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Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng Huize Han zhipu fan Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in *** adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in *** summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

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One-pot preparation of nanodispersion with readily available components for localized tumor photothermal and photodynamic therapy

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 120-128页

作者： Anpu Yang Yanan Sun Bochen Lyu Binlong Chen zhipu fan Minghui Li Yao Zhao Jijun Fu Bing He Hua Zhang Xueqing Wang Wenbing Dai Qiang Zhang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciencesxueyuan road 38haidian districtPeking UniversityBeijing 100191China Beijing Key Laboratory of Molecular Pharmaceutics School of Pharmaceutical SciencesPeking UniversityBeijing 100191China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.

关键词： Photodynamic therapy Photothermal therapy Carbon nanohorn Zinc phthalocyanine

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Effects of carbon content on the microstructure and tensile properties of a low-density steel

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 391-401页

作者： Yongxuan Shang Mingyu fan Shuyong Jiang Zhongwu Zhang Key Laboratory of Superlight Materials and Surface Technology Ministry of EducationCollege of Materials Science and Chemical EngineeringHarbin Engineering UniversityHarbin 150001China State Key Laboratory of Metal Material for Marine Equipment and Application Iron&Steel Research Institute of Ansteel Group CorporationAnshan 114009China

Carbon can change the phase components of low-density steels and influence the mechanical *** this study,a new method to control the carbon content and avoid the formation ofδ-ferrite by decarburization treatment was *** microstructural changes and mechanical characteristics with carbon content induced by decarburization were systematically ***-Jaoul(C-J)analysis was employed to examine the work hardening characteristics during the tensile *** decarburization by heat treatments,the carbon content within the austenite phase decreased,while Mn and Al were almost unchanged;this made the steel with full austenite transform into the austenite and ferrite dual ***,(Ti,V)C carbides existed in both matrix phase and the mole fraction almost the *** addition,the formation of other carbides *** loss induced a decrease in strength due to the weakening of the carbon solid *** the steel with the single austinite,the deformation mode of austenite was the dislocation planar glide,resulting in the formation of *** the dual-phase steel,the deformation occurred by the dislocation planar glide of austenite first,with the increase in strain,the cross slip of ferrite took place,forming dislocation cells in *** the late stage of deformation,the work hardening of austinite increased rapidly,while that of ferrite increased slightly.

关键词： low-density steels carbon content decarburization strengthening mechanisms work hardening behavior

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Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： Andrew Gregory Chengyun Tang fan fan Department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

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Tackling the microlensing wave effects of strong lensing gravitational waves with TAAH

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 257-258页

作者： Zuhui fan South-Western Institute for Astronomy Research Yunnan University

The rapid development of gravitational wave（GW） observations since their first detection in 2015 [1] has opened a completely new window for exploring the Universe. Consequently, astronomical research has entered the multimessenger era, allowing us to use different tracers to view the cosmos from various perspectives. Among others, the appealing application of gravitational wave events from compact binary mergers is that they can act as standard sirens to determine absolute cosmic distances entirely independent of standard candles. This approach is one of the most promising means to solve the current H0tension problem.

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Bandgap characteristics analysis and graded design of a novel metamaterial for flexural wave suppression

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 1-24页

作者： fan YANG Zhaoyang MA Xingming GUO Shanghai Key Laboratory of Mechanics in Energy Engineering Shanghai Institute of Applied Mathematics and Mechanics School of Mechanics and Engineering ScienceShanghai University Shanghai Institute of Aircraft Mechanics and Control

A novel elastic metamaterial is proposed with the aim of achieving lowfrequency broad bandgaps and bandgap regulation. The band structure of the proposed metamaterial is calculated based on the Floquet-Bloch theorem, and the boundary modes of each bandgap are analyzed to understand the effects of each component of the unit cell on the bandgap formation. It is found that the metamaterials with a low elastic modulus of ligaments can generate flexural wave bandgaps below 300 Hz. Multi-frequency vibrations can be suppressed through the selective manipulation of bandgaps. The dual-graded design of metamaterials that can significantly improve the bandgap width is proposed based on parametric studies. A new way that can regulate the bandgap is revealed by studying the graded elastic modulus in the substrate. The results demonstrate that the nonlinear gradient of the elastic modulus in the substrate offers better bandgap performance. Based on these analyses, the proposed elastic metamaterials can pave the way for multi-frequency vibration control, low-frequency bandgap broadening, and bandgap tuning.

