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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus

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World Journal of Gastroenterology 2016年第46期22卷 10131-10139页

作者： Kyung Sik Park Kwang Bum Cho Il Seon Hwang Jae Hyung Park Byung Ik Jang Kyeong Ok Kim Sung Woo Jeon Eun Soo Kim Chang Sik Park joong goo kwon Department of Internal Medicine Keimyung University School of Medicine Department of Pathology Keimyung University School of Medicine Department of Physiology Keimyung University School of Medicine Department of Internal Medicine Youngnam University College of Medicine Department of Internal Medicine Kyungpook National University School of Medicine Department of Advanced Materials Convergence Korea Institute of Ceramic Engineering and Technology Department of Internal Medicine Catholic University of Daegu School of Medicine

AIM To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus(DM).METHODS Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5(PGP9.5), neuronal nitric oxide synthase(n NOS), vasoactive intestinal peptide(VIP), neurokinin-1(NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha,(PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also conducted.RESULTS Twenty-six controls and 35 diabetic patients(21 shortduration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index(BMI)(higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group(P < 0.01). On immunohistochemical staining, c-Kit- and PDGFRα-positive immunoreactivity were significantly decreased in the DM group compared with the control group(P < 0.05). There were no statistically significant differences in PGP9.5, n NOS, VIP, and neurokinin 1 expression. On immunofluorescent staining, cellularity of interstitial cells of Cajal(ICC) was observed to decrease with increasing duration of DM.CONCLUSION Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

关键词：糖尿病 mellitus Cajal 的空隙的房间像成纤维细胞的房间 Gastroparesis 伤寒神经系统

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Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

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World Journal of Gastroenterology 2022年第44期28卷 6294-6309页

作者： Kang Nyeong Lee Oh Young Lee Hoon Jai Chun Jin Il Kim Sung Kook Kim Sang Woo Lee Kyung Sik Park Kook Lae Lee Suck Chei Choi Jae-Young Jang Gwang Ha Kim In-kyung Sung Moo In Park joong goo kwon Nayoung Kim Jae Jun Kim Soo Teik Lee Hyun Soo Kim Ki Bae Kim Yong Chan Lee Myung-Gyu Choi Joon Seong Lee Hwoon-Yong Jung Kwang Jae Lee Jie-Hyun Kim Hyunsoo Chung Department of Internal Medicine Hanyang University College of MedicineSeoul 04763South Korea Department of Internal Medicine Korea University Anam HospitalSeoul 02841South Korea Department of Internal Medicine The Catholic University of KoreaYeouido ST.Mary’s HospitalSeoul 07260South Korea Department of Internal Medicine Kyungpook National University HospitalDaegu 41944South Korea Department of Internal Medicine Korea University Ansan HospitalAnsan-si 15355South Korea Department of Internal Medicine Keimyung University Dongsan HospitalDaegu 42601South Korea Department of Internal Medicine Seoul Metropolitan Government Seoul National University Boramae Medical CenterSeoul 07061South Korea Department of Internal Medicine Wonkwang University HospitalIksan 54538South Korea Department of Internal Medicine KyungHee University Medical CenterSeoul 02447South Korea Department of Internal Medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 47241South Korea Department of Internal Medicine KKonkuk University Medical CenterSeoul 05030South Korea Department of Internal Medicine Kosin University Gaspel HospitalBusan 49267South Korea Department of Internal Medicine Daegu Catholic University Medical CenterDaegu 42471South Korea Department of Internal Medicine Seoul National University Bundang HospitalSeongnam-si 13620Gyeonggi-doSouth Korea Department of Internal Medicine Samsung Medical CenterSeoul 06351South Korea Department of Internal Medicine Chonbuk National University HospitalJeonju-si 54907South Korea Department of Internal Medicine Chonnam National University HospitalGwangju 61469South Korea Department of Internal medicine Chungbuk National University School of MedicineCheong Ju 28644South Korea Department of Internal Medicine Severance HospitalSeoul 03722South Korea Department of Internal Medicine The Catholic University of KoreaSeoul ST.Mary’s HospitalSeoul 06591South Korea Digestive Disease Center Soon

