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In recent years, nanoscale thermal cloaks have attracted the interest of researchers. Several different types of nanoscale thermal cloak have been developed with their performance been experimental...

A simple powder forging process was presented herein to fabricate an Fe-14Cr-4.5Al-2W-0.4Ti-0.5Y2O3 ODS FeCrAl alloy. The forged alloy exhibits a high density that exceeds 97 % of the theoretical density. The ODS alloy was investigated in terms of the residual porosity, morphology and phase structure of oxide nanoparticles, impact toughness and tensile properties. It was found that refined grains were obtained during powder forging. A residual porosity less than 1.1 % has no impact on the precipitation of oxide nanoparticles. The average diameter of the oxide particles is 7.99 nm, with a number density of 2.75 × 1022 m−3. Almost all of the oxides are identified as orthorhombic YAlO3 particles. The refined grains and uniformly distributed oxide nanoparticles enable the alloy to show excellent mechanical strength and ductility below 700 °C, and enable the ductile-to-brittle transition temperature to be close to room temperature. However, a slight decrease in strength at 1000 °C and the Charpy upper shelf energy has been suggested to be due to the residual porosity. These results indicate that powder forging can be used as a promising technique for the fabrication of ODS alloys.

This study presents the fabrication of 14Cr Fe–Cr–Al oxide dispersion strengthened (ODS) alloy by a direct oxidation process. In order to explain how oxide nanoparticles are formed in the consolidation process, the powders after oxidation are subjected to vacuum thermal treatment at high temperatures. Differential scanning calorimeter, X-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron microscopy techniques are used to detect the generation, evolution of oxides on both the surface and interior of the powder, as well as the type of oxide nanoparticles in the fabricated ODS alloy. It is found that an iron oxide layer is formed on the surface of the powder during low temperature oxidation. And the iron oxide layer would be decomposed after thermal treatment at high temperature. In the consolidation process, the oxygen required by the reaction of alumina and yttrium oxide to produce nanoscale Y–Al–O particles mainly derives from the decomposition of iron oxide layer at elevated temperature and the inward diffusion of oxygen. Using the direct oxidation process, YAlO3 nanoparticles are dispersed in the grains and at the grain boundaries of Fe–Cr–Al ODS alloy.

We synthesized a mesoporous film based on TiO2–reduced graphene oxide (RGO) hybrids using a one-step vapor-thermal method without the need for an additional annealing process. The vapor-thermally prepared TiO2-graphene hybrid (VTH) features unique structures with an ultra-large specific surface area of ˜260 m2 g−1 and low aggregation, giving rise to enhanced light harvesting and increased charge generation and separation efficiency. It was observed that a mesoporous film with uniform pore distribution is simultaneously obtained during the VTH growth process. When a 5.0 wt% RGO VTH film was used as the active layer in photocatalysis, the highest photocatalytic activity for degradation of methyl orange was achieved. For another, when a 0.75 wt% RGO VTH film was used as the photoanode in a dye-sensitized solar cell, the power conversion efficiency reached 7.58%, which represents an increase of 73.1% compared to a solar cell using an a photoanode of pure TiO2 synthesized by a traditional solvothermal method. It is expected that this facile method for the synthesis of TiO2/graphene hybrid mesoporous films will be useful in practical applications for preparing other metal oxide/graphene hybrids with ultra-high photocatalytic activity and photovoltaic performance.

Heavy forgings are the core components of major equipment and even play an indispensable role in national security and the national economy. Traditionally, heavy forgings are usually manufactured with ingots of more than 100 tons. However, there are serious macroscopic segregation, shrinkage porosity and other defects in heavy forgings due to size effect of metal solidification process, which seriously affect the quality of heavy forgings and have become a worldwide problem. Avoiding the traditional concept in which a heavy forging must be created using a large steel ingot, Institute of Metal Research, Chinese Academy of Sciences first put forward a novel technology to manufacture heavy high-quality forgings by additive forging (AF). Small-sized slabs with excellent quality are used as the base elements. After surface cleaning, stacking, assembling, vacuum packaging, and deformation process characterized by pressure-forging and multi-directional forging at high temperature, the homogenized heavy forgings can be obtained with completely healed interface, which realizes the new manufacturing technology of “by making greatly small”. Through in-depth research on the microstructural evolution and bonding mechanism of the interface, we found the self-decomposition phenomenon of interface oxides. With the decomposed oxygen ions diffusing toward the matrix, oxide particles precipitated around both sides of the interface, forming the particle precipitation zone (PPZ). As the holding time increased, the width of the PPZ increased and the oxide precipitates in the PPZ transformed from MnCr x Al2– x O4 to Mn x Al3– x O4 and finally to γ-Al2O3, depending on the local oxygen activity. After holding for 24 h, the interfacial oxides completely decomposed and only a few nano-scale γ-Al2O3 oxide precipitates remained dispersed far away from the bonding interface, leading to the recovery of the mechanical properties of the bonding joints. This recovery mechanism should be of great importance to the engineering application of Additive Forging. Besides, we illustrated the dynamic recrystallization (DRX) mechnism of the bonding interface. The bonding of joints is related with interfacial grain boundary (IGB) bulging process, which is considered as a nucleation process of DRXed grain under different deformation environments. During recrystallization process, the bonded interface moved due to strain-induced boundary migration (SIBM) process. Stored energy difference (caused by accumulation of dislocations or difference of subgrain size at the bonding interface) was the dominant factor for SIBM during DRX. This technology has been applied to hydroelectric alloy steel spindles (110 tons in weight) and nuclear power stainless steel giant rings (15.6 m in diameter), which plays an important role in promoting the rapid development of high-end equipment in China and ensuring the independence and control of core materials for major equipment.

