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Interspecies transmission and evolution of the emerging coronaviruses: perspectives from bat physiology and protein

Baicheng HUANG, Kegong TIAN

《农业科学与工程前沿（英文）》 2020年第7卷第2期页码 218-226 doi: 10.15302/J-FASE-2020324

摘要：

Emergent coronaviruses (CoVs) such as SARS-CoV and MERS-CoV have posed great threats to public health worldwide over the past two decades. Currently, the emergence of SARS-CoV-2 as a pandemic causes greater public health concern. CoV diversity is due to the large size and replication mechanisms of the genomes together with having bats as their optimum natural hosts. The ecological behavior and unique immune characteristics of bats are optimal for the homologous recombination of CoVs. The relationship of spatial structural characteristics of the spike protein, a protein that is critical for recognition by host receptors, in different CoVs may provide evidence in explaining the coevolution of CoVs and their hosts. This information may help to enhance our understanding of CoV evolution and thus provide part of the basis of preparations for any future outbreaks.

关键词： bat coronavirus evolution host receptor spike protein transmission

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Molecular aspects of MERS-CoV

null

《医学前沿（英文）》 2017年第11卷第3期页码 365-377 doi: 10.1007/s11684-017-0521-z

摘要：

Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoV ancestors may be found in Old World bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

关键词： MERS-CoV Saudi Arabia spike protein transmission evolution vaccine

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中东呼吸综合征病毒（MERS-CoV）蛋白的分子特征、功能及其致病性 Review

李艳华, 胡晨雨, 吴南屏, 姚航平, 李兰娟

《工程（英文）》 2019年第5卷第5期页码 940-947 doi: 10.1016/j.eng.2018.11.035

摘要：

中东呼吸综合征（MERS）是由一种新型冠状病毒——中东呼吸综合征冠状病毒（MERS-CoV）引起的病毒性呼吸道疾病，病死率高。然而，MERS-CoV感染人类的机制仍不清楚。除了完整人免疫球蛋白G（IgG）多克隆抗体（SAB-301）的安全性和耐受性得到一定的验证之外，目前尚无其他针对MERS-CoV的有效的预防性疫苗或抗体特效治疗手段。尽管目前正在研究病毒的快速诊断技术并加强公共卫生的管理，但感染MERS-CoV的病例仍在不断出现。因此，需要实施各种有效措施防止疫情恶化。进一步研究病毒的流行病学特征和发病机制，以及开发有效的抗MERS-CoV感染的治疗和预防性药物是十分必要的。为此，我们需要明确MERS-CoV各种蛋白的详细信息。在文中论述了MERS-CoV的主要结构蛋白和非结构蛋白，并总结了抑制MERS-CoV感染的各种潜在的策略。计算生物学和病毒学的结合可以促进抗MERS-CoV的有效肽治疗剂的设计和开发。总之，本文提供了遏制MERS进展（从预防到治疗）的重要信息。

关键词： MERS-CoV 刺突蛋白结构蛋白辅助蛋白非结构蛋白

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新型冠状病毒HCoV-19 S蛋白与人ACE2蛋白表面糖链和独特翻译后修饰的质谱分析 Article

孙泽宇, 任科燚, 张兴, 陈景华, 姜正一, 江静, 季飞洋, 欧阳晓希, 李兰娟

《工程（英文）》 2021年第7卷第10期页码 1441-1451 doi: 10.1016/j.eng.2020.07.014

摘要：

当下新型冠状病毒肺炎（COVID-19）的国际大流行促使全球科学家努力尝试揭秘新冠病毒HCoV-19的生物学特性。质谱分析（MS）发现，在HCoV-19 S蛋白的21个潜在糖基化修饰位点中，有20个位点完全被N-糖链占据，其糖型以低聚甘露糖为主。人血管紧张素转换酶2（hACE2）的7个糖基化位点完全被复合型N-糖链占据。然而，糖基化修饰并不能直接影响HCoV-19 S蛋白与hACE2之间的结合亲和力。另外，我们还发现了S蛋白和hACE2的多个甲基化修饰位点，以及hACE2的多个羟脯氨酸修饰位点。通过在最近发表的冷冻电镜（cryo-EM）结构的基础上加入N-糖链和蛋白质翻译后修饰（PTM），我们构建了HCoV-19 S蛋白和hACE2的精细结构模型。本研究揭示的HCoV-19 S蛋白和hACE2的PTM及糖基化图谱为研究病毒的宿主黏附、免疫反应，以及相关药物和疫苗的研发提供了更多的蛋白质结构细节。

