치과용 임플란트로서의 지르코니아의 골적합성을 증가시키기 위한 졸 젤 법을 활용한 하이드록시아파타이트 코팅

학위논문(박사) -- 서울대학교대학원 : 공과대학 재료공학부, 2021.8. 김진영.다양한 이유로 상실되는 치아를 대체하기 위한 치과용 임플란트는 널리 사용되고 있는 경조직 임플란트이다. 치과용 임플란트로 가장 널리 사용되는 재료는 티타늄(Ti)으로 우수한 강도와 생체 친화성을 장점으로 가지고 있다. 하지만 이 티타늄은 금속 특유의 광채를 갖는 표면 때문에 심미적으로 거부감을 갖을 수 있으며, 금속에서의 비특이적 면역 반응과 침 등의 생체 물질에 의한 부식 등이 문제가 되고 있다. 한편 지르코니아는 우수한 기계적 물성과 미적 효과와 부식과 면역 반응에서 자유롭다는 점에서 최근 새로운 치과용 임플란트 소재로 주목 받고있다. 하지만 지르코니아는 상대적으로 낮은 골적합성을 가지고 있다는 단점이 존재한다. 하이드록시아파타이트는 인체 뼈의 대표적인 구성 물질로 체내에 많이 존재하는 생체 친화성 세라믹이다. 특유의 우수한 생체 친화성 덕분에 수많은 생체 재료의 표면을 코팅하기 위한 재료로 사용되고 있다. 지르코니아의 생체 적합성 향상을 위한 하이드록시아파타이트 (HA) 코팅 관련 연구가 많이 진행되었지만 두꺼운 두께와 고온 소결에서의 부산물 생성 등에 의한 안정성 저하가 문제가 되고 있다. 이 연구에서는 지르코니아의 생체 적합성을 증가시키기 위해 졸-젤법을 이용하여 하이드록시아파타이트를 코팅하고자한다. 졸-젤법을 이용하여 코팅층의 나노 및 마이크로 구조를 변화시켜 생체 적합성을 더욱 더 증진시키고, 소결 온도를 조절하여 부산물이 없는 얇고 안정적인 하이드록시아파타이트 코팅 층을 형성하고자 한다. 먼저 하이드록시아파타이트 코팅층의 표면 구조를 변화시키기 위해 소결온도 및 하이드록시아파타이트 졸의 에이징 시간을 조절하였고, 주사전자현미경 (SEM) 관찰을 통해 표면 구조를 관찰하여 소결온도가 나노 구조에, 에이징 시간이 마이크로 구조에 영향을 끼침을 알았다. 또한 투과전자현미경 (TEM) 관찰을 통해 에이징 시간에 따른 하이드록시아파타이트 졸 내의 입자 크기의 변화를 확인하였고, 이 변화가 코팅층의 마이크로 구조 변화의 원인임을 알 수 있었다. 집속 이온 빔 (FIB)을 통한 두께를 측정하였을 때, 코팅 층은 150 nm 정도, 마이크로 구조를 가지는 부분은 800 nm 정도의 크기를 가짐을 확인하였다. 또한 비접촉 3D 표면 분석을 통해 Ra가 마이크로 구조를 가질 경우 350 nm 정도로 마이크로 구조가 없을 때의 100 nm 정도보다 증가함을 확인하였다. 또한 X-선 회절 분석기 (XRD)와 X-선 광전자 분광법 (XPS)을 통해 소결 온도를 섭씨 800도로 진행했을 때 HA와 지르코니아 이외의 결정상은 없던 반면, 1000도로 진행했을 때 불순물인 칼슘 지르코네이트가 생성된 것을 확인하였다. 코팅층과 지르코니아의 접촉 강도는 Instron을 통한 tensile test로 진행되었고, 약 40 MPa 이상의 값을 가져 치과용 임플란트 응용 분야로 적절하였다. 이런 부분들을 종합하여 섭씨 800도 조건 하에 마이크로 구조의 형성을 조절하여 조골 세포를 통한 세포 실험을 진행하였고, 마이크로 구조를 가지는 경우가 세포 특성이 증가함을 확인하였다. 이를 바탕으로 생체 내 동물 실험을 비교군인 티타늄과 더불어 하이드록시 아파타이트가 코팅된 지르코니아와 지르코니아에 실행한 결과, 지르코니아의 골 적합성이 하이드록시 아파타이트 코팅에 의해 극적으로 향상됨을 입증했으며, 이는 기존 티타늄 임플란트와 비슷한 수준이었다. 이 연구를 통해 하이드록시 아파타이트를 통한 지르코니아의 골적합성 증가를 이뤄낼 수 있었다. 또한 하이드록시아파타이트 졸의 에이징 시간 및 소결 시간을 조절하여 코팅 층의 나노 및 마이크로 구조를 조절할 수 있었으며, 특히 소결 시간을 조절하여 지르코니아와 하이드록시아파타이트의 부산물인 칼슘 지르코네이트의 생성을 억제할 수 있었다. 이를 기반으로 생성한 졸 젤 기반 HA 코팅 지르코니아가 치과용 임플란트 재료로 사용하기에 큰 잠재력을 가지고 있음을 세포 실험 및 생체 내 동물 실험을 통해 입증하였다.Dental implants for replacing teeth lost for various reasons are widely used hard tissue implants. The most widely used material for dental implants is titanium (Ti), which has excellent strength and biocompatibility. However, titanium can have an aesthetic rejection because of its unique shiny surface, and non-specific immune reactions in the metal and corrosion by biomaterials such as saliva are problematic. Meanwhile, zirconia is attracting attention as a new dental implant material in that it is free from corrosion and immune reactions, as well as excellent mechanical properties and aesthetic effects. However, zirconia has a disadvantage in that it has relatively low bone compatibility. Hydroxyapatite is a biocompatible ceramic that exists in a large number of human bones as a representative component of human bone. Due to its unique excellent biocompatibility, it is used as a material for coating the surface of numerous biomaterials. There have been many studies related to hydroxyapatite (HA) coating for improving the biocompatibility of zirconia, but there is a problem with a thick thickness and deterioration of stability due to by-product formation in high-temperature sintering. In this study, to increase the biocompatibility of zirconia, we intend to coat hydroxyapatite using the sol-gel method. The sol-gel method is used to further improve biocompatibility by changing the nano and micro structures of the coating layer, and to form a thin and stable hydroxyapatite coating layer without by-products by controlling the sintering temperature. First, in order to change the surface structure of the hydroxyapatite coating layer, the sintering temperature and the aging time of the hydroxyapatite sol were adjusted, and the surface structure was observed through scanning electron