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Unlocking the Therapeutic Applicability of LNP-mRNA:Chemistry,Formulation,and Clinical Strategies

Research 2025年第1期7卷 450-476页

作者： Xiaonan Huang Yishan Ma Guanghui Ma Yufei Xia Sinovac Biotech Ltd. BeijingPR China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijingPR China School of Chemical Engineering University of Chinese Academy of SciencesBeijingPR China

Messenger RNA(mRNA)has emerged as an innovative therapeutic modality,offering promising avenues for the prevention and treatment of a variety of *** tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019(COVID-19)evidences the unlimited medical and therapeutic potential of mRNA *** challenges related to mRNA stability,immunogenicity,and precision targeting has been made possible by recent advancements in lipid nanoparticles(LNPs).This review summarizes state-of-the-art LNP-mRNA-based therapeutics,including their structure,material compositions,design guidelines,and screening ***,we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions,cancer immunotherapy,gene editing,and rare-disease *** attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of *** explore concerns in the aspects of inadequate extrahepatic targeting efficacy,elevated doses,safety concerns,and challenges of large-scale production *** discussion may offer insights and perspectives on near-and long-term clinical development prospects for LNP-mRNA therapeutics.

关键词： therapeutic applicability lipid nanoparticles lnps clinical strategies messenger rna mrna

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Redox-Active Dihydrophenazine-Based Macrocycle:Synthesis,Conformation-Adaptive Behavior and Host-Guest Complexation with Tetracyanoquinodimethane

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Chinese Journal of Chemistry 2024年第16期42卷 1895-1900页

作者： Qiong-Yan Hong Bin Huang Meng-Xiang Wu Lin Xu Xiao-Li Zhao Xueliang Shi Hai-Bo Yang Shanghai Key Laboratory of Green Chemistry and Chemical Processes State Key Laboratory of Petroleum Molecular&Process EngineeringSchool of Chemistry and Molecular EngineeringEast China Normal University3663 N.Zhongshan RoadShanghai 200062China

A novel macrocycle based on conformation-adaptive and electron-rich dihydrophenazine was designed and *** the one hand,the macrocycle showed host-guest interactions with tetracyanoquinodimethane(TCNQ)driving by charge transfer interaction between ***,host-guest complexation was accompanied by fluorescence quenching and conformational change of the *** the other hand,the oxidation of the macrocycle resulted in its diradical cation analogue and induced the release of the guest molecule TCNQ,thereby accomplishing reversible binding ***,this work wellillustrates the chemical and structural versatility of dihydrophenazine in the synthesis of macrocycles and their host-guest chemistry.

关键词： Dihydrophenazine Macrocycle Conformational adaptation Redox-active Host-guest interactions Charge transfer interaction Organic radical Supramolecular chemistry

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Nucleic acid therapy for metabolic-related diseases

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Chinese Chemical Letters 2025年第3期36卷 83-94页

作者： Jing Guo Zhi-Guo Lu Rui-Chen Zhao Bao-Ku Li Xin Zhang College of Pharmaceutical Sciences Hebei UniversityBaoding 071002China 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 Key Laboratory of Biopharmaceutical Preparation and Delivery Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China

Metabolism is a general term for a series of ordered chemical reactions in an organism used to maintain life,mainly divided into anabolic and catabolic *** acid therapy can not only precisely up-regulate and down-regulate the expression of target genes but also correct mutated disease-causing genes,which demonstrates irreplaceable and outstanding advantages in the treatment of metabolismrelated diseases and has been applied to the clinical treatment of metabolism-related *** this review,we introduce the structures of several major nucleic acid drugs and the mechanism of nucleic acid ***,we describe the mechanisms of various biomolecular and tissue metabolisms and the etiology of metabolic disorders,classified according to metabolic *** analyze the signal pathways and potential targets affecting the metabolism of each substrate and describe the nucleic acid drugs applied to these targets and their delivery *** review aims to provide new ideas and targets for treating these diseases by investigating the role played by metabolism in developing diseases and providing guidance for the selection and design of nucleic acid drugs.

关键词： Metabolism-related diseases Signal pathways Target genes Nucleic acid therapy Delivery technologies

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Celebrating 40 Years of Chemical Research in Chinese Universities

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Chemical Research in Chinese Universities 2024年第4期40卷 561-563页

作者： YU Jihong WANG Dan State Key Laboratory of Inorganic Synthesis and Preparative Chemistry International Center of Future ScienceJilin UniversityChangchun 130012P.R.China State Key Laboratory of Biochemical Engineering Key Laboratory of Biopharmaceutical Preparation and DeliveryInstitute of Process EngineeringChinese Academy of SciencesBeijing 100190P.R.China

Chemical Research in Chinese Universities was founded in 1984 as a comprehensive academic journal in the field of *** has since become a repository of intellectual treasures,documenting the evolving landscape of chemical science within the academic *** the past 40 years,Chemical Research in Chinese Universities has witnessed the rapid development of chemical research in universities.

