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Graphical abstract Schematic illustration of the swapping process in CH 4 -C 2 H 6 -C 3 H 8 ternary hydrates by CO 2. Highlights: • The replacement of CH 4 -C 2 H 6 -C 3 H 8 ternary hydrates by gaseous and liquid CO 2 is experimentally investigated. • CH 4 , C 2 H 6 and C 3 H 8 are recovered heterogeneously from gas hydrates by CO 2 replacement. • There is a structural transformation followed by an isostructural conversion in sII hydrate replacement. • The spatial distribution of gas compositions in the replaced hydrates is obtained based on shrinking-core model. • A power function relation was found to exist between the replacement efficiency and mole ratio of CO 2 to hydrate. Abstract The replacement of CH 4 -C 2 H 6 -C 3 H 8 ternary hydrates in sandy sediments by gaseous and liquid CO 2 was studied to explore the gas recovery from structure II (sII) gas hydrate reservoirs. It was found that the swapping pattern in sII mixed hydrates is significantly different from that in the pure methane hydrate, which is a structure I (sI) hydrate. CH 4 , C 2 H 6 and C 3 H 8 can be recovered heterogeneously from the mixed hydrates by CO 2 replacement. The results showed CH 4 was the easiest to replace in all of the experimental runs. In addition, there was a preferential release of C 3 H 8 over C 2 H 6 with higher mole ratio of CO 2 to initial hydrate. The guest-to-cavity size ratio was used to qualitatively study the gas exchange kinetics in the mixed hydrates. It was proposed that the isostructural conversion and structural transition coexisted in the mixed hydrates replacement. The spatial distribution of multiple components in the replaced hydrate particles was obtained by coupling gas production measurements with compositional analysis of the hydrate dissociation. It was found that further hydrate structure-transition from sII to sI occurred in deeper layers of the hydrate particles in replacement with higher mole ratio of CO 2 to initial hydrate. A power function relation was found to exist between the replacement efficiency and mole ratio of CO 2 to hydrate. These results are of significance for guiding successful sII hydrate recovery and CO 2 sequestration. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90 α inhibitory activity with IC 50 value of 5.3 nM and an excellent growth inhibition with GI 50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC 50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results. [ABSTRACT FROM AUTHOR]

Objective The study was aimed to investigate the impact of CX3CR1 expression on the proliferation and apoptosis of osteoarthrosis (OA) chondrocytes through Wnt/ β-catenin pathway. Methods The expression levels of CX3CR1 and Wnt/β-catenin pathway-related genes mRNA and protein in OA chondrocytes were examined by qRT-PCR and western blot. MTT and flow cytometry (FCM) assays were employed to assess cell proliferation, cell cycle and apoptosis. XAV-939, a Wnt/β-catenin pathway inhibitor, was used to inhibit the pathway. Results CX3CR1 was significantly overexpressed in OA cartilages than that in normal articular cartilages ( P  < 0.05). After si CX3CR1 transfection, the expression level of Wnt 3, nuclear β-catenin, Cyclin D1, MMP-13 and phosphorylated GSK-3β significantly increased, while cytoplasm β-catenin, GSK-3β and phosphorylated β-catenin expression was inhibited ( P < 0.05). XAV-939abolished the effects of si CX3CR1 on proliferation, apoptosis and cell cycle progression of OA chondrocytes ( P < 0.05). Conclusions CX3CR1 regulated chondrocyte proliferation and apoptosis through Wnt/β-catenin signaling pathway. The overexpression of CX3CR1 in chondrocytes of OA may be closely related to the pathogenesis and progression of OA. [ABSTRACT FROM AUTHOR]

In this paper, Z -scheme heterojunction Bi-doped LaFeO 3 /CQDs/CN (LBFO/CQDs/CN) photocatalysts were successfully synthesized. Compared to CN, LFO, LBFO, and their two-component composites, LBFO/CQDs/CN exhibits better degradation performance of pollutants such as RhB, TCL, MB, and MO. The main reason is that Bi doping could facilitate the extended absorption of visible light and the promotion of oxygen vacancies by LFO. On the other hand, CQDs, as a medium for electron migration between CN and LBFO, effectively enhance the efficiency of electron migration in Z -scheme heterojunctions and achieve spatial separation of electrons and holes. The successful preparation of the three-component material and its good performance was confirmed by various characterization methods. In addition, capture experiments demonstrate that superoxide radicals (·O 2 −) are the main active species in the reaction, while the formation of Z -scheme heterojunctions is demonstrated using a carrier migration mechanism. [Display omitted] • A novel Z -scheme photocatalyst Bi-doped LaFeO 3 /CQDs/CN was synthesized. • Bi3+ doping facilitated the formation of oxygen vacancies. • CQDs acted as intermediaries and enhanced charge transfer. • It exhibited excellent photocatalytic activity and cyclic stability. [ABSTRACT FROM AUTHOR]

