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Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood-brain barrier

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药学学报:英文版 2023年第9期13卷 3834-3848页

作者： Thuy Giang Nguyen Cao Ji Hee Kang Su Jin Kang Quan Truong Hoang Han Chang Kang won jong rhee Yu Shrike Zhang Young Tag Ko Min Suk Shim Division of Bioengineering Incheon National UniversityIncheon 22012Republic of Korea College of Pharmacy Gachon UniversityIncheon 21936Republic of Korea Department of Pharmacy Integrated Research Institute of Pharmaceutical Sciencesand BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future PharmacyCollege of Pharmacythe Catholic University of KoreaGyeonggi-do 14662Republic of Korea Research Center for Bio Materials&Process Development Incheon National UniversityIncheon 22012Republic of Korea Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA

Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ability.Herein,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB.To enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into bEVs.TPPconjugated Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation.Moreover,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM cells.An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis.As such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.

关键词： Extracellular vesicle Chlorin e6 Triphenylphosphonium Mitochondria-targeting photosensitizer Photodynamic therapy Blood-brain barrier Glioblastoma Transferrin receptor

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Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

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World Journal of Stem Cells 2019年第10期11卷 803-816页

作者： Jeong Ah Kim Soohyun Hong won jong rhee Research Center for Bioconvergence Analysis Korea Basic Science InstituteCheongju 28119South Korea Department of Bio-Analytical Science University of Science and TechnologyDaejeon 34113South Korea Program in Biomicro System Technology Korea UniversitySeoul 02841South Korea Division of Bioengineering Incheon National UniversityIncheon 22012South Korea Department of Bioengineering and Nano-Bioengineering Incheon National UniversityIncheon 22012South Korea

Although the recent advances in stem cell engineering have gained a great deal of attention due to their high potential in clinical research,the applicability of stem cells for preclinical screening in the drug discovery process is still challenging due to difficulties in controlling the stem cell microenvironment and the limited availability of high-throughput systems.Recently,researchers have been actively developing and evaluating three-dimensional(3D)cell culture-based platforms using microfluidic technologies,such as organ-on-a-chip and organoid-on-a-chip platforms,and they have achieved promising breakthroughs in stem cell engineering.In this review,we start with a comprehensive discussion on the importance of microfluidic 3D cell culture techniques in stem cell research and their technical strategies in the field of drug discovery.In a subsequent section,we discuss microfluidic 3D cell culture techniques for high-throughput analysis for use in stem cell research.In addition,some potential and practical applications of organ-on-a-chip or organoid-on-a-chip platforms using stem cells as drug screening and disease models are highlighted.

关键词： Stem cell Microfluidic technology Three-dimensional cell culture Highthroughput screening

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Isolation of cabbage exosome-like nanovesicles and investigation of their biological activities in human cells

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Bioactive Materials 2021年第12期6卷 4321-4332页

作者： Jae Young You Su Jin Kang won jong rhee Department of Bioengineering and Nano-Bioengineering Incheon National University Incheon22012Republic of Korea Division of Bioengineering Incheon National University Incheon 22012Republic of Korea

There are extensive studies on the applications of extracellular vesicles(EVs)produced in cell culture for therapeutic drug development.However,large quantities of EVs are needed for in vivo applications,which requires high production costs and time.Thus,the development of new EV sources is essential to facilitate their use.Accordingly,plant-derived exosome-like nanovesicles are an emerging alternative for culture-derived EVs.Until now,however,few studies have explored their biological functions and uses.Therefore,it is necessary to elucidate biological activities of plant-derived exosome-like nanovesicles and harness vesicles for biomedical applications.Herein,cabbage and red cabbage were used as nanovesicle sources owing to their easy cultivation.First,an efficient method for nanovesicle isolation from cabbage(Cabex)and red cabbage(Rabex)was developed.Furthermore,isolated nanovesicles were characterized,and their biological functions were assessed.Both Cabex and Rabex promoted mammalian cell proliferation and,interestingly,suppressed inflammation in immune cells and apoptosis in human keratinocytes and fibroblasts.Finally,therapeutic drugs were encapsulated in Cabex or Rabex and successfully delivered to human cells,demonstrating the potential of these vesicles as alternative drug delivery vehicles.Overall,the current results provide strong evidence for the wide application of Cabex and Rabex as novel therapeutic biomaterials.

