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Regulatory mechanism and functional analysis of

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《医学前沿（英文）》 2017年第11卷第1期页码 87-96 doi: 10.1007/s11684-016-0469-4

摘要：

S100A9, a calcium-binding protein, participates in the inflammatory process and development of various tumors, thus attracting much attention in the field of cancer biology. This study aimed to investigate the regulatory mechanism of and its function involvement in APL. We used real-time quantitative PCR to determine whether PML/RARα affects the expression of in NB4 and PR9 cells upon ATRA treatment. ChIP-based PCR and dual-luciferase reporter assay system were used to detect how PML/RARα and PU.1 regulate promoter activity. CCK-8 assay and flow cytometry were employed to observe the viability and apoptosis of NB4 cells when was overexpressed. Results showed that was an ATRA-responsive gene, and PML/RARα was necessary for the ATRA-induced expression of in APL cells. In addition, PU.1 could bind to the promoter of , especially when treated with ATRA in NB4 cells, and promote its activity. More importantly, overexpression of induced the apoptosis of NB4 cells and inhibited cell growth. Collectively, our data indicated that PML/RARα and PU.1 were necessary for the ATRA-induced expression of in APL cells. Furthermore, promoted apoptosis in APL cells and affected cell growth.

关键词： S100A9 S100A9 PU.1 PML/RARα ATRA APL

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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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Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent

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《医学前沿（英文）》 2017年第11卷第3期页码 410-422 doi: 10.1007/s11684-017-0527-6

摘要：

Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5′-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29±0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

关键词： annexin A2-S100A10 heterotetramer PML/RARα fusion protein plasmin cell invasion acute promyelocytic leukemia

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Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal

Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang

《医学前沿（英文）》 2020年第14卷第1期页码 91-100 doi: 10.1007/s11684-019-0696-6

摘要： Pancreatic ductal adenocarcinoma (PDAC) is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China. AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well. However, the role of AcK27-HOXB9 in PDAC is unclear. The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC. Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay, respectively. HOXB9 was upregulated ( <0.0001), and AcK27-HOXB9 ( =0.0023) was downregulated in patients with PDAC. HOXB9 promoted ( =0.0115), while AcK27-HOXB9 ( =0.0279) inhibited PDAC progression. AcK27-HOXB9 predicted favorable outcome in patients with PDAC ( =0.0412). AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay. The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression. The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.

关键词： HOXB9 AcK27-HOXB9 PDAC

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Fabrication of MIL-100(Fe)@SiO

Yinlong Hu,Shuang Zheng,Fumin Zhang

《化学科学与工程前沿（英文）》 2016年第10卷第4期页码 534-541 doi: 10.1007/s11705-016-1596-9

摘要： Heterogeneous catalysts with convenient recyclability and reusability are vitally important to reduce the cost of catalysts as well as to avoid complex separation and recovery operations. In this regard, magnetic MIL-100(Fe)@SiO @Fe O microspheres with a novel core-shell structure were fabricated by the self-assembly of a metal-organic MIL-100(Fe) framework around pre-synthesized magnetic SiO @Fe O particles under relatively mild and environmentally benign conditions. The catalytic activity of the MIL-100(Fe)@SiO @Fe O catalyst was tested for the liquid-phase acetalization of benzaldehyde and glycol. The MIL-100(Fe)@SiO @Fe O catalyst has a significant amount of accessible Lewis acid sites and therefore exhibited good acetalization catalytic activity. Moreover, due to its superparamagnetism properties, the heterogeneous MIL-100(Fe)@SiO @Fe O catalyst can be easily isolated from the reaction system within a few seconds by simply using an external magnet. The catalyst could then be reused at least eight times without significant loss in catalytic efficiency.

