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#36485031 
2022/12/09
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Minor Copper-Doped Aluminum Alloy Enabling Long-Lifetime Organic Light-Emitting Diodes.
Aluminum has been extensively used as a conductor material in numerous electronic devices, including solar cells, light-emitting diodes (LEDs), organic LEDs (OLEDs), and thin-film transistors. However, its spiking surface and easy electromigration have limited its performance. To overcome this, a trace amount of nonprecious copper dopant has been proven effective in enhancing device reliability. Nevertheless, a comprehensive investigation regarding the effect of copper doping on the morphology at the aluminum conductor-organic interface is yet to be done. We had hence fabricated a series of green OLED devices to probe how copper doping affected the aluminum conductor, morphologically and electrically, and the corresponding device's efficiency and lifetime performance. We found 4 wt % copper doping to be highly effective in enabling a spike-less and smoother aluminum interface, which in turn enabled the fabrication of devices with much higher efficiency and lifetime. Specifically, the corresponding power efficacy at 1000 cd/m was increased from 32 to 42 lm/W and the lifetime increased from 75 to 263 h, an increment of 250%. Atomic force microscopy confirmed that the copper doping did help smooth out the conductor interface as deposited and reduce electromigration upon operation.Yun-Jie Lin, Chia-Sheng Huang, Pei-Chung Tsai, Yu-Lun Hsiao, Cheng-Yu Chen, Jwo-Huei Jou
2543 related Products with: Minor Copper-Doped Aluminum Alloy Enabling Long-Lifetime Organic Light-Emitting Diodes.
1mg100ug6 ml1 mg 6 ml Ready-to-use 100ug Lyophilized50 ug 1 mg
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#36485006 2022/12/09
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Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe.
A transcriptional regulatory system called heat shock response (HSR) has been developed in eukaryotic cells to maintain proteome homeostasis under various stresses. Heat shock factor-1 (Hsf1) plays a central role in HSR, mainly by upregulating molecular chaperones as a transcription factor. Hsf1 forms a complex with chaperones and exists as a monomer in the resting state under normal conditions. However, upon heat shock, Hsf1 is activated by oligomerization. Thus, oligomerization of Hsf1 is considered an important step in HSR. However, the lack of information about Hsf1 monomer structure in the resting state, as well as the structural change via oligomerization at heat response, impeded the understanding of the thermosensing mechanism through oligomerization. In this study, we applied solution biophysical methods, including fluorescence spectroscopy, nuclear magnetic resonance, and circular dichroism spectroscopy, to investigate the heat-induced conformational transition mechanism of Hsf1 leading to oligomerization. Our study showed that Hsf1 forms an inactive closed conformation mediated by intramolecular contact between leucine zippers (LZs), in which the intermolecular contact between the LZs for oligomerization is prevented. As the temperature increases, Hsf1 changes to an open conformation, where the intramolecular LZ interaction is dissolved so that the LZs can form intermolecular contacts to form oligomers in the active form. Furthermore, since the interaction sites with molecular chaperones and nuclear transporters are also expected to be exposed in the open conformation, the conformational change to the open state can lead to understanding the regulation of Hsf1-mediated stress response through interaction with multiple cellular components.Soichiro Kawagoe, Munehiro Kumashiro, Takuya Mabuchi, Hiroyuki Kumeta, Koichiro Ishimori, Tomohide Saio
2955 related Products with: Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe.
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#36485005 2022/12/09
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Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.
The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS-MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST-1 and DCF-DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS-MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress-associated proteins were analyzed. Only the positively charged PS-MPs (NH -PS-MPs) showed cytotoxicity and increased ROS generation in BEAS-2B cells. Similarly, only NH -PS-MPs significantly increased the expression and secretion of the pro-inflammatory cytokine IL-β in the animal experiments. The expression of ER stress proteins indicated that NH -PS-MPs increased ER stress via PERK-EIF2α and ATF4-CHOP pathways. Moreover, accumulation of NH -PS-MPs in lysosomes and deformity of the nucleus were observed in BEAS-2B cells with autophagy induction. Taken together, our results demonstrated that NH -PS-MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks.Mi Seon Jeon, Jun Woo Kim, Yu Bin Han, Mi Ho Jeong, Ha Ryong Kim, Hyung Sik Kim, Yong Joo Park, Kyu Hyuck Chung
1030 related Products with: Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.
1.00 flask25 100ug Lyophilized100ug Lyophilized1.00 flask1 mg1.00 flask10 ug1.00 flask25 TESTS100 µg1x10e7 cells
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#36485001 2022/12/09
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Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.
Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) is gaining momentum and demonstrating durable responses in patients with advanced melanoma. Although increasingly considered as a treatment option for select patients with melanoma, TIL therapy is not yet approved by any regulatory agency. Pioneering studies with first-generation TIL therapy, undertaken before the advent of modern melanoma therapeutics, demonstrated clinical efficacy and remarkable long-term overall survival, reaching beyond 20 months for responding patients. TIL therapy is a multi-step process of harvesting patient-specific tumor-resident T cells from tumors, ex vivo T-cell expansion, and re-infusion into the same patient after a lymphodepleting preparative regimen, with subsequent supportive interleukin-2 administration. Objective response rates between 30% and 50% have consistently been observed in heavily pretreated metastatic melanoma patients, including those who have progressed after modern immune checkpoint inhibitors and BRAF targeted agents, a population with high unmet medical need. Although significant strides have been made in modern TIL therapeutics, refinement strategies to optimize patient selection, enhance TIL production, and improve efficacy are being explored. Here, we review past and present experience, current challenges, practical considerations, and future aspirations in the evolution of TIL therapy for the treatment of melanoma as well as other solid tumors.Allison Betof Warner, Pippa G Corrie, Omid Hamid
2454 related Products with: Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.
10 1 mg100 mg
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#36484997 2022/12/09
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An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4.
Activity-based protein profiling (ABPP) is a versatile strategy for identifying and characterizing functional protein sites and compounds for therapeutic development. However, the vast majority of ABPP methods for covalent drug discovery target highly nucleophilic amino acids such as cysteine or lysine. Here, we report a methionine-directed ABPP platform using Redox-Activated Chemical Tagging (ReACT), which leverages a biomimetic oxidative ligation strategy for selective methionine modification. Application of ReACT to oncoprotein cyclin-dependent kinase 4 (CDK4) as a representative high-value drug target identified three new ligandable methionine sites. We then synthesized a methionine-targeting covalent ligand library bearing a diverse array of heterocyclic, heteroatom, and stereochemically rich substituents. ABPP screening of this focused library identified 1oxF11 as a covalent modifier of CDK4 at an allosteric M169 site. This compound inhibited kinase activity in a dose-dependent manner on purified protein and in breast cancer cells. Further investigation of 1oxF11 found prominent cation-π and H-bonding interactions stabilizing the binding of this fragment at the M169 site. Quantitative mass-spectrometry studies validated 1oxF11 ligation of CDK4 in breast cancer cell lysates. Further biochemical analyses revealed cross-talk between M169 oxidation and T172 phosphorylation, where M169 oxidation prevented phosphorylation of the activating T172 site on CDK4 and blocked cell cycle progression. By identifying a new mechanism for allosteric methionine redox regulation on CDK4 and developing a unique modality for its therapeutic intervention, this work showcases a generalizable platform that provides a starting point for engaging in broader chemoproteomics and protein ligand discovery efforts to find and target previously undruggable methionine sites.Angel Gonzalez-Valero, Audrey G Reeves, Annika C S Page, Patrick J Moon, Edward Miller, Katia Coulonval, Steven W M Crossley, Xiao Xie, Dan He, Patricia Z Musacchio, Alec H Christian, Jeffrey M McKenna, Richard A Lewis, Eric Fang, Dustin Dovala, Yipin Lu, Lynn M McGregor, Markus Schirle, John A Tallarico, Pierre P Roger, F Dean Toste, Christopher J Chang
1263 related Products with: An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4.
100ul100ug Lyophilized100ug Lyophilized100μg25 µg100ug Lyophilized 100ul100ug100ug Lyophilized 100ul100ug Lyophilized
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#36484984 2022/12/09
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Crystal Structure of the RNA Lariat Debranching Enzyme Dbr1 with Hydrolyzed Phosphorothioate RNA Product.
The RNA lariat debranching enzyme is the sole enzyme responsible for hydrolyzing the 2'-5' phosphodiester bond in RNA lariats produced by the spliceosome. Here, we test the ability of Dbr1 to hydrolyze branched RNAs (bRNAs) that contain a 2'-5'-phosphorothioate linkage, a modification commonly used to resist degradation. We attempted to cocrystallize a phosphorothioate-branched RNA (PS-bRNA) with wild-type Dbr1 (EhDbr1) but observed in-crystal hydrolysis of the phosphorothioate bond. The crystal structure revealed EhDbr1 in a product-bound state, with the hydrolyzed 2'-5' fragment of the PS-bRNA mimicking the binding mode of the native bRNA substrate. These findings suggest that product inhibition may contribute to the kinetic mechanism of Dbr1. We show that Dbr1 enzymes cleave phosphorothioate linkages at rates ∼10,000-fold more slowly than native phosphate linkages. This new product-bound crystal structure offers atomic details, which can aid inhibitor design. Dbr1 inhibitors could be therapeutic or investigative compounds for human diseases such as human immunodeficiency virus (HIV), amyotrophic lateral sclerosis (ALS), cancer, and viral encephalitis.Nathaniel E Clark, Adam Katolik, Anastasia Welch, Christoph Schorl, Stephen P Holloway, Jonathan P Schuermann, P John Hart, Alexander B Taylor, Masad J Damha, William G Fairbrother
2305 related Products with: Crystal Structure of the RNA Lariat Debranching Enzyme Dbr1 with Hydrolyzed Phosphorothioate RNA Product.
