学　术

       为搭建我校博士后之间的学术交流平台，促进学术水平提升，学校人力资源部博士后和教师引进管理办公室组织开展博士后学术沙龙活动。本次沙龙由我校博士后李政、何宇、何韵琪、刘燕青和桑纳分享其研究成果，诚挚邀请感兴趣的师生参加。

　　一、时　间：2023年6月29日（周四）09：30

　　二、地　点：成都医学城三医创新中心三期8栋6楼会议室

                     　　腾讯会议ID：859-251-402

　　三、主办单位：人力资源部博士后和教师引进管理办公室

　　四、承办单位：医学院   电子科技大学博士后联谊会

　　五、活动安排：

　　报告一：     

　　（1）主　题：Role of UC-MSC-derived exosomes on NaIO3-induced retinal-choroidal injury

　　（2）主讲人：李政  医学院博士后

　　（3）交流内容：

　　The exosomes are 30-100 nm diameter microvesicles surrounded by lipids such as proteins, mRNA, and microRNA, which can be released into the extracellular matrix by fusing the intracellular multivesicular body (MVB) with the cell membrane. Human umbilical cord mesenchymal stem cell (UC-MSC)-derived exosomes have been shown to play an important role in many aspects, especially in tumor treatment and wound healing. However, its role in the treatment of eye diseases, particularly age-related macular degeneration, remains unclear. In our study, we used the characteristics that NaIO3 injection into the abdominal cavity of mice could cause damage to the choroidal layer structure to mimic dry age-related macular degeneration, and then treated this model mice with UC-MSC-derived exosomes. The results showed that the visual function of model mice could be significantly improved after 3 days or 7 days with the exosomes treatment. Furthermore, the transcriptomics data analysis showed that the expression level of crystal protein gene and KLK6 gene in the exosomes treatment group were upregulated. we speculated that the exosomes treatment group were conducive to the recovery of visual function by promoting the expression of crystal protein gene and KLK6 gene. Above all, our findings will provide a new strategy for UC-MSC-derived exosomes in the treatment of dry age-related macular degeneration.

　　（4）主讲人简介：

　　Zheng Li received a genetics Ph.D. degree from Southwest University in 2022. During doctoral studies, he published three research articles as the first or co-first author in PNAS, Nucleic Acids Res, and Cell Rep, respectively. After graduating from Southwest University, he joined Sichuan Provincial People's Hospital affiliated to the school of medicine in UESTC as a postdoctoral. His current main research interest is molecular genetic mechanisms and treatment of eye diseases.

 　　报告二：    

　　（1）主　题：New frontiers against sorafenib resistance in kidney renal clear cell carcinoma

　　（2）主讲人：何宇  医学院博士后

　　（3）交流内容：

　　Kidney renal clear cell carcinoma (KIRC) is a highly vascularized tumor and prone to distant metastasis. Sorafenib is the first targeted multikinase inhibitor and first-line chemical drug approved for KIRC therapy. In fact, only a small number of KIRC patients benefit significantly from sorafenib treatment, while the growing prevalence of sorafenib resistance has become a major obstacle for drug therapy effectivity of sorafenib.

　　Our previous study found that tumor hypoxia and abnormally elevated glycolysis are one of the important reasons for the failure of sorafenib treatment, and that the glycolytic metabolic enzyme PGK1 contributes to tumorigenesis and sorafenib resistance of KIRC via activating CXCR4/ERK signaling pathway and accelerating glycolysis. These results suggest that PGK1 may represent a potentially valuable target for overcoming sorafenib resistance in KIRC. However, currently no approved PGK1 inhibitor is available in the market. Terazosin is a competitive inhibitor of PGK1 at high dosages (2.5-25 μM) by occupying the ADP-binding pocket of PGK1. Based on the crystal structure of PGK1/terazosin complex, small-molecule inhibitors of PGK1 were identified by using structure-based virtual screening and a series of biochemical and biophysical analyses, and their anti-KIRC activities were investigated in vitro and in vivo. The compound Z57346765 from Kinase Library and compound CHR-6494 from Bioactive Compound Library were screened as potential PGK1 inhibitors. Our research is expected to provide new ideas and experimental basis for the development of small-molecule inhibitors of PGK1 and the treatment of KIRC after sorafenib resistance.

　　（4）主讲人简介：

　　Yu He graduated from the State Key Laboratory of Biotherapy of Sichuan University in 2022, and obtained a doctor’s degree in biochemistry and molecular biology. He is currently working as a postdoctoral fellow at Sichuan Provincial People’s Hospital affiliated to University of Electronic Science and Technology of China. His research fields of interest include the mechanism of drug resistance and targeted therapy of tumors, and the application of CRISPR/Cas9 gene editing technology in retinal diseases.

　　报告三：

　　（1）主题：Novel truncating variants in CTNNB1 cause familial exudative vitreoretinopathy

　　（2）主讲人： 何韵琪  医学院博士后 

　　（3）交流内容：

　　Familial exudative vitreoretinopathy (FEVR) is an inheritable blinding disorder with clinical and genetic heterogeneity. Heterozygous variants in the CTNNB1 gene have been reported to cause FEVR. However, the pathogenic basis of CTNNB1-associated FEVR has not been fully explored.

