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Piperazine-derived ionizable lipids for enhanced mRNA delivery and cancer immunotherapy

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Nano Research 2024年第8期17卷 7357-7364页

作者： Kai Xu Yujia Xu jin sun Xinwei Cheng Chenxi Lu Wenzhong Chen Bingfang He Tianyue jiang School of Pharmaceutical Sciences Nanjing Tech UniversityNanjing 211816China Department of Nano Formulation Nanjing GeneLeap BiotechnologyNanjing 210061China

Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in *** the clinical success of LNPs as vehicles have been achieved,developing LNPs with enhanced mRNA transmembrane delivery and transfection efficiency in a non-toxic manner is highly desirable and *** this study,we designed a series of new ionizable amino lipids with piperazinederived headgroups and constructed a group of LNPs to promote the transfection activity of mRNA *** them,LNP formulated with lipid 10(L10-LNP)can efficiently package mRNA and perform superior transfection efficiency both in vitro and in vivo,which is mainly attributed to the improved intracellular uptake and effective endosomal *** verified that a single administration of L10-LNP packaging interleukin(IL)-12 mRNA induced tumor shrink and even regression by robust activation of immune effector CD8^(+)T cells and stimulating the generation of IFN-γwithout causing systemic toxicity,which provides a promising platform for clinical cancer immunotherapy.

关键词： ionizable lipid lipid nanoparticle piperazine-derived lipid mRNA therapeutics cancer immunotherapy

Tillage force and disturbance characteristics of different geometric-shaped subsoilers via DEM

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Advances in Manufacturing 2020年第3期8卷 392-404页

作者： jin Tong Xiao-Hu jiang Yue-Ming Wang Yun-Hai Ma Jun-Wei Li Ji-Yu sun Key Laboratory of Bionic Engineering Ministry of EducationJilin UniversityChangchun130022People’s Republic of China College of Biology and Agricultural Engineering Jilin UniversityChangchun130022People’s Republic of China College of Mechanical and Electrical Engineering Shihezi UniversityShihezi832000XinjiangPeople’s Republic of China

With the increased use of agricultural machinery in field operations,soil compaction has become increasingly severe,and the plough pan has become *** is an excellent way to address this ***,it is limited by high energy consumption,which is closely related to tillage *** investigate the effect of the geometric shape of shanks and tines on tillage force and soil disturbance in loam,a layered soil model in accordance with the actual conditions was established and five different subsoilers were simulated via discrete element *** results indicated that the shank impacted soil disturbance and tine impacted tillage *** draft force of curved shank and chisel tine was 8%less than that of the straight shank and sweep *** straight shank and sweep tine produced a larger furrow profile and a higher furrow *** subsoiler with curved shank and chisel tine(C-C)exhibited the lowest specific resistance(12.87,17.52,19.46 and 21.18 kN/m^2 in the 30,35,40 and 45 cm tillage depth,respectively)considering the draft force and soil disturbance ***,these results will facilitate in the selection of a suitable subsoiler and design of new subsoilers with lower energy consumption requirements for loam areas worldwide.

关键词： Subsoiler Discrete element method(DEM) Tillage force Soil disturbance Soil compaction

Intestinal OCTN2-and MCT1-targeted drug delivery to improve oral bioavailability

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 158-172页

作者： Gang Wang Lichun Zhao Qikun jiang Yixin sun Dongyang Zhao Mengchi sun Zhonggui He jin sun Yang Wang Zhuang Yao Medicine Center of Engineering and Technology Guang Xi University of Chinese MedicineNanning 530200China School of Pharmacy Guang Xi University of Chinese MedicineNanning 530200China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs,thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug *** particular,intestinal carnitine/organic cation transporter 2(OCTN2)and mono-carboxylate transporter protein 1(MCT1)possess high transport capacities and complementary ***,we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this ***,basic information of the two transporters is reviewed,including their topological structures,characteristics and functions,expression and key features of their ***,progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed,including improvements in the oral absorption of anti-inflammatory drugs,antiepileptic drugs and anticancer ***,the potential of a dual transporter-targeting strategy is discussed.

