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Neural Architecture Search (NAS) is a highly challenging task that requires consideration of search space, search efficiency, and adversarial robustness of the network. In this paper, to accelerate the training speed, we reformulate NAS as a multi-armed bandit problem and present Anti-Bandit NAS (ABanditNAS) method, which exploits Upper Confidence Bounds (UCB) to abandon arms for search efficiency and Lower Confidence Bounds (LCB) for fair competition between arms. Based on the presented ABanditNAS, the adversarially robust optimization and architecture search can be solved in a unified framework. Specifically, our proposed framework defends against adversarial attacks based on a comprehensive search of denoising blocks, weight-free operations, Gabor filters, and convolutions. The theoretical analysis on the rationality of the two confidence bounds in ABanditNAS are provided and extensive experiments on three benchmarks are conducted. The results demonstrate that the presented ABanditNAS achieves competitive accuracy at a reduced search cost compared to prior methods. [ABSTRACT FROM AUTHOR]

An excellent passivation technique is a crucial factor for obtaining high efficiency of solar cells. Our previous work demonstrated that a novel material strategy, using poly(4-styrenesulfonic acid) (PSS) polymer thin film, possesses high-quality passivation effect which can rival the record level of high-temperature (1000 °C) annealed SiO2. However, the thermal budget of the PSS thin film and its subsequent failure mechanism have not been reported yet. Here, PSS thin film maintains a superb passivation effect with the annealed temperatures up to 200 °C and hardly presents passivation effect with the annealed temperatures beyond 250 °C, which is similar to the thermal behavior of the industry's champion passivation material hydrogenated amorphous silicon (a-Si:H). To explain the failure mechanism, on the macro level, the surface morphology, optical and electrical performance, and thermogravimetric analysis (TGA) are investigated, and on the micro level, chemical composition and vibrational bands characteristic of the molecular of the PSS thin films are studied. This low temperature, vacuum-free and high passivation effect of silicon surfaces passivation technique has been a candidate for flexible photovoltaics, which holds great potential for reducing cost and integrating perovskite-silicon tandem solar cells. [ABSTRACT FROM AUTHOR]

In the present paper, single-crystal PbMoO4 nanorods and nanowires were synthesized via a simple sonochemical process without any templates or surfactants for the first time. The samples were analyzed by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and electron diffraction (ED). Experimental results indicated that the obtained PbMoO4 nanowires were single-crystal in structure and the aspect ratio was about 200. The pH value and precursor were found to be critical factors to the controlled preparation of PbMoO4 nanorods and nanowires. The possible mechanism for the synthesis of PbMoO4 nanorods and nanowires was also discussed and other one-dimensional nanomaterials can also be successfully prepared by the present method. [ABSTRACT FROM AUTHOR]

A portable smartphone device is reported that uses 3D printing technology for the primary diagnosis of diseases by detecting acetone. The key part of the device consists of red carbon dots (RCDs), which are used as internal standards, and a sensing reagent (3-N,N-(diacethydrazide)-9-ethylcarbazole (2-HCA)) for acetone. With an excitation wavelength of 360 nm, the emission wavelengths of 2-HCA and RCDs are 443 nm and 619 nm, respectively. 2-HCA effectively captures acetone to form a nonfluorescent acylhydrazone via a condensation reaction occurring in aqueous solution, resulting in obvious color changes from blue-violet to dark red. The detection limit for acetone is 2.62 μM (~ 0.24 ppm). This is far lower than the ketone content in normal human blood (≤ 0.50 mM) and the acetone content in human respiratory gas (≤ 1.80 ppm). The device has good recovery rates for acetone detection in blood and exhaled breath, which are 90.56–109.98% (RSD ≤ 5.48) and 92.80–108.00% (RSD ≤ 5.07), respectively. The method designed here provides a reliable way to provide health warnings by visually detecting markers of ketosis/diabetes in blood or exhaled breath. [ABSTRACT FROM AUTHOR]

Lilium davidii var. unicolour Salisb is an important edible and medicinal plant. In vitro plantlet regeneration in L. davidii var. unicolour Salisb and identification of genetic stability are the premises of large-scale cultivation, and also a way to meet the increasing global demand. The purpose of this study is to establish an efficient, rapid plant propagation process for L. davidii var. unicolour Salisb, and to define the genetic stability of its regenerants in vitro under optimised conditions. The effects of different concentrations of 6-benzyladenine (6-BA) and thidiazuron (TDZ) on shoot multiplication and growth of L. davidii var. unicolour Salisb were investigated individually, or in combination with α-naphthalene acetic acid (NAA), using Murashige and Skoog (MS) solid or liquid medium. Inter-sample sequence repeat markers were used to assess genetic fidelity among plantlets. The results were that we achieved efficient and reliable regeneration, using scales as explants for shoot induction. The highest mean number (16.8) of shoots was differentiated de novo from the lower portion of the outer scales. After 4 weeks of incubation, superior multiplication rates (9.8%), mean shoot number (3.38), and length (5.46 cm) were achieved using MS liquid medium supplemented with TDZ. Auxins, such as indole butyric acid (IBA) and NAA, were employed for in vitro root induction, and the maximum rooting rate (100%) was observed when samples were cultured on half-strength MS medium supplemented with NAA. In vitro rooted plantlets of L. davidii var. unicolour Salisb were acclimatised in a greenhouse and plants grew well with a 90% survival rate. Inter-sample sequence repeat markers were used to assess genetic fidelity among plantlets, the best ISSR primer UBC 808 had the highest number of reproducible bands and produced 15 distinct bands and all micropropagated plants and the mother plant could be grouped in a single cluster with a 94% similarity level, indicating a low level of genetic polymorphism in micropropagated plants. The developed protocol described herein is simple and reliable for large-scale production of L. davidii var. unicolour Salisb, which provides a good technical support for large-scale cultivation of L. davidii var. unicolour Salisb. [ABSTRACT FROM AUTHOR]

Key message: Drastic changes in soil water content can activate the short-term high expression of key enzyme-encoding genes involved in secondary metabolite synthesis thereby increasing the content of secondary metabolites. Bupleurum chinense DC. is a traditional medicinal herb that is famous for its abundant saikosaponins. In the current study, the effects of drought–re-watering–drought on the photosynthesis physiology and biosynthesis of saikosaponins were investigated in 1-year-old B. chinense. The results showed that alterations in soil moisture altered the photosynthesis physiological process of B. chinense. The dry weight and fresh weight of the roots, photosynthesis capacity, chlorophyll fluorescence parameters, and SOD, POD and CAT activities were significantly reduced, and the contents of SP, soluble sugars, PRO and MDA increased. There were strong correlations between different physiological stress indices. All indices promoted and restricted each other, responded to soil moisture changes synergistically, maintained plant homeostasis and guaranteed normal biological activities. It was found that RW and RD_1 were the key stages of the water-control experiment affecting the expression of saikosaponin-related genes. At these two stages, the expression of multiple genes was affected by changes in soil moisture, with their expression levels reaching several-fold higher than those at the previous stage. We noticed that the expression of saikosaponin synthesis genes (which were rapidly upregulated at the RW and RD_1 stages) did not coincide with the rapid accumulation of saikosaponins (at the RD-2 stage), which were found to correspond to each other at the later stages of the water-control experiment. This finding indicates that there is a time lag between gene expression and the final product synthesis. Rapid changes in the external environment (RW to RD_1) have a short-term promoting effect on gene expression. This study reveals that short-term stress regulation may be an effective way to improve the quality of medicinal materials. [ABSTRACT FROM AUTHOR]

Telomerase is one of the most common markers of human malignant tumors, such as uterine, stomach, esophageal, breast, colorectal, laryngeal squamous cell, thyroid, bladder, and so on. It is necessary to develop some sensitive but convenient detection methods for telomerase activity determination. In this study, a label-free and ultrasensitive electrochemiluminescence (ECL) biosensor has been fabricated to detect the activity of telomerase extracted from HeLa cells. Thiolated telomerase substrate (TS) primer was immobilized on the gold electrode surface through gold-sulfur (Au-S) interaction and then elongated by telomerase specifically. Then, it was hybridized with complementary DNA to form double-stranded DNA (dsDNA) fragments on the electrode surface, and Ru(phen) has been intercalated into the dsDNA grooves to act as the ECL probe. The enhanced ECL intensity has a linear relationship with the number of HeLa cells in the range of 5∼5000 and with a detection limit of 2 HeLa cells. The proposed ECL biosensor has high specificity to telomerase in the presence of common interferents. The relative standard deviations (RSDs) were <5 % at 100 HeLa cells. The proposed method provides a convenient approach for telomerase-related cancer screening or diagnosis. [ABSTRACT FROM AUTHOR]

Caveolin-1 is the principle membrane protein of caveolae and plays an important role in various cellular processes. The protein contains two helices (H1 and H2) connected by a three-residue break. Although caveolin-1 is assumed to adopt a U-shaped conformation in the transmembrane domain, with both the N-terminus and C-terminus exposed to the cytoplasm, the structure and dynamics of caveolin-1 in membranes are still unclear. Here, we performed six molecular dynamics simulations to characterize the structure and dynamics of caveolin-1 (residues D82-S136; Cav1) in a caveolae-mimicking asymmetric lipid bilayer. The simulations reveal that the structure of the caveolin scaffolding domain of caveolin-1 is dynamic, as it could be either fully helical or partly unstructured. Cav1 inserts into the inner leaflet of the asymmetric lipid bilayer with a stable U-shaped conformation and orients almost vertical to the bilayer surface. The simulations also provide new insights into the effects of caveolin-1 on the morphology of caveolae and the possible interacting site of cholesterol on caveolin-1. [ABSTRACT FROM AUTHOR]

Finding new applications for existing pharmaceuticals, known as drug repositioning, is a validated strategy for resolving the problem of high expenditure but low productivity in drug discovery. Currently, the prevalent computational methods for drug repositioning are focused mainly on the similarity or relevance between known drugs based on their 'features', including chemical structure, side effects, gene expression profile, and/or chemical-protein interactome. However, such drug-oriented methods may constrain the newly predicted functions to the pharmacological functional space of the existing drugs. Clinically, many drugs have been found to bind 'off-target' (i.e. to receptors other than their primary targets), which can lead to undesirable effects. In this study, which integrates known drug target information, we propose a disease-oriented strategy for evaluating the relationship between drugs and disease based on their pathway profile. The basic hypothesis of this method is that drugs exerting a therapeutic effect may not only directly target the disease-related proteins but also modulate the pathways involved in the pathological process. Upon testing eight of the global best-selling drugs in 2010 (each with more than three targets), the FDA (Food and Drug Administration, USA)-approved therapeutic function of each was included in the top 10 predicted indications. On average, 60% of predicted results made using our method are proved by literature. This approach could be used to complement existing methods and may provide a new perspective in drug repositioning and side effect evaluation. [ABSTRACT FROM AUTHOR]

Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are G protein-coupled receptors (GPCRs) that are expressed at excitatory synapses in brain and spinal cord. GPCRs are often negatively regulated by specific G protein-coupled receptor kinases and subsequent binding of arrestin-like molecules. Here we demonstrate an alternative mechanism in which group I mGluRs are negatively regulated by proline-directed kinases that phosphorylate the binding site for the adaptor protein Homer, and thereby enhance mGluR-Homer binding to reduce signaling. This mechanism is dependent on a multidomain scaffolding protein, Preso1, that binds mGluR, Homer and proline-directed kinases and that is required for their phosphorylation of mGluR at the Homer binding site. Genetic ablation of Preso1 prevents dynamic phosphorylation of mGluR5, and Preso1?/? mice exhibit sustained, mGluR5-dependent inflammatory pain that is linked to enhanced mGluR signaling. Preso1 creates a microdomain for proline-directed kinases with broad substrate specificity to phosphorylate mGluR and to mediate negative regulation. [ABSTRACT FROM AUTHOR]

Schistosoma japonicum is the pathogen responsible for schistosomiasis japonica, one of the major infectious diseases targeted for prevention nationally in China. Expression of heat shock proteins (HSPs) following stress plays a very important biological role in many organisms including S. japonicum. Among the HSP family, the 70-kDa HSPs are most responsible for intracellular chaperone and extracellular immunoregulatory functions. Based on the published sequences in GenBank/EMBL (AF044412.1), open reading frame belonging to HSP70 protein corresponds to a full-length cDNA containing an open reading frame of 1,947 bp encoded of 648 amino acids was identified as HSP70 from schistosome. In this study, the coding region that we named r Sj648/hsp70 was amplified from S. japonicum adult worm cDNA library, and the recombinant protein was expressed in vector pET32a(+) and purified using a Ni-NTA purification system. The target protein r Sj648/hsp70 was determined by matrix-assisted laser desorption/ionization mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blotting analysis confirmed that Sj648/hsp70 could be expressed in the eggs, normal cercariae, ultraviolet-attenuated cercariae (UVAC), and adult worms of S. japonicum. Real-time quantitative PCR analysis indicated that Sj648/hsp70 was expressed significantly higher in eggs than that in cercariae and adult worms, and the expression in UVAC was higher than that in normal cercariae. A thermotolerance assay showed that r Sj648/hsp70 could protect Escherichia coli cells from heat damage. The detection of specific antibody levels by indirect enzyme-linked immunosorbent assay demonstrated that mice immunized with r Sj648/hsp70 induced higher level of specific anti-r Sj648/hsp70 IgG1 compared with those vaccinated with adjuvant alone, indicating that r Sj648/hsp70 was able to elicit Th2-type bias immune response. Our results suggest that Sj648/hsp70 might be an important molecule in parasite-host interaction and display potential roles in mice immunoregulation system. [ABSTRACT FROM AUTHOR]

The redundancy in convolutional neural networks (CNNs) causes a significant number of extra parameters resulting in increased computation and less diverse filters. In this paper, we introduce filter pruning via expectation-maximization (FPEM) to trim redundant structures and improve the diversity of remaining structures. Our method is designed based on the discovery that the filter diversity of pruned networks is positively correlated with its performance. The expectation step divides filters into groups by maximum likelihood layer-wisely, and averages the output feature maps for each cluster. The maximization step calculates the likelihood estimation of clusters and formulates a loss function to make the distributions in the same cluster consistent. After training, the intra-cluster redundant filters can be trimmed and only intra-cluster diverse filters are retained. Experiments conducted on CIFAR-10 have outperformed the corresponding full models. On ImageNet ILSVRC12, FPEM reduces 46.5 % FLOPs on ResNet-50 with only 0.36 % Top-1 accuracy decrease, which advances the state-of-arts. In particular, the FPEM offers strong generalization performance on the object detection task. [ABSTRACT FROM AUTHOR]

The remarkable effect of a double primary support has been proven in squeezing soft rock tunnels, but the research on the excavation and support time is still insufficient. In this study, the causes and failure mechanism of the large deformation in the Dongmachang I tunnel were investigated from the geostress field and the surrounding rock conditions. The supporting mechanism of the single and double primary supports in a tunnel and the deformation laws of different bench excavation lengths and support times were analyzed. Based on the Burgers model, creep materials similar to the argillaceous siltstone and materials similar to the concrete and steel arch of the double primary support were designed. The effects of the different bench lengths and the second primary support time on tunnel stability were evaluated by model tests. It was shown that increasing the bench length and delaying the second primary support time makes the second primary support safer, but if the bench length was too long or the second primary support time was too late, then the tunnel supporting structure failed. In the model test of this study, a middle bench length of 20.4 m and a second primary support time of 28 days were more satisfactory. [ABSTRACT FROM AUTHOR]

Chemical sensing for the sensitive and reliable detection of mercury(II) ions (Hg2+) is of great importance in environmental protection, food safety, and biomedical applications. Due to the bio-enrichment property of Hg2+ in organisms, it is particularly meaningful to develop an effective tool that can in situ and rapidly monitor the level of Hg2+ in living organisms. In this work, we report ligand functionalized gold-silver bimetallic nanoclusters with bright red fluorescence as intracellular probes for imaging Hg2+ in living cells and zebrafish. The bimetallic nanoclusters of DTT-GSH@Au/AgNCs (DG-Au/AgNCs) with strong fluorescence that benefited from the synergistic effect of Au and Ag atoms were obtained through a one-pot synthesis method, incorporating glutathione (GSH) and dithiothreitol (DTT) as the reducers and functionalized ligands. Attractively, the bright red fluorescence of DG-Au/AgNCs could be rapidly and selectively quenched by Hg2+ within 1 min with a very low detection limit of 1.01 nM. Additionally, DG-Au/AgNCs had a great advantage in the detection of Hg2+ in living cells and zebrafish owing to its notably strong red fluorescence at 665 nm, which could avoid effectively auto-fluorescence interference from the organism. Such easily prepared bimetallic fluorescent nanoclusters would be expected to provide a noninvasive and sensitive approach in the detection of heavy metals in situ for environmental protection. [ABSTRACT FROM AUTHOR]

Quantifying the phenotypic features of rare diseases such as inborn errors of immunity (IEI) helps clinicians make diagnoses, classify disorders, and objectify the disease severity at its first presentation as well as during therapy and follow-up. Furthermore, it may allow cross-sectional and cohort comparisons and support treatment decisions such as an evaluation for transplantation. On the basis of a literature review, we provide a descriptive comparison of ten selected scores and measures frequently used in IEI and divide these into three categories: (1) diagnostic tools (for Hyper-IgE syndrome, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome), (2) morbidity and disease activity measures (for common variable immune deficiency [CVID], profound combined immune deficiency, CTLA-4 haploinsufficiency, immune deficiency and dysregulation activity [IDDA], IPEX organ impairment, and the autoinflammatory disease activity index), and (3) treatment stratification scores (shown for hypogammaglobulinemia). The depth of preclinical and statistical validations varies among the presented tools, and disease-inherent and user-dependent factors complicate their broader application. To support a comparable, standardized evaluation for prospective monitoring of diseases with immune dysregulation, we propose the IDDA2.1 score (comprising 22 parameters on a 2–5-step scale) as a simple yet comprehensive and powerful tool. Originally developed for use in a retrospective study in LRBA deficiency, this new version may be applied to all IEI with immune dysregulation. Reviewing published aggregate cohort data from hundreds of patients, the IDDA kaleidoscope function is presented for 18 exemplary IEI as an instructive phenotype–pattern visualization tool, and an unsupervised, hierarchically clustered heatmap mathematically confirms similarities and differences in their phenotype expression profiles. [ABSTRACT FROM AUTHOR]

Venetoclax (VEN)-based regimens are the standard of care for elderly or unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). Some single-arm studies have implied that hypomethylating agents (HMAs) plus priming regimens may potentially provide an alternative therapeutic approach, owing to encouraging efficacy seen. However, no comparative data exists yet regarding these two treatment approaches. In this retrospective multi-center cohort study, we enrolled 294 ND AML patients, allocating 167 to the HMA + priming group and 127 to the VEN-based group. Treatment response and overall survival (OS) were compared between groups. Molecular subgroup analyses were also conducted. With a median of two cycles for HMA + priming group, the overall response (ORR) was 65.3%, including 55.1% complete remission (CR), 9.6% CR with incomplete hematologic recovery (CRi) and 0.6% morphologic leukemia-free state (MLFS). With a median of two cycles for VEN-based group, the ORR was 70.9%, including 46.5% CR, 18.9% CRi, and 5.5% MLFS. Response differences (ORR or CR/CRi) between groups were not significant (p > 0.05). With a median follow-up of 10.1 months, median OSs were similar between groups (20.9 vs 16.3 months, p = 0.41). However, VEN regimens demonstrated superior CR/CRi for patients with mutations in FLT3, IDH1/2, and NPM1 compared to HMA + priming (80.0% vs 35.0%, p = 0.01; 90.9% vs 65.5%, p = 0.02; 90.9% and 65.5%, p = 0.02, respectively). In conclusion, HMAs plus modified priming regimens might be a potential alternative therapeutic approach for patients with ND AML, but VEN-based regimens presented predominance in specific molecular subgroups. Molecular characteristics contribute to guiding choice of treatment. [ABSTRACT FROM AUTHOR]

Farnesyl (Far) and palmitoyl (Pal) anchors play important roles in the traffic of many lipidated proteins. Herein, we show the distinctive interactions and influences of the two lipid modifications on lipid rafts (LRs) and non-raft-like membranes using molecular dynamics simulations. Palmitoyl anchors behave in a more ordered fashion, pack tighter with the lipids of LRs and diffuse at a slower rate than farnesyl anchors in LRs. When interacting with non-raft-like membranes these two types of anchors become less ordered, pack more loosely with lipids, and diffuse at a higher rate. By calculating both the number of contacts per chain and the number of contact atoms per carbon of the two anchors with the lipid components, we found that the palmitoyl chains preferred to associate with the saturated chains of lipids and cholesterol molecules in LRs, while farnesyl chains favored association with saturated chains and unsaturated chains. For non-raft-like membranes, these two lipid anchors had roughly the same preference for the three types of contact lipid chains. Additionally, palmitoyl anchors caused cholesterol to orient more perpendicular to the membrane surface, surrounding lipids to become more ordered, and lipid lateral fluidity to reduce significantly, compared to farnesyl anchors in LRs. By contrast, the POPE and DSPC became much less ordered, cholesterol became more tilted, and lipids became more fluid, when the two types lipid anchors were inserted in non-raft-like membranes. These findings are useful for understanding the traffic mechanisms of lipidated proteins with farnesyl and palmitoyl modifications in cell membranes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether radiomics signature of pericoronary adipose tissue (PCAT) based on coronary computed tomography angiography (CCTA) could improve the prediction of future acute coronary syndrome (ACS) within 3 years. Methods: We designed a retrospective case-control study that patients with ACS (n = 90) were well matched to patients with no cardiac events (n = 1496) during 3 years follow-up, then which were randomly divided into training and test datasets with a ratio of 3:1. A total of 107 radiomics features were extracted from PCAT surrounding lesions and 14 conventional plaque characteristics were analyzed. Radiomics score, plaque score, and integrated score were respectively calculated via a linear combination of the selected features, and their performance was evaluated with discrimination, calibration, and clinical application. Results: Radiomics score achieved superior performance in identifying patients with future ACS within 3 years in both training and test datasets (AUC = 0.826, 0.811) compared with plaque score (AUC = 0.699, 0.640), with a significant difference of AUC between two scores in the training dataset (p = 0.009); while the improvement of integrated score discriminating capability (AUC = 0.838, 0.826) was non-significant. The calibration curves of three predictive models demonstrated a good fitness respectively (all p > 0.05). Decision curve analysis suggested that integrated score added more clinical benefit than plaque score. Stratified analysis revealed that the performance of three predictive models was not affected by tube voltage, CT version, different sites of hospital. Conclusion: CCTA-based radiomics signature of PCAT could have the potential to predict the occurrence of subsequent ACS. Radiomics-based integrated score significantly outperformed plaque score in identifying future ACS within 3 years. Key Points: • Plaque score based on conventional plaque characteristics had certain limitations in the prediction of ACS. • Radiomics signature of PCAT surrounding plaques could have the potential to improve the predictive ability of subsequent ACS. • Radiomics-based integrated score significantly outperformed plaque score in the identification of future ACS within 3 years. [ABSTRACT FROM AUTHOR]

The study was intended to determine the antineoplastic effects of two new iridium(III) complexes [Ir(ppy)2(PTTP)](PF6) (1) (ppy = 2-phenylpyridine) and [Ir(piq)2(PTTP)](PF6) (2) (piq = 1-phenylisoquinoline, PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene). In MTT assay, the ligand PTTP displayed ineffective inhibition on cell growth in SGC-7901, BEL-7402, HepG2 as well as NIH3T3 cell lines, while complexes 1 and 2 showed high cytotoxic activity on SGC-7901 cells with an IC50 value of 0.5 ± 0.1 µM and 4.4 ± 0.6 µM, respectively. Cellular uptake, cell cloning experiments, wound healing assay and cell cycle arrest indicated that the two complexes can inhibit the cell proliferation in SGC-7901 and induce cell cycle arrest at G0/G1 phase. Additionally, reactive oxygen species (ROS) and mitochondrial membrane potential suggested that the two complexes induced cell apoptosis through disrupting mitochondrial functions. Further, western blot analysis illustrated that the two complexes caused apoptosis via regulating expression levels of Bcl-2 family proteins. Moreover, complex 1 could suppress tumor growth in vivo with an inhibitory rate of 49.41%. Altogether, these results demonstrated that complexes 1 and 2 exert a potent anticancer effect against SGC-7901 cells via mitochondrial apoptotic pathway and have a potential to be developed as antineoplastic drug candidates for human gastric cancer. [ABSTRACT FROM AUTHOR]

The authors report that a glassy carbon electrode modified with the [Ni(phen)] complex and single-walled carbon nanotubes represents a useful sensor for simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The material was characterized by scanning electron microscopy, and the electrode by cyclic voltammetry and electrochemical impedance spectroscopy. The experiments showed that this electrode responds to AA, DA and UA, best at working potentials of 0.130 V, 0.334 V, 0.486 V (vs. SCE), over the wide linear ranges from 30 to 1546 μM (for AA), 1 to 780 μM (for DA), and 1 to 1407 μM (for UA). The respective detection limits are 12 μM, 1 μM and 0.76 μM at an S/N ratio of 3. The modified electrode was successfully applied to the determination of AA, DA and UA in real samples. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. It is indispensable to understanding molecular mechanisms of HCC progression and to developing clinically useful biomarkers for this disease.Aim: In this article, we examined whether HOXC8 was associated with the poor prognosis of hepatocellular carcinoma and explored the possible underlying mechanism.Methods: The HOXC8 and Ki67 expression levels in 86 patients with hepatocellular carcinoma were examined using immunohistochemistry. HOXC8 levels in HCC cells were downregulated by siRNA transfection. The cycle progression and cell proliferation status of HCC cells and the oxaliplatin effectiveness were evaluated by flow cytometry and CCK-8 assay. HOXC8, CyclinD1, PCNA, Nkd2, and cleaved caspase-3 levels were detected by western blot.Results: HOXC8 was upregulated in HCC tissues, compared with adjacent non-tumor ones. HOXC8 expression levels in 86 patients with hepatocellular carcinoma were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that HOXC8 was a significant predictor for overall survival of HCC patients. HOXC8 siRNA knockdown delayed the G1-S phase transition, inhibited cell proliferation, and attenuated resistance to oxaliplatin.Conclusions: HOXC8 promoted HCC proliferation and predicted poor prognosis. Furthermore, upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The diversity, community structure and seasonal variation in demersal nekton off the Changjiang (Yangtze) River estuary was evaluated using monthly trawl survey data, collected between December 2008 and November 2009. A total of 95 species (56 teleosts, 11 cephalopods, and 28 decapod crustaceans) from 69 genera, 49 families and 15 orders were collected. These species could be classified into six groups on the basis of temporal distribution patterns. The resident crab Ovalipes punctatus dominated the community, both in number and biomass. A clear seasonal succession was observed in the species composition. Cluster analysis revealed three primary seasonal groups corresponding to the samples collected in winter-spring, late spring-summer and late summer-autumn. The highest biomass and lowest diversity were observed in summer, while the lowest biomass and highest diversity in winter. The abundance-biomass comparison curves and community composition suggested that the investigated community was moderately disturbed. The results suggest that reduction in fishing pressure and in the degree of seasonal hypoxia are essential for sustainable resource management off the Changjiang River estuary. [ABSTRACT FROM AUTHOR]

Investigation of the potential therapeutic mechanisms of drug candidates is an essential step in the process of new drug discovery. With the rapid development of systems biology, recent network analyses of proteins, drugs, and diseases have enabled great progress in delineating the molecule mechanisms of drug candidates. However, most analyses perform a direct association between gene/protein and disease levels without considering the intermediate biological pathways regulated by the drugs. Given that a protein performs its biological roles through pathways, we propose using a novel pathway-pathway network analysis to investigate the potential therapeutic functions of the drug candidates. Many studies have demonstrated that salvianolic acid B (Sal B) of Salvia miltiorrhiza is an effective therapy for cardiovascular diseases (CVD). Using molecular docking methods to identify direct interacting targets of Sal B, we collected all Sal B-regulated proteins with supporting experimental evidence in PubMed abstracts. FDA-approved CVD drugs and their corresponding targets were also collected. From a traditional drug-protein network analysis, we found that Sal B could affect ACE and REN of the renin-angiotensin-aldosterone system to relax vessels and alleviate hypertension. Subsequent pathway-pathway network analysis was attempted to study the mechanisms of Sal B in treating CVD, and demonstrated that Sal B regulates immunity/inflammation, apoptosis, ion transport and basic metabolism processes in the treatment of CVD. Regulating the immune/inflammation process may be the major mechanism of Sal B. We believe that pathway-pathway network analysis is a novel method for studying the therapeutic mechanisms of herbal ingredients. [ABSTRACT FROM AUTHOR]

Macrophages as a principal component of immune system play an important role in the initiation, modulation, and final activation of immune response against pathogens including schistosomes. Classical (M1) or alternative (M2) activation states of macrophage have different functions during infections. Previously, we report that the schistosomal-derived anti-inflammatory molecule coding gene (named Sj16) was isolated and the recombinant Sj16 (rSj16) was expressed in Escherichia coli. rSj16 has been demonstrated to have definite anti-inflammatory effect in vivo and in vitro on rodent model. To study the molecular basis on anti-inflammatory of rSj16, in the present paper, we investigate the effects of rSj16 on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that rSj16 inhibited LPS-induced activation of RAW264.7, as evidenced by impacting the proliferation, phagocytosis, and migration of the RAW264.7. After pretreated with rSj16, it showed the most potent inhibitory effects of rSj16 on the nitric oxide production in RAW264.7 cells. Furthermore, rSj16 also significantly decreased the levels of proinflammatory cytokines such as PGE2, IL-1β, IL-6, IL-12, IL-23, and TNF-α, whereas it increased the levels of immunosuppressive cytokine IL-10. rSj16 can also inhibit the LPS-induced activation of NF-κβ. These results further imply that Sj16 contributes to the immune evasion of Schistosoma japonicum through alternatively activated macrophage (M2), and rSj16 is expected to serve as a potential drug source for the medication of inflammatory disorders. [ABSTRACT FROM AUTHOR]

mTOR signaling pathway is deregulated in most cancers and uncontrolled cell cycle progression is a hallmark of cancer cell. However, the precise molecular mechanisms of the regulation of DNA replication and chromatin metabolism by mTOR signaling are largely unknown. We herein report that mTOR signaling promotes the loading of MCM2-7 helicase onto chromatin and upregulates DNA replication licensing factor CDC6. Pharmacological inhibition of mTOR kinase resulted in CHK1 checkpoint activation and decreased MCM2-7 replication helicase and PCNA associated with chromatins. Further pharmacological and genetic studies demonstrated CDC6 is positively controlled by mTORC1-S6K1 and mTORC2 signaling. miRNA screening revealed mTOR signaling suppresses miR-3178 thereby upregulating CDC6. Analysis of TCGA data found that CDC6 is overexpressed in most cancers and associates with the poor survival of cancer patients. Our findings suggest that mTOR signaling may control DNA replication origin licensing and replisome stability thereby cell cycle progression through CDC6 regulation. [ABSTRACT FROM AUTHOR]

The Yiyuan hominin fossil site is one of the few localities in China where a partial skullcap and several loose teeth of Homo erectus have been discovered. Yiyuan was previously assigned broadly to the Middle Pleistocene by biostratigraphical correlation and ESR/U-series dating. Here, we report the first application of a radio-isotopic dating method to the site. 26Al/10Be burial dating results derived from two sand samples from the fossiliferous deposits show that the hominin fossils can be confidently dated to 0.64 ± 0.08 Ma (million years ago). The reliability of this age is supported by the zero age of modern fluvial sediment near the cave. Our result is consistent with the age estimation based on biostratigraphic correlation and supports the argument that the Yiyuan and Zhoukoudian Locality 1 H. erectus fossils are contemporaneous. The results presented here, along with other recent chronological studies on Chinese Middle Pleistocene hominin sites, indicate that the time span from 600–400 ka (thousand years ago) is a critical period for human evolution in East Asia. Importantly, this time bracket includes several major climatic changes that would have influenced hominins, both morphologically and behaviorally. [ABSTRACT FROM AUTHOR]

Three genome-wide association studies (GWAS) have been conducted on the genetic susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), two of which consistently identified tagging single nucleotide polymorphisms (SNPs) around HLA-DQ/DR. In contrast, large multi-centre association studies between HBV genotype, mutations and the risk of HCC are relatively rare, and their interactions with host variants are even less. We performed a multi-centre study of 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers as controls to evaluate the effects of HBV genotype, mutations, GWAS-identified HLA-DQ/DR SNPs (rs9272105 and rs9275319) and their interactions on HCC risk. We found HBV genotype C was more frequent in HBV-related HCC. And 11 HBV hotspot mutations were independently and significantly associated with HCC risk. We also detected significant interactions of rs9272105 with both the HBV genotype and mutations. Through stepwise regression analysis, HBV genotype, the 11 mutations, HLA-DQ/DR SNPs, and the interaction of rs9272105 with mutation A1752G were all entered into the HCC prediction model, and the area under the curve for the panel including the HLA-DQ/DR SNPs, HBV genotype and mutations was 0.840. The HBV genotype, the mutations and the HLA-DQ/DR SNPs may serve as biomarkers for the surveillance of HBV persistent carriers. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) treatment has been commonly used to treat Chronic Hepatitis B (CHB) in Asian countries based on TCM syndrome diagnosis, also called 'ZHENG'. The syndrome is identified through the four-diagnostic methods, with certain degree of subjectivity and ambiguity from individual doctors. Normally those CHB patients also receive series of parameters from modern clinical examination, while they are routinely believed to be unrelated with the TCM syndrome diagnosis. In this study, we investigated whether these biomedical indexes in modern medicine could be beneficial to TCM syndrome diagnostics in an integrative way. Based on 634 patient samples from health controls and three subtypes of CHB syndromes, a two-view based hierarchical classification model was tested for TCM syndromes prediction based on totally 222 parameters integrated from both TCM practice and modern clinical tests. The results indicated that the performance of syndrome classification based on a proper integration of TCM and modern clinical indexes was significantly higher than those based on one view of parameters only. Furthermore, those indexes correlated with CHB syndrome diagnosis were successfully identified for CM indexes and biochemical indexes respectively, where potential associations between them were hinted to the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]