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Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate
Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.
Zhi-Qiang Wang,Zhi-Qiang Long,Xiao-Long Li 대한전기학회 2019 Journal of Electrical Engineering & Technology Vol.14 No.3
It is observed in test operation that for permanent magnet electro-magnetic suspension (PEMS) type high speed maglev train, when a single levitation unit in an end joint structure fails to work, the performance of the entire joint structure deteriorates rapidly, whereas in electro-magnetic suspension (EMS) type maglev system, there is no such phenomenon under the same failure. To solve this problem and to enhance system performance under faulty condition, fi rstly a comparative modeling of EMS and PEMS maglev end joint structure system was made to analyze the underlying reasons. Then a dynamic compensation method and a disturbance rejection method based on disturbance estimation and feedback linearization were proposed respectively. The performances of the proposed measures are verifi ed and compared in simulations.
Zhi-long Wang,Ming-nian Wang,Dagang Liu 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.12
Convergence-confinement method (CCM) has become a common method for tunnel design due to its simplicity and practicality. The ground reaction curve (GRC), the support characteristic curve (SCC) and the longitudinal deformation profile (LDP) are all considered in this method. One of these is the LDP, which serves as a unique identifier for the location of the tunnel support. The installation point of the tunnel support is one of the most important outcomes of the method. LDP is more impacted by the reinforcement of the tunnel face. However, more existing LDP calculation methods do not consider the reinforcement of the tunnel face. A study on methods for calculating LDP considering the tunnel face reinforcement was carried out to address this constraint of CCM. Firstly, the transformation of tunnel face extrusion deformation and pre-convergence deformation at the tunnel face is realized in accordance with equivalent volume. Then a model of LDP with the tunnel face extrusion deformation as the variable was established considering the tunnel face reinforcement effect. The proposed model's accuracy is assessed in comparison with other typical models. We conclude with parametric analyses concerning the tunnel face reinforcement's effects on the point of support installation, as well as convergence deformation of the tunnel. By taking into account tunnel faces' reinforcement effects, tunnel support design can be more accurate, and the construction costs can be reduced.
Zhi-Long Wang,Ru-Lin Miao,Chao Gao,Lei Tang,Zi-Yu Li,Ying-Shi Sun,Jia-Fu Ji 대한영상의학회 2019 Korean Journal of Radiology Vol.20 No.3
Objective: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). Materials and Methods: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. Results: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). Conclusion: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.
<i>Chd7</i> Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish
Liu, Zhi-Zhi,Wang, Zi-Long,Choi, Tae-Ik,Huang, Wen-Ting,Wang, Han-Tsing,Han, Ying-Ying,Zhu, Lou-Yin,Kim, Hyun-Taek,Choi, Jung-Hwa,Lee, Jin-Soo,Kim, Hyung-Goo,Zhao, Jian,Chen, Yue,Lu, Zhuo,Tian, Xiao-L Elsevier 2018 The American journal of pathology Vol.188 No.4
<P>Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T cells have been noted in CHARGE syndrome. However, the mechanisms underlying T lymphopenia are largely unexplored. Herein, we observed dramatic decrease of T cells in both chd7knockdown and knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T-cell decrease. Further analysis demonstrated that both the organogenesis and homing function of the thymus were seriously impaired. Chd7 might regulate thymus organogenesis through modulating the development of both neural crest cell-derived mesenchyme and pharyngeal endoderm-derived thymic epithelial cells. The expression of faxn1, a central regulator of thymic epithelium, was remarkably down-regulated in the pharyngeal region in chd7-deficient embryos. Moreover, the T-cell reduction in chd7-deficient embryos was partially rescued by overexpressingfoxnl, suggesting that restoring thymic epithelium may be a potential therapeutic strategy for treating immunodeficiency in CHARGE syndrome. Collectively, the results indicated that chd7 was critical for thymic development and T-lymphopenia in CHARGE syndrome may be mainly attributed to the defects of thymic organogenesis. The current finding may benefit the diagnosis and therapy of T lymphopenia and immunodeficiency in CHARGE syndrome.</P>
Tie Jun Wang,Chen Guang Wang,Tie Jun Wang,Yan Gao,Chuang Zhi Wu,Long Long Ma 한국화학공학회 2008 Korean Journal of Chemical Engineering Vol.25 No.4
With naphthalene as biomass tar model compound, partial oxidation reforming (with addition of O2) and dry reforming of biomass fuel gas were investigated over nickel-based monoliths at the same conditions. The results showed that both processes had excellent performance in upgrading biomass raw fuel gas. Above 99% of naphthalene was converted into synthesis gases (H2+CO). About 2.8 wt% of coke deposition was detected on the catalyst surface for dry reforming process at 750 oC during 108 h lifetime test. However, no coke deposition was detected for partial oxidation reforming process, which indicated that addition of O2 can effectively prohibit the coke formation. O2 can also increase the CH4 conversion and H2/CO ratio of the producer gas. The average conversion of CH4 in dry and partial oxidation reforming process was 92% and 95%, respectively. The average H2/CO ratio increased from 0.95 to 1.1 with the addition of O2, which was suitable to be used as synthesis gas for dimethyl ether (DME) synthesis.