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Here, we show a novel energy conversion design with a dynamic MIM structure. This is realized though grafting CF3 group which shows high tunnelling current density of up to 7.6 × 106 Am−2. This can further fulfill the macroscopic energy harvesting.

Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl

Noninfectious liver injury, including the effects of chemical material, drugs and diet, is a major cause of liver diseases worldwide. In chemical and drugs-induced liver injury, innate inflammatory responses are mediated by extracellular danger signals. The S100 protein can act as danger signals, which can promote the migration and chemotaxis of immune cells, promote the release of various inflammatory cytokines, and regulate the body's inflammatory and immune responses. However, the role of S100A6 in inflammatory response in chemical and drugs-induced sterile liver injury remains unclear. We constructed the model of sterile liver injury induced by carbon tetrachloride (CCl

Objective Evaluation of the accuracy and effectiveness of 3D printed guides to assist femoral tunnel preparation in individualised reconstruction of the anterior cruciate ligament. Design Randomised controlled studies. Patients/participants Sixty patients who attended the Affiliated Hospital of Binzhou Medical College for autologous hamstring single bundle reconstruction of the anterior cruciate ligament from October 2018 to October 2020 were selected and randomly divided into two groups, including 31 cases in the 3D printing group (14 males and 17 females, mean age 41.94 ± 10.15 years) and 29 cases in the control group (13 males and 16 females, mean age 37.76 ± 10.34 years). Main outcome measures Patients in both groups were assessed for intraoperative femoral tunnel accuracy, the number of intraoperative positioning and the time taken to prepare the femoral tunnel, the length of the anteromedial approach incision, the pre-planned bone tunnel length and intraoperative bone tunnel length in the 3D printed group, IKDC score and Lysholm score preoperatively and at 3, 6 and 12 months postoperatively, the Lachman、pivot-shift test preoperatively and at 6 months postoperatively, gait analysis to assess internal and external rotation in flexion of the knee at 12 months postoperatively and postoperative complications in both groups. Results There was no statistical difference in functional knee scores and anteromedial approach incision length between the 3D printed and control groups (p > 0.05), while there was a statistical difference in the accuracy of tunnel positioning, the time taken to prepare the femoral bone tunnel and the degree of external rotation of the knee in flexion between the two groups (p 0.05). Complications: One case in the 3D printing group developed intermuscular vein thrombosis in the affected lower limb after surgery, which disappeared after treatment, while three cases in the control group developed intermuscular vein thrombosis in the affected lower limb. No complications such as bone tunnel rupture, deep vein thrombosis in the lower limb and infection occurred in either group. Conclusions 3D printed guides assisted with individualized ACL reconstruction can improve the accuracy of femoral tunnel positioning, which is safe and effective, while reducing the operative time and the number of intraoperative positioning, without increasing the length of incision, and can obtain higher functional scores and rotational stability of the knee joint, which is in line with the concept of individualized ACL reconstruction. Level of Evidence Therapeutic Level Ⅰ.

MOOSE (Multiphysics Object-Oriented Simulation Environment) is a powerful finite element multi-physics coupling framework, whose object-oriented, extensive system is conducive to the development of various simulation tools. In this work, a full-core MOOSE-based Neutron Diffusion application is developed, and a 3D PWR benchmark 3D-IAEA with given group constants is applied for code verification. Then the MOOSE-based Neutron Diffusion application is applied to the calculation of a Sodium-cooled Fast Reactor (SFR) benchmark, together with the research on homogenized few-group constants generation based on Monte Carlo method. The calculation adopts a 33-group cross section sets, which is generated using Monte Carlo code OpenMC. Considering the long neutron free path and strong global neutron spectrum coupling of liquid metal cooled reactor (LMFR), a full-core homogeneous model is used in OpenMC to generate the homogenized few-group constants. In addition, transport correction is used in the process of cross section generation, considering the prominent anisotropic scattering of fast reactor. The calculated results, including effective multiplication factor (keff) and assembly power distributions, are in good agreement with the reference values and the calculation results of OpenMC, which proves the accuracy of the neutron diffusion application, and also shows that the Monte Carlo method can be applied to generation of homogenized few-group constants for LMFR analysis.

