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Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan sun Xiu-Na Yang Shuang-Shuang Yang Yi-Zhu Lyu Bing Zhang Kai-Wen Liu Na Li Jia-chen Cui Guang-Xiang Huang cheng-Lin Liu Jie Xu Jian-Qing Mi Zhu chen Xiao-Hu Fan Sai-Juan chen Shuo chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China National Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular ***,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based *** co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple *** we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated *** analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in ***-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived *** results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi chen Chang-Zhen Ren Ke-Yan sun Hao Liu Shao-Hua Song Zhi-Ren Fu Department of Organ Transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China Department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various ***,little is known about its effect on hepatic ischemia-reperfusion(I/R)*** study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying ***:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R *** alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver *** severity related to the inflammatory response and reactive oxygen species(ROS)production was also ***,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in ***:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and *** oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin *** addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in *** blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling ***:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

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Biomimetic Phosphohydrolase Nanozyme Based on Defect-Engineered Metal-Organic Framework

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CCS Chemistry 2024年第7期6卷 1821-1835页

作者： Xiaoxue Kou Yuhong Lin Yong Shen Linjing tong Rui Gao Suya Liu Siming Huang Fang Zhu Guosheng chen Gangfeng Ouyang MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of ChemistrySun Yat-sen UniversityGuangzhou 510006 Shanghai NanoPort Thermo Fisher ScientificPudong DistrictShanghai 200120 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436

Phosphodiester bonds are the backbone linkages of all the nucleic acids which store and transfer biological *** hydrolysis of phosphodiester bonds is of great importance to the replication,recombination,and damage repair of DNA as well as the maturation and processing of ***,the spontaneous scission of individual phosphodiester linkages is kinetically challenging under physiological conditions,with an estimated half-life of 30 million ***,we discover a defect-engineered Zr-metal-organic framework(Zr-MOF)nanozyme containing cluster-missing reo defects,named UiO-66 REO,that possesses intrinsic phosphodiesterase-like activity that allows for the cleavage of the phosphodiester bond in physiological condition(pH=7.4 and 37℃),outperforming the activityrecording *** atomic-level structure of the UiO-66 REO nanozyme has been directly identified by the synchrotron radiation absorption spectrum and integrated differential phase contrast-scanning transmission electron *** find that both the defective boundary regions and unusual Zr6-clusters formed in the reo phase of the UiO-66 REO nanozyme contribute to the improvement in efficiency of phosphodiesterase-like hydrolysis,which realizes the cleavage of DNA in mild *** work offers a new insight into biomimetic enzymology using crystal and defect engineering and opens up new possibilities for the development of low-cost,structurally stable and sustainable phosphodiesterase nanozymes for different biological applications.

关键词： nanozyme metal-organic framework biomimetic catalysis hydrolase-like activity defective engineering

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A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid

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Science China Life Sciences 2024年第10期67卷 2213-2223页

作者： Jingge Lian Liu Yang Hanbo Tan Shaoyi Su Leonor Serrano Lopes Fangxiao cheng Junhao Yan Yu Fu Wanyi Fu Zhaoheng Xie Jianfei sun Jicong Zhang Zhiqian tong Yajuan Gao Hongbin Han Department of Radiology Peking University Third Hospital Beijing Key Laboratory of Magnetic Resonance Imaging Technology Institute of Medical Technology Peking University Health Science Center Department of Informatics Technical University of Munich Department of Anatomy and Histology School of Basic Medical SciencesPeking University Department of Neurology Peking University Third Hospital Department of Electronic Engineering Tsinghua University State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast University School of Biological Science and Medical Engineering Beihang University Key Laboratory of Alzheimer's Disease of Zhejiang Province Institute of AgingSchool of Mental HealthWenzhou Medical University NMPA Key Laboratory for Evaluation of Medical Imaging Equipment and Technique

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation(EAI), for accelerating interstitial fluid(ISF)drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS). In this study, the method of EAI was modified(m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model. The results demonstrated the accumulation of IL-1β, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

关键词： ischemic stroke brain extracellular space interstitial fluid modified epidural arterial implantation

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Opportunities for production and property research of neutron-rich nuclei around N=126 at HIAF

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Nuclear Science and Techniques 2024年第6期35卷 101-113页

作者： Shao-Bo Ma Li-Na Sheng Xue-Heng Zhang Shi-Tao Wang Kai-Long Wang Chun-Wang Ma Hool-Jin Ong Zhi-Yu sun Shu-Wen Tang Yu-Hong Yu Xin-tong Du Xiao-Bao Wei Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Advanced Energy Science and Technology Guangdong Laboratory Huizhou 516000China University of Chinese Academy of Sciences Beijing 100049China College of Physics Henan Normal UniversityXinxiang 453007China Institute of Nuclear Science and Technology Henan Academy of ScienceZhengzhou 450046China Joint-Department for Nuclear Physics Lanzhou University and Institute of Modern PhysicsLanzhou 730000China Research Center for Nuclear Physics Osaka UniversityOsaka 567-0047Japan RIKEN Nishina Center Saitama 351-0198Japan Northwest Normal University Lanzhou 730070China

