Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

Potential therapeutic use of plant flavonoids in AD and PD.

Background: Millions of people suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) worldwide. Due to their complex pathology, no effective pharmacological treatment has been found to date, despite extensive research. Developing new, effective therapeutic agents to cure these disease remains a major challenge. Although the cause of AD and PD remains illusive, numerous studies indicates that oxidative stress and neuro-inflammation lead to neurodegeneration in the central nervous system and play vital role in AD and PD morbidity and progression. Flavonoids, which are found widely in nature, exhibit anti-oxidative, anti-inflammatory, anti-mutative, anti-microbial, and neuroprotective properties, so have potential to treat these two kinds of diseases. Methods: In this review, we focus on the anti-oxidative and neuroprotective action of flavonoids in attenuating Alzheimer's and Parkinson's disease, and how they might be harnessed in the development of new pharmacological agents to treat these two diseases. Result: Some flavonoid compounds, like hesperidin, naringin, naringenin, tangeretin, nobiletin, silibinin, Epigallocatechin-3-gallate, displayed to be effective in both AD and PD. Conclusion: Considerable studies have demonstrated the anti-AD and anti-PD effects of flavonoids through various in vitro and in vivo models. However, more rigorous studies are needed to be done for flavonoids to develop into effective drugs and apply them to clinical practice.

Microstructure and Friction Properties of CoCrFeMnNiTix High-Entropy Alloy Coating by Laser Cladding.

To enhance the friction and wear properties of 40Cr steel's surface, CoCrFeMnNi high-entropy alloy (HEA) coatings with various Ti contents were prepared using laser cladding. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) were used to characterize the phase composition, microstructure, and chemical composition of the samples. The findings demonstrated that the CoCrFeMnNiTix HEA coatings formed a single FCC phase. Fe2Ti, Ni3Ti, and Co2Ti intermetallic compounds were discovered in the coatings when the molar ratio of Ti content was greater than 0.5. The EDS findings indicated that Cr and Co/Ni/Ti were primarily enriched in the dendrite and interdendrite, respectively. Ti addition can effectively enhance the coating's mechanical properties. The hardness test findings showed that when the molar ratio of Ti was 0.75, the coating's microhardness was 511 HV0.5, which was 1.9 times the hardness of the 40Cr (256 HV0.5) substrate and 1.46 times the hardness of the CrCrFeMnNi HEA coating (348 HV0.5). The friction and wear findings demonstrated that the addition of Ti can substantially reduce the coating's friction coefficient and wear rate. The coating's wear resistance was the best when the molar ratio of Ti was 0.75, the friction coefficient was 0.296, and the wear amount was 0.001 g. SEM and 3D morphology test results demonstrated that the coating's wear mechanism changed from adhesive wear and abrasive wear to fatigue wear and abrasive wear with the increase in Ti content.

Ultrasound cavitation induced nucleation in metal solidification: An analytical model and validation by real-time experiments.

Microstructural refinement of metallic alloys via ultrasonic melt processing (USMP) is an environmentally friendly and promising method. However, so far there has been no report in open literature on how to predict the solidified microstructures and grain size based on the ultrasound processing parameters.In this paper, an analytical model is developed to calculate the cavitation enhanced undercooling and the USMP refined solidification microstructure and grain size for Al-Cu alloys. Ultrafast synchrotron X-ray imaging and tomography techniques were used to collect the real-time experimental data for validating the model and the calculated results. The comparison between modeling and experiments reveal that there exists an effective ultrasound input power intensity for maximizing the grain refinement effects for the Al-Cu alloys, which is in the range of 20-45 MW/m2. In addition, a monotonous increase in temperature during USMP has negative effect on producing new nuclei, deteriorating the benefit of microstructure refinement due to the application of ultrasound.

The growth restriction effect of TiCN nanoparticles on Al-Cu-Zr alloys via ultrasonic treatment.

Ex situ and in situ synchrotron X-radiography study on Al-Cu-Zr alloys with addition of Al-5Ti-1B and TiCN nanoparticles (TiCNnp) were carried out at different cooling rates. Al-Zr alloy can be effectively refined by TiCNnp via Ultrasonic treatment as compared with Al-5Ti-1B which has Zr poisoning effect. The influence of cooling rate on the nucleation and growth of grains have been studied quantitatively. The results show that the grain size was decreased and the growth rate was increased with the increasing of cooling rate. At the same cooling rate, the grain size with addition of 0.5% TiCNnp was smaller than that with the same addition of Al-5Ti-1B. The blocking factor f of TiCNnp decreases with increasing cooling rate. Based on the free growth model, a new numerical model considering the growth restriction effect of nanoparticles was established. The growth of grain was inhibited by the combining effect of solute and nanoparticles. The growth rate of grain is reduced due to part of the solid/liquid interface coated by nanoparticles. The blocking factor f is linearly decreased with the coverage ratio ω which is proportional to the critical grain radius. The grain size decreases with increasing cooling rate and decreasing f . This study is especially beneficial for Al alloys that have poisoning phenomenon inoculated by traditional refiner.

