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In this study, the thermal stability of H13 hot-work tool steel was significantly improved through the use of nitrogen as a substitute for carbon. The results indicated that the 0.3C-0.2N and 0.2C-0.3N steels exhibited better hardness stability than H13 steel (0.4C-0N). In particular, the 0.2C-0.3N steel exhibited substantially improved hardness stability. The softening resistance mechanism was revealed from the perspectives of precipitates, dislocations, laths, and variants through first-principles calculations, thermodynamic and kinetic models, and variant reconstruction. First, for precipitate stability, the results of first-principles calculations and kinetic analysis showed that substituting N with C reduced the formation energy of carbides and facilitated the formation of carbonitrides. For 0.2C-0.3N steel, which had the highest activation energy, both the diffusion of alloying elements and the coarsening of carbonitrides were significantly inhibited. Second, in terms of dislocation evolution, the most stable lattice constant, highest interstitial atom content and lowest carbide precipitation content were the keys to inhibiting dislocation recovery. Finally, the dislocation and heat-induced boundary migration stimulated the selection of variants, resulting in the coarsening and coalescence of laths. The change from V17 to V1 variant pairs was dominant for the lath coalescence of 0.2C-0.3N steel. [ABSTRACT FROM AUTHOR]

Aging is a primary risk factor for cognitive impairment and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing, insulin signaling, and histone deacetylation activity. Therefore, a pharmaceutical intervention of aging that targets distinct but overlapping pathways provides a basis for testing combinations of drugs as a cocktail. Our previous study showed that middle-aged mice treated with a cocktail of rapamycin, acarbose, and phenylbutyrate for 3 months had increased resilience to age-related cognitive decline. This finding provided the rationale to investigate the transcriptomic and molecular changes within the brains of mice that received this cocktail treatment or control treatment. Transcriptomic profiles were generated through ribonucleic acid (RNA) sequencing, and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured using immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or control. Results showed that biological processes that enhance aging were suppressed, with an increased trend of autophagy in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways. [ABSTRACT FROM AUTHOR]

By analyzing element segregation and dendritic growth kinetics in combination with microstructure observation and thermodynamic calculation, the influence mechanism of vanadium addition on the dendritic structure and precipitated phase in 30Cr15Mo1N ingots was elucidated. With vanadium addition, the carbonitride types in 30Cr15Mo1N ingots include lamellar M23(C,N)6, globular M2(C,N), and blocky M(C,N). The as-cast structure of the 30Cr15Mo1N ingot is divided into two parts: the dendritic structure, which is mainly composed of martensite and residual austenite, and the interdendritic region, which is primarily composed of precipitated phases like proeutectoid ferrite and carbonitrides. On the one hand, increasing the vanadium content can reduce the amount of martensite and residual austenite in the ingot by suppressing the growth of dendrites and reducing the size of dendrites. On the other hand, the amount of proeutectoid ferrite in the 30Cr15Mo1N ingots increased with an increase in vanadium content and distance from the center due to element segregation in the residual molten steel of the interdendritic region. Under the combined effect of element segregation in the interdendritic region and restricted dendritic growth, the size of carbonitrides showed an increasing trend with increasing the vanadium content. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), an important endocrine disrupting compound, has infiltrated human daily lives through electronic devices, food containers, and children's toys. Developing of novel BPA assay methods with high sensitivity holds tremendous importance in valuing the pollution state. Here, we constructed an ultrasensitive photoelectrochemical (PEC) aptasensor for BPA determination by regulating photoactivities of CdS/Ni-based metal–organic framework (CdS/Ni-MOF) with [Ru(bpy)2dppz]2+ sensitizer. CdS/Ni-MOF spheres exhibited excellent photocatalytic performance, serving as a potential sensing platform for the construction of target recognition process. [Ru(bpy)2dppz]2+ were embedded into DNA double-stranded structure, functioning as sensitizer for modulating the signal response of the developed PEC aptasensor. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (0.1 to 1000.0 nM), low detection limit (0.026 nM, at 3σ/m), excellent selectivity, and high stability. This work provides a perspective for the design of ideal photosensitive materials and signal amplification strategies and extends their application in environment analysis. [ABSTRACT FROM AUTHOR]

In this research paper, we investigate a generalization of Vincze's type functional equations involving several (up to four) unknown functions in connection with the maximum functional equation as max { ψ (x y) , ψ (x y - 1) } = ψ (x) η (y) + ψ (y) , max { ψ (x y) , ψ (x y - 1) } = ψ (x) η (y) + χ (y) , max { ψ (x y) , ψ (x y - 1) } = ϕ (x) η (y) , max { ψ (x y) , ψ (x y - 1) } = ϕ (x) η (y) + χ (y) , where G is an arbitrary group, x , y ∈ G , and ψ , η , χ , ϕ : G → R are unknown functions. [ABSTRACT FROM AUTHOR]

