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This paper presented a non-linear modeling approach for bolted joint connection interfaces and identified the micro-slip model’s parameters through quasi-static experiments based on an improved micro-slip model. Firstly, considering the contact pressure’s spatial distribution characteristics on the connection interface, a new density function of critical sliding force was proposed. The contact pressure is distributed annularly on the interface. Then, the critical sliding force’s density function was applied to the Iwan model, and an improved micro-slip model was proposed. The residual shear stiffness on the connection interface during macro-slip and separation was also taken into account simultaneously. The piecewise linear model and the improved micro-slip model were adopted to reproduce the different tensile and compressive stiffness of the bolted joint and the friction on the interface, and the non-linear mechanical model of the bolted joint was obtained. Finally, this paper proposed a method for parameter identification of the micro-slip model on the connection interface. The hysteresis loops were obtained through quasi-static shear experiments, and corresponding parameters were identified.

Previously, it has been shown that obesity may be considered as a risk factor for breast cancer in postmenopausal women. Leptin, a hormone whose level is elevated in obesity, has been suggested to be involved in the development of breast cancer, and univariate survival analyses have shown that over-expression of ACAT2, an enzyme that is involved in the production of cholesteryl esters, may be associated with a poor prognosis. Here, we aimed to investigate the effect of leptin on the proliferation, migration and invasion of breast cancer cells, as well as to elucidate its underlying mode of action. Gene expression changes in leptin treated breast cancer-derived MCF-7, T47D and BT474 cells were assessed using PCR array, qRT-PCR and Western blot analyses. The expression patterns of Ob-R (leptin receptor) and ACAT2 in breast cancer cells and primary breast cancer tissue samples were analyzed using immunofluorescence and immunohistochemistry, respectively. Leptin-induced proliferation of breast cancer cells was assessed using a CCK8 assay, and scratch wound and Transwell assays were used to assess breast cancer cell invasion and migration. We found that, among the genes tested, ACAT2 expression exhibited the most significant changes in the leptin treated cells. In addition, we found that inhibition of ACAT2 expression using pyripyropene A (PPPA) or siRNA-mediated gene silencing significantly decreased leptin-induced proliferation, migration and invasion of MCF-7 and T47D cells. Subsequent Western blot analyses strongly indicated that the PI3K/AKT/SREBP2 signaling pathway was involved in leptin-induced ACAT2 upregulation in both MCF-7 and T47D cells. Finally, through the analysis of primary breast cancer tissue samples we found that ACAT2 may affect cancer progression through activation of the Ob-R. Our data indicate that leptin may enhance the proliferation, migration and invasion of breast cancer cells via ACAT2 up-regulation through the PI3K/AKT/SREBP2 signaling pathway. Therefore, the leptin/ACAT2 axis may represent an attractive therapeutic target for breast cancer, particularly in postmenopausal and/or obese women.

Primary cutaneous amyloidosis (PCA) is a localized skin disorder that is characterized by the abnormal deposition of amyloid in the extracellular matrix (ECM) of the dermis. The pathogenesis of PCA is poorly understood. The objective of the present study was to survey proteome changes in PCA lesions in order to gain insight into the molecular basis and pathogenesis of PCA. Total protein from PCA lesions and normal skin tissue samples were extracted and analyzed using the isobaric tags for relative and absolute quantitation technique. The function of differentially expressed proteins in PCA were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction analysis. The proteins that were most upregulated in PCA lesions were further analyzed by immunohistochemistry. A total of 1,032 proteins were identified in PCA lesions and control skin samples, with 51 proteins differentially expressed in PCA lesions, of which 27 were upregulated. In PCA lesions, the upregulated proteins were primarily extracellulary located. In addition, GO analysis indicated that the upregulated proteins were significantly enriched in the biological processes of epidermal development, collagen fiber organization and response to wounding (adjusted P

To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down’s syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down’s syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down’s syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down’s syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down’s syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a “before and after” two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation.Impact statementChildren born with Down’s syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down’s syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down’s syndrome and to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down’s syndrome. Results demonstrate that fetal cfDNA can significantly reduce false-positive rate close to none while distinguishing all true positives. Thus, we recommend that fetal cfDNA analysis to be utilized as a secondary screening tool atop of the primary blood protein screening to further minimize the capacity of undesirable invasive diagnostic operations.

The replacement of a damaged temporomandibular joint (TMJ) disc remains a long-standing challenge in clinical settings. No study has reported a material with comprehensively excellent properties similar to a natural TMJ disc. In this work, we designed a novel artificial TMJ disc using polyvinyl alcohol (PVA) hydrogel crosslinked by cyclic freeze-thaw and reinforced by 3D-printed polycaprolactone (PCL) implants. The mechanical properties and surface morphologies of the artificial TMJ disc and the natural goat TMJ disc were tested and compared via compression, tensile, cyclic compression/tensile, creep, friction, scanning electron microscopy, and atomic force microscopy. The fibroblasts and chondrocytes were cultured on the artificial TMJ disc for 1, 3, and 5 d for cytotoxicity testing. Importantly, the artificial discs were placed into the TMJs of goats in an innovative way to induce disc defect repair for 12 wk. The PVA + PCL artificial disc demonstrated mechanical strength similar to that of natural disc, as well as 1) better fatigue resistance, viscoelasticity, and hydrophilicity; 2) less creep; and 3) low friction, cytotoxicity, and cell adhesion. By repairing the defects of the TMJ disc in goats, the artificial disc demonstrated the ability to maintain joint stability and protect condylar cartilage and bone from damage. These promising results indicate the feasibility of using a PVA + PCL artificial TMJ disc in a clinical context.

