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Abstract Background Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. Methods Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method. Results We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. Conclusion The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49’s function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.

Tropical Asian collections of Inosperma are usually poisonous mushrooms that have caused many poisoning incidents. However, the species diversity and the toxic mechanisms of these Inosperma species are still unclear. In this study, we describe the discovery of Inosperma wuzhishanense sp. nov. from Wuzhishan City, Hainan Province, tropical China. The new species was identified based on morphological and multi-locus (ITS, nrLSU, and RPB2) phylogenetic analyses. The new species is characterized by its reddish-brown pileus, fibrillose stipes with finely protruding fibrils, rather crowded lamellae, smooth and ellipsoid basidiospores, and mostly clavate, thin-walled cheilocystidia. The new species is phylogenetically nested in the Old World tropical clade 2 and is sister to the tropical Indian taxa I. akirnum. Detailed descriptions, color photos of the new species, and comparisons with its closely related species are provided. Additionally, the muscarine content of the new species was analyzed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS). The muscarine contents ranged from 4,359.79 ± 83.87 mg/kg to 7,114.03 ± 76.55 mg/kg, 2,748.37 ± 106.85 mg/kg to 4,491.35 ± 467.21 mg/kg, and 2,301.36 ± 83.52 mg/kg to 2,775.90 ± 205.624 mg/kg in the stipe, pileus, and lamellae, respectively. The elemental composition and concentration were determined using inductively coupled plasma-mass spectrometry (ICP-MS). A total of 24 elements were detected. Among the heavy metals detected, arsenic showed the highest level of toxicity with a concentration of 36.76 ± 0.43 mg/kg.

Abstract It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r 2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

The effect of Ca addition on the solidification microstructure of hypoeutectic Al-Si casting alloys was investigated using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods with particular attention focused on the change of morphologies of primary α-Al and eutectic silicon. Meanwhile, solute distribution in solid-liquid was simulated according to Scheil-Gulliver law. Results showed that primary α-Al and eutectic silicon were refined as Ca content increased because of the variation of the solute concentration in liquid. The addition of Ca increased the nucleation sites like Al3Ti or Al2Cu to promote the nucleation of primary α-Al. Affected by modification effect of Ca, the shape of eutectic silicon changed from flake to fibrous structure. In addition, coarse plate Ca-rich phases could be found along the grain boundary with high Ca content.

HfO2 thin film is deposited on p-Si substrates by RF magnetron sputtering apparatus and annealed at 750 °C for 10 min with O2 atmosphere. Spectral analysis shows that HfO2 thin films have good transmittance to light, especially ultraviolet band. The HfO2 layers belong monoclinic phase and its thickness is about 50 nm. In the Au/HfO2/p-Si structure, photodiode characteristics were studied at room temperature and compared with the light current generated under white light, the response current generated under ultraviolet light is more prominent. The photocurrent reaches 80 μA and the repeatable response of device under 23.5 mW/cm2 ultraviolet illuminating is stable. It's found that the working mechanism of this photodiode could have three different states: the majority carrier stacking state of reverse bias, the majority carrier depletion state of forward bias with dark condition and the minority carrier inversion state of forward bias with ultraviolet illumination. The device also has a high damage threshold and its photocurrent is still not saturated at bias 8 V, indicating that it can be applied as a new type of UV detector. Keywords: HfO2 thin films, MOS device, Photodiode, Photocurrent, Free carriers

The resistive switching (RS) characteristics of flexible films deposited on mica substrates have rarely been reported upon, especially flexible HfO2 films. A novel flexible Au/HfO2/Pt/mica resistive random access memory device was prepared by a sol-gel process, and a Au/HfO2/Pt/Ti/SiO2/Si (100) device was also prepared for comparison. The HfO2 thin films were grown into the monoclinic phase by the proper annealing process at 700 °C, demonstrated by grazing-incidence X-ray diffraction patterns. The ratio of high/low resistance (off/on) reached 1000 and 50 for the two devices, respectively, being relatively stable for the former but not for the latter. The great difference in ratios for the two devices may have been caused by different concentrations of the oxygen defect obtained by the X-ray photoelectron spectroscopy spectra indicating composition and chemical state of the HfO2 thin films. The conduction mechanism was dominated by Ohm’s law in the low resistance state, while in high resistance state, Ohmic conduction, space charge limited conduction (SCLC), and trap-filled SCLC conducted together.

As regression testing size and cost increase,test suite reduction becomes more important to promote its efficiency.Du-ring the selection of test suite subset,we are supposed to consider the representativeness and diversity of subset,and apply an effective algorithm to solve it.Aimed at test suite reduction,a submodular function maximization based algorithm,SubTSR,is proposed in this paper.Although the introduced discrete optimization problem is an NP-hard problem,the heuristic greedy search is used in this paper to find the suboptimal solution with approximation guarantee by exploiting the submodularity of the objective function.To validate the effectiveness of the SubTSR algorithm,the SubTSR algorithm is experimented on fifteen datasets with changes of topic count in LDA and distance for similarity measurement,and compared with other test suite reduction algorithms about the average percentage of fault-detection,fault detection loss rate,first faulty test's index and other metrics.The experiment results show that the SubTSR algorithm has significant improvement in fault detection performance compared with other algorithms,and its performance remains relatively stable on different datasets.Under the text representation change due to topic count change,the SubTSR combined with Manhattan distance keeps relatively stable compared with other algorithms.