Conformal structured TiO2-reduced graphene oxide composite nanosheets (TiO2@rGO CNS) have been synthesized by a one-step hydrothermal method. The prepared TiO2 composite features a two-dimensional (2D) structure with an ultra-large specific surface area of 269 m2 g–1 and homogeneous TiO2 nanoparticles directly grown on the surface of reduced graphene oxide (rGO) sheets. With this special architecture of 2D sheet, it gives rise to improve light-harvesting and photo-to-electron conversion efficiency. When the TiO2@rGO CNS incorporated into the photoanode, it exhibits a greatly enhanced absorption in the visible range and low charge transfer resistance of 10.16 Ω compared with that of bare TiO2-based electrode (15.22 Ω). When the rGO content in TiO2@rGO CNS is 0.8 wt%, the fabricated solar cell obtains a remarkably enhanced power conversion efficiency (up to 7.05%), compared with that of the bare TiO2-based solar cell (4.36%), where the short-circuit current density, open-circuit voltage, and fill factor of the device are 13.63 mA cm– 2, 0.712 V, and 0.69, respectively. With the above-mentioned merits, this work supplies a feasible approach for the functionalization of 2D materials decorated with controlled metal oxide nanoparticles, which is expected as a promising material in high-performance photovoltaic devices for practical applications.

The title compound, a major animal feed supplement, abbreviated as HMTBA and alternatively called DL-methionine hydroxy analogue, C5H10O3S, (I), was isolated in pure anhydrous monomeric form. The melting point is 302.5 K and the compound crystallizes in the monoclinic space group P21/c, with two conformationally non-equivalent molecules [(I A ) and (I B )] in the asymmetric unit. The crystal structure is formed by alternating polar and non-polar layers running along the bc plane and features an extensive hydrogen-bonding network within the polar layers. The Hirshfeld surface analysis revealed a significant contribution of non-polar H...H and H...S interactions to the packing forces for both molecules.

Lithium-sulfur (Li-S) batteries are highly attractive for their theoretical energy density and natural abundance, but the drawbacks of low sulfur utilization and rapid capacity fade in high-sulfur-loading cathodes still retard their practical use. To enhance kinetics in high-sulfur-loading Li-S cells, it is important to first understand and control the deposition of Li2S/Li2S from highly soluble lithium polysulfide (LiPS) during discharge processes. Here, we presented a series of multiphase-derived self-standing papers with diverse electronic conductivity and LiPS affinity for highly concentrated LiPS discharge processes and explained the Li2S/Li2S deposition behavior in detail. We demonstrated that high rate capacity and long cycle life of as-assembled paper-LiPS cathodes can be greatly depended on their phase material with high conductivity and LiPS affinity. A high-performance self-standing LiPS host-multiwalled carbon nanotube (MWCNT)/cellulose nanofiber (CNF)/NiCo2S4 (3.5 mg cm-2) can catalyze 2.85 mg cm-2 (based on sulfur) loaded LiPS to deliver a high specific capacity of 1154 mAh g-1 at 0.1C and a high rate performance of 963 mAh g-1 at 1C. We suggest that the insulating phase defect of nano-CNF and both highly electronic conductive (above 50 S cm-1) and LiPS adsorptive NiCo2S4 can promote the local concentration effect of LiPS, thus contributing to fast and stable heterogeneous particle-shaped deposition of Li2S2/Li2S and leading to high kinetics of the LiPS cathode.

Although numerous denitrifying bacteria have been isolated and characterized, their capacity is seriously compromised by traditional inoculant addition and environmental stress in open bioreactors for wastewater treatment. In this study, a biocompatible material, chitosan, was used as a carrier to immobilize a simultaneously heterotrophic nitrifying–aerobic denitrifying bacterium Klebsiella sp., KSND, for continuous nitrogen removal from domestic wastewater in an open purification tank. The results showed that immobilization had no significant effect on cell viability and was beneficial for the reproduction and adhesion of cells. The entrapped KSND exhibited a slightly higher nitrogen removal efficiency of 90.09% than that of free KSND (87.69%). Subsequently, repeated batch cultivation experiments and analysis of the effects of organic contaminants and metal ions were performed using artificial wastewater and domestic wastewater. The findings revealed that the immobilized KSND beads presented desirable biophysical properties with good mechanical stability, cell viability, and enrichment, remarkable stability in organic contaminants and metal ions, and high efficiency nitrogen removal capacity. In conclusion, the developed immobilized denitrifying bacteria system has great potential for continuous wastewater treatment in open bioreactors.

High-carbon chromium bearing steels with different rare earth (RE) contents were prepared to investigate the effects of RE on inclusions and impact toughness by different techniques. The results showed that RE addition could modify irregular Al2O3 and MnS into regular RE inclusions. With the increase of RE content, the reaction sequence of RE and potential inclusion forming elements should be O, S, As, P and C successively. RE inclusions containing C might precipitate in molten steel and solid state, but the precipitation temperature was significantly higher than that of carbides in high-carbon chromium bearing steel. For experimental bearing steels, the volume fraction of inclusions increased steadily with the increase of RE content, but smaller and more dispersed inclusions could be obtained by 0.018% RE content compared with bearing steel without RE, whereas the continuous increase of RE content led to an increasing trend for inclusion size and a gradual deterioration for inclusion distribution. RE addition could improve the transverse impact toughness and isotropy of bearing steel, and for modified high-carbon chromium bearing steel by RE alloying, the increase of RE content continuously increased both transverse and longitudinal impact toughness until excessive RE addition.