　　We performed whole-exome sequencing on the genomic DNA of probands. Dual-luciferase reporter assay, western blotting and co-immunoprecipitation were used to characterise the impacts of variants. Quantitative real-time PCR, EdU (5-ethynyl-2′-deoxyuridine) incorporation assay and immunocytochemistry were performed on the primary human retinal microvascular endothelial cells (HRECs) to investigate the effect of CTNNB1 depletion on the downstream genes involved in Norrin/β-catenin signalling, cell proliferation and junctional integrity, respectively. Transendothelial electrical resistance assay was applied to measure endothelial permeability. Heterozygous endothelial- specific Ctnnb1-knockout mouse mice were generated to verify FEVR-like phenotypes in the retina. Together, we identified two novel heterozygous variants (p.Leu103Ter and p.Val199LeufsTer11) and one previously reported heterozygous variant (p.His369ThrfsTer2) in the CTNNB1 gene. These variants caused truncation and degradation of β-catenin that reduced Norrin/β-catenin signalling activity. Additionally, knockdown (KD) of CTNNB1 in HRECs led to diminished mRNA levels of Norrin/β-catenin targeted genes, reduced cell proliferation and compromised junctional integrity. The Cre-mediated heterozygous deletion of Ctnnb1 in mouse endothelial cells (ECs) resulted in FEVR-like phenotypes. Moreover, LiCl treatment partially rescued the defects in CTNNB1-KD HRECs and EC-specific Ctnnb1 heterozygous knockout mice.

　　Our findings reinforced the current pathogenesis of Norrin/β-catenin for FEVR and expanded the causative variant spectrum of CTNNB1 for the prenatal diagnosis and genetic counselling of FEVR.

　　（4）主讲人简介：

　　Y.Q. He received the Bachelor degree from Sichuan University, Master degree from The University of Edinburgh and Ph.D. degree from the University of Chinese Academy of Sciences, in 2016, 2017 and 2022, respectively. She currently works as a Postdoctoral Fellow in the Medical School of UESTC. Dr.He is working in the field of the pathogenesis of genetic diseases, mainly focusing on Ophthalmic genetic disease.

 　　报告四：

　　（1）主题：Radical/Radical Cross-Coupling Reactions Enabled by N-Heterocyclic Carbene Organocatalysis

　　（2）主讲人： 刘燕青  医学院博士后 

　　（3）交流内容：

　　Radical/radical cross-coupling reactions provide an efficient and straightforward approach for the construction of chemical bonds and have drawn increasing attention over the past decades. According to the persistent radical effect (PRE), a persistent radical could be coupled with a transient radical and achieve synthetically useful transformations. To date, known transient radicals far outnumber the known types of free persistent radicals, limiting the widespread application of the PRE. Meanwhile, recently uncovered NHC-derived ketyl radicals generated through organocatalysis are a type of catalytically generated free persistent radicals. NHC-catalyzed radical transformations of aldehydes and carboxylic acid derivatives have enabled the disclosure of an ever-increasing number of interesting reactions, which are different from traditional NHC-catalyzed ionic processes, offering otherwise inaccessible activation modes. These discoveries have opened a door to NHC organocatalysis for the manipulation of radical reactions. Here, we briefly discuss this emerging field due to its obvious potential in synthetic organic chemistry, and there are two parts including ketyl radicals generated via single-electron oxidation using NHC catalysis and ketyl radicals generated via single-reduction oxidation using NHC catalysis.

　　（4）主讲人简介：

　　Yan-Qing Liu received the Bachelor degree and Ph.D. degree from the Chengdu University of TCM, in 2019 and 2022, respectively. She currently works as a Postdoctoral researcher in the School of Medicine of UESTC. Her main research interests include radical NHC catalysis, small-molecule catalytic polar chemistry, construction and modification of biologically relevant skeletons. 

　　报告五：

　　（1）主题：The Role of SMPD3 of Lipid Metabolism in the Metastasis of Colorectal Cancer

　　（2）主讲人：桑纳 医学院博士后

　　（3）交流内容：

　　In this talk, we briefly discuss The Role of SMPD3 of Lipid Metabolism in the Metastasis of Colorectal Cancer. There are three issues: (1) How we find the SMPD3, (2) The relationship between SMPD3 and Lipid Metabolism, (3) how we prove the Role of SMPD3 in the Metastasis of Colorectal Cancer.

　　First, we detected the lipid content in four colorectal cancer cells. Compared with the low- metastasis cell strain, the ceramide content in the high metastasis strain was significantly increased. After detecting the enzyme content of ceramide synthesis related pathway, SMPD3 was found to be the most relevant to colorectal cancer metastasis, so we focus on SMPD3 to study. And the purpose of our study is studying the role of SMPD3 of lipid metabolism in the metastasis of colorectal cancer.

　　Then, we increased the level of SMPD3 in SW480 cells since it has low expression of SMPD3 and knock down the in SMPD3 in DLD-1 cells since it has high expression of SMPD3. Testing the ability of metastasis of this kind of cell lines in vitro and in vivo.

　　Finally, we proved SMPD3 is the key gene to regular the ability of metastasis in colorectal cancer by changing the lipid metabolism. This study provides a targeted foundation for the development of new drugs.

　　（4）主讲人简介：

　　Na Sang is a post-doctor majored in Pharmacology. She obtained bachelor’s degree in Pharmacy in Southwestern Medical University, then performed Master and PhD research in Sichuan University. Dr.Sang’s research interests include evaluation of anti-tumor drugs, discovery of new genes for tumor, drugs discovery in the cardiovascular diseases.

                                       　　　　　　　　　　人力资源部博士后和教师引进管理办公室

                                                 　　　　　　 　　　　　　2023年6月21日