Osteoprotegerin (OPG) is a member of the TNF receptor superfamily and plays a critical role in the development of osteoclasts from precursor cells. OPG is produced by a variety of cells of ...mesenchymal origin and has been demonstrated to be present in osteoblasts and osteocytes. However, the mechanisms of regulation of OPG production and secretion are not known. Using a highly specific polyclonal antibody, we demonstrate that OPG is synthesized and secreted by osteoblast-like cells in culture. We further show that phorbol myristate acetate, an activator of protein kinase C, activated the secretion of OPG. Further, the increased secretion of OPG correlated well with a corresponding increase in OPG mRNA abundance. In addition, OPG promoter stably integrated into an osteoblast cell line was activated by phorbol myristate acetate. The increase in OPG expression was blocked by an inhibitor of protein kinase C, although the basal OPG expression was not altered. These results suggest that activation of the protein kinase C pathway may play a critical role in OPG expression.
Transforming growth factor-β (TGF-β) regulates osteoclastogenesis and osteoclast survival, in part through the induction of
osteoprotegerin (OPG), a protein known to inhibit osteoclast formation ...and function. To explore the molecular basis of TGF-β
regulation of OPG expression, we evaluated the effects of TGF-β on osteoclast formation, OPG protein secretion, mRNA expression,
and gene transcription. The marked inhibitory effect of TGF-β on osteoclast differentiation was confirmed in a co-culture
model utilizing murine stromal/osteoblastic BALC cells and bone marrow hematopoietic precursors. This inhibition in osteoclast
differentiation was preceded by a decrease in RANKL mRNA expression (5-fold) and a reciprocal increase in OPG mRNA (6.1-fold)
and protein (7.1-fold) expression in BALC cells. At the promoter/transcriptional level, TGF-β treatment resulted in a 3â10-fold
increase in reporter gene activity directed by a 5.9-kilobase fragment of the human OPG promoter in transfection assays performed
in UMR106 cells. The effect of TGF-β was mimicked by TGF-β2 and -β3 but not by BMP-4, suggesting a TGF-β signal-specific effect.
Deletion analysis revealed that a 183-base pair region (â372 to â190) in the promoter was required for TGF-β responsiveness,
and this region was sufficient to confer TGF-β inducibility to a heterologous (osteocalcin) minimal promoter. Substitution
mutations that disrupted the Cbfa1- and/or Smad-binding elements present in the 183-base pair region resulted in a decrease
in base-line expression and in the responsiveness to TGF-β and Cbfa1. Collectively, these studies indicate the involvement
and possible interaction of Cbfa1 and Smad proteins in mediating the effects of TGF-β on OPG transcription.
Transforming growth factor-β (TGF-β) regulates osteoclastogenesis and osteoclast survival, in part through the induction of osteoprotegerin (OPG), a protein known to inhibit osteoclast formation and ...function. To explore the molecular basis of TGF-β regulation of OPG expression, we evaluated the effects of TGF-β on osteoclast formation, OPG protein secretion, mRNA expression, and gene transcription. The marked inhibitory effect of TGF-β on osteoclast differentiation was confirmed in a co-culture model utilizing murine stromal/osteoblastic BALC cells and bone marrow hematopoietic precursors. This inhibition in osteoclast differentiation was preceded by a decrease in RANKL mRNA expression (5-fold) and a reciprocal increase in OPG mRNA (6.1-fold) and protein (7.1-fold) expression in BALC cells. At the promoter/transcriptional level, TGF-β treatment resulted in a 3–10-fold increase in reporter gene activity directed by a 5.9-kilobase fragment of the human OPG promoter in transfection assays performed in UMR106 cells. The effect of TGF-β was mimicked by TGF-β2 and -β3 but not by BMP-4, suggesting a TGF-β signal-specific effect. Deletion analysis revealed that a 183-base pair region (−372 to −190) in the promoter was required for TGF-β responsiveness, and this region was sufficient to confer TGF-β inducibility to a heterologous (osteocalcin) minimal promoter. Substitution mutations that disrupted the Cbfa1- and/or Smad-binding elements present in the 183-base pair region resulted in a decrease in base-line expression and in the responsiveness to TGF-β and Cbfa1. Collectively, these studies indicate the involvement and possible interaction of Cbfa1 and Smad proteins in mediating the effects of TGF-β on OPG transcription.
•Thermally activated persulfate (TAP) technology can decompose CBZ efficiently.•Sulfate radicals play the primary role in TAP oxidation.•The best CBZ degradation can be achieved at acidic ...conditions.•Coexisting anions and cations exhibit opposite effect on the CBZ degradation.•Six intermediate products are identified using LC–MS/MS.