This paper presents a method based on Darcy's law to determine the pressure drop between the dendrite tip and root during the formation of porosity. After verification by the measurement result of the porosity region in 30Cr15Mo1N ingot, this method is employed to investigate the change in the pressure drop with solidification pressure, considering various factors such as the second dendrite arm spacing, solid fraction, cooling rate, temperature gradient, density, liquidus temperature, and solidus temperature. The relationship between the pressure drop and solidification pressure determines the formation of porosity. The results demonstrate that as the solidification pressure increases from 0.3 to 0.7 MPa, the pressure drop decreases from 1.572 to 0.676 MPa. When the solidification pressure is below 0.6 MPa, the pressure drop consistently exceeds the solidification pressure, leading to inadequate interdendritic feeding of the molten steel and subsequent porosity formation. Conversely, when the solidification pressure ranges between 0.6 and 0.7 MPa, the pressure drop undergoes minimal change and is approximately equal to the solidification pressure, which leads to sufficient interdendritic feeding. Consequently, increasing the solidification pressure effectively suppresses the formation of porosity by reducing the hindrance to molten steel feeding and enhancing its feeding capacity. Furthermore, a more accurate determination of the constant kC was obtained to calculate the pressure drop in 30Cr15Mo1N ingot, within the range of 2.77 to 3.11. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer is a rapidly progressive and lethal disease characterized by early visceral metastasis, poor prognosis, and limited treatment options. Uncovering the oncogenic mechanisms could lead to the discovery of potential therapeutic avenues. Here, we demonstrate that the RNA-binding protein ELAVL3 is specifically upregulated in neuroendocrine prostate cancer and that overexpression of ELAVL3 alone is sufficient to induce the neuroendocrine phenotype in prostate adenocarcinoma. Mechanistically, ELAVL3 is transcriptionally regulated by MYCN and subsequently binds to and stabilizes MYCN and RICTOR mRNA. Moreover, ELAVL3 is shown to be released in extracellular vesicles and induce neuroendocrine differentiation of adenocarcinoma cells via an intercellular mechanism. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppresses tumor growth, reduces metastatic risk, and improves survival in neuroendocrine prostate cancer mouse models. Our results identify ELAVL3 as a critical regulator of neuroendocrine differentiation in prostate cancer and propose a drug repurposing strategy for targeted therapies. Neuroendocrine prostate cancer (NEPC) is an aggressive subtype with limited effective therapeutic options. Here, the authors identify the RNA-binding protein ELAVL3 as a driver of differentiation into NEPC via a positive feedback loop with MYCN and demonstrate the use of the repurposed drug pyrvinium pamoate to target this axis using preclinical models of NEPC. [ABSTRACT FROM AUTHOR]

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The evolution of inclusions in pressurized electroslag remelting (PESR) ingots and the effects of atmosphere and Na2O in slag on inclusion characteristics were studied by experiments and thermodynamic analyses. The inclusions in the electrode were numerous MnS and complex oxides with MnS layer. The MgO·Al2O3 and Al2O3 oxides formed first in liquid steel during cooling, and subsequently MnS precipitated independently or with oxides as core in virtue of micro-segregation. The (P)ESR process exerted remarkable desulfurization and inclusion removal, while the average size of inclusions increased due to elimination of small-size MnS. During remelting, the original sulfides were dissociated as dissolved sulfur and were mostly removed, but then a few sulfides re-formed during solidification. The Al2O3 and MgO·Al2O3 were difficult to be completely dissolved, and were partially absorbed by slag. Compared with air atmosphere, the quantity of sulfur-containing inclusions in ingots remelted under pressurized nitrogen significantly increased because of the weakened gasifying desulfurization, while the effect of pressure was negligible. Na2O addition in slags reduced the sulfide inclusions in ingots by enhancing desulfurization ability. It also decreased the area ratio and size of inclusions by promoting the adsorption of original large-size inclusions. However, 8 wt pct Na2O addition caused the slight increases in oxygen content and inclusion quantity due to Na2O decomposition. [ABSTRACT FROM AUTHOR]

Purpose: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers. Methods: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety. Results: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373–0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227–0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350–0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230–0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1–2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions. Conclusion: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment. Trial registration: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939). [ABSTRACT FROM AUTHOR]

A novel high-nitrogen (N) (0.18 wt pct) M42 high-speed steel (HSS) was fabricated by pressurized metallurgy. The microstructural characteristics and mechanical properties of N-free and high-N M42 HSS austenitized at 1373 K to 1433 K and tempered at 813 K were comparatively studied, and the strengthening and toughening mechanisms were analyzed in detail. The results showed that the precipitates primarily consisted of undissolved M2C + M6C carbides and nano-sized M2C secondary carbides after tempering. High N addition or increasing austenitizing temperature decreased the fraction of undissolved precipitates, increased the content of retained austenite and the dislocation density and nano-hardness of the tempered martensite matrix, promoted the precipitation of M2C secondary carbides, while barely affecting the average martensite block width. The major strengthening mechanisms of steels were dislocation and precipitation strengthening, and the precipitate-shearing strengthening played a decisive role in precipitation strengthening. High N addition or increasing austenitizing temperature enhanced the bulk hardness and compressive strength of M42 HSS by reinforcing some strengthening factors, but decreased the impact toughness due to the decreased fracture ductility of the tempered martensite matrix. The bulk hardness and compressive strength of high-N M42 HSS were at least 1.0 HRC and 145 MPa higher than those of N-free M42 HSS at the same austenitizing temperature. Overall, high-N M42 HSS could meet higher requirements of modern industry to make cutting tools. [ABSTRACT FROM AUTHOR]

