Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

Yilei Chen,Hongxing Huang,Yin Liu,Zhanghao Wang,Lili Wang,Quanxiao Wang,Yan Zhang,Hua Wang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. Materials and Methods nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. Results A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. Conclusion nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells. PurposeThe purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells.Materials and MethodsnABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells <i>in vitro</i>.ResultsA high-affinity peptide (nABPD1, K_D=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (K_D=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the <i>in vitro</i> antitumor activity of ICIK cells.ConclusionnABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

Effect of IgY on Periodontitis and Halitosis Induced by Fusobacterium nucleatum

( Fang Wang ),( Wu Qiao ),( Bin Bao ),( Shujun Wang ),( Joe Mac Regenstein ),( Yilei Shi ),( Wenhui Wu ),( Ming Ma ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.2

Fusobacterium nucleatum is a morbific agent in periodontitis and halitosis. Egg yolk antibody (IgY) was obtained from egg yolks from chickens stimulated with F. nucleatum. This study was to assess the effectiveness of IgY on periodontitis and halitosis caused by F. nucleatum in vitro and in vivo. The growth of F. nucleatum was inhibited (p <0. 05) by different concentrations of IgY in vitro and the results of a Halimeter show volatile sulfur compounds (VSCs) were reduced to 904 ± 57 ppb at a concentration 40 mg/ml of IgY. The changes of fatty acids of F. nucleatum were determined using GC-MS. The scores for odor index of rat saliva were decreased. The major constituent of volatile organic compounds (VOCs) including short-chain acids decreased 46.2% in 10 mg/ml IgY, ammonia decreased 70% in 40 mg/ml IgY, while aldehydes and olefine ketones were almost unchanged. The ELISA assay revealed that IL-6 and TNF-α were decreased after 4 weeks’ IgY treatment. Morphometric (X-ray) and histological analyses (HE) showed that IgY reduced alveolar bone loss and collagen fibers became orderly in rat models. As a result, IgY may have the potential to treat periodontitis and halitosis.

The characteristic of Cu2ZnSnS4 thin film solar cells prepared by sputtering CuSn and CuZn alloy targets

Yilei Lu,Shurong Wang,Xun Ma,Xin Xu,Shuai Yang,Yaobin Li,Zhen Tang 한국물리학회 2018 Current Applied Physics Vol.18 No.12

Recent study shows that the main reason for limiting CZTS device performance lies in the low open circuit voltage, and crucial factor that could affect the Voc is secondary phases like ZnS existing in absorber layer and its interfaces. In this work, the Cu2ZnSnS4 thin film solar cells were prepared by sputtering CuSn and CuZn alloy targets. Through tuning the Zn/Sn ratios of the CZTS thin films, the crystal structure, morphology, chemical composition and phase purity of CZTS thin films were characterized by X-Ray Diffraction (XRD), scanning electron microscopy (SEM) equipped with an energy dispersive spectrometer (EDS) and Raman spectroscopy. The statistics data show that the CZTS solar cell with a ratio of Zn/Sn=1.2 have the best power convention efficiency of 5.07%. After HCl etching process, the CZTS thin film solar cell with the highest efficiency 5.41% was obtained, which demonstrated that CZTS film solar cells with high efficiency could be developed by sputtering CuSn and CuZn alloy targets.

Structure evolution in carbon molecular sieve membranes derived from binaphthol-6FDA polyimide and their gas separation performance

Guoxiong Deng,Yilei Wang,Xueping Zong,Jiangzhou Luo,Xuezhen Wang,Chunxue Zhang,Song Xue 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.94 No.-

Here we reported a causal relationship between the molecular structure of binaphthol-based polyimideprecursor and the pore-size distribution of the derived carbon membrane. The binaphthol-basedpolyamide acid is synthesized from 2,20-diol-1,10-binaphthyl-6,60-diamine and 4,40-(hexafluoroisopro-pylidene)diphthalic anhydride (6FDA). Then, an azeotropic imidiaztion method was used to synthesizethe polyimide with naphthol groups (XS1). When the imidization is carried out by using acetic anhydride,the polyimide with acetyl groups (XS4) is achieved. The CMS membranes prepared by pyrolyzing XS1 andXS4 at 500, 550, and 600 ℃ are named using the temperature as the suffix, such as XS1-500. Their poreevolution has been investigated using TGA, FTIR, XRD, and Raman measurements. The trimodal pore-sizedistribution is in the carbon molecular sieve (CMS) membranes derived from XS4 and the CMS onesderived from XS1 exhibit a bimodal pore structure. Among them, XS4-500 exhibits the highest gaspermeabilities of 3332 barrer for CO2, 773 barrer for O2, and 119 barrer for N2. XS1-500 only affords theCO2, O2, and N2 permeabilities of 1086, 230, and 30.2 barrer. The esterification of naphthol not justdisturbs the hydrogen bonds between polyimide chains but also affects the pore generation of thederived CMS membranes. Our work provides an effective way to enhance the gas permeability of a CMSmembrane derived from the binaphthol-based polyimide.

The Digital Transformation of Power Grid under the Background of Artificial Intelligence

Li Liu,Zhiqi Li,Sujuan Deng,Yilei Zhao,Yuening Wang 한국정보처리학회 2023 Journal of information processing systems Vol.19 No.3

Artificial intelligence (AI) plays a crucial role in the intelligent development of China’s power system. It is alsoan important part of the digital development of the power grid. The development of AI determines whether thedigital transformation of China’s power system can be successfully implemented. Therefore, this paperdiscusses the digital transformation of the power grid based on AI technologies. The author has established adigital evaluation index system to reflect the development of the power grid in one province. Both qualitativeand quantitative methods have been adopted in the analysis, which delves into the economic effectiveness,quality, and coordination of power grid development in the province in a comprehensive way. Results showthat, to meet the needs of the power grid’s digital transformation, the correlation coefficient between the powergrid’s development and the province’s overall coordination has been increasing in recent years.