Metastasis, a powerful prognostic indicator of oral squamous cell carcinoma (OSCC), is chiefly responsible for poor cancer outcomes. Despite an increasing number of studies examining the mechanisms underlying poor outcomes, the development of potent strategies is hindered by insufficient characterization of the crucial regulators. Long noncoding RNAs (lncRNAs) have recently been gaining interest as significant modulators of OSCC metastasis; however, the detailed mechanisms underlying lncRNA-mediated OSCC metastasis remain relatively uncharacterized. Here, we identified a novel alternative splice variant of oral cancer overexpressed 1 ( ORAOV1), named as ORAOV1-B, which was subsequently validated as an lncRNA and correlated with OSCC lymph node metastasis; significantly increased invasion and migration were observed in ORAOV1-B–overexpressing OSCC cells. RNA pulldown and mass spectrometry identified Hsp90 as a direct target of ORAOV1-B, and cDNA microarrays suggested TNFα as a potential downstream target of ORAOV1-B. ORAOV1-B was shown to directly bind to and stabilize Hsp90, which maintains the function of client proteins, receptor-interaction protein, and IκB kinase beta, thus activating the NF-κB pathway and inducing TNFα. Additionally, TNFα reciprocally enhanced p-NF-κB-p65 and the downstream epithelial-mesenchymal transition. ORAOV1-B effects were reversed by a TNFα inhibitor, demonstrating that TNFα is essential for ORAOV1-B–regulated metastatic ability. Consistent epithelial-mesenchymal transition in the ORAOV1-B group was demonstrated via an orthotopic model. In the metastatic model, ORAOV1-B significantly contributed to OSCC-related lung metastasis. In summary, the novel splice variant ORAOV1-B is an lncRNA, which significantly potentiates OSCC invasion and metastasis by binding to Hsp90 and activating the NF-κB-TNFα loop. These findings demonstrate the versatile role of ORAOV1 family members and the significance of genes located within 11q13 in promoting OSCC. ORAOV1-B might serve as an attractive OSCC metastasis intervention target.

A unified method is presented to analyze free vibrations of dual-functional graded nanocomposite laminated cylindrical shells reinforced by carbon nanotubes (CNTs) under arbitrary boundary conditions. Especially, the matrix material of the carbon nanotubes is metal-ceramic functional gradient material (FGM), and the CNT is also assumed to be a gradient distribution in the matrix, constituting the dual-functional graded materials. Based on the first-order shear deformation theory (FSDT) and artificial spring technology, the Chebyshev polynomials was selected as the admissible function, and the Rayleigh-Ritz method was used to derive the vibration differential equation of the laminated shell. Further, the effects of volume fraction of CNTs, change of matrix material, the thickness of the middle layer, and geometric parameters on the natural frequency were discussed.

Aims Intervertebral disc (IVD) degeneration (IDD), a common musculoskeletal disease with limited self-healing ability, is challenging to treat. The development of innovative therapies to reverse IDD depends on the elucidation of its regulatory mechanisms. Therefore, the role of Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) in the pathogenesis of IDD and the therapeutic effect of its small-molecule inhibitor, SHP099, were investigated. Materials and methods The expression of SHP2 by nucleus pulposus (NP) cells in IVD was investigated in vitro and in vivo, and its molecular mechanism in IDD was explored using transfection technology. Injectable N-isopropylacrylamide-based thermosensitive hydrogels were synthesized for SHP099 delivery. Key findings SHP2 was highly expressed in degenerated IVDs, where its overexpression in NP cells inhibited the expression of Sry-related HMG box-9 (Sox9), leading to the decreased expression of key proteins (collagen II and aggrecan) and consequently to IDD. SHP099 reversed the degeneration of NP cells in vitro. Moreover, its administration in rats via the injectable thermosensitive hydrogel had a therapeutic effect on IDD. Significance Our results suggest that SHP2 is a key factor in IDD progression, and SHP099 inhibits both its expression and NP cell degeneration. Therefore, SHP099 delivery via injectable thermosensitive hydrogels is a potential treatment strategy for IDD.

Highly defective hierarchical cuprous oxide was synthesized through a rapid and facile route. The morphology and structure of nanourchin cuprous oxide was characterized by transmission electron microscope, field emission-scanning electron microscope, X-ray diffraction, and Raman spectroscopy analyses. Electrochemical performance was investigated by cyclic voltammetry and amperometric response measurements. The biosensor fabricated with cuprous oxide exhibited excellent properties at a potential of 0.45 V, good linear range of 18.75–1089 μM, detection limit of 18.5 μM (S/N = 3), and a high sensitivity of 1231.7 μA mM−1 cm−2. The reinforced performance of cuprous oxide was attributed to the special 3D hierarchical structure of the material and the high concentrations of defects. A possible mechanism was also deduced.

Construction as well as characterization of a polish wheat transcriptome is a crucial step to study useful traits of polish wheat. In this study, a transcriptome, including 76,014 unigenes, was assembled from dwarf polish wheat (DPW) roots, stems, and leaves using the software of Trinity. Among these unigenes, 61,748 (81.23%) unigenes were functionally annotated in public databases and classified into differentially functional types. Aligning this transcriptome against draft wheat genome released by the International Wheat Genome Sequencing Consortium (IWGSC), 57,331 (75.42%) unigenes, including 26,122 AB-specific and 2,622 D-specific unigenes, were mapped on A, B, and/or D genomes. Compared with the transcriptome ofT. turgidum, 56,343 unigenes were matched with 103,327 unigenes ofT. turgidum. Compared with the genomes of rice and barley, 14,404 and 7,007 unigenes were matched with 14,608 genes of barley and 7,708 genes of rice, respectively. On the other hand, 2,148, 1,611, and 2,707 unigenes were expressed specifically in roots, stems, and leaves, respectively. Finally, 5,531 SSR sequences were observed from 4,531 unigenes, and 518 primer pairs were designed.

Because of the significance in photosynthesis, nutrient dynamics, trophodynamics and biological activity, dissolved organic matter (DOM) is important to the microbial community in the coastal plume zone. In this study, we investigated the hydrodynamic processes, photodegradation and biodegradation of DOM at the Yangtze River plume in the East China Sea through analyzing water quality and optical properties of DOM. Surface water samples were collected to examine water quality and fluorescence properties of fluorescent dissolved organic matter (FDOM). The results indicated that dilution was the key factor in the multiple processes, and the mixing process gradually increased from nearshore to offshore in coastal water. Four components of FDOM representing humic-like substances (C1 & C4) and protein-like substances (C2 & C3) were identified, and all components showed nearly conservative behaviors. Protein-like substances were more mutable compared to humic-like substances. The photodegradation of humic-like substances caused brown algae blooms to some extent. The molecular weight of humic substances gradually decreased along the mixing process. FDOM in the plume zone was both of terrigenous and autochthonous origins, and the characteristic of terrigenous origin was obvious compared to that of autochthonous origin.

Graphene/Co3O4 composites have been considered as promising electrode materials for high-performance supercapacitors; however, their practical applications have been limited by the complex synthesis technologies and narrow potential window of around 0.5 V. Herein we report a facile and economical approach to the massive production of graphene/Co3O4 composites through the one-pot ball-milling of graphite, (NH4)2CO3, and Co(CH3COO)2. During the process, graphite was intercalated by (NH4)2CO3 and synchronously exfoliated into few-layer graphene sheets containing functional groups. Co3O4 nanocrystals were then in-situ grown on the surface of graphene sheets via mechanochemical reactions between (NH4)2CO3 and Co(CH3COO)2. The as-prepared graphene/Co3O4 composites exhibit a high specific capacitance of 570 F g−1 at 1 A g−1, and retain 93% of initial capacitance when the current density is increased by 20 times. The excellent electrochemical performance can be attributed to the synergistic effect between the highly-conductive graphene and nanostructured Co3O4 capable of accelerating the electron conduction and ion transport for increasing the capacitive contribution. Asymmetric supercapacitors were also assembled using graphene and graphene/Co3O4 as negative and positive electrodes, respectively. The asymmetric devices demonstrate a wide operating potential window up to 1.6 V, thus achieving a high specific capacitance of 190 F g−1 at 1 A g−1. Accordingly, the energy density is as high as 67.5 W h kg−1 at the power density of 0.8 kW kg−1. This work provides an affordable and scalable approach to prepare graphene-based composites with metal oxides for high-performance electrode materials for electrochemical energy storage.

Aims It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells. Main methods The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin β was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed. Key findings In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased. Significance Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.

The measurement sensor of the partially-filled pipe electromagnetic flowmeter must be installed where the fluid is fully developed. For partially-filled pipe electromagnetic flowmeters, the boundary conditions vary with the fullness of the pipe, and the distance from the pipe inlet to the fully developed is not the same as the distance of the full-filled pipe flowmeter. Therefore, in the partially-filled pipe state, the mounting position of the electrode sensor is also different from the mounting position at full-filled pipe state. Based on the measurement principle of electromagnetic flowmeter, the finite element simulation method is used to simulate the flow field development of partially-filled pipe electromagnetic flowmeter. First, according to the knowledge of hydraulics, the variable boundary constraint is established, and then the simulation model of flowmeter fluid development process is established. Second, the Comsol Multiphysics finite element simulation software is adopted to solve the fluid development process, and the required distance for the full development of the partially-filled pipe fluid is obtained. Finally, the optimal installation position of the partially-filled pipe electromagnetic flowmeter sensor was determined based on the distance. The simulation results prove the feasibility of the proposed method, which can provide powerful theoretical support for the fabrication of partially-filled pipe electromagnetic flowmeters.

