Abstract N6-methyladenosine (m6A) is one of widespread post-transcriptional mRNA modifications in eukaryotes and the m6A modification plays critical roles in various human cancers. However, the role of m6A-binding proteins in cancer metabolism remains elusive. Here, we report that YTH domain family 2 (YTHDF2) is upregulated in lung cancer tissues, promotes lung cancer cell growth and enhances the pentose phosphate pathway (PPP) flux, which is crucial for tumor growth. Mechanistically, YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase (6PGD) three prime untranslated region (3′-UTR) to promote 6PGD mRNA translation in lung cancer cells. Collectively, our data indicate that YTHDF2 acts as a tumor promoter to enhance tumor growth via facilitating 6PGD mRNA translation.

A series of nonlinear optical (NLO) chromophores were successfully prepared, in which pyrrole moieties were the conjugated bridge. In comparison with their analogues containing furan or thiophene groups as the bridge, these chromophores demonstrated similar or enhanced NLO effects (up to 3.3 times) and interesting optical behavior. While the acceptor groups were malononitrile (Mal), 3-phenyl-5-isoxazolone (Iso), and 1,3-diethylthiobarbituric acid (Bar), the chromophores exhibited much blue-shifted maximum absorption wavelengths (lambda max) (up to 36 nm); however, the lambda max of the chromophore containing tricyanovinyldihydrofuran (TCF) as acceptor became much longer than that of the analogue (up to 75 nm).

This is the accepted version of the paper.This version of the publication may differ from the final published version. Permanent repository link City Research Online Abstract-In this paper, the design and underpinning technical principles of the novel design of a negative pressure wave (NPW)-based pipeline leak detection (PLD) system has been reported, which is configured using Fiber Bragg Grating (FBG) pressure sensors. To evaluate this, a pipeline leakage test platform has been established and experiments have been conducted, to verify the performance of a system using this FBG-based approach. The results show that a system using FBG-based sensors can accurately determine the pressure change trends along the pipeline and thus allow the calculation of the NPW velocity online. A key comparison is made with traditional NPW detection techniques, showing that the novel detection system is capable of achieving the higher leak-location accuracy and the detection of smaller leakage volumes. This arises from the ability of the FBG-based system to allow an increased number of sensors to be multiplexed along the pipeline. Their corresponding output signals generated show a very satisfactory, high signal-to-noise ratio. The system has been evaluated, especially in its response to extraneous signals and thus disturbances caused by the pump starting or stopping can be eliminated. This was achieved through an analysis of the time sequence of the pressure changes captured by the multi-sensor array being carried out and thus immunity to such effects demonstrated. The system has thus been designed to minimize the instances where a false alarm occurs.Index Terms-Pipeline leak detection (PLD), negative pressure wave (NPW), pressure sensor, fiber Bragg grating (FBG), pressure change.

Our previous studies have demonstrated that both the RhoA/Rho kinase and the protein kinase C (PKC) signaling pathways are involved in the low-dose endothelial monocyte-activating polypeptide-II (EMAP-II)-induced blood-tumor barrier (BTB) opening. In the present study, an in vitro BTB model was used to investigate which isoforms of PKC were involved in this process as well as the interactions between the RhoA/Rho kinase and the PKC signaling pathways. Our results showed that EMAP-II-activated PKC-α, β, and ζ and induced translocations of them from the cytosolic to the membrane fractions of rat brain microvascular endothelial cells. The EMAP-II-induced alterations in BTB permeability and tight junction (TJ) protein expression were partially blocked by GÖ6976, the inhibitor of PKC-α/β, and PKC-ζ pseudosubstrate inhibitor (PKC-ζ-PI). Meanwhile, we observed that GÖ6976 partly inhibited the EMAP-II-induced rearrangement of actin cytoskeleton as well as phosphorylation of myosin light chain and cofilin, whereas PKC-ζ-PI had no effect on these above-mentioned changes induced by EMAP-II. Also, our data revealed that inhibition of RhoA or inhibition of Rho kinase significantly diminished the activities and the translocations of PKC-α and PKC-β induced by EMAP-II, whereas PKC-ζ was unaffected. However, inhibition of PKC-α/β or inhibition of PKC-ζ did not cause any changes in the RhoA and Rho kinase activities. The effects of EMAP-II on BTB permeability and TJ proteins expression were completely blocked by inhibition of both RhoA and PKC-ζ, whereas inhibition of both RhoA and PKC-α/β had an effect similar to that of inhibition of RhoA alone. In summary, this study demonstrates for the first time that three PKC isoforms, PKC-α, β, and ζ, are involved in the EMAP-II-induced BTB opening. It is PKC-α/β, but not PKC-ζ, which serves as the downstream target for RhoA and Rho kinase, suggesting that EMAP-II induces BTB opening via the RhoA/Rho kinase/PKC-α/β signaling pathways. However, PKC-ζ is involved in this process by other mechanisms.

