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A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1093-1109页

作者： Sae-Bom Yoon Hyowon Hong Hee-Jong Lim Ji Hye choi Yoon Pyo choi Seong wook Seo Hyuk woo Lee chong Hak Chae woo-Kyu Park Hyun Young Kim Daeyoung Jeong Tran Quang De Chang-Seon Myung Heeyeong cho Therapeutics&Biotechnology Division Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea Department of Pharmacology Chungnam National University College of PharmacyYuseong-guDaejeon 34134Republic of Korea Future Medicine Co. Ltd.Rm616 LH-Business Growth CenterSeongnamGyeonggido 13449Republic of Korea Department of Chemistry College of Natural SciencesCan Tho UniversityCan Tho city 9000Viet Nam

Interleukin-1 receptor-associated kinase 4(IRAK4)is a pivotal enzyme in the Toll-like receptor(TLR)/MYD88 dependent signaling pathway,which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL).Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of ***,proviral integration site for Moloney murine leukemia virus 1(PIM1)functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib *** developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in *** rheumatoid arthritis mouse models,treatment with KIC-0101 significantly ameliorated cartilage damage and ***-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in *** addition,KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 *** results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

关键词： Drug discovery IRAK4 PIM1 NF-κB pathway Rheumatoid arthritis ABC-DLBCL Ibrutinib resistance Dual inhibitor

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Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer:Focused on the rate of decrease in serum bilirubin

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World Journal of Gastroenterology 2008年第7期14卷 1102-1107页

作者： Yun Mee choi Eung-Ho cho Keon-Young Lee Seung-Ik Ahn Sun Keun choi Sei Joong Kim Yoon Seok Hur Young Up cho Kee-Chun Hong Seok-Hwan Shin Kyung Rae Kim Ze-Hong woo Department of Surgery College of MedicineInha UniversityIncheonKorea

AIM: To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct ***: A retrospective study was performed in 49 consecutive patients who underwent pancrea-ticoduodenectomy for distal common bile duct cancer. Potential risk factors were compared between the complicated and uncomplicated groups. Also, the rates of decrease in serum bilirubin were compared pre- and postoperatively. RESULTS: Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%). Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49), respectively. The presence or absence of PBD was not different between the complicated and uncomplicated groups. In patients with PBD, neither the absolute level nor the rate of decrease in serum bilirubin was significantly different. Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5 ± 4.4 μmol/L vs -1.7 ± 9.9 μmol/L, P = 0.004).CONCLUSION: PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer. There is a certain group of patients with a compromised hepatic excretory function, which is represented by the slow rate of decrease in serum bilirubin after PBD.

关键词： Distal bile duct cancer Drainage Bilirubin Rate

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Surface-modified Ag@Ru-P25 for photocatalytic CO_(2) conversion with high selectivity over CH_(4) formation at the solid–gas interface

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Carbon Energy 2024年第1期6卷 182-196页

作者： Chaitanya B.Hiragond Sohag Biswas Niket SPowar Junho Lee Eunhee Gong Hwapyong Kim Hong Soo Kim Jin-woo Jung Chang-Hee cho Bryan M.Wong Su-Il In Department of Energy Science&Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)DaeguRepublic of Korea Department of Chemical&Environmental Engineering Materials Science&Engineering ProgramDepartment of ChemistryDepartment of Physics&AstronomyUniversity of California-RiversideRiversideCaliforniaUSA Department of Physics and Chemistry Daegu Gyeongbuk Institute of Science and Technology(DGIST)DaeguRepublic of Korea NiceScience Corporation DaeguRepublic of Korea

Systematic optimization of the photocatalyst and investigation of the role of each component is important to maximizing catalytic activity and comprehending the photocatalytic conversion of CO_(2) reduction to solar fuels.A surface-modified Ag@Ru-P25 photocatalyst with H_(2)O_(2) treatment was designed in this study to convert CO_(2) and H_(2)O vapor into highly selective *** doping followed by Ag nanoparticles(NPs)cocatalyst deposition on P25(TiO_(2))enhances visible light absorption and charge separation,whereas H_(2)O_(2) treatment modifies the surface of the photocatalyst with hydroxyl(–OH)groups and promotes CO_(2) ***-resonance transmission electron microscopy,X-ray photoelectron spectroscopy,X-ray absorption near-edge structure,and extended X-ray absorption fine structure techniques were used to analyze the surface and chemical composition of the photocatalyst,while thermogravimetric analysis,CO_(2) adsorption isotherm,and temperature programmed desorption study were performed to examine the significance of H_(2)O_(2) treatment in increasing CO_(2) reduction *** optimized Ag1.0@Ru1.0-P25 photocatalyst performed excellent CO_(2) reduction activity into CO,CH4,and C2H6 with a~95%selectivity of CH4,where the activity was~135 times higher than that of pristine TiO_(2)(P25).For the first time,this work explored the effect of H_(2)O_(2) treatment on the photocatalyst that dramatically increases CO_(2) reduction activity.

