Description: The cold tongue mode (CTM) is the second EOF mode of sea surface temperature anomaly (SSTA) variability over the tropical Pacific, and represents the out–of–phase relationship in SSTA variability between the Pacific cold tongue region and elsewhere in the tropical Pacific. A positive CTM is characterized by cold SSTA in the Pacific cold tongue region and warm SSTA in the rest of the tropical Pacific, with conditions reversed for a negative CTM. The CTM is a coupled air–sea mode, and its long–term variability is most probably induced by ocean dynamical processes in response to global warming [ Zhang et al ., 2010]. This study focuses on the specific ocean dynamical processes associated with the CTM and its possible relationship with global warming. A heat budget diagnosis of ocean temperature in the eastern equatorial Pacific shows that the net heat flux plays a damping role and the four ocean advection terms ( , and ) contribute to the temperature change associated with the CTM. Among them, the vertical advection of the anomalous temperature by the mean upwelling ( ) makes a dominant contribution to the long–term change in the CTM. The long–term change of the term is controlled mainly by the decreasing vertical gradient of the ocean temperature anomaly . The other three advection terms make a minor contribution to the long–term change in the CTM. This article is protected by copyright. All rights reserved.

Description: 3-Oxotaraxer-14-en-30-al ( 1 ), a new taraxastane-type triterpene, together with 14 known compounds, taraxerone ( 2 ), 3-epiursolic acid ( 3 ), 2 α ,3 β -dihydroxyurs-12-en-28-oic acid ( 4 ), lupeol ( 5 ), betulinic acid ( 6 ), casticin ( 7 ), artemetin ( 8 ), luteolin ( 9 ), 4-hydroxybenzoic acid ( 10 ), docosanoic acid ( 11 ), tetracosanoic acid ( 12 ), cerotic acid ( 13 ), β -sitosterol ( 14 ), and β -daucosterol ( 15 ), was isolated from the leaves and twigs of Vitex trifolia var. simplicifolia . Compounds 2 – 6 were found for the first time in this plant. Their structures were established by spectroscopic analysis, including 2D-NMR techniques. Cytotoxic activities of compounds 3 , and 5 – 10 were tested on the three cancer cell lines, PANC-1, K562, and BxPC-3. Results revealed that 7 exhibited cytotoxicity against PANC-1, K562, and BxPC-3, with IC 50 values of 4.67, 0.72, and 4.01 μg/ml, respectively, whereas 8 was inactive against these cancer cell lines. The structure activity relationship of compound 7 and 8 indicated that the 3′-OH group in polymethoxyflavonoids is essential for antitumor activity.

Description: DNA methylation plays a crucial role in lots of biological processes and cancer. 5-azacytidine (5-AC), a DNA methylation inhibitor, has been used as a potential chemotherapeutic agent for cancer. In this study, we used 5-AC treatment to investigate whether DNA methylation was involved in regulation of programmed cell death (PCD) in mouse embryo fibroblast NIH-3T3 cells which could undergo PCD after treatment with TNF-α and cycloheximide (CHX). The results showed that the genomic DNA of NIH-3T3 cells was hypermethylated during PCD induced by TNF-α and CHX, and 5-AC might prevent this PCD process. However, treatment with the other three DNA methylation inhibitors, 5-aza-deoxycytidine, 6-thioguanine and RG108, did not interfere with the NIH-3T3 cell PCD process. Additionally, knockdown of DNMT1 did not affect the apoptosis process. The present results and observations indicated that 5-AC specifically inhibited the NIH-3T3 apoptosis process via a genomic DNA methylation-independent pathway. During the TNF-α and CHX-inducing apoptosis process, the PCD related BCL-2 family proteins were significantly down-regulated. Furthermore, after the small interference RNA-mediated knockdown of BCL-XL, one of the BCL-2 family proteins, 5-AC did not inhibit the apoptosis process, suggesting that 5-AC inhibited the PCD process induced by TNF-α and CHX by affecting the anti-apoptotic protein BCL-XL. This article is protected by copyright. All rights reserved

Description: The Journal of Organic Chemistry DOI: 10.1021/acs.joc.8b01362

Description: Programmed death ligand 1 promotes lymph node metastasis and glucose metabolism in cervical cancer by activating integrin β4/SNAI1/SIRT3 signaling pathway Programmed death ligand 1 promotes lymph node metastasis and glucose metabolism in cervical cancer by activating integrin β4/SNAI1/SIRT3 signaling pathway, Published online: 30 April 2018; doi:10.1038/s41388-018-0252-x Programmed death ligand 1 promotes lymph node metastasis and glucose metabolism in cervical cancer by activating integrin β4/SNAI1/SIRT3 signaling pathway

