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Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid leukemia

Weina Zhang, Ying Lu, Tao Zhen, Xinjie Chen, Ming Zhang, Ping Liu, Xiangqin Weng, Bing Chen, Yueying Wang

《医学前沿(英文)》 2019年 第13卷 第3期   页码 388-397 doi: 10.1007/s11684-018-0624-1

摘要: Collaboration of c-KIT mutations with AML1–ETO (AE) has been demonstrated to induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8; 21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE cleavage. Therefore, studies should explore the efficacy of combination therapy with oridonin and HHT in t(8; 21) AML. In this study, we investigated the synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML cell line and mouse model. The two drugs synergistically inhibited cell viability and induced significant mitochondrial membrane potential loss and apoptosis. Oridonin and HHT induced significant downregulation of c-KIT and its downstream signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21) leukemia mouse survival. In conclusion, oridonin and HHT exert synergistic effects against t(8; 21) leukemia and , thereby indicating that their combination may be an effective therapy for t(8; 21) leukemia.

关键词: AML1–ETO     c-KIT     homoharringtonine     oridonin     t(8     21) AML     synergistic effect    

Innate and adaptive T cells in influenza disease

null

《医学前沿(英文)》 2018年 第12卷 第1期   页码 34-47 doi: 10.1007/s11684-017-0606-8

摘要:

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词: influenza     innate T cells     CD4+ and CD8+ T cells     vaccination    

sup>CD117dim/CD34+CD117bri myeloblast-associated gene expression in t(8;21) acute myeloid leukemia

Xueping Li, Yuting Dai, Bing Chen, Jinyan Huang, Saijuan Chen, Lu Jiang

《医学前沿(英文)》 2021年 第15卷 第4期   页码 608-620 doi: 10.1007/s11684-021-0836-7

摘要: t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34 CD117 and CD34 CD117 ) were previously identified in t(8;21) AML, and CD34 CD117 cell proportion was determined as an independent factor for this disease outcome. Here, we examined the impact of CD34 CD117 /CD34 CD117 myeloblast-associated gene expression on t(8;21) AML clinical prognosis. In this study, 85 patients with t(8;21) AML were enrolled. The mRNA expression levels of CD34 CD117 -associated genes ( , , and ) and CD34 CD117 -associated genes ( , , and ) were measured using quantitative reverse transcription PCR. Associations between gene expression and clinical outcomes were determined using Cox regression models. Results showed that patients with high , , or expression had significantly inferior overall survival (OS), whereas those with high or expression showed relatively favorable prognosis. Univariate analysis revealed that CD19, CD34 CD117 proportion, mutation, minimal residual disease (MRD), and expression levels of , , , and were associated with OS. Multivariate analysis indicated that mutation, MRD and and expression levels were independent prognostic variables for OS. Identifying the clinical relevance of CD34 CD117 /CD34 CD117 myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21) AML.

关键词: t(8     21)(q22     q22) AML     CD34+CD117dim/ CD34+CD117bri cell population     gene expression     prognosis    

用于环境催化的MoS2/ZIF-8复合材料——太阳能驱动的抗生素降解工程 Article

陈文倩, 李琳悦, 李林, 裘文慧, 唐量, 徐玲, 许科军, 吴明红

《工程(英文)》 2019年 第5卷 第4期   页码 755-767 doi: 10.1016/j.eng.2019.02.003

摘要: 在本文中,我们提供了一种MoS2/ZIF-8复合光催化剂,它可以使环丙沙星(CIP)和盐酸四环素(TC)的光催化降解率分别达到1T/2H-MoS2的1.21倍和MoS2/ZIF-8纳米复合材料的产氢率是MoS2的1.79倍。这项工作通过优化表面纳米异质结结构的构造,为探索原始和高效的1T/2H-MoS2/MOF基光催化剂提供了新的方向。我们发现复合光催化剂经久耐用,其催化性能在稳定性测试下得以保持。因此,1T/2H-MoS2/MOF基光催化剂具有良好的抗生素降解工程应用前景。

关键词: 1T/2H-MoS2     ZIF-8     抗生素降解     光催化    

A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

null

《医学前沿(英文)》 2018年 第12卷 第3期   页码 324-329 doi: 10.1007/s11684-017-0558-z

摘要:

Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes>200×109/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19+, CD20+, HLA-DR+, CD22+, CD5+, Kappa+, CD25dim, CD71dim, Lambda, CD7, CD10, CD23, CD34, CD33, CD13, CD14, CD117, CD64, CD103, and CD11c. The karyotype showed complex abnormality: 46XX,+3,−10, t(8;14)(q24;q32)[11]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

关键词: splenic lymphoma with villous lymphocytes     splenic marginal zone lymphoma     transformation     chromosome translocation    

Zeolitic imidazolate framework-8 (ZIF-8) for drug delivery: A critical review

Simin Feng, Xiaoli Zhang, Dunyun Shi, Zheng Wang

《化学科学与工程前沿(英文)》 2021年 第15卷 第2期   页码 221-237 doi: 10.1007/s11705-020-1927-8

摘要: Zeolitic imidazolate framework-8 (ZIF-8), composed of Zn ions and imidazolate ligands, is a class of metal-organic frameworks, which possesses a similar structure as conventional aluminosilicate zeolites. This material exhibits inherent porous property, high loading capacity, and pH-sensitive degradation, as well as exceptional thermal and chemical stability. Extensive research effort has been devoted to relevant research aspects ranging from synthesis methods, property characterization to potential applications of ZIF-8. This review focuses on the recent development of ZIF-8 synthesis methods and its promising applications in drug delivery. The potential risks of using ZIF-8 for drug delivery are also summarized.

关键词: zeolitic imidazolate framework-8 (ZIF-8)     synthesis methods     applications     drug delivery    

Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 72-76 doi: 10.1007/s11684-014-0347-x

摘要:

Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3 ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91±143.89 ng/ml and 348.26±202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P<0.001; for CAL, r = 0.54, P<0.001; for GI, r = 0.49, P<0.001; and for PI, r = 0.63, P<0.001). The results of this study demonstrate elevated concentrations of MMP-8 in individuals with chronic periodontitis.

关键词: matrix metalloproteinase-8     chronic periodontitis     pocket probing depth     clinical attachment level     gingival index     plaque index    

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

《医学前沿(英文)》 2012年 第6卷 第3期   页码 248-262 doi: 10.1007/s11684-012-0206-6

摘要:

The AML1-ETO fusion transcription factor is generated by the t(8;21) translocation, which is present in approximately 4%–12% of adult and 12%–30% of pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary events. In this review, we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies for t(8;21) positive AML that involve targeting the fusion protein itself, the proteins that bind to it, or the genes that it regulates. Recently published studies suggest that a targeted therapy for t(8;21) positive AML is feasible and may be coming sometime soon.

关键词: AML1-ETO     mouse model     leukemia     t(8     21)     pathway hits     mutation     hematopoiesis     Kasumi-1     CD34+    

Protective efficacy of vaccination with NcMIC3 and NcMIC8 against

Taotao ZHANG, Xiao ZHANG, Qun LIU, Jianhai XU, Jing LIU

《农业科学与工程前沿(英文)》 2019年 第6卷 第2期   页码 188-196 doi: 10.15302/J-FASE-2019253

摘要:

Microneme proteins (MICs) are important for Apicomplexan parasite invasion due to their adhesion to host cells. Several studies have indicated that MIC3 and MIC8 are important adhesion factors and potential vaccine candidates against neosporosis. In this study, we evaluated the protective efficacy of recombinant proteins and DNA vaccines of NcMIC3 and NcMIC8. BALB/c mice were immunized with rNcMIC3, rNcMIC8, pcDNA3.1-NcMIC3 and pcDNA3.1-NcMIC8 respectively, and challenged with tachyzoites. The immune responses were evaluated through cytokine, antibody measurements and the parasite burden in the mice brain tissues. Serological analysis showed that recombinant protein vaccines induced higher levels of immunoglobulin G (IgG) than other groups. The percentage of IgG1 and IgG2a in the recombinant protein groups was higher than the other groups, and with a predominance of IgG1 over IgG2a, suggesting that recombinant protein vaccines elicited a Th2-type immune response, while DNA vaccines mainly produce a Th1-type immune response. In addition, mice immunized with rNcMIC3 and rNcMIC8 a had lower parasite burden in brain tissue compared with the other groups. These results demonstrate that rNcMIC3 and rNcMIC8 could induce humoral and Th2-type immune response, leading to a considerable level of resistance against neosporosis.

关键词: NcMIC3     NcMIC8     Neospora caninum     vaccination    

青岛地铁8号线海底隧道

贺维国, 刘鹏

《工程(英文)》 2018年 第4卷 第2期   页码 167-169 doi: 10.1016/j.eng.2018.03.012

8英寸绝缘栅双极型晶体管 (IGBT) 关键技术研究 Article

刘国友,丁荣军,罗海辉

《工程(英文)》 2015年 第1卷 第3期   页码 361-366 doi: 10.15302/J-ENG-2015043

摘要:

基于8英寸绝缘栅双极型晶体管 (IGBT) 生产线的建设,重点解决了8英寸IGBT先进工艺技术、第四代高压双扩散金属氧化物半导体 (DMOS+) IGBT技术和第五代沟槽栅IGBT技术等关键技术问题,实现了高压IGBT芯片制造从6英寸到8英寸的技术突破,自主开发的1600 A/1.7 kV与1500 A/3.3 kV IGBT模块已经被成功制造并通过考核,现已应用于轨道交通牵引系统。

