CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation

Runx2, an essential transactivator for osteoblast differentiation, is tightly regulated at both the transcriptional and posttranslational levels. In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism. CHIP interacts with Runx2 in vitro and in vivo. In the presence of increased Runx2 protein levels, CHIP expression decreases, whereas the expression of other E3 ligases involved in Runx2 degradation, such as Smurf1 or WWP1, remains constant or increases during osteoblast differentiation. Depletion of CHIP results in the stabilization of Runx2, enhances Runx2-mediated transcriptional activation, and promotes osteoblast differentiation in primary calvarial cells. In contrast, CHIP overexpression in preosteoblasts causes Runx2 degradation, inhibits osteoblast differentiation, and instead enhances adipogenesis. Our data suggest that negative regulation of the Runx2 protein by CHIP is critical in the commitment of precursor cells to differentiate into the osteoblast lineage

Sea Ice Monitoring with CFOSAT Scatterometer Measurements Using Random Forest Classifier

The Ku-band scatterometer called CSCAT onboard the Chinese–French Oceanography Satellite (CFOSAT) is the first spaceborne rotating fan-beam scatterometer (RFSCAT). This paper performs sea ice monitoring with the CSCAT backscatter measurements in polar areas. The CSCAT measurements have the characteristics of diverse incidence and azimuth angles and separation between open water and sea ice. Hence, five microwave feature parameters, which show different sensitivity to ice or water, are defined and derived from the CSCAT measurements firstly. Then the random forest classifier is selected for sea ice monitoring because of its high overall accuracy of 99.66% and 93.31% in the Arctic and Antarctic, respectively. The difference of features ranked by importance in different seasons and regions shows that the combination of these parameters is effective in discriminating sea ice from water under various conditions. The performance of the algorithm is validated against the sea ice edge data from the EUMETSAT Ocean and Sea Ice Satellite Application Facility (OSI SAF) on a global scale in a period from 1 January 2019 to 10 May 2021. The mean sea ice area differences between CSCAT and OSI SAF product in the Arctic and Antarctic are 0.2673 million km2 and −0.4446 million km2, respectively, and the sea ice area relative errors of CSCAT are less than 10% except for summer season in both poles. However, the overall sea ice area derived from CSCAT is lower than the OSI SAF sea ice area in summer. This may be because the CSCAT is trained by radiometer sea ice concentration data while the radiometer measurement of sea ice is significantly affected by melting in the summer season. In conclusion, this research verifies the capability of CSCAT in monitoring polar sea ice using a machine learning-aided random forest classifier. This presented work can give guidance to sea ice monitoring with radar backscatter measurements from other spaceborne scatterometers, particular for the recently launched FY-3E scatterometer (called WindRad)

One-Pot Solution Synthesis of Cubic Cobalt Nanoskeletons

Cubic Co nanoskeletons with an edge length of 100nm are prepared by a facile one-pot solution method. The cubic Co nanoskeletons synthesized exhibit excellent magnetic properties and mesopore structures. This work may provide an easy way to control the synthesis of hollow metal nanopolyhedra by introducing an appropriate etching agent into the synthetic process

Suppression of Th17 Cell Response in the Alleviation of Dextran Sulfate Sodium-Induced Colitis by Ganoderma lucidum Polysaccharides

Background. Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. Methods. The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2.5% DSS dissolved in drinking water with GLP or water treatment for 6 days. The mice were killed on day 7 after induction of colitis. Survival rates, body weight loss, colon lengths, histological changes, and disease activity index scores (DAI) were evaluated. Results. GLP significantly improved survival rates, colon length shortening, body weight loss, histopathological score, and DAI scores in mice with DSS-induced colitis. GLP markedly suppressed the secretions of TNF-α, IL-1β, IL-6, IL-17A, and IL-4 and significantly affected populations of Th17 cells, B cells, NK cells, and NKT cells in the lamina propria lymphocytes. Conclusions. GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis

ZNF536, a Novel Zinc Finger Protein Specifically Expressed in the Brain, Negatively Regulates Neuron Differentiation by Repressing Retinoic Acid-Induced Gene Transcription▿

Neuronal differentiation is tightly regulated by a variety of factors. In a search for neuron-specific genes, we identified a highly conserved novel zinc finger protein, ZNF536. We observed that ZNF536 is most abundant in the brain and, in particular, is expressed in the developing central nervous system and dorsal root ganglia and localized in the cerebral cortex, hippocampus, and hypothalamic area. During neuronal differentiation of P19 cells induced by retinoic acid (RA), ZNF536 expression is increased at an early stage, and it is maintained at a constant level in later stages. Overexpression of ZNF536 results in an inhibition of RA-induced neuronal differentiation, while depletion or mutation of the ZNF536 gene results in an enhancement of differentiation. We further demonstrated that ZNF536 inhibits expression of neuron-specific marker genes, possibly through the inhibition of RA response element-mediated transcriptional activity, as overexpression of RA receptor α can rescue the inhibitory role of ZNF536 in neuronal differentiation and neuron-specific gene expression. Our studies have identified a novel zinc finger protein that negatively regulates neuron differentiation

IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses

Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4+T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis