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Intracellular uptake of nanocrystals:Probing with aggregation-induced emission of fluorescence and kinetic modeling

Acta Pharmaceutica Sinica B 2021年第4期11卷 1021-1029页

作者： Jifen Zhang Clairissa DCorpstein tonglei li College of Pharmaceutical Sciences Southwest UniversityChongqing 400716China Department of Industrial and Physical Pharmacy Purdue UniversityWest LafayetteIN 47907USA

Nanocrystal formulations have been explored to deliver poorly water-soluble drug *** various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole *** this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of *** uptake studies were conducted with KB cells and characterized by confocal microscopy,fow cytometry,and quantitative *** results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved *** cellular uptake was found to be concentration-and *** addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and *** modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on frst-order ordinary differential equations(ODEs).By ftting the kinetic model against experimental measurements,it was found that the initial nanocrystal concentration had a great infuence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE *** the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the effux of THPE molecules from cells.

关键词： Nanocrystal Intracellular uptake Aggregation-induced emission Pharmacokinetics Tetrakis(4-hydroxyphenyl)ethylene Fate Dissolution kinetics Absorption mechanism

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Editorial of Special Issue“The Biological Fate of Drug Nanocarriers”

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Acta Pharmaceutica Sinica B 2021年第4期11卷 850-851页

作者： Wei Wu tonglei li Ying Zheng Key Laboratory of Smart Drug Delivery of MOE School of Pharmacy Fudan University Shanghai 201203 China. Center for Medical Research and Innovation Shanghai Pudong Hospital Fudan University Pudong Medical Center Shanghai 201399 China. Department of Industrial and Physical Pharmacy College of Pharmacy Purdue University West Lafayette IN 47907 USA. State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau China.

According to the Merriam-Webster dictionary,the word"fate"refers to"final outcome",among various definitions,and has such synonyms as"destiny","consequence",and"ending".With regard to the biological or in vivo fate of an exogenous ingredient,the wording may refer to the eventual destiny-for example,the end products-of the entity that enters the biological system or the body.

关键词： word consequence system

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Reactivity of triacetone triperoxide and diacetone diperoxide： Insights from nuclear Fukui function

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Frontiers of Chemical Science and Engineering 2015年第1期9卷 114-123页

作者： Matthew J. SWADLEY Panpan ZHOU tonglei li Pharmaceutical Sciences University of Kentucky Lexington Kentucky 40536 USA Department of Chemistry Lanzhou University Lanzhou 730000 Gansu China Industrial & Physical Pharmacy Purdue University West Lafayette Indiana 47907 USA

Triacetone triperoxide （TATP） is more sensitive than diacetone diperoxide （DADP） in the solid-state explosion. To explain this reactivity difference, we analyzed the electronic structures and properties of the crystals of both compounds by using Ab initio method to calculate the structures of their individual molecules as well as their lattice structures and particularly calculating Nuclear Fukui function to gain insight into the sensitivity of the initial, rate-determining step of their decomposition. Our results indicate that TATP and DADP crystal structures exhibit significantly different electronic proper- ties. Most notably, the electronic structure of the TATP crystal shows asymmetry among its reactive oxygen atoms as supported by magnitudes of their nuclear Fukui functions. The greater explosion sensitivity of crystalline TATP may be attributed to the properties of its electronic structure. The electronic calculations provided valuable insight into the decomposition sensitivity difference between TATP and DADP crystals.

关键词： nuclear Fukui function electronic perturbation Hellmann-Feynman force organic crystals unimole-cular decomposition

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Preparation and characterization of multimodal hybrid organic and inorganic nanocrystals of camptothecin and gold

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Acta Pharmaceutica Sinica B 2019年第1期9卷 128-134页

作者： Christin P. Hollis Alan K. Dozier Barbara L. Knutson tonglei li Department of Pharmaceutical Sciences University of Kentucky Electron Microscopy Center University of Kentucky Department of Chemical Engineering and Material Sciences University of Kentucky Department Industrial & Physical Pharmacy College of Pharmacy Purdue University

We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography(CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope(TEM) and further quantified by energy dispersive X-ray spectrometry(EDS) and inductively coupled plasma-optical emission spectrometers(ICP-OES). Due to gold's high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded gold atoms and clusters are expected to share the same biological fate as the camptothecin nanocrystals, reaching and accumulating in tumor site due to the enhanced permeation and retention(EPR) effect.