关键词： metal-organic frameworks heterogeneous catalysis magnetically recoverable catalysts core-shell structure acetalization

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Analysis of 100 consecutive cases of resectable pancreatic neuroendocrine neoplasms: clinicopathological

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《医学前沿（英文）》 2016年第10卷第4期页码 444-450 doi: 10.1007/s11684-016-0471-x

摘要：

The incidence rate of pancreatic neuroendocrine neoplasms (pNENs) has increased rapidly in recent years. However, the clinicopathological characteristics of pNENs are poorly understood. Medical records of patients who underwent surgery and were confirmed as pNENs by pathological examination from January 2003 to February 2015 in Qilu Hospital were reviewed retrospectively. A total of 100 patients, 36 males and 64 females, were included with a mean operation age of 46.26±13.41 years. Among the 100 cases, 76 had insulinomas and 24 had non-functional pNENs. Tumor size ranged from 0.5 cm to 9 cm, and the mean size was 2.20±1.40 cm. The percentages of TNM stages I, II, III, and IV tumors were 89.0%, 8.0%, 0.0%, and 3.0%, respectively. Based on the WHO classification, pNENs were classified into three grades: G1, G2, and G3. G1, G2, and G3 tumors were confirmed in 72.9%, 23.7%, and 3.4% patients, respectively. The positive rates of CgA and Syn immunohistochemical staining were 94.5% (69/73) and 100% (74/74), respectively. Compared with insulinoma, non-functional pNENs have larger tumor sizes, more advanced TNM staging, a higher Ki-67 index, and a higher rate of liver metastasis (P<0.05). In conclusion, pNENs are heterogeneous tumors with varying clinical manifestations, diverse tumor biological characteristics, and different prognoses. Non-functional pNENs present a more aggressive behavioral model and have poorer prognosis than functional pNENs.

关键词： pancreatic neuroendocrine neoplasms clinicopathological characteristic Ki-67 liver metastasis outcomes

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662 A/G gene variation in human tumor necrosis factor receptor superfamily, member 9 (TNFRSF9)

QU Yanchun, YANG Ze, SUN Liang, JI Linong

《医学前沿（英文）》 2008年第2卷第3期页码 283-285 doi: 10.1007/s11684-008-0053-7

摘要： The aim of this paper is to report a new coding variance of the gene, a candidate for autoimmune diseases. We found the variation in two families with type 2 diabetes mellitus by D-HPLC mutation screening method and confirmed our results by direct sequencing and PCR-RFLP. Although without changing the amino acid coding, the variance may have an effect on codon usage and play a role in disease development, such as type 2 diabetes mellitus. However, we cannot define the role of this variance because the frequency of the minor allele is low in the Chinese population and no homozygote of the variance was found. More research in multiple populations will be necessary to define the role of this variance.

关键词： D-HPLC mutation development autoimmune PCR-RFLP candidate

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Lignin-based electrospun nanofiber membrane decorated with photo-Fenton Ag@MIF-100(Fe) heterojunctions

《化学科学与工程前沿（英文）》 2023年第17卷第7期页码 930-941 doi: 10.1007/s11705-023-2309-9

摘要： Membrane technology for wastewater remediation has aroused wide interest owing to its unique properties and potential applications. However, it remains challenging to explore green, efficient and robust membrane material and technique for complex wastewater treatment. Herein, we proposed using a simple electrospinning and in situ seeding method to fabricate a lignin-based electrospun nanofiber membrane (LENM) decorated with photo-Fenton Ag@MIL-100(Fe) heterojunctions for efficient separation of oil/water emulsions and degradation of organic dye. Thanks to the embedded lignin in LENM, an ultrahigh MIL-100(Fe) loading (53 wt %) with good wettability and high porosity was obtained. As a result, the hybrid Ag@MIL-100(Fe)/LENM exhibited excellent oil/water emulsions separation efficiency (more than 97%) without a compromise of water flux. Moreover, the hybrid membrane showed an excellent dye removal with degradation of 99% methylene blue within 30 min under illumination, which is attributed to a synergy of dye adsorption/enrichment and photo-Fenton catalytic degradation from Ag@MIL-100(Fe). Therefore, the lignin-based photo-Fenton hybrid membrane can lay the foundation for the preparation and application of green, sustainable and versatile membrane materials and technologies for efficient complex wastewater remediation.

