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H_(2)S-releasing adhesive hydrogel as oral radioprotectant for gastrointestinal tract radioprotection

Chinese Chemical Letters 2024年第1期35卷 392-400页

作者： Peng Shan Jing Liao Jiayi Li Chengyan Wang Jie Zhou Linqiang Mei yunlu dai Qiang Wang Wenyan Yin Laboratory for Micro-sized Functional Materials Department of Chemistry and College of Elementary EducationCapital Normal UniversityBeijing 100048China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Department of Pharmacy Southwest HospitalThe Third Military Medical UniversityChongqing 400038China Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China

Radiation damage can cause a series of gastrointestinal(GI)tract *** development of safe and effective GI tract radioprotectants still remains a great challenge ***,we firstly report an oral radioprotectant Gel@GYY that integrates a porous gelatin-based(Gel)hydrogel and a pH-responsive hydrogen sulfide(H2S)donor GYY4137(morpholin-4-ium 4 methoxyphenyl(morpholino)phosphinodithioate).Gel@GYY has a remarkable adhesion ability and long retention time,which not only enables responsive release of low-dose H2S in stomach and subsequently sustained release of H2S in the whole intestinal tract especially in the colon,but also ensures a close contact between H2S and GI *** released H2S can effectively scavenge free radicals induced by X-ray radiation,reduce lipid peroxidation level,repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase ***,the released H2S inhibits radiation-induced activation of nuclear factorκB(NF-κB),thus reducing inflammatory cytokines levels in GI *** treatment,Gel@GYY displays efficient excretion from mice body due to its *** work provides a new insight for therapeutic application of intelligent H2S-releasing oral delivery system and potential alternative to clinical GI physical damage protectant.

关键词： Radiation Gastrointestinal tract radioprotection Hydrogen sulfide gas therapy Gelatin-based hydrogel Free radicals scavenging

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IR780/Gemcitabine-conjugated metal-phenolic network enhanced photodynamic cancer therapy

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Chinese Chemical Letters 2024年第1期35卷 305-309页

作者： Songtao Zhou Hao Tian Jie Yan Zhan Zhang Guohao Wang Xinying Yu Wei Sang Bei Li Greta S.P.Mok Jie Song yunlu dai Cancer Center and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao 999078China MoE Frontiers Science Center for Precision Oncology University of MacaoMacao 999078China Institute of Basic Medicine and Cancer(IBMC) Chinese Academy of SciencesThe Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China Biomedical Imaging Laboratory(BIG) Department of Electrical and Computer EngineeringFaculty of Science and TechnologyUniversity of MacaoMacao 999078China

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate toxic reactive oxygen species (ROS) to damage biomolecules like DNA. At the same time, some chemotherapy drugs like nucleotide analogues can provide mechanism-guided promotion in the treatment efficacy of PDT. However, the photosensitizer and chemotherapy drugs used in PDT is usually organic molecules, which suffers from bad solubility, fast clearance, and acute toxicity. To achieve targeted treatment, a reasonable delivery system is necessary. Therefore, we reported a metal-phenolic network where IR780 and gemcitabine were coupled chemically to overcome these shortcomings. The enhanced PDT effects can be realized by the promoted cell death both in vitro and in vivo. Moreover, the synergistic therapy also induced T-cell mediated anti-tumor immune response, which was significant for the inhibition of distant tumor growth. This work expanded the biomedical application of metal-phenolic materials and contribute to the wider application of photodynamic cancer therapy.

关键词： Metal phenolic network IR780 Photodynamic therapy Breast cancer Gemcitabine

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A"three musketeers"tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy

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Nano Research 2022年第4期15卷 3458-3470页

作者： Wenxi Li Lisi Xie Yi Ju Zhan Zhang Bei Li Jie Li Wei Sang Guohao Wang Hao Tian yunlu dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao 999078China MOE Frontiers Science Center for Precision Oncology University of MacaoMacao 999078China School of Health and Biomedical Sciences RMIT UniversityBundooraVictoria 3083Australia

Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune ***,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal *** this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor ***-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of *** turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 ***,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.

