► Magnetron sputtered TiAlN/VN exhibits strongly temperature-dependent friction, wear and oxidation ► The hydroxide lubricious tribofilm exists only at temperatures lower than 100
°C ► Comprehensive ...friction and wear mechanism study by state-of-the-art TEM-EELS-EDX techniques.
In this paper, a magnetron sputtered nano-structured multilayer coating TiAlN/VN, grown on hardened tool steel substrate, has been investigated in un-lubricated ball-on-disk sliding tests against an alumina counterface, to study the friction and wear behaviours at a broad range of testing temperatures from 25 to 700
°C, followed by comprehensive analysis of the worn samples using FEG-SEM, cross-sectional TEM, EDX, as well as micro/nano indentations. The experiment results indicated significant temperature-dependent friction and wear properties of the coating investigated. Below 100
°C, the coating showed low friction coefficient at
μ
≤
0.6 and low wear rate in the scale of 10
−17
m
3
N
−1
m
−1 dominated by mild oxidation wear. From 100 to 200
°C, a progressive transition to higher friction coefficient occurred. After that, the coating exhibited high friction of
μ
=
0.9 at temperatures between 200 and 400
°C, and simultaneously higher wear rates of (10
−16 to 10
−15) m
3
N
−1
m
−1. The associated wear mechanism changed to severe wear dominated by cracking and spalling. From 500
°C and so on, accelerated oxidation of the TiAlN/VN became the controlling process. This led first to the massive generation of oxide debris and maximum friction of
μ
=
1.1 at 500
°C, and then to fast deterioration of the coating despite the lowest friction coefficient of
μ
<
0.3 at 700
°C.
Iterative clipping and filtering (ICF) is a widely used technique to reduce the peak-to-average power ratio (PAPR) of orthogonal frequency division multiplexing (OFDM) signals. However, the ICF ...technique, when implemented with a fixed rectangular window in the frequency-domain, requires many iterations to approach specified PAPR threshold in the complementary cumulative distribution function (CCDF). In this paper, we develop an optimized ICF method which determines an optimal frequency response filter for each ICF iteration using convex optimization techniques. The design of optimal filter is to minimize signal distortion such that the OFDM symbol's PAPR is below a specified value. Simulation results show that our proposed method can achieve a sharp drop of CCDF curve and reduce PAPR to an acceptable level after only 1 or 2 iterations, whereas the classical ICF method would require 8 to 16 iterations to achieve a similar PAPR reduction. Moreover, the clipped OFDM symbols obtained by our optimized ICF method have less distortion and lower out-of-band radiation than the existing method.
Short chain fatty acids (SCFAs) are the main products of indigestible carbohydrates that are fermented by microbiota in the hindgut. This study was designed to investigate the effects of oral SCFAs ...administration on the lipid metabolism of weaned pigs. A total of 21 barrows were randomly allocated into three groups, including control group (orally infused with 200 mL physiological saline per day), low dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 20.04 mM, propionic acid 7.71 mM and butyric acid 4.89 mM per day), and high dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 40.08 mM, propionic acid 15.42 mM and butyric acid 9.78 mM per day). The results showed that the average daily feed intake of SCFAs groups were lower than that of control group (P<0.05). Oral administration of SCFAs decreased the concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol and insulin (P<0.05), and increased the leptin concentration in serum (P<0.05). The total fat, as well as TC and TG levels in liver, was decreased by oral SCFAs administration (P<0.05). In addition, SCFAs down-regulated the mRNA expressions of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (P<0.05), and enhanced the mRNA expression of carnitine palmitoyltransferase-1α (CPT-1α) in liver (P<0.05). SCFAs also decreased FAS, acetyl-CoA carboxylase (ACC) and peroxisome proliferator activated receptor σ mRNA expressions in longissimus dorsi (P<0.05). And in abdominal fat, SCFAs reduced FAS and ACC mRNA expressions (P<0.05), and increased CPT-1α mRNA expression (P<0.05). These results suggested that oral administration of SCFAs could attenuate fat deposition in weaned pigs via reducing lipogenesis and enhancing lipolysis of different tissues.
Background
Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. ...Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer.
Methods
The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography–mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice.
Results
GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1.
Conclusions
Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.
Aim
Brown and beige adipose tissues dissipate energy in the form of heat via mitochondrial uncoupling protein 1, defending against hypothermia and potentially obesity. The latter has prompted renewed ...interest in understanding the processes involved in browning to realize the potential therapeutic benefits. To characterize the temporal profile of cold‐induced changes and browning of brown and white adipose tissues in mice.
Methods
Male C57BL/6J mice were singly housed in conventional cages under cold exposure (4 °C) for 1, 2, 3, 4, 5 and 7 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological, immunohistochemical, gene and protein expression analysis.
Results
Upon cold exposure, food intake increased, whilst body weight and adipocyte size were found to be transiently reduced. iBAT mass was found to be increased, whilst sWAT and eWAT were found to be transiently decreased. A combination of morphological, genetic (Ucp‐1, Pgc‐1α and Elov13) and biochemical (UCP‐1, PPARγ and aP2) analyses demonstrated the depot‐specific remodelling in response to cold exposure.