关键词： chemistry. landscape journal

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A purely green approach to low-cost mass production of zeolitic imidazolate frameworks

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green Energy & Environment 2023年第3期8卷 775-784页

作者： Hai Li Wan Chen Bei Liu Mingke Yang Zixuan Huang Changyu Sun Chun Deng Dapeng Cao Guangjin Chen State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing102249China State Key Lab of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing100029China Key Laboratory of Green Process and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190China

Although zeolitic imidazolate frameworks(ZIFs)have bright prospects in wide fields like gas storage/separation,catalysis and medicine,etc.,their large-scale applications are bottlenecked by the absence of their low-cost commercial production ***,we report an uncon ventional method suitable for environmentally friendly and low-cost mass-production of *** this method,taking the synthesis of ZIF-8 as an example,ZnO was used instead of Zn(NO_(3))_(2) in traditional solvent synthesis methods and CO_(2) was introduced to dissolve ZnO in aqueous solution of 2-methylimidazole(HMeim)and form water soluble salt([ZnMeim]^(+)[MeimCOO]^(-))at room ***,by removing CO_(2) through heating or vacuuming,Meim-ions are produced and instantaneously assemble with[ZnMeim]^(+)s to generate ZIF-8 without any by *** to the absence of strong acid anions(such as NO^(-)_(3) and Cl^(-) et al.)in solution,the washing of filter cake required in the conventional approaches could be omitted and the filtrate containing only water and HMeim could be reused *** method is really green as no waste gas or liquid generates because CO_(2) and water could be recycled *** overcomes almost all bottlenecks occurred in commercial production of ZIF-8 when using traditional methods.A pilot plant was established for mass-production of ZIF-8 and hundreds kilograms of ZIF-8 was produced,which indicates that the new method is not only environmentally friendly but also low cost and commercial *** is expected that the new method would open an avenue for commercial applications of ZIFs.

关键词： Zeolitic imidazolate frameworks Mass production Metal oxide Carbon dioxide Environmentally friendly

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A STIR nucleic acid drug delivery system for stirring phenotypic switch of microglia in Parkinson’s disease treatments

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Nano Research 2023年第5期16卷 7216-7226页

作者： Yanyue Wu Wenli Wang Xinyu Qiu Zhiguo Lu Weihong Ji Jie Shen Huan Peng Ruichen Zhao Jingwen Wang Tianlu Zhang Jun Yang Xin Zhang 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

Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate *** studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory ***,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease *** the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease *** STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted *** results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s ***,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.

关键词： sequential targeting inflammation regulation phenotypic switch of microglia targeted drug delivery siRNA-based gene therapy responsive release Parkinson’s disease

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Enzymatically prepared alginate oligosaccharides improve broiler chicken growth performance by modulating the gut microbiota and growth hormone signals

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Journal of Animal Science and Biotechnology 2023年第5期14卷 2107-2127页

作者： A La Teng Zhu La Yuqing Feng Die Hu Yimei Feng Xiaolu Jin Dan Liu Yuming Guo Gong Cheng Yongfei Hu State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China

Background Alginate oligosaccharide(AOS)holds great potential as a novel feed supplement in farm ***,the effects of AOS on chicken health and the underlying mechanisms are not fully *** study aimed to optimize the enzymatic preparation of AOS by using bacterial alginate lyases expressed in yeast,investigate the effects of the prepared AOS on the growth performance and gut health of broiler chickens,and reveal the underlying *** Five alginate lyases from bacteria were cloned into Pichia pastoris GS115 and the alginate lyase PDE9 was expressed at relatively high yield,activity and stability in *** trials were carried out using 3201-day-old male Arbor Acres broilers(four groups;8 replicates/group×10 chicks/replicate)receiving either a basal diet or the same diet supplemented with 100,200 and 400 mg/kg PDE9-prepared AOS for 42 *** results showed that dietary supplementation of 200 mg/kg AOS displayed the highest activity in promoting the birds’ADG and ADFI(P<0.05).AOS ameliorated the intestinal morphology,absorption function and barrier function,as indicated by the enhanced(P<0.05)intestinal villus height,maltase activity,and the expression of PEPT,SGLT1,ZNT1,and *** also increased serum insulin-like growth factor-1,ghrelin(P<0.05),and growth hormone(P<0.1).Moreover,the concentrations of acetate,isobutyrate,isovalerate,valerate,and total SCFAs in cecum of birds fed AOS were significantly higher than the control birds(P<0.05).Metagenomic analysis indicated that AOS modulated the chicken gut microbiota structure,function,and microbial interactions and promoted the growth of SCFAs-producing bacteria,for example,Dorea sp.002160985;SCFAs,especially acetate,were found positively correlated with the chicken growth performance and growth-related hormone signals(P<0.05).We further verified that AOS can be utilized by Dorea *** grow and to produce acetate in *** We demonstrated that the enzymatically

