Introduction
Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with ...potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke‐ and dementia‐free subjects harboring confluent WMH on magnetic resonance imaging (MRI).
Methods
In this single‐center, randomized, double‐blind, placebo‐controlled study, we randomized stroke‐ and dementia‐free subjects with confluent WMHs to receive cilostazol or placebo for 2 years in a 1:1 ratio. The primary outcome was change in WMH volume over 2 years. Secondary outcomes were changes in brain volumes, lacunes, cerebral microbleeds, perivascular space, and alterations in white matter microstructural integrity, cognition, motor function, and mood.
Results
We recruited 120 subjects from October 27, 2014, to January 21, 2019. A total of 55 subjects in the cilostazol group and 54 subjects in the control group were included for intention‐to‐treat analysis. At 2‐year follow‐up, the changes in WMH volume were not statistically different between cilostazol treatment and placebo (0.3±1.0 mL vs −0.1±0.8 mL, p = 0.167). Secondary outcomes, bleeding and vascular events, were also not statistically different between the two groups.
Discussion
In this trial with stroke‐ and dementia‐free subjects with confluent WMHs, cilostazol did not impact WMH progression but demonstrated an acceptable safety profile. Future studies should address the treatment effects of cilostazol on subjects at different clinical stages of SVD.
The JC virus (JCV) may infect human oligodendrocytes and consequently cause progressive multifocal leukoencephalopathy (PML) in patients with immune deficiency. In addition, the virus has also been ...detected in other human tissues, including kidney, B lymphocytes, and gastrointestinal tissue. The recombinant major structural protein, VP1, of JCV is able to self-assemble to form a virus-like particle (VLP). It has been shown that the VLP is capable of packaging and delivering exogenous DNA into human cells for gene expression. However, gene transfer is not efficient when using in vitro DNA packaging methods with VLPs. In this study, a novel in vivo DNA packaging method using the JCV VLP was used to obtain high efficiency gene transfer. A reporter gene, the green fluorescence protein, and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in Escherichia coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intraperitoneal administration of ganciclovir in the tk-VLP-treated mice greatly reduced tumor volume. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human colon cancer therapy in the future.
Abstract
Due to the lack of Boiling Water Reactor (BWR) fuel examination data after dry storage, Taiwan Power Company and Institute of Nuclear Energy Research jointly launched the “Taiwan Nuclear ...Fuel Storage Demonstration Project” to collect fuel characteristics data under simulated dry storage. To meet the project requirements, BWR fuel rods in different fuel designs will be selected and then store in simulated storage containers in different environments for 10 years. The interface considerations and design results of the auxiliary equipment for spent nuclear fuel storage, transfer, and non-destructive testing in the simulation stage of spent fuel dry storage were summarized. In addition, the possibility of operating at high heating power and avoiding deformation of the components due to thermal extension of the storage containers after heating was included in the design consideration. A simplification concept was introduced, with frequent NDT (Non-destructive Testing) inspections that will be performed through the spent fuel transfer process. The test results showed that the interface design can meet the requirements of long-term experiment, maintenance and radiation protection requirements, and is ready for further demonstration.
A new C 3-symmetric Schiff-base fluorescent probe (L) based on 8-hydroxy-2-methylquinoline has been developed. As expected, the probe L can display high fluorescent selectivity for Cd2+ over Zn2+ and ...most other common ions in neutral ethanol aqueous medium. Moreover, the mechanism of the L–Cd2+ complex has been confirmed by X-ray crystallography and density functional theory calculation results. More importantly, L could be used to image Cd2+ within living cells.
A high efficient assembly technique for large proton exchange membrane fuel cell (PEMFC) stacks is proposed to obtain the optimal clamping load. The stack system is considered as a mechanical ...equivalent stiffness model consisting of numerous elastic elements (springs) in either series or parallel connections. We first propose an equivalent stiffness model for a single PEM fuel cell, and then develop an equivalent stiffness model for a large PEMFC stack. Based on the equivalent stiffness model, we discuss the effects of the structural parameters and temperature on the internal stress of the components and the contact resistance at the contact interfaces, and show how to determine the assembly parameters of a large fuel cell stack using the equivalent stiffness model. Finally, a three-dimensional finite element analysis (FEA) for a single PEMFC is compared with what the equivalent stiffness model predicts. It is found that the presented model gives very good prediction accuracy for the component stiffness and the clamping load.
