Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death

Lee Ga-Eun,Bang Geul,Byun Jiin,Lee Cheol-Jung,Chen Weidong,Jeung Dohyun,An Hyun-Jung,Kang Han Chang,Lee Joo Young,Lee Hye Suk,Hong Young-Soo,Kim Dae Joon,Keniry Megan,Kim Jin Young,Choi Jin-Sung,Fanto 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins and chromatin DNA. This interaction maintains a balance between the outward force exerted by tightly packed DNA and the inward constraining force, thereby preserving INM integrity. Under endoplasmic reticulum (ER) stress, aberrant cleavage of CREB3-FL at the INM leads to abnormal accumulation of the cleaved form of CREB3 (CREB3-CF). This accumulation disrupts the attachment of CREB3-FL to the INM, resulting in sudden rupture of the nuclear membrane and the onset of karyoptosis. Proteomic studies revealed that CREB3-CF overexpression induces a DNA damage response akin to that caused by UVB irradiation, which is associated with cellular senescence in cancer cells. These findings demonstrated that the dysregulation of CREB3-FL cleavage is a key factor in karyoptotic cell death. Consequently, these findings suggest new therapeutic strategies in cancer treatment that exploit the process of karyoptosis.

The Comparison of Endoscopic Biliary Drainage in Malignant Hilar Obstruction by Cholangiocarcinoma: Bilateral Metal Stents versus Multiple Plastic Stents

( Jun Young Kim ),( Sang-geul Lee ),( Danbee Kang ),( Dong Kyu Lee ),( Joo Kyung Park ),( Kyu Taek Lee ),( Jong Kyun Lee ),( Kwang Hyuck Lee ) 대한간학회 2021 Gut and Liver Vol.15 No.6

Background/Aims: For the management of hilar malignant biliary obstruction (HMBO), endoscopic biliary drainage (EBD) is preferred over percutaneous transhepatic biliary drainage (PTBD) because of its convenience. However, there is no established guideline for malignant hilar obstruction that requires multiple stenting. In this study, we compared the efficacy of bilateral metal stents (BMS) versus multiple plastic stents (MPS). Methods: In this retrospective study, we analyzed 102 patients who underwent EBD with either BMS or MPS due to HMBO caused by hilar cholangiocarcinoma between 1996 and 2018 at Samsung Medical Center. We compared the successful drainage rates, cholangitis events, overall complications, mortality, and conversion rates to PTBD between the two groups. Results: The successful drainage rates in the BMS group and the MPS group were 71.4% (25/35) and 65.6% (44/67), respectively, with no significant difference. The MPS group had a higher cholangitis risk (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.21 to 3.58) and higher 6-month mortality (HR, 2.91; 95% CI, 1.26 to 6.71) than the BMS group. There were no significant differences in overall complications or the conversion rate to PTBD between the groups. Conclusions: In patients with malignant HMBO, the BMS group showed better outcomes in terms of the cholangitis rate and 6-month mortality than the MPS group. Therefore, if possible, bilateral metal stenting is recommended for HMBO caused by hilar cholangiocarcinoma. (Gut Liver 2021;15:922-929)

Composite Phase-Change Material Mold for Cost-Effective Production of Free-Form Concrete Panels

Lee, Donghoon,Lee, Soon-Geul,Kim, Sunkuk American Society of Civil Engineers 2017 Journal of construction engineering and management Vol.143 No.6

<P>Because free-form concrete panels are cast in different shapes depending on the part, the mold to produce these panels must vary by size and shape, making it difficult to reuse the mold. In addition, manufacturing a curve-shaped mold is difficult and requires a lot of labor. To solve this problem, a technology to manufacture molds made of phase-changing materials (PCMs) that can be semipermanently reused to produce various types of curved shapes was developed. However, because of the characteristics of the PCM mold materials, crystallization occurs within the mold, which increases cooling times and causes deformation in the mold due to shrinkage. This paper describe the development of a composite phase-changing material mold for quality production of free-form concrete panels, and this composite is used to solve the problems mentioned previously. The composite PCM mold developed herein does not induce crystallization, which reduces the cooling energy and cooling time by 50% or more, and improves the solidification shrinkage rate to 95% or better. The composite described in this paper will help increase the productivity of free-form concrete members and reduce production costs. (C) 2017 American Society of Civil Engineers.</P>

Cyclic Structural Transformations from Crystalline to Crystalline to Amorphous Phases and Magnetic Properties of a Mn(II)-Based Metal-Organic Framework

Lee, Han Geul,Jo, Hyuna,Eom, Sunhwi,Kang, Dong Won,Kang, Minjung,Hilgar, Jeremy,Rinehart, Jeffrey D.,Moon, Dohyun,Hong, Chang Seop The American Chemical Society 2018 CRYSTAL GROWTH AND DESIGN Vol.18 No.6

