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Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo

Acta Pharmaceutica Sinica B 2024年第3期14卷 1302-1316页

作者： Xinyuan Xu Qian zhang Xufeng wang Jing Jin Chengwei Wu Li Feng Xiuyan Yang Mingzhu zhao Yingyi Chen Shaoyong Lu Zhen Zheng Xiaobing Lan Yi wang Yan Zheng Xuefeng Lu Qiufen zhang Jian zhang State Key Laboratory of Medical Genomics National Research Center for Translational Medicine at ShanghaiRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Medicinal Chemistry and BioinformaticsCenter Shanghai Jiao Tong University School of MedicineShanghai 200025China department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghai 200040China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medicine and Medical CenterUniversity of Science and Technology of ChinaHefei 230026China department of Assisted Reproduction Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Pharmacy Ningxia Medical UniversityYinchuan 750004China department of Pancreatic Surgery Shanghai General HospitalShanghai Key Laboratory of Pancreatic DiseaseInstitute of Pancreatic DiseaseShanghai Jiao Tong University School of MedicineShanghai 200080China

Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour ***6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic ***,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be ***,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/***,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/*** allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural ***,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver *** our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic *** not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

关键词： SIRT6 Inhibitor Allosteric Selectivity Cocrystal Pancreatic cancer metastasis

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Two-photon spectroscopic behaviors and photodynamic effect on the BEL-7402 cancer cells of the new chlorophyll photosensitizer

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Science china Chemistry 2008年第6期51卷 529-538页

作者： zhao PeiDe1,2,CHEN Ping1,TANG GuoQing1,LIU JinWei2,LIN Lie1,GUO Peng1,YU Qing2, YAO JianZhong3,MA DongMing4,zhang GuiLan1 & CHEN WenJu1 1 Key Laboratory of Optoelectronic Information Science and Technology,Ministry of Education,Institute of Modern Optics,Nankai university,Tianjin 300071,china 2 department of Physics,Hebei university of Technology,Tianjin 300130,china 3 College of Pharmacy,Second Military Medical university,shanghai 200433,china 4 Tianjin College of the Traditional Chinese Medicine,Tianjin 300193,china Key Laboratory of Optoelectronic Information Science and Technology Ministry of Education Institute of Modern Optics Nankai University Tianjin China department of Physics Hebei University of Technology Tianjin China College of Pharmacy Second Military Medical University Shanghai China Tianjin College of the Traditional Chinese Medicine Tianjin China

The spectroscopic properties of a new chlorophyll derivate photosensitizer (CDP) are studied under the excitation wavelengths at 800 and 400 nm using femtosecond pulses from a Ti: sapphire laser. The damaging effect of CDP on the BEL-7402 cancer cells is also investigated upon two-photon illumination at 800 nm. The normalized fluorescence spectra of CDP in tetrahydrofuran (THF) show that two-photon and one-photon spectra have the same distributions and the same emission bands (675 nm). The lifetimes of two- and one-photon induced fluorescence of this molecule are of the order of 5.0 ns. By comparing the data it is shown that there is some difference between the two lifetimes, but the difference is less than one nanosecond. The two-photon absorption cross section of the molecule is also measured at 800 nm and estimated as about σ'_2 ≈ 31.5x10^(-50)cm^4·s·photon^(-1). The results of two-photon photodynamic therapy (TPPDT) tests show that CDP can kill all of the tested cancer cells according to the usual Eosine assessment. Our results indicate that the two-photon-induced photophysical, photochemical and photosensitizing processes of CDP may be basically similar to those of one-photon excitation. These behaviors of the sample suggest that one may find other possible methods to estimate some photosensitizers' effects in details such as their distribution in cells and the reactive targets of the sub-cellular parts of some tumor cells via two-photon excitation techniques.

关键词： photosensitizer chlorophyll derivate two-photon fluorescence two-photon absorption cross-section TPPDT BEL-7402 cell

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Expression and Comparative Analysis of Genes Encoding Outer Membrane Proteins LipL21,LipL32 and OmpL1 in Epidemic Leptospires

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Acta Biochimica et Biophysica Sinica 2005年第10期37卷 7+650-656页

