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Acta Pharmaceutica Sinica B 2021年第1期11卷 143-155页

作者： Jie Cheny Yan Wangy di zhao Lingyuan Zhang Weimin Zhang Jiawen Fan Jinting Li Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

Among current novel druggable targets,proteineprotein interactions(PPIs)are of considerable and growing *** kinase a(DGKα)interacts with focal adhesion kinase(FAK)band 4.1-ezrin-radixin-moesin(FERM)domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma(ESCC)*** is a multi-functional bioactive flavonoid,and possesses potential anticancer activity,whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC *** this study,we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAKcontrolled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo,whereas produced no toxicity to the normal *** validation specifically demonstrated that Asp435 site in the catalytic domain of DGKαcontributed to chrysin-mediated inhibition of the assembly of DGKα/FAK *** study has illustrated DGKα/FAK complex as a target of chrysin for the first time,and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

关键词： Chrysin Esophageal squamous cell carcinoma DGKα FAK Proteineprotein interactions

Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1111-1122页

作者： Jie Chen Yan Wang Weimin Zhang di zhao Lingyuan Zhang Jiawen Fan Jinting Li Qimin Zhan Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina

Reactive oxygen species(ROS)localized at the precise subcellular compartments are essential for regulating the activity of signaling ***,ROS are master regulators of tumor malignant progression that respond to a diverse set of environmental stress,especially *** oxidases(NOXs)appear to be activated within discrete subcellular compartments to facilitate local ROS ***,the subcellular function of NOXs in hypoxic tumor is still *** this study,we demonstrated that NOX5 was greatly upregulated in clinical esophageal squamous cell carcinoma(ESCC)tumors,ESCC cell lines or primary ESCC cells,and elevated NOX5 was correlated to malignancy of ESCC tumors and poor ***5 induced the malignant progression of ESCC by activating Src,especially under hypoxic ***,we showed that hypoxia promoted the interaction between NOX5 and Pyk2 on cell membrane via facilitating Ca^(2+)-mediated Pyk2 Tyr^(402)site ***,Pyk2 acted as a scaffold for c-Abl phosphorylating the catalytic domain of NOX5 Tyr^(476/478)sites,which in turn upregulated hydrogen peroxide(H_(2)O_(2))inside the Pyk2/NOX5 complex to oxidize and activate local *** findings provide insights into the biological significance of NOX5 in the development of ESCC.

关键词： malignancy elevated esophageal

Effects of sepsis on hippocampal volume and memory function

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World Journal of Emergency Medicine 2020年第4期11卷 223-230页

作者： Miao Yuan ding-yi Yan Fang-shi Xu Yi-di zhao Yang Zhou Long-fei Pan Emergency Department the Second Affi liated Hospital of Xi’an Jiaotong UniversityXi’anChina 2 Department of CardiologyXi’an No.3 HospitalXi’anChina

BACKGROUND:This study aimed to determine the effects of sepsis on brain integrity,memory,and executive ***:Twenty sepsis patients who were not diagnosed with sepsis-associated encephalopathy(SAE)but had abnormal electroencephalograms(EEGs)were *** control group included twenty healthy persons.A neuropsychological test of memory and executive function and a brain magnetic resonance imaging scan were *** volumes of cortex and subcortex were measured using the FreeSurfer *** Physiology and Chronic Health Evaluation II(APACHE II)score was used to determine the disease ***:In the sepsis group,the levels of immediate free recall,immediate cued recall,and delayed cued recall in the California Verbal Learning Test-II(CVLT-II)were significantly lower;the explicit memory(recollection process)in the process dissociation procedure test was lower;and the volumes of the left and right hippocampi were significantly lower compared with the control *** volume of the presubiculum in the hippocampus of sepsis patients showed statistically signifi cant *** the sepsis group,the volumes of the left and right hippocampi were negatively correlated with the APACHE II score and positively with immediate free recall,immediate cued recall,and delayed cued recall in the CVLT-II;moreover,the hippocampal volume was significantly correlated with recollection but not with ***:Patients with abnormal EEGs during hospitalization but with no SAE still have reduced hippocampal volume and memory defi *** fi nding indicates that sepsis leads to damage to specifi c parts of the hippocampus.

