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Pickering emulsion transport in skeletal muscle tissue:A dissipative particle dynamics simulation approach

Chinese Journal of Chemical Engineering 2024年第4期68卷 65-75页

作者： Xuwei Liu Wei Chen yufei xia Guanghui Ma Reiji Noda Wei Ge State Key Laboratory of Mesoscience and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China Division of Environmental Engineering Science Graduate School of Science and TechnologyGunma University1-5-1 Tenjin-choKiryuGunma 376-8515Japan State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

Lymph node targeting is a commonly used strategy for particulate vaccines,particularly for Pickering emulsions.However,extensive research on the internal delivery mechanisms of these emulsions,especially the complex intercellular interactions of deformable Pickering emulsions,has been surprisingly sparse.This gap in knowledge holds significant potential for enhancing vaccine efficacy.This study aims to address this by summarizing the process of lymph-node-targeting transport and introducing a dissipative particle dynamics simulation method to evaluate the dynamic processes within cell tissue.The transport of Pickering emulsions in skeletal muscle tissue is specifically investigated as a case study.Various factors impacting the transport process are explored,including local cellular tissue environmental factors and the properties of the Pickering emulsion itself.The simulation results primarily demonstrate that an increase in radial repulsive interaction between emulsion particles can decrease the transport efficiency.Additionally,larger intercellular gaps also diminish the transport efficiency of emulsion droplet particles due to the increased motion complexity within the intricate transport space compared to a single channel.This study sheds light on the nuanced interplay between engineered and biological systems influencing the transport dynamics of Pickering emulsions.Such insights hold valuable potential for optimizing transport processes in practical biomedical applications such as drug delivery.Importantly,the desired transport efficiency varies depending on the specific application.For instance,while a more rapid transport might be crucial for lymph-node-targeted drug delivery,certain applications requiring a slower release of active components could benefit from the reduced transport efficiency observed with increased particle repulsion or larger intercellular gaps.

关键词： Pickering emulsion Skeletal muscular cells Transport phenomena Dissipative particle dynamics Drug delivery

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Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable,safe and efficient vaccine adjuvant

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Frontiers of Chemical Science and Engineering 2022年第6期16卷 973-984页

作者： Lili Yuan xiao-Dong Gao yufei xia Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

To increase antibody secretion and dose sparing,squalene-in-water aluminium hydrogel(alun^-stabilised emulsions(ASEs)have been developed,which offer increased surface areas and cellular interactions for higher antigen loading and enhanced immune responses.Nevertheless,the squalene(oil)in previous attempts suffered from limited oxidation resistance,thus,safety and stability were compromised.From a clinical translational perspective,it is imperative to screen the optimal oils for enhanced emulsion adjuvants.Here,because of the varying oleic to linoleic acid ratio,soybean oil,peanut oil,and olive oil were utilised as oil phases in the preparation of aluminium hydrogel-stabilised squalene-in-water emulsions,which were then screened for their stability and immunogenicity.Additionally,the underlying mechanisms of oil phases and emulsion stability were unravelled,which showed that a higher oleic to linoleic acid ratio increased anti-oxidative capabilities but reduced the long-term storage stability owing to the relatively low zeta potential of the prepared droplets.As a result,compared with squalene-in-water ASEs,soybean-in-water ASEs exhibited comparable immune responses and enhanced stability.By optimising the oil phase of the emulsion adjuvants,this work may offer an alternative strategy for safe,stable,and effective emulsion adjuvants.

关键词： pickering emulsion vaccine adjuvant alum-stabilised emulsion oleic to linoleic acid ratio stability

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Molecular dynamics simulations of ovalbumin adsorption at squalene/water interface

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Chinese Journal of Chemical Engineering 2022年第10期50卷 369-378页

作者： Qingxia Xiong Ying Ren yufei xia Guanghui Ma Reiji Noda Wei Ge State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China Division of Environmental Engineering Science Graduate School of Science and TechnologyGunma University1-5-1 Tenjin-choKiryuGunma 376-8515Japan State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

The adsorption of protein molecules to oil/water(O/W)interface is of critical importance for the product design in a wide range of technologies and industries such as biotechnology,food industry and pharmaceutical industry.In this work,with ovalbumin(OVA)as the model protein,the adsorption conformations at the O/W interface and the adsorption stability have been systematically studied via multiple simulation methods,including all-atom molecular dynamic(AAMD)simulations,coarse-grained molecular dynamic(CGMD)simulations and enhanced sampling methods.The computational results of AAMD and CGMD show that the hydrophobic tail of OVA tends to be folded under long time relaxation in aqueous phase,and multiple adsorption conformations can exist at the interface due to heterogeneous interactions raising from oil and water respectively.To further study the adsorption sites of the protein,the adsorption kinetics of OVA at the O/W interface is simulated using metadynamics method combined with CGMD simulations,and the result suggests the existence of multiple adsorption conformations of OVA at interface with the head-on conformation as the most stable one.In all,this work focuses on the adsorption behaviors of OVA at squalene/water interface,and provides a theoretical basis for further functionalization of the proteins in emulsion-based products and engineering.