作者： Xiang-Yan zhang~(1#) Yang YU~(2,3#) Ping HE~1 Yi-Xuan zhang~(2,3) Bao-Yu HU~1 Yang YANG~1 Yi-Xin NIE~4 Xiu-Gao JIANG~4 Guo-Ping zhao~(2,3) Xiao-Kui GUO~(1*) 1 department of Medical Microbiology and Parasitology,shanghai Jiaotong university,shanghai 200025,china 2 Research Center of Biotechnology,shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,shanghai 200031,china 3 Chinese National Human Genome Center at shanghai,zhangjiang High Tech Park,shanghai 201203,china 4 Institute for Infectious Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,china department of Medical Microbiology and Parasitology Shanghai Jiaotong UniversityShanghai 200025 China Research Center of Biotechnology Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031 China Chinese National Human Genome Center at shanghai Zhangjiang High Tech ParkShanghai 201203 China Institute for Infectious Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206 China

Leptospiral outer membrane proteins (OMPs) are highly conserved in different species,andplay an essential role in the development of new immunoprotection and serodiagnosis *** genesencoding LipL21,LipL32 and OmpL1 were cloned from the complete genome sequence of Leptospirainterrogans serovar lai strain Lai and expressed in *** comparison analysis revealed that the threegenes were highly conserved among distinct epidemic leptospires,including three major epidemic speciesLeptospira interrogans,Leptospira borgpetersenii and Leptospira weilii,in *** analysis wasfurther performed to scrutinize 15 epidemic Leptospira reference strains using the antisera of the *** immunoblot assay and reverse transcription-polymerase chain reaction demonstrated that thesethree OMPs were conservatively expressed in pathogenic *** strains and other pathogenic ***,the use of these recombinant OMPs as antigens in enzyme-linked immunosorbent assay (ELISA)for serodiagnosis of leptospirosis was *** recombinant LipL32 and OmpL1 proteins showed ahigh degree of ELISA reactivity with sera from patients infected with *** strain Lai and otherpathogenic *** results may contribute to the identification of candidates for broad-rangevaccines and immunodiagnostic antigens in further research.

关键词： outer membrane protein expression comparative analysis epidemic leptospire

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Studies of low-lying states of even-even Xe isotopes within the nucleon pair approximation

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Science china(Physics,Mechanics & Astronomy) 2011年第S1期54卷 103-108页

作者： zhang LiHua1, JIANG Hui1,2 & zhao YuMin1,3,4 1Institute of Nuclear, Particle, Astrophysics and Cosmology, department of Physics, shanghai Jiao Tong university, shanghai 200240, china 2School of Arts and Sciences, shanghai Maritime university, shanghai 200135, china 3Center of Theoretical Nuclear Physics, National Laboratory of Heavy Ion Accelerator, Lanzhou 730000, china 4CCAST, World Laboratory, P.O. Box 8730, Beijing 100080, china Institute of Nuclear Particle Astrophysics and Cosmology Department of Physics Shanghai Jiao Tong University Shanghai China School of Arts and Sciences Shanghai Maritime University Shanghai China Center of Theoretical Nuclear Physics National Laboratory of Heavy Ion Accelerator Lanzhou China CCAST World Laboratory Beijing China

We study the relevance of nucleon pairs with higher spins, in addition to spin-zero and spin-two pairs (i.e., S D pairs), in low-lying states of even-even Xe nuclei. By including those higher-spin pairs in our configuration, we recalculate energy level schemes, elec trical quadrupole moments, magnetic moments and electric quadrupole transition rates, for low-lying states of even-even 128-142Xe nuclei. The agreement between our calculated results and the experimental data is substantially improved in comparison with previous studies.

关键词： nucleon pair approximation shell model configuration space low-lying states

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Pipeline Embolization Device for intracranial aneurysms presenting with mass effect:a large Chinese cohort

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Stroke & Vascular Neurology 2024年第1期9卷 50-58页

作者： Yang zhao Junlin Lu Hongqi zhang Tianxiao LI Donglei Song Sheng Guan Aisha Maimaitili Yunyan wang Wenfeng Feng Yang wang Jieqing Wan Guohua Mao Huaizhang Shi Xinjian Yang Jianmin Liu Yuanli zhao department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Neurosurgery Peking University International HospitalBeijingChina department of Neurosurgery West China HospitalSichuan UniversityChengduSichuanChina department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Interventional Neuroradiology Zhengzhou University People's HospitalZhengzhouHenanChina department of Neurosurgery Shanghai Donglei Brain HospitalShanghaiChina department of Interventional Neuroradiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina department of Neurosurgery The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangChina department of Neurosurgery Qilu Hospital of Shandong University QingdaoJinanShandongChina department of Neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina department of Neurosurgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of Neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Neurosurgery The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of Neurosurgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina department of Neurosurgery Changhai HospitalNaval Medical UniversityShanghaiChina

