MicroRNA-1296-5p suppresses the proliferation, migration, and invasion of human osteosarcoma cells by targeting NOTCH2.

Osteosarcoma (OS) is a highly aggressive bone tumor with a poor prognosis. MicroRNAs are revealed to exerts essential roles in the carcinogenesis and tumor invasion of OS. But, the function of miR-1296-5p and its related mechanism in OS progression have not yet been studied. This study discovered the levels of miR-1296-5p in OS and corresponding noncancerous tissues, and we demonstrated that miR-1296-5p level was markedly downregulated in tumor specimens as compared with nontumor tissues. In addition, we discovered that miR-1296-5p was also underexpressed in OS cells compared with the hFOB1.19 osteoblast cells. Interestingly, the reduced expression of miR-1296-5p was confirmed to associated with large tumor size, advanced tumor stages, and distance metastasis, respectively. Patients with OS low-expressing miR-1296-5p showed a prominent shorter survival. In addition, gain-of-function assays verified that miR-1296-5p overexpression remarkably repressed OS cell proliferation, migration, and invasion. Conversely, depletion of miR-1296-5p facilitated the growth and mobility of OS cells. Notably, miR-1296-5p inversely modulated notch receptor 2 (NOTCH2) in OS cells. The level of NOTCH2 messenger RNA was negatively correlated with miR-1296-5p level in OS samples. NOTCH2 knockdown markedly suppressed the abilities of MG-63 cell proliferation and mobility. More importantly, the restoration of NOTCH2 prominently rescued miR-1296-5p-induced tumor-suppressive effects on MG-63 cells. In conclusion, our study identified the reduced expression of miR-1296-5p, which contributed to OS progression. miR-1296-5p might be a promising prognostic marker and therapeutic target in OS.

MicroRNA-552 promotes migration and invasion of osteosarcoma through targeting TIMP2.

Aberrant miRNAs play important roles in tumor development and progression. Previous studies reported that miR-552 was dysregulated expressed in multiple cancers. However, its biological effects and underlying mechanism in osteosarcoma remains largely unknown. In present research, we demonstrated that miR-552 was significantly up-regulated in both osteosarcoma cell lines and tissues for the first time. Its high-expression was significantly associated with poor prognostic features and overall survival of osteosarcoma patients. Gain- and loss-of-function experiment confirmed that miR-552 promoted cell migration, invasion and MMPs expression. Moreover, TIMP2 was a direct downstream target of miR-552. miR-552 inversely correlated with TIMP2 in osteosarcoma tissues. TIMP2 restoration at least partially abolished the migration, invasion and MMPs expression of miR-552 on osteosarcoma cells. Above all, our data suggest that miR-552 promoted migration, invasion and MMPs expression of osteosarcoma by targeting TIMP2, and represent a novel potential therapeutic target for osteosarcoma.

Interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma after hepatectomy: a multicenter population-based study.

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making.

The Fabrication of Ultrahigh-Strength Steel with a Nanolath Structure via Quenching-Partitioning-Tempering.

A novel low-alloy ultrahigh-strength steel featuring excellent mechanical properties and comprising a nanolath structure was fabricated in this work using a quenching-partitioning-tempering (Q-P-T) process. The Q-P-T process comprised direct quenching and an isothermal bainitic transformation for partitioning after thermo-mechanical control processing (online Q&P) and offline tempering (reheating and tempering). The ultrafine nanolath martensite/bainite mixed structure, combined with residual austenite in the form of a thin film between the nanolaths, was formed, thereby conferring excellent mechanical properties to the steel structures. After the Q-P-T process, the yield and tensile strengths of the steels reached 1450 MPa and 1726 MPa, respectively. Furthermore, the Brinell hardness and elongation rate were 543 HB and 11.5%, respectively, with an average impact energy of 20 J at room temperature.

Atomic scale disorder and reconstruction in bulk infinite-layer nickelates lacking superconductivity.

The recent discovery of superconductivity in infinite-layer nickelate films has sparked significant interest and expanded the realm of superconductors, in which the infinite-layer structure and proper chemical doping are both of the essence. Nonetheless, the reasons for the absence of superconductivity in bulk infinite-layer nickelates remain puzzling. Herein, we investigate atomic defects and electronic structures in bulk infinite-layer Nd0.8Sr0.2NiO2 using scanning transmission electron microscopy. Our observations reveal the presence of three-dimensional (3D) block-like structural domains resulting from intersecting defect structures, disrupting the continuity within crystal grains, which could be a crucial factor in giving rise to the insulating character and inhibiting the emergence of superconductivity. Moreover, the infinite-layer structure, without complete topotactic reduction, retains interstitial oxygen atoms on the Nd atomic plane in bulk nickelates, possibly further aggravating the local distortions of NiO2 planes and hindering the superconductivity. These findings shed light on the existence of structural and atomic defects in bulk nickelates and provide valuable insights into the influence of proper topotactic reduction and structural orders on superconductivity.

Approaching the Ideal Linearity in Epitaxial Crystalline-Type Memristor by Controlling Filament Growth.

Brain-inspired neuromorphic computing has attracted widespread attention owing to its ability to perform parallel and energy-efficient computation. However, the synaptic weight of amorphous/polycrystalline oxide based memristor usually exhibits large nonlinear behavior with high asymmetry, which aggravates the complexity of peripheral circuit system. Controllable growth of conductive filaments is highly demanded for achieving the highly linear conductance modulation. However, the stochastic behavior of the filament growth in commonly used amorphous/polycrystalline oxide memristor makes it very challenging. Here, the epitaxially grown Hf0.5Zr0.5O2-based memristor with the linearity and symmetry approaching ideal case is reported. A layer of Cu nanoparticles is inserted into epitaxially grown Hf0.5Zr0.5O2 film to form the grain boundaries due to the breaking of the epitaxial growth. By combining with the local electric field enhancement, the growth of filament is confined in the grain boundaries due to the fact that the diffusion of oxygen vacancy in crystalline lattice is more difficult than that in the grain boundaries. Furthermore, the decimal operation and high-accuracy neural network are demonstrated by utilizing the highly linear and multi-level conductance modulation capacity. This method opens an avenue to control the filament growth for the application of resistance random access memory (RRAM) and neuromorphic computing.

Bortezomib inhibits hepatocellular carcinoma via the Hippo-Yes-associated protein signalling pathway.

Hepatocellular carcinoma (HCC) is one of the principle causes of cancer-associated death throughout the world. However, the patients with HCC are insensitive to traditional drugs and lack effective therapeutic drugs. Dysregulation of Hippo-Yes-associated protein (YAP) signalling is closely associated with HCC. Bortezomib (BTZ) is mainly used in clinical multiple myeloma. It has recently been confirmed that BTZ could suppress cell proliferation in many different types of cancer. Nevertheless, the precise effects of BTZ on HCC and its possible interactions with the Hippo-YAP signalling pathway in HCC cells remain largely unknown. In this study, HCC cell lines (HepG2 and Huh7) and nude mice with xenograft tumours were used to evaluate the influences of BTZ. Furthermore, we focused on exploring whether BTZ exerts its anti-HCC effect through the Hippo-YAP signalling pathway and aimed to lay a theoretical foundation for BTZ as a potential therapeutic drug for HCC. Herein, our results disclose a new mechanism of BTZ in controlling the cell growth of HCC. BTZ downregulates the level of YAP by promoting LATS1 expression to inhibit the growth of HCC cells, which leads to the phosphorylation of YAP and limits YAP nuclear translocation. In sum, our data confirmed that the Hippo-YAP signalling pathway mediates the anti-HCC effects of BTZ.

EuHD1 protects against inflammatory injury driven by NLRP3 inflammasome.

Non-steroidal anti-inflammatory drugs (NSAIDs) possessing anti-inflammatory, analgesic and antipyretic activities, are widely used in the treatment of osteoarthritis, rheumatism and rheumatoid arthritis. However, its long-term or large use will cause serious gastrointestinal injury or cardiovascular adverse reactions, which limits its clinical application. We have synthesized a new class of NSAIDs, EuHD1, which can release hydrogen sulfide and have better gastrointestinal safety. However, the anti-inflammatory molecular mechanism of the drug is still unclear. In this paper, we explored the mechanism of EuHD1 on NLRP3 inflammasome and its effects on acute lung injury and acute liver injury in mice. In vitro results demonstrated that EuHD1 inhibited macrophage pyroptosis and LDH release induced by LPS combined with ATP. In addition, EuHD1 blocked NLRP3 inflammasome activation and suppressed following Caspase-1 activation and secretion of mature IL-1ß. EuHD1 restrained intracellular ROS production and the formation of ASC oligomers, which inhibited the assembly and activation of NLRP3 inflammasome. In vivo results further showed that EuHD1 alleviated LPS-induced acute lung injury in mice, and inhibited the production of mature IL-1ß and Caspase-1 (p20). Besides, EuHD1 improved D-GalN/LPS-induced acute liver injury, and inhibited SOD/MDA levels and oxidative stress injury, and blocked the activation of NLRP3 inflammasome. In summary, we found that EuHD1 inhibits the assembly and activation of NLRP3 inflammasome through restraining the production of ROS and the formation of ASC oligomers, and has therapeutic effects on acute lung injury and liver injury in mice, indicating that EuHD1 has the potential to treat NLRP3 inflammasome-related diseases.

Visualizing the Atomic Configuration of Carbonate Groups in a (Cu,C)Ba2 Ca3 Cu4 O11+δ Superconductor.

Carbonates (CO3 2- ) have always been known as impurities to degrade the superconductivity in cuprate high-Tc superconductors. Herein, the atomic arrangement of carbonates is directly visualized in (Cu,C)Ba2 Ca3 Cu4 O11+δ via integrated differential phase contrast (iDPC) combined with state-of-the-art scanning transmission electron microscopy. The carbon atoms replace Cu atoms in the charge-reservoir layers, contributing to the formation of carbonates through strong orbital hybridization with the surrounding oxygen atoms. Using first-principles calculations, the spatial configuration of the carbonate groups is confirmed and their influence on the local crystal lattice and electronic states is further investigated. The carbonates not only accommodate distortions by improving the flatness of the outer CuO2 layers but also reduce the density of states at the Fermi level. These two factors play competitive roles to affect the superconductivity. This study provides direct evidence of the presence of CO3 2- groups and gains an insight into the underlying mechanism of superconductivity in oxycarbonate superconductors.

Polarity Modulation Induced High Electrostrain Performance with Near-Zero Hysteresis in a (Sr0.7Bi0.2□0.1)TiO3-Based System.

High-precision piezo actuators necessitate dielectrics with high electrostrain performance with low hysteresis. Polarity-modulated (Sr0.7Bi0.2□0.1)TiO3-based ceramics exhibit extraordinarily discrete multiphase coexistence regions: (i) the relaxor phase coexistence (RPC) region with local weakly polar tetragonal (T) and pseudocubic (Pc) short-range polar nanodomains and (ii) the ferroelectric phase coexistence (FPC) region with T long-range domains and Pc nanodomains. The RPC composition features a specially high and pure electrostrain performance with near-zero hysteresis (S ∼ 0.185%, Q33 ∼ 0.038 m4·C-2), which is double those of conventional Pb(Mg1/3Nb2/3)O3-based ceramics. Particular interest is paid to the RPC and FPC with multiscale characterization to unravel local structure-performance relationships. Guided by piezoelectric force microscopy, scanning transmission electron microscopy, and phase-field simulations, the RPC composition with multiphase low-angle weakly polar nanodomains shows local structural heterogeneity and contributes to a flat local free energy profile and thus to nanodomain switching and superior electrostrain performance, in contrast to the FPC composition with a macroscopic domain that shows stark hysteresis. This work provides a paradigm to design high-precision actuator materials with large electrostrain and ultralow hysteresis, extending our knowledge of multiphase coexistence species in ferroelectrics.

Opening the Bandgap of Metallic Half-Heuslers via the Introduction of d-d Orbital Interactions.

Half-Heusler compounds with semiconducting behavior have been developed as high-performance thermoelectric materials for power generation. Many half-Heusler compounds also exhibit metallic behavior without a bandgap and thus inferior thermoelectric performance. Here, taking metallic half-Heusler MgNiSb as an example, a bandgap opening strategy is proposed by introducing the d-d orbital interactions, which enables the opening of the bandgap and the improvement of the thermoelectric performance. The width of the bandgap can be engineered by tuning the strength of the d-d orbital interactions. The conduction type and the carrier density can also be modulated in the Mg1- x Tix NiSb system. Both improved n-type and p-type thermoelectric properties are realized, which are much higher than that of the metallic MgNiSb. The proposed bandgap opening strategy can be employed to design and develop new half-Heusler semiconductors for functional and energy applications.