<P>A three-dimensional Mn(II) framework, [Mn<SUB>2</SUB>(H<SUB>2</SUB>L)(L)<SUB>0.5</SUB>(MeOH)(DEF)]·0.1MeOH·0.1DEF·1.4H<SUB>2</SUB>O (<B>1</B>; H<SUB>4</SUB>L = 2,3-dioxido-1,4-benzenedicarboxylic acid), was synthesized under solvothermal conditions in diethylformamide/methanol (DEF/MeOH), where the Mn centers adopt octahedral and unusual pentagonal bipyramidal geometries. The ligand H<SUB>4</SUB>L was subject to deprotonation to create μ<SUB>4</SUB>-H<SUB>2</SUB>L<SUP>2-</SUP> and μ<SUB>6</SUB>-L<SUP>4-</SUP> anionic bridges, leading to the construction of a coordination network. The MeOH exchange process of crystalline <B>1</B> allowed for another crystalline phase (<B>1a</B>), which reversibly returned to the original crystalline state upon resolvation in DEF/MeOH. After evacuation of <B>1a</B>, the amorphous phase <B>1b</B> was irreversibly formed, followed by the restoration of the original phase <B>1</B> upon resolvation in DEF/MeOH. Consequently, this framework underwent cyclic structural transformations from the crystalline (<B>1</B>) to crystalline (<B>1a</B>) to amorphous (<B>1b</B>) and back to crystalline (<B>1</B>) phase, which are unique transformations for soft coordination networks. Magnetic measurements demonstrated that antiferromagnetic interactions were operative between the Mn(II) ions and were effectively mediated by the oxygen moieties of the μ<SUB>6</SUB>-L<SUP>4-</SUP> bridge.</P><P>A three-dimensional Mn(II) metal−organic framework exhibits substantial structural flexibility associated with phase transformations from crystalline to crystalline to amorphous states.</P> [FIG OMISSION]</BR>

Changes in Diagnosis of Poisoning in Patients in the Emergency Room Using Systematic Toxicological Analysis with the National Forensic Service

Lee Je Seop,Cha Yong Sung,Yeon Seonghoon,Kim Tae Youn,Lee Yoonsuk,Choi Jin-Geul,Cha Kyoung-Chul,Lee Kang Hyun,Kim Hyun 대한의학회 2021 Journal of Korean medical science Vol.36 No.18

Background: It is difficult to diagnose patients with poisoning and determine the causative agent in the emergency room. Usually, the diagnosis of such patients is based on their medical history and physical examination findings. We aimed to confirm clinical diagnoses using systematic toxicological analysis (STA) and investigate changes in the diagnosis of poisoning. Methods: The Intoxication Analysis Service was launched in June 2017 at our hospital with the National Forensic Service to diagnose intoxication and identify toxic substances by conducting STA. Data were collected and compared between two time periods: before and after the initiation of the project, i.e., from June 2014 to May 2017 and from June 2017 to May 2020. Results: A total of 492 and 588 patients were enrolled before and after the service, respectively. Among the 588 after-service patients, 446 underwent STA. Among the 492 before-service patients, 69.9% were diagnosed clinically, whereas the causative agent could not be identified in 35 patients. After starting the service, a diagnosis was confirmed in 84.4% of patients by performing a hospital-available toxicological analysis or STA. Among patients diagnosed with poisoning by toxins identified based on history taking, only 83.6% matched the STA results, whereas 8.4% did not report any toxin, including known substances. The substance that the emergency physician suspected after a physical examination was accurate in 49.3% of cases, and 12% of cases were not actually poisoned. In 13.4% of patients who visited the emergency room owing to poisoning of unknown cause, poisoning could be excluded after STA. Poisoning was determined to be the cause of altered mental status in 31.5% of patients for whom the cause could not be determined in the emergency room. Conclusion: A diagnosis may change depending on the STA results of intoxicated patients. Therefore, appropriate STA can increase the accuracy of diagnosis and help in making treatment decisions.

청소년의 사회자본이 인터넷 사용에 미치는 영향

이영글(Lee Yeong-Geul),김아래미(Kim Ah-Rae-Mi),김주일(Kim Ju-Ill) 한국청소년정책연구원 2011 한국청소년연구 Vol.22 No.3

