A Novel Aptamer LL4A Specifically Targets Vemurafenib-Resistant Melanoma through Binding to the CD63 Protein.

Melanoma is a highly aggressive tumor with a poor prognosis, and half of all melanoma patients harbor BRAF mutations. A BRAF inhibitor, vemurafenib (PLX4032), has been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat advanced melanoma patients with BRAFV600E mutation. However, the efficacy of vemurafenib is impeded by adaptive resistance in almost all patients. In this study, using a cell-based SELEX (systematic evolution of ligands by exponential enrichment) strategy, we obtained a DNA aptamer (named LL4) with high affinity and specificity against vemurafenib-resistant melanoma cells. Optimized truncated form (LL4A) specifically binds to vemurafenib-resistant melanoma cells with dissociation constants in the nanomolar range and with excellent stability and low toxicity. Meanwhile, fluorescence imaging confirmed that LL4A significantly accumulated in tumors formed by vemurafenib-resistant melanoma cells, but not in control tumors formed by their corresponding parental cells in vivo. Further, a transmembrane protein CD63 was identified as the binding target of aptamer LL4A using a pull-down assay combined with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. CD63 formed a supramolecular complex with TIMP1 and β1-integrin, activated the nuclear factor кB (NF-кB) and mitogen-activated protein kinase (MAPK) signaling pathways, and contributed to vemurafenib resistance. Potentially, the aptamer LL4A may be used diagnostically and therapeutically in humans to treat targeted vemurafenib-resistant melanoma

Galactic Disk Bulk Motions as Revealed by the LSS-GAC DR2

We report a detailed investigation of the bulk motions of the nearby Galactic stellar disk, based on three samples selected from the LSS-GAC DR2: a global sample containing 0.57 million FGK dwarfs out to $\sim$ 2 kpc, a local subset of the global sample consisting $\sim$ 5,400 stars within 150 pc, and an anti-center sample containing $\sim$ 4,400 AFGK dwarfs and red clump stars within windows of a few degree wide centered on the Galactic anti-center. The global sample is used to construct a three-dimensional map of bulk motions of the Galactic disk from the solar vicinity out to $\sim$ 2 kpc with a spatial resolution of $\sim$ 250 pc. Typical values of the radial and vertical components of bulk motion range from $-$15 km s$^{-1}$ to 15 km s$^{-1}$, while the lag behind the circular speed dominates the azimuthal component by up to $\sim$ 15 km s$^{-1}$. The map reveals spatially coherent, kpc-scale stellar flows in the disk, with typical velocities of a few tens km s$^{-1}$. Bending- and breathing-mode perturbations are clearly visible, and vary smoothly across the disk plane. Our data also reveal higher-order perturbations, such as breaks and ripples, in the profiles of vertical motion versus height. From the local sample, we find that stars of different populations exhibit very different patterns of bulk motion. Finally, the anti-center sample reveals a number of peaks in stellar number density in the line-of-sight velocity versus distance distribution, with the nearer ones apparently related to the known moving groups. The "velocity bifurcation" reported by Liu et al. (2012) at Galactocentric radii 10--11 kpc is confirmed. However, just beyond this distance, our data also reveal a new triple-peaked structure.Comment: 27 pages, 17 figures, Accepted for publication in a special issue of Research in Astronomy and Astrophysics on LAMOST science

Expression and Activity of the Signaling Molecules for Mitogen-Activated Protein Kinase Pathways in Human, Bovine, and Rat Lenses

PURPOSE. The mitogen-activated protein kinase (MAPK) pathways play distinct roles in the lens. However, the expression patterns and activity levels of various components for these pathways have not been well-documented in vertebrate lenses, especially human lens. In the present study, the expressions and activities of extracellular signal-regulated kinase (ERK)-1/ 2/3, c-Jun NH2-terminal kinase (JNK)-1/2, p38 kinase, mitogenactivated protein kinase kinase (MEK)-1/2, and RAF1 were recorded in human, bovine, and rat lenses. METHODS. Human, bovine, and rat lenses were isolated from intact eyes. The epithelia and different layers of fiber cells were isolated from these lenses. Total proteins extracted from these samples were subject to analysis of the expression patterns and activity levels of the MAPKs and the activating kinases of ERK1/2. RESULTS. ERK1 and ERK2 were the most abundant MAPKs in terms of both protein and activity levels in all lenses. JNK1 and JNK2 were highly expressed in bovine lens, which differed from the pattern shared by human and rat lenses. p38 kinase was similarly expressed in bovine and rat lenses, but different from that in human lens. However, p38 kinase activity was exclusively detected in the epithelia. All lenses had MEK1/2 activity in their epithelia but the expression patterns of MEK1 and MEK2 differed in these lenses. RAF1 was expressed in the epithelia of all lenses, but its activity was detected only in rat lens. CONCLUSIONS. ERK1 and ERK2 are the most abundant MAPKs in the ocular lens, providing the basis for their multiple functions in lens development and pathogenesis. The dominant epithelial distribution of JNK1/2 and p38 kinase suggests that the lens epithelium is a major site for stress response. ERK1, p38 kinase, and PKC␣ can be used as molecular markers for aging. (Invest Ophthalmol Vis Sci. 2003;44:5277-5286