100 U1000 units5 X 1000 U200ul10 nmol500 Units50 mg1ml 50 UG5 X 1000 U200ul250ul
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#36484982 2022/12/09
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Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells.
Endometriosis is a chronic gynecological disease in women of childbearing age, which leads to infertility with risk of endometrial and ovarian cancer. The pathogenesis of endometriosis is poorly understood, and cure/treatment for it is not available, except for symptomatic treatment. The recurrence rate of endometriosis is high. SLP-2 is an inner mitochondrial membrane protein whose participation has been explained in cases of endometrial stromal cell growth, differentiation and migration, but its role in endometriosis is yet to be understood. Previous studies have found altered expression of stomatin-like protein 2 (SLP-2) in the serum of endometriotic patients. Therefore, we have studied the possible role of SLP-2 in the development of endometriosis. We found the ubiquitous and high expression of SLP-2 in the endometriotic tissue of both human endometriosis patients and rat endometriosis model. SLP-2 is seen in the glandular epithelial cells and stromal cells in the eutopic/normal or non-endometriosis group endometrium from human subjects. Finding high expression levels of SLP-2 in endometriotic tissue and ovarian cystic cells derived from endometriosis patients, we explored the possible role of SLP-2 in the cell aggregation, colonization, migration, and invasion in the human endometriotic cells associated with the progression of the endometriosis. Transient silencing of SLP-2 by its siRNA hinders endometriotic cells, aggregation, migration, and invasion into the extracellular matrix, which confirms SLP-2 involvement in endometriotic disease onset and progression. This study unravels the ubiquitous expression of SLP-2 in the human ectopic endometrial tissue and its role in the endometriotic cell migration, colonization, aggregation, and invasion leading to endometriosis progression.Suparna Kumari, Pushplata Sankhwar, Rupal Tripathi, Ajay K Kawale, Satish Gupta, Rajesh Kumar Jha
2344 related Products with: Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells.
25UG250ul20000 U250ul1000 TESTS/0.65ml200ml25ml 5 x 200ul/Unit250ul25ml100ug Lyophilized
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#36484979 2022/12/09
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Uncertain resection of highest mediastinal lymph node positive among pN2 non-small cell lung cancer patients: survival analysis of postoperative radiotherapy and driver gene mutations.
The role of postoperative radiotherapy (PORT) in uncertain resection of pN2 non-small cell lung cancer (NSCLC) with highest mediastinal lymph node positive has not been determined. We aim to evaluate the effect of PORT and driver gene mutation status (DGMS) on survival in such patients.Qianyue Deng, Huan Wang, Weigang Xiu, Xiaoman Tian, Youling Gong
1247 related Products with: Uncertain resection of highest mediastinal lymph node positive among pN2 non-small cell lung cancer patients: survival analysis of postoperative radiotherapy and driver gene mutations.
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#36484975 2022/12/09
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Profiling and Bioinformatics Analyses of Differential Circular RNA Expression in Glioblastoma Multiforme Cells Under Hypoxia.
The hypoxia microenvironment is highly associated with GBM's malignant phenotypes. CircRNAs were reported involved in GBM's biological characteristics and regulated by HIF-1α. However, the differential expression profile and role of circRNAs in GBM cells under hypoxia are still unclear. The expression profiles of circRNAs in LN229 and T98G under hypoxia were explored via circRNA sequencing analysis. Those circRNAs significantly dysregulated both in LN229 and T98G and could be found in circBase were selected and validated by qRT-PCR, RNase R digestion reaction, and Sanger sequencing. Normal cell line and fresh GBM tissues were also used for qRT-PCR validation. The roles of differentially expressed circRNAs were evaluated by bioinformatics analyses. There were 672 dysregulated circRNAs in LN229 and 698 dysregulated circRNAs in T98G. GO analysis indicated that the alteration of circRNA expression related to GBM cell's biogenesis and metabolism. KEGG analysis demonstrated that TGF-β signaling pathway, HIF-1 signaling pathway, and metabolism-related signaling pathway were closely associated with differentially expressed circRNAs under hypoxia. These results were confirmed by GSEA analysis. The 6 selected and dysregulated circRNAs both in LN229 and T98G including hsa_circ_0000745, hsa_circ_0020093, hsa_circ_0020094, hsa_circ_0000943, hsa_circ_0004874, and hsa_circ_0002359 were validated by qRT-PCR. Inhibition of hsa_circ_0000745 inhibited GBM cell's proliferation, migration, and invasion. HIF-1α centered circRNA-miRNA-mRNA networks analysis showed that the 6 validated circRNAs could cross-talk with 11 related miRNAs. The circRNA expressions are dysregulated in GBM cell under hypoxia. The 6 validated circRNAs could participate in GBM's development and progression when hypoxia occurs. They might be the candidates for prognostic markers and adjuvant therapeutics of GBM in the future.Zheng Chen, Shaohua Su, Min Yang, Fei Wang, Ming Chen