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Neuroscience Bulletin 2022年第3期38卷 263-274页

作者： Ming-Shuo Shao Xiao Yang Chen-Chun Zhang Chang-You Jiang Ying Mao Wen-Dong Xu Lan Ma Fei-Fei Wang Departments of Neurosurgery and Hand Surgery Huashan HospitalState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceSchool of Basic Medical SciencesInstitutes of Brain ScienceFudan UniversityShanghai200032China

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways,and its disturbance has been found in neurodegenerative diseases and metabolic ***,its role in the mesolimbic dopamine(DA)system,especially in the ventral tegmental area(VTA),needs to be ***,we found that injection of Thiamet G,an O-GlcNAcase(OGA)inhibitor,in the VTA and nucleus accumbens(NAc)of mice,facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod *** with DAergic neuron-specific knockout of O-GlcNAc transferase(OGT)displayed severe metabolic abnormalities and died within 4–8 weeks after ***,mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose,and impaired motor learning in the rotarod ***,overexpression of OGT in GABAergic neurons in the VTA had no effect on these *** results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

关键词： O-GlcNAcylation Dopaminergic neurons Natural reward Motor learning

CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients:promising findings from a prospective,open-label,randomized,phase III trial

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Cancer Communications 2019年第1期39卷 258-270页

作者： Yuankai Shi Jin Li Jianming Xu Yan Sun Liwei Wang Ying Cheng Wei Liu Guoping Sun Yigui Chen Li Bai Yiping Zhang Xiaohui He Yi Luo Zhehai Wang Yunpeng Liu Qiang Yao Yuhong Li Shukui Qin Xiaohua Hu Feng Bi Rongsheng Zheng Xuenong Ouyang Department of Medical Oncology Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted DrugsNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Fudan University Shanghai Cancer Center Shanghai 200032P.R.China The Affiliated Hospital of Military Medical Sciences Beijing 100071P.R.China Shanghai General Hospital Shanghai 200080P.R.China Jilin Cancer Hospital Changchun 130012JilinP.R.China Tumor Hospital of Hebei Province Shijiazhuang 050011HebeiP.R.China The First Affiliated Hospital of Anhui Medical University Hefei 230022AnhuiP.R.China Fujian Provincial Cancer Hospital Fuzhou 350014FujianP.R.China Chinese People’s Liberation Army General Hospital Beijing 100853P.R.China Zhejiang Cancer Hospital Hangzhou 310022ZhejiangP.R.China Hunan Cancer Hospital Changsha 410013HunanP.R.China Shandong Cancer Hospital Jinan 250117ShandongP.R.China The First Hospital of China Medical University Shenyang 110001LiaoningP.R.China Tianjin People’s Hospital Tianjin 300121P.R.China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhou 510060GuangdongP.R.China Chinese People’s Liberation Army Bayi Hospital Nanjing 210002JiangsuP.R.China The Guangxi Zhuang Autonomous Region Tumor Hospital Nanning 530021GuangxiP.R.China West China Hospital Chengdu 610041SichuanP.R.China First Affiliated Hospital of Bengbu Medical College Bengbu 233004AnhuiP.R.China Fuzhou People’s Liberation Army General Hospital Fuzhou 350025FujianP.R.China

Background:The 5-fluorouracil/leucovorin plus oxaliplatin(FOLFOX)regimen is the standard first-line treatment for metastatic colorectal cancer(mCRC),however,the optimal second-line regimen for KRAS wild-type mCRC patients is still *** this study,we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC ***:Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were ran-domly assigned in a 2:1 ratio,to receive CMAB009 plus irinotecan or *** receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 *** primary endpoints were overall response rate(ORR)and median progression-free survival(PFS).The second-ary endpoints were median overall survival(OS),disease control rate(DCR),clinical benefit rate(CBR),and duration of response(DOR).Results:The CMAB009 plus irinotecan arm demonstrated significantly improved ORR(33.2%vs.12.8%;P<0.001)and longer median PFS(169 days vs.95 days;P<0.001)as compared to the irinotecan-only *** receiv-ing CMAB009 plus irinotecan also demonstrated improved DCR(80.1%vs.65.2%,P<0.001),CBR(30.0%vs.14.6%,P<0.001),and DOR(210 days vs.109 days;P<0.001)as compared to ***,patients treated with CMAB009 had an increased risk of skin rash(66.9%vs.5.5%,P<0.001)and paronychia(9.8%vs.0.0%,P<0.001).Anti-drug antibodies(ADA)were detected in 3.6%of patients,and only 0.9%of patients who received CMAB009 experienced hypersensitivity *** patients receiving sequential-CMAB009 therapy after failure with irinotecan,their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940). Conclusions: Treatment with CMAB009 plus irinotecan was found

