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ABSTRACT Background Lung squamous cell carcinoma (LUSC) is a type of lung cancer that develops in the squamous cells. It is known to be promoted by the activation of various signaling pathways and the dysregulation of key regulatory molecules. One such molecule, 5′‐nucleotidase domain containing 2 (NT5DC2), has been identified as a critical regulator in various cancers including lung cancer. However, there are no data regarding its role in LUSC. Methods The mRNA expression of insulin‐like growth factor 2 mRNA–binding protein 3 (IGF2BP3), CCCTC‐binding factor (CTCF), and NT5DC2 was analyzed using quantitative real‐time polymerase chain reaction (qRT‐PCR), whereas their protein expression was assessed using a western blotting assay. Cell proliferation was determined using a cell counting kit‐8 (CCK‐8) assay. Cell apoptosis, CD11b expression, and CD206 expression were analyzed using flow cytometry. Tube formation was assessed through a tube formation assay. Glucose consumption, lactate production, and ATP levels were measured using colorimetric methods. The effect of NT5DC2 on the malignant progression of LUSC cells was analyzed using a xenograft mouse model assay. The levels of transforming growth factor‐beta 1 (TGF‐β1) and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assays. The associations among IGF2BP3, CTCF and NT5DC2 were identified using dual‐luciferase reporter assay, RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. Results The expression of NT5DC2 was found to be upregulated in LUSC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Silencing of NT5DC2 inhibited LUSC cell proliferation, tube formation, glycolysis, M2 macrophage polarization, and tumor formation while inducing cell apoptosis. In addition, CTCF was found to transcriptionally activate NT5DC2 in LUSC cells. IGF2BP3 stabilized the mRNA expression of CTCF through m6A methylation. Further, overexpression of CTCF or NT5DC2 attenuated the effects of IGF2BP3 silencing in both NCI‐520 and SK‐MES‐1 cells. Conclusion The IGF2BP3/CTCF axis–dependent NT5DC2 promotes M2 macrophage polarization, thereby enhancing the malignant progression of LUSC. This study was the first to reveal the role of NT5DC2 in LUSC and the underlying mechanism. The result suggests that targeting the IGF2BP3/CTCF/NT5DC2 axis may have clinical significance in the treatment of LUSC.

Friction stir welding of dissimilar Al/Mg thick plates still faces severe challenges, such as poor formability, formation of thick intermetallic compounds, and low joint strength. In this work, two joint configurations, namely inclined butt (conventional butt) and serrated interlocking (innovative butt), are proposed for improving weld formation and joint quality. The results show that a continuous and straight intermetallic compound layer appears at the Mg side interface in conventional butt joint, and the maximum average thickness reaches about 60.1 µm. Additionally, the Mg side interface also partially melts, forming a eutectic structure composed of Mg solid solution and Al12Mg17 phase. For the innovative butt joint, the Mg side interface presents the curved interlocking feature, and intermetallic compounds can be reduced to less than 10 µm. The joint strength of innovative butt joint is more than three times that of conventional butt joint. This is due to the interlocking effect and thin intermetallic compounds in the innovative joint.

Futures trading in developing countries is now attracting more attention since investors may easily generate more excess return compared to the markets in developed countries, especially in Chinese market. In this paper, we analyzed the relationship between the centrality of commodity in the Chinese commodity futures market network and the optimal weight of each commodity in a portfolio, empirically examined the market systemic factors and commodity idiosyncratic factors that affect the centrality of commodity, and evaluated the effect of network structure on the optimization of commodity portfolio selection under the mean-variance framework. We found that the commodities with high network centrality are often related to industrial products with high volatility and small portfolio weights. We put forward a kind of commodity futures investment strategy based on this network and results showed that cumulative yield is better than other benchmark portfolios. The main contribution of this paper is to apply complex network theory to optimize futures portfolio selection by establishing the relationship between portfolio weight and commodity centrality in Chinese market, which is still under explored.

Abstract Metal–organic frameworks (MOFs) are recognized as promising electrocatalysts for the oxygen evolution reaction (OER) because of their permanent porosity and rich architectural diversity; however, ionic MOFs enabling fast ions exchange during OER are rarely explored. Here, an ionic MOF (Ni‐btz) constructed with an azolate ligand is selected, and continuous 3D bimetallic MOF (NiFe‐btz) films deriving from high‐degree intergrowth of microsized MOFs particles are fabricated. The as‐prepared NiFe‐btz/NF‐OH electrode exhibits excellent OER performance with a low overpotential of 239 mV at 10 mA cm−2 under alkaline condition. The OER charge transfer process and bimetallic coupling effect in ionic NiFe‐btz are probed by density functional theory calculations and confirmed via X‐ray photoelectron spectroscopy and in situ Raman measurements. The partial density of states of NiFe‐btz indicates that the main contribution for electron density around the Fermi level is from Cl ions clarifying the profitable impact of ionic MOF framework. This work systematically demonstrates the relationship of electronic structure and OER activity in ionic, bimetallic MOFs and expands the scope of 3D MOF films for efficient OER.

