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High-performance non-noble electrocatalysts for oxygen reduction reaction (ORR) are the prerequisite for large-scale utilization of fuel cells. Herein, a type of sandwiched-like non-noble electrocatalyst with highly dispersed FeNx active sites embedded in a hierarchically porous carbon/graphene heterostructure was fabricated using a bottom-up strategy. The in situ ion substitution of Fe3+ in a nitrogen-containing MOF (ZIF-8) allows the Fe-heteroatoms to be uniformly distributed in the MOF precursor, and the assembly of Fe-doped ZIF-8 nano-crystals with graphene-oxide and in situ reduction of graphene-oxide afford a sandwiched-like Fe-doped ZIF-8/graphene heterostructure. This type of heterostructure enables simultaneous optimization of FeNx active sites, architecture and interface properties for obtaining an electron-catalyst after a one-step carbonization. The synergistic effect of these factors render the resulting catalysts with excellent ORR activities. The half-wave potential of 0.88 V vs. RHE outperforms most of the none-noble metal catalyst and is comparable with the commercial Pt/C (20 wt %) catalyst. Apart from the high activity, this catalyst exhibits excellent durability and good methanol-tolerance. Detailed investigations demonstrate that a moderate content of Fe dopants can effectively increase the intrinsic activities, and the hybridization of graphene can enhance the reaction kinetics of ORR. The strategy proposed in this work gives an inspiration towards developing efficient noble-metal-free electrocatalysts for ORR.

Modern pharmacological studies have shown that Fructus Tribuli can improve sexual function and treat cardiovascular diseases. In this study, we focused on comparing the pharmacokinetics of crude Fructus Tribuli (CFT) and stir-fried Fructus Tribuli (SFT) to further clarify the changes in chemical composition in vivo. The quantitation of six analytes was performed in a triple quadrupole mass spectrometer using the multiple reaction monitoring mode. Separation was performed on a Halo® C18 column using 0.05% formic acid and 5 μmol/L sodium formate in water, and 0.05% formic acid and 5 μmol/L sodium formate in acetonitrile as the mobile phase. The selectivity, precision, accuracy, extraction recovery, matrix effect and stability of the method were fully validated. Compared with the crude group, the parameters Cmax and AUC0-t of terrestroside B and terrestrosin K increased significantly (P < 0.05), but the Cmax and AUC0-t of polianthoside D, terrestrinin D, tribuluside A and terrestrosin D were decreased, terrestrosin D being especially decreased (P < 0.05), after oral administration of SFT extract. These results showed that the developed method was suitable for pharmacokinetic analysis of the six steroid saponins of CFT and SFT in rat plasma, and can be used to facilitate future clinical studies.

PURPOSE The appropriate depth of right internal jugular venous (RIJV) catheterization is still under debated. In this study, transesophageal echocardiography (TEE) is used to develop a prediction formula for fixed RIJV catheter depth. METHODS Eighty patients with indications for intraoperative TEE and central line placement were enrolled. After intubation, a RIJV catheter was inserted via the middle approach using the Seldinger technique. When the J-tip of the guide wire appeared at the junction of the superior vena cava and the right atrium under TEE guidance, the guide wire was pulled back by approximately 2-3 cm, until its tip was out of the pericardial fold. This depth was regarded as the insertion depth of the central venous catheter. Body landmark distance was measured, and the prediction formula was generated. RESULTS The mean central line depth after TEE-guided placement was 15.1 ± 1.7 cm. The prediction formula developed is as follows: Insertion depth = (Height ÷ 20) + (D ÷ 2), where D equals the distance from the insertion point to the sternal angle via the right sternoclavicular joint (r = 0.595, r2 = 0.354, P

The genetic covariance matrix conditional on pedigree is proportional to the pedigree-based additive relationship matrix (PARM), which is twice the matrix of identity-by-descent (IBD) probabilities. In genomic prediction, IBD probabilities in the PARM, which are expected genetic similarities between relatives that are derived from the pedigree, are substituted by realized similarities that are derived from genotypes to obtain a genomic additive relationship matrix (GARM). Different definitions of similarity lead to different GARMs, and two commonly used GARMS are the matrix G, which is based on an allele substitution effect model, and the matrix T, which is based on an allele effect model. We show that although the two matrices T and G are not proportional, they give identical predictions of differences between breeding values. When genomic information is used for variance component estimation, the GARM Gx is computed from genotype covariates that have been standardized to have unit variance. That approach is equivalent to fitting a random regression model using the same standardized covariates. We show that under Hardy-Weinberg and linkage equilibria (LE) that the genetic variance is kσγ2, where σγ2 is the variance of a randomly sampled element from the vector of k substitution effects. However, if linkage disequilibrium (LD) has been generated through selection, covariances between genotypes at different loci will be negative, and therefore, the additive genetic variance will be lower than kσγ2. When the GARM Gx is assumed to be proportional to the genetic covariance matrix, the parameter being estimated is kσγ2. We have demonstrated by simulation that kσγ2 overestimates the additive genetic variance when LD is generated by selection. We argue that unlike the PARM, GARMs are not proportional to a genetic covariance matrix conditional on the observed causal genotypes. The objective here is to recognize the difference between these covariance matrices and its implications.

The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon-guidance-receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading-related ROBO1 polymorphisms were genotyped, and diffusion and structural MRI were acquired to measure the fiber microstructure of the corpus callosum (CC), the major white-matter tract that connects inter-hemispheric cortical regions. The results confirmed the significant influence of the ROBO1 polymorphisms on reading scores. The fiber microstructures of the midline-CC segments around the genu and splenium were also affected by the ROBO1 polymorphisms. Moreover, a mediation analysis further revealed that the genu could significantly mediate the effects of the ROBO1 polymorphisms on word-list reading performance, which suggests a ROBO1-to-genu-to-reading pathway. The genu-linked cortical morphology, however, was not associated with either the ROBO1 polymorphisms or reading performance. These findings offer direct evidence supporting ROBO1-callosum association in humans and also provide valuable insight into the functions of ROBO1 and the gene-to-brain mechanisms that underlie human reading. Hum Brain Mapp 38:2616-2626, 2017. © 2017 Wiley Periodicals, Inc.

The ruthenium complex Ru(terpyridine)(2,6-pyridinedicarboxylate) was successfully grafted onto MCM-41 using a multi-step grafting method. The immobilized ruthenium complex was characterized thoroughly using Fourier transform infrared, Raman, UV–visible diffuse reflectance and energy-dispersive X-ray spectroscopies, X-ray diffraction, N2 adsorption, scanning electron microscopy, thermogravimetric analysis and inductively coupled plasma analysis. This immobilized ruthenium complex showed excellent performance in the oxidation of various secondary alcohols to their corresponding ketones with tert-butyl hydroperoxide as oxidant under solvent-free conditions, and had the advantages of easy recovery and good reusability. Copyright © 2016 John Wiley & Sons, Ltd.

A recent gene expression classification of hepatocellular carcinoma (HCC) includes a poor survival subclass termed S2 representing about one-third of all HCC in clinical series. S2 cells express E-cadherin and c-myc and secrete AFP. As the expression of fibroblast growth factor receptors (FGFRs) differs between S2 and non-S2 HCC, this study investigated whether molecular subclasses of HCC predict sensitivity to FGFR inhibition. S2 cell lines were significantly more sensitive (p < 0.001) to the FGFR inhibitors BGJ398 and AZD4547. BGJ398 decreased MAPK signaling in S2 but not in non-S2 cell lines. All cell lines expressed FGFR1 and FGFR2, but only S2 cell lines expressed FGFR3 and FGFR4. FGFR4 siRNA decreased proliferation by 44% or more in all five S2 cell lines (p < 0.05 for each cell line), a significantly greater decrease than seen with knockdown of FGFR1-3 with siRNA transfection. FGFR4 knockdown decreased MAPK signaling in S2 cell lines, but little effect was seen with knockdown of FGFR1-3. In conclusion, the S2 molecular subclass of HCC is sensitive to FGFR inhibition. FGFR4-MAPK signaling plays an important role in driving proliferation of a molecular subclass of HCC. This classification system may help to identify those patients who are most likely to benefit from inhibition of this pathway.

The intralaminar and interlaminar damages of U3160/3266 laminated composites toughened by polyamide nonwoven fabric (PNF) under low velocity impact are investigated through a numerical model which considers both the three-dimensional continuum damage mechanics (CDM) and the bilinear cohesive zone model (CZM). The analysis of the intralaminar damage is implemented by the ABAQUS/Explicit finite element code coupled with a user-defined subroutine VUMAT where the longitudinal failure, transverse matrix cracking, and nonlinear shear of the material are taken into account. Then the effects of the thickness and strength of PNF/3266 interlayer on the damage of composites are numerically analyzed. The results reveal that damage morphology can be simulated qualitatively compared to the experimental counterparts. With the decreasing interlayer thickness or the increasing interlayer strength, the damage area is effectively reduced. This work provides an effective model to predict the low velocity impact damage of composites, and is helpful for the optimization of interlayer toughened composites. POLYM. COMPOS., 2015. © 2015 Society of Plastics Engineers

Background & Aims Hepatocellular carcinoma (HCC) is the second most lethal cancer caused by lack of effective therapies. Although promising, HCC molecular classification, which enriches potential responders to specific therapies, has not yet been assessed in clinical trials of anti-HCC drugs. We aimed to overcome these challenges by developing clinicopathological surrogate indices of HCC molecular classification. Methods Hepatocellular carcinoma classification defined in our previous transcriptome meta-analysis (S1, S2 and S3 subclasses) was implemented in an FDA-approved diagnostic platform (Elements assay, NanoString). Ninety-six HCC tumours (training set) were assayed to develop molecular subclass-predictive indices based on clinicopathological features, which were independently validated in 99 HCC tumours (validation set). Molecular deregulations associated with the histopathological features were determined by pathway analysis. Sample sizes for HCC clinical trials enriched with specific molecular subclasses were determined. Results Hepatocellular carcinoma subclass-predictive indices were steatohepatitic (SH)-HCC variant and immune cell infiltrate for S1 subclass, macrotrabecular/compact pattern, lack of pseudoglandular pattern, and high serum alpha-foetoprotein (>400 ng/ml) for S2 subclass, and microtrabecular pattern, lack of SH-HCC and clear cell variants, and lower histological grade for S3 subclass. Macrotrabecular/compact pattern, a predictor of S2 subclass, was associated with the activation of therapeutically targetable oncogene YAP and stemness markers EPCAM/KRT19. BMP4 was associated with pseudoglandular pattern. Subclass-predictive indices-based patient enrichment reduced clinical trial sample sizes from 121, 184 and 53 to 30, 43 and 22 for S1, S2 and S3 subclass-targeting therapies respectively. Conclusions Hepatocellular carcinoma molecular subclasses can be enriched by clinicopathological indices tightly associated with deregulation of therapeutically targetable molecular pathways.

Based on the continuum damage mechanics (CDM) and the cohesive zone model (CZM), a numerical analysis method for the evaluation of damage in composite laminates under low-velocity impact is proposed. The intraply damage including matrix crack and fiber fracture is represented by the CDM which takes into account the progressive failure behavior in the ply, using the damage variable to describe the intraply damage state. The delamination is characterized by a special contact law including the CZM which takes into account the normal crack and the tangential slip. The effect of the interlaminar toughness on the impact damage is investigated, which is as yet seldom discussed in detail. The results reveal that as the interlaminar fracture toughness enhances, the delamination area and the dissipated energy caused by delamination decrease. The contribution of normal crack and tangential slip to delamination is evaluated numerically, and the later one is the dominant delamination type during the impact process. Meanwhile, the numerical prediction has a good agreement with the experimental results. The study is helpful for the optimal design and application of composite laminates, especially for the design of interlaminar toughness according to certain requirements. POLYM. COMPOS., 2014. © 2014 Society of Plastics Engineers

A new numerical simulation method was proposed to predict the mechanical behavior of carbon fiber reinforced resin composites under low-velocity impact load. The impact damage evolution can be characterized in the form of energy dissipation which can be calculated through the new numerical model. The evolution mechanism of delamination was analyzed through distinguishing between the normal induced delamination and tangential slip induced delamination. The drop weight tests were conducted on composite laminates with five kinds of stacking sequence. Experimental analysis was also presented in this article. The damage area and distribution was investigated through ultrasonic C-scan. The prediction had a good agreement with the experimental results through the comparison of impact response. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44374.