关键词： interferon-γ(IFN-γ) anti-PD-L1(aPD-L1) IDO-1 inhibitor(NLG919) neutralization tumoricidal positive anti-tumor feedback loop

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A platinum@polymer-catechol nanobraker enables radio-immunotherapy for crippling melanoma tumorigenesis, angiogenesis, and radioresistance

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Bioactive Materials 2023年第4期22卷 34-46页

作者： Wenxi Li Jie Yan Hao Tian Bei Li Guohao Wang Wei Sang Zhan Zhang Xuanjun Zhang yunlu dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR999078China MOE Frontiers Science Center for Precision Oncology University of MacaoMacao SAR999078China

Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent *** melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor ***,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma *** aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,***,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal ***,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic *** an ingenious tactic may provide substantial benefits to clinical melanoma patients.

关键词： platinum@polymer-catechol nanobrakers Melanoma PD-1:PD-L1 interaction blockade Radio-sensitization effect Anti-tumorigenesis Anti-angiogenesis

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Light-triggered nitric oxide release and structure transformation of peptide for enhanced intratumoral retention and sensitized photodynamic therapy

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Bioactive Materials 2022年第6期7卷 303-313页

作者： Lingdong Jiang Danyang Chen Zhaokui Jin Chao Xia Qingqing Xu Mingjian Fan yunlu dai Jia Liu Yuanpei Li Qianjun He Marshall Laboratory of Biomedical Engineering School of Biomedical EngineeringHealth Science CenterShenzhen UniversityNo.1066 Xueyuan AvenueShenzhen518060GuangdongChina Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Optoelectronic EngineeringShenzhen UniversityShenzhen518060GuangdongChina Central Laboratory Longgang District People’s Hospital of Shenzhen&The Third Affiliated Hospital(Provisional)of The Chinese University of Hong KongShenzhen518172GuangdongChina Department of Biochemistry and Molecular Medicine UC Davis Comprehensive Cancer CenterUniversity of California DavisSacramentoCA95817USA Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR999078China

Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side ***,nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical *** this work,we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide(NO)release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy(PDT).The designed nanoparticle is self-assembled from a chimeric peptide monomer,TPP-RRRKLVFFK-Ce6,which contains a photosensitive moiety(chlorin e6,Ce6),aβ-sheet-forming peptide domain(Lys-Leu-Val-Phe-Phe,KLVFF),an oligoarginine domain(RRR)as NO donor and a triphenylphosphonium(TPP)moiety for targeting *** irradiated by light,the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod,enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light *** importantly,the conversion of generated NO and reactive oxygen species(ROS)in a light-responsive way to peroxynitrite anions(ONOO􀀀)with higher cytotoxicity enables NO to sensitize PDT in cancer *** in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors *** light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.

关键词： Nitric oxide Photodynamic therapy Structural transformation Peptide Enhanced intratumoral retention Nanomedicine

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NIR-Ⅱ-absorbing conjugated polymer-based theranostic agent for NIR-Ⅱfluorescence imaging-guided photothermal therapy acting synergistically with tumor microenvironment-responsive nitric oxide therapy

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ChemPhysMater 2022年第1期1卷 51-55页

作者： Jie Li Lisi Xie Wei Sang Wenxi Li Guohao Wang Hao Tian Zhan Zhang Jianhua Liu Quli Fan yunlu dai Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China Department of Radiology The Second Hospital of Jilin UniversityChangchun 130041China Key Laboratory for Organic Electronics and Information Displays&Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)Nanjing University of Posts&TelecommunicationsNanjing 210023China MoE Frontiers Science Center for Precision Oncology University of MacaoMacao SAR 999078China

Despite tremendous advances in gas therapy,there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug *** near-infrared(NIR-Ⅱ)window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive *** this study,we engineered an NIR-Ⅱlaser-activated theranostic agent(named CP-bF@PEG)that was composed of amphiphilic polymers(Pluronic F127,with polyethylene glycol,PEG,moieties)coated with an NIR-Ⅱ-absorbing conjugated polymer(PTTBBT,CP)and nitric oxide(NO)donor(benzofuroxan,bF),which served as an NIR-Ⅱphotothermal inducer and NO *** deep tissue penetration of NIR-Ⅱlaser irradiation,CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal ***,CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable *** NIR-Ⅱ-absorbing polymer for high-contrast NIR-Ⅱfluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy,as evidenced by pronounced tumor therapeutic efficacy and few side *** nanotheranostic agent is a highly promising candidate for high-contrast NIR-Ⅱimaging-guided precision photothermal therapy combined with gas therapy against cancer.