Characterization of the complete plastid genome of Gaultheria griffithiana (Ericaceae).

Gaultheria griffithiana is an evergreen shrub in the family Ericaceae. It is used as a source of the Chinese traditional medicine, Tougucao, with distribution of the junction of eastern Himalaya and Hengduan Mountain. The chloroplast genome of G. griffithiana is 175,649 bp in length with 135 genes, including eight rRNA genes, 39 tRNA genes, and 85 protein-coding genes. Phylogenetic analysis has converged on the placement of G. griffithiana as sister to G. praticola, G. nummularioides, and G. hookeri within the Leucothoides clade of Gaultheria in this study.

Dynamics of particle retention and physiology in Euonymus japonicus Thunb. var. aurea-marginatus Hort. with severe exhaust exposure under continuous drought.

Frequent drought events and particulate matter pollution from vehicular exhaust seriously affect urban plant growth and provisioning of ecological services. Yet, how plants respond physiologically and morphologically to these two combined stressors remains unknown. Here, we assessed particle retention dynamics and plant morphology and physiology of Euonymus japonicus Thunb. var. aurea-marginatus Hort. under continuous drought with severe exhaust exposure. Our results showed that continuous drought insignificantly lowered particle retention in each of three size fractions by 1.02 µg·cm-2 on average in the first 28 days, but significantly lowered total particle retention by 35.75 µg·cm-2 on the 35th day. We observed evident changes in morphology, leaf mass per area (LMA), pigments, gas exchange in all stressed plants. Compared with single stress, combined drought and pollution caused earlier yellowing and shedding of old leaves, significantly lowered LMA by 1.21 mg·cm-2, caused a greater decline in pigments and net photosynthetic rate (Pn). Large particles may mainly explain pigment reduction, lower weekly LMA increases, and stomatal restriction, while coarse particles may be the main drivers of the decline in Pn. Continuous drought mediated the influence of all three particle sizes on some parameters, such as weakening the impact of total particles on LMA, strengthening the impact of fine particles on photosynthesis. Our findings suggest that drought accelerates the physiological responses of plants to exhaust pollution. Under controlled severe exhaust pollution conditions, the optimal time to maintain high particle retention during continuous drought without decline in physiological conditions for E. japonicus var. aurea-marginatus was 14 days. Some additional interventions after 14 days (it could be postponed appropriately under field conditions) may help ensure healthy growth of plants and retention of particulate matter.

Polarization-Controlled Surface Defect Formation in a Hybrid Perovskite.

Hybrid perovskites have two properties that are absent in traditional inorganic photovoltaic materials, namely, polarization and mobile ionic defects, the interaction between which may introduce new features into the materials. By using the first-principles calculations, we find that the formation energies of the vacancy defects at a tetragonal MAPbI3(110) surface are highly related to the surface polarization. The positive total polarization and local polarization of MA facilitate the formation of surface MA vacancies, whereas the negative total polarization and local polarization of MAI are favorable for the formation of surface iodine vacancies. The phenomena can be explained quantitatively on the basis of the two kinds of Coulomb interactions between the charged defect and the polarization-induced electrostatic field. The comprehensive insights into the interaction between the polarization and the ionic defects in hybrid perovskites can provide a new avenue for defect control for high-performance perovskite solar cells via surface polarization.

High Temperature Behaviors of a Casting Nickel-Based Superalloy Used for 815 °C.

The hot deformation behaviors of the SJTU-1 alloy, the high-throughput scanned casting Nickel-based superalloy, was investigated by compression test in the temperature range of 900 to 1200 °C and strain rate range of 0.1-0.001 s-1. The hot processing map has been constructed with the instability zone. At the beginning of hot deformation, the flow stress moves rapidly to the peak value with the increased strain rates. Meanwhile, the peak stress is decreased with the increased temperature at the same strain rates. However, the peak stress shows the same tendency with the strain rates at the same temperature. The optimum hot deformation condition was determined in the temperature range of 1000-1075 °C, and the strain rate range of 0.005-0.1 s-1. The microstructure investigation indicates the strain rate significantly affects the characteristics of the microstructure. The deformation constitutive equation has also been discussed as well.

Design of high-ductile medium entropy alloys for dental implants.

