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Development Trajectories in the Biotechnology Industry:China versus Leading Countries

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China & World Economy 2011年第3期19卷 105-123页

作者： Yantai Chen Laijun Luo yaguang zhang Yunhe Distinguished Fellow College of Economics and Management Zhejiang University of Technology Hangzhou China Associate Professor School of Economics Renmin University of China Beijing China Assistant Professor School of Economics Peking University Beijing China

The present paper examines China＇s biotechnology industry from a global perspective and explores how its development trajectory differs from that of countries that are leaders in biotechnology. We draw on diverse data to demonstrate the unique development trajectory of the industry in China. China has benefited through targeted spin-offs of R＆D-oriented foreign direct investment from developed countries driven by the effects of globalization, government-encouraged collaboration between the domestic academia and industry, and the input of overseas returnees. Together with an increasing focus of the government and domestic enterprises on independent innovation, such developments have enabled China to catch up with the global biotechnology industry. However, its small scale and low capacity for commercializing innovations under China ＂s current regulations and other barriers pose challenges for the development of the industry. Suggestions for the sustainable development of China＇s biotechnology industry are presented in this study.

关键词： biotechnology industry development trajectories global innovation network institutional regime

Computational fluid dynamics simulation of a novel bioreactor forsophorolipid production

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Chinese Journal of Chemical Engineering 2017年第6期25卷 732-740页

作者： Xiaoqiang Jia Lin Qi yaguang zhang Xue Yang Hongna Wang Fanglong Zhao Wenyu Lu Department of Biochemical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Key Laboratory of Systems Bioengineering (Tianjin University) Ministry of Education Tianjin 300072 China Synthetic Biology Platform Collaborative Innovation Center of Chemical Science and Engineering (Tiarljin) Tianjin 300072 China

This paper describes three-dimensional computational fluid dynamics(CFD) simulations of gas–liquid flow in a novel laboratory-scale bioreactor contained dual ventilation-pipe and double sieve-plate bioreactor(DVDSB)used for sophorolipid(SL) production. To evaluate the role of hydrodynamics in reactor design, the comparisons between conventional fed-batch fermenter and DVDSB on the hydrodynamic behavior are predicted by the CFD methods. Important hydrodynamic parameters of the gas–liquid two-phase system such as the liquid phase velocity field, turbulent kinetic energy and volume-averaged overall and time-averaged local gas holdups were simulated and analyzed in detail. The numerical results were also validated by experimental measurements of overall gas holdups. The yield of sophorolipids was significantly improved to 484 g·L^(-1)with a 320 h fermentation period in the new reactor.

关键词： Bioreactors Gas hold-up Computational fluid dynamics (CFD)Hydrodynamics Sophorolipid production

Advancing RAS inhibition: broad-spectrum targeting and tumor-selective activity of RMC-7977 in cancer therapy

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Science China Life Sciences 2024年

作者： Qunli Xiong yaguang zhang Laboratory of Gastrointestinal Tumor Epigenetics and Genomics Frontiers Science Center for Disease-related Molecular Network West China Hospital Sichuan University Abdominal Oncology Ward Cancer Center West China Hospital Sichuan University

In cancer, the proto-oncogene RAS frequently mutates at codons 12, 13, and61, with these mutations propelling tumor progression by locking RAS proteins in their active, GTP-bound state(Pylayeva-Gupta et al., 2011; Yang et al.,2023). Despite the recent approval of small molecule inhibitors targeting KRAS(G12C) for non-small cell lung cancer(de Langen et al., 2023), a broadspectrum small molecule inhibitors for multiple RAS mutations have remained elusive.

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Trim28 citrullination maintains mouse embryonic stem cell pluripotency via regulating Nanog and Klf4 transcription

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Science China(Life Sciences) 2023年第3期66卷 545-562页