• A rapid and sensitive MSPD-LC-MS/MS method was developed for the determination of HBCD enantiomers in animal meat. • The developed MSPD procedure could be accomplished with only 5 mL solvent for each sample and environmental friendliness. • MSPD conditions were optimized by the Box–Behnken design through RSM. • The method showed high sensitivity with the LODs at trace levels (ng g−1). A rapid and sensitive method was developed based on matrix solid phase dispersion (MSPD) for the determination of hexabromocyclododecane enantiomers (±α, ±β and ± γ-HBCD) in animal meat. The instrumental analysis was employed with liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) at trace level (ng g−1). To obtain excellent efficiency, the key parameters, including the type of dispersive adsorbent and elution solvent, were investigated by single-factor experiments. The volume of elution solvent and amount of dispersive adsorbent were optimized by the Box–Behnken design through response surface methodology. Under optimized conditions, the developed method exhibited excellent methodologic characteristics and was applied to the determination of HBCD enantiomers in real chicken and pork meat. Experimental results indicated that the proposed method would be an efficient, rapid and application method for the determination of lipophilic organic pollutants in animal meat. [ABSTRACT FROM AUTHOR]

HDAC6 and Hsp90, existing as a cytosolic complex play an important role in maintaining the protein homeostasis. The interplay of HDAC6 and Hsp90 has attracted wide attention due to their important role and promise as therapeutic targets in malignant cancers. Therefore, the discovery of dual inhibitors targeting HDAC6 and Hsp90 is of high importance. In the present study, we describe the design, synthesis, and biological evaluation of bifunctional inhibitors against HDAC6 and Hsp90 interplay. In particular, compound 6e shows a significant inhibitory activity against both HDAC6 and Hsp90 with IC 50 values of 106 nM and 61 nM, respectively. Compound 6e promotes the acetylation of HDAC6 substrate proteins such as α -tubulin and Hsp90 via HDAC6 inhibition, and also induces the degradation of Hsp90 clients such as Her2, EGFR, Met, Akt, and HDAC6 via Hsp90 inhibition. Compound 6e consequently furnishes potent antiproliferative effect on gefitinib-resistant H1975 non-small cell lung cancer (NSCLC) with a GI 50 value of 1.7 μM. In addition, compound 6e successfully achieved significant tumor growth inhibition in H1975 NSCLC xenograft model without noticeable abnormal behavior, body weight changes, and apparent ocular toxicity. We conclude that compound 6e constitutes an excellent tool as well as a valuable lead for assessment of Hsp90 and HDAC6 dual inhibition with a single molecule. [Display omitted] • Design, synthesis, and biological evaluation of Hsp90-HDAC6 dual inhibitors are presented. • Compound 6e displays highly potent anti-proliferation effect on H1975 cancer cells. • Compound 6e inhibits the tumor growth in H1975 xenografts mice models. [ABSTRACT FROM AUTHOR]

This study proposes an artificial freezing method that consumes low energy by combining air-cooling and a conventional method. The method fully utilizes a naturally low air temperature in a cold region, which reduces freezing costs and avoids environmental influence. A refrigeration experimental platform is designed to study the refrigeration effects of natural cold sources. A mathematical model is built to analyze the evolution of temperature. And the temperature field was simulated by software----ANSYS. The simulated results match the experimental data well and verify the feasibility of the proposed method. Moreover, air-cooling economy and conventional refrigeration are analyzed. The running cost and power of the air-cooling method are respectively reduced by 52% and 53.4% when compared with the values for the conventional method. This approach effectively reduces refrigeration power load and project cost, consumes low energy, and is environment friendly. This study can thus serve as a reference for new ideas on underground artificial freezing. [ABSTRACT FROM AUTHOR]