Two-dimensional layered molybdenum disulfide (MoS2) exhibits great potential for applications in optoelectronic devices, especially photodetectors. However, most of the reported MoS2-based photodetectors only show limited absorption in visible range, resulting in narrow spectral response with poor sensitivity. Integrating plasmonic nanoparticles with MoS2 provides a promising approach to enhance light-matter interactions and detector responsibility. We here report a plasmon-enhanced photodetector based on Au/MoS2 heterostructure with Au nanoparticles (NPs) deposited on the surface of few-layer MoS2 by magnetron sputtering. By coupling with Au NPs, the interactions between ultra-thin MoS2 and incident lights are greatly enhanced via localized surface plasmon resonance. With this new architecture, the spectral response of few-layer MoS2 based photodetector is extended to near-infrared region (700–1600 nm). Further, measurements show that significant improvement of photocurrent is observed with the highest value reaching up to 64 mAW−1 at incident wavelength of 980 nm. With the demonstrated superb performance the proposed detector represents a viable path towards implementing ultra-sensitive near-infrared detection.

To understand the effects of nitrogen on precipitation and tensile behaviors at elevated temperatures, 25Cr 20Ni austenitic stainless steels with different nitrogen contents (0.065 wt %, 0.13 wt % and 0.17 wt %) were tensioned from room temperature to 1000 °C. Results show that the elongation and area reduction change differently with temperature increasing from 800 °C to 1000 °C, which are caused by different fracture modes. The necking concentrates in a small zone in the tensile samples of 0.17 wt % N steel, while the necking deformation occurs in all gauge length in specimens of other two steels. The local necking in 0.17 wt % N steel is induced by the enhanced recrystallization softening effect during tensile deformation. As the dislocation recovery are retarded by more solute nitrogen atoms and nitrides in 0.17 wt % N steel, the dislocation density difference between deformed grains and recrystallized grains turns larger, which results in a higher recrystallization rate and enhanced softening effect in further deformation. Additionally, the content of M23C6 precipitates unexpectedly increases with the increasing nitrogen after tensile test at 800 °C. This is because the increasing nitrogen promotes the formation of NbCrN in higher nitrogen steels during solution heat treatment, instead of Nb(C, N) in lower nitrogen steels. The precipitation of NbCrN releases carbon into austenitic matrix, leading to the acceleration of M23C6 precipitation during tensile test at 800 °C.

The oxidation behaviour of austenite stainless steel in vacuum and the evolution of oxide scales during vacuum hot-compression bonding were investigated combining XPS and TEM. The results indicate that thick duplex oxide scale with outer MnFe2O4 and inner FeCr2O4 layer was formed in a low vacuum and the complex oxide scale transformed into interfacial oxides MnCr2O4 remaining at the bonding interface after hot-compression bonding at 1200 °C. While in a high vacuum, nanoscale-thick oxide scale with outer Fe3O4 and inner Fe- and Cr-rich layer was observed and it decomposed during the subsequent hot-compression bonding procedure, leading to a well-bonded interface.

The mechanical properties of solid state bonding joints have always been greatly deteriorated due to surface oxide scales. Here, we report a method to completely heal solid state bonding joints with recovered mechanical properties by hot compression bonding and post-holding treatment. Using scanning electron microscopy and transmission electron microscopy, we discovered that the recovery of mechanical properties of the bonding joint is attributed to the dissolution and evolution of the interfacial oxides. While holding the joint at 1200 °C, the interfacial oxides (MnCr2O4) gradually decomposed. With the decomposed oxygen ions diffusing toward the matrix, oxide particles precipitated around both sides of the interface, forming the particle precipitation zone (PPZ). As the holding time increased, the width of the PPZ increased and the oxide precipitates in the PPZ transformed from MnCrxAl2−xO4 to MnxAl3−xO4 and finally to γ-Al2O3, depending on the local oxygen activity. After holding for 24 h, the interfacial oxides completely decomposed and only a few nano-scale γ-Al2O3 oxide precipitates remained dispersed far away from the bonding interface, leading to the recovery of the mechanical properties of the bonding joints. This recovery mechanism may be of great importance to the design and manufacture of high-quality heavy bonding joints. Keywords: Hot compression bonding, Interfacial oxides, Mechanical properties, TEM, Interface healing

This study aims to clarify the effects of aluminum and sulfur content on fatigue property together with corresponding crack initiation and propagation behavior of bearing steel in the very high cycle fatigue (VHCF) regime. For these purposes, ultrasonic tensile-compression fatigue tests were carried out on fatigue specimens with different directions extracted from bearing steel bars containing different aluminum and sulfur content. As a result, high aluminum content in bearing steel leads to worse fatigue property by forming a large collection area of Al2O3 particles. MnS inclusions can cause fatigue failure of low sulfur bearing steel at the 45-degree angle and contribute to fatigue anisotropy. However, there are no MnS inclusions to be found at crack initiation region of failed specimens with ultralow sulfur content. For the VHCF fracture of bearing steel, fracture surface can be simply divided into four different areas according to crack propagation path except fatigue source. The stress intensity factor at the periphery of fine granular area (FGA) ΔKFGA can be regarded as the critical driving force for crack propagating through martensite laths. In addition, crack initiation and propagation are the result of mutual coordination and matching of the driving force ΔK, crack propagation speed and microstructure. Dislocations and precipitated carbides play an important role in the formation of FGA by helping form the corresponding nanoscale grain boundary.

