抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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Self-assembled monolayers of thiolates on metals as a form of nanotechnology.

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

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Microfluidics: Fluid physics at the nanoliter scale

Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

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Gold nanoparticles in chemical and biological sensing.

5.1. Detection Formats 475 5.2. Food Quality and Safety Analysis 477 5.2.1. Pathogens 477 5.2.2. Toxins 479 5.2.3. Veterinary Drugs 479 5.2.4. Vitamins 480 5.2.5. Hormones 480 5.2.6. Diagnostic Antibodies 480 5.2.7. Allergens 481 5.2.8. Proteins 481 5.2.9. Chemical Contaminants 481 5.3. Medical Diagnostics 481 5.3.1. Cancer Markers 481 5.3.2. Antibodies against Viral Pathogens 482 5.3.3. Drugs and Drug-Induced Antibodies 483 5.3.4. Hormones 483 5.3.5. Allergy Markers 483 5.3.6. Heart Attack Markers 484 5.3.7. Other Molecular Biomarkers 484 5.4. Environmental Monitoring 484 5.4.1. Pesticides 484 5.4.2. 2,4,6-Trinitrotoluene (TNT) 485 5.4.3. Aromatic Hydrocarbons 485 5.4.4. Heavy Metals 485 5.4.5. Phenols 485 5.4.6. Polychlorinated Biphenyls 487 5.4.7. Dioxins 487 5.5. Summary 488 6. Conclusions 489 7. Abbreviations 489 8. Acknowledgment 489 9. References 489

Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species

2 Objectives: Checkpoint immunotherapy treatments are showing great promise for cancer patients; however, the mechanisms and predictors of response are still largely mysteries, especially for CTLA-4-targeted treatments, which have particularly heterogeneous response patterns. Imaging of these immunotherapy targets using positron emission tomography (PET) can allow for noninvasive monitoring of their dynamic expression and biodistribution, and may allow for patient stratification in the future. Therefore, two tracers targeting human CTLA-4, one a full antibody and the other a F(ab’)2 fragment, were radiolabeled with 64Cu and validated in humanized mouse models.
 Methods: Ipilimumab was enzymatically digested to develop ipilimumab-F(ab’)2, and both the intact antibody and the fragment were conjugated with NOTA to chelate 64Cu for PET. Both tracers maintained their specificity for activated CTLA-4+ T-cells in vitro. The tracers were administered to both control NBSGW mice and humanized mice (PBL mice, which were engrafted with human peripheral blood lymphocytes), and PET was conducted out to 48 h post-injection. The onset of graft-versus-host disease in these humanized mice causes their salivary glands to dysfunction and sequestration of the foreign cells there, providing a localized site for exploration of CTLA-4+ tissue uptake. PET region-of-interest analysis, ex vivo biodistribution studies, and tissue staining were used to confirm that the tracers specifically accumulated in CTLA-4+ tissues.
 Results: Following intravenous injection of the respective tracers (n=3-5 per group), specific uptake was noted in the salivary gland tissues of the humanized mice. This uptake, as a result of graft-versus-host disease onset, was proven to be due to the presence of human T-cells through staining of the tissues for human CD3 and CTLA-4. 64Cu-NOTA-ipilimumab demonstrated the highest absolute uptake in the salivary glands of PBL mice, peaking at 7.00 ± 2.19 %ID/g, 24 h post-injection. In contrast, 64Cu-NOTA-ipilimumab-F(ab’)2 uptake was at 2.40 ± 0.86 %ID/g at the same time point. However, the F(ab’)2 agent cleared from circulation much more quickly than the intact antibody, providing higher salivary gland-to-blood ratios, which reached 1.78 ± 0.72 at 48 h post-injection, compared to 64Cu-NOTA-ipilimumab at 1.19 ± 0.49. Comparison with a nonspecific IgG, with a salivary gland-to-blood ratio of only 0.34 ± 0.08, verified the specificity of the salivary gland uptake with the targeted tracers. Uptake of the tracers in the salivary glands of control mice, and the nonspecific tracer in the PBL mice, was lower than that of the related targeted tracers at all imaging time points. Ex vivo studies verified all the trends found through PET analysis.
 Conclusions: PET imaging with both 64Cu-NOTA-ipilimumab and 64Cu-NOTA-ipilimumab-F(ab’)2 was able to localize CTLA-4+ tissues. These tracers may thus help elucidate the mechanisms of response to, and possibly toxicity from, CTLA-4-targeted checkpoint immunotherapy treatments.

