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Nitrogen metabolism in Saccharomyces cerevisiae is complex and tightly regulated, involving multiple regulatory factors. Eaf3p has been identified as a central regulator of nitrogen metabolism in S. cerevisiae, but its mechanism of action is unclear. In this study, the effect of overexpressing histone H4 acetylation gene EAF3 on nitrogen metabolic genes was investigated. The results indicated that Eaf3p regulates the expression of multiple nitrogen metabolic genes by regulating histone acetylation of the promoter regions via the histone acetyltransferase NuA4 complex. Eaf3p regulated the nitrogen metabolic genes GAT1, CAN1, LYP1, GLN3, and HIP1 by binding to their respective promoters. Eaf3p was recruited with Pho2p, as well as other transcription factors, to up-regulate the expression of target genes. These findings make a significant contribution to improving understanding of the mechanism of S. cerevisiae nitrogen metabolism regulation, which will contribute to future metabolic engineering of S. cerevisiae to improve its suitability for industrial applications. [ABSTRACT FROM AUTHOR]

This article introduces an ultra-compact fourway quadrature power splitter (4W-QPS) based on a novel transmission-line compression technique called double-path zigzag microstrip line (DP-ZML). Detailed design techniques with modular approach are disclosed for the state-of-the-art 5G low-band applications. The theoretical predictions are verified with experimental results through a fabricated prototype that operates from 696.55 to 876.03 MHz with >15 dB return-losses and isolations, and 90°±4° quadrature phase between adjacent outputs. The compact size of this 4W-QPS is achieved at 0.21λgx0.21λg at a center frequency of 786 MHz. [ABSTRACT FROM AUTHOR]

(2S)-Sakuranetin is a 7-O-methylflavonoid that has anticancer, antiviral, and antimicrobial activities. Methylation process is involved in biosynthesizing (2S)-sakuranetin from (2S)-naringenin, in which S-adenosylmethionine (SAM) serves as the methyl donor. In this study, after methyl donor and substrate inhibition were identified as limiting factors for (2S)-sakuranetin biosynthesis, an efficient (2S)-sakuranetin-producing strain was constructed by enhancing methyl donor supply and cell tolerance to (2S)-naringenin. Firstly, PfOMT3 from Perilla frutescens was selected as the optimal flavonoid 7-O-methyltransferase (F7-OMT) for the conversion of (2S)-naringenin to (2S)-sakuranetin. Then, the methylation process was upregulated by regulating pyridoxal 5′ - phosphate (PLP) content, key enzymes in methionine synthesis pathway, and the availability of ATP. Furthermore, genes that can enhance cell resistance to (2S)-naringenin were identified from molecular chaperones and sRNAs. Finally, by optimizing the fermentation process, 681.44 mg/L of (2S)-sakuranetin was obtained in 250- mL shake flasks. The titer of (2S)-sakuranetin reached 2642.38 mg/L in a 5-L bioreactor, which is the highest titer ever reported. This work demonstrates the importance of cofactor PLP in methylation process, and provides insights to biosynthesize other O-methylated flavonoids efficiently in E. coli. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: ATP citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl‐CoA), an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein acetylation. The aberrant expression and activity of ACLY has been documented in multiple human cancers. ETC‐1002 is an indirect ACLY inhibitor, and it has recently been approved by the FDA as an additional therapeutic option in high‐risk hypercholesterolemia patients unable to meet goals with standard therapy. In this work, we identified a series of novel long‐chain alkenyl diacids as potent direct ACLY inhibitors, and comprehensive structure‐activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5 μmol/L. Subsequent ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a lethal metabolic syndrome featuring muscle wasting with preferential loss of fast-twitching muscle mass through an undefined mechanism. Here, we show that cancer induces muscle wasting by selectively degrading myosin heavy chain (MHC) subtypes IIb and IIx through E3 ligase UBR2-mediated ubiquitylation. Induction of MHC loss and atrophy in C2C12 myotubes and mouse tibialis anterior (TA) by murine cancer cells required UBR2 up-regulation by cancer. Genetic gain or loss of UBR2 function inversely altered MHC level and muscle mass in TA of tumor-free mice. UBR2 selectively interacted with and ubiquitylated MHC-IIb and MHC-IIx through its substrate recognition and catalytic domain, respectively, in C2C12 myotubes. Elevation of UBR2 in muscle of tumor-bearing or free mice caused loss of MHC-IIb and MHC-IIx but not MHC-I and MHC-IIa or other myofibrillar proteins, including a-actin, troponin, tropomyosin, and tropomodulin. Muscle-specific knockout of UBR2 spared KPC tumor-bearing mice from losing MHC-IIb and MHC-IIx, fasttwitching muscle mass, cross-sectional area, and contractile force. The rectus abdominis (RA) muscle of patients with cachexia-prone cancers displayed a selective reduction of MHC-IIx in correlation with higher UBR2 levels. These data suggest that UBR2 is a regulator of MHC-IIb/IIx essential for cancer-induced muscle wasting, and that therapeutic interventions can be designed by blocking UBR2 up-regulation by cancer. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the prognostic values of serum PIVKA-II (prothrombin induced by vitamin K absence–II) and α-fetoprotein (AFP) and the combination of these analytes for identifying hepatocellular carcinoma (HCC), and to analyze the correlation between biomarkers and clinicopathological features of HCC. Methods The levels of PIVKA-II and AFP in 331 case individuals were determined by upconverting phosphor technology-based immune lateral flow (UPT-LF) assay. We used the ROC curve to determine the diagnostic value; the relationships between the biomarkers and clinicopathological features of HCC also were analyzed. Results AFP and PIVKA-II have good diagnostic performance in the diagnosis of HCC; the best AUC was 0.76, 0.74. High levels of PIVKA-II were more advantageous than AFP in predicting tumor size, portal-vein embolism, and vascular invasion (all P  <.05). Conclusion Levels of PIVKA-II and AFP showed good diagnostic value for HCC, but the level of PIVKA-II was more closely related to the clinicopathological features of HCC. [ABSTRACT FROM AUTHOR]

