DC32, a Dihydroartemisinin Derivative, Ameliorates Collagen-Induced Arthritis Through an Nrf2-p62-Keap1 Feedback Loop

Artemisinins have been reported to have diverse functions, such as antimalaria, anticancer, anti-inflammation, and immunoregulation activities. DC32 [(9α,12α-dihydroartemisinyl) bis(2′-chlorocinnmate)], a dihydroartemisinin derivative possessing potent immunosuppressive properties, was synthesized in our previous study. Collagen-induced arthritis (CIA) in DBA/1 mice and inflammatory model in NIH-3T3 cells were established to evaluate the effect of DC32 on RA and discover the underlying mechanisms. The results showed that DC32 could markedly alleviate footpad inflammation, reduce cartilage degradation, activate the Nrf2/HO-1 signaling pathway, and increase the transcription of p62 in DBA/1 mice with CIA. Further mechanistic exploration with NIH-3T3 cells indicated that DC32 could increase the transcription, expression, and nuclear translocation of Nrf2. In addition, DC32 promoted degradation of Keap1 protein and upregulated HO-1 and p62 expression. Furthermore, the effect of DC32 on Keap1 degradation could be prevented by p62 knockdown using siRNA. Administration of DC32 could inhibit the activation of Akt/mTOR and ERK, and pretreatment of NIH-3T3 cells with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the degradation of Keap1 induced by DC32. These results suggest that DC32 inhibits the degradation of Nrf2 by promoting p62-mediated selective autophagy and that p62 upregulation contributed to a positive feedback loop for persistent activation of Nrf2. In summary, our present study demonstrated that DC32 significantly suppressed rheumatoid arthritis (RA) via the Nrf2-p62-Keap1 feedback loop by increasing the mRNA and protein levels of Nrf2 and inducing p62 expression. These findings provide new mechanisms for artemisinins in RA treatment and a potential strategy for discovering antirheumatic drugs

Atoh8, a bHLH Transcription Factor, Is Required for the Development of Retina and Skeletal Muscle in Zebrafish

Math6/atoh8, a bHLH transcription factor, is thought to be indispensable for early embryonic development and likely has important roles in vertebrate tissue-specific differentiation. However, the function of Atoh8 during early development is not clear because homozygous knockout causes embryonic lethality in mice. We have examined the effects of the atoh8 gene on the differentiation of retina and skeletal muscle during early development in zebrafish.We isolated a Math6 homologue in zebrafish, designated as zebrafish atoh8. Whole -mount in situ hybridization analysis showed that zebrafish atoh8 is dynamically expressed mainly in developing retina and skeletal muscle. Atoh8-MO knock-down resulted in reduced eye size with disorganization of retinal lamination. The reduction of atoh8 function also affected the arrangement of paraxial cells and differentiated muscle fibers during somite morphogenesis.Our results show that Atoh8 is an important regulator for the development of both the retina and skeletal muscles necessary for neural retinal cell and myogenic differentiation during zebrafish embryogenesis

Correcting a major error in assessing organic carbon pollution in natural waters

Microbial degradation of dissolved organic carbon (DOC) in aquatic environments can cause oxygen depletion, water acidification, and CO2 emissions. These problems are caused by labile DOC (LDOC) and not refractory DOC (RDOC) that resists degradation and is thus a carbon sink. For nearly a century, chemical oxygen demand (COD) has been widely used for assessment of organic pollution in aquatic systems. Here, we show through a multicountry survey and experimental studies that COD is not an appropriate proxy of microbial degradability of organic matter because it oxidizes both LDOC and RDOC, and the latter contributes up to 90% of DOC in high-latitude forested areas. Hence, COD measurements do not provide appropriate scientific information on organic pollution in natural waters and can mislead environmental policies. We propose the replacement of the COD method with an optode-based biological oxygen demand method to accurately and efficiently assess organic pollution in natural aquatic environments

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Evaluate High Potential Areas for Overweight Trucks and Truck Accidents in California

To increase operational efficiency, reduce congestion, and meet federal requirements concerning truck size and weight limits, the California Department of Transportation (Caltrans) is exploring new plans and feasible projects designed to increase enforcement and reduce pavement damage due to overweight trucks. Installation of Weigh-in-motion (WIM) systems or Virtual Weigh Station (VWS) by Caltrans will provide information to the California Highway Patrol (CHP) that they can use to better enforce commercial vehicle laws in those areas. To support the effective deployment of WIM/VWIM facilities in California, this project was initiated to determine where future WIM/VWS should be located to maximize their effectiveness in commercial truck weight enforcement