关键词： Hybrid inorganic-organic Drug delivery Camptothecin Gold nanoparticles Computed tomography(CT) contrast agent Cancer therapy and diagnosis

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采用PBPK/PD指导处方设计（英文）

采用PBPK/PD指导处方设计（英文）

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2018年第十二届中国药物制剂大会

作者： tonglei li 普渡大学

Physiologically based pharmacokinetics（PBPK） modeling is an enabling approach for establishing IVIVC（in vitro and in vivo correlation）, allowing a formulation scientist to better understand the impact of formulation design on the in vivo drug release and absorption kinetics of a drug product. It may be integrated with pharmacodynamics（PD） modeling for predicting the in vivo performance of the product. Herein, we use our recent study of warfarin as an example to illustrate the prowess of the modeling and simulation approach for understanding possible reasons of bio-inequivalence between brand-name and generic products.

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复方白头翁散超微粉对貉部分生化免疫指标及抗氧化功能的影响

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黑龙江畜牧兽医 2016年第10期 193-196页

作者：张召兴贾青辉张香斋张艳英高桂生李蕴玉张志强吴同垒李佩国史秋梅河北科技师范学院河北省预防兽医学重点实验室河北秦皇岛066604

为了研究复方白头翁散超微粉对貉部分生化免疫指标及抗氧化功能的影响,试验选择80只45日龄体重相近的断奶仔貉,随机分成2组,每组40只;Ⅰ组(对照组)饲喂基础日粮,Ⅱ组(试验组)在基础日粮中添加1%复方白头翁散超微粉方剂,试验期为10周;Ⅰ... 详细信息

为了研究复方白头翁散超微粉对貉部分生化免疫指标及抗氧化功能的影响,试验选择80只45日龄体重相近的断奶仔貉,随机分成2组,每组40只;Ⅰ组(对照组)饲喂基础日粮,Ⅱ组(试验组)在基础日粮中添加1%复方白头翁散超微粉方剂,试验期为10周;Ⅰ组、Ⅱ组分别在2,4,6,8,10周采血,检测部分生化免疫指标总蛋白(TP)、白蛋白(ALB)、免疫球蛋白(Ig G)以及抗氧化功能指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)及尿素氮(BUN)。结果表明:在每个试验阶段,Ⅱ组血清中的TP、Ig G GSH-Px、T-AOC水平均明显高于Ⅰ组,Ⅱ组血清中BUN含量低于Ⅰ组。说明在饲料中添加1%复方白头翁散超微粉方剂能提高貉部分生化免疫指标及抗氧化功能;降低貉体内BUN含量,提高机体BUN的代谢,改善肾脏功能。

关键词：貉复方白头翁散超微粉生化免疫指标抗氧化功能

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A Refractive Index Sensor Based on Four-Wave Mixing in D-Shaped Tellurite Photonic Crystal Fiber

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Photonic Sensors 2023年第3期13卷 90-98页

作者： Yuanhongliu GAO Xin YAN Xiaoyu CHEN Bin li tonglei CHENGCollege of Information Science and Engineering State Key Laboratory of Synthetical Automation for Process Industries Northeastern University Shenyang 110819China

In this study,we design a refractive index(RI)sensor using a novel cadmium telluride photonic crystal fiber(TPCF).Based on four-wave mixing(FWM),the changes in RI can be accurately detected,and RI sensing in the mid-infrared region(MIR)can be achieved by detecting wavelength shifts in the Stokes and anti-Stokes spectra caused by the changes in RI of the liquid to be *** the pump wavelength of FWM lies in the normal and abnormal dispersion regions of the TPCF,the RI response of the idler frequency wave and the signal wave are analyzed by numerical simulation *** simulation results show that the RI sensitivity of the sensor can be as high as 7692 nm/RIU with a linearity is up to 99.9%at the pump wavelength of 3380 *** our knowledge,the RI sensing sensitivity of the MIR is presented for the first time in this study by using FWM in the non-silicon PCF.

关键词： Refractive index sensing tellurite photonic crystal fiber parametric gain,four wave mixing mid-infrared region

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Digital intelligence and synergy of pollution reduction and carbon reduction: “Dividend” or “gap”?

