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The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro–computed tomography and histological staining. Our findings indicate that MZF1−/− mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1−/− and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1−/− group produced more tartrate-resistant acid phosphatase–positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1−/− group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1−/− group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism. [ABSTRACT FROM AUTHOR]

Metastasis‐associated protein 1 (MTA1), belonging to metastasis‐associated proteins (MTA) family, which are integral parts of nucleosome remodelling and histone deacetylation (NuRD) complexes. However, the effect of MTA1 on osteoclastogenesis is unknown. Currently, the regulation of MTA1 in osteoclastogenesis was reported for the first time. MTA1 knockout cells (KO) were established by CRISPR/Cas9 genome editing. RAW264.7 cells with WT and KO group were stimulated independently by RANKL to differentiate into mature osteoclasts. Further, western blotting and quantitative qRT‐PCR were used to explore the effect of MTA1 on the expression of osteoclast‐associated genes (including CTSK, MMP9, c‐Fos and NFATc1) during osteoclastogenesis. Moreover, the effects of MTA1 on the expression of reactive oxygen species (ROS) in osteoclastogenesis was determined by 2′, 7′ ‐dichlorodihydrofluorescein diacetate (DCFH‐DA) staining. Nuclear translocation of Nrf2 was assessed by immunofluorescence staining and western blotting. Our results indicated that the MTA1 deletion group could differentiate into osteoclasts with larger volume and more TRAP positive. In addition, compared with WT group, KO group cells generated more actin rings. Mechanistically, the loss of MTA1 increased the expression of osteoclast‐specific markers, including c‐Fos, NFATc1, CTSK and MMP‐9. Furthermore, the results of qRT‐PCR and western blotting showed that MTA1 deficiency reduced basal Nrf2 expression and inhibited Nrf2‐mediated expression of related antioxidant enzymes. Immunofluorescence staining demonstrated that MTA1 deficiency inhibited Nrf2 nuclear translocation. Taken together, the above increased basal and RANKL‐induced intracellular ROS levels, leading to enhanced osteoclast formation. [ABSTRACT FROM AUTHOR]

Different scales of the objects pose a great challenge for the segmentation of remote sensing images of special scenes. This paper focuses on the problem of large-scale variations of the target objects via a dynamical receptive field of the deep network. We construct a Gaussian dynamic convolution network by introducing a dynamic convolution layer to enhance remote sensing image understanding. Moreover, we propose a new Gaussian pyramid pooling (GPP) for multi-scale object segmentation. The proposed network can expand the size of the receptive field and improve its efficiency in aggregating contextual information. Experiments verify that our method outperforms the popular semantic segmentation methods on large remote sensing image datasets, including iSAID and LoveDA. Moreover, we conduct experiments to demonstrate that the Gaussian dynamic convolution works more effectively on remote sensing images than other convolutional layers. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) has severely affected human health, which is characterized by abnormal differentiation of osteoclasts. Urolithin B (UB), as a potential natural drug, has been reported to exhibit numerous biological activities including antioxidant and anti‐inflammatory but its effects on OP, especially on RANKL‐stimulated osteoclast formation and activation, are still understood. In our study, we have demonstrated for the first time that UB inhibits RANKL‐induced osteoclast differentiation and explored its potential mechanisms of action. The RAW264.7 cells were cultured and induced with RANKL followed by UB treatment. Then, the effects of UB on mature osteoclast differentiation were evaluated by counting tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells and F‐actin ring analysis. Moreover, the effects of UB on RANKL‐induced reactive oxygen species (ROS) were measured by 2′, 7′‐dichlorodihydrofluorescein diacetate (DCFH‐DA) staining. Further, we explored the potential mechanisms of these downregulation effects by performing Western blotting and quantitative RT‐PCR examination. We found that UB represses osteoclastogenesis, F‐actin belts formation, osteoclast‐specific gene expressions and ROS activity in a time‐ and concentration‐dependent manner. Mechanistically, UB attenuates intracellular ROS levels by upregulation of Nrf2 and other ROS scavenging enzymes activation. Furthermore, UB also inhibited RANKL‐induced NF‐κB, MAPK and Akt signalling pathway and suppressed expression of c‐Fos and nuclear factor of activated T cells 1 (NFATc1), which is the master transcription factor of osteoclast differentiation. Taken together, our findings confirm that UB is a polyphenolic compound that can be a potential therapeutic treatment for osteoclast‐related bone diseases such as osteoporosis. [ABSTRACT FROM AUTHOR]