microscope (SEM) observation. It was found to have an effect on the microstructure. In addition, through transmission electron microscopy (TEM) observation, the change in the particle size in the hydroxyapatite sol according to the aging time was confirmed, and this change was found to be the cause of the change in the microstructure of the coating layer. When the thickness was measured through a focused ion beam (FIB), it was confirmed that the coating layer had a size of about 150 nm, and the portion having a microstructure had a size of about 800 nm. In addition, through non-contact 3D surface analysis, it was confirmed that when Ra has a microstructure, it is about 350 nm, which is higher than about 100 nm when there is no microstructure. In addition, when the sintering temperature was 800 oC through X-ray diffraction analyzer (XRD) and X-ray photoelectron spectroscopy (XPS), there was no crystal phase other than HA and zirconia. It was confirmed that was generated. The contact strength between the coating layer and the zirconia was conducted by a tensile test through Instron, and had a value of about 40 MPa or more, which was suitable for dental implant applications. Cell experiments were conducted through osteoblasts by controlling the formation of microstructures under conditions of 800 oC, and it was confirmed that the in vitro cell characteristics increased when the microstructure was formed. Based on this, as a result of conducting in vivo animal experiments on zirconia and zirconia coated with hydroxyapatite along with titanium as a comparative group, it was proved that the bone compatibility of zirconia was dramatically improved by hydroxyapatite coating, which is similar to that of conventional titanium implants. Through this study, it was possible to achieve an increase in the bone compatibility of zirconia through hydroxyapatite. In addition, by controlling the aging time and sintering time of the hydroxyapatite sol, the nano and microstructure of the coating layer could be controlled. In particular, by controlling the sintering time, the formation of calcium zirconate, a by-product of zirconia and hydroxyapatite, could be suppressed. It was proved through in vitro cell experiments and in vivo animal experiments that the sol gel-based HA-coated zirconia produced based on this has great potential for use as a dental implant material.Chapter 1. Introduction 1 1.1. Biomaterials for dental implant 2 1.2. Hydroxyapatite coating for enhacing osseointegration 4 1.3. Issue of hydroxyapatite coating on zirconia Introduction 6 1.3.1. surface modification of hydroxyaptite coating layer 8 1.3.2. limitation of hydroxyapatite coating on zirconia 13 1.4. Purpose of this study 15 Chapter 2. Materials and methods 19 2.1. Materials for HA-coated zirconia 20 2.1.1. Preparation of the zirconia substrates 20 2.1.2. Ha sol synthesis 20 2.2. HA-coated zirconia preparation 21 2.3. Characterization of HA-coated zirconia 22 2.4. In-vitro osseointegration of the HA-coated zirconia 23 2.5. In-vivo osseointegration of the HA-coated zirconia 24 2.6. Statistical analysis 26 Chapter 3. Results and discussion 30 3.1. Control the surface morphology of the HA layer 31 3.1.1. Sintering temperature 31 3.1.2. HA sol aging time 33 3.2. Control the reaction of HA and zirconia by adjusting sintering temperature 37 3.2.1. Characteristics of HA coated zirconia with various sintering temperature 37 3.2.2. Coating stability of HA coated zirconia 40 3.3. Comparision of HA-coated zirconia with and without micro roughness 43 3.4. In-vitro osseointegration of the HA-coated zirconia 46 3.4.1. Osteoconductivity of roughness difference 46 3.4.2. Osteoconductivity of HA-coated zirconia 47 3.5. In-vivo osseointegration of the HA-coated zirconia 48 Chapter 4. Conclusions 68 4.1. Conclusions 69 Reference 73 Abstract in Korean 89박