关键词： Molecular dynamicssimulation Metadynamics Protein adsorption Structural stability Ovalbumin

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Inside-out assembly of viral antigens for the enhanced vaccination

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3144-3157页

作者： Fengqiang Cao Sha Peng Yaling An Kun Xu Tianyi Zheng Lianpan Dai Kenji Ogino To Ngai yufei xia Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190PR China Graduate School of Bio-Applications and Systems Engineering Tokyo University of Agriculture and Technology2-24-16 NakachoKoganeiTokyo184-8588Japan Institute of Global Innovation Research Tokyo University of Agriculture and Technology2-24-16 NakachoKoganei-shiTokyo184-8588Japan CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101PR China Savaid Medical School University of Chinese Academy of SciencesBeijingPR China Key Laboratory of Tropical Translational Medicine of Ministry of Education School of Tropical Medicine and Laboratory MedicineThe First Affiliated HospitalHainan Medical UniversityHainan571199PR China Zhejiang University School of Medicine Hangzhou310058PR China Department of Chemistry The Chinese University of Hong KongShatinN.T.Hong Kong999077PR China University of Chinese Academy of Sciences Beijing100049PR China Innovation Academy for Green Manufacture Chinese Academy of Sciences Beijing100190PR China

Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens,but neglect that pathogens evolve to evade the immune system rather than to provoke it.In the case of enveloped RNA viruses,it is the natural dissemination of nucleocapsid protein(NP,core antigen)and surface antigen that delays NP exposure to immune surveillance.Here,we report a multi-layered aluminum hydroxide-stabilized emulsion(MASE)to dictate the delivery sequence of the antigens.In this manner,the receptor-binding domain(RBD,surface antigen)of the spike protein was trapped inside the nanocavity,while NP was absorbed on the outside of the droplets,enabling the burst release of NP before RBD.Compared with the natural packaging strategy,the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance,which subsequently boosted CD40+DC activations and the engagement of the lymph nodes.In both H1N1 influenza and SARS-CoV-2 vaccines,rMASE significantly increased antigen-specific antibody secretion,memory T cell engagement,and Th1-biased immune response,which diminished viral loads after lethal challenge.By simply reversing the delivery sequence of the surface antigen and core antigen,the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

关键词： vaccination outside evolve

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Aggregating particles on the O/W interface:Tuning Pickering emulsion for the enhanced drug delivery systems

Aggregate

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Aggregate 2022年第2期3卷 3-21页

作者： Yali Ming yufei xia Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190P.R.China University of Chinese Academy of Sciences Beijing 100049P.R.China

The rational design of drug delivery systems has led to enhanced targeting,increased efficiency,and a reduction of side effects in chemotherapies and vaccines.As most biological reactions took place at the interface,particle-stabilized emulsion(Pickering emulsion),may offer major implications for the advanced drug loading,delivery,and controlled release.In fact,it is the aggregating particles that determined the multi-level structure,multi-valent cellular interactions,and the multi-functional physiochemical properties in drug delivery.A deeper understanding on the tunable aggregating patterns and properties,as well as the underlying mechanisms,may pave the way for the efficient drug delivery,and also aided the progressing of“Aggregology”beyond molecules to particles,emulsions,and the biomedical applications.Here,the recent development of Pickering emulsions and their applications in drug delivery were thoroughly reviewed.Strategies to control over the physiochemical properties were illustrated based on particle properties,energy input,and the choices of continuous and dispersion phases.In particular,enough emphasis was attached on the structure-effect relationship between the tunable physiochemical properties and the delivery process,such as the multi-level structure for effective loading,flexibility and permeability for enhanced delivery,and the stimuli-responsiveness for the controlled release.By channeling the unique interfacial properties and the enhanced drug delivery efficiency,this work may shed light on the rational design of Pickering emulsions for the efficient drug delivery.

