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Effects of molecular interaction and liver sinusoidal mechanical properties on leukocyte adhesions

BIOPHYSICAL JOURNAL 2025年第3期124卷 480-493页

作者： Zhu, Jingchen Chen, Shenbao zhou, luwen Gong, Xiaobo Cui, Yuhong Zhang, Yan Long, Mian Lu, Shouqin Chinese Acad Sci Inst Mech Ctr Biomech & Bioengn Key Lab MicrogravNatl Micrograv LabBeijing Key L Beijing Peoples R China Chinese Acad Sci Inst Mech CAS Ctr Excellence Complex Syst Mech Beijing Peoples R China Univ Chinese Acad Sci Sch Engn Sci Beijing Peoples R China Ningbo Univ Sch Mech Engn & Mech Smart Mat & Adv Struct Lab Ningbo Zhejiang Peoples R China Shanghai Jiao Tong Univ Sch Naval Architecture Ocean & Civil Engn Dept Engn Mech Key Lab HydrodynamMinist Educ Shanghai Peoples R China Tianjin Univ Dept Mech Tianjin Peoples R China

It is interesting to find pathologically that leukocytes, especially neutrophils, tend to adhere in the liver sinusoids dominantly but not in the postsinusoidal venules. While both views of receptor-ligand interactions and physical trapping are proposed for mediating leukocyte adhesion in liver sinusoids, integrated investigations for classifying their respective contributions are poorly presented. With a combination of Monte Carlo simulation and immersed boundary method, this study explored numerically the effects of molecular interaction kinetics and sinusoidal mechanical properties on leukocyte adhesion in liver sinusoid jointly. Results showed that, within the range of biological limitations, the lumen stenosis ratio, leukocyte stiffness, Disse space stiffness and endothelium permeability regulate the comprehensive adhesion process in a descending order of significance in the presence of receptor-ligand interactions. While leukocyte adhesions could be mutually promoted with proper combinations of leukocyte stiffness, lumen stenosis, and molecular interaction, the binding affinity is insensitive under the conditions with low leukocyte stiffness in normal lumen stenosis and high leukocyte stiffness in high lumen stenosis. This work deepens the understanding of recruitment mechanism of leukocyte in liver sinusoids.

关键词： Liver sinusoid immersed boundary method leukocyte adhesion receptor-ligand interaction sinusoidal mechanical properties

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50-Fold Adjuvant and 20-Fold Antigen Vaccine Dose Sparing from Nanoliposome Display of a Stabilized Malarial Protein Antigen

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ACS NANO 2025年第10期19卷 10103-10112页

作者： Song, Yiting Huang, Wei-Chiao Ivanochko, Danton Long, Carole Li, Qinzhe zhou, luwen Julien, Jean-Philippe Miura, Kazutoyo Lovell, Jonathan F. SUNY Buffalo Dept Biomed Engn Buffalo NY 14260 USA Hosp Sick Children Res Inst Program Mol Med Toronto ON M5G 0A4 Canada NIAID Lab Malaria & Vector Res NIH Rockville MD 20852 USA

Displaying soluble vaccine protein antigens onto the surface of adjuvanted nanoliposomes can enhance the magnitude of elicited antibody responses. In this study, we examine this approach with respect to dose sparing, for not only the antigen component but also the adjuvant dose in the vaccine. Using a structurally stabilized Pfs48/45 derived malarial protein as a model antigen, we confirmed the protein rapidly displayed on the surface of immunogenic liposomes containing cobalt porphyrin phospholipid (CoPoP;for antigen display via His-tag interaction) along with the immunostimulatory adjuvants monophosphoryl lipid A (MPLA) and QS-21. Mice were immunized with a fixed protein antigen dose with varying adjuvant doses to estimate the extent of adjuvant sparing. In mice vaccinated at a fixed protein antigen dose, liposome-bound Pfs48/45 achieved superior antibody IgG titers compared to the soluble (nonbound) form at all assessed adjuvant doses, reflecting MPLA and QS-21 adjuvant dose sparing of at least 50-fold. The primary driver of adjuvant sparing in these conditions was presentation of the antigen in a nanoparticle format, and potent responses were achieved even without co-delivery of antigen and adjuvant within the same particle, provided that adjuvant and liposome-displayed antigen were co-administered to the same injection site. By keeping the adjuvant dose fixed and varying the antigen dose in a comparable experimental design, similar to 20-fold antigen dose sparing was observed with liposome display. This case study illustrates the potential of antigen-display nanotechnologies, such as CoPoP nanoliposomes, to achieve substantial adjuvant and antigen dose sparing, which could theoretically facilitate the deployment of future vaccines.