BACKGROUND Fexuprazan,a novel potassium-competitive acid blocker,reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells.Fexuprazan’s suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.AIM To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis(EE).METHODS Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks.The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8.The secondary endpoints included the healing rate of EE at week 4,symptom response,and quality of life assessment.Safety profiles and serum gastrin levels were compared between the groups.RESULTS Of the 263 randomized,218 completed the study per protocol(fexuprazan 40 mg,n=107;esomeprazole 40 mg,n=111).Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8[99.1%(106/107)vs 99.1%(110/111)].There were no between-group differences in the EE healing rate at week 4[90.3%(93/103)vs 88.5%(92/104)],symptom responses,and quality of life assessments.Additionally,serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.CONCLUSION Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8.We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

关键词： Gastroesophageal reflux Esophagitis Proton pump inhibitors Heartburn Quality of life

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Predictors and prognostic impact of post-operative atrial fibrillation in patients with hip fracture surgery

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World Journal of Clinical Cases 2022年第11期10卷 3379-3388页

作者： Seong Jun Bae Chang Hee kwon Tae-Young Kim Haseong Chang Bum Sung Kim Sung Hea Kim Hyun-joong Kim Department of Internal Medicine Konkuk University Medical CenterSeoul 05030South Korea Department of Orthopaedic Surgery Konkuk University Medical CenterSeoul 05030South Korea

BACKGROUND Atrial fibrillation(AF)is the most common arrhythmia developing in postoperative patients.Limited data are available regarding pre-operative risk factors and prognostic impact of post-operative AF(POAF)following hip fracture surgery(HFS)in Korean population.AIM We aimed to investigate the incidence,predictors,and hospital prognosis of POAF in HFS patients.METHODS This study included 245 patients without history of AF who underwent HFS between August 2014 and November 2016.POAF was defined as new-onset AF that occurred during hospitalization after HFS.RESULTS Twenty patients(8.2%)experienced POAF after HFS.POAF developed on median post-operative day 2(interquartile range,1–3).Multivariable logistic regression analysis showed that age[odds ratio(OR),1.111;95%confidence interval(CI),1.022–1.209],chronic obstructive pulmonary disease(COPD)(OR,6.352;95%CI,1.561–25.841)and E/e’ratio(OR,1.174;95%CI,1.002–1.376)were significant predictors of POAF.Patients with POAF had a significantly higher intensive care unit admission rate(55.0%vs 14.7%,P<0.001)and incidence of congestive heart failure(45.0%vs 10.7%,P<0.001).In multivariable logistic regression analysis,POAF was significantly associated with increased incidence of congestive heart failure(OR,4.856;95%CI,1.437–16.411)and intensive care unit admission(OR,6.615;95%CI,2.112–20.718).CONCLUSION POAF was frequently developed in elderly patients following HFS.Age,COPD and elevated E/e’ratio were found as significant predictors of POAF in HFS patients.Patients with POAF significantly experienced intensive care unit admission and incident congestive heart failure during hospitalization.

关键词： Atrial fibrillation Post-operative Predictor Prognosis Hip fracture surgery

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Scratch formation and its mechanism in chemical mechanical planarization (CMP)

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Friction 2013年第4期1卷 279-305页

作者： Tae-Young kwon Manivannan RAMACHANDRAN Jin-goo PARK Department of Materials Engineering Hanyang UniversityAnsan 426-791Korea

Chemical mechanical planarization(CMP)has become one of the most critical processes in semiconductor device fabrication to achieve global planarization.To achieve an efficient global planarization for device node dimensions of less than 32 nm,a comprehensive understanding of the physical,chemical,and tribo-mechanical/chemical action at the interface between the pad and wafer in the presence of a slurry medium is essential.During the CMP process,some issues such as film delamination,scratching,dishing,erosion,and corrosion can generate defects which can adversely affect the yield and reliability.In this article,an overview of material removal mechanism of CMP process,investigation of the scratch formation behavior based on polishing process conditions and consumables,scratch formation mechanism and the scratch inspection tools were extensively reviewed.The advantages of adopting the filtration unit and the jet spraying of water to reduce the scratch formation have been reviewed.The current research trends in the scratch formation,based on modeling perspective were also discussed.

