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Accumulating evidence shows that high expression of casein kinase 2 (CK2) and phosphorylated acetyl CoA carboxylase (pACC) in patients with squamous cell carcinoma of the head and neck (SCCHN) correlates with decreased survival rates. Computational analysis has shown that ACC is a potential substrate for CK2, and its inhibition can suppress ACC phosphorylation in vitro. CX-4945, also known as silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2 and is under clinical investigation as a treatment for malignancies. We hypothesize that inhibition of CK2 by CX-4945 can reduce CK2-downstream phosphorylation of ACC as a therapeutic strategy against SCCHN.Three aggressive SCCHN cell lines (OSC-19, FaDu and HN31) were cultured to investigate the anticancer mechanism of the CK2 inhibitor, CX-4945. Cell cycle analysis, Annexin V/PI staining, and cleavage of PARP were performed to detect apoptosis. Western blot, electron microscopy and analysis of acidic vesicular organelle development were used to detect autophagy. Interference with cellular metabolism by CX-4945 treatment was determined by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry.Cellular metabolism was impeded by CX-4945 in aggressive SCCHN cells by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry, and consequently time- and dose-dependent lipid droplet accumulation and non-apoptotic cell death were observed. The lipogenic enzyme ACC was demonstrated to be associated with CK2, and its repressive phosphorylation could be removed by the CK2 inhibitor CX-4945. Overexpression of ACC resulted in impaired cell survival following transient transfection.The findings demonstrate that CK2 inhibition impairs normal cellular energy metabolism and may be an attractive therapy for treating aggressive SCCHN.

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, the alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we developed a photoenzymatic strategy for the radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals via an ene-reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-chiral carbonyl compounds in good yields and stereoselectivities. This work further expands the reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.

Rhodium(I)/bisoxazolinephosphine combination has been developed as a general catalyst to achieve the dynamic kinetic asymmetric allylation of a variety of nitrogen, carbon, oxygen, and sulfur pronu...

In multi-label learning, it is rather expensive to label instances since they are simultaneously associated with multiple labels. Therefore, active learning, which reduces the labeling cost by actively querying the labels of the most valuable data, becomes particularly important for multi-label learning. A good multi-label active learning algorithm usually consists of two crucial elements: a reasonable criterion to evaluate the gain of querying the label for an instance, and an effective classification model, based on whose prediction the criterion can be accurately computed. In this paper, we first introduce an effective multi-label classification model by combining label ranking with threshold learning, which is incrementally trained to avoid retraining from scratch after every query. Based on this model, we then propose to exploit both uncertainty and diversity in the instance space as well as the label space, and actively query the instance-label pairs which can improve the classification model most. Extensive experiments on 20 datasets demonstrate the superiority of the proposed approach to state-of-the-art methods.

Bulk heterojunction is one key concept leading to breakthrough in organic photovoltaics. The active layer is expectantly formed of distinct morphologies that carry out their respective roles in photovoltaic performance. The morphology-performance relationship however remains stymied, because unequivocal morphology at the nanoscale is not available. We used scattering-type scanning near-field optical microscopy operating with a visible light source (visible s-SNOM) to disclose the nanomorphology of P3HT:PCBM and pBCN:PCBM blends. Donor and acceptor domain as well as intermixed phase were identified and their intertwined distributions were mapped. We proposed energy landscapes of the BHJ active layer to shed light on the roles played by these morphologies in charge separation, transport and recombination. This study shows that visible s-SNOM is capable of profiling the morphological backdrop pertaining to the operation of high performance organic solar cells.

Conventional interleaved half-bridge flyback converters can recycle the leakage energy stored in leakage inductance to clamp the voltage across the main power switches at a dc input voltage. However, such converters still suffer from high switching losses, especially turn- off losses. In this paper, a novel turn- off zero-current-transition (ZCT) circuit is proposed for reducing the turn- off switching losses. The proposed ZCT interleaved half-bridge flyback converter operates at a fixed frequency without increasing the voltage stresses of the main switches. To verify the design, a laboratory prototype is implemented with 100 kHz, an input voltage of 400 V, and an output voltage of 24 V/480 W. The experimental results reveal that the proposed converter at full load and 20% load has efficiencies of 93.05% and 89.06%, yielding efficiency improvements of 1.17% and 4.12%, respectively, compared with the conventional interleaved half-bridge flyback converter.

Reprogramming of cellular energy metabolism, such as lipid metabolism, is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). However, whether protein expression related to fatty acid oxidation (FAO) affects survival in SCCHN remains unclear. We aimed to investigate FAO-related enzyme expression and determine its correlation with clinicopathological variables in SCCHN patients. Immunohistochemical analysis (IHC) of FAO-related protein expression, including carnitine palmitoyltransferase 1 (CPT1), the acyl-CoA dehydrogenase family, and fatty acid synthase (FAS), was performed using tissue microarrays from 102 resected SCCHN tumors. Expressions were categorized according to IHC scores, and the statistical association with clinicopathological factors was determined. Moderate-to-high expression of long-chain acyl-CoA dehydrogenase (LCAD) had a protective role against cancer-related death (adjusted hazard ratio (HR), 0.2, 95% confidence interval (CI), 0.05&ndash, 0.87) after covariate adjustment. Age and clinical stage remained independent predictors of survival (adjusted HR, 1.75, 95% CI, 1.22&ndash, 2.49 for age, adjusted HR, 14.33, 95% CI, 1.89&ndash, 108.60 for stage III/IV disease). Overexpression of medium-chain acyl-CoA dehydrogenase and FAS correlated with advanced tumor stage (T3/T4), however, none of these factors were independent predictors of survival. Several FAO-related enzymes were upregulated and LCAD overexpression had a protective effect on overall survival in advanced SCCHN patients. FAO-related-enzyme expression might have a prognostic impact on survival outcomes in SCCHN.

A highly branch- and enantioselective 1,4-enynes synthesis from readily available terminal alkynes and racemic allylic carbonates by Sonogashira type synergistic Rh and Cu catalysis under neutral conditions has been developed. Aliphatic and aromatic terminal alkynes with various functional groups could be used directly. An inner-sphere reductive elimination C(sp)-C(sp3) bond formation mechanism is supported by the stoichiometric reaction.

Cobalt-catalyzed highly branched- and enantioselective allylic alkylation of malononitriles has been developed. Chiral γ,δ-unsaturated malononitriles could be synthesized with >20:1 branched/linear regioselectivity and up to 99% enantiomeric excess from easily accessible racemic allylic carbonates under mild reaction conditions. The electron-rich and sterically less hindered bisoxazolinephosphine ligand is essential to realize the high reactivity in the carbon-carbon bond formation process.

Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up. Via pathway-driven massive parallel genomic sequencing, a germline mutation at FANCA D1359Y was identified. We identified several recurrent mutations in DNA methylation (TET1, V873I), the β-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) by comparing the genetic events between benign and malignant gastric polyps. Furthermore, we revealed gastric polyposis susceptible genes and genetic events promoting malignant transformation using pathway-driven targeted gene sequencing.

Aiming at the demand of position control of power line inspection robot flight mode, a design method of PID position controller based on ROS platform is proposed. The three-channel control model is derived theoretically, and the controller design and simulation are completed in Simulink. The steady state performance and anti-interference ability of the controller are evaluated by defining the RMS of the measured steady state in the Gazebo environment. After the actual flight verification, the designed controller has high control precision under steady state.

Light controls vegetative and reproductive development of plants. For a plant, sensing the light input properly ensures coordination with the ever-changing environment. Previously, we found that LIGHT-REGULATED WD1 (LWD1) and LWD2 regulate the circadian clock and photoperiodic flowering. Here, we identified Arabidopsis YET ANOTHER KINASE1 (AtYAK1), an evolutionarily conserved protein and a member of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), as an interacting protein of LWDs. Our study revealed that AtYAK1 is an important regulator for various light responses, including the circadian clock, photomorphogenesis and reproductive development. AtYAK1 could antagonize the function of LWDs in regulating the circadian clock and photoperiodic flowering. By examining phenotypes of atyak1, we found that AtYAK1 regulated light-induced period-length shortening and photomorphogenic development. Moreover, AtYAK1 mediated plant fertility especially under inferior light conditions including low light and short-day length. This study discloses a new regulator connecting environmental light to plant growth.

MicroRNAs (miRNAs) have been shown to play a crucial role in the progression of human cancers, including urothelial carcinoma (UC), the sixth-most common cancer in the world. Among them, miR-34a has been implicated in the regulation of cancer stem cells (CSCs), however, its role in UC has yet to be fully elucidated. In this study, bioinformatics and experimental analysis confirmed that miR-34a targets CD44 (a CSC surface marker) and c-Myc (a well-known cell cycle regulator) in UC. We found that, surprisingly, most UC cell lines and patient samples did express miR-34a, although epigenetic silencing by promoter hypermethylation of miR-34a expression was observed only in UMUC3 cells, and a subset of patient samples. Importantly, overexpression of c-Myc, a frequently amplified oncogene in UC, was shown to upregulate CD44 expression through a competing endogenous RNA (ceRNA) mechanism, such that overexpression of the c-Myc 3&prime, UTR upregulated CD44, and vice versa. Importantly, we observed a positive correlation between the expression of c-Myc and CD44 in clinical samples obtained from UC patients. Moreover, overexpression of a dominant-negative p53 mutant downregulated miR-34a, but upregulated c-Myc and CD44, in UC cell lines. Functionally, the ectopic expression of miR-34a was shown to significantly suppress CD44 expression, and subsequently, suppression of cell growth and invasion capability, while also reducing chemoresistance. In conclusion, it appears that aberrant promoter methylation, and c-Myc-mediated ceRNA mechanisms, may attenuate the function of miR-34a, in UC. The tumor suppressive role of miR-34a in controlling CSC phenotypes in UC deserves further investigation.

Background The effectiveness in surveillance colonoscopy largely depends on the quality of bowel preparation. We aimed to investigate the quality of bowel preparation segmentally and its effect on Adenoma Detection Rate (ADR) and Advanced Adenoma Detection Rate (AADR) at corresponding bowel segments. Methods This is a single-centered and cross-sectional study. A consecutive of 5798 patients who underwent colonoscopy examination were included. Bowel preparation was evaluated based on Bowel Bubble Scale (BBS) in general and Boston Bowel Preparation Scale (BBPS) in each segment (right side, transverse and left side of colon) and total BBPS scores. The quality of bowel preparation was correlated with ADR and AADR. Results Four thousand nine hundred forty colonoscopies (14,820 bowel segments) were included in the final analysis. In which 30.9% scored 3, 57.5% scored 2, 11.2% scored 1 and 0.4% scored 0 on basis of BBPS. For each score, ADR were 10.8, 7.7, 4.9 and 3.2%, respectively; whereas AADR were 4.5, 2.8,1.8 and 1.6% (P

In order to solve the problem that the surface electromyography signal is not accurate enough for the quantitative identification of the human motion angle, this paper used PCA-based third-order cumulant analysis method to extract sEMG signal features, and used this features as input for a single-layer BP neutal network to predict the joint angle of the human body. In the identification of shoulder joint motion, the root mean square error of the prediction result was 5.19, and the correlation coefficient was 0.95, which is obviously superior to the AR model method and the RMS method.

When the robot uses the flat scrub head to clean the outer surface of the fuel tank, the recessed structure near the ends of the fuel tank cannot be in good contact. In this paper, the outer contour of the fuel tank is detected by laser ranging sensor and described by NURBS curve. The interference between the scrub head and the fuel tank is divided into 16 cases. It is further divided into 4 types, and different adjustment algorithms are studied for different types. The article also studies the motion characteristics of the end trajectory. The results show that the proposed algorithm can greatly improve the contact area between the scrubbing head and the fuel tank surface, and ensure that the motion characteristic curve is smooth and will not impact the robot.

In this study, a bioactivity-guided isolation of antioxidant activity components of extracts from Sophora flavescens Ait. based on TLC bioautography and column chromatography was provided. The antioxidant activity of S. flavescens Ait. with different origins was evaluated by TLC bioautography, using 2,2-diphenyl-1-picrylhydrazyl radical as a detection reagent. The results showed that S. flavescens Ait. from different origins all expressed antioxidant activity. Then, based on a bioactivity-guided isolation principle, ten antioxidant activity ingredients including trifolirhizin(1), nor-anhydroicaritin(2), calycosin(3), isoxanthohumol(4), trifohrhizin-6′-monoacetate(5), 8-lavandulyl-5,7,4′-trihydroxyflavonol(6), kurarinone(7), sophoraflavanone G(8), maackiain(9) and formononetin(10) were yielded by the separation and purification of column chromatography. Their structures were elucidated by NMR data analysis. The results showed that the primary antioxidant constituents of S. flavescens Ait. were flavonoids, and significantly, prenylated flavonoids with phenolic hydroxyl in ring B had a stronger antioxidant effect than others. The study suggested that TLC bioautography-guided isolation of antioxidant components from S. flavescens Ait. was a kind of simple, rapid and effective means.

Rationale The diagnosis of anaplastic lymphoma kinase (ALK)-negative inflammatory myofibroblastic tumors (IMT) remains challenging because of their morphological resemblance with spindle cell sarcoma with myofibroblastic characteristics. Patient concerns A 69-year-old female patient presented with loco-regional recurrent IMT several times within 8 years after primary treatment and neck lymph node metastasis 3.5 years after last recurrence. Diagnosis The primary, recurrence, and lymph node metastasis lesions were diagnosed as ALK-negative IMTs based on the histopathological features. Interventions Biopsy samples were obtained during repeated surgeries and evaluated for genomic alterations during first and recurrent presentations. The evaluation was done using pathway-driven massive parallel sequencing, and genomic alterations between primary and recurrent tumors were compared. Outcomes Copy number gains and overexpression of mouse double minute 2 homolog (MDM2) and cyclin dependent kinase 4 (CDK4) were observed in the primary lesion, and additional gene amplification of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), Succinate Dehydrogenase Complex II subunit C (SDHC), and thyroid stimulating hormone receptor (TSHR) Q720H were found in the recurrent tumors. Metastases to the neck lymph node were observed 3.5 years after recurrence. Lessons Our results indicated genetic evolution in a microscopically benign condition and highlighted the importance of molecular characterization of fibro-inflammatory lesions of uncertain malignant potential.

This study aims to identify suitable lactobacilli that have anti-carbapenem-resistantFifty-sevenOf the 57Some

This paper presents the proposed interleaved half-bridge flyback converter, which is integrates leakage energy recycling and the turn-on zero-voltage transition technique. This novel interleaved half-bridge flyback converter can be used to reduce the turn-on switching loss by replacing the clamp diodes with auxiliary switches. The proposed circuit, designed with dual-transformer flyback topology, uses the antiparallel diodes of the auxiliary switches to recycle the leakage energy of the transformers. The voltages across the main power switches are clamped at the DC input voltage. In addition, the auxiliary switches are turned on to provide reverse current through the anti-parallel diodes of the main switches. In this manner, the main and auxiliary switches can achieve turn-on zero-voltage switching and turn-on low-voltage switching, respectively.

// Chia-Ming Yeh 1,2,* , Pi-Che Chen 3,* , Hsiao-Yen Hsieh 2,5 , Yeong-Chin Jou 3 , Chang-Te Lin 3 , Ming-Hsuan Tsai 1 , Wen-Yu Huang 1,2 , Yi-Ting Wang 1,2 , Ru-Inn Lin 1,6 , Szu-Shan Chen 1,2 , Chun-Liang Tung 4 , Shu-Fen Wu 1,2 , De-Ching Chang 1,2 , Cheng-Huang Shen 3 , Cheng-Da Hsu 5 and Michael W.Y. Chan 1,2,* 1 Department of Life Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan 2 Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan 3 Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan 4 Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan 5 Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan 6 Departments of Radiation Oncology, Buddhist Dalin Tzu Chi General Hospital, Chia Yi, Taiwan * These authors have contributed equally to this work Correspondence to: Michael W.Y. Chan, email: // Keywords : urothelial carcinoma, DNA methylation, urine, ZNF671 Received : April 03, 2015 Accepted : July 16, 2015 Published : July 22, 2015 Abstract The molecular mechanism underlying the lethal phenomenon of urothelial carcinoma (UC) tumor recurrence remains unresolved. Here, by methylation microarray, we identified promoter methylation of the zinc-finger protein gene, ZNF671 in bladder UC tumor tissue samples, a finding that was independently validated by bisulphite pyrosequencing in cell lines and tissue samples. Subsequent assays including treatment with epigenetic depressive agents and in vitro methylation showed ZNF671 methylation to result in its transcriptional repression. ZNF671 re-expression in UC cell lines, via ectopic expression, inhibited tumor growth and invasion, in possible conjunction with downregulation of cancer stem cell markers (c-KIT, NANOG, OCT4). Clinically, high ZNF671 methylation in UC tumor tissues (n=96; 63 bladder, 33 upper urinary tract) associated with tumor grade and poor locoregional disease-free survival. Quantitative MSP analysis in a training (n=97) and test (n=61) sets of voided urine samples from bladder UC patients revealed a sensitivity and specificity of 42%-48% and 89%-92.8%, respectively, for UC cancer detection. Moreover, combining DNA methylation of ZNF671 and 2 other genes ( IRF8 and sFRP1 ) further increased the sensitivity to 96.2%, suggesting a possible three-gene UC biomarker. In summary, ZNF671 , an epigenetically silenced novel tumor suppressor, represents a potential predictor for UC relapse and non-invasive biomarker that could assist in UC clinical decision-making.

Background Estrogen was reported to protect against obesity, however the mechanism remains unclear. We aimed to investigate the impact of 17β-estradiol (17β-E2) on triglyceride metabolism in adipocytes with or without lipopolysacchride (LPS) stimulating, providing novel potential mechanism for estrogen action. Methods 3T3-L1 adipocytes were cultured and differentiated into mature adipocytes in vitro. The differentiated 3T3-L1 cells were divided into six groups: (i) control group, treated with 0.1% DMSO alone; (ii) 17β-E2 group, treated with 1, 0.1, or 0.001 μM 17β-E2 for 48 h; (iii) 17β-E2 plus MPP group, pre-treated with 10 μM MPP (a selective ERα receptor inhibitor) for 1 h, then incubated with 1 μM 17β-E2 for 48 h; (iv) 17β-E2 plus PHTPP group, pre-treated with 10 μM PHTPP (a selective ERβ receptor inhibitor), then incubated with 1 μM 17β-E2 for 48 h; (v) LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 0.1% DMSO alone for 48 h; (vi) 17β-E2 plus LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 1 μM 17β-E2 for 48 h. The levels of triglyceride and adipose triglyceride lipase (ATGL) in differentiated 3T3-L1 cells and the concentrations of interleukin-6 (IL-6) in culture medium were measured. Results Comparing with control group, 1 μM and 0.1 μM 17β-E2 decreased the intracellular TG levels by about 20% and 10% respectively (all P 0.05). There was no significant difference in the triglyceride contents of differentiated 3T3-L1 cells among control group, LPS group and 17β-E2 + LPS group (all P > 0.05). ATGL expression in 17β-E2 group was significantly higher than control group (P

Light controls vegetative and reproductive development of plants. For a plant, sensing the light input properly ensures coordination with the ever-changing environment. Previously, we found that LIGHT-REGULATED WD1 (LWD1) and LWD2 regulate the circadian clock and photoperiodic flowering. Here, we identified Arabidopsis YET ANOTHER KINASE1 (AtYAK1), an evolutionarily conserved protein and a member of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), as an interacting protein of LWDs. Our study revealed that AtYAK1 is an important regulator for various light responses, including the circadian clock, photomorphogenesis and reproductive development. AtYAK1 could antagonize the function of LWDs in regulating the circadian clock and photoperiodic flowering. By examining phenotypes of atyak1, we found that AtYAK1 regulated light-induced period-length shortening and photomorphogenic development. Moreover, AtYAK1 mediated plant fertility especially under inferior light conditions including low light and short-day length. This study discloses a new regulator connecting environmental light to plant growth.

The effects of hydrated lime, potassium dihydrogen phosphate, straw ash and silkworm excrement on the extractability of heavy metals, pH and organic matter content in soil were studied. The results showed that the application of the four organic-inorganic complex treatments decreased the concentration of available Pb by 22.2 to 48.9 percent, and reduced the concentration of available Cd by 29.1 to 58.4 percent, which was obviously superior to the single organic or inorganic treatments. The addition of hydrated lime had the greatest effects on soil pH, while the application of silkworm excrement significantly increased the organic matter content in soil.

Concentrations, distributions and sources of PAHs were investigated in surface sediments from Lijiang River, South China. The total PAHs concentrations ranged from 160 to 602 ng g(-1) dry weight.The total PAHs concentrations from different area descended in the order: middle reach > upper reach > down reach. Based on the PAHs indicators and the surrounding along Lijiang River, PAHs were mainly derived from the burning of coal. The ecological risk assessment suggested that the probability of negative toxic effective caused by PAHs in Lijiang River was lower than 25 %.

This paper analyzes the bioavailability of soil heavy metal with morphology, geochemical facies, activity coefficient, migration coefficient, metastasis coefficient of soil heavy metal in the Puyu village, Huayin city. The research results show that: firstly, physiochemical properties of soil (include moisture content, available P, available K, total N, soil texture and so on) are key influencing factors for heavy metal activity, and correlation between total content and various morphology content of heavy metal too; secondly, antagonism and synergism are discovered among various heavy metal; thirdly, the correlation between the total content of heavy metal and physiochemical properties of soil such as PH value, moisture content, available P, available K, total N, soil texture is significant.