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Targeting “undruggable” c-Myc protein by synthetic lethality

Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu

《医学前沿（英文）》 2021年 第15卷 第4期   页码 541-550 doi: 10.1007/s11684-020-0780-y

摘要： Synthetic lethal screening, which exploits the combination of mutations that result in cell death, is a promising method for identifying novel drug targets. This method provides a new avenue for targeting “undruggable” proteins, such as c-Myc. Here, we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network, whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells. We further discuss strategies to identify these functional nodes in the context of synthetic lethality. We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

关键词： synthetic lethality     undruggable     transcription factor     c-Myc    

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Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

FU Juan, JIANG Yiguo, CHEN Xuemin

《医学前沿（英文）》 2008年 第2卷 第4期   页码 380-385 doi: 10.1007/s11684-008-0073-3

摘要： Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a]P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c- in human bronchial epithelial cells (16HBE-T) transformed by exposure to anti-BPDE. The levels of mRNA and protein of c-Myc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different methods respectively, including reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical methods. The level of c- mRNA appeared to be significantly increased in 16HBE-T, as compared with those of the 16HBE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclusion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mechanism of anti-BPDE.

关键词： transcriptase-polymerase     vehicle-treated     understood     molecular mechanism     different    

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Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

《医学前沿（英文）》 2022年 第16卷 第3期   页码 442-458 doi: 10.1007/s11684-021-0877-y

摘要： T-cell acute lymphoblastic leukemia (T-ALL) is one of the most dangerous hematological malignancies, with high tumor heterogeneity and poor prognosis. More than 60% of T-ALL patients carry NOTCH1 gene mutations, leading to abnormal expression of downstream target genes and aberrant activation of various signaling pathways. We found that chidamide, an HDAC inhibitor, exerts an antitumor effect on T-ALL cell lines and primary cells including an anti-NOTCH1 activity. In particular, chidamide inhibits the NOTCH1-MYC signaling axis by down-regulating the level of the intracellular form of NOTCH1 (NICD1) as well as MYC, partly through their ubiquitination and degradation by the proteasome pathway. We also report here the preliminary results of our clinical trial supporting that a treatment by chidamide reduces minimal residual disease (MRD) in patients and is well tolerated. Our results highlight the effectiveness and safety of chidamide in the treatment of T-ALL patients, including those with NOTCH1 mutations and open the way to a new therapeutic strategy for these patients.

关键词： T-cell acute lymphoblastic leukemia     HDAC inhibitor     chidamide     NOTCH1     MYC     ubiquitination    

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The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 412-425 doi: 10.1007/s11684-018-0650-z

摘要：

Transcription factor networks have evolved in order to control, coordinate, and separate, the functions of distinct network modules spatially and temporally. In this review we focus on the MYC network (also known as the MAX-MLX Network), a highly conserved super-family of related basic-helix-loop-helix-zipper (bHLHZ) proteins that functions to integrate extracellular and intracellular signals and modulate global gene expression. Importantly the MYC network has been shown to be deeply involved in a broad spectrum of human and other animal cancers. Here we summarize molecular and biological properties of the network modules with emphasis on functional interactions among network members. We suggest that these network interactions serve to modulate growth and metabolism at the transcriptional level in order to balance nutrient demand with supply, to maintain growth homeostasis, and to influence cell fate. Moreover, oncogenic activation of MYC and/or loss of a MYC antagonist, results in an imbalance in the activity of the network as a whole, leading to tumor initiation, progression and maintenance.

关键词： network     transcription     cancer     MYC     MAX     MLX    

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Valveless pumping using a two-stage impedance pump

C.-C. LEE, Y. A. ABAKR, K.-C. WOO

《机械工程前沿（英文）》 2013年 第8卷 第3期   页码 311-318 doi: 10.1007/s11465-013-0270-x

摘要：

Impedance pump is defined as a type of valveless pumping mechanism, where an elastic tube is joined with a tube of different impedance, a periodic asymmetrical compression on part of the elastic tube will produce a unidirectional flow. Numerical and experimental studies had been conducted in the past, but little experimental work was found to exploit the principle of multi-stage impedance pumping for fluid transportation. This paper concentrates on the fluid behavior for an open-loop two-stage system experimentally. The aim of this work is to have an insight on the deliverable head and pumping rate of an open-loop two-stage impedance pumping system. This paper generally investigates the effect of different parameters towards the generation of unidirectional flows and composite flow of two opposite directions. Results obtained are of significant values.