关键词： Chemical mechanical planarization(CMP) defects,scratch post-CMP cleaning defect source

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Caenorhabditis elegans deep lipidome profiling by using integrative mass spectrometry acquisitions reveals significantly altered lipid networks

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Journal of Pharmaceutical Analysis 2022年第5期12卷 743-754页

作者： Nguyen Hoang Anh Young Cheol Yoon Young Jin Min Nguyen Phuoc Long Cheol Woon Jung Sun Jo Kim Suk Won Kim Eun goo Lee Daijie Wang Xiao Wang Sung Won kwon College of Pharmacy Seoul National UniversitySeoul08826Republic of Korea School of Pharmaceutical Sciences Shandong Analysis and Test CenterQilu University of Technology(Shandong Academy of Sciences)Jinan250014China Biological Engineering Technology Innovation Center of Shandong Province Heze Branch of Qilu University of Technology(Shandong Academy of Sciences)HezeShandong274000China

Lipidomics coverage improvement is essential for functional lipid and pathway construction.A powerful approach to discovering organism lipidome is to combine various data acquisitions,such as full scan mass spectrometry(full MS),data-dependent acquisition(DDA),and data-independent acquisition(DIA).Caenorhabditis elegans(C.elegans)is a useful model for discovering toxic-induced metabolism,highthroughput drug screening,and a variety of human disease pathways.To determine the lipidome of C.elegans and investigate lipid disruption from the molecular level to the system biology level,we used integrative data acquisition.The methyl-tert-butyl ether method was used to extract L4 stage C.elegans after exposure to triclosan(TCS),perfluorooctanoic acid,and nanopolystyrene(nPS).Full MS,DDA,and DIA integrations were performed to comprehensively profile the C.elegans lipidome by Q-Exactive Plus MS.All annotated lipids were then analyzed using lipid ontology and pathway analysis.We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways.The biological investigations revealed that when C.elegans were exposed to nPS,lipid droplets were disrupted,whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group.The nPS treatment caused a significant disruption in lipid storage.Triacylglycerol,glycerophospholipid,and ether class lipids were those primarily hindered by toxicants.Finally,toxicant exposure frequently involved numerous lipid-related pathways,including the phosphoinositide 3-kinase/protein kinase B pathway.In conclusion,an integrative data acquisition strategy was used to characterize the C.elegans lipidome,providing valuable biological insights into hypothesis generation and validation.

关键词： Caenorhabditis elegans Lipidomics Data-dependent acquisition Data-independent acquisition

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Optimal rotor wear design in hypotrochoidal gear pump using genetic algorithm

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Journal of Central South University 2011年第3期18卷 718-725页

作者： kwon Soon-man KIM Chang-Hyun SHIN joong-ho Department of Mechanical Design and Manufacturing Engineering Changwon National University

The wear rate between the rotors of a hypotrochoidal gear pump is characterized.Using the knowledge of shape design on the rotors,the contact stresses without hydrodynamic effect between the rotor teeth were evaluated through the calculation of the Hertzian contact stress.Based on the above results and the sliding velocity between the rotors,a genetic algorithm (GA) was used as an optimization technique forminimizing the wear rate proportional factor (WRPF).The result shows that the wear rate or the WRPF can be reduced considerably,e.***.approximately 12.8%,throughout the optimization using GA.

关键词：遗传算法形状设计磨损率齿轮泵转子 GA优化水动力作用接触应力

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Clinical advantages of single port laparoscopic hepatectomy

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World Journal of Gastroenterology 2018年第3期24卷 379-386页

作者： Jae Hyun Han Young Kyoung You Ho joong Choi Tae Ho Hong Dong goo Kim Division of Hepatobiliary-Pancreas Surgery and Liver Transplantation Department of SurgerySeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of Korea

AIM To evaluate the clinical advantages of single-port laparoscopic hepatectomy(SPLH) compare to multiport laparoscopic hepatectomy(MPLH).METHODS We retrospectively reviewed the medical records of 246 patients who underwent laparoscopic liver resection between January 2008 and December 2015 at our hospital. We divided the surgical technique into two groups; SPLH and MPLH. We performed laparoscopic liver resection for both benign and malignant disease. Major hepatectomy such as right and left hepatectomy was also done with sufficient disease-free margin. The operative time, the volume of blood loss, transfusion rate, and the conversion rate to MPLH or open surgery was evaluated. The post-operative parameters included the meal start date after operation, the number of postoperative days spent in the hospital, and surgical complications was also evaluated.RESULTS Of the 246 patients, 155 patients underwent SPLH and 91 patients underwent MPLH. Conversion rate was 22.6% in SPLH and 19.8% in MPLH(P = 0.358). We performed major hepatectomy, which was defined as resection of more than 2 sections, in 13.5% of patients in the SPLH group and in 13.3% of patients in the MPLH group(P = 0.962). Mean operative timewas 136.9 ± 89.2 min in the SPLH group and 231.2 ± 149.7 min in the MPLH group(P < 0.001). The amount of blood loss was 385.1 ± 409.3 m L in the SPLH group and 559.9 ± 624.9 m L in the MPLH group(P = 0.016). The safety resection margin did not show a significant difference(0.84 ± 0.84 cm in SPLH vs 1.04 ± 1.22 cm in MPLH, P = 0.704). Enteral feeding was started earlier in the SPLH group(1.06 ± 0.27 d after operation) than in the MPLH group(1.63 ± 1.27 d)(P < 0.001). The mean hospital stay after operation was non-significantly shorter in the SPLH group than in the MPLH group(7.82 ± 2.79 d vs 7.97 ± 3.69 d, P = 0.744). The complication rate was not significantly different(P = 0.397) and there was no major perioperative complication or mortality case in both groups. CONCLUSION Single-port laparoscopic liver surgery seems

