Role of subduction dynamics on the unevenly distributed volcanism at the Middle American subduction system.

A typical subduction of an oceanic plate beneath a continent is expected to be accompanied by arc volcanoes along the convergent margin. However, subduction of the Cocos plate at the Middle American subduction system has resulted in an uneven distribution of magmatism/volcanism along strike. Here we construct a new three-dimensional shear-wave velocity model of the entire Middle American subduction system, using full-wave ambient noise tomography. Our model reveals significant variations of the oceanic plates along strike and down dip, in correspondence with either weakened or broken slabs after subduction. The northern and southern segments of the Cocos plate, including the Mexican flat slab subduction, are well imaged as high-velocity features, where a low-velocity mantle wedge exists and demonstrate a strong correlation with the arc volcanoes. Subduction of the central Cocos plate encounters a thick high-velocity feature beneath North America, which hinders the formation of a typical low-velocity mantle wedge and arc volcanoes. We suggest that the presence of slab tearing at both edges of the Mexican flat slab has been modifying the mantle flows, resulting in the unusual arc volcanism.

AGO2a but not AGO2b mediates antiviral defense against infection of wild-type cucumber mosaic virus in tomato.

Evolutionarily conserved antiviral RNA interference (RNAi) mediates a primary antiviral innate immunity preventing infection of broad-spectrum viruses in plants. However, the detailed mechanism in plants is still largely unknown, especially in important agricultural crops, including tomato. Varieties of pathogenic viruses evolve to possess viral suppressors of RNA silencing (VSRs) to suppress antiviral RNAi in the host. Due to the prevalence of VSRs, it is still unknown whether antiviral RNAi truly functions to prevent invasion by natural wild-type viruses in plants and animals. In this research, for the first time we applied CRISPR-Cas9 to generate ago2a, ago2b, or ago2ab mutants for two differentiated Solanum lycopersicum AGO2s, key effectors in antiviral RNAi. We found that AGO2a but not AGO2b was significantly induced to inhibit the propagation of not only VSR-deficient Cucumber mosaic virus (CMV) but also wild-type CMV-Fny in tomato; however, neither AGO2a nor AGO2b regulated disease induction after infection with either virus. Our findings firstly reveal a prominent role of AGO2a in antiviral RNAi innate immunity in tomato and demonstrate that antiviral RNAi evolves to defend against infection of natural wild-type CMV-Fny in tomato. However, AGO2a-mediated antiviral RNAi does not play major roles in promoting tolerance of tomato plants to CMV infection for maintaining health.

Study on the Potential for Stimulating Mulberry Growth and Drought Tolerance of Plant Growth-Promoting Fungi.

Drought stress often leads to heavy losses in mulberry planting, especially for fruits and leaves. Application of plant growth-promoting fungi (PGPF) endows various plant beneficial traits to overcome adverse environmental conditions, but little is known about the effects on mulberry under drought stress. In the present study, we isolated 64 fungi from well-growing mulberry trees surviving periodical drought stress, and Talaromyces sp. GS1, Pseudeurotium sp. GRs12, Penicillium sp. GR19, and Trichoderma sp. GR21 were screened out due to their strong potential in plant growth promotion. Co-cultivation assay revealed that PGPF stimulated mulberry growth, exhibiting increased biomass and length of stems and roots. Exogenous application of PGPF could alter fungal community structures in the rhizosphere soils, wherein Talaromyces was obviously enhanced after inoculation of Talaromyces sp. GS1, and Peziza was increased in the other treatments. Moreover, PGPF could promote iron and phosphorus absorption of mulberry as well. Additionally, the mixed suspensions of PGPF induced the production of catalase, soluble sugar, and chlorophyll, which in turn enhanced the drought tolerance of mulberry and accelerated their growth recovery after drought. Collectively, these findings might provide new insights into improving mulberry drought tolerance and further boosting mulberry fruit yields by exploiting interactions between hosts and PGPF.

