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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong ling Yingdan huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Anticancer carbazole alkaloids and coumarins from Clausena plants： A review

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Chinese Journal of Natural Medicines 2017年第12期15卷 881-888页

作者： huang Li FENG zhe-ling WANG Yi-Tao LIN Li-Gen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of MacaoMacao 999078 China

Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena(family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.

关键词： Clausena Anticancer Carbazole alkaloids Coumarins

High-efficiency and pollution-controlling in-situ gasification chemical looping combustion system by using CO_2 instead of steam as gasification agent

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Chinese Journal of Chemical Engineering 2018年第11期26卷 2368-2376页

作者： zhe Shen Zhiyu huang State Key Laboratory of Oil and Gas Reservoir Geology and Exploration Southwest Petroleum University School of Energy and Architecture Xi'an Aeronautical University

Using CO_2 as gasification agent instead of steam in in-situ coal gasification chemical looping combustion(i G-CLC)power plant can eliminate energy consumption for steam generation, thus obtaining higher system efficiency. In this work, a comparative study of iG-CLC power plant using steam and CO_2 as gasification agent is concentrated on. The effects of steam to carbon ratio(S/C) and CO_2 to carbon ratio(CO_2/C) on the fuel reactor temperature,char conversion, syngas composition and CO_2 capture efficiency are separately investigated. An equilibrium carbon conversion of 88.9% is achieved in steam-based case as S/C ratio increases from 0.7 to 1.1, whereas a maximum conversion of 84.2% is obtained in CO_2-based case with CO_2/C ranging from 0.7 to 1.1. Furthermore the effects of oxygen carrier to fuel ratio(φ) on system performances are investigated. Increasing φ from 1.0 to1.4 helps to achieve char conversion from 75.9% to 88.9% in steam-based case, by contrast the char conversion can achieve 66.3%–84.2% in CO_2-based case within the same φ range. In terms of iG-CLC power plant, recycling partial CO_2 to the fuel reactor improves the overall performance. Approximately 3.9% of net power efficiency are increased in CO_2-based plant, from steam-based plant. Higher CO_2 capture efficiency and lower CO_2 emission rate are observed in CO_2-gasified iG-CLC power plant, expecting to be 90.63% and 85.18 kg·MW-1·h-1,respectively.

关键词： CO2 Steam iG-CLC Comparative study

德谷门冬双胰岛素治疗2型糖尿病有效性和安全性Meta分析

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中国药业 2025年第1期34卷 101-109页

作者：鲜树雍黄哲沈阳药科大学辽宁沈阳110000

目的系统评价德谷门冬双胰岛素治疗2型糖尿病(T2DM)的有效性与安全性。方法采用计算机检索PubMed,Embase,The Cochrane Library,Clinicaltrials及中国知网(CNKI)、万方(WanFang)数据库中自建库起至2024年3月关于比较德谷门冬双胰岛素(... 详细信息

目的系统评价德谷门冬双胰岛素治疗2型糖尿病(T2DM)的有效性与安全性。方法采用计算机检索PubMed,Embase,The Cochrane Library,Clinicaltrials及中国知网(CNKI)、万方(WanFang)数据库中自建库起至2024年3月关于比较德谷门冬双胰岛素(试验组)与基础胰岛素或预混胰岛素(对照组)治疗T2DM的随机对照试验(RCT)。采用Cochrane偏倚风险评估量表对纳入文献进行质量评价,采用RevMan 5.3软件进行Meta分析。结果共纳入15项RCT,涉及患者4484例。Meta分析结果显示,与基础胰岛素比较,德谷门冬双胰岛素降低糖化血红蛋白(HbA1C)和空腹血糖(FBG)水平,增加体质量,降低低血糖事件、不良事件和严重不良事件的发生风险均无显著差异(P=0.86,0.89,0.08,0.13,0.81,0.07);与预混胰岛素比较,德谷门冬双胰岛素能显著降低FBG水平[MD=-1.42,95%CI(-1.44,-1.40),P<0.00001]和低血糖事件发生风险[RR=0.92,95%CI(0.86,0.98),P=0.010],但降低HbA1C水平、增加体质量、降低不良事件和严重不良事件的发生风险均无显著差异(P=0.19,0.69,0.58,0.09)。结论德谷门冬双胰岛素治疗T2DM的疗效显著,且安全性高。

关键词：德谷门冬双胰岛素糖化血红蛋白空腹血糖不良事件 Meta分析

Facile Synthesis of Functional Poly (ε-caprolactone) via Janus Polymerization

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Chinese Journal of Polymer Science 2019年第9期37卷 858-865页

作者： Huan Qiu zhe-Ning Yang Jun ling Ministry of Education Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University

Functionalized aliphatic polyesters attract increasing attentions as biocompatible and biodegradable polymers with broad applications in biological science. In this contribution, we propose a facile and controllable synthetic technique for functional poly(ε-caprolactone)(PCL) via Janus polymerization, which comprises cationic ring-opening copolymerization (ROP) of ε-caprolactone (CL) with 3,3-bis(chloromethyl)oxacyclobutane (CO) and (coordinated) anionic ROP of CL at a single propagating chain by rare earth metal triflates (RE(OTf)3)and propylene oxide, thus generating block copolymers in one step. The compositions of the copolymers of poly(CLb-(CL-r-CO)) can be modulated by various RE(OTf)3. Scandium triflate catalyzes Janus polymerization to yield the copolymers containing the highest CO contents among all the RE(OTf)3 catalysts used with complete conversion of CL. The chlorine in CO repeating units is ready to be transferred into azide group which affords the modification sites to react with 9-ethynyl-9-fluorenol and mPEG-alkyne, respectively, via copper(I)-catalyzed azide-alkyne cycloaddition reaction with quantitative conversions of azides, as confirmed by FTIR analyses. According to NMR and SEC analyses, copolymers (PCC-g-PEG) bearing a homo-PCL block and a PEG-grafted block of poly(CO-co-CL) demonstrate well-defined chemical structures. The investigations on thermal properties reveal the strong phase separation between PCL and PEG blocks. The amphiphilic PCC-g-PEG is able to sei住assemble into micelles in aqueous solution while cylindrical and lamellar morphologies are observed in bulk. We provide an efficient protocol to synthesize functional PCL combining onestep Janus polymerization and precise post-polymerization click reaction.

