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Developing small-angle neutron scattering techniques at compact accelerator-driven neutron sources (CANS) is of great importance for expanding the user community and advancing CANS capability. At the Compact Pulsed Hadron Source (CPHS) at Tsinghua University, neutron-focusing mirrors are under intensive research to address the challenge. A grazing-incidence focusing SANS (gif-SANS) project is initialized. It employs a nested supermirror assembly with a large collecting area to achieve ⩾ 10 5 n/s neutron intensity at Q min ⩽ 0.007 Å − 1 . It will equip two detectors, one being a 3He detector for normal Q-range measurements, and the other being a high-resolution detector for extending the Q min down to 10 − 3 Å − 1 . In this work, we present the conceptual design of the gif-SANS at CPHS. Such a scheme is conducive to enable high-performance SANS measurements at CANS.

This work reports the first direct observations of binding and complex formation between transforming growth factor beta 1 (TGF-β1) and cartilage oligomeric matrix protein (COMP) using high-resolution atomic force microscopy (AFM). Each COMP molecule consists of pentamers whose five identical monomeric units bundle at N-termini. From this central point, the five monomers’ flexible arms extend outward with C-terminal domains at the distal ends, forming a bouquet-like structure. In commonly used buffer solutions, TGF-β1 molecules typically form homodimers (majority), double dimers (minority), and aggregates (trace amount). Mixing of TGF-β1 and COMP leads to rapid binding and complex formation. The TGF-β1/COMP complexes contain one to three COMP and multiple TGF-β1 molecules. For complexes with one COMP, the structure is more compact and less flexible than that of COMP alone. For complexes with two or more COMP molecules, the conformation varies to a large degree from one complex to another. This is attributed to the presence of double dimers or aggregates of TGF-β1 molecules, whose size and multiple binding sites enable binding to more than one COMP. The number and location of individual TGF-β1 dimers are also clearly visible in all complexes. This molecular-level information provides new insight into the mechanism of chondrogenesis enhancement by TGF-β1/COMP complexes, i.e. simultaneous and multivalent presentation of growth factors. These presentations help explain the high efficacy in sustained activation of the signalling pathway to augment chondrogenesis.

Background The purpose of this study was to gather temporal trends on bacteria epidemiology and resistance of intraoperative bone culture from chronic ostemyelitis at an affiliated hospital in South China. Method Records of patients with chronic osteomyelitis from 2003 to 2014 were retrospectively reviewed. The medical data were extracted using a unified protocol. Antimicrobial susceptibility testing was carried out by means of a unified protocol using the Kirby-Bauer method, results were analyzed according to Clinical and Laboratory Standards Institute definitions. Result Four hundred eighteen cases met our inclusion criteria. For pathogen distribution, the top five strains were Staphylococcus aureus (27.9%); Pseudomonas aeruginosa (12.1%); Enterobacter cloacae (9.5%); Acinetobacter baumanii (9.0%) and Escherichia coli (7.8%). Bacterial culture positive rate was decreased significantly among different year-groups. Mutiple bacterial infection rate was 28.1%. One strain of Staphylococcus aureus was resistant to linezolid and vancomycin. Resistance of Pseudomonas aeruginosa stains to Cefazolin, Cefuroxime, Cefotaxime, and Cefoxitin were 100% nearly. Resistance of Acinetobacter baumanii stains against Cefazolin, Cefuroxime were 100%. Ciprofloxacin resistance among Escherichia coli isolates increased from 25 to 44.4%. On the contrary, resistance of Enterobacter cloacae stains to Cefotaxime and Ceftazidime were decreased from 83.3 to 36.4%. Conclusions From 2003 to 2014, positive rate of intraoperative bone culture of chronic osteomyelitis was decreased; the proportion of Staphylococcus aureus was decreased gradually, and our results indicate the importance of bacterial surveilance studies about chronic osteomyelitis.

The Multipurpose Physics neutron diffractometer (MP) will be built at the China Spallation Neutron Source (CSNS) in the coming years. It is a time of flight diffractometer dedicated to the study of complex crystalline materials through the total scattering or pair distribution function (PDF) technique. The MP diffractometer will be able to determine the PDF from the atomic to the nanometer scale. We present a validation of the main physical parameters of the MP diffractometer through Monte Carlo simulation. In particular the moderator choice, guide system and placement of the chopper system is investigated. The best momentum transfer resolution δ Q/Q is reached in backscattering and is expected to be in the order of 0.2 %, the neutron flux at the sample is of the order of 10 7 n/s/cm2 and the momentum transfer range in the order of 0.08–100 A −1.

Black phosphorous (BP) is recognized as an effective reinforcement for polymer scaffold because of its excellent mechanical property and biocompatibility. Nevertheless, its poor stability in physiological environment limits its application in bone repair. In this work, BP was modified with dopamine by self-polymerization approach (donated as BP@PDA) to improve its stability, and then was introduced into poly-L-lactic acid (PLLA) scaffold fabricated by selective laser sintering technology. Results showed the compressive and tensile strength of PLLA/BP@PDA scaffold were improved by 105% and 50%, respectively. The enhanced strength was ascribed to the increased stability of BP and the improved compatibility of BP@PDA with PLLA matrix after modifying with polydopamine. Simultaneously, the bioactivity of PLLA scaffold was significantly improved. It was attributed to that BP@PDA provided the sustained source of PO43- ions which could capture Ca2+ ions from physiological medium to facilitate in situ biomineralization, thereby promoting cell adhesion, proliferation and differentiation. This study demonstrated the great potential of BP@PDA in bone repair.