The electrochemical carbon dioxide (CO2) reduction provides a means to upgrade CO2 into value‐added chemicals. When powered by renewable electricity, CO2 electroreduction holds the promise of chemical manufacturing with carbon neutrality. A commercially relevant CO2 electroreduction process should be highly selective and productive toward desired products, energetically efficient for power conversion, and stable for long‐term operation. To achieve these goals, designing gas‐diffusion catalytic electrodes and prototyping reactors built upon in‐depth understandings of the reaction mechanisms are of paramount importance. In this review, the fundamentals of gas‐diffusion electrodes are briefly presented. Then, the most recent advances in developing high‐performance CO2 reduction using gas‐diffusion electrodes are overviewed. Reactor engineering aiming at enhancing productivity, energy efficiency, CO2 single‐pass utilization, and operating lifetime is further discussed. Challenges in developing CO2 electroreduction systems are included. The prospects for advancing CO2 electroreduction toward practical applications are also narrated.

With the promulgation of industry guidelines, near infrared spectroscopy (NIRS) monitoring the uniformity of solid oral preparations has become one of the most reported studies. The purpose of the present study is to develop a near infrared (NIR) method for the in-line assessment of the active pharmaceutical ingredient (API) content in the fluidized bed mixing process, as well as to introduce a portable NIR sensor to monitor the fluidized bed production visually. A portable NIR sensor was used to monitor the content of the API in the fluidized bed mixing process. An experimental fluidized bed was performed and the corresponding NIR spectra were collected in-line. The spectrum selection method of cosine distance for in-line spectra was performed, and four wavelength optimization methods were compared to improve the accuracy of the model. Throughout the mixing process, the content uniformity of the API was a critical quality attribute (CQA). The partial least squares regression (PLSR) quantitative model of API content was established. The results showed that the cosine distance combined with the multi-variable selection methods (CC, VIP, RATC, and UVE) could obtain more useful information than the single method. The root mean square error of cross validation (RMSECV) and root mean square error of prediction (RMSEP) values of the optimal PLSR model were 1.8588% and 1.5296%, respectively. Based on the results obtained, this study could be used as a reference for the pilot of in-line monitoring of miniature NIR sensors and the connection of key process parameters to realize intelligent production of solid preparations.

Helium cooled solid breeder blanket as an important blanket candidate of the Tokamak fusion reactor uses ceramic pebble bed for tritium breeding. Considering the poor effective thermal conductivity of the ceramic breeder pebble bed, thin structure of tritium breeder pebble bed is usually adopted in the blanket design. The container wall has a great influence on the thin pebble bed packing structure, especially for the assembly of mono-sized particles, and thin pebble bed will appear anisotropic effective thermal conductivity phenomenon. In this paper, thin ceramic pebble beds composed of 1 mm diameter L i 4 S i O 4 particles are generated by the EDEM 2.7. The effective thermal conductivity of different thickness pebble beds in the three-dimensional directions are analyzed by three-dimensional thermal network method. It is observed that thin L i 4 S i O 4 pebble bed showing anisotropic effective thermal conductivity under the practical design size. Normally, the effective thermal conductivity along the bed vertical direction is higher than the horizontal direction due to the gravity effect. As the thickness increases from 10 mm to 40 mm, the effective thermal conductivity of the pebble bed gradually increases.

This paper studies the structural parameters of fuel assemblies suitable for high neutron flux density environments. Due to the high neutron flux density in the core, high-flux reactors provide an experimental environment for neutron irradiation. However, high neutron flux leads to high heat flux density on the fuel assembly surface, which brings challenges to the design of fuel assembly. Therefore, it is very important to study the structural design of fuel assemblies suitable for high neutron flux density environments. Through theoretical derivation of the thermal model of the fuel assembly and sensitivity analysis of the design parameters of the fuel assembly using a single-channel program, the results show that the liquid metal cooling plate fuel element can be well adapted to the high neutron flux Density environment; at relatively low neutron flux densities, bundle fuel elements can also meet reactor design requirements.

