.Here we show that the bivalency of an affinity maturated fully human singledomain antibody(n3113.1-Fc)exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus,and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2(ACE2)humanized mice.The crystal structure of n3113 in complex with the receptor-binding domain(RBD)of SARS-CoV-2,combined with the cryo-EM structures of n3113 and spike ecto-domain,reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2.The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion,expanding our recognition of neutralization by antibodies against SARS-CoV-2.Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages,including Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),and Delta(B.1.617.2)for n3113.1-Fc with Y58L mutation,demonstrating the potential of n3113.1-Fc(Y58L)as a promising candidate for clinical development to treat COVID-19. | Zhenlin Yang Yulu Wang Yujia Jin Yuanfei Zhu Yanling Wu Cheng Li Yu Kong Wenping Song Xiaolong Tian Wuqiang Zhan Ailing Huang Shanshan Zhou Shuai Xia Xiaoxu Tian Chao Peng Cuicui Chen Yibing Shi Gaowei Hu Shujuan Du Yuyan Wang Youhua Xie Shibo Jiang Lu Lu Lei Sun Yuanlin Song Tianlei Ying | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 1 |
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