Elimination mechanism of shrinkage porosity during pressurized solidification process of 19Cr14Mn4Mo1N high-nitrogen steel ingot was systematically investigated by experimental and calculational methods. According to the formation mechanism and morphological characterization, there are three types of shrinkage porosity in the 19Cr14Mn4Mo1N ingots, namely conventional shrinkage porosity, gas-shrinkage porosity, and gas-induced shrinkage porosity. It is shown that with increasing solidification pressure from 0.3 to 0.4 MPa, the dominant type of shrinkage porosity transfers from gas-shrinkage porosity to conventional shrinkage porosity, and the size of gas-shrinkage porosity under 0.3 MPa is larger than that of under 0.4 MPa. Under 0.6 MPa, the shrinkage porosity virtually disappears completely. The results demonstrate that increasing solidification pressure can eliminate shrinkage porosity. Since there are only a few variations in the cooling rate at the center of ingots with increasing solidification pressure from 0.3 to 0.6 MPa, increasing the solidification pressure cannot eliminate shrinkage porosity defects by changing the cooling rate of 19Cr14Mn4Mo1N ingot. Therefore, increasing the solidification pressure eliminates shrinkage porosity mainly by inhibiting the nucleation and growth of nitrogen pore and promoting the feeding flow. [ABSTRACT FROM AUTHOR]

High cleanliness is an important guarantee for the long-service of bearing steel. In this study, the effect of crucible materials on cleanliness and inclusion characteristics of high-nitrogen stainless bearing steel (HNSBS) during vacuum carbon deoxidation was comprehensively investigated by microstructure characterization and thermodynamic analysis. The results showed that the ultimate O contents using MgO·Al2O3, MgO, and ZrO2 (MA, M, and Z) crucibles could be decreased from about 0.0060 to 0.0028, 0.0012, and 0.0022 wt pct, respectively. The ranking of crucible thermodynamic stability during vacuum carbon deoxidation was M < MA < Z, representing the decreasing of oxygen transfer rate due to crucible decomposition. The deoxidation rate of carbon–oxygen reaction increased with the decreasing of CO partial pressure, and the ranking of deoxidation rate using various crucibles was Z < MA < M. Meanwhile, the main oxide inclusions in steel using MA, M, and Z crucibles transformed from Al2O3 to MgO·Al2O3, MgO, and ZrO2, respectively. The area and average size of inclusions in steel using M crucible were smaller than the others owing to the decreasing of large-size Al2O3 inclusions and the increasing of percentage of low-density Mg-containing inclusions, while the existence of high-density ZrO2 inclusions in steel using Z crucible restricted the floating and removal of inclusions. Therefore, MgO crucible was more appropriate to melt high-cleanliness HNSBS with lower O content and fewer deleterious inclusions. [ABSTRACT FROM AUTHOR]

Drawing on job demands-resources theory, we propose that perceived red tape, as a hindrance job demand, triggers attitudinal and behavioral precursors of turnover in employees (turnover intentions and job search behaviors) by reducing their work engagement. In addition, we hypothesize that career adaptability, as a personal resource, buffers the detrimental effects of perceived red tape. In Study 1, three-wave data collected from employees (N = 202) working in Tanzanian public sector organizations supports the finding that work engagement mediates the effect of red tape on turnover intentions. Study 2 confirms this mediation, using data (N = 405) collected at three time points from a Chinese private organization, further verifying the mediating role of work engagement in the effect of red tape on job search behaviors. Supporting the moderating role of career adaptability, Study 2 also found that career adaptability attenuated the influence of red tape on work engagement and, subsequently, on turnover intentions and job search behaviors. Our article theoretically and empirically contributes to the understanding of how and when perceived red tape in organizations leads employees to consider leaving and prepare to leave. [ABSTRACT FROM AUTHOR]

An improved approach for constrained large-eddy simulations (CLES) of wall-bounded compressible transitional flows is proposed by introducing an intermittency factor. The improved model is tested and validated with compressible channel flows at various Mach numbers and Reynolds numbers that are transitioning from laminar to turbulent states. The improved model is compared against traditional dynamic Smagorinsky model (DSM) and Direct Numerical Simulations (DNS), where the improved model is in better agreement with DNS results than traditional DSM model, in terms of mean velocity profiles, total Reynolds stress and total heat flux. Therefore, the proposed method can be used to accurately predict the temporal laminar-turbulent transition process of compressible wall-bounded flows. [ABSTRACT FROM AUTHOR]

In this paper, the influence mechanisms of nitrogen pore formation on the evolution of precipitated phase and dendritic structure during solidification process in 30Cr15Mo1N ingot have been investigated by microstructure observation, component analysis, thermodynamic calculation, and secondary dendrite arm spacing statistics. There are ferrite phase, austenite phase, and M23(C,N)6 at the edge of nitrogen pore. In the columnar region, the M23(C,N)6 is precipitated in the position where the nitrogen bubble stops growing. In the equiaxed region, M23(C,N)6 is precipitated not only in the position where the nitrogen bubble stops growing, but also in other positions of the edge of nitrogen pore. In addition, the growth direction of columnar dendrite on both sides in front of the nitrogen pore cap is deflected. It is caused by the larger solute undercooling and the larger temperature gradient between the front and both sides of the nitrogen pore cap. The presence of nitrogen bubble reduces the heat transfer because of the larger thermal resistance of nitrogen gas. It leads to the smaller cooling rate in front of the nitrogen pore cap. As a result, the secondary dendrite arm spacing in front of the nitrogen pore cap is larger than that in front inferior of the nitrogen pore cap. [ABSTRACT FROM AUTHOR]

Hastelloy with Ni-Cr-Mo as the main component is a kind of highly corrosion-resistant alloy, and is widely used in aerospace, nuclear industry, and petrochemical. Reasonable addition of nitrogen can improve the mechanical and anti-corrosion properties of Ni-based alloys, thus accurate prediction of nitrogen solubility has important guiding significance for controlling nitrogen content. The solubility of nitrogen in molten Ni, Ni-Cr, Ni-Mo, and Ni-Cr-Mo systems was investigated by sampling method and thermodynamic analysis. The experiments were carried out at temperatures from 1823 K to 1923 K and nitrogen pressures from 0.1 to 1.6 MPa. The nitrogen solubility of molten Ni-35Cr system under high nitrogen pressure deviated significantly from Sieverts' law, and e N N = 0.8234 - 1309.64 / T was obtained to describe the deviation of nitrogen solubility from Sieverts' law. According to the studies of nitrogen solubility in molten Ni-Cr and Ni-Mo systems with chromium and molybdenum contents up to 35 wt pct, the interaction parameters were obtained as e N Cr = 0.0055 - 171.85 / T , r N Cr = - 0.00050 + 2.102 / T , e N Mo = - 0.0491 + 29.09 / T , r N Mo = 0.00130 - 2.302 / T , respectively. For molten Ni-Cr-Mo system, the second-order cross-interaction parameter was determined as r N Cr,Mo = 0.00129 - 1.609 / T . The nitrogen solubility model that could accurately predict the nitrogen solubility of molten Ni-Cr-Mo system under normal pressure and high nitrogen pressure was established. [ABSTRACT FROM AUTHOR]

Aiming at the challenge of reproducing the continuous casting (CC) steel in the laboratory, we developed a novel physical simulator to simulate the solidification process of CC slab. One characteristic physical simulation (PS) sample was obtained from the physical simulator, whose cooling intensity was controlled by cooling water to simulate the heat transfer of the CC slab. The simulation accuracy and reliability were verified by comparing the similarities of surface heat flux and solidification structure between the PS sample and the CC slab. The results demonstrate that the PS sample could accurately reproduce the heat transfer and solidification process of the CC slab. In the mold cooling stage, a similar air gap rapidly formed on both the PS sample and CC slab surface, leading to a similarly sharp reduction in the heat flux. In the stage corresponding to secondary cooling zone, the heat transfer on the PS sample surface via a thickening air gap was also basically similar to that on the CC slab surface through a vapor film, resulting in a similarly slow decrease in the heat flux. Additionally, the PS sample has similar solidification structure characteristics with the CC slab due to heat transfer similarity. Particularly, the crystal zone proportion, columnar to equiaxed transition position, and variation trends of dendrite arm spacing and Mo segregation in both were almost identical. [ABSTRACT FROM AUTHOR]

The traditional large-loop transient electromagnetic method (TEM) is strongly affected by the large terrain undulations and limited working space in mountainous areas. A multi-turn small-loop TEM is thus more convenient and flexible in these environments because of the small size of the working loop. However, notable mutual inductance occurs between the transmitting and receiving loops in the multi-turn small-loop configuration, which leads to low inversion resistivity values and an inaccurate time–depth conversion, which therefore results in inconsistencies between the inversion result and actual situation. In this paper, a method based on joint geophysical prospecting is used to constrain the multi-turn small-loop TEM data processing procedure and overcome the shortcomings of this configuration. A karst detection experiment was conducted in Zhijin County, Guizhou Province, China. Borehole data with intuitive and accurate strata information were used to determine the depth coefficient and adjust the karst burial depth. Electrical resistivity tomography (ERT), which could provide more accurate resistivity values than TEM when it has sufficient geological information to constrain the inversion process, was thus used to reduce the TEM errors and obtain a more accurate time–depth conversion and resistivity. A three-dimensional model of the karst channel was established according to the corrected resistivity and burial depth parameters, and the model reliability was verified by a separate borehole. [ABSTRACT FROM AUTHOR]

