Biomimetic Superstructured Interphase for Aqueous Zinc-Ion Batteries.

The practical application of aqueous zinc-ion batteries (AZIBs) is greatly challenged by rampant dendrites and pestilent side reactions resulting from an unstable Zn-electrolyte interphase. Herein, we report the construction of a reliable superstructured solid electrolyte interphase for stable Zn anodes by using mesoporous polydopamine (2D-mPDA) platelets as building blocks. The interphase shows a biomimetic nacre's "brick-and-mortar" structure and artificial transmembrane channels of hexagonally ordered mesopores in the plane, overcoming the mechanical robustness and ionic conductivity trade-off. Experimental results and simulations reveal that the -OH and -NH groups on the surface of artificial ion channels can promote rapid desolvation kinetics and serve as an ion sieve to homogenize the Zn2+ flux, thus inhibiting side reactions and ensuring uniform Zn deposition without dendrites. The 2D-mPDA@Zn electrode achieves an ultralow nucleation potential of 35 mV and maintains a Coulombic efficiency of 99.8% over 1500 cycles at 5 mA cm-2. Moreover, the symmetric battery exhibits a prolonged lifespan of over 580 h at a high current density of 20 mA cm-2. This biomimetic superstructured interphase also demonstrates the high feasibility in Zn//VO2 full cells and paves a new route for rechargeable aqueous metal-ion batteries.

A novel method of measuring proptosis with computed tomography.

BACKGROUND: Computed tomography (CT) can avoid interference factors and has been imported into some software to measure proptosis clinically as the golden standard. PURPOSE: To establish a new method for semi-automatically measuring the proptosis on CT and evaluate its accuracy and reproducibility. MATERIAL AND METHODS: A total of 50 orbital CT images were collected of healthy individuals, 25 patients with Graves ophthalmopathy (GO), and 25 patients with orbital fracture (OF). A new image processing software, MedrawHDC, was developed to semi-automatically measure the proptosis (MedrawHDC method). The classic radiological (CR) method (measuring proptosis with the software called Mimics) and MedrawHDC method were applied in all three groups (measured by observer S). Hertel's exophthalmometer (HE) method was also applied in the GO group. Moreover, two other observers were asked to measure the proptosis using MedrawHDC, to evaluate its reproducibility. RESULTS: The MedrawHDC method was highly consistent with the CR method in measuring proptosis (normal group: intraclass correlation coefficient [ICC] = 0.989; GO group: ICC = 0.979; OF group: ICC = 0.979). In the GO group, the value of proptosis measured by two radiological methods were consistent with that measured by the HE method (CR method: ICC = 0.703; MedrawHDC method: ICC = 0.697). Bland-Altman plots showed similar results. The measurements obtained by three observers were highly reproducible (ICC = 0.995). CONCLUSION: The newly established MedrawHDC method, with high accessibility, convenience, and repeatability, is reliable in assessing proptosis. It shows high potential for wide application, having clinical value for scientific evaluation of proptosis.

Application of optical flow algorithm for drift correction in electron microscopy images.

Transmission electron microscopy (TEM) image drift correction has been effectively addressed using diverse approaches, including the cross correlation algorithm (CC) and other strategies. However, most of the strategies fall short of achieving sufficient accuracy or cannot strike a balance between time consumption and accuracy. The present study proposes a TEM image drift correction strategy that enhances accuracy without any additional time consumption. Unlike the CC algorithm that matches pixels one by one, our approach involves the extraction of multiple feature points from the first TEM image and then uses the Lucas-Kanade (LK) optical flow algorithm to calculate the optical field of these feature points in the subsequent TEM images. The LK algorithm is used to calculate the instantaneous velocity of these feature points, which can help track the movement of the TEM image series. In addition, a high-precision sub-pixel level correction strategy by the utilization of linear interpolation during the correction process is developed in this work. Experimental results confirm that this strategy offers superior accuracy in comparison with the CC algorithm and also is insensitive to the size of the image. Furthermore, we offer a semantic segmentation neural network for electron microscope image pre-processing, thereby expanding the applicability of our methodology.

