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Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

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Chinese Chemical Letters 2016年第10期27卷 1626-1629页

作者： Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng ai-hua nie Wen-Xia Zhou Beijing Institute of Pharmacology and Toxicology Beijing100850China

By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.

关键词： Alzheimer's diseaseBACE inhibitor SecretaseDrug discoveryCyclic acylguanidine

Design and synthesis of 3＇-(prop-2-yn-1-yloxy)-biphenyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

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Chinese Chemical Letters 2016年第6期27卷 961-963页

作者： Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng ai-hua nie Wen-Xia Zhou Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

Based on the lead compounds 1 and 2, a series of novel BACE1 inhibitors were designed and synthesized,among which compound 9h exhibited a 60 fold improvement in potency over the lead compound 1. This represents a good lead for the discovery of more promising BACE1 inhibitors for the potential treatment of AD. The result also showed that the prop-2-yn-1-yloxy is a suitable fragment for modification of cyclic acylguanidine BACE1 inhibitors.

关键词： Alzheimer’s disease BACE1 inhibitor Prop-2-yn-1-yloxy Cyclic acylguanidine

Design and synthesis of cyclic acylguanidines as BACE1 inhibitors

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Chinese Chemical Letters 2015年第10期26卷 1327-1330页

作者： Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Wen-Xia Zhou ai-hua nie Beijing Institute of Pharmacology and Toxicology

Based on the lead compound 1 reported in literature, a series of novel BACE1 inhibitors were designed and synthesized, among which compound 11 exhibited a 14-fold improvement in potency over the lead compound 1. This ... 详细信息

关键词： Alzheimer’s disease BACE1 inhibitor Cyclic acylguanidine

Convergence analysis for complementary-label learning with kernel ridge regression

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Applied Mathematics(A Journal of Chinese Universities) 2024年第3期39卷 533-544页

作者： nie Wei-lin WANG Cheng XIE Zhong-hua School of Mathematics and Statistics Huizhou UniversityHuizhou 516007China School of Computer Science and Engineering Huizhou UniversityHuizhou 516007China

Complementary-label learning(CLL)aims at finding a classifier via samples with complementary *** data is considered to contain less information than ordinary-label *** transition matrix between the true label and the complementary label,and some loss functions have been developed to handle this *** this paper,we show that CLL can be transformed into ordinary classification under some mild conditions,which indicates that the complementary labels can supply enough information in most *** an example,an extensive misclassification error analysis was performed for the Kernel Ridge Regression(KRR)method applied to multiple complementary-label learning(MCLL),which demonstrates its superior performance compared to existing approaches.

关键词： multiple complementary-label learning partial label learning error analysis reproducing kernel Hilbert spaces

Advancements in S-scheme heterojunction materials for photocatalytic environmental remediation

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Journal of Materials Science & Technology 2024年第2期169卷 182-198页

作者： Changliang nie Xiaohan Wang Ping Lu Yukun Zhu Xin Li hua Tang School of Environmental Science and Engineering State Key Laboratory of Bio-fibers and Eco-textilesQingdao UniversityQingdao266071China Institute of Biomass Engineering Key Laboratory of Energy Plants Resource and UtilizationMinistry of Agriculture and Rural AffairsSouth China Agricultural UniversityGuangzhou510642China School of Environmental Science and Engineering Shandong UniversityQingdao266237China

Recently,S-scheme heterojunctions have gained considerable attention in the field of photocatalytic environmental remediation as their potential to achieve efficient spatial charge separation coupled with strong redox ***,this review provides an overview of the current state-of-the-art in the development of S-scheme-based photocatalysts for the purification of environmental *** review first covers the fundamentals of heterogeneous photocatalysis for environmental ***,an introduction to the background,mechanism,design principles,and characterization techniques of S-scheme heterojunctions is ***,the review presents a comparison and summary of using various S-scheme photocatalysts for the removal of several target pollutants,such as bacteria,heavy metals,nitrogen oxides,antibiotics,and ***,the modification strategies of S-scheme heterojunction photocatalysts are also ***,a brief discussion of the challenges and prospects associated with S-scheme photocatalytic systems is demonstrated.