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Dynamic behaviors of graphene platelets-reinforced metal foam piezoelectric beams with velocity feedback control

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 63-80页

作者： Jie CHEN Xinyue ZHANG Mingyang fan School of Mathematics Statistics and Mechanics Beijing University of Technology College of Mechanical & Energy Engineering Beijing University of Technology

Graphene platelets(GPLs)-reinforced metal foam structures enhance the mechanical properties while maintaining the lightweight characteristics of metal foams. Further bonding piezoelectric actuator and sensor layers on the surfaces of GPLs-reinforced metal foam beams enables active vibration control, greatly expanding their applications in the aerospace industry. For the first time, this paper investigates the vibration characteristics and active vibration control of GPLs-reinforced metal foam beams with surfacebonded piezoelectric layers. The constant velocity feedback scheme is used to design the closed-loop controller including piezoelectric actuators and sensors. The effects of the GPLs on the linear and nonlinear free vibrations of the beams are numerically *** Newmark-β method combined with Newton's iteration technique is used to calculate the nonlinear responses of the beams under different load forms including harmonic loads,impact loads, and moving loads. Additionally, special attention is given to the vibration reduction performance of the velocity feedback control on the responses of the beam.

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The impact of Rho GTPases on the cell uptake of single-walled carbon nanohorns

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Journal of Chinese Pharmaceutical Sciences 2017年第6期26卷 395-403页

作者：傅洪哲宋佳芳宋歌宋思洋樊志璞杨岸蒲何冰代文兵张华王学清张强北京大学医学部药学院天然药物及仿生药物国家重点实验室药学院药剂学系北京100191

Rho GTPases play an important role on the regulation of cytoskeleton, which can affect the cell morphogenesis, cell migration, endocytosis and vesicle transport by controlling the growth and maintenance of microfilaments and microtubules. It has been known that regulation of cell cytoskeleton is inseparable from the cell uptake of nano-medicine or nano-drug delivery systems. However, only few studies have focused on the impacts of Rho GTPases on cell uptake of nano-medicine or nano-drug delivery systems. This study selected single-walled carbon nanohoms （SWCNHs）, which have emerged as promising drug delivery systems, to explore the impacts of Rho GTPases on cell uptake of nano-drug delivery systems. SWCNHs were oxidized with concentrated nitric acid and prepared into nano dispersion by ultrasonic dispersion. Confocal laser scanning microscope （CLSM） and transmission electron microscopy （TEM） were used to observe the cell uptake and intracellular distribution of nanoparticles after incubated A549 cells with the dispersion mentioned above. Mechanism of cell uptake was assessed using various inhibitors. The results showed that the cell uptake of oxSWCNHs was significantly reduced when RhoA was inhibited. The oxSWCNHs were internalized through clathrin-mediated endocytosis and mainly positioned in lysosomes ofA549 cells.

关键词： Rho GTPases Single-walled carbon nanohoms A549 cells Cell uptake

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Rational modulation of fluorophosphate cathode by anionic groups to reduce the polarization behavior for fast-charging sodium-ion batteries

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Journal of Energy Chemistry 2025年第1期100卷 509-521页

作者： Xinyuan Wang fan Zhang Xingyu Zhou Qian Wang Changyu Liu Yangyang Liu Hui Wang Xiaojie Liu Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry & Materials Science Northwest University

Na3V2（PO4）2O2F （VP） is recognized as a promising cathode material for sodium-ion batteries due to its stable structural framework and high specific *** functional theory （DFT） and finite element simulations show that incorporating SO42-into VP decreases its band gap,lowers the migration energy barrier,and ensures a uniform Na+concentration gradient and stress distribution during charge and discharge ***,the average Na+diffusion coefficient of Na3V2（PO4）1.95（SO4）0.05O2F（VPS-1） is roughly double that of VP,leading to enhanced rate capability (80 C,75.5 mAh g-1) and cycling stability (111.0 mAh g-1capacity after 1000 cycles at 10 C current density) for ***-1 exhibits outstanding fast-charging capabilities,achieving an 80%state of charge in just 8.1 *** assembled VPS-1//SbSn/NPC full cell demonstrated stable cycling over 200 cycles at a high 5 C current,maintaining an average coulombic efficiency of 95.35%.

关键词： Anionic group modulation Polarization behavior Fast-charging Sodium-ion battery Fluorophosphate Cathode

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