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Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

Genes & Diseases 2024年第4期11卷 411-425页

作者： Mengmeng Guo Pan Hu Jiayi Xie Kefu Tang Shixiu Hu Jialiang Sun Yundong He Jing Li Weiqiang Lu Huirong Liu Mingyao Liu zhengfang yi Shihong Peng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai 200241China Prenatal Diagnosis Center Department of Clinical LaboratoryChangning Maternity and Infant Health HospitalEast China Normal UniversityShanghai 200051China Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 201203China Fengxian Hospital Affiliated to Southern Medical University Shanghai 201400China Shanghai Yuyao Biotech Co. Ltd.Shanghai 200241China

Gastric cancer is highly prevalent among digestive tract *** to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric ***,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric *** our previous study,we identified a novel small molecule EP4 receptor antagonist called *** with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse ***,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 ***,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than *** findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关键词： EP4 Immunomodulation Synergy Tumor microenvironment YY001

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Ailanthone:a new potential drug for castration-resistant prostate cancer

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Chinese Journal of Cancer 2017年第5期36卷 207-208页

作者： Shihong Peng zhengfang yi Mingyao Liu East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal University Department of Molecular and Cellular Medicine Center for Cancer and Stem Cell BiologyInstitute of Biosciences and TechnologyTexas A&M University Health Sciences Center

Prostate cancer (PCa) is the most common male cancer [1, 2]. PCa initially depends on androgen receptor (AR) signaling for growth and survival. Androgen deprivation therapy causes a temporary reduction in PCa tumor burden, but the tumor eventually develops into castrationresistant prostate cancer (CRPC) with the ability to grow again in the absence of androgens [3]. Mechanisms of CRPC progression include AR amplification and overexpression [4], AR gene rearrangement promoting synthesis of constitutively-active truncated AR splice variants (ARVs) [4], and induction of intracrine androgen metabolic enzymes [3]. Current anti-androgen therapies including MDV3100 (Enzalutamide) and abiraterone have focused on the androgen-dependent activation of AR through its ligand-binding domain (LBD), but do not provide a continuing clinical benefit for patients with CRPC and presumably fail due to multiple mechanisms including the expression of AR-Vs lacking the LBD [5]. These AR-Vs signal in the absence of ligand and are therefore resistant to LBD-targeting AR antagonists or agents that repress androgen biosynthesis [6].

关键词： Ailanthone potential castration

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Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

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Science China(Life Sciences) 2017年第4期60卷 417-428页

作者： Xuexiang ying Anling Huang Yajing Xing Liping Lan zhengfang yi Pingqing He Department of General Surgery Shanghai Jiaotong University Affiliated Sixth People's Hospital Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University

Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their *** in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis.

关键词： metastasis inducing inhibited invasion paclitaxel blocking migration suppressed chemotherapy toxicity

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Novel hemostatic agents based on gelatin-microbial transglutaminase mix

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Science China(Life Sciences) 2017年第4期60卷 397-403页

作者： Fang Lv Xiaonan Cong Wenshu Tang yiming Han Yu Tang Yongrui Liu Liqiang Su Mingyao Liu Mingfei Jin zhengfang yi Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University

Hemostasis is a major challenge in surgical procedures and traumas. Conventional hemostatic methods have limited efficacy and may cause additional tissue damage. In this study, we designed a novel hemostatic agent based on the in situ gel formation of gelatin cross-linked by a novel microbial transglutaminase(mTGase), in which the amino acid sequences differed from commercial mTGases. The new hemostatic agent showed the same biochemical crosslinking chemistry as the final stages of the blood coagulation cascade while using gelatin as a "structural" protein(rather than fibrin) and a calcium-independent mTGase as the crosslinking catalyst(rather than factor XIIIa). In rat liver hemostasis models, the hemostatic agent not only showed a similar hemostatic effect as that of SURGIFLO~(positive control), but also stronger adhesion strength and elasticity than SURGIFLO~.Therefore, this biomimetic gelatin-mTGase mix hemostatic is a novel and effective surgical sealant.

