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Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 147-156 doi: 10.1007/s11684-010-0030-9

摘要： The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in sci

关键词： influenza A virus     H1N1 subtype     pandemic     pathogenesis     virulence factors     immunity     management     antiviral    

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从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用 Article

Ram Prasad Aganja, Amal Senevirathne, Chandran Sivasankar, John Hwa Lee

《工程（英文）》 2024年 第32卷 第1期   页码 42-57 doi: 10.1016/j.eng.2023.08.001

摘要：

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RdRp-dependent eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4+ and CD8+ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4+ and CD8+ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA     Influenza A     Salmonella     Vaccine     Broad spectral protection    

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Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

Jiao HU,Xiufan LIU

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 11-24 doi: 10.15302/J-FASE-2016092

摘要： The H9N2 and H5N1 avian influenza viruses (AIVs) have been circulating in poultry in China and become endemic since 1998 and 2004, respectively. Currently, they are prevalent in poultry throughout China. This endemicity makes them actively involved in the emergence of the novel lineages of other subtypes of influenza viruses, such as the well-known viruses of the highly pathogenic avian influenza (HPAI) H5N2 and the 2013 novel H7N7, H7N9 and H10N8 subtypes, thereby threatening both the poultry industry and public health. Here, we will review briefly the prevalence and evolution, pathogenicity, transmission, and disease control of these two subtypes and also discuss the possibility of emergence of potentially virulent and highly transmissible AIVs to humans.

关键词： avian influenza virus     H9N2     H5N1     novel viruses     public health    

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Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7subtype viruses?

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要：

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词： universal influenza virus vaccine     hemagglutinin stalk     H7N9    

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A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 103-111 doi: 10.1007/s11705-021-2064-8

摘要： Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are enzymes involved in the biotransformation of important endogenous compounds such as steroids, bile acids, and hormones as well as exogenous substances including drugs, environmental toxicants, and carcinogens. Here, a novel fluorescent probe BDMP was developed based on boron-dipyrromethene (BODIPY) with high sensitivity for the detection of UGT1A8. The glucuronidation of BDMP not only exhibited a red-emission wavelength (λex/λem = 500/580 nm), but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration. Based on this perfect biocompatibility and cell permeability, BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines (LoVo and HCT15) in real time. In addition, BDMP could also be used to visualize UGT1A8 in tumor tissues. These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.

关键词： UDP-glucuronosyltransferase 1A8     fluorescent probe     subtype selectivity     fluorescence imaging    

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Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

《化学科学与工程前沿（英文）》 2023年 第17卷 第2期   页码 123-138 doi: 10.1007/s11705-022-2194-7

摘要： The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many tissues. NAD(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most cancers. Therefore, it could be a target for cancer therapy. Because it is a quinone reductase, many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose tumours. Its expression is higher in tumours than in normal tissues, and using target drugs such as β-lapachone to reduce side effects in normal tissues can help. However, the physicochemical properties of β-lapachone limit its application. The problem can be solved by using nanosystems to deliver β-lapachone. This mini-review summarizes quinone-based fluorescent, near-infrared and two-photon fluorescent probes, as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drug β-lapachone. This review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

关键词： NAD(P)H:quinone oxidoreductase 1     cancer therapy     target     probe     nanosystem    

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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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Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要：

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词： molecular classification     precision medicine     pembrolizumab     PD-1/PD-L1     MSI-H    

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Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 305-309 doi: 10.1007/s11705-009-0021-z

摘要： A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound , , , , , , and were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B in VERO cells.

关键词： benzimidazole     coxsackie virus B3     antiviral properties    

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Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

《化学科学与工程前沿（英文）》 2020年 第14卷 第1期   页码 97-104 doi: 10.1007/s11705-019-1828-x

摘要： Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

关键词： NIR-fluorophores     live cell imaging     NIR-AZA    

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Histone variants: critical determinants in tumour heterogeneity

Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin

《医学前沿（英文）》 2019年 第13卷 第3期   页码 289-297 doi: 10.1007/s11684-018-0667-3

摘要： Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

关键词： cancer-testis     TH2B     TH2A     H1T     H1.0     H1F0     linker histones    

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

《工程（英文）》 2024年 第32卷 第1期   页码 58-69 doi: 10.1016/j.eng.2023.09.019

摘要：

Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9)     Epigenetics     Hepatocyte nuclear factor 1 alpha (HNF1A)     Hepatocyte nuclear factor 4 alpha (HNF4A)     Forkhead box protein A2 (FOXA2)     N-glycosylation     HepG2 cells    

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A 7-year follow-up study of the features and transformations of elderly male patients with OGTT-1h hyperglycemia