关键词： Hepatectomy Laparoscopy Minimally invasive surgery Treatment outcome Feasibility study

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Kinematical system of breadth cam profile design

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Journal of Central South University 2011年第2期18卷 451-457页

作者： SHIN joong-ho 李琳 YANG Hyun-dai kwon Soon-man Department of Mechanical Design & Manufacturing Changwon National University

The design solutions for breadth cam mechanism was presented. The main topics of the shape design for breadth cam was to calculate the coordinate at each contact point to determine the cam profile. The proposed method according to velocity and geometric relationships of instant velocity centers can easily determine each contact point at any instant moment. The cam profile was defined by contouring of the contact points. And also a program was developed by using Microsoft Visual C++ program,which can quickly and easily draw a 2D cam profile through the displacement diagram. Finally,the program was used to confirm the accuracy on the breadth cam profile design by computer animation graphically.

关键词：轮廓设计凸轮机构运动学 Microsoft 系统凸轮轮廓即时速度外形设计

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Comparative long-term outcomes for pancreatic volume change, nutritional status, and incidence of new-onset diabetes between pancreatogastrostomy and pancreatojejunostomy after pancreaticoduodenectomy

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Hepatobiliary Surgery and Nutrition 2020年第3期9卷 284-295页

作者： Bong Jun Kwak Ho joong Choi Young Kyoung You Dong goo Kim Tae Ho Hong Department of Hepatobiliary and Pancreas Surgery Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea

Background:The difference in volume change in a pancreatic remnant according to the type of pancreaticoenterostomy after pancreaticoduodenectomy(PD)for long-term follow-up is unknown.Also,there are few studies that evaluate the difference in general nutritional status and pancreatic endocrine function,including new-onset diabetes mellitus(NODM)depending on the type of pancreaticoenterostomy.This study aimed to compare serial pancreatic volume changes in pancreatic remnants between pancreatogastrostomy(PG)and pancreatojejunostomy(PJ)after PD and to evaluate the difference in general nutritional status and incidence of NODM between PG and PJ.Methods:This study enrolled 115 patients who had survived for more than 3 years after PD.They were divided into the PG group and the PJ group.Their clinicopathologic factors were collected and analyzed.We calculated serial pancreas volume and pancreatic duct size precisely from preoperative stage to 5 years after surgery by image-processing software specifically designed for navigation and visualization of multimodality and multidimensional images.Consecutive changes of albumin and body mass index(BMI)as related to general nutritional status were compared between the PG and PJ groups.To evaluate the incidence and risk factors of NODM following PD,subgroup analysis was performed in 88 patients who did not have diabetes preoperatively.Results:Most patient demographics were not significantly different between the PG group(n=45)and PJ group(n=70).There was no significant difference in volume reduction between the groups from postoperative 1 month to 5 years(PG group?18.21±14.66 mL versus PJ group?14.43±13.05 mL,P=0.209).But there was a significant difference in increased pancreatic duct size between the groups from postoperative 1 month to 5 years(PG group 1.66±2.20 mm versus PJ group 0.54±1.54 mm,P=0.007).There was no significant difference in the increase of total serum albumin between the groups for 5 years after surgery(PG group 0.51±0.47 g/dL,14.3%versus PJ group 0.42±0.60 g/d

关键词： Pancreaticojejunostomy pancreaticoduodenectomy(PD) nutritional status diabetes mellitus

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