Obtaining the information on the cropping system in a region accurately and timely is important for optimizing the regional agricultural resource allocation and crop layout. However, there are still technical bottlenecks such as poor spatial resolution, low precision and the lack of imagery in the application of remote sensing research in the spatial and temporal distribution of the cropping system. In this study, a more accurate remote sensing monitoring method for the regional cropping system was proposed. The imagery with wide field of view (WFV) of multi-temporal GF-1 satellite was used to construct a temporal extraction model of the cropping system, which was based on normalized difference vegetation index (NDVI). Using the method proposed in this paper, remote sensing monitoring of the main farming system in Suqian City, Jiangsu Province was carried out, which could provide reference for the extraction of the crop system in southern cloud and rain regions. The results showed that the whole crop development period of the main planting system (rice-winter wheat and winter wheat-summer maize) in the study area was covered by selecting the high time density GF-1 / WFV with 16 m resolution remote sensing imagery acquired from 2016 to 2017 as the data sources, and the complementarity of the multi-temporal imagery avoided the imagery loss caused by the cloudy climate in the middle and lower reaches of the Yangtze River in China. By building a mask and marking the “polluted” areas of the cloud, the interference of cloud imagery on crop information extraction was reduced effectively. In addition, the decision condition was optimized several times by the human-computer interaction, and the key parameter was determined to ensure the accuracy of the temporal extraction model. According to the result of monitoring the major cropping system in Suqian City, the overall classification accuracy was 93.56%, Kappa coefficient was 0.85 and the relative margin of error for individual crops was 7.53%, which met the accuracy requirements for application of agricultural achievements. These results showed that, in comparison with previous remote sensing methods, the method proposed in this study can monitor the regional main crop planting system accurately and can be used to monitor the cropping system based on the high-resolution imagery in multiple ripening areas. In this way, this approach will provide theoretical basis and technical support for the development of the precision agriculture, the optimization of regional cropping patterns and the efficient utilization of agricultural resources.

The North China District (NCD) is one of the main grain production regions in China. The double cropping system of irrigation has been leading to the groundwater table decline at the speed of 1&ndash, 2 m per year. Climate change leads to uncertainty surrounding the future of the NCD agricultural system, which will have great effects on crop yields and crop water demands. In this research, the Meteorological dataset from 54 weather station sites over the period 1960&ndash, 2015 were collected to quantify the long-term spatial and temporal trends of meteorological data, including daily minimum temperature (Tmin), maximum temperature (Tmax), precipitation, solar radiation, reference evapotranspiration (ET0), and aridity index (AI). The results show that the long-term wheat and maize growing season and annual average air temperatures (Tmin and Tmax) showed strong north to south increasing trends throughout the NCD. The average annual precipitation was 632.9 mm across the NCD, more than 70% of which was concentrated in the maize growing season. The regional average annual ET0 was 1026.1 mm, which was 531.2 and 497.4 mm for the wheat and maize growing season, respectively. The regional precipitation decreased from northwest to southeast in each growing season and annual timescale. The funnel areas have lower precipitation and higher ET0 than the regional average, which may lead to the mining of the groundwater funnel area. The regional average annual AI is 0.63, which lies in the humid class. For temporal analysis, the regional average trends in annual Tmin, Tmax, solar radiation, ET0, precipitation, and AI were 0.37 &deg, C/10a, 0.15 &deg, C/10a, &minus, 0.28 MJ/day/m2/10a, &minus, 2.98 mm/10a, &minus, 12.04 mm/10a, and 0.005/10a, respectively. The increasing trend of temperature and the decreasing trend of solar radiation may have a negative effect on the regional food security. The funnel area AI showed a significant increasing trend for the winter wheat growing season and a decreasing trend for maize, which indicated that more irrigation will be needed for the maize growing season and the winter fallow policy may lead to the increasing trend precipitation being wasted. Analyzing the growing season and the annual meteorological elements of the spatiotemporal trends can help us better understand the influence of climate change on the natural resources and agricultural development in both the past and the future, and will provide us with invaluable information for the modification of cropping patterns to protect the regional and national water and food security.

To assess the application value in prenatal diagnosis using karyotype analysis combined with BACs-on-Beads (BoBs) assay.Nine hundred sixty five pregnant women were subjected to amniocentesis, chromosomal karyotype analysis and detection of BoBs were employed simultaneously for abnormal number of chromosomes and 9 chromosome microdeletion syndrome in prenatal diagnosis.Fifty cases common chromosome aneupoidies were successfully detected by both karyotype analysis and BoBs which included 31 cases of trisomy 21,10 cases of trisomy 18 and 9 cases with sex chromosome abnormality. BoBs in addition detected 1 case of DiGeorge-1 microdeletion syndrome and 1 case of 7q11.23 microduplication syndrome. All 9 fetuses with chromosome abnormalities detected by karyotyping were missed by BoBs, including 2 cases of marker chromosomes,4 cases of chromosomal translocation,1 case of chromosomal inversion, 2 cases of Sex chromosome mosaicism; 2 cases of fetal inherited from the parents,7 cases for novel mutations.Karyotype analysis combined with BoBs dedtection is a rapid, effective and highly accurate prenatal diagnosis model that may should be widely used in clinical diagnosis.

