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Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3806-3817页

作者： Yangzhuo Gu Jingyun Yang Cai He Tingmei Zhao Ran Lu Jian Liu xianming mo Fuqiang Wen Huashan Shi Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Division of Pulmonary Diseases State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Stem Cell Biology and Department of Pediatric Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious *** of mRNA vaccines have been underway,among which boosting of efficacy is of great ***2Cys,a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor(TLR)2/6 pathway,eliciting both humoral and cellular adaptive immune responses,is an interesting candidate *** investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys,the adjuvant was incorporated into mRNA-lipid nanoparticles(LNPs)to achieve co-delivery with *** with the resulting mRNA-LNPs(Pam2Cys)shaped up the immune milieu in the draining lymph nodes(dLNs)through the induction of IL-12 and IL-17,among other *** presentation was carried out mainly by migratory and dLNresident conventional type 2 DCs(cDC2s)and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4^(+) and CD8^(+) T cell-dependent *** memory antitumor immunity was also ***,the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic *** but not the least,the new vaccines exhibited good preliminary safety profiles in murine *** facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

关键词： vaccines immunity diseases

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成体干细胞与干细胞疾病

中国修复重建外科杂志 2007年第7期21卷 759-762页

作者：莫显明四川大学华西医院生物治疗国家重点实验室.血液室成都610041

目的结合文献对成体干细胞的特性进行总结,描述干细胞疾病的定义及特性。方法广泛查阅近期相关文献,回顾成体干细胞及干细胞疾病。结果成体干细胞是一类位于成熟组织器官内、维持正常组织细胞数量和功能的原始细胞,具有自我更新和多潜... 详细信息

目的结合文献对成体干细胞的特性进行总结,描述干细胞疾病的定义及特性。方法广泛查阅近期相关文献,回顾成体干细胞及干细胞疾病。结果成体干细胞是一类位于成熟组织器官内、维持正常组织细胞数量和功能的原始细胞,具有自我更新和多潜能分化能力,随着生物个体生命周期增长,成体干细胞出现老化。起源于干细胞的疾病可视为干细胞疾病。当成体干细胞自我更新能力增强和/或分化障碍时,细胞增殖能力变强,引起增生性疾病特别是肿瘤疾病。当成体干细胞自我更新减弱,提前老化或分化不全时,可导致功能细胞形成减少,如不能满足组织器官功能的需要,将导致相应器官功能衰竭,形成退行性疾病。结论对成体干细胞自我更新、分化及老化的研究,在理论上将指导干细胞疾病的研究,并有助于发展干细胞疾病的诊断及治疗方法。

关键词：成体干细胞干细胞疾病综述

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Mid1ip1b modulates apical reorientation of non-centrosomal microtubule organizing center in epithelial cells

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Journal of Genetics and Genomics 2018年第8期45卷 433-442页

作者： Xin Zhou Chun Xiao Yu Li Yanna Shang Dongqin Yin Siying Li Bo Xiang Ran Lu Yi Ji Yang Wu Wentong Meng Hongyan Zhu Jin Liu Huozhen Hu xianming mo Hong Xu Department of Pediatric Surgery and Laboratory of Stem Cell Biology State Key Laboratory of Biotherapy West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy National Clinical Research Center of Geriatrics West China Hospital Sichuan University

In most kinds of animal cells, the centrosome serves as the main microtubule organizing center （MTOC） that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracellular transport. Whereas in epithelial cells, non-centrosomal MTOCs are established in the apical domain for generating asymmetric microtubule fibers and cilia in epithelial cells for the organ morphogenesis during embryonic development. However, the mechanism by which MTOCs localize to the apical domain in epithelial cells remains largely unknown. Here, we show that Mid liplb has a close interaction with γ-tubulin protein, the central component of MTOC, and modulates lumen opening of the neural tube, gut, intestine, and kidney of zebrafish. Knockdown or dominant negative effect of Mid 1ip 1 b resulted in failure of lumen formation of the organs as aforementioned. moreover, the non-centrosomal MTOCs were unable to orientate to the apical domain in Midliplb knockdown epithelial cells, and the centrosomal MTOCs were inaccurately placed in the apical domain, resulting in defective formation of asymmetric microtubules and misplacement of cilia in the apical domain. These data uncover a molecule that controls the proper localization of MTOCs in the apical domain in epithelial cells for organ morphogenesis during embryonic development.

