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Albumin-based multidrug delivery system enriched in Golgi apparatus against metastatic breast cancer

Nano Research 2023年第4期16卷 5640-5652页

作者： Chenqi Guo Xiong Peng Ting Zhao Jiaxing Feng Zhaofei Guo Mengying Wu Rongping Zhang xun sun Yuan Huang Zhirong Zhang Tao Gong Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Breast cancer and metastasis remain great challenges in clinical *** with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired ***-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)*** drug combination strategy is still required to be improved due to some unsatisfactory clinical trial *** processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi ***,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and *** COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the *** this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 *** to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.

关键词： albumin Golgi apparatus metastatic breast cancer adjuvant chemotherapy cyclooxygenase-2(COX-2)inhibitors

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High-Index Faceted Nanocrystals as Highly Efficient Bifunctional Electrocatalysts for High-Performance Lithium-Sulfur Batteries

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Nano-Micro Letters 2022年第2期14卷 324-338页

作者： Bo Jiang Da Tian Yue Qiu Xueqin Song Yu Zhang xun sun Huihuang Huang Chenghao Zhao Zhikun Guo Lishuang Fan Naiqing Zhang State Key Laboratory of Urban Water Resource and Environment School of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbin 150001People’s Republic of China Academy of Fundamental and Interdisciplinary Sciences Harbin Institute of TechnologyHarbin 150001People’s Republic of China School of Energy Science and Engineering Harbin Institute of TechnologyHarbin 150001People’s Republic of China

Precisely regulating of the surface structure of crystalline materials to improve their catalytic activity for lithium polysulfides is urgently needed for high-performance lithium-sulfur(Li-S)***,high-index faceted iron oxide(Fe_(2)O_(3))nanocrystals anchored on reduced graphene oxide are developed as highly efficient bifunctional electrocatalysts,effectively improving the electrochemical performance of Li-S *** theoretical and experimental results all indicate that high-index Fe_(2)O_(3)crystal facets with abundant unsaturated coordinated Fe sites not only have strong adsorption capacity to anchor polysulfides but also have high catalytic activity to facilitate the redox transformation of polysulfides and reduce the decomposition energy barrier of Li_(2)*** Li-S batteries with these bifunctional electrocatalysts exhibit high initial capacity of 1521 mAh g^(-1)at 0.1 C and excellent cycling performance with a low capacity fading of 0.025%per cycle during 1600 cycles at 2 *** with a high sulfur loading of 9.41 mg cm^(-2),a remarkable areal capacity of 7.61 mAh cm^(-2)was maintained after 85 *** work provides a new strategy to improve the catalytic activity of nanocrystals through the crystal facet engineering,deepening the comprehending of facet-dependent activity of catalysts in Li-S chemistry,affording a novel perspective for the design of advanced sulfur electrodes.

关键词： High-index faceted Fe_(2)O_(3)nanocrystals Unsaturated coordinated Lithium-sulfur batteries Electrocatalysis

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Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2934-2949页

作者： Jiao Xue Yining Zhu Shuting Bai Chunting He Guangsheng Du Yuandong Zhang Yao Zhong Wenfei Chen Hairui Wang xun sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Photothermal therapy has been intensively investigated for treating cancer in recent ***,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and *** address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor ***,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor ***,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of *** the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and *** results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

关键词： Photothermal therapy Immunotherapy Rough surface Polydopamine-coated silica nanoparticles JQ-1 Melanoma

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冲击波致裂在青海一里坪卤水开采中的增渗效果

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盐湖研究 2024年第3期32卷 78-86页

作者：侯昭飞唐发满张杨杨佺忠尚立涛孙逊赵福垚五矿盐湖有限公司青海省低渗透性盐湖卤水绿色开采及高效利用工程技术研究中心青海芒崖816400 中国石油集团工程技术研究院有限公司北京102206 长治医学院生物医学工程系山西长治046000

青海一里坪盐湖赋存丰富的液体锂矿(晶间卤水),但传统井采方式的卤水产量严重依赖于随机性很大的地层性质。通过对井壁附近的地层进行冲击波致裂,可以使岩土层裂隙增多,从而加速渗流而提高产量。针对本次试验的地层,12次的冲击次数相对... 详细信息

青海一里坪盐湖赋存丰富的液体锂矿(晶间卤水),但传统井采方式的卤水产量严重依赖于随机性很大的地层性质。通过对井壁附近的地层进行冲击波致裂,可以使岩土层裂隙增多,从而加速渗流而提高产量。针对本次试验的地层,12次的冲击次数相对而言比较安全。相关技术成果对卤水和石油开采等液体采矿行业有很好的参考价值。

关键词：冲击波致裂卤水增渗

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PbrChiA:a key chitinase of pear in response to Botryosphaeria dothidea infection by interacting with PbrLYK1b2 and down-regulating ROS accumulation

