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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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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon Nayeon shim Hong Yeol Yoon Sehoon Kim Man Kyu shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Hepatocellular carcinoma with macrovascular invasion:need a personalized medicine for this complicated event

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 188-190页

作者： Hyeonseung Hwang Ju Hyun shim Jin Hyoung Kim Department of Radiology and Research Institute of Radiology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

Hepatocellular carcinoma(HCC)is a hypervascular tumor and has a tendency to invade portal vein(PV)or hepatic vein(HV).HCC with macrovascular invasion(MVI)is associated with poor prognosis(1).HCC invasion of PV can lead to rapid intrahepatic tumor *** addition,portal vein tumor thrombus(PVTT)may result in deterioration of hepatic function,as well as increased risk of portal hypertensive complications(2).HCC invasion of HV is associated with increased risk of systemic ***.

关键词： invasion hepatic hypertensive

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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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The PRR-EC complex and SWR1 chromatin remodeling complex function cooperatively to repress nighttime hypocotyl elongation by modulating PIF4 expression in Arabidopsis

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Plant Communications 2024年第9期5卷 184-199页

作者： Jin Hoon Won Jeonghyang Park Hong Gil Lee Sangrae shim Hongwoo Lee Eunkyoo Oh Pil Joon Seo Department of Chemistry Seoul National UniversitySeoul 08826Republic of Korea Department of Life Sciences Korea UniversitySeoul 02841Republic of Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Republic of Korea Department of Forest Resources Kangwon National UniversityChuncheon 24341Republic of Korea

The circadian clock entrained by environmental light-dark cycles enables plants to fine-tune diurnal growth and developmental ***,we show that physical interactions among evening clock components,including PSEUDO-RESPONSE REGULATOR 5(PRR5),TIMING OF CAB EXPRESSION 1(TOC1),and the Evening Complex(EC)component EARLY FLOWERING 3(ELF3),define a diurnal repressive chromatin structure specifically at the PHYTOCHROME-INTERACTING FACTOR 4(PIF4)locus in *** three clock components act interdependently as well as independently to repress nighttime hypocotyl elongation,as hypocotyl elongation rate dramatically increased specifically at nighttime in the prr5-1 toc1-21 elf3-1 mutant,concomitantly with a substantial increase in PIF4 *** repression of PIF4 by ELF3,PRR5,and TOC1 is mediated by the SWI2/SNF2-RELATED(SWR1)chromatin remodeling complex,which incorporates histone H2A.Z at thePIF4 locus,facilitating robust epigenetic suppression ofPIF4 during the ***,these findings demonstrate that the PRR-EC-SWR1 complex represses hypocotyl elongation at night through a distinctive chromatin domain covering PIF4 chromatin.

关键词： hypocotyl elongation circadian clock PRR Evening Complex histone H2A.Z SWR1 complex

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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG shim JIN HYOUNG KANG Division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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Mixed-dimensional stacked nanocomposite structures for a specific wavelength-selectable ambipolar photoresponse

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Nano Research 2024年第6期17卷 5549-5558页

作者： Young Jae Park Jaeho shim Joo Song Lee Kyu Seung Lee Ji-Yeon Kim Kang Bok Ko Sang-Youp Yim Seongjun Kim Hoon-Kyu Shin Donghee Park Yong Ju Yun Dong Ick Son Institute of Advanced Composite Materials Korea Institute of Science and TechnologyJeollabuk-do 55324Republic of Korea National Institute for Nanomaterials Technology Pohang University of Science and TechnologyGyeongsangbuk-do 37673Republic of Korea Department of Semiconductor Science and Technology Semiconductor Physics Research CenterJeonbuk National UniversityJeonju 54896Republic of Korea Advanced Photonics Research Institute Gwangju Institute of Science and TechnologyGwangju 61005Republic of Korea Center for Opto-Electronic Materials and Devices Post-Silicon Semiconductor InstituteKorea Institute of Science and TechnologySeoul 02792Republic of Korea Graduate School of Energy and Environment(KU-KIST Green School) Korea UniversitySeoul 02841Republic of Korea KIST School Department of Nanomaterials and Nano ScienceUniversity of Science and Technology(UST)Daejeon 34113Republic of Korea

