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Lentivector-mediated RNAi efficiently downregulates expression of murine cdk4 gene

Feng JIANG PhD , Xuezhen WANG PhD , Zheng XUE MD , Suming ZHANG PhD , Siyu FANG BM , Min ZHANG MD, PhD ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 287-291 doi: 10.1007/s11684-009-0050-5

摘要： In order to explore the role of cyclin-dependent kinase 4 (cdk4) in neurodegenerative diseases, lentiviral-delivered RNA interference (RNAi) was used to silence the expression of the murine cdk4 gene . Three cdk4-shRNAs of mouse and a negative sequence were designed. After synthesis and annealing, double strand oligonucleotides were cloned into a linearized pSIH1-H1-copGFP shRNA vector. It was confirmed by polymerase chain reaction (PCR) and sequencing that three pairs of cdk4-shRNAs and a negative shRNA were correctly inserted into the pSIH1-H1-copGFP vector. The above recombinants were transfected by lipofectamine into BV-2 cells. The gene silencing efficacy rates of the 3 targets were compared by Western blotting. The cdk4-siRNA2 was the most effective in silencing cdk4. The optimized pSIH1-cdk4-siRNA2 and pSIH-negative-siRNA were co-transfected into 293T cells with the lentiviral packaging plasmids respectively. The culture supernatant was harvested and condensed at the 24th and 48thh after transfection. Interference efficiency of the lentivirus expressing cdk4-siRNA was determined by reverse transcriptase-PCR (RT-PCR) and Western blotting in BV-2 cells. Lentivector-mediated RNAi could efficiently down-regulate the expression of the murine cdk4 gene , which provides a potential tool for studying and treating cdk4-related diseases.

关键词： cyclin-dependent kinase 4     RNA interference     plasmid     lentiviral vector    

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Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma

《医学前沿（英文）》 doi: 10.1007/s11684-023-0999-5

摘要： Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

关键词： thyroid carcinoma     mesenchymal stem cell     extracellular vesicle     GTF2I     FAT1     CDK4    

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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

《医学前沿（英文）》 2023年 第17卷 第2期   页码 290-303 doi: 10.1007/s11684-022-0956-8

摘要： Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine     cyclin-dependent kinase 2     patient-derived xenograft     esophageal squamous cell carcinoma    

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Discovery of small molecule degraders for modulating cell cycle

《医学前沿（英文）》   页码 823-854 doi: 10.1007/s11684-023-1027-5

摘要： The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

关键词： PROTAC     molecular glue     degrader     cell cycle     CDK     cyclin    

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The role of CDK1 siRNA interference in cell cycle and cell apoptosis

Hui XIAO PhD, Ming TIAN MM, Junna GE MM, Xin Wei MD, Zhaoming LI MM, Xiaolan LI MS, Deding TAO PhD, Junbo HU MD, Jianping GONG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 384-389 doi: 10.1007/s11684-009-0070-1

摘要： In the present report, cyclin-dependent kinase1 (CDK1) siRNA was transfected into cells to silence the CDK1 gene expression and study its role in the cell cycle and cell apoptosis. The siRNA targeting CDK1 gene was chemically synthesized and transfected into Hela cells by lipofectamine 2000. The expression levels of CDK1 gene and protein were examined by real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. The cell cycle was analyzed by using DNA content analysis by flow cytometry. Cell apoptosis was detected by the Annexin V/PI method. The morphological changes of transfected cells were examined under the microscopy by Wright-Giemsa stain. CDK1 gene was successfully silenced by its siRNA, and the CDK1 protein expression level was decreased significantly, especially from 48thh to 60thh after transfection. The DNA content analysis showed that transfection of CDK1 siRNA led to cells accumulating in G/M phase. There was no significant difference in the apoptotic rate between transfected cells and the control cells after transfection of CDK1 siRNA for 48 or 60h. More double nucleus or multinucleus cells could be seen under the microscopy among the transfected cells. The decreased CDK1 expression by siRNA silencing gave rise to cell cycle arrest in G/M phase but did not induce apoptosis.

