화학적으로 표면 개질된 그래핀 양자점을 이용한 광촉매적 수소 생산 시스템에 대한 연구

학위논문(박사) -- 서울대학교대학원 : 공과대학 재료공학부, 2023. 2. 박수영.Hydrogen energy, one of the most promising renewable energy resources, has recently attracted a lot of attention due to its advantages such as convenience of movement and transportation, and high energy density. To produce hydrogen efficiently, it is required to find efficient photocatalyst material for hydrogen evolution reaction (HER). One of the most promising photocatalyst materials is graphene quantum dot (GQD). GQD have already been studied several times as HER photocatalysts, but low visible light absorption and charge trap sites on the surface limit GQD to have high HER performance. Therefore, research on modification and design is still needed for efficient HER performance. This thesis focused on designing efficient HER photocatalysts through chemical modification and dye-sensitization strategies for GQD. In chapter 2, ethylene diamine (EDA) functionalized GQD was synthesized by amide bond formation reaction. EDA functionalized GQD exhibited significantly increased HER performance (342 μmol/g of hydrogen after 10 hours) compared to bare GQD (150 μmol/g of hydrogen after 10 hours). Importantly, the HER performance of EDA functionalized GQD increased proportionally to pH and peaked at pH = 10, in stark contrast to the simple decreasing HER performance with the pH of bare GQDs. Through linear sweep voltage measurement and electrochemical impedance spectroscopy, it is confirmed that the covalently bonded EDA acts as a water dissociation site to improve the photocatalyst HER in the alkali medium. In chapter 3, amphiphilic GQD functionalized with hexylamine was synthesized through amide bond formation reaction. It was confirmed that hexylamine functionalized GQD (GQD-HA) is amphiphilic and can act as photocatalyst and templating surfactant simultaneously. GQD-HA can form much more stable composite nanoparticles with a thermally activated delayed fluorescence (TADF) photosensitizer than bare GQDs. Importantly, the HER performance and stability of the composite system are significantly improved after HA functionalization (11.64 mmol/g of hydrogen after 14 hours). Through electrochemical analysis, it was confirmed that the composite nanoparticles with GQD-HA and the photosensitizer have efficient charge separation and fast charge transfer characteristics. In Chapter 4, a highly efficient photocatalytic HER system with GQD-HA incorporating visible light sensitizing dyes was demonstrated. It was confirmed that HA functionalization helps GQD produce hydrogen more efficiently by providing trap passivation properties and availability of dye sensitization. GQD-HA formed modified nanostructures through strong interactions with photosensitizers. Dye-mixed GQD-HA nanostructures showed efficient HER performance (initial rates of 0.182 mmol/g·h and 1.303 mmol/g of hydrogen after 15 hours) and AQY of 22.5% under 500 nm light irradiation. It also showed enhanced stability in both pure and simulated seawater. Dye-sensitized GQD-HA showed high charge separation and efficient charge transfer characteristics through electrochemical analysis.대표적인 신재생에너지 자원 중 하나인 수소에너지는 이동과 교통이 편리하고 에너지 밀도가 높아 최근 많은 관심을 받고 있다. 수소 에너지를 효율적으로 생산하기 위해서는 수소 생산 반응(HER)을 위한 효율적인 광촉매 물질을 찾는 것이 요구된다. 가장 유망한 광촉매 물질 중 하나는 그래핀 양자점(GQD)으로, 이미 HER 광촉매로 여러 차례 연구된 유망한 HER 광촉매 소재 중 하나이지만, 가시광선 흡수율이 낮고 표면에 분포 되어있는 전하 트랩 영역으로 인해 HER 성능이 제한된다. 