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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang Hee Seung Lee moon jae chung Jeong Youp Park Seungmin Bang Seung Woo Park Si Young Song Division of Gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

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World Journal of Gastrointestinal Oncology 2018年第11期10卷 421-430页

作者： Huapyong Kang Jung Hyun Jo Hee Seung Lee moon jae chung Seungmin Bang Seung Woo Park Si Young Song Jeong Youp Park Division of Gastroenterology Department of Internal Medicine Yonsei University College of Medicine

AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic *** One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity *** The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX *** m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.

关键词： Dose modification Adverse event Pancreatic cancer Adenocarcinoma FOLFIRINOX Chemotherapy

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Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

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World Journal of Gastrointestinal Oncology 2018年第12期10卷 505-515页

作者： moon jae chung Huapyong Kang Ho Gak Kim Jong Jin Hyun Jun Kyu Lee Kwang Hyuck Lee Myung Hwan Noh Dae Hwan Kang Sang Hyub Lee Seungmin Bang 无 Division of Gastroenterology Department of Internal Medicine Yonsei University College of Medicine Seoul 03722 South Korea Department of Internal Medicine Daegu Catholic University School of Medicine Daegu 42471 South Korea Department of Internal Medicine Korea University Ansan Hospital Korea University College of Medicine Ansan 15355 South Korea Department of Internal Medicine Dongguk University Ilsan Hospital Dongguk University College of Medicine Goyang 10326 South Korea Division of Gastroenterology Department of Internal Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 06351 South Korea Department of Internal Medicine Dong-A University College of Medicine Busan 49201 South Korea Department of Internal Medicine Medical Research Institute Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital Yangsan 50612 South Korea Departments of Internal Medicine and Liver Research Institute Seoul National University Hospital Seoul National University College of Medicine Seoul 03080 South Korea Pancreatobiliary Cancer Study Group of Korean Society of Gastrointestinal Cancer

AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on *** Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.

关键词： Pancreatic cancer FOLFIRINOX Clinical Trial, Phase Ⅱ Chemotherapy Gemcitabine refractory

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FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

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World Journal of Gastrointestinal Oncology 2020年第2期12卷 182-194页

作者： In Rae Cho Huapyong Kang Jung Hyun Jo Hee Seung Lee moon jae chung Jeong Youp Park Seung Woo Park Si Young Song Chansik An Mi-Suk Park Seungmin Bang Department of Internal Medicine International Saint Mary’s HospitalCatholic Kwandong University College of MedicineIncheon 22711South Korea Department of Medicine Yonsei University Graduate School50-1 Yonsei-roSeoul 03722South Korea Division of Gastroenterology Department of Internal MedicineYonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea Department of Radiology Yonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer ***,studies that compared these two regimens and studies in Asian populations are *** To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean *** Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort *** efficacy,treatment-related adverse events and economic aspects were *** Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at *** median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX ***≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX *** drug costs of both regimens were *** Treatment efficacy and economic burdens were comparable between the two ***,the details of adverse event were ***+nabPTX regimen might be considered preferentially in certain conditions.

关键词： Pancreatic cancer Chemotherapy FOLFIRINOX Gemcitabine Nabpaclitaxel Survival

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Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

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World Journal of Gastroenterology 2017年第18期23卷 3301-3308页

作者： Jang Han Jung Hyun Jik Lee Hee Seung Lee Jung Hyun Jo In Rae Cho moon jae chung Jeong Youp Park Seung Woo Park Si Young Song Seungmin Bang Division of Gastroenterology Department of Internal Medicine Hallym University Dongtan Sacred Heart Hospital Division of Gastroenterology Department of Internal Medicine and Yonsei Institute of Gastroenterology Yonsei University College of Medicine

To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative *** median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.

关键词： Klatskin tumor Locally advanced Survival rate Neoadjuvant therapy Chemoradiotherapy

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Comparison of macular changes according to the etiology of optic neuritis:a cross-sectional study

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 686-692页

作者： Yeji moon Sung-Min Kim jae Ho Jung Department of Ophthalmology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Department of Neurology Seoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Seoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Seoul National University College of MedicineSeoul 03080Republic of Korea

AIM:To compare the macular structure including foveal thickness among patients with optic neuritis(ON)according to the etiology and to investigate the possible correlation between structural and visual outcomes METHODS:In this retrospective cross-sectional study,the clinical data of patients with aquaporin-4 immunoglobulin G-related ON(AQP4 group,40 eyes),myelin oligodendrocyte glycoprotein IgG-related ON(MOG group,31 eyes),and multiple sclerosis-related ON(MS group,24 eyes)were *** retinal thickness of the foveal,parafoveal and perifoveal regions were *** acuity(VA),visual field index and mean deviation were measured as visual ***:The AQP4 group showed a significantly thinner fovea(226.4±13.4μm)relative to the MOG(236.8±14.0μm,P=0.015)and MS(238.9±14.3μm,P=0.007)*** thickness in the parafoveal area also was thinner in the AQP4 group,though the difference in perifoveal retinal thickness was not *** thickness was correlated with VA in the AQP4 group(coefficientρ=-0.418,P=0.014),but not in the MOG and MS groups(P=0.218 and P=0.138,respectively).There was no significant correlation between foveal thickness and visual field test in all three ***:The significant thinning in the fovea and parafoveal areas in the AQP4 group compared to the MOG and MS groups are ***,macular changes in AQP4-ON show a significant correlation with *** results provide the possibility that retinal structural damage could reflect functional damage in AQP4-ON,distinct from MOGON and MS-ON.

