CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

Jingbo Ma,Xiaolong Xu,Chunjin Fu,Peng Xia,Ming Tian,Liuhai Zheng,Kun Chen,Xiaolian Liu,Yilei Li,Le Yu,Qinchang Zhu,Yangyang Yu,Rongrong Fan,Haibo Jiang,Zhifen Li,Chuanbin Yang,Chengchao Xu,Ying Long,J 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobodybased immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.

The 14-3-3 Gene Function of Cryptococcus neoformans Is Required for its Growth and Virulence

( Jingbo Li ),( Yun C. Chang ),( Chun Hua Wu ),( Jennifer Liu ),( Kyung J. Kwon Chung ),( Sheng He Huang ),( Hiro Shimada ),( Rob Fante ),( Xiaowei Fu ),( Ambrose Jong ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.5

Cryptococcus neoformans is a life-threatening pathogenic yeast that causes devastating meningoencephalitis. The mechanism of cryptococcal brain invasion is largely unknown, and recent studies suggest that its extracellular microvesicles may be involved in the invasion process. The 14-3-3 protein is abundant in the extracellular microvesicles of C. neoformans, and the 14-3-3-GFP fusion has been used as the microvesicle’s marker. However, the physiological role of 14-3-3 has not been explored. In this report, we have found that C. neoformans contains a single 14-3-3 gene that apparently is an essential gene. To explore the functions of 14-3-3, we substituted the promoter region of the 14-3-3 with the copper-controllable promoter CTR4. The CTR4 regulatory strain showed an enlarged cell size, drastic changes in morphology, and a decrease in the thickness of the capsule under copper-enriched conditions. Furthermore, the mutant cells produced a lower amount of total proteins in their extracellular microvesicles and reduced adhesion to human brain microvascular endothelial cells in vitro. Proteomic analyses of the protein components under 14-3-3-overexpressed and -suppressed conditions revealed that the 14-3-3 function(s) might be associated with the microvesicle biogenesis. Our results support that 14-3-3 has diverse pertinent roles in both physiology and pathogenesis in C. neoformans. Its gene functions are closely relevant to the pathogenesis of this fungus.

Geographical distribution patterns of Metaeuchromius in Asia and description of a new species from China (Lepidoptera, Crambidae)

Jingbo Yang,Wei Liu,Weichun Li 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.3

The geographical distribution patterns of Asian Metaeuchromius are analysed with MaxEnt and ArcGIS based on known localities and nineteen environmental variables. The results suggest that the most highly suitable area of the genus located in southeastern China. Precipitation of the warmest quarter (Bio18) and temperature seasonality (Bio4) are the most significant variables affecting geographical distribution Metaeuchromius. Furthermore, a new species from Jiangxi Province, southeast China is added to the genus, Metaeuchromius grandispinata Li, sp. nov. Its habitus, tympanic organs and genitalia are illustrated, and two maps showing geographical distribution patterns of Metaeuchromius in Asia are provided.

Extraction of Pigment from Sugarcane Juice Alcohol Wastewater and Evaluation of Its Antioxidant and Free Radical Scavenging Activities

Jingbo Li,Lei Liang,Jingrong Cheng,Yunan Huang,Ming-Jun Zhu,Shizhong Liang 한국식품과학회 2012 Food Science and Biotechnology Vol.21 No.5

Pigment was extracted to decolor the sugarcane juice alcohol wastewater and its antioxidant activities were evaluated. The pigment was extracted using ion exchange fiber along with macroporous resin D-101 as the absorbent and an ethanol-water mixture (6:4, v/v) as the eluent. Total flavonoid and phenolic contents of the pigment were determined. DPPH radical scavenging ability and reducing power of 1.0 mg/mL of the pigment were approximately 78.5 and 16.8%, respectively, compared to 1.0 mg/mL of the tea polyphenol (positive control). The hydroxyl radical scavenging ability of 10.0 mg/mL of the pigment was about 92.5% compared to that of positive control. The DPPH radical scavenging ability of the pigment was enhanced significantly with thermal treatment at 70 and 100oC. The result shows the proposed procedure can be effective to decolor such wastewater and to get antioxidative pigment.

