NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

Maximizing the visible light photoelectrochemical activity of B/N-doped anatase TiO2 microspheres with exposed dominant {001} facets

This work was supported by the Major Basic Research Program, Ministry of Science and Technology of China (2014CB239401), the National Natural Science Fundation of China (51422210, 21633009, 51629201 and 51521091), the Key Research Program of Frontier Sciences CAS (QYZDB-SSW-JSC039). Liu G thanks Newton Advanced Fellowship.Anatase TiO2 microspheres with exposed dominant BBBBB001BBBBB facets were doped with interstitial boron to have a concentration gradient with the maximum concentration at the surface. They were then further doped with substitutional nitrogen by heating in an ammonia atmosphere at different temperatures from 440 to 560°C to give surface N concentrations ranging from 7.03 to 15.47 at%. The optical absorption, atomic and electronic structures and visible-light photoelectrochemical water oxidation activity of these materials were investigated. The maximum activity of the doped TiO2 was achieved at a nitrogen doping temperature of 520°C that gave a high absorbance over the whole visible light region but with no defect-related background absorption.PostprintPostprintPeer reviewe

Elevated expression of Toll-like receptor 4 and cytokines in both serum and myometrium at term may serve as promising biomarkers for uterine activation preceding labor

ObjectiveIncreased inflammation and cytokine levels are considered risk factors and promoters of preterm birth (PTB). However, the regulatory mechanism of pregnancy-related inflammation remains unclear. Toll-like receptor 4 (TLR4) plays a critical role in inflammatory responses in various diseases. Therefore, our study aimed to investigate whether TLR4 is involved in the inflammatory responses during uterine activation for labor, with the goal of identifying potential biomarkers for uterine activation at term.Materials and methodsWe used flow cytometry to detect TLR4 expression on CD14+ maternal blood monocytes in the first, second, and third trimesters. ELISA was employed to measure TLR4 and cytokines levels in the maternal serum of term non-labor (TNL), term labor (TL) women and LPS induced preterm labor and PBS injected controls. TLR4siRNA was transfected into the human myometrial smooth muscle cells (HMSMCs), which were subsequently treated with IL-1β. The mRNA and protein levels of TLR4, uterine contraction-related protein connexin 43 (CX43), oxytocin receptor (OTR), MAPK/NF-κB signaling pathway, and cytokines were analyzed using qRT-PCR, western blotting, and immunohistochemistry.ResultsThe study revealed TLR4 expression on CD14+ maternal blood monocytes was higher in the third trimester group compared to the first and second trimester groups (p<0.001). Maternal serum concentrations of TLR4 and cytokines were significantly higher in the TL group than the TNL group (p<0.001). TLR4, OTR, CX43, activated MAPK/NF-κB expression, and cytokines levels were upregulated in TL group, and similarly significantly higher in the LPS-induced preterm group than in the control group. Using the HMSMCs we demonstrated that TLR4siRNA transfection suppressed contractility. Interfering with TLR4 expression reduced the expression of OTR, CX43, cytokines, and MAPK/NF-κB activation. There was a significant positive relationship between TLR4 expression and the inflammatory status in the myometrium. ROC analysis indicated that TLR4 and cytokines may serve as potential biomarkers for predicting uterine activation for labor.ConclusionOur data suggest that TLR4 and cytokines can act as stimulators of uterine activation for labor at term. Furthermore, the MAPK/NF-κB pathway appears to be one of the potential signaling pathways mediating TLR4’s regulation of parturition initiation

Interfacial chemistry effects in the electrochemical performance of silicon electrodes under lithium‐ion battery conditions

Understanding the solid electrolyte interphase (SEI) formation and (de)lithiation phenomena at silicon (Si) electrodes is key to improving the performance and lifetime of Si‐based lithium‐ion batteries. However, these processes remain somewhat elusive, and, in particular, the role of Si surface termination merits further consideration. Here, scanning electrochemical cell microscopy (SECCM) is used in a glovebox, followed by secondary ion mass spectrometry (SIMS) at identical locations to study the local electrochemical behavior and associated SEI formation, comparing Si (100) with a native oxide layer (SiO x /Si) and etched with hydrofluoric acid (HF‐Si). HF‐Si shows greater spatial electrochemical heterogeneity and inferior lithiation reversibility than SiO x /Si. This is attributed to a weakly passivating SEI and irreversible lithium trapping at the Si surface. Combinatorial screening of charge/discharge cycling by SECCM with co‐located SIMS reveals SEI chemistry as a function of depth. While the SEI thickness is relatively independent of the cycle number, the chemistry – particularly in the intermediate layers – depends on the number of cycles, revealing the SEI to be dynamic during cycling. This work serves as a foundation for the use of correlative SECCM/SIMS as a powerful approach to gain fundamental insights on complex battery processes at the nano‐ and microscales

