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Abstract: Lymph-node metastasis is a main factor causing poor prognosis of patients with gastric cancer (GC). In order to determine the genes involved in lymph-node metastasis, we compared primary tumors with their synchronous lymph-node metastases for DNA sequence copy number aberrations (DSCNAs) in 20 patients diagnosed as having intestinal-type GC using comparative genomic hybridization (CGH). The results showed that some DSCNAs (gains at 8q, 13q, 5p, 7 and X, and losses at 1p, 17p, 19, 21q and 22q) were frequently found in both primary tumors and their metastases. However, metastases often contained DSCNAs that were not found in corresponding primary tumors, and gain at 20q12–13 and losses at 21qcen-21, 4q and 14q22-ter were significantly more frequently observed in metastatic lesions than in their primary tumors (10:2, 9:0, 6:0, and 7:0 between metastases and corresponding primary tumors, respectively). Our data indicate that gain at 20q12–13 and losses at 21qcen-21, 4q, and 14q22-ter are involved in lymph-node metastases, and that these chromosomal regions may contain the genes related to lymph-node metastases in intestinal-type GC. [Copyright &y& Elsevier]

Astrocytes provide structural, metabolic and trophic supports for neurons. However, there are no direct evidences whether astrocytes involve in the regulation of synaptic proteins expression and tau phosphorylation until now. Here, we injected 1 nmol fluorocitrate (FC), which preferentially taken up by astrocytes and results in reversible inhibition of the astrocytic tricarboxylic acid cycle, into the left lateral ventricle of the brain in the SD rats for 1 h, and found that FC treatment decreased several memory-related proteins levels, such as AMPA receptor GluR1/2, postsynaptic density protein 93/95, Arc and phosphorylated cAMP response element binding proteins, while increased synaptophysin and synapsin I levels in the hippocampus. FC treatment also increased the levels of phosphorylated tau at multiple Alzheimer-related phosphorylation sites, as well as activation of glycogen synthase kinase-3β and inactivation of protein phosphatase-2A. Similar effects were also observed in the primary hippocampal neurons, which were cultured with the conditioned media from FC-treatment primary astrocytes. Our data suggest that astrocytes regulate neuronal tau phosphorylation and several synaptic proteins expression. [ABSTRACT FROM AUTHOR]

The low intensity of the X-ray pulsar signal and the strong X-ray background radiation lead to low signal-to-noise ratio (SNR) of the X-ray pulsar observed profile obtained through epoch folding, especially when the observation time is not long enough. This signifies the necessity of denoising of the observed profile. In this paper, the statistical characteristics of the X-ray pulsar signal are studied, and a signal-dependent noise model is established for the observed profile. Based on this, a profile noise reduction method by performing a local linear minimum mean square error filtering in the un-decimated wavelet domain is developed. The detail wavelet coefficients are rescaled by multiplying their amplitudes by a locally adaptive factor, which is the local variance ratio of the noiseless coefficients to the noisy ones. All the nonstationary statistics needed in the algorithm are calculated from the observed profile, without a priori information. The results of experiments, carried out on simulated data obtained by the ground-based simulation system and real data obtained by Rossi X-Ray Timing Explorer satellite, indicate that the proposed method is excellent in both noise suppression and preservation of peak sharpness, and it also clearly outperforms four widely accepted and used wavelet denoising methods, in terms of SNR, Pearson correlation coefficient and root mean square error. [ABSTRACT FROM AUTHOR]

Breast cancers bear overexpression of neurokinin-1 (NK-1). The aim of this study was to investigate the relationship between NK-1 and EGFR in triple negative breast cancers (TNBCs). Immunohistochemistry was performed to investigate NK-1 and EGFR expressions in TNBCs. [Sar 9 , \Met(O 2 ) 11 ] substance P (SMSP) was used to activate NK-1 in two TNBC cell lines, MDA-MB-231 and MDA-MB-468. L-733060 and siRNA against NK-1 were used to inhibit NK-1. The in vitro regulatory effect of NK-1 was determined using CCK-8 proliferation assay. The effects of NK-1 activation and inhibition on EGFR and its downstreaming pathway were analyzed using western blot and real-time quantitative PCR. We found that the proportion of EGFR positive cases was increased with the increasement of NK-1 levels. SMSP could promote the proliferation of TNBC cells, while L-733060 and siRNA could inhibit cell proliferation and induce apoptosis. Moreover, SMSP could enhance expressions of phosphorylation (p)-EGFR and EGFR, and activate p-Akt and p-Erk. NK1-siRNA could decrease p-EGFR, p-Akt and p-Erk. In the presence of cetuximab (0.2 mg/mL), SMSP still could stimulate cell proliferation, and activate p-EGFR. However, in the presence of erlotinib (10 μM), SMSP could not stimulate cell proliferation and could not activate p-EGFR. Our study showed the interaction between NK-1 and EGFR in TNBCs. These results suggested that NK-1 may regulate TNBC proliferation through EGFR phosphorylation, and the curative effect of EGFR monoclonal antibodies may be affected by NK-1 activation. [ABSTRACT FROM AUTHOR]