关键词： S-scheme heterojunctions Photocatalyst Pollutant Environmental remediation

Identification and Characteristics Analysis of Micro-Seismic Signals in the Haima Seep Area

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Journal of Earth Science 2024年第1期35卷 288-291页

作者： Xiangchun Wang Bing nie Zhiyu Wu Weiwei Wang hua Chen China University of Geosciences Beijing 100083China CNOOC China Limited Shenzhen BranchShenzhen 518000China Guangzhou Marine Geological Survey Guangzhou 511458China CNOOC China Limited Shanghai BranchShanghai 200335China

*** recent years,with the steady development of offshore energy exploration technology,submarine gas seepage sites,and their products are gradually being identified and *** submarine cold seep is a seepage phenomenon in which hydrocarbon gases stored deep in the seafloor are transported to seawater by gushing or seepage under the action of tectonic compression(Roy et al.,2019;Tinivella and Giustiniani,2016).

关键词： submarine Seismic offshore

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1690-1704页

作者： Shu-Chang nie Yan-hua Jing Lu Lu Si-Si Ren Guang Ji Han-Chen Xu Institute of Digestive Diseases Longhua HospitalChina-Canada Center of Research for Digestive DiseasesShanghai University of Traditional Chinese MedicineShanghai 200032China Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation Shanghai 200032China State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine(Shanghai University of Traditional Chinese Medicine) Shanghai 200032China

Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of *** create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer ***,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor *** this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC *** study provides ideas and methods to enhance survival rates in patients with CRC.

关键词： Myeloid-derived suppressor cells Tumor microenvironment Colorectal cancer Therapy Immunosuppression

Facile and effective synthesis strategy for terbium-doped hydroxyapatite toward photoelectric devices and flexible functional fibers

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Rare Metals 2024年第4期43卷 1713-1723页

作者： Xiao-Dong Zhang Kun nie Zi-Yao Hu Ran-Ran Zhou Xiu-Qiang Duan Wu-Bin Dai Song-Song nie Song-Jun Yao Luo-Xin Wang Le-Fu Mei hua Wang Yi-Yi Yao Xiao-Xue Ma Hubei Key Laboratory for New Textile Materials and Applications and State Key Laboratory of New Textile Materials and Advanced Processing Technology School of Materials Science and EngineeringWuhan Textile UniversityWuhan430200China Key Laboratory of Testing and Tracing of Rare Earth Products for State Market Regulation Jiangxi University of Science and TechnologyGanzhou341000China Hubei Key Laboratory of Plasma Chemistry and Advanced Materials and Key Laboratory of Green Chemical Engineering Process of Ministry of Education Wuhan Institute of TechnologyWuhan430205China

As a material with good biocompatibility,hydroxyapatite(HAP)can have optical properties after doping with various rare earth *** a biocompatible fluorescent material,doped HAP could have broad applications in biological probes,drug delivery,optoelectronic materials,fluorescence anti-counterfeiting,and other *** this paper,we put forward the preparation of HAP doped with terbium(Ⅲ)ions(Tb^(3+))by hydrothermal *** controlling the Tb^(3+)doping content in reaction and the reaction time,the changes in HAP's structure,morphology,and luminescence properties under different conditions were *** the doping amount of Tb^(3+)reached an optimal value,the dipole-quadrupole would occur and the concentration would be *** control experiment showed that the optimal Tb3+content was 7.5×10^(-5)mol,which showed the best fluorescence ***,a non-luminous material,was rarely used in the field of fluorescent anti-counterfeiting and photoelectric *** proposed to prepare a luminescent aramid/polyphenylene sulfide(ACFs/PPS)fiber paper and a new light-emitting diode(LED)using the Tb-doped HAP *** composite sample exhibited an excellent stability and fluorescence performance,which also demonstrated a possibility of HAP applications in anticounterfeiting and *** introduction of Tb3+dopant HAP was done to give HAP optical properties and broaden the application range of HAP.

关键词： Hydroxyapatite Rare earth luminescence Photoelectric device Aramid Polyphenylene sulfide fiber paper Luminescent fiber

Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1869-1877页

作者： Bang Liu Zhao-Xiong Zhang Xin-Yang nie Wei-Lin Sun Yong-Jia Yan Wei-hua Fu Department of General Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this *** To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these *** Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation *** between the training and validation groups were *** training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram *** The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,***(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was *** Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon *** nomogram model exhibited good agreement and accuracy.

关键词： T4N0M0 colon cancer Prognosis Multivariate analysis Nomogram Colon cancer