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

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

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Polymeric Nanotherapeutics for Alzheimer's Disease:Summary and Outlook

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Chinese Journal of Polymer Science 2023年第6期41卷 839-841页

作者： lin-lin xu Fan Huang lin-Qi Shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai University Key Laboratory of Radiopharmacokinetics for Innovative Drugs Chinese Academy of Medical Sciencesand Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical College State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai University Haihe Laboratory of Sustainable Chemical Transformations

Alzheimer’s disease(AD),one of the most prevalent progressive neurodegenerative disorders,is characterized by neurological dysfunction and is closely linked to learning and memory *** tremendous effort being involved,several anti-AD drugs come into clinical trials difficult to succeed due to the complex AD pathogenesis and the blood-brain barrier(BBB).

关键词： Alzheimer drugs clinical

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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

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Case Report:Subglottic adenoid cystic carcinoma mistaken for asthma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第9期10卷 707-710页

作者： Hua-lin WANG lin xu Fu-jun LI Department of Otorhinolaryngology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Adenoid cystic carcinoma rarely occurs within the subglottic larynx. In this study, a case of subglottic adenoid cystic carcinoma was reported. A 54 year-old Chinese woman developed a sudden onset of chest distress and cough worsening after physical exertion, and was diagnosed with, and treated as, bronchial asthma. Regular anti-asthmatic therapy did not improve the symptoms. Until a sudden dyspnea, a cervicothoracic computerized tomography （CT） revealed that her upper airway was obstructed by a laryngeal tumor. The patient was diagnosed with a subglottic adenoid cystic carcinoma and treated with complete surgical excision and adjuvant radiation therapy. Follow-up endoscopy and laryngeal magnetic resonance imaging （MR1） at six months showed no recurrence of the tumor. The diagnosis of subglottic adenoid cystic carcinoma should be considered in patients who are characterized by dyspnea, cough, and stridor, but do not respond to regular anti-asthmatic therapy.

关键词： Subglottic adenoid cystic carcinoma Larynx Asthma

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Poly(meta-phenylene) Derivative with Rigid Twisted Biphenyl Units in Backbone:Synthesis,Structural Characterization,Photophysical Properties and Electroluminescence

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Chemical Research in Chinese Universities 2007年第6期23卷 720-725页

作者： ZHENG Yan YANG Bing ZHANG Hai-quan LU Ping SHEN Fang-zhong LIU lin-lin xu Hai YANG Guang-di MA Yu-guang Key Lab for Supramolecular Structure and Materials of Ministry of Education Jilin University Changchun 130012 P. R. China

A soluble poly（meta-phenylene） derivative with rigid twisted biphenyl unit was synthesized by the Yamamoto coupling reaction. The polymer is soluble in common organic solvents, and the number-average molecular weight is about 6500. The UV-Vis and quantum chemical calculation indicate that the different conformation segments named ＂conformers＂ exist in the polymer backbones; it was also further confirmed by the single crystal X-ray diffraction study of the dimeric model compound. The π-π^＊ transition of biphenyl segments of twisted and planar conformations made the polymer exhibit a strong absorption around 256 nm and a weak absorption at about 300 nm. Furthermore, the polymer exhibits a strong UV photoluminescence at 372 nm when the excitation wavelengths are longer than 300 run. The ultraviolet-emitting electroluminescence（EL） device with the single layer structure shows EL λmax of the derivative at 370 nm.

关键词： Poly(phenylene) Conformation UV light-emitting

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Laser-induced convenient fabrication of CdS nanocages with super-adsorption capability for methyl blue solution

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Chinese Physics B 2017年第8期26卷 293-298页

作者：刘乐徐林林张华陈明 Shandong Univ Sch PhysJinan 250100ShandongPeoples R China

We report on the successful synthesis of cadmium sulfide （CdS） nanocages by laser ablation of bulk Cd target in thioacetamide （TAA） solution. The CdS nanocages exhibit obvious interior hollow spaces and distinctive porous-shell structures. After laser ablation of Cd target in liquid condition, the unique structure should be attributed to the initial forma- tion of Cd micro-gas bubble via a model of micro-explosive boiling model. Surprisingly, the obtained CdS nanocages can provide a super-adsorption of methyl blue （MB） solution. The maximum adsorption capacity reaches up to 11813.3 mg/g, which is much higher than that reported in many previous researches. Without using any complicated stabilizers or soft directing agents, the pure CdS nanocages fabricated by laser ablation will serve as advanced absorbents in further research.