Study of Data Stream Clustering Based on MSF

Yingmei Li,Min Li,Jingbo Shao,Gaoyang Wang 보안공학연구지원센터 2015 International Journal of Database Theory and Appli Vol.8 No.1

Nowadays with the rapid development of wireless sensor networks, and network traffic monitoring, stream data gradually becomes one of the most popular data models. Stream data is different from the traditional static data. Clustering analysis is an important technology for data mining, so that many researchers pay their attention to the clustering of stream data. In this paper, MSFS algorithm is proposed. By means of the experimental verification analysis, based on biologically inspired computational model, higher clustering purity on both the real dataset and the simulation datasets existence is demonstrated for the proposed algorithm. In other words, the cluster result of MSFS algorithm is advantageous over previous method.

Coordinated Attitude Control for Synthetic Aperture Radar Satellites with Quantization and Communication Delay

Jingbo Fu,Ming Liu,Huayi Li,Xibin Cao 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.7

This paper studies the coordinated attitude control problem of synthetic aperture radar satellites andproposes two types of terminal sliding mode control schemes. The first control law is investigated based on theconventional non-singular terminal sliding mode approach and modified Rodrigues parameters with the consideration of signal quantization and communication delay. Based on the first control scheme, we develop the secondcontrol method with an integral-based event triggering condition to reduce the updating frequency of the controlcommand from controllers to actuators. Finally, numerical simulation examples based on a cluster of three satellitesare presented to show the effectiveness of the proposed two designed control methods.

Effects of Marbling on Meat Quality Characteristics and Intramuscular Connective Tissue of Beef Longissimus Muscle

Li, Chunbao,Zhou, Guanghong,Xu, Xinglian,Zhang, Jingbo,Xu, Shuqin,Ji, Yanfeng Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.12

This study was designed to explore the effects of marbling on meat quality characteristics and intramuscular connective tissue of beef longissimus muscle. Chemical determinations, histological and mechanical measurements were performed on the raw and cooked meat at d 4 postmortem. The results showed that crude fat, collagen, fiber diameter and maximum transition temperature of intramuscular connective tissue increased (p<0.05) with the increase of marbling score. The cooking losses, collagen solubility, WBSF and perimysial thickness decreased (p<0.05) with the increasing marbling. WBSF correlated (p<0.05) with moisture, crude fat, collagen, cooking losses, sarcomere length and perimysial thickness. The development of marbling results in the decline in cooking losses, the avoidance of sarcomere shortening, and the disorganization of the perimysia, which accounts for the improvement of beef tenderness.

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix

Jingbo Sun,He Li,Jinghui Sun,Huimin Liu,JianGuang Chen,Chunmei Wang 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.8

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L9(34)], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography–mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Database Performance Optimization for SQL Server Based on Hierarchical Queuing Network Model

Jingbo Shao,Xiaoxiao Liu,Yingmei Li,Jingyu Liu 보안공학연구지원센터 2015 International Journal of Database Theory and Appli Vol.8 No.1

With the ever-increasing complexity and variety of database workload, database application system has been imposed on higher and higher performance requirements. Database system consists of software and hardware. And the factors that affect database performance are uncertain. In order to tackle the issue of database system for SQL server, this paper proposes hierarchical queuing network model for performance prediction, and a model is established for both software resources and hardware resources, the nested resources are linearized by hierarchical calling, thus finding out the main factors for system performance bottleneck, and system performance is adjusted and optimized accordingly. The performance tuning algorithm for SQL server database based on the hierarchical queuing network is presented in detail. And TPC-C benchmark is adopted for simulation. Experimental results show the proposed method achieves 16.8% performance increase on average, and TPS is improved by 40% compared to previous method.

Enriched finite element method for 2-D and 3-D blunt crack problems in a viscoelastic medium

Jingbo Duan,Yongjun Lei,Daokui Li 대한기계학회 2012 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.26 No.3

The analysis of two-dimensional and three-dimensional blunt crack problems in a linear viscoelastic medium is numerically investigated using the enriched finite element method. The enriched crack-tip elements are established by enriching the asymptotic displacement fields at the blunt crack front to the regular elements. The corresponding transition elements are formulated to eliminate displacement field incompatibility. The viscoelastic incremental formulations for the enriched finite element method in time domain are derived according to the Boltzmann superposition principle. The time-dependent deformations of crack are presented and the stress intensity factors are directly obtained from the enriched degree of freedoms. The numerical examples indicate that the enriched finite element method is extremely suitable for dealing with complicated blunt crack problems.