关键词： Carnitine/organic cation transporter 2(OCTN2) Monocarboxylate transporter protein 1(MCT1) Transporter-targeting Nanoparticle Prodrug

Point defect concentrations of L12-Al3X(Sc, Zr, Er)

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Rare Metals 2018年第8期37卷 699-706页

作者： Shun-Ping sun Xiao-Ping Li Jie Yang Hong-jin Wang Yong jiang Dan-Qing Yi School of Materials Engineering Jiangsu University of Technology Changzhou 213001 China School of Materials Science and Engineering Central South University Changsha 410083 China

The point defect concentrations of L12-A13X（Sc, Zr, Er） were systematically investigated using the first- principle calculations with thermodynamics approach. The results show that the constitutional point defects of off- stoichiometric L12-A13X（Sc, Zr, Er） prefer to occur in X sublattice, that is X anti-site in X-rich alloy and X vacancy in Al-rich alloy, respectively. And A1 anti-site also has a high density in Al-rich Llz-A13X（Sc, Er）. It is found that the point defect concentrations of stoichiometric L12-A/3X（Sc, Zr） follow in the sequence as： A1 vacancies （VA0 〉 X vacancies （Vx）〉 X anti-sites （XA1）〉 A1 anti- sites （Alx）. The point defect concentration of stoichio- metric A13Er is similar to that of L12-A13X（Sc, Zr）. The result suggests that the A1 vacancy （VA1） is a dominant point defect in L12-A13X（Sc, Zr, Er）. A simple parameter Hvx-HVA1 can be used for a rough estimation of the point defect concentrations in L12-A13X structure. Some rules of point defect concentrations for L12-A13X（Sc, Zr, Er） are also revealed.

关键词： L12-A13X(Sc Zr Er) Point defect First-principle calculation

Phosphorus fixation capacity of CaO-SiO_(2)-Al_(2)O_(3)-MnO-Ce_(2)O_(3) slag based on structural considerations

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Journal of Rare Earths 2023年第3期41卷 446-453,I0005页

作者： Jiali sun Chengjun Liu Maofa jiang Key Laboratory for Ecological Metallurgy of Multimetallic Ores(Ministry of Education) Northeastern UniversityShenyang 110819China School of Metallurgy Northeastern UniversityShenyang 110819China

The phosphorus fixation capacity of some slag systems,such as Ce_(2)O_(3)-containing slag,has hardly been investigated from a thermodynamics view due to the lack of relevant thermodynamic *** the macroscopic properties are primarily determined by the microscopic structure,the correlation between phosphorus fixation capacity and slag structure was explored by spectroscopy(XPS),Raman spectroscopy,and ferromanganese dephosphorization *** results show that the predominant species of P^(5+)are Q_(P)^(0)(PO_(4)^(3-))and Q_(P)^(1)(P_(2)O_(7)^(4-))units in the CaO^(-)SiO_(2)-Al_(2)O_(3)-MnO^(-)Ce_(2)O_(3)-P_(2)O_(5)quenched slag,and the phosphorus fixation capacity increases with the Q_(P)^(1)(P_(2)O_(7)^(4-))unit to Q_(P)^(0)(PO_(4)^(3-))unit transformation(the P-O^(0) bond to P-O^(-)bond transformation)since the electron cloud density between P and O atoms increases and the average radius of P-O bonds ***,CaO or Ce_(2)O_(3) as a network modifier can release the O_(2)-and promote the P-O^(0) bond to P-O^(-)bond(connected to Ca^(2+),/Ce^(3+))transformation in the quenched ***,the phosphorus enrichment phases in the slow cooling slag are confirmed as nCa_(2)SiO_(3)-Ca_(3)P_(2)O_(8)(nC_(2)S-C3P)and CePO_(4) solid solutions by the scan electron microscopy(SEM),transmission electron microscopy(TEM),and energy-dispersive spectrometer(EDS)*** re sults show Ce_(2)O_(3) can depolymerize the polyphosphate structure partially replacing CaO after introducing Ce_(2)O_(3) into CaO based slag because of its strong ability to donate *** above results not only help to understand the dependence of phosphorus fixation capacity on slag composition from a structural view,but also provide the theoretical guidance for optimizing the composition of Ce_(2)O_(3)-containing dephosphorization slag.

关键词： Phosphorus fixation capacity Slag structure X-ray photoelectron spectroscopy Raman spectroscopy Ce_(2)O_(3) CePO_(4)

Recent Advancements in Nanomedicine for‘Cold’Tumor Immunotherapy

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Nano-Micro Letters 2021年第6期13卷 143-189页

作者： Qinjun Chen Tao sun Chen jiang Key Laboratory of Smart Drug Delivery(Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of Pharmaceuticsand School of PharmacyResearch Center on Aging and MedicineFudan UniversityShanghai 201203People’s Republic of China

Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI *** the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these *** has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic *** review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.

