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Bicyclic stapled peptides based on p53 as dual inhibitors for the interactions of p53 with MDM2 and MDMX

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Chinese Chemical Letters 2022年第3期33卷 1254-1258页

作者： Hongjin Li Xiangyan Chen Minghao Wu panpan song Xia Zhao Key Laboratory of Marine Drugs Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology Qingdao 266237China

In recent years, the strategy of inhibiting the interactions of p53 with murine double minute 2(MDM2)and murine double minute X(MDMX) has been proved to be a promising approach for tumor ***, the poor proteolytical stability and low intracellular delivery efficiency of peptide inhibitors limit their clinical application. Here, we designed and synthesized the bicyclic stapled peptides based on p53 by combining all-hydrocarbon stapling and lactam stapling strategies. We demonstrated that bicyclic stapled peptide p53-16 significantly improved α-helicity and proteolytic stability. Especially, p53-16showed nanomolar binding affinity for MDM2 and MDMX. In addition, p53-16 could penetrate the cell membrane, and selectively inhibited the activity of tumor cells via activating p53 pathway in vitro. Our data suggest that p53-16 is a potential dual inhibitor of MDM2 and MDMX interactions. The bicyclic stapling strategy is a promising drug design strategy for protein–protein interactions inhibitors.

关键词： p53 MDM2 MDMX All-hydrocarbon stapling strategy Lactam stapling strategy Bicyclic stapling strategy

Experimental study of a micro-scale solar organic Rankine cycle system based on compound cylindrical Fresnel lens solar concentrator

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Science China(Technological Sciences) 2019年第12期62卷 2184-2194页

作者： MENG Jia song panpan WEI MingShan TIAN GuoHong ZHAO Meng ZHENG HongFei HU GuangDa School of Mechanical Engineering Bejing Institute of TechnologyBeijing 100081China Department of Mechanical Engineering Sciences University of SurreyGuildford GU27HXUK

In the present study, a micro-scale solar organic Rankine cycle power generation system was developed. The system comprises of a solar collection system based on compound cylindrical Fresnel lens concentrator and an organic Rankine cycle power generation system integrated with a scroll expander. YD320 and R245 fa were used as the heat transfer fluid and the working fluid, respectively. The effects of the evaporation pressure, the degree of superheat, and the mass flow rate of the working fluid were analyzed to evaluate the solar collection efficiency, the electric power output, the thermal efficiency and exergy efficiency of the system. The results illustrate that both the increasing evaporation pressure and decreasing superheat degree have positive impacts on solar collection efficiency. The electric power increases as the evaporation pressure increases, while the thermal efficiency and the exergy efficiency decrease. However, the system overall efficiency decreases slowly due to the increase of solar collection efficiency. The electric power increases with the increment of the working fluid mass flow rate. The increasing mass flow rate has no visible impact on the thermal and exergy efficiencies of organic Rankine cycle subsystem, whereas a slightly increase of the thermal and exergy efficiencies of the integrated system. The electric power decreases with the increase of the superheat degree, whereas the thermal and the exergy efficiencies of the system increase. The system works more suitably with a higher degree of superheat for the small mass flow rate condition.

关键词： micro-scale SORC cylindrical Fresnel lens concentrator solar collection efficiency overall performance

Research on Operation of Electrothermal Integrated Energy System Including Heat Pump and Thermal Storage Units Based on Capacity Planning

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Energy Engineering 2021年第3期118卷 535-548页

作者： Taihong Liu Dingchen Wu Fei Xu panpan song Mingshan Wei Jian Wu Xiaochun Bai Power Science Research Institute of Shaanxi Electric Power Company of State Grid Xi’anChina School of Mechanical Engineering Beijing Institute of TechnologyBeijingChina Department of Electric Engineering Tsinghua UniversityBeijingChina

In view of the Three North areas existing wind power absorption and environment pollution problems,the previous scholars have improved the wind abandon problem by adding electrothermal coupling equipment or optimizing power grid *** this paper,an electrothermal integrated energy system including heat pump and thermal storage units was *** scheduling model was based on the load data and the output characteristics of power units,each power unit capacity was programmed without constraints,and the proposed scheduling model was compared with the traditional combined heat and power scheduling *** showed that the investment and pollutant discharge of the system was reduced *** power was fully *** with the traditional thermal power unit,the proportion of the output was significantly decreased by the proposed *** proposed system could provide a new prospect for wind power absorption and environment protection.

关键词： Electrothermal integrated energy system capacity planning thermal storage unit heat pump

Polydopamine and ammonium bicarbonate coated and doxorubicin loaded hollow cerium oxide nanoparticles for synergistic tumor therapy

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Nano Research 2019年第12期12卷 2947-2953页

作者： Keqiang Xu Yan Cheng Jiao Yan Yanlin Feng Runxiao Zheng Xiaqhig Wu Yanjing Wang panpan song Haiyuan Zhang Laboratory of Chemical Biology Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology cf China Hefei 230026China

The development of effective nanoplatforms is extremely necessary for cancer ***,we prepared polydopamine(PDA)andammonium bicarbonate(NH4HCO3)coated and doxorubicin(Dox)loaded hollow cerium oxide(CeO2)NPs(PDAC NPs),which showedexcellent synergistic effect for photothermal therapy,chemotherapy and chemodynamic *** near infrared laser irradiation,PDA shell could absorb the incident light and convert it into heat,which could not only kill tumor cells with hyperthermia,but also trigger thedecomposition of NH4HCO3 into gaseous carbon dioxide and ammonia,leading to the destroy of PDA *** leakage of PDA furtheraccelerated Dox release and exposed CeO2 surface,in which Dox could enter into cell nucleus to induce chemotherapy,and CeO2 couldcatalyze cellular hydrogen peroxide into hydroxyl radical to present chemodynamic *** fact,PDAC NPs showed an excellenttherapeutic efficacy both in vitro and in *** design provides a new strategy for synergistic tumor therapy.

关键词： photothermal therapy chemotherapy chemodynamic therapy polydopamine cerium oxide

Synthesis, Cytotoxic Activity Evaluation of Novel 1,2,3-Triazole Linked Quinazoline Derivatives

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Chinese Journal of Chemistry 2017年第10期35卷 1633-1639页

作者： panpan song Fei Cui Na Li Jingchao Xin Qisheng Ma Xiangchuan Meng Chaojie Wang Qinpo Cao Yifei Gu Yu Ke Qiurong Zhang Hongmin Liu School of Pharmaceutical Sciences Zhengzhou University Zhengzhou Henan 450001 China Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou Henan 450001 China Key Laboratory of Henan Province for Drug Quality and Evaluation Zhengzhou Henan 450001 China Key Laboratory of Technology of Drug Preparation (Zhengzhou University) Ministry of Education Zhengzhou Henan 450001 China

A series of novel 1,2,3-triazole-quinazoline derivatives were synthesized in five steps starting from anthranila- mide by conventional methods. All the title compounds 10a-10r were evaluated for cytotoxic activity against four human cancer cell lines （MGC-803, EC-109, MCF-7 and HGC-27） using MTT assay in vitro. Some of the synthe- sized compounds exhibited moderate to potent activity against tested cancer cell lines. Among them, compounds 10h and 10q exhibited excellent growth inhibition against HGC-27 and compound 10m also possessed excellent ac- tivity against MCF-7, with IC50 values less than 1 μmol/L. Especially, compound 10h was more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines.

关键词： quinazoline triazole synthesis cytotoxicity

Harnessing decellularised extracellular matrix microgels into modular bioinks for extrusion-based bioprinting with good printability and high post-printing cell viability

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Biomaterials Translational 2023年第2期4卷 115-127页

作者： Hanyu Chu Kexin Zhang Zilong Rao panpan song Zudong Lin Jing Zhou Liqun Yang Daping Quan Ying Bai Key Laboratory for Polymeric Composite&Functional Materials of Ministry of Education School of ChemistrySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Engineering Technology Research Centre for Functional Biomaterials Key Laboratory for Polymeric Composite&Functional Materials of Ministry of EducationSchool of Materials Science and EngineeringSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and *** this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput *** gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from *** integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell *** DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based ***,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials ***,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.