The key role of crystal boron in enhanced degradation of refractory contaminants using heterogeneous Fe3+/SPC system.

An origin Fenton-like system was discussed for the abatement of refractory contaminants. Sodium percarbonate (SPC) was utilized as the source of H2O2 and crystal boron (C-boron) was applied to enhance the activation of H2O2. Under the conditions of 0.50 mM Fe3+, 0.34 mM SPC, and heterogeneous catalysis using 100 mg L-1 C-boron, four target pollutants, at the initial concentrations of 20 µM, could be efficiently degraded by the Fenton-like system, with a degradation rate within 20 min up to 81.1% (aspirin, ASA), 92.8% (nitrobenzene, NB), 94.7% (flunixin meglumine, FMME), and 94.3% (benzoic acid, BA) respectively and total organic carbon removal up to 25.0%. The increase of Fe2+ concentration indicated that the conversion of Fe2+/Fe3+ was remarkably promoted by C-boron. Degradation reactions at acidic pH were comparatively fast, with pH-dependent kobs of 9.9 × 10-2 min-1 (ASA), 1.5 × 10-1 min-1 (NB), 1.7 × 10-1 min-1 (FMME), and 1.9 × 10-1 min-1 (BA), whereas those at neutral and alkaline pH were slower. Furthermore, reactive oxygen species including ·OH, 1O2, and O2·- were identified by in-situ electron paramagnetic resonance tests. The contribution ratios of ·OH turned out to be about 71.3-86.7% for the decomposition of four contaminants. The elimination of natural organic matter and the performance of material recycling highlighted the potential for its application in water treatment. The inhibition rate of Chlorella pyrenoidosa reached 211.9% in the C-boron/Fe3+/SPC system. The relatively high algae toxicity limited its application scope, which requires additional research to resolve.

Endophytic Klebsiella aerogenes HGG15 stimulates mulberry growth in hydro-fluctuation belt and the potential mechanisms as revealed by microbiome and metabolomics.

Growth promotion and stress tolerance induced by endophytes have been observed in various plants, but their effects on mulberry regularly suffering flood in the hydro-fluctuation belt are less understood. In the present study, endophytic Klebsiella aerogenes HGG15 was screened out from 28 plant growth promotion (PGP) bacteria as having superior PGP traits in vitro and in planta as well as biosafety for silkworms. K. aerogenes HGG15 could actively colonize into roots of mulberry and subsequently transferred to stems and leaves. The 16S ribosomal RNA (V3-V4 variable regions) amplicon sequencing revealed that exogenous application of K. aerogenes HGG15 altered the bacterial community structures of mulberry roots and stems. Moreover, the genus of Klebsiella was particularly enriched in inoculated mulberry roots and was positively correlated with mulberry development and soil potassium content. Untargeted metabolic profiles uncovered 201 differentially abundant metabolites (DEMs) between inoculated and control mulberry, with lipids and organo-heterocyclic compounds being particularly abundant DEMs. In addition, a high abundance of abiotic stress response factors and promotion growth stimulators such as glycerolipid, sphingolipid, indole, pyridine, and coumarin were observed in inoculated mulberry. Collectively, the knowledge gained from this study sheds light on potential strategies to enhance mulberry growth in hydro-fluctuation belt, and microbiome and metabolite analyses provide new insights into the growth promotion mechanisms used by plant-associated bacteria.

Removal and kinetics of cadmium and copper ion adsorption in aqueous solution by zeolite NaX synthesized from coal gangue.

Zeolite can remove the heavy metals in wastewater, but the removal efficiency was determined by the types of zeolites and the treatment conditions. In this study, a kind of zeolite NaX synthesized from the coal gangue, a by-product of coal production, was used and the removal efficiency of Cd2+ and Cu2+and the kinetic models were studied. The effects of its dosage, initial pH value of wastewater, and adsorption temperature on its adsorption of heavy metals Cd2+ and Cu2+ in the simulated wastewater were studied through the indoor experiments in laboratory, and the adsorption mechanism was analyzed by the adsorption kinetic model based on its adsorption efficiency and its structures. The results show that the zeolite NaX synthesized from coal gangue has a good adsorption effect on Cd2+ and Cu2+. The adsorption reaches the best effect when the dosage of zeolite is 2 g/L, the initial pH of simulated wastewater is 5, the adsorption temperature is room temperature (25 ℃), and the removal efficiency of Cd2+ and Cu2+ (100 mg/L) is more than 90%. Additionally, the Langmuir, Freundlich, and Temkin isothermal adsorption models were used to compare and analyze the adsorption effects. The equilibrium data was better fitted by the Langmuir model with the maximum adsorption capacities of 100.11 mg/g (Cd2+) and 95.29 mg/g (Cu2+), and both separation coefficients were 0-1, which shows that the process was the favorable adsorption. Weber Morris diffusion model shows that the adsorption process at 120 min was more consistent with the pseudo-second-order kinetics model, and the adsorption efficiency was simultaneously controlled by the liquid diffusion step and intraparticle diffusion step. Moreover, the removal mechanism of Cd2+ and Cu2+ mainly includes physical adsorption and ion exchange. Therefore, the adsorption effect of zeolite synthesized from coal gangue is remarkable, which will provide a feasible and potential alternative for its resource application.

Circ_0016760 Serves as a Cancer Promoter in Non-small Cell Lung Cancer Through miR-876-3p/NOVA2 Axis.

Non-small cell lung cancer (NSCLC) is a serious threaten to human health globally. Circular RNAs (circRNAs) were testified to alter the progression of NSCLC. This work intended to investigate the functional role of circ_0016760 in NSCLC development and the potential mechanism. Expression of circ_0016760, microRNA (miR)-876-3p and NOVA alternative splicing regulator 2 (NOVA2) was determined via quantitative reverse transcription-PCT (qRT-PCR) or western blotting. Cell viability, clonogenicity and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry, respectively. Transwell assay was performed to examine cell migration and invasion. Western blotting was also conducted to detect the levels of epithelial-to-mesenchymal transition (EMT)-related proteins. Role of circ_0016760 in vivo was evaluated via xenograft model assay. Moreover, the interaction between miR-876-3p and circ_0016760 or NOVA2 was verified by dual-luciferase reporter assay or RNA Immunoprecipitation (RIP) assay. Circ_0016760 and NOVA2 were upregulated, while miR-876-3p expression was decreased in NSCLC tissues and cells. Circ_0016760 depletion suppressed NSCLC cell proliferation and metastasis in vitro, as well as hampered tumor growth in vivo. Circ_0016760 acted as a sponge of miR-876-3p, and miR-876-3p could target NOVA2. Circ_0016760 might play vital roles in NSCLC by regulating miR-876-3p/NOVA2 axis. Circ_0016760 could promote the malignant development of NSCLC through miR-876-3p/NOVA2 axis, at least in part.

LYAR Promotes Colorectal Cancer Progression by Upregulating FSCN1 Expression and Fatty Acid Metabolism.

Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, is expressed at a higher level in CRC tissue than in adjacent normal tissue and that LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, but knockdown (KD) of LYAR in CRC cells also inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with a chromatin immunoprecipitation (ChIP) assay, gene reporter assay, and rescue experiment indicated that FSCN1 (encoding fascin actin-bundling protein 1 (Fascin-1)) serves as a novel key regulator of LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells and leads to the downregulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by upregulating FSCN1 expression and affecting fatty acid metabolism in CRC.

Anti-inflammatory drugs degradation during LED-UV365 photolysis of free chlorine: roles of reactive oxidative species and formation of disinfection by-products.