关键词： cyclin-dependent kinase1     siRNA interference     cell cycle     apoptosis    

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ZnFe2O4/BiVO4 Z-scheme heterojunction for efficient visible-light photocatalytic

《化学科学与工程前沿（英文）》 2023年 第17卷 第11期   页码 1728-1740 doi: 10.1007/s11705-023-2322-z

摘要： A novel Z-scheme ZnFe2O4/BiVO4 heterojunction photocatalyst was successfully synthesized using a convenient solvothermal method and applied in the visible light photocatalytic degradation of ciprofloxacin, which is a typical antibiotic contaminant in wastewater. The heterostructure of as-synthesized catalysts was confirmed using X-ray diffraction, scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy characterizations. Compared with the single-phase counterparts, ZnFe2O4/BiVO4 demonstrated considerably enhanced photogenerated charge separation efficiencies because of the Z-scheme transfer mechanism of electrons between the composite photocatalysts. Consequently, the 30% ZnFe2O4/BiVO4 catalyst afforded a degradation rate of up to 97% of 20 mg/L ciprofloxacin under 30 min of visible light irradiation with a total organic carbon removal rate of 50%, which is an excellent activity compared with ever reported BiVO4-based catalysts. In addition, the liquid chromatography-mass spectrometry and quantitative structure-activity relationships model analyses demonstrated that the toxicity of the intermediates was lower than that of the parent ciprofloxacin. Moreover, the as-synthesized ZnFe2O4/BiVO4 heterojunctions were quite stable and could be reused at least four times. This study thus provides a promising Z-scheme heterojunction photocatalyst for the efficient removal and detoxication of antibiotic pollutants from wastewater.

关键词： ZnFe2O4/BiVO4     Z-scheme heterojunction     photocatalytic degradation     ciprofloxacin    

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Li4SiO4-coated LiNi0.5Mn1.5O4 as the high performance

Shifeng YANG, Wenfeng REN, Jian CHEN

《能源前沿（英文）》 2017年 第11卷 第3期   页码 374-382 doi: 10.1007/s11708-017-0494-2

摘要： The preparation of Li SiO -coated LiNi Mn O materials by sintering the SiO -coated nickel-manganese oxides with lithium salts using abundant and low-cost sodium silicate as the silicon source was reported. The samples were characterized by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. It was found that a uniform and complete SiO coating layer could be obtained at a suitable pH value of 10, which transformed to a good Li SiO coating layer afterwards. When used as the cathode materials for lithium-ion batteries, the Li SiO -coated LiNi Mn O samples deliver a better electrochemical performance in terms of the discharge capacity, rate capability, and cycling stability than that of the pristine material. It can still deliver 111.1 mAh/g at 20 C after 300 cycles, with a retention ratio of 93.1% of the stable capacity, which is far beyond that of the pristine material (101.3 mAh/g, 85.6%).

关键词： lithium-ion batteries     cathode material     LiNi0.5Mn1.5O4     lithium-ion conductor     coating    

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Enhanced debromination of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) by zero-valent zinc with ascorbic

Chaojin Jiang, Xiaoqian Jiang, Lixun Zhang, Yuntao Guan

《环境科学与工程前沿（英文）》 2020年 第14卷 第3期 doi: 10.1007/s11783-020-1224-2

摘要： Highly efficient debromination of BDE-47 was achieved in the ZVZ/AA system. BDE-47 debromination by the ZVZ/AA can be applied to a wide range of pH. AA inhibits the formation of (hydr)oxide and accelerates the corrosion of ZVZ. Reduction mechanism of BDE-47 debromination by the ZVZ/AA system was proposed. A new technique of zero-valent zinc coupled with ascorbic acid (ZVZ/AA) was developed and applied to debrominate the 2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), which achieved high conversion and rapid debromination of BDE-47 to less- or non-toxic forms. The reaction conditions were optimized by the addition of 100 mg/L ZVZ particles and 3 mmol/L AA at original solution pH= 4.00 using the solvent of methanol/H2O (v:v= 4:6), which could convert approximately 94% of 5 mg/L BDE-47 into lower-brominated diphenyl ethers within a 90 min at the ZVZ/AA system. The high debromination of BDE-47 was mainly attributed to the effect of AA that inhibits the formation of Zn(II)(hydr)oxide passivation layers and promotes the corrosion of ZVZ, which leads to increase the reactivity of ZVZ. Additionally, ion chromatography and gas chromatography mass spectrometry analyses revealed that bromine ion and lower-debromination diphenyl ethers formed during the reduction of BDE-47. Furthermore, based on the generation of the intermediates products, and its concentration changes over time, it was proposed that the dominant pathway for conversion of BDE-47 was sequential debromination and the final products were diphenyl ethers. These results suggested that the ZVZ/AA system has the potential for highly efficient debromination of BDE-47 from wastewater.

关键词： 2     2′     4     4′-tetrabromodiphenyl ether (BDE-47)     Ascorbic acid     Reductive debromination     Zero-valent zinc    

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Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

《医学前沿（英文）》 2023年 第17卷 第1期   页码 132-142 doi: 10.1007/s11684-022-0938-x

摘要： Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

关键词： nasopharyngeal carcinoma     WGCNA     RFC4     proliferation    

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4D打印定律 Article

Farhang Momeni, Jun Ni

《工程（英文）》 2020年 第6卷 第9期   页码 1035-1055 doi: 10.1016/j.eng.2020.01.015

摘要： 相应地，四维(4D)打印是一个涉及多个研究领域的制造工艺。4D打印保留了3D打印的一般属性(如减少材料浪费、消除注射模具、冲压模具和机械加工过程)，并且随着时间的推移能实现产品第四维度的智能行为。3D和4D打印结构的主要区别是4D打印存在一个附加的维度，这个维度可以随着时间的推移进行智能进化。然而，目前还没有用于建模和预测这个附加维度的一般公式。本文从基本原理开始，导出并验证了一个具有特定格式的一般双指数公式，该公式可以模拟几乎所有4D结构的时间相关性行为(如水、光化学、光热、溶剂、pH、湿度、电化学、电热、超声波等响应)。研究表明，需要利用两种类型的时间常数来捕捉4D多材料的正确的时间相关性行为。本文引入了4D多材料结构中主动材料和被动材料的界面错配压力的概念，从而得到了两个时间常数之一。本文的结果从最基本的概念开始，并以控制方程结束，可以作为未来4D打印领域研究的一般设计原则，其中时间相关性行为应该被正确地理解、建模和预测。

关键词： 制造业     刺激响应材料     材料力学     时间常数     4D打印    

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Synthesis, insecticidal activities and DFT study of pyrimidin-4-amine derivatives containing the 1,2,4

《化学科学与工程前沿（英文）》 2022年 第16卷 第7期   页码 1090-1100 doi: 10.1007/s11705-021-2091-5

摘要： Twenty six novel pyrimidin-4-amine derivatives containing the 1,2,4-oxadiazole motif were synthesized. Their chemical structures were confirmed by 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrography. The insecticidal activity results indicated that some of them possessed excellent insecticidal activity (100%) against Mythimna separate, especially for compounds 6d, 6f, 6o, 6w, 6y and 6z. These compounds exhibited no activity against the insects Aphis medicagini and Tetranychus cinnabarinus. The structure- insecticidal activity relationships are discussed. Density functional theory analysis can potentially be used to design more active compounds. These results provide useful insecticide design information for further optimization.

关键词： synthesis     pyrimidin-4-amine derivatives     1     2     4-oxadiazole     insecticidal activity     structure-activity relationship    

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Identifying stakeholders’ roles and relevant project documents for 4D-based collaborative decision making

Veronika BOLSHAKOVA, Annie GUERRIERO, Gilles HALIN

《工程管理前沿（英文）》 2020年 第7卷 第1期   页码 104-118 doi: 10.1007/s42524-019-0041-4

摘要： To fully understand and effectively implement 4D building information modelling (BIM) models and methods, we need to develop a precise knowledge of which project digital documents should be used and how they influence the decision-making (DM) process. This article studies the convergence between uses of 4D BIM and digital project documents. We hypothesize that a clear visualization of the construction simulation through a 4D model is a useful source of information and a support for DM at collaborative meetings. Through this research, we continue to progress toward a new 4D-based collective decision device, so these elements will contribute to propose 4D BIM as DM support on architecture engineering construction (AEC) projects. Further, the present research will be complemented by results from questionnaires given at a later research stage. The article presents a brief review of BIM context to consider ways of fostering the implementation of all 4D BIM uses (not only visualization). It then introduces a proposition for 4D BIM uses implementation by the project development phase. It concludes by summarizing stakeholders’ roles and documents relevant to 4D BIM uses.

关键词： BIM     4D BIM     4D BIM use     AEC project management     collaboration     decision making    

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4Pi荧光超分辨显微术综述 Review

郝翔, 李依明, 傅爽, 李旸晖, 许迎科, 匡翠方, 刘旭

《工程（英文）》 2022年 第11卷 第4期   页码 146-153 doi: 10.1016/j.eng.2020.07.028

摘要： 回顾这些历程，一个重要的里程碑是基于两个对置物镜的4Pi 显微架构及其超分辨版本的出现。鉴于此，本文综述了4Pi 超分辨显微术的近期进展。总体上，4Pi 超分辨显微镜为透明样品观测提供了一
种能够突破衍射极限、非侵入、各向同性的三维分辨率的技术手段。具体而言，本文针对目标开关和随机开关两个主要4Pi 超分辨显微术版本，讨论了它们的架构、原理、应用和未来发展趋势。

关键词： 荧光超分辨显微术     超分辨成像     4Pi超分辨显微术     isoSTED     4Pi-SMLM    

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对双层组件4D打印可逆性的初步研究 Article

Amelia Yilin Lee, Jia An, Chee Kai Chu, Yi Zhang

《工程（英文）》 2019年 第5卷 第6期   页码 1159-1170 doi: 10.1016/j.eng.2019.09.007

摘要：

增材制造的快速发展和形状记忆聚合物材料的进步推动了四维（4D）打印技术的进展。随着设计方面的不断改进，逐渐证明有可能实现可逆4D打印或双向4D打印。这项技术将完全消除对人为干预的需要，因为编程完全由外部刺激驱动，这使得4D打印部件可以在多个周期内启动。本研究提出了一种新的可逆4D打印驱动方法，其中弹性体的溶胀和热量用于编程阶段，以及热量用于恢复阶段。本研究的主要重点在于自驱动设计这一步骤。采用这种方式理解曲率可以提供对可逆4D打印结构的高度控制。

关键词： 4D打印     增材制造     形状记忆聚合物     可逆4D打印     双向4D打印     溶胀弹性体    

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Recombinant aspartate aminotransferase-catalyzed synthesis of L-4-fluorophenylalanine

CHEN Meijuan, JIA Honghua, CHEN Yongsheng, JIANG Min, WEI Ping

《化学科学与工程前沿（英文）》 2008年 第2卷 第2期   页码 220-223 doi: 10.1007/s11705-008-0041-0

摘要： L-4-Fluorophenylalanine (FPhe) was prepared from 4-fluorophenylpyruvate (FPPA) catalyzed by aspartate aminotransferase (Asp-AT) of the recombinant BL21-pET/aspC. After 12 h enzymatic reaction, the FPPA conversion was over 90% and the yield of FPhe could be above 85% under the following optimal conditions: 37°C, pH value range of 5.0–8.0, 5.5 mass ratio of cell to FPPA, 0.6% (w/v) of Tween 80, 7.08 g/L FPPA, and 1.6 of molar ratio of L-Asp to FPPA.

关键词： L-4-Fluorophenylalanine     Asp-AT     aspartate aminotransferase     4-fluorophenylpyruvate     FPPA    

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标题 作者 时间 类型 操作

Lentivector-mediated RNAi efficiently downregulates expression of murine cdk4 gene

Feng JIANG PhD , Xuezhen WANG PhD , Zheng XUE MD , Suming ZHANG PhD , Siyu FANG BM , Min ZHANG MD, PhD ,

期刊论文

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma

期刊论文

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

期刊论文

Discovery of small molecule degraders for modulating cell cycle

期刊论文

The role of CDK1 siRNA interference in cell cycle and cell apoptosis

Hui XIAO PhD, Ming TIAN MM, Junna GE MM, Xin Wei MD, Zhaoming LI MM, Xiaolan LI MS, Deding TAO PhD, Junbo HU MD, Jianping GONG MD,

期刊论文

ZnFe2O4/BiVO4 Z-scheme heterojunction for efficient visible-light photocatalytic

期刊论文

Li4SiO4-coated LiNi0.5Mn1.5O4 as the high performance

Shifeng YANG, Wenfeng REN, Jian CHEN

期刊论文

Enhanced debromination of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) by zero-valent zinc with ascorbic

Chaojin Jiang, Xiaoqian Jiang, Lixun Zhang, Yuntao Guan

期刊论文

Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

期刊论文

4D打印定律

Farhang Momeni, Jun Ni

期刊论文

Synthesis, insecticidal activities and DFT study of pyrimidin-4-amine derivatives containing the 1,2,4

期刊论文

Identifying stakeholders’ roles and relevant project documents for 4D-based collaborative decision making

Veronika BOLSHAKOVA, Annie GUERRIERO, Gilles HALIN

期刊论文

4Pi荧光超分辨显微术综述

郝翔, 李依明, 傅爽, 李旸晖, 许迎科, 匡翠方, 刘旭

期刊论文

对双层组件4D打印可逆性的初步研究

Amelia Yilin Lee, Jia An, Chee Kai Chu, Yi Zhang

期刊论文

Recombinant aspartate aminotransferase-catalyzed synthesis of L-4-fluorophenylalanine

CHEN Meijuan, JIA Honghua, CHEN Yongsheng, JIANG Min, WEI Ping

期刊论文