Photoinduced intramolecular carbosulfonylation of alkynes: access to sulfone-containing dibenzazepines from sulfur dioxide.

A photoinduced three-component reaction of N-benzyl-N-(2-ethynylaryl)amides, sulfur dioxide and aryldiazonium tetrafluoroborates is developed, providing an efficient and straightforward approach for the synthesis of diverse vinylsulfonylated dibenzazepine derivatives in moderate to good yields under mild conditions. This transformation proceeds smoothly at room temperature in the presence of visible light, which shows a wide range of substrate scope with good functional group compatibility. The synthetic utility of this methodology is further demonstrated through Suzuki coupling. Mechanistic studies show that this reaction is triggered by the addition of an arylsulfonyl radical to an alkyne from sulfur dioxide, followed by vinyl radical cyclization to afford the desired sulfonated dibenzazepines.

Automatic orbital computed tomography coordinating method and quantitative error evaluation based on signed distance field.

BACKGROUND: Orbital computed tomography (CT) is commonly used for the diagnosis and digital evaluation of orbital diseases. Yet, this approach requires longer scanning time, increased radiation exposure, and, especially, difficult patient positioning that can affect judgment and data processing. According to high-quality research on orbital imaging, computer-assisted surgery, and artificial intelligent diagnostic development, the correction of a coordinate system is a necessary procedure. Nevertheless, existing manual calibration methods are challenging to reproduce and there is no objective evaluation system for errors. PURPOSE: To establish a method for automatic calibration of orbital CT images and implementation of quantitative error evaluation. MATERIAL AND METHODS: A standard three-dimensional (3D) orbit model was manually adjusted, and optimized orbital models were reconstructed based on the initial registration of the skull-bound directed bounding box and the registration of the mutual information method. The calibration error was calculated based on the signed distance field. Seventeen cases of orbital CT were quantitatively evaluated. RESULTS: A new method for automatic calibration and quantitative error evaluation for orbital CT was established. The calibrated model error with ±2 mm accounted for 81.61% ± 6.91% of the total models, and the error of ±1 mm accounted for 53.49% ± 7.07% of the total models. CONCLUSION: This convenient tool for orbital CT automatic calibration may promote the related quantitative research based on orbital CT. The automated operation and small error are beneficial to the popularization and application of the tool, and the quantitative evaluation facilitates other coordinate systems.

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways.

BACKGROUND: Aseptic prosthetic loosening is one of the main factors causing poor prognosis of limb function after joint replacement and requires troublesome revisional surgery. It is featured by wear particle-induced periprosthetic osteolysis mediated by excessive osteoclasts activated in inflammatory cell context. Some natural compounds show antiosteoclast traits with high cost-efficiency and few side effects. Tussilagone (TUS), which is the main functional extract from Tussilago farfara generally used for relieving cough, asthma, and eliminating phlegm in traditional medicine has been proven to appease several RAW264.7-mediated inflammatory diseases via suppressing osteoclast-related signaling cascades. However, whether and how TUS can improve aseptic prosthetic loosening via modulating osteoclast-mediated bone resorption still needs to be answered. METHODS: We established a murine calvarial osteolysis model to detect the preventative effect of TUS on osteolysis in vivo. Micro-CT scanning and histomorphometric analysis were used to determine the variation of bone resorption and osteoclastogenesis. The anti-osteoclast-differentiation and anti-bone-resorption bioactivities of TUS in vitro were investigated using bone slice resorption pit evaluation, and interference caused by cytotoxicity of TUS was excluded according to the CCK-8 assay results. Quantitative polymerase chain reaction (qPCR) analysis was applied to prove the decreased expression of osteoclast-specific genes after TUS treatment. The inhibitory effect of TUS on NF-κB and p38 MAPK signaling pathways was testified by Western blot and NF-κB-linked luciferase reporter gene assay. RESULTS: TUS better protected bones against osteolysis in murine calvarial osteolysis model with reduced osteoclasts than those in the control group. In vitro studies also showed that TUS exerted antiosteoclastogenesis and anti-bone-resorption effects in both bone marrow macrophages (BMMs) and RAW264.7 cells, as evidenced by the decline of osteoclast-specific genes according to qPCR. Western blotting revealed that TUS treatment inhibited IκBα degradation and p38 phosphorylation. CONCLUSIONS: Collectively, our studies proved for the first time that TUS inhibits osteoclastogenesis by suppressing the NF-κB and p38 MAPK signaling pathways, therefore serving as a potential natural compound to treat periprosthetic osteolysis-induced aseptic prosthetic loosening.