关键词： Acetate Alginate lyases Alginate oligosaccharides Dorea sp. Gut microbiota

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Microfluidic reactors for paired electrosynthesis:Fundamentals,applications and future prospects

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green Energy & Environment 2025年第3期10卷 471-499页

作者： Hao Xue Zhi-Hao Zhao Menglei Yuan Guangjin Zhang Queen Mary University of London Engineering School Northwestern Polytechnical University710129Xi'anChina State Key Laboratory of Solidification Processing and School of Materials Science and Engineering Northwestern Polytechnical University710072Xi'anChina CAS Key Laboratory of Green Process Engineering Institute of Process EngineeringChinese Academy of Sciences100190BeijingChina Center of Materials Science and Optoelectronics Engineering University of ChineseAcademy of Sciences100049BeijingChina

Paired electrosynthesis has received considerable attention as a consequence of simultaneously synthesizing target products at both cathode and anode,whereas the related synthetic efficiency in batch reactors is still undesirable under certain ***,laminar microfluidic reactor offers prospective options that possess controllable flow characteristics such as enhanced mass transport,precise laminar flow control and the ability to expand production scale *** this comprehensive review,the underlying fundamentals of the paired electrosynthesis are initially summarized,followed by categorizing the paired electrosynthesis including parallel paired electrosynthesis,divergent paired electrosynthesis,convergent paired electrosynthesis,sequential paired electrosynthesis and linear paired ***,a holistic overview of microfluidic reactor equipment,integral fundamentals and research methodology as well as channel extension and scale-up strategies is *** established fundamentals and evaluated metrics further inspired the applications of microfluidic reactors in paired *** work stimulated the overwhelming investigation of mechanism discovery,material screening strategies,and device assemblies.

关键词： Paired electrosynthesis Microfluidic reactor Laminar flow Scaling-up strategy

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

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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 ***,extensive research on the internal delivery mechanisms of these emulsions,especially the complex intercellular interactions of deformable Pickering emulsions,has been surprisingly *** gap in knowledge holds significant potential for enhancing vaccine *** 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 *** transport of Pickering emulsions in skeletal muscle tissue is specifically investigated as a case *** factors impacting the transport process are explored,including local cellular tissue environmental factors and the properties of the Pickering emulsion *** simulation results primarily demonstrate that an increase in radial repulsive interaction between emulsion particles can decrease the transport ***,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 *** study sheds light on the nuanced interplay between engineered and biological systems influencing the transport dynamics of Pickering *** insights hold valuable potential for optimizing transport processes in practical biomedical applications such as drug ***,the desired transport efficiency varies depending on the specific *** 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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Microscale spherical TiO_(2)powder prepared by hydrolysis of TiCl_(4)solution:Synthesis and kinetics

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Particuology 2024年第1期84卷 60-71页

作者： Peiyi Yan Ying Zhang Shili Zheng School of Rare Earths University of Science and Technology of ChinaHefei230026China Ganjiang Innovation Academy Chinese Academy of SciencesGanzhou341119China Key Laboratory of Green Process and Engineering National Engineering Research Center of Green Recycling for Strategic Metal ResourcesInstitute of Process EngineeringChinese Academy of SciencesBeijing100190China State Key Laboratory of Vanadium and Titanium Resources Comprehensive Utilization Panzhihua617000China

Hydrolysis of TiCl_(4)solution is capable of preparing microscale TiO_(2)*** research studied the synthesis of microscale spherical TiO_(2)powders and the hydrolysis *** effects of the flow field generated by different agitators and baffles in the crystallizer,the initial free acid concentration,the initial equivalent TiO_(2)concentration,and the temperature on the hydrolysis progress and powder morphology were systematically *** results show that the flow field in a crystallizer can significantly affect the morphology and particle size of the powders,and the axial flow can improve the sphericity of the *** increased free HCl and equivalent TiO_(2)concentrations in the pregnant solution inhibit the forward hydrolysis reaction,prolong the time to reach equilibrium,and reduce the *** appropriate temperature matching the compositions of the pregnant solution is crucial for the powder morphology and *** with sizes ranging from around 5 um-40μm can be tuned under controlled flow field,solution compositions,and temperature *** addition,the Cheng and Wunderlich modified Avrami equation was used for the crystallization kinetic *** effects of the free HCl concentration,equivalent TiO_(2)concentration,and hydrolysis temperature are reflected in the reaction rate constant and active nuclei reduction *** the free HCl and equivalent TiO_(2)concentrations will reduce the reaction rate constant and accelerate the deactivation of the active nuclei,thus increasing the final powder size,while increasing the temperature will lead to the opposite results.

关键词： TiCl_(4) Hydrolysis Microscale TiO_(2) Spherical Kinetics

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