Developing new materials with high strength and ductility, low modulus and high biocompatibility is a continuing demand in the field of surgical implants. Inspired by the high-entropy design philosophy, two medium entropy alloys (MEAs), i.e. equiatomic TiZrHf and equi-weight Ti40Zr20Hf10Nb20Ta10 were designed and their mechanical properties and biocompatibility were assessed. Both the single-phase hexagonal close-packed (HCP) structured TiZrHf alloy and the single-phase body-centered cubic (BCC) structured Ti40Zr20Hf10Nb20Ta10 alloy show high strength-ductility combinations close to commercial Ti-6Al-4V wrought alloy and remarkably lower young's modulus than commercial pure titanium (CP-Ti) and Ti-6Al-4V. From the aspects of adhesion, proliferation, toxicity and related gene expression of human gingival fibroblasts (HGFs), the Ti40Zr20Hf10Nb20Ta10 alloy exhibits distinctively better biocompatibility than that of CP-Ti while the TiZrHf shows only slightly better biocompatibility as compared with CP-Ti. These results indicate that these two ductile MEAs are potential candidates for dental application.

Reversible Photodriven Droplet Motion on Ti3C2 MXene Film for Diverse Liquids.

The manipulation of liquid droplets on a specific surface with reversible wettability is of great importance for various applications from science to industry. Herein, the concept of a smart, flexible photodriven droplet motion (PDM) device with programmable wettability is designed using the 2D material of MXene film. Because of the MXene photothermal property, the Vaseline layer in the device is in transition between solid and liquid states under the heat transformation due to light illumination, thus attractively producing a reversible wettability for liquid motion with respect to sliding and pinning. Multifarious pathways for liquid motion could be designed through the flexibility of light illumination, which is a revolutionary enhancement in diverse liquid motion to form the desired pathways. In addition, we demonstrated liquid motion under illumination of the back face, which has a profound influence on applications, such as microfluidic systems, microengines, and liquid manipulation.

Intrinsic interaction between in-plane ferroelectric polarization and surface adsorption.

The chemical properties of a ferroelectric surface are polarization dependent, the underlying nature of which is, however, far from being completely understood. One of the reasons is that when the polarization direction is perpendicular to the surface, the depolarization field may induce electronic or atomic reconstruction and thus change the chemistry of the ferroelectric surface in complicated ways. Instead, the in-plane polarization results in no depolarization field. Therefore, the chemical properties of a ferroelectric surface can be more intrinsically reflected by the interplay between the in-plane polarization and the surface adsorption. By using first-principles calculations, we study the effect of the strain-induced in-plane polarization on the adsorption of a series of molecules on the reduced rutile TiO2(110) surface. We reveal that it is the surface doping caused by the charge transfer between the adsorbates and the TiO2(110) surface that dominates the polarization-induced change of the adsorption energy, as a result of screening long-range Coulomb interactions. The electrostatic interaction between the polarization of the substrate and the polar molecule is of relatively less importance. We propose that charge transfer effects generally occur for ferroelectric surfaces with no localized surface states.

Formation Mechanism of Spherical TiC in Ni-Ti-C System during Combustion Synthesis.

The formation mechanism of TiC particles in a Ni-Ti-C system were revealed by using differential thermal analysis (DTA), XRD, and SEM to identify the reaction products in different temperature ranges. The results indicated that the synthesis mechanism of TiC in Ni-Ti-C system was complex; several reactions were involved in the combustion synthesis of TiC-Ni composite. The Ni-Ti intermediate phases play important roles during the formation of TiC. Moreover, the influence of heating rate on the size range of TiC was also discussed.

Effect of Mg on the Microstructure and Corrosion Resistance of the Continuously Hot-Dip Galvanizing Zn-Mg Coating.

The microstructure of continuously hot-dip galvanizing Zn-Mg coating was investigated in order to obtain the mechanism of the effects of Mg on the corrosion resistance. In this paper, the vertical section of the Zn-0.20 wt % Al-Mg ternary phase diagram near the Al-low corner was calculated. The results indicates that the phase composition of the Zn-0.20 wt % Al-Mg ternary phase diagram near the Al-low corner is the same as Zn-Mg binary phase diagram, suggesting Al in the Zn-Mg (ZM) coatings mainly concentrates on the interfacial layer between the coating and steel substrate. The microstructure of continuously hot-dip galvanizing ZM coatings with 0.20 wt % Al containing 1.0-3.0 wt % Mg was investigated using tunneling electron microscopy (TEM). The morphology of Zn in the coating changes from bulk to strip and finally to mesh-like, and the MgZn2 changes from rod-like to mesh-like with the Mg content increasing. Al in the ZM coatings mainly segregates at the Fe2Al5 inhibition layer and the Mg added to the Zn bath makes this inhibition layer thinner and uneven. Compared to GI coating, the time of the first red rust appears increases by more than two-fold and expansion rate of red rust reduces by more than four-fold in terms of salt spray experiment. The ZM coating containing 2.0 wt % Mg has the best corrosion resistance. The enhanced corrosion resistance of ZM coatings mainly depends on different corrosion products.