关键词： valveless pumping     open-loop     two-stage     unidirectional     composite    

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基于S3C2410的GPRS数据终端的设计

孙学用

《中国工程科学》 2007年 第9卷 第12期   页码 94-96

摘要： 提出了以S3C2410处理器为核心，以SIM100-E为GPRS通信模块,构建了一套嵌入式Internet数据终端的方案，对其硬件构成及工作流程进行了讨论，描述了其软件层次结构，并详细讲解了基于该平台的

关键词： GPRS；嵌入式Internet；S3C2410；SIM100-E    

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Bioinspired C/TiO

Jian LI, Likun GAO, Wentao GAN

《农业科学与工程前沿（英文）》 2017年 第4卷 第4期   页码 459-464 doi: 10.15302/J-FASE-2017178

摘要： butterfly wings were replicated by a sol-gel method and a calcination process, which could take advantage of the spatial features of the wing to enhance their photocatalytic properties. Hierarchical structures of -carbon-TiO (PP-C-TiO ) were confirmed by SEM observations. By applying the Brunauer-Emmett-Teller method, it was concluded that in the presence of wings the product shows higher surface area with respect to the pure TiO made in the absence of the wings. The higher specific surface area is also beneficial for the improvement of photocatalytic property. Furthermore, the conduction and valence bands of the PP-C-TiO are more negative than the corresponding bands of pure TiO , allowing the electrons to migrate from the valence band to the conduction band upon absorbing visible light. That is, the presence of C originating from wings in the PP-C-TiO could extend the photoresponsiveness to visible light. This strategy provides a simple method to fabricate a high-performance photocatalyst, which enables the simultaneous control of the morphology and carbon element doping.

关键词： bioinspired     butterfly wings     C/TiO2     photocatalyst     visible light    

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Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism:

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 319-323 doi: 10.1007/s11684-017-0553-4

摘要：

Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in and lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of and were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in and a short deletion variant c.572_574delAGA in . This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the and gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

关键词： antithrombin deficiency     protein C activity     mutation     variant     venous thromboembolism     anticoagulants    

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Atomistic simulations of plasma catalytic processes

Erik C. Neyts

《化学科学与工程前沿（英文）》 2018年 第12卷 第1期   页码 145-154 doi: 10.1007/s11705-017-1674-7

摘要： There is currently a growing interest in the realisation and optimization of hybrid plasma/catalyst systems for a multitude of applications, ranging from nanotechnology to environmental chemistry. In spite of this interest, there is, however, a lack in fundamental understanding of the underlying processes in such systems. While a lot of experimental research is already being carried out to gain this understanding, only recently the first simulations have appeared in the literature. In this contribution, an overview is presented on atomic scale simulations of plasma catalytic processes as carried out in our group. In particular, this contribution focusses on plasma-assisted catalyzed carbon nanostructure growth, and plasma catalysis for greenhouse gas conversion. Attention is paid to what can routinely be done, and where challenges persist.

关键词： atomic scale simulation     plasma-catalyst    

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Elevated C-reactive protein levels predict worsening prognosis in Chinese patients with first-onset stroke

Jiangtao YAN, Rutai HUI, Daowen WANG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 30-35 doi: 10.1007/s11684-009-0005-x

摘要： The role of high sensitivity C-reactive protein (hsCRP) in predicting prognosis after stroke in the Asian population has not been investigated. We hypothesized that elevated levels of hsCRP were associated with worsening prognosis after stroke in Chinese patients. Two hundred and ninety consecutive patients with first-onset stroke and 290 age- and gender-matched control subjects without any cerebrovascular disease were enrolled for study. Plasma hsCRP level was detected and subsequent vascular events and death were recorded in both groups over a 5-year period. Compared to control group, patients presenting with stroke had higher plasma hsCRP level (3.3 ± 3.8 1.3 ± 2.2 mg/L, < 0.01). Furthermore, in the group of patients with stroke, the mean plasma hsCRP level was higher in patients who developed subsequent vascular diseases or died as compared with the patients without further complications (4.4 ± 4.3 2.7 ± 3.3 mg/L, < 0.01). Compared to the lowest tertile of hsCRP level, the relative risk for vascular events or death in stroke patients was 2.91 in the highest tertile of hsCRP (95% CI, 1.54–5.50, = 0.001). This increase in relative risk for vascular events or death in stroke patients continued after adjustment for age, sex and other cardiovascular risk factors such as hypertension and diabetes ( : 2.771, 95% CI: 1.367–5.617, = 0.005). These findings indicate that increased hsCRP level is associated with worsening prognosis after stroke in Chinese patients and suggests that inflammation is correlated with stroke outcome.