关键词： Mid1ip1b Microtubule organizing center Non-centrosomal MTOC Microtubule Epithelial cell

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Neurons generated from carcinoma stem cells support cancerprogression

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Signal Transduction and Targeted Therapy 2017年第1期2卷 320-329页

作者： Ran Lu Chuanwen Fan Wenqi Shangguan Yuan Liu Yu Li Yanna Shang Dongqin Yin Shengliang Zhang Qiaorong Huang Xue Li Wentong Meng Hong Xu Zongguang Zhou Jiankun Hu Weimin Li Lunxu Liu xianming mo Laboratory of Stem Cell Biology State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Institute of Digestive Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Gastrointestinal Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Laboratory of Gastric Cancer State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Respiratory and Critical Care Medicine State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Thoracic Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China hospitalSichuan UniversityChengduChina.

Recent evidences show that nervous system acts as a crucial part of cancer *** of nerve fibers into cancer microenvironment has an important active role in cancer *** stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been ***,how the nervous system is built in cancer is largely *** we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor *** stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer *** down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse *** data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.

关键词： cancer inhibited stimulation

ApoA-ll directs zebrafish morphogenetic movements during gastrulation by regulating nucleus division in yolk syncytial layer

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ApoA-ll directs zebrafish morphogenetic movements during gas...

SCGN deficiency is a risk factor for autism spectrum disorder

2010·第一届斑马鱼学术研讨会

作者： Ting Zhang,Chun Xiao,Meilin Qian,Shaohua Yao,xianming mo

Prior to epiboly,the zebrafish embryo undergoes meroblastic cleavage to generate a blastoderm cap on top of a single large yolk *** at the boundary with the yolk cell collapse to release their nuclei into the yolk syn...

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Signal Transduction and Targeted Therapy 2023年第2期8卷 657-671页

作者： Zhe Liu Shuai Tan Lianyu Zhou Li Chen Mingfeng Liu Wang Wang Yingying Tang Qin Yang Sensen Chi Peiyan Jiang Yue Zhang Yonghua Cui Junhong Qin Xiao Hu Shenglong Li Qi Liu Lu Chen Song Li Ezra Burstein Wei Li Xiaohu Zhang xianming mo Da Jia Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of PaediatricsWest China Second University HospitalState Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapySichuan University610041ChengduChina Department of Immunology College of Basic MedicineChongqing Medical University400010ChongqingChina Department of Neurosurgery Xinqiao HospitalArmy Medical UniversityChongqingChina Beijing Key Laboratory for Genetics of Birth Defects Beijing Pediatric Research Institute100045BeijingChina moE Key Laboratory of Major Diseases in Chidren Beijing Children’s HospitalCapital Medical University100045BeijingChina Department of Psychology Beijing Children’s HospitlCapital Medical University100045BeijingChina Department of Internal Medicine University of Texas Southwestern Medical CenterDallasTX75390USA Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine West China Second University HospitalSichuan UniversityChengduChina Department of Pediatric Surgery and Laboratory of Stem Cell Biology State Key Laboratory of BiotherapyWest China HospitalSichuan University610041ChengduChina

Autism spectrum disorder(ASD)affects 1-2%of all children and poses a great social and economic challenge for the *** a highly heterogeneous neurodevelopmental disorder,the development of its treatment is extremely *** pathways have been linked to the pathogenesis of ASD,including signaling involved in synaptic function,oxytocinergic activities,immune homeostasis,chromatin modifications,and mitochondrial ***,we identify secretagogin(SCGN),a regulator of synaptic transmission,as a new risk gene for *** heterozygous loss-of-function mutations in SCGN are presented in ASD *** of Scgn in zebrafish or mice leads to autism-like behaviors and impairs brain ***,Scgn deficiency disrupts the oxytocin signaling and abnormally activates inflammation in both animal *** ASD probands carrying Scgn mutations also show reduced oxytocin ***,we demonstrate that the administration of oxytocin and anti-inflammatory drugs can attenuate ASD-associated defects caused by SCGN ***,we identify a convergence between a potential autism genetic risk factor SCGN,and the pathological deregulation in oxytocinergic signaling and immune responses,providing potential treatment for ASD patients suffering from SCGN *** study also indicates that it is critical to identify and stratify ASD patient populations based on their disease mechanisms,which could greatly enhance therapeutic success.

