Investigation on Mechanism of Microstructure Evolution during Multi-Process Hot Forming of GH4169 Superalloy Forging.

Typically, in the manufacturing of GH4169 superalloy forgings, the multi-process hot forming that consists of pre-deformation, heat treatment and final deformation is required. This study focuses on the microstructural evolution throughout hot working processes. Considering that δ phase can promote nucleation and limit the growth of grains, a process route was designed, including pre-deformation, aging treatment (AT) to precipitate sufficient δ phases, high temperature holding (HTH) to uniformly heat the forging, and final deformation. The results show that the uneven strain distribution after pre-deformation has a significant impact on the subsequent refinement of the grain microstructure due to the complex coupling relationship between the evolution of the δ phase and recrystallization behavior. After the final deformation, the fine-grain microstructure with short rod-like δ phases as boundaries is easy to form in the region with a large strain of the pre-forging. However, necklace-like mixed grain microstructure is formed in the region with a small strain of the pre-forging. In addition, when the microstructure before final deformation consists of mixed grains, dynamic recrystallization (DRX) nucleation behavior preferentially depends on kernel average misorientation (KAM) values. A large KAM can promote the formation of DRX nuclei. When the KAM values are close, a smaller average grain size of mixed-grain microstructure is more conductive to promote the DRX nucleation. Finally, the interaction mechanisms between δ phase and DRX nucleation are revealed.

Effects of Aging Treatment on the Microstructures and Mechanical Properties of a TC18 Alloy.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

Modeling Dynamic Recrystallization Behavior in a Novel HIPed P/M Superalloy during High-Temperature Deformation.

The dynamic recrystallization (DRX) features and the evolution of the microstructure of a new hot isostatic pressed (HIPed) powder metallurgy (P/M) superalloy are investigated by hot-compression tests. The sensitivity of grain dimension and DRX behavior to deformation parameters is analyzed. The results reveal that the DRX features and grain-growth behavior are significantly affected by deformation conditions. The DRX process is promoted with a raised temperature/true strain or a reduced strain rate. However, the grains grow up rapidly at relatively high temperatures. At strain rates of o.1 s-1 and 1 s-1, a uniform microstructure and small grains are obtained. Due to the obvious differences in the DRX rate at various temperatures, the piecewise DRX kinetics equations are proposed to predict the DRX behavior. At the same time, a mathematical model for predicting the grain dimension and the grain growth behavior is established. To further analyze the DRX behavior and the changes in grain dimension, the hot deformation process is simulated. The developed grain-growth equation as well as the piecewise DRX kinetics equations are integrated into DEFORM software. The simulated DRX features are consistent with the test results, indicating that the proposed DRX kinetics equations and the established grain-growth model can be well used for describing the microstructure evolution. So, they are very useful for the practical hot forming of P/M superalloy parts.

Microstructure Evolution and a Unified Constitutive Model of Ti-55511 Alloy Compressed at Stepped Strain Rates.

The flow behavior and microstructure change of the Ti-55511 alloy are investigated by thermal compression experiments with stepped strain rates. The phase transformation features, the dynamic recrystallization (DRX) behavior of the ß matrix, the dynamic spheroidization mechanism of the lamellar α phase and the evolution of the ß sub-grain size are quantitatively analyzed. A unified constitutive model is constructed to characterize the hot deformation features of the Ti-55511 alloy. In the established model, the work hardening effect is taken into account by involving the coupled effects of the equiaxed and lamellar α phases, as well as ß substructures. The dynamic softening mechanisms including the dynamic recovery (DRV), DRX and dynamic spheroidization mechanisms are also considered. The material parameters are optimized by the multi-objective algorithm in the MATLAB toolbox. The consistency between the predicted and experimental data indicates that the developed unified model can accurately describe the flow features and microstructure evolution of the hot compressed Ti-55511 at stepped strain rates.

Microstructural Variation and a Physical Mechanism Model for a Ti-55511 Alloy during Double-Stage Hot Deformation with Stepped Strain Rates in the ß Region.

The microstructural variation and high-temperature flow features of a Ti-55511 alloy in the ß region are studied by utilizing double-stage compression with a stepped strain rate. The results demonstrate that the stresses in the latter stage of hot compression markedly reduce as the strain at the previous stage or the strain rate at the previous/latter stage drops. Moreover, the annihilation/interaction of substructures is promoted, and the distinct refinement of the dynamic recrystallization (DRX) in the ß grain can be found. However, the coarsening of the ß grain and the consumption of dislocation substructures are accelerated at high temperatures. Furthermore, the principal DRX nucleation mechanism of the Ti-55511 alloy during double-stage compression with a stepped strain rate in the ß region is discontinuous DRX. Additionally, by using the microstructural variation characteristics related to the forming parameters, a physical mechanism equation is modeled to forecast the forming features, the DRX fraction, and the size of the ß grain in the investigated alloy. The forecasted results are in accordance with the tested results, indicating that the established model can accurately forecast the microstructure variation and flow features of the studied alloy.