의사결정 모델을 이용한 음소 분류과제의 선택과 반응시간 예측

학위논문 (석사)-- 서울대학교 대학원 : 뇌인지과학과, 2013. 2. 이상훈.Despite crucial roles of pre-lexical units in speech perception, modeling efforts so far have been heavily focused on information processing at lexical or post-lexical stages, impeding the mechanistic investigation of speech perception. Given this dearth of frameworks for studying pre-lexical units, the current study proposes a system-level neural model for phoneme classification. A lynchpin idea behind the proposed model is that the brain represents phonemes as probabilistic quantities, likelihoods. With this idea, our model bridges three well-known canonical computations in the brain – sensory encoding, likelihood decoding and evidence accumulation - along a cascade hierarchy of neural processing towards generating inputs to a next stage of speech perception. At the initial stage, sensory neurons with different tuning curves for physical properties relevant to phoneme discrimination compute individual likelihoods for the presence of those properties. Phoneme neurons at the following stage compute likelihoods for specific phonemes by summing the outputs of those sensory encoding neurons with weighting curves tuned for their preferred phonemes. At the final stage, evidence-accumulation neurons compute and accumulate over time evidence to reach a discrete phoneme classification by integrating outputs of phoneme neurons in a task-optimal manner over time. The accumulation-to-bound mechanism operating at this stage translates probabilistic information represented in the phoneme neurons output into concrete choices at a certain time. This translation allowed us to test the empirical viability of our model by assessing its capability of predicting actual patterns of choice fractions and reaction times exhibited by human listeners engaging in phoneme classification under various listening conditions. Using a small number of parameters, the model predicted not only the static, categorical structure of phoneme classification as a function of physical stimulus property, but also the adaptation-induced, dynamic changes in classification on an identical stimulus. Furthermore, the model was flexible enough to cover the wide range of individual differences in phoneme classification behavior. With these behavioral constraints in conjunction with neural and computational constraints exercised in model construction, our model provides a framework for studying neural mechanisms underlying initial stages of speech processing by generating hypotheses and predictions that are testable by neurophysiological and behavioral experiments.1. Introduction 1 1.1. Likelihood model of Phoneme Classification 5 2. Phoneme classification on a cyclic spectrum of stimuli varying in frequency modulation 9 2.1 Methods 9 2.2 Results 12 3. Dynamic changes in phoneme representation following adaptation 15 3.1 Methods 15 3.2 Results 23 4. Simultaneous fit of the likelihood model to phoneme classification responses with and without adaptation 24 5. Discussion 32 6. References 35Maste

