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Long-term in vivo chimeric cells tracking in non-human primate

Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang zhenzhen chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

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Current status and impact of the Young Scientist Foundation of the National Natural Science Foundation on Chinese young scholars in cardiovascular research

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Science China Life Sciences 2024年

作者： Fei Gao zhenzhen chen Wendong Li Hujun Jiang Rui Wang Department of Cardiology Beijing Anzhen HospitalCapital Medical University Hypertension Center Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular Diseases Department of Vascular Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School Department of Health Sciences National Natural Science Foundation of China

Cardiovascular disease (CVD) remains the leading cause of disease burden globally,and continued efforts are required in identifying new targets for CVD prevention and treatment (Vaduganathan et al.,2022).Breakthroughs in basic research are urgently needed to fully understand the CVD mechanism and improve clinical treatment modality.

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Multiplexed single-cell transcriptome analysis reveals molecular characteristics of monkey pluripotent stem cell lines

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 418-429页

作者： Shuang LI zhenzhen chen Chuanxin chen Yuyu NIU State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Bioland Laboratory Guangzhou 510005China Guangzhou Laboratory Guangzhou 510005China

Efforts have been made to establish various human pluripotent stem cell lines.However,such methods have not yet been duplicated in non-human primate cells.Here,we introduce a multiplexed single-cell sequencing technique to profile the molecular features of monkey pluripotent stem cells in published culture conditions.The results demonstrate suboptimized maintenance of pluripotency and show that the selected signaling pathways for resetting human stem cells can also be interpreted for establishing monkey cell lines.Overall,this work legitimates the translation of novel human cell line culture conditions to monkey cells and provides guidance for exploring chemical cocktails for monkey stem cell line derivation.

关键词： Monkey pluripotent stem cell Multiplexed single-cell sequencing Naive pluripotency Extended pluripotent stem cells

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Recent advance of fluorescent probes for detection of drug-induced liver injury markers

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Chinese Chemical Letters 2022年第10期33卷 4478-4494页

作者： Dongqin Sun zhenzhen chen Jiali Hu Huajin Zeng Lingbo Qu Ran Yang School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China The College of Chemistry Zhengzhou UniversityZhengzhou 450001China

Drug-induced liver injury(DILI)is a common and serious adverse drug reaction.At present,DILI is perfectly diagnozed in clinical settings using Roussel Uclaf causality assessment method(RUCAM)in its original version published 1993 and its updated version published 2016,well established worldwide as a diagnostic algorithm with a high sensitivity and specificity.Nevertheless,the search for additional detection methods supporting RUCAM continues.In recent years,with the development of optical imaging technology,fluorescent probes have gradually shown great advantages in the detection and diagnosis of DILI markers such as high sensitivity,anti-interference,real-time monitoring and non-invasive measurement.In this review,the recent advances of fluorescent probes for evaluation of DILI in experimental studies were summarized according to various markers of DILI.We believe that learning about the design and practical application of these probes will contribute to the further development of detection sensors for DILI markers.

关键词： Fluorescent probe Drug-induced liver injury(DILI) Roussel uclaf causality assessment method(RUCAM) Clinical markers Imaging

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Analyzing the Effect of the Intra-Pixel Position of Small PSFs for Optimizing the PL of Optical Subpixel Localization

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Engineering 2023年第8期27卷 140-149页

作者： Haiyang Zhan Fei Xing Jingyu Bao Ting Sun zhenzhen chen Zheng You Li Yuan Department of Precision Instrument Tsinghua UniversityBeijing 100084China State Key Laboratory of Precision Measurement Technology and Instruments Tsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Integrated Circuits Tsinghua UniversityBeijing 100084China Joint International Research Laboratory of Advanced Photonics and Electronics Beijing Information Science and Technology UniversityBeijing 100192China Beijing Institute of Control Engineering Beijing 100190Chin

