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The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo wang Tian Liu yuetong Huang Chaoying Du Danping wang Xiyan wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

High-performance wood-based thermoelectric sponges for thermal energy harvesting and smart buildings

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Nano Research 2024年第6期17卷 5349-5357页

作者： Ding Zhang Qi Li Yanjie Fang Peijia Bai Lili Liu Jiaqi Guo Guangfa wang yuetong Zhou Rujun Ma School of Materials Science and Engineering National Institute for Advanced MaterialsSmart Sensing Interdisciplinary Science CenterNankai UniversityTianjin 300350China

The development of renewable woods for power generation can help improve the energy efficiency of buildings,and promote the concept design and implementation of“smart buildings”.Here,with specific chemical treatment and hydrothermal synthesis,we demonstrated the practical value of natural wood for thermoelectric power generation in smart buildings.The prepared wood-based thermoelectric sponges show high Seebeck coefficients of 320.5 and 436.6μV/K in the vertical and parallel directions of the longitudinal channel of wood.After 500 cycles of the compressive strain at 20%,the corresponding Seebeck coefficients increase up to 413.4 and 502.1μV/K,respectively,which is attributed to the improved contact and connection between tellurium thermoelectric nanowires.The Seebeck coefficients are much larger than those of most reported inorganic thermoelectric materials.Meanwhile,the thermoelectric sponges maintain excellent thermoelectric and mechanical stability.We further modeled the application value of wood-based thermoelectric sponges in smart buildings for power generation.Relatively high thermoelectric electricity can be obtained,such as in Beijing with over 1.5 million kWh every year,demonstrating the great potential in thermal energy harvest and energy supply.

关键词： wood thermoelectric effect thermal energy harvesting smart buildings energy supply

Microfluidic Generation of Multicomponent Soft Biomaterials

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Engineering 2022年第6期8卷 128-143页

作者： yuetong wang Luoran Shang Yuanjin Zhao Lingyun Sun Department of Rheumatology and Immunology Nanjing Drum Tower Hospital&School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNanjing 210046China Shanghai Xuhui Central Hospital&Zhongshan-Xuhui Hospital&Shanghai Key Laboratory of Medical Epigenetics&International Co-Laboratory of Medical Epigenetics and Metabolism of Ministry of Science and Technology Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China

Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.

关键词： Soft biomaterial Microfluidics Multicomponent Microparticle Microfiber

A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice

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National Science Review 2023年第12期10卷 98-110页

作者： Guohao wang Shuhan Jin Jiaqi Liu Xu Li Peng Dai yuetong wang Steven X.Hou The Basic Research Laboratory Center for Cancer ResearchNational Cancer Institute at FrederickNational Institutes of Health Department of Cell and Developmental Biology at the School of Life Sciences State Key Laboratory of Genetic EngineeringInstitute of Metabolism and Integrative BiologyHuman Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University

Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases(NDs).However, the mechanisms that link the central nervous system(CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate(ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γ δ T cells in meninges. The activated γ δ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1astrocyte-C3-neuronal C3a R neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.

关键词： neurodegenerative diseases disease-associated microglia γδT cells reactive astrocyte IFN- γ C3

DSEMR: A database for special environment microorganisms resource and associating them with synthetic biological parts

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Synthetic and Systems Biotechnology 2023年第4期8卷 647-653页

作者： Yuzhou wang Jinyi Qian Fang Yan yuetong wang Tianqiong Shi Zhidong Zhang Chao Ye He Huang School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNanjing210023China Institute of Microbiology Xinjiang Academy of Agricultural SciencesUrumqi830091China

Special environmental microorganisms are considered to be of great industrial application value because of their special genotypes,physiological functions and metabolites.The research and development of special environmental microorganisms will certainly bring about some innovations in biotechnology processes and change the face of bioengineering.The Special Environmental Microbial Database(DSEMR)is a comprehensive database that provides information on special environmental microbial resources and correlates them with synthetic biological parts.DSEMR aggregates information on specific environmental microbial genomes,physiological properties,culture media,biological parts,and metabolic pathways,and provides online tool analysis data,including 5268 strains from 620 genera,31 media,and 42,126 biological parts.In short,DSEMR will become an important resource for the study of microorganisms in special environments and actively promote the development of synthetic biology.

关键词： Special environment microorganism Physiological functions Synthetic biological parts

Alkaloid Dimers Isolated from Thalictrum baicalense Have Antitumor Activities

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Chinese Journal of Chemistry 2022年第15期40卷 1831-1841页

作者： Jingjing Xue yuetong wang Fangshen Liu Hangao Yang Bin Lin Zhanlin Li Yongkui Jing Dahong Li Huiming Hua Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyangLiaoning 110016China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China

Comprehensive Summary A pair of heterodimeric isoquinoline alkaloid enantiomers,(+)thaliberberine A,five new thalifaberine-type aporphine-benzylisoquinoline(ABl)alkaloids,thalicultratines M-Q,and thirteen known analogues were isolated from the roots of Thalictrum baicalense Turcz.ex Ledeb.The structures were determined by extensive spectroscopic methods and ECD calculations.Thaliberberine A featuring a novel carbon skeleton coupled by two different classes of isoquinoline alkaloids,protoberberine and phthalidoisoquinoline,represents the first natural product with the berberine skeleton substituted at C-6.Plausible biosynthetic routes of 1 are proposed.

