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Quantitative assessment of the relevance of organic-aniontransporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

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Journal of Pharmaceutical Analysis 2023年第6期13卷 660-672页

作者： Ji-Hun Jang seung-hyun jeong Yong-Bok Lee Department of Pharmacy College of PharmacyChonnam National UniversityGwangju61186Republic of Korea Department of Pharmacy College of PharmacySunchon National UniversitySuncheon-si57922Republic of Korea

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.

关键词： OATP1B1 OATP2B1 Fexofenadine Population pharmacometrics Genetic polymorphism

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Biochemical consequences of glucocerebrosidase 1 mutations in Parkinson’s disease

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Neural Regeneration Research 2024年第4期19卷 725-727页

作者： jeong hyun Yoon Chiao-Yin Lee Anthony HV Schapira Department of Clinical and Movement Neurosciences University College London Institute of Neurology Faculty of Medicine Imperial College London Aligning Science Across Parkinson's(ASAP)Collaborative Research Network

Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural instability.It usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic dysfunction.The gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.***.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).

关键词： cerebro consequences

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Metabolic relationships between marine red algae and algae‑associated bacteria

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Marine Life Science & Technology 2024年第2期6卷 298-314页

作者： Kyung hyun Kim jeong Min Kim Ju Hye Baek Sang Eun jeong Hocheol Kim Hwan Su Yoon Che Ok Jeon Department of Biological Sciences and Biotechnology Hannam UniversityDaejon 34054Republic of Korea Department of Life Science Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biological Sciences Sungkyunkwan UniversitySuwon 16419Republic of Korea

Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their success-ful survival in the ocean,but little is known about their metabolic relationships.Here,bacterial communities in the algal sphere(AS)and bulk solution(BS)of nine marine red algal cultures were analyzed,and Roseibium and Phycisphaera were identified significantly more abundantly in AS than in BS.The metabolic features of Roseibium RMAR6-6(isolated and genome-sequenced),Phycisphaera MAG 12(obtained by metagenomic sequencing),and a marine red alga,Porphyridium purpureum CCMP1328(from GenBank),were analyzed bioinformatically.RMAR6-6 has the genetic capability to fix nitrogen and produce B vitamins(B1,B2,B5,B6,B9,and B12),bacterioferritin,dimethylsulfoniopropionate(DMSP),and phenylacetate that may enhance algal growth,whereas MAG 12 may have a limited metabolic capability,not producing vitamins B9 and B12,DMSP,phenylacetate,and siderophores,but with the ability to produce bacitracin,possibly modulating algal microbiome.P.purpureum CCMP1328 lacks the genetic capability to fix nitrogen and produce vitamin B12,DMSP,phenylacetate,and siderophore.It was shown that the nitrogen-fixing ability of RMAR6-6 promoted the growth of P.pur-pureum,and DMSP reduced the oxidative stress of P.purpureum.The metabolic interactions between strain RMAR6-6 and P.purpureum CCMP1328 were also investigated by the transcriptomic analyses of their monoculture and co-culture.Taken together,potential metabolic relationships between Roseibium and P.purpureum were proposed.This study provides a bet-ter understanding of the metabolic relationships between marine algae and algae-associated bacteria for successful growth.

关键词： Metabolic relationship Marine red algae Symbiotic bacteria Roseibium Phycisphaera Porphyridium

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Depolarization mitigated in ferroelectric Hf_(0.5)Zr_(0.5)O_(2)ultrathin films(<5 nm)on Si substrate by interface engineering

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Journal of Advanced Ceramics 2024年第3期13卷 282-292页

作者： Se hyun Kim Younghwan Lee Dong hyun Lee Geun Hyeong Park hyun Woo jeong Kun Yang Yong Hyeon Cho Young Yong Kim Min Hyuk Park Department of Materials Science and Engineering College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Research Institute of Advanced Materials College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Inter-university Semiconductor Research Center College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Pohang Accelerator Laboratory Pohang University of Science&TechnologyPohang 790784Republic of Korea