关键词： Vaccine Malaria Antigen Sparing Adjuvant Sparing Liposome

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Plastic Rooftop Rainwater Harvesting Technology in Arid Greenhouse Vegetable Cropping System in Anding, Gansu, China 3

Plastic Rooftop Rainwater Harvesting Technology in Arid Gree...

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3rd International Conference on Environmental Prevention and Pollution Control Technologies, EPPCT 2021

作者： Wang, Junde Jin, Yanzhao zhou, luwen Gansu Research Institute for Water Conservancy Lanzhou Gansu730000 China

Several greenhouse vegetable cropping models have been established to deal with the natural, arid, water deficit weather condition in Anding District. Irrigation requirement is computed based on various irrigation schemes. Rainwater harvesting technology is utilized to estimate the water collection amount with the greenhouse plastic rooftop using the water-balance rationale. Different water demand and runoff collection surface needs are determined based on the supplemental irrigation requirements of the various vegetable cropping models using regulatory benefit principle. The required capacity of rainwater storage is then evaluated for each cropping model. These results provide valuable references for rainwater harvesting technology using greenhouse plastic rooftop for agricultural production. © Published under licence by IOP Publishing Ltd.

关键词： Greenhouses

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Numerical simulation of flow characteristics in a permeable liver sinusoid with leukocytes

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BIOPHYSICAL JOURNAL 2022年第23期121卷 4666-4678页

作者： Chen, Shenbao Zhu, Jingchen Xue, Jian Wang, Xiaolong Jing, Peng zhou, luwen Cui, Yuhong Wang, Tianhao Gong, Xiaobo Lu, Shouqin Long, Mian Chinese Acad Sci Inst Mech Ctr Biomech & Bioengn CAS Ctr Excellence Complex Syst Mech Beijing Peoples R China Univ Chinese Acad Sci Sch Engn Sci Beijing Peoples R China Inst Mech Chinese Acad Sci State Key Lab Nonlinear Mech LNM Beijing Peoples R China Shanghai Jiao Tong Univ Shanghai Peoples R China Tianjin Univ Dept Mech Tianjin Peoples R China

Double-layered channels of sinusoid lumen and Disse space separated by fenestrated liver sinusoidal endothelial cells (LSECs) endow the unique mechanical environment of the liver sinusoid network, which further guarantees its biological function. It is also known that this mechanical environment changes dramatically under liver fibrosis and cirrhosis, including the reduced plasma penetration and metabolite exchange between the two flow channels and the reduced Disse space deformabil-ity. The squeezing of leukocytes through narrow sinusoid lumen also affects the mechanical environment of liver sinusoid. To date, the detailed flow-field profile of liver sinusoid is still far from clear due to experimental limitations. It also remains elusive whether and how the varied physical properties of the pathological liver sinusoid regulate the fluid flow characteristics. Here a numerical model based on the immersed boundary method was established, and the effects of Disse space and leukocyte elas-ticities, endothelium permeability, and sinusoidal stenosis degree on fluid flow as well as leukocyte trafficking were specified upon a mimic liver sinusoid structure. Results showed that endothelium permeability dominantly controlled the plasma penetra-tion velocity across the endothelium, whereas leukocyte squeezing promoted local penetration and significantly regulated wall shear stress on hepatocytes, which was strongly related to the Disse space and leukocyte deformability. Permeability and elas-ticity cooperatively regulated the process of leukocytes trafficking through the liver sinusoid, especially for stiffer leukocytes. This study will offer new insights into deeper understanding of the elaborate mechanical features of liver sinusoid and corresponding biological function.

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Super-Amphiphilic Na2Ti3O7 Nanofibrous Film Enabling Water-Oil Miscibility

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ADVANCED MATERIALS INTERFACES 2022年第32期9卷

作者： Hu, Conghu Hua, Licheng Huang, Bin zhou, luwen Li, Jinbang Du, Jianke Ningbo Univ Sch Mech Engn & Mech Smart Mat & Adv Struct Lab Ningbo 315211 Zhejiang Peoples R China Ningbo Univ Sch Mech Engn & Mech Minist Educ Key Lab Impact & Safety Engn Ningbo 315211 Zhejiang Peoples R China Nanjing Univ Aeronaut & Astronaut Minist Educ Key Lab Intelligent Nano Mat & Devices Nanjing 210016 Peoples R China Ningbo Univ Sch Mech Engn & Mech Ningbo 315211 Zhejiang Peoples R China

Due to their extraordinary affinity for both water and oil, super-amphiphilic materials have garnered considerable interest. A Na2Ti3O7 (NTO) film with super-amphiphilic properties that enable water and oil miscibility is offered. Multiple nanofibrous 3D porous nanostructures compose the super-amphiphilic NTO layer. Up to 32-36 times its weight, the film has a high absorption capacity for water and poly-alpha-olefin (PAO). The average miscibility ratio of water to oil in the film is approximate to 6:5. The discovery of NTO nanofibrous film's super-amphiphilic behavior has significant implications for the development of superwetting materials and their potential applications in the oil emulsion purification and catalyst anchoring industries.