Sulfate radicals-based advanced oxidation processes have been applied in water treatment and in situ chemical oxidation. Batch experiments were conducted to investigate the influencing factors including persulfate dosage, initial carbamazepine (CBZ) concentrations, solution pH, coexisting inorganic anions and cations on the decomposition of CBZ using thermally activated persulfate (TAP) technology. The results showed that TAP oxidation was efficient process for the CBZ degradation in water. The generation of sulfate radicals was accounted for the CBZ degradation in TAP system. The CBZ degradation rate constant increased as persulfate dosage increased and decreased as the initial CBZ concentrations increased. The CBZ decomposition rate decreased with the increasing pH and the best degradation occurred at pH 3. The exception was the strong alkaline condition under which a higher CBZ degradation performance was achieved. Coexisting inorganic anions slowed down the CBZ degradation to different degrees and the inhibiting effect abided by the following order: CO32->HCO3->Cl->SO42->NO3-. In contrast, coexisting cations could significantly enhance the CBZ degradation, and the promoting effect was in the order of Fe2+>Cu2+>Fe3+. In this study, six major intermediate products were generated during the TAP oxidation.
Void defects have appeared inevitably during the manufacturing process of braided composites, which directly affect the mechanical properties and strength of braided composites. First, the influence ...of internal void and porosity on the mechanical properties of resin was predicted. Second, the evolution in the mechanical properties of three dimensional (3D) braided composites was obtained using the Mori-Tanaka method. Finally, the strength prediction, failure mode, stress and strain field of 3D braided composites with void defects were investigated by means of finite element simulation based on the progressive damage theory in ABAQUS, which will compare the simulation results with the theoretical results and other scholar's experiments. The innovation of this work is to establish the constitutive model and finite element model of 3D braided composite material with voids and predict the evolution of the mechanical properties of 3D braided composite material with defects. The results will provide the theoretical and design basis for evaluating the influence of void defects on the mechanical properties of 3D braided composites.
Abstract Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its ...pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.
Metasurfaces, composed of specifically designed subwavelength units in a two-dimensional plane, offer a new paradigm to design ultracompact optical elements that show great potentials for ...miniaturizing optical systems. In the past few decades, metasurfaces have drawn broad interests in multidisciplinary communities owing to their capability of manipulating various parameters of the light wave with plentiful functionalities. Among them, pixelated polarization manipulation in the subwavelength scale is a distinguished ability of metasurfaces compared to traditional optical components. However, the inherent ohmic loss of plasmonic-type metasurfaces severely hinders their broad applications due to the low efficiency. Therefore, metasurfaces composed of high-refractive-index all-dielectric antennas have been proposed to achieve high-efficiency devices. Moreover, anisotropic dielectric nanostructures have been shown to support large refractive index contrast between orthogonal polarizations of light and thus provide an ideal platform for polarization manipulation. Herein, we present a review of recent progress on all-dielectric metasurfaces for polarization manipulation, including principles and emerging applications. We believe that high efficient all-dielectric metasurfaces with the unprecedented capability of the polarization control can be widely applied in areas of polarization detection and imaging, data encryption, display, optical communication and quantum optics to realize ultracompact and miniaturized optical systems.
Cytokines are key mediators of immune responses that can modulate the antitumor activity of immune cells. Cytokines have been explored as a promising cancer immunotherapy. However, there are several ...challenges to cytokine therapy, especially a lack of tumor targeting, resulting in high toxicity and limited efficacy. To overcome these limitations, novel approaches have been developed to engineer cytokines with improved properties, such as chimeric cytokines. Chimeric cytokines are fusion proteins that combine different cytokine domains or link cytokines to antibodies (immunocytokines) or other molecules that can target specific receptors or cells. Chimeric cytokines can enhance the selectivity and stability of cytokines, leading to reduced toxicity and improved efficacy. In this review, we focus on two promising cytokines, IL2 and IL15, and summarize the current advances and challenges of chimeric cytokine design and application for cancer immunotherapy. Most of the current approaches focus on increasing the potency of cytokines, but another important goal is to reduce toxicity. Cytokine engineering is promising for cancer immunotherapy as it can enhance tumor targeting while minimizing adverse effects.
Amid the ever-accelerated development of wireless communication technology, we have become increasingly demanding for location-based service; thus, passive indoor positioning has gained widespread ...attention. Channel State Information (CSI), as it can provide more detailed and fine-grained information, has been followed by researchers. Existing indoor positioning methods, however, are vulnerable to the environment and thus fail to fully reflect all the position features, due to limited accuracy of the fingerprint. As a solution, a CSI-based passive indoor positioning method was proposed, Wavelet Domain Denoising (WDD) was adopted to deal with the collected CSI amplitude, and the CSI phase information was unwound and transformed linearly in the offline phase. The post-processed amplitude and phase were taken as fingerprint data to build a fingerprint database, correlating with reference point position information. Results of experimental data analyzed under two different environments show that the present method boasts lower positioning error and higher stability than similar methods and can offer decimeter-level positioning accuracy.
PDF
