The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box

MiR-137 Targets Estrogen-Related Receptor Alpha and Impairs the Proliferative and Migratory Capacity of Breast Cancer Cells

ERRα is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRα in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRα is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRα 3′UTR at nt 480–486 and nt 596–602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRα expression at both protein level and mRNA level, and the miR-137 induced ERRα-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137mimics suppressed at least two downstream target genes of ERRα–CCNE1 and WNT11, which are important effectors of ERRα implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRα expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRα by microRNAs has the potential to influence breast cancer progression

Contrasting metal detoxification in polychaetes, bivalves and fish from a contaminated bay

Jinzhou Bay in Bohai, Northern China, is historically contaminated with metals, but the organisms living in such contaminated environments are much less well studied. In this study, we contrasted the different subcellular and detoxification responses of polychaetes, bivalves and fish collected from different contaminated sites in Jinzhou Bay. In polychaete Neanthes japonica, metal-rich granule (MRG) was the main biologically detoxified metal compartment, and metallothionein-like protein (MTLP) detoxified a relatively smaller fraction of accumulated metals. The importance of MRG increased whereas that of MTLP decreased with increasing metal bioaccumulation. Detoxification in the two bivalves was similar to that in the polychaetes. However, the MRG appeared to play only a minor role in metal binding and detoxification in the gills and livers of fish, whereas MTLP was the dominating detoxification pool. Cellular debris was an important pool binding with metals in the three marine animals. Our study highlighted the contrasting cellular binding and detoxification among different marine organisms living in contaminated environments. (C) 2014 Elsevier B.V. All rights reserved

Mechanical Properties of Rocks under Complex Stress Conditions: Investigations Using Experimental and Numerical Methods

Rock engineering constructions are widely attested in energy mining, geothermal development, and underground energy storage projects [...

Mineral Composition, Pore Structure, and Mechanical Characteristics of Pyroxene Granite Exposed to Heat Treatments

In deep geoengineering, including geothermal development, deep mining, and nuclear waste geological disposal, high temperature significantly affects the mineral properties of rocks, thereby changing their porous and mechanical characteristics. This paper experimentally studied the changes in mineral composition, pore structure, and mechanical characteristics of pyroxene granite heated to high temperature (from 25 °C to 1200 °C). The results concluded that (1) the high-temperature effect can be roughly identified as three stages: 25–500 °C, 500–800 °C, 800–1200 °C. (2) Below 500 °C, the maximum diffracted intensities of the essential minerals are comparatively stable and the porous and mechanical characteristics of granite samples change slightly, mainly due to mineral dehydration and uncoordinated thermal expansion; additionally, the failure mechanism of granite is brittle. (3) In 500–800 °C, the diffraction angles of the minerals become wider, pyroxene and quartz undergo phase transitions, and the difference in thermal expansion among minerals reaches a peak; the rock porosity increases rapidly by 1.95 times, and the newly created pores caused by high heat treatment are mainly medium ones with radii between 1 μm and 10 μm; the P-wave velocity and the elastic modulus decrease by 62.5% and 34.6%, respectively, and the peak strain increases greatly by 105.7%, indicating the failure mode changes from brittle to quasi-brittle. (4) In 800–1200 °C, illite and quartz react chemically to produce mullite and the crystal state of the minerals deteriorate dramatically; the porous and mechanical parameters of granite samples all change significantly and the P-wave, the uniaxial compressive strength (UCS), and the elastic modulus decrease by 81.30%, 81.20%, and 92.52%, while the rock porosity and the shear-slip strain increase by 4.10 times and 11.37 times, respectively; the failure mechanism of granite samples transforms from quasi-brittle to plastic, which also was confirmed with scanning electron microscopy (SEM)

Parkin Mediates Cannabidiol Prevention of Amyloid-Beta-Induced Senescence in Human Astrocytes

Introduction: As aging is the leading risk factor for Alzheimer\u27s disease (AD), ablation of senescent cells is a promising therapeutic approach to prevent AD. It is known that astrocytes lose their ability to maintain a healthy brain environment when aging. Studies have recently shown that cannabidiol (CBD) provides a promising therapeutic avenue for AD; however, if or how CBD prevents astrocyte aging is not known. Materials and Methods: In this study, human astrocytes were employed to measure amyloid-beta (Aβ)-induced senescence features, including senescence-associated β-galactosidase (SA-β-gal), p16INK4A, p21WAF1, and p53. The effects of CBD on the production of mitochondrial dysfunction and mitophagy pathway were measured by Western blot and fluorescence assay. Caenorhabditis elegans was used as in vivo AD model to investigate the effects of CBD on life span and health span. All experimental procedures were approved by the Human Research Ethics Committee, University of Wollongong, Australia. Results: In human astrocytes, we show that treatment with Aβ, an endogenous pathogenic agent of AD, results in an increase in the percentage of SA-β-gal-positive cells and induces mitochondrial reactive oxygen species (ROS). However, CBD treatment protects from Aβ-induced senescence. Furthermore, the anti-senescence and anti-apoptotic activities of CBD were observed to be mediated through the protective effect of Parkin-dependent mitophagy. In C. elegans, we used the transgenic GRU102 strain, which expresses the human Aβ peptide, and found that CBD treatment extended life span, improved pumping rate, and decreased mitochondrial ROS. Conclusion and Significance: Our results demonstrate that CBD prevents the human astrocyte senescence induced by Aβ by a mechanism involving the Parkin-mediated mitophagy pathway. Our findings support the new therapeutic avenues of CBD for the treatment of AD patients

Power Coefficient Analysis of Double-blade Half-rotating Impeller Tidal Turbine Operating at Yaw

The double-blade half-rotating impeller tidal turbine (DHITT) is a new type of vertical shaft tidal current turbine with lift and resistance performance. The power coefficient of the DHITT is affected by the flow direction. In order to research the power coefficient (CP) of the DHITT under different flow direction, the optimal attack flow angle of a half-impeller turbine was explored, and the fluctuation of power coefficient of the DHITT operating at yaw was analyzed based on the optimal attack flow angle. The unsteady flow of the turbine was simulated by overlapping grid technique, and the fluctuation of the turbine’s power coefficient under different flow directions was analyzed, which was verified by experiments. The results have demonstrated that the power coefficient at the optimal angle of attack is 0.53. As the yaw angle greater than 30º, the power reduction is nearly 40%, but the average efficiency loss is only 3.7% in the range of -3º to 3º

Mercury and methylmercury bioaccumulation in a contaminated bay

The bioaccumulation and the main source of total Hg (THg) and methylmercury (MMHg) in the deposit-feeding polychaete Neanthes japonica collected in Jinzhou Bay, China, were investigated. Compared with the historical data, THg bioaccumulation in polychaetes collected in sediment of Jinzhou Bay was distinctly higher due to higher sediment THg concentration, but MMHg bioaccumulation was significantly lower. THg accumulation in polychaetes mainly derived from its accumulation in sediment. However, MMHg bioaccumulation in polychaetes did not correlate with Hg concentration in sediment. Besides sediment ingestion, MMHg accumulation in polychaetes may partially source from the process of in vivo transformation. The in vivo Hg methylation may take place in polychaetes, according to the excellent correlation between MMHg concentration and THg and inorganic Hg concentration in polychaetes. The biochemical characters in polychaete body, the oxidation-reduction environment and the microbial activity in polychaete gut may be beneficial to in vivo Hg methylation