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Molecular mechanisms of leukemia-associated protein degradation

Ying-Li WU, Guo-Qiang CHEN, Hu-Chen ZHOU,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 363-370 doi: 10.1007/s11684-010-0210-7

摘要： Chemical biology, using small molecules as probes to study the cellular signaling network, has developed rapidly in recent years. The interaction between chemistry and biology not only provides new insight into the understanding of cellular activities, but also generates new lead compounds for the treatment of diseases. Transcription factors and kinases such as retinoic acid receptor-alpha (RARα), acute myeloid leukemia 1 (AML1), CAAT/enhancer-binding protein α (C/EBPα), c-myc, and c-abl play important roles in the differentiation of hematopoietic stem/progenitor cells. Abnormalities in these proteins may cause the dysregulation of hematopoiesis and even the occurrence of leukemia. Ubiquitin-mediated protein degradation represents a critical mechanism in regulating the cellular levels and functions of these proteins. Thus, targeting protein degradation has been emerging as an important strategy to conquer malignant diseases. In this review, we will summarize the recent advances in the understanding of the roles of protein degradation in leukemia, with an emphasis on the mechanisms revealed by small molecules.

关键词： protein degradation     leukemia     chemical biology     transcription factors     oncoprotein    

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Regulation of NLR stability in plant immunity

Tao WANG, Jiaxin LI, Qian-Hua SHEN

《农业科学与工程前沿（英文）》 2019年 第6卷 第2期   页码 97-104 doi: 10.15302/J-FASE-2018248

摘要：

Plant nucleotide binding domain and leucine-rich repeat (NLR) receptors recognize pathogen effectors directly or indirectly and mediate innate immune responses. NLR-mediated immunity also has direct impacts on plant growth and development, as well as yield and survival. The levels of NLR proteins are therefore intricately controlled in plants to balance defense responses and other processes. In recent years, the ubiquitination-26S proteasome system and the HSP90 chaperones have emerged as having key functions in the regulation of NLR stability. The N-end rule pathway of protein degradation is also directly linked to NLR stability. Recent progress in the regulation of NLR stability and turnover is summarized here, focusing on the key components and pathways.

关键词： E3 ubiquitin ligase     degradation     nucleotide-binding leucine-rich repeat receptor     plant immunity     proteasome     protein stability     ubiquitination    

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通过蛋白质工程提高聚酯水解酶对PET 塑料的降解效率 Article

马渊, 姚明东, 李炳志, 丁明珠, 何博, 陈思, 周晓, 元英进

《工程（英文）》 2018年 第4卷 第6期   页码 888-893 doi: 10.1016/j.eng.2018.09.007

摘要：

来自Ideonella sakaiensis 的聚对苯二甲酸乙二醇酯水解酶（PETase）在室温下具有很强的降解聚对苯二甲酸乙二醇酯（PET）的能力，因此被认为是解决聚酯塑料污染问题的潜在工具。在本研究中，基于PETase 和底物2PET 结合时的相互作用模型，分析了PETase 与底物2PET 之间的相互作用，从而对底物结合沟壑周围的六个关键残基进行改造。为了更加快速地筛选突变体酶的活性，本研究利用无细胞蛋白表达体系对设计的PETase 突变体进行高通量的表达和验证。最终发现三种突变体（R61A、L88F 和I179F）的酶活性相比野生型分别提高了1.4 倍、2.1 倍和2.5 倍。其中，I179F突变体的酶活性最高，降解效率为22.5 mg·μmol–1·d–1。因此，本研究通过蛋白质工程对PETase 的关键疏水位点进行设计和改造，获得了降解效果提高的酶突变体，并进一步证实了其生物降解塑料的潜力。

关键词： 聚酯酶     PET降解     无细胞蛋白质合成     聚酯     PET酶    

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mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

《医学前沿（英文）》 2021年 第15卷 第2期   页码 221-231 doi: 10.1007/s11684-020-0812-7

摘要： The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.