따라서 효율적인 HER을 위한 개조 및 설계에 대한 연구가 여전히 필요하다. 본 논문은 GQD에 대한 화학적 표면 개질 전략과 염료 감응 전략을 통해 효율적인 HER 광촉매를 설계하는 데 초점을 맞췄다. 제2장에서는 아미드 결합 형성 반응에 의해 에틸렌다이아민(EDA)이 기능화된 GQD를 합성하였다. EDA 기능화된 GQD(GQD-EDA)는 GQD(10시간 동안 150μmol/g의 수소)에 비해 현저하게 증가된 HER 성능(10시간 동안 342μmol/g의 수소)을 보였다. 중요한 것은 GQD-EDA의 HER 성능이 pH에 비례하여 증가하고 pH = 10에서 가장 높은 성능을 보였다는 점인데, 이는 보통의 GQD의 HER 성능이 pH와 함께 감소하는 것과는 대조적이다. 선형 스위프 전압 측정 및 전기화학적 임피던스 분광법을 통해 공유결합된 EDA가 물 해리 부위로 작용하여 알칼리 매질 내 광촉매 HER을 향상시키는 것을 확인할 수 있다. 제3장에서는 아미드 결합 형성 반응을 통해 헥실아민(HA)으로 기능화된 양친매성 GQD를 합성하였다. 헥실아민 기능화된 GQD(GQD-HA)는 양친매성이며, 광촉매와 계면활성제로 동시에 작용할 수 있음을 확인하였다. GQD-HA는 TADF 특성을 가진 소수성 광감응제와 함께 기존 GQD보다 훨씬 더 안정적인 복합 나노입자를 형성할 수 있다. 중요한 것은 HA 기능화 후 복합 시스템의 HER 성능(14시간 동안 11.64 mmol/g의 수소)과 안정성이 크게 향상된다는 것이다. 전기화학적 분석을 통해 GQD-HA가 광감응제와 함께 형성한 나노입자가 효율적인 전하분리 및 빠른 전하전달 특성을 가짐을 확인하였다. 제4장에서는 가시광선 감응 염료를 포함하는 GQD-HA의 고효율 광촉매 HER 시스템이 시연되었다. HA 기능화는 전하 트랩 구역을 부동태화 함과 동시에 염료 감음 전략의 적용 가능성을 제공함으로써 GQD가 수소를 보다 효율적으로 생산할 수 있도록 돕는다는 것을 확인하였다. GQD-HA는 광감응제와의 강력한 상호작용을 통해 변형된 나노구조를 형성하였다. 염료가 혼합된 GQD-HA 나노구조물은 효율적인 HER 성능(초기 속도 0.182 mmol/g·h, 15시간 후 수소 1.303 mmol/g)과 500 nm 광조사 하에서 22.5%의 AQY를 나타냈다. 또한 증류수와 모의 해수 모두에서 향상된 안정성을 보였다. 전기화학적 분석을 통해 확인한 결과, 염료 감응형 GQD-HA는 높은 전하분리 및 효율적인 전하전달 특성을 나타내었다.Chapter 1. Introduction 1 1.1 Photocatalytic Hydrogen Evolution Reaction 1 1.2 Graphene Quantum Dots 11 1.3 Purpose of Research 13 Chapter 2. Ethylenediamine functionalized graphene quantum dots as alkaline HER photocatalyst 22 2.1 Introduction 22 2.2 Experimental details 28 2.2.1 Chemical used 28 2.2.2 Synthesis of graphene oxide 28 2.2.3 Synthesis of GQD 29 2.2.4 Synthesis of GQD–EDA 30 2.2.5 Characterizations of the material 30 2.2.6 Photocatalytic HER measurements 32 2.2.7 Electrochemical measurements 32 2.3 Results & discussion 33 2.3.1 Structural analysis of the catalyst 33 2.3.2 Photocatalytic HER Activity and Mechanism 40 2.3.3 Electrochemical Measurements 47 2.3.4 Fluorescence Lifetime Measurement 49 2.3.5 Effect of Amine Sources with Different Chain Lengths on HER Performance of Functionalized GQD 50 2.4 Conclusion 51 Chapter 3. Amphiphilic graphene quantum dots as HER photocatalyst via encapsulation of TADF photosensitizer 57 3.1 Introduction 57 3.2 Experimental details 62 3.2.1 Chemical used 62 3.2.2 Synthesis of GO 62 3.2.3 Synthesis of GQD 63 3.2.4 Synthesis of GQD-HA 64 3.2.5 Synthesis of NAPTPA-2Br 64 3.2.6 Characterizations of the material 67 3.2.7 Photocatalytic HER experiments 68 3.2.8 Photoelectrochemical measurements 69 3.3 Results & discussion 69 3.3.1 Characterizations of GQD-HA 69 3.3.2 Structural analysis of the photocatalytic system 80 3.3.3 Photocatalytic HER performance 83 3.3.4 Electrochemical & photoelectrochemical measurements 86 3.4 Conclusion 92 Chapter 4. Dye-sensitized amphiphilic graphene quantum dots for visible-light-driven photocatalytic HER in seawater 100 4.1 Introduction 100 4.2 Experimental details 105 4.2.1 Chemicals used 105 4.2.2 Synthesis of graphene oxide (GO) 106 4.2.3 Characterization of the materials 112 4.2.4 Photocatalytic HER experiments 113 4.2.5 Electrochemical & photoelectrochemical measurements 114 4.3 Results & discussion 115 4.3.1 Characterization of the materials 115 4.3.2 Structural characterization of HER system 123 4.3.3 Photocatalytic HER performance 128 4.3.4 Electrochemical measurements 131 4.4 Conclusion 134 List of Publications 140 List of Presentations 141 List of Patents 142 Abstract in Korean 143박

