Regulating Benzene Ring Number as Connector in Covalent Organic Framework for Boosting Photosynthesis of H2O2 from Seawater.

Photosynthesis of H2O2 from seawater represents a promising pathway to acquire H2O2, but it is still restricted by the lack of a highly active photocatalyst. In this work, we propose a convenient strategy of regulating the number of benzene rings to boost the catalytic activity of materials. This is demonstrated by ECUT-COF-31 with adding two benzene rings as the connector, which can result in 1.7-fold enhancement in the H2O2 production rate relative to ECUT-COF-30 with just one benzene ring as the connector. The reason for enhancement is mainly due to the release of *OOH from the surface of catalyst and the final formation of H2O2 being easier in ECUT-COF-31 than in ECUT-COF-30. Moreover, ECUT-COF-31 provides a stable photogeneration of H2O2 for 70 h, and a theoretically remarkable H2O2 production of 58.7 mmol per day from seawater using one gram of photocatalyst, while the cost of the used raw material is as low as 0.24 $/g.

From Oxygen Redox to Sulfur Redox: A Paradigm for Li-Rich Layered Cathodes.

The utilization of anionic redox chemistry provides an opportunity to further improve the energy density of Li-ion batteries, particularly for Li-rich layered oxides. However, oxygen-based hosts still suffer from unfavorable structural rearrangement, including the oxygen release and transition metal (TM)-ion migration, in association with the tenuous framework rooted in the ionicity of the TM-O bonding. An intrinsic solution, by using a sulfur-based host with strong TM-S covalency, is proposed here to buffer the lattice distortion upon the highly activating sulfur redox process, and it achieves howling success in stabilizing the host frameworks. Experimental results demonstrate the prolonged preservation of the layered sulfur lattice, especially the honeycomb superlattice, during the Li+ extraction/insertion process in contrast to the large structural degeneration in Li-rich oxides. Moreover, the Li-rich sulfide cathodes exhibited a negligible overpotential of 0.08 V and a voltage drop of 0.13 mV/cycle, while maintaining a substantial reversible capacity upon cycling. These superior electrochemical performances can be unambiguously ascribed to the much shorter trajectories of sulfur in comparison to those of oxygen revealed by molecular dynamics simulations at a large scale (∼30 nm) and a long time scale (∼300 ps) via high-dimensional neural network potentials during the delithiation process. Our findings highlight the importance of stabilizing host frameworks and establish general guidance for designing Li-rich cathodes with durable anionic redox chemistry.

A Building Extraction Method for High-Resolution Remote Sensing Images with Multiple Attentions and Parallel Encoders Combining Enhanced Spectral Information.

Accurately extracting pixel-level buildings from high-resolution remote sensing images is significant for various geographical information applications. Influenced by different natural, cultural, and social development levels, buildings may vary in shape and distribution, making it difficult for the network to maintain a stable segmentation effect of buildings in different areas of the image. In addition, the complex spectra of features in remote sensing images can affect the extracted details of multi-scale buildings in different ways. To this end, this study selects parts of Xi'an City, Shaanxi Province, China, as the study area. A parallel encoded building extraction network (MARS-Net) incorporating multiple attention mechanisms is proposed. MARS-Net builds its parallel encoder through DCNN and transformer to take advantage of their extraction of local and global features. According to the different depth positions of the network, coordinate attention (CA) and convolutional block attention module (CBAM) are introduced to bridge the encoder and decoder to retain richer spatial and semantic information during the encoding process, and adding the dense atrous spatial pyramid pooling (DenseASPP) captures multi-scale contextual information during the upsampling of the layers of the decoder. In addition, a spectral information enhancement module (SIEM) is designed in this study. SIEM further enhances building segmentation by blending and enhancing multi-band building information with relationships between bands. The experimental results show that MARS-Net performs better extraction results and obtains more effective enhancement after adding SIEM. The IoU on the self-built Xi'an and WHU building datasets are 87.53% and 89.62%, respectively, while the respective F1 scores are 93.34% and 94.52%.

Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis 'Tomentosa', has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). AIM OF STUDY: The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. STUDY DESIGN: We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. MATERIALS AND METHODS: We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. RESULTS: Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. CONCLUSIONS: Our results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD.

Oxygen Redox Activation at Initial Cycle to Improve Cycling Stability for the Na0.83Li0.12Ni0.22Mn0.66O2 System.

Oxygen reactions are commonly used to increase the specific capacities of Na-ion batteries, especially for the NaxLiyTMO2 systems. Previous research focused on improving the stabilities of oxygen reactions to enhance cycling stability. However, the effects of oxygen reactions on the distribution of Li ions in the transition metal (TM) and alkali metal (AM) layers for the Na-ion battery are relatively unexplored and rarely employed. In this study, we employ a layered P2-Na0.83Li0.12Ni0.22Mn0.66O2 cathode to control the effects of the oxygen reactions on the distributions of Li ions in two layers. With oxygen-redox-activation-at-first-cycle (ORAFIC)-cycling, which cycled first within 2.0-4.6 V to activate oxygen redox and then cycled within 2.0-4.2 V, this cathode exhibited better cycling stability compared to low-voltage (LV)-cycling of 2.0-4.2 V and high-voltage (HV)-cycling of 2.0-4.6 V. Using nuclear magnetic resonance spectroscopy, electron paramagnetic resonance, inductively coupled plasma experiments, and X-ray diffraction, it is confirmed that ORAFIC-cycling stabilizes the crystal structure and distributions of Li ions in the TM and AM layers and reduces Li-ion loss, thus improving the cycling stability.

Quantitative and space-resolved in situ 1D EPR imaging for the detection of metallic lithium deposits.

The ability to monitor lithium deposition on the anodes in real time is becoming progressively more important due to the development of advanced anode technology. Given the fact that the detrimental Li deposits are always on the micron scale, electron paramagnetic resonance (EPR) happens to be a very effective and selective detection technology due to the skin effect. Here, quantitative in situ 1D EPR imaging is carried out with a magnetic field gradient to achieve a one-dimensional spatial resolution along the Li growth direction in a capillary cell. The quantification of Li deposits is carefully calibrated using a 1,1-diphenyl-2-picrylhydrazyl standard, and a processing method is presented to correct the double integration of the Dysonian line from the metallic Li. The Li deposition processes are compared in two different electrolytes. For the electrolyte containing fluoroethylene carbonate (FEC) additive, the fitting results of Dysonian lines suggest that the plated Li has a larger dimension of the microstructure and the stripping proceeds more uniformly. It thus accounts for the higher Coulombic efficiency in the electrolyte with FEC. In situ EPR imaging also suggests that the Sand's capacity varies with the electrolytes. The forced growth of dendritic Li is carried out at a very large current density using a derivative operando EPR method to monitor the growth locus of the Li dendrites, indicating a tip-growing mechanism. This work can be instructive for those who are engaged in the study of electro-deposited lithium using in situ EPR imaging technology.

Vanadium dissolution at 30 °C and its suppression at a low temperature of -20 °C for a Na3V1.5Cr0.5(PO4)3 cathode.

Na3V1.5Cr0.5(PO4)3 cycled at 30 °C shows fast capacity decay, due to the migration of V ions into the electrolyte and the loss of V3+/V4+ redox. A low temperature of -20 °C attenuates V-ion dissolution, retains V3+/V4+ redox and improves the electrochemical performance, favorable for use in cold climates and high-altitude drones.

Dual Honeycomb-Superlattice Enables Double-High Activity and Reversibility of Anion Redox for Sodium-Ion Battery Layered Cathodes.

Anion redox contributes to the anomalous capacity exceeding the theoretical limit of layered oxides. However, double-high activity and reversibility is challenging due to the structural rearrangement and potential oxygen loss. Here, we propose a strategy for constructing a dual honeycomb-superlattice structure in Na2/3 [Li1/7 Mn5/14 ][Mg1/7 Mn5/14 ]O2 to simultaneously realize high activity and reversibility of lattice O redox. Theoretical simulation and electrochemical tests show that [Li1/7 Mn5/14 ] superlattice units remarkably trigger the anion redox activity and enable the delivery of a record capacity of 285.9 mA g-1 in layered sodium-ion battery cathodes. Nuclear magnetic resonance and in situ X-ray diffraction reveal that [Mg1/7 Mn5/14 ] superlattice units are beneficial to the structure and anion redox reversibility, where Li+ reversibly shuttles between Na layers and transition-metal slabs in contrast to the absence of [Mg1/7 Mn5/14 ] units. Our findings underline the importance of multifunctional units and provide a path to advanced battery materials.

Influence of Patella Position on Soft Tissue Balance and Clinical Outcomes in Patients Undergoing Minimally Invasive Total Knee Arthroplasty, a Randomized Clinical Trial.

BACKGROUND: We hypothesized that subluxating patellar during minimally invasive total knee arthroplasty (MIS-TKA) would affect intraoperative soft tissue balance and postoperative clinical outcome. METHODS: From December 2018 to May 2020, 189 patients receiving primary MIS-TKA were enrolled. The gap-balance technique was used, with patients randomly assigned to undergo osteotomy and balance of soft tissue with patella reduced (group A; n = 93) or subluxated (group B; n = 96). The gap and varus?valgus angle were compared between groups in both extension and flexion position. The gap and varus?valgus angle were also compared before and after reducing patellar in group B. Femoral prosthesis rotation, mechanical femoral axis-to-tibial axis angle, Knee Society Score (KSS), visual analog scale (VAS), and range of motion (ROM) were compared postoperatively between two groups. Follow-up was 12 months. RESULTS: The flexion gap and the varus angle were significantly greater (0.4 mm and 0.7 degree) after patella reduction than before reduction, but the extension joint gap and varus angle were comparable before and after patella reduction. The femoral prosthesis tended to be internally rotated (0.65 degree) in group B. ROM and VAS was better in the group A than in group B at 1 month after surgery, but the differences were not significant at 3, 6 and 12 months. KSS was comparable between the groups after surgery. CONCLUSIONS: During MIS-TKA, as far as possible, soft tissue balance should be achieved with the patella reduced; otherwise, the femoral prosthesis may be installed more internally and, after patella reduction, the flexion gap and varus angle would increase. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000034106, https://www.chictr.org.cn/hvshowproject.aspx?id=39987.

Photothermal-triggered immunogenic nanotherapeutics for optimizing osteosarcoma therapy by synergizing innate and adaptive immunity.

Inadequate immune response remains a critical cause of immunotherapy failure in various tumor treatments. Herein, we offer a new approach to achieve a cross-talk between innate and adaptive immune responses based on a new nanoplatform for photothermal therapeutics. The nanoplatform was formed by linking titanium carbide MXene with Mn2+-contained ovalbumin (OVA), where it can trigger efficient mt-DNA presentation and the release of OVA and Mn2+ upon the irradiation of near-infrared laser. More importantly, the released mt-DNA and Mn2+ synergistically activate innate immunity via the cGAS-stimulator of the interferon genes signaling pathway, and the OVA and protein antigens from tumor cells enhance adaptive immunity. Furthermore, in an osteosarcoma model, we observed that the proposed nanoplatform leads to the effective presentation of tumor antigens, which boost the maturation of dendritic cells (DCs) to the hilt and thus improve the infiltration of cytotoxic T lymphocyte in primary and distant tumors. Collectively, our work not only demonstrates a method for constructing a new nanoplatform for photothermal therapeutics but also provides a general strategy for synchronously activating innate and adaptive immunities to promote the maturation of DCs for antimetastasis tumor therapy.

Macroporous chitin microspheres prepared by surfactant micelle swelling strategy for rapid capture of lead (II) from wastewater.

Heavy metal pollution of water source continues to be one of the most serious environmental problems which have attracted major global concern. Here, a macroporous chitin microsphere is prepared by surfactant micelle swelling strategy followed by modification with tetraethylenepentamine for Pb2+ removal from wastewater. The resultant adsorbent not only exhibits fast adsorption kinetic (>80% of its equilibrium uptake within 20 min) but also has high adsorption capacity of 218.4 ± 6.59 mg/g and excellent reusability (>75% of its initial adsorption capacity after five adsorption/desorption cycles). More importantly, under the continuous operating mode, the adsorbent can treat about 39,000 kg water/kg adsorbent, and the Pb2+ concentration decreases from 2000 µg/L to smaller than 10 µg/L, meeting the drinking water standard recommended by the World Health Organization (10 µg/L). All results indicate that the tetraethylenepentamine-modified macroporous chitin microspheres have great potential in the treatment of heavy metal contamination.

Heavy Fluorination via Ion Exchange Achieves High-Performance Li-Mn-O-F Layered Cathode for Li-Ion Batteries.

Lithium-excess manganese layered oxide Li2 MnO3 , attracts much attention as a cathode in Li-ion batteries, due to the low cost and the ultrahigh theoretical capacity (≈460 mA h g-1 ). However, it delivers a low reversible practical capacity (<200 mA h g-1 ) due to the irreversible oxygen redox at high potentials (>4.5 V). Herein, heavy fluorination (9.5%) is successfully implemented in the layered anionic framework of a Li-Mn-O-F (LMOF) cathode through a unique ion-exchange route. F substitution with O stabilizes the layered anionic framework, completely inhibits the O2 evolution during the first cycle, and greatly enhances the reversibility of oxygen redox, delivering an ultrahigh reversible capacity of 389 mA h g-1 , which is 85% of the theoretical capacity of Li2 MnO3 . Moreover, it also induces a thin spinel shell coherently forming on the particle surface, which greatly improves the surface structure stability, making LMOF exhibit a superior cycling stability (a capacity retention of 91.8% after 120 cycles at 50 mA g-1 ) and excellent rate capability. These findings stress the importance of stabilizing the anionic framework in developing high-performance low-cost cathodes for next-generation Li-ion batteries.

Adaptive Appointed-Time Consensus Control of Networked Euler-Lagrange Systems With Connectivity Preservation.

With consideration of motion control performance and efficient information communication, the synchronization problem on communication connectivity preservation and guaranteed consensus performance for networked mechanical systems has attracted considerable attention in recent years. Different from the existing works, this article investigates a brand-new appointed-time consensus control approach for uncertain networked Euler-Lagrange systems on a directed graph via exploring the prescribed performance control structure. First, a two-layer prescribed performance envelope is formulated via using an appointed-time convergent function for position-related and velocity-related consensus errors, respectively. Then, a simple state-feedback virtual controller with online adaptive performance adjustment is developed to preserve the communication connectivity. Moreover, to guarantee the velocity consensus of the networked systems and improve the position consensus accuracy, an appointed-time adaptive controller is designed by applying the norm inequality to the system uncertainties and external disturbances. Compared to the existing consensus control approaches, the prime advantage of the proposed one is that the constraints generated from the communication ranges are approximated by a time-varying contractive performance envelope, wherein, the appointed-time convergence and steady-state tracking accuracy are preassigned a priori. Meanwhile, no repeated logarithmic error transformations are required in the relevant controller design, which implies that the complexity of the devised control laws has decreased dramatically. Finally, two groups of illustrative examples are organized to validate the effectiveness of the proposed consensus control approach.

CXCR4 blockade sensitizes osteosarcoma to doxorubicin by inducing autophagic cell death via PI3K­Akt­mTOR pathway inhibition.