关键词： mTOR     cancer therapy     resistance     GSK3     protein degradation     E3 ubiquitin ligase     PD-L1    

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Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

《农业科学与工程前沿（英文）》 2016年 第3卷 第2期   页码 102-112 doi: 10.15302/J-FASE-2016100

摘要： Plants are frequently affected by pathogen infections. To effectively defend against such infections, two major modes of innate immunity have evolved in plants; pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. Although the molecular components as well as the corresponding pathways involved in these two processes have been identified, many aspects of the molecular mechanisms of the plant immune system remain elusive. Recently, the rapid development of omics techniques (e.g., genomics, proteomics and transcriptomics) has provided a great opportunity to explore plant–pathogen interactions from a systems perspective and studies on protein–protein interactions (PPIs) between plants and pathogens have been carried out and characterized at the network level. In this review, we introduce experimental and computational identification methods of PPIs, popular PPI network analysis approaches, and existing bioinformatics resources/tools related to PPIs. Then, we focus on reviewing the progress in genome-wide PPI networks related to plant–pathogen interactions, including pathogen-centric PPI networks, plant-centric PPI networks and interspecies PPI networks between plants and pathogens. We anticipate genome-wide PPI network analysis will provide a clearer understanding of plant–pathogen interactions and will offer some new opportunities for crop protection and improvement.

关键词： plant–pathogen interactions     systems biology     omics     plant immunity     protein–protein interaction     network    

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Influence of construction-induced damage on the degradation of freeze–thawed lightweight cellular concrete

《结构与土木工程前沿（英文）》 2021年 第15卷 第3期   页码 781-792 doi: 10.1007/s11709-021-0733-9

摘要： During the construction of lightweight cellular concrete (LCC), material damage frequently occurs, causing the degradation and deterioration of the mechanical performance, durability, and subgrade quality of LCC. The construction-induced damage can be more significant than those from the service environment of LCC, such as freeze–thaw (F–T) action in cold regions. However, the effect of construction-induced damage on LCC during F–T cycles is often ignored and the deterioration mechanisms are not yet clarified. In this study, we investigated the factors causing damage during construction using a sample preparation method established to simulate the damage in the laboratory setting. We conducted F–T cycle tests and microstructural characterization to study the effect of microstructural damage on the overall strength of LCC with different water contents under F–T actions. We established the relationship between the pore-area ratio and F–T cycle times, pore-area ratio, and strength, as well as the F–T cycle times and strength under different damage forms. The damage evolution is provided with the rationality of the damage equation, verified by comparing the measured and predicted damage variables. This study would serve as a guide for the construction and performance of LCC in cold regions.

关键词： lightweight cellular concrete     construction-induced damage     freeze-thaw action     microstructure     degradation mechanism    

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Efficient degradation of orange II by ZnMn

Qingzhuo Ni, Hao Cheng, Jianfeng Ma, Yong Kong, Sridhar Komarneni

《化学科学与工程前沿（英文）》 2020年 第14卷 第6期   页码 956-966 doi: 10.1007/s11705-019-1907-z

摘要： A ZnMn O catalyst has been synthesized via a sucrose-aided combustion method and characterized by various analytical techniques. It is composed of numerous nanoparticles (15–110 nm) assembled into a porous structure with a specific surface area (SSA) of 19.1 m ·g . Its catalytic activity has been investigated for the degradation of orange II dye using three different systems, i.e., the photocatalysis system with visible light, the chemocatalysis system with bisulfite, and the photo-chemical catalysis system with both visible light and bisulfite. The last system exhibits the maximum degradation efficiency of 90%, much higher than the photocatalysis system (15%) and the chemocatalysis system (67%). The recycling experiments indicate that the ZnMn O catalyst has high stability and reusability and is thus a green and eximious catalyst. Furthermore, the potential degradation mechanisms applicable to the three systems are discussed with relevant theoretical analysis and scavenging experiments for radicals. The active species such as Mn(III), O , h , e , SO and HO are proposed to be responsible for the excellent degradation results in the photo-chemical catalysis system with the ZnMn O catalyst.

