Towards Discovering Inhibitors of Cytochrome c Biogenesis

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Spring 2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Robert Kranz and Deanna Mende

Spatio-Temporal Change of LakeWater Extent in Wuhan Urban Agglomeration Based on Landsat Images from 1987 to 2015

Urban lakes play an important role in urban development and environmental protection for the Wuhan urban agglomeration. Under the impacts of urbanization and climate change, understanding urban lake-water extent dynamics is significant. However, few studies on the lake-water extent changes for the Wuhan urban agglomeration exist. This research employed 1375 seasonally continuous Landsat TM/ETM+/OLI data scenes to evaluate the lake-water extent changes from 1987 to 2015. The random forest model was used to extract water bodies based on eleven feature variables, including six remote-sensing spectral bands and five spectral indices. An accuracy assessment yielded a mean classification accuracy of 93.11%, with a standard deviation of 2.26%. The calculated results revealed the following: (1) The average maximum lake-water area of the Wuhan urban agglomeration was 2262.17 km2 from 1987 to 2002, and it decreased to 2020.78 km2 from 2005 to 2015, with a loss of 241.39 km2 (10.67%). (2) The lake-water areas of loss of Wuhan, Huanggang, Xianning, and Xiaogan cities, were 114.83 km2, 44.40 km2, 45.39 km2, and 31.18 km2, respectively, with percentages of loss of 14.30%, 11.83%, 13.16%, and 23.05%, respectively. (3) The lake-water areas in the Wuhan urban agglomeration were 226.29 km2, 322.71 km2, 460.35 km2, 400.79 km2, 535.51 km2, and 635.42 km2 under water inundation frequencies of 5%–10%, 10%–20%, 20%–40%, 40%–60%, 60%–80%, and 80%–100%, respectively. The Wuhan urban agglomeration was approved as the pilot area for national comprehensive reform, for promoting resource-saving and environmentally friendly developments. This study could be used as guidance for lake protection and water resource management

Effects of Charge Transport Materials on Blue Fluorescent Organic Light-Emitting Diodes with a Host-Dopant System

High efficiency blue fluorescent organic light-emitting diodes (OLEDs), based on 1,3-bis(carbazol-9-yl)benzene (mCP) doped with 4,4’-bis(9-ethyl-3-carbazovinylene)-1,1’-biphenyl (BCzVBi), were fabricated using four different hole transport layers (HTLs) and two different electron transport layers (ETLs). Fixing the electron transport material TPBi, four hole transport materials, including 1,1-Bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC), N,N’-Di(1-naphthyl)-N,N’-diphenyl-(1,1’-biphenyl)-4’-diamine(NPB), 4,4’-Bis(N-carbazolyl)-1,1,-biphenyl (CBP) and molybdenum trioxide (MoO3), were selected to be HTLs, and the blue OLED with TAPC HTL exhibited a maximum luminance of 2955 cd/m2 and current efficiency (CE) of 5.75 cd/A at 50 mA/cm2, which are 68% and 62% higher, respectively, than those of the minimum values found in the device with MoO3 HTL. Fixing the hole transport material TAPC, the replacement of TPBi ETL with Bphen ETL can further improve the performance of the device, in which the maximum luminance can reach 3640 cd/m2 at 50 mA/cm2, which is 23% higher than that of the TPBi device. Furthermore, the lifetime of the device is also optimized by the change of ETL. These results indicate that the carrier mobility of transport materials and energy level alignment of different functional layers play important roles in the performance of the blue OLEDs. The findings suggest that selecting well-matched electron and hole transport materials is essential and beneficial for the device engineering of high-efficiency blue OLEDs

Improved Efficiency of Perovskite Light-Emitting Diodes Using a Three-Step Spin-Coated CH3NH3PbBr3 Emitter and a PEDOT:PSS/MoO3-Ammonia Composite Hole Transport Layer