Imaging CTLA-4+ T-cells in humanized mouse models

농업생명과학연구원The quality characteristics and antioxidant activity of three kinds of tofu made from lipoxygenase (LOX)-free genotypes soybeans were compared to the Taekwang (LOX-present) tofu as the control. The mineral contents of Jinyang tofu were significantly higher than those of the control. The hardness and gumminess of tofu made from LOX-free genotypes were significantly higher than those of the control. Gaechuck#2 tofu showed higher sensory evaluation results than the other kinds of tofu in terms of taste, flavor and overall acceptability. The total isoflavone contents were higher in the LOX-free genotypes than in the control. The total phenol content was similar for the Gaechuck#1, #2 and Taekwang tofu. The flavonoid content was higher in Gaechuck#1 and #2 tofu than in the control. The antioxidant activities were the highest in Gaechuck#1 tofu, followed by the Gaechuck#2. During the 15-day storage at 4, the turbidity of the immersing water tended to increase, but Gaechuck#1 and #2 tofu were significantly lower than in the control after 15-day storage. Therefore it is suggested that Gaechuck#2 tofu could be the suitable genotype for tofu products because it is the most effective in terms of overall acceptability, antioxidant activity, and storage stability. Key wordstofu, lipoxygenase-free genotypes, isoflavone, antioxidant activity

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Quality characteristics and antioxidant activity of tofu made from lipoxygenase-free genotypes

/pdf/electrochemical-biosensing-from-the-bench-to-the-real-world-3pp98wy4tj.pdf

Electrochemical Biosensing: From the Bench to the Real World

Voltammetric sandwich assays were constructed by integrating capture bioreceptors-conjugated magnetic nanocomposites, namely Fe3O4/MIL-101(Fe)-(NH)(CO)-COOH (FO/MOF) and alkaline phosphatase (ALP)-labeled detection antibodies on an eight-well screen-printed carbon ink electrode (SPCIE) for the simultaneous detection of liver cancer biomarkers, human tissue transglutaminase 2 (TGM2) and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). Magnetic FO/MOF nanocomposites were prepared via a simple microwave-assisted method; these not only provided large surface areas for covalently attaching capture bioreceptors, but also acted as a separator for the sandwich nanocomposites magnetically isolated from solutions. TGM2 and hnRNP A1 were first adsorbed onto anti-TGM2 (JU30–02)- and hnRNP A1 aptamer-FO/MOF conjugates, respectively, in buffer or serum followed by the corresponding adsorption of ALP-anti-TGM2 (2F4) and ALP-anti-hnRNP A1 to form the sandwich complexes of anti-TGM2 (JU30–02)-FO/MOF/TGM2/ALP-anti-TGM2 (2F4) and hnRNP A1 aptamer-FO/MOF/hnRNP A1/ALP-anti-hnRNP A1. After being magnetically accumulated on each well of the SPCIE surface, eight different voltammetric responses due to the reaction of ALP in the sandwich nanocomplex with 4-aminophenyl phosphate to produce 4-aminophenol and subsequently oxidize to 4-quinoneimine were concurrently measured for the quantitative analyses of both biomarkers. TGM2 and hnRNP A1 dynamic ranges in a buffer were 0.05–1.5 and 0.1–5 nM, respectively, with sensitivity of 0.331 and 0.104 μA/nM and detection and quantification limits of 6.7 and 22.3 and 19.6 and 65.3 pM, respectively. The performance was much less sensitive for undiluted serum samples, possibly due to the unavoidable matrix effect. Finally, the magneto-sandwich sensor was employed to directly analyze TGM2 and hnRNP A1 concentrations in various clinical serum samples. 

A spatially multiplexed voltammetric magneto-sandwich assay involving Fe3O4/Fe-based metal-organic framework for dual liver cancer biomarkers

The effects of dietary supplementation of Gaeddongssuk (Artemisia annua L.) powder were evaluated in terms of performance and physicochemical properties of the chicken (Woorimatdag). The chickens were divided into five treatments: group feed basal diet (Control), group added 0.25% antibiotics in the drink water (Antibiotics), and groups supplemented Gaeddongssuk powder with 5%(TA-1), 6%(TA-2) and 7%(TA-3) in the diet. Body weight was significantly higher in TA-1 and TA-2 compared to the control(p<0.05). Feed conversion rate in the TA-1 and TA-2 groups were significantly lower compared to the control(p<0.05), but TA-3 was similar to the control. Content of crude protein was significantly higher in the TA-1 and TA-2 to the control(p<0.05). The pH of breast meat was significantly higher in the TA-2(p<0.05), and

Hye Jin Lee

Papers

Imaging CTLA-4+ T-cells in humanized mouse models

Quality characteristics and antioxidant activity of tofu made from lipoxygenase-free genotypes

Electrochemical Biosensing: From the Bench to the Real World

A spatially multiplexed voltammetric magneto-sandwich assay involving Fe3O4/Fe-based metal-organic framework for dual liver cancer biomarkers

Effect of Dietary Supplementation of Gaeddongssuk (Artemisia annua L.) on the Meat Quality in the Chicken (Woorimatdag)