关键词： Hippocampus Magnetic resonance imaging Memory Sepsis-associated encephalopathy

A splice site mutation in the FvePHP gene is associated with leaf development and f lowering time in woodland strawberry

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Horticulture Research 2023年第1期10卷 274-287页

作者： Baotian Wang Weijia Li Kexin Xu Yingying Lei di zhao Xue Li Junxiang Zhang Zhihong Zhang Liaoning Key Laboratory of Strawberry Breeding and Cultivation College of HorticultureShenyang Agricultural UniversityShenyang110866China Laboratory of Protected Horticulture(Shenyang Agricultural University) Ministry of EducationShenyang110866China Institute of Carbon Materials Science Shanxi Datong UniversityDatong037009China Analytical and Testing Center Shenyang Agricultural UniversityShenyang110866China

Leaves and f lowers are crucial for the growth and development of higher *** this study we identified a mutant with narrow leaf lets and early f lowering(nlef)in an ethyl methanesulfonate-mutagenized population of woodland strawberry(Fragaria vesca)and aimed to identify the candidate *** analysis revealed that a single recessive gene,nlef,controlled the mutant *** found that FvH4_1g25470,which encodes a putative DNA polymeraseαwith a polymerase and histidinol phosphatase domain(PHP),might be the candidate gene,using bulked segregant analysis with whole-genome sequencing,molecular markers,and cloning analyses.A splice donor site mutation(C to T)at the 5-end of the second intron led to an erroneous splice event that reduced the expression level of the full-length transcript of FvePHP in mutant *** was localized in the nucleus and was highly expressed in *** of FvePHP using the virus-induced gene silencing method resulted in partial developmental defects in strawberry *** of the FvePHP gene can largely restore the mutant *** expression levels of FveSEP1,FveSEP3,FveAP1,FveFUL,and FveFT were higher in the mutants than those in‘Yellow Wonder’plants,probably contributing to the early f lowering phenotype in mutant *** results indicate that mutation in FvePHP is associated with multiple developmental *** results aid in understanding the role of DNA polymerase in strawberry development.

关键词： straw PHP narrow

Effect of Zr on solidification and microstructure of a Ni-based superalloy with high Al and Ti contents

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China Foundry 2022年第1期19卷 17-26页

作者： Guang-di zhao Xi-min Zang Fang Liu Wei-wei Zhang Shuo Gao Xue Li Jing Guo School of Materials and Metallurgy University of Science and Technology LiaoningAnshan 114051LiaoningChina Institute of Metal Research Chinese Academy of SciencesShenyang 110016China

The total content of Al and Ti in advanced Ni-based wrought superalloys is up to 7.5wt.%,which makes it easier to form harmful nonequilibrium eutectic(γ+γ′)andη*** has been reported that the addition of certain amount of Zr can modify precipitation of the nonequilibrium phases obviously,but the mechanism is still *** effect of Zr ranging fromdification behavior,segregation and microstructure of a Ni-based superalloy with high Al and Ti contents was investigated,eliminating the interferences of C and *** show that increase in Zr content significantly promotes the formation of eutectic(γ+γ′),ηand Zr-rich phase in the interdendritic *** the Zr-rich phase,Zr dissolves slightly in the eutecticγ′and obviously in theη*** interesting phenomenon is discovered that the Zr addition significantly increases the area fraction of liquid pools and enlarges the forming range ofγdendrites,which suggests that Zr markedly retards the *** affects the eutectic(γ+γ′)andηformation mainly due to the retard of solidification and dissolution of Zr in *** retard of solidification obviously increases the residual liquid fraction and *** can serve as a forming element for the eutectic(γ+γ′)andηphase,and the obvious dissolution of Zr inηphase significantly decreases the critical concentration of Ti for its precipitation.

