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Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

Neural Regeneration Research 2024年第8期19卷 1842-1848页

作者： Lu He Qinming Zhou Chaoyang xiu Yaping Shao Dingding shen Huanyu Meng Weidong Le sheng Chen Department of Neurology and Institute of Neurology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Center for Translational Research on Neurological Diseases the First Affiliated HospitalDalian Medical UniversityDalianLiaoning ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Institute of Neurology Sichuan Academy of Medical Sciences-Sichuan Provincial HospitalChengduSichuan ProvinceChina Department of Neurology Xinrui HospitalWuxiJiangsu ProvinceChina

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively d

关键词： amyotrophic lateral sclerosis cathelicidin-related antimicrobial peptide hemoglobin label-free quantitative proteomics multi-protein combined diagnostic panel serum biomarkers talin-1 translationally-controlled tumor protein zyxin

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Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 117-122页

作者： Xin Yang Lu Lu Wen-Wei Zhu Yi-Feng Tao Cong-Huan shen Jin-Hong Chen Zheng-Xin Wang Lun-xiu Qin Hepatobiliary Surgery and Liver Transplantation Centers Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan UniversityShanghai 200040China

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

关键词： Ex vivo liver resection Liver auto-transplantation Oncology Liver malignancies

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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of Interventional Radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells.Cancer cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis.Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment.However,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown.Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC progression.KN93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells.Above all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

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The plant circadian clock regulates autophagy rhythm through transcription factor LUX ARRHYTHMO

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Journal of Integrative Plant Biology 2022年第11期64卷 2135-2149页

作者： Ming-Kang Yang Xiao-Jie Zhu Chu-Min Chen Xu Guo Shu-Xuan Xu Ya-Rou Xu shen-xiu du Shi Xiao Bernd Mueller-Roeber Wei Huang Liang Chen State Key Laboratory for Conservation and Utilization of Subtropical Agro‐Bioresources College of Life SciencesSouth China Agricultural UniversityGuangzhou 510642China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou 510642China Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms South China Agricultural UniversityGuangzhou 510642China State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources School of Life SciencesSun Yat‐Sen UniversityGuangzhou 510275China Department of Molecular Biology Institute of Biochemistry and BiologyUniversity of Potsdam14476 Potsdam‐GolmGermany Max Planck Institute of Molecular Plant Physiology 14476 Potsdam‐GolmGermany

Autophagy is an evolutionarily conserved degradation pathway in eukaryotes;it plays a critical role in nutritional stress tolerance.The circadian clock is an endogenous timekeeping system that generates biological rhythms to adapt to daily changes in the environment.Accumulating evidence indicates that the circadian clock and autophagy are intimately interwoven in animals.However,the role of the circadian clock in regulating autophagy has been poorly elucidated in plants.Here,we show that autophagy exhibits a robust circadian rhythm in both light/dark cycle(LD)and in constant light(LL)in Arabidopsis.However,autophagy rhythm showed a different pattem with a phase-advance shift and a lower amplitude in LL compared to LD.Moreover,mutation of the transcription factor LUX ARRHYTHMO(LUX)removed autophagy rhythm in LL and led to an enhanced amplitude in LD.LUX represses expression of the core autophagy genes ATG2,ATG8 a,and ATG11 by directly binding to their promoters.Phenotypic analysis revealed that LUX is responsible for improved resistance of plants to carbon starvation,which is dependent on moderate autophagy activity.Comprehensive transcriptomic analysis revealed that the autophagy rhythm is ubiquitous in plants.Taken together,our findings demonstrate that the LUXmediated circadian clock regulates plant autophagy rhythms.

关键词： autophagy carbon starvation circadian clock LUX rhythm

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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-Yuan Zhang Lu Wang Mei-Yu Lv Xiang-Peng Li Peng Zhang Yue-Ze Wang Lei shen xiu-Hai Wu Bo Fu Peng-Yu Guo Zi-Qi Wang Dong-Bing Cheng Hao Wang Wanhai Xu NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Department of Urology Harbin Medical University Cancer Hospital CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages.Briefly, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

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XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-sheng Zhang Li-Ping Wang Wen-Wei Hu De-sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong shen Yi Zhang Jing-Ting Jiang xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of Stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains poor.This phase 3 trial(ClinicalTrials.gov:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and bevacizumab.The main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 months.Median PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths reported.The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

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民族地区社会保障经办服务的实践及逻辑

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云南大学学报（社会科学版） 2024年第3期23卷 98-106页

作者：沈澈党秀云中央民族大学北京100081

服务与质量并重是社会保障高质量发展的客观要求。中华人民共和国成立后,党和国家不断健全社会保障经办服务模式,在民族地区先后实行了临时性、组织化、社会化、标准化及数字化经办服务模式。民族地区通过自身能力建设与国家专项支持,... 详细信息

服务与质量并重是社会保障高质量发展的客观要求。中华人民共和国成立后,党和国家不断健全社会保障经办服务模式,在民族地区先后实行了临时性、组织化、社会化、标准化及数字化经办服务模式。民族地区通过自身能力建设与国家专项支持,在服务主体上由中央和地方政府形成叠加合力,服务对象上倡导公民资格与制度标准,服务目标上夯实各民族福利共同体,实现了社会保障经办服务从无到有、从有到均、从均到优,建立了一体共享的服务格局。进入社会主义新时代,民族地区应坚持并优化整体性经办路径,通过外部的人才、技术支持提升自身经办能力,逐步消弭服务边界以促进人才及劳动力合理流动,促进社会保障经办服务惠及边疆地区,通过公共服务共同体进一步铸牢中华民族共同体意识。

关键词：民族地区社会保障经办服务整体性共享

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A likely paleo-autotetraploidization event shaped the high conservation of Nyssaceae genome