The biological denitrification for wastewater treatment in winter is often seriously compromised due to the effects of low-temperature (Moraxella osloensis LT-01 was isolated by iterative domestication. The strain LT-01 retained about 60% maximal growth activity at 10 °C. Under initial concentrations of 100 mg/L, average ammonium, nitrate and nitrite removal efficiencies for domestic wastewater (C/N 4:1) at 10 °C were 70.35%, 65.39% and 61.74% in 24 h, respectively. Nitrogen balance analysis showed that about 46% of TN was directed toward in the dissimilation form of gas, and 16% of TN was assimilated for cell growth. Key genes hydroxylamine reductase gene (HAO) and nitrite reductase (NirS) involved in nitrification and denitrification processes were identified by gene-specific PCR, indicating that strain LT-01 perform nitrogen removal efficiently via unique simultaneous nitrification and denitrification. These results suggest the bacterium LT-01 has great potential as an effective performer for treating domestic wastewater in winter.

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.

In recent years, there is a strong interest in thermal cloaking at the nanoscale, which has been achieved by using graphene and crystalline silicon films to build the nanoscale thermal cloak according to the classical macroscopic thermal cloak model. Silicon carbide, as a representative of the third-generation semiconductor material, has splendid properties, such as the high thermal conductivity and the high wear resistance. Therefore, in the present study, we build a nanoscale thermal cloak based on silicon carbide. The cloaking performance and the perturbation of the functional area to the external temperature filed are analyzed by the ratio of thermal cloaking and the response temperature, respectively. It is demonstrated that silicon carbide can also be used to build the nanoscale thermal cloak. Besides, we explore the influence of inner and outer radius on cloaking performance. Finally, the potential mechanism of the designed nanoscale thermal cloak is investigated by calculating and analyzing the phonon density of states (PDOS) and mode participation rate (MPR) within the structure. We find that the main reason for the decrease in the thermal conductivity of the functional area is phonon localization. This study extends the preparation method of nanoscale thermal cloaks and can provide a reference for the development of other nanoscale devices.

Background Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL. Methods Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and primary hepatocytes. Results Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in hepatocytes of NAFL mice. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides in hepatocytes of NAFL mice, leading to aggressive hepatic I/R injury with upregulation of oxidative stress and increase of reactive oxygen species (ROS). In contrast, administration of exogenous S1P protected hepatocytes of NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of S1P generation by I/R in liver specimens of NAFL patients. In vitro studies on the L02 human hepatocytes consolidated that inhibiting the generation of S1P by knocking down SPHK1 exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL. Conclusions Generation of S1P by SPHK1 is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

Overload of palmitic acids is linked to the dysregulation of ceramide metabolism in nonalcoholic steatohepatitis (NASH), and ceramides are important bioactive lipids mediating the lipotoxicity of palmitic acid in NASH. However, much remains unclear about the role of ceramidases that catalyze the hydrolysis of ceramides in NASH. By analyzing the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, we found that alkaline ceramidase 3 (ACER3) is upregulated in livers of patients with NASH. Consistently, we found that Acer3 mRNA levels and its enzymatic activity were also upregulated in mouse livers with NASH induced by a palmitate-enriched Western diet (PEWD). Moreover, we demonstrated that palmitate treatment also elevated Acer3 mRNA levels and its enzymatic activity in mouse primary hepatocytes. In order to investigate the function of Acer3 in NASH, Acer3 null mice and their wild-type littermates were fed a PEWD to induce NASH. Knocking out Acer3 was found to augment PEWD-induced elevation of C18:1-ceramide and alleviate early inflammation and fibrosis but not steatosis in mouse livers with NASH. In addition, Acer3 deficiency attenuated hepatocyte apoptosis in livers with NASH. These protective effects of Acer3 deficiency were found to be associated with suppression of hepatocellular oxidative stress in NASH liver. In vitro studies further revealed that loss of ACER3/Acer3 increased C18:1-ceramide and inhibited apoptosis and oxidative stress in mouse primary hepatocytes and immortalized human hepatocytes induced by palmitic-acid treatment. These results suggest that ACER3 plays an important pathological role in NASH by mediating palmitic-acid-induced oxidative stress.

The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her‐2/phosphoinositide 3‐kinases (PI3K)/PKB protein kinase (AKT)‐regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER‐2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab‐treated patients. MLH1 loss decreases CTX sensitivity through Her‐2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while MLH1 overexpression increases CTX sensitivity. Blocking Her‐2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her‐2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer., Mismatch repair (MMR) genes deficiency can drive genomic instability and therapeutic resistance in colorectal cancer (CRC). Nevertheless, many of the mechanisms of MMR affecting drug resistance in CRC are still enigmatic. It is revealed that mutL homolog 1 deficiency decreases cetuximab sensitivity through Her‐2/phosphoinositide 3‐kinases/PKB protein kinase signaling, which provides a mechanism of overcoming cetuximab resistance potentially by HER‐2/epidermal growth factor receptor dual inhibition.

Background: Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL. Methods: Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and human cultured hepatocytes. Findings: Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in mouse NAFL. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides, leading to aggressive hepatic I/R injury with increased oxidative stress in NAFL mice. In contrast, administration of exogenous S1P protected NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of SPHK1/S1P pathway by I/R in liver specimens of NAFL patients. In vitro studies on cultured human hepatocytes consolidated that inhibiting the SPHK1/S1P pathway exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL. Interpretations: Activation of SPHK1/S1P pathway is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL. Funding Statement: This work was supported by Dean Foundation of Nanfang Hospital, Southern Medical University (2018C029) to JPQ, Guangdong Province Science and Technology Program (2014A020212174) to CJL, Guangdong Province Science and Technology Program (2017A030313684) to JZ, National Natural Science Foundation of China (81803063) to YYL, National Natural Science Foundation of China (81600462) and the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University (2016006) to KW. Declaration of Interests: The authors declare no competing of interest. Ethics Approval Statement: All experiments using human samples were carried out following the protocols approved by the Medical Ethics Committee of Nanfang Hospital Southern Medical University (NFEC-2019-029).