关键词： gas-phase CO_(2) reduction H_(2)O_(2) treatment plasmonic nanoparticles solar fuel photocatalyst surface modification

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Sucrose induces flowering by degradation of the floral repressor Ghd7 via K48-linked polyubiquitination in rice

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Journal of Integrative Plant Biology 2024年第12期66卷 2683-2700页

作者： Lae-Hyeon cho Jinmi Yoon Gibeom Baek Win Tun Hyeok Chan Kwon Dae-woo Lee Seok-Hyun choi Yang-Seok Lee Jong-Seong Jeon Gynheung An Department of Plant Bioscience College of Natural Resources and Life SciencePusan National UniversityMiryang 50463Korea Life and Industry Convergence Research Institute Pusan National UniversityMiryang 50463Korea Department of Biological Sciences Inha UniversityIncheon 22212Korea Department of Biological Sciences and Bioengineering Inha University/Industry-Academia Interactive R&E Center for Bioprocess InnovationInha UniversityIncheon 22212Korea Crop Biotech Institute and Graduate School of Green-Bio Science Kyung Hee UniversityYongin 17104Korea

Sucrose functions as a signaling molecule in several metabolic pathways as well as in various developmental ***,the molecular mechanisms by which sucrose regulates these processes remain largely *** the present study,we demonstrate that sucrose promotes flowering by mediating the stability of a regulatory protein that represses flowering in *** application of sucrose promoted flowering by inducing florigen gene *** of sucrose levels in the phloem through genetic modifications,such as the overexpression of the vacuolar invertase OsVIN2 or the mutation of OsSUT2,a sucrose transporter,delayed *** of relative transcript levels of floral regulatory genes showed that sucrose activated Ehd1 upstream of the florigen,with no significant effect on the expression of other upstream *** of protein stability after sucrose treatment of major floral repressors revealed that the Ghd7 protein was specifically *** Ghd7 protein interacted with the E3 ligase IPA INTERACTING PROTEIN1(IPI1),and sucrose-induced K48-linked polyubiquitination of Ghd7 via IPI1,leading to protein *** defective in IPI1 delayed flowering,confirming its role in modulating proteins involved in *** conclude that sucrose acts as a signaling molecule to induce flowering by promoting Ghd7 degradation via IPI1.

关键词： flowering time Ghd7 IPI1 K48-linked poly-ubiquitination rice sucrose

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Evaluation of esophageal function in patients with esophageal motor abnormalities using multichannel intraluminal impedance esophageal manometry

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World Journal of Gastroenterology 2006年第39期12卷 6349-6354页

作者： Yu Kyung cho Myung-Gyu choi Jae Myung Park Jung Hwan Oh Chang Nyol Paik Joon wook Lee In Seok Lee Sang woo Kim In-Sik Chung Division of Gastroenterology Department of Internal Medicine The Catholic University of Korea Seoul Korea

AIM: To evaluate the functional aspect of esophageal motility in healthy subjects and in patients who were referred for esophageal function testing using multichannel intraluminal impedance-esophageal manometry (MII-EM), and to assess the clinical utility of MII-EM. METHODS: From September 2003 to January 2004, we performed the MII-EM on healthy volunteers and all the patients who were referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. We analyzed the results, the impedance and the manometric findings. Some of the subjects had additional ambulatory 24-h pH study performed to diagnose gastroesophageal reflux disease (GERD). RESULTS: Among 89 studied subjects, the MII-EM findings showed normal esophageal motility in 50 (56.17%), ineffective esophageal motility (IEM) in 17 (19.10%), nutcracker esophagus in 7 (7.86%), achalasia in 4 (4.49%), and scleroderma esophagus in 11 (12.35%) cases. The completeness and the speed of bolus transit were in the order of nutcracker esophagus, normal manometry and IEM. Some of the swallows showing normal manometry and IEM had incomplete transit. In the achalasia and scleroderma esophagus, almost all the swallows had incomplete transit. The body amplitudes were higher for the swallows with complete transit than for the swallows with incomplete transit. There was not a significant difference in the manometric and impedance findings between the subjects with and without GERD. CONCLUSION: MII-EM is a useful tool in assessing theesophageal function in the patients having esophageal motility abnormality. The primary factors influencing the bolus transit are the amplitude of the esophageal body and normal peristalsis.