(Hf,Zr)O_(2)offers considerable potential for next-generation semiconductor devices owing to its nonvolatile spontaneous polarization at the nanoscale.However,scaling this material to sub-5 nm thickness poses several challenges,including the formation of an interfacial layer and high trap concentration.In particular,a low-k SiO_(2)interfacial layer is naturally formed when(Hf,Zr)O_(2)films are directly grown on a Si substrate,leading to high depolarization fields and rapid reduction of the remanent polarization.To address these issues,we conducted a study to significantly improve ferroelectricity and switching endurance of(Hf,Zr)O_(2)films with sub-5 nm thicknesses by inserting a TiO_(2)interfacial layer.The deposition of a Ti film prior to Hf_(0.5)Zr_(0.5)O_(2)film deposition resulted in a high-k TiO_(2)interfacial layer and prevented the direct contact of Hf_(0.5)Zr_(0.5)O_(2)with Si.Our findings show that the high-k TiO_(2)interfacial layer can reduce the SiO_(2)/Si interface trap density and the depolarization field,resulting in a switchable polarization of 60.2μC/cm^(2)for a 5 nm thick Hf_(0.5)Zr_(0.5)O_(2)film.Therefore,we propose that inserting a high-k TiO_(2)interfacial layer between the Hf_(0.5)Zr_(0.5)O_(2)film and the Si substrate may offer a promising solution to enhancing the ferroelectricity and reliability of(Hf,Zr)O_(2)grown on the Si substrate and can pave the way for next-generation semiconductor devices with improved performance.

关键词： ferroelectric charge trapping hafnia depolarization

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Tailoring local structures of atomically dispersed copper sites for highly selective CO2 electroreduction

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Carbon Energy 2024年第4期6卷 79-90页

作者： Kyung‐Jong Noh Byoung Joon Park Ying Wang Yejung Choi Sang‐Hoon You Yong‐Tae Kim Kug‐seung Lee jeong Woo Han Department of Chemical Engineering Pohang University of Science and Technology(POSTECH)PohangGyeongbukRepublic of Korea Department of Materials Science and Engineering Pohang University of Science and Technology(POSTECH)PohangGyeongbukRepublic of Korea Pohang Accelerator Laboratory(PAL) Beamline DivisionPohangGyeongbukRepublic of Korea

Atomically‐dispersed copper sites coordinated with nitrogen‐doped carbon(Cu–N–C)can provide novel possibilities to enable highly selective and active electrochemical CO_(2) reduction reactions.However,the construction of optimal local electronic structures for nitrogen‐coordinated Cu sites(Cu–N_(4))on carbon remains challenging.Here,we synthesized the Cu–N–C catalysts with atomically‐dispersed edge‐hosted Cu–N_(4) sites(Cu–N_(4)C_(8))located in a micropore between two graphitic sheets via a facile method to control the concentration of metal precursor.Edge‐hosted Cu–N_(4)C_(8) catalysts outperformed the previously reported M–N–C catalysts for CO_(2)‐to‐CO conversion,achieving a maximum CO Faradaic efficiency(FECO)of 96%,a CO current density of–8.97 mA cm–2 at–0.8 V versus reversible hydrogen electrode(RHE),and over FECO of 90%from–0.6 to–1.0 V versus RHE.Computational studies revealed that the micropore of the graphitic layer in edge‐hosted Cu–N_(4)C_(8) sites causes the d‐orbital energy level of the Cu atom to shift upward,which in return decreases the occupancy of antibonding states in the*COOH binding.This research suggests new insights into tailoring the locally coordinated structure of the electrocatalyst at the atomic scale to achieve highly selective electrocatalytic reactions.