Abstract: The optimal solution of a multi-objective optimization problem (MOP) corresponds to a Pareto set that is characterized by a tradeoff between objectives. Genetic Pareto Set Identification Algorithm (GPSIA) proposed for reliability-redundant MOPs is a hybrid technique which combines genetic and heuristic principles to generate non-dominated solutions. Series–parallel system with active redundancy is studied in this paper. Reliability and cost were the research objective functions subject to cost and weight constraints. The results reveal an evenly distributed non-dominated front. The distances between successive Pareto points were used to evaluate the general performance of the method. Plots were also used to show the computational results for the type of system studied and the robustness of the technique is discussed in comparison with NSGA-II and SPEA-2. [Copyright &y& Elsevier]

Abstract: The mechanism of magnetic exchange interaction in an interesting CuII coordination polymer with the CuI 2X2 (X=I or Br) moiety bridge is investigated by the calculations based on density functional theory combined with the broken-symmetry approach (DFT-BS). Surprisingly, different from the experiment results, the calculations reveal that the complex between the magnetic CuII centers has a fairly weak antiferromagnetic interaction for the long distance (∼10Å). The analyses show of the molecular orbitals and the spin density distribution favor the very weak antiferromagnetic coupling interactions of the systems. [Copyright &y& Elsevier]

Abstract: The magnetic properties of a series of dinuclear MnII systems are investigated by the calculations based on density functional theory combined with broken-symmetry approach (DEF-BS). It is found that there are weak antiferromagnetic interactions in these systems with different bridging ligands. The changing trend of the magnetic coupling constants J indicates that with the electronegativity of the increasing bridging ligands, the antiferromagnetic coupling interaction is weakened. The analyses of the magnetic orbitals and the spin densities show that the weakly antiferromagnetic couplings in these systems are due to the vertical magnetic d orbitals and the weak spin delocalization. These results should be instructive for the design of new molecular magnetic materials. [Copyright &y& Elsevier]

Abstract: This Letter studies the robustness problem of pinning a general complex dynamical network toward an assigned synchronous evolution. Several synchronization criteria are presented to guarantee the convergence of the pinning process locally and globally by construction of Lyapunov functions. In particular, if a pinning strategy has been designed for synchronization of a given complex dynamical network, then no matter what uncertainties occur among the pinned nodes, synchronization can still be guaranteed through the pinning. The analytical results show that pinning control has a certain robustness against perturbations on network architecture: adding, deleting and changing the weights of edges. Numerical simulations illustrated by scale-free complex networks verify the theoretical results above-acquired. [Copyright &y& Elsevier]

Abstract: On the basis of the theory of system, epistemology, and feedback control, a novel securities pricing model — stochastic volatility pricing model (SVPM) with jump and feedback mechanism is proposed. This model overcomes the defect of traditional SVPM models that neglect the important events happening frequently in financial markets, and also considers the interaction between investors and securities price. Theoretical analysis and numerical simulations indicate that this model can simulate the complex behaviors of real securities price better than traditional SVPMs. Comparisons suggest that the simulated return rates have the same statistical characteristics as the real stocks’. Finally, practical applications of this model show that this is of high precision, efficiency, robustness, and universality. [Copyright &y& Elsevier]

Abstract: A two-dimensional polynuclear complex [Ni(μ1,3-SCN)2(μ-mpyo)] n (where mpyo=4-methylpyridine N-oxide) has been synthesized and its crystal structure determined by X-ray crystallography. In the complex there exist two kinds of bridging ligands, namely, μ1,3-SCN− bridging ligand and μ-mpyo bridging ligand. The two kinds of bridging ligands coordinate to Ni(II) ions in alternate fashion and it led to the formation of a two-dimensional sheet. The density functional calculations have been carried out on the binuclear model complexes to analyze the magnetic coupling mechanisms. The variable temperature (4–300K) magnetic measurements were performed and the experimental data were fitted by using a binuclear Ni(II) magnetic coupling formula. The magnetic coupling constants from calculations are J =−61.81cm−1 for μ-mpyo bridging ligand and J =−13.31cm−1 for μ1,3-SCN− bridging ligand, and the experimental value is J =−36.22cm−1. In the area of magneto-structure theoretical calculation study this is the first paper that deals with the complexes with mixed bridging ligands. [Copyright &y& Elsevier]

