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RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Bone Research 2024年第2期12卷 407-420页

作者： Minhee kim jin Hee Park Miyeon Go Nawon Lee Jeongin Seo Hana Lee Doyong kim Hyunil Ha Taesoo kim Myeong Seon Jeong Suree kim Taesoo kim Han Sung kim Dongmin Kang Hyunbo Shim Soo Young Lee Department of Life Science Ewha Womans UniversitySeoul 03760South Korea The Research Center for Cellular Homeostasis Ewha Womans UniversitySeoul 03760South Korea Department of Biomedical Engineering Yonsei UniversityWonju 26493South Korea KM Convergence Research Division Korea Institute of Oriental MedicineDaejeon 34054South Korea Chuncheon Center Korea Basic Science InstituteChuncheon 24341South Korea Fluorescence Core Imaging Center and Bioimaging Data Curation Center Ewha Womans UniversitySeoul 03760South Korea Multitasking Macrophage Research Center Ewha Womans UniversitySeoul 03760South Korea

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled ***,the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely ***,we show with GeneChip analysis that RUN and FYVE domain-containing protein 4(RUFY4)is strongly upregulated during *** lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in ***,deleting Rufy4 did not affect osteoclast differentiation,but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes,their trafficking to the membrane,and their secretion of cathepsin K into the extracellular ***,RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary ***,Rufy4-deficient mice were highly protected from lipopolysaccharide-and ovariectomy-induced bone ***,RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

关键词： osteoclast inhibited traffic

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se jin Im Tae jin kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki kim Bum Jun kim Seungyon Koh Hyo jin Cho Xuelian jin Byung Gon kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Electrochemically Deposited CZTSSe Thin Films for Monolithic Perovskite Tandem Solar Cells with Efficiencies Over 17%

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Energy & Environmental Materials 2024年第1期7卷 147-152页

作者： Sun Kyung Hwang Ik Jae Park Se Won Seo Jae Hyun Park So Jeong Park jin Young kim Department of Materials Science and Engineering Seoul National UniversitySeoul 08826Korea Department of Applied Physics Sookmyung Women's UniversitySeoul 04310Korea Research Institute of Advanced Materials and Systems Sookmyung Women's UniversitySeoul 04310Korea Research Institute of Advanced Materials(RIAM) Seoul National UniversitySeoul 08826Korea

In spite of the high potential economic feasibility of the tandem solar cells consisting of the halide perovskite and the kesterite Cu2ZnSn(S,Se)4(CZTSSe),they have rarely been demonstrated due to the difficulty in implementing solution-processed perovskite top cell on the rough surface of the bottom ***,we firstly demonstrate an efficient monolithic two-terminal perovskite/CZTSSe tandem solar cell by significantly reducing the surface roughness of the electrochemically deposited CZTSSe bottom *** surface roughness(R_(rms))of the CZTSSe thin film could be reduced from 424 to 86 nm by using the potentiostatic mode rather than using the conventional galvanostatic mode,which can be further reduced to 22 nm after the subsequent ion-milling *** perovskite top cell with a bandgap of 1.65 eV could be prepared using a solution process on the flattened CZTSSe bottom cell,resulting in the efficient perovskite/CZTSSe tandem solar *** the current matching between two subcells involving the thickness control of the perovskite layer,the best performing tandem device exhibited a high conversion efficiency of 17.5%without the hysteresis effect.

关键词： CZTSSe monolithic tandem solar cells perovskite solution process surface roughness control

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Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon kim jin Woo Lee Min-Kyoo Shin Sang Hee Shim Natural Products Research Institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea College of Pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

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A study on dynamic group signature scheme with threshold traceability for blockchain

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High-Confidence Computing 2024年第2期4卷 73-81页

作者： Hyo-jin Song Teahoon kim Yong-Woon Hwang Daehee Seo Im-Yeong Lee Department of Software Convergence Soonchunhyang UniversityAsan 31538Republic of Korea Faculty of Artificial Intelligence and Data Engineering Sangmyung UniversitySeoul 03016Republic of Korea Department of Computer Software Engineering Soonchunhyang UniversityAsan 31538Republic of Korea

Blockchain technology provides transparency and reliability by sharing transactions and maintaining the same information through consensus among all ***,single-signature applications in transactions can lead to user identification issues due to the reuse of public *** address this issue,group signatures can be used,where the same group public key is used to verify signatures from group members to provide anonymity to ***,in dynamic groups where membership may change,an attack can occur where a user who has left the group can disguise themselves as a group member by leaking a partial *** problem cannot be traced back to the partial key *** this paper,we propose assigning different partial keys to group members to trace partial key leakers and partially alleviate the damage caused by partial key *** schemes have shown that arbitrary tracing issues occurred when a single administrator had exclusive key generation and tracing *** paper proposes a group signature scheme that solves the synchronization problem by involving a threshold number of TMs while preventing arbitrary tracing by distributing authority among multiple TMs.

关键词： Blockchain Group signature Privacy Anonymity Traceability

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Origami multi-layer space shield for cylindrical space structure

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Chinese Journal of Aeronautics 2024年第10期37卷 294-312页

作者： Ji-Hun CHA Ji-Sub NOH Sarath Kumar SATHISH KUMAR Dohyeon jin Dae-Young LEE Chun-Gon kim Department of Aerospace Engineering Chosun UniversityGwangju 61452Republic of Korea Department of Aerospace and Software Engineering Gyeongsang National UniversityGyeongsangnam-do 52828Republic of Korea Department of Aerospace Engineering Seoul National UniversitySeoul 08826Republic of Korea Department of Aerospace Engineering KAISTDaejeon 34141Republic of Korea

The multidisciplinary space environment,encompassing orbital debris,cosmic radiation,and solar radiative heat,poses significant risks to spacecraft and astronauts,necessitating efficient and effective shielding solutions.A multi-layer shield with wide spacing has been proven to be an effective way to shield the spacecraft from space debris impact;however,due to the limited volume of the payload fairing,it was not feasible to apply a multi-layer shield to the spacecraft *** the origami design,the shield maintains a compact form during launch and subsequently expands in outer space to enhance *** geometric analysis,it has been confirmed that the deployable multi-layer space shield can occupy less space than conventional space shield structures while expanding into wider shield intervals and multiple *** hypervelocity impact experiments,it was confirmed that as the bumper spacing of the multi-layer space shield expands,its ballistic performance becomes superior to conventional space *** deployable multi-layer space shield can reduce not only hypervelocity impacts but also solar radiative heat using the same mechanism as multi-layer *** cosmic radiation dose analysis,it has been confirmed that the multi-layer space shield is effective in cosmic radiation shielding compared to conventional space structures.

关键词： Hybrid composite Origami Hypervelocity impact Space environment Space debris Cosmic radiation

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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha Eun Shin Jun-Hyeok Han Seungyong Shin Ga-Hyun Bae Boram Son Tae-hyung kim Hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

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Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3177-3182页

作者： Hyo-Sik Park Jae-hyung kim Department of Interventional Physiatry Eulji University Medical CenterSeo-GuDaejeonSouth Korea

BACKGROUND Supernumerary phantom limb(SPL)sensation is the experience of additional limbs,either single or a pair of *** to traumatic spinal cord injuries,we report effect of transcranial direct current stimulation(tDCS)on SPL pain in a patient with cervical cord *** SUMMARY The subject was a 57-year-old man who was diagnosed with complete spinal cord injury(C6/C5,motor level;C5/C5,sensory level;AIS-A)approximately three months *** a period of 2 wk,we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 *** that treatment,the patient experienced a decrease of SPL pain intensity and frequency,which lasted for 1 week after the end of *** Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

关键词： Supernumerary phantom limb pain Spinal cord injury transcranial Direct Current Stimulation Neuromodulation Case report

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng kim Mi-Hwa kim Yoon-Sun Yi Sangmi Jun Bum-Tae kim Jong-Won Oh Aleem Siddiqui Seong-Jun kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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