关键词： CMAB009 Cetuximab Irinotecan Second-line mCRC EGFR KRAS Immunogenicity Fluoropyrimidine Oxaliplatin failure

The composite phenotype analysis identifies potential concerted responses of physiological systems to high altitude exposure

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National Science Review 2023年第5期10卷 109-111页

作者： Yi Li Meng Hao Zixin Hu Yanyun Ma Kun Wang Xiaoyu Liu Xianhong Yin Menghan Zhang Yi Wang Meng Liang Yuan Guo Lei Bao Shixuan Zhang Shiguan Le Chenyuan Wu Dayan Sun Yang Wei Fei Wu Rui Zhang Lingxian Zhu Hui Zhang Shuai Jiang Xingdong Chen Xiaofeng Wang Yao Zhang Longli Kang Wenyuan Duan Bin Qiao Jiucun Wang Li Jin State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and DevelopmentSchool of Life Sciences and Human Phenome InstituteFudan University Institute for Six-sector Economy Fudan University International Human Phenome Institutes Ministry of Education Key Laboratory of Contemporary Anthropology Department of Anthropology and Human GeneticsSchool of Life SciencesFudan University Greater Bay Area Institute of Precision Medicine(Guangzhou) School of Life SciencesFudan University Artificial Intelligence Innovation and Incubation Institute Fudan University Shanghai Pudong Hospital Fudan University Pudong Medical Center Fudan-Taizhou Institute of Health Sciences Key Laboratory of High-Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region School of MedicineXizang Minzu University Institute of Cardiovascular Disease Shandong Provincial Western Hospital Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences

Environmental stresses,such as temperature,disease and altitude could induce systematic changes of biological systems which manifests as concerted responses across multiple systems within a certain period of time[1].High altitude acclimatization (HAA) refers to a series of adaptive physiological responses to hypoxic *** these processes,

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Presence of Rare Variants is Associated with Poorer Survival in Chinese Patients with Amyotrophic Lateral Sclerosis

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Phenomics 2023年第2期3卷 167-181页

作者： Siqi Dong Xianhong Yin Kun Wang Wenbo Yang Jiatong Li Yi Wang Yanni Zhou Xiaoni Liu Jiucun Wang Xiangjun Chen Department of Neurology Huashan Hospital and Institute of NeurologyFudan UniversityShanghai 200040China National Center for Neurological Disorders Shanghai 200040China Department of Anthropology and Human Genetics School of Life SciencesFudan UniversityShanghai 200438China Human Phenome Institute Fudan UniversityShanghai 200433China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disorder with phenotypic and genetic *** studies have suggested an oligogenic basis of ALS,in which the co-occurrence of two or more genetic variants has additive or synergistic deleterious *** assess the contribution of possible oligogenic inheritance,we profiled a panel of 43 relevant genes in 57 sporadic ALS(sALS)patients and eight familial ALS(fALS)patients from five pedigrees in east *** filtered rare variants using the combination of the Exome Aggregation Consortium,the 1000 Genomes and the HuaBiao *** analyzed patients with multiple rare variants in 43 known ALS causative genes and the genotype–phenotype ***,we detected 30 rare variants in 16 different genes and found that 16 of the sALS patients and all the fALS patients examined harbored at least one variant in the investigated genes,among which two sALS and four fALS patients harbored two or more *** note,the sALS patients with one or more variants in ALS genes had worse survival than the patients with no ***,in one fALS pedigree with three variants,the family member with three variants(Superoxide dismutase 1(SOD1)p.V48A,Optineurin(OPTN)p.A433V and TANK binding kinase 1(TBK1)p.R573H)exhibited much more severe disease phenotype than the member carrying one variant(TBK1 p.R573H).Our findings suggest that rare variants could exert a negative prognostic effect,thereby supporting the oligogenic inheritance of ALS.

