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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong yang wenqin yang Guo Cheng Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China Laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD ***,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of *** this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβ*** vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB *** engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3471-3488页

作者： Fan Tong Haili Hu Yanyan Xu yang Zhou Rou Xie Ting Lei Yufan Du wenqin yang Siqin He Yuan Huang Tao Gong Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China

As known,the benefits of photothermal therapy(PTT)are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins(HSPs).Then HSPs further trigger the formation of stress granules(SGs)that regulate protein expression and cell viability under various stress *** of SG formation can sensitize tumor cells to ***,we developed PEGylated pH(low)insertion peptide(PEG-pHLIP)-modified hollow copper sulfide nanoparticles(HCuS NPs)encapsulating the SG inhibitor ISRIB,with the phase-change material lauric acid(LA)as a gatekeeper,to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system(IL@H-PP).The nano medicine could specifically target slightly acidic tumor *** irradiation,IL@H-PP realized PTT,and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT,thereby increasing the antitumor effect and inducing potent immunogenic cell death(ICD).Moreover,IL@H-PP could promote the production of reactive oxygen species(ROS)by tumor-associated macrophages(TAMs),repolarizing them towards the M1 phenotype and remodeling the immunosuppressive *** vitro/vivo results revealed the potential of PTT combined with SG inhibitors,which provides a new paradigm for antitumor and antimetastases.

关键词： Hollow coppersulfide nanoparticles Sensitized PTT SG inhibition TAMs repolarization pH-driven targeting Photothermal responsiveness Immunotherapy Anti-metastases

Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis

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Chinese Chemical Letters 2024年第3期35卷 406-414页

作者： Haili Hu Weiwei Zhang Lei Lei Fan Tong Huilin Zhang Yiwei Zhang wenqin yang Yilu Tang Ruyi Lin Xue Xia Jiamei Li Shiyong Song Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China School of Pharmacy Henan UniversityKaifeng 475004China Department of Public Health Chengdu Medical CollegeChengdu 610500China

The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer *** still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune *** solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor *** irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ***,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic *** vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.

关键词： Targeted drug delivery system Hollow copper sulfide nanoparticles Photothermal therapy Hyaluronic acid Breast cancer Anti-metastasis

Counteracting Alzheimer's disease via normalizing neurovascular unit with a self-regulated multi-functional nano-modulator

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Acta Pharmaceutica Sinica B 2024年第12期14卷 5464-5478页

作者： Xia, Xue Wei, Ya Huang, Qianqian Zhou, yang Wang, Xiaorong Shi, Yulong yang, Xiaotong yang, wenqin Zhang, Yiwei Lei, Ting Huang, Yuan Li, Hanmei Qin, Meng Gao, Huile Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province West China School of Pharmacy Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs West China Hospital Sichuan University Chengdu 610041 China Key Laboratory of Coarse Cereal Processing School of Food and Biological Engineering Chengdu University Chengdu 610106 China

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms. © 2024 The Authors

关键词： Alzheimer's disease Anti-inflammation Gene delivery Neurovascular unit Pathological blood–brain barrier Receptor for advanced glycation end products Synergetic therapy Targeted delivery

Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury

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Bioactive Materials 2023年第9期27卷 1-14页

作者： wenqin yang Ning Ding Ran Luo Qian Zhang Zhenhua Li Fengchun Zhao Shuixian Zhang Xuyang Zhang Tengyuan Zhou Haomiao Wang Long Wang Shengli Hu Guixue Wang Hua Feng Rong Hu Department of Neurosurgery Key Laboratory of NeurotraumaSouthwest HospitalThird Military Medical University(Army Medical University)400038ChongqingChina Bioengineering College of Chongqing University Chongqing400030China Medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038ChongqingChina Affiliated Dongguan Hospital Southern Medical UniversityDongguan523059China Key Laboratory of Biorheological and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing400030China JinFeng Laboratory Chongqing401329China

Intracerebral hemorrhage (ICH), as a type of life-threatening and highly disabled disease, has limited therapeutic approaches. Here, we show that exosomes derived from young healthy human plasma exhibiting typical exosomes features could facilitate functional recovery of ICH mice. When these exosomes are intraventricularly delivered into the brain after ICH, they mainly distribute around the hematoma and could be internalized by neuronal cells. Strikingly, exosomes administration markedly enhanced the behavioral recovery of ICH mice through reducing brain injury and cell ferroptosis. MiRNA sequencing revealed that microRNA-25-3p (miR-25- 3p) was differentially expressed miRNA in the exosomes from young healthy human plasma, compared with exosomes from the old control. Importantly, miR-25-3p mimicked the treatment effect of exosomes on behavioral improvement, and mediated the neuroprotective effect of exosomes against ferroptosis in ICH. Furthermore, luciferase assay and western blotting data illustrated that P53 as assumed the role of a downstream effector of miR-25-3p, thereby regulating SLC7A11/GPX4 pathway to counteract ferroptosis. Taken together, these findings firstly reveal that exosomes from young healthy human plasma improve functional recovery through counteracting ferroptotic injury by regulating P53/SLC7A11/GPX4 axis after ICH. Given the easy availability of plasma exosomes, our study provides a potent therapeutic strategy for ICH patients with quick clinical translation in the near future.