Background Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding,relieves symptoms and improve the quality of life for *** study aimed to assess the safety and efficacy of Pipeline Embolization Device(PED,Covidien/Medtronic,Irvine,CA)treatment for intracranial aneurysms presenting with mass effect in real-world *** We selected patients from the PED in china Post-Market Multi-Center Registry Study with mass effect *** study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up(3–36 months).We conducted multivariate analysis to identify factors associated with mass effect *** analyses by aneurysm location,size and form were also *** This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0%(162/218).The postoperative mass effect deterioration rate was 9.6%(21/218).During a median follow-up period of 8.4 months,the mass effect relief rate was 71.6%(156/218).Notably,immediate aneurysm occlusion following treatment was significantly associated with mass effect relief(OR 0.392,95%CI,0.170 to 0.907,p=0.029).Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms,while dense embolism impeded symptom relief in aneurysms10mm and saccular *** Our data confirmed the efficacy of PED in relieving mass *** findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial *** registration number NCT03831672.

关键词： aneurysm intracranial Irvine

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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science china(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting wang Liping wang Yanxin Huang Zhibin Qiao Shanru Yi Weina zhang Jing wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong zhao Hong wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational Research Center of shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China shanghai Institute of Stem Cell Research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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Thermo-hydro-mechanical (THM) coupled simulation of the land subsidence due to aquifer thermal energy storage (ATES) system in soft soils

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Journal of Rock Mechanics and geotechnical engineering 2024年第6期16卷 1952-1966页

作者： Yang wang Fengshou zhang Fang Liu department of geotechnical engineering College of Civil EngineeringTongji UniversityShanghai200092China Key Laboratory of geotechnical and Underground engineering of Ministry of Education Tongji UniversityShanghai200092China shanghai engineering and Technology Research Center of Shallow Geothermal Energy Shanghai200072China

Aquifer thermal energy storage(ATES)system has received attention for heating or cooling ***,it is well known that land subsidence becomes a major environmental concern for ATES ***,the effect of temperature on land subsidence has received practically no attention in the *** paper presents a thermo-hydro-mechanical(THM)coupled numerical study on an ATES system in shanghai,*** water wells were installed for seasonal heating and cooling of an agriculture *** target aquifer at a depth of 74e104.5 m consisted of alternating layers of sand and silty sand and was covered with *** level,temperature,and land subsidence data from 2015 to 2017 were collected using field monitoring *** by data,we constructed a field scale three-dimensional(3D)model using TOUGH(Transport of Unsaturated Groundwater and Heat)and FLAC3D(Fast Lagrangian Analysis of Continua)equipped with a thermo-elastoplastic constitutive *** effectiveness of the numerical model was validated by field *** model was used to reproduce groundwater flow,heat transfer,and mechanical responses in porous media over three years and capture the thermo-and pressure-induced land *** results show that the maximum thermoinduced land subsidence accounts for about 60%of the total *** thermo-induced subsidence is slightly greater in winter than that in summer,and more pronounced near the cold well area than the hot well *** study provides some valuable guidelines for controlling land subsidence caused by ATES systems installed in soft soils.

关键词： Aquifer thermal energy storage(ATES) Land subsidence TOUGH-FLAC3D Thermo-elastoplastic constitutive model

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Efficient and stable hybrid perovskite-organic light-emitting diodes with external quantum efficiency exceeding 40 per cent

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Light(Science & Applications) 2024年第7期13卷 1364-1371页

作者： Lingmei Kong Yun Luo Qianqian Wu Xiangtian Xiao Yuanzhi wang Guo Chen Jianhua zhang Kai wang Wallace CHChoy Yong-Biao zhao Hongbo Li Takayuki Chiba Junji Kido Xuyong Yang Key Laboratory of Advanced Display and System Applications of Ministry of Education Shanghai UniversityShanghai 200072China. Institute of Nanoscience and Applications Department of Electrical and Electronic EngineeringSouthern University of Science and TechnologyShenzhen 518055China. department of Electrical and Electronic engineering The University of Hong KongHong KongChina. department of Physics and Lakeside AR/VR Laboratory International Joint Research Center for Optoelectronic and Engineering ResearchYunnan UniversityKunming 650091China. Experimental Center of Advanced Materials School of Materials Science and EngineeringBeijing Institute of TechnologyBeijing 100081China. Graduate School of Organic Materials Science Frontier Center for Organic MaterialsYamagata University4-3-16 JonanYonezawa 992–8510Japan

Light-emitting diodes(LEDs)based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies,but still suffer from severe instability driven by electric ***,we develop a stable,efficient and highcolor purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of *** LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission *** designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating,the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm,a peak luminance of over 176,000 cd m^(−2),a maximum external quantum efficiency of over 40%,and an operational half-lifetime of over 42,000 h.