关键词： drug delivery system multi-valent interactions particle aggregation Pickering emulsion softness

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Spatiotemporal miRNA and transcriptomic network dynamically regulate the developmental and senescence processes of poplar leaves

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Horticulture Research 2023年第10期10卷 162-173页

作者： Kang Du Shenxiu Jiang Hao Chen yufei xia Ruihua Guo Aoyu Ling Ting Liao Wenqi Wu xiangyang Kang State Key Laboratory of Tree Genetics and Breeding National Engineering Research Center of Tree Breeding and Ecological RestorationCollege of Biological Sciences and BiotechnologyBeijing Forestry UniversityBeijing 100083China Institute of Forestry and Pomology Beijing Academy of Agriculture and Forestry SciencesBeijing 100093China Institute of Crop Sciences Chinese Academy of Agricultural SciencesBeijing 100081China

Poplar is an important afforestation and urban greening species.Poplar leaf development occurs in stages,from young to mature and then from mature to senescent;these are accompanied by various phenotypic and physiological changes.However,the associated transcriptional regulatory network is relatively unexplored.We first used principal component analysis to classify poplar leaves at different leaf positions into two stages:developmental maturity(the stage of maximum photosynthetic capacity);and the stage when photosynthetic capacity started to decline and gradually changed to senescence.The two stages were then further subdivided into five intervals by gene expression clustering analysis:young leaves,the period of cell genesis and functional differentiation(L1);young leaves,the period of development and initial formation of photosynthetic capacity(L3-L7);the period of maximum photosynthetic capacity of functional leaves(L9-L13);the period of decreasing photosynthetic capacity of functional leaves(L15-L27);and the period of senescent leaves(L29).Using a weighted co-expression gene network analysis of regulatory genes,high-resolution spatiotemporal transcriptional regulatory networks were constructed to reveal the core regulators that regulate leaf development.Spatiotemporal transcriptome data of poplar leaves revealed dynamic changes in genes and miRNAs during leaf development and identified several core regulators of leaf development,such as GRF5 and MYB5.This in-depth analysis of transcriptional regulation during leaf development provides a theoretical basis for exploring the biological basis of the transcriptional regulation of leaf development and the molecular design of breeding for delaying leaf senescence.

关键词： network leaves breeding

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血运重建治疗对伴慢性多血管病变的急性肠系膜缺血导致的短肠综合征患者肠康复治疗效果的影响

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中华普通外科杂志 2024年第3期39卷 172-182页

作者：夏宇飞齐欣朱旻怡高学金章黎孙羽东王新颖东南大学医学院南京210009 南京大学医学院附属金陵医院全军普通外科研究所南京210002

目的探索伴慢性多血管病变的急性肠系膜缺血(acute mesenteric ischemia,AMI)导致的短肠综合征(short bowel syndrome,SBS)患者在肠康复治疗(intestinal rehabilitation therapy,IRT)前接受血运重建治疗能否优化IRT的疗效。方法回顾性分析2012年1月至2023年10月期间在中国人民解放军东部战区总医院诊断由伴慢性多血管病变的AMI导致SBS并接受IRT的住院患者18例的临床资料。结果在IRT后,血运重建组的四肢骨骼肌指数和握力的增加量显著高于对照组,分别为[(0.28±0.26)kg/m^(2)比(0.02±0.21)kg/m^(2),P=0.033]和[(0.97±0.33)kg比(0.48±0.34)kg,P=0.007]。同样,血运重建组肠内营养(EN)摄入量的增加量显著高于对照组[(572.5±93.6)ml/d比(375.2±176.3)ml/d,P=0.012],并伴随着肠道氮吸收率更高的提升[(25.06±14.06)%比(13.84±4.62)%,P=0.034]和肠道症状评定量表评分更大幅度的降低[(-15.88±3.94)分比(-6.33±5.13)分,P=0.030],且两组EN制剂类型的组成在IRT后也有显著差异(P=0.046)。此外,血运重建组出院时的简明健康量表(SF-36)在躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、精神健康(MH)等五项指标的得分上显著高于对照组(P<0.05)。结论由伴慢性多血管病变的AMI导致SBS的患者接受血运重建治疗不能使其在IRT中获得体重和血液学营养指标上更高的增长,但有利于患者改善肌肉功能、改善EN吸收、提高摆脱肠外营养的机会、缓解胃肠道症状并提高生活质量。

关键词：肠系膜缺血短肠综合征康复研究血运重建

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The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma

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中华医学杂志(英文版) 2024年第11期137卷 2024 May 13页

作者： Zhang Jiaqian Zhang Zhicheng Wu Zhangfan Wang yufei Zhang Zerui xia Limin Department of Gastroenterology Institute of Liver and Gastrointestinal Diseases Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University Xi’an Shaanxi China

In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.