Objective Microtia/atresia is a severe malformation of the external ear. Previous studies have reported the potential risk factors on microtia, whereas few focused on severe microtia/atresia. The aim of the study was to investigate the effects of maternal exposure to environmental risk factors in patients with severe microtia/atresia in China. Methods A case-control study was conducted. Cases were patients with severe microtia/atresia who presented to PUMCH between January 2014 and October 2017. A total of 322 patients with severe microtia/atresia were enrolled and 322 normal controls matched 1:1 with the patients by sex, age and nationality were enrolled. The designed questionnaires were completed and data were gathered. Odds ratios were estimated with logistic regression models along with 95% confidence intervals in severe microtia/atresia. Results Most cases were males(68.6%), and the cases were observed more common in unilateral(80.7%), right-sided (54.0%). Multivariate logistic regression analysis showed that threatened abortion (OR 4.066,95% CI = 2.360–7.007), NSAIDs (OR 2.576,95% CI = 1.079–6.148), virus infection (OR 1.933,95% CI = 1.148–3.256), anemia (OR 1.902,95% CI = 1.026–3.526), miscarriages (OR 1.804,95% CI = 1.425–2.285), maternal age (OR 1.079,95% CI = 1.015–1.148) and paternal age (OR 1.061,95% CI = 1.003–1.122) were associated with a higher risk of severe microtia/atresia. Conclusion These results support that some maternal risk factors could be associated with severe microtia/atresia.

Objective To investigate the effects of verteporfin on the proliferation, invasion and migration of human breast cancer MDA-MB-231 cells and the underlying mechanism. Methods MDA-MB-231 cells in the logarithmic growth phase were randomly divided into control group and verteporfin treatment group. After MDA-MB-231 cells were treated with (0, 4, 8, 12, 16) μmol/mL verteporfin, the minimal inhibitory concentration was determined by CCK-8 assay. After treatment with 4 μmol/mL verteporfin, the invasion and migration abilities of MDA-MB-231 cells were detected by Transwell

Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor–independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1–mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.

Breast cancer is a common cause of cancer‑related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.

To explore the application of combined techniques for the prenatal diagnosis of a case with 7q11.23 duplication.Amniocentesis was performed in the second trimester for a mother with a high risk suggested by serological prenatal screening. G-banded chromosomal analysis was performed on cultured amniocytes and peripheral blood samples from both parents. DNA from amniotic fluid sample was isolated for a BACs-on-Beads (BoBs) assay. To define the range of duplication, copy number variation was determined with single nucleotide polymorphism array (SNP array, Affymetrix CytoScan 750K) and fluorescence in situ hybridization (FISH) analysis.Chromosomal analysis suggested that the fetus and both parents all had a normal karyotype, while a duplication of 7q11.23 was detected by the BoBs assay. SNP array revealed a 1.5 Mb duplication in chromosome 7q11.23, which was confirmed by FISH.Combined prenatal BoBs, SNP array and FISH has enabled effective diagnose of a case with 7q11.23 syndrome.

Puhe Coal Mine is a typical Tertiary coal in Shenbei mining area. With an increase in mining depth, tectonic stress field becomes more complex, leading to increased deformation and failure of the soft rock roadway. Stress becomes an important factor of mine safety and stability. This paper analyzes the distribution of the regional tectonic field, and determines the distribution of situ stress measurement through measuring the ground stress field in the main mining area level of Puhe Coal Mine using stress relief method. The acquired in situ stress data at different locations and depths provide a reference for the rational arrangement of the stop and mine roadway supporting design, which are of great significance for the efficient safety production of the mine. Keywords: Coal mine, Tertiary, Soft rock, Stress, Distribution rule

Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

Calculation of the fetal DNA fraction (FF) is important for reliable and accurate noninvasive prenatal testing (NIPT) for fetal genetic abnormalities. The aim of the study was to develop and validate a novel method for FF determination.FF was calculated using the chromosome Y (ChrY) sequence read assay and by circulating single molecule amplification and re-sequencing technology of 76 autosomal SNPs.By Pearson correlation for FF (4.73-22.11%) in 33 male pregnancy samples, the R(2) co-efficient for the 76-SNP versus the ChrY assay was 0.9572 (p0.001). In addition, the co-efficient of variation (CV) of FF measurement by the 76-SNP assay was low (0.15-0.35). As a control, the FF measurement for four non-pregnant plasma samples was virtually zero. In prospective longitudinal studies of 14 women with normal pregnancies, FF generally increased with gestational age. However, in eight women (71%) there was a significant decrease in FF between the first trimester (11-13 weeks) and the second trimester (15-19 weeks), and this was attributable to significant maternal weight gain.The novel 76-SNP cSMART assay has the precision to accurately measure FF in all pregnancies at a detection threshold of 5%. Based on FF trends in individual pregnancies, our results suggest that the end of the first trimester may be a more optimal window for performing NIPT.

This paper proposes a novel immune genetic algorithm to increase the performances in the complex optimization problems. Rough search and local normal search are applied to immune genetic algorithm to improve convergence speed and solution accuracy separately. Numerical simulations are arranged among the proposed strategies, other three immune algorithms and some state-of-art-algorithms. The simulation results indicate that the proposed strategy outperforms the other algorithms in convergence speed and solution quality. It is also applied into a practical application of wastewater treatment process (WWTP) and can reduce the energy consumption effectively.