Background New-onset heart failure (HF) is associated with poor prognosis and high healthcare utilization. Early identification of patients at increased risk incident-HF may allow for focused allocation of preventative care resources. Health information exchange (HIE) data span the entire spectrum of clinical care, but there are no HIE-based clinical decision support tools for diagnosis of incident-HF. We applied machine-learning methods to model the one-year risk of incident-HF from the Maine statewide-HIE. Methods and results We included subjects aged ≥ 40 years without prior HF ICD9/10 codes during a three-year period from 2015 to 2018, and incident-HF defined as assignment of two outpatient or one inpatient code in a year. A tree-boosting algorithm was used to model the probability of incident-HF in year two from data collected in year one, and then validated in year three. 5,668 of 521,347 patients (1.09%) developed incident-HF in the validation cohort. In the validation cohort, the model c-statistic was 0.824 and at a clinically predetermined risk threshold, 10% of patients identified by the model developed incident-HF and 29% of all incident-HF cases in the state of Maine were identified. Conclusions Utilizing machine learning modeling techniques on passively collected clinical HIE data, we developed and validated an incident-HF prediction tool that performs on par with other models that require proactively collected clinical data. Our algorithm could be integrated into other HIEs to leverage the EMR resources to provide individuals, systems, and payors with a risk stratification tool to allow for targeted resource allocation to reduce incident-HF disease burden on individuals and health care systems.

No abstract

Colorectal cancer (CRC) is one of the most common malignancies in the world. Easier recurrence and metastasis is the main cause of mortality in CRC patients, and the markers applied for diagnosis and treatment of CRC is still urgently needed to early diagnose and evaluate therapeutic effect. Long noncoding RNA (lncRNA) is a class of noncoding RNA that the length is more than 200 nucleotides. With the development of sequencing technique about transcriptome, increasing lncRNAs are focused on their function and mechanism related to the nosogenesis and pathology of CRC. Recent studies report that lncRNAs acted as crucial role in CRC and could be as biomarker for CRC diagnosis and treatment. In this review, we display the regulation of lncRNA by interacting with DNA, RNA and protein and highlight the double role of lncRNAs as oncogene or anti-tumor gene involved in Wnt signaling pathway, p53 signaling pathway or others to be an regulator in CRC development. Lastly, we discuss some new finding of lncRNAs, especially lncRNA in exosome, which could be as potential markers for diagnosis and treatment of CRC in future.

This paper presents a study on the carbonation reaction heat and products of tricalcium silicate (C3S) paste exposed to carbon dioxide (CO2) for rapid curing. Reaction heat was measured using a retrofitted micro-calorimeter. The highest heat flow of a C3S paste subject to carbonation curing was 200 times higher than that by hydration, and the cumulative heat released by carbonation was three times higher. The compressive strength of a C3S paste carbonated for 2 h and 24 h was 27.5 MPa and 62.9 MPa, respectively. The 24-h carbonation strength had exceeded the hydration strength at 28 days. The CO2 uptake of a C3S paste carbonated for 2 h and 24 h was 17% and 26%, respectively. The X-ray diffraction (XRD), transmission electron microscope coupled with energy dispersive spectrometer (TEM-EDS), and 29Si magic angle spinning–nuclear magnetic resonance (29Si MAS-NMR) results showed that the products of a carbonated C3S paste were amorphous silica (SiO2) and calcite crystal. There was no trace of calcium silicate hydrate (C–S–H) or other polymorphs of calcium carbonate (CaCO3) detected.