Progressive supranuclear palsy (PSP) is a rare movement disorder and often difficult to distinguish clinically from Parkinson's disease (PD) and multiple system atrophy (MSA) in early phases. In this study, we report reproducible disease-related topographies of brain network and regional glucose metabolism associated with PSP in clinically-confirmed independent cohorts of PSP, MSA, and PD patients and healthy controls in the USA and China. Using F-FDG PET images from PSP and healthy subjects, we applied spatial covariance analysis with bootstrapping to identify a PSP-related pattern (PSPRP) and estimate its reliability, and evaluated the ability of network scores for differential diagnosis. We also detected regional metabolic differences using statistical parametric mapping analysis. We produced a highly reliable PSPRP characterized by relative metabolic decreases in the middle prefrontal cortex/cingulate, ventrolateral prefrontal cortex, striatum, thalamus and midbrain, covarying with relative metabolic increases in the hippocampus, insula and parieto-temporal regions. PSPRP network scores correlated positively with PSP duration and accurately discriminated between healthy, PSP, MSA and PD groups in two separate cohorts of parkinsonian patients at both early and advanced stages. Moreover, PSP patients shared many overlapping areas with abnormal metabolism in the same cortical and subcortical regions as in the PSPRP. With rigorous cross-validation, this study demonstrated highly comparable and reproducible PSP-related metabolic topographies at network and regional levels across different patient populations and PET scanners. Metabolic brain network activity may serve as a reliable and objective marker of PSP, although cross-validation applying recent diagnostic criteria and classification is warranted.

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Fe 3 O 4 @astragalus polysaccharide core-shell nanoparticles (Fe 3 O 4 @APS NPs) were demonstrated to be an efficient therapeutic drug for treating iron deficiency anemia (IDA) in vivo. The Fe 3 O 4 @APS NPs have been synthesized using a two steps approach involving hydrothermal synthesis and subsequent esterification. Transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy studies show that APS are attached on the surfaces of the highly monodisperse Fe 3 O 4 NPs. Dynamic light scatting (DLS) and magnetic characterizations reveal that the Fe 3 O 4 @APS NPs have outstanding water solubility and stability. Cytotoxicity assessment using Hela cells and pathological tests in mice demonstrate their good biocompatibility and low toxicity. The IDA treatment in rats shows that they have efficient therapeutic effect, which is contributed to both the iron element supplement from Fe 3 O 4 and the APS-stimulated hematopoietic cell generation. Moreover, the Fe 3 O 4 @APS NPs are superparamagnetic and thus able to be used for magnetic resonance imaging (MRI). This study has demonstrated the potential of nanocomposites involving purified natural products from Chinese herb medicine for biomedical applications. 3

To increase the intra-articular (IA) retention time of osteoarthritis drugs in the synovial cavity and slow down the burst release of microspheres (MPs), we prepared a novel drug delivery system named nanoparticles-in-microspheres (NiMs). The system was constructed by dispersing the brucine-loaded nanoparticle, which was prepared by an emulsification method in the MPs. The NiMs were characterized by scanning electron microscope, Fourier transform infrared spectra and differential scanning calorimetry. After investigating the biocompatibility with synovium of NiMs in rats, the pharmacokinetics was studied and FX-imaging was used to visualize the transmission of nanoparticles after IA administration in rats. From the results, we know that the NiMs were spherical, there was no chemical bond between the drug and the polymer, and the drug was dispersed in the polymer in an amorphous form. Compared with MPs (41%), the burst release of NiMs could be slowed down to 9%. After that, the drug was released from NiMs by diffusion. The results of FX imaging in rats showed that the NiMs could stay in the articular cavity for over 11 d. The studies of pharmacokinetics revealed that the NiMs could slow down the burst release and improve retention in vivo. This study demonstrates the feasibility of using NiMs to slow down the burst release and increase the retention of therapeutic agents in articular joints.

Solid lipid nanoparticles (SLN) containing beta-elemene, a volatile oil used for the treatment of cancer, were prepared by the method combining probe sonication and membrane extrusion. Effects of the formulations and procedures on the characteristics of SLN were investigated. Body distribution of beta-elemene SLN in rats after intravenous administration was compared with that of the commercial emulsion. The results showed that dispersing the surfactant in the melted lipid matrix could obtain smaller particles than that dispersing in the water phase. Increasing the ratio of monostearin in the lipid matrix or the concentration of surfactant reduced the mean volume size of the SLN. Optimized formulation was composed of monostearin and precirol ATO 5 at a mass ratio of 3:7, which was quite stable for 8 months at room temperature. In vitro release of beta-elemene from the SLN was slow and stable without obvious burst release and was found to follow the Higuich equation. After intravenous administration, the beta-elemene levels after 5 min injection of SLN formulation were 1.5, 2.9, and 1.4 times higher than those of beta-elemene emulsion in liver, spleen, and kidney, respectively, while the concentrations of beta-elemene were decreased 30% in heart and lung. Therefore, the SLN containing beta-elemene might be an attractive candidate for the treatment of liver cancer.

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This paper focuses on the monthly operations of an interprovincial hydropower system (IHS) connected by ultrahigh voltage direct current lines. The IHS consists of the Xiluodu Hydropower Project, which ranks second in China, and local plants in multiple recipient regions. It simultaneously provides electricity for Zhejiang and Guangdong provinces and thus meets their complex operation requirements. This paper develops a multi-objective optimization model of maximizing the minimum of total hydropower generation for each provincial power grid while considering network security constraints, electricity contracts, and plant constraints. The purpose is to enhance the minimum power in dry season by using the differences in hydrology and regulating storage of multiple rivers. The TOPSIS method is utilized to handle this multi-objective optimization, where the complex minimax objective function is transformed into a group of easily solved linear formulations. Nonlinearities of the hydropower system are approximatively described as polynomial formulations. The model was used to solve the problem using mixed integer nonlinear programming that is based on the branch-and-bound technique. The proposed method was applied to the monthly generation scheduling of the IHS. Compared to the conventional method, both the total electricity for Guangdong Power Grid and Zhejiang Power Grid during dry season increased by 6% and 4%, respectively. The minimum monthly power also showed a significant increase of 40% and 31%. It was demonstrated that the hydrological differences between Xiluodu Plant and local hydropower plants in receiving power grids can be fully used to improve monthly hydropower generation.