Background and aims Recent clinical evidences show that patients with atherosclerotic cardiovascular disease can benefit from a targeting IL-1β treatment. Caspase-1 is an important factor for pyroptosis and is responsible for mature and release of interleukin (IL)-1β. Here we investigated the effect of caspase-1 inhibitor VX-765 on atherosclerosis and vascular smooth muscle cells (VSMCs) pyroptosis. Methods Human carotid artery plaques and aortas from ApoE−/− mice which were gavaged with VX-765 or vehicle while fed with western diet were examined for plaque burden using Oil Red O staining and Immunohistochemistry staining. Dedifferentiated primary cultured mice VSMCs treated with oxidized low-density lipoprotein (OxLDL) were applied to examine cell pyroptosis. Results The distribution of a-SMA and active pyroptotic indicators had a lot of overlaps near the necrotic core, at the lesion surface and in the intra-plaque hemorrhage area in human or mice plaque. In vitro studies further demonstrated that OxLDL induced VSMCs pyroptosis through activating NLRP3 inflammasome. What's more, VX-765 significantly inhibited the progression of established atheroma and the development of atherosclerosis, without substantially influence lipoprotein level in plasma. VX-765 also significantly reduced VSMCs pyroptosis and IL-1β processing induced by OxLDL. Conclusions VX-765 inhibits VSMCs pyroptosis during atherogenesis and targeting caspase-1 activity may be a potential treatment strategy for atherosclerotic diseases.

In order to elucidate the role of various M -alloying additions in the fcc-type γ phase of nickel-based superalloys, we have performed a comprehensive and systematical computation on all 3 d -, 4 d - and 5 d - M alloying additions substituting in the Ni lattice using the same standard of the first-principles calculations within the framework of the density functional theory. The results show that the substitution enthalpies of Sc, Ti, V, Mn, Fe, Co, Zn, Zr, Nb, Hf, Ta, and Pt are negative, while the others elements have positive substitution enthalpies. To further explore the contributions of various factors to the substitution enthalpy, we have attempted to divide the substitution enthalpy into two parts. The first one is the mechanical deformation energy caused by the atomic volume change because of the M -alloying additions substituting in fcc Ni and the other one is the chemical and magnetic energy through electronic hybridizations and local magnetic interactions. It is found that the substitution enthalpy is a consequence of the balancing of these two contributions. Furthermore, we have attempted to correlate their mechanical deformation energies with metallic atomic radii of substitutional M -alloying addition with respect to Ni, and the chemical and magnetic energies with transferred charges between M -alloying addition and Ni, which are indeed associated with the so-called electronegativity difference.

Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study. The activation of autophagy and EMT markers of cancer cells were monitored by Western blotting and quantitative real-time PCR assay in the presence or absence of rapamycin (autophagy activator) and 3-MA (autophagy inhibitor). The expression of Beclin-1 in selected cell lines was modulated using small interfering RNA, and consequentially EMT markers, and cancer cell behaviors including migration and invasion, were also explored. Activation or inhibition of autophagy in colon cancer cells had positive or negative impacts on the expression of EMT markers and malignant behaviors such as cell migration and invasion. Knockdown of beclin-1 by siRNA apparently inhibited the activation of autophagy induced by rapamycin, consequentially resulted in suppression of EMT and attenuation of invasiveness of colon cancer cells. The results in this study demonstrated an association between activation of autophagy and EMT in colon cancer cells. The results showed suppression of Beclin-1 expression significantly reduced EMT and invasive behaviors in colon cancer cells.

The localized corrosion behaviors (intergranular corrosion, pitting, and interdendritic corrosion) of Ni-Cr-Fe-based weld metals with different niobium concentrations were investigated both in the as-welded and heat-treated conditions using the modified Huey test (ASTM A262-2010). Results indicated that Nb could reduce the intergranular corrosion susceptibility of Ni-Cr-Fe-based weld metals by preventing Cr carbides from precipitating at grain boundaries. However, the degree of pitting corrosion became more severe with the increase of Nb. The Laves phase could be corroded easily in the oxidizing environment, which increased the pitting corrosion sensitivity of weld metals. Interdendritic corrosion became the main corrosion type of weld metals that were heat treated at 620°C for 29 h. The depletions of elements Cr and Ni occurred in the interdendritic region, which resulted in the interdendritic corrosion of the heat-treated weld metals. With increasing Nb, the degree of Cr and Ni depletions became higher ...

Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model). Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo. Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.

The oxidation resistance of 9 wt.% Cr heat resistance steel with silicon content ranging from 0 to 1.36 wt.% in 550 °C lead-bismuth eutectic was investigated. The silicon content had little influence on the macro-structure of the oxide film. The oxide film presented a three-layers structure. The outer layer was PbO·xFe 2 O 3 and Fe 3 O 4 while the inner layer was mainly FeCr 2 O 4 . The formation of thin continuous dense Cr 2 O 3 and SiO 2 mixture layer impeded the growth of Fe-rich oxide film, which improved the oxidation resistance in high silicon content. A oxidation process model was put forward to well explain this phenomenon.

Ultrathin films of $\ensuremath{\beta}$-tungsten $(\ensuremath{\beta}\text{\ensuremath{-}}\mathrm{W})$ is attracting extensive attentions because of its promising application in spintronics due to giant spin Hall effect and its fundamental interest in superconductivity. By means of first-principles calculations, we have elucidated its nontrivial topological nature with multiple Dirac nodal lines in the $\ensuremath{\beta}\text{\ensuremath{-}}\mathrm{W}$ metal when spin-orbit coupling (SOC) is ignored. The analysis of electronic structures reveal that its topology is associated with the band inversion between the ${d}_{xz}+{d}_{yz}$ and ${d}_{{z}^{2}}$ orbitals at the $M$ point in its Brillouin zone. By switching on the SOC, these Dirac nodal lines become gapped, as accompanied with the occurrence of 24 massive Dirac fermions at the energy of 87 meV below the Fermi level. Different from the exact gapless Dirac fermions with the linear band crossings, we have identified that these massive Dirac fermions all open a tiny gap of 7 meV. In addition, we have observed the topologically protected nontrivial surface arc states connecting these massive Dirac fermions. The existence of these massive Dirac fermions in the $\ensuremath{\beta}\text{\ensuremath{-}}\mathrm{W}$ phase would be important to understand its giant spin Hall effect according to a recent study [Nature 555, 638 (2018)] where massive Dirac fermions were identified to generate Berry-curvature-induced Hall conductivity.

The reaction mechanisms of potassium glycine (KG)–CO2 absorption, thermal desorption and mineralization desorption with CaO were studied based on the contents of carbamate, bicarbonate/carbonate, and KG/protonated KG analyzed by 13C-quantitative nuclear magnetic resonance (13C qNMR). KG as the absorbent shows the CO2 absorption efficiency up to 76% which has 57% due to the bicarbonate/carbonate formation and 43% due to the carbamate formation. Mineralization has a higher CO2 desorption efficiency of 59% than that of thermal desorption (47%), and the results also indicate that carbamate is less stable under mineralization than under heat although both processes show the similar profiles as a function of pH value for carbamate and bicarbonate/carbonate. A new mechanism has been proposed to explain carbamate increasing with significantly decreasing bicarbonate/carbonate at the early stage of mineralization desorption while the other mechanisms reported in literatures have also been confirmed in this study.

In this study, paper supported flexible electrodes for supercapacitors are prepared by paper-making process with the hardwood fiber (HWF), multi-walled carbon nanotube (MWCNT) and NiCo2S4 powder. Compared with previous reported cellulose nanofiber (CNF), nickel foam and carbon cloth supported electrodes, the HWF supported paper electrodes demonstrate its advantages of low-cost, mass production, low-thickness and superior flexibility. It can achieve a high specific capacitance of 1725 F g−1 at 1 A g−1, a remarkable rate retention of 79.3 % from 1 A g−1 to 10 A g−1, an ultrahigh volumetric specific capacitance of 246.4 F cm−3 at 1 mA cm−2 and an excellent cycling stability at 20 A g−1 after 5000 cycles. The as-fabricated HWF supported flexible asymmetric supercapacitors (ASCs) have achieved excellent volumetric specific capacitance of 10.25 F cm−3 and energy density of 10.1 mWh cm−3 with power density of 93.9 mW cm−3. All results suggest that the paper-making method and the HWF supported paper electrodes provide great opportunity for developing high-performance flexible energy-storage electrodes with the feasibility of mass production.

The compatibility of T91 steels having different preparation processes with oxygen-saturated stagnant lead-bismuth eutectic have been investigated at 450 °C and 550 °C. It is found that cold rolling decreases the thickness of the oxide scale of T91 steel by forming a continuous enhanced Cr-rich belt in the inner oxide layer next to the internal oxidation zone, which is attributed to the rapid diffusion of Cr induced by numerous non-equilibrium grain boundaries and migrating dislocations.

Effects of niobium and solution treatment temperature on pitting corrosion of Super304H austenitic stainless steels were investigated by potentiodynamic and potentiostatic polarization tests and surface analysis. Results indicated that niobium in solid solution stabilised passive films against pit initiation and formed insoluble niobium-rich corrosion products partially covering pit walls inhibiting pit growth, whereas niobium as carbonitride accelerated metastable pit growth by reducing nitrogen in austenite matrix. Niobium additions more than a critical amount ennobled the pitting potential of Super304H. Moreover, increasing solution treatment temperature increased pitting potential for niobium-bearing Super304H samples but had little influence on that for niobium-free ones.

The toxicity and degradation effects of erythromycin on a phenanthrene degrading strain of Sphingomonas sp. GY2B and a pyrene degrading strain of Mycobacterium gilvum CP13 were investigated. The minimum inhibitory concentration (MIC) of erythromycin to GY2B was 0.25 mg L−1, but the MIC of erythromycin to CP13 was 16 mg L−1. Total superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) activity were significantly reduced when the erythromycin concentration exceeded the MIC. Erythromycin also reduced the growth of the strains and the biodegradation of polycyclic aromatic hydrocarbons (PAHs). Addition of erythromycin decreased GY2B phenanthrene removal efficiency by 0.81–86.03% compared to the control. Erythromycin also reduced CP13 pyrene degradation. The lowest pyrene removal efficiency was 10.78% when the erythromycin concentration was 256 mg L−1. The toxicity of erythromycin inhibited the growth of both GY2B and CP13.

The competitive growth of microstructures in the entire weld pool for both the Al–Cu alloy and the pure aluminum was simulated by the cellular automata method to comparatively investigate the micro-mechanisms for the morphological evolution of the axial structure and the curved columnar grain in the weld. The competitive mechanism of grains during the epitaxial growth and the morphological evolution of the grain structure in the weld with various welding speeds were studied. The results indicate that both the thermal conditions and the solidification characteristic of the weld metal exert an important influence on the grain competition and the resulting structure in the weld. For the Al–Cu alloy, the dendritic structure with a large S/L interface curvature appears during the epitaxial growth. The preferential orientation affects the competition result obviously. Owing to the anisotropic growth kinetics, the straight axial structure forms at low welding speeds. With the increase of the welding speed, the width of the axial region decreases and eventually disappears. For the pure aluminum, the S/L interface during the epitaxial growth is planar, and the grain competition is controlled by the thermal conditions completely. The columnar grains curve gradually to follow the highest temperature gradient direction at low welding speeds and become straight at high welding speeds.