Light-emitting diode (LED) is environmentally friendly with longer life compared with traditionally mercury lamps. This study investigated the non-steroidal anti-inflammatory drugs (NSAIDs)- phenacetin (PNT) and acetaminophen (ACT)- removal during LED-UV (365 nm) photolysis of free available chlorine (FAC). Degradation of PNT and ACT during LED-UV365/FAC treatment at pH 5.5-8.5 followed the pseudo-first order kinetics. The presence of hydroxyl radicals (·OH), reactive chlorine species (RCS), and ozone (O3, transformed from O (3P)) were screened by using scavengers of ethanol (EtOH), tert-Butanol (TBA), and 3-buten-2ol, and 4-hydroxy-2,2,6,6-tetramethylpiperidine (TEMP), and quantified by competition kinetics with probing compounds of nitrobenzene (NB), benzoate acid (BA), 1,4-dimethoxybenzene (DMOB). Higher pH would lead to decrease of ·OH contribution and an increase of FAC contribution to PNT and ACT degradation. It has been determined that the contribution of O3 to degradation of PNT and ACT was less than 5% for all pHs, and O3(P) reacts toward EtOH with second-order constant of 1.52 × 109 M-1s-1. LED-UV365/FAC system reduced the formation of five typical CX3-R type disinfection by-products (DBPs) as well as the cytotoxicity and genotoxicity of water samples at pH 5.5 and 8.5, compared with FAC alone. The decrease of DBPs formation resulted from fast FAC decomposition upon LED-UV365 irradiation. A feasible reaction pathway of DBPs formation in the LED-UV365/FAC system was examined with density functional theory (DFT). For FAC decay during LED-UV365/FAC with effluent from wastewater, the residual FAC in 15 min was 0.8 mg/L (lower than limit of 0.2 mg/L) once initial FAC was 2.0 mg/L. The results indicate that more tests on the balance of target pollutant removal efficiency, residual FAC and cost should be explored in LED-UV365/FAC system for application.

Reactive oxygen species generation in FeOCl nanosheets activated peroxymonosulfate system: Radicals and non-radical pathways.

Iron oxychloride (FeOCl) is utilized as a activator of peroxymonosulfate (PMS) for the degradation of paracetamol (APAP) and phenacetin (PNCT) in response to the water pollution by persistent pharmaceuticals. The degradation process was well fitted with a pseudo-first order kinetic pattern, and the excellent catalytic performance towards APAP (100 % removal) and PNCT (86.5 % removal) was obtained in the presence of 0.2 g/L FeOCl and 2.0 mM PMS at pH 7.0 in 30 min. In-situ electron spin resonance (ESR) and scavenging tests revealed the generation of a series of ROS (·OH, SO4-, O2-, 1O2), which was highly dependent on pH. Besides, the non-radical pathways process involved 1O2 was dominant in APAP oxidation, while both ·OH and 1O2 are significant in PNCT removal. Furthermore, the formation of disinfection by-products (DBPs) during post-chlorination showed neglectable increment at neutral and alkaline condition with FeOCl/PMS pre-oxidation, and the calculated cytotoxicity would experience a continuous deterioration with pH increase. These results displayed high efficiency of FeOCl/PMS system in micropollutants degradation and a relatively comprehensive activation process of PMS, which may promote practical application in environmental remediation.

Measurement of dilation pulses using a pulse-dilation framing camera.

A pulse-dilation framing camera (PFC) and its working principle are introduced. The influence of the dilation pulse on the exposure time is discussed. The measurement of the dilation pulse using the PFC are theoretically analyzed and experimentally verified. The waveform and the entire time history of the potential of the dilation pulse are simulated by the known dilation factors of the PFC in theory, with the potential deviation at the end of the dilation time of pulse being approximately 3.2%. In the experiment, the exposure time and dilation factors of the PFC are measured by using an array of fiber bundles and in taking many measurements, the waveform and the entire time history of the potential of dilation pulse are achieved by the dilation factors, with the potential deviation at the end of the dilation time of pulse being approximately 6.3%. The research results show that the experimental measurement is consistent with theoretical analysis, although there are some deviations, and it is feasible to measure the waveform and the entire time history of the potential of dilation pulse using the PFC. Moreover, the research may provide an idea for new applications of the framing camera.