关键词： miscibility nanofilm porous nanostructures super-amphiphilic materials

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Engineering of a plant-produced virus-like particle to improve the display of the Plasmodium falciparum Pfs25 antigen and ransmission-blocking activity of the vaccine candidate

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VACCINE 2023年第4期41卷 938-944页

作者： Tottey, Stephen Shoji, Yoko Jones, R. Mark Musiychuk, Konstantin Chichester, Jessica A. Miura, Kazutoyo zhou, luwen Lee, Shwu-Maan Plieskatt, Jordan Wu, Yimin Long, Carole A. Streatfield, Stephen J. Yusibov, Vidadi Fraunhofer USA Ctr Midatlant Biotechnol Div 9 Innovat Way Newark DE 19711 USA NIAID Lab Malaria & Vector Res NIH 12735 Twinbrook Pkwy Rockville MD 20852 USA PATHs Malaria Vaccine Initiat Washington DC 20001 USA

Malaria kills around 409,000 people a year, mostly children under the age of five. Malaria transmissionblocking vaccines work to reduce malaria prevalence in a community and have the potential to be part of a multifaceted approach required to eliminate the parasites causing the disease. Pfs25 is a leading malaria transmission-blocking antigen and has been successfully produced in a plant expression system as both a subunit vaccine and as a virus-like particle. This study demonstrates an improved version of the viruslike particle antigen display molecule by eliminating known protease sites from the prior A85 variant. This re-engineered molecule, termed B29, displays three times the number of Pfs25 antigens per viruslike particle compared to the original Pfs25 virus-like particle. An improved purification scheme was also developed, resulting in a substantially higher yield and improved purity. The molecule was evaluated in a mouse model and found to induce improved transmission-blocking activity at lower doses and longer durations than the original molecule.

关键词： Malaria Pfs25 Plant -based vaccine Plasmodium falciparum Transmission -blocking vaccine Virus -like particle

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Dissipative particle dynamics simulation of cell entry into a micro-channel

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ENGINEERING ANALYSIS WITH BOUNDARY ELEMENTS 2019年 107卷 47-52页

作者： zhou, luwen Feng, Shiliang Liu, Hantao Chang, Jianzhong Ningbo Univ Fac Mech Engn & Mech Ningbo 315211 Zhejiang Peoples R China North Univ China Lab Energy & Environm Engn & Computat Fluid Dynam Taiyuan 030051 Shanxi Peoples R China

Cell deformability is an important biomarker which can be used to distinguish and sort between healthy and cancer cells. In this paper, we presented a dissipative particle dynamics (DPD) model for investigating cell entry into micro-channels. The cell membrane is represented by a network of DPD particles (beads) connected by wormlike chain (WLC) springs, which is able to mimic the viscoelastic effect of the membrane. The entry process of benign breast epithelial cells (MCF-10A) and non-metastatic tumor breast cells (MCF-7) through a constricted micro-channel are comparatively investigated using this DPD model. It is shown that both the time histories of the cell displacement and the dynamic behaviors of cell entry agree with experimental observations. The entry time of MCF-10A cell is approximately four times of that of MCF-7 cell since MCF-10A cells are stiffer than MCF-7 cells. It is demonstrated that the presented DPD method is effective in modeling cell deformability, and the obtained results can be helpful in understanding how cells with different mechanical properties respond to physical loads.

关键词： Cell entry Micro-channel Dissipative particle dynamics (DPD)

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A human-serum-free medium can induce more infectious P. falciparum gametocytes than a conventional human-serum-containing medium

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SCIENTIFIC REPORTS 2024年第1期14卷 1-7页

作者： Miura, Kazutoyo Deng, Bingbing Varadharajan Suresh, Ragavan Gebremicale, Yonas T. zhou, luwen Pham, Thao P. Roche, Kyle Diouf, Ababacar Lovell, Jonathan F. Julien, Jean-Philippe Long, Carole A. Natl Inst Allergy & Infect Dis NIH Lab Malaria & Vector Res Rockville MD 20852 USA SUNY Buffalo Dept Biomed Engn Buffalo NY 14260 USA Hosp Sick Children Res Inst Program Mol Med Toronto ON M5G 0A4 Canada Univ Toronto Dept Biochem & Immunol Toronto ON M5S 1A8 Canada Natl Inst Allergy & Infect Dis NIH Lab Malaria & Vector Res 12735 Twinbrook Pkwy Rockville MD 20852 USA Fdn Adv Educ Sci Acad Programs Bethesda MD 20892 USA