Topology-Aware Mapping of Spiking Neural Network to Neuromorphic Processor

Neuromorphic processors, the new generation of brain-inspired non-von Neumann computing systems, are developed to better support the execution of spiking neural networks (SNNs). The neuromorphic processor typically consists of multiple cores and adopts the Network-on-Chip (NoC) as the communication framework. However, an unoptimized mapping of SNNs onto the neuromorphic processor results in lots of spike messages on NoC, which increases the energy consumption and spike latency on NoC. Addressing this problem, we present a fast toolchain, NeuToMa, to map SNNs onto the neuromorphic processor. NeuToMa exploits the global topology of SNNs and uses the group optimization strategy to partition SNNs into multiple clusters, significantly reducing the NoC traffic. Then, NeuToMa dispatches the clusters to neuromorphic cores, minimizing the average hop of spike messages and balancing the NoC workload. The experimental results show that compared with the state-of-the-art technique, NeuToMa reduces the spike latency and energy consumption by up to 55% and 86%, respectively

Identification of Novel Reference Genes Suitable for qRT-PCR Normalization with Respect to the Zebrafish Developmental Stage

<div><p>Reference genes used in normalizing qRT-PCR data are critical for the accuracy of gene expression analysis. However, many traditional reference genes used in zebrafish early development are not appropriate because of their variable expression levels during embryogenesis. In the present study, we used our previous RNA-Seq dataset to identify novel reference genes suitable for gene expression analysis during zebrafish early developmental stages. We first selected 197 most stably expressed genes from an RNA-Seq dataset (29,291 genes in total), according to the ratio of their maximum to minimum RPKM values. Among the 197 genes, 4 genes with moderate expression levels and the least variation throughout 9 developmental stages were identified as candidate reference genes. Using four independent statistical algorithms (delta-CT, geNorm, BestKeeper and NormFinder), the stability of qRT-PCR expression of these candidates was then evaluated and compared to that of <i>actb1</i> and <i>actb2</i>, two commonly used zebrafish reference genes. Stability rankings showed that two genes, namely <i>mobk13 (mob4)</i> and <i>lsm12b</i>, were more stable than <i>actb1</i> and <i>actb2</i> in most cases. To further test the suitability of <i>mobk13</i> and <i>lsm12b</i> as novel reference genes, they were used to normalize three well-studied target genes. The results showed that <i>mobk13</i> and <i>lsm12b</i> were more suitable than <i>actb1</i> and <i>actb2</i> with respect to zebrafish early development. We recommend <i>mobk13</i> and <i>lsm12b</i> as new optimal reference genes for zebrafish qRT-PCR analysis during embryogenesis and early larval stages.</p></div

Investigation Into Hybrid Configuration In Electrospun Nafion/Silica Nanofiber

Organic-inorganic composites with nanostructure could exhibit a diverse range of multi-functional properties. In this study, nafion/silica composite nanofibers were successfully fabricated by using electrospinning technique with nafion coated surface. The tunable wettability of composite nanofiber was controlled by addition of nafion or flame-treatment. The thermal stability of nafion has been improved as it hybridized with silica nanofiber. Interestingly, the hydrophobic behavior still existed after heat-treatment with 500 °C for 2 h. The fire resistant property of composite nanofiber has been characterized. The effect of nafion polymer and post treatment on the morphology and wettability of composite nanofiber was evaluated. The mechanism of formation of nafion/silica composite nanofiber during electrospinning process has been proposed. The results of this study improve the understanding of the structure rearrange in organic-inorganic sols during high voltage field

Self-Assembled Multi-Layered Carbon Nanofiber Nanopaper For Significantly Improving Electrical Actuation Of Shape Memory Polymer Nanocomposite

This study presents an effective approach to significantly improve the electrical properties of shape memory polymer (SMP) nanocomposites that show Joule heating triggered shape recovery. Carbon nanofibers (CNFs) were self-assembled to form multi-layered nanopaper to enhance the bonding and shape recovery behavior of SMP, respectively. It was found that both glass transition temperature (Tg) and electrical properties of the SMP nanocomposites have been improved by incorporating multi-layers of self-assembled nanopapers. The electrically actuated shape recovery behavior and the temperature profile during the actuation were monitored and characterized at a voltage of 30 V. © 2013 Elsevier Ltd. All rights reserved