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Heat shock protein 90 (HSP90) has been recognized as a crucial target in cancer cells. However, various toxic reactions targeting the ATP binding site of HSP90 may not be the best choice for HSP90 inhibitors. In this paper, an ellagic acid derivative, namely, okicamelliaside (OCS), with antitumor effects was found. To identify potential anti-cancer mechanisms, an OCS photosensitive probe was applied to target fishing and tracing. Chemical proteomics and protein-drug interaction experiments have shown that HSP90 is a key target for OCS, with a strong binding affinity (K(D) = 6.45 μM). Mutation analysis of the target protein and molecular dynamics simulation revealed that OCS could competitively act on the key Glu-47 site at the N-terminal chaperone pocket of HSP90, where the co-chaperone CDC37 binds to HSP90, affect its stability and reduce the ∆G(bind) of HSP90-CDC37. It was demonstrated that OCS destroys the protein–protein interactions of HSP90-CDC37; selectively affects downstream kinase client proteins of HSP90, including CDK4, P-AKT(473), and P-ERK1/2; and exerts antitumor effects on A549 cells. Furthermore, tumor xenograft experiments demonstrated high antitumor activity and low toxicity of OCS in the same way. Our findings identified a novel N-terminal chaperone pocket natural inhibitor of HSP90, that is, OCS, which selectively inhibits the formation of the HSP90-CDC37 protein complex, and provided further insight into HSP90 inhibitors for anti-cancer candidate drugs. [Image: see text]

Background Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task. Results In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-d-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. Conclusions GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.

Objective A retrospective study of the clinical and radiological results between local bone graft with a cage and without cage in patients treated with unilateral fixation and posterior lumbar interbody fusion surgery. Methods A total of 52 patients who underwent PLIF in our institution were evaluated from January 2015 to January 2018. 30 of these patients received PLIF with local bone graft combined with using one cage, and 22 patients received PLIF with local bone graft without using cage. The clinical data and perioperative complications of the two groups were recorded. X-ray were taken before, after operation and at the end of follow-up to calculate the height of intervertebral disc and the fusion rate. SUK's criteria were used to evaluate the quality of spinal fusion at the follow-up time. The results between the cage and non- cage group were compared. Results There was no statistical difference in baseline data between the two groups, and The mean follow-up time was 18.43 months in cage group and 17.50 months in non- cage group (P = 0.553). In additions, the significant difference was not found in the comparison of perioperative evaluation data between the two groups, such as operation time (P = 0.299), blood loss (P = 0.342) and incidence of complications (P = 1.000). Furthermore, the significant difference of VAS score cannot be found in preoperation (Pleg=0.731, Plowback=0.786), postoperation (Pleg=0.534, Plowback=0.725) and the final follow-up (Pleg=0.654, Plowback=0.362) between the two groups. The same results were also obtained in the comparison of ODI index (Ppre=0.682, Pfinal=0.712) and intervertebral height (Ppost=0.363, Pfinal=0.094). The final fusion rates were 96.7% (cage group) and 86.4% (non- cage group) respectively, and there was no statistical difference (P = 0.553). Conclusion Local bone graft has the same advantages as a cage in unilateral PLIF. Comparing with local bone graft using cage, we believe that the local bone graft is a more ideal way in unilateral PLIF, and decrease operation cost.

Objective Fuzi Banxia is one of eighteen antagonisms, previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment. The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism. Methods Monocrotaline (MCT)-induced cor pulmonale were used in this study. Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function. Semi automatic biochemical analyzer was used to test myocardial enzyme LDH, CK, and CK-MB in serum. The heart tissues were stained with HE, and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis. The expression of hypertrophy and apoptosis associated genes: ANP, BNP, β-MHC, Bax, and Bcl-2 in the right ventricle were determined by RT-PCR. Results Fuzi Banxia combined with ginseng obviously attenuated mortality, decreased RVHI, and increased cardiac index; RVSP and mPAP were significantly reduced, and EF and FS were raised obviously; Myocardial enzymes LDH, CK, and CK-MB were pronounced attenuated; heart diameter reduced, right ventricular dilatation was significantly decreased, inflammatory cell infiltration notably reduced, and cardiac apoptosis rate was decreased obviously. Meanwhile, the expression of hypertrophy-related ANP, BNP, and β-MHC mRNA were up-regulated, the expression of apoptosis-related Bax mRNA was down-regulated, and the expression of anti-apoptosis-related Bcl-2 mRNA and Bcl-2/Bax ratio were up-regulated. Conclusion Ginseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes, and thus delay the occurrence and development of heart failure.

Two new cembrane diterpenoids, named populeuphrines A and B (

Populusone (1), a cembrane-type macrocyclic trinorditerpenoid, was isolated from the exudates of Populus euphratica and shown to have an unprecedented carbon skeleton, The structure was identified using spectroscopic methods and X-ray crystallography. A possible pathway for the biosynthesis of 1 was proposed. Populusone (10 μM) was found to promote proliferation and differentiation of umbilical cord derived mesenchymal stem cells into keratinocyte like cells.

In the study, a software program named “SUPER CE/SE” is developed for the simulation of hypervelocity impact problems with large deformations, high strain rates and spall fractures. In the software program, an Eulerian method consisting of an improved CE/SE (Space-time Conservation Element and Solution Element Method) scheme is used. A void growth model which takes the Bauschinger Effect (BE) into account and a newly proposed front tracking method are adopted in the simulation. The formation and propagation of a crack is described by a newly developed automatic crack growth algorithm. Numerical simulation of spall fracture in a plate when impacted by a spherical projectile at a velocity of 6.0 km/s is carried out. The numerical results are in qualitative agreement with the corresponding experimental data. It turns out that the BE has obvious influence on the length of the crack and better agreement with the experiment is obtained when the BE is considered. It is also validated that the newly proposed front tracking method is feasible and reliable for representing the cracks in the problems with large deformation and high strain rates. According to those research results, it is proved that the software program SUPER CE/SE is robust and effective in the simulation of hypervelocity impact problems.

The nickel-based nanoparticles such as nickel oxide, carbon coated nickel, carbon coated nickel carbide and their mixtures were synthesized by systematically varying the component of explosive precursors and technological parameters. The features of the as-obtained nanoparticles were characterized with TEM, HRTEM, EDX, XRD and XRF. The data from these optimally designed experimental can govern the different types of nickel-based nanoparticles. The formation mechanism during the detonation process were also discussed and analyzed.

Carbon-encapsulated iron-based alloy nanoparticles with a core-shell structure were prepared by detonation decomposition of nitrate complex explosives containing multi-metallic ions. The size and magnetic properties of the as-prepared composite particles were revealed by X-ray powder diffraction, transmission electron microscopy, energy dispersive X-ray detector and magnetic measurements. Results showed that the different sizes of the ferronickel and ferrocobalt nanocrystal core and the thickness of the carbon shell could be yielded by adjusting the component materials of the explosives. The composite particles had a gamma- or alpha- ferronickel or bcc-ferrocobalt nanocrystal core with a coating of graphitic carbon layers. Magnetic measurements indicated these composite nanoparticles were superparamagnetism at the room temperature, with some variation in the values of saturation magnetization, remanences and coercive forces.

FeCoZr magnetic thin films with high uni-axial anisotropy were fabricated by RF co-sputtering followed by post magnetic annealing. The crystal size of FeCoZr films was less than 15 nm, as calculated by Scherrer equation from X-ray diffraction patterns. By adding Zr element, FeCoZr films exhibited a uni-axial anisotropy after magnetic field annealing at 400 °C for 1 hr. Optimal high frequency ferromagnetic properties were achieved in film with 19 at.% Zr, in which strong uni-axial anisotropy field of 300 Oe and high ferromagnetic resonance frequency in excess of 5.2 GHz were obtained. These facts suggest that FeCoZr nano-crystalline film is a potential candidate in high frequency electromagnetic devices operating at GHz bands. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Crashworthiness requirement of fuel tanks is one of the important requirements in helicopter designs. The relations among the protection frame, textile layer and rubber layer of the fuel tank are introduced. Two appropriate FE models are established, one is for an uncovered helicopter fuel tank without protection frame, and the other is for fuel tank with protection frame. The dynamic responses of the two types of fuel tanks impinging on the ground with velocities of 17.3 m/s are numerically simulated for the purpose of analyzing energy-absorbing capabilities of the textile layer and protection frame. The feasibility of the current crashworthiness design of the fuel tank is examined though comparing the dynamic response behaviors of the two fuel tanks.

The three-dimensional premixed H2-O2 detonation propagation in rectangular ducts is simulated using an in-house parallel detonation code based on the second-order space–time conservation element and solution element (CE/SE) scheme. The simulation reproduces three typical cellular structures by setting appropriate cross-sectional size and initial perturbation in square tubes. As the cross-sectional size decreases, critical cellular structures transforming the rectangular or diagonal mode into the spinning mode are obtained and discussed in the perspective of phase variation as well as decreasing of triple point lines. Furthermore, multiple cellular structures are observed through examples with typical aspect ratios. Utilizing the visualization of detailed three-dimensional structures, their formation mechanism is further analyzed.

CrSb film was deposited on KCl (100) substrates by magnetron sputtering. Strong ferromagnetism was observed in the CrSb film, which can be attributed to the CrSb phase with ferromagnetic zinc-blended structure. The investigated ZB-CrSb film about 5 nm in thickness is sufficiently thicker to be investigated the half-metallic nature of ZB-CrSb and to be practically applied in spintronics devices.

Carbon-coated copper (Cu@C) nanoparticles with a core–shell structure were prepared by detonation decomposition of energetic Cu ion doped sol–gel explosive precursors. The composite nanoparticles were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), high resolution TEM, energy dispersive X-ray spectroscopy, and Raman spectroscopy, respectively. The results indicate that the as-obtained core–shell structure Cu@C nanoparticles are with diameter about 10–40 nm. The composite nanoparticles are composed of face-centered cubic-Cu and the amorphous/graphitic carbon coating shells. The thermal stability of the obtained samples was studied by a difference scanning calorimetry–thermogravimetric analyzer. By varying the composition of initial mixtures that contain Cu ion explosive precursors, the different size and chemical composition of composite nanoparticles are shown in this study. The growth mechanism of Cu@C was also briefly discussed.