Malaria remains a global health problem, and the standard membrane feeding assay (SMFA) is a key functional assay for development of new interventions to stop malaria transmission from human to mosquito. For SMFA, media with similar to 10% of human serum has been used for infectious gametocyte cultures, however, there are multiple challenges to obtain a suitable human serum. Here we show a human-serum-free culture medium (HSF), which was a mixture of two stem cell culture media and AlbuMAX, supported infectious gametocyte growth. Moreover, the HSF-induced gametocytes elicited significantly higher numbers of oocysts compared to gametocytes cultured with conventional human serum medium (Conv). While some caution is required when comparing percent transmission reducing activity data generated from HSF-SMFA and Conv-SMFA, the HSF method can facilitate the establishment of gametocyte cultures or SMFA by bypassing the need for human serum. Thus, this study will support future development of P. falciparum transmission-blocking interventions.

关键词： Plasmodium Falciparum: malaria Gametocyte Gametocyte culture Serum free Standard membrane-feeding assay SMFA Transmission-blocking

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杠铃运动的生物力学分析与优化

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中国科学：物理学、力学、天文学 2024年第12期54卷 107-118页

作者：赵彬皓石智勇徐异宁黄斌周吕文顾耀东张明华杜建科宁波大学机械工程与力学学院浙江-意大利智能材料与先进结构联合实验室宁波315211 宁波大学体育学院宁波315832

不正确的杠铃硬拉和深蹲动作会增加腰椎间盘的压力,从而导致损伤风险.本文建立了一个以踝、膝、髋等关节为节点的三维人体生物力学模型,显著优于传统的二维提拉模型.该三维模型能更全面地模拟杠铃运动中的动态力学行为,允许准确计算在... 详细信息

不正确的杠铃硬拉和深蹲动作会增加腰椎间盘的压力,从而导致损伤风险.本文建立了一个以踝、膝、髋等关节为节点的三维人体生物力学模型,显著优于传统的二维提拉模型.该三维模型能更全面地模拟杠铃运动中的动态力学行为,允许准确计算在复杂运动姿态下的关节压力和剪力.模型计算了不同运动姿态对腰椎L5/S1关节的压力和剪力,探讨了不同站姿角度和踝关节最大屈曲角对L5/S1关节压力峰值的影响.结果表明,增大踝关节的最大屈曲角对减轻腰椎压力峰值具有显著效果,而通过调整站姿角度对压力峰值的降低作用不明显.此外,本研究还针对特定个体(奥运举重冠军石智勇)进行了模拟,验证了模型的个性化适用性.本研究不仅为理解和优化杠铃运动提供了科学依据,也为设计安全有效的训练计划提供了数字化指导.

关键词：杠铃运动生物力学运动优化

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Flow field analyses of a porous membrane-separated,double-layered microfluidic chip for cell co-culture

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Acta Mechanica Sinica 2020年第3期36卷 754-767页

作者： Shenbao Chen Jian Xue Jinrong Hu Qihan Ding luwen zhou Shiliang Feng Yuhong Cui Shouqin Lu Mian Long Center of Biomechanics and Bioengineering Key Laboratory of Microgravity(National Microgravity Laboratory)Beijing Key Laboratory of Engineered Construction and Mechanobiologyand CAS Center for Excellence in Complex System MechanicsInstitute of MechanicsChinese Academy of SciencesBeijing100190China School of Engineering Science University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Nonlinear Mechanics(LNM) Institute of MechanicsChinese Academy of SciencesBeijing 100190China Faculty of Mechanical Engineering and Mechanics Ningbo UniversityNingbo 315211ZhejiangChina Department of Mechanics Tianjin UniversityTianjin 300072China

Organs-on-chips composed of a porous membrane-separated,double-layered channels are used widely in elucidating the effects of cell co-culture and flow shear on biological *** the diversity of channel geometry and membrane permeability is applied,their quantitative correlation with flow features is still *** boundary methods(IBM)simulations and theoretical modelling were performed in this *** simulations showed that channel length,height and membrane permeability jointly regulated the flow features of flux,penetration velocity and wall shear stress(WSS).Increase of channel length,lower channel height or membrane permeability monotonically reduced the flow flux,velocity and WSS in upper channel before reaching a *** the flow flux in lower channel monotonically increased with the increase of each factor,the WSS surprisingly exhibited a biphasic pattern with first increase and then decrease with increase of lower channel ***,the transition threshold of maximum WSS was sensitive to the channel length and membrane *** modeling,integrating the transmembrane pressure difference and inlet flow flux with chip geometry and membrane permeability,was in good agreement with IBM *** analyses provided theoretical bases for optimizing flow-specified chip design and evaluating flow microenvironments of in vivo tissue.

关键词： Immersed boundary method Porous membrane Wall shear stress Penetration velocity Microfluidic chip

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