Copper oxide has attracted much attention in the field of anode materials for lithium-ion batteries because of its high capacity. However, in the long-term cyclic charge and discharge, due to the volume change, the electrode material is powdered, resulting in the rapid attenuation of capacity. In this paper, reduced graphene oxide is added to alleviate the volume problem of copper oxide charge and discharge, increase the contact area between active material and electrolyte, and finally improve the electrochemical performance of the material. Coated Copper oxide/reduced graphene oxide composites are synthesized by a one-pot method as anode materials for lithium-ion batteries. Herein, the morphology of the composite and the interface relationship in the reaction process have been systematically studied, and the relationship between the electrochemical properties of the composite and the composition ratio of the sample has been analyzed. The results indicate that the cycle capacity of the material increased first and then decreased with the increase of copper acetate content. When the content of copper acetate is 100 mg/140 ml, the cycle capacity reaches the highest and its value reaches 504 mAh g−1. This result is circulated for 100 times at 200 mA g−1 current density. [ABSTRACT FROM AUTHOR]

One important challenge in producing high-speed steels (HSSs) by conventional route is how to improve their hot workability. In this work, the effect of high-temperature annealing on the microstructure evolution and hot deformation behavior of the as-cast high-nitrogen M42 HSS was studied. The results indicated that the as-cast microstructure of high-nitrogen M42 HSS mainly consisted of the dendrite cells of matrix, interdendritic network of M2C eutectic carbides, primary M(C,N) carbonitrides, and intradendritic fine M2C secondary carbides. After high-temperature annealing, M2C eutectic carbides were transformed into M6C and M(C,N) products via a diffusion-driven reaction of M2C + matrix → M6C + M(C,N), and M6C carbides were the dominant products. Initially, M6C and M(C,N) nucleated at the M2C/matrix interface, and then grew inward from outside. With increasing annealing temperature and time, the average length–width ratio of interdendritic mixed carbides of M2C and M6C gradually decreased. The full decomposition and breaking of M2C eutectic carbides in the as-cast high-nitrogen M42 HSS could be achieved by annealing at 1100 °C for 8 hours. Meanwhile, high-temperature annealing led to the decreased amount of intradendritic M2C secondary carbides and the formation of M6C carbides within the intradendritic region. The high-temperature annealed steel exhibited higher flow stress than the as-cast steel at most deformation conditions, but lower deformation activation energy. The macroscopic morphologies showed that the hot workability of the high-temperature annealed steel was evidently better than that of the as-cast steel, which could be attributed to its better deformation compatibility and more sufficient dynamic recrystallization (DRX). Moreover, high-temperature annealing treatment led to a more uniform carbide distribution after hot compression. Therefore, high-temperature annealing treatment may provide an opportunity to further maintain or even improve the competitiveness of HSS produced by conventional route compared with those by powder metallurgy. [ABSTRACT FROM AUTHOR]

Background: Targeted delivery of chemotherapeutic drugs to tumour cells is a major challenge for cancer chemotherapy. Recent studies show that tumour cell-derived microparticles can be used as vectors to package chemotherapeutic drugs, and selectively deliver drugs to tumour cells. Nevertheless, since the particle size range of microparticles is relatively wide, the sizes may exhibit different pharmacokinetic characteristics in the body, which will have a great impact on the application of drug-loaded microparticles. Here in this report, we compare the characteristics, distribution in vivo and antitumour efficacy of small microparticles (SMPs, ≤ 200 nm) and large microparticles (LMPs, > 200 nm) which loaded with methotrexate, in order to screen out more suitable carrier sizes. Results: In vivo and in vitro studies have proved that the drug-loaded vesicles of SMPs (mainly 100–200 nm) are more reasonable, and the drug content and maintenance in tumour tissues. The time is significantly higher than that of LMPs (mainly 400–500 nm). At the same time, we found that SMPs can be better taken up and processed by DC cells to promote the proliferation of specific T cells. SMPs show obvious advantages in both drug delivery and immune activation, which is verified by the comparison of the efficacy of SMPs and LMPs in the treatment of solid tumours in mice. Conclusions: The present data demonstrate that the SMPs had a higher cumulative concentration in tumour tissue, and the tumour suppressive effect was also significantly better than that of LMPs. It provides important process parameters for the drug-loaded vesicle delivery system. Future works will aim to expand production scale and improve the separation and purification process of the microparticles. Although the research and application of drug-loaded vesicles derived from tumour cells is still in its infancy, it has broad prospects for tumour therapy. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) ferromagnets with high Curie temperature TC are desirable for spintronics applications. However, they are rarely obtained in experiments mainly due to the challenge of synthesizing high-quality 2D crystals, and their TC values are below room temperature. Using first-principles calculations, we design a family of stable 2D FenGeTe2 (4 ≤ n ≤ 7) ultrathin films with coexisting itinerant and localized magnetism. Among them, 2D Fe3GeTe2 and Fe4GeTe2 are ferromagnetic metals with TC = 138 and 68 K; 2D Fe5GeTe2, Fe6GeTe2, and Fe7GeTe2 are Néel's P-, R-, and R-type ferrimagnetic metals with TC = 320, 450, and 570 K. A thickness-induced magnetic phase transition originates from competition between itinerant and localized states, and also correlates with Fe3+ and Fe2+ content. A valence/orbital-dependent magnetic exchange model is proposed for these effects. Our results reveal a universal mechanism for magnetic coupling in complex magnetic systems. 2D magnetism offers the prospect of ordered and controllable magnetic states at reduced dimensions and there is a desire to obtain materials which can realise these properties at room temperature. Here, the authors use first-principles calculations to demonstrate that a family of 2D FenGeTe-based ultrathin films with varying Fe content can exhibit a range of magnetic properties at elevated temperatures. [ABSTRACT FROM AUTHOR]

The cleanliness and inclusion characteristics are crucial to the service life of bearing steels. In this work, the effects of addition order and contents of Mg and Ce on cleanliness and inclusion characteristics in high-nitrogen stainless bearing steels were systematically investigated by microstructure characterization and thermodynamic analysis. The results showed that the O and S contents could be decreased from about 0.0040 wt pct and 0.0028 wt pct to 0.0012 wt pct and 0.0014 wt pct, respectively. The inclusion evolution processes by Mg pretreatment and Ce addition (MgCe) were: Al2O3 → MgO and MnS → MgS + Ce–O–S, and those of Ce pretreatment and Mg addition (CeMg) were: Al2O3 → Ce–O–S and MnS → Ce–O–S + MgS, which were consistent with thermodynamic calculation. For MgCe treatment, owing to the high Ce content (0.018 wt pct), the number density (NA), total area (S) and average size (d) of inclusions were large, and those would decreased by reducing the Ce content to 0.012 wt pct. For CeMg treatment, a large number of Mg-containing inclusions (especially deleterious Mg3N2) formed because of the high Mg content (0.0066 wt pct). As the Mg content decreased to 0.0043 wt pct, the NA and S of inclusions increased instead. In this study, the optimum addition order was Mg pretreatment and Ce addition, and the optimized contents were about 0.0044 wt pct and 0.012 wt pct, respectively. [ABSTRACT FROM AUTHOR]

In this paper, the influence mechanism of pressure on nitrogen bubble formation during solidification process in 30Cr15Mo1N ingot was investigated by experimental and calculation methods. The effects of pressure on the critical nucleation radius and the growth rate of nitrogen bubbles were investigated. The growth of nitrogen bubbles was closely associated with the direction of solidification. In addition, nitrogen bubbles were generally egg-shaped and spherical in the columnar and equiaxed regions, respectively. With increasing pressure from 0.3 to 0.5 MPa, an increment existed in the critical nucleation radius and a decrement in the growth rate of nitrogen bubbles, mainly caused by the increment of the Gibbs free energy change of the system for nucleation and the internal pressure in the nitrogen bubbles, respectively. It led to decrements in number and mean area of nitrogen bubbles in 30Cr15Mo1N ingots with increasing pressure from 0.3 to 0.5 MPa. Based on the effect of pressure on formation of nitrogen bubbles, a special fitting formula was proposed to obtain the critical pressure for the 30Cr15Mo1N cylindrical ingot without nitrogen bubbles: P c = max 0.8867 [ pct\;N ] 0 + 0.098 , 0.053 e [ pct\; N ] 0 / 0.212 + 0.0415 , which is applicable under low pressure (≤ 2 MPa). [ABSTRACT FROM AUTHOR]

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase 3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase 3 activity were evaluated using commercial kits. Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment-induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer. [ABSTRACT FROM AUTHOR]

The AlN inclusion induced by high aluminum content is a serious threat for the high quality of high nitrogen stainless bearing steels produced by pressurized electroslag remelting (PESR). In this study, based on the lab-scale experiments and thermodynamic analyses, the reaction mechanism of aluminum increase during PESR was revealed, and the effects of atmosphere, slag and steel compositions on aluminum content were investigated to restrain aluminum increase. The results show that aluminum pickup was accompanied with noticeable silicon loss in steel and SiO2 increase in slag. The aluminum content in the ingots was dominated by the thermodynamic equilibrium of [Si] + (Al2O3) reaction between slag and steel. The high-temperature condition in electroslag metallurgy process promoted aluminum increase, and the reaction temperature was determined as approximately 1973 K. Due to the severer silicon loss that induced by the electrode oxidation in air, the aluminum content in ESR ingot was relatively lower than that in PESR. Increasing the SiO2 content in slags to 4.5 to 6 mass pct was an effective way to achieve low-aluminum content, but excessive SiO2 led to the high oxygen content and burning loss of alloying elements in ingots. Moreover, reducing the initial silicon content in electrodes from 0.45 to 0.18 mass pct further decreased the aluminum content in ingots. Through the process optimization, the restriction on aluminum increment in HNSBSs during PESR was well realized and the AlN inclusions almost disappeared. [ABSTRACT FROM AUTHOR]

The modification effects of surface-active element Mg on the inclusions and macro/microstructure of as-cast M42 high-speed steel were investigated by microscopy analyses, thermodynamic calculations, and first-principles DFT calculations. The results indicated that Mg treatment changed the inclusion type from MgO·Al2O3 and MnS to MgO and MgS. The contents of O and S as well as the average size and number density of inclusions gradually decreased with the increase of Mg addition amount due to the accelerated floating up of inclusions. Increasing Mg content reduced the secondary dendrite arm spacing and the average thickness of eutectic ledeburite. The refinement of as-cast microstructure by Mg treatment could be attributed to the combined effects of heterogeneous nucleation of primary austenite on MgS inclusions and the solute segregation effect of Mg. The enrichment of solute Mg in the interdendritic regions was identified by ToF-SIMS. Increasing Mg content significantly reduced the precipitation of eutectic carbides by decreasing Mo enrichment and C activity in the residual liquid. Moreover, increasing Mg content inhibited the formation of M6C eutectic carbides and promoted the precipitation of M2C eutectic carbides by increasing C segregation and decreasing Mo segregation, and thus, significantly improved the homogeneity of as-cast macrostructure. [ABSTRACT FROM AUTHOR]