关键词： spectrum bands autism

Stat3 signaling target Efemp2 controls the assembly of Fibronectin and Laminin for gastrula anterior cell migration

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Stat3 signaling target Efemp2 controls the assembly of Fibro...

Zygotic wnt8 expression is controlled by a novel kruppel zinc finger protein for ventro-lateral cell fate in zebrafish embryos

2012全国发育生物学大会

作者： Ting Zhang,Zhaoran Ying,xianming mo Laboratory of Stem Cell Biology,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu, 610041

Fibronectin and Laminin are the principal components of extracellular matrix,and the assembly into fibrils to form basement membrane is required for cell *** embryos,the assembly of Fibronectin and Laminin is first observed at early gastrulation and coupled with the anterior movement of mesendoderm *** embryonic gastrulation,the molecular basis of the process of matrix assembly has not been fully *** we showed that Efemp2,an extracellular protein,was able to interact with Fibronectin and Laminin to modulate their self-assembly or cell-driven assembly into fibrillar matrix directly in *** of Efemp2 function in zebrafish embryos prevented the assembly of Fibronectin and Laminin into basement membrane rather than their expression,and thereby induced the anterior leading edge cells fail to form the orient protrusions and reduced E-Cadherin-mediated cell-cell contact,resulting in moving random. In addition,we found out that Efemp2 was the downstream effector of Stat3 signalling,because Efemp2 expression was regulated by Stat3 activiy and the phenotype of anterior migration induced by knocking down Stat3 was partially restored by exogenous Efemp2. Conclusion:Our data indicate that proper activity of Stat3-Efemp2 signalling is required for the construction of extracellular matrix and suggest that Efemp2 as a novel factor modulates matrix assembly to control cells migration,and finally regulates early embryonic morphogenesis.

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Zygotic wnt8 expression is controlled by a novel kruppel zin...

Enhancing anion conductivity in a highly alkali-stable eta topologic Cu(Ⅰ) framework via strong electrostatic repulsion

2010·第一届斑马鱼学术研讨会

作者： Shaohua Yao,Meilin Qian,Senyi Deng,Lifang Xie,Hanshuo Yang,Chun Xiao,Ting Zhang, Hong Xu,Xia Zhao,Lijuan Chen,Hongxin Deng,Min Song,Pei Li,Yu-quan Wei~*,xianming mo~*

During vertebrate embryonic development,the body axis formation requires active Wnt signals and their *** zebrafish,zygotic canonical wnt8 expression appears exclusively at the ventrolateral margin and mediates Wnt/ -...

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Science China Chemistry 2025年

作者： Xiaolu Wang Shaohui Guo Chao Suo Fuqiang Zhang Junhao Wang Wenjing Wang Daqiang Yuan Linfeng Liang xianming Zhang College of Chemistry Taiyuan University of Technology Institute of Crystalline Materials Shanxi University School of Chemistry and Materials Science Shanxi Normal University State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences

Metal-organic frameworks （moFs） based on anion exchange membranes （AEMs） have garnered considerable interest,particularly for their potential to enhance ion conductivity by pre-introducing anions into *** approach is recognized as straightforward and effective for improving ion ***,developing high-performance AEMs is limited by the inherent instability and low resistance of *** study presents a novel 1,3,5-triazineμ3-bridged neutral Cu（I） framework,designated SXU-120 （where SXU represents Shanxi University）.This framework is synthesized using melamine,a widely available industrial product,as the starting material,achieving a high space-time yield exceeding 1.1 kg *** organic ligands and metal ions in SXU-120 are 3-connected,forming a rare eta topology with the point symbol 8～***-120 exhibits exceptional stability,even in a 10 M KOH solution,due to its high density of uncoordinated–NH2and carbonyl ***,the framework’s unique one-dimensional channels,characterized by their electronegativity,interact electrostatically with OH-ions,thereby accelerating OH-ion transfer along these ***,the OH-conductivity of this material reaches an impressive 0.49 S cm-1at 90°C under full humidity for 100 h,representing the highest OH-conductivity reported for moF-based conductors to *** properties make SXU-120 a promising candidate for efficient AEM materials in next-generation industrial applications.

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