Achieving Record-High Photoelectrochemical Photoresponse Characteristics by Employing Co3O4 Nanoclusters as Hole Charging Layer for Underwater Optical Communication.

The physicochemical properties of a semiconductor surface, especially in low-dimensional nanostructures, determine the electrical and optical behavior of the devices. Thereby, the precise control of surface properties is a prerequisite for not only preserving the intrinsic material quality but also manipulating carrier transport behavior for promoting device characteristics. Here, we report a facile approach to suppress the photocorrosion effect while boosting the photoresponse performance of n-GaN nanowires in a constructed photoelectrochemical-type photodetector by employing Co3O4 nanoclusters as a hole charging layer. Essentially, the Co3O4 nanoclusters not only alleviate nanowires from corrosion by optimizing the oxygen evolution reaction kinetics at the nanowire/electrolyte interface but also facilitate an efficient photogenerated carrier separation, migration, and collection process, leading to a significant ease of photocurrent attenuation (improved by nearly 867% after Co3O4 decoration). Strikingly, a record-high responsivity of 217.2 mA W-1 with an ultrafast response/recovery time of 0.03/0.02 ms can also be achieved, demonstrating one of the best performances among the reported photoelectrochemical-type photodetectors, that ultimately allowed us to build an underwater optical communication system based on the proposed nanowire array for practical applications. This work provides a perspective for the rational design of stable nanostructures for various applications in photo- and biosensing or energy-harvesting nanosystems.

A Review of SMA-Based Actuators for Bidirectional Rotational Motion: Application to Origami Robots.

Shape memory alloys (SMAs) are a group of metallic alloys capable of sustaining large inelastic strains that can be recovered when subjected to a specific process between two distinct phases. Regarding their unique and outstanding properties, SMAs have drawn considerable attention in various domains and recently became appropriate candidates for origami robots, that require bi-directional rotational motion actuation with limited operational space. However, longitudinal motion-driven actuators are frequently investigated and commonly mentioned, whereas studies in SMA-based rotational motion actuation is still very limited in the literature. This work provides a review of different research efforts related to SMA-based actuators for bi-directional rotational motion (BRM), thus provides a survey and classification of current approaches and design tools that can be applied to origami robots in order to achieve shape-changing. For this purpose, analytical tools for description of actuator behaviour are presented, followed by characterisation and performance prediction. Afterward, the actuators' design methods, sensing, and controlling strategies are discussed. Finally, open challenges are discussed.

On the Evolution of Temperature and Combined Stress in a Work Roll under Cyclic Thermo-Mechanical Loadings during Hot Strip Rolling and Idling.

An accurate prediction of temperature and stress evolution in work rolls is crucial to assess the service life of the work roll. In this paper, a finite element method (FEM) model with a deformable work roll and a meshed, rigid body considering complex thermal boundary conditions over the roll surface is proposed to assess the temperature and the thermal stress in work rolls during hot rolling and subsequent idling. After that, work rolls affected by the combined action of temperature gradient and rolling pressure are investigated by taking account of the hot strip. The accuracy of the proposed model is verified through comparison with the calculation results obtained from the mathematical model. The results show that thermal stress is dominant in the bite region of work rolls during hot rolling. Afterwards, the heat treatment residual stresses which are related to thermal fatigue are simulated and introduced into the work roll as the initial stress to evaluate the redistribution under the thermal cyclic loads during the hot rolling process. Results show that the residual stress significantly changed near the roll surface.

Development of a Multiresidue Method for Endocrine-Disrupting Pesticides by Solid Phase Extraction and Determination by UHPLC-MS/MS from Drinking Water Samples.

A rapid and efficient method based on solid phase extraction and liquid chromatography-tandem mass spectrometry was validated, allowing the determination of the endocrine-disrupting herbicides (acetochlor, alachlor, amitrole and atrazine), fungicides (carbendazim, triadimefon, penconazole and propiconazole), and insecticides (carbaryl and carbofuran) in drinking water. Low method detection limits (0.01-0.64 ng/L) and method quantification limits (0.03-2.13 ng/L) were obtained with satisfactory recoveries and precision for the endocrine-disrupting pesticides. The method was applied for real drinking water samples collected in the area of the city of Hangzhou (Zhejiang, China); the results showed that carbendazim, atrazine and acetochlor were detected in the drinking water samples and acetochlor was the most detected analyte.

LncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis.

Long non-coding RNAs (lncRNAs) play a key role in regulating tumor growth and metastasis of osteosarcoma (OS). Recent studies have reported that lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in OS tissues and contributes to the proliferation, migration and invasion of OS cells. However, the molecular mechanism involved in the oncogenic role of SNHG16 in OS remains poorly known. In the current study, we confirmed that SNHG16 expression was markedly up-regulated in OS tissues compared to paracancerous tissues. The elevated level of SNHG16 closely associated with advanced tumor stages, larger tumor size and more distance metastasis. Furthermore, OS patients with high SNHG16 level had a significant poorer overall survival compared to patients with low SNHG16 level. Knockdown of SNHG16 suppressed the proliferation, migration and invasion of U2OS and MG63 cells. Mechanistically, SNHG16 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-1301 and inversely regulated its abundance in OS cells. Notably, suppression of miR-1301 rescued SNHG16 knockdown attenuated OS cell proliferation, migration and invasion. SNHG16 knockdown reduced the expression of BCL9 protein in OS cells. Accordingly, BCL9 restoration facilitated the proliferation, migration and invasion of OS cells with SNHG16 knockdown. Collectively, these results suggest that SNHG16 is a potential prognostic biomarker for OS patients. SNHG16 promotes BCL9 expression by sponging miR-1301 to facilitate the proliferation, migration and invasion of OS cells.

MicroRNA-1301 inhibits migration and invasion of osteosarcoma cells by targeting BCL9.

Increasing reports demonstrated that miRNAs play a critical role in tumor development and progression. Previous studies revealed that miR-1301 was abnormally expressed in various cancers. However, its function and underlying mechanism in osteosarcoma (OS) remains unknown. In this study, miR-1301 expression was significantly down-regulated in both OS tissues and cell lines. Down-regulated miR-1301 was obviously associated with malignant clinical features and poor overall survival of OS patients. miR-1301 overexpression inhibited cell proliferation, migration and invasion. In addition, we identified BCL9 act as a direct target of miR-1301 by directly binding to its 3'-UTR. In clinical OS tissues, miR-1301 negatively correlated BCL9 expression. BCL9 was up-regulated in OS tissues and cells. BCL9 overexpression promoted OS progression. Moreover, restoration of BCL9 expression at least partially abolished the proliferation, migration and invasion of miR-1301 on OS cells. In conclusion, our data indicated that miR-1301 inhibited cell proliferation, migration and invasion of OS by targeting BCL9, and may represent a novel potential therapeutic target and prognostic marker for OS.

Derivatization method for sensitive determination of fluorotelomer alcohols in sediment by liquid chromatography-electrospray tandem mass spectrometry.

Fluorotelomer alcohols (FTOHs) are the main precursors of environmentally ubiquitous perfluorinated acids, and determination of FTOHs at low concentrations presents significant challenges. In this study, a new liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) method in conjunction with low-energy collision dissociation tandem mass spectrometry (CID-MS/MS) was developed by employing an optimized derivatization reaction with dansyl chloride (DNS) in acetonitrile under catalysis of 4-(dimethylamino)-pyridine (DMAP). The instrument detection limits (IDLs) of the newly developed method were 0.014, 0.015, 0.014, 0.0075 and 0.0093µg/L for 4:2 FTOH, 6:2 FTOH, 8:2 FTOH, 10:1 FTOH and 10:2 FTOH respectively, which were 7.5-241 times lower than those without derivatizaiton and 57-357 times lower than previous GC/MS method. The method was successfully applied to analyze FTOHs in sediments combined with WAX and silica cartridges cleanup. The overall method recoveries were from 67±6.0% to 83±9.4% with matrix effects of <15%. The limits of quantification for all FTOHs were 0.017-0.060ng/gdry weight (dw). The method was applied to analyze six marine sediment samples from Liaodong Bay, China. All FTOHs except for 10:1 FTOH were detected, and the total concentrations of FTOHs were 0.19-0.52ng/gdw. The developed method provides a new method to sensitively determine FTOHs in environmental matrices.