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A zincophilic PAN@Zn(OTF)2 (PZO) separator with an extremely thin thickness of 65.6 μm is introduced. This separator with a low cost of 6.1 $ m−2, exhibiting excellent mechanical and wettability properties. The cell with the PZO separator exhibits impressive electrochemical performances both in symmetrical Zn‖‖Zn cell and Zn‖‖NVO full cell. [ABSTRACT FROM AUTHOR]

Background: High expression of inhibitor of DNA binding 1 (ID1) correlates with poor prognosis in colorectal cancer (CRC). Aberrant enhancer activation in regulating ID1 transcription is limited. Methods: Immunohistochemistry (IHC), quantitative RT-PCR (RT-qPCR) and Western blotting (WB) were used to determine the expression of ID1. CRISPR-Cas9 was used to generate ID1 or enhancer E1 knockout cell lines. Dual-luciferase reporter assay, chromosome conformation capture assay and ChIP-qPCR were used to determine the active enhancers of ID1. Cell Counting Kit 8, colony-forming, transwell assays and tumorigenicity in nude mice were used to investigate the biological functions of ID1 and enhancer E1. Results: Human CRC tissues and cell lines expressed a higher level of ID1 than normal controls. ID1 promoted CRC cell proliferation and colony formation. Enhancer E1 actively regulated ID1 promoter activity. Signal transducer and activator of transcription 3 (STAT3) bound to ID1 promoter and enhancer E1 to regulate their activity. The inhibitor of STAT3 Stattic attenuated ID1 promoter and enhancer E1 activity and the expression of ID1. Enhancer E1 knockout down-regulated ID1 expression level and cell proliferation in vitro and in vivo. Conclusions: Enhancer E1 is positively regulated by STAT3 and contributes to the regulation of ID1 to promote CRC cell progression and might be a potential target for anti-CRC drug studies. [ABSTRACT FROM AUTHOR]

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) has been reported to be expressed in many mammalian tissues and cells. However, the functions and exact mechanisms of PHLDA1 remain unclear. In this study, we found that PHLDA1 expression was significantly altered in macrophages after exposure to lipopolysaccharide (LPS) in vitro , suggesting that PHLDA1 may be involved in the regulation of TLR4 signaling pathway activated by LPS. PHLDA1 attenuated the production of LPS-stimulated proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Further research showed that the phosphorylation levels of some important signal molecules in TLR4/MyD88-mediated MAPK and NF-κB signaling pathways were reduced by PHLDA1, which in turn impaired the transcription factors NF-κB and AP1 nuclear translocation and their responsive element activities. Furthermore, we found that PHLDA1 repressed LPS-induced proinflammatory cytokine production via binding to Tollip which restrained TLR4 signaling pathway. A mouse model of endotoxemia was established to confirm the above similar results. In brief, our findings demonstrate that PHLDA1 is a negative regulator of LPS-induced proinflammatory cytokine production by Tollip, suggesting that PHLDA1 plays an anti-inflammatory role through inhibiting the TLR4/MyD88 signaling pathway with the help of Tollip. PHLDA1 may be a novel therapeutic target in treating endotoxemia. [ABSTRACT FROM AUTHOR]

Objective: Limiting purine intake, inhibiting xanthine oxidoreductase (XOR) and inhibiting urate reabsorption in proximal tubule by uricosuric drugs, to reduce serum uric acid (UA) levels, are recognized treatments for gout. However, the mechanism of increased how XOR expression and activity in hyperuricemia and gout remains unclear. This study aims to explore whether exogenous purines are responsible for increased XOR expression and activity. Methods: HepG2 and Bel-7402 human hepatoma cells were stimulated with exogenous purine, or were exposed to conditioned growth medium of purine-stimulated Jurkat cells, followed by measurement of XOR expression and UA production to determine the effect of lymphocyte-secreted cytokines on XOR expression in hepatocytes. The expression of STAT1, IRF1 and CBP and their binding on the XDH promoter were detected by western blotting and ChIP-qPCR. The level of DNA methylation was determined by bisulfite sequencing PCR. Blood samples from 117 hyperuricemia patients and 119 healthy individuals were collected to analyze the correlation between purine, UA and IFN-γ concentrations. Results: Excess of purine was metabolized to UA in hepatocyte metabolism by XOR that was induced by IFN-γ secreted in the conditioned growth medium of Jurkat cells in response to exogenous purine, but it did not directly induce XOR expression. IFN-γ upregulated XOR expression due to the enhanced binding of STAT1 to IRF1 to further recruit CBP to the XDH promoter. Clinical data showed positive correlation of serum IFN‐γ with both purine and UA, and associated risk of hyperuricemia. Conclusion: Purine not only acts as a metabolic substrate of XOR for UA production, but it induces inflammation through IFN-γ secretion that stimulates UA production through elevation of XOR expression. [ABSTRACT FROM AUTHOR]

Smart technologies bring innovation to the life and sports arena. To adapt to diverse play styles and improve unconventional technique of table tennis players, a smart table tennis racket with tunable stiffness based on anisotropic electrorheological elastomers (EREs) is developed. The EREs are prepared in the designed mold under the electric field to form an anisotropic structure that consisted of electrorheological particles and facilitated the generation of interparticle saturation surface polarization and the local electric field. Therefore, the electrorheological property of anisotropic EREs is significantly promoted, attaining a relative electrorheological effect of 17 160% in shear mode, and the incremental shear storage and compression modulus of 5.2 and 6.4 MPa. By applying an electric field, the smart racket successfully changes the trajectory of balls, reduced ejection angle by 11% and increased ejection velocity by 2%. [ABSTRACT FROM AUTHOR]

Key points: Rat somatosensory neurons express a junctional protein, junctophilin‐4 (JPH4)JPH4 is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the junctions between plasma membrane and endoplasmic reticulum in these neurons.Knockdown of JPH4 impairs endoplasmic reticulum Ca2+ store refill and junctional Ca2+ signalling in sensory neurons.In vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly attenuated experimentally induced inflammatory pain in rats.Junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms. Junctions of endoplasmic reticulum and plasma membrane (ER‐PM junctions) form signalling nanodomains in eukaryotic cells. ER‐PM junctions are present in peripheral sensory neurons and are important for the fidelity of G protein coupled receptor (GPCR) signalling. Yet little is known about the assembly, maintenance and physiological role of these junctions in somatosensory transduction. Using fluorescence imaging, proximity ligation, super‐resolution microscopy, in vitro and in vivo gene knockdown we demonstrate that a member of the junctophilin protein family, junctophilin‐4 (JPH4), is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the ER‐PM junctions in rat somatosensory neurons. Thus we show that JPH4 localises to the ER‐PM junctional areas and co‐clusters with SOCE proteins STIM1 and Orai1 upon ER Ca2+ store depletion. Knockdown of JPH4 impairs SOCE and ER Ca2+ store refill in sensory neurons. Furthermore, we demonstrate a key role of the JPH4 and junctional nanodomain Ca2+ signalling in the pain‐like response induced by the inflammatory mediator bradykinin. Indeed, an in vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly shortened the duration of nocifensive behaviour induced by hindpaw injection of bradykinin in rats. Since the ER supplies Ca2+ for the excitatory action of multiple inflammatory mediators, we suggest that junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms. Key points: Rat somatosensory neurons express a junctional protein, junctophilin‐4 (JPH4)JPH4 is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the junctions between plasma membrane and endoplasmic reticulum in these neurons.Knockdown of JPH4 impairs endoplasmic reticulum Ca2+ store refill and junctional Ca2+ signalling in sensory neurons.In vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly attenuated experimentally induced inflammatory pain in rats.Junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms. [ABSTRACT FROM AUTHOR]

Background: Oral tongue squamous cell carcinoma (OTSCC) is a devastating tumor with poor prognosis. There is an urgent need for reliable biomarkers to help predict prognosis and guide treatment for OTSCC. In the current study, we aimed to develop a robust multi-gene signature and prognostic nomogram to predict the prognosis of patients with non-distant metastatic OTSCC. Methods: OTSCC-related differentially-expressed genes were screened from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression based on 1,000 bootstrap replicates, LASSO regression and stepwise multivariate Cox regression were utilized to develop a novel multi-mRNA signature for predicting overall survival in OTSCC. The concordance index, area under receiver operating characteristic (ROC AUC) and calibration curve were employed to assess the prediction capacity of the novel multi-gene model. In addition, a prognostic nomogram was constructed to facilitate the clinical use of the fitted model. The Kaplan-Meier with log-rank test was employed to assess differences in overall survival. Results: We successfully established a novel 15-mRNA prognostic model for predicting overall survival of non-distant metastatic OTSCC, involving ADTRP, ITGA3, RFC4, CCDC96, CYP2J2, NELL2, SPHK1, SPAG16, HBEGF, S100A9, EGFL6, ADGRG6, PDE4D, ABCA4 , and CTTN. The prediction ability of this 15-gene signature was independent of other clinicopathological factors, with an HR of 11.5 (95% CI: 4.70–28.3). Moreover, internal validation by bootstrap analysis yielded a C-index of 0.849, with a 3-year AUC of 0.907 and 5-year AUC of 0.944, which implied excellent prediction accuracy of the fitted model. In addition, external validation by using the GEO dataset (GSE41116) yielded a C-index of 0.804, with a 3-year AUC of 0.868 and 5-year AUC of 0.855, which also indicated good prediction ability of the 15-gene model. Finally, a prognostic nomogram integrating risk group, grade, T stage and N stage was established. Conclusion: Our results demonstrate our 15-gene signature was independently associated with overall survival in non-distant metastatic OTSCC. Moreover, the prognostic nomogram integrating the 15-gene signature and clinicopathological factors has potential to be developed as a prognostic tool. [ABSTRACT FROM AUTHOR]

Silicon and oxygen are potential light elements in Earth's core because their stronger affinity to metal observed with increasing temperature posits that significant amounts of both can be incorporated into the core. It was proposed that an Fe–Si–O liquid alloy could expel SiO2 at the core‐mantle boundary during secular cooling, leaving the core with either silicon or oxygen, not both. This was recently challenged in a study showing no exsolution but immiscibility in the Fe–Si–O system. Here we investigate the liquidus field of Fe–Si and Fe–O binaries and Fe–Si–O ternaries at core‐mantle boundary pressures and temperatures using ab initio molecular dynamics. We find that the liquids remain well mixed with ternary properties identical to mixing of binary properties. Two‐phase simulations of solid SiO2 and liquid Fe show dissolution at temperatures above 4100 K, suggesting that SiO2 crystallization as well as liquid immiscibility in Fe–Si–O is unlikely to occur in Earth's core. Plain Language Summary: The standard hypothesis is that Earth's core inherited its composition (iron‐nickel alloy + lighter elements such as Si, O, S, and C) during core formation by interaction with Earth's silicate magma ocean and has since remained fixed and well mixed through geological time. It was recently proposed, on the basis of high‐pressure experiments, that silicon and oxygen dissolved in the core could crystallize as SiO2 at the core‐mantle boundary during secular cooling, challenging our understanding of core composition and evolution. While other experimental studies have not corroborated these findings, a recent study involving experiments and calculations proposed no SiO2 exsolution but rather liquid‐liquid immiscibility in the iron‐silicon‐oxygen system. In this study, we use ab initio molecular dynamics simulations to theoretically investigate the liquidus field of Fe–Si, Fe–O and Fe–Si–O alloys. We find that (1) the liquid alloys remain stable and well mixed, with the volumes of iron, silicon, and oxygen mixing ideally at core conditions; (2) no sign of SiO2 crystallization or phase separation (i.e., immiscibility); and (3) simulations of solid SiO2 in contact with liquid Fe show mixing of both phases, ruling out silica precipitation out of the core. Key Points: Liquid Fe‐Si‐O alloys are well mixed at core‐mantle boundary conditions; properties are identical to ideal volume mixing of binariesTwo‐phase ab initio molecular dynamics simulations show that solid SiO2 and liquid Fe mix at and above 4100 K at 136 GPaSiO2 crystallization from an Fe‐Si‐O alloy is unlikely for a range of plausible temperatures at the core‐mantle boundary [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is associated with nonalcoholic fatty liver disease (NAFLD). orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is involved in hepatic lipid metabolism. However, the potential role of NR4A1 in Hcy‐associated NAFLD remains elusive. We aimed to elucidate the regulation of NR4A1 and its significance in Hcy‐induced NAFLD. Hcy induced steatosis and elevated the expression of CD36 and FATP2 in HepG2 cells. Furthermore, Hcy enhanced p300 and decreased HDAC7 recruitment to the NR4A1 promoter, resulting in histone H3K27 hyperacetylation and NR4A1 upregulation. Moreover, NR4A1 depletion not only mimicked but also exaggerated the effects of Hcy on steatosis, whereas NR4A1 agonist Cytosporone B (CsnB) blocked Hcy‐induced steatosis. In hyperhomocysteinemia (HHcy) mice, CsnB attenuated HHcy‐induced hepatic steatosis. Thus, Hcy transiently and rapidly induces NR4A1 expression to reduce Hcy‐induced steatosis. [ABSTRACT FROM AUTHOR]

