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Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

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Military Medical Research 2022年第4期9卷 419-431页

作者： Dan-Dan Zhou Wei-Qi Bai Xiao-Tian Zhai li-Ping Sun Yong-Su Zhen zhuo-rong li Qing-Fang Miao NHC Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.1 Tiantan XilBeijing 100050China Department of Organic Chemistry Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.1 Tiantan XiliBeijing 100050China

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to d

关键词： Triple-negative breast cancer Epidermal growth factor receptor Antibody–drug conjugate Targeted therapy Antitumor effect

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MicroRNA and mRNA profiling of cerebral cortex in a transgenic mouse model of Alzheimer’s disease by RNA sequencing

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Neural Regeneration Research 2021年第10期16卷 2099-2108页

作者： li Zeng Hai-Lun Jiang Ghulam Md Ashraf zhuo-rong li Rui liu Organic Chemistry and Function Laboratory Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina King Fahd Medical Research Center King Abdulaziz UniversityJeddahSaudi Arabia Department of Medical Laboratory Technology Faculty of Applied Medical SciencesKing Abdulaziz UniversityJeddahSaudi Arabia

In a previous study,we found that long non-coding genes in Alzheimer’s disease(AD)are a result of endogenous gene disorders caused by the recruitment of microRNA(miRNA)and mRNA,and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD.In this study,we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level.To this aim,we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD.Overall,129 mRNAs and 68 miRNAs were aberrantly expressed.Among these,eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets.The main enriched signaling pathways involved mitogen-activated kinase protein,phosphatidylinositol 3-kinase-protein kinase B,mechanistic target of rapamycin kinase,forkhead box O,and autophagy.An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed.These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies,early diagnosis,and prevention of AD.The present results provide a novel perspective on the role of miRNAs and mRNAs in AD.This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing,China(approval No.IMB-201909-D6)on September 6,2019.

关键词： 3ʹ-untranslated region Alzheimer’s disease biomarker cerebral cortex Gene Ontology high-throughput sequencing intracellular neurofibrillary tangles microtubule-associated protein-τ miRNA-mRNA network presenilin 1

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Electrochemical Reduction of Benzo[b]thiophene 1,1-Dioxides with HFIP as Hydrogen Donor

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Chinese Journal of Chemistry 2024年第6期42卷 585-591页

作者： Ming-Zhong Guo Mei-Jin Mou zhuo Chen Shao-Fei Ni Ming li li-rong Wen lin-Bao Zhang State Key Laboratory Base of Eco-Chemical Engineering College of Chemistry and Molecular EngineeringQingdao University of Science & TechnologyQingdaoShandong266042 China Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province Shantou UniversityShantouGuangdong515063 China

A straightforward electrochemical reduction of benzo[b]thiophene 1,1-dioxides with HFIP as the hydrogen donor has been reported in an undivided cell under metal-free conditions.Moreover,the tolerance of various functi... 详细信息

关键词： Electrochemistry Reduction Benzo[b]thiophene 1,1-dioxides Deuterium Hydrogen source

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Total synthesis of cajanine and its antiproliferative activity against human hepatoma cells

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Acta Pharmaceutica Sinica B 2011年第2期1卷 93-99页

作者： Xing-yue Ji Si-tu Xue Guang-hui Zheng Yan-xing Han Zong-ying liu Jian-dong Jiang zhuo-rong li Department of Medicinal Chemistry Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.

关键词： Total synthesis Cajanine Longistyline A Antiproliferative activity

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Optimal geometrical configuration and oxidation state of cobalt cations in spinel oxides to promote the performance of li-O_(2) battery

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Nano Research 2024年第1期17卷 221-227页

作者： Yu Zhang Shuting Zhang Mengwei Yuan Yufeng li rong liu Caiyun Nan Chen Chen Engineering Research Center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084China Beijing Key Laboratory of Energy Conversion and Storage Materials Institution College of ChemistryBeijing Normal UniversityBeijing 100875China X-ray diffraction Lab Analytical and Testing CenterBeijing Normal UniversityBeijing 100875China