关键词： Amyotrophic lateral sclerosis Oligogenic inheritance Survival Superoxide dismutase 1 TANK-binding kinase 1 Optineurin

Embedding expert demonstrations into clustering buffer for effective deep reinforcement learning

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Frontiers of Information Technology & Electronic Engineering 2023年第11期24卷 1541-1556页

作者： Shihmin WANG Binqi ZHAO Zhengfeng ZHANG Junping ZHANG Jian PU Shanghai Key Laboratory of Intelligent Information Processing School of Computer ScienceFudan UniversityShanghai 200433China Institute of Science and Technology for Brain-inspired Intelligence Fudan UniversityShanghai 200433China

As one of the most fundamental topics in reinforcement learning(RL),sample efficiency is essential to the deployment of deep RL *** most existing exploration methods that sample an action from different types of posterior distributions,we focus on the policy sampling process and propose an efficient selective sampling approach to improve sample efficiency by modeling the internal hierarchy of the ***,we first employ clustering methods in the policy sampling process to generate an action candidate *** we introduce a clustering buffer for modeling the internal hierarchy,which consists of on-policy data,off-policy data,and expert data to evaluate actions from the clusters in the action candidate set in the exploration *** this way,our approach is able to take advantage of the supervision information in the expert demonstration *** on six different continuous locomotion environments demonstrate superior reinforcement learning performance and faster convergence of selective *** particular,on the LGSVL task,our method can reduce the number of convergence steps by 46.7%and the convergence time by 28.5%.Furthermore,our code is open-source for *** code is available at https://***/Shihwin/SelectiveSampling.

关键词： Reinforcement learning Sample eficiency Sampling process Clustering methods Autonomous driving

SARS-CoV-2 infection and the antiviral innate immune response

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Journal of Molecular Cell Biology 2020年第12期12卷 963-967页

作者： Hui Yang Yingying Lyu Fajian Hou Department of Neurosurgery Huashan HospitalInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceShanghai Medical CollegeFudan UniversityShanghai 200032China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200032China

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak be-gan in December 2019,causing the illness known as the novel coronavirus disease 2019(COVID-19).The virus spread rapidly worldwide to become a global public health *** of November 15,2020,more than 53 million confirmed cases and over 1 million deaths worldwide have been reported(World Health Organization,2020).

关键词： acute respiratory infection

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

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Journal of Genetics and Genomics 2021年第10期48卷 928-935页

作者： Zhuoma Basang Shixuan Zhang La Yang Deji Quzong Yi Li Yanyun Ma Meng Hao WeiLin Pu Xiaoyu Liu Hongjun Xie Meng Liang Jiucun Wang Qiangba Danzeng High Altitude Medical Research Center of Tibet University/Center of Tibetan Studies(Everest Research Institute) Tibet University10 East Zangda RoadLhasaTibet 850000China State Key Laboratory of Genetic Engineering School of Life Sciences&Human Phenome InstituteFudan UniversityShanghai 200438China Institute for Six-sector Economy Fudan UniversityShanghai 200433China Ministry of Education Key Laboratory of Contemporary Anthropology Department of Anthropology and Human GeneticsSchool of Life SciencesFudan UniversityShanghai 200438China Tibet University-Fudan University Joint Laboratory for Biodiversity and Global Change Tibet University10 East Zangda RoadLhasaTibet 850000China

High altitude is an extreme environment that imposes hypoxic pressure on physiological processes,and natives living at high altitudes are more adaptive in certain physiological *** far,epigenetic modifications under extreme changes in hypoxic pressures are relatively less ***,we recruit 32 Tibetan elite alpinists(TEAs),who have successfully mounted Everest(8848 m)at least five *** samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers(non-TEAs)are collected for ***-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs(P_(adj)0.1)between the two *** differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L,MAP3K7CL,SEPTI-9,and *** addition,Gene ontology enrichment analysis reveals several inflammation-related *** analysis indicates that 12 phenotypes are significantly different between the two *** particular,TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count,platelet count,and heart *** DNA methylation association analysis,we find that two CpGs(cg16687447,cg06947206)upstream of PTEN were associated with platelet *** conclusion,extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA,providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.

关键词： Adaptive potentials Extreme hypoxia environment DNA methylation Phenotype association Elite alpinists Mountaineering

Scanning and Splicing Atom Lithography for Self-traceable Nanograting Fabrication

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Nanomanufacturing and Metrology 2022年第2期5卷 179-187页

作者： Xiao Deng Wen Tan Zhaohui Tang Zichao Lin Xinbin Cheng Tongbao Li MOE Key Laboratory of Advanced Micro-Structured Materials Tongji UniversityShanghai200092China Institute of Precision Optical Engineering School of Physics Science and EngineeringTongji UniversityShanghai200092China

Atom lithography is a unique method to fabricate self-traceable pitch standards and angle standards,but extending its structure area to millimeter-level for application is *** this paper,on the one hand,we put forward a new approach to fabricate a full-covered self-traceable Cr nanograting by inserting and scanning a Dove prism in the Gaussian beam direction of atom *** the other hand,we extend the structure area along the standing-wave direction by splicing two-step atom *** nanostructures manufactured via scanning atom lithography and splicing atom lithography demonstrate good pitch accuracy,parallelism,continuity,and homogeneity,which opens a new way to fabricate centimeter-level full-covered self-traceable nanograting and lays the basis for the application of square ruler and optical encoders at the nanoscale.