The controls of cleanliness and inclusion characteristics are important issues for the manufacturing of bearing steels. In this work, the method of Mg pretreatment and Ce addition was firstly proposed, and its effect on cleanliness and inclusion evolution in high-nitrogen stainless bearing steels was systematically investigated by microstructure observation and thermodynamic calculation. The results showed that Mg pretreatment and Ce addition decreased O and S contents to 0.0004 and 0.0012 wt pct, respectively. The main inclusions before Mg pretreatment were large-size Al2O3 and elongated MnS. With the increase in Mg content to 0.0079 wt pct, the inclusion evolution processes were Al2O3 → MgO·Al2O3 → MgO, and MnS → MgS. After adding Ce to about 0.015 wt pct, the inclusion evolution processes were Al2O3 → CeAlO3 → Ce–O–S, MgO·Al2O3 → MgO, and MnS → Ce–O–S. Specially, Mg3N2 inclusion formed when Mg content was higher than 0.0040 wt pct, which would induce formation of deleterious AlN. Furthermore, large-size Ce–O–S attached by low-density MgO inclusion tended to float upward because of the decreasing density, thus reducing size and number density of inclusions. However, as Mg content increased to 0.0079 wt pct with same Ce addition, the size and number density of Mg-containing inclusions (MgO, MgS, and Mg3N2) increased. Finally, the optimum Mg content of Mg pretreatment with 0.015 wt pct Ce addition was 0.0026~0.0040 wt pct. [ABSTRACT FROM AUTHOR]

In this research, the effect of solidification pressure on phase transformation temperature and sequence, amount of proeutectoid ferrite, characteristics of pearlite and carbonitrides have been investigated by microstructure observation, crystal structure and component analysis, and thermodynamic calculation. The microstructure of 30Cr15Mo1N ingot is mainly composed of martensite, austenite, pearlite, ferrite, M23(C,N)6 and M2(C,N). With increasing solidification pressure, M23(C,N)6 precipitation temperature, austenite (γ) and ferrite (δ) formation temperature increase, and M2(C,N) precipitation temperature and ferrite (α) formation temperature decrease. Under 0.5 MPa, the precipitation sequence during solidification process of 30Cr15Mo1N ingot is "L → δ → γ → M2(C,N) → M23(C,N)6 → α + martensite/retained austenite → pearlite". There is a negligible change in phase transformation sequence with increasing solidification pressure from 0.5 to 2 MPa. In addition, the increment in solidification pressure is beneficial to significantly increase the amount of proeutectoid ferrite and reduce pearlite lamellar spacing by enhancing cooling of 30Cr15Mo1N ingot. Meanwhile, with increasing solidification pressure from 0.5 to 2 MPa, the size of M2(C,N) and the amount of precipitated phases (pearlite and carbonitrides) have a decreasing trend, and the change in the size of M23(C,N)6 can be neglected. [ABSTRACT FROM AUTHOR]

The heavy metal cadmium (Cd2+) is an environmental pollutant that poses serious health hazards. Due to the increasing contamination of aquatic systems with Cd2+, the increased accumulation of Cd2+ in fish has become a food safety and public health concern. Heme oxygenase (HO) is an important antioxidant enzyme that plays a key role in defending the body against oxidative damage, but little research has been done in common carp. In this study, 6 HO genes were identified in the common carp genome database. Comparative genomics analysis showed considerable expansion of the HO genes and verified the four-round whole genome duplication (WGD) event in common carp. Phylogenetic analysis revealed that all HO genes of common carp were clustered into orthologous groups, indicating high conservation during evolution. In addition, the tissue distribution results showed that most HO genes had extensive tissue distribution and showed tissue-specific expression patterns. Exposure to 0.5 mg/L Cd2+ significantly reduced the expression of TGF-β and IL-10 in common carp, which may indicate that Cd2+ exposure can destroy the physical barrier function of the intestine, inhibit intestinal immune defense and induce intestinal inflammation. To find a suitable concentration of Bacillus coagulans that could activate HO-1 genes and the immunity of the organism, we investigated the changes in HO-1 gene expression levels in the intestinal tract of common carp under Cd2+ stress at 30 days and 60 days by adding different concentrations of B. coagulans to the feed. Compared with the Cd2+ stress group without supplementation, the expression levels of the HO-1 gene in the gut of three different concentrations of B. coagulans were almost increased. And B. coagulans with L2 concentrations had better activation effect on the HO-1 gene. Similarly, compared to the Cd2+ stressed group, adding B. coagulans to the diet can almost cause the early upregulation of IL-10 and TGF-β genes. Therefore, the addition of appropriate concentrations of B. coagulans may be a good way to activate HO-1, IL-10, and TGF-β genes, reduce oxidative damage, and encourage the immune. [ABSTRACT FROM AUTHOR]