Effects of Aging Treatment on Corrosion Behavior of a Tensile Deformed Al-Cu-Mn-Fe-Zr Alloy in 3.5% NaCl Solution.

In this paper, the effects of an aging treatment on the corrosion resistance/mechanism of a tensile deformed Al-Cu-Mn-Fe-Zr alloy are investigated. The impedance magnitude and polarization resistance increase, while the corrosion current decreases with the increased aging time and temperature. The discontinuously-distributed precipitates and precipitation-free zone, which can cut the corrosion channels, appear at grain boundaries when the temperature is relatively high and the aging time is relatively long. They can improve the corrosion resistance. Additionally, the intergranular and pitting corrosion are the main mechanisms. The intergranular corrosion is likely to occur in an under-aged alloy. This is because the potential difference between the grain boundaries and grains is high, due to the segregation of Cu atoms. When the aging degree is increased, the grain boundary precipitates reduce the potential difference, and the intragranular precipitates make the surrounding matrix prone to dissolution. As such, the pitting corrosion is likely to occur in the over-aged alloys.

Evolution of Annealing Twins in a Hot Deformed Nickel-Based Superalloy.

The hot deformation characteristics of a GH4169 superalloy are investigated at the temperature and strain rate ranges of 1193-1313 K and 0.01-1 s-1, respectively, through Gleeble-3500 simulator. The hot deformed microstructures are analyzed by optical microscopy (OM), transmission electron microscopy (TEM), and electron backscattered diffraction (EBSD) technology. The effects of deformation parameters on the features of flow curves and annealing twins are discussed in detail. It is found that the shapes of flow curves are greatly affected by the deformation temperature. Broad peaks appear at low deformation temperatures or high strain rates. In addition, the evolution of annealing twins is significantly sensitive to the deformation degree, temperature, and strain rate. The fraction of annealing twins first decreases and then rises with the added deformation degree. This is because the initial annealing twin characters disappear at the relatively small strains, while the annealing twins rapidly generate with the growth of dynamic recrystallized grains during the subsequent hot deformation. The fraction of annealing twins is relatively high when the deformation temperature is high or the strain rate is low. In addition, the important role of annealing twins on dynamic recrystallization (DRX) behaviors are elucidated. The obvious bulging at initial twin boundaries, and the coherency of annealing twin boundaries with dynamic recrystallized grain boundaries, indicates that annealing twins can motivate the DRX nucleation during the hot deformation.

Xyloketal B exerts antihypertensive effect in renovascular hypertensive rats via the NO-sGC-cGMP pathway and calcium signaling.

Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. (No 2508). We previously showed that Xyl-B promoted endothelial NO release and protected against atherosclerosis through the Akt/eNOS pathway. Vascular NO production regulates vasoconstriction in central and peripheral arteries and plays an important role in blood pressure control. In this study, we examined whether Xyl-B exerted an antihypertensive effect in a hypertensive rat model, and further explored the possible mechanisms underlying its antihypertensive action. Administration of Xyl-B (20 mg·kg-1·d-1, ip, for 12 weeks) significantly decreased the systolic and diastolic blood pressure in a two-kidney, two-clip (2K2C) renovascular hypertensive rats. In endothelium-intact and endothelium-denuded thoracic aortic rings, pretreatment with Xyl-B (20 µmol/L) significantly suppressed phenylephrine (Phe)-induced contractions, suggesting that its vasorelaxant effect was attributed to both endothelial-dependent and endothelial-independent mechanisms. We used SNP, methylene blue (MB, guanylate cyclase inhibitor) and indomethacin (IMC, cyclooxygenase inhibitor) to examine which endothelial pathway was involved, and found that MB, but not IMC, reversed the inhibitory effects of Xyl-B on Phe-induced vasocontraction. Moreover, Xyl-B increased the endothelial NO bioactivity and smooth muscle cGMP level, revealing that the NO-sGC-cGMP pathway, rather than PGI2, mediated the anti-hypertensive effect of Xyl-B. We further showed that Xyl-B significantly attenuated KCl-induced Ca2+ entry in smooth muscle cells in vitro, which was supposed to be mediated by voltage-dependent Ca2+ channels (VDCCs), and reduced ryanodine-induced aortic contractions, which may be associated with store-operated Ca2+ entry (SOCE). Taken together, these findings demonstrate that Xyl-B exerts significant antihypertensive effects not only through the endothelial NO-sGC-cGMP pathway but also through smooth muscle calcium signaling, including VDCCs and SOCE.