In this study, a thermal-hydraulic analysis is carried out for the core of natural circulation lead-cooled fast reactor SNCLFR-100. Steady-state and transient analysis are performed with porous medium approach-based code TWOPORFLOW. In the steady-state analysis, mass flow distribution and temperature distributions of the assemblies are analyzed in assembly-wise mode. At the same time, the hottest assembly is analyzed in pin level and the safety performance is investigated. In the transient analysis, a typical Design Extension Conditions unprotected over-power transient is simulated with one-way coupling method.

Lead-based reactors mostly adopt integrated pool structures to simplify the design of reactor and have high inherent safety. As an important safety facility in the primary circuit, the reliability of the reactor vessel is critical for the safe operation of the whole reactor. The reactor vessel of natural circulation lead-cooled fast reactor SNCLFR-100 was taken as the object, and the corresponding simplified model was established. Based on ANSYS, the fluid-thermal-mechanical coupling analysis was carried out under the steady-state to study the influence of flow field and temperature field on the reactor vessel, and to reveal the distribution law of key thermal and mechanical parameters under the steady-state operation in this paper. The results of mechanical calculations were evaluated based on American society of Mechanical Engineers (ASME) standards, and the preliminary design scheme of reactor solid structure was optimized. The results showed that the stress evaluation results of the SNCLFR-100 reactor vessel meet the requirements of ASME standards in steady-state operation conditions. After optimizing the original solid structure, the stress evaluation results show that the maximum stress value was reduced by 43.3%, and the stress concentration was obviously suppressed, which indicates that the reactor container has a higher safety margin under the optimization scheme. The Steady-state calculation based on normal operation conditions provides a certain research basis for the subsequent transient calculation under accident conditions.

(1) Background: Although the research on benefit finding (BF) in China has increased in recent years, it remains in its infancy. Few previous studies have focused on early-stage cancer patients. Therefore, this research study aimed to explore BF and its influencing factors for early-stage cancer patients in China. (2) Methods: From April to August 2019, 319 patients with early-stage cancer in the treatment period were selected by the convenience sampling method and evaluated using the Benefit Finding of Cancer Patients Scale-Chinese (BFS-C), Perceived Social Support Scale (PSSS), and Medical Coping Modes Questionnaire (MCMQ). (3) Results: The mean BF score was 47.57 (SD = 12.26). The results of the correlation analysis show that benefit finding was positively correlated with social support, but negatively correlated with acceptance-resignation. In addition, social support was negatively correlated with avoidance and acceptance-resignation. The results of the multiple linear regression indicate that the variables of self-assessment of disease severity, exercise time, coping mode (acceptance-resignation), and social support, affect BF. Finally, social support was shown to exert an intermediary effect on acceptance-resignation and BF. (4) Conclusions: In this study, the score of BF of patients with early-stage cancer was low. Medical staff should be more aware of the health behavior of patients with early-stage cancer, guide them to actively face the disease, and fully mobilize the social support of patients’ friends and family, so as to help patients increase their disease BF.

BackgroundThe phagocytic S100 protein, which mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage, has long been known to be expressed in cells of myeloid origin. S100A6 belongs to the A group of the S100 protein family of Ca2+-binding proteins. Currently, the mechanism by which S100A6 mediates the inflammatory response and recruits inflammatory cells to the tissue injury site is unknown.MethodsA mouse model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was established, and the transcriptomes of postinjury 2d and 5d liver tissues were sequenced. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) in the supernatant of the liver. Immunohistochemical analysis confirmed the expression of S100A6 in the liver cells. In vitro experiments proved the pro-inflammatory function of S100A6, and western blotting (WB) showed that the pathways were activated. The transwell experiment showed the infiltration of mononuclear/macrophages.ResultsWe found that S100A6 is highly expressed in liver cells during the most severe period of ALI, suggesting that it acts as an endogenous danger signal and has a pro-inflammatory function. In vitro, the mouse S100A6 recombinant protein was used to stimulate liver Kupffer cells to promote the secretion of TNF-α, IL-1β, IL-6, and IL-8. Further mechanistic experiments revealed that S100A6 acts as an endogenous danger signal to activate p-P38 and p-JNK downstream of the TLR4 and P65 pathways. Similarly, transcriptome data showed that S100A6 can activate the inflammatory response in Kuffer cells. WB revealed that S100A6 had no significant effect on cell apoptosis. To continue to explore the mechanism of monocyte/macrophage infiltration, we found that TNF-α stimulates liver cells as the main source of CCL2. TNF-α can initiate the p-P38 and p-JNK pathways of liver cells to produce CCL2, thereby recruiting the infiltration of mononuclear/macrophages. ConclusionsTaken together, S100A6 is an endogenous danger signal that mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage.

Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). LncRNA small nucleolar RNA host gene 8 (LncRNA SNHG8) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the molecular mechanisms by which lncRNA SNHG8 contributes to hepatocellular carcinoma (HCC) still remains unclear. In the present study, we reported that lncRNA SNHG8 was abnormally up-regulated in liver cancer tissues and HCC cell lines. Moreover, knockdown of lncRNA SNHG8 significantly attenuated the proliferation, migration, invasion process of HCC cell line HepG2 in vitro. Mechanistically, we first reported that suppression of lncRNA SNHG8 evidently enhanced miR-542-3p and miR-4701-5p expression and decreased TET3 expression at posttranscriptional level. Furthermore, lncRNA SNHG8 upregulated TET3 expression by sponging miR-542-3p and miR-4701-5p by competing binding. Taken together, our results confirmed the oncogene role of lncRNA SNHG8 and discovered the underlying mechanism that lncRNA SNHG8 upregulated TET3 through the sponging or decaying of miR-542-3p and miR-4701-5p in human hepatocellular carcinoma, suggesting that lncRNA SNHG8 may serve as a potential diagnostic marker and therapeutic target for patients with hepatocellular carcinoma.

Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.

Near-infrared spectroscopy (NIRS) is an excellent process analytical technology (PAT) tool for active pharmaceutical ingredient (API) quantification during fluidized granulation. Therefore, a portable near-infrared spectrometer combined with a new innovative method of extended iterative optimization technique (EIOT) was used to in-line monitor the API content uniformity during fluidized bed granulation. The principal component analysis (PCA) and partial least squares regression (PLSR) were also used to characterize and predict API concentration with changes from 75% to 125% of the label claim to prove the superiority of EIOT. The API content prediction accuracy of the EIOT method was verified through offline High Performance Liquid Chromatography (HPLC) measurement. Also, the spatial distribution of API in granules was visualized by Raman imaging technology. The results showed that the established NIRS method was suitable for the prediction of API content in fluidized bed granulation, which provides a new idea for the determination of API content during granulation.

Fragmentation warhead is the main weapon used to damage personnel and light armored objectives, with the lethal parameters primarily consisting of the number and velocity of fragments. Increasing the lethality of fragmentation warhead is currently the most important development direction for fragmentation warhead. The formation process of natural fragment is complicated and there are several factors that affect the properties of fragment, so there are still many techniques of developing the lethality of fragmentation warhead. In this paper, our object is to focus on the optimization design for the lethality of fragmentation warhead, based on the optimal Latin hypercube test design method and the radial basis function neural network surrogate modelling, taking the number of effective fragments per unit mass and the average kinetic energy of the effective fragments as the optimization objectives, and the explosive charge, the fragment material, the overall structure and initiation method are considered, respectively. The Pareto optimal solution sets under different design variables are obtained, and the optimal matching of multiple design parameters is realized, establishing the integration design method for “explosive - material-structure” of the fragmentation warhead. The research results can provide technical support for the structural optimization design of the fragmentation warhead.

58SiMn and 50SiMnVB are commonly used shell materials in bombs, and their dynamic constitutive model and fracture properties directly determine the mass distribution of the bomb. Tensile tests were carried out on two high-strength steels, and the parameters of the yield point, tensile strength and plastic failure strain as well as the John-Cook model were determined. The fracture morphologies of the two steels in the quasi-static tension and in the dynamic tension were analyzed. The research results show that the yield strength of 58SiMn steel remains unchanged with increasing strain rate. The yield strength and tensile strength of 50SiMnVB increase as the rate of elongation increases, and the ability to plastically deform decreases, which shows the properties of embrittlement under high speed loading. With the same elongation rate, 50SiMnVB steel has higher strength and toughness. 58SiMn steel is a tensile brittle fracture from a macroscopic point of view and a quasi-split fracture from a microscopic point of view; 50SiMnVB steel is a mixed lap shear fracture under axial tensile load. With increasing loading rate, the tensile fracture tends to pure shear fracture.

