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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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Anticipating the lifespan: Predicting the durability of an anode-supported solid oxide fuel cell short stack over 50,000 h

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Progress in Natural Science:Materials International 2024年第3期34卷 606-613页

作者： Muhammad Zubair Khan Amjad Hussain Seung-bok lee Tak-Hyoung Lim Rak-Hyun Song Department of Materials Science & Engineering Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology Mang Haripur Hydrogen Energy Research Division Korea Institute of Energy Research Department of Advanced Energy and System Engineering Korea University of Science and Technology (UST)

In the present study, the operational lifetime of a solid oxide fuel(SOFC) short stack is predicted by investigating the performance degradation of both the short stack and its cells throughout 1000 h at 800°C. The short stack and integral cell voltages are continuously measured during the long-term test, with electrochemical impedance spectroscopy(EIS) conducted every 200 h. The short stack voltage decreased rapidly for the initial 200–300 h and afterwards, it decreased at a slow rate due to the increase in the Ohmic and polarization resistances in the same manner. Scanning electron microscopy results show that there is no delamination or cracking among constituent layers of the short-stack cells. The single degradation effects of the Ni coarsening in the anode, cation migration and surface segregation in cathode and oxide scale growth in metallic interconnect mesh are successfully integrated into a comprehensive lifetime prediction model. The experimentally measured voltage degradation data of the short stack fits well with the developed mathematical model and allows the successful prediction of the lifetime up to 50,000 h.

关键词： Degradation Impedance Lifetime SOFC Stack

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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 properties.Here,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 wavelength.It 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 QDs.We also demonstrated the negative photoresponse,which could be due to increased carrier collision probability and non-radiative recombination.Device modeling and simulation reveal that Auger recombination among the types of non-radiative recombination is the main cause of negative photocurrent generation.Consequently,we discovered ambipolar photoresponse near a specific wavelength corresponding to the energy of quantum dots.Our 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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SUMS OF DUAL TOEPLITZ PRODUCTS ON THE ORTHOGONAL COMPLEMENTS OF FOCK-SOBOLEV SPACES

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Acta Mathematica Scientia 2024年第3期44卷 810-822页

作者：陈泳 Young Joo lee Department of Mathematics Hangzhou Normal UniversityHangzhou311121China Department of Mathematics Chonnam National UniversityGwangju61186Korea

We consider dual Toeplitz operators on the orthogonal complements of the FockSobolev spaces of all nonnegative real orders.First,for symbols in a certain class containing all bounded functions,we study the problem of when an operator which is finite sums of the dual Toeplitz products is compact or zero.Next,for bounded symbols,we construct a symbol map and exhibit a short exact sequence associated with the C^(*)-algebra generated by all dual Toeplitz operators with bounded symbols.

关键词： dual Toeplitz operators Fock-Sobolev spaces symbol map

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Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration Research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati Sang Chul lee Jae Il Shin yong Wook Kim Department and Research Institute of Rehabilitation Medicine Yonsei University College of MedicineSeoulSouth Korea Department of Physical Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran Department of Pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgro

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

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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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Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

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World Journal of Clinical Cases 2024年第5期12卷 913-921页

作者： Tae In Kim Sung yong Han Jonghyun lee Dong Uk Kim Division of Gastroenterology Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Internal Medicine Pusan National UniversityCollege of MedicineYangsan 50612South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,Pupper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

关键词： Intrahepatic bile duct stone Cholangiocarcinoma Percutaneous transhepatic cholangioscopy Endoscopic retrograde cholangiopancreatography Carbohydrate antigen 19-9

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Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressionsin Pancreas and Liver Tissues

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Chinese Journal of Integrative Medicine 2024年第2期30卷 125-134页

作者： Piao Wang Yi Liu Seok yong Kang Chenzi Lyu Xiang Han Tianjun Ho Kyung Jae lee Xianglong Meng yong-Ki Park Hyo Won Jung Department of Herbology College of Korean MedicineDongguk UniversityGyeongju 38066Korea College of Pharmacy&Graduate School of Pharmaceutical Sciences Ewha Womans UniversitySeoul 03760Korea Korean Medicine R&D Center Dongguk UniversityGyeongju 38066Korea Shanxi Key Laboratory of Traditional Herbal Medicines Processing Shanxi University of Chinese MedicineJinzhong(030619)ShanxiProvinceChina