Objectives: In minimally invasive and robotic mitral valve surgery, a blade retractor is used to elevate the left atrial roof, which often distorts tissue and impairs visualization. We tested the hemodynamic and histologic changes of intra-atrial suction, using a new suction retractor that may improve stabilization and visualization. Methods: Swine were divided into 3 equal (n = 4) groups: blade retractor, suction retractor, and arrested heart control. Left atrial ultrasonic crystals were used to record ejection fractions. After cardioplegic arrest, the atrium was opened and sampled for preretractor histology. Retractors remained in place for 1 hour, followed by postretractor histologic sampling. Controls were crossclamped for an equivalent time and postarrest histologic data obtained. Animals were weaned from bypass, data were collected for 4 hours, and postsacrifice atrial histologic samples were obtained. Results: The main effect due to treatment was not statistically significant (P = .52) between the 3 groups, with the 4-hour average ejection fraction for blade retractor, suction retractor, and control being statistically equivalent at 33.3% ± 8.3, 35.3% ± 12.1, and 40.8% ± 9.9 (mean ± standard deviation), respectively. Histology showed equivalent amounts of myocyte fragmentation, interstitial edema, eosinophilia, and wavy fibers between blade retraction and suction retraction, while the latter showed slightly increased amounts of hemorrhage. Conclusions: Atrial endocardial suction retraction appears to be safe with no acute changes in the left atrial ejection fraction or significant acute histologic differences, compared to blade retraction. Furthermore, intra-atrial suction may be applicable to procedures other than minimally invasive and robotic mitral valve repair for providing improved stabilization. [Copyright &y& Elsevier]

In this study, the crystallization behavior of a CaO–MgO–Al 2 O 3 –SiO 2 based glass ceramics with Nb 2 O 5 addition was investigated by using DSC, XRD and TEM techniques. It was found that three crystalline phases, namely, CaNb 2 O 6 , diopside and Gehlenite (Ca 2 Al 2 SiO 7), were formed from the glass matrix during the crystallization heat treatment. The CaNb 2 O 6 phase was the first to precipitate from the glass matrix at around 850 °C, acting as a nucleating agent that facilitated the formation of Gehlenite (Ca 2 Al 2 SiO 7) at 900–950 °C. The TEM observation revealed a consistent orientation relationship between the CaNb 2 O 6 and the Gehlenite (Ca 2 Al 2 SiO 7) phases, indicating that CaNb 2 O 6 could induce the epitaxial growth of Gehlenite (Ca 2 Al 2 SiO 7). This result provides a new insight into the preparation of Gehlenite epitaxial films and glass ceramics. [ABSTRACT FROM AUTHOR]

The biogeochemical cycles of the metalloid elements arsenic and antimony in the East China Sea (ECS), one of the most important marginal seas for western Pacific, were examined in May 2011. Dissolved inorganic arsenic (As(V) and As(III)) and antimony (Sb(V) and Sb(III)) species were determined by selective hydride generation–atomic fluorescence spectrometry (HG-AFS). Results show that total dissolved inorganic arsenic (TDIAs; [TDIAs]=[As(V)]+[As(III)]) were moderately depleted in the surface water and enriched in the deep water. Arsenite (As(III)) showed different vertical profiles with that of TDIAs, with significant surface enrichment in the middle shelf region where the concentrations of phosphate were extremely low. Speciation of dissolved arsenic was subtly controlled by the stoichiometric molar ratio of arsenate (As(V)) to phosphate. The average As(V)/P ratio for the ECS in spring 2011 was 10.8×10 −3 , which is higher than previous results and indicates the arsenate stress. The concentrations of total dissolved inorganic antimony (TDISb; [TDISb]=[Sb(V)]+[Sb(III)]) were high near the Changjiang Estuary and the coastal area of Hangzhou Bay and decreased moderately off the coast. TDISb displayed moderate conservative behavior in the ECS that confirms by the correlations with salinity and dissolved aluminum. Different with that of As(III), antimonite (Sb(III)) concentrations were extremely lower in the ECS, with relative higher concentration appeared at the bottom layer which indicates the contribution from sediment-water interface. A preliminary box model was established to estimate the water-mass balance and antimony budgets for the ECS. Compared with other areas in the world, the concentrations of dissolved inorganic arsenic and antimony in the ECS remain at natural levels. [ABSTRACT FROM AUTHOR]

