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Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： Mingyang Zhang yifan miao Can Zhao Tong Liu Xiyan Wang Zixuan Wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

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人工智能在动力电池健康状态预估中的研究综述

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机械工程学报 2024年第4期60卷 391-408页

作者：戴国洪张道涵彭思敏苗一凡卓悦杨瑞鑫于全庆常州大学机械与轨道交通学院常州213164 盐城工学院电气工程学院盐城224051 北京理工大学机械与车辆学院北京100081 哈尔滨工业大学(威海)汽车工程学院威海264209

目前先进的电动汽车开发和应用已成为实现“脱碳”的关键技术。准确的电池健康状态(State of health,SOH)预估可有效地表征动力电池性能,对电动汽车动力电池维护和寿命管理具有重要意义。近年来,以深度学习、强化学习和大数据技术等为... 详细信息

目前先进的电动汽车开发和应用已成为实现“脱碳”的关键技术。准确的电池健康状态(State of health,SOH)预估可有效地表征动力电池性能,对电动汽车动力电池维护和寿命管理具有重要意义。近年来,以深度学习、强化学习和大数据技术等为代表的新一代人工智能技术在电动汽车电池状态预估的应用已成为研究热点。首先简要介绍人工智能技术、SOH的含义以及影响SOH主要因素,然后分别从电池单体与电池系统的角度对几种人工智能模型在SOH预估中的研究进行总结与讨论,最后结合大数据、云计算、区域链等新兴技术,对电池健康状态预估问题进行展望,为提升当前动力电池全生命周期管理能力提供一些思路。

关键词：人工智能健康状态电池系统现状与趋势

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Boosting SN38-based oral chemotherapy to combine reductionbioactivated structured lipid-mimetic prodrug with ascorbic acid

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Nano Research 2022年第10期15卷 9092-9104页

作者： Helin Wang Qi Lu yifan miao Jiaxuan Song Mingyang Zhang Zixuan Wang Haotian Zhang Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

The reduction-responsive disulfide bonds have been widely used as bioactive linkages to facilitate a rapid release of anticancer drugs into tumor ***,the activation can be hindered by the kinetics of the thiol-disulfide exchange *** with an additional reductant is a promising strategy to further boost drug ***,inspired by the specific absorption mechanism of triglyceride fat,structured lipid-mimetic oral prodrugs of 7-ethyl-10-hydroxycamptothecin(SN38)were designed to improve intestinal permeability and bypass the first-pass ***38 prodrugs were prepared into lipid formulations that could self-emulsify into nano-sized particles after entering the gastrointestinal ***,we found that the oral bioavailability of the prodrug lipid formulation could be up to 2.69-fold higher than that of the parent SN38,indicating an effective oral *** addition,the reduction-responsive disulfide bond was used as a linker,and ascorbic acid(ASC)was coadministrated to further promote the efficient release of SN38 from the *** enhanced the oral antitumor effect of the reduction-responsive oral prodrug and exhibited good *** summary,the combination of a structured lipid-mimetic prodrug and ASC was firstly demonstrated to boost the oral chemotherapy effect of the difficult-for-oral chemotherapeutics.

关键词： oral chemotherapy structured lipid-mimetic prodrug 7-ethyl-10-hydroxycamptothecin(SN38) ascorbic acid

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Erratum to:Boosting SN38-based oral chemotherapy to combine reduction-bioactivated structured lipid-mimetic prodrug with ascorbic acid

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Nano Research 2023年第4期16卷 6010-6011页

作者： Helin Wang Qi Lu yifan miao Jiaxuan Song Mingyang Zhang Haotian Zhang Zhonggui He Zixuan Wang Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

Erratum to Nano Research 2022,15(10):9092-9104 https://***/10.1007/s12274-022-4544-7 Figure 9 was unfortunately mistakenly *** error did not affect any of the conclusions from the published paper.