关键词： Intracerebral hemorrhage Exosomes Young human plasma Ferroptosis Functional recovery

Ho:YVO_4晶体中Ho^(3+)光谱参数的计算

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光谱学与光谱分析 2001年第1期21卷 28-31页

作者：杨文琴吴梅琴陈金铠庄健福建师范大学实验中心福州350007 中科院福建物质结构所福州350002

根据Ho3+在Ho :YVO4 晶体的吸收谱和 0 6～ 2 1μm波段的荧光谱 ,用J O理论计算了Ho3+的强度参数Ωλ ,并由此计算了激发能级的振子强度、自发辐射跃迁几率、荧光分支比和积分发射截面等光谱参数 ,讨论了Ho :YVO4 晶体作为红外激光材... 详细信息

根据Ho3+在Ho :YVO4 晶体的吸收谱和 0 6～ 2 1μm波段的荧光谱 ,用J O理论计算了Ho3+的强度参数Ωλ ,并由此计算了激发能级的振子强度、自发辐射跃迁几率、荧光分支比和积分发射截面等光谱参数 ,讨论了Ho :YVO4 晶体作为红外激光材料的可能性。

关键词：掺钬钒酸钇晶体二极管泵浦强度参数振子强度红外激光发射红外激光材料光谱参数

网络课程论坛与外语专业研究生教学的整合——以一英语专业研究生语言学课程论坛为例

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鸡西大学学报（综合版） 2008年第4期8卷 7-8页

作者：杨雯琴西北师范大学

以一英语专业研究生语言学课程论坛为例,探讨了网络课程论坛与外语专业研究生教学整合的必要性、可行性及优势,以期拓展网络教育应用的空间。

关键词：网络课程论坛外语专业研究生教学必要性可行性优势

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编写火电厂电气设备操作票专家系统

华北电力学院学报 1989年第1期16卷 1-6页

作者：龙明张文勤杨以涵华北电力学院电力系

编写火电厂电气设备倒闸操作票的专家系统是人工智能技术在电力工业中的实际应用。使用本系统保证了开出的操作票正确无误,可防止误操作和提高火电厂运行管理的自动化水平。本专家系统由数据库、知识库和推理机三级构成,具有开新票、进... 详细信息

编写火电厂电气设备倒闸操作票的专家系统是人工智能技术在电力工业中的实际应用。使用本系统保证了开出的操作票正确无误,可防止误操作和提高火电厂运行管理的自动化水平。本专家系统由数据库、知识库和推理机三级构成,具有开新票、进行修改以及学习新知识的功能。全部开出了焦作电厂网控、集控管理的电气操作票共600多张,在更换知识库和数据库后,可移植到其他发电厂使用。

关键词：火电厂电气设备操作票专家系统

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支撑灭火救援作战指挥决策的大数据应用研究

科技创新导报 2021年第26期18卷 166-168页

作者：杨雯钦广元市消防救援支队四川广元628040

随着消防救援行动的日益增多,大数据时代对公安消防队的数据采集、分析和部署提出了新的要求。本文首先分析了大数据技术在消防救援行动指挥系统应用中的可行性,然后探讨了消防救援行动指挥系统的应用方法,包括信息支持和决策应用。本... 详细信息

随着消防救援行动的日益增多,大数据时代对公安消防队的数据采集、分析和部署提出了新的要求。本文首先分析了大数据技术在消防救援行动指挥系统应用中的可行性,然后探讨了消防救援行动指挥系统的应用方法,包括信息支持和决策应用。本文结合消防救援指挥系统中的大数据案例,将大数据技术应用于消防指挥系统,提供丰富的信息支持,对提高作战指挥的有效性,降低指挥的盲目性,改变作战指挥机制,提高战斗技能是非常重要的。

关键词：灭火救援作战指挥大数据决策

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从心理词汇的表征、发展看中式英语的成因

沈阳大学学报 2008年第5期20卷 77-80页

作者：杨雯琴西北师范大学外国语学院甘肃兰州730070

从心理语言学中成人二语词汇习得三阶段模型入手,进行先导实验,对"伪友词"、搭配错误、"隐形不地道现象"这三个典型现象展开研究,探析中式英语的成因。认为母语词目中介使中国英语学习者的语言产出带上了明显或隐含的中国味,促使中式英... 详细信息

从心理语言学中成人二语词汇习得三阶段模型入手,进行先导实验,对"伪友词"、搭配错误、"隐形不地道现象"这三个典型现象展开研究,探析中式英语的成因。认为母语词目中介使中国英语学习者的语言产出带上了明显或隐含的中国味,促使中式英语的出现。

关键词：二语词汇习得中式英语心理语言学