In the fiber sensing research area, a pair of sharp contradictions is highlighted: high sensitivity and large dynamic range. In addition, the question of how to enable user-editable features for fiber optic sensors is gaining more and more attention. This letter presents a fiber acoustic sensor with real-time controllable sensitivity based on the optical vernier effect, which is possibly a solution to such a problem. The optical vernier structure with amplified and real-time tunable detection sensitivity is formed by cascading a Sagnac interferometer and a laboratory-made tunable Fabry–Perot interferometer (FPI). Sound pressure and frequency of the acoustic signal can be all-optically demodulated simultaneously by spectral reading and spectral scanning method, respectively. Experimental results show a real-time controllable acoustic sensitivity (1×, 5×, and 10× are demonstrated) and a maximum sensitivity is as high as 37.1 nm/Pa (10× of single FPI) within relatively large sound pressure range of 62.2–92.4 dB. By adjusting the FPI cavity length in real time, sensitivity can be controlled to meet the needs of different users or occasions. The proposed sensor has merits of controllable sensitivity in real time, high sensitivity, and large dynamic range, enabling the applications related but not limited to acoustic sensing. [ABSTRACT FROM AUTHOR]

Graphene-based temperature sensor is characterized by low absorption coefficient and large thermal conductivity. We report a grapheme-coated microfiber (GCM) structure based sensor, which is demodulated with a dual-wavelength erbium-doped fiber laser (DWEDFL). The “thermophoresis effect” of GCM and gain competition between the two lasing wavelengths allow us to achieve an ultrahigh temperature sensitivity up to 2.10 dB/°C. To the best of our knowledge, it is the highest one among the intensity-type temperature sensors reported so far. The sensor has the potential in sensing application for its merits including high sensitivity and convenience of demodulation. Our results demonstrate that the GCM structure combined with the gain competition scheme offers an alternative way for high-sensitivity optical fiber sensing applications. [ABSTRACT FROM AUTHOR]

Although many studies have described the roles of microRNAs (miRNAs) in the modulation of the endothelial response to shear stress, the mechanisms remain incompletely understood. Here, we demonstrate that miR-34a expression in endothelial cells was downregulated by atheroprotective physiological high shear stress (HSS), whereas it was upregulated by atheroprone oscillatory shear stress (OSS). Blockade of endogenous miR-34a dramatically decreased basal vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression levels. Conversely, miR-34a overexpression increased the protein levels of VCAM-1 and ICAM-1, consequently promoting monocyte adhesion to endothelial cells. Furthermore, miR-34a overexpression attenuated HSS-mediated suppression of VCAM-1 protein expression on endothelial cells, but promoted HSS-induced ICAM-1 expression. In addition, the OSS induction of endothelial cell VCAM-1 and ICAM-1 was suppressed by using an miR-34a inhibitor, which led to a reduction of monocyte adhesion to endothelial cells. Mechanistically, sirtuin 1 overexpression partially prevented miR-34a-induced VCAM-1 and ICAM-1 expression. Subsequent investigation demonstrated that miR-34a increased nuclear factor KB (NF-KB) p65 subunit (also known as RelA) acetylation (on residue Lys310), and silencing NF-KB signaling reduced miR-34a-induced VCAM-1 and ICAM-1 protein expression. These results demonstrate that miR-34a is involved in the flow-dependent regulation of endothelial inflammation. [ABSTRACT FROM AUTHOR]

The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed to mark a cardiovascular progenitor cell lineage that gives rise to cardiomyocytes, endothelial cells, and smooth muscle cells. The aim of this study was to investigate whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) influenced the differentiation capacity and angiogenic properties of hMSCs. The lentiviral vector, EF1α-ISL1, was constructed using the Multisite Gateway System and used to transduce hMSCs. We found that ISL1 overexpression did not alter the proliferation, migration, or survival of hMSCs or affect their ability to differentiate into osteoblasts, adipocytes, cardiomyocytes, or endotheliocytes. However, ISL1-hMSCs differentiated into smooth muscle cells more efficiently than control hMSCs. Furthermore, conditioned medium from ISL1-hMSCs greatly enhanced the survival, migration, and tube-formation ability of human umbilical vein endothelial cells (HUVECs) in vitro. In vivo angiogenesis assays also showed much more vascular-like structures in the group cotransplanted with ISL1-hMSCs and HUVECs than in the group cotransplanted with control hMSCs and HUVECs. Quantitative RT-PCR and antibody arrays detected monocyte chemoattractant protein-3 (MCP3) at a higher level in conditioned medium from ISL1-hMSCs cultures than in conditioned medium from control hMSCs. Neutralization assays showed that addition of an anti-MCP3 antibody to ISL1-hMSCs-conditioned medium efficiently abolished the angiogenesis-promoting effect of ISL1-hMSCs. Our data suggest that overexpression of ISL1 in hMSCs promotes angiogenesis in vitro and in vivo through increasing secretion of paracrine factors, smooth muscle differentiation ability, and enhancing the survival of HUVECs. S tem C ells 2014;32:1843-1854 [ABSTRACT FROM AUTHOR]