Fractional-order derivatives provide a powerful tool for the characterization of mechanical properties of viscoelastic materials. Fractional oscillators are mechanical models of viscoelastically damped structures, the viscoelastic damping of which is described by fractional-order constitutive equations. This paper proposes sliding mode control for a two-degree-of-freedom fractional Zener oscillator. Firstly, a virtual fractional oscillator is generated by means of a state transformation. Then, the total mechanical energy in the virtual oscillator is determined as the sum of the kinetic energy, the potential energy, and the fractional energy. Furthermore, sliding mode control for the fractional Zener oscillator is designed, in which the Lyapunov function is defined by the total mechanical energy. Finally, numerical simulations are conducted to validate the effectiveness of the proposed controllers. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is a global threat presenting health, economic, and social challenges that continue to escalate. Metapopulation epidemic modeling studies in the susceptible–exposed– infectious–removed (SEIR) style have played important roles in informing public health policy making to mitigate the spread of COVID-19. These models typically rely on a key assumption on the homogeneity of the population. This assumption certainly cannot be expected to hold true in real situations; various geographic, socioeconomic, and cultural environments affect the behaviors that drive the spread of COVID-19 in different communities. What’s more, variation of intracounty environments creates spatial heterogeneity of transmission in different regions. To address this issue, we develop a human mobility flow-augmented stochastic SEIR-style epidemic modeling framework with the ability to distinguish different regions and their corresponding behaviors. This modeling framework is then combined with data assimilation and machine learning techniques to reconstruct the historical growth trajectories of COVID-19 confirmed cases in two counties in Wisconsin. The associations between the spread of COVID-19 and business foot traffic, race and ethnicity, and age structure are then investigated. The results reveal that, in a college town (Dane County), the most important heterogeneity is age structure, while, in a large city area (Milwaukee County), racial and ethnic heterogeneity becomes more apparent. Scenario studies further indicate a strong response of the spread rate to various reopening policies, which suggests that policy makers may need to take these heterogeneities into account very carefully when designing policies for mitigating the ongoing spread of COVID-19 and reopening. [ABSTRACT FROM AUTHOR]

In this paper, 80GeO2-8Ga2O3-10BaO-2Nb2O5-6PbO (in mol%) glass samples with different Tm2O3 concentrations (0, 0.5, 0.75, 1, 1.25, and 1.5 mol. %) were prepared by traditional meltquenching method. According to the measurement of thermal properties of the host glass, the glass transition temperature is 596.7 °C and no crystallization peak is observed. Judd-Ofelt parameters Ωt (t=2, 4, 6) and fluorescent lifetimes were obtained by Judd-Ofelt theory. The similar values of Judd-Ofelt parameters and the full-width at half-maximums of ~1800 nm indicate the local environment of Tm3+ changes little with increment of Tm2O3 concentrations. Maximum stimulated emission cross-section of ~1800 nm is 6.22×10-21 cm² as calculated by Fuchtbauer-Ladenburg formula. Energy migration among Tm3+ ions was analyzed by the extended overlap integral method. The non-radiative transition rates between mainly energy levels of Tm3+ were calculated. Non-radiative transition rate of ³F4 energy level caused by OH was analyzed by rate equation and deduced by fitting the fluorescence decay curve. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma remains a virtually incurable hematologic malignancy, which is featured with the aberrant growth of malignant plasma cells. Aims: To elucidate the functions of miR-19a-3p in multiple myeloma. Study Design: Cell study. Methods: Cell counting kit-8 assay was performed to detect cell viability, and flow cytometry was conducted to detect cell apoptosis. Bioinformatics analysis predicted miR-19a-3p-associated biological function, pathway, core regulatory network, and target genes. Luciferase reporter assay verified the target sequence of miR-19a-3p regulating FBXO32. Results: miR-19a-3p is upregulated in multiple myeloma cells (p<0.01) and patients with multiple myeloma (p<0.001). Overexpressed miR-19a-3p significantly increased cell viability (p<0.05) and inhibited cell apoptosis (p<0.01). FBXO32 is a target gene of miR-19a-3p (p<0.01). Moreover, FBXO32 is downregulated in MM, and it significantly decreased cell viability (p<0.05) and promoted cell apoptosis (p<0.01). FBXO32 significantly rescued the influence of miR-19a-3p-inhibiting cell apoptosis (p<0.05). Conclusion: miR-19a-3p promoted cell proliferation and inhibited cell apoptosis by degrading the target FBXO32 mRNA in multiple myeloma. [ABSTRACT FROM AUTHOR]

In this paper, the continuous on-line measurements of isoprene in the atmosphere have been carried out by using the Differential Optical Absorption Spectroscopy (DOAS) in the band of 202.71-227.72 nm for the first time. Under the zero optical path in the laboratory, different equivalent concentrations of isoprene were measured by the combination of known concentration gas and series calibration cells. The correlation between the measured concentrations and the equivalent concentrations was 0.9996, and the slope was 1.065. The correlation coefficient between DOAS and on-line VOCs instrument is 0.85 and the slope is 0.86 in the comparison of 23 days field observation. It is estimated that the detection limit of isoprene with DOAS is about 0.1 ppb at an optical path of 75 m, and it is verified that isoprene could be measured in the ultraviolet absorption band using DOAS method with high temporal resolution and low maintenance cost. [ABSTRACT FROM AUTHOR]

The grounded electrical source airborne transient electromagnetic (GREATEM) system is an important method for obtaining subsurface conductivity distribution as well as outstanding detection efficiency and easy flight control. However, the signals are the superposition of useful signals and various noise signals. The baseline wander caused by the receiving coil motion always exists in the process of data acquisition to affect the measurement results. The baseline wander is one of the main noise sources of data, which has the low frequency, large amplitude, non-periodic and non-stationary and so on. Consequently, it is important to correction baseline wander for inversion explanation of GREATEM. In this paper, we propose improving method EEMD-AF based on ensemble empirical mode decomposition (EEMD) to correction baseline wander. The EEMD-AF method will decompose the electromagnetic signal into multi-stage intrinsic mode function (IMF) components and adaptively filter high-order IMF component which containing the baseline wander. To examine the performance of our introduced method, we used the EEMD-AF method for the signal baseline correction and compared with sym8 wavelet with 10 decomposition levels and EEMD with deleted higher-order components directly. The various methods were applied to process the synthetic data and field data. Through the evaluation of the signal-to-noise ratio (SNR) and mean-square-error (MSE), the correction result indicates that the signal using EEMD-AF method can get higher SNR and lower MSE. Comparing correctional signal using the EEMD-AF and the wavelet-based method in the anomaly curves profile images of the response signal, it is proved that the EEMD-AF method is a practical and effective method for removal of the baseline wander on GREATEM signal. [ABSTRACT FROM AUTHOR]

Transition-metal-based phosphides (TMPs) have been considered as attractive electrocatalysts for water splitting due to their earth-abundance and remarkable catalytic activity. As a representative type of precursors, metal-organic frameworks (MOFs) provide ideal plateaus for the design of nanostructured TMPs. In this work, the hierarchically structured iron phosphide nanobundles (FeP-500) were fabricated by one-step phosphorization of an iron-based MOF (MET(Fe)) precursor. The derived FeP-500 nanobundles were constructed by quasi-paralleled one-dimensional nanorods with uneven surface, which provided channels for electrolyte penetration, mass transport, and effective exposure of active sites during the water-splitting process. With the addition of conductive Super P, the obtained FeP-500-S exhibited a good electrocatalytic performance towards the hydrogen evolution reaction in alkaline electrolyte (1 molL-1 KOH). Furthermore, to investigate the influence of secondary metal doping, a series of isoreticular MOF precursors and bimetallic TMPs were fabricated. The results indicated that the catalytic performance is structure dominated. [ABSTRACT FROM AUTHOR]

Aims: This study aims to observe the preliminary clinical efficacy of percutaneous interstitial brachytherapy using iodine‑125 seeds for the treatment of advanced malignant lung tumors. Subjects and Methods: This retrospective study enrolled 24 patients in our hospital with advanced malignant lung tumors between June 2013 and November 2017. Computed tomography (CT)‑guided iodine‑125 seed implantation therapy was administered to these patients. All patients were followed up at 3, 6, and 12 months after the operation. The clinical efficacy was evaluated by CT. Results: Among the 24 patients, the objective response rates at 3, 6, and 12 months after the procedure were 50.0%, 50.0%, and 33.3%, respectively. Recent occurrence of adverse reactions were observed, including four cases of pneumothorax, three cases of hemoptysis, and two cases of particle displacement. Conclusions: CT‑guided percutaneous interstitial brachytherapy with iodine‑125 seeds can be used for the treatment of lung malignant tumors. Its clinical curative effect is remarkable and it results in limited trauma, reducing the incidence of adverse reactions and improving patient quality of life. [ABSTRACT FROM AUTHOR]

Due to their superior machining quality, efficiency, and availability, five-axis machine tools are important for the manufacturing of complicated parts of freeform surfaces. In this study, a new type of the five-axis machine tool was designed that is composed of four rotary axes as well as one translational axis. Given the structure of the proposed machine tool, an inverse kinematics analysis was conducted analytically, and a set of methods was then proposed to address the issues in the kinematic analysis, e.g., the singularity and multi-solution problems. Compared with traditional five-axis machine tools, which are typically composed of three linear axes and two rotary axes, the proposed machine tool exhibited better kinematic performance with machining parts with hub features, such as impellers, which was validated by simulations and real cuttings. [ABSTRACT FROM AUTHOR]

The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with β-elemene (BE) being its main active compound, along with trace amounts of β-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo , then the in vitro half-inhibitory concentration (IC 50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC 50 of EE and its main active components, BE and BC, was around 60 μg/mL. Flow cytometry analysis showed that BE and BC blocked the G 2 /M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis. [Display omitted] • Non-targeted metabonomics revealed elemene's potential pathways against lung cancer cells. • Elemene reduces GSH content and GSH/GSSG ratio in lung cancer cells. • Elemene downregulates glutaminase, SLC7A11, and GS to decrease GSH synthesis. [ABSTRACT FROM AUTHOR]

The lightweight aluminum 3D curved structure part has the characteristics of high structural strength, excellent aerodynamic performance, and flowing geometric shape. It is increasingly used in the fields of railway transportation, aerospace, and other high-end vehicle manufacture industry. However, with the increase of forming dimensions, as well as the large, thin-walled, complex forming features, it is urgent to study the precise plastic forming method for this kind of difficult-to-deform materials. Based on the new type of flexible multi-points 3D stretch-bending (3D FSB) process, the precision forming method for these hard-to-deform parts was studied in this paper. Extensive numerical simulations for the 3D FSB forming of the target parts have been performed by finite element methods. The simulation results show good agreement with the experiment results, and the max shape error of springback prediction is less than 0.3 mm. Then, based on the measured shape error of the 3D formed parts, an iterative overbending method for envelope surface of the multi-point die (MPD) is proposed to realize precise forming of the 3D curved structure parts. After four times adjustment of MPD, the simulation results show that the contour error is reduced from 1.01 to 0.06%, the maximum springback error changes from 30.16 to 1.66 mm. According to the adjustment parameters acquired in the optimization process, the actual experimental measured contour error is 0.05%, the maximum springback error is 1.41 mm, which achieved the forming requirements of the target parts and verified the effectiveness of the compensation method. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of finding the optimal routing policies with only trajectory information in a stochastic time-dependent network where all link travel times are temporally and spatially correlated. Two equivalent definitions are given for trajectory-adaptive routing policy. The first definition follows the mapping definition in a series of previous studies, where the trajectory information is included in the state variable. With that definition, any subpolicy of an optimal routing policy must also be optimal, and the algorithm developed in previous studies could serve as an exact solution, but the nature of the definition that trajectory information is included in the state variable determines that the number of states is prohibitively huge. Therefore, a second definition is given as a recursive definition, where the trajectory information is not included in the state variable. It is shown that, with the second definition, a subpolicy of an optimal/nondominated routing policy is not necessarily optimal/nondominated, but any subpolicy of a pure routing policy must also be pure which is a new property defined based on nondominance. An exact algorithm is designed to find optimal trajectory-adaptive routing policies based on the aforementioned property of pure routing policy. A comparison is made between the optimal trajectory-adaptive routing policies and the optimal paths in the same test networks to investigate the benefit of being adaptive. The results show that the benefit of being adaptive to trajectory information is more significant with a higher risk aversion, a higher correlation, and/or a larger network. [ABSTRACT FROM AUTHOR]

Background: A growing amount of evidence has indicated that PSAT1 is an oncogene that plays an important role in cancer progression and metastasis. In this study, we explored the expression and function of PSAT1 in estrogen receptor (ER)-negative breast cancer. Method: The expression level of PSAT1 in breast cancer tissues and cells was analyzed using real-time-PCR (RT-PCR), TCGA datasets or immunohistochemistry (IHC). The overall survival of patients with ER-negative breast cancer stratified by the PSAT1 expression levels was evaluated using Kaplan-Meier analysis. The function of PSAT1 was analyzed using a series of in vitro assays. Moreover, a nude mouse model was used to evaluate the function of PSAT1 in vivo. qRT-PCR and western blot assays were used to evaluate gene and protein expression, respectively, in the indicated cells. In addition, we demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation (ChIP) assays. Results: mRNA expression of PSAT1 was up-regulated in ER-negative breast cancer. A tissue microarray that included 297 specimens of ER-negative breast cancer was subjected to an immunohistochemistry assay, which demonstrated that PSAT1 was overexpressed and predicted a poor clinical outcome of patients with this disease. Our data showed that PSAT1 promoted cell proliferation and tumorigenesis in vitro and in vivo. We further found that PSAT1 induced up-regulation of cyclin D1 via the GSK3β/β-catenin pathway, which eventually led to the acceleration of cell cycle progression. Furthermore, ATF4 was also overexpressed in ER-negative breast cancers, and a positive correlation between the ATF4 and PSAT1 mRNA levels was observed in ER-negative breast cancers. We further demonstrated that knockdown of ATF4 by siRNA reduced PSAT1 expression. Finally, chromatin immunoprecipitation (ChIP) assays showed that PSAT1 was a target of ATF4. Conclusions: PSAT1, which is overexpressed in ER-negative breast cancers, is activated by ATF4 and promotes cell cycle progression via regulation of the GSK3β/β-catenin/cyclin D1 pathway. [ABSTRACT FROM AUTHOR]

Low-temperature reduction of perovskite Tb0.5Ca0.5MnO3-x yields novel crystal-structured noncentrosymmetric compound Tb0.50Ca0.50Mn0.962.33+O2.37, which unusually crystallizes in cubic lattice I23 (a ∼ 15.27 Å) based on a 4ap × 4ap × 4ap expansion relative to the simple cubic perovskite unit cell. Rietveld refinements and HAADF-STEM images are used for the structure determination, revealing a rare-typed metal-anion coordination framework which consists of corner-shared tetrahedra and pyramids, and edge-shared bipyramids and octahedra. 2/64 B-site Mn-ordered vacancies are observed for the first time acting as the apex and body center of the I lattice in reduced systems. Room-temperature piezoelectricity is detected, with a quasistatic d33 value of ∼0.32 pC N-1 and inverse d33 value of ∼10.5 pm V-1. This phase primarily exhibits antiferromagnetic ordering below TN ∼ 70 K, with ferromagnetic responses resulted from spin-canting below 40 K. This work provides a new way toward synthesizing unconventional acentric materials, in the absence of second-order Jahn-Teller active "distortion centers". [ABSTRACT FROM AUTHOR]

IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. [ABSTRACT FROM AUTHOR]

Good characterization of traffic interactions among urban roads can facilitate traffic-related applications, such as traffic control and short-term forecasting. Most studies measure the traffic interaction between two roads by their topological distance or the correlation between their traffic variables. However, the distance-based methods neglect the spatial heterogeneity of roads' traffic interactions, while the correlation-based methods cannot capture the non-linear dependency between two roads' traffic variables. In this paper, we propose a novel approach called Road2Vec to quantify the implicit traffic interactions among roads based on large-scale taxi operating route data using a Word2Vec model from the natural language processing (NLP) field. First, the analogy between transportation elements (i.e., road segment, travel route) and NLP terms (i.e., word, document) is established. Second, the real-valued vectors for road segments are trained from massive travel routes using the Word2Vec model. Third, the traffic interaction between any pair of roads is measured by the cosine similarity of their vectors. A case study on short-term traffic forecasting is conducted with artificial neural network (ANN) and support vector machine (SVM) algorithms to validate the advantages of the presented method. The results show that the forecasting achieves a higher accuracy with the support of the Road2Vec method than with the topological distance and traffic correlation based methods. We argue that the Road2Vec method can be effectively utilized for quantifying complex traffic interactions among roads and capturing underlying heterogeneous and non-linear properties. [ABSTRACT FROM AUTHOR]

To investigate the anticancer effects of curcumin-induced autophagy and its effects on the human lung adenocarcinoma A549 cell line, inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT assay was used to measure cell viability. Autophagy was detected using acridine orange (AO) staining and 3-methyladenine (3-MA) was used as an autophagy-specific inhibitor. Dose- and time-dependent A549 cell viability inhibition was observed following curcumin treatment. A dose-dependent increase in the red fluorescent structures in A549 cells was identified following curcumin treatment for 48 h through AO staining. In addition, the activation of autophagy was determined through changes in the number of autophagic vesicles (AVs; fluorescent particles) infected with monodansylcadaverine (MDC). The fluorescence intensity and density of AVs in the curcumin-treated groups were higher at 48 h compared with the control group. Finally, the MTT assay demonstrated that the survival rates of the curcumin-treated cells were increased when pretreated with 3-MA for 3 h, indicating that the inhibitory effect of curcumin on A549 cells is reduced following the inhibition of autophagy. Furthermore, AO and MDC staining confirmed that 3-MA does inhibit the induction of autophagy. Thus, it was hypothesized that the induction of autophagy is partially involved in the reduction of cell viability observed following curcumin treatment. The anticancer effects of curcumin on A549 cells can be reduced using autophagy inhibitors. This suggests a possible cancer therapeutic application of curcumin through the activation of autophagy. These findings have improved the understanding of the mechanism underlying the anticancer property of curcumin. [ABSTRACT FROM AUTHOR]

Existing CAPTCHA solutions are a major source of user frustration on the Internet today, frequently forcing companies to lose customers and business. Game CAPTCHAs are a promising approach which may make CAPTCHA solving a fun activity for the user. One category of such CAPTCHAs - called Dynamic Cognitive Game (DCG) CAPTCHA - challenges the user to perform a game-like cognitive (or recognition) task interacting with a series of dynamic images. Specifically, it takes the form of many objects floating around within the images, and the user's task is to match the objects corresponding to specific target(s), and drag/drop them to the target region(s). In this paper, we pursue a comprehensive analysis of DCG CAPTCHAs. We design and implement such CAPTCHAs, and dissect them across four broad but overlapping dimensions: (1) usability, (2) fully automated attacks, (3) human-solving relay attacks, and (4) hybrid attacks that combine the strengths of automated and relay attacks. Our study shows that DCG CAPTCHAs are highly usable, even on mobile devices and offer some resilience to relay attacks, but they are vulnerable to our proposed automated and hybrid attacks. [ABSTRACT FROM AUTHOR]

Seven new species of the Scaptodrosophila brunnea species group are described from east Asia: S. maculata sp. n., S. melanogaster sp. n., S. nigricostata sp. n., S. nigripecta sp. n., S. obscurata sp. n., S. protenipenis sp. n. and S. rhina sp. n. Three known species, S. parabrunnea (Tsacas & Chassagnard), S. pressobrunnea (Tsacas & Chassagnard) and S. scutellimargo (Duda) are redescribed. A key to all the examined species in the brunnea group is provided. Species delimitations have been improved by integrating the DNA sequences with morphological information. The intra- and interspecific pairwise p-distances (proportional distance) are summarized. Some nucleotide sites with fixed status in the alignment of the COI sequences (664 nucleotide sites in length) are used as “pure” molecular diagnostic characters to delineate species in the brunnea group. [ABSTRACT FROM AUTHOR]

B-cell translocation gene 2 (BTG2), a tumor suppressor gene, is downregulated in several types of human cancer cell. However, its function in skin cancer cells has not been fully elucidated. Therefore, the present study investigated the expression and function of BTG2 in skin cancer cells, and investigated the underlying molecular mechanism. The results indicated that BTG2 expression was downregulated in skin cancer cell lines. Overexpression of BTG2 significantly inhibited cell proliferation, cell cycle progression, and the invasion and migration of skin cancer cells. Furthermore, it was determined that overexpression of BTG2 significantly decreased the protein expression levels of β-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog in skin cancer cells. This suggests that BTG2 may function as a tumor suppressor by interfering with the Wnt/β-catenin signaling pathway in skin cancer cells. Thus, novel therapeutic strategies and agents targeting BTG2 may be potential treatments for skin cancer. [ABSTRACT FROM AUTHOR]

(-)-α-Bisabolol is naturally occurring in many plants and has great potential in health products and pharmaceuticals. However, the current extraction method from natural plants is unsustainable and cannot fulfil the increasing requirement. This study aimed to develop a sustainable strategy to enhance the biosynthesis of (-)-α-bisabolol by metabolic engineering. By introducing the heterologous gene MrBBS and weakening the competitive pathway gene ERG9, a de novo (-)-α-bisabolol biosynthesis strain was constructed that could produce 221.96 mg/L (-)-α-bisabolol. Two key genes for (-)-α-bisabolol biosynthesis, ERG20 and MrBBS, were fused by a flexible linker (GGGS)3 under the GAL7 promoter control, and the titer was increased by 2.9-fold. Optimization of the mevalonic acid pathway and multi-copy integration further increased (-)-α-bisabolol production. To promote product efflux, overexpression of PDR15 led to an increase in extracellular production. Combined with the optimal strategy, (-)-α-bisabolol production in a 5 L bioreactor reached 7.02 g/L, which is the highest titer reported in yeast to date. This work provides a reference for the efficient production of (-)-α-bisabolol in yeast. [ABSTRACT FROM AUTHOR]

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. [ABSTRACT FROM AUTHOR]

A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized and their anti-proliferative activities on cancer cell lines were investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited cell proliferation of a panel of different human cancer cell lines including A549, HepG2, OVCAR-3, HeLa and K562 and SGC-790 cell lines, and displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we found EM-d-Rha (3-(2”,3”-Di-O-acetyl-α-L-rhamnopyranosyl-(1→4)-2’,3’-di-O-acetyl-α-L-rhamnopyranosyl)-emodin) substantially induced cellular apoptosis of HepG2 and OVCAR-3 cells in the early growth stage. Furthermore, EM-d-Rha led to the decrease of mitochondrial transmembrane potential, and up-regulated the express of cells apoptosis factors in a concentration- and time-dependent manner. The results indicated the EM-d-Rha may inhibit the growth and proliferation of HepG2 cells through the pathway of apoptosis induction, and the possible molecular mechanism may due to the activation of intrinsic apoptotic signal pathway. [ABSTRACT FROM AUTHOR]

An azido-bridged chair-like decanuclear cluster: [CoII10(bzp)8(Metz)2(N3)18]·4MeOH·3H2O (1, bzp = 2-benzoylpyridine and HMetz = 5-methyl-1H-tetrazole) was prepared with in situ tetrazolate anions as templates in a sealed system. 1 containing both octahedral and tetrahedral Co(ii) ions exhibited slow relaxation of magnetization with an effective barrier of 26 K under an applied dc field of 1 kOe. [ABSTRACT FROM AUTHOR]

Text information contained in scene images is very helpful for high-level image understanding. In this study, the authors propose to learn co-occurrence of local strokes for scene text recognition by using a spatiality embedded dictionary (SED). Unlike spatial pyramid partitioning images into grids to incorporate spatial information, the authors SED associates every codeword with a particular response region and introduces more precise spatial information for robust character recognition. After localised soft coding and max pooling of the first layer, a sparse dictionary is learned to model cooccurrence of several local strokes, which further improves classification performance. Experimental results on two scene character recognition datasets ICDAR2003 and CHARS74 K demonstrate that their character recognition method outperforms state-of-the-art methods. Besides, competitive word recognition results are also reported for four benchmark word recognition datasets ICDAR2003, ICDAR2011, ICDAR2013 and street view text when combining their character recognition method with a conditional random field language model. [ABSTRACT FROM AUTHOR]

X-ray crystallographic data obtained on the metallocene hydrides, [(C5Me5)2LnH]2 (Ln = Gd, Tb, and Dy), of interest for their magnetic properties, have revealed unexpected structural variability in a closely related series of rare earth complexes that can complicate magnetic analysis. Crystals of the two larger metals, Gd and Tb, were structurally straightforward and isomorphous with crystals of [(C5Me5)2SmH]2. However, only for Tb were the locations of the hydride ligands in this structural type identified for the first time and found to be consistent with a (C5Me5)2Ln(µ-H)2Ln(C5Me5)2 structure. In contrast, for Ln = Dy, the [(C5Me5)2H]3- ligand set does not appear to have one optimum crystal structure. Two different types of crystals and one other solid form of [(C5Me5)2DyH]2 were repeatedly isolated upon crystallization and demonstrated that the structure of any particular crystalline sample selected for magnetic analysis could be variable. Asymmetric structures with a single hydride bridge, (C5Me5)2Dy(µ-H)DyH(C5Me5)2, were identifiable for the two crystalline forms. This demonstrated uncertainty in structure and highlights the importance of having a coordination environment with one preferred form for magnetically interesting complexes. [ABSTRACT FROM AUTHOR]

The interactions between hydrophobic anions of ionic liquids (ILs) and Triton X-114 (TX-114) micelles were studied in this work. The 1-alkyl-3-methylimidazolium based ILs with the anions bromide (Br-), tetrafluoroborate (BF4-), hexafluorophosphate (PF6-) and bis(trifluoromethylsulfonyl)imide (NTf2-) were selected to study their effects on physicochemical properties of the TX-114 micellar solution. Both the hydrophilic ILs with long alkyl (e.g., C12mimBr) and hydrophobic ILs (e.g., C4mimNTf2) significantly influenced the aggregate size and increased the absolute value of zeta potential as well as the cloud point. However, C4mimNTf2 changed the critical micellar concentration (CMC) and the aggregation number much less whereas made the micellization enthalpy decrease more obviously than C12mimBr did. It was suggested that the hydrophobic IL anions (PF6-, NTf2-) are located at the head group area of TX-114 micelles and interact with the ethylene oxide groups of TX-114 molecules. This work gives a further understanding of the interactions between IL cation/anion and micelles. [ABSTRACT FROM AUTHOR]

• Bifunctional Fe 3 O 4 /GO/Ag composite microspheres were prepared. • The Fe 3 O 4 /GO/Ag as SERS substrates could detect methylene blue low to 10−9 M. • The catalytic activity of Fe 3 O 4 /GO/Ag were evaluated by the degradation of MB and CIP. • The Fe 3 O 4 /GO/Ag effectively followed the degradation reaction process of MB by SERS. It is greatly significant to remove organic dyes and antibiotics in water because they are extremely harmful for human health and environment. In this work, we successfully developed magnetic Fe 3 O 4 /GO/Ag composite microspheres, using Fe 3 O 4 microspheres as cores to wrap graphene oxide (GO) interlayer and further in situ depositing silver nanoparticles onto GO layer. The microspheres were characterized by SEM, XRD, XPS and Raman spectroscopy. As compared to Fe 3 O 4 /Ag microspheres, Fe 3 O 4 /GO/Ag composite microspheres displayed higher activity for SERS detection, and also catalytic reaction due to the synergistic interaction of GO nanosheets and Ag nanoparticles. Subsequently, the Fe 3 O 4 /GO/Ag composite microspheres were employed to quantitatively detect aromatic molecules, methylene blue (MB) in aqueous solution, showing the limit of detection was low down to 10−9 M and the correlation coefficients (R2) of the linear relationship between SERS intensities and logarithmic concentrations was high up to 0.91. Moreover, the Fe 3 O 4 /GO/Ag composite microspheres as catalysts completely degraded methylene blue and ciprofloxacin in 12 min with the presence of NaBH 4. Finally, Fe 3 O 4 /GO/Ag composite microspheres were utilized to effectively follow the degradation reaction process of MB by SERS. Taken together, Fe 3 O 4 /GO/Ag composite microspheres present SERS application potentials in terms of trace and quantitative detection of chemicals, and in-situ monitoring catalytic degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

Aim Copper deficiency could cause fatal hematological and neurological disorders or other diseases. Amino acids are involved in the absorption of copper ions. The purpose of this study is to evaluate the absorption of copper in amino acid complex forms and determine its mechanism in the Caco-2 cell culture model. Main methods The human colonic adenocarcinoma cell line Caco-2 culture model was used to determine the permeability of copper ions in inorganic form (CuSO4) and the amino acid complex forms. Lysine and methionine, as well as carboplatin were used to determine the possible involvement of amino acid transporters or copper transporter 1 (CTR1). Key findings The results showed that all of the amino acid complex forms facilitated copper absorption. The apparent permeabilities of copper ions in these complex forms were at least 7.6 fold higher than those in the CuSO4 form. The permeability rank order of copper in various amino acid complex forms was Cu-glutamate < Cu-lysine = Cu-aspartic acid = Cu methionine < Cu-arginine < Cu-(lysine/glutamate). Mechanistic studies revealed that the enhanced absorption of copper in copper amino acid complexes could be the result of enhanced uptake (as in Cu-methionine complex) or enhanced basolateral efflux (as in Cu-lysine complex). Copper transporter 1 (or CTR1) inhibitor carboplatin did not affect the absorption of copper in Cu-methionine complex, suggesting that the dominant pathway for copper amino acid complexes is not CTR1. Significance Enhanced absorption of copper ions in amino acid complex appears to be mediated by amino acid transporters. [ABSTRACT FROM AUTHOR]

Because of the early onset of local invasion and distant metastasis, pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a 5-year survival rate of less than 5%. In this study, we investigated the role of fascin, a prometastasis actin-bundling protein, in PDAC progression, invasion, and the molecular mechanisms underlying fascin overexpression in PDAC. Our data showed that the expression levels of fascin were higher in cancer tissues than in normal tissues, and fascin overexpression correlated with the PDAC differentiation and prognosis. Fascin overexpression promoted PDAC cell migration and invasion by elevating matrix metalloproteinase-2 (MMP-2) expression. Fascin regulated MMP-2 expression through protein kinase C and extracellular signal--regulated kinase. Importantly, our data showed that hypoxia induced fascin overexpression in PDAC cells by promoting the binding of hypoxia-inducible factor-1 (HIF-1) to a hypoxia response element on the fascin promoter and transactivating fascin mRNA transcription. Intriguingly, HIF-1 a expression levels in PDAC patient specimens significantly correlated with fascin expression. Moreover, immunohistochemistry staining of consecutive sections demonstrated colocalization between HIF-1α and fascin in PDAC specimens, suggesting that hypoxia and HIF-1α were responsible for fascin overexpression in PDAC. When ectopically expressed, fascin was able to rescue PDAC cell invasion after HIF-1α knockdown. Our results demonstrated that fascin is a direct target gene of HIF-1. Our data suggested that the hypoxic tumor microenvironment in PDAC might promote invasion and metastasis by inducing fascin overexpression, and fascin might be targeted to block PDAC progression. [ABSTRACT FROM AUTHOR]

A dual-band flexible frequency selective surface (FSS) with miniaturized elements and maximally flat (Butterworth) response is presented in this paper. It is composed of three metallic layers, which are fabricated on thin flexible polyimide substrates and bonded together using thin bonding films. The overall thickness of the proposed structure is only about 0.3 mm, making it an attractive choice for conformal FSS applications. All the three layers can constitute a miniaturized-element FSS (MEFSS) and produce the first pass-band with miniaturization property, while the up and bottom layers can constitute a symmetric biplanar FSS and produce the second pass-band with maximally flat (Butterworth) response. The two pass-bands are independent and there is a wide band spacing up to 30 GHz between them. The principles of operation, the simulated results by using the vector modal matching method, and the experimental values of the fabricated prototype are also presented and discussed. [ABSTRACT FROM AUTHOR]

In this work, we present the synthesis of three novel 3D Cd(II) coordination polymers, {[Cd(IN)2].H2O}n (1), [Cd2(IN)2(SO4)(DMF)2]n (2) and {[Cd3(IN)5.5].0.5OH-}n (3) (HIN = isonicotinic acid). Coordination polymers 1 and 2 were obtained via solvothermal reactions. The synthesis of coordination polymer 3 was realized by a simple temperature induced single crystal to single crystal transition from 1. Single-crystal X-ray diffraction analyses revealed that 1-3 exhibit three different structural types: 1 displays a (6,3)-connected rtl net with the Schläfli symbol (4.62)2 (42.610.83) constructed from mononuclear [CdO4N2] clusters with the help of HIN. 2 is defined as a 6-connected pcu net with the Schläfli symbol {412.63} which is built from binuclear [Cd2(SO2)2] clusters and HIN linkers. 3 can be regarded as a 9-connected ncd net with the Schläfli symbol {36.422.58}, which consists of paddlewheel trinuclear [Cd3(O2C)5] clusters and a bridging HIN. Coordination polymers 1-3 display luminescence with emission maxima containing deep blue, blue, light blue and green at 298 K or 77 K both in solvents (polarity: DMF > CH3OH > CH2Cl2) and in the solid state. The lifetime of all the molecules is in microsecond scale. [ABSTRACT FROM AUTHOR]

Chronic inflammation is associated with cachexia-induced skeletal muscle mass loss in cancer. Levels of IL-6 cytokine family members are increased during cancer-related cachexia and induce intracellular signaling through glycoprotein130 (gp130). Although muscle STAT3 and circulating IL-6 are implicated in cancer-induced muscle wasting, there is limited understanding of muscle gp130's role in this process. Therefore, we investigated the role of skeletal muscle gp130 (skm-gp130) in cancer-induced alterations in the regulation of muscle protein turnover. Lewis lung carcinoma (LLC) cells were injected into 8-wk-old skm-gp130-knockout (KO) mice or wild-type mice. Skeletal muscle loss was attenuated by 16% in gp130-KO mice, which coincided with attenuated LLC-induced phosphorylation of muscle STAT3, p38, and FOXO3. gp130 KO did not restore mTOR inhibition or alter AMP-activated protein kinase (AMPK) expression. The induction of atrogin expression and p38 phosphorylation in C2C12 myotubes exposed to LLC-treated medium was attenuated by gp130 inhibition, but mTOR inhibition was not restored. STAT signaling inhibition in LLC-treated myotubes did not attenuate the induction of p38 or AMPK phosphorylation. We concluded that, during LLC-induced cachexia, skm-gp130 regulates muscle mass signaling through STAT3 and p38 for the activation of FOXO3 and atrogin, but does not directly regulate the suppression of mTOR. [ABSTRACT FROM AUTHOR]

In neutral media, reactions of gadolinium ethylenediaminetetraacetates with phosphorous acid result in the formation of the mixed-ligand polymeric complex K3n[Gd(EDTA)(HPO3)]n∙7nH2O (1) and dimeric complex Na6[Gd2(EDTA)2(HPO3)2]∙2.5NaCl∙21H2O (2) (H4EDTA = ethylenediaminetetraacetic acid) in warm solution. Further substitution with citric acid gives the monomeric gadolinium citrate with EDTA (NH4)2Na[Gd(EDTA)(H2cit)]∙4H2O (3). The compounds were characterized by elemental analysis, single crystal X-ray diffraction, FT-IR, ESI-MS and thermogravimetric analysis. Structural analysis indicates that three coordinated water molecules in the gadolinium ethylenediaminetetraacetate trihydrates are replaced by phosphite ions (HPO3 2-) in the compounds 1 and 2. Gadolinium atoms are octa-coordinated by EDTA and the phosphite ion, the latter links adjacent Gd-EDTA units to generate an infinite onedimensional chain in compound 1 and a dimeric octatomic ring in 2. In complex 3, coordinated water molecules were substituted by the α-hydroxy, α-carboxy and β-carboxy groups of citrate. Citrate is favourable for inhibiting the formation of Gd-EDTA phosphite. All the complexes are very easily soluble in water. The solution behavior of the isostructural lanthanum complexes was probed with 13C and 31P NMR spectra in D2O for comparison. ESI-MS analysis and recrystallization proved that complexes 1 and 2 dissociate to the monomeric unit of Gd-EDTA and free HPO3 2- in aqueous solution. Substitutions of gadolinium ethylenediaminetetraacetates to 1 and 2 are attributed to be the cause of nephrogenic systemic fibrosis in some way. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine (TCM), diagnosis and prescriptions are based on the signs and symptoms which are recognized as ZHENG. The cornerstone of TCM is to differentially treat one ZHENG from others, which is also known as syndrome differentiation, and this relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, the expressions of 384 cancer-related miRNAs in salivary supernatant of patients with pancreatic cancer were assessed by miRNApolymerase chain reaction (PCR) array, and the different expression patterns of miRNA in three different groups of ZHENG were studied with use of real-time quantitative PCR (qRT-PCR). Some miRNAs were found to be specifically expressed in some ZHENGs, for instance, miR-17, miR-21, and miR-181b in Shi-Re ZHENG and miR-196a in Pi-Xu ZHENG. This indicates that these miRNAs may play important roles in different ZHENG condition. Therefore, this study to some extent revealed the molecular basis of TCM ZHENG in pancreatic cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT In this article, a novel compact double band-notched antenna with nonequiwidth W-shaped slot and '6'-shaped resonance loop on the two sides of the feed line is proposed, which consists of a cone-shaped monopole patch with nonequiwidth W-shaped slot and '6'-shaped resonance loop on the two sides of the feed line, the metal earth-plate with step slot is designed on other side of the substrate. The simulated and experimental results demonstrate that the proposed antenna can obtain the double band-notched feature within the bandwidth of 3.3-3.8 GHz and 5.0-6.0 GHz, the impedance bandwidth can achieve from 2.4 to 11.6 GHz (VSWR < 2),which is more than 131%. © 2013 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:2405-2410, 2013 [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD+ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance. [ABSTRACT FROM AUTHOR]

Objective: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Methods: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. Results: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than = 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. Conclusions: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microneedle transdermal drug delivery has the advantages of minimally invasive, safe and efficient. • The core–shell type microneedle is obtained by a vacuuming and hot melting strategy. • The microneedle system is designed to release drugs quickly and improve the utilization rate of drugs. • The photothermal conversion efficiency of Cu-PDA NPs is increased to 50.40%. • Transdermal delivery of Cu-PDA NPs using MNs exhibited PTT-CDT synergistic therapy against skin melanoma. Multimodal nanoformulations with limited side-effects for tumor theranostics that catalyze a cascade of intracellular reactions show great potentials for tumor treatment with high specificity and efficiency. In this study, Cu-doped polydopamine nanoparticles (Cu-PDA NPs) have been prepared and embedded into microneedles (MNs) for photothermal and chemodynamic synergistic therapy against skin melanoma, by virtue of enhanced drug transdermal delivery owing to the unique core–shell structure of MNs. This multimodal tumor therapeutic strategy accumulates the high photothermal effect of Cu-PDA NPs (~50.40%) to acquire the energy from NIR irradiation and convert it into heat, and good Fenton-like catalytic activity of Cu+ ions to produce toxic free hydroxyl groups (‧OH) by reaction with excessive H 2 O 2 in tumor cells, leading to the generation of a new minimally invasive synergistic therapy. The B16F10 mouse melanoma model demonstrates that the active delivery of Cu-PDA NPs results in greatly inhibit proliferation of tumor and induce mixed necrosis/apoptosis of tumor cells in vivo. This study offers a new avenue for the development of microneedles-based microdevices for skin melanoma by a minimally invasive delivery of multimodal nanoformulation. [ABSTRACT FROM AUTHOR]

The chemical vapor deposition (CVD) fabrication of high-density three-dimension graphene macroscopic objects (3D-GMOs) with a relatively low porosity has not yet been realized, although they are desirable for applications in which high mechanical and electrical properties are required. Here, we explore a method to rapidly prepare the high-density 3D-GMOs using nickel chloride hexahydrate (NiCl2·6H2O) as a catalyst precursor by CVD process at atmospheric pressure. Further, the free-standing 3D-GMOs are employed as electrolytic electrodes to remove various heavy metal ions. The robust 3D structure, high conductivity (~12 S/cm) and large specific surface area (~560 m2/g) enable ultra-high electrical adsorption capacities (Cd2+~434 mg/g, Pb2+~882 mg/g~ Ni2+~1,683 mg/g, Cu2+~3,820 mg/g) from aqueous solutions and fast desorption. The current work has significance in the studies of both the fabrication of high-density 3D-GMOs and the removal of heavy metal ions. [ABSTRACT FROM AUTHOR]