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Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation

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Chinese Journal of Polymer Science 2024年第11期42卷 1710-1718,I0009页

作者： Hui Wang lin-lin Xu lin-qi shi Ru-Jiang Ma Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer ChemistryState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Amyloidosis is characterized by the deposition of fibrillar aggregates,with a specific peptide or protein as the primary component,in affected tissues or *** proliferation and deposition of amyloid fibrils can cause organismal dysfunction and lethal pathological outcomes associated with *** this study,a nanochaperone(nChap-NA)was developed to inhibit protein misfolding and fibrillation by simulating the function of natural molecular *** nanochaperone was prepared by self-assembly of two block copolymers PEG-b-PCL and PCL-b-P(NIPAM-co-AANTA),which had a phase-separated surface consisting of hydrophobic PNIPAM microdomains with coordinative NTA(Zn)moieties and hydrophilic PEG *** hydrophobic interaction of the PNIPAM microdomain and the coordination of NTA(Zn)synergistically work together to effectively trap the amyloid monomer and block its fibrillation *** and human islet amyloid polypeptide(hIAPP)were used as model proteins to investigate the nanochaperone's inhibition of amyloid misfolding and *** was proved that the nanochaperone could stabilize the natural conformation of the trapped insulin and hIAPP,and effectively inhibit their *** vivo study demonstrated that the nanochaperone could effectively preserve the bioactivity of insulin and reduce the cytotoxicity caused by hIAPP *** study may provide a promising strategy for the prophylactic treatment of amyloidosis.

关键词： Nanochaperone Amyloidosis Insulin hIAPP Inhibit fibrillation

Responsive Polymeric Nanoparticles for Biofilm-infection Control

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Chinese Journal of Polymer Science 2021年第11期39卷 1376-1391页

作者： lin-Zhu Su Yong Liu Yuan-Feng Li Ying-Li An lin-qi shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin 300071China Engineering Research Center of Clinical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province Wenzhou InstituteUniversity of Chinese Academy of SciencesOujiang LaboratoryWenzhou 325000China

With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public *** frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic *** address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared *** subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing *** advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.

关键词： Antibacterial Biofilm Multidrug resistance Polymeric nanoparticles Stimuli-responsive

Triclosan-conjugated,Lipase-responsive Polymeric Micelles for Eradication of Staphylococcal Biofilms

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Chinese Journal of Polymer Science 2024年第6期42卷 718-728页

作者： Yan-qiang Huang Yuan-Feng Li Yong Liu lin-qi shi Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance Youjiang Medical University for NationalitiesBaise533000China Translational Medicine Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325035China Wenzhou Institute University of Chinese Academy of SciencesWenzhou325001China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of Educationand Institute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China

Bacterial biofilms present a significant challenge in treating drug-resistant infections,necessitating the development of innovative *** this study,we introduce triclosan-conjugated,lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery *** micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization ofε-caprolactone(CL)and triclosan-containing cyclic trimethylene carbonate(MTC-Tri).Poly(ethylene glycol)(PEG-OH)acted as the macro-initiator,resulting in micelles with a PEG shell that facilitated their penetration into bacterial *** important advantage of our micelles lies in their interaction with local bacterial lipases within *** lipases triggered rapid micelle degradation,releasing triclosan in a controlled *** liberated triclosan effectively eliminated bacteria embedded in the ***,the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts,indicating their biocompatibility and *** finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial *** triclosan-conjugated,lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial *** harnessing biofilm properties and implementing a responsive drug delivery system,we seek to provide an effective solution in the fight against drug-resistant bacteria.