Kinetic mechanism of ozone activated peroxymonosulfate system for enhanced removal of anti-inflammatory drugs.

Peroxymonosulfate (PMS) was employed as an activator of ozone (O3) to degrade non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin (ASA) and phenacetin (PNT)) in study. The combination of PMS in O3 system promoted the O3 decomposition and NSAIDs removal significantly. O3 molecule, hydroxyl radical (OH) and sulfate radical (SO4-) were responsible for the removal of target pollutants in O3/PMS system. The second-rate constants between O3, OH and SO4- with ASA were determined to be 7.32, 4.18 × 109 and 3.46 × 108 M-1·s-1, and 37.3, 4.99 × 109 and 5.64 × 108 M-1·s-1 for PNT, respectively. The pattern of pollutant removal and contributions of oxidative species were fitted by experiments and two models. Nevertheless, the wide variety of two models suggested that a comprehensive model for O3/PMS based on a first-principles approach was not yet possible, due to the number of radicals and subsequent chain reaction, such as SO5- or O3-. In addition, the formation of five typical CX3R -type disinfection by products was evaluated from post­chlorine tests and theoretically calculation by frontier electron density calculation. The calculated toxicity of typical CX3R -type DBPs was found to decrease with the increase of pH. The results of this study provide a basis for exploring the mechanism of pollutant degradation in O3 system.

Facile synthesis of 3D silk fibroin scaffolds with tunable properties for regenerative medicine.

Silk fibroin (SF) porous scaffolds provide mechanical support and biochemical signals to encourage cell attachment and modify biological performance. The available methods for the preparation of SF scaffolds are still required. The crosslinkers used are likely to impact the biocompatibility. Herein, water-insoluble SF scaffolds were prepared by physical methods. The phosphate solution promoted SF molecules aggregate from SF/heparin mixed solution. Then SF scaffolds were prepared in centrifuge tubes under different centrifugal speed. The phosphate was leached from the scaffolds, leaving porous structure. The centrifugal force produced shear-induced silk crystallinity to tune the mechanical performance like the natural silkworm gland. The relationship between performance and second structure of the scaffolds have been revealed by X-ray Diffraction (XRD) and deconvoluting Fourier Transform Infrared spectroscopy (FTIR). Due to changes in the ß-sheet content, pore structure, mechanical strength, and drug-loaded behavior was adjustable. The scaffolds performed excellent on the Activated Partial Thromboplastin Time (APTT) value, and it can keep sustainable released for 7 days. The scaffolds prepared in mild environment showed tunable stiffness, good anticoagulation, and improved cell compatibility, suggesting its potential application in regenerative medicine.

Improving the consolidation properties of hydrophilic polyurethane for feldspathic sandstone water erosion prevention.

Feldspathic sandstone is a type of sandstone that is severely eroded by wind, rainfall, and gravity forces. The land surface in feldspathic area is degraded and covered with extremely low vegetation coverage. In this study, we propose a type of hydrophilic polyurethane (W-OH) to control its erosion and conduct the experiment to evaluate the consolidation performances. The results showed that the cementing materials (such as montmorillonite) are the main reason for the vulnerability of feldspathic sandstone to erosion, which expands by absorbing water. Additionally, the organic content is extremely low and is not suitable for vegetation growth. However, when the different concentrations of W-OH solution were sprayed on the feldspathic sandstone surface, the solution could penetrate in several minutes and form a flexible and porous consolidation layer. The anti-scourability index (K) of the layer could increase from approximately 0.2 to 1.0 which significantly increased the water resistance. The water retention benefit increased by 50%. In the simulated rainfall test, the sediment yield reduction in the treated slopes sprayed with the W-OH solution could reach 99% compared with that on the control slopes. The SEM images indicated that the W-OH solution enveloped the feldspathic sandstone particles and connected them tightly together. Therefore, the consolidation layer could decrease water erosion rate and reduce evaporation.