作者： yaguang zhang Xiaowen Wan Lei Qiu Lian Zhou Qing Huang Mingtian Wei Xueqin Liu Sicheng Liu Bo zhang Junhong Han State Key Laboratory of Biotherapy and Cancer Center National Clinical Research Center for Geriatricsand Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Department of Gastrointestinal Surgery and Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Protein citrullination,including histone H1 and H3 citrullination,is important for transcriptional regulation,DNA damage response,and pluripotency of embryonic stem cells(ESCs).Tripartite motif containing 28(Trim28),an embryonic development regulator involved in ESC self-renewal,has recently been identified as a novel substrate for citrullination by ***,the physiological functions of Trim28 citrullination and its role in regulating the chromatin structure and gene transcription of ESCs remain *** this paper,we show that Trim28 is specifically citrullinated in mouse ESCs(m ESCs),and that the loss of Trim28 citrullination induces loss of ***,Trim28 citrullination enhances the interaction of Trim28with Smarcad1 and prevents chromatin ***,Trim28 citrullination regulates m ESC pluripotency by promoting transcription of Nanog and Klf4 which it does by increasing the enrichment of H3K27ac and H3K4me3 and decreasing the enrichment of H3K9me3 in the transcriptional regulatory ***,our findings suggest that Trim28citrullination is the key for the epigenetic activation of pluripotency genes and pluripotency maintenance of ***,these results uncover a role Trim28 citrullination plays in pluripotency regulation and provide novel insight into how citrullination of proteins other than histones regulates chromatin compaction.

关键词： citrullination chromatin embryonic stem cell pluripotency Trim28

Lactate anions participate in T cell cytokine production and function

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Science China(Life Sciences) 2021年第11期64卷 1895-1905页

作者： Jing Wen Shipeng Cheng yaguang zhang Ran Wang Jiefang Xu Zhiyang Ling Liyan Ma Xinghao Ai Bing Sun School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China School of Life Science University of Science and Technology of ChinaHefei 230026China Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China University of Chinese Academy of Sciences Beijing 100049China

After antigen stimulation, T cells preferentially increase aerobic glycolysis to meet the bioenergetic and biosynthetic demands of T cell activation, proliferation, and effector functions. Lactate, a by-product of glycolysis, has been reported to function as an important energy source and signaling molecule. Here, we found that lactate anions are involved in cytokine production in Tcells after TCR activation. During ex vivo T cell activation, the addition of excess sodium lactate(Na L) increased the production of cytokines(such as IFNγ/IL-2/TNFα) more than the addition of sodium chloride(NaCl). This enhanced cytokine production was dependent on TCR/CD3 activation but not CD28 activation. In vivo, Na L treatment inhibited tumour growth in subcutaneously transplanted tumour models in a T cell-dependent manner, which was consistent with increased T cell cytokine production in the Na L treatment group compared to the Na Cl treatment group. Furthermore, a mechanistic experiment showed that this enhanced cytokine production was regulated by GAPDH-mediated post-transcriptional regulation. Taken together, our findings indicate a new regulatory mechanism involved in glycolysis that promotes T cell function.

关键词： lactate glycolysis TCR activation immunometabolism

Regulation and application of m6A modification in tumor immunity

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Science China Life Sciences 2024年

作者： Qunli Xiong yaguang zhang Ying Zheng Qing Zhu Division of Abdominal Tumor Multimodality Treatment Cancer Center Department of General Surgery West China Hospital Sichuan University Laboratory of Gastrointestinal Tumor Epigenetics and Genomics Frontiers Science Center for Disease-related Molecular Network West China Hospital Sichuan University

The m6A modification is an RNA modification that impacts various processes of RNA molecules, including transcription, splicing, stability,and translation. Recently, researchers have discovered that the presence of m6A modification can influence the interaction between tumor cells and immune cells and also play a role in regulating the expression of immune response-related genes. Additionally, m6A modification is intricately involved in the regulation of tumor immune evasion and drug resistance. Specifically, certain tumor cells can manipulate the gene expression through m6A modification to evade immune system attacks. Therefore, it might be possible to enhance tumor immune surveillance and improve the effectiveness of immune-based therapies by manipulating m6A modification. This review systematically discusses the role of m6A modification in tumor immunity, specifically highlighting its regulation of immune cells and immune-related genes in tumor cells. Furthermore, we explore the potential of m6A modification inhibitors as anti-cancer therapies and the significance of m6A regulatory factors in predicting the efficacy of tumor immune therapy.

