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| 1 | CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys显示文摘Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson’s disease(PD)with selective neurodegeneration.Unfortunately,current PINK1 knockout(KO)mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1’s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2(T1)and exon 4(T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys(Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.A T7E1 assay and sequencing of PCR products from the injected embryos showed high efficiency(61.5%)in targeting PINK1(Fig.1b and Supplementary information,Fig.S1).Transfer of 87 embryos to 28 surrogate rhesus monkeys resulted in 11 pregnancies(39.2%)(Fig.1b).Eleven fetuses developed to term and were born naturally.Of these live monkeys,eight carried PINK1 mutations(M),and three were wild type(WT).However,three mutant monkeys(M1,M3 and M4)were newborn triplets that struggled to survive and died 3-4 days after birth.One WT newborn monkey also died after a difficult labor.Another mutant monkey(M2)died 7 days after birth without noticeable warning signs or symptoms.The other three mutant monkeys(M6,M7 and M8)have lived for three years;M5,however,reduced its food intake and showed weakness at the age of 1.5 years,and died 30 days after anesthesia for MRI examination. | Weili Yang Yunbo Liu Zhuchi Tu Chong Xiao Sen Yan Xishan Ma Xiangyu Guo Xiusheng Chen Peng Yin Zhengyi Yang Su Yang Tianzi Jiang Shihua Li Chuan Qin Xiao-Jiang Li | 2019 | Cell Research2019，29，4： | 12 |
| 2 | Spinal Cord Stimulation Frequency Influences the Hemodynamic Response in Patients with Disorders of Consciousness显示文摘Spinal cord stimulation(SCS) is a promising technique for treating disorders of consciousness(DOCs).However, differences in the spatio-temporal responsiveness of the brain under varied SCS parameters remain unclear. In this pilot study, functional near-infrared spectroscopy was used to measure the hemodynamic responses of 10 DOC patients to different SCS frequencies(5 Hz, 10 Hz, 50 Hz, 70 Hz, and 100 Hz). In the prefrontal cortex, a key area in consciousness circuits, we found significantly increased hemodynamic responses at 70 Hz and 100 Hz, and significantly different hemodynamic responses between 50 Hz and 70 Hz/100 Hz. In addition, the functional connectivity between prefrontal and occipital areas was significantly improved with SCS at 70 Hz. These results demonstrated that SCS modulates the hemodynamic responses and long-range connectivity in a frequency-specific manner(with 70 Hz apparently better), perhaps by improving the cerebral blood volume and information transmission through the reticular formation-thalamus-cortex pathway. | Juanning Si Yuanyuan Dang Yujin Zhang Yaxin Li Wenyue Zhang Yi Yang Yue Cui Xiaoping Lou Jianghong He Tianzi Jiang | 2018 | Neuroscience Bulletin2018，34，4： | 10 |
| 3 | The long rather than the short allele of 5-HTTLPR predisposes Han Chinese to anxiety and reduced connectivity between prefrontal cortex and amygdala显示文摘The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants (n = 233). In contrast to findings in Caucasians, we found that long-allele (L) carriers had higher anxiety scores. In another group (n = 64) experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex (PFC), which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications. | Haixia Long Bing Liu Bing Hou Chao Wang Jin Li Wen Qin Dawei Wang Yuan Zhou Keith M. Kendrick Chunshui Yu Tianzi Jiang | 2013 | Neuroscience Bulletin2013，29，1： | 9 |
| 4 | Research Progress of Medicinal Secondary Metabolites and Gene Cloning of Dendrobium officinale显示文摘Dendrobium officinale is one of the most precious medicinal plants in China. Its main medicinal ingredients are its secondary metabolites. However,it has the characteristics of limited sources,low active ingredient content and high cost,limiting the use of D. officinale.Studying the network structure and rate-limiting steps of secondary metabolites of medicinal components of D. officinale,analyzing the secondary metabolic synthesis process,mastering the production rules of its medicinal components and carrying out gene cloning or biosynthesis,etc.are of great significance for the rational development and utilization of D. officinale resources. This paper briefly reviews the progress of the research on the secondary metabolites of D. officinale,including the detection and identification of metabolites and the identification and cloning of key metabolic enzymes. | Ye LIANG Caihua ZOU Jindu LI Shilong LI Tianzi LI | 2019 | Medicinal Plant2019，10，3： | 8 |
