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Visualization of nasal powder distribution using biomimetic human nasal cavity model

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Acta Pharmaceutica Sinica B 2024年第1期14卷 392-404页

作者： Jiawen Su Yan Liu Hongyu Sun Abid Naeem Huipeng Xu Yue Qu Caifen Wang Zeru Li Jianhua Lu Lulu Wang Xiaofeng Wang Jie Wu Lixin Sun Jiwen Zhang Zhigang Wang Rui Yang Li Wu Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Key Laboratory of Molecular Pharmacology and drug evaluation School of PharmacyMinistry of EducationYantai UniversityYantai 264005China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201210China Nantong Haimen People’s Hospital Nantong 226199China Yangtze Delta drug Advanced Research Institute Nantong 226126China Shenyang Pharmaceutical University Shenyang 110016China National Institutes for Food and drug Control Beijing 100000China Nanjing University of Chinese Medicine Nanjing 210023China

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal ***,no reliable method is currently available to assess its impact on delivery *** this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal *** results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and *** nasal cavity model was modified with dimethicone and validated to be suitable for the deposition *** experimental device produced the most satisfactory results with five spray ***,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,***,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo *** conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

关键词： Nasal drug deposition Nasal drug distribution Nasal drug delivery Biomimetic nasal model Nasal powder Three-dimensional reconstruction Three-dimensional printing Nasal drug distribution

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer drugs via Mitophagy-induced Apoptosis

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Current Medical Science 2024年第4期44卷 809-819页

作者： Chen-guang YAO Zi-jia ZHAO Ting TAN Jiang-ning YAN Zhong-wei CHEN Jun-tao XIONG Han-luo LI Yan-hong WEI Kang-hong HU Sino-German Biomedical center Hubei Provincial Key Laboratory of Industrial MicrobiologyCooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province)Key Laboratory of Fermentation Engineering(Ministry of Education)National“111”Center for Cellular Regulation and Molecular PharmaceuticsHubei University of TechnologyWuhan430068China center for evaluation of Hubei Medical Products Administration Wuhan430068China

Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor *** study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying *** Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side *** colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related *** MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer *** was found that MO-4 induced the apoptosis of multiple types of breast cancer ***,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in *** vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 *** Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

关键词： antitumor breast cancer polyoxometalate mitochondria mitophagy

In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4102-4117页

作者： Yuan Li Fan Tong Yufan Wang Jing Wang Manqi Wu Hanmei Li Hongyan Guo Huile Gao Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Key Laboratory of drug Targeting and drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China

Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate ***,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and ***,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian *** CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@*** from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T ***,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in ***,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

关键词： In situ nano-vaccine Lymph node targeting MMP-2 responsive PD-1 Combination therapy CpG Ovarian cancer Metastases

Atlantic blocking events in a simplified nonlinear baroclinic model for local finite-amplitude wave activity

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Atmospheric and Oceanic Science Letters 2024年第4期17卷 41-45页

作者： Ning Shi Bamidele Abiodun Paul Wencai Liu Collaborative Innovation center on Forecast and evaluation of Meteorological Disasters School of Atmospheric SciencesNanjing University of Information Science and TechnologyNanjingChina Nigerian Meteorological Agency AbujaNigeria

为研究北大西洋阻高的形成机制,本文在局部有限振幅波活动(LWA)框架下进行了一系列数值实验.采用的数值模型能显式地描绘出两种重要的大气内部动力过程,即非线性纬向位涡通量和Rossby波包传播.模拟结果显示,这两种动力学过程均是形成大... 详细信息

为研究北大西洋阻高的形成机制,本文在局部有限振幅波活动(LWA)框架下进行了一系列数值实验.采用的数值模型能显式地描绘出两种重要的大气内部动力过程,即非线性纬向位涡通量和Rossby波包传播.模拟结果显示,这两种动力学过程均是形成大西洋阻高的重要机理.具体地,非线性纬向位涡通量和Rossby波包传播,分别是大西洋阻高南部和北部LWA形成的主导因子.因此,本研究综合了前人关于大西洋阻高的研究成果,为其形成机理提供了新的认识.