본 연구는 한국청소년패널 4, 5차년도의 자료를 이용하여 2,300명의 청소년을 연구대상으로 청소년의 인터넷 사용과 사회자본과의 관계를 검증하였다. 분석방법으로는 구조방정식모형을 통하여 변수들의 영향관계를 분석하였고, 잠재평균분석과 집단 간 경로계수 비교를 통하여 성별간의 차이를 분석하였다. 분석결과, 청소년의 사회자본으로서 부모, 교사, 친구와의 사회적 관계수준이 낮을수록 인터넷 사용시간이 증가하였다. 관계목적의 인터넷 사용은 인터넷 사용시간을 증가시켰고, 학습목적의 인터넷 사용은 인터넷 사용시간을 감소시켰다. 인터넷 사용목적은 부모, 교사와의 관계와 인터넷 사용시간의 관계를 매개하는 효과를 보여주었다. 여자청소년에 비하여 남자청소년의 인터넷 사용시간이 더 많았고, 사회적 자본수준은 더 낮았다. 남자청소년의 경우, 친구와의 관계와 관계목적의 인터넷 사용에서 정적인 관계가 나타났다. This study examined the impact of social capital on adolescent Internet use. More specifically, this study examined the application of a longitudinal model regarding social capital in terms of relationships with parents, teachers and friends, and Internet use in terms of purposes of and hours of Internet use. A sample of 2,300 adolescents taken from the two-wave data of Korean Youth Panel Surveys was used. Structural equation modeling was first employed to examine the longitudinal model regarding the relationships between social capital and Internet use among Korean adolescents. Next, a latent mean difference score model was tested to check if there were significant differences between males and females in terms of both social capital and Internet use. Lastly, in order to investigate the effects of gender upon the relationships between social capital and adolescent Internet use, the longitudinal model across gender was examined. The longitudinal model degree of fit in regards to the data was good; (χ²=1145.44, p<.000, CFI=.930, TLI=.912, RMSEA=.067) and several significant relationships between social capital and Internet use among Korean adolescents were found. These findings highlight the important relationships between social capital and Internet use among Korean adolescents. The implications of this study and the application of these findings for establishing a guideline for adolescent Internet use was also discussed.

Comparison of Long-Term Outcome for Single Small Hepatocellular Carcinoma between Different Treatment Modalities According to the Size and Tumor Marker

( Sang-geul Lee ),( Dong Hyun Sinn ),( Gye-seong Choi ),( Jong Man Kim ),( Tae Wook Kang ),( Min Woo Lee ),( Dongho Hyun ),( Wonseok Kang ),( Geum-youn Gwak ),( Yong-han Paik ),( Moon Seok Choi ),( Jo 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: For single small hepatocellular carcinoma (HCC), different therapeutic modalities can be tried for patients with preserved liver function. We aim to identify prognostic factors associated with overall survival, that can be used to guide treatment selection. Methods: Between 2010 and 2013, we analyzed 896 patients who received resection, radiofrequency (RF) ablation or transarterial chemoembolization (TACE) as a first-line therapy for single, small (<3cm) HCC. We first identified risk factors associated overall survival in patients who were treated with RF ablation, and then compared long-term outcome according treatment modalities, stratified based on risk factors. Results: Among 425 patients treated with RF ablation, tumor size and PIVKA-II levels were independent factors associated with overall survival. When patients were stratified according to the tumor size and PIVKA-II levels, overall survival of patients treated with RF ablation was significantly different by subgroups (group 1: tumor sized = 2 cm with low PIVKA-II levels (< 30 mAU/ml); group 2: tumor sized 2-3 cm with low PIVKA-II levels (< 30 mAU/ml) or tumor sized = 2 cm with elevated PIVKA-II levels (= 30 mAU/ml); group 3: tumor sized 2-3cm with elevated PIVKA-II levels (= 30 mAU/ml)). When compared to resection, overall survival of those treated with RF ablation was not different to those who received resection in group 1 or group 2, but was significantly lower in group 3. When compared to TACE, those treated with RF ablation showed better survival in group 1 or group 2, but was not different in group 3. Conclusions: Tumor size and PIVKA-II levels were associated with overall survival of patients treated with RF ablation. When patients were stratified according to tumor size and PIVKA-II levels, different long-term outcome by treatment modalities was observed. Our data suggests that these two factors can be a valuable factors in choosing first-line treatment option for single small HCC.

[Ⅰ. WelcomeMessages] Organizing Chair

Soon-Geul Lee 제어로봇시스템학회 2016 제어로봇시스템학회 국제학술대회 논문집 Vol.2016 No.10

Mobility Improvement of P3HT Thin Film by High-Voltage Electrostatic Field-Assisted Crystallization

Soon-Won Lee,김철현,Sang-Geul Lee,정준호,최준혁,이응숙 대한금속·재료학회 2013 ELECTRONIC MATERIALS LETTERS Vol.9 No.4

High-temperature annealing, assisted by the in-plane application of a high-voltage electric field, was used to form thin films of poly(3-hexylthiophene) (P3HT), boasting increased crystallite size and enhanced charge mobility. In-plane crystallite growth and surface morphology were characterized by atomic force microscopy. X-ray diffraction analyses showed that the application of an electric field decreased film thickness and increased the dimensions of the crystalline domains by 25.6% during subsequent high-temperature annealing. Crystalline domains were 13.4% larger, and exhibited 70% higher mobility, than those obtained with thermal annealing in the absence of an electric field.

접촉 반력을 이용한 4족 보행로봇의 경사면 감저 및 보행 알고리즘

이순걸(Soon-Geul Lee) Korean Society for Precision Engineering 1999 한국정밀공학회지 Vol.16 No.4