Subpixel localization techniques for estimating the positions of point-like images captured by pixelated image sensors have been widely used in diverse optical measurement fields.With unavoidable imaging noise,there is a precision limit(PL)when estimating the target positions on image sensors,which depends on the detected photon count,noise,point spread function(PSF)radius,and PSF’s intra-pixel position.Previous studies have clearly reported the effects of the first three parameters on the PL but have neglected the intra-pixel position information.Here,we develop a localization PL analysis framework for revealing the effect of the intra-pixel position of small PSFs.To accurately estimate the PL in practical applications,we provide effective PSF(e PSF)modeling approaches and apply the Cramér–Rao lower bound.Based on the characteristics of small PSFs,we first derive simplified equations for finding the best PL and the best intra-pixel region for an arbitrary small PSF;we then verify these equations on real PSFs.Next,we use the typical Gaussian PSF to perform a further analysis and find that the final optimum of the PL is achieved at the pixel boundaries when the Gaussian radius is as small as possible,indicating that the optimum is ultimately limited by light diffraction.Finally,we apply the maximum likelihood method.Its combination with e PSF modeling allows us to successfully reach the PL in experiments,making the above theoretical analysis effective.This work provides a new perspective on combining image sensor position control with PSF engineering to make full use of information theory,thereby paving the way for thoroughly understanding and achieving the final optimum of the PL in optical localization.

关键词： Optical measurement Subpixel localization Precision limit optimization Small point spread functions Centroiding Star sensors

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rtcisE2F promotes the self-renewal and metastasis of liver tumorinitiating cells via N^(6)-methyladenosine-dependent E2F3/E2F6 mRNA stability

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Science China(Life Sciences) 2022年第9期65卷 1840-1854页

作者： zhenzhen chen Lan Huang Kaili Wang Lulu Zhang Xiang Zhong Zhongyi Yan Benyu Liu Pingping Zhu School of Life Sciences Zhengzhou UniversityZhengzhou 450001China Biotherapy Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of Basic Medical Sciences Henan UniversityKaifeng 475004China Research Center of Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhou 450052China

Liver cancer is highly heterogeneous,and the tumor tissue harbors a variety of cell types.Liver tumor initiating cells(TICs)well contribute to tumor heterogeneity and account for tumor initiation and metastasis,but the molecular mechanisms of liver TIC self-renewal are elusive.Here,we identified a functional read-through rt-circRNA,termed rtcisE2F,that is highly expressed in liver cancer and liver TICs.rtcisE2F plays essential roles in the self-renewal and activities of liver TICs.rtcisE2F targets E2F6 and E2F3 mRNAs,attenuates mRNA turnover,and increases E2F6/E2F3 expression.Mechanistically,rtcisE2F functions as a scaffold of N^(6)-methyladenosine(m^(6)A)reader IGF2BP2 and E2F6/E2F3 mRNA.rtcisE2F promotes the association of E2F6/E2F3 mRNAs with IGF2BP2,and inhibits their association with another m^(6)A reader,YTHDF2.IGF2BP2 inhibits E2F6/E2F3 mRNA decay,whereas YTHDF2 promotes E2F6/E2F3 mRNA decay.By switching m^(6)A readers,rtcisE2F enhances E2F6/E2F3 mRNA stability.E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation,and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis.In conclusion,the rtcisE2F-IGF2BP2/YTHDF2-E2F6/E2F3-Wnt/β-catenin axis drives liver TIC self-renewal and initiates liver tumorigenesis and metastasis,and may provide a strategy to eliminate liver TICs.

关键词： circular RNA tumor-initiating cells self-renewal metastasis N^(6)-methyladenosine

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Average conditions for permanence and extinction in nonautonomous single-species Kolmogorov systems

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International Journal of Biomathematics 2017年第2期10卷 219-233页

作者： Jiandong Zhao zhenzhen chen School of Mathematics and Statistics Science Ludong University Yantai Shandong 264025 P. R. China Department of Mathematics Swinburne University of Technology Melbourne Victoria 3122 Australia

The nonautonomous single-species Kolmogorov system is studied in this paper. Average conditions are obtained for permanence, global attractivity and extinction in the system. Applications of our main results to logistic equation and generalized logistic equation are given. It is shown that our average conditions are improvement of those in Vance and Coddington [ J. Math. Biol. 27 (1989) 491–506] and some published literature on the system.