关键词： atomic local structure density functional theory electrochemical CO_(2)reduction metal nitrogen‐doped carbon single‐atom catalyst

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative diseases.However,the molecular mechanisms underlying neuromuscular dysfunction are currently unclear.Recent studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle maintenance.In the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using Hb9-Cre.mnKO exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and lethality.Prmt1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve injury.The transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and mitochondria.Consistently,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor neurons.Furthermore,Prmt1 inhibition in motor neurons elicited mitochondrial dysfunction.Our findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle loss.Thus,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 47-54页

作者： Hoibin jeong Dong-joo Lee Sung-Pil Kwon SeonJu Park Song-Rae Kim seung hyun Kim Jae-Il Park Deug-chan Lee Kyung-Min Choi WonWoo Lee Ji-Won Park Bohyun Yun Su-Hyeon Cho Kil-Nam Kim Seoul Center Korea Basic Science InstituteSeoul 02841Republic of Korea Chuncheon Center Korea Basic Science InstituteChuncheon 24341Republic of Korea Research&Development Center Chungdam CDC JNPharm LLC.Chuncheon 24341Republic of Korea Department of Biomedical Technology Kangwon National UniversityChuncheon 24341Republic of Korea Yonsei Institute of Pharmaceutical Sciences College of PharmacyYonsei UniversityIncheon 21983Republic of Korea Gwangju Center Korea Basic Science InstituteGwangju 61751Republic of Korea Honam National Institute of Biological Resources 99Gohadoan-gilMokpo-siJeollanam-do58762Republic of Korea Department of Bio-analysis Science University of Science&TechnologyDaejeon34113Republic of Korea

Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.

关键词： Catalpa bignonioides Skeletal muscle Cell proliferation Mitochondria Energy metabolism C2C12

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Pharmacokinetic comparison with different assays for simultaneous determination of cis-,trans-cefprozil diastereomers in human plasma

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Journal of Pharmaceutical Analysis 2021年第3期11卷 351-363页

作者： seung-hyun jeong Ji-Hun Jang Hea-Young Cho Yong-Bok Lee College of Pharmacy Chonnam National University77 Yongbong-roBuk-guGwangju61186Republic of Korea College of Pharmacy CHA University335 Pangyo-roBundang-guSeongnam-siGyeonggi-Do13488Republic of Korea

The purpose of this study was to compare pharmacokinetic(PK)parameters obtained using two newly developed assays,HPLC-UV and UPLC-ESI-MS/MS.Selection of assay and results obtained therefrom are very important in PK studies and can have a major impact on the PK-based clinical dose and usage settings.For this study,we developed two new methods that are most commonly used in biosample analysis and focused on PK parameters obtained from them.By HPLC-UV equipped with a Luna-C8 column using UV detector,cefprozil diastereomers were separated using water containing 2%(V/V)acetic acid and acetonitrile as a mobile phase.By UPLC-ESI-MS/MS equipped with a HALO-C18 column,cefprozil diastereomers were separated using 0.5%(V/V)aqueous formic acid containing 5 mM ammoniumformate buffer and methanol as a mobile phase.Chromatograms showed high resolution,sensitivity,and selectivity without interference by plasma constituents.Both intra-and inter-day precisions(CV,%)were within 8.88%for HPLC-UV and UPLC-ESI-MS/MS.Accuracy of both methods was 95.67%-107.50%.These two analytical methods satisfied the criteria of international guidance and could be successfully applied to PK study.Comparison of PK parameters between two assays confirmed that there is a difference in the predicted minimum plasma concentrations at steady state,which may affect clinical dose and usage settings.Furthermore,we confirmed possible correlation between PK parameters and various biochemical parameters after oral administration of 1000 mg cefprozil to humans.