关键词： Conjugated polymer NIR-II fluorescence Photothermal therapy Tumor environment response Nitric oxide therapy

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超声激活的金属多酚配位纳米抗生素在体内抗耐药菌治疗中的应用

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Science China Materials 2023年第1期66卷 395-406页

作者：卢畅田野田浩李蓓彭博郑军代云路 Cancer Center and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR999078China MoE Frontiers Science Center for Precision Oncology University of MacaoMacao SAR999078China School of Life Sciences Sun Yat-Sen UniversityGuangzhou 510006China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266071China

抗生素的滥用引发了漫延全球的抗生素耐药危机.多重耐药细菌的出现对人类生命健康构成了极大的威胁.此外,传统抗生素在体内杀死病原菌的同时,对人体正常微生物菌群的破坏也增加了导致其他感染和疾病的风险.因此,新型抗生素的研发显得日... 详细信息

抗生素的滥用引发了漫延全球的抗生素耐药危机.多重耐药细菌的出现对人类生命健康构成了极大的威胁.此外,传统抗生素在体内杀死病原菌的同时,对人体正常微生物菌群的破坏也增加了导致其他感染和疾病的风险.因此,新型抗生素的研发显得日益紧迫.在本文中,我们合成了一种超声激活的金属多酚配位纳米抗生素(PEG-P18-Ag NPs),其可在感染部位被选择性激活,从而避免了对体内正常微生物群体的影响.实验证实PEG-P18-Ag NPs在未激活时不具有抗菌活性.经超声激活后,其可引起大量活性氧物种(ROS)的产生,从而杀死多种多重耐药菌及生物膜.通过RNA测序技术,本文进一步证实PEG-P18-Ag NPs对细菌细胞的细胞膜、核糖体、染色质及鞭毛等结构造成了严重损伤.总之,本研究合成了一种靶向体内耐药菌的新型抗生素,可实现广谱、快速和可控的抗多重耐药菌治疗.

关键词：多重耐药菌新型抗生素正常微生物群抗生素耐药多重耐药细菌严重损伤活性氧物种细菌细胞

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叶用芥菜抽薹速率与现蕾期生理生化特征的关系

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北方园艺 2020年第21期 27-33页

作者：严奉君刘独臣代云璐巩雪峰常伟李跃建四川省农业科学院园艺研究所蔬菜种质与品种创新四川省重点实验室四川成都610066 农业部西南地区园艺作物生物学与种质创制重点实验室四川成都610066 阿坝州理县朴头镇人民政府四川理县623100

以3个不同耐抽薹性芥菜材料F7212、F7073与F7170为研究对象,采用调查各材料抽薹特性及分析芥菜现蕾前0~4 d叶片生理生化变化特征进行综合分析评价的方法,研究了芥菜现蕾期叶片生理生化指标的变化特征以及与抽薹速率的相互关系,以期揭示... 详细信息

