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Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host–microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome–dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2–OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1. Plant ubiquitin regulatory domain-containing proteins (PUX) play vital roles in CDC48-mediated protein quality control processes. Here Shi et al. show that a conserved core Magnaporthe oryzae effector (MoNLE1) can specially target the rice PUX protein OsPUX8B.2 and interfere with host immune responses. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) is a major form of reactive oxygen species that play an important role in the survival, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). The regulatory mechanisms of H2O2 homeostasis in BMSCs are not fully understood. Here we demonstrate for the first time that aquaglyceroporin AQP7 is a functional peroxiporin expressed in BMSCs and remarkably upregulated upon adipodenic induction. The proliferation ability of BMSCs from AQP7−/− mice was significantly decreased, as indicated by fewer clonal formation and cell cycle arrest compared with wildtype BMSCs. AQP7 deficiency caused accumulation of intracellular generated H2O2 during BMSCs proliferation, leading to oxidative stress and inhibition of PI3K/AKT and STAT3 signaling pathways. After adipogenic induction, however, the AQP7−/− BMSCs exhibited greatly reduced adipogenic differentiation with fewer lipid droplets formation and lower cellular triglycerides content than wildtype BMSCs. In such case AQP7 deficiency was found to diminish import of extracellular H2O2 produced by plasma membrane NADPH Oxidases, resulting in altered AMPK and MAPK signaling pathways and reduced expression of lipogenic genes C/EBPα and PPARγ. Our data revealed a novel regulatory mechanism of BMSCs function through AQP7-mediated H2O2 transport across plasma membrane. [ABSTRACT FROM AUTHOR]

Introduction: The revision of the N descriptor in non-small-cell lung cancer has been widely discussed in the past few years. Many different subclassification methods based on number or location of lymph nodes have been proposed for better distinguishing different N patients. This study aimed to systematically collect them and provide a comprehensive comparison among different subclassification methods in a large cohort. Method: Pathological N1 or N2 non-small-cell lung cancer patients undergoing surgical resection between 2005 and 2016 in the Western China Lung Cancer Database were retrospectively reviewed. A literature review was conducted to collect previous subclassification methods. Kaplan-Meier and multivariable Cox analyses were used to examine the prognostic performance of subclassification methods. Decision curve analysis, Akaike's information criterion, and area under the receiver operating curve concordance were also performed to evaluate the standardized net benefit of the subclassification methods. Results: A total of 1625 patients were identified in our cohort. Eight subclassification methods were collected from previous articles and further grouped into subclassification based on number categories (node number or station number), location categories (lymph node zone or chain) or combination of number and location categories. Subclassification based on combination of lymph node location and number tended to have better discrimination ability in multivariable Cox analysis. No significant superiority among the different subclassification methods was observed in the three statistical models. Conclusion: Subclassification based on the combination of location and number could be used to provide a more accurate prognostic stratification in surgically resected NSCLC and is worth further validation. [ABSTRACT FROM AUTHOR]

In this paper, a novel crack and void identification method is proposed based on the scaled boundary finite element method (SBFEM) with the pixel-based quadtree mesh and the parameter level set method (PLSM), in which the particle swarm optimization method (PSO) is applied to optimize the objective function. It fully exploits the advantages of fast image-based quadtree mesh generation and efficient assembly of global stiffness matrix to accomplish a fast analysis of the forward problem and accelerate the efficiency of the inversion. Furthermore, multiple level set functions are introduced to represent cracks and voids simultaneously. The application of PSO dexterously avoids the difficulty of solving sensitivity. Numerical examples show that the proposed method can identify the position and shape of cracks and voids accurately by discussing different influencing factors. In addition, the method has shown certain anti-noise performance. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) can affect bone metabolism and homeostasis of serum electrolytes that are associated with abnormal levels of vitamin D. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant with the active metabolite mycophenolic acid (MPA). The area under the plasma concentration–time curve (AUC) of MPA is often monitored during the treatment to assess the exposure levels. This study aims to explore the association between exposure levels of MPA and 25-hydroxyvitamin D [25(OH)D] levels in children with SLE. Methods: Repeated measured data of children with SLE who were treated with MMF and under therapeutic drug monitoring (TDM) were retrospectively collected from the electronic medical records. MPA exposure levels were reflected by the area under the concentration–time curve over 24 h (AUC0–24h). Univariate and multivariate linear regression models were employed to analyze factors associated with 25(OH)D levels. Hierarchical linear models were developed to analyze the intra- and inter-individual effects of AUC0–24h on the variance of 25(OH)D levels. Results: Data from 184 children with SLE (142 female and 42 male) with 518 follow-ups were collected. The median age was 14 years (range 3–18 years) at TDM. Children with normal 25(OH)D levels had significantly higher AUC0–24h than children with low 25(OH)D levels (98.71 vs. 84.05 mg·h/L, P = 0.004). Intra- and inter-individual effects of AUC0–24h on 25(OH)D levels were similar ( γ 10 = 0.034 vs. γ 01 = 0.037) but only the intra-individual effect was significant (P = 0.001) in hierarchical models. Other associated factors include age, sex, season at measurement, glucocorticoid daily dose, and external vitamin D3 supplements. Conclusion: 25(OH)D levels are associated with MPA exposure levels, and may serve as a potential indicator to optimize the exposure level of MPA during treatment. AUC0–24h of 98.71 mg·h/L or AUC0–12h of 49.36 mg·h/L could be the targeted exposure level for children with SLE. [ABSTRACT FROM AUTHOR]