Bulk-fill 복합레진 수복시 치아-수복물 계면 파괴와 관련된 중합수축, 탄성계수, 수축응력

학위논문 (박사)-- 서울대학교 대학원 : 치의과학과, 2015. 2. 이인복.Objectives. The aim of the present study was to measure the polymerization shrinkage, modulus, and shrinkage stress of bulk-fill and conventional composites during polymerization and to investigate the relationship between tooth-composite interfacial debonding and polymerization shrinkage stress of the composites. Methods. Polymerization shrinkage, dynamic modulus, and shrinkage stress of two non-flowable bulk-fill: SonicFill (SF) and Tetric N-Ceram Bulk-Fill (TNB)two flowable bulk-fill: Filtek Bulk-Fill (FB) and SureFil SDR Flow (SDR)one non-flowable conventional: Filtek Z250 (Z250)and one flowable conventional: Filtek Z350 XT Flowable (Z350F) composites were measured using custom-made instruments. Acoustic emission (AE) analysis was performed to evaluate the tooth-composite interfacial debonding during polymerization of the composites in Class 1 cavities on extracted third molars. Results. Polymerization shrinkage (%) of Z350F (3.53) at 10 min was the highest, followed by FB (3.05), SDR (2.99), TNB (2.22), Z250 (2.09), and SF (2.05). Complex shear modulus (MPa) after 20 s of light-curing was highest in SF (996.2), followed by Z250 (831.8), TNB (723.6), Z350F (553.2), SDR (421.3), and FB (334.8). Polymerization shrinkage stress values (MPa) were: Z350F (3.51), TNB (2.42), Z250 (2.38), SF (2.36), FB (2.24), and SDR (1.68). The numbers of AE events were: Z350F (12.6), TNB (7.0), Z250 (7.0), FB (6.8), SF (6.6), and SDR (6.0). Z350F showed the highest polymerization shrinkage stress and AE event number (p 0.05). Conclusions. Composites that exhibited greater polymerization shrinkage stress generated more tooth-composite interfacial debonding. In contrast to similar outcomes among the non-flowable composites (conventional: Z250, bulk-fill: TNB and SF), the flowable bulk-fill composites (FB and SDR) demonstrated lower polymerization shrinkage stress and tooth-composite interfacial debonding than did the flowable conventional composite (Z350F).Contents Abstract (in English) 1. Introduction …………………………………………………… 1 2. Materials and Methods …………………………………… 5 3. Results ……………………………………………………… 12 4. Discussion …………………………………………………… 15 5. Conclusions ………………………………………………… 22 6. References …………………………………………………… 23 Table and Figures ……………………………………………… 29 Abstract (in Korean) …………………………………………… 40Docto