关键词： C-reactive protein     inflammation     stroke    

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A simple, azulene-based colorimetric probe for the detection of nitrite in water

Lloyd C. Murfin, Carlos M. López-Alled, Adam C. Sedgwick, Jannis Wenk, Tony D. James, Simon E. Lewis

《化学科学与工程前沿（英文）》 2020年 第14卷 第1期   页码 90-96 doi: 10.1007/s11705-019-1790-7

摘要： We describe the synthesis and evaluation of an azulene-based chemodosimeter for nitrite. The probe was found to undergo two distinct color changes upon introduction aqueous nitrite ion. A near-instant formation of a grey color provides a qualitative indication of the presence of nitrite, followed by the formation of a deep-yellow/orange color, the endpoint from which quantitative data can be derived. The azulene probe exhibits 1:1 stoichiometry of reaction with nitrite in water, and is selective for nitrite over other anions. The azulene probe was applied to determine nitrite content in cured meat, and compared with the British Standard testing procedure (Griess test). The value obtained from the azulene-based probe agreed closely with the standard test. Our procedure only requires the preparation of one standard solution, instead of the three required for the standard Griess test.

关键词： azulene     nitrite     diazoquinone    

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Comments on the special issue of

Neil C. TURNER

《农业科学与工程前沿（英文）》 2017年 第4卷 第2期   页码 254-255 doi: 10.15302/J-FASE-2017156

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Comments on the special issue on tropical crops of

Luiz J C B CARVALHO

《农业科学与工程前沿（英文）》 2016年 第3卷 第4期   页码 375-376 doi: 10.15302/J-FASE-2016129

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Enhancing the efficiency of nitrogen removing bacterial population to a wide range of C:N ratio (1.5:1 to 14:1) for simultaneous C & N removal

《环境科学与工程前沿（英文）》 2022年 第16卷 第8期 doi: 10.1007/s11783-022-1522-y

摘要：

• Simultaneous C & N removal in Methammox occurs at wide C:N ratio.

关键词： Methanogens     Biological Nitrogen Removal (BNR)     Simultaneous     Methammox     C:N ratio    

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Uncertainty propagation analysis by an extended sparse grid technique

JIA, C. JIANG, C. M. FU, B. Y. NI, C. S. WANG, M. H. PING

《机械工程前沿（英文）》 2019年 第14卷 第1期   页码 33-46 doi: 10.1007/s11465-018-0514-x

摘要： In this paper, an uncertainty propagation analysis method is developed based on an extended sparse grid technique and maximum entropy principle, aiming at improving the solving accuracy of the high-order moments and hence the fitting accuracy of the probability density function (PDF) of the system response. The proposed method incorporates the extended Gauss integration into the uncertainty propagation analysis. Moreover, assisted by the Rosenblatt transformation, the various types of extended integration points are transformed into the extended Gauss-Hermite integration points, which makes the method suitable for any type of continuous distribution. Subsequently, within the sparse grid numerical integration framework, the statistical moments of the system response are obtained based on the transformed points. Furthermore, based on the maximum entropy principle, the obtained first four-order statistical moments are used to fit the PDF of the system response. Finally, three numerical examples are investigated to demonstrate the effectiveness of the proposed method, which includes two mathematical problems with explicit expressions and an engineering application with a black-box model.

关键词： uncertainty propagation analysis     extended sparse grid     maximum entropy principle     extended Gauss integration     Rosenblatt transformation     high-order moments analysis    

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标题 作者 时间 类型 操作

Targeting “undruggable” c-Myc protein by synthetic lethality

Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu

期刊论文

Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

FU Juan, JIANG Yiguo, CHEN Xuemin

期刊论文

Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

期刊论文

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

null

期刊论文

Valveless pumping using a two-stage impedance pump

C.-C. LEE, Y. A. ABAKR, K.-C. WOO

期刊论文

基于S3C2410的GPRS数据终端的设计

孙学用

期刊论文

Bioinspired C/TiO

Jian LI, Likun GAO, Wentao GAN

期刊论文

Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism:

null

期刊论文

Atomistic simulations of plasma catalytic processes

Erik C. Neyts

期刊论文

Elevated C-reactive protein levels predict worsening prognosis in Chinese patients with first-onset stroke

Jiangtao YAN, Rutai HUI, Daowen WANG

期刊论文

A simple, azulene-based colorimetric probe for the detection of nitrite in water

Lloyd C. Murfin, Carlos M. López-Alled, Adam C. Sedgwick, Jannis Wenk, Tony D. James, Simon E. Lewis

期刊论文

Comments on the special issue of

Neil C. TURNER

期刊论文

Comments on the special issue on tropical crops of

Luiz J C B CARVALHO

期刊论文

Enhancing the efficiency of nitrogen removing bacterial population to a wide range of C:N ratio (1.5:1 to 14:1) for simultaneous C & N removal

期刊论文

Uncertainty propagation analysis by an extended sparse grid technique

JIA, C. JIANG, C. M. FU, B. Y. NI, C. S. WANG, M. H. PING

期刊论文