Largemouth bass (Micropterus salmoides) is an economically important species in China. Contrary to its rapidly increasing yield during the last decades, the domestic genetic diversity of largemouth bass has gradually declined. In this study, 37 single nucleotide polymorphism (SNP) markers were developed based on genotyping-by-sequencing data and characterized by genotyping 32 individuals using the PCR–restriction fragment length polymorphism method. The effective number of alleles (Ne), observed heterozygosity (Ho), expected heterozygosity (He), and polymorphic information content (PIC) of these SNPs ranged from 1.168 to 1.998, 0.156 to 0.844, 0.146 to 0.507, and 0.134 to 0.375, respectively. Totally, five loci deviated significantly from Hardy–Weinberg equilibrium (p < 0.05), while there existed no linkage disequilibrium at all loci. These novel polymorphic markers will lay the foundation for future rationally excavation and utilization of germplasm resources in M. salmoides. [ABSTRACT FROM AUTHOR]

High cleanliness is a crucial factor determining the service performance of bearing steel. Considering the strong deoxidation ability of carbon under vacuum, vacuum carbon deoxidation was adopted in the cleanliness control of high nitrogen stainless bearing steel. In this paper, a mathematical model for vacuum carbon deoxidation during pressure/vacuum induction melting (PVIM) was proposed considering the occurrence of carbon–oxygen reaction at the free surface of molten pool and at the interface between CO bubbles and molten steel as well as crucible decomposition. The effect of electromagnetic stirring on the mass transfer of oxygen was analyzed using the finite element numerical method and the effect of CO bubbles on the deoxidation process was also considered. The influence of pressure, temperature and initial carbon content on deoxidization was studied and experimentally verified. The results indicated that the predicted variation of oxygen content in molten steel with time agreed well with the experimental results. Electromagnetic stirring effectively promoted the mass transfer of oxygen in molten steel and the carbon–oxygen reaction at free surface of molten pool was the main pathway for deoxidization. The pressure, temperature and initial carbon content influenced the vacuum carbon deoxidation process by affecting the carbon–oxygen reaction rate, crucible decomposition and mass transfer coefficient of oxygen. Finally, optimum melting parameters were recommended. [ABSTRACT FROM AUTHOR]

Dissimilatory arsenate reduction from arsenic (As)-bearing minerals into highly mobile arsenite is one of the key mechanisms of As release into groundwater. To detect the microbial diversity and As-metabolizing gene clusters of indigenous arsenate-reducing bacteria in high As groundwater in the Hetao Plain of Inner Mongolia, China, three anaerobic arsenate-reducing bacteria were isolated and arrA and arsC gene-based clone libraries of four in situ groundwater samples were constructed. The strains IMARCUG-11(G-11), IMARCUG-C1(G-C1) and IMARCUG-12(G-12) were phylogenetically belonged to genera Paraclostridium, Citrobacter and Klebsiella, respectively. They could reduce >99% of 1 mM arsenate under anoxic conditions with lactate as a carbon source in 60 h, 72 h and 84 h, respectively. As far as we know, this was the first report of arsenate reduction by genus Paraclostridium. Compared with strain G-11 (arsC) and G-C1 (arsRBC), strain G-12 contained two incomplete ars operons (operon1: arsABC, operon2: arsBC), indicating that these strains might present different strategies to resist As toxicity. Phylogenetic analysis illuminating by the arrA genes showed that in situ arsenate-reducing bacterial communities were diverse and mainly composed of Desulfobacterales (53%, dominated by Geobacter), Betaproteobacteria (12%), and unidentified groups (35%). Based on the arsC gene analysis, the indigenous arsenate-reducing bacterial communities were mainly affiliated with Omnitrophica (88%) and Deltaproteobacteria (11%, dominated by Geobacter and Syntrophobacterales). Results of this study expanded our understanding of indigenous arsenic-reducing bacteria in high As groundwater aquifers. [ABSTRACT FROM AUTHOR]

The existence of angular and hard AlN inclusions would seriously deteriorate the service life of high-nitrogen stainless bearing steels (HNSBSs). In this work, the formation mechanism of AlN inclusion in HNSBSs under as-cast, annealing and austenitizing states was systematically investigated by microstructure observation and thermodynamic, kinetic analyses. The results showed that the concentration product of Al and N could exceed the critical solubility of AlN inclusion at liquidus temperature with the Al content higher than 0.050 wt pct, which led to the formation of AlN inclusions about 1 to 5 μm (equivalent diameter) in liquid steel. Based on the 'Clyne-Kurz' model, AlN inclusion could form at the solidifying front due to the enrichment of N in the residual liquid steel with the Al content higher than 0.030 wt pct. Besides, the precipitation of Cr2N and the extremely low diffusion coefficient of Al in α phase restrained the precipitation of AlN during annealing at 1023 K. However, AlN and AlN-MnS composite inclusions less than 0.6 μm could precipitate during austenitizing at 1323 K with the Al content higher than 0.006 wt pct, which was the critical Al content to avoid AlN formation in HNSBSs after melting, solidification, and heat treatment processes. [ABSTRACT FROM AUTHOR]