关键词： Impedance manometry Esophageal function Motility Bolus transit

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Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement:A systematic review and meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2024年第6期23卷 559-565页

作者： Min Kyu Kim Jin Ho choi In Rae cho Sang Hyub Lee Ji Kon Ryu Yong-Tae Kim woo Hyun Paik Department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Internal Medicine Liver Research InstituteSeoul National University HospitalSeoul National University College of MedicineSeoulKorea

Background:The efficacy of adjuvant treatment(AT)in ampullary cancer(AmC)remains *** systematic review and meta-analysis aimed to evaluate the role of AT for *** sources:A comprehensive systematic search was performed in PubMed,EMBASE,Cochrane Library,and Web of Science *** comparing overall survival(OS)and recurrence-free survival(RFS)of patients who underwent AT or not following AmC resection were ***:A total of 3971 patients in 21 studies were *** pooled data showed no significant difference in effect on the OS by AT[hazard ratio(HR)=0.998,95%confidence interval(CI):0.768–1.297].No significant difference in recurrence between the AT and non-AT(nAT)groups was noted(HR=1.158,95%CI:0.764–1.755).In subgroup analysis,patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC(HR=0.627,95%CI:0.451–0.870).Neither AT consisted of adjuvant chemotherapy with radiotherapy(HR=0.804,95%CI:0.563–1.149)nor AT with adjuvant chemotherapy(HR=0.883,95%CI:0.642–1.214)showed any significant effect on the ***:The effect of AT in AmC on survival and recurrence did not show a significant ***,effectiveness according to AT strategies did not show enhancement in *** had an advantage in survival compared with nAT strategy in nodal-positive *** cases of AmC with positive lymph nodal involvement,AT may be warranted regardless of detailed strategies.

关键词： Ampulla of Vater Adjuvant chemotherapy Adjuvant chemoradiotherapy Meta-analysis

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Effect of focal laser photocoagulation in eyes with mild to moderate non-proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2016年第10期9卷 1439-1443页

作者： Seong Hun Jeong Jung Il Han Sung Won cho Dong Won Lee Chul Gu Kim Tae Gon Lee Jong woo Kim Department of Ophthalmology Kim's Eye HospitalMyung-Gok Eye Research InstituteKonyang University College of Medicine

AIM：To report the effect of focal laser photocoagulation on both the severity of hard exudates（HEs） and the rate of disease progression in eyes with mild to moderate non-proliferative diabetic retinopathy（NPDR）.METHODS： We retrospectively reviewed the medical records of 33 patients（60 eyes） who had been diagnosed with mild to moderate NPDR between January 2006 and December *** patients were divided into 2 groups：Group A（38 eyes in 20 patients treated using focal laser photocoagulation） and Group B（treated without laser photocoagulation）.We also reviewed the best corrected visual acuity measurements,and the fundus photographs taken at both baseline and follow-up visits. RESULTS： In Group A,HE severity grade had decreased significantly from baseline to the final visit（P 〈0.05）,but this was not the case in Group B（P =0.662）.The cumulative probabilities of retinopathy progression at 5y were 26% in Group A and 30% in Group *** survival curves showed no significant difference between the groups with regard to retinopathy progression（P =0.805）.CONCLUSION： Focal laser photocoagulation reduced the levels of HEs in eyes with mild to moderate ***,the treatment was not able to decelerate the progression of DR.