TIAN Hui, LI Chunlin, ZHONG Wenwen, PAN Changyu, LU Juming, CAO Xiutang

《医学前沿（英文）》 2008年 第2卷 第4期   页码 396-399 doi: 10.1007/s11684-008-0076-0

摘要： The aim of this paper is to investigate the clinical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia (≥ 11.1 mmol/L) 1 hour after oral glucose tolerance test (OGTT-1h HG). Seven years of follow-up visits were performed on 189 elderly male outpatients with OGTT-1h HG and data was recorded on their body mass index (BMI), blood pressure, serum cholesterol and triglyceride test results and on their glucose tolerance changes every 1–2 years after taking OGTT; their possible causes were analysed. Follow-up visits revealed that 19 patients with OGTT-1h HG were diagnosed with diabetes (10.1%), 78 patients with impaired glucose tolerance (IGT, 41.3%), 2 patients transformed to normal glucose tolerance (NGT, 1.1%) and the remaining 90 patients (47.6%) remained unchanged. Synchronized comparison with IGT patients showed that the ratio of OGTT-1h HG patients turning to diabetes was lower than that of IGT patients (21.1%, = 13.05, < 0.01), and the ratio of OGTT-1h HG patients transforming to NGT was slightly higher (0.4%, = 2.46, > 0.05). The prevalence of complications of hypertension, coronary heart disease, cerebral vascular diseases and dyslipidemia in patients with OGTT-1h HG were higher than those with NGT ( < 0.05) and were similar to that of IGT patients. As a special phenotype of OGTT and as part of an abnormal glucose tolerance conformation, patients with OGTT-1h HG warrant special attention, since about half of them were found to have developed diabetes or IGT, and their risk of suffering from vascular diseases were also increased.

关键词： special attention     prevalence     unchanged     dyslipidemia     elderly    

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适用于低轨微小卫星的大视场红外地球敏感器

王昊1,王志远1,王本冬1,金仲和1,John L. CRASSIDIS2

《信息与电子工程前沿（英文）》 2021年 第22卷 第2期   页码 141-286 doi: 10.1631/FITEE.1900358

摘要： 红外地球敏感器广泛应用于卫星姿态确定和控制系统中。静态红外地球敏感器的主要缺点是视场较小，其典型视场约为20°至30°，可能不适用于近地轨道的微型卫星。设计了一种新型的小型红外地球敏感器，其视场接近180°。该地球敏感器包括全景环形透镜（PAL）和红外CMOS传感器。PAL镜头用于增强视场，从而从近地轨道获得完整的地球红外图像，据此提出一种补偿PAL引起的畸变和计算地球矢量的算法。新型红外地球敏感器结构紧凑，功耗低，精度高。利用ZDPS-2微小卫星获得在轨红外图像和模拟图像，评估新型红外地球敏感器的性能，实验表明其精度约为0.032°。

关键词： 红外地球敏感器；微小卫星；姿态确定系统    

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Nonlinear dynamic analysis for elastic robotic arms

H. KORAYEM, H. N. RAHIMI

《机械工程前沿（英文）》 2011年 第6卷 第2期   页码 219-228 doi: 10.1007/s11465-011-0218-y

摘要：

The aim of the paper is to analyze the nonlinear dynamics of robotic arms with elastic links and joints. The main contribution of the paper is the comparative assessment of assumed modes and finite element methods as more convenient approaches for computing the nonlinear dynamic of robotic systems. Numerical simulations comprising both methods are carried out and results are discussed. Hence, advantages and disadvantages of each method are illustrated. Then, adding the joint flexibility to the system is dealt with and the obtained model is demonstrated. Finally, a brief description of the optimal motion generation is presented and the simulation is carried out to investigate the role of robot dynamic modeling in the control of robots.

关键词： robotic arms     elastic link     elastic joint     nonlinear dynamics     optimal control    

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标题 作者 时间 类型 操作

Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

期刊论文

从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用

Ram Prasad Aganja, Amal Senevirathne, Chandran Sivasankar, John Hwa Lee

期刊论文

Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

Jiao HU,Xiufan LIU

期刊论文

Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7subtype viruses?

null

期刊论文

A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living

期刊论文

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

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

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

期刊论文

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

期刊论文

Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

期刊论文

Histone variants: critical determinants in tumour heterogeneity

Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin

期刊论文

转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

期刊论文

A 7-year follow-up study of the features and transformations of elderly male patients with OGTT-1h hyperglycemia

TIAN Hui, LI Chunlin, ZHONG Wenwen, PAN Changyu, LU Juming, CAO Xiutang

期刊论文

适用于低轨微小卫星的大视场红外地球敏感器

王昊1,王志远1,王本冬1,金仲和1,John L. CRASSIDIS2

期刊论文

Nonlinear dynamic analysis for elastic robotic arms

H. KORAYEM, H. N. RAHIMI

期刊论文