Description: G protein-regulated cell function is crucial for cardiomyocytes, and any deregulation of its gene expression or protein modification can lead to pathological cardiac hypertrophy. Herein, we report that protein prenylation, a lipidic modification of G proteins that facilitates their association with the cell membrane, might control the process of cardiomyocyte hypertrophy. We found that geranylgeranyl diphosphate synthase (GGPPS), a key enzyme involved in protein prenylation, played a critical role in the postnatal heart growth through regulating the cardiomyocyte size. Cardiac-specific knockout of GGPPS in mice led to spontaneous cardiac hypertrophy beginning from 4 th week, accompanied with the persistent enlargement of cardiomyocytes. This hypertrophic effect occurred by altered prenylation of G proteins. Evaluation of the prenylation, membrane association and hydrophobicity showed that Rheb was hyperactivated and increased mTORC1 signaling pathway after GGPPS deletion. Protein farnesylation or mTORC1 inhibition blocked GGPPS knockdown-induced mTORC1 activation and suppressed the larger neonatal rat ventricle myocyte size and cardiomyocyte hypertrophy in vivo , demonstrating a central role of FPP/Rheb/mTORC1 axis for GGPPS deficiency-induced cardiomyocyte hypertrophy. The sustained cardiomyocyte hypertrophy progressively provoked cardiac decompensation and dysfunction, ultimately causing heart failure and adult death. Importantly, GGPPS was downregulated in the hypertrophic hearts of mice subjected to transverse aortic constriction (TAC) and in the failing human hearts. Moreover, HPLC-MS/MS detection revealed that myocardial farnesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP) ratio was enhanced after pressure overload. Our observations conclude that the alteration of protein prenylation promotes cardiomyocyte hypertrophic growth, which acts as a potential cause for pathogenesis of heart failure and may provide a new molecular target for hypertrophic heart disease clinical therapy.

Description: A traffic flow Lighthill, Whitham, and Richards (LWR) model is studied by means of a proper orthogonal decomposition (POD) technique. A POD-based reduced-order finite difference (FD) extrapolating algorithm (FDEA) with lower dimension and fully second-order accuracy is established. Two numerical experiments are used to show that the POD reduced-order FDEA is feasible and efficient for finding numerical solutions of traffic flow LWR model.MSC: 76M20, 65M12, 65M15.

Description: Estradiol (E2) is a major determinant of gender-based differences in the development of hepatic fibrosis. MicroRNAs (miRNAs) are endogenous 19-25 nucleotide, noncoding, single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs and play an important role in liver fibrosis. The mechanisms underlying the regulation of miRNAs by E2 remain largely unknown. In this study, miR-19b levels were higher and were associated with lower GRB2 mRNA and protein levels in female rats more than in male rats. We also showed that miR-19b levels were down-regulated, were associated with the up-regulation of GRB2 mRNA and protein levels in PS (porcine serum-induced hepatic fibrosis) versus NS (normal control) groups and were up-regulated when associated with the down-regulation of GRB2 mRNA and protein levels in PS+E2 versus PS and in aHSC+E2 (estradiol treated aHSC) versus aHSC groups. MiR-19b expression inhibited cell proliferation in aHSCs, and also down-regulated GRB2 protein expression. The overexpression of miR-19b inhibited cell growth and suppressed COL1A1 protein levels by decreasing the levels of GRB2. However, the forced expression of GRB2 partly rescued the effect of miR-19b in the cells, attenuated cell proliferation, and suppressed the GRB2 protein level by up-regulating the levels of GRB2. Taken together, these findings will shed light on the role of miR-19b in regulating aHSC proliferation via the miR-19b/GRB2 axis. This newly identified miR-19b/GRB2 interaction provided novel insights into the suppressive effect of E2 on HSC proliferation and might facilitate the development of therapies targeting hepatic fibrosis. This article is protected by copyright. All rights reserved

Description: Article Sea surface temperature anomalies in the tropical Pacific can influence global atmospheric circulation, yet prediction of this atmospheric signal is limited to less than 1 year. Here, the authors present observational and modelling evidence for multi-year predictability. Nature Communications doi: 10.1038/ncomms7869 Authors: Yoshimitsu Chikamoto, Axel Timmermann, Jing-Jia Luo, Takashi Mochizuki, Masahide Kimoto, Masahiro Watanabe, Masayoshi Ishii, Shang-Ping Xie, Fei-Fei Jin

Description: We show that a carbon nanotube (CNT) diode fabricated by asymmetric contacts shows a linear photocurrent in response to illumination for over six decades or dynamic range of 120 dB; in particular, it shows no sign of degradation under illumination intensity of up to 100 kW/cm 2 . This CNT diode also exhibits a continued response for incident wavelength from 1165 nm to 2100 nm, promising potentials applications in robust and wide bandwidth light sensing.