关键词： zirconium Ni-based superalloy solidification behavior segregation

Tumor-associated macrophage(TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma(ESCC)

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Cellular & Molecular Immunology 2022年第9期19卷 1054-1066页

作者： Jie Chen di zhao Lingyuan Zhang Jing Zhang Yuanfan Xiao Qingnan Wu Yan Wang Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing100142China Peking University International Cancer Institute Peking UniversityBeijing100191China Research Unit of Molecular Cancer Research Chinese Academy of Medical SciencesBeijingChina Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen518107China

Tumor cell dependence on activated oncogenes is considered a therapeutic target,but protumorigenic microenvironment-mediated cellular addiction to specific oncogenic signaling molecules remains to be further ***,we showed that tumor-associated macrophages(TAMs)produced an abundance of C-C motif chemokine 22(CCL22),whose expression in the tumor stroma was positively associated with the level of intratumoral phospho-focal adhesion kinase(pFAK Tyr^(397)),tumor metastasis and reduced patient ***,CCL22-stimulated hyperactivation of FAK was correlated with increased malignant progression of cancer ***22-induced addiction to FAK was demonstrated by the persistent suppression of tumor progression upon FAK-specific ***,we identified that diacylglycerol kinaseα(DGKα)acted as a signaling adaptor to link the CCL22 receptor C-C motif chemokine receptor 4(CCR4)and FAK and promoted CCL22-induced activation of the FAK/AKT ***22/CCR4 signaling activated the intracellular Ca^(2+)/phospholipase C-γ1(PLC-γ1)axis to stimulate the phosphorylation of DGKαat a tyrosine residue(Tyr^(335))and promoted the translocation of DGKαto the plasma membrane to assemble the DGKα/FAK signalosome,which critically contributed to regulating sensitivity to FAK inhibitors in cancer *** identification of TAM-driven intratumoral FAK addiction provides opportunities for utilizing the tumor-promoting microenvironment to achieve striking anticancer effects.

关键词： Tumor-associated macrophages Esophageal squamous cell carcinoma FAK Oncogene addiction

Src heterodimerically activates Lyn or Fyn to serve as targets for the diagnosis and treatment of esophageal squamous cell carcinoma

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Science China(Life Sciences) 2023年第6期66卷 1245-1263页

作者： Jing Zhang di zhao Lingyuan Zhang Yuanfan Xiao Qingnan Wu Yan Wang Jie Chen Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing100142China Peking University International Cancer Institute Peking UniversityBeijing100191China Research Unit of Molecular Cancer Research Chinese Academy of Medical SciencesBeijing100142China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen518107China

Although Src is one of the oldest and most investigated oncoproteins,its function in tumor malignancy remains to be defined *** this study,we demonstrated that the inhibition of Src activity by ponatinib effectively suppressed several malignant phenotypes of esophageal squamous cell carcinoma(ESCC)both in vitro and in vivo,whereas it did not produce growthinhibitory effects on normal esophageal epithelial cells(NEECs).Importantly,we combined phosphoproteomics and several cellular and molecular biologic strategies to identify that Src interacted with the members of Src-family kinases(SFKs),such as Fyn or Lyn,to form *** interactions with Fyn and Lyn phosphorylated the tyrosine sites in SH2(Fyn Tyr^(185)or Lyn Tyr^(183))and kinase domains(Fyn Tyr^(420) or Lyn Tyr^(397)),which critically contributed to ESCC *** contrast,Src could not form heterodimers with Fyn or Lyn in *** used RNA sequencing to comprehensively demonstrate that the inhibition of Src activity effectively blocked several critical tumor-promoting pathways,such as JAK/STAT,mTOR,stemness-related,and metabolism-related *** of the real-time polymerase chain reaction(RT-PCR)assay confirmed that Lyn and Fyn were critical effectors for the Src-mediated expression of tumor growth or metastasis-related ***,results of the clinical ESCC samples showed that the hyperactivation of pSrc Tyr^(419),Fyn Tyr^(185) or Tyr^(420),and Lyn Tyr^(183)or Tyr^(397)could be biomarkers of ESCC *** study illustrates that Src/Fyn and Src/Lyn heterodimers serve as targets for the treatment of ESCC.