关键词：斜压模式局地有限振幅波活动罗斯贝波传播非线性效应

A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie Yang Jie Li Qiao Kong Siming Zhou Hongbao Sun Lili Pan Qiyong Gong Ping Feng Haoxing Wu Department of Radiology and Huaxi MR Research center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key Laboratory of drug-Targeting and drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of Nuclear Medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China Clinical Trial center and National Medical Products Administration Key Laboratory for Clinical Research and evaluation of Innovative drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

Synthesis of Diverse Oxetane Amino Acids via Visible-Light-Induced Photocatalytic Decarboxylative Giese-Type Reaction

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Chinese Journal of Chemistry 2024年第12期42卷 1341-1346页

作者： Haoliang Shi Yi Wan Yongqiang Zhang Shanghai Frontiers Science center of Optogenetic Techniques for Cell Metabolism Shanghai Key Laboratory of New Drug Designand School of PharmacyEast China University of Science and TechnologyShanghai200237 China

The divergent synthesis of versatile 3,3′-disubstituted oxetane amino acids by utilizing visible-light-induced photocatalytic decarboxylative Giese-type reaction has been demonstrated.3-Methyleneoxetane-derived substrates are readily available in a single-step and highly reactive as radical acceptors,allowing the production of versatile oxetaneγ-andα-amino acids in high yields.A distinct ring strain release-driven radical addition mechanism was preliminarily *** preparative power was further highlighted by the application in the synthesis of oxetane-containing dipeptides and azetidine amino acids,as well as the transformation of the product into novel oxetane-containing spiro-heterocycle pharmacophore.

关键词： Photoredox catalysis Decarboxylative Giese-type reaction Oxetane amino acids Amino acids Synthesis Radical reactions

Design,synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells

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Chinese Chemical Letters 2024年第5期35卷 287-289页

作者： Wenyi Mei Lijuan Xie Xiaodong Zhang Cunjian Shi Fengzhi Wang Qiqi Fu Zhenjiang Zhao Honglin Li Yufang Xu Zhuo Chen Shanghai Key Laboratory of New drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Innovation center for AI and drug Discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological *** clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)*** them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent ***,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy *** MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and *** all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.

关键词： Pentacyclic triterpenoid Ursolic acid Fluorescent derivatives Autophagy Apoptosis

Rh(Ⅱ)catalyzed efficient sigmatropic rearrangement reaction of pyridotriazoles and sulfides

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Green Synthesis and Catalysis

Green Synthesis and Catalysis 2024年第2期5卷 77-79页

作者： Yuting Chen Guanghui Lv Zhiyang Li Meiling Ye Tianle Huang Li Hai Yong Wu 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 UniversityChengdu610041China Department of Pharmacy Taihe HospitalHubei University of MedicineShiyan442000China

The[2,3]-and[1,2]-sigmatropic rearrangement reactions between pyridotriazoles and sulfides catalyzed by rhodium(II)were *** utilization of pyridotriazoles as the carbene precursors in this kind of reaction efficiently... 详细信息

关键词： Pyridotriazole Sulfide -Sigmatropic rearrangement -Sigmatropic rearrangement Rhodium catalysis

El Niño and the AMO Sparked the Astonishingly Large Margin of Warming in the Global Mean Surface Temperature in 2023

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Advances in Atmospheric Sciences 2024年第6期41卷 1017-1022页

作者： Kexin LI Fei ZHENG Jiang ZHU Qing-Cun ZENG International center for Climate and Environment Sciences Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Collaborative Innovation center on Forecast and evaluation of Meteorological Disasters Nanjing University of Information Science&TechnologyNanjing 210044China University of Chinese Academy of Sciences Beijing 100049China

In 2023,the majority of the Earth witnessed its warmest boreal summer and autumn since *** 2023 will indeed turn out to be the warmest year on record and what caused the astonishingly large margin of warming has become one of the hottest topics in the scientific community and is closely connected to the future development of human *** analyzed the monthly varying global mean surface temperature(GMST)in 2023 and found that the globe,the land,and the oceans in 2023 all exhibit extraordinary warming,which is distinct from any previous year in recorded *** on the GMST statistical ensemble prediction model developed at the Institute of Atmospheric Physics,the GMST in 2023 is predicted to be 1.41℃±0.07℃,which will certainly surpass that in 2016 as the warmest year since 1850,and is approaching the 1.5℃ global warming *** to 2022,the GMST in 2023 will increase by 0.24℃,with 88%of the increment contributed by the annual variability as mostly affected by El Niñ***,the multidecadal variability related to the Atlantic Multidecadal Oscillation(AMO)in 2023 also provided an important warming background for sparking the GMST *** a result,the GMST in 2023 is projected to be 1.15℃±0.07℃,with only a 0.02℃ increment,if the effects of natural variability—including El Niño and the AMO—are eliminated and only the global warming trend is considered.

关键词： record-breaking temperature global mean surface temperature El Niño AMO global warming