以3个不同耐抽薹性芥菜材料F7212、F7073与F7170为研究对象,采用调查各材料抽薹特性及分析芥菜现蕾前0~4 d叶片生理生化变化特征进行综合分析评价的方法,研究了芥菜现蕾期叶片生理生化指标的变化特征以及与抽薹速率的相互关系,以期揭示芥菜现蕾期生理生化特征以及为抽薹特性的相互关系研究提供了参考依据。结果表明:各芥菜材料在现蕾前0~4 d叶片可溶性蛋白质含量、过氧化物酶(POD)、超氧化物歧化酶(SOD)与过氧化氢酶(CAT)活性均呈逐渐上升的趋势,而可溶性糖含量则逐渐降低。在各时期叶片可溶性蛋白质含量与CAT活性均随芥菜抽薹速率的降低而增加,以F7212最高,分别较其它材料提高0.12%~0.91%与14.54%~149.86%。SOD活性则随芥菜抽薹耐性的增加而降低,F7212分别较其它材料降低2.68%~116.00%。此外低抽薹速率芥菜材料(F212)在可溶性蛋白质含量与SOD活性方面具有大跨度的上升幅度,而在POD以及CAT活性上则表现为平稳的上升。相关研究表明芥菜抽薹速率与POD活性、CAT活性有显著相关关系,而与可溶性蛋白质、可溶性糖含量及SOD活性无显著相关关系。通径分析表明,可溶性糖与SOD活性对芥菜抽薹速率直接作用最大(-0.80~1.09),但可溶性蛋白质含量、POD活性与CAT活性间接作用于可溶性糖含量及SOD活性,表明芥菜叶片SOD活性升高以及叶片可溶性糖快速向外部转移是加速芥菜抽薹速率的重要因素,而植株体内稳定及活跃POD与CAT能够显著减缓芥菜抽薹速率。

关键词：芥菜现蕾期过氧化物酶过氧化氢酶超氧化物歧化酶抽薹速度

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变压器谐波条件下铁损建模及材料对比

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变压器 2024年第3期61卷 59-66页

作者：代晨瑀李启灿卢锐昊郭轩青岛云路先进材料技术股份有限公司山东青岛266232

本文旨在给出谐波条件下变压器的铁损建模方法,并据此比较非晶、硅钢等不同材料的变压器在谐波条件下的铁损性能。首先介绍了单频条件下斯坦梅斯公式的拟合方法,并据此进行不同材料在单频条件下的特性对比。然后给出了电压谐波条件下的... 详细信息

本文旨在给出谐波条件下变压器的铁损建模方法,并据此比较非晶、硅钢等不同材料的变压器在谐波条件下的铁损性能。首先介绍了单频条件下斯坦梅斯公式的拟合方法,并据此进行不同材料在单频条件下的特性对比。然后给出了电压谐波条件下的铁损分析方法,并在电压谐波条件下对不同材料的性能进行了对比。试验表明,无论是在单频条件下,还是谐波条件下,非晶变压器的铁损均低于硅钢变压器。

关键词：变压器谐波铁损材料对比

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中西太平洋渔业委员会公海登临和检查制度的分析和探讨

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上海海洋大学学报 2015年第1期24卷 115-120页

作者：滕云路戴小杰田思泉上海海洋大学海洋科学学院上海201306 上海海洋大学大洋渔业资源可持续开发省部共建教育部重点实验室上海201306 上海海洋大学农业部大洋渔业资源环境科学观测试验站上海201306

中西太平洋渔业委员会是唯一建立公海登临和检查制度的区域性金枪鱼渔业管理组织,旨在通过实施公海登临和检查以推进缔约方遵守和执行其养护管理措施,自2006年中西太平洋公海登临检查制度实施以来,一些国家或地区陆续开始对中西太平洋... 详细信息

中西太平洋渔业委员会是唯一建立公海登临和检查制度的区域性金枪鱼渔业管理组织,旨在通过实施公海登临和检查以推进缔约方遵守和执行其养护管理措施,自2006年中西太平洋公海登临检查制度实施以来,一些国家或地区陆续开始对中西太平洋海域公海作业的渔船进行登临和检查,公海登临和检查的实施方的数量和实施次数逐年增加,严格的登临和检查对我国该海域金枪鱼渔业生产的履约责任带来较大的挑战。本文探讨了中西太平洋公海登临和检查制度的演变和发展,分析了中西太平洋公海登临和检查制度自执行以来实施的情况和特点,通过研究我国渔船自2011年来在中西太平洋地区接受公海登临和检查的案例,归纳和总结我国渔船违规情况的类型和原因,从而为确保中国金枪鱼渔业渔船在中西太平洋海域的生产秩序提供帮助,并建议:政府、企业、协会和科研单位等履约主体应协同配合,加强我国金枪鱼渔业自身能力建设,减少渔船违规作业,履行相关国际义务。

关键词：公海登临和检查区域性金枪鱼渔业管理组织中西太平洋渔业委员会养护管理措施

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