The study of nuclide production and its properties in the N=126 neutron-rich region is prevalent in nuclear physics and astrophysics *** upcoming High-energy FRagment Separator(HFRS)at the High-Intensity heavy-ion Accelerator Facility(HIAF),an in-flight separator at relativistic energies,is characterized by high beam intensity,large ion-optical acceptance,high magnetic rigidity,and high momentum resolution *** provides an opportunity to study the production and properties of neutron-rich nuclei around N=*** this paper,an experimental scheme is proposed to produce neutron-rich nuclei around N=126 and simultaneously measure their mass and lifetime based on the HFRS separator;the feasibility of this scheme is evaluated through *** results show that under the high-resolution optical mode,many new neutron-rich nuclei approaching the r-process abundance peak around A=195 can be produced for the first time,and many nuclei with unknown masses and lifetimes can be produced with high *** the time-of-flight corrected by the measured dispersive position and energy loss information,the cocktails produced from 208 Pb fragmentation can be unambiguously ***,the masses of some neutron-rich nuclei near N=126 can be measured with high precision using the time-of-flight magnetic rigidity *** indicates that the HIAF-HFRS facility has the potential for the production and property research of neutron-rich nuclei around N=126,which is of great significance for expanding the chart of nuclides,developing nuclear theories,and understanding the origin of heavy elements in the universe.

关键词： HFRS Fragmentation Neutron-rich nuclei around N=126 Mass measurement Lifetime

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Efficacy of Sailuotong(塞络通)on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer's disease

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Journal of Traditional Chinese Medicine 2024年第2期44卷 289-302页

作者： sun Linjuan LI chengfu LIU Jiangang LI Nannan HAN Fuhua QIAO Dandan TAO Zhuang ZHAN Min chen Wenjie ZHANG Xiaohui tong chenguang chen Dong Qi Jiangxia LIU Yang LIANG Xiao ZHENG Xiaoying ZHANG Yunling Department of Neurology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China China Population and Development Research Center Beijing 100081China Department of Institute of Population Research Peking UniversityBeijing 100087China Graduate School of China Academy of Chinese Medical Sciences Beijing 100700China Graduate School of Beijing University of Chinese Medicine Beijing 100029China

OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a *** Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of *** hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red *** ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western *** mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by *** results of HE staining showed that SLT restored the pathological changes of the *** Congo red staining results revealed that SLT also improved the scattered

关键词： Alzheimer disease amyloid beta-protein precursor presenilin-1 mice transgenic replenishing Qi and activating blood neurovascular unit Sailuotong

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北京2022年冬奥会六足冰壶机器人机构设计与运动规划

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Engineering 2024年第4期35卷 15-31页

作者： Ke Yin Yue Gao Feng Gao Xianbao chen Yue Zhao Yuguang Xiao Qiao sun Jing sun School of Electronic Information and Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Mechanical System and Vibration School of Mechanical EngineeringShanghai Jiao Tong UniversityShanghai 200240China

When a curling rock slides on an ice sheet with an initial rotation,a lateral movement occurs,which is known as the curling *** force of friction between the curling rock and the ice sheet changes continually with changes in the environment;thus,the sport of curling requires great skill and *** throwing of the curling rock is a great challenge in robot design and control,and existing curling robots usually adopt a combination scheme of a wheel chassis and gripper that differs significantly from human throwing movements.A hexapod curling robot that imitates human kicking,sliding,pushing,and curling rock rotating was designed and manufactured by our group,and completed a perfect show during the Beijing 2022 Winter Olympics *** switching between the walking and throwing tasks is realized by the robot’s morphology transformation based on leg configuration *** robot’s controlling parameters,which include the kicking velocity v_(k),pushing velocity v_(p),orientation angle θc,and rotation velocityω,are determined by aiming and sliding models according to the estimated equivalent friction coefficientμ_(equ)and ratio e of the front and back *** stable errors between the target and actual stopping points converge to 0.2 and 1.105 m in the simulations and experiments,respectively,and the error shown in the experiments is close to that of a well-trained wheelchair curling *** robot holds promise for helping ice-makers rectify ice sheet friction or assisting in athlete training.