Light dark matter and Z′Z' dark force at colliders

Light Dark Matter, $<10$ GeV, with sizable direct detection rate is an interesting and less explored scenario. Collider searches can be very powerful, such as through the channel in which a pair of dark matter particle are produced in association with a jet. It is a generic possibility that the mediator of the interaction between DM and the nucleus will also be accessible at the Tevatron and the LHC. Therefore, collider search of the mediator can provide a more comprehensive probe of the dark matter and its interactions. In this article, to demonstrate the complementarity of these two approaches, we focus on the possibility of the mediator being a new $U(1)'$ gauge boson, which is probably the simplest model which allows a large direct detection cross section for a light dark matter candidate. We combine searches in the monojet+MET channel and dijet resonance search for the mediator. We find that for the mass of $Z'$ between 250 GeV and 4 TeV, resonance searches at the colliders provide stronger constraints on this model than the monojet+MET searches.Comment: 23 pages and 14 figure

The Next-to-Minimal Supersymmetric Standard Model

We review the theoretical and phenomenological aspects of the Next-to-Minimal Supersymmetric Standard Model: the Higgs sector including radiative corrections and the 2-loop beta-functions for all parameters of the general NMSSM; the tadpole and domain wall problems, baryogenesis; NMSSM phenomenology at colliders, B physics and dark matter; specific scenarios as the constrained NMSSM, Gauge Mediated Supersymmetry Breaking, U(1)'-extensions, CP and R-parity violation.Comment: 144 pages, 11 figures, corrections in Eqs.(2.2), (2.21), (B.9

A novel PCR-based method for high throughput prokaryotic expression of antimicrobial peptide genes

<p>Abstract</p> <p>Background</p> <p>To facilitate the screening of large quantities of new antimicrobial peptides (AMPs), we describe a cost-effective method for high throughput prokaryotic expression of AMPs. EDDIE, an autoproteolytic mutant of the N-terminal autoprotease, Npro, from classical swine fever virus, was selected as a fusion protein partner. The expression system was used for high-level expression of six antimicrobial peptides with different sizes: Bombinin-like peptide 7, Temporin G, hexapeptide, Combi-1, human Histatin 9, and human Histatin 6. These expressed AMPs were purified and evaluated for antimicrobial activity.</p> <p>Results</p> <p>Two or four primers were used to synthesize each AMP gene in a single step PCR. Each synthetic gene was then cloned into the pET30a/His-EDDIE-GFP vector via an <it>in vivo </it>recombination strategy. Each AMP was then expressed as an Npro fusion protein in <it>Escherichia coli</it>. The expressed fusion proteins existed as inclusion bodies in the cytoplasm and the expression levels of the six AMPs reached up to 40% of the total cell protein content. On <it>in vitro </it>refolding, the fusion AMPs was released from the C-terminal end of the autoprotease by self-cleavage, leaving AMPs with an authentic N terminus. The released fusion partner was easily purified by Ni-NTA chromatography. All recombinant AMPs displayed expected antimicrobial activity against <it>E. coli</it>, <it>Micrococcus </it>luteus and <it>S. cerevisia</it>.</p> <p>Conclusions</p> <p>The method described in this report allows the fast synthesis of genes that are optimized for over-expression in <it>E. coli </it>and for the production of sufficiently large amounts of peptides for functional and structural characterization. The Npro partner system, without the need for chemical or enzymatic removal of the fusion tag, is a low-cost, efficient way of producing AMPs for characterization. The cloning method, combined with bioinformatic analyses from genome and EST sequence data, will also be useful for screening new AMPs. Plasmid pET30a/His-EDDIE-GFP also provides green/white colony selection for high-throughput recombinant AMP cloning.</p