MicroRNA (miRNA) are a class of small, single-stranded, non-coding RNA that regulate mRNA expression at the post-transcriptional level and play important roles in many fundamental biological ...processes. There is emerging evidence that miRNA are critical regulators of widespread cellular functions, such as differentiation, proliferation, and migration. At present, little is known about miRNA expression profiles related to skeletal muscle growth in aquatic organisms. This study aimed to investigate the phenotypic variation in the body growth of the Nile tilapia (Oreochromis niloticus) and to identify and quantify the differential expression levels of selected growth-related transcriptomic miRNA in the skeletal muscle of this fish. To this end, we performed next-generation sequencing to define the full miRNA transcriptome in muscle tissue from Nile tilapia and to detect differentially expressed miRNA between 2 strains of Nile tilapia. These tilapia strains exhibited significant (P < 0.05) phenotypic variation with respect to growth-related traits (body length and BW), mitochondrial DNA (mtDNA) haplotype diversity, and the differential expression of selected growth-related genes. The results obtained from the transcriptome analysis and real-time quantitative reverse transcription PCR (qRT-PCR) revealed significant differences in miRNA expression between fast-growing and control strains of tilapia. Digital gene expression (DGE) profiling was performed based on the obtained read abundance, and we identified down-regulated miRNA, including let-7j, miR-140, miR-192, miR-204, miR-218a, miR-218b, miR-301c, and miR-460, and up-regulated miRNA, including let-7b, let-7c, miR-133, miR-152, miR-15a, miR-193a, miR-30b, and miR-34, associated with body growth in tilapia. These results were further validated using real-time qRT-PCR and microarray profiling. In summary, the up- and down-regulation of miRNA involved in the GH/IGF-1 axis signaling pathway suggests that the differential expression levels of growth-related miRNA may serve as molecular markers that are predictive of specific functional and diagnostic implications. The obtained data on genetic polymorphisms in miRNA-target interactions are particularly useful for Nile tilapia breeding programs.
Anomalous Hall effect is commonly used as a simple technique to study the magnetization reversal of perpendicularly magnetized thin films. Yet, in most applications, the easy-magnetization direction ...is in the film-plane. We here propose photo-induced anomalous Hall effect as a new magneto-metric technique to reconstruct the in-plane magnetization loop of metallic thin films. Nickel thin films were deposited on intrinsic silicon to form a Schottky contact. Photo-induced Hall voltage was found hysteretic with the in-plane, magnetic field. The measured voltage-loop was found to mimic the magnetization loop as measured by a magnetometer.
Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns ...surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host. However, efforts to assemble patient-derived macromolecules into structures with the same degree of size and shape tunability as their exogenous counterparts remains a significant challenge. Here we solve this problem by creating a new class of size- and shape-tunable personalized protein nanoparticles (PNP) made entirely from patient-derived proteins. PNPs are built into different sizes and shapes with the same degree of tunability as gold nanoparticles. They are biodegradable and do not activate innate or adaptive immunity following single and repeated administrations in vivo. PNPs can be further modified with specific protein cargos that remain catalytically active even after intracellular delivery in vivo. Finally, we demonstrate that PNPs created from different human patients have unique molecular fingerprints encoded directly into the structure of the nanoparticle. This new class of personalized nanomaterial has the potential to revolutionize how we treat patients and can become an integral component in the diagnostic and therapeutic toolbox.
Identification of mechanisms that decrease cadmium accumulation in plants is a prerequisite for minimizing dietary uptake of cadmium from contaminated crops. Here, we show that cadmium inhibits ...nitrate transporter 1.1 (NRT1.1)-mediated nitrate (NO₃⁻) uptake in Arabidopsis (Arabidopsis thaliana) and impairs NO₃⁻ homeostasis in roots. In NO₃⁻-containing medium, loss of NRT1.1 function in nrt1.1 mutants leads to decreased levels of cadmium and several other metals in both roots and shoots and results in better biomass production in the presence of cadmium, whereas in NO₃⁻-free medium, no difference is seen between nrt1.1 mutants and wild-type plants. These results suggest that inhibition of NRT1.1 activity reduces cadmium uptake, thus enhancing cadmium tolerance in an NO₃⁻ uptake-dependent manner. Furthermore, using a treatment rotation system allowing synchronous uptake of NO₃⁻ and nutrient cations and asynchronous uptake of cadmium, the nrt1.1 mutants had similar cadmium levels to wild-type plants but lower levels of nutrient metals, whereas the opposite effect was seen using treatment rotation allowing synchronous uptake of NO₃⁻ and cadmium and asynchronous uptake of nutrient cations. We conclude that, although inhibition of NRT1.1-mediated NO₃⁻ uptake by cadmium might have negative effects on nitrogen nutrition in plants, it has a positive effect on cadmium detoxification by reducing cadmium entry into roots. NRT1.1 may regulate the uptake of cadmium and other cations by a common mechanism.
Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding ...normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions.
A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement.
The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints).
This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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