Earth's core is essentially composed of a light-element bearing iron-nickel alloy (Birch 1964). The nickel content in the core has negligible effects on physical properties such as density and compressibility (e.g., Lin et al. 2003; Kantor et al. 2007; Martorell et al. 2013; Badro et al. 2014). This deters any attempt to determine or even estimate the nickel content of the core using seismological models, as in the case of light elements. It was recently proposed that the presence of nickel should fractionate iron isotopes in small planetary cores (Elardo and Shahar 2017), but the effect for a large (hot) planet such as the Earth would not be measurable; this observation, however, opens up the possibility that Ni can have an effect on element partitioning between the metallic alloy and the silicate melt during core formation. In this case, the siderophile trace-element composition of the mantle would, in turn, constrain the Fe/Ni ratio in the core. Here, we investigated the effect of nickel concentration in the metallic alloy on the partitioning of other elements at conditions directly relevant to core formation, using the laser-heated diamond-anvil cell. We found no measurable effect of nickel concentration on the partitioning of Ni, Cr, and V; the Fe-Ni alloy is chemically ideal over a broad range of Ni concentrations (3.5 to 48.7 wt%). The ideality of the Fe-Ni solution across a wide range of nickel concentration shows that Fe and Ni are not only twins from the standpoint for material properties, but also from that of chemical properties in those high P-T conditions. [ABSTRACT FROM AUTHOR]

We describe a method for the cross-coupling of fluoroarenes with amines. The reaction involves an N-heterocycle- assisted selective C–F bond cleavage, and does not require a transition-metal catalyst. The cross-coupling reaction is significantly promoted by an Li/F interaction. Unexpectedly, amination of an ortho C–F bond on the pyridine ring was observed for 2-(2-fluorophenyl)-6-fluoropyridine, while the C–F bond on the benzene ring remained intact. [ABSTRACT FROM AUTHOR]

Aims: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. Results: SP acutely inhibited T-type voltage-gated Ca2+ channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca2+ channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K+ channels described earlier. Innovation: Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca2+ current and concurrent enhancement of anti-algesic M-type K+ current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. Conclusion: SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233-251. [ABSTRACT FROM AUTHOR]

T-type Ca 2+ channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca 2+ currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca 2+ channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E 2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca 2+ currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B 2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect Ca V 3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a ‘reserve pool’ of Ca V 3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. [ABSTRACT FROM AUTHOR]

Hypercholesterolaemia and inflammation are correlated with atherogenesis. Orphan nuclear receptor NR4A1, as a key regulator of inflammation, is closely associated with lipid levels in vivo. However, the mechanism by which lipids regulate NR4A1 expression remains unknown. We aimed to elucidate the underlying mechanism of NR4A1 expression in monocytes during hypercholesterolaemia, and reveal the potential role of NR4A1 in hypercholesterolaemia-induced circulating inflammation. Circulating leucocytes were collected from blood samples of 139 patients with hypercholesterolaemia and 139 sex- and age-matched healthy subjects. We found that there was a low-grade inflammatory state and higher expression of NR4A1 in patients. Both total cholesterol and low-density lipoprotein cholesterol levels in plasma were positively correlated with NR4A1 mRNA level. ChIP revealed that acetylation of histone H3 was enriched in the NR4A1 promoter region in patients. Human mononuclear cell lines THP-1 and U937 were treated with cholesterol. Supporting our clinical observations, cholesterol enhanced p300 acetyltransferase and decreased HDAC7 (histone deacetylase 7) recruitment to the NR4A1 promoter region, resulting in histone H3 hyperacetylation and further contributing to NR4A1 up-regulation in monocytes. Moreover, cytosporone B, an NR4A1 agonist, completely reversed cholesterol-induced IL-6 (interleukin 6) and MCP-1 (monocyte chemoattractant protein 1) expression to below basal levels, and knockdown of NR4A1 expression by siRNA not only mimicked, but also exaggerated the effects of cholesterol on inflammatory biomarker up-regulation. Thus we conclude that histone acetylation contributes to the regulation of NR4A1 expression in hypercholesterolaemia, and that NR4A1 expression reduces hypercholesterolaemia-induced inflammation. [ABSTRACT FROM AUTHOR]