『에베소서』 5:21-33의 해석과 한국 젠더 문제에의 시사점: 근본·복음주의, 페미니스트, 포스트콜로니얼 페미니스트 성서해석을 중심으로

In this paper, I analyze three major interpretive approaches--conservative fundamental/evangelical, (radical) feminist, and postcolonial feminist--to Ephesians 5:21-33 and discuss their implications on current gender problems of modern-day Korea. While these approaches differ in their assumptions of biblical authority and the main agenda of Eph 5, they all shed light on addressing the gender issues in Korea. Conservative fundamental/evangelical interpretation stresses mutual submission in family and the church's role in challenging the cultural gender inequality. Feminist interpretation debunks the ideological role of Eph 5 in legitimizing the male-dominance, cautioning us about the misuse of the text for oppressing women. Postcolonial feminist interpretation, by observing the political structure of dominance implied in the text, forces us to see different forms of oppression among women in Korea

The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes

Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.ope

Income Tax Policy Suggestions for Improvement of the Elderly Employment

본 연구에서는 OECD가 출간한 『Taxing Wages』와 국세청이 출간한 『국세통계연보』를 이용하여 한국의 소득세 부담을 주요 외국과 비교하고 연령별 세부담 구조를 분석하였으며, 현행의 소득세제가 노년층의 고용에 미치는 영향에 대해 살펴보았다. 우리나라의 소득세 유효세율은 외국에 비하여 낮은 수준이지만, 청장년층에 비하여 소득이 낮은 50~60대 노년층의 유효세율이 오히려 높은 것으로 나타났다. 이는 현행의 소득세제하에서의 조세지원이 주로 소득공제로 이루어지므로 상대적으로 소득이 높은 청년층에 조세지원이 편중되기 때문이다. 또 가구전체의 세부담을 줄이기 위해 가구 내 소득이 가장 높은 가구원에게 소득공제를 집중하여 적용하는 세제상 이차거래로 인해 청장년층의 세부담이 줄어드는 점에도 기인한다. 소득이 낮고 노동공급 탄력성이 높은 노인층의 세부담을 줄이기 위해 인적공제제도 및 근로소득공제 개편과 조세지원방식을 소득공제에서 세액공제로 전환하는 방안을 제시하였다.We analyzed the age structure of effective income tax rates using Taxing Wages published by OECD and The Statistical Yearbook of National Tax of Korea. We found that the effective income tax rates of Korea are lower than those of most of OECD countries. However, the effective tax rates for the elderly are higher than those of non-elderly, because under the current income tax system, tax relieves are provided primarily through tax deductions, which benefit high-income earners more than low-income earners. It is also because of the tax arbitrage which allocates tax deductions to high-income earners within a household. Therefore, we suggest a structural revision of personal deduction, employment income deduction, and reinforcement of the role of tax credits, to improve the efficiency and equity by lowering tax burden of the elderly, who earn less than non-elderly and whose labor supply elasticity is high

Suppressive Effect of Autocrine FGF21 on Autophagy-Deficient Hepatic Tumorigenesis

Mice with hepatocyte-specific deletion of autophagy-related 7 (Atg7 ΔHep mice) develop hepatoma, suggesting that autophagy deficiency could be a factor in the initiation of tumorigenesis. We have shown that FGF21 is induced as a 'mitokine' when Atg7 is disrupted in insulin target tissues such as the liver, which could affect systemic metabolism through endocrine activity. Since FGF21 or other endocrine FGF such as FGF19 can affect tumor growth, we hypothesized that FGF21 produced by Atg7-knockout (KO) hepatocytes may affect the behavior of Atg7-KO hepatoma in an autocrine manner. We, thus, crossed Atg7 ΔHep mice with systemic Fgf21-KO (Fgf21 -/-) mice to generate Atg7 ΔHep Fgf21 -/- mice. The number and size of hepatoma of Atg7 ΔHep mice were significantly increased by additional Fgf21 KO. The proliferation of Atg7-KO hepatocyte was significantly increased by Fgf21 KO. pYAP1/YAP1 representing YAP1 degradation was significantly decreased in the liver of Atg7 ΔHep Fgf21 -/- mice compared to Atg7 ΔHep Fgf21 +/+ mice. Consistently, expression of YAP1/TAZ downstream genes was significantly increased in the liver of Atg7 ΔHep Fgf21 -/- mice compared to Atg7 ΔHep Fgf21 +/+ mice, which could explain the increased size of hepatoma in Atg7 ΔHep Fgf21 -/- mice. Accumulation of ROS and ROS-mediated DNA damage were increased in the liver of Atg7 ΔHep Fgf21 +/+ mice, which was further aggravated by additional Fgf21 KO probably due to the absence of positive effect of FGF21 on mitochondrial function, explaining the increased number of hepatoma in Atg7 ΔHep Fgf21 -/- mice compared to Atg7 ΔHep Fgf21 +/+ mice. These results show that FGF21 produced by autophagy-deficient hepatocytes could have autocrine or paracrine effects on the number and proliferation of autophagy-deficient hepatoma, suggesting that hormones or factors released from autophagy-deficient tumors can influence the behavior or prognosis of the tumor in addition to the effects on host metabolism.ope