Abnormal mitochondria have long been hypothesized to be involved in tumorigenesis. Mitochondrial DNA (mtDNA) mutations have been found in various cancer cells, yet their role in tumorigenesis remains largely unknown. Our long-term goal is to understand the role of mtDNA polymorphism and mtDNA mutations in tumorigenesis. We focused on the role of the mtDNA haplogroup; a 4,977 bp common mtDNA deletion; mtDNA mutations in the main control region of mtDNA or displacement loop; and mtDNA heteroplasmy in cancer occurrence and cancer development. Our results indicate that qualitative and quantitative changes in mtDNA play an important role in cancer development.

Community detection offers an important way to understand the structures and functions of social network. The label propagation algorithm has attracted vast attention since it is very suitable for discovering communities from large-scale networks. However, the algorithm suffers from the instability and inefficiency problem caused by the random policies it adopted. In this paper, we propose a novel label propagation approach based on local optimization to deal with the problem. The approach introduces a pre-propagation mechanism to optimize randomly initialized labels according to special factors, for example, node compactness. After that, it traverses and relabels nodes in the descending order of aggregate influence. The experiment results demonstrate the usefulness and effectiveness of our approach.

The aim of this study was to determine the relationship between nuclear factor κB and the prognosis of patients with nasopharyngeal carcinoma. We used immunohistochemical studies to examine nuclear factor κB expression in 42 patients with nasopharyngeal carcinoma. The results showed that tumors positive for nuclear factor κB were associated with an increased relapse potential, poor disease-free survival, and reduced overall survival in nasopharyngeal carcinoma. Our study indicates that nuclear factor κB could be an independent molecular marker for predicting poor prognosis among patients with nasopharyngeal carcinoma. Understanding the biology of nuclear factor κB-mediated pathways may lead to the development of novel therapeutic strategies for nasopharyngeal carcinoma.

As resveratrol derivatives, resveratrol aliphatic acids were synthesized in our laboratory. Previously, we reported the improved pharmaceutical properties of the compounds compared to resveratrol, including better solubility in water and much tighter binding with human serum albumin. Here, we investigate the role of resveratrol aliphatic acids in Toll-like receptor 2 (TLR2)-mediated apoptosis. We showed that resveratrol aliphatic acid (R6A) significantly inhibits the expression of TLR2. In addition, overexpression of TLR2 in HEK293 cells caused a significant decrease in apoptosis after R6A treatment. Moreover, inhibition of TLR2 by R6A decreases serum deprivation-reduced the levels of phosphorylated Akt and phosphorylated glycogen synthase kinase 3beta (GSK3beta). Our study thus demonstrates that the resveratrol aliphatic acid inhibits cell apoptosis through TLR2 by the involvement of Akt/GSK3beta pathway.

Dwarfing polish wheat is a dwarfing accession of Triticum polonicum L. from Xinjiang of China. In the present study, the artificial hybridization between dwarfing polish wheat and two accessions of Aegilops tauschii Cosson. (AS60 and AS65) was carried out, and the F1 hybrids were obtained successfully without using embryo rescue techniques for the first time. The crossabilities of hybrids T. polonicum x Ae. tauschii (AS60) and T. polonicum x Ae. tauschii (AS65) were 1.67% and 0.60% respectively. Only the hybrids of T. polonicum x Ae. tauschii (AS60) germinated well, and 24 Fl hybrid plants were obtained. All the F1 hybrid plants grew vigorously, and the morphological traits were similar to bread wheat. The F1 plants had some obvious traits inherited from T. polonicum and Ae. tauschii and were completely sterile. Chromosome pairing in the hybrid was characterized by a large number of univalents, with an average of 20.56 and 0.22 bivalents per PMC, and no ring bivalents and multivalents were observed. Furthermore, the potential value of the F1 hybrids between T. polonicum and Ae. tauschii for studying wheat origin and breeding are discussed.

In the natural populations of common wheat landrace Kaixianluohanmai, there was a phKL gene which promotes homoeologous pairing of wheat-alien hybrids. In the present study, the effects of phKL gene on crossability and homoeologous pairing of Triticum aestivum × Psathyrostachys huashanica Keng ex Kuo hybrids were comparatively analyzed. The crossability of the hybrid between Sichuan wheat landrace Kaixianluohanmai and P. huashanica was highest in all the hybrid combinations with 3.18%. The hybrids T. aestivum (Kaixianluohanmai) × P. huashanica showed a pairing configuration of 21.70 univalents + 2.68 rod bivalents + 0.34 ring bivalents + 0.06 trivalents + 0.02 quadrivalents and 3.54 chiasma per PMC at MI. However, the chiasma in hybrids of CS, CS ph1b, CS ph2a and CS ph2b with P. huashanica was 0.56, 1.90, 0.87 and 0.60, respectively. Compared with the hybrids of CS, CS ph1b, CS ph2a and CS ph2b with P. huashanica, a significant increase in the chiasma of homoeologous pairing was observed in the hybrids of T. aestivum (Kaixianluohanmai) × P. huashanica. The effects were shown in the increment of rod bivalents, ring bivalents and trivalents and reduction of univalents. The results indicated that phKL showed a higher effect on promoting homoeologous pairing than ph1 and ph2 in T. aestivum × P. huashanica. The wheat landrace Kaixianluohanmai with phKL gene is probably a more desirable material for alien gene transferring than Ph2 -deficiency lines.

A one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) using a TaqMan probe to quantitatively detect spring viremia of carp virus (SVCV) is described. In this assay, a pair of primers amplifying an 81-bp DNA fragment and a TaqMan probe was designed targeting the conserved region at the SVCV glycoprotein (G) gene. To avoid the disadvantages arising from plasmids, an extension adding a T7 phage polymerase promoter to the 5' end of the antisense primer was carried out to obtain viral cRNA. Standardized cycle threshold (Ct) values for 10-fold serial dilutions of SVCV cRNA were achieved by real-time RT-PCR and used to create standard curves. A regression line between the mean Ct values and viral template concentrations over a 1:10(7) dilution range with an r(2) value (0.9916) and a slope (-3.36) and the coefficient of variation (intra- or inter-assay is

Stage III/IV extranodal natural killer/T cell lymphoma (ENKL) has a poor response and poor survival. Given the sensitivity of ENKL to radiotherapy and the fact that there is no consensus on standard chemotherapy, we conducted a clinical trial of LVDP regimen, combining LVDP chemotherapy (containing etoposide, dexamethasone, L-asparaginase, and cisplatin), followed by radiotherapy as a consolidation therapy regimen, for newly diagnosed patients with stage III/IV ENKL to evaluate the efficacy and safety of this regimen. The primary endpoints were overall response rate (ORR) and survival [overall survival (OS) and progression-free survival (PFS)] at 1 or 2 years, while the secondary endpoints were toxicity and adverse effects. In total, 18 patients were enrolled in this trial from July 2010 to September 2013. The mean completed cycles of chemotherapy was 4.04 (range 1-8 cycles), and the ORR was 50 %. During a mean follow-up of 21.8 months (range 2-51 months), the 1-year OS and PFS rates were 72.2 and 50.0 %, respectively, the 2-year OS and PFS rates were 33.3 and 22.2 %, respectively, and the median OS and PFS were 23.0 and 10.5 months, respectively. Severe adverse effects during therapy included six cases of grade 3/4 bone marrow suppression and one case of grade 3 transaminase increase. Sex, eastern cancer oncology group, performance status, Korean Prognostic Index, International Prognostic index, and bone marrow infiltration may influence the prognosis of advanced-stage ENKL.

To study the value of second trimester maternal serum soluble Fms-like tyrosine kinase 1 (sFlt-1), placenta grouth factor (PlGF) and their ratio in the prediction of preeclampsia.In this nested case-control study, we collected second trimester maternal serum samples at 15-20 weeks and 24-28 weeks of gestation from those who developed gestational hypertensive disorders. Maternal serum sFlt-1 and PlGF were measured by electrochemiluminescence immunoassay on an automated platform. The value of sFlt-1, PlGF and their ratio were compared between gestational hypertensive group and the control group.Totally 41 patients with preeclampsia, 44 patients with gestational hypertension and 88 women with normal pregnancy outcomes were included in this study. There was no difference of age, gravidity, parity and preconception body mass index (BMI) between these three groups (P0.05) .Gestational week at delivery and neonatal birth weight were different between preeclampsia group and the control group (P0.01). The mean value of sFlt-1, PlGF and sFlt-1/PlGF ratio was (1 658 ± 488) µg/L, (141 ± 80) µg/L and 17 ± 9 in preeclampsia group, (1 945 ± 575) µg/L, (143 ± 52) µg/L and 15 ± 6 in gestational hypertension group, and (2 084 ± 741) µg/L, (65 ± 58) µg/L and 16 ± 9 in the control group at 15-20 weeks of gestation. There was no difference of sFlt-1, PlGF value and their ratio among the three groups at 15-20 weeks of gestation (P0.05) . The median value of sFlt-1, PlGF and sFlt-1/PlGF ratio were 8 525 µg/L, 35 µg/L and 398.0 in preeclampsia group, 905 µg/L, 336 µg/L and 2.7 in gestational hypertension group, 1 028 µg/L, 477 µg/L and 2.3 in the control group at 24-28 weeks of gestation. The value of sFlt-1, PlGF and their ratio was significantly different between preeclampsia group and the control group at 24-28 weeks of gestation (P0.01) . PlGF value was different between gestational hypertension group and the control group (P0.01) . The sensitivity and specificity of serum sFlt-1, PlGF and sFlt-1/PlGF ratio at 24-28 weeks of gestation to predict preeclampsia were 93% and 99% for sFlt-1 (cut off value 2 500 µg/L), 92% and 77% for PlGF (cut off value 270 µg/L) , 89% and 99% for sFlt-1/PlGF ratio (cut off value 11) .The value of sFlt-1, PlGF and their ratio at 24-28 weeks of gestation was significantly changed before clinical onset of preeclampsia.Use these serum indicators to predict preeclampsia will hopefully provide objective evidence for the management of patients who will develop preeclampsia later.

THE soft-shelled turtle Trionyx sinesis, because of its nutritional and medicinal values, has...