Conclusion
Our results demonstrate the differential responses to cold‐induced changes across discrete BAT and WAT depots and support the notion that the effects of short‐term cold exposure are achieved by expansion, activation and increasing thermogenic capacity of iBAT, as well as browning of sWAT and, to a lesser extent, eWAT.
The Wnt/β-catenin pathway has important roles in chemoresistance and multidrug resistance 1 (MDR1) expression in some cancers, but its involvement in breast cancer and the underlying molecular ...mechanism are undefined. In this study, we demonstrated that the Wnt/β-catenin pathway is activated in chemoresistant breast cancer cells. Using a Wnt pathway-specific PCR array screening assay, we detected that Pygo2, a newly identified Wnt/β-catenin pathway component, was the most upregulated gene in the resistant cells. Additional experiments indicated that Pygo2 activated MDR1 expression in the resistant cells via the Wnt/β-catenin pathway. Moreover, the inhibition of Pygo2 expression restored the chemotherapeutic drug sensitivity of the resistant cells and reduced the breast cancer stem cell population in these cells in response to chemotherapy. Importantly, these activities induced by Pygo2 were mediated by MDR1. We also determined the effect of Pygo2 on the sensitivity of breast tumors resistant to doxorubicin in a mouse model. Finally, RNA samples from 64 paired patient tumors (before and after chemotherapy) highly and significantly overexpressed Pygo2 and/or MDR1 after treatment, thus underlining a pivotal role for the Pygo2-mediated Wnt/β-catenin pathway in the clinical chemoresistance of breast cancer. Our data represent the first implication of the Wnt/β-catenin pathway in breast cancer chemoresistance and identify potential new targets to treat the recurrence of breast cancer.
Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The ...goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.
The water surface response to subcritical turbulent flow over a backward-facing step (BFS) is studied via high-resolution large-eddy simulation (LES). The LES method is validated first using data of ...previously reported experiments. The LES-predicted water surface is decomposed into different types of gravity waves as well as turbulence-driven forced waves. Analysis of the LES data reveals the interplay between low-frequency large-scale turbulence structures, which are the result of flow separation from the step and reattachment behind the step, and the dynamics of the water surface. The water surface deformation is mainly the result of freely propagating gravity waves and forced waves, owing to turbulence in the form of rollers and/or hairpin vortices. Gravity waves with zero group velocity define the characteristic spatial and temporal scales of the surface deformations at higher frequencies, while large eddies determine their low-frequency modulation. These deformations are mainly confined in lateral bands that propagate downstream following the advection of the near-surface streamwise vortices (rollers) that are shed from the step. Steeper surface waves are observed in regions of negative perturbation velocity gradient and down-welling, downstream of the larger rollers, and are associated with thin isolated regions of high vorticity near the surface. The investigation of such a complex flow has shown that the decomposition of the water surface fluctuations into its different physical components may be used to identify the dynamics of the underlying flow structure.
The mechanical properties from room temperature to cryogenic temperature were investigated for a novel high-Mn cryogenic steel with 0.5C, 25Mn and 4Cr (in wt. %) based on understanding the ...relationship between stacking fault energy (SFE), microstructural evolution and deformation mechanism. The superior cryogenic toughness around ∼201 J was achieved and no ductile-brittle transformation temperature was found due to the highly thermal stable austenite. Only ∼2.5% ε-martensite was detected in impact sample fractured at −196 °C and consequently the ductile-dimpled fracture is dominant from room temperature to cryogenic temperature. The yield strength of 350 MPa, tensile strength of 810 MPa at room temperature increased to 820 MPa and 1380 MPa at −196 °C. It is controlled by the dominant twin deformation hardening mechanism with the SFE of 24.1 mJ/m2 at room temperature and combination of twin deformation hardening mechanism and martensitic transformation hardening mechanism at −196 °C. Due to the lower SEF at cryogenic temperature, and encountered by strain and stress, martensite transformation should be enhanced.
To investigate the origin of running-in friction in unlubricated sliding wear, a magnetron sputtered multilayer coating TiAlN/VN was tested on a ball-on-disc tribometer for a series of sliding ...durations from 10 to 1000 cycles, followed by careful observation of the obtained worn surfaces using an field-emission gun scanning electron microscope. Three steps of friction variation were found: (1) prior to wear particle generation, low initial friction coefficient was around 0.2-0.25 purely attributed to the asperity contact; (2) then it increased steeply to a range of 0.4-0.5 in the first 100 cycles following the generation, breaking and agglomeration of wear particles, and in particular the scaling-up of fish-scale-like tribofilm; (3) eventually it approached to a steady-state value around 0.5 when the friction was governed by the viscous shearing of the tribofilm. It is concluded that, under unlubricated sliding wear, the friction behaviour of transition metal nitride hard coating is dominated by the viscous shearing of tribofilm adhesively bonding to the parent nitride coating.
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