An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer

We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.ope

Comparison of Mechanical Property of Conventional Rods versus Growing Rods for Pediatric Early Onset Scoliosis

STUDY DESIGN: This is a mechanical study. OBJECTIVES: We wanted to investigate the mechanical properties of newly developed dual growing rods for obtaining approval for their clinical application. SUMMARY OF LITERATURE REVIEW: The current expandable spinal implant system appears effective for controlling progressive early onset scoliosis, and it allows for spinal growth and improving lung development. MATERIALS AND METHODS: We investigate the yield load and ultimate load during compression, tension and torsion of the growing rods and the conventional rods assembly using UHMWPE blocks, and the diameter of the rods was 6.0 mm and they expanded 5cm long. We also performed a fatigue test with growing rods, and the diameter of which was 6.0 mm and it expanded 2.5cm long. The guideline for the American Society for Testing Materials was followed during the entire mechanical test. With the growing rods and conventional rods, we tested for each mechanical property7 times with the new rods and blocks. RESULTS: The yield load of the growing rods and conventional rods were 845.2+/-18.2 (N) and 812.9+/-29.9 (N), respectively, and the ultimate load of the growing rods and conventional rods were 961.9+/-31.1 (N) and 914.9+/-25.6 (N), respectively, when compression force was applied. The yield load and ultimate load of the growing rods were statistically higher than those of the conventional rods (p0.05). The yield loads of the growing rods and conventional rods were 11.56+/-0.59 (Nm) and 12.46+/-0.71 (Nm), respectively, the ultimate loads of the growing rods and conventional rods were 16.97+/-0.94 (Nm) and 17.42+/-2.66 (Nm) during the torsion, respectively. The yield load and ultimate load of the growing rods were statistically lower than that of the conventional rods (p<0.05). CONCLUSIONS: The newly developed growing rods have a higher yield load and ultimate load under compression, a similar ultimate load under tension and a lower yield load and ultimate load under torsion. The differences of the yield load and ultimate load under torsion were minimal, and so the growing rods and conventional rods have similar mechanical propertiesope

A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes

Autophagy is a critical regulator of cellular homeostasis, dysregulation of which is associated with diverse diseases. Here we show therapeutic effects of a novel autophagy enhancer identified by high-throughput screening of a chemical library against metabolic syndrome. An autophagy enhancer increases LC3-I to LC3-II conversion without mTOR inhibition. MSL, an autophagy enhancer, activates calcineurin, and induces dephosphorylation/nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy gene expression. MSL accelerates intracellular lipid clearance, which is reversed by lalistat 2 or Tfeb knockout. Its administration improves the metabolic profile of ob/ob mice and ameliorates inflammasome activation. A chemically modified MSL with increased microsomal stability improves the glucose profile not only of ob/ob mice but also of mice with diet-induced obesity. Our data indicate that our novel autophagy enhancer could be a new drug candidate for diabetes or metabolic syndrome with lipid overload.ope