An efficient and general selective method for the synthesis of 8-aminoquinoline derivatives has been disclosed through transition metal direct C–N coupling from fluoroquinolines and arylamines. Significantly, good chemo- and regio-selectivity was observed for polyfluoroquinolines in which only C–F bond on 8-substituted position was broken. Thus, this methodology proves its value as an inexpensive and efficient synthetic way to access quinolin-8amine derivatives in moderate to good yields. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that mammalian peripheral somatosensory neurons express functional receptors for gamma-aminobutyric acid, GABA A and GABA B . Moreover, local release of GABA by pain-sensing (nociceptive) nerve fibres has also been suggested. Yet, the functional significance of GABA receptor triggering in nociceptive neurons is not fully understood. Here we used patch-clamp recordings from small-diameter cultured DRG neurons to investigate effects of GABA B receptor agonist baclofen on voltage-gated Ca 2+ currents. We found that baclofen inhibited both low-voltage activated (LVA, T-type) and high-voltage activated (HVA) Ca 2+ currents in a proportion of DRG neurons by 22% and 32% respectively; both effects were sensitive to G i/o inhibitor pertussis toxin. Inhibitory effect of baclofen on both current types was about twice less efficacious as compared to that of the μ-opioid receptor agonist DAMGO. Surprisingly, only HVA but not LVA current modulation by baclofen was partially prevented by G protein inhibitor GDP-β-S. In contrast, only LVA but not HVA current modulation was reversed by the application of a reducing agent dithiothreitol (DTT). Inhibition of T-type Ca 2+ current by baclofen and the recovery of such inhibition by DTT were successfully reconstituted in the expression system. Our data suggest that inhibition of LVA current in DRG neurons by baclofen is partially mediated by an unconventional signaling pathway that involves a redox mechanism. These findings reinforce the idea of targeting peripheral GABA receptors for pain relief. [ABSTRACT FROM AUTHOR]

EP3, one of four prostaglandin E2 (PGE2) receptors, is significantly lower in atherosclerotic plaques than in normal arteries and is localized predominantly in macrophages of the plaque shoulder region. However, mechanisms behind this EP3 expression pattern are still unknown. We investigated the underlying mechanism of EP3 expression in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages with oxidized low-density lipoprotein (oxLDL) treatment. We found that oxLDL decreased EP3 expression, in a dose-dependent manner, at both the mRNA and protein levels. Moreover, oxLDL inhibited nuclear factor-κB (NF-κB)-dependent transcription of the EP3 gene by the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Finally, chromatin immunoprecipitation revealed decreased binding of NF-κB to the EP3 promoter with oxLDL and PPAR-γ agonist treatment. Our results show that oxLDL suppresses EP3 expression by activation of PPAR-γ and subsequent inhibition of NF-κB in macrophages. These results suggest that down-regulation of EP3 expression by oxLDL is associated with impairment of EP3-mediated anti-inflammatory effects, and that EP3 receptor activity may exert a beneficial effect on atherosclerosis. [ABSTRACT FROM AUTHOR]