关键词： gelatin fibrin microbial sealant elasticity coagulation mutant challenge biochemical collagen

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A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

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Science China(Life Sciences) 2017年第2期60卷 202-214页

作者： Yongrui Liu Yuan He Feifei Yang Xiaonan Cong Jinhua Wang Shihong Peng Dan Gao Weifang Wang Liping Lan Xuexiang ying Mingyao Liu yihua Chen zhengfang yi Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of General Surgery Shanghai Jiaotong University Affiliated Sixth People’s HospitalShanghai 200000China Center for Cancer and Stem Cell Biology Institute of Biosciences and Technology and Department of Molecular and Cellular MedicineTexas A & M University Health Science CenterHouston 77030USA

Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 （VEGFR2） inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway. In this study, we established a high-profile compounds library and certificated a novel compound named N-（N-pyrrolidylacetyl）-9-（4-bromobenzyl）-l,3,4,9-tetrahydro-^-carboline （YF-452）, which remarkably inhibited the migration, invasion and tube-like structure formation of human umbilical vein endothelial cells （HUVECs） with little toxicity invitro. Rat thoracic aorta ring assay indicated that YF-452 significantly blocked the formation ofmicrovascular exvivo. In addition, YF-452 inhibited angiogenesis in chick chorioallantoic membrane （CAM） and mouse corneal micropocket assays. Moreover, YF-452 remarkably suppressed tumor growth in xenografts mice model. Furthermore, investigation of molecular mechanism revealed that YF-452 inhibited VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including extracellular signal regulated kinase （ERK）, focal adhesion kinase （FAK） and Src. These results indicate that YF-452 inhibits angiogenesis and may be a potential antiangiogenic drug candidate for cancer therapy.

关键词： YF-452 angiogenesis HUVECs VEGFR2

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Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

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Food Science and Human Wellness 2024年第3期13卷 1485-1493页

作者： Fuhuan Yuan Yu Fu Liang Ma Hankun Zhu Yong Yu Xin Feng yi Sun Hongjie Dai Xin Liu zhengfang Liu Yuhao Zhang College of Food Science Southwest UniversityChongqing 400715China Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing Chongqing 400715China Key Laboratory of Luminescence Analysis and Molecular Sensing(Southwest University) Ministry of EducationChongqing 400715China Angel Yeast Co. Ltd.Yichang 443003China

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating *** peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were *** structural characterization revealed that RBCP successfully chelated with calcium ***,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two ***,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

关键词： Rabbit bone Collagen peptide Peptide-calcium chelate Chelation mechanism Liquid chromatography-tandem mass(LC-MS/MS)

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重载列车模糊自适应模型预测控制方法研究

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控制与信息技术 2024年第4期 36-43页

作者：易杰江帆罗源张征方白金磊钟谱华株洲中车时代电气股份有限公司湖南株洲412001

机车自动驾驶系统本身是一个非线性、时变系统。列车在运行过程中,会遇到各种不同的线路情况,因此控制器不仅要具备预测控制功能,控制器的参数也需要根据实际的运行线路情况进行动态调整。为此,文章提出了一种重载列车模糊自适应模型预... 详细信息

机车自动驾驶系统本身是一个非线性、时变系统。列车在运行过程中,会遇到各种不同的线路情况,因此控制器不仅要具备预测控制功能,控制器的参数也需要根据实际的运行线路情况进行动态调整。为此,文章提出了一种重载列车模糊自适应模型预测控制方法。该方法在建立非线性多质点模型的基础上,构造了考虑多优化目标及多运行约束条件的优化问题,搭建了基于重载列车多质点模型的模型预测控制系统框架,对列车运行状态进行预测和动态调节;针对固定的控制器参数无法适应不同线路情况的问题,文章利用模糊控制与模型预测控制方法相结合的方法,通过对模型预测控制器的权重系数进行自适应整定,从而实现列车在不同运行线路上自适应优化控制。仿真结果表明,模糊自适应模型预测控制器具有良好的控制性能,不仅能够实现对列车的精确控制,将速度误差控制在±1km/h范围内,而且能够保证列车运行的平稳性。

关键词：重载列车机车自动驾驶自适应模型预测模糊控制

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A landscape of differentiated biological processes involved in the initiation of sex differentiation in zebrafish

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Water Biology and Security 2022年第3期1卷 77-87页

作者： Ding Ye yi-Xuan Tu Houpeng Wang Mudan He Yaqing Wang zhengfang Chen Zhen-Xia Chen Yonghua Sun State Key Laboratory of Freshwater Ecology and Biotechnology Hongshan LaboratoryInstitute of HydrobiologyInnovation Academy for Seed DesignChinese Academy of SciencesWuhan430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing100049China Hubei Hongshan Laboratory Huazhong Agricultural UniversityWuhan430070China Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityShenzhen518000China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518000China

Zebrafish(Danio rerio)has been used as a promising animal model to study gonadal development and *** previous studies have identified critical molecules participating in zebrafish gonad differentiation,a landscape view of the biological processes involved in this process is still *** we isolated intact zebrafish differentiating gonads,at 25 days post-fertilization(dpf)and 30 dpf and conducted RNA-seq analyses on the juvenile gonads that tended to develop into ovaries or *** study demonstrates that the juvenile ovary and testis at 25 dpf and 30 dpf are different at the biological process *** ovary differentiation,the biological processes related to metabolic activities in the production of energy and maternal substances,RNA degradation,and DNA repair were *** testis differentiation,the biological processes related to cell proliferation,differentiation,and morphogenesis were enriched,with a total of 15 signaling ***,we reveal that the immune-related processes are extensively involved in the regulation of testis ***,this study provides a landscape of differentiated biological processes and novel insights into the initiation of sex differentiation in zebrafish.

关键词： Gonad differentiation Maternal materials Ovary Sex differentiation Spermatogenesistestis Zebrafish

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高速列车自动驾驶前馈自适应广义预测控制方法研究

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控制与信息技术 2024年第1期 14-22页

作者：罗源易杰白金磊张征方株洲中车时代电气股份有限公司湖南株洲412001

高速列车自动驾驶(ATO)系统本质上是强非线性和不确定性的系统,针对高速列车模型参数非线性和时变性等特点,文章提出了一种前馈自适应广义预测控制(FA-GPC)的方法对ATO系统进行动态优化控制,并设计了一种带约束的多目标预测控制器。首先... 详细信息

高速列车自动驾驶(ATO)系统本质上是强非线性和不确定性的系统,针对高速列车模型参数非线性和时变性等特点,文章提出了一种前馈自适应广义预测控制(FA-GPC)的方法对ATO系统进行动态优化控制,并设计了一种带约束的多目标预测控制器。首先,基于列车多质点模型,分析附加阻力的改变对列车运行的影响;然后,结合列车运行过程中的速度跟踪精度、停车精度及运行舒适性等关键指标,构建包含控制输入约束的多目标性能指标函数,设计基于多目标函数的前馈广义预测速度跟踪控制算法,解决了由于附加阻力变化导致控制器超调的问题并加快了控制收敛速度。由于列车运行过程中受外界环境、乘客流动等因素影响,阻力变化大,难以建立精确的数学模型,因此采用带约束的变遗忘因子递推最小二乘法来辨识出列车控制系统在不同工况下受控自回归积分滑动平均模型(CARIMA),进而提高控制系统的鲁棒性。仿真结果表明,相比传统的无前馈GPC和PID控制器,前馈广义控制器在不同线路条件下巡航控速速度跟踪精度在±0.5km/h范围内,具有良好的跟踪性;在强扰动情况下通过引入自适应改进的前馈广义预测控制算法,具有较强的鲁棒性。

关键词：高速列车自动驾驶自适应广义预测控制参数辨识

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输油泵故障智能诊断研究综述

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石油化工设备 2024年第5期53卷 55-61页

作者：杨露露孙文孙薇孙维张译航李艺天津市正方科技发展有限公司天津300270

油气管道的运行离不开输油泵,输油泵故障智能诊断是保障输油系统正常运转、防止输油系统失效引起重大事故的关键。回顾了输油泵常见故障和故障信号,研究了输油泵的故障诊断依据和信号处理方法,归纳了智能诊断方法和2种故障维护方法,讨... 详细信息

油气管道的运行离不开输油泵,输油泵故障智能诊断是保障输油系统正常运转、防止输油系统失效引起重大事故的关键。回顾了输油泵常见故障和故障信号,研究了输油泵的故障诊断依据和信号处理方法,归纳了智能诊断方法和2种故障维护方法,讨论了输油泵故障类型,分析了不同信号判断依据提取方法的优缺点,提出了输油泵智能诊断方法存在的问题,展望了输油泵发展方向,总结了输油泵故障智能诊断方法。

关键词：输油泵故障诊断信号处理方法

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