Effect of DEC1 on the proliferation, adhesion, invasion and epithelial-mesenchymal transition of osteosarcoma cells.

Differentiated embryonic chondrocyte-expressed gene 1 (DEC1) is associated with various types of human cancer; however, there is limited data regarding the functions of DEC1 in osteosarcoma. The present study aimed to examine the expression of DEC1 in human osteosarcoma tissues and cell lines. Furthermore, the effects of DEC1 on the proliferation, adhesion, invasion and epithelial-mesenchymal transition (EMT) of osteosarcoma cells were investigated. Using reverse transcription-quantitative PCR and western blot analysis, it was found that the expression levels of DEC1 were higher in human osteosarcoma tissues and osteosarcoma cell lines than in the controls. Both gain- and loss-of-function experiments suggested that DEC1 promotes the proliferation, adhesion and invasion of osteosarcoma cells in vitro, as determined by MTT, cell adhesion and cell invasion assays, respectively. Additionally, DEC1 was found to upregulate the mesenchymal markers N-cadherin and vimentin, whilst downregulating the epithelial marker E-cadherin. In conclusion, this present study showed increased expression levels of DEC1 in human osteosarcoma tissues and cell lines, and identified that DEC1 may exert its effect on osteosarcoma progression by promoting cell proliferation, adhesion and invasion. Furthermore, DEC1 was shown to have an inducible effect on EMT in osteosarcoma cell lines, thus contributing to the aggressiveness of osteosarcoma cells. This initial study indicated that DEC1 may serve as a novel molecular target for the treatment of osteosarcoma.

Correction: Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.

[This corrects the article DOI: 10.18632/oncotarget.22930.].

Proanthocyanidins attenuate breast cancer-induced bone metastasis by inhibiting Irf-3/c-jun activation.

We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.

Glycyrrhizic acid suppresses osteoclast differentiation and postmenopausal osteoporosis by modulating the NF-κB, ERK, and JNK signaling pathways.

Postmenopausal osteoporosis, mainly caused by osteoclast-induced bone resorption, has become a global public health burden. Natural compounds are emerging as potential therapeutics for postmenopausal osteoporosis. In vitro osteoclastogenesis assay was conducted to investigate the effect of Glycyrrhizic acid (Gly) on osteoclast differentiation without cytotoxity. We applied bone resorption pit assessment and F-actin immunofluoresence to explore the effect of Gly on osteoclasts function in vitro. RT-qPCR was used to evaluate the expression level of RANKL-induced osteoclast-specific gene. Western blotting was conducted for analyzing potential mechanisms of inhibitory influence of Gly on the formation and function of osteoclasts in vitro. Ovariectomized (OVX) mice model, micro-CT and histomorphometry was used to survey the potential effect of Gly on the resorption of bone in vivo. Gly inhibited osteoclast differentiation and function without significant cytotoxicity at a dose of no more than 8 mM in vitro. Gly attenuated mRNA expression of osteoclast-specific genes including NFATc1, c-fos, TRAP, CTR, cathepsin K, and V-ATPase d2 in vitro. Gly inhibited degradation of IκBα, phosphorylation of ERK and JNK without disturbing phosphorylation of p38 after treating osteoclasts in vitro. In OVX mice, Gly attenuates osteoclast formation and preserves bone mass and trabecular structure. Gly can effectively inhibit osteoclast maturation and bone resorption by suppressing NF-κB, ERK, and JNK pathway in vitro and exhibits an osteoprotective effect in OVX mice.

CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice.

Osteoblastic bone formation and osteoclastic bone resorption dynamically maintain the bone homeostasis; in the present study, we attempt to investigate the mechanism of the excessive activation of osteoclasts inducing the deregulation of bone homeostasis from the perspective of non-coding RNA regulation. Differentially expressed patterns of circRNAs were examined in non-treated and RANKL + CSF1-treated bone marrow monocyte/macrophage (BMM) cells and differentially-expressed miRNAs during osteoclast differentiation were analyzed and identified. We found that circRNA_28313 was significantly induced by RANKL + CSF1 treatment. circRNA_28313 knockdown significantly inhibited RANKL + CSF1-induced differentiation of osteoclasts within BMM cells in vitro, while suppressed ovariectomized (OVX)-induced bone resorption in mice in vivo. Via bioinformatics analyses, it has been demonstrated that miR-195a might bind to circRNA_28313 and CSF1 and together form a circRNA-miRNA-mRNA network. circRNA_28313 relieves miR-195a-mediated suppression on CSF1 via acting as a ceRNA, therefore modulating the osteoclast differentiation in BMM cells. In conclusion, circRNA_28313, miR-195a, and CSF1 form a ceRNA network to function in RANKL + CSF1-induced osteoclast differentiation, thus affecting OVX-induced bone absorption in mice.

Proanthocyanidins inhibit osteoclast formation and function by inhibiting the NF-κB and JNK signaling pathways during osteoporosis treatment.

Osteoporosis is a metabolic bone lesion in which the bone mass is reduced per unit volume due to increased bone resorption. Its main characteristics are bone pain and increasing danger of fragility fracture. Excessive osteoclast activation is known to be responsible for extensive bone resorption. Thus, inhibition of osteoclastic bone resorption and regulation of the bone microenvironment are vital treatment strategies for osteoporosis. For the first time, we investigated the effect of proanthocyanidins (PACs) extracted from grape seed, which significantly inhibited osteoclast formation and differentiation from bone marrow macrophages (BMMs) and the RAW264.7 cell line and efficiently attenuated osteoclastic bone resorption without toxicity. These findings were confirmed by changes in the NF-κB and JNK/mitogen-activated protein kinase (MAPK) signaling pathways, which are major and classical signaling pathways involved in RANKL-mediated osteoclastogenesis in vitro. The PACs inhibited osteoclast formation and differentiation by inhibiting the NF-κB and JNK signaling pathways and might be useful for the treatment of osteoporosis.

Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.

Bone is the most common target organ of metastasis of breast cancers. This produces considerable morbidity due to skeletal-related events, and severely reduces the quality of life. Increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of hypericin, a natural plant compound, led us to investigate whether hypericin could inhibit bone metastasis and osteolysis caused by breast cancer. We find that hypericin inhibited the upregulation of osteoclasts stimulated by breast cancer cells. The activity of hypericin on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of NFATc1 signaling pathway and attenuation of Ca2+ oscillation. Furthermore, hypericin suppresses invasion and migration in breast cancer cells, but has little effect on breast cancer-cell induced RANKL/OPG ratio in osteoblast or the expression of osteoclast-activating factors. Administration of hypericin could reduce tumor burden, osteolysis induced by direct inoculation of MDA-MB-231 cells into the bone marrow cavity of the tibia as well as metastasis of bone and improve survival in an experimental metastasis model by intracardiac injection of MDA-MB-231 breast cancer cells. Taken together, these results suggest that hypericin may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.