| 5 | Separate Neural Networks for Gains and Losses in Intertemporal Choice显示文摘An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses. Using psychophysiological interaction and dynamic causal modeling analyses, we investigated the functional interactions between regions involved in the decisionmaking process while participants performed temporal discounting tasks in both the gains and losses domains. We found two distinct intrinsic valuation systems underlying temporal discounting in the gains and losses domains:gains were specifically evaluated in the medial regions,including the medial prefrontal and orbitofrontal cortices,and losses were evaluated in the lateral dorsolateral prefrontal cortex. In addition, immediate reward or punishment was found to modulate the functional interactions between the dorsolateral prefrontal cortex and distinct regions in both the gains and losses domains: in the gains domain, the mesolimbic regions; in the losses domain, the medial prefrontal cortex, anterior cingulate cortex, and insula. These findings suggest that intertemporal choice of gains and losses might involve distinct valuation systems,and more importantly, separate neural interactions may implement the intertemporal choices of gains and losses.These findings may provide a new biological perspective for understanding the neural mechanisms underlying intertemporal choice of gains and losses. | Yang-Yang Zhang Lijuan Xu Zhu-Yuan Liang Kun Wang Bing Hou Yuan Zhou Shu Li Tianzi Jiang | 2018 | Neuroscience Bulletin2018，34，5： | 6 |
| 6 | Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese显示文摘Alzheimer's disease is the most common neurodegenerative disease,and has a high level of genetic heritability and population heterogeneity.In this study,we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease,followed by independent validation,imaging analysis and function characterization.We identified an exome-wide significant rare missense variant rs3792646(p.K420Q)in the C7 gene in the discovery stage(P=1.09×10^(-6),odds ratio=7.853)and confirmed the association in different cohorts and a combined sample(1615 cases and 2832 controls,P_(combined)=2.99×10^(-7),odds ratio=1.930).The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood,thus resulting in an earlier age of disease onset.Overexpression of the mutant p.K420Q disturbed cell viability,immune activation and β-amyloid processing.Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons.These findings suggested that C7 is a novel risk gene for Alzheimer’s disease in Han Chinese. | Deng-Feng Zhang Yu Fan Min Xu Guihong Wang Dong Wang Jin Li Li-Li Kong Hejiang Zhou Rongcan Luo Rui Bi Yong Wu Guo-Dong Li Ming Li Xiong-Jian Luo Hong-Yan Jiang Liwen Tan Chunjiu Zhong Yiru Fang Chen Zhang Nengyin Sheng Tianzi Jiang Yong-Gang Yao | 2019 | National Science Review2019，6，2： | 6 |
| 7 | An App knock-in rat model for Alzheimer’s disease exhibiting Aβand tau pathologies,neuronal death and cognitive impairments显示文摘A major obstacle in Alzheimer’s disease(AD)research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy.Transgenic mice overexpressing amyloid precursor protein(App)gene manifest non-physiological and ectopic expression of APP and its fragments in the brain,which is not observed in AD patients.The App knock-in mice circumvented some of these problems,but they do not exhibit tau pathology and neuronal death.We have generated a rat model,with three familiar App mutations and humanized Aβsequence knocked into the rat App gene.Without altering the levels of full-length APP and other APP fragments,this model exhibits pathologies and disease progression resembling those in human patients:deposit of Aβplaques in relevant brain regions,microglia activation and gliosis,progressive synaptic degeneration and AD-relevant cognitive deficits.Interestingly,we have observed tau pathology,neuronal apoptosis and necroptosis and brain atrophy,phenotypes rarely seen in other APP models.This App knock-in rat model may serve as a useful tool for AD research,identifying new drug targets and biomarkers,and testing therapeutics. | Keliang Pang Richeng Jiang Wei Zhang Zhengyi Yang Lin-Lin Li Makoto Shimozawa Simone Tambaro Johanna Mayer Baogui Zhang Man Li Jiesi Wang Hang Liu Ailing Yang Xi Chen Jiazheng Liu Bengt Winblad Hua Han Tianzi Jiang Weiwen Wang Per Nilsson Wei Guo Bai Lu | 2022 | Cell Research2022，32，2： | 6 |