关键词： focal laser diabetic retinopathy retina non-proliferative diabetic retinopathy

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A conformal titanyl phosphate amorphous overlayer for enhancing photoelectrochemical hydrogen peroxide production

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Journal of Energy Chemistry 2023年第11期86卷 399-408,I0009页

作者： Jaekyum Kim Young Eun Kim Minyeong Je Won Tae Hong Chang-Lyoul Lee Tae-Hoon Kim Sung Min cho Chang Hyuck choi Heechae choi woo-Seok choe Jung Kyu Kim School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Theoretical Materials&Chemistry Group Institute of Inorganic ChemistryUniversity of CologneGreinstr.650939CologneGermany Advanced Photonics Research Institute(APRI) Gwangju Institute of Science and Technology(GIST)Gwangju 61005Republic of Korea Department of Materials Science and Engineering Chonnam National UniversityGwangju 61186Republic of Korea Department of Chemistry Pohang University of Science and Technology(POSTECH)Pohang 37673Republic of Korea Institute for Convergence Research and Education in Advanced Technology(I-CREATE) Yonsei UniversitySeoul 03722Republic of Korea Department of Chemistry Xi’an Jiaotong-Liverpool UniversitySuzhou 215123JiangsuChina

Photoelectrochemical(PEC)H_(2)O_(2)production through water oxidation reaction(WOR)is a promising strategy,however,designing highly efficient and selective photoanode materials remains challenging due to competitive reaction ***,for highly enhanced PEC H_(2)O_(2)production,we present a conformal amorphous titanyl phosphate(a-TP)overlayer on nanoparticulate TiO_(2)surfaces,achieved via lysozyme-molded in-situ surface *** a-TP overlayer modulates surface adsorption energies for reaction intermediates,favoring WOR for H_(2)O_(2)production over the competing O_(2)evolution *** density functional theory calculations reveal that a-TP/TiO_(2)exhibits a substantial energy uphill for the O·*formation pathway,which disfavors O_(2)evolution but promotes H_(2)O_(2)***,the a-TP overlayer strengthens the built-in electric field,resulting in favorable ***,a-TP/TiO_(2)exhibits 3.7-fold higher Faraday efficiency(FE)of 63%at 1.76 V *** hydrogen electrode(RHE)under 1 sun illumination,compared to bare TiO_(2)(17%),representing the highest FE among TiO_(2)-based WOR H_(2)O_(2)production *** the a-TP overlayer constitutes a promising strategy for controlling reaction pathways and achieving efficient solar-to-chemical energy conversion.

关键词： Solar H_(2)O_(2) production In-situ surface reforming Titanyl phosphate Amorphous overlayer Reaction pathway control

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Overexpression of S100A4 is closely associated with progression of colorectal cancer

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World Journal of Gastroenterology 2005年第31期11卷 4852-4856页

作者： Yong-Gu cho Chang-Jae Kim Suk-woo Nam Shin-Hee Yoon Sug-Hyung Lee Nam-Jin Yoo Jung-Young Lee Won-Sang Park Department of Pathology Department of Physiology

AIM： To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS： A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS： Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 （55.6%） of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 （69.4%） of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes＇ stage and lymph node metastasis. Nuclear staining was also observed in 24 （19.4%） of 124 samples and closely associated with Dukes＇ stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION： Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.

关键词： S100A4 Mutation Immunohistochemistry Colorectal cancer Tumor stage

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Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis

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Acta Pharmaceutica Sinica B 2024年第12期14卷 5451-5463页

作者： Seok-Jun Mun Euni cho woo Jin Gil Seong Jae Kimc Hyo Keun Kim Yu Seong Ham Chul-Su Yang Department of Bionano Engineering Hanyang UniversitySeoul 04673Republic of Korea Center for Bionano Intelligence Education and Research Ansan 15588Republic of Korea Department of Molecular and Life Science Hanyang UniversityAnsan 15588Republic of Korea Department of Medicinal and Life Science Hanyang UniversityAnsan 15588Republic of Korea

The pathophysiology of sepsis is characterized by a systemic inflammatory response to infec-tion;however,the cytokine blockade that targets a specific early inflammatory mediator,such as tumor necrosis factor,has shown disappointing results in clinical *** sepsis,excessive endotoxins are internalized into the cytoplasm of immune cells,resulting in dysregulated pyroptotic cell death,which induces the leakage of late mediator alarmins such as HMGB1 and *** late mediators of lethal sepsis,overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE re-ceptors,thereby amplifying inflammation during early-stage *** this study,we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide(TMR peptide)derived from the HMGB1/PTX3-receptors interacting *** TMR peptide successfully attenuated HMGB1/PTX3-and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and ***,we developed TMR peptide-conjugated liposomes(TMR-Lipo)to improve the peptide *** combination therapy,moderately antibiotic-loaded TMR-Lipo demon-strated a significant therapeutic effect in a mouse model of cecal ligation-and puncture-induced *** identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.

关键词： Sepsis High mobility group box 1 Pentraxin 3 Liposome Antibiotics

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