Abstract: In order to evaluate influences of roots on soil shear strength, a triaxial compression test was carried out to study the shear strength of plain soil samples and composites comprised of roots of Robinia pseucdoacacia and soil from the Loess Plateau in Northwest China. Roots were distributed in soil in three forms: vertical, horizontal, and vertical–horizontal (cross). All samples were tested under two different soil water contents. Test results showed that roots have more impacts on the soil cohesion than the friction angle. The presence of roots in soil substantially increased the soil shear strength. Among three root distribution forms, the reinforcing effect of vertical–horizontal (cross) root distribution was the most effective. Increase in soil water content directly induced a decline in soil cohesion of all test samples and resulted in a decrease in shear strength for both plain soil samples and soil–root composites. It was concluded that the triaxial compression test can be effectively used to study influences of roots on soil shear strength. [Copyright &y& Elsevier]

We propose a geometry-guided neural network architecture for robust and detail-preserving surface normal estimation for unstructured point clouds. Previous deep normal estimators usually estimate the normal directly from the neighbors of a query point, which lead to poor performance. The proposed network is composed of a weight learning sub-network (WL-Net) and a lightweight normal learning sub-network (NL-Net). WL-Net first predicates point-wise weights for generating an optimized point set (OPS) from the input. Then, NL-Net estimates a more accurate normal from the OPS especially when the local geometry is complex. To boost the weight learning ability of the WL-Net, we introduce two geometric guidance in the network. First, we design a weight guidance using the deviations between the neighbor points and the ground truth tangent plane of the query point. This deviation guidance offers a "ground truth" for weights corresponding to some reliable inliers and outliers determined by the tangent plane. Second, we integrate the normals of multiple scales into the input. Its performance and robustness are further improved without relying on multi-branch networks, which are employed in previous multi-scale normal estimators. Thus our method is more efficient. Qualitative and quantitative evaluations demonstrate the advantages of our approach over the state-of-the-art methods, in terms of estimation accuracy, model size and inference time. Code is available at https://github.com/2429581027/local-geometric-guided. • A new two-step normal estimation method. • Integrate geometric priors into deep learning framework. • Replace multi-scale architecture by multi-scale geometric input. • Achieve 10.79 angle error in comparison with the previous state of the art of 11.78. [ABSTRACT FROM AUTHOR]

Hepalatide blocks uptake of bile acids by NTCP receptor on hepatocytes, and leads to an increase in bile acids which act on FXR on the liver for the improvements of lipid metabolism, glucose consumption and insulin sensitivity. Increased bile acids stimulate TGR5 on muscle and adipose tissue to increase the thermogenesis and energy expenditure. BAs: bile acids; FXR: farnesoid X receptor; NTCP: sodium taurocholate cotransporting polypeptide; TG: triglyceride; TGR5: Takeda G-protein-coupled receptor 5. • Hepalatide treatment reduced body and liver weight in a murine NASH model. • Hepalatide treatment attenuated hepatic steatohepatitis in mice. • Hepalatide treatment improved insulin resistance in NASH mice. • Hepalatide treatment blocked hepatic fibrosis progression in NASH mice. • An increase in bile acids is responsible for Hepalatide's effects as an NTCP blocker. No FDA-approved medications are available for the treatment of nonalcoholic steatohepatitis (NASH). The present study aimed to assess the effects of Hepalatide, a sodium taurocholate cotransporting polypeptide (NTCP) receptor-binding agent, on metabolic and histopathologic changes of a mouse model of NASH caused by high fat/calorie diet plus high fructose/glucose in drinking water (HFCD-HF/G) for 16 weeks. Male mice were randomly divided into 4 groups: controls (normal diet), HFCD-HF/G group, HFCD-HF/G plus low or high dose of Hepalatide (20 or 60 mg/kg, LH or HH, s.c. from 9 to 16 weeks). Compared to HFCD-HF/G-fed mice, serum triglyceride and cholesterol levels in mice fed HFCD-HF/G plus LH or HH were decreased. The treatment with Hepalatide decreased serum alanine aminotransferase levels significantly. Liver histology and TUNEL staining showed that Hepalatide remarkably attenuated inflammation, hepatocellular steatosis and apoptosis. Hepalatide treatment decreased fasting blood glucose, serum insulin and HOMA insulin resistance index in the HH group. Moreover, Masson's staining, semi-quantitative score of fibrosis, and hydroxyproline content demonstrated that Hepalatide mitigated fibrotic progression in this murine NASH model. Additionally, most components of liver and few serum bile acids were increased in mice treated with HH. Hepalatide effectively alleviated the pathological process, metabolic profile, hepatocellular steatosis and injury, insulin resistance, halted hepatic fibrotic progression in a mouse model of NASH, most likely through the increase of serum bile acids. [ABSTRACT FROM AUTHOR]