关键词： Thalictrum baicalense Heterodimeric isoquinoline alkaloid Thalifaberine-type ABI alkaloids Antitumor activity Apoptosis

Blockade of Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-κB-CCL5 pathway

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Life Metabolism 2023年第5期2卷 25-37页

作者： Na wang Tiange Yao Chenfei Luo Ling Sun yuetong wang Steven X.Hou Department of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic EngineeringInstitute of Metabolism and Integrative BiologyHuman Phenome InstituteFudan UniversityShanghai 200438China

Tumor immunotherapy has achieved breakthroughs in a variety of tumors. However, the systemic absence of T cells in tumors and immunosuppressive tumor microenvironment so far limits the efficacy of immunotherapy to a small population of patients. Therefore, novel agents to increase T-cell tumor infiltration are urgently needed in the clinic. We recently found that inhibition of the ADP-ribosylation factor 1 (Arf1)-mediated lipid metabolism not only kills cancer stem cells (CSCs) but also elicits an anti-tumor immune response. In this study, we revealed a mechanism that targeting Arf1 promotes the infiltration of cytotoxic T lymphocytes (CTLs) into tumors through the C-C chemokine ligand 5 (CCL5)- C-C chemokine receptor type 5 (CCR5) pathway. We found that blockage of Arf1 induces the production of the unsaturated fatty acid (PE 18:1) that binds and sequestrates peroxisome proliferator- activated receptor-γ (PPARγ) from the PPARγ-nuclear factor-κB (NF-κB) cytoplasmic complex. The released NF-κB was then phospho-rylated and translocated into the nucleus to regulate the transcription of chemokine CCL5. CCL5 promoted infiltration of CTLs for tumor regression. Furthermore, the combination of the Arf1 inhibitor and programmed cell death protein 1 (PD-1) blockade induced an even stronger anti-tumor immunity. Therefore, targeting Arf1 represents a novel anti-tumor immune approach by provoking T-cell tumor infiltration and may provide a new strategy for tumor immunotherapy.

关键词： immune checkpoint blockade cancer stem cells cytotoxic T cells PPARγ CCL5-CCR5 pathway Arf1

Smart Microneedles for Therapy and Diagnosis

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Research 2020年第1期2020卷 1295-1320页

作者： Xiaoxuan Zhang yuetong wang Junjie Chi Yuanjin Zhao State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of Rheumatology and Immunology Institute of Translational MedicineThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China

Microneedles represent a cutting-edge and idea-inspiring technology in biomedical engineering,which have attracted increasing attention of scientific researchers and medical staffs.Over the past decades,numerous great achievements have been made.The fabrication process of microneedles has been simplified and becomes more precise,easy-to-operate,and reusable.Besides,microneedles with various features have been developed and the microneedle materials have greatly expanded.In recent years,efforts have been focused on generating smart microneedles by endowing them with intriguing functions such as adhesion ability,responsiveness,and controllable drug release.Such improvements enable the microneedles to take an important step in practical applications including household drug delivery devices,wearable biosensors,biomedical assays,cell culture,and microfluidic chip analysis.In this review,the fabrication strategies,distinctive properties,and typical applications of the smart microneedles are discussed.Recent accomplishments,remaining challenges,and future prospects are also presented.

关键词： smart accomplishment enable

Boston Ivy-Inspired Disc-Like Adhesive Microparticles for Drug Delivery

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Research 2021年第1期2021卷 1604-1614页

作者： Lijun Cai Guopu Chen yuetong wang Cheng Zhao Luoran Shang Yuanjin Zhao State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Zhongshan-Xuhui Hospital The Shanghai Key Laboratory of Medical EpigeneticsThe International Co-Laboratory of Medical Epigenetics and MetabolismMinistry of Science and Technologyand Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Department of Rheumatology Immunology Institute of Translational MedicineThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China

Microparticles with strong adherence are expected as efficient drug delivery vehicles.Herein,we presented an ingenious hydrogel microparticle recapitulating the adhesion mechanism of Boston ivy tendrils adhesive discs(AD)for durable drug delivery.The particles were achieved by replicating a silica colloidal crystal aggregates assembled in a droplet template after rapid solvent extraction.Due to their unique shape,the nanostructure,and the sticky hydrogel component,such novel microparticles exhibited prominent adhesive property to the wet tissue environment.It was demonstrated that the bioinspired microcarriers loading with dexamethasone had a good therapeutic effect for ulcerative colitis due to the strong adhesion ability for prolonging the maintenance of drug availability.These virtues make the biomimetic microparticles potentially ideal for many practical clinical applications,such as drug delivery,bioimaging,and biodiagnostics.

关键词： environment Boston template