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Colorectal cancer-derived extracellular vesicles induce liver premetastatic immunosuppressive niche formation to promote tumor early liver metastasis

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1357-1360页

作者： Xuyang Yang yaguang zhang Yang zhang Huifang Li Li Li Yangping Wu Xiangzheng Chen Lei Qiu Junhong Han Ziqiang Wang Colorectal Cancer Center Department of General SurgeryState Key Laboratory of Biotherapy and Cancer Centerand Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041 Sichuan ProvinceChina State Key Laboratory of Biotherapy and Cancer Center and Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041 Sichuan ProvinceChina Core Facility Institute of Clinical PathologyDepartment of Respiratory and Critical Care Medicineand Department of Liver Surgery&Liver TransplantationState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China

Dear Editor,To date,the effect of colorectal cancer(CRC)-derived extracellular vesicles(EVs)on liver pre-metastatic niche(PMN)remain incompletely understood.1 To investigate the role of CRC-derived EVs in the remodeling of the liver PMN,we isolated EVs from CT26 cell culture *** characteristics of EVs(the morphology,size,and markers)were identified by transmission electron microscopy(TEM),Nanoparticle Tracking Analysis(NTA),and western blotting(Supplementary Fig.S1a–e).Then,BALB/c mice with an intact liver immune status were pretreated with CRCderived EVs and phosphate-buffered saline(PBS)for one month,and a liver metastasis model was established via spleen injection of tumor cells to determine whether EVs influence liver metastasis(Fig.1a).Two hours after the operation,in vivo imaging indicated that the animal model was successfully established,and the tumor fluorescence intensity in the liver was consistent between the two groups(Supplementary Fig.S2a,b).Amazingly,the liver tumor fluorescence intensity in the EVs group was significantly stronger than that in the PBS group after 24 h(Fig.1b;Supplementary Fig.S2c,d).The number of liver tumor nodules in the EVs group was also significantly higher than that in the PBS group on day 4(Fig.1c;Supplementary Fig.S2e,f).

关键词： metastasis metastatic cancer

Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy

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Signal Transduction and Targeted Therapy 2023年第1期8卷 250-265页

作者： Yang Meng Lei Qiu Xinyi Zeng Xiaoyan Hu yaguang zhang Xiaowen Wan Xiaobing Mao Jian Wu Yongfeng Xu Qunli Xiong Zhixin Chen Bo zhang Junhong Han Research Laboratory of Tumor Epigenetics and Genomics Department of General SurgeryFrontiers Science Center for Disease-related Molecular Network and National Clinical Research Center for GeriatricsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Division of Cancer Cell Biology The Graduate School of Frontier SciencesThe University of Tokyo4-6-1 ShirokanedaiMinato-kuTokyo 108-8639Japan Division of Hematology/Oncology Department of MedicineVirginia Commonwealth UniversityRichmondVAUSA Abdominal Oncology Ward Cancer CenterWest China Hospital of Sichuan UniversityChengdu 610041China

Chemoresistance has long been the bottleneck of ovarian cancer(OC)*** has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC,but the underlying mechanisms remain ***,we demonstrate a new mechanism where CRL4^(CUL4A/DDB1)manipulates OC cell chemoresistance by regulating mitochondrial dynamics and ***4^(CUL4A/DDB1)depletion enhanced mitochondrial fission by upregulating AMPKα^(Thr172)and MFF^(Ser172/Ser146)phosphorylation,which in turn recruited DRP1 to ***4^(CUL4A/DDB1)loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented ***,CRL4^(CUL4A/DDB1)loss inhibited OC cell proliferation,whereas inhibiting autophagy partially reversed this *** findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission,mitophagy,and OC *** of CRL4^(CUL4A/DDB1)and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC.

关键词： inhibited cancer chemotherapy

Community Structure of Endophytic Fungi in Ginseng and Its Correlation Analysis with Active Components

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Medicinal Plant 2021年第5期12卷 1-6,11页

作者： yaguang zhang Yanxin zhang Qi GAO SPH Xing Ling Sci. & Tech. Pharmaceutical Co. Ltd. Shanghai 201703 China

[Objectives]The paper was to explore the correlation between active components of ginseng and community structure of endophytic fungi in ginseng under different cultivation methods.[Methods]Using ginsengs under two main planting patterns in Huanren County,Liaoning Province as the samples,the community structure of endophytic fungi was studied by molecular means,and the chemical components were identified and the content of chemical markers was measured via ***,the correlation between medicinal components of ginseng and diversity of endophytic fungal flora was analyzed.[Results]The diversity and active components of endophytic fungi of ginseng were *** diversity analysis showed that the medicinal components of ginseng were positively correlated with some fungal groups in ginseng.[Conclusions]Artificial intervention in the planting process would affect the endophytic fungi in medicinal materials,and further affect the chemical components of ginseng medicinal materials.

关键词： Forest ginseng Cultivated ginseng Active component Endophytic fungi Correlation analysis