关键词: 绝缘栅双极型晶体管 (IGBT)     高功率密度     沟槽栅     8英寸     轨道交通    

Prohibitin regulates mTOR pathway via interaction with FKBP8

Jiahui Zhang, Yanan Yin, Jiahui Wang, Jingjing Zhang, Hua Liu, Weiwei Feng, Wen Yang, Bruce Zetter, Yingjie Xu

《医学前沿(英文)》 2021年 第15卷 第3期   页码 448-459 doi: 10.1007/s11684-020-0805-6

摘要: The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K–Akt–mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a “switch” type regulator. We identified through immunoprecipitation–mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

关键词: prohibitin 1     FKBP8     mTOR     cell proliferation     cancer    

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic

《医学前沿(英文)》 2022年 第16卷 第6期   页码 909-918 doi: 10.1007/s11684-021-0890-1

摘要: In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor α and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood–brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

关键词: acute promyelocytic leukemia     intracranial hemorrhage     cytokines     biomarker    

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to

《医学前沿(英文)》 2022年 第16卷 第3期   页码 403-415 doi: 10.1007/s11684-021-0858-1

摘要: The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P <0.05) and IRF4 (P<0.001) and between white blood cell (WBC) count and IRF4 expression (P <0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P <0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%, 10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

关键词: myeloproliferative neoplasms     IRF4     IRF8     hydroxyurea     essential thrombocythemia    

Parametric study on the mixed solvent synthesis of ZIF-8 nano- and micro-particles for CO adsorption:

Alireza Hadi, Javad Karimi-Sabet, Abolfazl Dastbaz

《化学科学与工程前沿(英文)》 2020年 第14卷 第4期   页码 579-594 doi: 10.1007/s11705-018-1770-3

摘要: The room temperature synthesis of ZIF-8 micro- and nano-particles was investigated using a mixed methanol-water solvent system. ZIF-8 particles of good quality and high crystallinity were obtained. Response surface methodology was used to determine the effect of the synthesis conditions on the ZIF-8 yield, particle size distribution, and mean particle size. The ligand/metal salt molar ratio followed by the amount of sodium formate (the deprotonating agent) and then the amount of water (i.e., the composition of the mixed solvent) respectively had the largest effects on both the ZIF-8 yield and particle size. Results showed that mixing of solvents with different strengths in producing ZIF-8 crystals is a practical method to size-controlled synthesis of ZIF-8 particles. This method is more favorable for industrial-scale ZIF-8 synthesis than using excess amounts of ligands or chemical additives (like sodium formate). In addition, ZIF-8 samples with different mean particle sizes (100, 500, and 1000 nm) were used for CO adsorption and the mid-sized ZIF-8 particles had the highest adsorption capacity.

关键词: metal organic frameworks     zeolitic imidazolate frameworks     ZIF-8     response surface methodology     Box Behnken design     CO adsorption    

标题 作者 时间 类型 操作

Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid leukemia

Weina Zhang, Ying Lu, Tao Zhen, Xinjie Chen, Ming Zhang, Ping Liu, Xiangqin Weng, Bing Chen, Yueying Wang

期刊论文

Innate and adaptive T cells in influenza disease

null

期刊论文

sup>CD117dim/CD34+CD117bri myeloblast-associated gene expression in t(8;21) acute myeloid leukemia

Xueping Li, Yuting Dai, Bing Chen, Jinyan Huang, Saijuan Chen, Lu Jiang

期刊论文

用于环境催化的MoS2/ZIF-8复合材料——太阳能驱动的抗生素降解工程

陈文倩, 李琳悦, 李林, 裘文慧, 唐量, 徐玲, 许科军, 吴明红

期刊论文

A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

null

期刊论文

Zeolitic imidazolate framework-8 (ZIF-8) for drug delivery: A critical review

Simin Feng, Xiaoli Zhang, Dunyun Shi, Zheng Wang

期刊论文

Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis

null

期刊论文

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

期刊论文

Protective efficacy of vaccination with NcMIC3 and NcMIC8 against

Taotao ZHANG, Xiao ZHANG, Qun LIU, Jianhai XU, Jing LIU

期刊论文

青岛地铁8号线海底隧道

贺维国, 刘鹏

期刊论文

8英寸绝缘栅双极型晶体管 (IGBT) 关键技术研究

刘国友,丁荣军,罗海辉

期刊论文

Prohibitin regulates mTOR pathway via interaction with FKBP8

Jiahui Zhang, Yanan Yin, Jiahui Wang, Jingjing Zhang, Hua Liu, Weiwei Feng, Wen Yang, Bruce Zetter, Yingjie Xu

期刊论文

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic

期刊论文

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to

期刊论文

Parametric study on the mixed solvent synthesis of ZIF-8 nano- and micro-particles for CO adsorption:

Alireza Hadi, Javad Karimi-Sabet, Abolfazl Dastbaz

期刊论文