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Hepatocellular carcinoma (HCC) tumors invariably develop resistance to cytotoxic and targeted agents, resulting in failed treatment and tumor recurrence. Previous in vivo short hairpin RNA (shRNA) screening evidence revealed mitochondrial-processing peptidase (PMPC) as a leading gene contributing to tumor cell resistance against sorafenib, a multikinase inhibitor used to treat advanced HCC. Here, we investigated the contributory role of the β subunit of PMPC (PMPCB) in sorafenib resistance. Silencing PMPCB increased HCC tumor cell susceptibility to sorafenib therapy, decreased liver tumor burden, and improved survival of tumor-bearing mice receiving sorafenib. Moreover, sorafenib + PMPCB shRNA combination therapy led to attenuated liver tumor burden and improved survival outcome for tumor-bearing mice, and it reduced colony formation in murine and human HCC cell lines in vitro. Additionally, PMPCB silencing enhanced PINK1-Parkin signaling and downregulated the anti-apoptotic protein MCL-1 in sorafenib-treated HCC cells, which is indicative of a healthier pro-apoptotic phenotype. Higher pre-treatment MCL-1 expression was associated with inferior survival outcomes in sorafenib-treated HCC patients. Elevated MCL-1 expression was present in sorafenib-resistant murine HCC cells, while MCL-1 knockdown sensitized these cells to sorafenib. In conclusion, our findings advocate combination regimens employing sorafenib with PMPCB knockdown or MCL-1 knockdown to circumvent sorafenib resistance in HCC patients.

We report the first catalytic, enantioselective reductive bis-functionalization of common amides, which provides a facile access to a variety of 2,2-disubstituted 3-iminoindolines in good yields and with excellent enantioselectivities. The reaction conditions are quite mild and can be run on a gram scale. In this one-pot reaction, three C-C bonds, one ring, and one nitrogen-containing tetrasubstituted carbon stereocenter are created in a catalytic enantioselective manner.

A facile method for the preparation of 2,3-dialkyl-substituted quinazolinones from readily available N-arylamides and commercial isocyanates was developed. This one-pot procedure involves the chemoselective activation of the secondary amide with Tf2O/2-Br-Pyr, the sequential addition of isocyanate, and cyclization. The mild reaction is general for a wide range of substrates and can be run on a gram scale.

G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10′s role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflammation-driven hepatocarcinogenesis. Via a targeted gene expression microarray screening alterations in GPCR family gene expression, we found CCR10 to be significantly upregulated in hepatocytes isolated from inflammation-driven human HCC tumors and matching paracancerous tissues. Tetrachloromethane (CCl4)-induced and diethylnitrosamine (DEN)-induced murine models of inflammatory hepatocarcinogenesis displayed significant hepatocellular TNF and CCR10 upregulation. Exogenous TNF applied to HepG2 and LO2 cell lines as well as wild-type (WT) mice significantly upregulated hepatocellular CCR10 expression, Akt phosphorylation, PCNA expression, and hepatocellular proliferation. Additionally, exogenous TNF significantly upregulated secretion of the natural CCR10 ligand-agonist CCL28 from both cell lines. Transgenic CCR10-knockout (CCR10 KO) in DEN-treated mice significantly increased hepatocellular apoptosis levels and significantly lowered compensatory hepatocellular proliferation but did not affect upstream TNF expression. In addition, DEN-treated CCR10 KO mice showed a significantly lower liver weight/body weight ratio, significantly lower liver tumor incidence, and significantly smaller tumors. Moreover, exogenous CCR10 expression significantly raised xenograft tumor growth in Balb/c nude mice. In vitro, CCR10 transfection or CCL28 treatment in HepG2 and LO2 cell lines significantly increased Akt phosphorylation, PCNA expression, and cell proliferation, while CCR10 silencing or Akt inhibition produced the opposite effects. In vivo, hepatocytes isolated from HCC tumor tissue and matching paracancerous tissue in DEN-treated CCR10 KO mice showed significantly lower Akt phosphorylation and PCNA expression relative to WT hepatocytes. In conclusion, inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation and shows promise as a potential therapeutic target for inflammation-driven HCC.

Catalytic C–C bond forming methods for the one-pot transformation of amides into other classes of compounds are highly demanding. In this report, we demonstrate the catalytic reductive addition of isocyanoacetates to tertiary lactams/amides to produce 5-methoxyoxazoles, including N-heterocyclic substituted oxazoles and sterically hindered amino oxazoles that are difficult to obtain by traditional oxazole-forming Ugi-type reactions. This one-pot procedure involves the Ir-catalysed partial reduction of lactams/amides and the sequential chemoselective addition of the isocyanide group in isocyanoacetates.

Carbon nanotube (CNT) is an attractive metal-free catalyst that can be explored in combination with ozone treatment. Using fluorescence microscopy image analysis, we investigated the production of hydroxyl radicals (HO ) within the solid-liquid interphase for CNT-mediated catalytic ozonation. The visualized results suggest that HO was vastly generated via catalysis and accumulated within a surface region of the CNT (we defined this region as the interphase “HO zone”). In this region, using 7-hydroxycoumarin as a HO marker, the radical abundance was at least 1000 times higher than that in the aqueous bulk phase. Owing to the observed inhomogeneity of HO , the CNT/ozone system effectively decomposed perfluorooctane sulfonate that was fairly resistant to non-catalytic ozonation, and the decomposition kinetics was not much inhibited by tert-butanol as bulk-phase HO scavenger due to the remaining “HO zone” at surface region available for reaction. A longevity trial revealed the sustained formation of the interphase “HO zone” and strongly indicated that the graphitic structure may optimize the density of surface active sites responsible for the proliferation and local concentration of HO . CNT, with good catalytic efficiency, longevity and stability, is anticipated as the basis of future nanomaterials able to promote HO exposure in ozone treatment for advanced oxidation process.

BACKGROUND The discovery of antineutrophil cytoplasm antibody (ANCA) makes the early diagnosis of primary vasculitis possible, and also has important guiding significance for the diagnosis and treatment of secondary vasculitis. This study aimed to investigate the clinical significance of ANCA. MATERIAL AND METHODS ANCA was detected by indirect immunofluorescence assay (IIF), and anti-myeloperoxidase (MPO) antibody, and anti-proteinase 3 (PR3) antibody were detected by ELISA. The results were analyzed retrospectively. RESULTS Among 118 730 patients, a total of 5853 (4.93%) were positive for ANCA. In the positive cases, 3.98% were male and 6.33% were female, with significant differences (χ²=123.38, P

Automatically product counting in the handmade process plays a vital role in the manufacturing industry, especially at the sewing industry. Nevertheless, there is currently a few methods to count the product number in the hand sewing process from surveillance video automatically. Due to the sewing procedure is a cyclical action, the product counting in hand sewing process is regarded as periodic action temporal localization and counting problem. In this paper, in order to solve this problem, we propose a novel two-path method, based on pose estimation and region-based convolutional neural network. The pose estimation method is used to obtain the trajectory information of human joint points, and the periodic action is located by detecting the periodic changes in joint trajectory. An effective two-threshold method is proposed to locate each action and count the number of periodic action from the trajectory information. To more accurately localization, we use a convolutional neural network to predict whether the workbench is empty or not. We fuse the results of joint trajectory and the status of the workbench to adjust the final periodic action localization and counting the number. To verify the proposed method, we built a new video database collected in the real sewing industry. The experimental results show that the proposed method is effective and constructive at periodic action localization and counting in the video for the sewing industry.

There is increasing evidence of long non-coding RNA (lncRNA) involvement in a variety of biological responses to environmental stresses. The toxic heavy metal cadmium (Cd) is one of the major inorganic contaminants in environments. How lncRNAs are involved in Cd stress-induced response and regulatory mechanism in dicot plants is unknown. The present study performed strand-specific RNA-sequencing (RNA-Seq) to profile lncRNAs in Cd-exposed rapeseed (Brassica napus). More than 60 million clean reads corresponding to 5038 unique B. napus lncRNAs were identified, in which 2546 lncRNAs were generated from the sense strand and 2492 were generated from natural antisense transcripts (lncNATs). A combinational analysis resulted in identification of 301 lncRNAs responding to Cd stress. Cd-induced expression of lncRNAs appeared to be associated with their nearby protein-coding genes. Many coding genes flanking lncRNA loci were involved in Cd uptake, translocation and stress-responses, suggesting that the associated lncRNAs might have similar functions. Four lncRNAs were identified as precursors of miR824, miR167d, miR156d and miR156e. Sixty-seven lncRNAs acted as competing endogenous target mimics (eTMs) for 36 miRNAs potentially involved in Cd stress response. The functional mimics were validated by transient transformation of three lncRNAs into B. napus protoplasts under control of double 35S promoter with a decoy lncRNA (d35S-lncRNAs-pAN580). These results suggest that a set of putative lncRNAs were involved in response to Cd stress in B. napus.

BACKGROUND Recent clinical studies have linked polymorphisms in the xeroderma pigmentosum group D (XPD) gene, a key repair gene involved in nucleotide excision repair, to increased risk of hepatocellular carcinoma (HCC). However, the cellular effects of XPD expression in cultured HCC cells remain largely uncharacterized. Therefore, the aim of this study was to characterize the in vitro cellular effects of XPD expression on the HCC cell line HepG2. MATERIAL AND METHODS HepG2 cells were transfected as follows to create four experimental groups: pEGFP-N2/XPD plasmid (XPD) group, EGFP-N2 plasmid (N2) control group, lipofectamine™ 2000 (lipid) control group, and non-transfected (CON) control group. An MTT cell proliferation assay, Annexin V-APC apoptosis assay, colony formation assay, scratch wound migration assay, Transwell migration assay, and Western blotting of the autophagic proteins LC3 and p62 were conducted. RESULTS XPD expression significantly inhibited HepG2 cell proliferation (p

We report the first one-pot reductive homocoupling reaction of secondary amides and cross-coupling reaction of secondary amides with ketones to give secondary vicinal diamines and amino alcohols. This method relies on the direct generation of α-amino carbon radicals from secondary amides by activation with trifluoromethanesulfonic anhydride, partial reduction with triethylsilane and samarium diiodide-mediated single-electron transfer. The reactions were run under mild conditions and tolerated several functional groups.

Amides are a class of highly stable carbonyl compounds, which are widely used as reliable synthetic intermediates in both organic synthesis and pharmaceutical chemistry. Thus, the direct transformation of amides into other classes of compounds under mild reaction conditions is highly desirable and in the meantime challenging. An efficient reductive Ugi-type reaction has been established. The method employs common secondary amides as starting materials. The reaction exhibited a broad substrate scope, good chemoselectivity and functional group tolerance and provides rapid access to a variety of functionalized α-acetamidoamides.

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes.

Versatile and chemoselective C–C bond forming methods for the one-pot transformation of amides into other classes of compounds are highly demanding. In this report, we demonstrate the reductive addition of isocyanoacetates to common amides and lactams to produce 5-methoxyoxazoles or bicyclic imidazolines. This one-pot procedure involves partial reduction of amides with Schwartz reagent and chemoselective addition of the carbon of isocyanide group or α-carbon in isocyanoacetates. The quite different reactivity of the isocyanoacetate is due to the different steric hindrance of the amides and lactams.

Trehalose synthase (TreS) from Meiothermus ruber was co-aggregated with polyethyleneimine (PEI) and precipitated with polyethylene glycol (PEG), followed by cross-linking with glutaraldehyde to obtain TreS-polyethyleneimine cross-linked enzyme aggregates (termed as CLEAs-PEI-PEG). The TreS solution at 0.5 mg mL(-1) protein concentration, with PEI at a mass ratio of 1:0.8 (enzyme/PEI, w/w) and 25 % (w/v) PEG concentration were found to be most adequate for the co-aggregation of TreS. CLEAs-PEI-PEG was most active with glutaraldehyde at a mass ratio of 1:0.5 (enzyme/glutaraldehyde, w/w) to cross-link the co-aggregates. The CLEAs-PEI-PEG prepared in this work had an optimum pH of 6.5 and optimum temperature of 60 °C. For lower concentrations of enzyme, using PEI could enhance the cross-linking efficiency of TreS. The thermal stability and pH tolerance of CLEAs-PEI-PEG were significantly improved. Scanning electron microscopy revealed that the main structure of CLEAs-PEI-PEG showed scaffolding morphology which was constituted by structured ball-like particles with a size of 1-2.5 μm in diameter.

Retinoid X receptor-alpha (RXRα), an intriguing and unique drug target, can serve as an intracellular target mediating the anti-cancer effects of certain non-steroidal anti-inflammatory drugs (NSAIDs), including Sulindac. We report the synthesis and characterization of two new Sulindac analogs, K-8008 and K-8012, which exert improved anti-cancer activities over Sulindac in a RXRα- dependent manner. The new analogs inhibit the interaction of the N-terminally truncated RXRα (tRXRα) with the p85α subunit of PI3K, leading to suppression of AKT activation and induction of apoptosis. Crystal structures of the RXRα ligand-binding domain (LBD) with K-8008 or K-8012 reveal that both compounds bind to tetrameric RXRα LBD at a site different from the classical ligand-binding pocket. Thus, these results identify K-8008 and K-8012 as new tRXRα modulators and define a new binding mechanism for regulating the nongenomic action of tRXRα.

The volume–capacity ratio ( v / c ) is one of the most important indexes to measure the congestion of a traffic network. If v / c is very small, the traffic demand is deficient and/or the transportation supply or capacity is surplus, leading to a waste of capacity; on the contrary, a large value of v / c means that the traffic network is seriously congested. This paper investigates the properties of v / c in complex small-world and scale-free networks by introducing the congestion effects, described by link cost functions. The relationship between v / c and the degree of the node is mainly discussed. Finally, a simple strategy is presented to balance the tradeoff between traffic congestion and a waste of capacity.

In this work, a novel method to prepare cross-linked enzyme aggregates (CLEA) in a water-in-oil emulsion was reported. Spherical CLEA of recombinant trehalose synthase (TreS) from Meiothermus rubber was obtained through the emulsion based process. By varying the experimental parameters, the optimum conditions for the preparation of spherical CLEA were determined. The optimum catalytic temperature and thermal stability of spherical CLEA were enhanced significantly compared with the free enzyme. Spherical CLEA was also more tolerant to metal ions and chemical denaturants. Optical and scanning electron microscopy analysis showed that instead of the amorphous clumping shape of conventionally prepared CLEA, spherical CLEA has a more structured ball-like appearance with a size of 20–60 μm in diameter that could be easily separated.

The kinetic models of COD removal and phosphorus release in anaerobic zone, and phosphorus uptake, nitrification, denitrification and COD removal in circulating corridors were established in this work, in order to provide the guidance on design and running of the modified oxidation ditch. At the same time, the coefficients of reaction rates were calculated. Using the kinetic models already been established and the coefficients already been calculated to simulate the experimental results, the results showed that the models can well simulate the removal effect of pollutants in the modified oxidation ditch.

National Basic Research Program (973 Program) of China [2010CB833200]; National Natural Science Foundation of China (NSFC) [21072160, 20832005]

In this paper, an evolution traffic network model considering the influence of the next-nearest neighbor is constructed. Using the model, we focus on studying the topology of the evolution traffic network in order to understand the traffic dynamics better. First, the influence of the next-nearest neighbor on the cumulative degree distribution is investigated by altering the values of the sensitivity coefficients; then the influence of some important parameters (density, the maximum velocity, etc.) is also discussed; subsequently, we study the trend of the degree of the hub when the values of the parameters change; some hubs of the evolution network are given at last. In this model, the hub is denoted as the node whose ranking of the degree is at the top a fixed percentage. By studying the statistical properties of the traffic network, we can grasp the traffic dynamics so as to take the appropriate methods for the better traffic situations.

National Basic Research Program (973 Program) of China [2010CB833200]; NSF of China [20832005, 21072160]; Natural Science Foundation of Fujian Province of China [2011J01054]

Cascaded hydro-thermal scheduling has many constraints increasing the difficulty of the scheduling. Furthermore, the limited energy storage capability of water reservoirs, along with the stochastic nature of their availability, make its solution a more difficult job. A multi-objective cascaded hydro-thermal scheduling model considering energy saving, emission reduction and cascade energy storage is presented. Every objective function is converted to fuzzy numbers, then it is reformulated into a single objective. Genetic algorithm is used to solve it. The simulation results show that this model increases generation benefits of hydroelectric power plants, reduces operation costs of thermal power plants, advances comprehensive benefits of power systems

With the development of component technology, there are many powerful third party components. TeeChart control as one of them was widely used for waveform display and processing. Combining the software development of multi-channel waveform analysis, this paper introduces the characteristics and attributes method of TeeChart control. With using the control, it can realize graphical display of keeping historical data, contrast analyze of the multiple wave etc. And the waveform can be saved as picture or PDF format. Be given the correlation realization code in the Delphi 7.0 development environment.

For knowing the dielectric loss of high-voltage capacitive electrical equipment timely and mastering the electrical insulation of high voltage equipment effectively to ensure the reliable operation of these voltage equipments, an online monitoring system is designed in this paper based on the practical project. The system is made up of two parts including lower computer and upper computer. Using the microcontroller C8051F023 as the core of the lower computer and adopting an improved zero-crossing comparison method, the measurement of dielectric loss is realized and the data are sent to upper computer by wireless way. SQL2000 is used in the upper computer for data management, which can be real-time displayed, inquired and printed in report forms. At present, this monitoring system has successfully applied in the Houqiao 330 kV transformer substation in Ningxia. The operating results show that the system can meet well the online monitoring demand of the high voltage capacitive electrical equipment.

Amides are a class of highly stable carbonyl compounds, which are widely used as reliable synthetic intermediates in both organic synthesis and pharmaceutical chemistry. Thus, the direct transformation of amides into other classes of compounds under mild reaction conditions is highly desirable and in the meantime challenging. An efficient reductive Ugi-type reaction has been established. The method employs common secondary amides as starting materials. The reaction exhibited a broad substrate scope, good chemoselectivity and functional group tolerance and provides rapid access to a variety of functionalized α-acetamidoamides.

National Basic Research Program (973 Program) of China [2010CB833200]; National Natural Science Foundation of China [20832005]; Natural Science Foundation of Fujian Province of China [2011J01054]

In this paper, a block mapping spatial modulation (BMSM) scheme is proposed to increase the transmit rate of multiple-input multiple-output (MIMO) wireless communication systems. In the BMSM scheme, the information to be transmitted is mapped into different combinations of transmit antenna indices and distinct constellation symbols at each time instant. Multiple transmit antennas are activated, which is different from spatial modulation (SM) and generalised spatial modulation (GSM) techniques, and also the information bits to be mapped to the digital constellation diagram exploits block mapping in the BMSM scheme. The multiplexing gain is obtained and the transmit rate is increased. The simulation results for some cases of channel states are presented which verifies the efficiency of the proposed BMSM scheme.

By introducing a partition line into the walking strategies of the bi-directional pedestrian model recently proposed by Baek et al. [S. K. Baek, P. Minnhagen, S. Bernhardsson, K. Choi, B. J. Kim, Phys. Rev. E80, 016111 (2009)], we propose three walking strategies when pedestrians are moving outside the partition line, and carry out numerical simulations. The results show the proposed walking strategies have a significant impact on pedestrians' average walking velocity, pedestrians' distribution and road utilization.