MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

This is the published version, also available here: http://dx.doi.org/10.1371/journal.pone.0006816.Background MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. Methodology/Principal Findings We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo. Conclusions/Significance Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53–miR34, potentially via inhibiting pancreatic cancer stem cells

MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting pancreatic cancer stem cells

Artificial coloration of ancient agate beads: a mineralogical study

Abstract The process of staining was frequently employed to enhance or alter the color of agate beads in ancient times. One of the key challenges in studying ancient beads is comprehending the intricate techniques employed to color agate stones. An understanding of the staining mechanism from a mineralogical standpoint offers insights into the level of technological advancement in different civilizations. In this study, the mineral structure of eight ancient agate beads from Xinjiang Uygur Autonomous Region, NW China, was analyzed using Micro X-ray fluorescence (µXRF), Raman spectroscopy, Scanning Electron Microscope (SEM), and Fourier Transform Infrared (FTIR) techniques. The color, transparency, mineral phase, and surface roughness of the beads were examined, revealing variations ranging from colorless to light violet to dark violet. Raman and FTIR spectroscopy were employed to determine the SiO2 phase and the changes in optical characteristics of agate beads after artificial staining. The black color of the beads was formed by carbon penetration, while the red color was produced by heating. The coexistence of α-quartz and moganite phases in the red, the dark red, the black, the idiochromatic white and the part translucent zones of the ancient beads was confirmed by the 464 cm−1 peak of α-quartz and the 502 cm−1 peak of moganite phase. The analyzed red, the dark red, the black, the idiochromatic white and the part translucent zones exhibited remarkably similar FTIR spectral features, with two prominent bands at ~ 1097 and ~ 1187 cm−1, as well as two weak bands at 798 and 778 cm−1, indicating the presence of moganite and α-quartz in the unetched ancient beads. In contrast to the idiochromatic white appearance of natural agate, the scattered white coloration in etched beads was generated by an etching reaction. Both Raman and FTIR spectroscopy indicated the absence of moganite in etched beads, indicating that the scattered white color was produced by the loss of moganite and a portion of α-quartz, resulting in a rough surface

Interplay between remote single-atom active sites triggers speedy catalytic oxidation

Understanding interaction between active sites in heterogeneous catalysis is a grand challenge owing to difficulty in extracting information from different active sites. We report a solution to this problem by showing that electron conduction can facilitate direct interplay of distant active sites. By fabricating two single-atom site catalysts (manganese dioxide-encapsulated metallic silver atomic wires) with one or two ending silver atoms of each wire exposed on surfaces, we find that only the catalyst with both ending silver atoms exposed can trigger low-temperature carbon monoxide oxidation, which provides unequivocal evidence that interaction between active sites is possible upon eligible electron conducting. This result indicates that the interaction between active sites might be universally present in catalysis reactions when there is effective communication between the active sites

Chirality engineering for carbon nanotube electronics

Carbon nanotubes (CNTs), tubular nanostructures consisting ofrolled-up graphene, are promising materials for electronic devices atthe nanometre and molecular regimes. Fundamentally, the electronicproperties of CNTs and their junctions depend on global and localchiralities, as defined by quantum boundary conditions along thecircumferential and longitudinal directions. As such, CNTs can behaveas a metal, a semiconductor or a quantum dot in an electronic device.Much of the progress in CNT electronics, going from single resistors andtransistors to complex functional logic and communication devices,thin films and flexible electronics, sensors and intelligent systems, hasbeen achieved through control over the ‘global chirality’ of CNTs —the distribution of chiralities at the macroscale. In this Review, wesummarize approaches to control global and local CNT chiralities bygrowth, separation and transformation strategies. We then discussopportunities and challenges for chirality engineering towardssurpassing the performance of conventional electronic devices, anddevelopment of unconventional CNT quantum electronics includingcoherent quantum transistors and quantum sensors

Stable single atomic silver wires assembling into a circuitry-connectable nanoarray

Atomic metal wires have great promise for practical applications in devices due to their unique electronic properties. Unfortunately, such atomic wires are extremely unstable. Here we fabricate stable atomic silver wires (ASWs) with appreciably unoccupied states inside the parallel tunnels of α-MnO2 nanorods. These unoccupied Ag 4d orbitals strengthen the Ag–Ag bonds, greatly enhancing the stability of ASWs while the presence of delocalized 5s electrons makes the ASWs conducting. These stable ASWs form a coherently oriented three-dimensional wire array of over 10 nm in width and up to 1 μm in length allowing us to connect it to nano-electrodes. Current-voltage characteristics of ASWs show a temperature-dependent insulator-to-metal transition, suggesting that the atomic wires could be used as thermal electrical devices.</p

Nuclear expression of Twist promotes lymphatic metastasis in esophageal squamous cell carcinoma

China Postdoctoral Science Foundation [20090461447]; National Natural Science Foundation of China [81172288]Twist-1 protein (also called Twist) has been suggested to be involved in tumor epithelial-mesenchymal transition (EMT) related progression, however, the mechanism by which Twist promotes lymph node metastasis is not fully understood. In the present study, we found that nuclear Twist expression is clearly correlated with lymph node (LN) metastasis as determined by immunohistochemistry (IHC). A highly invasive EC109 cell subline, EC109-P, was established by repeated in vitro transwell isolations for the cell model. Immunofluorescence (IF) assay demonstrated that nuclear Twist expression was markedly higher in the highly invasive EC109-P cell line when compared with EC109 and EC9706 cells. Based on our cell model, the function and mechanism by which Twist regulates LN metastasis in ESCC was investigated. The results showed that the overexpression of Twist could significantly increase the invasion and VEGF-C expression of EC9706 cells, whereas the knockdown of Twist expression results in the opposite effects. This finding was further strengthened by the results of the analysis of co-expression of Twist and VEGF-C by IHC in ESCC clinical samples. In summary, our study indicates that nuclear Twist plays an important role in ESCC lymphatic metastasis by increasing the expression of VEGF-C. The combination of Twist and VEGF-C detection could be a reliable prediction of LN metastasis in ESCC

Few-layer graphitic shells networked by low temperature pyrolysis of zeolitic imidazolate frameworks

Few-layer graphitic shell networks show great promise in energy storage applications such as electrochemical accommodation of alkaline ions. However, the networking and graphitization processes remain a challenge because of the complicated procedures and high temperature used for fabrication. In this work, we report a simple synthetic method by employing low-temperature solid-state pyrolysis of ZIF-67 crystals to weave graphitic shells consisting of 3-10 layers into capsules. Owing to their unique structure, the few-layer graphitic shell networks show excellent electrochemical performance for fast sodium ion storage