关键词： foveal thickness optic neuritis aquaporin-4 immunoglobulin myelin oligodendrocyte glycoprotein multiple sclerosis

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Anion storing,oxygen vacancy incorporated perovskite oxide composites for high-performance aqueous dual ion hybrid supercapacitors

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Journal of Energy Chemistry 2024年第7期94卷 646-655页

作者： Taehun Kang Puritut Nakhanivej Kyung jae Wang Yu Chen Yongchul G chung Ho Seok Park School of Chemical Engineering Sungkyunkwan University(SKKU)2066Seobu-roJangan-guSuwonGyeonggi-do 16419Republic of Korea Warwick Manufacturing Group(WMG) University of WarwickCoventry CV47ALUnited Kingdom School of Chemical Engineering Pusan National UniversityGeumjeong-guBusanGyeongsangnam-do 46241Republic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan University2066SeoburoJangan-guSuwon 440-746Republic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan University2066SeoburoJangan-guSuwon 440-746Republic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology(SAIHST)Sungkyunkwan UniversitySuwon 16419Republic of Korea

Dual ion storage hybrid supercapacitors(HsCs)are considered as a promising device to overcome the limited energy density of existing supercapacitors while preserving high power and long ***,the development of high-capacity anion-storing materials,which can be paired with fast charg-ing capacitive electrodes,lags behind cation-storing ***,we demonstrate the surface faradaic OH-storage mechanism of anion storing perovskite oxide composites and their application in high-performance dual ion *** oxygen vacancy and nanoparticle size of the reduced LaMnO_(3)(r-LaMnO_(3))were controlled,while r-LaMnO_(3) was chemically coupled with ozonated carbon nanotubes(oCNTs)for the improved anion storing capacity and cycle *** taken by in-situ and ex-situ spectroscopic and computational analyses,OH-ions are inserted into the oxygen vacancies coordi-nating with octahedral Mn with the increase in the oxidation state of Mn during the charging process or vice *** OH-storing r-LaMnO_(3)/oCNT composite with Na*storing MXene,the as-fabricated aqueous dual ion HSCs achieved the cycle performance of 73.3%over 10,000 cycles,delivering the max-imum energy and power densities of 47.5 w h kg^(-1) and 8 kw kg^(-1),respectively,far exceeding those of previously reported aqueous anion and dual ion storage *** research establishes a foundation for the unique anion storage mechanism of the defect engineered perovskite oxides and the advancement of dual ion hybrid energy storage devices with high energy and power densities.

关键词： Anion storage Dual ion storage Defect engineered perovskites Hybrid supercapacitors Nanocomposites

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The processed C-terminus of AvrRps4 effector suppresses plant immunity via targeting multiple WRKYs

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Journal of Integrative Plant Biology 2024年第8期66卷 1769-1787页

作者： Quang-Minh Nguyen Arya Bagus Boedi Iswanto Hobin Kang Jiyun moon Kieu Anh Thi Phan Geon Hui Son Mi chung Suh Eui-Hwan chung Walter Gassmann Sang Hee Kim Division of Applied Life Science(BK21 Four Program) Plant Molecular Biology and Biotechnology Research CenterGyeongsang National UniversityJinju 52828Korea Department of Life Science Sogang UniversitySeoul 04107Korea Department of Plant Biotechnology Korea UniversitySeoul 02841Korea Division of Plant Science and Technology Christopher S.Bond Life Sciences Center and Interdisciplinary Plant GroupUniversity of MissouriColumbiaMissouri 65211USA Division of Life Science and Research Institute of Molecular Alchemy Gyeongsang National UniversityJinju 52828Korea

Pathogens generate and secrete effector proteins to the host plant cells during pathogenesis to promote virulence and *** the plant carries resistance(R)proteins that recognize pathogen effectors,effector-triggered immunity(ETI)is activated,resulting in a robust immune response and hypersensitive response(HR).The bipartite effector AvrRps4 from Pseudomonas syringae *** has been well studied in terms of avirulence *** planta,AvrRps4 is processed into two *** Cterminal fragment of AvrRps4(AvrRps4^(C))induces HR in turnip and is recognized by the paired resistance proteins AtRRS1/AtRPS4 in ***,we show that AvrRps4^(C)targets a group of Arabidopsis WRKY,including WRKY46,WRKY53,WRKY54,and WRKY70,to induce its virulence ***,AvrRps4^(C)suppresses the general binding and transcriptional activities of immune-positive regulator WRKY54 and WRKY54-mediated ***4^(C)interferes with WRKY54's binding activity to target gene SARD1 in vitro,suggesting WRKY54 is sequestered from the SARD1 promoter by AvrRps4^(C).Through the interaction of Avr Rps4^(C)with four WRKYs,AvrRps4 enhances the formation of homo-/heterotypic complexes of four WRKYs and sequesters them in the cytoplasm,thus inhibiting their function in plant ***,our results provide a detailed virulence mechanism of AvrRps4 through its C-terminus.