| 8 | Wearable wireless real-time cerebral oximeter for measuring regional cerebral oxygen saturation显示文摘Monitoring regional cerebral oxygen saturation throughout the perioperative clinical process is important for successful patient outcomes.Cerebral oximeters based on near-infrared spectroscopy(NIRS)have already been used for monitoring brain oxygenation and hemodynamics to avoid intraoperative ischemic stroke and reduce postoperative cognitive dysfunction.The current devices are all designed to be used as a bedside monitor,limiting their use to situations that center around a hospital bed.There is a current lack of wearable,miniaturized,wireless equipment that can extend brain oxygenation monitoring to motion tasks or tight spaces.We design a head-mounted wearable wireless oxygen saturation monitoring on head(WORTH)band based on NIRS for monitoring regional cerebral oxygen saturation.The band is embedded with a highly integrated central block,which comprises an optical module,a microprocessor unit,a wireless communication module,and a power management module.The performance of the WORTH band is evaluated by a controlled hypoxia experiment and a squat-to-stand experiment.The results confirm that the WORTH band can record cerebral oxygen saturation with an accuracy comparable to that of a clinical monitor and demonstrate that it is also effective during motion tasks. | Juanning SI Xin ZHANG Meng LI Jian YU Zhiyong ZHANG Qing HE Shaohua CHEN Lianqing ZHU Tianzi JIANG | 2021 | Science China(Information Sciences)2021，64，1： | 4 |
| 9 | Effect of combined medicated thread moxibustion plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica显示文摘OBJECTIVE: To investigate the effect and underlying mechanisms of combined medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica.METHODS: One hundred Wistar rats, of specific pathogen free level, were randomly divided into five groups: normal control group, model group,medicated thread moxibustion group, needle picking group, and combination group. Each group contained 20 rats. In the model, medicated thread moxibustion, needle picking, and combination groups,sciatica models were established through chronicconstriction injury of the sciatic nerve. After the model was established, the rats in the medicated thread moxibustion, needle picking, and combination groups were given the corresponding therapies for 21 days. The control and model groups received no treatment. Reactive oxygen species, superoxide dismutase, malondialdehyde, and total antioxidant capacity changes were determined.Nicotinamide adenine dinucleotide phosphate(NADPH) oxidase subunit NADPH oxidases 4(NOX4) m RNA expression and the morphology of cells were observed to detect apoptosis of gamma-aminobutyric acid ergic(GABAergic) neurons.RESULTS: Compared with control group, reactive oxygen species and malondialdehyde levels rose significantly in the model group(P < 0.01), while superoxide dismutase and total antioxidant capacity levels were lowered(P < 0.05). Compared with the model group, reactive oxygen species and malondialdehyde decreased in the needle picking group(P < 0.05), while superoxide dismutase levels were increased(P < 0.05); reactive oxygen species and malondialdehyde significantly decreased in the combination group(P < 0.01). In addition, the model group had higher NOX4 m RNA expression than that of the control group(P < 0.05), and the combination group had lower expression levels than that of the model group(P < 0.05). Apoptosis of GABAergic neurons was observed in the model group, and was attenuated after combined therapy.CONCLUSION: The medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine can prevent oxidative damage in the rat model of sciatica via down-regulating NOX4 expression, improving antioxidant capacity, and in-hibiting the oxidative damage pathway of GABAergic neurons. | Tang Hanqing Zheng Jianyu Li Tianzi Li Keming Li Xiaohua Dou Xibin Huang Chunchuan Liang Ye | 2016 | Journal of Traditional Chinese Medicine2016，36，6： | 4 |
| 10 | Reconstruction of behavior-relevant individual brain activity:an individualized fMRI study显示文摘Different patterns of brain activity are observed in various subjects across a wide functional domain.However,these individual differences,which are often neglected through the group average,are not yet completely understood.Based on the fundamental assumption that human behavior is rooted in the underlying brain function,we speculated that the individual differences in brain activity are reflected in the individual differences in behavior.Adopting 98 behavioral measures and assessing the brain activity induced at seven task functional magnetic resonance imaging states,we demonstrated that the individual differences in brain activity can be used to predict behavioral measures of individual subjects with high accuracy using the partial least square regression model.In addition,we revealed that behavior-relevant individual differences in brain activity transferred between different task states and can be used to reconstruct individual brain activity.Reconstructed individual brain activity retained certain individual differences which were lost in the group average and could serve as an individual functional localizer.Therefore,our results suggest that the individual differences in brain activity contain behavior-relevant information and should be included in group averaging.Moreover,reconstructed individual brain activity shows a potential use in precise and personalized medicine. | Dongya Wu Xin Li Tianzi Jiang | 2020 | Science China(Life Sciences)2020，63，3： | 3 |