关键词： chemotherapy Figure combine

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The evolving views of hematopoiesis:from embryo to adulthood and from in vivo to in vitro

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Journal of Genetics and Genomics 2024年第1期51卷 3-15页

作者： yifan Zhang Feng Liu Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology School of Life SciencesShandong UniversityQingdaoShandong 266237China State Key Laboratory of Membrane Biology Institute of ZoologyInstitute for Stem Cell and RegenerationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China

The hematopoietic system composed of hematopoietic stem and progenitor cells(HSPCs)and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate *** gastrulation onwards,there successively emerge primitive hematopoiesis(that produces specialized he-matopoietic cells),pro-definitive hematopoiesis(that produces lineage-restricted progenitor cells),and definitive hematopoiesis(that produces multipotent HSPCs).These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic *** development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental *** to the progressive methodology(e.g.,high-throughput lineage tracing and single-cell functional and omics analyses),our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated;meanwhile,new paradigms to characterize rare cell types,cell heterogeneity and its causes,and comprehensive regulatory landscapes have been ***,we review the evolving views of HSPC biology during developmental and postnatal ***,we discuss recent advances in the in vitro induction and expansion of HSPCs,with a focus on the implications for clinical applications.

关键词： Hematopoietic stem and progenitor cell Developmental hematopoiesis Postnatal hematopoiesis In vitro hematopoiesis

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Theoretical insights of the pharmaceutical compound fluoxetine in water:Role in direct photolysis and indirect photolysis by free radicals

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Journal of Environmental Sciences 2024年第8期142卷 269-278页

作者： Ying Lu Se Wang yifan Shen School of Environmental Science and Engineering Collaborative Innovation Center of Atmospheric Environment and Equipment TechnologyJiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution ControlNanjing University of Information Science and TechnologyNanjing 210044China

The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness,which may pose a major threat to the aquatic *** this study,photodegradation(direct and indirect photolysis)of two different dissociation states of fluoxetine(FLU)was investigated in water,mainly including the determination of photolytic transition states and products,and the mechanisms of indirect photodegradation with·OH,CO_(3)^(*-)and NO_(3)^(*).The main direct photolysis pathways are defluorination and C–C bond *** addition,the indirect photodegradation of FLU in water is mainly through the reactions with·OH and NO_(3)^(*),and the photodegradation reaction with CO_(3)^(*-)is relatively difficult to occur in the water *** results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.

关键词： Fluoxetine Photochemical mechanism Direct photolysis Free radical reaction DFT

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State-Based Opacity Verification of Networked Discrete Event Systems Using Labeled Petri Nets

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IEEE/CAA Journal of Automatica Sinica 2024年第5期11卷 1274-1291页

作者： yifan Dong Naiqi Wu Zhiwu Li The authors are with the Institute of Systems Engineering Macao University of Science and TechnologyTaipa 999078MacaoChina

The opaque property plays an important role in the operation of a security-critical system,implying that pre-defined secret information of the system is not able to be inferred through partially observing its *** paper addresses the verification of current-state,initial-state,infinite-step,and K-step opacity of networked discrete event systems modeled by labeled Petri nets,where communication losses and delays are *** on the symbolic technique for the representation of states in Petri nets,an observer and an estimator are designed for the verification of current-state and initial-state opacity,***,we propose a structure called an I-observer that is combined with secret states to verify whether a networked discrete event system is infinite-step opaque or K-step *** to the utilization of symbolic approaches for the state-based opacity verification,the computation of the reachability graphs of labeled Petri nets is avoided,which dramatically reduces the computational overheads stemming from networked discrete event systems.

关键词： infinite system symbolic

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co-Condensation Synthesis of Salicylaldimine Calcium Complex Containing Mesoporous Silica Nanoparticles as Carriers for Drug Release

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Chemical Research in Chinese Universities 2014年第4期30卷 531-537页

作者： TANG Duihai ZHANG Weiran WANG yifan miao Jing QIAO Zhen'an HUO Qisheng ZHANG Lirong State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of Chemistry Jilin University Changchun 130012 P. R. China

A series of functional mesoporous silica nanoparticles（MSNs） was synthesized by a one-step simple synthesis approach involving co-condensation of tetraethoxysilane（TEOS） and salicylaldimine ligand（Sal-Si） in the presence of cetyltrimethylammonium chloride（CTAC） under basic *** target MSNs with different sizes （50,100 and 200 nm,respectively） were ***,the Ca^2＋ cations were also introduced into *** prepared nanoparticles were characterized by means of infrared（IR） spectra,thermogravimetric analysis（TGA）,inductively coupled plasma（ICP）,CHN elemental analysis,nitrogen adsorption-desorption,scanning electron microscope（SEM） and transmission electron microscope（TEM）.Ibuprofen（IBU） which contains carboxyl groups was selected as a model *** results of drug loading and release reveal that the loading capacities and release behaviors of the model drug are highly dependent on the Ca^2＋ cations in *** release of IBU from the MSNs functionalized by Ca^2＋ cations is found to be effectively controlled when compared to the release from the MSNs without the functionalization of Ca^2＋ cations,which is due to the ionic interaction between carboxyl groups in IBU and Ca^2＋ cations in MSNs.