The details of the special three-dimensional micro-nano scale ripples with a period of hundreds of microns on the surfaces of a Zr-based and a La-based metallic glass irradiated separately by single laser pulse are investigated. We use the small-amplitude capillary wave theory to unveil the ripple formation mechanism through considering each of the molten metallic glasses as an incompressible viscous fluid. A generalized model is presented to describe the special morphology, which fits the experimental result well. It is also revealed that the viscosity brings about the biggest effect on the monotone decreasing nature of the amplitude and the wavelength of the surface ripples. The greater the viscosity is, the shorter the amplitude and the wavelength are.

A new strategy was applied to effectively synthesize spherical core shell structural graphite-coated iron (Fe@G) composite nanoparticles, which were characterized by XRD, TEM, EDX, SAED and XPS.

The graphite-coated copper nanoparticles were synthesized by the detonation decomposition of a copper-doped emulsion explosive and their structure and chemical composition were characterized by TEM, HRTEM, EDX and XRD analysis.

In the present paper, a three-dimensional (3D) Eulerian technique for the 3D numerical simulation of high-velocity impact problems is proposed. In the Eulerian framework, a complete 3D conservation element and solution element scheme for conservative hyperbolic governing equations with source terms is given. A modified ghost fluid method is proposed for the treatment of the boundary conditions. Numerical simulations of the Taylor bar problem and the ricochet phenomenon of a sphere impacting a plate target at an angle of 60° are carried out. The numerical results are in good agreement with the corresponding experimental observations. It is proved that our computational technique is feasible for analyzing 3D high-velocity impact problems.

An essentially conservative adaptive space time conservation element and solution element (CE/SE) method is proposed for the effective simulation of shock-induced instability with low computational cost. Its implementation is based on redefined conservation elements (CEs) and solution elements (SEs), optimized interpolations and a Courant number insensitive CE/SE scheme. This approach is used in two applications, the Woodward double Mach reflection and a two-component Richtmyer—Meshkov instability experiment. This scheme reveals the essential features of the investigated cases, captures small unstable structures, and yields a solution that is consistent with the results from experiments or other high order methods.

The mechanism of the shift of the band-gap in phononic crystal (PC) with different initial confining pressures is studied experimentally and numerically. The experimental results and numerical analysis simultaneously indicate that the confining pressure can efficiently tune the location in and the width of the band-gap. The present work provides a basis for tuning the band-gap of phononic crystal in engineering applications.

Different types of carbon coated iron (Fe) based nanoparticles were controllably synthesized by detonation decomposition of urea nitrate metal complex explosive precursors. In order to control the detonation synthesis of the Fe-based composite nanoparticles, the main components of the urea nitrate metal complex explosive precursors were optimally designed. The components, morphologies, structures and various Fe-based phase composition of the as-obtained composite nanoparticles were further investigated by x-ray diffraction, transmission electron microscopy, electron diffraction spectroscopy and energy dispersive x-ray spectroscopy. The results show that discrete, spherical, uniformly sized (~55 nm) iron oxide nanocrystals and core-shell structural composite nanoparticles (graphite coated Fe) were effectively synthesized by adjusting the densities, oxygen balances and mole ratios of C:Fe of these compound explosive precursors. The formation mechanism of these carbon coated Fe-based composites during the instantaneous detonation reaction process is further discussed.

A void growth model considering the Bauschinger effect (BE) is proposed for ductile materials sustaining impact loading. Numerical simulations of two high-velocity impact problems are carried out by our newly developed Eulerian programs. The proposed model is tested by a plate impact problem and a qualitative agreement with the experiment is obtained. Then a more complicated problem, a plate impacted by a spherical projectile at a velocity of 6.0 km/s, is simulated. The numerical results are in better accordance with the experimental data when the BE is considered. The proposed model reveals that the BE has an obvious effect on the spall process.

A series of relatively thicker CrSb films were deposited on NaCl (1 0 0) substrates by magnetron sputtering. Strong ferromagnetism was observed in the CrSb films with a zinc-blende CrSb (ZB-CrSb) phase epitaxially grown on the NaCl sustrate. The critical thickness of the ZB-CrSb film was close to 4 nm, which is sufficiently thick to investigate the half-metallicity nature of ZB-CrSb and to be practically applied in spintronics devices.

Theoretical analysis and numerical calculations of Love wave propagation in layered graded composites with imperfectly bonded interface are described in this paper. On the basis of WKB method, the approximate analytic solutions for Love waves are obtained. By the interface shear spring model, the dispersion relations for Love waves in layered graded composite structures with rigid, slip, and imperfectly bonded interfaces are given, and the effects of the interface conditions on the phase velocities of Love waves in SiC/Al layered graded composites are discussed. Numerical analysis shows that the phase velocity decreases when the defined flexibility parameter is greater. For the general imperfectly bonded interface, the phase velocity changes in the range of the velocities for the rigid and slip interface conditions.