| 11 | ASAF: altered spontaneous activity fingerprinting in Alzheimer’s disease based on multisite fMRI显示文摘Several monocentric studies have noted alterations in spontaneous brain activity in Alzheimer's disease (AD), although there is no consensus on the altered amplitude of low-frequency fluctuations in AD patients. The main aim of the present study was to identify a reliable and reproducible abnormal brain activity pattern in AD. The amplitude of local brain activity (AM), which can provide fast mapping of spontaneous brain activity across the whole brain, was evaluated based on multisite rs-fMRI data for 688 subjects (215 normal controls (NCs), 221 amnestic mild cognitive impairment (aMCI) 252 AD). Two-sample t-tests were used to detect group differences between AD patients and NCs from the same site. Differences in the AM maps were statistically analyzed via the Stouffer's meta-analysis. Consistent regions of lower spontaneous brain activity in the default mode network and increased activity in the bilateral hippocampus/parahippocampus, thalamus, caudate nucleus, orbital part of the middle frontal gyrus and left fusiform were observed in the AD patients compared with those in NCs. Significant correlations (P? | Jiachen Li Dan Jin Ang Li Bing Liu Chengyuan Song Pan Wang Dawei Wang Kaibin Xu Hongwei Yang Hongxiang Yao Bo Zhou Alexandre Bejanin Gael Chetelat Tong Han Jie Lu Qing Wang Chunshui Yu Xinqing Zhang Yuying Zhou Xi Zhang Tianzi Jiang Yong Liu Ying Han | 2019 | Science Bulletin2019，64，14： | 3 |
| 12 | Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study显示文摘 | Yong He Liang Wang Yufeng Zang Lixia Tian Xinqing Zhang Kuncheng Li Tianzi Jiang | 2006 | Neuroimage2006，，2： | 1 |
| 13 | Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study显示文摘 | Yong He Liang Wang Yufeng Zang Lixia Tian Xinqing Zhang Kuncheng Li Tianzi Jiang | 2006 | Neuroimage2006，，2： | 1 |
| 14 | Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: Evidence from resting state fMRI显示文摘 | Liang Wang Yufeng Zang Yong He Meng Liang Xinqing Zhang Lixia Tian Tao Wu Tianzi Jiang Kuncheng Li | 2005 | Neuroimage2005，，2： | 1 |
| 15 | Authors' response to “Maternal age as a potential explanation of the role of the L allele of the serotonin transporter gene in anxiety and depression in Asians”显示文摘In the letter to the editor,Dr.Comings et al.proposed a potential explanation of our findings that the L allele rather than S allele of 5-HTTLPR was associated with higher anxiety levels and reduced amygdala-prefrontal cortex(PFC)connectivity in Han Chinese[1],which demonstrated an‘allele reversal’in the genetics of the 5-HTTLPR gene in Asians | Haixia Long Bing Liu Bing Hou Chao Wang Jin Li Tianzi Jiang | 2014 | Neuroscience Bulletin2014，30，3： | 0 |
| 16 | Elastic Model of Flexure-Based Linkage under Motion Constrains and External Load显示文摘For a flexible mechanism with several-stage flexible linkage, the flexible linkage is equivalent to work under the actions of an external load and motion constrains. This paper aims to deal with a simplified elastic model on the kinematic characteristics of a flexure-based linkage under these conditions. The elastic modeling method was developed based on motion constrains and the elastic beam theorem(EBT). Effects of a constant force, an elastic force with a constant stiffness, and the materials were taken into account. The proposed modeling method was verified by comparing with the finite element method(FEM). Further, the developed modeling method was used to optimize a flexure-based mechanism based on a two-stage flexible linkage to realize a maximum displacement amplification ratio of 6.56. The flexure-based mechanism was employed to drive a miniature sucker, which performed with a negative pressure of 2.45 kPa at a frequency of 13.2 kHz. | Peibo Li Jihao Liu Tianzi Zhao Helei Zhu Yanzheng Zhao | 2021 | Journal of Harbin Institute of Technology(New Series)2021，28，3： | 0 |