关键词： Mesoporous silica nanoparticle co-Condensation method Release of ibuprofen Calcium ion

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Numerical Simulation of the Settling Flux of Biodeposition in a Bay with Cage Culture Through Similarity Theory and a Simplified Pollution Source

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Journal of Ocean University of China 2024年第1期23卷 247-254页

作者： LIU Yao CHEN yifan GE Changzi Marine College Shandong UniversityWeihai 264209China

The settling flux of biodeposition affects the environmental quality of cage culture areas and determines their environmental carrying *** and effective simulation of the settling flux of biodeposition is extremely important for determining the spatial distribution of ***,biodeposition in cage culture areas without specific emission rules can be simplified as point source *** is a fluid simulation software that can simulate the dispersion of particulate matter simply and *** on the simplification of pollution sources and bays,the settling flux of biodeposition can be easily and effectively simulated by Fluent fluid *** the present work,the feasibility of this method was evaluated by simulation of the settling flux of biodeposition in Maniao Bay,Hainan Province,China,and 20 sampling sites were selected for determining the settling *** sampling sites P1,P2,P3,P4,P5,Z1,Z2,Z3,Z4,A1,A2,A3,A4,B1,B2,C1,C2,C3 and C4,the measured settling fluxes of biodeposition were 26.02,15.78,10.77,58.16,6.57,72.17,12.37,12.11,106.64,150.96,22.59,11.41,18.03,7.90,19.23,7.06,11.84,5.19 and 2.57 g d^(−1)m^(−2),*** simulated settling fluxes of biodeposition at the corresponding sites were 16.03,23.98,8.87,46.90,4.52,104.77,16.03,8.35,180.83,213.06,39.10,17.47,20.98,9.78,23.25,7.84,15.90,6.06 and 1.65 g d^(−1)m^(−2),*** was a positive correlation between the simulated settling fluxes and measured ones(R=0.94,P=2.22×10^(−9)<0.05),which implies that the spatial differentiation of biodeposition flux was well ***,the posterior difference ratio of the simulation was 0.38,and the small error probability was 0.94,which means that the simulated results reached an acceptable level from the perspective of relative ***,if nonpoint source pollution is simplified to point source pollution and open waters are simplified based on similarity theory,the setting flux of biodeposition i

关键词： fluent fluid simulation software pollution source simplification posterior difference ratio similarity theory Spear-man correlation

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Why Are Arctic Sea Ice Concentration in September and Its Interannual Variability Well Predicted over the Barents–East Siberian Seas by CFSv2?

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Journal of Meteorological Research 2024年第1期38卷 53-68页

作者： yifan XIE Ke FAN Hongqing YANG School of Atmospheric Sciences Sun Yat-sen Universityand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082

To further understand the prediction skill for the interannual variability of the sea ice concentration(SIC)in specific regions of the Arctic,this paper evaluates the NCEP Climate Forecast System version 2(CFSv2),in predicting the autumn SIC and its interannual variability over the Barents–East Siberian Seas(BES).It is found that CFSv2 presents much better prediction skill for the September SIC over BES than the Arctic as a whole at 1–6-month leads,and high prediction skill for the interannual variability of the SIC over BES is displayed at 1–2-month leads after removing the linear ***2 can reasonably reproduce the relationship between the SIC over BES in September and such factors as the surface air temperature(SAT),200-hPa geopotential height,sea surface temperature(SST),and North Atlantic *** addition,it is found that the prescribed SIC initial condition in August as an input to CFSv2 is also ***,the above atmospheric and oceanic factors,as well as an accurate initial condition of SIC,all contribute to a high prediction skill for SIC over BES in *** on a statistical prediction method,the contributions from individual predictability sources are further *** high prediction skill of CFSv2 for the interannual variability of SIC over BES is largely attributable to its accurate predictions of the SAT and SST,as well as a better initial condition of SIC.

关键词： sea ice concentration the Barents-East Siberian Seas Climate Forecast System version 2(CFSv2) prediction skill predictability source atmospheric and oceanic factors initial condition

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