Surgical Outcomes of Sphenoid Wing Meningioma with Periorbital Invasion

Objective: The aim of this study was to evaluate the clinical outcome of sphenoid wing meningioma with periorbital invasion (PI) after operation. Methods: Sixty one patients with sphenoid wing meningioma were enrolled in this study. Their clinical conditions were monitored after the operation and followed up more than 5 years at the outpatient clinic of a single institution. Clinical and radiologic information of the patients were all recorded including the following parameters : presence of PI, presence of peri-tumor structure invasion, pathologic grade, extents of resection, presence of hyperostosis, exophthalmos index (EI), and surgical complications. We compared the above clinical parameters of the patients with sphenoid wing meningioma in the presence or absence of PI (non-PI), then linked the analyzed data with the clinical outcome of the patients. Results: Of 61 cases, there were 14 PI and 47 non-PI patients. PI group showed a significantly higher score of EI (1.37±0.24 vs. 1.00±0.01, p<0.001), more frequent presence of hyperostosis (85.7% vs. 14.3%, p<0.001), and lower rate of gross total resection (GTR) (35.7% vs. 68.1%, p=0.032). The lower score of pre-operative EI, the absence of both PI and hyperostosis, smaller tumor size, and the performance of GTR were associated with lower recurrence rates in the univariate analysis. However, in the multivariate analysis, the performance of GTR was the only significant factor to determine the recurrence rate (p=0.043). The incidences of surgical complications were not statistically different between the subtotal resection (STR) and GTR groups, but it was strongly associated tumor size (p=0.017). Conclusion: The GTR group showed lower recurrence rate than the STR group without differences in the surgical complications. Therefore, the GTR is strongly recommended to treat sphenoid wing meningioma with PI for the better clinical outcome.ope

Prognostic factors to predict the efficacy of surgical interventions against brain metastasis secondary to thyroid cancer

Introduction: Brain metastasis in differentiated thyroid cancer (DTC) is rare (frequency < 1%) and has a poor prognosis. Treatment strategies for brain metastasis are not well established. Objectives: We conducted a retrospective analysis to identify predictive factors for patient outcomes and verify surgical indications for patients with brain metastasis and DTC. Methods: The study included 34 patients with pathologically confirmed DTC with brain metastasis from March 2008 to November 2020. The associations between overall survival (OS) and clinical factors were evaluated. Cox regression analysis was used to determine the relationship between clinical factors and OS. To assess the survival benefit of craniotomy, Kaplan-Meier survival analysis was performed for each variable whose statistical significance was determined by Cox regression analysis. Results: The median OS of the entire patient sample was 11.4 months. Survival was affected by the presence of lung metastasis (P = 0.033) and the number of brain metastases (n > 3) (P = 0.039). Only the subgroup with the number of brain metastases ≤3 showed statistical significance in the subgroup analysis of survival benefit following craniotomy (P = 0.048). Conclusions: The number of brain metastases and the existence of lung metastasis were regarded more essential than other clinical factors in patients with DTC in this study. Furthermore, craniotomies indicated a survival benefit only when the number of brain metastases was ≤3. This finding could be beneficial in determining surgical indications in thyroid cancer with brain metastasis.ope

Recent Update on Neurosurgical Management of Brain Metastasis

Brain metastasis (BM), classified as a secondary brain tumor, is the most common malignant central nervous system tumor whose median overall survival is approximately 6 months. However, the survival rate of patients with BMs has increased with recent advancements in immunotherapy and targeted therapy. This means that clinicians should take a more active position in the treatment paradigm that passively treats BMs. Because patients with BM are treated in a variety of clinical settings, treatment planning requires a more sophisticated decision-making process than that for other primary malignancies. Therefore, an accurate prognostic prediction is essential, for which a graded prognostic assessment that reflects next-generation sequencing can be helpful. It is also essential to understand the indications for various treatment modalities, such as surgical resection, stereotactic radiosurgery, and whole-brain radiotherapy and consider their advantages and disadvantages when choosing a treatment plan. Surgical resection serves a limited auxiliary function in BM, but it can be an essential therapeutic approach for increasing the survival rate of specific patients; therefore, this must be thoroughly recognized during the treatment process. The ultimate goal of surgical resection is maximal safe resection; to this end, neuronavigation, intraoperative neuro-electrophysiologic assessment including evoked potential, and the use of fluorescent materials could be helpful. In this review, we summarize the considerations for neurosurgical treatment in a rapidly changing treatment environment.ope

Surgical Treatment for Falcotentorial Meningiomas.

Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience.ope

Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.ope

Association between survival and levetiracetam use in glioblastoma patients treated with temozolomide chemoradiotherapy

This study was conducted to assess whether levetiracetam (LEV) affects the survival of patients with glioblastoma (GBM) treated with concurrent temozolomide (TMZ) chemotherapy. To this end, from 2004 to 2016, 322 patients with surgically resected and pathologically confirmed isocitrate dehydrogenase (IDH)-wildtype GBM who received TMZ-based chemoradiotherapy were analysed. The patients were divided into two groups based on whether LEV was used as an anticonvulsant both at the time of surgery and the first visit thereafter. The median overall survival (OS) and progression-free survival (PFS) were compared between the groups. The OS was 21.1 and 17.5 months in the LEV (+) and LEV (-) groups, respectively (P = 0.003); the corresponding PFS was 12.3 and 11.2 months (P = 0.017). The other prognostic factors included age, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and Karnofsky Performance Status (KPS) score. The multivariate analysis showed age (hazard ratio [HR], 1.02; P < 0.001), postoperative KPS score (HR 0.99; P = 0.002), complete tumour resection (HR 0.52; P < 0.001), MGMT promoter methylation (HR 0.75; P < 0.001), and LEV use (HR 0.72; P = 0.011) were significantly associated with OS. In conclusion, LEV use was associated with prolonged survival in patients with GBM treated with concurrent TMZ chemoradiotherapy.ope

The behavior of residual tumors following incomplete surgical resection for vestibular schwannomas

The management of vestibular schwannoma (VS) with residual tumor following incomplete resection remains controversial and little is known regarding postoperative tumor volume changes. The behavior of residual tumors was analyzed for 111 patients who underwent surgery for newly diagnosed VS between September 2006 and July 2017. The postoperative tumor volume changes were assessed during a mean follow-up of 69 months (range 36-147 months). Fifty-three patients underwent imaging surveillance following incomplete resection. There was no residual tumor growth in 44 patients (83%). A significant regression of residual tumor volume was noted in the no growth group at postoperative 1 year (p = 0.028), 2 years (p = 0.012), but not from 3 years onwards. Significant predictors of regrowth were immediate postoperative tumor volume ≥ 0.7 cm3 (HR 10.5, p = 0.020) and residual tumor location other than the internal auditory canal (IAC) (HR 6.2, p = 0.026). The mean time to regrowth was 33 months (range 5-127 months). The 2-, 5-, and 10-year regrowth-free survival rates were 90.6%, 86.8%, and 83%, respectively. In conclusion, significant residual tumor regression could occur within 2 years for a VS with an immediate postoperative tumor volume less than 0.7 cm3 or residual tumor in IAC.ope

The Extent of Necrosis in Brain Metastases May Predict Subtypes of Primary Cancer and Overall Survival in Patients Receiving Craniotomy

Although necrosis is common in brain metastasis (BM), its biological and clinical significances remain unknown. We evaluated necrosis extent differences by primary cancer subtype and correlated BM necrosis to overall survival post-craniotomy. We analyzed 145 BMs of patients receiving craniotomy. Necrosis to tumor ratio (NTR) was measured. Patients were divided into two groups by NTR: BMs with sparse necrosis and with abundant necrosis. Clinical features were compared. To investigate factor relevance for BM necrosis, multivariate logistic regression, random forests, and gradient boosting machine analyses were performed. Kaplan-Meier analysis and log-rank tests were performed to evaluate the effect of BM necrosis on overall survival. Lung cancer was a more common origin for BMs with abundant necrosis (42/72, 58.33%) versus sparse necrosis (23/73, 31.51%, p &lt; 0.01). Primary cancer subtype and tumor volume were the most relevant factors for BM necrosis (p &lt; 0.01). BMs harboring moderately abundant necrosis showed longer survival, versus sparse or highly abundant necrosis (p = 0.04). Lung cancer BM may carry larger necrosis than BMs from other cancers. Further, moderately abundant necrosis in BM may predict a good prognosis post-craniotomy.ope

Delirium-related factors and their prognostic value in patients undergoing craniotomy for brain metastasis

Background: Delirium is characterized by acute brain dysfunction. Although delirium significantly affects the quality of life of patients with brain metastases, little is known about delirium in patients who undergo craniotomy for brain metastases. This study aimed to identify the factors influencing the occurrence of delirium following craniotomy for brain metastases and determine its impact on patient prognosis. Method: A total of 153 patients who underwent craniotomy for brain metastases between March 2013 and December 2020 were evaluated for clinical and radiological factors related to the occurrence of delirium. Statistical analysis was conducted by dividing the patients into two groups based on the presence of delirium, and statistical significance was confirmed by adjusting the clinical characteristics of the patients with brain metastases using propensity score matching (PSM). The effect of delirium on patient survival was subsequently evaluated using Kaplan-Meier analysis. Results: Of 153 patients, 14 (9.2%) had delirium. Age (P = 0.002), sex (P = 0.007), and presence of postoperative hematoma (P = 0.001) were significantly different between the delirium and non-delirium groups. When the matched patients (14 patients in each group) were compared using PSM, postoperative hematoma showed a statistically significant difference (P = 0.036) between the delirium and non-delirium groups. Kaplan-Meier survival analysis revealed that the delirium group had poorer prognosis (log-rank score of 0.0032) than the non-delirium group. Conclusion: In addition to the previously identified factors, postoperative hematoma was identified as a strong predictor of postoperative delirium. Also, the negative impact of delirium on patient prognosis including low survival rate was confirmed.ope