Objective:To investigate the effects of Clean-DM1(C-DM1),a polyherbal formulation of Radix Scrophulariae,Radix Astragali,Rhizoma Atractylodis,and Radix Salviae Miltiorrhizae,on high-fat diet(HFD)-induced diabetes mice.Methods:The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis.Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry(HPLC-MS)analysis were conducted for quality control.For in vivo study,mice were induced diabetes by HFD for 12 weeks.The mice in the normal group(Nor)were maintained with a regular diet and treated with saline by gavage.The HFD model mice were randomly divided into 3 groups,including a HFD diabetic model group,a C-DM1 extract-administered group(C-DM1,500 mg/kg),and metformin-administered groups(Met,500 mg/kg),8 mice in each group.Food intake,body weight(BW),and fasting blood glucose(FBG)levels were recorded weekly for 4 weeks.After 4 weeks of treatment,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood glucose,low-density lipoprotein cholesterol(LDL-C)were determined using an automated clinical chemistry analyzer,and homeostatic model for assessing insulin resistance(HOMA-IR)levels and oral glucose tolerance test(OGTT)were detected.The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining.Insulin receptor substrate(IRS)/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)and adenosine 5'-monophosphate-activated protein kinase(AMPK)expressions in liver and pancreas tissues were detected by Western blot analysis.Results:HPLC-MS identified dihydroisotanshinone,dihydroisotanshinone I,cryptotanshinone,harpagoside,and atractyloside A in C-DM1 extract.The administration of C-DM1 extract significantly decreased body weight,calorie intake,and the levels of blood glucose and insulin in the diabetic mice(P<0.05 or P<0.01).The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance

关键词： high-fat diet type 2 diabetes mellitus herbal formulation insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B adenosine 5'-monophosphate-activated protein kinase network pharmacology high performance liquid chromatography-mass spectrometry analysis

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Enhancement of vertical phase separation in sequentially deposited organic photovoltaics through the independent processing of additives

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Journal of Energy Chemistry 2024年第7期94卷 768-777页

作者： Damin lee Changwoo Park Gayoung Ham Young yong Kim Sung-Nam Kwon Junyeong lee Sungjin Jo Seok-In Na Hyojung Cha Department of Hydrogen and Renewable Energy Kyungpook National UniversityDaegu 41566Republic of Korea Department of Energy Convergence and Climate Change Kyungpook National UniversityDaegu 41566Republic of Korea Pohang Accelerator Laboratory(PAL) Pohang University of Science and Technology(POSTECH)PohangGyeongbuk 37673Republic of Korea Department of Flexible and Printable Electronics Jeonbuk National UniversityJeonju-siJeollabuk-do 54896Republic of Korea School of Energy Engineering Kyungpook National UniversityDaegu 41566Republic of Korea

Herein,the impact of the independent control of processing additives on vertical phase separation in sequentially deposited(SD)organic photovoltaics(OPVs)and its subsequent effects on charge carrier kinetics at the electron donor-acceptor interface are investigated.The film morphology exhibits notable variations,significantly depending on the layer to which 1,8-diodooctane(DIO)was applied.Grazing incidence wide-angle X-ray scattering analysis reveals distinctly separated donor/acceptor phases and vertical crystallinity details in SD films.Time-of-flight secondary ion mass spectrometry analysis is employed to obtain component distributions in diverse vertical phase structures of sD films depending on additive control.In addition,nanosecond transient absorption spectroscopy shows that DIO control significantly affects the dynamics of separated charges in SD films.In SD OPVs,DIO appears to act through distinct mechanisms with minimal restriction,depending on the applied layer.This study emphasizes the significance of morphological optimization in improving device performance and underscores the impor-tance of independent additive control in the advancement of oPV technology.

关键词： Sequential deposition Vertical phase separation Charge dynamics Organic photovoltaics Nonfullerene acceptors

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Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of Stem Cells 2024年第3期16卷 257-266页

作者： Min Young Park yong Sik Yoon Jae Ha Park Jong Lyul lee Chang Sik Yu Division of Colon and Rectal Surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal Surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula Stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab

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