关键词： Exosome-like nanovesicles Cabbage Inflammation Apoptosis Drug delivery

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Benefit in physical function and quality of life to nonsurgical treatment of varicose veins: Pilot study

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World Journal of Clinical Cases 2024年第3期12卷 517-524页

作者： Gwon-Min Kim BoKun Kim Minwoo Jang jong-Hwan Park Miju Bae Chung won Lee jong won Kim Up Huh Medical Research Institute Pusan National University School of MedicineYangsan 50612South Korea Future Convergence Research Institute Changwon National UniversityChangwon 51140South Korea Department of Convergence Medical Science School of MedicinePusan National UniversityYangsan 50612South Korea Health Convergence Medicine Laboratory Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Thoracic and Cardiovascular Surgery Pusan National University School of MedicineBiomedical Research InstitutePusan National University HospitalBusan 49241South Korea

BACKGROUND Studies on varicose veins have focused its effects on physical function;however,whether nonsurgical treatments alter muscle oxygenation or physical function remains unclear.Moreover,the differences in such functions between individuals with varicose veins and healthy individuals remain unclear.AIM To investigate changes in physical function and the quality of life(QOL)following nonsurgical treatment of patients with varicose veins and determine the changes in their muscle oxygenation during activity.METHODS We enrolled 37 participants(those with varicose veins,n=17;healthy individuals,n=20).We performed the following measurements pre-and post-nonsurgical treatment in the varicose vein patients and healthy individuals:Calf muscle oxygenation during the two-minute step test,open eyes one-leg stance,30 s sit-to-stand test,visual analog scale(VAS)for pain,Pittsburgh sleep quality index,physical activity assessment,and QOL assessment.RESULTS Varicose veins patients and healthy individuals differ in most variables(physical function,sleep quality,and QOL).Varicose veins patients showed significant differences between pre-and post-nonsurgical treatment—results in the 30 sit-to-stand test[14.41(2.45)to 16.35(4.11),P=0.018],two-minute step test[162.29(25.98)to 170.65(23.80),P=0.037],VAS for pain[5.35(1.90)to 3.88(1.73),P=0.004],and QOL[39.34(19.98)to 26.69(17.02),P=0.005];however,no significant difference was observed for muscle oxygenation.CONCLUSION Nonsurgical treatment improved lower extremity function and QOL in varicose veins patients,bringing their condition close to that of healthy individuals.Future studies should include patients with severe varicose veins requiring surgery to confirm our findings.

关键词： Varicose vein Nonsurgical treatment Physical function Quality of life Near infrared spectroscopy

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A review of understanding electrocatalytic reactions in energy conversion and energy storage systems via scanning electrochemical microscopy

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Journal of Energy Chemistry 2024年第4期91卷 155-177页

作者： Jihye Park jong Hwan Lim Jin-Hyuk Kang Jiheon Lim Ho won Jang Hosun Shin Sun Hwa Park Interdisciplinary Materials Measurement Institute Korea Research Institute of Standards and ScienceDaejeon 34113Republic of Korea Department of Material Science and Engineering Seoul National UniversitySeoul 08826Republic of Korea Department of Applied Measurement Science University of Science and TechnologyDaejeon 34113Republic of Korea

To address climate change and promote environmental sustainability,electrochemical energy conversion and storage systems emerge as promising alternative to fossil fuels,catering to the escalating demand for energy.Achieving optimal energy efficiency and cost competitiveness in these systems requires the strategic design of electrocatalysts,coupled with a thorough comprehension of the underlying mechanisms and degradation behavior occurring during the electrocatalysis processes.Scanning electrochemical microscopy(SECM),an analytical technique for studying surface electrochemically,stands out as a powerful tool offering electrochemical insights.It possesses remarkable spatiotemporal resolution,enabling the visualization of the localized electrochemical activity and surface topography.This review compiles crucial research findings and recent breakthroughs in electrocatalytic processes utilizing the SECM methodology,specifically focusing on applications in electrolysis,fuel cells,and metal–oxygen batteries within the realm of energy conversion and storage systems.Commencing with an overview of each energy system,the review introduces the fundamental principles of SECM,and aiming to provide new perspectives and broadening the scope of applied research by describing the major research categories within SECM.