Co_(3)O_(4) is considered as one of promising cathode catalysts for lithium oxygen(li-O_(2))batteries,which contains both tetrahedral Co^(2+)sites(Co^(2+)Td)and octahedral Co^(3+)sites(Co^(3+)Oh).It is important to reveal the effect of optimal geometric configuration and oxidation state of cobalt ion in Co_(3)O_(4) to improve the performance of li-O_(2) batteries.Herein,through regulating the synthesis process,Co^(2+)and Co^(3+)sites in Co_(3)O_(4) were replaced with Zn and Al atoms to form materials with a unique Co site.The li-O_(2) batteries based on ZnCo_(2)O_(4) showed longer cycle life than that of CoAl_(2)O_(4),suggesting that in Co_(3)O_(4),the Co^(3+)Oh site is a relatively better geometric configuration than Co^(2+)Td site for li-O_(2) batteries.Theoretical calculations revealed that Co^(3+)Oh sites provide higher catalysis activity,regulating the adsorption energy of the intermediate liO_(2) and accelerating the kinetics of the reaction in batteries,which further leads to the change of the morphology of the discharge product and ultimately improves the electrochemical performance of the batteries.

关键词： lithium oxygen(li-O_(2))batteries geometrical configuration oxidation state lithium peroxide

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CHD4-induced up-regulation of ERα activity contributes to breast cancer progression

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Genes & Diseases 2024年第3期11卷 132-135页

作者： Aman Sattout Xiaomin Yu zhuo Sun Yanan li Yulin li Shujing li Wei Huo Huijian Wu School of Bioengineering&Key Laboratory of Protein Modification and Disease Liaoning ProvinceDalian University of TechnologyDalianLiaoning 116024China Department of Oncology Central Hospital Affiliated with Dalian University of TechnologyDalianLiaoning 116089China

The estrogen signaling system is a crucial regulator of metabolicandphysiologicalprocesses.However,abnormal activation of estrogen signaling may play a role in breast cancer initiation and progression.Crucial to this pathway is the interaction between estrogen receptor alpha(ERa)and various co-transcription activators.1 Although numerous studies have investigated ER coregulators,the protein-protein interaction networks of ERa are not fully understood.Recent research has shown that high chromodomain helicase DNA-binding 4(CHD4)expression is linked to poor prognosis in various cancers.2,?In this study,we demonstrated that both CHD4 and ERαcontribute to breast cancer progression while providing evidence of the regulatory processes and functional interplay between these two proteins.

关键词： breast cancer ERα

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Thermal fatigue and wear of compacted graphite iron brake discs with various thermomechanical properties

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China Foundry 2024年第3期21卷 248-256页

作者： Gui-quan Wang zhuo Xu Zhong-li liu Xiang Chen Yan-xiang li School of Nuclear Equipment and Nuclear Engineering Yantai UniversityYantai 264005ShandongChina School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationBeijing 100084China

The increase in payload capacity of trucks has heightened the demand for cost-effective yet high performance brake discs.In this work,the thermal fatigue and wear of compacted graphite iron brake discs were investigated,aiming to provide an experimental foundation for achieving a balance between their thermal and mechanical properties.Compacted graphite iron brake discs with different tensile strengths,macrohardnesses,specific heat capacities and thermal diffusion coefficients were produced by changing the proportion and strength of ferrite.The peak temperature,pressure load and friction coefficient of compacted graphite iron brake discs were analyzed through inertia friction tests.The morphology of thermal cracks and 3D profiles of the worn surfaces were also discussed.It is found that the thermal fatigue of compacted graphite iron discs is determined by their thermal properties.A compacted graphite iron with the highest specific heat capacity and thermal diffusion coefficient exhibits optimal thermal fatigue resistance.Oxidization of the matrix at low temperatures significantly weakens the function of alloy strengthening in hindering the propagation of thermal cracks.Despite the reduced hardness,increasing the ferrite proportion can mitigate wear loss resulting from low disc temperatures and the absence of abrasive wear.

关键词： compacted graphite iron brake disc thermomechanical properties thermal fatigue wear

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NbN quantum dots anchored hollow carbon nanorods as efficient polysulfide immobilizer and lithium stabilizer for li-S full batteries

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Journal of Energy Chemistry 2024年第1期88卷 260-271,I0007页

作者： Fei Ma zhuo Chen Katam Srinivas Ziheng Zhang Yu Wu Dawei liu Hesheng Yu Yue Wang Xinsheng li Ming-qiang Zhu Qi Wu Yuanfu Chen School of Integrated Circuit Science and Engineering and State Key Laboratory of Electronic Thin Films and Integrated DevicesUniversity of Electronic Science and TechnologyChengdu 610054SichuanChina College of Science and Institute of Oxygen Supply Center of Tibetan Studies(Everest Research Institute)Tibet UniversityLhasa 850000TibetChina College of Mechanical and Electronic Engineering Northwest A&F UniversityXianyang 712100ShaanxiChina