关键词： Cefprozil diastereomers Comparison HPLC-UV UPLC-ESI-MS/MS Pharmacokinetic parameter Biochemical parameters

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Oxygen vacancy engineering for tuning the catalytic activity of LaCoO_(3) perovskite

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Journal of Rare Earths 2024年第3期42卷 506-514,I0003页

作者： jeong hyun Cho Minjae Kim Inchan Yang Kyung Tae Park Chang Houn Rhee Hai Woong Park Ji Chul Jung Department of Chemical Engineering Myongji UniversityYongin 17058Republic of Korea Institute of Advanced Composite Materials Korea Institute of Science and TechnologyWanju-gunJeollabuk-do 55324Republic of Korea Iron&Steel Process Engineering Research Group POSCOPohang 37859Republic of Korea Hydrogen Research Center Research Institute of Industrial Science&Technology(RIST)Pohang 37673Republic of Korea

Herein, we attempted to engineer oxygen vacancies on the surface of LaCoO_(3) perovskite through simple post-treatments(acid or reductive thermal treatments). Acid treatment induces oxygen vacancies through the selective etching of the La cations, whereas thermal treatment in a reducing atmosphere generates oxygen vacancies by directly removing lattice oxygen. The characterization results confirm that the number of surface oxygen vacancies, which are crucial in various catalytic oxidation reactions,considerably increases in the LaCoO_(3) catalysts treated with acid or reducing gas. Acid treatment enriches the oxygen vacancies while maintaining the structure of the LaCoO_(3) catalysts, which can not be achieved through reductive thermal treatment. Therefore, the acid treatment is considered a promising technique for oxygen vacancy engineering of perovskite catalysts for tuning their catalytic activities. Furthermore,the catalytic activities of the posttreated LaCoO_(3) catalysts for CO oxidation were evaluated and are noted to be considerably better than those of the pristine LaCoO_(3) catalyst due to their abundant oxygen vacancies. Consequently, we conclude that the oxygen vacancies of perovskite catalysts can be effectively engineered via two simple methods and play a significant role in CO oxidation.

关键词： LaCoO_(3)perovskite Acid treatment Reductive thermal treatment Oxygen vacancy CO oxidation Rare earths

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The learning curve for transurethral enucleation with bipolar energy for benign prostate hyperplasia:a single-surgeon experience of 494 patients

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Asian Journal of Andrology 2024年第3期26卷 288-294页

作者： Byeongdo Song Sang Hun Song Seong Jin jeong Department of Urology Seoul National University Bundang HospitalSeongnam 13620Korea Department of Urology Seoul National University College of MedicineSeoul 03080Korea

This study was performed to investigate the learning curve of transurethral enucleation with bipolar energy(TUEB)for benignprostatic hyperplasia.The study involved 494 consecutive patients who underwent TUEB for benign prostatic hyperplasia fromAugust 2018 to March 2022 by one surgeon(SJJ,Seoul National University Bundang Hospital,Seongnam,Korea).The patientswere followed up at 1 week,1 month,3 months,and 6 months postoperatively.To evaluate the learning curve of TUEB,perioperativeparameters including the enucleation ratio(enucleated tissue weight/transitional zone volume),TUEB efficiency(enucleatedtissue weight/operation time),and enucleation efficiency(enucleated tissue weight/enucleation time)were analyzed.Functionaloutcomes and postoperative complications were also assessed,including the International Prostate Symptom Score(IPSS),IPSSquality-of-life(QoL)score,and uroflowmetry outcomes.The patients’median age was 72(interquartile range[IQR]:66–78)years,and the estimated prostate volume and transitional zone volume were 63.0(IQR:46.0–90.6)ml and 37.1(IQR:24.0–60.0)ml,respectively.The enucleation ratio,TUEB efficiency,and enucleation efficiency were 0.60(IQR:0.46–0.54)g ml−1,0.33(IQR:0.22–0.46)g min−1,and 0.50(IQR:0.35–0.72)g min−1,respectively,plateauing after 70 cases.The functional outcomes,including total IPSS,IPSS QoL score,and uroflowmetry outcomes,significantly improved at 6 months after TUEB(all P<0.05),but without significant differences over the learning curve.Sixty-five(13.2%)patients developed complications after TUEB,21.5%of whom experienced major complications(Clavien–Dindo grade≥3).The rate of major complications declined as the number ofTUEB cases increased(P=0.013).Our results suggest that the efficiency of TUEB stabilized within 70 procedures.

关键词： benign prostate hyperplasia learning curve perioperative efficiency prostate transurethral enucleation with bipolar energy

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