关键词： Scanning atom lithography Splicing atom lithography Nanograting Self-traceability Dove prism

Scattering exceptional point in the visible

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Light(Science & Applications) 2023年第10期12卷 2228-2235页

作者： Tao He Zhanyi Zhang Jingyuan Zhu Yuzhi Shi Zhipeng Li Heng Wei Zeyong Wei Yong Li Zhanshan Wang Cheng-Wei Qiu Xinbin Cheng MOE Key Laboratory of Advanced Micro-Structured Materials Shanghai 200092China Institute of Precision Optical Engineering School of Physics Science and EngineeringTongji UniversityShanghai 200092China Shanghai Institute of Intelligent Science and Technology Tongji UniversityShanghai 200092China Shanghai Frontiers Science Center of Digital Optics Shanghai 200092China Shanghai Professional Technical Service Platform for Full-Spectrum and High-Performance Optical Thin Film Devices and Applications Shanghai 200092China Department of Electronic Science and Technology Tongji UniversityShanghai 201804China Department of Electrical and Computer Engineering National University of SingaporeSingapore 117583Singapore Institute of Acoustics School of Physics Science and EngineeringTongji UniversityShanghai 200092China

Exceptional point (EP) is a special degeneracy of non-Hermitian systems. One-dimensional transmission systems operating at EPs are widely studied and applied to chiral conversion and sensing. Lately, two-dimensional systems at EPs have been exploited for their exotic scattering features, yet so far been limited to only the non-visible waveband. Here, we report a universal paradigm for achieving a high-efficiency EP in the visible by leveraging interlayer loss to accurately control the interplay between the lossy structure and scattering lightwaves. A bilayer framework is demonstrated to reflect back the incident light from the left side ( | r_(−1) | >0.999) and absorb the incident light from the right side ( | r_(+1) | < 10^(–4)). As a proof of concept, a bilayer metasurface is demonstrated to reflect and absorb the incident light with experimental efficiencies of 88% and 85%, respectively, at 532 nm. Our results open the way for a new class of nanoscale devices and power up new opportunities for EP physics.

关键词： visible exceptional incident

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort

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Phenomics 2021年第1期1卷 3-14页

作者： Yi Li Yanyun Ma Kun Wang Menghan Zhang Yi Wang Xiaoyu Liu Meng Hao Xianhong Yin Meng Liang Hui Zhang Xiaofeng Wang Xingdong Chen Yao Zhang Wenyuan Duan Longli Kang Bin Qiao Jiucun Wang Li Jin State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and DevelopmentSchool of Life Sciences and Human Phenome InstituteFudan UniversityShanghai 200438China Ministry of Education Key Laboratory of Contemporary Anthropology Department of Anthropology and Human GeneticsSchool of Life SciencesFudan UniversityShanghai 200438China Institute for Six‑Sector Economy Fudan UniversityShanghai 200433China Fudan-Taizhou Institute of Health Sciences Taizhou 225300China Key Laboratory of High Altitude Environment and Genes Related To Diseases of Tibet Autonomous Region School of MedicineXizang Minzu UniversityXianyang 712082China Institute of Cardiovascular Disease Shandong Provincial Western HospitalJinanShandong 250022China Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases(2019RU058) Chinese Academy of Medical SciencesBeijing 100730China

Altitude acclimatization is a human physiological process of adjusting to the decreased oxygen *** several physiological processes are involved and their correlations are complicated,the analyses of single traits are insufficient in revealing the complex mechanism of high-altitude *** this study,we examined these physiological responses as the composite phenotypes that are represented by a linear combination of physiological *** developed a strategy that combines both spectral clustering and partial least squares path modeling(PLSPM)to define composite phenotypes based on a cohort study of 883 Chinese Han *** addition,we captured 14 composite phenotypes from 28 physiological traits of high-altitude *** these composite phenotypes,we applied k-means clustering to reveal hidden population physiological heterogeneity in high-altitude ***,we employed multivariate linear regression to systematically model(Models 1 and 2)oxygen saturation(SpO_(2))changes in high-altitude acclimatization and evaluated model fitness *** phenotypes based on Model 2 fit better than single trait-based Model 1 in all measurement *** new strategy of using composite phenotypes may be potentially employed as a general strategy for complex traits research such as genetic loci discovery and analyses of phenomics.

关键词： Altitude acclimatization Composite phenotypes Hypoxia Complex traits Phenomics