Effects of rainfall intensity, slope angle, and vegetation coverage on the erosion characteristics of Pisha sandstone slopes under simulated rainfall conditions.

The water loss and soil erosion in the Pisha sandstone region in the middle reaches of the Yellow River are extremely severe, leading to extremely harmful effects on the ecological environment and safety of the lower reaches. In this paper, the effects of the slope angle (20, 30, and 40°), rainfall intensity (20, 50, and 80 mm/h), and vegetation coverage (10, 30, and 50%) on the erosion characteristics of the Pisha sandstone slopes are studied using indoor-simulated rainfall tests. The results show that the infiltration into the Pisha sandstone is only 10~15%. It is found that rainfall intensity has the most significant effect on runoff, which gradually increases with increasing rainfall intensity. Vegetation significantly affects runoff reduction when the rainfall intensity is low (approximately 20 mm/h), but this effect decreases with increasing rainfall intensity. Rainfall intensity has an extremely significant effect (P < 0.01) on the sediment yield, followed by vegetation coverage, and slope angle. When the vegetation coverage is approximately 50%, the reduction in sediment yield reaches approximately 70%. Additionally, the sediment reduction benefit is more significant than the runoff reduction benefit. The presence of the eroded gullies on slopes with vegetation is less compared to that on the bare slopes. Therefore, relatively high vegetation coverage (≥ 50%) is required for soil and water conservation in Pisha sandstone area. The findings will provide some reference for Pisha sandstone conservation.

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition.

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic activity. Further studies showed that 11e suppressed tumour growth in human breast cancer (MCF-7) xenograft models without obvious side effects. Evaluation of the mechanism revealed that 11e targeted the epithelial to mesenchymal transition (EMT) process in MCF-7 cells and inhibited HUVEC migration and then contributed to hindrance of angiogenesis. Thus, 11e may be a promising antitumour agent with excellent efficacy and low toxicity.

LncRNA UCA1 sponges miR-26a to regulate the migration and proliferation of vascular smooth muscle cells.

BACKGROUND: Recent studies have shown that the long non-coding RNA urothelial carcinoma-associated (UCA1) plays a key role in cardiovascular injury. However, the potential biological role of UCA1 in progression of atherosclerosis (AS) remains unclear. The aim of the present study is to identify the regulation of lncRNA UCA1 on atherosclerosis-related vascular dysfunction via miR-26a targeting phosphatase and tensin homolog (PTEN), and investigate the underlying mechanisms in the development of atherosclerosis. METHODS: The proliferation and migration were detected using CCK-8 assay, Wound healing assay and Transwell assay. The expression of miR-26a and its target gene in vascular smooth muscle cells was detected by qRT-PCR, the complementary binging of miRNA and lncRNA was verified by luciferase assays. PTEN was predicted to be the target of miR-26a and the prediction was verified by luciferase assays. RESULTS: Expression of miR-26a was up-regulated in ox-LDL (50 mg/l) induced vascular smooth muscle cell (VSMCs), and overexpression of miR-26a inhibited PTEN expression and promoted PCNA α-SMA and SM22-α expression (qRT-PCR and WB). CONCLUSION: The expression of UCA1 antagonized the effect of miR-26a on the downregulation of its target PETN and contraction phenotype. This study reveals that lncRNA UCA1 act as an endogenous sponge of miR-26a and downregulates miR-26a expression levels, and thereby relieving the inhibition of its target gene PTEN and alleviates VSMCs proliferation against atherosclerosis.