关键词： ZnMn2O4     photo-chemical catalysis     bisulfite     dye degradation    

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The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 70-76 doi: 10.1007/s11684-011-0119-9

摘要：

Protein kinase C epsilon (PKC ?) is one of major isoforms in novel PKC family. Although it has been extensively characterized in the past decade, the role of PKC ? in neuron is still not well understood. Advances in molecular biology have now removed significant barriers to the direct investigation of PKC ? functions in vivo, and PKC ? has been increasingly implicated in the neural biological functions and associated neurogenic diseases. Recent studies have provided important insights into the influence of PKC ? on cortical processing at both the single cell level and network level. These studies provide compelling evidence that PKC ? could regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKC ? signal pathway in the developing brain.

关键词： protein kinase C ?     signal transduction     neurogenic disease    

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Wheat gluten protein and its impacts on wheat processing quality

Wujun MA, Zitong YU, Maoyun SHE, Yun ZHAO, Shahidul ISLAM

《农业科学与工程前沿（英文）》 2019年 第6卷 第3期   页码 279-287 doi: 10.15302/J-FASE-2019267

摘要：

Before the advent of the wheat genomic era, a wide range of studies were conducted to understand the chemistry and functions of the wheat storage proteins, which are the major determinants of wheat flour the suitability of wheat flour for various end products, such as bread, noodles and cakes. Wheat grain protein is divided into gluten and non-gluten fractions and the wheat processing quality mainly depends on the gluten fractions. Gluten provides the unique extensibility and elasticity of dough that are essential for various wheat end products. Disulfide bonds are formed between cysteine residues, which is the chemical bases for the physical properties of dough. Based on the SDS-extractability, grain protein is divided into SDS-unextractable polymeric protein (UPP) and SDS-extractable polymeric protein. The percentage of UPP is positively related to the formation of disulfide bonds in the dough matrix. In the wheat genomic era, new glutenins with long repetitive central domains that contain a high number of consensus hexapeptide and nonapeptide motifs as well as high content of cysteine and glutamine residues should be targeted.

关键词： wheat gluten     consensus motifs     disulfide bonds     SDS-unextractable polymeric protein     glutenins     gliadins     processing quality     storage protein    

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Promotive effect of pyridine on indole degradation by activated sludge under anoxic conditions

LI Yongmei, GU Guowei, LI Wenshu

《环境科学与工程前沿（英文）》 2007年 第1卷 第4期   页码 493-497 doi: 10.1007/s11783-007-0079-0

摘要： Batch experiments were carried out to investigate the promotive effect of pyridine on indole degradation under denitrifying conditions. The seed sludge was obtained from a local coal-coking wastewater treatment facility and was acc

关键词： wastewater treatment     coal-coking wastewater     promotive     degradation    

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Construction of sustainable, colored and multifunctional protein silk fabric using biomass riboflavin

《化学科学与工程前沿（英文）》 2023年 第17卷 第8期   页码 1131-1139 doi: 10.1007/s11705-023-2321-0

摘要： Riboflavin sodium phosphate has been confirmed as a promising biomass product derived from natural plants. In this paper, a novel method of dyeing and multifunctional modification of silk fabric by impregnation with riboflavin sodium phosphate was proposed, such that protein silk fabric can be endowed with bright yellow color and multi-functionality. The results of this paper confirmed that the pH and concentration of riboflavin sodium phosphate solution are critical factors for dyeing and multifunctional modification. Attractively, the photochromic performance was one of the most distinctive features of the modified silk fabric, and the dyed silk fabric turned into fluorescent green from original yellow under 365 nm ultraviolet lamp. Furthermore, the modified silk fabric exhibited good antibacterial properties with a high inhibition rate of 92% for Escherichia coli. Besides, the flame retardancy of silk fabric was significantly improved after modification. The damaged length of modified silk fabric with 40% owf riboflavin sodium phosphate was lower than 10.4 cm and passed the B1 classification. As revealed by the result of this paper, riboflavin sodium phosphate is sufficiently effective in serving as an eco-friendly multifunctional agent for strengthening the add-value of silk textiles.