关键词： Legged robot Curling robot Winter Olympics Mechanism design Motion planning

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Advances and perspectives in environmental health research in China

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Frontiers of Environmental Science & Engineering 2024年第6期18卷 105-113页

作者： tong Zhu Yingjun Liu Shunqing Xu Guanghui Dong Cunrui Huang Nan Sang Yunhui Zhang Guanyong Su Jingwen chen Jicheng Gong Guohua Qin Xinghua Qiu Jing Shang Haobo Wang Pengpeng Wang Mei Zheng SKL-ESPC&SEPKL-AERM Department of Environmental HealthCollege of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China Center for Environment and Health Peking UniversityBeijing 100871China School of Life and Health Sciences Huainan UniversityHaikou 570228China Joint International Research Laboratory of Environment and Health(Ministry of Education) Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk AssessmentDepartment of Occupational and Environmental HealthSchool of Public HealthSun Yat-sen UniversityGuangzhou 510080China Vanke School of Public Health Tsinghua UniversityBeijing 100084China Research Center of Environment and Health College of Environment and ResourceShanxi UniversityTaiyuan 030006China Department of Environmental Health School of Public HealthFudan UniversityShanghai 200032China School of Environmental and Biological Engineering Nanjing University of Science and TechnologyNanjing 210094China Key Laboratory of Industrial Ecology and Environmental Engineering(Ministry of Education) Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention TechnologySchool of Environmental Science and TechnologyDalian University of TechnologyDalian 116024China Department of Occupational and Environmental Health College of Public HealthZhengzhou UniversityZhengzhou 450001China

Environmental health research aims to identify environmental conditions suitable for the healthy living and reproduction of human *** the interdisciplinary research bridging environmental sciences and health/medical sciences,the impacts of physical,chemical,and biological environmental factors on human health are *** includes identifying environmental factors detrimental to human health,evaluating human exposure characteristics to environmental factors,clarifying causal relationships between environmental exposure and health effects,analyzing the underlying biochemical mechanisms,linking environmental factors to the onset and progression of diseases,establishing exposure-response relationships,and determining effect ***,the results of environmental health research can serve as a scientific basis for formulating environmental management strategies and guiding prevention and intervention measures at both the public and individual *** paper summarizes the recent advances and future perspectives of environmental health research in China,as reported by a group of Chinese scientists who recently attended a workshop in Hainan,*** it is not intended to provide a comprehensive review of this expansive field,it offers a glimpse into the significant progress made in understanding the health impacts of environmental factors over the past *** ahead,it is imperative not only to sustain efforts in studying the health effects of traditional environmental pollution,but also to prioritize research on the health impacts of emerging pollutants and climate change.

关键词： Environmental pollution Emerging pollutants Climate change Exposure Mechanism

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Microbiomics and metabolomics insights into the microbial regulation on the formation of flavor components in the traditional fermentation process of Chinese Hongqu aged vinegar

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Food Science and Human Wellness 2024年第5期13卷 2765-2778页

作者： Shangong tong Wenlong Li Yuandong Rao Yanqin Xiao Yingyin Yan Weiling Guo Xucong Lü Jinyuan sun Lianzhong Ai Li Ni Institute of Food Science and Technology College of Biological Science and EngineeringFuzhou UniversityFuzhou 350108China Food Nutrition and Health Research Center School of Advanced ManufacturingFuzhou UniversityJinjiang 362200China School of Food Science and Technology Jiangnan UniversityWuxi 214122China Beijing Laboratory for Food Quality and Safety Beijing Technology and Business UniversityBeijing 100048China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China

This study aimed to investigate microbial succession and metabolic dynamics during the traditional fermentation of Hongqu aged vinegar,and explore the core functional microbes closely related to the formation of flavor *** analysis demonstrated that Lactobacillus,Acetobacter,Bacillus,Enterobacter,Lactococcus,Leuconostoc and Weissella were the predominant bacterial genera,while Aspergillus piperis,Aspergillus oryzae,Monascus purpureus,Candida athensensis,***,Penicillium ochrosalmoneum and Simplicillium aogashimaense were the predominant fungal *** analysis revealed that Acetobacter was positively correlated with the production of tetramethylpyrazine,acetoin and acetic acid,Lactococcus showed positive correlation with the production of 2-nonanone,2-heptanone,ethyl caprylate,ethyl caprate,1-hexanol,1-octanol and 1-octen-3-ol,*** and *** were positively associated with the production of diethyl malonate,2,3-butanediyl diacetate,acetoin,benzaldehyde and ***,non-volatile metabolites were also detected through ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.A variety of amino acids and functional dipeptides were identified during the traditional brewing of Hongqu aged *** analysis revealed that Lactobacillus was significantly associated with DL-lactate,indolelactic acid,D-(+)-3-phenyllactic acid,pimelic acid,pregabalin and 3-aminobutanoic *** study is useful for understanding flavor formation mechanism and developing effective strategies for the suitable strains selection to improve the flavor quality of Hongqu aged vinegar.

关键词： Hongqu aged vinegar Traditional fermentation Microbial dynamics Flavor components Bidirectional orthogonal partial least squares

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui sun Xiao Jin Guangquan chen Guang Ning Lin Li Weiqing Wang Yanan Cao Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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