关键词： esophageal squamous cell carcinoma heterodimer Src-family kinase Src tyrosine phosphorylation

Process Control for Structure of Martensite/Austenite Islands of 15.3 mm X100 Pipeline Steel in BX Steel

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Journal of Iron and Steel Research International 2011年第S1期18卷 487-491页

作者： XU Xue-li,zhao Ke,zhao di,WANG Wen-fei (Technical Center of BX Steel,Benxi 117000,Liaoning,China) Tech Ctr BX Steel Benxi 117000 Liaoning Peoples R China

This paper mainly studies the influence of deformation amount and cooling rate,which existed in X100 pipeline steel rolled at 2300mm rolling mill in BX STEEL,on morphology,size relations and distribution of M/A islands of steel plate *** results show that structures of M/A islands are homogenized and refined under the conditions of appropriately increasing the deformation amount in non-recrystallization region on basis of rational deformation amount in recrystallization region and cooling rate after deformation,***,according to the actual situation of 2300mm hot rolling mill,this paper gives rational deformation amount and cooling rate used to obtain ideal structure of M/A islands.

关键词： X100 pipeline steel martensite/austenite (M/A) islands deformation amount cooling rate

Microreactor platform for continuous synthesis of electronic doped quantum dots

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Nano Research 2022年第10期15卷 9647-9653页

作者： Yuxi Li Yanbin Li Xinyuan Li Tailei Hou Chen Qiao Yunpeng Tai Xiaole Gu di zhao Le Sang Jiatao Zhang Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications Key Laboratory of Medical Molecule Science and Pharmaceutics EngineeringMOE Key Laboratory of Cluster ScienceSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China State Key Laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China School of Chemistry and Chemical Engineering Beijing Institute of TechnologyBeijing 102488China

Electronic doped quantum dots(Ed-QDs),by heterovalent cations doping,have held promise for future device concepts in optoelectronic and spin-based technologies due to their broadband Stokes-shifted luminescence,enhanced electrical transport and tailored magnetic *** their scale-up requirement and the low yielding of several current colloidal synthesis methods,a stable and efficient bulk synthesis strategy must be *** have long been recognized as an effective platform for producing nanomaterials and fabricating large-scale ***,we chose microreactor platform for continuous synthesis of Ed-QDs in the air at low *** original reverse cation exchange reaction mechanism together with varying the kinetic conditions of microreactor platform,such as liquid flow rate,the Ag doped CdS(CdS:Ag)Ed-QDs with higher yield have been synthesized successfully due to the continuous synthesis advantages with a high degree of size *** by microreactor engineering simulation,this research not only provides a new synthetic method towards scale-up production but also enables to improve chemical mass production of similar functional QDs for optical devices,bioimaging and innovative information processing applications.

关键词： quantum dots microreactor continuous synthesis scale-up

Preparation of large-size Al_(2)O_(3)/GdAlO_(3)/ZrO_(2)ternary eutectic ceramic rod by laser directed energy deposition and its microstructure homogenization mechanism

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Journal of Materials Science & Technology 2021年第26期85卷 218-223页

作者： Haifang Liu Haijun Su Zhonglin Shen di zhao Yuan Liu Yinuo Guo Min Guo Jun Zhang Lin Liu Hengzhi Fu State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an710072China

Laser 3D printing based on melt growth has great potential in rapid preparation of Al_(2)O_(3)-based eutectic ce *** this work,la rge-scale Al_(2)O_(3)/GdAlO_(3)/ZrO_(2)ternary eutectic ceramic rod with diameter of 4-5 mm and height higher than 250 mm was additively manufactured by laser directed energy ***,heat treatment was applied to eliminate the microstructure heterogeneity in the as-deposited eutectic ceramic,and the microstructure homogenization mechanism was studied in *** results indicate that colonies and banded structures completely disappear after the heat treatment,producing a homogeneous network eutectic *** microstructure homogenization is revealed to experience three stages of discontinuous coarsening,continuous coarsening and microstructure ***,it is found that the eutectic spacing linearly increases with the heat treatment time,meaning that the coarsening behavior of the laser 3D-printed Al_(2)O_(3)/GdAlO_(3)/ZrO_(2)eutectic ceramic satisfies well with the Graham-Kraft model.

关键词： Oxide eutectic ceramic Laser 3D printing Melt growth Heat treatment Microstructure homogenization