关键词： Scanning electrochemical microscopy Electrocatalyst Electrocatalysis Water splitting Fuel cell Metal-oxygen battery

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Towards high-performance and robust anion exchange membranes(AEMs)for water electrolysis:Super-acid-catalyzed synthesis of AEMs

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Journal of Energy Chemistry 2024年第6期93卷 478-510,I0012页

作者： Geun Woong Ryoo Sun Hwa Park Ki Chang Kwon jong Hun Kang Ho won Jang Min Sang Kwon Department of Materials Science and Engineering Research Institute of Advanced Materials(RIAM)Seoul National UniversitySeoul 08826Republic of Korea Interdisciplinary Materials Measurement Institute Korea Research Institute of Standards and Science(KRISS)Daejeon 34113Republic of Korea Department of Chemical and Biological Engineering and Institute of Chemical ProcessSeoul National UniversitySeoul 08826Republic of Korea Department of Applied Measurement Science University of Science and TechnologyDaejeon 34113Republic of Korea

The increasing demand for hydrogen energy to address environmental issues and achieve carbon neutrality has elevated interest in green hydrogen production,which does not rely on fossil fuels.Among various hydrogen production technologies,anion exchange membrane water electrolyzer(AEMWE)has emerged as a next-generation technology known for its high hydrogen production efficiency and its ability to use non-metal catalysts.However,this technology faces significant challenges,particularly in terms of the membrane durability and low ionic conductivity.To address these challenges,research efforts have focused on developing membranes with a new backbone structure and anion exchange groups to enhance durability and ionic conductivity.Notably,the super-acid-catalyzed condensation(SACC)synthesis method stands out due to its user convenience,the ability to create high molecular weight(MW)polymers,and the use of oxygen-tolerant organic catalysts.Although the synthesis of anion exchange membranes(AEMs)using the SACC method began in 2015,and despite growing interest in this synthesis approach,there remains a scarcity of review papers focusing on AEMs synthesized using the SACC method.The review covers the basics of SACC synthesis,presents various polymers synthesized using this method,and summarizes the development of these polymers,particularly their building blocks including aryl,ketone,and anion exchange groups.We systematically describe the effects of changes in the molecular structure of each polymer component,conducted by various research groups,on the mechanical properties,conductivity,and operational stability of the membrane.This review will provide insights into the development of AEMs with superior performance and operational stability suitable for water electrolysis applications.

关键词： Green hydrogen production Water electrolysis Anion exchange membrane water electrolyzer(AEMWE) Anion exchange membranes(AEMs) Super-acid-catalyzed condensation(SACC)

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SUV39H1-driven NFATc1 methylation is essential for the c-Cbl-mediated degradation of NFATc1 in an osteoclast lineage

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Genes & Diseases 2024年第4期11卷 86-89页

作者： Do-won Jeong Hye-Jin Kim jong-Wan Park Seulbee Lee Hyeryeon Jung Eugene C.Yi Nacksung Kime Yang-Sook Chun Department of Biomedical Sciences Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Physiology Seoul National University College of MedicineSeoul 03080Republic of Korea Ischemic/Hypoxic Disease Institute Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and Technology and College of Medicine Or College of PharmacySeoul National UniversitySeoul 03080Republic of Korea Department of Pharmacology Chonnam National University Medical SchoolGwangju 61469Republic of Korea

Bone undergoes continuous remodeling by tightly-coordinated actions of bone-resorbing osteoclasts and boneforming osteoblasts.1 Recent studies document that the dysregulation of histone methylation profiles is associated with the progression of osteoclastogenesis.However,the specific epigenetic modifiers are incompletely understood.In this study,we demonstrate an inhibitory role of a variegation 3-9 homolog 1(SUV39H1)in osteoclast formation.

关键词： osteoclast remodeling incomplete

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Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi jong-won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang Xiaochao Ma Wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor PAPS.The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been reported.Here,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer.Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)mice.Apc^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory axis.Chondroitin sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal tumorigenesis.In summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling.Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

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Quantitative detection of citrate for early stage diagnosing of prostate cancer:Discriminating normal to cancer in prostate tissues

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Chinese Chemical Letters 2024年第2期35卷 501-506页

作者： Selvaraj Muthusamy Kanagaraj Rajalakshmi Palanisamy Kannan Yun-Sik Nam Dongwei Zhu Yeonggil Seo jong-won Song Dong Nyoung Heo Il Keun Kwon Yuanguo Xu School of Chemistry and Chemical Engineering Jiangsu UniversityZhenjiang 212013China College of Biological Chemical Sciences and EngineeringJiaxing UniversityJiaxing 314001China Advanced Analysis Center Korea Institute of Science & TechnologySeongbuk-guSeoul02792Republic of Korea School of Medicine Jiangsu UniversityZhenjiang 212013China Department of Chemistry Education Daegu UniversityGyeongsan-siGyeongsangbuk-do 38453Republic of Korea Department of Dental Materials School of DentistryKyung Hee UniversitySeoulRepublic of Korea

Prostate cancer(PC)biomarker-citrate detection is clinically important to diagnose PC in early stages.Methylquinolinium iodide(Q)conjugated indole-phenylboronic acid(IB)was designed as a red-emissive QIB probe for the detection of citrate through Lewis acid-base reaction and intramolecular charge transfer(ICT)sensing mechanisms.Boronic acid acts as Lewis acid as well as citrate(Lewis base)recognition unit.The probe reacted with citrate,showing enhanced red emissions.Since the probe has excellent water solubility and great biocompatibility,practical application in biological systems is possible.Citrate was monitored precisely in the mitochondria organelle(in vitro)of living cells with a positive charge on QIB.Also,endogenous(in situ)citrate was detected quantitatively to discriminate non-cancerous and PC mice,observed strong and lower(negligible)emission intensity on non-cancerous and cancerous prostate tissues,respectively.Because,the concentration of citrate is higher in healthy prostate compared with PC prostate.Furthermore,the analysis of sliced prostate tissues can give PC-related information for clinical diagnosis to prevent and treat PC in the initial stages.Therefore,we believe that the present probe is a promising biochemical reagent in diagnosing PC.

关键词： Prostate cancer Biomarker-citrate Boronic acid Lewis acid/base-ICT Red-emissive Mitochondria targeting Prostate tissue

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Hyperreflective photonic crystals created by shearing colloidal dispersions at ultrahigh volume fraction

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Microsystems & Nanoengineering 2024年第1期10卷 161-173页

作者： Minji Kim jong Bin Kim Shin-Hyun Kim Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea

Colloidal crystallization serves as one of the most economic and scalable production methods for photonic crystals.However,insufficient optical performance,nonuniformity and low reproducibility remain challenges for advanced high-value applications.In this study,we optimally formulate a photocurable dispersion of silica particles and apply shear flow to unify the orientation of the colloidal crystals,ensuring high optical performance and uniformity.The silica particles experience strong repulsion at ultrahigh volume fractions of 50%but demonstrate low mobility,leading to polycrystalline structures.Applying shear flow to the dispersions allows the silica particles to rearrange into larger crystalline domains with a unidirectional orientation along the flow.This shear-induced structural change produces absolute reflectivity at the stopband as high as 90%and a high transparency of 90%at off-resonant wavelengths with minimal diffusive scattering.Furthermore,the strong interparticle repulsion ensures a uniform volume fraction of particles throughout the dispersion,reducing deviations in the optical properties.We intricately micropattern the photocurable dispersions using photolithography.Additionally,the photonic films and patterns can be stacked to form multiple layers,displaying mixed structural colors and multiple reflectance peaks without sacrificing reflectivity.These superior photonic materials hold promise for various optical applications,including optical components and anticounterfeiting patches.

关键词： properties. dispersion reflectivity

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