High efficiency perovskite light-emitting diodes (PeLEDs) using PEDOT:PSS/MoO3-ammonia composite hole transport layers (HTLs) with different MoO3-ammonia ratios were prepared and characterized. For PeLEDs with one-step spin-coated CH3NH3PbBr3 emitter, an optimal MoO3-ammonia volume ratio (0.02) in PEDOT:PSS/MoO3-ammonia composite HTL presented a maximum luminance of 1082 cd/m2 and maximum current efficiency of 0.7 cd/A, which are 82% and 94% higher than those of the control device using pure PEDOT:PSS HTL respectively. It can be explained by that the optimized amount of MoO3-ammonia in the composite HTLs cannot only facilitate hole injection into CH3NH3PbBr3 through reducing the contact barrier, but also suppress the exciton quenching at the HTL/CH3NH3PbBr3 interface. Three-step spin coating method was further used to obtain uniform and dense CH3NH3PbBr3 films, which lead to a maximum luminance of 5044 cd/m2 and maximum current efficiency of 3.12 cd/A, showing enhancement of 750% and 767% compared with the control device respectively. The significantly improved efficiency of PeLEDs using three-step spin-coated CH3NH3PbBr3 film and an optimum PEDOT:PSS/MoO3-ammonia composite HTL can be explained by the enhanced carrier recombination through better hole injection and film morphology optimization, as well as the reduced exciton quenching at HTL/CH3NH3PbBr3 interface. These results present a promising strategy for the device engineering of high efficiency PeLEDs

Plasmonic-Enhanced Organic Light-Emitting Diodes Based on a Graphene Oxide/Au Nanoparticles Composite Hole Injection Layer

Organic light-emitting diodes (OLEDs) have drawn a great deal of attention due to their broad applications in lighting and displaying. With the development of nanotechnology, surface plasmas have been widely used in photonics, microscopes, solar cells and biosensors. In this paper, by inserting graphene oxide (GO), Au nanoparticles (Au NPs) and GO/Au NP composite structures between the hole transport layer (NPB) and indium tin oxide (ITO) anode, respectively, the electroluminescent performance of Alq3-based OLEDs was significantly enhanced. Compared to the reference devices, the devices with the composite inserting layer containing 10% GO/Au NP doping have the best electroluminescent performance, which improved 47.9% in maximum luminance, 49.2% in maximum current efficiency and 45.3% in maximum external quantum efficiency (EQE). Such substantial enhancement of photoelectric performance can be attributed to the combined effects of LSPR coupling and the better hole transport property by introducing Au NPs and a graphene oxide-doped layer

Vascular endothelial growth factor and the risk of venous thromboembolism: A genetic correlation and two-sample Mendelian randomization study

Background: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. Methods: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran’s Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. Results: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95 % confidence interval (CI), 1.009 – 1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (β = -0.021, 95 % CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. Conclusions: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted

p53/p21 Pathway Involved in Mediating Cellular Senescence of Bone Marrow-Derived Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients

Our and other groups have found that bone marrow-derived mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited senescent behavior and are involved in the pathogenesis of SLE. Numerous studies have shown that activation of the p53/p21 pathway inhibits the proliferation of BM-MSCs. The aim of this study was to determine whether p53/p21 pathway is involved in regulating the aging of BM-MSCs from SLE patients and the underlying mechanisms. We further confirmed that BM-MSCs from SLE patients showed characteristics of senescence. The expressions of p53 and p21 were significantly increased, whereas levels of Cyclin E, cyclin-dependent kinase-2, and phosphorylation of retinoblastoma protein were decreased in the BM-MSCs from SLE patients and knockdown of p21 expression reversed the senescent features of BM-MSCs from SLE patients. Our results demonstrated that p53/p21 pathway played an important role in the senescence process of BM-MSCs from SLE

Enhanced photocatalysis by coupling of anatase TiO2 film to triangular Ag nanoparticle island

In order to overcome the low utilization ratio of solar light and high electron-hole pair recombination rate of TiO(2), the triangular Ag nanoparticle island is covered on the surface of the TiO(2) thin film. Enhancement of the photocatalytic activity of the Ag/TiO(2) nanocomposite system is observed. The increase of electron-hole pair generation is caused by the enhanced near-field amplitudes of localized surface plasmon of the Ag nanoparticles. The efficiently suppressed recombination of electron-hole pair caused by the metal-semiconductor contact can also enhance the photocatalytic activity of the TiO(2) film

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy

Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau.

Funder: Science and Technology Commission of Shanghai Municipality; FundRef: http://dx.doi.org/10.13039/501100003399Funder: Dr. John T. MacDonald Foundation; FundRef: http://dx.doi.org/10.13039/100010239Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration