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Aims There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. Methods and results A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2−/− mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. Conclusions Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.

Lung cancer is one of the malignant tumors which is still threating to human health. Early lung cancer generally shows no obvious symptoms, one of the diagnostic methods of lung cancer is the detection of tumor markers. However, the specificity and detection rate of the existing lung cancer diagnostic markers are rather low, discovering new lung cancer markers is an urgent need for clinical diagnosis. The method of systematic evolution of ligands by exponential enrichment (SELEX) was used for screening aptamers recognizing A549 excreta in cell culture media in a single-stranded DNA library using magnetic beads as supporter, the cell culture media as target and Real-time Quantitative PCR as monitor system. Our study is the first time to apply the method of screening tumor secretory components by using the culture medium with tumor cells as the screening target which is less interfered by other components, so the probability of the screened aptamers targeting tumor excreta with high accuracy is much higher than other methods. Using A549 cell culture media as positive target and the HMVEC cell culture media as negative control target, nine rounds of selection were conducted and some specific aptamers were gradually enriched. After further high-throughput sequencing, artificial selection and structure prediction, we screened seven aptamers as candidate targeting the excreta of A549 cells. Among them, the aptamer Cell APT-2 and Cell APT-4 showed high affinity and strong selectivity to A549 cell culture media with an equilibrium dissociation constant (Kd) of 8.723 ± 2.180 nM and 7.079 ± 1.336 nM respectively. Moreover, the aptamer Cell APT-2 exhibits strong selectivity to lung cancer serum and the aptamer Cell APT-4 showed strong selectivity to A549 cell culture media. In order to further clarify the specificity of aptamers targeted to lung cancer serum, we used 10 lung cancer patients' serum, 10 normal human serum and 10 colorectal cancer patients' serum for specific verification. The results showed that the detection rate of serum with lung cancer was higher than 80%. Therefore, the aptamer Cell APT-2 probably can be used as a probe to catch specific lung cancer secretory protein for the discovery of new tumor markers.

A novel method of oriented immobilization was presented: affinity Langmuir-Blodgett (LB) technique. Firstly, a long carbon chain was bond to a ligand of Horseradish Peroxidase (HRP). The ligand derivative appears surface activity with the hydrophobic carbon chain oriented to air and the hydrophilic ligand faced to water. Then, this derivative was put onto the water/air surface to assemble a LB film and formed the affinity interaction with the active site of HRP. After that, the affinity LB film with the enzyme was transferred onto the support to obtain the oriented immobilized HRP. The specific activity of HRP immobilized by affinity LB (182.1 ± 14 U/mg) was higher than that by adsorption (40.5 ± 5 U/mg). HRP immobilized by affinity LB could maintain a more native conformation, compared to that by adsorption. This method could be effectively used to immobilize protein with orientation and show widely promising applications in many fields including biosensor and bioreactor.

Three new silver(I)/copper(I)-thioarsenates KAgAsIIS2 (1), RbCu2AsIIIS3 (2) and RbCu4AsIIIS4 (3) have been solvothermally synthesized and structurally characterized. 1 exhibits a two-dimensional anionic network built up by As−As bond connecting the left- and right-handed helical [AgS2]4− chains, and represents the first examples of thioarsenates(II). The structure of 2 consists of two kinds of helical [Cu2S3]4– chains linked by the arsenic atoms to form double layers with rubidium ions between the layers. Compound 3 is built up of infinite [Cu2S2]2– chain and layered [Cu6As2S6] linked to form a three-dimensional anionic framework, [Cu4AsS4]–, and containing channels in which the rubidium cations reside. The optical properties of 1–3 have been investigated by UV–vis spectroscopy.

Osteosarcoma is the most common malignant bone tumor. In recent years, although a lot of research in the mechanism of osteosarcoma development and metastasis had been done, the molecular mechanisms are still elusive. MicroRNAs (miRs), as small noncoding RNA sequences, are dysregulated in various diseases, including cancer, negatively modulating the target genes expression by posttranscriptional repression. MicroRNA-143 (miR-143) has been reported to be reduced in cancers, including pituitary, colorectal, prostate cancer and cervical. We were aimed to detect the effects of miR-143 on osteosarcoma cell invasion and migration as well as to indicate the potential molecular mechanisms by which miR-143 regulated osteosarcoma. After miR-143 transfection, the cancer cells migration and invasion were examined. And Western blot, RT-PCR, flow cytometry and immunochemistry assays were performed to analyze the role of miR-143 in osteosarcoma progression. The results suggested that miR-143 expressed lessly in osteosarcoma cell lines and could suppress cell migration and invasion in U2-OS and MG-63 cells. To our knowledge, it was the first time to target Bcl-2 directly to explore the underlying mechanism by which miR-143 performed its role to induce apoptosis in tumor cells, thus improving osteosarcoma progression. The present study indicated that miR-143 could inhibit Bcl-2 expression, causing Caspas3 activation, thus inducing apoptosis in osteosarcoma cells. MiR-143 may therefore sreve as a potential biomarker for osteosarcoma, and the regulation of its expression might be a novel therapeutic strategy for osteosarcoma treatment.

The graded coating of Ni–Cr–B–Si alloy was prepared on a low carbon steel substrate by a laser cladding process. Its microstructure, hardness and flame erosion mechanisms were measured and analyzed. The flame erosion tests at 1300 °C were carried out with variable angle, velocity and time duration of particle impacting. It is found that the coating consists mainly of γ-Ni solid solution, FeNi 3 /Ni 33 Si 12 eutectic and CrB ceramic phase, and has a graded hardness variation with an average value of about seven times that of the substrate material. The main flame erosion mechanism of the coating changed from brittle to ductile deformation depending on impact time, angle and velocity, and manifested by lamellar stratifying, oxide particle splashing, incising, grooving and extrusion. The impact angle is found to play a key role in the mass loss of the coating under flame erosion.

Atrial fibrosis causes abnormal conduction through the atria, creating a substrate for atrial fibrillation (AF). In a rabbit model, rapid atrial pacing produces significant atrial fibrosis and the substrate for AF maintenance. This atrial remodeling is a potential therapeutic target.To evaluate the effects of the losartan on atrial fibrosis.Thirty rabbit AF models were produced by rapid atrial stimulation. They were randomly divided into three groups: sham group, rapid atrial pacing group, and rapid atrial pacing with losartan group. We performed AF vulnerability studies, atrial histologic, and molecular analyses after 4 weeks.Only rabbits in the rapid atrial pacing group developed sustained AF (30 min, 4of 10 rabbits). Treatment with losartan resulted in a significant reduction in left atrial fibrosis and AF duration (P.01). real-time polymerase chain reaction analyses demonstrated the drug's effects on the expression of Collagen I, Collagen III, and TGF-β/Smads signaling pathway.The treatment of losartan results in significantly reduced atrial fibrosis and AF vulnerability. Pharmacological therapy targeted at the fibrotic substrate itself may play an important role in the management of AF.

Two new copper(І)-thioarsenates(ІІІ), CsCu2AsS3(1) and KCu4AsS4(2), have been synthesized solvothermally in the presence of copper powder. Compound 1 is built up of trigonal AsS3 pyramid, tetrahedral CuAsS3 and CuS3 moieties forming 4-membered, 5-membered and 6-membered rings. The fusion of these rings produces layered anions [Cu2AsS3]−, and cesium cations are located between metal-sulfide layers. The structure of 2 consists of infinite [Cu2S2]2− chain and layered [Cu6As2S6] linked to form a three-dimensional anionic framework, [Cu4AsS4]–, and containing channels in which the potassium cations reside.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, H-PLN) was isolated from Plumbago zeylanica , the anticancer traditional Chinese medicine (TCM). Five new lanthanide(III) complexes of deprotonated plumbagin: [Y(PLN) 3 (H 2 O) 2 ] ( 1 ), [La(PLN) 3 (H 2 O) 2 ] ( 2 ), [Sm(PLN) 3 (H 2 O) 2 ]⋅H 2 O ( 3 ), [Gd(PLN) 3 (H 2 O) 2 ] ( 4 ), and [Dy(PLN) 3 (H 2 O) 2 ] ( 5 ) were synthesized by the reaction of plumbagin with the corresponding lanthanide salts, in amounts equal to ligand/metal molar ratio of 3:1. The PLN–lanthanide(III) complexes were characterized by different physicochemical methods: elemental analyses, UV–visible, IR and 1 H NMR and ESI-MS (electrospray ionization mass spectrum) as well as TGA (thermogravimetric analysis). The plumbagin and its lanthanide(III) complexes 1 – 5 , were tested for their in vitro cytotoxicity against BEL7404 (liver cancer) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The five PLN–lanthanide (III) complexes 1 – 5 effectively inhibited BEL7404 cell lines growth with IC 50 values of 11.0 ± 3.5, 5.1 ± 1.3, 6.1 ± 1.1, 6.4 ± 1.3, and 9.8 ± 1.5 μM, respectively, and exhibited a significantly enhanced cytotoxicity compared to plumbagin and the corresponding lanthanide salts, suggesting a synergistic effect upon plumbagin coordination to the Ln(III) ion. The lanthanide complexes under investigation also exerted dose- and time-dependent cytotoxic activity. [La(PLN) 3 (H 2 O) 2 ] ( 2 ) and plumbagin interact with calf thymus DNA (ct-DNA) mainly via intercalation mode, but for [La(PLN) 3 (H 2 O) 2 ] ( 2 ), the electrostatic interaction should not be excluded; the binding affinity of [La(PLN) 3 (H 2 O) 2 ] ( 2 ) to DNA is stronger than that of free plumbagin, which may correlate with the enhanced cytotoxicity of the PLN–lanthanide(III) complexes.

Ranking-aware queries have been gaining much attention recently in many applications such as multimedia databases, search engines and data streams. They are, however, not only restricted to such applications but are also very useful in On-Line Analytical Processing (OLAP) applications. In this paper, we introduce aggregation ranking queries in OLAP data cubes motivated by an online advertisement tracking data warehouse application. These queries aggregate information over a specified range and then return the ranked order of the aggregated values. For instance, an advertiser might be interested in the top-k publishers over the last three months in terms of sales obtained through the online advertisements placed on the publishers. They differ from range aggregate queries in that range aggregate queries are mainly concerned with an aggregate operator such as SUM and MIN/MAX over the selected ranges of all dimensions in the data cubes. Existing techniques for range aggregate queries are not able to process aggregation ranking queries efficiently. Hence, in this paper we propose new algorithms to handle this problem. The essence of the proposed algorithms is based on both ranking and cumulative information to progressively rank aggregation results. Furthermore we empirically evaluate our techniques and the experimental results show that the query cost is improved significantly.

Based on the hysteretic theory of the giant magnetostrictive material (RE-GMM) and the nonlinear characteristic of the giant magnetostrictive actuator (GMA), the composite nonlinear mathematic model was established with Bouc-Wen hysteretic model, and the hysteresis properties and the hysteresis loop of the transducer were investigated. Then with Multi-scale method, the analytic solution of the response and the expression of the frequency-response properties, which the giant magnetostrictive actuator with hysteretic and geometric nonlinear vibration characteristic included, were achieved, and the t-x curve was obtained. Then, after the discussing about the different cases, the frequency-response curves were obtained with damp case and without damp case, and the affect of frequency-response characteristic with damp expressed by the dynamic excitation f , piezomagnetic coefficient d 33 and magnetic conductivity μ33 T to the curve of the frequency-response is discussed. Results indicated that the effect of f , d 33 and μ33 T to the amplitude and nonlinear of the system was obvious. At the same time, the frequency-response curve had the phenomenon of double hopping.

In the absence of efficient systemic chemotherapy, immunotherapy is considered a hopeful treatment for controlling recurrence of hepatocellular carcinoma (HCC). The identification of proper antigenic peptides presented by MHC class I molecules is a critical step for the development of therapeutic vaccines against tumors. Currently, the "reverse immunology" approach is the most commonly used technique in the identification of the tumor-associated T cell epitopes. However, it is based on T cell dependent approach and cannot fully reflect the actual presentation of epitope in tumor in vivo. In the present study, we managed to identify the naturally presented MAGE epitopes of HCC directly by epitope prediction, HPLC differential analysis and MS detection. We successfully detected a naturally processed peptide FLWGPRALV (MAGE-3(271-279), HLA-A2-restricted) with an estimated number of 38-39 copies/cell in HCC. To our knowledge, this is the first evidence that the naturally processed MAGE-3(271-279) can be isolated and identified from the tumor tissue of HCC patient. Furthermore, specific CD8(+) T cell responses to this epitope were also found after tumor relapse by IFN-gamma release Cytospot and tetramer assay indicating that MAGE-3(271-279) was indeed presented by HCC cells in vivo. In addition, another new antigen peptide was found, which may be derived from MAGE-1. Our findings demonstrate the potential of the direct approach for identification of tumor-associated epitopes. This approach may become a useful tool for the development of vaccine against cancer in the future.

A microporous chiral complex KMn2[(L-C4H2O6)2B] · 3H2O was synthesized solvothermally in the presence of l -tartaric acid. In this framework, Mn2+ ions exhibit distorted octahedral coordination and the tartrate group is bonded to the B atom as a bidentate ligand via oxygen atoms of neighbouring hydroxyl groups.

The $\Lambda_b \to p$ semileptonic decay is analyzed by using QCD sum rules within the framework of heavy quark effective theory. The Isgur-Wise function of $\Lambda_b \to p l \bar\nu$ has been calculated. The decay width is given.