The shuttle effect of lithium polysulfides(liPSs)and uncontrollable lithium dendrite growth seriously hinder the practical application of lithium-sulfur(li-S)batteries.To simultaneously address such issues,monodispersed Nb N quantum dots anchored on nitrogen-doped hollow carbon nanorods(NbN@NHCR)are elaborately developed as efficient li PSs immobilizer and li stabilizer for high-performance li-S full batteries.Density functional theory(DFT)calculations and experimental characterizations demonstrate that the sulfiphilic and lithiophilic NbN@NHCR hybrid can not only efficiently immobilize the soluble li PSs and facilitate diffusion-conversion kinetics for alleviating the shuttling effect,but also homogenize the distribution of li+ions and regulate uniform li deposition for suppressing li-dendrite growth.As a result,the assembled li-S full batteries(NbN@NHCR-S||Nb N@NHCR-li)deliver excellent long-term cycling stability with a low decay rate of 0.031%per cycle over 1000 cycles at high rate of 2 C.Even at a high S loading of 5.8 mg cm^(-2)and a low electrolyte/sulfur ratio of 5.2μL mg^(-1),a large areal capacity of 6.2 mA h cm^(-2)can be achieved in li-S pouch cell at 0.1 C.This study provides a new perspective via designing a dual-functional sulfiphilic and lithiophilic hybrid to address serious issues of the shuttle effect of S cathode and dendrite growth of li anode.

关键词： Dual-functional host NbN quantum dots Shuttle effect Dendrite-free li anode li-S full batteries

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Vibration Control of A Flexible Marine Riser System Subject to Input Dead Zone and Extraneous Disturbances

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China Ocean Engineering 2024年第2期38卷 271-284页

作者： ZHOU li WANG Guo-rong WAN Min School of Mechatronic Engineering Southwest Petroleum UniversityChengdu 610500China Energy Equipment Institute Southwest Petroleum UniversityChengdu 610500China National Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum UniversityChengdu 610500China

An observer-based adaptive backstepping boundary control is proposed for vibration control of flexible offshore riser systems with unknown nonlinear input dead zone and uncertain environmental disturbances.The control algorithm can update the control law online through real-time data to make the controller adapt to the environment and improve the control precision.Specifically,based on the adaptive backstepping framework,virtual control laws and Lyapunov functions are designed for each subsystem.Three direction interference observers are designed to track the timevarying boundary disturbance.On this basis,the inverse of the dead zone and linear state transformation are used to compensate for the original system and eliminate the adverse effects of the dead zone.In addition,the stability of the closed-loop system is proven by Lyapunov stability theory.All the system states are bounded,and the vibration offset of the riser converges to a small area of the initial position.Finally,four examples of flexible marine risers are simulated in MATLAB to verify the effectiveness of the proposed controller.

关键词： adaptive backstepping control disturbance observer flexible marine riser input dead zone vibration control

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Temporal and Spatial Trends in HIV Positivity Rate for VCT Clinics—China,2015–2022

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China CDC weekly 2024年第1期6卷 6-11页

作者： Yi liu rong Su Dongmin li Shaorong Wang Mengjie Han National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina

Introduction:Human immunodeficiency virus(HIV)voluntary counseling and testing(VCT)clinics play a critical role in identifying and diagnosing HIV cases.This study aimed to describe the trend of HIV positivity rate(HPR)among Chinese VCT clinics between 2015 and 2022.Methods:This study utilized data from the China Information System for Disease Control and Prevention to analyze the trend in the HPR for VCT clinics from 2015 to 2022.The HPR was calculated by dividing the number of newly-reported HIV cases by the number of HIV tests,multiplied by 100%.To identify temporal and spatial trends in the HPR,we employed joinpoint regression analysis and the Getis-Ord hotspot analysis.Results:From 2015 to 2022,VCT clinics in China performed a total of 22,075,386 HIV tests,leading to the identification of 260,353 HIV cases,resulting in a HPR of 1.18%.The HPR consistently declined over the study period,with an average annual percent change(AAPC)of−7.5%(95%confidence interval:−12.6%,−2.2%,Plinics in China have played a significant role in identifying HIV cases.The declining HPR observed in these clinics may indicates the progress has been made in some degree in mitigating HIV among high-risk populations.Therefore,it is crucial to further improving the utilization of VCT clinics for HIV testing.

关键词： VCT dividing Spatial

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