关键词： diodes narrow quantum

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Recent progress on Sn_(3)O_(4)nanomaterials for photocatalytic applications

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International Journal of Minerals,Metallurgy and Materials 2024年第2期31卷 231-244页

作者： Xin Yu Congcong Li Jian zhang Lili zhao Jinbo Pang Longhua Ding Institute for Advanced Interdisciplinary Research(iAIR) School of Chemistry and Chemical EngineeringUniversity of JinanJinan 250022China School of Sino-German engineering Shanghai Technical Institute of Electronics and InformationShanghai 201411China Division of Systems and Synthetic Biology Department of Life SciencesChalmers University of Technology41296 GöteborgSweden

Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence *** has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable *** comprehensive review is aimed at providing a detailed overview of the latest advance-ments in research,applications,advantages,and challenges associated with Sn_(3)O_(4)photocatalytic *** fundamental con-cepts and principles of Sn_(3)O_(4)are ***_(3)O_(4)possesses a unique crystal structure and optoelectronic properties that allow it to ab-sorb visible light efficiently and generate photoexcited charge carriers that drive photocatalytic ***,strategies for the control and improved performance of Sn_(3)O_(4)photocatalytic nanomaterials are *** control,ion doping,and hetero-structure construction are widely employed in the optimization of the photocatalytic performance of Sn_(3)O_(4)*** effective imple-mentation of these strategies improves the photocatalytic activity and stability of Sn_(3)O_(4)***,the review explores the diverse applications of Sn_(3)O_(4)photocatalytic nanomaterials in various fields,such as photocatalytic degradation,photocatalytic hydro-gen production,photocatalytic reduction of carbon dioxide,solar cells,photocatalytic sterilization,and optoelectronic *** discus-sion focuses on the potential of Sn_(3)O_(4)-based nanomaterials in these applications,highlighting their unique attributes and ***,the review provides an outlook on the future development directions in the field and offers guidance for the exploration and de-velopment of novel and efficient Sn_(3)O_(4)-based *** the identification of emerging research areas and potential avenues for improvement,this review aims to stimulate further advancements in Sn_(3)O_(4)-based photocatalysis and facilitate the translation of this promising technology into practical applications.

关键词： photocatalysis Sn_(3)O_(4)nanomaterials building heterostructures antibacterial therapy water splitting

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Preparation of grain size controlled boron-doped diamond thin films and their applications in selective detection of glucose in basic solutions

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Science china Chemistry 2010年第6期53卷 1378-1384页

作者： zhao JianWen1,2,wang JinLiang3,ZHI JinFang3 & zhang ZhiMing4 1College of Chemistry and Chemical engineering,Jishou university,Jishou 416000,china 2Schools of Materials Science and engineering,Nanyang Technological university,639798,Singapore 3Laboratory of Organic Optoelectronic Functional Materials and Molecular engineering,Technical Institute of Physics and Chemistry & Graduate university of Chinese Academy of Sciences,Beijing 100080,china 4Research Institute of Micro-Nano Science and Technology,shanghai Jiao Tong university,shanghai 200030,china College of Chemistry and Chemical engineering Jishou University Jishou China Schools of Materials Science and engineering Nanyang Technological University Singapore Singapore Laboratory of Organic Optoelectronic Functional Materials and Molecular engineering Technical Institute of Physics and Chemistry & Graduate University of Chinese Academy of Sciences Beijing China Research Institute of Micro-Nano Science and Technology Shanghai Jiao Tong University Shanghai China

Boron-doped diamond (BDD) thin films with different crystal grain sizes were prepared by controlling the reacting gas pressure using hot filament chemical vapor deposition (HFCVD).The morphologies and structures of the prepared diamond thin films were characterized by scanning electron microscopy (SEM) and Raman *** electrochemical responses of K4Fe(CN)6 on different BDD electrodes were *** results suggested that electron transfer was faster at the boron-doped nanocrystalline diamond (BDND) thin film electrodes in comparison with that at other BDD thin film *** prepared BDD thin film electrodes without any modification were used to directly detect glucose in the basic *** results showed that the as-prepared BDD thin film electrodes exhibited good selectivity for detecting glucose in the presence of ascorbic acid (AA) and uric acid (UA).The higher sensitivity was observed on the BDND thin film grown on the boron-doped microcrystalline diamond (BDMD) thin film surface,and the linear response range,sensitivity and the low detection limit were 0.25–10 mM,189.1 μA mmol-1 cm-2 and 25 μM (S/N=3) for glucose in the presence of AA and UA,respectively.

关键词： diamond thin films electrochemical properties selective glucose detection

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