| 17 | De novo engineering of nanoformulation from traditional Chinese medicine mixtures for psoriasis显示文摘Nanotechnology has been widely applied in the development of traditional Chinese medicine(TCM).Interestingly,we found that nanostructures intrinsically existed in 12 clinically applied TCM mixtures(TCMMs).However,the role of these nanostructures in TCMMs and their potential value in improving the development of TCMMs remain unknown.Taking Qingxuechushi mixture as an example,we demonstrated that nanoparticles could be the most efficient part through the pharmacodynamics study on psoriasis model.By imitating the physical properties and chemical composition of isolated nanoparticles in Qingxuechushi mixture,a novel nanoformulation with definite components and good therapeutic effect was developed,which not only mimicked the prescription composition rules in the original TCMMs but also possessed the advantage of nanotechnology.This novel nanoformulation could notably alleviate the psoriasis-like manifestations and reduce the levels of pro-inflammatory factors in serum in the psoriasis mouse model.This work organically integrates the advantages of TCMMs and nanotechnology,which may provide a new approach and inspiration for the development of TCM. | Yang Li Dan Zhang Tianzi Shi Yulin Yu Yinmei Tian Qi Xie Jingyu Shi Li Kong Conglian Yang Zhiping Zhang | 2023 | Nano Research2023，16，4： | 0 |
| 18 | COVID-19 Stay-At-Home Orders and Older Adults’ Cognitive Health — United States, June 2018–February 2022显示文摘What is already known about this topic?Lack of social activities is known to negatively impact cognitive functioning and increase risk of cognitive impairment,including dementia,among older adults.What is added by this report?Coronavirus disease 2019(COVID-19)stay-at-home orders implemented in the U.S.early during the pandemic were not found to negatively affect cognitive functioning of older adults.What are the implications for public health practice?There may have been no severe,unintended consequences of the COVID-19 stay-at-home orders in terms of their impact on cognitive functioning and risk of dementia among older adults,lending further support to use of such orders. | Nam Sun Choi Tianzi Li Jingxiang Pan Selena Yue Jing Li | 2022 | China CDC weekly2022，4，45： | 0 |
| 19 | Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design显示文摘The global 'myopia boom' has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies(GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent(SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou(631 <-6.00 D and 574 > 0.00 D) and Wenzhou(593 <-6.00 D and54 >-1.75 D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1 q25.2 FAM163 A, 10 p11.22 NRP1/PRAD3, and 10 p11.21 ANKRD30 A/MTRNR2 L7, together explaining 3.34% of SE variance. 10 p11.21 is successfully replicated.The allele frequencies of all three loci show significant differences between major continental groups(P < 0.001). The SE reducing(more myopic) allele of rs10913877(1 q25.2 FAM163 A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans(EAS = 0.60,EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities. | Xiaotong Han Tianzi Liu Xiaohu Ding Jialin Liu Xingyan Lin Decai Wang Moeen Riaz Paul N.Baird Zhi Xie Yuan Cheng Yi Li Yuki Mori Masahiro Miyake Hengtong Li Ching-Yu Cheng Changqing Zeng Kyoko Ohno-Matsui Xiangtian Zhou Fan Liu Mingguang He | 2022 | Journal of Genetics and Genomics2022，49，1： | 0 |
| 20 | Unsupervised Anomaly Detection Approach Based on Adversarial Memory Autoencoders for Multivariate Time Series显示文摘The widespread usage of Cyber Physical Systems(CPSs)generates a vast volume of time series data,and precisely determining anomalies in the data is critical for practical production.Autoencoder is the mainstream method for time series anomaly detection,and the anomaly is judged by reconstruction error.However,due to the strong generalization ability of neural networks,some abnormal samples close to normal samples may be judged as normal,which fails to detect the abnormality.In addition,the dataset rarely provides sufficient anomaly labels.This research proposes an unsupervised anomaly detection approach based on adversarial memory autoencoders for multivariate time series to solve the above problem.Firstly,an encoder encodes the input data into low-dimensional space to acquire a feature vector.Then,a memory module is used to learn the feature vector’s prototype patterns and update the feature vectors.The updating process allows partial forgetting of information to prevent model overgeneralization.After that,two decoders reconstruct the input data.Finally,this research uses the Peak Over Threshold(POT)method to calculate the threshold to determine anomalous samples from normal samples.This research uses a two-stage adversarial training strategy during model training to enlarge the gap between the reconstruction error of normal and abnormal samples.The proposed method achieves significant anomaly detection results on synthetic and real datasets from power systems,water treatment plants,and computer clusters.The F1 score reached an average of 0.9196 on the five datasets,which is 0.0769 higher than the best baseline method. | Tianzi Zhao Liang Jin Xiaofeng Zhou Shuai Li Shurui Liu Jiang Zhu | 2023 | Computers, Materials & Continua2023，，7： | 0 |
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