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Horticulture Research 2023年第10期10卷 185-201页

作者： Qiming Chen Huizhen Dong Qionghou Li xun sun Xin Qiao Hao Yin Zhihua Xie Kaijie Qi Xiaosan Huang Shaoling Zhang State Key Laboratory of Crop Genetics and Germplasm Enhancement Centre of Pear Engineering Technology ResearchNanjing Agricultural UniversityNanjing 210095China

Pear ring rot,caused by the pathogenic fungi Botryosphaeria dothidea,seriously affects pear *** the infection-induced reactive oxygen species(ROS)burst of infected plants limits the proliferation of *** during the early infection stage,high ROS levels can also contribute to their growth during the later necrotrophic infection ***,it is important to understand how plants balance ROS levels and resistance to pathogenic *** during the later *** this study,we identified PbrChiA,a glycosyl hydrolases 18(GH18)chitinase-encoding gene with high infection-induced expression,through a comparative transcriptome *** substitution,stable overexpression,and virus induced gene silencing(VIGS)experiments demonstrated that PbrChiA can positively regulate pear resistance as a secreted chitinase to break down *** mycelium in vitro and that overexpression of PbrChiA suppressed infection-induced ROS *** analysis revealed that PbrChiA can bind to the ectodomain of PbrLYK1b2,and this interaction suppressed PbrLYK1b2-mediated chitin-induced ROS ***,we propose that the combination of higher antifungal activity from abundant PbrChiA and lower ROS levels during later necrotrophic infection stage confer resistance of pear against ***.

关键词： infection ChiA resistance

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Discovery of a first-in-class ANXA3 degrader for the treatment of triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1686-1698页

作者： Yongxi Liang Delin Min Hulin Fan Kunlin Liu Juchuanli Tu Xueyan He Bingjie Liu Lu Zhou Suling Liu xun sun School of Pharmacy Fudan UniversityShanghai 201203China The Institutes of Integrative Medicine of Fudan University Shanghai 200040China Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences State Key Laboratory of Genetic EngineeringFudan UniversityShanghai 200032China

Triple-negative breast cancer(TNBC)is a nasty disease with extremely high malignancy and poor *** A3(ANXA3)is a potential prognosis biomarker,displaying an excellent correlation of ANXA3 overexpression with patients'poor *** the expression of ANXA3effectively inhibits the proliferation and metastasis of TNBC,suggesting that ANXA3 can be a promising therapeutic target to treat ***,we report a first-in-class ANXA3-targeted small molecule(R)-SL18,which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells.(R)-SL18 directly bound to ANXA3 and increased its ubiquitination,thereby inducing ANXA3 degradation with moderate family ***,(R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft ***,(R)-SL18 could reduce theβ-catenin level,and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC ***,our data suggested that targeting degradation of ANXA3 by(R)-SL18 possesses the potential to treat TNBC.

关键词： Annexin A3(ANXA3) Degrader Triple-negative breast cancer Ubiquitination Patient-derived xenograft

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Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres

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Nano Research 2019年第10期12卷 2451-2459页

作者： Luyao Wang Bingjie Zhou Shiqi Huang Mengke Qu Qing Lin Tao Gong Yuan Huang xun sun Qin He Zhirong Zhang Ling Zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacyCollege of Polymer Science and EngineeringSichuan UniversityChengdu 610041China

Currently,prostate cancer is the most frequently diagnosed cancer in males and chemotherapy is often essential for treating advaneed prostate ***,common chemotherapies for prostate cancer suffer from serious adverse effects due to poor drug targeting ability and tissue penetration,even with the help of conventional drug delivery ***,encouraged by recent studies showing possible drug retention and tissue pen etration advan tages of unconventional non-spherical nan oparticles over conventional spherical nan oparticles,we design and construct a novel non-spherical nano disk drug delivery system for treating prostate *** to enhance tumor-targeting capability,these nanodisks are further modified with targeting peptide,Cys-Arg-Glu丄ys?Ala peptide with N-methylated Glu(CR(NMe)EKA),which recognizes extracellular matrix fibronectin and its complexes specifically expressed on the walls of tumor vessels and in tumor *** with conventional nano spheres,the nano disks achieve much higher drug accumulati on at prostate tumor *** loaded with paclitaxel,the CR(NMe)EKA-modified nan odisks display superior an titumor efficacy to free paclitaxel,unmodified nan odisks and nano *** summary,our study provides an attractive therapeutic strategy for targeted therapy against prostate cancer with simple preparation,high efficiency and low toxicity,and supplements a theoretical support for treatments realized by different shaped nano *** study also offers valuable data for understa nding biological effects of non-spherical nano disks and highlights the great pote ntial of unconventional nan oparticles in biomedical applicati ons.