关键词： Self-assembly Polymer prodrug Ring-opening polymerization Biofilm eradication Cytotoxicity

Bioinspired Self-assembly Nanochaperone Inhibits Tau-Derived PHF6 Peptide Aggregation in Alzheimer’s Disease

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Chinese Journal of Polymer Science 2022年第9期40卷 1062-1070页

作者： lin Zhu Ming-qing Zhang Hao-Ren Jing Xi-Peng Zhang lin-lin Xu Ru-Jiang Ma Fan Huang lin-qi shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai UniversityTianjin 300071China Key Laboratory of Radiopharmacokinetics for Innovative Drugs Chinese Academy of Medical Sciencesand Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300192China Nankai University School ofMedicine Nankai UniversityTianjinChina Department of Colorectal SurgeryTianjin Union Medical CenterTianjin 300074 China Department of Colorectal Surgery Tianjin Union Medical CenterTianjin 300121China

After repeated frustrations with amyloid beta(Aβ)-targeted clinical trials for Alzheimer’s disease(AD)in recent years,the therapeutic focus of AD has gradually shifted from Aβto tau *** misfolding and aggregation of tau protein into neurofibrillary tangles(NFTs)cause neuron death and synaptic dysfunction,and the deposition of NFTs is more closely related to the severity of AD than Aβ***,it has great potential to target tau protein aggregation for AD *** hexapeptide VqiVYK(known as PHF6)in tau protein has been found to play a dominant role for tau aggregation and was widely used as a model to design tau protein aggregation ***,inspired by natural heat shock protein(HSPs),we fabricated a self-assembly nanochaperone based on mixed-shell polymeric micelle(MSPM)as a novel tau-targeted AD *** tunable phase-separated microdomains on the surface,the nanochaperone could effectively bind with PHF6 aggregates,inhibit PHF6 aggregation,block neuronal internalization of PHF6 species,thus significantly alleviating PHF6 mediated ***,the as-prepared nanochaperone could work with proteinase to facilitate the degradation of PHF6 *** bioinspired nanochaperone demonstrated a new way to target tau protein and provided a promising strategy for AD treatment.

关键词： Alzheimer’s disease Tau protein PHF6 Nanochaperone Inhibition

A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

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Chinese Journal of Polymer Science 2024年第5期42卷 559-569,I0005页

作者： Sai-Nan Liu Jia-Hui Meng Li-Yun Cui Hua Chen lin-qi shi Ru-Jiang Ma Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of protein drugs is critical for protein *** combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer ***,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different ***,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)*** PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release *** the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their *** cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two *** cytoplasm,the high level of GSH removed the modification of 2-APBA on *** restored RNase A and DOX show a synergistic and enhanced antic-cancer *** system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.

关键词： Drug co-delivery Combination therapy Dynamic covalent bond

Novel Receptor for the Rapid Reaction and Colorimetric Detection of HSO3- in Aqueous Solutions

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Chemical Research in Chinese Universities 2013年第2期29卷 236-238页

作者： YANG Wen-long LI qiao WEI Tai-bao ZHANG You-ming lin qi shi Bing-bing ZHANG Peng Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education of China" Key Laboratory ofPolymer Materials of Gansu Province College of Chemistry and Chemical Engineering Northwest Normal University Lanzhou 730070 P. R. China

A novel high-yield Schiff base was designed and synthesized as an anion receptor that specifically select HSO3 anions in aqueous solutions of H20/DMSO（15：85, volume ratio）, which can be detected via colorimetry under direct visualization. The sensor exhibited different results for other anions, such as F, CI, Br, I-, H2PO4-, AcO-, HSO4 and C104. The changes in the UV-Vis spectra also show the specific recognition of HSO3 , rather than similar anions H2PO4- and HSO4- in the same aqueous solution. The detection limit of HSO3- was 1×10-6 mol/L.

关键词： Bisulfite anion sensor 2-Aminobenzimidazole Aqueous solution Single recognition Colorimetry

Plasma N-terminal pro-brain natriuretic peptide levels in elderly patients with isolated diastolic dysfunction

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Journal of Geriatric Cardiology 2005年第4期2卷 211-215页

作者： Yixin SONG qing lin Xiaomin shi Yunyun qi Department of Geriatric Medicine First Hospital of Beijing University Beijing 100034 China Department of Geriatric Medicine First Hospital of Beijing University Beijing 100034 China Department of Geriatric Medicine First Hospital of Beijing University Beijing 100034 China Department of Geriatric Medicine First Hospital of Beijing University Beijing 100034 China