关键词： Kolmogorov system permanence extinction global attractivity logistic equation

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Investigation on induction brazing of profiled cBN wheel for grinding of Ti-6Al-4V

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Chinese Journal of Aeronautics 2021年第4期34卷 132-139页

作者： Qilin LI Kai DING Weining LEI Jiajia chen Qingshan HE zhenzhen chen School of Mechanical Engineering Jiangsu University of TechnologyChangzhou 213001China Nanjing Forestry University Nanjing 210010China Henan University of Technology Zhenzhou 450007China Key Laboratory of Special Purpose Equipment and Advanced Processing Technology Ministry of Education&Zhejiang ProvinceZhejiang University of TechnologyHangzhou 310032China

Profiled monolayer cBN wheel was induction brazed for grinding of titanium dovetail slot in this study.Aimed at acquiring a uniform temperature distribution along the profiled surface and reducing the thermal deformation of the brazed wheel,a finite element model was established to investigate the temperature uniformity during induction brazing.A suitable induction coil and the related working parameters were designed and chosen based on the simulation results.Ag-Cu-Ti alloy and cBN grains were applied in the induction brazing experiment.The results showed geometric deformation of the brazed wheel was no more than 0.01 mm and chemical reaction layer were found on the brazed joint interface.Further validation tests were carried out by grinding of Ti-6 Al-4 V alloy.Compared to the electroplated wheel,the brazed wheel showed better performance such as low specific grinding energy and good ground quality in grinding of Ti-6 Al-4 V alloy.Abrasion wear was found to be the main failure mode for the induction brazed wheel,while adhesion and grains pull-out were the main failure mode for the electroplated wheel.

关键词： Grinding performance Induction brazing Profiled cBN wheel Specific grinding energy Temperature uniformity

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人工智能与全球价值链重构:理论机制与中国对策

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西安财经大学学报 2024年第4期37卷 3-14页

作者：何宇陈珍珍盛三化三峡大学经济与管理学院湖北宜昌443002

人工智能作为引领新一轮科技革命和产业变革的战略性技术,正在对社会生产方式和全球价值链分工格局产生广泛而深刻的影响,在此背景下,探索人工智能技术对全球价值链分工的影响机理,是值得深入研究的前沿科学问题.与已有文献将人工智能... 详细信息

人工智能作为引领新一轮科技革命和产业变革的战略性技术,正在对社会生产方式和全球价值链分工格局产生广泛而深刻的影响,在此背景下,探索人工智能技术对全球价值链分工的影响机理,是值得深入研究的前沿科学问题.与已有文献将人工智能技术作为自动化技术或者具体计算机算法技术不同,本文基于对人工智能技术的经济学本质特征探索,提出“人工智能技术是数据要素驱动的自动化技术”,将数据要素纳入人工智能经济学模型.借鉴新结构经济学的要素禀赋结构理论,通过构建“要素禀赋结构技术利用结构要素利用结构”逻辑框架,进一步探索人工智能技术影响全球价值链重构的理论机制和中国对策.研究发现:(1)要素禀赋结构是决定一国的企业进行适宜性技术选择的重要因素,发达国家和发展中国家的要素禀赋结构存在异质性,这导致各国对于人工智能技术的适应性也存在差异,进而导致发展中国家和发达国家的全球价值链分工差距持续扩大;(2)数据要素具有高时效性和高折旧率特征,导致数据要素存量主要由当期数据要素流量决定,而当期数据要素流量又与数字化、智能化生产和应用的规模正相关,因此市场规模是决定数据要素存量的重要因素,这意味着通过发挥市场规模优势促进数据要素积累,优化面向数字化和智能化生产场景下的要素禀赋结构,是发展中国家抢抓人工智能技术发展机遇和实现人工智能技术“弯道超车”的重要路径;(3)政策上一方面应该着力推进优化传统要素禀赋结构政策加上对结构性失业的配套补救政策,另一方面应该利用中国超大规模市场优势促进中国数据资源向数据要素转化,以优化面向数字化和智能化时代的要素禀赋结构.

关键词：人工智能全球价值链要素禀赋数据要素数字经济

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Effect of mesopores on solidification of sirolimus self-microemulsifying drug delivery system

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Chinese Chemical Letters 2018年第12期29卷 1849-1852页

作者： Chun Tao Yue Yu zhenzhen chen Minxin Zhang Linlin Liu Zhihong Liu Jialiang Zhang Qian Zhang Hongtao Song Department of Pharmacy Fuzong Clinical Medical College of Fujian Medical University (Fuzhou General Hospital) College of Pharmacy Fujian Medical University

To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.

关键词： Mesopores Mesoporous silica nanospheres SBA-15 Self-microemulsifying drug delivery system Sirolimus Bioavailability

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