• Structure and properties of pyrolite melt change gradually at mantle conditions. • Sixfold Si-O coordination transition is protracted in depolymerized silicate melts. • Metal-silicate partitioning of Ni shows similar smooth dependence on pressure. Structure and properties of terrestrial magma oceans control the co-evolution of the core, mantle and atmosphere of the early Earth, but are poorly understood because discrepancies remain between experiments and theoretical calculations. Here we combine acoustic velocity measurements and ab initio simulations on pyrolite glass/melt with a silicate Earth-like composition. In the complex system, we find a gradual increase of sound velocity with increasing pressure. Through ab initio simulations, this is explicable by the transition from four- to six-fold coordinated Si occurring over the entire mantle regime. These results are at odds with recent X-ray diffraction measurements, which show an abrupt change in Si-O coordination at 35 GPa. It is however consistent with recent high-pressure data, where Ni partitioning between molten metal and silicate exhibits a similar gradual change with pressure. Unlike amorphous silica, smooth structural evolution in a multicomponent system implies progressive changes in magma ocean properties with depth, such as density, element partitioning and transport properties, which, when incorporated into magma ocean models, may improve our understanding of early history of the Earth and other rocky planets. [ABSTRACT FROM AUTHOR]

Activation of the AMP-dependent protein kinase (AMPK) is linked to cancer cell survival in a variety of cancer cell lines, particularly under conditions of stress. As a potent activator of AMPK, metformin has become a hot topic of discussion for its effect on cancer cell. Here, we report that AMPK activated by metformin promotes HeLa-S3 cell survival and growth in vivo. Our results show that metformin inhibited cell proliferation in MCF-7 cells, but not in LKB1-deficient HeLa-S3 cells. Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition. Moreover, AMPK activation exerted a protective effect in HeLa-S3 cells by relieving ER stress, modulating ER Ca2+ storage, and finally contributing to cellular adaptation and resistance to apoptosis. Our findings identify a link between AMPK activation and cell survival in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by metformin in cancer cell, and suggests a discrete re-evaluation on the role of metformin/AMPK activation on tumor cell growth, proliferation, and on clinical application in cancer therapy. © 2014 IUBMB Life, 66(6):415-423, 2014 [ABSTRACT FROM AUTHOR]

Nonionic-zwitterionic hybrid surfactants, namely N, N-dimethyl- N-dodecyl polyoxyethylene (3) amine oxide, and the corresponding betaine and/or sulfobetaine, have been synthesized. Their molecule structures were characterized by means of electrospray ionization mass spectrometry and H nuclear magnetic resonance. Compared to the structurally related conventional amine oxide, betaine and sulfobetaine, the critical micelle concentrations of the three hybrid surfactants are one order of magnitude smaller than those of traditional ones. The polyoxyethylene segment between the hydrophilic head group and the hydrophobic tail makes the surface activities of the hybrid surfactants superior to their structure-related counterparts. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer whose underlying molecular mechanisms are poorly understood. The natural antisense transcript (NAT) WRAP53 regulates p53 expression and WRAP53 protein is a component of telomerase. NATs play key roles in carcinogenesis, and although WRAP53 is known to increase cancer cell survival, its role in ESCC clinicopathology is unknown. The aim of this study was to investigate WRAP53 expression in ESCC and to correlate it with clinicopathological characteristics. Methods: WRAP53 mRNA and protein expression was measured by quantitative PCR (qRT-PCR) and western blotting, respectively, in 4 ESSC cells lines and in 45 paired ESCC and non-neoplastic esophageal mucosa tissues. To correlate WRAP53 protein expression with clinicopathological characteristics, immunohistochemistry (IHC) was performed on 134 ESCC and 85 non-neoplastic esophageal mucosa tissues. Results: Expression of WRAP53 was detected in all ESCC cell lines and was upregulated in the ESCC tissues compared with the corresponding non-neoplastic tissues (P<0.01). More cells expressed WRAP53 protein in the ESCC tissues than in the non-neoplastic tissues (P<0.01). Overexpression of WRAP53 was significantly correlated with tumor infiltration depth (P = 0.000), clinical stage (P = 0.001), and lymph node metastasis (P = 0.025). Wrap53 expression was not correlated with age, gender, or tumor differentiation. Conclusion: This report indicates increased expression of WRAP53 in ESCC and that WRAP53 overexpression is correlated with tumor progression. WRAP53 may play a significant role in ESCC; accordingly, WRAP53 could be a useful biomarker for ESCC. [ABSTRACT FROM AUTHOR]