The distribution of boron and the microstructure of grain boundary (GB) precipitates (M23(C, B)6 and M2B) have been analyzed with their effects on the susceptibility of ductility-dip-cracking (DDC) and tensile properties for NiCrFe-7 weld metal, using optical microscopy (OM), secondary ion mass spectroscopy (SIMS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results show that boron segregates at GBs in NiCrFe-7 weld metal during the welding process. The segregation of boron at GBs promotes the formation of continuous M23(C, B)6 carbide chains and M2B borides along GBs. The addition of boron aggravates GB embrittlement and causes more DDC in the weld metal, by its segregation at GBs presenting as an impurity, and promoting the formation of larger and continuous M23(C, B)6 carbides, and M2B borides along GBs. DDC in the weld metal deteriorates the ductility and tensile strength of the weld metal simultaneously.

In this study, we report a method to manufacture heavy stainless steel forgings using a newly-developed multilayer hot-compression bonding method. In particular, the interfacial healing mechanism and mechanical properties of hot-compression bonding joints under various deformation and holding conditions were systematically investigated. The results indicate that the bonding interface can be hardly healed when holding at 900 °C and 1000 °C since the interfacial oxides are difficult to decompose at the low temperatures, resulting in poor tensile properties of the bonding joints. As holding temperature increases to 1100 °C, the interfacial oxides are partially decomposed, and therefore the interface bonding effect improves with the partial restoration of tensile properties. Especially, after holding at a higher temperature, i.e., 1200 °C for 18 h, the tensile properties of the bonding joint with deformation strain of up to 35 % can be fully recovered to the level of the base material, owing to the complete decomposition of broken interfacial oxides. Based on the optimal deformation and holding conditions for interface bonding, a heavy plate with excellent mechanical properties was successfully manufactured using the multilayer hot-compression bonding method.

This study aims to clarify the effect of rare earth (RE) addition on the very high cycle fatigue (VHCF) behavior of high-carbon chromium bearing steel. For this purpose, ultrasonic tension-compression fatigue tests were carried out on specimens extracted from bearing steels with and without RE addition. As a result, RE addition can prolong the fatigue life of bearing steel over 10 times and improve the fatigue limit at 109 cycles by 9.4% from 720 MPa to 788 MPa, which mainly result from the modification of RE elements to common CaO-Al2O3-MgO-SiO2-CaS inclusions, forming complex RE inclusions and leading to the decrease of inclusion size and the volume fraction of inclusions in bearing steel with RE addition. On the VHCF fracture of bearing steels with and without RE addition, both internal cracking mode and interface cracking mode exist at inclusions. Compared with bearing steel with RE addition, bearing steel without RE addition exhibits a longer crack initiation life due to stronger internal binding force of complex inclusions and interfacial binding force between complex inclusions and the matrix. However, smaller complex RE inclusions make crack propagation life of the former significantly longer than that of the latter. In addition, fine granular area (FGA) can be used to estimate the fatigue limit of different fatigue life in the VHCF regime and the fatigue limit at 109 cycles evaluated based on FGA indicates an error of around 2% with respect to the fatigue limit measured by staircase method.

The isothermal oxidation behaviors of the Fe-25Cr-20Ni-χNb (0–1.6 wt.%) weld metals have been investigated in air at 1100 °C. Results showed that niobium has a detrimental effect on the elevated temperature oxidation resistance of the chromia-forming weld metals. In the Nb content range studied, the Nb content of 1.6 wt.% showed the most deleterious effect on the chromia layer. Niobium promoted the chromium depletion underneath the oxide/matrix interface by impeding the chromium diffusion, which ruined the compactness of the chromia layer. The oxidation of niobium at the oxide layer/metal interface can further cause severe damage to the chromia layer, resulting in catastrophic oxide spallation.

Background Autophagy is a conserved catabolic process with complicated roles in tumor development. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF-β) family of regulatory proteins, plays a crucial role in human malignancies. However, whether BMP4 contributes to the regulation of autophagy in hepatocellular carcinoma (HCC) progression remains elusive. Methods Functional analysis of BMP4 on HCC proliferation and autophagy was performed both in vitro and in vivo in HepG2 and HCCLM3 cells. Autophagic activity was estimated by Western blot for autophagic marker proteins and by transmission electron microscopy (TEM). Transfection of mRFP-GFP-LC3 adenovirus was applied to observe autophagic flux and high content screening was used for quantification. The signaling pathway of BMP4-regulated HCC proliferation and autophagy was investigated by Western blot. Results BMP4 treatment promoted HCC cells proliferation and induced autophagy. The in vivo xenograft model supported that BMP4 overexpression promoted the growth of HCC cells and autophagy induction while BMP4 knockdown exerted the opposite effect. 3-MA pre-treatment or knockdown of Beclin-1 (BECN1) blocked HCC autophagy by decreasing the expression of LC3-II and subsequently attenuated BMP4-induced autophagy and cells proliferation enhanced by BMP4 in vitro and in vivo. Mechanistic study revealed that the induction of autophagy by BMP4 was mediated through activating the JNK1/Bcl2 pathway. Furthermore, the JNK1 inhibitor and knockdown of JNK1 could attenuate autophagy induced by BMP4 and eliminated BMP4-promoted HCC cells growth. Conclusions BMP4 promoted HCC proliferation by autophagy activation through JNK1/Bcl-2 signaling. Electronic supplementary material The online version of this article (10.1186/s13046-018-0828-x) contains supplementary material, which is available to authorized users.