Doxorubicin is one of the most frequently used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to treatment failure. C­X­C motif chemokine receptor 4 (CXCR4) has been demonstrated to regulate OS progression and metastasis. However, whether CXCR4 is also involved in OS chemoresistance and its molecular mechanisms has yet to be fully elucidated. In the present study, CXCR4­mediated autophagy for OS chemotherapy was investigated by western blot analysis, transmission electron microscopy and confocal microscopy. CXCR4 silencing enhanced doxorubicin­induced apoptosis by reducing P­glycoprotein in CXCR4+ LM8 cells, while CXCR4 overexpression promoted OS doxorubicin resistance in CXCR4­ Dunn cells. Furthermore, CXCR4 silencing with or without doxorubicin increased the expression of beclin 1 and light chain 3B, and the number of autophagosomes and autolysosomes, as well as induced autophagic flux activation by suppressing the PI3K/AKT/mTOR signaling pathway. In addition, pretreatment with the autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogation­induced cell death. Finally, the CXCR4 antagonist AMD3100 synergistically reinforced the antitumor effect of doxorubicin in an orthotopic OS mouse model. Taken together, the present study revealed that CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Therefore, targeting the CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.

Bisphosphonated-immobilized porous cellulose monolith with tentacle grafting by atom transfer radical polymerization for selective adsorption of lysozyme.

Here, a m-xylene bisphosphonate immobilized tentacle-type cellulose monolith (BP-PCM) is prepared by atom transfer radical polymerization for lysozyme purification. In the preparation, the m-xylene bisphosphonate was anchored glycidyl methacrylate and then polymerized to enhance the flexibility of the ligands to improve lysozyme adsorption capacity, and glycerol monomethacrylate serves as spacer to further optimize the layers structure and ligands density of the grafted tentacles for satisfactory adsorption capacity. The maximum static and dynamic adsorption capacity (10% breakthrough) of BP-PCM reach to 169.6 and 102.6 mg mL-1, respectively. Moreover, BP-PCM displays weak nonspecific adsorption and is able to successfully enrich lysozyme from diluted chicken egg white, indicating the excellent selectivity. The results demonstrated that BP-PCM is promising for use as high-capacity protein chromatography.

'White cord syndrome', a rare but disastrous complication of transient paralysis after posterior cervical decompression for severe cervical spondylotic myelopathy and spinal stenosis: A case report.

Transient paralysis following spinal decompression surgery is a rare but devastating postoperative complication. Spinal cord ischemia-reperfusion injury has been identified as one of the crucial pathogenic factors contributing to the sudden neurological deterioration associated with spinal decompression surgery. 'White cord syndrome' is a characteristic imaging manifestation of spinal cord ischemia-reperfusion injury, referring to high intramedullary signal changes in the sagittal T2-weighted MRI scan with unexplained neurological deficits following surgical decompression. The present study reported on the case of a 51-year old male patient who suffered from acute left limb hemiplegic paralysis following posterior cervical laminectomy decompression for severe cervical spondylotic myelopathy and spinal stenosis, which were caused by ossification of the posterior longitudinal ligament. The patient's neurological function gradually improved after the immediate administration of high-dose methylprednisolone therapy combined with mannitol and neurotrophic drugs. At the 2-month follow-up, the intensity of the spinal cord signal on MRI had almost returned to normal and the 'white cord syndrome' had disappeared. However, the patient complained of postoperative neck swelling pain caused by cerebrospinal fluid leakage; therefore, an additional cerebrospinal fluid leakage exploration and neoplasty were performed. At 2 weeks after the second surgery, the patient's neck swelling pain was relieved and the area of cerebrospinal fluid leakage was significantly reduced. Despite the low incidence rate, surgeons should be aware of this complication, particularly when treating chronic severe cervical spinal stenosis with anterior or posterior decompression. Once transient paralysis occurs, early diagnosis and interventions are essential to reverse the neurological deficit.

Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children and adolescents. Currently, surgical resection combined with adjuvant chemotherapy has been standardized for OS treatment. Despite great advances in chemotherapy for OS, its clinical prognosis remains far from satisfactory; this is due to chemoresistance, which has become a major obstacle to improving OS treatment. Autophagy, a catabolic process through which cells eliminate and recycle their own damaged proteins and organelles to provide energy, can be activated by chemotherapeutic drugs. Accumulating evidence has indicated that autophagy plays the dual role in the regulation of OS chemoresistance by either promoting drug resistance or increasing drug sensitivity. The aim of the present review was to demonstrate thatautophagy has both a cytoprotective and an autophagic cell death function in OS chemoresistance. In addition, methods to detect autophagy, autophagy inducers and inhibitors, as well as autophagy­mediated metastasis, immunotherapy and clinical prognosis are also discussed.

MiR-92a modulates proliferation, apoptosis, migration, and invasion of osteosarcoma cell lines by targeting Dickkopf-related protein 3.

Osteosarcoma (OS) is recognized as a common malignant tumor with a high trend of metastasis and diffusion. Despite the progresses that have been made in surgery, chemotherapy, and radiotherapy in the recent decades, the prognosis of patients with OS still remains poor. MiRNAs are being increasingly considered as new therapeutic targets for OS treatment. Our research aims to investigate the regulatory impact of miR-92a in the development of OS. Quantitative real-time PCR (qRT-PCR) results revealed that the expression of miR-92a was aberrantly overexpressed in human OS cell lines. By using cell counting kit-8 (CCK-8) assays, colony formation assays, flow cytometric analyses and Transwell assays, our data suggested that up-regulation of miR-92a promoted the proliferation, migration, and invasion of MNNG and U2OS cells, while inhibiting their apoptosis. In contrast, the knockdown of miR-92a effectively reversed these cellular biological behaviors. Furthermore, bioinformatics analysis indicated that Dickkopf-related protein 3 (DKK3) was a possible target of miR-92a. Subsequently, negative regulation of miR-92a on DKK3 was observed, which further supported the direct binding between them. In addition, silencing DKK3 rescued the inhibitory effect of miR-92a inhibitor on the development of OS. To sum up, our study revealed that miR-92a played a carcinogenic role in the growth of OS by promoting the tumorigenesis of OS cells via targeting of DKK3, thus revealing a new therapeutic target for OS.

Alternol, a natural compound, exerts an anti-tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways.

Osteosarcoma (OS) is the most frequent primary malignant bone tumour. Alternol, a novel compound purified from microbial fermentation products exerts anti-tumour effects across several cancer types. The effect of alternol on human OS remains to be elucidated. We first evaluated the anti-tumour effect of alternol in several human OS cell lines in vitro and investigated its underlying mechanism. Alternol inhibited OS cell proliferation, migration and induced caspase-dependent apoptosis, G2/M cell cycle arrest in a dose and time-dependent manner. Moreover, alternol treatment inhibited signal transducer and activator of transcription-3 (STAT3) phosphorylation in 143B and MG63 human OS cells, as evaluated using a STAT3-dependent dual luciferase reporter system. Exposure to alternol resulted in excessive reactive oxygen species (ROS) generation and Jun amino-terminal kinases (JNK), extracellular signal-regulated kinases (ERK1/2) and p38 activation. Furthermore, alternol-induced cell death was significantly restored in the presence of the ROS scavenger, N-acetyl-l-cysteine (NAC) or a caspase inhibitor Z-VAD-FMK. NAC also prevented G2/M phase arrest and phosphorylation of mitogen-activated protein kinases (MAPK), but did not reverse STAT3 inactivation. Finally, alternol suppressed tumour growth in vivo in the nude mouse OS tibia orthotopic model. Immunohistochemistry revealed that alternol treatment resulted in down-regulation of phosph-STAT3 Tyr705 and up-regulation of cleaved caspase-3 and phosph-SAPK (Stress-activated protein kinases)/JNK expression. Taken together, our results reveal that alternol suppresses cell proliferation, migration and induces apoptosis, cell cycle arrest by modulating of ROS-dependent MAPK and STAT3 signalling pathways in human OS cells. Therefore, alternol is a promising candidate for developing anti-tumour drugs target OS.