Natural rubber (NR), as a biomacromolecule, has superior properties to its man-made substitute, thus its structure has attracted intensive studies in recent years. However, a detailed rheological study on the network structure of NR is still lacking up to now. Herein, we study the viscoelastic behaviors of NR, deproteinized NR (DPNR) and transesterified DPNR (TEDPNR) in bulk and in solution to reveal the effects of proteins and phospholipids on the network formation of NR. In bulk, removing proteins from NR only leads to a slight reduction of storage modulus, but further removing phospholipids from DPNR leads to an obvious reduction. The stress relaxation experiment demonstrates that there are steady networks in NR and DPNR, while there is only transient network in TEDPNR. By studying the recovery process and re-entanglement kinetics, we find the remarkable restriction of proteins and phospholipids on the entanglements, which is important to the formation of steady network in NR and DPNR. In solution, the swelling of toluene weakens the contribution of entanglements, thus NR displays obviously higher modulus, higher shear viscosity and better network integrity than DPNR and TEDPNR. In addition, the results by Cox-Merz rule demonstrate the existence of reversible bonds on the terminals of NR and DPNR, which is also important for their network formation. Based on these results, we propose the network structure of NR and its structural evolution upon shearing. [ABSTRACT FROM AUTHOR]

The authors describe biocompatible nanomicelle based drug carriers that can be used for simultaneous (a) fluorescence tracking, (b) pH-controlled release of the cancer drug doxorubicin (DOX), and (c) targeting the folate receptor. The pH-sensitive triblock copolymer is composed of poly-2-(diisopropylamino) ethyl methacrylate and methoxypoly (ethylene glycol) which were prepared by radical polymerization and 'click' chemistry. The copolymers undergo self-assembly to form spherical micelles with diameters between 100 and 200 nm and a pH-trigger capability at pH values from 5.8 to 6.2. The micelles enabled DOX to be released at pH 5.0 at a much higher rate than at pH 7.4. Studies on cellular uptake revealed selective internalization of the DOX-loaded nanomicelles into HeLa cells where they can be imaged fluorometrically. Quantitative analysis of the green fluorescence indicated that the FITC-labeled micelles possess a transfection efficiency of about 79% while that of the nanomicellles with folate is only ∼40% under the same conditions. Confocal laser scanning microscopy indicates that the micelles invade the lysosome of HeLa cells and that the DOX released by micelles causes strong cell lethality. In our preception, this work provides useful insights in terms of designing multifunctional drug carriers and of improving the applicability of copolymer micelles for drug delivery systems. [ABSTRACT FROM AUTHOR]

A highly specific and broadly reactive monoclonal antibody against hepatitis B virus X (HBx) protein was developed that detected, in both immunoblotting and immunofluorescence, HBx proteins of seven of the eight currently known genotypes of HBV, which were overexpressed in cultured cells. Evaluation of HBx expression levels in cultured hepatocytes using this monoclonal antibody showed that cells transiently and stably transfected with HBV genomes expressed far less HBx protein than cells transiently transfected with an HBx overexpression plasmid routinely used for studying HBx functions. The availability of such sensitive and broadly reactive monoclonal antibodies against HBx will enable more-quantitative studies of HBx functions. [ABSTRACT FROM AUTHOR]

A valveless micropump actuated by thermal bubbles which are generated by an electrode heater mounted with a pair of diffuser nozzles has been numerically studied by commercial CFD software FLUENT. The relationships between the net flow rate and the superheating and heat supplying frequency have been investigated. The depth of the diffuser-nozzle micropump is 200 μm, the diameter of the actuating chamber is 1 mm, and a pair of diffuser nozzles whose gap has been expanded from 30 μm to 274 μm with an open angle of 7° are connected to the actuating chamber. The working fluid is methanol. In the numerical simulation, the flow pattern is laminar. The results show that the pump has different optimal driving frequencies at different superheating. A cycle resulting from bubble growth and shrinking costs more time at higher superheating temperature; different superheating has different optimal driving frequency; when the superheating increases, the maximum volume flow rate and the maximum pump pressure will increase simultaneously, and the optimal driving frequency decreases as well, the maximum volume flow rate and pump pressure also have the same tendency; in the condition of uncontrolled condensing, the bubble shrinking process is longer than the growth process, thus it is the determining factor to affect the pump performance. The maximum volume flow rate is 9.02 μL/min at Δ T = 15°C, and the maximum pump pressure is 680 Pa. With the increase of wall superheat, cycle including the bubble growth and condensation will become longer, resulting in a significant impact on the pumping flow; different wall superheat has different optimized frequency, increasing superheat will bring increased pumping flow and pump pressure, the optimized driving frequency will be reduced; liquid supply phase is longer than pumping phase. [ABSTRACT FROM AUTHOR]