关键词： N-糖基化 COVID-19 棘突蛋白 hACE2 蛋白结构

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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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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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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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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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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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Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing

《医学前沿（英文）》 2022年第16卷第6期页码 919-931 doi: 10.1007/s11684-021-0918-6

摘要： Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

关键词： preeclampsia recombinant protein diannexin microparticle NLRP3 inflammasome phosphatidylserin

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Investigation of hydrolysis conditions and properties on protein hydrolysates from flatfish skin

Hua ZHANG, Hongji ZHU, Shipeng WANG, Weihua WANG

《化学科学与工程前沿（英文）》 2013年第7卷第3期页码 303-311 doi: 10.1007/s11705-013-1341-6

摘要： Response surface method (RSM), based on Box-Behnken design, was used to optimize the enzymatic hydrolysis conditions of flatfish skin protein hydrolysates (FSPH). Among the tested proteases, the combination of nutrase and trypsin was selected. The optimal hydrolysis conditions were as follows: pH 7.3, temperature 51.8°C, and the enzyme/substrate (E/S) ratio 2.5; under these conditions, the maximum peptide yield (PY) was 69.41±0.43%. The physiochemical analysis showed that the amino acids (His, Asp and Glu) of FSPH accounted for 18.15%, and FSPH was a mixture of polypeptides mostly distributed among 900–2000 Da. FSPH could exhibit a 93% chelating effect on ferrous ion at a concentration of 400 μg/mL, and also a notable reducing power. This study showed bioprocess for the production of FSPH for the first time, which had a good potential for valuable ingredients in the food, cosmetic and medicine industries.

关键词： flatfish skin protein hydrolysates metal chelating activity reducing power

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Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity

Liang ZHUANG, Shiying YU, Xiaoyuan HUANG, Yang CAO, Huihua XIONG

《医学前沿（英文）》 2009年第3卷第1期页码 26-29 doi: 10.1007/s11684-009-0008-7

摘要： DNA double-strand break (DSB) is generally regarded as the most lethal of all DNA lesions after radiation. Ku80, DNA-PK catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) proteins are major DSB repair proteins. In this study, survival fraction at 2Gy (SF2) values of eight human tumor cell lines (including four human cervical carcinoma cell lines HeLa, SiHa, C33A, Caski, three human breast carcinoma cell lines MCF-7, MDA-MB-231, MDA-MB-453, and one human lung carcinoma cell line A549) were acquired by clone formation assay, and western blot was applied to detect the expressions of Ku80, DNA-PKcs and ATM protein. The correlativity of protein expression with SF2 value was analyzed by Pearson linear correlation analysis. We found that the expression of same protein in different cell lines and the expression of three proteins in the same cell line had a significant difference. The SF2 values were also different in eight tumor cell lines and there was a positive correlativity between the expression of DNA-PKcs and SF2 ( ＝0.723, = 0.043), but Ku80 and ATM expression had no correlation with SF2 ( >0.05). These findings suggest that the expression level of DNA-PKcs protein can be an indicator for predicting the radiosensitivity of tumor cells.

关键词： Ku80 DNA-PK(cs)-binding protein human ataxia telangiectasia mutated protein tumor cell lines radiosensitivity

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Protein phosphatase 2A, a key player in Alzheimer’s disease

Rong LIU, Qing TIAN

《医学前沿（英文）》 2009年第3卷第1期页码 8-12 doi: 10.1007/s11684-009-0017-6

摘要： Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer’s disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neurofibrillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation underlie PP2A inactivation in AD. β-amyloid (Aβ) over-production, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer’s disease.

关键词： protein phosphatase 2A Alzheimer’s disease holoenzyme composition protein phosphatase 2A inhibitors Leu309 demethylation Tyr307 phosphorylation

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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