关键词： Janus polymerization Functional poly(ε-caprolactone) Poly(3,3-bis(chloromethyl)oxacyclobutane) Ring-opening polymerization Rare earth metal catalysts

A Novel Design of Efficient Multi-channel UART Controller Based on FPGA

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Chinese Journal of Aeronautics 2007年第1期20卷 66-74页

作者： HU zhe ZHANG Jun LUO Xi-ling Department of Electronic Information Engineering BeO＇ing University of Aeronautics and Astronautics Beijing 100083 China

In traditional universal asynchronous receiver transmitter （UART） controller, the data transmission is inefficient and the data bus utilization ratio is low. A novel design is provided to solve these problems. The architecture of the system is introduced, the flow charts of data processing as well as the implementation state machine are also presented in detail. This paper is concluded by comparing the performance of this design, which is realized on field programmable gate army （FPGA） using Verilog hardware description language （HDL）, with other traditional UART controllers.

关键词： serial communication UART multi-channel FPGA

A discretely damped SDOF model for the rocking response of freestanding blocks

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Earthquake Engineering and Engineering Vibration 2022年第3期21卷 729-740页

作者： Liu Hanquan huang Yuli Qu zhe Key Laboratory of Earthquake Engineering and Engineering Vibration Institute of Engineering MechanicsChina Earthquake AdministrationKey Laboratory of Earthquake Disaster MitigationMinistry of Emergency ManagementHarbin 150080China Sanhe 065201China Arup San FranciscoCA 94105USA

This paper presents a single-degree-of-freedom(SDOF)constitutive model for assessing the performance of freestanding block contents of *** model incorporates a bespoke damper to account for energy dissipation associated with *** is advantageous in its direct correlation,via energy conservation,to the restitution coefficient for impact during rocking.A comparative study with the existing SDOF rocking models shows that the proposed model significantly improves the accuracy of free-rocking simulations,in which inherent damping predominantly affects *** provides a promising and efficient tool for computationally intensive performance evaluation of nonstructural components.

关键词： contents rigid block equivalent viscous damping free rocking forced rocking single-degree-of-freedom system

Approach to conceptual data integration for multidimensional data analysis in e-commerce

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Journal of Systems Engineering and Electronics 2006年第3期17卷 635-641页

作者： Zhang zhe huang Pei School of Management Fudan Univ. Shanghai 200433P. R. China School of Management Shanghai Jiaotong Univ. Shanghai 200052 P. R. China

In e-commerce the multidimensional data analysis based on the Web data needs integrating various data sources such as XML data and relational data on the conceptual level. A conceptual data description approach to multidimensional data model the UML galaxy diagram is presented in order to conduct multidimensional data analysis for multiple subjects. The approach is illuminated using a case of 2_roots UML galaxy diagram that takes marketing analysis of TV products involved one retailer and several suppliers into consideration.

关键词： conceptual data integration multidimensional data analysis e-commerce

Review of characterization and modeling of polymer electrolyte fuel cell catalyst layer： The blessing and curse of ionomer

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Frontiers in Energy 2017年第3期11卷 334-364页

作者： Jun huang zhe LI Jianbo ZHANG Department of Automotive Engineering State Key Laboratory of Automotive Safety and Energy Tsinghua University Beijing 100084 China College of Chemistry and Chemical Engineering Central South University Changsha 410083 China Beijing Co-innovation Center for Electric Vehicles Beijing Institute of Technology Beijing 100081 China

Ionomer impregnation represents a milestone in the evolution of polymer electrolyte fuel cell （PEFC） catalyst layers. Ionomer acts as the binder, facilitates proton transport, and thereby drastically improves catalyst utilization and effectiveness. However, advanced morpho- logical and functional characterizations have revealed that up to 60% of Pt nanoparticles can be trapped in the micropores of carbon support particles. Ionomer clusters and oxygen molecules can hardly enter into micropores, leading to low Pt utilization and effectiveness. Moreover, the ionomer thin-films covering Pt nanoparticles can cause significant mass transport loss especially at high current densities. Ionomer-free ultra-thin catalyst layers （UTCLs） emerge as a promising alternative to reduce Pt loading by improving catalyst utilization and effectiveness, while theoretical issues such as the proton conduction mechan- ism remain puzzling and practical issues such as the rather narrow operation window remain unsettled. At present, the development of PEFC catalyst layer has come to a crossroads： staying ionomer-impregnated or going iono- mer-free. It is always beneficial to look back into the past when coming to a crossroads. This paper addresses the characterization and modeling of both the conventional ionomer-impregnated catalyst layer and the emerging ionomer-free UTCLs, featuring advances in characterizing microscale distributions of Pt particles, ionomer, support particles and unraveling their interactions; advances in fundamental understandings of proton conduction and flooding behaviors in ionomer-free UTCLs; advances in modeling of conventional catalyst layers and especially UTCLs; and discussions on high-impact research topics in characterizing and modeling of catalyst layers.

关键词： polymer electrolyte fuel cell ultra-thin cata-lyst layer electrostatic interactions characterization andmodeling structure-property-performance relation watermanagement