关键词： AvrRps4 bacterial effector effector-triggered immunity immune response suppression transcription factor WRKY

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Stable immobilization of lithium polysulfides using three-dimensional ordered mesoporous Mn_(2)O_(3) as the host material in lithium-sulfur batteries

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Carbon Energy 2024年第6期6卷 99-112页

作者： Sung Joon Park Yun Jeong Choi Hyun-seung Kim Min Joo Hong Hongjun Chang Janghyuk moon Young-Jun Kim Junyoung Mun Ki jae Kim Department of Energy Science Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea Department of Energy Engineering Konkuk UniversitySeoulRepublic of Korea Advanced Batteries Research Center Korea Electronic Technology InstituteSeongnamRepublic of Korea Department of Future Energy Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Department of Energy Systems Engineering Chung-Ang UniversitySeoulRepublic of Korea SKKU Advanced Institute of Nanotechnology Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea School of Advanced Materials Science and Engineering Sungkyunkwan UniversitySuwonRepublic of Korea

Lithium-sulfur batteries(LSBs)have drawn significant attention owing to their high theoretical discharge capacity and energy ***,the dissolution of long-chain polysulfides into the electrolyte during the charge and discharge process(“shuttle effect”)results in fast capacity fading and inferior electrochemical *** this study,Mn_(2)O_(3)with an ordered mesoporous structure(OM-Mn_(2)O_(3))was designed as a cathode host for LSBs via KIT-6 hard templating,to effectively inhibit the polysulfide shuttle ***-Mn_(2)O_(3)offers numerous pores to confine sulfur and tightly anchor the dissolved polysulfides through the combined effects of strong polar-polar interactions,polysulfides,and sulfur chain *** OM-Mn_(2)O_(3)/S composite electrode delivered a discharge capacity of 561 mAh g^(-1) after 250 cycles at 0.5 C owing to the excellent performance of OM-Mn_(2)O_(3).Furthermore,it retained a discharge capacity of 628mA h g^(-1) even at a rate of 2 C,which was significantly higher than that of a pristine sulfur electrode(206mA h g^(-1)).These findings provide a prospective strategy for designing cathode materials for high-performance LSBs.

关键词： host material lithium-sulfur battery ordered mesoporous structure shuttle effect transition-metal oxides

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Synergistically coupling of Ni–Fe LDH arrays with hollow Co–Mo sulfide nanotriangles for highly efficient overall water splitting

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Rare Metals 2024年第2期43卷 522-532页

作者： Yun jae Lee Seung-Keun Park Department of Advanced Materials Engineering Chung-Ang UniversityAnseongGyeonggi-do17546Republic of Korea Department of Intelligent Energy and Industry Chung-Ang University84 Heukseok-ro Dongjak-guSeoul06974Republic of Korea Western Seoul Center Korea Basic Science Institute150 Bugahyeon-roSeodaemun-guSeoul03759Republic of Korea

Developing bifunctional catalysts that can catalyze both oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is pivotal to commercializing large-scale water ***,a novel hollow nanotriangle composed of NiFe LDH-CoMoS_(x) heterojunction(H-CMSx@NiFe LDH)is proposed as a highly efficient bifunctional electrocatalyst for both OER and *** fabricate a heterojunction system,ultra-thin nickel–iron layered double hydroxide(NiFe LDH)nanosheets are uniformly electrodeposited onto a metal–organic framework-derived hollow CoMoS_(x) *** strong coupling of CoMoS_(x) and NiFe LDH catalysts forms the intimate heterojunction interfaces to facilitate interfacial charge transfer,which is favorable to enhance the bifunctional catalytic ***,the large void of CoMoS_(x) nanotriangles and interconnected ultra-thin NiFe LDH nanosheets result in good electrolyte penetration and gas ***,the as-prepared H-CMSx@NiFe LDH on nickel foam(NF)exhibits an impressive catalytic activity and durability for OER and HER activities,delivering a current density of 100 mA·cm^(−2) at the small overpotentials of 214 and 299 mV in OER and HER,***,H-CMSx@NiFe LDH/NF proves to be an effective electrode for an alkaline electrolyzer,as a voltage of only 1.99 V is enough to achieve a current density voltage of only 1.99 V is enough to achieve a current density of 400 mA·cm^(−2) with no degradation in performance over 50 h.

关键词： Overall water splitting Metal-organic framework Molybdenum sulfide Layered double hydroxide Heterojunction

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