Seven guanylate-binding proteins (GBPs, GBP1–7), identified as a subfamily of interferon-γ-induced guanosine triphosphate hydrolases (GTPases), has been reported to be closely associated with tumor progression, metastasis, and prognosis of cancer patients in recent years. However, the expression patterns, prognostic value, immune infiltration relevance, and biological functions of GBPs in lower-grade glioma (LGG) remain elusive. In this study, by analysis and verification through multiple public data platforms, we found that GBP1, 2, 3, 4 were significantly upregulated in LGG tissues vs normal brain tissue. Analysis based on the Cox proportional hazard ratio and Kaplan–Meier plots demonstrated that the high expressions of GBP 1, 2, 3, 4 were significantly correlated with the poor prognosis of LGG patients. Correlation analysis of clinical parameters of LGG patients indicated that the expressions of GBP 1, 2, 3, 4 were significantly associated with the histological subtype and tumor histological grade of LGG. Furthermore, the correlation analysis of immune infiltration showed that the expressions of GBP1, 2, 3, 4 were significantly and positively correlated with the level of tumor immune-infiltrating cells. In particular, GBP1, 2, 3, 4 expressions were strongly correlated with the infiltration levels of monocyte, TAM, and M1/M2 macrophage, revealing their potential to regulate the polarity of macrophages. Finally, we used the GSEA method to explore the signaling pathways potentially regulated by GBP1, 2, 3, 4 and found that they were all closely associated with immune-related signaling pathways. Collectively, these findings suggested that GBP1, 2, 3, 4 were potent biomarkers to determine the prognosis and immune cell infiltration of LGG patients.

Abstract Background In mammalian cells, Aurora serine/threonine kinases (Aurora A, B, and C) are expressed in a cell cycle-dependent fashion as key mitotic regulators required for the maintenance of chromosomal stability. Aurora-A (AURKA) has been proven to be an oncogene in a variety of cancers; however, whether its expression relates to patient survival and the association with radiotherapy remains unclear in non-small cell lung cancer (NSCLC). Methods Here, we first analyzed AURKA expression in 63 NSCLC tumor samples by immunohistochemistry (IHC) and used an MTS assay to compare cell survival by targeting AURKA with MLN8237 (Alisertib) in H460 and HCC2429 (P53-competent), and H1299 (P53-deficient) cell lines. The radiosensitivity of MLN8237 was further evaluated by clonogenic assay. Finally, we examined the effect of combining radiation and AURKA inhibition in vivo with a xenograft model and explored the potential mechanism. Results We found that increased AURKA expression correlated with decreased time to progression and overall survival (p = 0.0447 and 0.0096, respectively). AURKA inhibition using 100 nM MLN8237 for 48 h decreases cell growth in a partially P53-dependent manner, and the survival rates of H460, HCC2429, and H1299 cells were 56, 50, and 77%, respectively. In addition, the survival of H1299 cells decreased 27% after ectopic restoration of P53 expression, and the radiotherapy enhancement was also influenced by P53 expression (DER H460 = 1.33; HCC2429 = 1.35; H1299 = 1.02). Furthermore, tumor growth of H460 was delayed significantly in a subcutaneous mouse model exposed to both MLN8237 and radiation. Conclusions Taken together, our results confirmed that the expression of AURKA correlated with decreased NSCLC patient survival, and it might be a promising inhibition target when combined with radiotherapy, especially for P53-competent lung cancer cells. Modulation of P53 function could provide a new option for reversing cell resistance to the AURKA inhibitor MLN8237, which deserves further investigation.

Ovate family proteins (OFPs) are a class of proteins with a conserved OVATE domain that contains approximately 70 amino acid residues. OFP proteins are plant-specific transcription factors that participate in regulating plant growth and development and are widely distributed in many plants. Little is known about OFPs in Brassica rapa to date. We identified 29 OFP genes in Brassica rapa and found that they were unevenly distributed on 10 chromosomes. Intron gain events may have occurred during the structural evolution of BraOFP paralogues. Syntenic analysis verified Brassica genome triplication, and whole genome duplication likely contributed to the expansion of the OFP gene family. All BraOFP genes had light responsive- and phytohormone-related cis-acting elements. Expression analysis from RNA-Seq data indicated that there were obvious changes in the expression levels of six OFP genes in the Brassica rapa hybrid, which may contribute to the formation of heterosis. Finally, we found that the paralogous genes had different expression patterns among the hybrid and its parents. These results provide the theoretical basis for the further analysis of the biological functions of OFP genes across the Brassica species.

The discovery of thermodynamically stable thermoelectric materials for power generation has relied on empirical methods that were not effective. Here, the authors apply the inverse design approach to identify and experimentally realize TaFeSb-based half Heuslers with high thermoelectric performance.

Identifying new compounds with intrinsically high conversion efficiency is the key to demonstrating next-generation thermoelectric modules. Here, Zhu et al. report the discovery of p-type ZrCoBi-based half Heuslers with thermoelectric conversion efficiency of 9% and large high-temperature stability.

Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups. Western blot was performed to analyze the expression of phosphorylated EGFR, AKT, DNA-dependent protein kinase, and catalytic subunit (DNA-PKcs) proteins. Immunofluorescence analyses were performed to examine the formation and changes in nuclear γ-H2AX foci. Cell apoptosis was examined by flow cytometry and Western blots for cleaved caspase-3, -8, -9, and cleaved poly ADP-ribose polymerase (PARP). Furthermore, we established xenograft models in mice and the effects of different treatments on tumor growth were then assessed.Results: Clonogenic survival assays revealed that HS-10182 significantly enhanced the radiosensitivity of H1975 cells but not A549 cells [dose enhancement ratios (DERs)=2.36 (P < 0.05) vs. 1.43 (P > 0.05)]. Western blot results showed that HS-10182 increased the levels of cleaved caspase-3, -8, -9, and cleaved PARP in H1975 cells but not in A549 cells. In addition, flow cytometry analysis showed that HS-10182 enhanced irradiation-induced apoptosis in H1975. Immunofluorescence results found that HS-10182 increased the average number of γ-H2AX foci after irradiation in H1975 cells, but not in A549 cells. Combined radiation and HS-10182 treatment increased the expression of DNA-PKcs but this increase was more significant in H1975 cells than in A549 cells. Moreover, HS-10182 suppressed the increased expression of Rad50 in H1975 cells in response to irradiation. In vivo experiments found that the combined therapy significantly inhibited tumor growth.Conclusions: HS-10182 enhances the radiosensitivity of H1975 cells which is possibly because that HS-10182 could enhance irradiation-induced apoptosis, increase irradiation-induced DNA damage, and cause a delay in DNA damage repair. Our findings suggest that radiotherapy combined HS-10182 is a novel treatment for lung cancer cells which have acquired the T790M mutation. HS-10182 could be brought to the clinic as a radiosensitizer in NSCLCs with the EGFR T790M mutation.

Characters in historical documents are typically densely distributed and are difficult to localize and segment by directly applying classic proposal and regression based methods. In this paper, we propose a novel method called recognition guided detector (RGD) that achieves tight Chinese character detection in historical documents. The proposed RGD consists of two simultaneously trained convolutional neural networks: a recognition guided proposal network that provides context information of the text and a detection network that applies this information to localize each of the characters accurately. To train and test the proposed method, we established two new datasets with character-level annotations, comprising ground truth character bounding boxes and ground truth characters in each of the boxes. The data in our datasets are scanned images collected from nine different versions of Tripitaka in Han. Experimental results show that, guided by a text recognition network with a test accuracy of 97.25%, the detection network in our proposed method achieves a much higher F-score with fewer parameters under a highly constrained evaluation criterion of intersection of union (IoU) ≥ 0.7, when comparing to several state-of-the-art object detection and text detection methods. The datasets are publicly available at https://github.com/HCIILAB/TKH_MTH_Datasets_Release for non-commercial use.

Background/Aims: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. Methods: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes’ definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. Results: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. Conclusion: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.

The dissemination of Klebsiella pneumoniae carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant Aeromonas taiwanensis isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among A. taiwanensis isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of blaKPC–2 and qnrS2 genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from Aeromonas spp. and IncP-6-type plasmid: 1 from Citrobacter freundii at 74% coverage. A 14,808 bp insertion sequence was observed between merT gene and hypothetical protein in p1713-KPC, which include the quinolone resistance qnrS2 gene. Emergence of plasmid-borned blaKPC and qnrS2 genes from A. taiwanensis isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored.

We present an investigation of the thermoelectric properties of cubic perovskite SrTiO3. The results are derived from a combination of calculated transport functions obtained from Boltzmann transport theory in the constant scattering time approximation based on the electronic structure and existing experimental data for La-doped SrTiO3. The figure of merit ZT is modeled with respect to carrier concentration and temperature. The model predicts a relatively high ZT at optimized doping and suggests that the ZT value can reach 0.7 at T = 1400 K. Thus ZT can be improved from the current experimental values by carrier concentration optimization.

We discuss and present search strategies for finding new thermoelectric compositions based on first principles electronic structure and transport calculations. We illustrate them by application to a search for potential n-type oxide thermoelectric materials. This includes a screen based on visualization of electronic energy isosurfaces. We report compounds that show potential as thermoelectric materials along with detailed properties, including SrTiO3, which is a known thermoelectric, and appropriately doped KNbO3 and rutile TiO2.

Appearance models play an important role in visual tracking. Effective modeling of the appearance of tracked objects is still a challenging problem because of object appearance changes caused by factors, such as partial occlusion, illumination variation and deformation, etc. In this paper, we propose a tracking method based on the patch descriptor and the structural local sparse representation. In our method, the object is firstly divided into multiple non-overlapped patches, and the patch sparse coefficients are obtained by structural local sparse representation. Secondly, each patch is further decomposed into several sub-patches. The patch descriptors are defined as the proportion of sub-patches, of which the reconstruction error is less than the given threshold. Finally, the appearance of an object is modeled by the patch descriptors and the patch sparse coefficients. Furthermore, in order to adapt to appearance changes of an object and alleviate the model drift, an outlier-aware template update scheme is introduced. Experimental results on a large benchmark dataset demonstrate the effectiveness of the proposed method.