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Chinese Journal of Population, Resources and Environment 2024年第4期22卷 389-398页

作者： Jiajia li Xianfeng Han tonglei Zhang Jian Xiao Longtao Chen School of Management and Economics Kunming University of Science and Technology Kunming 650500 China School of Economics Xinjiang University of Finance and Economics Urumqi 830012 China

At the intersection of the “dual carbon” goal and the era of digital intelligence (DI), exploring the synergy between pollution and carbon reduction (SPCR) within the context of DI is important for promoting a comprehensive green transformation of economic and social development. This study, based on urban panel data from 281 prefecture-level cities in Mainland China from 2010 to 2020, developed a DI indicator system for these cities and employed a double machine learning algorithm for the first time to investigate the intrinsic mechanisms and incentivizing effects of DI on SPCR. The results showed that: ① DI significantly promotes SPCR. ② Mechanism tests demonstrated that DI can indirectly enhance SPCR by optimizing resource allocation and reinforcing government interventions. ③ Further analysis showed that the impact of DI on SPCR was more substantial in regions with lower levels of economic and environmental competition. Moreover, the SPCR driven by DI exhibited heterogeneity, characterized by stronger effects in “resource-based cities > non-resource-based cities” and “non-capital economic zones > capital economic zones”. The conclusions of this study hold significant implications for fully harnessing the synergy between digitization and intelligence to empower SPCR. In addition, the findings are valuable for the government’s integrated promotion of the “dual carbon” goal and the “digital China” strategy.

关键词： Digital intelligence Synergy of pollution reduction and carbon reduction Double machine learning “Dual carbon” goal

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Study on Antibacterial Effect of Single Chinese Herbs on Staphylococcus aureus

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Agricultural Biotechnology 2018年第3期7卷 118-121页

作者： Yonghui li tonglei WU Qiumei SHI Fei ZHAO Shuang WANG Dan li Huijun BI Zhiqiang ZHANG The Second Hospital of Qinhuangdao Qinhuangdao 066600 China Preventive Veterinary Medicine Key Laboratory Hebei Normal University of Science &Technology Qinhuangdao 066600 China Changli Traditional Chinese Medicine Hospital Qinhuangdao 066600 China

[Objectives] This study was conducted to determine in-vitro antibacterial effect of 58 Chinese herbs on Staphylococcus aureus,and screen single Chinese herbs with better in-vitro antibacterial effect for formulation of prescription. [Methods]Effective components in Chinese herbs were extracted with water,and inhibition zone diameters and minimal inhibitory concentrations of the 58 Chinese herbs against S. aureus were determined by agar plate punching method and micro two-fold method,respectively. [Results] Twenty two kinds of Chinese herbs including Terminalia chebula Retz.,Anemarrhena asphodeloides Bunge.,Prunella vulgaris L,Rheum palmatum L. and Mosla chinensis Maxim. had better antibacterial effect,among which T. chebula Retz.,A. asphodeloides Bunge.,P. vulgaris L,R. palmatum L. and C. sappan linn showed the best antibacterial effect,with average inhibition zone over 20 mm and MIC lower than 15. 6 mg/ml.[Conclusions]Traditional Chinese herbs have certain antibacterial effect,and this study will provide important theoretical reference for clinical medication and development of prescription.

关键词： Staphylococcus aureus Multi-drug resistance Chinese herbal medicine In-vitro anitbacterial experiment Antibacterial effect

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Diversity and independent evolutionary profiling of rodent-borne viruses in Hainan,a tropical island of China

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Virologica Sinica 2023年第5期38卷 651-662页

作者： Youyou li Chuanning Tang Yun Zhang Zihan li Gaoyu Wang Ruoyan Peng Yi Huang Xiaoyuan Hu Henan Xin Boxuan Feng Xuefang Cao Yongpeng He tonglei Guo Yijun He Haoxiang Su Xiuji Cui lina Niu Zhiqiang Wu Jian Yang Fan Yang Gang Lu Lei Gao Qi Jin Meifang Xiao Feifei Yin Jiang Du NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100005China Department of Clinical Laboratory Center for Laboratory MedicineHainan Women and Children's Medical CenterHaikou571199China Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Medical UniversityHaikou571199China Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases Hainan Medical UniversityHaikou571199China Department of Pathogen Biology Hainan Medical UniversityHaikou571199China

The risk of emerging infectious diseases(EID)is increasing *** than 60%of EIDs worldwide are caused by animal-borne *** study aimed to characterize the virome,analyze the phylogenetic evolution,and determine the diversity of rodent-borne viruses in Hainan Province,*** collected 682 anal and throat samples from rodents,combined them into 28 pools according to their species and location,and processed them for next-generation sequencing and bioinformatics *** diverse viral contigs closely related to mammals were assigned to 22 viral *** clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus,coronavirus,astrovirus,pestivirus,parvovirus,and *** identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling,and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species,and their rodent hosts have not been previously reported to carry these *** results expand our knowledge of viral classification and host range and suggest that there are highly diverse,undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.

关键词： Rodents Virome Phylogenetic analysis Novel viruses Wildlife

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