Piezoelectric composites have shown great potential in constructing electrical microenvironment for bone healing since their integration of polymer flexibility and ceramic piezoelectric coefficient. Herein, core-shell structured BaTiO

© 2018 American Chemical Society. This work presents the first direct evidence of multivalent binding between bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) using high-resolution atomic force microscopy (AFM) imaging. AFM topographic images reveal the molecular morphology of COMP, a pentameric protein whose five identical monomer units bundle together at N-termini, extending out with flexible chains to C-termini. Upon addition of BMP-2, COMP molecules undergo conformational changes at the C-termini to enable binding with BMP-2 molecules. AFM enables local structural changes of COMP to be revealed upon binding various numbers, 1-5, of BMP-2 molecules. These BMP-2/COMP complexes exhibit very different morphologies from those of COMP: much more compact and thus less flexible. These molecular-level insights deepen current understanding of the mechanism of how the BMP-2/COMP complex enhances osteogenesis among osteoprogenitor cells, i.e., multivalent presentation of BMP-2 via the stable and relatively rigid BMP-2/COMP complex could form a lattice of interaction between multiple BMP-2 and BMP-2 receptors. These ligand-receptor clusters lead to fast initiation and sustained activation of the Smad signaling pathway, resulting in enhanced osteogenesis. This work is also of translational importance as the outcome may enable use of lower BMP-2 dosage for bone repair and regeneration.

Long noncoding RNAs (lncRNAs) have been identified to have increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. Recent studies have demonstrated that lncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is decreased in several cancers; however, the role of NBR2 in the development of osteosarcoma has not been elucidated. In our study, we found that NBR2 expression was downregulated in osteosarcoma tissues, and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall survival time compared with those with higher NBR2 expression. NBR2 overexpression inhibited osteosarcoma cell proliferation, invasion, and migration but did not increase apoptosis. Furthermore, RNA-binding protein immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein. Furthermore, overexpression of Notch1 in NBR2-overexpressing osteosarcoma cells reversed the effects of NBR2 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition. The in vivo results showed that NBR2 overexpression inhibited tumor growth in nude mice that were inoculated with osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA) expression of Notch1, N-cadherin, and vimentin and increased the mRNA expression of E-cadherin in the tumor tissues. These data indicated that NBR2 served as a tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell proliferation, invasion, and migration. The current study provides a novel insight and treatment strategy for osteosarcoma.

Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Autophagy modulation has been considered a potential therapeutic strategy for osteosarcoma, and previous study indicated that arsenic trioxide (ATO) exhibits significant anti-carcinogenic activity. However, the ability of ATO to induce autophagy and its role in osteosarcoma cell death remains unclear. In the present study, we showed that ATO increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased ATO -induced cell death, indicating that ATO triggered autophagic cell death in MG-63 cells. Mechanistically, ATO induced TFEB(Ser142) dephosphorylation, activated TFEB nuclear translocation and increased TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63 cells. Importantly, ATO triggered the generation of ROS in MG-63 cells. Furthermore, NAC, an ROS scavenger, abrogated the effects of ATO on TFEB-dependent autophagic cell death. Taken together, these data demonstrate that ATO induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS-TFEB pathway. The present study provides a new anti-tumor mechanism of ATO treatment in osteosarcoma.

Piezoelectric composites have shown great potential in constructing electrical microenvironment for bone healing since their integration of polymer flexibility and ceramic piezoelectric coefficient. Herein, core-shell structured BaTiO3@carbon (BT@C) hybrid nanoparticles were prepared by in situ oxidative self-polymerization and template carbonization. Then the BT@C was introduced into polyvinylidene fluoride (PVDF) scaffolds manufactured by selective laser sintering. On one hand, the carbon shell could strengthen the local electric field loaded on BT in poling process owing to it served as a diffusion layer to provide space for charge transfer and accumulation. In this case, more electric domain within BT would be aligned along the polarization field direction and thus promoted the paly of BT's piezoelectric activity. On the other hand, the carbon shell could induce the formation of β phase due to the sp2 hybrid-bonded carbon atoms in carbon shell forming electrostatic interaction with hydrogen atoms in PVDF chains, which further enhanced the piezoelectric response of the scaffolds. Results showed that the scaffold presented augmented piezoelectric performance with output voltage of 5.7 V and current of 79.8 nA. The improved electrical signals effectively accelerated cell proliferation and differentiation. Furthermore, the scaffold displayed improved mechanical performance due to rigid particle strengthen effect.

Aiming at the feature of picking for the biological fruits, an intelligent design of the 5 degree of freedom of lichi picking manipulator was introduced. Based on the first version of the manipulator, its mechanism and manufacture processes were improved, and the key technology in the mechanism design of the manipulator was studied, including some novel design thought and methods of the arm joint and end-effector. Meanwhile, according to the design scheme, the Denavit-Hatenberg method, which is a common method for solving robot kinematics, and a geometry method were adopted to analyze and calculate the manipulator’s kinematics solution and its inverse solution. It provides the foundation of continuous optimization of the manipulator’s mechanism and control design. At last, the Intelligent design system of picking manipulator was developed in the platform of Microsoft VisualC++, the design scheme and structure design of the manipulator can be optimized in the design system, moreover, through the human-computer interaction, the realtime simulation of the mechanism motion and coordinate inverse calculation can be realized.

In order to process the study of Picking Manipulator for litchi, multi-field unified modeling language Modelica is used to model and simulate Picking Manipulator. In this paper, the structure of Picking Manipulator is analyzed and the mathematical model of manipulator control system is built by adopting multi-cooperating controlling model. More, the process of modeling Picking Manipulator under Modelica/Dymola is introduced, and the model of Picking Manipulator system is built while the extensible modeling base is established. Finally, the model will be simulated and the validity of models will be validated. Through the thesis, the basic for the further study of Litchi Picking Manipulator will be provided.