关键词： Cys-Arg-Glu-Lys-Ala peptide with N-methylated Glu(CR(NMe)EKA) fibronectin nanodisks prostate cancer tumor-targeting

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ANALYTICAL MODELS OF FLOATING BRIDGES SUBJECTED BY MOVING LOADS FOR DIFFERENT WATER DEPTHS

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Journal of Hydrodynamics 2008年第5期20卷 537-546页

作者： ZHANG Jun MIAO Guo-ping LIU Jian-xun sun Wen-jun The First Engineers Scientific Research Institute of the General Armaments Department Wuxi 214035 China School of Naval Architecture Ocean and Civil Engineering Shanghai Jiao Tong University Shanghai 200030China The First Engineers Scientific Research Institute of the General Armaments Department Wuxi 214035 China

There are two types of floating bridge such as discrete-pontoon floating bridges and continuous-pontoon floating bridges. Analytical models of both floating bridges subjected by raoving loads are presented to study the dynamic responses with hydrodynamic influence coefficients for different water depths. The beam theory and potential theory are introduced to produce the models. The hydrodynamic coefficients and dynamic responses of bridges are evaluated by the boundary element method and by the Galerkin method of weighted residuals, respectively. Considering causal relationship between the frequencies of the oscillation of floating bridges and the added mass coefficients, an iteration method is introduced to compute hydrodynamic frequencies. The results indicate that water depth has little influence upon the dynamic responses of both types of floating bridges, so that the effect of water depth can be neglected during the course of designing floating bridges.

关键词： floating bridge analytical model moving load water depth

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Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer

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World Journal of Gastroenterology 2018年第42期24卷 4773-4786页

作者： Ji Li xun sun Ping He Wan-Qi Liu Ya-Bin Zou Quan Wang Xiang-Wei Meng Department of Gastroenterology The First Hospital of Jilin University Department of Pathology The First Hospital of Jilin University Gastrointestinal Surgery The First Hospital of Jilin University

AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) *** Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell *** cytometry was used for cell cycle *** healing and Transwell assays were conducted to examine the effects of Uba2 on migration and *** levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase *** Uba2 expression was higher in GC than in normal *** Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic *** Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.

关键词： Ubiquitin-like modifier activating enzyme 2 Gastric cancer Epithelial-mesenchymal transition Wnt/β-catenin signaling pathway

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抗血管内皮生长因子联合地塞米松植入物治疗糖尿病黄斑水肿患者的临床观察

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临床和实验医学杂志 2024年第6期23卷 601-604页

作者：孙逊杨主敏李英琦铁金军杨丽丽刘玮王鲜贵州医科大学附属医院眼科

目的研究抗血管内皮生长因子(VEGF)联合地塞米松植入物(DEX)治疗糖尿病黄斑水肿(DME)患者的临床效果。方法前瞻性选择2021年1月至2022年12月贵州医科大学附属医院收治的DME患者90例(90眼),依据随机数字表法将其分为试验组(n=45)、对照... 详细信息

目的研究抗血管内皮生长因子(VEGF)联合地塞米松植入物(DEX)治疗糖尿病黄斑水肿(DME)患者的临床效果。方法前瞻性选择2021年1月至2022年12月贵州医科大学附属医院收治的DME患者90例(90眼),依据随机数字表法将其分为试验组(n=45)、对照组(n=45)。对照组行抗VEGF治疗，试验组行抗VEGF联合DEX治疗。观察两组治疗前及治疗3个月后黄斑中心凹视网膜厚度(CMT)、患眼最佳矫正视力(BCVA)及眼压；房水中血小板源性生长因子(PDGF)、微小RNA-377-3p(miR-377-3p)及内皮抑制素(ES)等DME相关因子，并比较2组临床疗效、术后并发症及复发情况。结果治疗3个月后，两组CMT、BCVA均较治疗前降低，且试验组CMT、BCVA分别为(286.77±31.22)μm、(0.50±0.06) logMAR,均低于对照组[(322.95±34.61)μm、(0.43±0.04) logMAR],差异均有统计学意义(P0.05)。治疗3个月后，两组房水PDGF及ES水平均较治疗前降低，房水miR-377-3p水平均较治疗前升高，且试验组房水PDGF及ES水平分别为(3.80±0.40) ng/mL、(89.95±9.27) ng/L,均低于对照组[(4.65±0.48)ng/mL、(102.26±11.34) ng/L],房水miR-377-3p水平为0.57±0.07,高于对照组(0.50±0.06),差异均有统计学意义(P0.05)。试验组复发率为2.22%,低于对照组(17.78%),差异有统计学意义(P<0.05)。结论抗VEGF联合DEX治疗DME可减小CMT,提高患眼最佳矫正视力，改善房水DME相关因子水平，疗效显著，术后并发症少，复发率低，且不显著增加眼压，值得推荐于临床。

关键词：糖尿病黄斑水肿地塞米松抗血管内皮生长因子疗效

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