48 research outputs found

    Application of stimuli-responsive nanomedicines for the treatment of ischemic stroke

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    Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply to the carotid artery or vertebrobasilar artery system. As the second leading cause of death in the world, IS has a high incidence and brings a heavy economic burden to all countries and regions because of its high disability rate. In order to effectively treat IS, a large number of drugs have been designed and developed. However, most drugs with good therapeutic effects confirmed in preclinical experiments have not been successfully applied to clinical treatment due to the low accumulation efficiency of drugs in IS areas after systematic administration. As an emerging strategy for the treatment of IS, stimuli-responsive nanomedicines have made great progress by precisely delivering drugs to the local site of IS. By response to the specific signals, stimuli-responsive nanomedicines change their particle size, shape, surface charge or structural integrity, which enables the enhanced drug delivery and controlled drug release within the IS tissue. This breakthrough approach not only enhances therapeutic efficiency but also mitigates the side effects commonly associated with thrombolytic and neuroprotective drugs. This review aims to comprehensively summarize the recent progress of stimuli-responsive nanomedicines for the treatment of IS. Furthermore, prospect is provided to look forward for the better development of this field

    Spatial distribution and controlling factors of sediment nitrogen forms in the mangrove wetland at Dongzhai Port, Hainan Province

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    The occurence of nitrogen in sediments directly affects the process, pathway and contribution of nitrogen in the nature, therefore exploring the environmental geochemical behavior of different nitrogen speciation in sediments is of great significance for studying nitrogen geochemical cycle. In this study, the surface sediment and sediment core were collected in the mangrove wetland at Dongzhai Port, Hainan Province.The different forms of transferable nitrogen were analyzed via hierarchical extraction.The spatial distribution characteristics and influencing factors were investigated. The results showed that the contents of total nitrogen (TN) and total transferable nitrogen (TTN) in the sediments ranged from 1 149.2 to 1 690.6 mg/kg and from 464.6 to 647.5 mg/kg, respectively, both of which presented a decreasing trend from the upstream to the estuary. The strong oxidant extracted nitrogen (SOEF-N) is the major nitrogen species in TTN, and positively correlated with TTN contents. According to C/N ratio, the organic matter in the study area is mainly from the discharge of a large number of pollutants.The significant positive correlation between TN, water content and TOC in the mangrove columnar sediments in Dongzhai Port, indicates that nitrogen and organic matter have similar sources

    New development of non-rigid registration

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    We propose a new nonrigid registration algorithm which is based on the optimal control approach. In our previously proposed methods, the Jacobian determinant and the curl vector were used as control functions. In this algorithm, we use a new set of control functions. A main advantage of using the new controls is that the positivity and normalization of the Jacobian determinant are satisfied automatically. Numerical results on large deformation brain images are provided to show the accuracy and efficiency of the algorithm. doi:10.1017/S144618111400009

    Improving the anti-toxin abilities of the CMG2-Fc fusion protein with the aid of computational design.

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    CMG2-Fc is a fusion protein composed of the extracellular domain of capillary morphogenesis protein 2 (CMG2) and the Fc region of human immunoglobulin G; CMG2-Fc neutralizes anthrax toxin and offers protection against Bacillus anthracis challenge. To enhance the efficacy of CMG2-Fc against anthrax toxin, we attempted to engineer a CMG2-Fc with an improved affinity for PA. Using the automatic design algorithm FoldX and visual inspection, we devised two CMG2-Fc variants that introduce mutations in the CMG2 binding interface and improve the computationally assessed binding affinity for PA. An experimental affinity assay revealed that the two variants showed increased binding affinity, and in vitro and in vivo toxin neutralization testing indicated that one of these mutants (CMG2-Fc(E117Q)) has superior activity against anthrax toxin and was suitable for further development as a therapeutic agent for anthrax infections. This study shows that the computational design of the PA binding interface of CMG2 to obtain CMG2-Fc variants with improving anti-toxin abilities is viable. Our results demonstrate that computational design can be further applied to generate other CMG2-Fc mutants with greatly improved therapeutic efficacy
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