关键词： Hepatocellular carcinoma Invasion Metastasis Lipid metabolism Tumor microenvironment

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铝佐剂颗粒化乳液制备及其免疫效果研究

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过程工程学报 2022年第2期22卷 195-203页

作者：彭沙夏宇飞高晓冬江南大学生物工程学院糖化学与生物技术教育部重点实验室江苏无锡214122 中国科学院过程工程研究所生化工程国家重点实验室北京100190

铝佐剂是我国唯一临床批准使用的疫苗佐剂,但其自身难以引发有效的细胞免疫应答,无法对机体产生综合性的保护,难以满足日益增长的疫苗佐剂需求。因此,如何合理化改造铝佐剂,保证疫苗佐剂的安全及高效诱导免疫反应是亟待解决的问题。本... 详细信息

铝佐剂是我国唯一临床批准使用的疫苗佐剂,但其自身难以引发有效的细胞免疫应答,无法对机体产生综合性的保护,难以满足日益增长的疫苗佐剂需求。因此,如何合理化改造铝佐剂,保证疫苗佐剂的安全及高效诱导免疫反应是亟待解决的问题。本工作通过对商品化铝佐剂制备乳液超声条件的优化,最终研究表明当颗粒浓度为2.0 mg/mL,水相缓冲液选择蒸馏水且pH为7.0时能制备得到稳定的颗粒化乳液(Alum Particulate Emulsion,APE),制备得到的乳液平均粒径为2723.7±435.3 nm,Zeta电位为+40.5±1.5 m V。离心发现此时体系中没有游离的铝佐剂,表明2.0 mg/mL是能稳定乳液的最小颗粒浓度。将乳液与抗原共混,测量抗原的吸附率,结果显示,抗原的吸附率接近100%,共聚焦的结果也验证了乳液对抗原的高吸附特性。当乳液与DC(Dendritic Cells)细胞共孵育,可以观察到乳液的内吞及溶酶体逃逸,而传统的铝佐剂无法实现。ELISpot结果显示,APE组脾细胞中分泌IFN-γ的T细胞数量比铝佐剂组增加300%左右。将铝佐剂通过颗粒化的策略制备得到APE以后,改变了佐剂增强抗原的免疫效果,显著提升了传统铝佐剂的细胞免疫效果。

关键词：疫苗 Pickering乳液铝佐剂细胞免疫溶酶体逃逸

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奥拉帕利在晚期卵巢癌患者维持治疗过程中的作用及对血清肿瘤标志物的影响

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中国妇产科临床杂志 2024年第3期25卷 253-256页

作者：侯萍韩宇飞高霞青岛市市立医院山东青岛266000

目的探讨奥拉帕利在晚期卵巢癌患者维持治疗过程中的作用及对血清肿瘤标志物的影响。方法回顾性分析青岛市市立医院2019年1月至2020年1月接受治疗的晚期卵巢癌68例患者的临床资料,按照治疗方式不同,分为观察组32例、对照组36例。对照组... 详细信息

目的探讨奥拉帕利在晚期卵巢癌患者维持治疗过程中的作用及对血清肿瘤标志物的影响。方法回顾性分析青岛市市立医院2019年1月至2020年1月接受治疗的晚期卵巢癌68例患者的临床资料,按照治疗方式不同,分为观察组32例、对照组36例。对照组采用贝伐珠单抗维持治疗,观察组在对照组基础上,联合奥拉帕利维持治疗,均持续治疗12个周期。比较两组治疗前后糖类抗原(CA)125、CA199、人附睾蛋白4(HE4)、甲胎蛋白(AFP)、T淋巴细胞亚群CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)的变化,并比较预后情况及不良反应发生率。结果观察组CA125、CA199、HE4、AFP均低于对照组,差异均有统计学意义(P<0.05);观察组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均高于对照组,差异均有统计学意义(P<0.05);随访至2022年12月,观察组无进展生存期(PFS)明显长于对照组,差异有统计学意义(P<0.05);观察组血液疾病发生率明显高于对照组,差异有统计学意义(P<0.05)。结论奥拉帕利在晚期卵巢癌患者维持治疗过程中的作用明显,可降低血清肿瘤标志物水平,延长患者PFS,值得临床推广。

关键词：卵巢癌维持治疗奥拉帕利贝伐珠单抗肿瘤标志物无进展生存期

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