An extraordinary high strength Mg-8Al-0.5Zn alloy has been developed through extrusion at a low temperature of 200°C and a slow speed of 0.07mm/s. The as-extruded alloy exhibited a tensile yield strength of 403MPa, an ultimate tensile strength of 437MPa, an elongation of 10.7%, and a low tension-compression yield asymmetry of 0.97. These superior mechanical properties are attributed to the combined effect of ultra-fine recrystallized grains, numerous nano-scale Mg=sub=17=/sub=Al=sub=12=/sub= precipitates, and strong basal texture. [ABSTRACT FROM AUTHOR]

Abstract: Borogermanate scintillating glasses with composition of 25B2O3–40GeO2–2Eu2O3–33RE2O3 (RE=Y, La and Gd) were synthesized by melt-quenching method. The effect of RE2O3 on the glass structure and performance including the density, transmittance as well as luminescent properties under both ultraviolet (UV) and X-ray excitation were compared and studied systematically. The enhanced intensity of Eu3+ emission under X-ray excitation is remarkably higher than that under UV excitation. The temperature-dependent emission spectra in the 75–295K temperature region reveal that the thermal quenching behavior of Eu3+ luminescence in Y2O3-based glass is slightly better than that in La2O3- or Gd2O3-based one. The covalency property of Eu O bond and the local environment of Eu3+ ions is evaluated by the values of Ω t parameter by employing the Judd–Ofelt analysis. The possible interconnection among the covalency nature of Eu O bond, the thermal quenching behavior of Eu3+ emission, and the thermal stability of the designed borogermanate scintillating is also discussed. [Copyright &y& Elsevier]

Abstract: In this paper, thermodynamic calculations of nozzle governing stage are taken based on APROS (Advanced Process Simulation), and verify through the comparison of experiment table data. The influence of partial admission on pressure ratio within the governing stage is also analyzed. The results show that partial admission not only leads to partial admission losses, but also makes an impact on pressure ratio, enthalpy and reaction degree, in turn, causes the change of efficiency. Then, the nozzle pressure ratio after the full-open valve and semi-open valve respectively, is expressed as a function of flow ratio based on dimensional analysis. This paper presents a method of thermodynamic calculation for nozzle governing stage. Comparing with the results calculated through APROS and discussing the change of pressure ratio and reaction degree, it shows that the method can reflect the influence of partial admission on pressure ratio exactly, and further improve the accuracy of existing thermodynamic calculation. [Copyright &y& Elsevier]

Abstract: In this paper, we present a simple rule which assigns fitness to each edge to generate random pseudofractal networks (RPNs). This RPN model is both scale-free and small-world. We obtain the theoretical results that the power-law exponent is for the tunable parameter , and that the degree distribution is of an exponential form for others. Analytical results also show that an RPN has a large clustering coefficient and can process hierarchical structure as that is in accordance with many real networks. And we prove that the mean distance scales slower logarithmically with network size N. In particular, we explain the effect of nodes with degree 2 on the clustering coefficient. These results agree with numerical simulations very well. [Copyright &y& Elsevier]

Abstract: It has been demonstrated that most complex networks display synchronization phenomena, and this problem has attracted great attention of various fields including science and engineering. In this paper, a generalized complex dynamical network model with time-varying delays was presented. Kronecker product was adopted to investigate this model. Moreover, several synchronization criteria were derived for both delay-independent and delay-dependent asymptotical stability. Especially, it has been shown that synchronization of such dynamical network is determined by the linear matrix inequality consisting of coupling configuration matrices, inner-coupling matrices and isolated cells. At last, illustrative examples were given to validate the above-acquired. [Copyright &y& Elsevier]

Abstract: A new one-dimensional coordination polymer [Co(μ1,3-SCN)(μ-MPyO)(SCN)(CH3OH)] n (where MPyO=4-methylpyridine N-oxide) has been synthesized and its crystal structure determined by X-ray crystallography. In the complexes, there exist two kinds of bridging ligands, namely, μ1,3-SCN− bridging ligand and μ-MPyO bridging ligand. The two kinds of bridging ligands coordinate to the Co(II) ions with alternating way and which led to the formation of the one-dimensional chain. The density function calculations have been carried out on the complex to analyze the magnetic coupling mechanism. The calculations reveal that magnetic coupling values are J =−20.32cm−1 from MPyO bridged Co(II) ions and J =−0.87cm−1 from μ1,3-SCN− bridged Co(II) ions. The fitting of the susceptibility data (4–300K) was performed by using one-dimensional Co(II) coupling formula which gave the J =−7.19cm−1 and J′=−1.28cm−1. [Copyright &y& Elsevier]

