Next generation sequencing as a new detection strategy for maternal cell contamination in clinical prenatal samples

Objectives: The maternal cell contamination in chorionic villus or amniotic fluid presents a serious preanalytical risk for prenatal misdiagnosis. The following study presents and validates a novel process for identifying MCC by detecting short tandem repeat markers on Ion Proton system. Initially, MCC testing was performed during the detection of chromosomal abnormalities so as to improve the detection efficiency and accuracy of this method. Material and methods: More than 70 STR loci were selected to establish the detection progress. Capillary electrophoresis was used to compare the next generation sequencing detection results, as well as to identify the optimal STR on Ion Proton system. Evaluation criteria for maternal cell contamination were set, and the automated data analysis was performed. The detection sensitivity was validated via 4 groups with mixed samples and different proportions. Results: Consequently, twenty-three clinical samples were tested to evaluate the detection accuracy. In addition, 14 reli­able STR loci, which were stably detected in more than 25 samples, were found. The detection sensitivity in maternal cell contamination was no less than 20%, while its accuracy reached 100% in clinical samples. Conclusions: Finally, we established and validated a novel detection procedure for maternal cell contamination in clinical prenatal samples using next generation sequencing. This procedure allowed us to simultaneously perform prenatal test­ing and MCC testing. Unlike the traditional capillary electrophoresis, this method is rapid, highly sensitive, and suitable for wide range of clinical applications

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

<p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X₇receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X₇system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X₇action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X₇-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X₇pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X₇specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X₇-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X₇receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X₇receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X₇-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X₇-dependent apoptosis is mediated by calcium influx via P2X₇pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X₇receptor. (d) Activation of P2X₇-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p

Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $\eta$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $\eta$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$

Wireless power transmission for remote-relay-nodes-aided smart metering

Wireless power transmission is a promising technique to provide continuous power supply for the limited capacitance of smart meters (SMs) with short distance communication. In this study, the authors propose a remote-relay-nodes (RRNs)-aided wireless SM system, where several geographically separated RRNs are connected to a concentrator or an acquire terminal via radio-over-fibre. A RRN selection scheme is employed in the wireless power transfer phase. With the energy harvested, the SM can report special or urgent events in the wireless information transfer phase. The asymptotic reporting probability and reliability of smart metering are derived in terms of close form over fading channels. Numerical results are provided to verify the theoretical analysis. The optimal deployment of RRNs can be also efficiently obtained by averaging the locations of a SM in the network

Silage Fermentation: A Potential Biological Approach for the Long-Term Preservation and Recycling of Polyphenols and Terpenes in Globe Artichoke (Cynara scolymus L.) By-Products

An economic and effective method for storage is necessary to make full use of the nature of active components in artichoke by-products and ease environmental pressure. In this paper, the potential of silage fermentation for the preservation and recycling of polyphenols and terpenes in artichoke by-products is evaluated. The silage of artichoke by-products is characterized by lactic acid bacteria fermentation. Silage distinctly increases the abundance of lactic acid bacteria in artichoke by-products, such as Lactobacillus, Lactococcus, Serratia, and Weissella, and greatly increases the abundance of Firmicutes. The improvement of the microorgan structure and composition is of great significance for the quality of artichoke by-products. Polyphenols in the stems and leaves of artichokes are preserved well in silage. Among the 18 polyphenol compounds detected by high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS), the contents of 11 phenolic acids and four flavonoids increased significantly. For terpenes detected by gas chromatography-mass spectrometry (GC-MS), the contents of four pentacyclic triterpenoids increased significantly, while two sterols were kept stable in the silage process. Silage is a potential biotechnology for the long-term preservation of bioactive components, such as polyphenols and terpenes in artichoke by-products, and the results provide a scientific basis for the efficient utilization of by-products

STING Signaling Promotes Inflammation in Experimental Acute&nbsp;Pancreatitis

Background &amp; aimsAcute pancreatitis (AP) is characterized by severe inflammation and acinar cell death. Transmembrane protein 173 (TMEM173 or STING) is a DNA sensor adaptor protein on immune cells that recognizes cytosolic nucleic acids and transmits signals that activate production of interferons and the innate immune response. We investigated whether leukocyte STING signaling mediates inflammation in mice with AP.MethodsWe induced AP in C57BL/6J mice (control) and C57BL/6J-Tmem173gt/J mice (STING-knockout mice) by injection of cerulein or placement on choline-deficient DL-ethionine supplemented diet. In some mice, STING signaling was induced by administration of a pharmacologic agonist. AP was also induced in C57BL/6J mice with bone marrow transplants from control or STING-knockout mice and in mice with disruption of the cyclic GMP-AMP synthase (Cgas) gene. Pancreata were collected, analyzed by histology, and acini were isolated and analyzed by flow cytometry, quantitative polymerase chain reaction, immunoblots, and enzyme-linked immunosorbent assay. Bone-marrow-derived macrophages were collected from mice and tested for their ability to detect DNA from dying acinar cells in the presence and absence of deoxyribonuclease (DNaseI).ResultsSTING signaling was activated in pancreata from mice&nbsp;with AP but not mice without AP. STING-knockout mice developed less severe AP (less edema, inflammation, and markers of pancreatic injury) than control mice, whereas mice given a STING agonist developed more severe AP than controls. In immune cells collected from pancreata, STING was expressed predominantly in macrophages. Levels of cGAS were increased in mice with vs without AP, and cGAS-knockout mice had decreased edema, inflammation, and other markers of pancreatic injury upon induction of AP than control mice. Wild-type mice given bone marrow transplants from STING-knockout mice had less pancreatic injury and lower serum levels of lipase and pancreatic trypsin activity following induction of AP than mice given wild-type bone marrow. DNA from dying acinar cells activated STING signaling in macrophages, which was inhibited by addition of DNaseI.ConclusionsIn mice with AP, STING senses acinar cell death (by detecting DNA from dying acinar cells) and activates a signaling pathway that promotes inflammation. Macrophages express STING and activate pancreatic inflammation in AP

In situ fabrication of high-permeance ZIF-8 tubular membranes in a continuous flow system

A high-permeance ZIF-8 membrane was successfully synthesized on the inner side of a porous hollow fiber ceramic tube in a simple flow system via in situ direct growth method. The continuously pumping fresh nutrients through the inner-surface favor increasing the heterogeneous nucleation of ZIF-8 crystals and the formation of continuous ZIF-8 membrane, thus leading to a high performance ZIF-8 membrane. The achieved ZIF-8 membrane was thin and dense, and has only a thickness of about 2.5 mu m. The membrane demonstrated remarkably high H-2 permeance of 1.9 x 10(-6) mol m(-2) s(-1) and excellent molecular sieving performance with H-2/N-2, and H-2/CH4 ideal selectivities of 12.9 and 15.6, respectively. (C) 2014 Elsevier B.V. All rights reserved