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Horticultural Plant Journal 2024年第3期10卷 911-930页

作者： Yishan Feng Zhenyi Wang Qimeng Xiao Jia Teng Jianyu Wang Zijian Yu Jiaqi Wang Qiang Xu Yan Zhang Shaoqi shen Shoutong Bao Yu Li Zimo Yan Yue Ding Zihan Liu Yuxian Li Tianyu Lei Min Yuan xiu-Qing Li Jinpeng Wang Department of Bioinformatics School of Life SciencesNorth China University of Science and TechnologyTangshanHebei 063000China Fredericton Research and Development Centre Agriculture and Agri-Food CanadaFrederictonNew Brunswick E3B 4Z7Canada State Key Laboratory of Systematic and Evolutionary Botany Institute of BotanyChinese Academy of ScienceBeijing 100093China University of Chinese Academy of Sciences Beijing 100049China

Scientific knowledge about the ancestral genome of core eudicot plant kingdom can potentially have profound impacts on both basic and applied research,including evolution,genetics,genomics,ecology,agriculture,forestry,and global climate.To investigate which plant conserves best the core eudicots common ancestor genome,we compared Arcto-Tertiary relict Nyssaceae and 30 other eudicot plant families.The genomes of Davidia involucrata(a known living fossil),Camptotheca acuminata and Nyssa sinensis,one per existent genus of Nyssaceae,were performed comparative genomic analysis.We found that Nyssaceae originated from a single Nyssaceae common tetraploidization event(NCT)-autotetraploidization 28-31 Mya after the core eudicot common hexaploidization(ECH).We identified Nyssaceae orthologous and paralogous genes,determined its chromosomal evolutionary trajectory,and reconstructed the Nyssaceae most recent ancestor genome.D.involucrata genome contained the entire seven paleochromosomes and 17 ECH-generated eudicot common ancestor chromosomes and was the slowest in mutation among the analyzed 42 species of 31 plant families.Combing both its high retention of paleochromosomes and its low mutation rate,D.involucrata provides the best case in conservation of the core eudicot paleogenome.

关键词： Nyssaceae Polyploidization Multigenome alignment Evolutionary rate Autotetraploidization Karyotype evolution

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Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models:A Cross-sectional Study in Rural Guangxi

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Biomedical and Environmental Sciences 2024年第1期37卷 3-18页

作者： LIANG Yu Jian RONG Jia Hui WANG Xue xiu CAI Jian sheng QIN Li Dong LIU Qiu Mei TANG Xu MO Xiao Ting WEI Yan Fei LIN Yin Xia HUANG shen Xiang LUO Ting Yu GOU Ruo Yu CAO Jie Jing HUANG Chu Wu LU Yu Fu QIN Jian ZHANG Zhi Yong Department of Environmental and Occupational Health School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina Key Laboratory of Tumor Immunology and Microenvironmental Regulation Guilin Medical UniversityGuilin 541199GuangxiChina Department of Environmental Health and Occupational Medicine School of Public HealthGuilin Medical UniversityGuilin 541199GuangxiChina Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi Key Laboratory of Environment and Health Research Guangxi Medical UniversityNanning 530021GuangxiChina Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care Guilin Medical UniversityGuilin 541199GuangxiChina

Objective This study aimed to investigate the potential relationship between urinary metals copper(Cu),arsenic(As),strontium(Sr),barium(Ba),iron(Fe),lead(Pb)and manganese(Mn)and grip strength.Methods We used linear regression models,quantile g-computation and Bayesian kernel machine regression(BKMR)to assess the relationship between metals and grip strength.Results In the multimetal linear regression,Cu(β=−2.119),As(β=−1.318),Sr(β=−2.480),Ba(β=0.781),Fe(β=1.130)and Mn(β=−0.404)were significantly correlated with grip strength(Pduction was−1.007(95%confidence interval:−1.362,−0.652;P<0.001)when each quartile of the mixture of the seven metals was increased.Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength,with Cu,As and Sr being negatively associated with grip strength levels.In the total population,potential interactions were observed between As and Mn and between Cu and Mn(P_(interactions) of 0.003 and 0.018,respectively).Conclusion In summary,this study suggests that combined exposure to metal mixtures is negatively associated with grip strength.Cu,Sr and As were negatively correlated with grip strength levels,and there were potential interactions between As and Mn and between Cu and Mn.

关键词： Urinary metals Handgrip strength Quantile g-computation Bayesian kernel machine regression

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Sequential enantioselective Ugi-4CR/post-Ugi transformation strategy:a precise construction of structurally diverse azaspiro polycyclic scaffolds

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Science China Chemistry 2024年第2期67卷 576-586页

作者： Xiao-Bao Wu Jun-xiu Shi Yi-Ming Ou Hua-Jie Jiang Yi-Jun Fang Qi-Ming Wang Quan Gao Jie Yu Department of Applied Chemistry Anhui Province Engineering Laboratory for Green Pesticide Development and ApplicationAnhui Province Key Laboratory of Crop Integrated Pest ManagementAnhui Agricultural UniversityHefei230036China

A privileged strategy has been developed for the precise construction of enantioenriched azaspiro polycyclic scaffolds.Structurally diverse azaspiro polycycles bearing multiple contiguous stereocenters are obtained with excellent results(up to 99:1 e.r.,>95:5 d.r.) via sequential enantioselective four-component Ugi reactions/post-Ugi transformations with substrates containing prerequisite functional groups in the presence of anionic stereogenic-at-cobalt(Ⅲ) complexes.

关键词： asymmetric catalysis post-Ugi transformation anionic stereogenic-at-cobalt(Ⅲ)complex azaspiro polycyclic scaffold one-pot synthesis

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