The in vitro dissolution profile is a key parameter which reflects the quality of sustained-release tablets. Most studies were used to determine the dissolution of tablets utilizing dissolution curves. This study aimed to investigate the role of water during nifedipine controlled release tablets dissolution process in order to provide a new way to understand the dissolution behavior. Dissolution liquid was added to the drug-containing layer slowly, and near infrared spectra were acquired according to the set time. NIR spectroscopy with aquaphotomics were introduced to determine different water patterns. The results showed that, the structural change of water was consistent with the dissolution process. During hydration stage, it was mainly Sr combined with the semi-permeable membrane to form a channel. Then S0, S1, S2 and S3 combined with the drug layer and the push layer. Finally, it was relied on the swelling of the push layer to push the drug layer out at the release process. This study not only deepens the understanding of the dissolution process, but also opens a new perspective in molecular interaction analysis in aqueous system by understanding the roles of water.

The tritium ceramic breeder pebble bed, used for tritium breeding and in nuclear fusion reactor, is a key constituent of helium cooled solid breeder blankets. The mechanical properties of the pebble beds, along with the integrity of the particles are very important for the extraction of tritium and safe operation of the solid blanket. In this paper, analysis is carried out on the effect of packing structure, with varying bed thicknesses and particle smoothness, on mechanical properties and the probability of particle crushing. Pebble beds are randomly packed by a single type of Li 4 SiO 4 particle, 1 mm in diameter. It is found that when the thickness of the Li 4 SiO 4 pebble bed (ranging from 15 mm to 25 mm) becomes thinner, or the coefficient of friction (ranging from 0.1 to 0.6) increases, the strain of the pebble bed and the probability of particle crushing increases under the same mechanical load. Pebble beds with different packing structures have the same probability distribution function of normalized contact forces. The results could serve to characterize the tritium pebble beds and to optimize the design of helium cooled solid breeder blankets.

The design and multiobjective optimization of graded foam-cored sandwich cylinders (GFSCs) composed of tubular face sheets and layered gradient foam core under internal air-blast loading were examined. The response surface method and nondominated sorting genetic algorithm were used in the defined optimization problem to determine the optimal face-sheet thickness and core gradient as well as achieve the minimum specific deflection of outer face sheet (SDF) and maximum specific energy absorption (SEA). Multiobjective optimization was subsequently conducted to obtain the Pareto front and improve the blast-resistant performance of the optimum GFSC configuration. Results obtained via these optimizations further indicated that the optimal GFSCs demonstrated better energy absorption characteristics than ordinary sandwich cylinders. Under the same SDF, SEA increased by 75.4% and 45.0% compared with that of the initial baseline design when the core gradient and face-sheet thickness were individually optimized, respectively. The joint optimization of face-sheet thicknesses and core gradient could significantly improve the blast-resistant performance by 171.1%. The optimization of GFSCs should primarily optimize the design variables with high-price performance ratio while reasonably arranging the design variable quantity, ensuring the controllable cost of calculation, and significantly improving the blast-resistant performance. The results also showed that the strength of CFSCs and the interaction between the face sheets and the core improved the blast-resistant capacity. The design optimization results could provide appropriate guidance in the crashworthiness design of GFSCs.

Summary Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu2+ to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250 nM DSF chelated with 10 µM CuCl2 for 24 h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner. Additionally, atomic force microscope (AFM) analysis at nanoscale level showed that the morphology of cell was significantly shrunk with destroyed filopodia and ultrastructure presented many irregular protuberances on the cell membrane after DSF-Cu treatment, which was closely associated with the re-arrangement of cytoskeleton. DSF-Cu induced the production of reactive oxygen species (ROS), increased the concentration of intracellular Ca2+ and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells resulting in a mitochondria-dependent apoptosis pathway. The results indicated that DSF-Cu has a potential anti-tumor activity in breast cancer by impairing the mitochondria functions. SCANNING 9999:1–12, 2016. © 2016 Wiley Periodicals, Inc.