Lysophosphatidic acid (LPA), an extracellular signaling molecule, influences diverse biological events, including the pathophysiological process induced after ischemic brain injury. However, the molecular mechanisms mediating the pathological change after ischemic stroke remain elusive. Here we report that asparagine endopeptidase (AEP), a lysosomal cysteine proteinase, is regulated by LPA during stroke. AEP proteolytically cleaves tau and generates tauN368 fragments, triggering neuronal death. Inhibiting the generation of LPA reduces the expression of AEP and tauN368, and alleviates neuronal cell death. Together, this evidence indicates that the LPA-AEP pathway plays a key role in the pathophysiological process induced after ischemic stroke. Inhibition of LPA could be a useful therapeutic for treating neuronal injury after stroke.

The effect of Cr-enriched M23C6 carbides distributed at lath boundaries on the oxidation behavior of a high-silicon 12% Cr ferritic/martensitic (HSiF/M) steel has been investigated. The M23C6 carbides were oxidized during the exposure of HSiF/M in air at 823 K. The oxidation of M23C6 carbides promotes the external oxidation of Si at lath boundaries due to the third-element effect, which induces inhomogeneous distribution of elements at the microscale in the oxidation products.

A double loop electrochemical potentiokinetic reactivation (DL-EPR) test was conducted to investigate the relationship between the evolution of delta-ferrite and the intergranular corrosion (IGC) of Ti-modified Super304H, which was aged at 650 °C for 4–500 h. Scanning electron microscopy and transmission electron microscopy were adopted to analyze the evolution of delta-ferrite. The results indicated that a higher fraction of delta-ferrite with poor stability increased the IGC sensitisation of Ti-modified Super304H. Moreover, the self-healing of the sensitisation of Ti-modified Super304H occurred after 48 h due to the diffusion of chromium atoms mainly from the adjacent primary austenite rather than the delta-ferrite.

The effects of boron on the microstructure and the pitting corrosion behavior, especially the metastable pitting, were investigated in Super304H austenitic stainless steels with 0-130 ppm boron solution treated at 1100 degrees C. The microstructures were analyzed using scanning electron microscopy, transmission electron microscopy with energy dispersive spectroscopy and secondary ion Mass spectroscopy. Meanwhile, the pitting corrosion behavior was evaluated by potentiodynamic and potentiostatic polarization tests in 3.5% NaCl solution at 25 degrees C. Microstructural characterizations showed that boron addition favored the precipitation of Cr-rich boride (M2B), which resulted in an asymmetric Cr-depleted zone around M2B and reduced the chromium content in the austenite matrix. The Cr-depleted zones could act as extra sites for pit initiation, along with the interfaces between the austenite matrix and non-metallic inclusions. The potentiodynamic polarization test results indicated that boron addition decreased the pitting potential. The potentiostatic test results revealed that boron addition promoted the initiation frequency and growth rate of metastable pits, and increased the probability of stable pitting. (C) 2015 The Electrochemical Society.

Because cancer cell invasion is a critical determinant of metastasis, targeting invasion is a viable approach to prevent metastasis. Utilizing a novel three-dimensional high-throughput invasion assay, we screened a National Cancer Institute compound library and discovered compounds demonstrating inhibitory effects on cancer cell invasion. One hit, trifluoperazine, suppresses invasion of human cancer cell lines while displaying a limited cytotoxicity profile. This inhibition is due to the interference with cancer cell migratory ability but not proteolytic activity. Treatment of cancer cells with trifluoperazine significantly reduces angiogenesis and prevents cancer cell invasion through a chorioallantoic basement membrane. Mechanistically, treatment results in decreased phosphorylated AKT (Ser(473) and Thr(308)) and β-catenin (Ser(552)). Lack of phosphorylation of Ser(552) of β-catenin prevents β-catenin nuclear relocation, resulting in decreased expression of vascular endothelial growth factor, likely mediated through dopamine receptor D2. Taken together, we demonstrated that trifluoperazine is responsible for reducing the angiogenic and invasive potential of aggressive cancer cells through dopamine receptor D2 to modulate the β-catenin pathway and propose that trifluoperazine may be used as an antimetastasis chemotherapeutic.

In order to guide the design of 9–12% Cr ferritic/martensitic (F/M) heat resistant steels appropriate for use in accelerator-driven system, the impact toughness and behavior of precipitation of a 12% Cr F/M heat resistant steel containing high C and Si concentrations have been investigated. Particular focus has been given to the interaction of carbon and carbonitride-forming element. Because of the presence of primary NbC and a large amount of M 23 C 6 , the impact toughness of the investigated steel was much lower than that of the commercial 9–12% Cr F/M heat resistant steels. The primary NbC crystallizes directly from liquid metal when the Nb concentration is higher than a critical value. The critical value of Nb decreases with increase in the carbon concentration. In addition, the higher content and faster precipitation kinetics of M 23 C 6 in the investigated steel during the tempering heat treatment also lowers the impact toughness.

Through first-principles calculations, we systematically investigated the hydrogen interactions with the oxygen-vacancy (O:V) pairs complex in bcc Fe matrix (mimic oxygen-enriched nanoclusters (NCs) of ODS steels) in comparison with the vacancy-alone defects. The results uncovered that the presence of the (O:V) pairs in oxygen-enriched NCs play a crucial role in prohibiting the growth and swelling of the hydrogen cluster but strongly trap a few hydrogen atoms around each cluster of vacancies. As accompanied with a high density of dispersed NCs in ODS steels, this fact significantly elevates the tolerance of the critical hydrogen concentration of ODS steels as compared with traditional steels. The underlying mechanism to pin the growth of hydrogen cluster has been elucidated to be strongly correlated with the viable charges transfer from the nearby Fe atoms around vacancies. This is the key to determine the trapped concentration and the distribution of hydrogen atoms in ODS steels.