关键词： laser-induced fabrication CdS nanocages

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Association between IRS-2 G1057D polymorphism and risk of gastric cancer

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World Journal of Gastrointestinal Oncology 2012年第1期4卷 9-15页

作者： Xiao-Mei Zhao Jie Chen Li Yang xuan Luo lin-lin xu Dong-Xiao Liu Su-Lan Zhai Ping Li xue-Rong Wang Nanjing Med Univ Dept Pharmacol 140 Hanzhong Rd Nanjing 210029 Jiangsu Peoples R China Southern Med Univ Affiliated Pingxiang Hosp Dept Pharm Pingxiang 337000 Jiangxi Peoples R China Nanjing Med Univ Affiliated Hosp 1 Dept Gen Surg Nanjing 210029 Jiangsu Peoples R China

AIM: To investigate the relationship between insulin receptor substrate-2 (IRS-2) G1057D polymorphism and the risk of gastric cancer (GC) in a Chinese population. METHODS: A case-control study with 197 GC patients and 156 age- and sex-matched control subjects was conducted. The genotypes of polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype frequencies of IRS-2 G1057D polymorphism in cases were obviously different from those in the control group (P = 0.031). Compared with GG genotype carriers, the risk for GC was significantly higher (adjusted odds ratio = 2.32, 95% CI: 1.03-5.23, P = 0.042) in the individuals with the IRS-2 DD geno-type. Furthermore, stratified analysis was performed based on age, sex, smoking status and residence, but no significant difference between the two groups was found. In addition, no significant association between genotypes and clinicopathological features was observed either. CONCLUSION: This study demonstrates that IRS-2 G1057D is involved in susceptibility to GC, although further large-sample studies are still needed.

关键词： Gastric cancer Insulin receptor substrate-2 Polymorphism Genotype Case-Control study

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Self-Collimation in Planar Photonic Crystals Fabricated by CMOS Technology

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Chinese Physics Letters 2010年第2期27卷 90-92页

作者：杨志峰武爱民方娜蒋寻涯林旭林王曦邹世昌 State Key Laboratory of Functional Materials for Informatics Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences Shanghai 200050

We report a self-collimating demonstration in planar photonic crystals （PhCs） fabricated in silicon-on-insulator （SOI） wafers using 0.18 μm silicon complimentary metal oxide semiconductor （CMOS） techniques. The emphasis was on demonstrating the self-collimation effect by using the standard CMOS equipment and process development of an optical test chip using a high-volume manufacturing facility. The PhCs are designed on the 230-nm-top-Si layer using a square lattice of air holes 280 nm in diameter. The lattice constant of the PhCs is 380 nm. The experimentally obtained wavelengths for self-collimation are in excellent agreement with theory.

关键词： Electronics and devices Semiconductors Optics quantum optics and lasers

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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie lin Weihong xu Department of Spinal Surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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Association betweenITGA2 C807T polymorphism and gastric cancer risk

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World Journal of Gastroenterology 2011年第23期17卷 2860-2866页

作者： Jie Chen Nan-Nan Liu Jia-Qi Li Li Yang Ying Zeng Xiao-Mei Zhao lin-lin xu xuan Luo Bin Wang xue-Rong Wang Department of Pharmacology Nanjing Medical University Nanjing210029 Jiangsu Province China Department of General Surgery First Affiliated Hospitalof Nanjing Medical University Nanjing 210029 Jiangsu Prov-ince China

AIM： To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer risk. METHODS： A hospital-based case-control study was conducted, including 307 gastric cancer patients and 307 age- and gender-matched control subjects. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS： The frequencies of the wild and variant genotypes in cases were significantly different from those of controls （P = 0.019）. Compared with individuals with the wild genotype CC, subjects with the variant genotypes （CT ＋ IT） had a significantly higher risk of gastric cancer （adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007）. In stratified analyses, the elevated gastric cancer risk was especially evident in older individuals aged 〉 58 years, nonsmokers and rural subjects. Further analyses revealed that the variant genotypes were associated with poor tumor differentiation and adjacent organ invasion in the sub-analysis of gastric cancer patients. CONCLUSION： The ITGA2 gene C807T polymorphism may be associated with an increased risk of gastric cancer, differentiation and invasion of gastric cancer.

关键词： Gastric cancer Integrin ITGA2 Polymor-phism Genotype

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