Objective To investigate plasma N-terminal pro-brain natriuretic peptide (NT-BNP) levels and to assess their clinical significance in elderly patients with isolated diastolic dysfunction. Methods Plasma NT-BNP level were measured by electrochemiluminescence immunoassay in 34 symptomatic patients (Group 1), 34 asymptomatic patients (Group 2) with isolated diastolic dysfunction, and in 16 elderly healthy subjects (control group, Group 3), serving controls. Colored Doppler echocardiography was performed to evaluate the patients' cardiac structures and functions. Results The plasma NT-BNP level in Group 1 was significantly higher than those in Group 2 and Group 3 and increased with the severity of heart failure. There was no significant difference of plasma NT-BNP levels between Group 2 and Group 3 (p>0.05). A NT-BNP value of 102.75 pg/mL showed a sensitivity of 88.2%, a specificity of 87.5%, and an accuracy of 88.1% for diagnosing diastolic dysfunction. Patients with restrictive filling pattern on echocardiography had higher NT-BNP levels than those of impaired relaxation pattern (1961.2±304.9 versus 460.1±92.7pg/mL, plinical value in the diagnosis of elderly patients with isolated diastolic dysfunction.

关键词： elderly isolated diastolic dysfunction N-terminal pro-brain natriuretic peptide echocardiography

Maternal Perfluorinated Compound Exposure and Risk of Early Pregnancy Loss: A Nested Case-control Study

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Biomedical and Environmental Sciences 2022年第2期35卷 174-179页

作者： MI Xin lin shi qi ZHANG Xiao Fen LI Jia Jia PEI Li Jun JIN Feng LIAO qi XIE Li Min WEI Li Cong HAO Chan Juan ZHANG Ya Wei LI Wei Shunyi Women’s and Children’s Hospital of Beijing Children’s Hospital Beijing 101300China Institute of Population Research/China Center on Population Health and Development Peking UniversityBeijing 100871China

Early pregnancy loss,defined as a nonviable intrauterine pregnancy occurring before 12 weeks of gestation,is estimated to affect 25%of clinically diagnosed pregnancies[1].Several demographic,lifestyle,and environmental risk factors have been reported to associate with the risk of early pregnancy loss,yet the causes of most early pregnancy losses remain elusive;thus,further studies are *** compounds(PFCs)are a class of widespread environmental pollutants that can adversely affect human reproductive *** are inevitably exposed to PFCs through diet,water,air and dust.A wealth of epidemiological and toxicological research using a variety of animal models has warned of the persistence,bioaccumulation,and toxicity of PFCs[2].

关键词： pregnancy viable Early

PPO-PDMS-PHS_n三元多嵌段共聚物的形态结构和性能

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化学学报 1998年第2期56卷 194-199页

作者：史林启郑国栋冯之榴中国科学院长春应用化学研究所长春130022

利用DMA,TEM和SAXS对以聚苯醚(PPO)为硬段、聚对羟基苯乙烯(PHS)为半硬段和聚二甲基硅氧烷(PDMS)为软段的三元多嵌段共聚物(?)PPO-PDMS-PHS(?)_n的形态结构和性能进行了研究.结果表明,(?)PPO-PDMS-PHS(?)_n以三种嵌段相容相为连续相,PPO... 详细信息

利用DMA,TEM和SAXS对以聚苯醚(PPO)为硬段、聚对羟基苯乙烯(PHS)为半硬段和聚二甲基硅氧烷(PDMS)为软段的三元多嵌段共聚物(?)PPO-PDMS-PHS(?)_n的形态结构和性能进行了研究.结果表明,(?)PPO-PDMS-PHS(?)_n以三种嵌段相容相为连续相,PPO与PHS的相容相和PDMS相为两种分散相,其tanδ随温度变化曲线在-100℃至200℃一直是一很高的平台,并具有优异的力学性能,较好地解决了含有机硅类嵌段共聚物强度低的弱点,同时又保留了嵌段共聚物微相分离的特性.

关键词： PPO PDMS PHS 结构嵌段三元多嵌段共聚物