Alterations in amino acid levels and metabolite ratio of spinal cord in rat with myocardial ischemia-reperfusion injury by proton magnetic resonance spectroscopy

Abstract Objectives The mechanism behind spinal metabolites and myocardial ischemia-reperfusion (IR) injury is not well understood. Proton magnetic resonance spectroscopic analysis of spinal cord extracts provides a quick evaluation of the specific metabolic activity in rats with myocardial IR injury. We investigated the relationship between the IR-related variables and the changes in spinal metabolites. Methods Proton magnetic resonance spectroscopy (1H-MRS) was used to assess the spinal metabolites of adult rats with and without myocardial IR injury (n=6 per group). Myocardial IR injury was reproduced using intermittent occlusion of the left anterior descending coronary artery. We studied the relationship between the metabolite ratio measurement and IR-related variables. All rats underwent 1H-MRS, with the ratio of interest placed in different spinal cord segments to measure levels of twelve metabolites including N-acetylaspartate (NAA), taurine (Tau),glutamate (Glu),gamma amino acid butyric acid (GABA),creatine (Cr), and myoinositol (MI), etc. Results Rats with myocardial IR injury had higher concentration of Tau in the upper thoracic spinal cord (p< 0.05), and lower concentration of Gly and Glu in the cervical segment of the spinal cord (p< 0.05), when compared to the Control group. The ratios of glutamate/taurine (Glu/Tau), Glu/(GABA+Tau) and Glu/Total were significantly different between the IR group and the Control group in the upper thoracic spinal cord (p< 0.05). So were the ratios of Glu/(GABA+Tau) in the cervical segment (p< 0.05),and Glu/Tau and Glu/(GABA+Tau) in the lower thoracic spinal cord (p< 0.05). Conclusions These findings suggest that myocardial IR injury may be related to spinal biochemical alterations. It is speculated that these observed changes in the levels of spinal metabolites may be involved in the pathogenesis and regulation of myocardial IR injury. Keywords: myocardial ischemia-reperfusion injury; spinal cord; metabolomics; proton nuclear magnetic resonanc

7-Hydroxy-4,6-dimethyl-3H-isobenzofuran-1-one

The structure of the title compound, C10H10O3, a colourless lump metabolite isolated from Diaporthe phaseolorum, was determined by X-ray analysis. The molecular packing in the crystal structure is stabilized by weak O - (HO)-O-... = C hydrogen-bonding interactions

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte

Designable ultra-smooth ultra-thin solid-electrolyte interphases of three alkali metal anodes

该研究是在毛秉伟教授和董全峰教授共同指导下，由2014级博士生谷宇、2016级博士生王卫伟、2013级博士生李艺娟等同学通力合作的成果。泉州师范学院吴启辉教授和上海应用物理研究所樊春海研究员分别在X射线光电子能谱表征和同步辐射表征中提供了大力支持。化学化工学院郑明森副教授、颜佳伟教授、吴德印教授、iChEM研究员丁松园博士在实验和理论计算方面给予了大力帮助；田中群教授和郑南峰教授等对此工作提出了宝贵意见。 金属锂是下一代高能量密度二次电池最理想的负极材料之一。在以金属锂作为负极的电池中，锂电沉积过程中枝晶的生长及溶解过程的死锂现象是制约电池库仑效率、稳定性和安全性的重要因素，而金属锂表面的微观平整性及固态电解质界面（SEI）膜的组成和结构及由其所决定的电学和力学性质对锂电沉积和溶解行为有重要影响。 课题组所发展的电化学调控方法可进一步拓展到钠、钾碱金属负极上，形成大范围原子平整的钠、钾表面和超薄超光滑的SEI膜。特别是金属钠平面电极可在2 mA cm–2（1 mAh cm–2）100% Na DOD下稳定循环550周以上且库伦效率近100%。这一基于电化学调控的碱金属表面抛光和SEI膜构筑的方法及多尺度联合表征，为解决碱金属负极问题提供了新的思路，也为开展表面科学基础研究提供高质量的碱金属表面。【Abstract】Dendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm-2 with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.This work was supported by the MOST projects (2015CB251102, 2012CB932902) and the NSFC projects (U1305246, 21621091, 21473147, 21533006, 21673193). 研究工作得到科技部973计划（项目批准号：2015CB251102、2012CB932902），国家自然科学基金（项目批准号：U1305246、21621091、21473147、21533006、21673193）等项目的资助