The influence of hydrodynamic conditions on membrane fouling was investigated. Ten experiments were designed and operated over a wide range of suspended solid (SS) concentrations (2–20 g l−1), filtration fluxes (4.5–27 l m−2 h−1) and aeration intensities (10–100 m3 m−2 h−1). In each experiment, the liquid cross-flow velocity was measured and the membrane filtration resistance was monitored. A modified model was set up for calculating the cross-flow velocity of the activated sludge over the membrane surface. The increasing rate of filtration resistance was deduced as a power function of the cross-flow velocities, filtration fluxes and SS concentrations, and a critical curve corresponding to a group of critical fluxes and critical aeration intensities was found. The membrane filtration resistance sharply increased at a flux over the critical flux or at an aeration intensity below the critical aeration intensity. [Copyright &y& Elsevier]

The structure–activity relationship for genistein to scavenge peroxyl radical was clarified by density functional theory (DFT) calculations using the B3LYP/6-31G(d,p) method. It was revealed that the conjugation of an electron-withdrawing 1,4-pyrone group with A-ring of genistein was not beneficial to enhance the radical-scavenging activities. Thus, hydroxyl in B-ring became the active center of genistein to scavenge peroxyl radical. [Copyright &y& Elsevier]

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC 50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors. [Display omitted] • HDAC6 inhibitors were designed, synthesized, and biologically evaluated. • Compound 8g preferentially inhibited HDAC6 and induce the acetylation of α-tubulin. • Compound 8g blocked the growth of H1975 non-small cell lung cancer cells. • Compound 8g inhibited tumor growth in H1975 xenografts mice models. [ABSTRACT FROM AUTHOR]

The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N -terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC 50 = 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI 50 values of 0.31 μM and 0.11 μM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gamma null mice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC 50 > 50 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

ot deformation behavior of a homogenized Mgâ€"8Snâ€"1Alâ€"1Zn (wt.%) (TAZ811) alloy was investigated at the temperature range of 523â€"673 K and the strain rate of 0.33â€"10 sâ' 1 to explore its potential as a wrought alloy. The kinetic analysis indicated that dislocation climb mechanism was likely to be an operative deformation mechanism for TAZ811 alloy. To obtain the optimum hot working parameters of the alloy, processing map consisting of a power dissipation map and an instability map was constructed. The practical processing window could be determined as T = 623â€"673 K and View the MathML source = 0.33â€"3.3 sâ' 1 with a peak efficiency of approximately 20% occurring at 673 K and ε= 0.33 sâ' 1. The flow instability region occurs at around the temperature of 523â€"598 K and stain rate of 0.33â€"0.66 sâ' 1. In addition, dynamic recrystallization (DRX) mechanisms were analyzed with respect to its microstructure, which was consistent with the predicted results from the processing map. [ABSTRACT FROM AUTHOR]

Parametric models of round wire rope structures in arbitrary centerlines were presented and their geometrical features were analyzed based on enveloping theory. Especially concerning on strand directions and types such as right/left Lang lay and on strand wire structures as single-helixes, double-helixes and super-coiled configurations, a series of recursive formulas of spatial enwinding equations of wires and strands were derived. Geometrically configuring accurate wire radii of multiple strands in undeformed way in which all wires touch the core wire and the adjacent one in Seals and Warrington, mathematical optimal models derived from envelopment were presented. Through analyzing the density of space curve groups, the geometric features in which they are usually in point contact between adjacent wires and strands rather than in line were expressed qualitatively. The curvature of wire surface stretching and warping was demonstrated by orthogonal parameterized curve nets. The modeling process was implemented on CATIA and MATLAB platforms. And mathematical representation of geometric features of wire strands was shown in detail. The results may support parametric modeling platform of wire ropes for fast indeterminate contact analysis statically and dynamically. [ABSTRACT FROM AUTHOR]

Highlights: [•] Analyses of Li, δ7Li for weathering and provincial identification. [•] The detritus δ7Li was possibly controlled by the loess sources. [•] Based on the CIA, the Tengger and Badain Juran Desert are likely sources of CLP. [•] Li carbonate fractions of loess is essentially derived from silicate weathering. [•] Li and δ7Li in the loess show similar compositions to illite and montmorillonite. [Copyright &y& Elsevier]