关键词： lignin electrospinning heterojunctions photo-Fenton catalysis wastewater remediation

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The 9th China Engineering Management Forum Guangzhou Consensus

《工程管理前沿（英文）》 2015年第2卷第2期页码 105-107 doi: 10.15302/J-FEM-2015019

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Mobile CRISPR-Cas9 based anti-phage system in E. coli

《化学科学与工程前沿（英文）》 2022年第16卷第8期页码 1281-1289 doi: 10.1007/s11705-022-2141-7

摘要： Escherichia coli is one of the most important microbial cell factories, but infection by bacteriophages in the environment may have a huge impact on its application in industrial production. Here, we developed a mobile CRISPR-Cas9 based anti-phage system for bacteriophages defense in E. coli. Two conjugative plasmids pGM1 (phosphoglucomutase 1) and pGM2 carrying one and two guide RNAs, respectively, were designed to defend against a filamentous phage. The results showed that the pGM1 and pGM2 could decrease the phage infection rate to 1.6% and 0.2% respectively in infected cells. For preventing phage infection in E. coli, the pGM2 decreased the phage infection rate to 0.1%, while pGM1 failed to block phage infection. Sequence verification revealed that point mutations in protospacer or protospacer adjacent motif sequences of the phage genome caused loss of the defense function. These results support the potential application of MCBAS in E. coli cell factories to defend against phage infections.

关键词： phage infections anti-phage CRISPR-Cas9 conjugative transfer synthetic biology

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REDUCTION OF NON-POINT SOURCE POLLUTION IN THE YONG’AN RIVER BY CONSTRUCTED WETLAND BASED ON 9 YEARS

《农业科学与工程前沿（英文）》 2023年第10卷第4期页码 627-638 doi: 10.15302/J-FASE-2023516

摘要：

The agricultural and livestock activities surrounding the rivers flowing into the lakes have caused non-point source pollution, leading to excessive amounts of nutrient salts in downstream rivers. Introducing river water into constructed wetlands along river course has proven to be an effective solution for decreasing nitrogen (N) and phosphorus (P) loads. This paper reports 9 years of monitoring the Yong’an River and its surrounding constructed wetlands in the upper reaches of Erhai Lake, located in Yunnan Province, China. This study analyzed the main types of pollutants in the river, and evaluated the removal efficiency of pollutants by the constructed wetlands. The findings indicate that total nitrogen (TN) and nitrate nitrogen (NO₃^–-N) are the primary pollutants in the Yong’an River, which exhibit variation throughout the year corresponding to the alternating wet and dry seasons. Although constructed wetlands are effective in removing NO₃^–-N and P, their efficacy in removing ammonium nitrogen (NH₄⁺-N) and organic pollutants is limited. This limitation can be attributed to the lack of timely disposal of aquatic plant residues. This research contributes to the understanding of the potential issues that may arise during the extended use of constructed wetlands and provides solutions to address them.

关键词： inflowing rivers surface-flow constructed wetland nutrients long-term monitoring

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Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

《医学前沿（英文）》 2009年第3卷第2期页码 141-147 doi: 10.1007/s11684-009-0041-6

摘要： Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome-to- -Golgi-network trafficking. To explore the possibility of Rab9-related gene therapy for neurodegenerative diseases, we packed Lentivirus encoding Rab9. The expressing plasmid pCDH1-MCF1-Rab9-EF1-copGFP was constructed by using molecular biological techniques. The Lentivirus encoding Rab9 cDNA was packed by Lifectamine-2000 mediated co-transfection of the plasmid pPACKH1- , pPACKH1- and pVSV- into 293T cells. DNA sequencing proved the successful construction of pCDH1-MCF1-Rab9-EF1-copGFP. After 72 hours, the expression of GFP could be detected in BV-2 cells. Western blotting revealed that the Rab9 gene expression in BALB/c mice brain was up-regulated significantly 4 weeks after injection with Lentivirus encoding Rab9, which evidenced a satisfactory increasing effect of this virus. Administration of Lenti-Rab9 to postnatal day 3 Niemann-Pick disease type C (NPC) mice reduced motor defects and prevented the weight loss associated with female NPC mice, as well as modulating the death rate of Purkinje neurons. It is concluded that the packaging of Lentivirus encoding Rab9 was successful. Lentivirus encoding Rab9 can increase the expression of Rab9 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.

关键词： Rab9 lentivirus gene therapy gene transfer

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CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

null

《医学前沿（英文）》 2017年第11卷第4期页码 554-562 doi: 10.1007/s11684-017-0543-6

摘要：

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

关键词： CAR-T CRISPR-Cas9 LAG-3