Hypoxia-inducible factor 1-α (HIF-1α) plays a critical role in angiogenesis-osteogenesis coupling during bone development and bone regeneration. Previous studies have shown that 17β-estradiol ...activates the HIF-1α signaling pathway and that mice with conditional activation of the HIF-1α signaling pathway in osteoblasts are protected from ovariectomy (OVX)-induced bone loss. In addition, it has been shown that hypoxia facilitates the osteogenic differentiation of mesenchymal stem cells (MSCs) and modulates Wnt/β-catenin signaling. Therefore, we hypothesized that activation of the HIF-1α signaling pathway by hypoxia-mimicking agents would prevent bone loss due to estrogen deficiency. In this study, we confirmed the effect of dimethyloxalylglycine (DMOG), a hypoxia-mimicking agent, on the HIF-1α signaling pathway and investigated the effect of DMOG on MSC osteogenic differentiation and the Wnt/β-catenin signaling pathway. We then investigated the effect of DMOG treatment on OVX-induced bone loss. Female C57BL/6J mice were divided into sham, OVX, OVX+L-DMOG (5 mg/kg/day), and OVX+H-DMOG (20 mg/kg/day) groups. At sacrifice, static and dynamic bone histomorphometry were performed with micro computed tomography (micro-CT) and undecalcified sections, respectively. Bone strength was assessed with the three-point bending test, and femur vessels were reconstructed and analyzed by micro-CT. Serum vascular endothelial growth factor (VEGF), osteocalcin, and C-terminal telopeptides of collagen type(CTX) were measured by ELISA. Tartrate-resistant acid phosphatase staining was used to assess osteoclast formation. Alterations in the HIF-1α and Wnt/β-catenin signaling pathways in the bone were detected by western blot. Our results showed that DMOG activated the HIF-1α signaling pathway, which further activated the Wnt/β-catenin signaling pathway and enhanced MSC osteogenic differentiation. The micro-CT results showed that DMOG treatment improved trabecular bone density and restored the bone microarchitecture and blood vessels in OVX mice. Bone strength was also partly restored in DMOG-treated OVX mice. Dynamic bone histomorphometric analysis of the femur metaphysic revealed that DMOG increased the mineralizing surface, mineral apposition rate, and bone formation rate. The serum levels of VEGF and osteocalcin were higher in DMOG-treated OVX mice. However, there were no significant differences in serum CTX or in the number of tartrate-resistant acid phosphatase-stained cells between DMOG-treated OVX mice and OVX mice. Western blot results showed that DMOG administration partly rescued the decrease in HIF-1α and β-catenin expression following ovariectomy. Collectively, these results indicate that DMOG prevents bone loss due to ovariectomy in C57BL/6J mice by enhancing angiogenesis and osteogenesis, which are associated with activated HIF-1α and Wnt/β-catenin signaling pathways.
This review summarizes the progress in the fluorination and fluoroalkylation of electron‐rich systems with diverse fluorine (F) and fluoroalkyl (Rfn) reagents employing hypervalent iodine compounds ...as initiators in the last few decades. Because of the strong electrophilicity, high oxidizing properties, low toxicity, air and moisture stability, ready availability, ease of handling, and mild reaction conditions, the hypervalent iodine reagents have been widely utilized in modern organic chemistry. In particular, the use of hypervalent iodine reagents to initiate the C−F and C−Rfn (Rfn=CF2H, CF3, perfluoroalkyl, OCH2CF3, SCF3, SeCF3 and etc) bond formation has been increasingly developed. In these reactions, hypervalent iodine compounds behave as powerful oxidants or electrophiles and activate the fluorination/fluoroalkylation reagents, the transition‐metal catalysts, or the substrates to in situ form electrophilic or radical intermediates, which subsequently participate in fluorination, difluoromethylation, trifluoromethylation, perfluoroalkylation, trifluoroethoxylation, fluoroalkylthiolation, trifluoromethylselenolation and others under mild conditions. Although great achievements have been made in this area, they are just the initial phase and still require a wide scope for improvement. It is anticipated that this review will draw much attention from the organic chemistry community and inspire more contributions in the development of new hypervalent‐iodine‐mediated fluorination and fluoroalkylation reactions.
Recent studies have indicated that the architectures of convolutional neural networks (CNNs) tailored for computer vision may not be best suited to image steganalysis. In this letter, we report a CNN ...architecture that takes into account knowledge of steganalysis. In the detailed architecture, we take absolute values of elements in the feature maps generated from the first convolutional layer to facilitate and improve statistical modeling in the subsequent layers; to prevent overfitting, we constrain the range of data values with the saturation regions of hyperbolic tangent (TanH) at early stages of the networks and reduce the strength of modeling using 1×1 convolutions in deeper layers. Although it learns from only one type of noise residual, the proposed CNN is competitive in terms of detection performance compared with the SRM with ensemble classifiers on the BOSSbase for detecting S-UNIWARD and HILL. The results have implied that well-designed CNNs have the potential to provide a better detection performance in the future.
Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, ...and carbamoyl fluorides under metal‐ and additive‐free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other “CO” sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal‐ and additive‐free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.
Back to basics: Trifluoromethyl trifluoromethanesulfonate is a promising click reagent for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal‐ and additive‐free conditions (see scheme). The click reactions are rapid, efficient, and selective, and simply carried out in benign solvents to afford products with minimal efforts for purification.
With the widespread popularity of the internet and smart electronic devices in China, the construction of MOOC quality courses in Chinese universities has developed rapidly with significant ...achievements. However, in the swift advancement of MOOC quality course construction in Chinese universities, some problems have gradually surfaced. This paper takes the "Chinese University MOOC" platform course "Performance and Appreciation of Chinese National Female Soprano Works" as a research case to discuss the existing problems in the construction of MOOC quality courses in Chinese universities. The results indicate that low registration numbers of learners, a student structure dominated by students from the host university, low participation in tests and assignments, and unsatisfactory interactive communication are the main existing problems. The primary causes of these issues include the focus of MOOC quality course construction primarily on students from the host university, neglecting social learners; an emphasis on construction over management, neglecting the organization and management of the teaching process; and excessive reliance on the MOOC platform for course promotion. Based on this, optimization suggestions are proposed, mainly to enhance the integration of MOOC course content, strengthen the organization and management of the MOOC course teaching process, innovate MOOC teaching models combining online and offline methods, and promote MOOC courses through multiple pathways and channels.
Reversible data hiding (RDH) into encrypted images is of increasing attention to researchers as the original content can be perfectly reconstructed after the embedded data are extracted while the ...content owner's privacy remains protected. The existing RDH techniques are designed for grayscale images and, therefore, cannot be directly applied to palette images. Since the pixel values in a palette image are not the actual color values, but rather the color indexes, RDH in encrypted palette images is more challenging than that designed for normal image formats. To the best knowledge of the authors, there is no suitable RDH scheme designed for encrypted palette images that has been reported, while palette images have been widely utilized. This has motivated us to design a reliable RDH scheme for encrypted palette images. The proposed method adopts a color partitioning method to use the palette colors to construct a certain number of embeddable color triples, whose indexes are self-embedded into the encrypted image so that a data hider can collect the usable color triples to embed the secret data. For a receiver, the embedded color triples can be determined by verifying a self-embedded check code that enables the receiver to retrieve the embedded data only with the data hiding key. Using the encryption key, the receiver can roughly reconstruct the image content. Experiments have shown that our proposed method has the property that the presented data extraction and image recovery are separable and reversible. Compared with the state-of-the-art works, our proposed method can provide a relatively high data-embedding payload, maintain high peak signal-to-noise ratio values of the decrypted and marked images, and have a low computational complexity.
Traditional apple-picking robots are unable to detect apples in real-time in complex environments. In order to improve detection efficiency, a fast CenterNet apple recognition method for multiple ...apple targets in dense scenes is proposed. This method can quickly and accurately identify multiple apple targets in dense scenes. The backbone network mainly consists of resnet-44 fully convolutional network, region of interest network (RPN), and region of interest (ROI). The experimental results show that the improved YoloV5 network model has a higher recognition accuracy of 94.1% and 95.8% for apple in the night environment, which improves the recognition accuracy of the occluded features and the features in the dark light, and the model is more robust in the actual data set.
Excellent electromagnetic interference (EMI) shielding ability, light weight, and good heat resistance are highly required for practical applications of EMI shielding materials, such as in areas of ...aerospace, aircraft, and automobiles. Herein, a lightweight and robust carbon nanotube (CNT)/polyimide (PI) foam was developed for efficient and heat-resistant EMI shielding. Thanks to poly(vinyl pyrrolidone) (PVP) as a surfactant that not only promotes the uniform dispersion of CNTs to form perfect CNT conductive networks but also can be removed in situ during the polymerization process, the density of resultant CNT/PI foam is only 32.1 mg·cm–3, and the EMI shielding effectiveness (EMI SE) is up to 41.1 dB, which represents one of the highest EMI SE values compared to previously reported polymer-based foams. The CNT/PI foam also achieves the absorption coefficient (A) of up to 82.3%, which is very impressive in CNT/polymer foams at comparable EMI SE levels. The PI matrix endows the foam with excellent heat resistance. The as-prepared CNT/PI foam presents a higher EMI SE than 35 dB even after being subjected to the flame of an alcohol burner. Moreover, the compressive strength and compressive modulus are up to 240.9 and 323.9 kPa. These results indicate its certain application potential in the harsh requirement of aeronautics and aerospace industries as a highly efficient and lightweight EMI shielding material.
A class of second order approximations, called the weighted and shifted Grünwald difference (WSGD) operators, are proposed for Riemann-Liouville fractional derivatives, with their effective ...applications to numerically solving space fractional diffusion equations in one and two dimensions. The stability and convergence of our difference schemes for space fractional diffusion equations with constant coefficients in one and two dimensions are theoretically established. Several numerical examples are implemented to test the efficiency of the numerical schemes and confirm the convergence order, and the numerical results for variable coefficients problem are also presented.
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