Mixed-dimensional composite structures using zero-dimensional(0D)quantum dots(QDs)and two-dimensional(2D)transition metal dichalcogenides(TMDs)materials are expected to attract great interest in optoelectronics due to the potential to generate new optical ***,we report on the unique optical characteristics of a devices with mixed dimensional vertically stacked structures based on tungsten diselenide(WSe_(2))/CdSeS QDs monolayer/molybdenum disulfide(MoS_(2))(2D/0D/2D).Specifically,it exhibits an ambipolar photoresponse characteristic,with a negative photoresponse observed in the 400-600 nm wavelength range and a positive photoresponse appeared at 700 nm *** resulted in the high negative responsivity of up to 52.22 mA·W^(−1)under 400 nm,which is 163 times higher than that of the photodetector without CdSeS *** also demonstrated the negative photoresponse,which could be due to increased carrier collision probability and non-radiative *** modeling and simulation reveal that Auger recombination among the types of non-radiative recombination is the main cause of negative photocurrent ***,we discovered ambipolar photoresponse near a specific wavelength corresponding to the energy of quantum *** study revealed interesting phenomenon in the mixed low-dimensional stacked structure and paved the way to exploit it for the development of innovative photodetection materials as well as for optoelectronic applications.

关键词： mixed-dimension quantum dot heterostructure photodetector ambipolar photoresponse

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Polarity-controllable magnetic skyrmion filter

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Chinese Physics B 2024年第10期33卷 400-404页

作者： Xiao-Lin Ai Hui-Ting Li Xue-Feng Zhang Chang-Feng Li Je-Ho shim Xiao-Ping Ma Hong-Guang Piao Hubei Engineering Research Center of Weak Magnetic-Field Detection College of ScienceChina Three Gorges UniversityYichang 443002China Department of Physics College of ScienceYanbian UniversityYanji 133002China

The skyrmion generator is one of the indispensable components for the future functional skyrmion devices,but the process of generating skyrmion cannot avoid mixing with other magnetic textures,such as skyrmionium and nested skyrmion *** mixed magnetic textures will inevitably lead to the blockage of skyrmion transport and even the distortion of data ***,the design of an efficient skyrmion filter is of great significance for the development of skyrmion-based spintronic *** this work,a skyrmion filter scheme is proposed,and the high-efficiency filtering function is demonstrated by micromagnetic *** results show that the filtering effect of the scheme depends on the structure geometry and the spin current density that drives the *** on this scheme,the polarity of the filtered skyrmion can be controlled by switching the magnetization state at the output end,and the“cloning”of the skyrmion can be realized by geometric optimization of the *** believe that in the near future,the skyrmion filter will become one of the important components of skyrmion-based spintronic devices in the future.

关键词： spintronics skyrmions skyrmion filter skyrmion polarity skyrmion clone

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Guaranteeing almost fault-free tracking performance from transient to steady-state:a disturbance observer approach

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Science China(Information Sciences) 2018年第7期61卷 227-243页

作者： Gyunghoon PARK Hyungbo shim ASRI Department of Electrical and Computer Engineering Seoul National University

In this paper, we propose an output-feedback fault-tolerant controller(FTC) for a class of uncertain multi-input single-output systems under float and lock-in-place actuator faults. Of particular interest is to recover a fault-free tracking performance of a(pre-defined) nominal closed-loop system, during the entire time period including the transients due to abrupt actuator faults. As a key component, a highgain disturbance observer(DOB) is employed to rapidly compensate the lumped disturbance, a compressed expression of all the effect of actuator faults(as well as model uncertainty and disturbance) on the *** implement this high-gain approach, a fixed control allocation(CA) law is presented in order to keep an extended system with a virtual scalar input to remain of minimum phase under any patterns of faults. It is shown via the singular perturbation theory that the proposed FTC, consisting of the high-gain DOB and the CA law, resolves the problem in an approximate but arbitrarily accurate sense. Simulations with the linearized lateral model of Boeing 747 are performed to verify the validity of the proposed FTC scheme.

关键词： disturbance observer fault-tolerant control robust control performance recovery actuator fault

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Estimation of vegetative mercury emissions in China

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Journal of Environmental Sciences 2008年第9期20卷 1070-1074页

作者： Shang Gyoo shim Korea Institute of Science and Technology

Vegetative mercury emissions were estimated within the framework of Biogenic Emission Inventory System (BEIS3 V3.11). In this estimation, the 19 categories of U.S. Geological Survey landcover data were incorporated to generate the vegetation-specific mercury emissions in a 81-km Lambert Conformal model grid covering the total Chinese continent. The surface temperature and cloud-corrected solar radiation from a Mesoscale Meteorological model (MM5) were retrieved and used for calculating the diurnal variation...

关键词： mercury emission Biogenic Emission Inventory System (BEIS3) natural source

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