关键词： 3D bioprinting bioinks cell viability decellularised extracellular matrix microgels

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民族学在我国西北地区的发展脉络

民族研究 2023年第6期 37-53,M0003页

作者：周传斌宋盼盼教育部人文社科重点研究基地兰州大学西北少数民族研究中心暨历史文化学院民族学系兰州市730020 教育部人文社科重点研究基地兰州大学西北少数民族研究中心暨历史文化学院兰州市730020

民族学在我国西北地区的发展,经历了晚清西北学、民国边政学、新中国民族学三个阶段,除了受到欧美人类学、苏联民族学等外来学术影响之外,也有着深厚的中华文化基因,植根于中国历史文化的沃土之上。对民族学在我国西北地区的独特发展脉... 详细信息

民族学在我国西北地区的发展,经历了晚清西北学、民国边政学、新中国民族学三个阶段,除了受到欧美人类学、苏联民族学等外来学术影响之外,也有着深厚的中华文化基因,植根于中国历史文化的沃土之上。对民族学在我国西北地区的独特发展脉络进行追溯、挖掘与呈现,为构建中国特色的民族学学科体系、学术体系、话语体系提供了有益的参考。

关键词：民族学西北学边政学西北地区

1992—2021年中国老年人群阿尔茨海默症及相关痴呆的疾病负担变化趋势及预测研究

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中国全科医学 2025年第8期28卷 996-1003页

作者：韩树奎任义涛马昕宋盼盼马金祥张紫钰陈虹汝青海大学医学院公共卫生系青海卫生职业技术学院医学技术系青海卫生职业技术学院临床医学系

背景老龄化社会背景下，我国老年阿尔茨海默症及相关痴呆（ADRD）患者数量逐年增加，给其主要家庭照顾者带来了沉重的照护压力，受到了国内外广泛关注。目的分析中国老年人ADRD疾病负担变化趋势，探究年龄、时期和队列因素对ADRD发病... 详细信息

背景老龄化社会背景下，我国老年阿尔茨海默症及相关痴呆（ADRD）患者数量逐年增加，给其主要家庭照顾者带来了沉重的照护压力，受到了国内外广泛关注。目的分析中国老年人ADRD疾病负担变化趋势，探究年龄、时期和队列因素对ADRD发病率和患病率的影响，并对2021年以后中国老年人群ADRD发病率进行预测，为相关部门制订防制措施提供依据。方法利用2021年全球疾病负担数据库（GBD 2021）中ADRD数据为数据来源，提取1992—2021年中国老年人ADRD粗发病率、粗患病率、粗死亡率及粗伤残调整寿命年（DALY）率，按照年龄标准化（简称标化）后运用Joinpoint回归模型分析变化趋势，并计算年度变化百分比（APC）与平均年度变化百分比（AAPC）。采用年龄-时期-队列模型分析年龄、时期及队列因素对中国老年人ADRD发病率和患病率的影响，并使用贝叶斯年龄-时期-队列-模型预测其2022—2030年的发病率。结果 1992—2021年中国老年人群的ADRD标化发病率、标化患病率总体均呈上升趋势（发病率：AAPC=0.57%,95%CI=0.41%～0.72%；患病率：AAPC=0.64%,95%CI=0.60%～0.68%）。其中男性标化发病率增速高于女性（AAPC:0.63%>0.60%），女性标化患病率增长高于男性（AAPC:0.68%>0.66%）。1992—2019年的三个区段中国老年人ADRD标化死亡率均呈下降趋势（APC分别为-0.11%、-0.41%、-0.08%）,2019—2021年标化死亡率呈升高趋势（APC=1.96%,95%CI=0.78%～3.15%）。年龄效应：60岁以上男性和女性ADRD的发病、患病风险均随着年龄的增长而增加。男、女性95岁以上人群发病风险分别为60～64岁组的13.24倍和13.53倍，患病风险是60～64岁组的13.55倍和16.05倍。时期效应：ADRD在男性和女性的发病、患病风险随年份推移而增加，均在2017—2021年达到最高。队列效应：男性和女性的ADRD的发病、患病风险在队列效应方面，均随着出生年份的推移而逐步下降。贝叶斯年龄-时期-队列模型预测结果显示，2022—2030年中国男性与女性ADRD的标化发病率呈现上升趋势，女性标化发病率高于男性，女性ADRD的标化发病率将从2021年的1 267.77/10万上升至1 820.80/10万，增幅约为43.62%；男性从2021年的920.22/10万增至2030年的1256.30/10万，增幅约为36.52%，男、女性2022—2030年的ADRD发病人数也在持续升高，2021—2030年男、女性发病人数增长幅度分别为89.74%和105.06%。结论中国老年人群ADRD的负担严重且呈现上升趋势，建议相关部门积极采取有效措施减轻患者的疾病负担，特别是加强对老年女性人群的防护。

关键词：阿尔茨海默病痴呆疾病负担老年人中国预测

TaCRT3 is a Positive Regulator of Resistance to Blumeria graminis *** in Wheat

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TaCRT3 is a Positive Regulator of Resistance to Blumeria gra...