1,947 research outputs found

    MicroRNA roles in beta-catenin pathway

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    β-catenin, a key factor in the Wnt signaling pathway, has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to various disease pathologies, including an important role in tumorigenesis. Here, we review the regulation of the Wnt signaling pathway as it relates to β-catenin signaling in tumorigenesis, with particular focus on the role of microRNAs. Finally, we discuss the potential of β-catenin targeted therapeutics for cancer treatment

    Discovery of Furanoquinone Derivatives as a Novel Class of DNA Polymerase and Gyrase Inhibitors for MRSA Eradication in Cutaneous Infection

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    Methicillin-resistant Staphylococcus aureus (MRSA) is the primary microbe responsible for skin infections that are particularly difficult to eradicate. This study sought to inhibit planktonic and biofilm MRSA using furanoquinone-derived compounds containing imine moiety. A total of 19 furanoquinone analogs were designed, synthesized, and assessed for anti-MRSA potency. Among 19 compounds, (Z)-4-(hydroxyimino)naphtho[1,2-b]furan-5(4H)-one (HNF) and (Z)-4-(acetoxyimino)naphtho[1,2-b]furan-5(4H)-one (ANF) showed antibacterial activity superior to the others based on an agar diffusion assay. HNF and ANF exerted a bactericidal effect with a minimum inhibitory concentration (MIC) of 9.7 ∼ 19.5 and 2.4 ∼ 9.7 μg/ml, respectively. Both compounds were able to reduce the MRSA count by 1,000-fold in biofilm as compared to the control. In vivo efficacy was evaluated using a mouse model of skin infection. Topical application of lead compounds significantly suppressed abscess occurrence and the MRSA burden, and also ameliorated the skin-barrier function. The biochemical assay indicated the compounds’ inhibition of DNA polymerase and gyrase. In silico docking revealed a favorable interaction of the compounds with DNA polymerase and gyrase although the binding was not very strong. The total DNA analysis and proteomic data suggested a greater impairment of some proteins by HNF than ANF. In general, HNF and ANF were similarly potent in MRSA inhibition in vitro and in vivo. The findings demonstrated that there was room for structural modification of furanoquinone compounds that could be used to identify anti-MRSA agent candidates

    Advantage of laparoscopic surgery in patients with generalized obesity operated for colorectal malignancy: A retrospective cohort study

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    BackgroundBecause of the progression of minimally invasive surgery skills and obesity in colorectal surgery, we aimed to evaluate the short-term outcomes of colorectal cancer resections in patients with generalized obesity at a single teaching hospital with mature surgical techniques and training programs.MethodsA total of 537 patients were diagnosed with CRC and had a body mass index ≥30 kg/m2 between January 2009 and December 2019 at a single institution. 265 patients underwent open surgery and 272 patients underwent laparoscopic surgery. Data were analysed to explore the independent risk factors for postoperative complications.ResultsThe laparoscopic group had less blood loss (73 ± 128 vs. 148 ± 290 ml, p < 0.001) and a shorter postoperative hospital stay (10.8 ± 17.1 vs. 11.7 ± 6.8 days, p < 0.001) than the open group. The number of harvested lymph nodes did not significantly differ between the two groups (30.9 ± 18.3 vs. 30.2 ± 15.3, p = 0.981). Although anastomotic leakage was significantly higher in the laparoscopic group (1.5% vs. 4.8%, p = 0.030), there were also similar overall postoperative morbidity and mortality rates between the open and laparoscopic groups for CRC patients with generalized obesity who underwent surgery.ConclusionLaparoscopic surgery can reduce blood loss, decrease the length of hospital stay, obtain a similar number of harvested lymph nodes, and achieve an acceptable conversion rate for CRC patients with generalized obesity. We suggest that laparoscopic surgery could become a standard method for CRC treatment in patients with generalized obesity

    Pervasive brain monitoring and data sharing based on multi-tier distributed computing and linked data technology

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    EEG-based Brain-computer interfaces (BCI) are facing grant challenges in their real-world applications. The technical difficulties in developing truly wearable multi-modal BCI systems that are capable of making reliable real-time prediction of users’ cognitive states under dynamic real-life situations may appear at times almost insurmountable. Fortunately, recent advances in miniature sensors, wireless communication and distributed computing technologies offered promising ways to bridge these chasms. In this paper, we report our attempt to develop a pervasive on-line BCI system by employing state-of-art technologies such as multi-tier fog and cloud computing, semantic Linked Data search and adaptive prediction/classification models. To verify our approach, we implement a pilot system using wireless dry-electrode EEG headsets and MEMS motion sensors as the front-end devices, Android mobile phones as the personal user interfaces, compact personal computers as the near-end fog servers and the computer clusters hosted by the Taiwan National Center for High-performance Computing (NCHC) as the far-end cloud servers. We succeeded in conducting synchronous multi-modal global data streaming in March and then running a multi-player on-line BCI game in September, 2013. We are currently working with the ARL Translational Neuroscience Branch and the UCSD Movement Disorder Center to use our system in real-life personal stress and in-home Parkinson’s disease patient monitoring experiments. We shall proceed to develop a necessary BCI ontology and add automatic semantic annotation and progressive model refinement capability to our system

    Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China

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    AimsThis study aims to describe the clinical characteristics, laboratory data and complications of hospitalized COVID-19 patients with type 2 diabetes mellitus (T2DM) since epidemic prevention and control optimization was adjusted in December 2022 in China.MethodsThis retrospective multicenter study included 298 patients with confirmed type 2 diabetes mellitus with or without COVID-19. We collected data from the first wave of the pandemic in The Fifth Affiliated Hospital of Guangzhou Medical University, Loudi Central Hospital and The First People’s Hospital of Xiangtan from December 1, 2022 to February 1, 2023. We extracted baseline data, clinical symptoms, acute complications, laboratory findings, treatment and outcome data of each patient from electronic medical records.ResultsFor among 298 hospitalized patients with type 2 diabetes, 136 (45.6%) were COVID-19 uninfected, and 162 (54.4%) were COVID-19 infected. We found that the incidence of cough, fatigue, fever, muscle soreness, sore throat, shortness of breath, hyposmia, hypogeusia and polyphagia (all p<0.01) were significantly higher in the exposure group. They showed higher levels of ketone (p=0.04), creatinine (p<0.01), blood potassium (p=0.01) and more diabetic ketoacidosis (p<0.01). Patients with COVID-19 less use of metformin (p<0.01), thiazolidinediones (p<0.01) and SGLT2 (p<0.01) compared with patients without COVID-19.ConclusionCOVID-19 patients with diabetes showed more severe respiratory and constitutional symptoms and an increased proportion of hyposmia and hypogeusia. Moreover, COVID-19 patients with diabetes have a higher incidence of acute complications, are more prone to worsening renal function, and are more cautious about the use of antidiabetic drugs

    Advances in Molecular Quantum Chemistry Contained in the Q-Chem 4 Program Package

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    A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    The Forward Physics Facility at the High-Luminosity LHC

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    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

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    Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio
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