The unit element calibration method is simulation analyzed in this paper. First, the effective space of flow meter is divided by grid method, then the number of optimal nodes is determined through the successive approximation method, further the optimal measurement step length is gotten under fixed diameter. The experimental results show that the optimal measurement step length is very close to actual step length made by experiment.

Three novel saponins, mabiosides C-E, were isolated from the bark of Colubrina elliptica together with the known mabioside B and [alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-alpha-L- arabinopyranosyl]-(1-->3)-jujubogenin. All the structures were established by spectroscopic methods.

Though urban transport data collection is not a new initiative in China, China Urban Transport Database (CUTD) is an integrated database, which supports central and local governments to make appropriate policies of sustainable transport development and to efficiently monitor effects of these policies. In this paper, we propose a CUTD framework which includes user management, data warehouse and application modules. Considering the characteristics of urban transport development in China, we introduce several indicators to assist transport policy making, to evaluate the quality of public transport, and to enrich the global knowledge base of urban transport. CUTD is three-year (2010–2013) project co-financed by Volvo Research and Educational Foundations (VREF) and Ministry of Transport of China.

Methods to determinate the reasonable cost of an urban public transport provider are essential for Chinese governments to figure out how much the financial subsidy should be supplied for sound development of urban public transport. Through research on the cost regulation of urban public transport in cities, as Shenzhen and Shanghai, authors put forward the objectives, principles, indicators and systems of the cost determination methods, based on analyzing the relevant laws, regulations, standards of the urban public transport industry, and the technical and economic features, cost levels of the providers in recent years. Case studies demonstrate that these methods can effectively identify the regulated cost of urban public transport providers, and make it acceptable by related aspects.

This study analyzes the existing investment and financing mechanism of China's public transport and the updated demand for its innovation. A new investment and financing mechanism is proposed to promote public transport priority. Innovated investment and financing modes, channels, regulations and performance evaluation systems have been used to form the new mechanism.

The CCP Central Committee Decision on Several Issues Related to Promoting Reform and Development for Suburban Areas, passed by the 17th National CCP Congress, stated that China has entered a new and dynamic era in which the development of agriculture is driven by industrial advancement, that is to say suburban areas are led by urban areas, intertwining the two and forcing an increasingly greater need for the integration of urban and suburban social economic development in tandem. During this process, it is important to further unify urban and suburban social economic development, and promote equitable public services to all individuals. In regards to the development of public service and general living quality in suburban areas, road construction should be enhanced in order to ensure the use of asphalt concrete roads leading to villages and towns by the end of the 11th Five-year Plan. Coupled with this form of road development, public transport services connecting the suburban areas to urban ones will be monumental in the establishment of an integrated, national passenger transport network. The development of urban and suburban passenger transport has been separated for a long time, noted particularly by deficient coordination. More and more conflicts arise from the development of both areas separately. Thus accomplishing the integration of urban and suburban passenger transport is an effective way to settle these conflicts. It complies with the strategy of a centralized government for the transport industry, and is a significant move toward promoting the construction of the New Socialist Countryside. The central government has determined to form the new Ministry of Transport in order to dedicate planning, construction and administration of passenger and freight transport in both urban and suburban areas in March, 2008. The Leading Party Members' Team of MOT brought out the initiatives on integrating urban and suburban public transport resources in October, 2008. It aims to achieve a speedy, safe, and streamlined green passenger transport network, improve public transport service levels, ensure an efficient movement of production elements between urban and suburban areas through enhanced coordination, and benefit all individuals by such transport development.

urban transport is one of the most outstanding problems facing urban development in the world. On the one hand, with accelerated urbanization and mobilization processes, the issue of traffic congestion in urban areas is becoming increasingly prominent. On the other hand, with the continuous growth of vehicle stock, as well as the aggravation of traffic congestion, GHG emissions in urban transport sector keep increasing. To effectively tackle the problems of emission reduction and traffic congestion is the most important and difficult task in urban transport sector, and is the requirement for addressing climate change and improving the people's livelihood during China's twelfth five-year-plan period. Drawing on extensively the international experience as well as relevant policies concerning urban transport development and carbon market formulation during China's twelfth five-year-plan period, this research work puts forward policy recommendations for easing traffic congestion and reducing GHG emissions in China's urban transport sector from the perspective of establishing comprehensive transport planning, developing public transport, utilizing clean fuel and implementing gradually the emission trading system.

This paper analyses the current bus vehicle status in China, including vehicle age, bus company size, emissions standards, fuel type and bus vehicles' distribution of the country. The analysis results show that nearly one fifth vehicles are more than 8 years old; and generally the size of bus companies is small; and high emission vehicles account for a large proportion of all vehicles (80.1%), and recent 2 years high-emission vehicles still enter the bus operating market; moreover, most of the vehicles use gasoline (16.65%) and diesel (69.3%), clean fuel vehicles, such as compressed natural gas (CNG) and liquefied petroleum gas (LPG), are at a very low percentage; the bus vehicles ownership is at different level in different provinces, the western region is clear behind the eastern. In order to reduce energy consumption and emission, several policy recommendations had been proposed.

One novel saponin, mabioside B (1), containing a seco ring D dammarane triterpenoid aglycone has been isolated from the bark of Colubrina elliptica. The structure was established by spectroscopic methods.