Effect of culture conditions on metabolites produced by the crinoid-derived fungus Aspergillus ruber 1017.

Two different culture media were used to cultivate fungus Aspergillus ruber 1017 and resulted in the isolation of one new compound (1) and 23 known compounds (2-24). Alkaloids were the major metabolite in soybean medium instead of anthraquinone from rice medium. The structures of these compounds were elucidated according to spectroscopic analysis and comparison with reported data. Antibacterial activities of compounds 1-12 against 12 aquatic bacteria were evaluated.

A New Terminal Cyano Group-containing Benzodiazepine Alkaloid from the Mangrove Endophytic Fungus Penicillium sp. .

A new benzodiazepine alkaloid containing terminal cyano group has been isolated from a mangrove endophytic fungus, Penicillium 299#. Structure elucidation was determined by 1D and 2D NMR spectroscopy and the absolute configuration was determined by electronic circular dichroism (ECD). The new compound showed no cytotoxic activities in vitro against human cancer lines MDA-MB-435, HepG2, HCT-116, and Calu-3.

Xyloketal B attenuates atherosclerotic plaque formation and endothelial dysfunction in apolipoprotein e deficient mice.

Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric oxide (NO) bioavailability are critical for the development of atherosclerotic lesion. We thus examined whether xyloketal B had an influence on the atherosclerotic plaque area in apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet and investigated the underlying mechanisms. We found in our present study that the administration of xyloketal B dose-dependently decreased the atherosclerotic plaque area both in the aortic sinus and throughout the aorta in apoE-/- mice fed a high-fat diet. In addition, xyloketal B markedly reduced the levels of vascular oxidative stress, as well as improving the impaired endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic mice. Moreover, xyloketal B significantly changed the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt without altering the expression of total eNOS and Akt in cultured human umbilical vein endothelial cells (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of Thr-495. Taken together, these findings indicate that xyloketal B has dramatic anti-atherosclerotic effects in vivo, which is partly due to its antioxidant features and/or improvement of endothelial function.

Anticancer activity and mechanism investigation of beauvericin isolated from secondary metabolites of the mangrove endophytic fungi.

One known cyclic peptide, beauvericin, was isolated from the secondary metabolites of mangrove endophytic fungi Fusarium sp. (No. DZ27) in South China Sea. Its structure was determined by spectral analyses and comparisons with reference data from literatures. Beauvericin inhibited growth of KB and KBv200 cells potently with IC50 values of 5.76 ± 0.55 and 5.34 ± 0.09 µM, respectively. Furthermore, beauvericin induced apoptosis through mitochondrial pathway, including decrease of relative oxygen species generation, loss of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-9 and -3, and cleavage of PARP. Additionally, regulation of Bcl-2 or Bax was not involved in the apoptosis induced by beauvericin in KB and KBv200 cells.

Two new macrosporin dimers from the fungus Alternaria sp. XZSBG-1.

Two new macrosporin dimers (1-2) along with four known compounds (3-6) were isolated from the extracts of the fungal strain Alternaria sp. XZSBG-1 from the sediment of the salt lake in the Bange, Tibetan, China. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectra. Compounds 1 and 2 are new macrosporin dimers with symmetric chemical structures. In the cytotoxicity assay and inhibited alpha-glucosidase activity assay, all these compounds showed no notable inhibitory activity.

Loddigesiinols G-J: α-glucosidase inhibitors from Dendrobium loddigesii.

Four new polyphenols, loddigesiinols G-J (compounds 1-4) and a known compound, crepidatuol B (5), were isolated from the stems of Dendrobium loddigesii that have long been used in Traditional Chinese Medicine and have recently been used to treat type 2 diabetes. Compounds 1-5 structures were elucidated based on spectroscopic analysis. The absolute configurations of compounds 1-4 were determined using theoretical calculations of electronic circular dichroism (ECD), and the absolute configuration of compound 5 was determined by a comparison of the experimental ECD spectra and the literature data. Compounds 1-5 are strong inhibitors of α-glucosidase, with IC50 values of 16.7, 10.9, 2.7, 3.2, and 18.9 µM, respectively. Their activities were significantly stronger than trans-resveratrol as a positive control (IC50 values of 27.9 µM).

Secondary metabolites of a mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) from the South China Sea.

The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6), 3ß,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7), 3ß,5α,14α-trihydroxy-(22E,24R)-ergosta-7, 22-dien-6-one (8), NGA0187 (9) and beauvericin (10), were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE) with IC50 values 2.01, 6.71, 1.89, and 3.09 µM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC50 values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68 and 1.14 (Hela), and 1.50 and 1.10 µM (KB), respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them.

Xyloketal B exhibits its antioxidant activity through induction of HO-1 in vascular endothelial cells and zebrafish.

We previously reported that a novel marine compound, xyloketal B, has strong antioxidative actions in different models of cardiovascular diseases. Induction of heme oxygenase-1 (HO-1), an important endogenous antioxidant enzyme, has been considered as a potential therapeutic strategy for cardiovascular diseases. We here investigated whether xyloketal B exhibits its antioxidant activity through induction of HO-1. In human umbilical vein endothelial cells (HUVECs), xyloketal B significantly induced HO-1 gene expression and translocation of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) in a concentration- and time-dependent manner. The protection of xyloketal B against angiotensin II-induced apoptosis and reactive oxygen species (ROS) production could be abrogated by the HO-1 specific inhibitor, tin protoporphyrin-IX (SnPP). Consistently, the suppressive effects of xyloketal B on NADPH oxidase activity could be reversed by SnPP in zebrafish embryos. In addition, xyloketal B induced Akt and Erk1/2 phosphorylation in a concentration- and time-dependent manner. Furthermore, PI3K inhibitor LY294002 and Erk1/2 inhibitor U0126 suppressed the induction of HO-1 and translocation of Nrf-2 by xyloketal B, whereas P38 inhibitor SB203580 did not. In conclusion, xyloketal B can induce HO-1 expression via PI3K/Akt/Nrf-2 pathways, and the induction of HO-1 is mainly responsible for the antioxidant and antiapoptotic actions of xyloketal B.

Synthesis and antitumor activities of derivatives of the marine mangrove fungal metabolite deoxybostrycin.

Deoxybostrycin (1) is an anthraquinone compound derived from the marine mangrove fungus Nigrospora sp. No. 1403 and has potential to be a lead for new drugs because of its various biological properties. A series of new derivatives (2-22) of deoxybostrycin were synthesized. The in vitro cytotoxicity of all the new compounds was tested against MDA-MB-435, HepG2 and HCT-116 cancer cell lines. Most of the compounds exhibit strong cytotoxicity with IC50 values ranging from 0.62 to 10 µM. Compounds 19, 21 display comparable cytotoxicity against MDA-MB-435 to epirubicin, the positive control. The primary screening results indicate that the deoxybostrycin derivatives might be a valuable source of new potent anticancer drug candidates.

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways.

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or L-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.

Antibacterial anthraquinone derivatives from a sea anemone-derived fungus Nigrospora sp.

Chemical investigation of a marine-derived fungus Nigrospora sp., isolated from an unidentified sea anemone, yielded two new hydroanthraquinone analogues, 4a-epi-9α-methoxydihydrodeoxybostrycin (1) and 10-deoxybostrycin (2), together with seven known anthraquinone derivatives (3-9). The structures of the two new compounds were established through extensive NMR spectroscopy as well as a single-crystal X-ray diffraction analysis using Cu Kα radiation. The antibacterial activities of compounds 1-9 and 10 acetyl derivatives (6a, 7a, 8a-8g, 9a) were evaluated in vitro. Compound 6a, the acetylated derivative of 6, exhibited promising activity against Bacillus cereus with an MIC value of 48.8 nM, which was stronger than that of the positive control ciprofloxacin (MIC = 1250 nM). Analysis of the antibacterial screening data for the metabolites and their acetyl derivatives revealed the key structural features required for this activity.

Bioactive hydroanthraquinones and anthraquinone dimers from a soft coral-derived Alternaria sp. fungus.

Five new hydroanthraquinone derivatives, tetrahydroaltersolanols C-F (1-4) and dihydroaltersolanol A (5), and five new alterporriol-type anthranoid dimers, alterporriols N-R (12-16), along with seven known analogues (6-11 and 17), were isolated from the culture broth and the mycelia of Alternaria sp. ZJ-2008003, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra as well as single-crystal X-ray crystallography. Compound 13 represents the first isolated alterporriol dimer with a C-4-C-4' linkage, and the absolute configuration of 4 was determined using the modified Mosher's method. Compounds 1 and 15 exhibited antiviral activity against the porcine reproductive and respiratory syndrome virus (PRRSV), with IC50 values of 65 and 39 µM, respectively. Compound 14 showed cytotoxic activity against PC-3 and HCT-116 cell lines, with IC50 values of 6.4 and 8.6 µM, respectively.