关键词： Tumor immune microenvironment Cold tumor Nanotechnology Immunosuppressive Combination therapy

Influence of Reinforcement Mesh Configuration for Improvement of Concrete Durability

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China Ocean Engineering 2017年第5期31卷 631-638页

作者： PAN Chong-gen jin Wei-liang MAO jiang-hong ZHANG Hua sun Li-hao WEI Dong Ningbo Institute of Technology Zhejiang University Institute of Structural Engineering Zhejiang University

Steel bar in concrete structures under harsh environmental conditions, such as chlorine corrosion, seriously affects its service life. Bidirectional electromigration rehabilitation （BIEM） is a new method of repair technology for reinforced concrete structures in such chloride corrosion environments. By applying the BIEM, chloride ions can be removed from the concrete and the migrating corrosion inhibit can be moved to the steel surface. In conventional engineering, the concrete structure is often configured with a multi-layer steel mesh. However, the effect of the BIEM in such structures has not yet been investigated. In this paper, the relevant simulation test is carried out to study the migration law of chloride ions and the migrating corrosion inhibitor in a concrete specimen with complex steel mesh under different energizing modes. The results show that the efficiency of the BIEM increases 50% in both the monolayer steel mesh and the double-layer steel mesh. By using the single-sided BIEM, 87% of the chloride ions are removed from the steel surface. The different step modes can affect the chloride ion removal. The chloride ions within the range of the reinforcement protective cover are easier to be removed than those in the concrete between the two layers of steel mesh. However, the amount of migrating corrosion inhibitor is larger in the latter circumstances.

关键词： bidirectional electromigration rehabilitation steel mesh chloride salt inhibitor

Block Copolymer Colloidal Particles with Unique Structures through Three-dimensional Confined Assembly and Disassembly

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Chinese Journal of Polymer Science 2019年第8期37卷 744-759页

作者： jiang-Ping Xu jin-Tao Zhu Key Laboratory of Material Chemistry for Energy Conversion and Storage Ministry of Education Hubei Key Laboratory of Materials Chemistry and Service Failure School of Chemistry and Chemical Engineering Huazhong University of Science and Technology (HUST) Wuhan 430074 China State Key Laboratory of Materials Processing and Mold Technology HUST Wuhan 430074 China

Structured block copolymer(BCP) particles have gained increasing attention due to their potential applications in separation,catalysis, controlled release, and other fields. Three-dimensional(3D) confined assembly has been proved as a facile yet robust approach for generating BCP particles with controllable shapes and internal structures. In this feature article, we summarized the preparation of structured polymeric particles through 3D confined self-assembly of BCPs. The effects of interfacial interactions, degree of confinement,and additives on the shape and internal structure of BCP microparticles were comprehensively discussed. In addition, we highlighted the recent progress in using disassembly as a route to synthesize colloidal particles with unique structures. Two strategies were introduced in this part:(a) disassembling the discrete domains resulted in mesoporous microparticles;(b) disassembling the continuous domains led to the dissociation of microparticles into micelle-like nano-objects. The applications of the structured colloidal particles in photonic crystals,controlled release, and directed growth of inorganic materials were also presented. Finally, we discussed the current challenges and future opportunities in this promising area.

关键词： Block copolymers Self-assembly Confinement Polymer particles Nano-objects

Input-Output Production Structure and Non-Linear Production Possibility Frontier

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Journal of Systems Science & Complexity 2021年第2期34卷 706-723页

作者： jiang Weimin FAN jin TIAN Kailan College of Economics and Management Nanjing Forestry UniversityNanjing 210037China

Input-output(Leontief)production function is widely used in economic *** diminishing marginal rate of return is a very well accepted economic *** production function normally results in a linear production possibility frontier(PPF)due to its linear feature,whereas diminishing marginal rate of return implies a non-linear *** this paper,the authors aim to fix this problem by considering multiple primary inputs in a simplified two-sector *** authors find that it is possible to curve a non-linear PPF by using Leontief production function when the authors add heterogeneous primary *** authors also discuss the PPF using non-linear production ***,the authors propose that three commonly used economic presumptions cannot hold in the same *** presumptions are"single primary input","fixed-proportion inputs"and"law of diminishing marginal returns".

关键词： Input output analysis marginal rate of transformation non-substitution theorem production possibility frontier