Hydrophilic Quaternary Ammonium-Group-Containing [FeFe]-Hydrogenase Models: Synthesis, Structures, and Electrocatalytic Hydrogen Production.

The first quaternary ammonium-group-containing [FeFe]-hydrogenase models [(µ-PDT)Fe2 (CO)4 {κ2 -(Ph2 P)2 N(CH2 )2 NMe2 BzBr}] (2; PDT=propanedithiolate) and [(µ-PDT)Fe2 (CO)4 {µ-(Ph2 P)2 N(CH2 )2 NMe2 BzBr}] (4) have been prepared by the quaternization of their precursors [(µ-PDT)Fe2 (CO)4 {κ2 -(Ph2 P)2 N(CH2 )2 NMe2 }] (1) and [(µ-PDT)Fe2 (CO)4 {µ-(Ph2 P)2 N(CH2 )2 NMe2 }] (3) with benzyl bromide in high yields. Although new complexes 1-4 have been fully characterized by spectroscopic and X-ray crystallographic studies, the chelated complexes 1 and 2 converted into their bridged isomers 3 and 4 at higher temperatures, thus demonstrating that these bridged isomers are thermodynamically favorable. An electrochemical study on hydrophilic models 2 and 4 in MeCN and MeCN/H2 O as solvents indicates that the reduction potentials are shifted to less-negative potentials as the water content increases. This outcome implies that both 2 and 4 are more easily reduced in the mixed MeCN/H2 O solvent than in MeCN. In addition, hydrophilic models 2 and 4 act as electrocatalysts and achieve higher icat /ip values and turnover numbers (TONs) in MeCN/H2 O as a solvent than in MeCN for the production of hydrogen from the weak acid HOAc.

Influence of strain on water adsorption and dissociation on rutile TiO2(110) surface.

The influence of externally applied strain on water adsorption and dissociation on a defect-free rutile TiO2(110) surface is studied by using first-principles calculations. We found that while compressive strain makes water adsorption and dissociation less favorable, tensile strain increases the energy gain of water adsorption, and decreases the energy cost of water dissociation. Specifically, dissociative water becomes more stable than molecular water when an 8% tensile in-plane strain is applied. Moreover, the dissociation barrier decreases with increasing strain more rapidly for more isolated water. The rate of decrease of this barrier for nearly isolated water is 0.017 eV per 1% biaxial strain. This demonstrates that applying strain is a possible way to engineer the surface adsorption and dissociation of water on a TiO2(110) surface, and therefore engineer the relevant surface reactivity.

Active sites and mechanisms for oxygen reduction reaction on nitrogen-doped carbon alloy catalysts: Stone-Wales defect and curvature effect.

Carbon alloy catalysts (CACs) are promising oxygen reduction reaction (ORR) catalysts to substitute platinum. However, despite extensive studies on CACs, the reaction sites and mechanisms for ORR are still in controversy. Herein, we present rather general consideration on possible ORR mechanisms for various structures in nitrogen doped CACs based on the first-principles calculations. Our study indicates that only a particular structure of a nitrogen pair doped Stone-Wales defect provides a good active site. The ORR activity of this structure can be tuned by the curvature around the active site, which makes its limiting potential approaching the maximum limiting potential (0.80 V) in the volcano plot for the ORR activity of CACs. The calculated results can be compared with the recent experimental ones of the half-wave potential for CAC systems that range from 0.60 to 0.80 V in the reversible-hydrogen-electrode (RHE) scale.

One-stage operation for rare multiple mirror intracranial aneurysms: a case report and literature review.

Although intracranial multiple aneurysms are not uncommon, multiple mirror aneurysms are relatively rare. A few isolated cases have been described. However, to the best of our knowledge, 3 pairs of pure symmetrical mirror aneurysms in one patient have not been reported yet. We present a case of multiple mirror aneurysms involving the bilateral middle cerebral artery (MCA) bifurcations and posterior communicating arteries (P-com A) confirmation by one-stage operation. The possibility of one-stage treatment must be considered before surgery. Missed diagnosis and misdiagnosis must be avoided before one-stage operation for multiple mirror aneurysms.

Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft.

BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.