关键词： biomass     riboflavin sodium phosphate     silk protein     multifunctional modification     flame retardant    

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anchored alginate/poly(acrylic acid/acrylamide) double-network hydrogel composites for efficient catalytic degradation

《化学科学与工程前沿（英文）》 2023年 第17卷 第7期   页码 893-905 doi: 10.1007/s11705-022-2290-8

摘要： A novel alginate/poly(acrylic acid/acrylamide) double-network hydrogel composite with silver nanoparticles was successfully fabricated using the sol–gel method. The presence of carboxyl and amide groups in the network structure provided abundant active sites for complexing silver ions, facilitating the in situ reduction and confinement of silver nanoparticles. In batch experiments, the optimal silver loading was 20%, and 5 mmol·L–1 of p-nitrophenol was completely degraded in 113 s with a rate constant value of 4.057 × 10−2 s–1. In the tap water system and simulated seawater system, the degradation time of p-nitrophenol at the same concentration was 261 and 276 s, respectively, with a conversion rate above 99%. In the fixed-bed experiment, the conversion rate remained above 74% after 3 h at a flowing rate of 7 mL·min–1. After 8 cycling tests, the conversion rate remained at 98.7%. Moreover, the catalyst exhibited outstanding performance in the degradation experiment of four typical organic dyes.

关键词： double-network hydrogel     dye degradation     silver nanoparticles     alginate    

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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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Sustainable wood-based nanotechnologies for photocatalytic degradation of organic contaminants in aquatic

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1346-6

摘要：

•Wood and its reassemblies are ideal substrates to develop novel photocatalysts.

关键词： Wood     Nanocatalysts     Photodegradation     Organic contaminants     Composites    

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标题 作者 时间 类型 操作

Molecular mechanisms of leukemia-associated protein degradation

Ying-Li WU, Guo-Qiang CHEN, Hu-Chen ZHOU,

期刊论文

Regulation of NLR stability in plant immunity

Tao WANG, Jiaxin LI, Qian-Hua SHEN

期刊论文

饶燏：小分子靶向蛋白降解技术及应用（2022年12月15日）

2022年12月22日

会议视频

通过蛋白质工程提高聚酯水解酶对PET 塑料的降解效率

马渊, 姚明东, 李炳志, 丁明珠, 何博, 陈思, 周晓, 元英进

期刊论文

mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

期刊论文

Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction

Hong LI,Ziding ZHANG

期刊论文

Influence of construction-induced damage on the degradation of freeze–thawed lightweight cellular concrete

期刊论文

Efficient degradation of orange II by ZnMn

Qingzhuo Ni, Hao Cheng, Jianfeng Ma, Yong Kong, Sridhar Komarneni

期刊论文

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

null

期刊论文

Wheat gluten protein and its impacts on wheat processing quality

Wujun MA, Zitong YU, Maoyun SHE, Yun ZHAO, Shahidul ISLAM

期刊论文

Promotive effect of pyridine on indole degradation by activated sludge under anoxic conditions

LI Yongmei, GU Guowei, LI Wenshu

期刊论文

Construction of sustainable, colored and multifunctional protein silk fabric using biomass riboflavin

期刊论文

anchored alginate/poly(acrylic acid/acrylamide) double-network hydrogel composites for efficient catalytic degradation

期刊论文

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

null

期刊论文

Sustainable wood-based nanotechnologies for photocatalytic degradation of organic contaminants in aquatic

期刊论文