The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time. For most drugs, sufficient
in vivo
circulation time is the basis of high bioavailability. Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system, to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect. The physical and chemical properties of drug carriers, such as size, shape, surface charge and surface modification, would affect their
in vivo
circulation time, metabolic behavior and biodistribution. The final circulation time of carriers is determined by the balance between macrophage recognitions, blood vessel penetration and urine excretion. Therefore, when designing the drug delivery system, we should pay much attention to the properties of drug carriers to get enough
in vivo
circulation time to arrive at target site eventually. This article mainly reviews the effect of carrier size, size, surface charge and surface properties on its circulation time
in vivo
, and discusses the mechanism of these properties affecting circulation time. This review has reference significance for the research of long-circulation drug delivery system.
Magnetic particle imaging (MPI) is a promising medical imaging techniqueproducing quantitative images of the distribution of tracer materials (superparamagnetic nanoparticles) without interference from the anatomical background of the imaging objects (either phantoms or lab animals). Theoretically, the MPI platform can image with relatively high temporal and spatial resolution and sensitivity. In practice, the quality of the MPI images hinges on both the applied magnetic field and the properties of the tracer nanoparticles. Langevin theory can model the performance of superparamagnetic nanoparticles and predict the crucial influence of nanoparticle core size on the MPI signal. In addition, the core size distribution, anisotropy of the magnetic core and surface modification of the superparamagnetic nanoparticles also determine the spatial resolution and sensitivity of the MPI images. As a result, through rational design of superparamagnetic nanoparticles, the performance of MPI could be effectively optimized. In this review, the performance of superparamagnetic nanoparticles in MPI is investigated. Rational synthesis and modification of superparamagnetic nanoparticles are discussed and summarized. The potential medical application areas for MPI, including cardiovascular system, oncology, stem cell tracking and immune related imaging are also analyzed and forecasted.
Subunit-selective
proteasome inhibitors are valuable tools to assess
the biological and medicinal relevance of individual proteasome active
sites. Whereas the inhibitors for the β1c, β1i, β5c,
and β5i subunits exploit the differences in the substrate-binding
channels identified by X-ray crystallography, compounds selectively
targeting β2c or β2i could not yet be rationally designed
because of the high structural similarity of these two subunits. Here,
we report the development, chemical synthesis, and biological screening
of a compound library that led to the identification of the β2c-
and β2i-selective compounds LU-002c (4; IC50 β2c: 8 nM, IC50 β2i/β2c: 40-fold)
and LU-002i (5; IC50 β2i: 220 nM, IC50 β2c/β2i: 45-fold), respectively. Co-crystal
structures with β2 humanized yeast proteasomes visualize protein–ligand
interactions crucial for subunit specificity. Altogether, organic
syntheses, activity-based protein profiling, yeast mutagenesis, and
structural biology allowed us to decipher significant differences
of β2 substrate-binding channels and to complete the set of
subunit-selective proteasome inhibitors.
BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA2 activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the potential role of Lp-PLA2 as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis.MethodsWe documented 118 consecutive patients with MetS and 70 age- and sex-matched healthy subjects served as controls. The patients were further divided into two groups: 39 with carotid plaques and 79 without carotid plaques to elucidate the influence of Lp-PLA2 on carotid atherosclerosis. The plasma Lp-PLA2 activity was measured by using ELISA method and carotid intimal-media thickness (IMT) was performed by ultrasound in all participants.ResultsLp-PLA2 activity was significantly increased in MetS subgroups when compared with controls, and was higher in patients with carotid plaques than those without plaques (P < 0.05). Furthermore, we found that significant difference in Lp-PLA2 was obtained between patients with three and four disorders of metabolic syndrome (P < 0.01). Age (β = 0.183, P = 0.029), LDL-cholesterol (β = 0.401, P = 0.000) and waist-hip ratio (β = 0.410, P = 0.000) emerged as significant and independent determinants of Lp-PLA2 activity. Multiple stepwise regression analysis revealed that LDL-cholesterol (β = 0.309, P = 0.000), systolic blood pressure (β = 0.322, P = 0.002) and age (β = 0.235, P = 0.007) significantly correlated with max IMT, and Lp-PLA2 was not an independent predictor for carotid IMT.ConclusionsLp-PLA2 may be a modulating factor for carotid IMT via age and LDL-cholesterol, not independent predictor in the pathophysiological process of carotid atherosclerosis in patients with MetS.
Smart living is a trending lifestyle that envisions lower energy consumption, sound public services, and better quality of life for human being. The Internet of Things (IoT) is a compelling platform connecting various sensors around us to the Internet, providing great opportunities for the realization of smart living. Spintronic sensors with superb measuring ability and multiple unique advantages can be an important piece of cornerstone for IoT. In this review, we discuss successful applications of spintronic sensors in electrical current sensing, transmission and distribution lines monitoring, vehicle detection, and biodetection. Traditional monitoring systems with limited sensors and wired communication can merely collect fragmented data in the application domains. In this paper, the wireless spintronic sensor networks (WSSNs) will be proposed and illustrated to provide pervasive monitoring systems, which facilitate the intelligent surveillance and management over building, power grid, transport, and healthcare. The database of collected information will be of great use to the policy making in public services and city planning. This work provides insights for realizing smart living through the integration of IoT with spintronic sensor technology.
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