Effects of intravenous anesthetics on the phosphorylation of cAMP response element­binding protein in hippocampal slices of adult mice.

cAMP response­element binding protein (CREB) functions in hippocampal synaptic plasticity and memory formation. However, it remains unknown whether intravenous anesthetics modulate CREB. The present study aimed to examine the effects of intravenous anesthetics on CREB phosphorylation in the mouse hippocampus. CREB phosphorylation was examined in hippocampal slices with and without pharmacological or intravenous anesthetics via immunoblotting. In a dose­response experiment, the concentrations of intravenous anesthetics ranged from 10­9 to 10­4 mol/l for 1 h. For the time­response experiment, these slices were incubated with 5x10­6 mol/l of propofol for 0, 1, 2, 5, 7, 9, 12, 15, 30 and 60 min. In order to examine whether CREB phosphorylation could be recovered following washing out the propofol, the slices were incubated in plain artificial cerebrospinal fluid at different time durations following 5 min incubation with propofol. Propofol, etomidate, ketamine and midazolam inhibited CREB phosphorylation (P<0.05) in a time­ and dose­dependent manner. This inhibition was reversible following the removal of propofol, and was rescued by CREB phosphorylation (P<0.05). The decrease in CREB phosphorylation revealed additive effects with 100 µM of chelerythrine and 20 µM of PD­98059, and the etomidate­induced decrease in CREB phosphorylation was blocked by 1 mM of NMDA. However, 0.1 µM of phorbol 12­myristate 13­acetate, 50 µM of U 73122, 100 µM of carbachol and 10 µM of MK801 were ineffective in the anesthetic­induced decrease in CREB phosphorylation. Intravenous anesthetics markedly decreased CREB phosphorylation in the mouse hippocampus, which was most likely via the protein kinase C and mitogen activated protein kinase pathways. This suggests that CREB represents a target for anesthetic action in the brain.

Three-dimensional variations of the slab geometry correlate with earthquake distributions at the Cascadia subduction system.

Significant along-strike variations of seismicity are observed at subduction zones, which are strongly influenced by physical properties of the plate interface and rheology of the crust and mantle lithosphere. However, the role of the oceanic side of the plate boundary on seismicity is poorly understood due to the lack of offshore instrumentations. Here tomographic results of the Cascadia subduction system, resolved with full-wave ambient noise simulation and inversion by integrating dense offshore and onshore seismic datasets, show significant variations of the oceanic lithosphere along strike and down dip from spreading centers to subduction. In central Cascadia, where seismicity is sparse, the slab is imaged as a large-scale low-velocity feature near the trench, which is attributed to a highly hydrated and strained oceanic lithosphere underlain by a layer of melts or fluids. The strong correlation suggests that the properties of the incoming oceanic plate play a significant role on seismicity.

Combination therapy of hTERTR and FAM96A for hepatocellular carcinoma through enhancing apoptosis sensitivity.

Avoidance of apoptosis induced by anticancer drugs is an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. Human telomerase reverse transcriptase receptor (hTERTR) is a potential anti-cancer agent for inhibiting tumor growth. Family with sequence similarity 96 member A (FAM96A) is a ubiquitous, conserved protein and possesses apoptosome-activating and pro-apoptotic tumor suppressor potential in hepatocellular carcinoma (HCC). In the present study, hTERTR and FAM96A were identified as efficient anti-cancer agents for activating apoptosomes and reducing tumor growth. The potential tumor suppressor function of combination treatment with hTERTR and FAM96A in HCC was also investigated. hTERTR and FAM96A proteins were expressed by genetic engineering and their anti-cancer function was explored in vitro and in vivo. Effects of hTERTR and FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and in a mouse model. The present results demonstrated that the therapeutic effects of hTERTR and FAM96A were effective for inhibiting tumor growth and inducing apoptosis of HCC cells in H22-bearing nude mice compared with single agent treatment. hTERTR and FAM96A were found to bind with apoptotic protease activating factor 1 and human telomerase reverse transcriptase, which enhanced the apoptosis of tumor cells and apoptosis sensitivity. In addition, hTERTR and FAM96A therapy enhanced cytotoxic effects by cytotoxic T lymphocyte responses, interferon-γ release, T lymphocytes infiltration and apoptosis on tumor cells. Furthermore, hTERTR and FAM96A protein inhibited tumor growth in HCC mice. In conclusion, the present findings suggested that combination therapy with hTERTR and FAM96A may serve as novel tumor suppressor agents.