Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of ...butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro. Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines’ secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.
A novel method to realize high spatial resolution distributed strain measurement is proposed based on phase demodulation scheme of optical frequency domain reflectometry (OFDR). Strain information ...can be demodulated directly by analyzing the phase change of Rayleigh backscattered light. Strain location can be obtained with high spatial resolution by cross-correlation method using a wide scanning range of tunable laser source. Based on the above scheme, breakpoint detection with 0.1 mm spatial resolution has been demonstrated, static and dynamic strain up to 100 Hz could be distributedly measured with 10 cm spatial resolution over 200 m sensing fiber, and the minimum measurable strain is about 1 με.
The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein ...phosphatases responsible for the dephosphorylation of EZH2‐S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT‐EZH2 axis is important in TGFβ‐induced epithelial‐mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2‐S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2‐S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2‐S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.
MYPT1/PP1 is identified as the specific protein phosphatase for dephosphorylating histone methyltransferase enhancer of zeste homolog 2 (EZH2) at S21 residue, demonstrating that EZH2 dephosphorylation/EZH2‐S21A expression causes global changes in multiple families of genes implicated in epithelial‐mesenchymal transition (EMT), contributing to fibrotic diseases, and revealing that AKT‐EZH2‐H3K27Me3 signal axis plays an important role in lens EMT induced by TGFβ and mediates pathogenesis of anterior subcapsular cataract (ASC).
Abstract Background: There are few reports on the chest computed tomography (CT) imaging features of children with coronavirus disease 2019 (COVID-19), and most reports involve small sample sizes. ...Objectives: To systematically analyze the chest CT imaging features of children with COVID-19 and provide references for clinical practice. Data sources: We searched PubMed, Web of Science, and Embase; data published by Johns Hopkins University; and Chinese databases CNKI, Wanfang, and Chongqing Weipu. Methods: Reports on chest CT imaging features of children with COVID-19 from January 1, 2020 to August 10, 2020, were analyzed retrospectively and a meta-analysis carried out using Stata12.0 software. Results: Thirty-seven articles (1747 children) were included in this study. The heterogeneity of meta-analysis results ranged from 0% to 90.5%. The overall rate of abnormal lung CT findings was 63.2% (95% confidence interval CI: 55.8%–70.6%), with a rate of 61.0% (95% CI: 50.8%–71.2%) in China and 67.8% (95% CI: 57.1%–78.4%) in the rest of the world in the subgroup analysis. The incidence of ground-glass opacities was 39.5% (95% CI: 30.7%–48.3%), multiple lung lobe lesions was 65.1% (95% CI: 55.1%–67.9%), and bilateral lung lesions was 61.5% (95% CI: 58.8%–72.2%). Other imaging features included nodules (25.7%), patchy shadows (36.8%), halo sign (24.8%), consolidation (24.1%), air bronchogram signs (11.2%), cord-like shadows (9.7%), crazy-paving pattern (6.1%), and pleural effusion (9.1%). Two articles reported 3 cases of white lung, another reported 2 cases of pneumothorax, and another 1 case of bullae. Conclusions: The lung CT results of children with COVID-19 are usually normal or slightly atypical. The lung lesions of COVID-19 pediatric patients mostly involve both lungs or multiple lobes, and the common manifestations are patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs; white lung, pleural effusion, and paving stone signs are rare. Therefore, chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool.
The purity of the synthesized orbital-angular-momentum (OAM) light in the fiber is inversely proportional to channel crosstalk level in the OAM optical fiber communication system. Here the ...relationship between the fiber structure and the purity is firstly demonstrated in theory. The graded-index optical fiber is proposed and designed for the OAM light propagation with the purity higher than 99.9%. 16 fiber modes (10 OAM modes) have been supported by a specific designed graded-index optical fiber with dispersion less than 35 ps/(km∙nm). Such fiber design has suppressed the intrinsic crosstalk to be lower than -30 dB, and can be potentially used for the long distance OAM optical communication system.
Site‐selective N‐1 and C‐3 arylation of indole has been sought after because of the prevalent application of arylindoles and the intricate reactivities associated with the multiple sites of the ...N‐unsubstituted indole. Represented herein is the first regioselective heteroarylation of indole via a radical–radical cross‐coupling by visible‐light irradiation. Steady and time‐resolved spectroscopic and computational studies revealed that the hydrogen‐bonding interaction of organic base and its conjugated acid, namely with indole and heteroarylnitrile, determined the reaction pathway, which underwent either proton‐coupled electron‐transfer or energy‐transfer for the subsequent radical–radical cross‐coupling, leading to the regioselective formation of C‐3 and N‐1 heteroarylation of indoles, respectively. The parallel methodologies for regioisomeric N‐1 and C‐3 heteroaryl indoles with good functional group compatibility could be applied to large‐scale synthesis and late‐stage derivatization of bioactive compounds under extremely mild reaction conditions.
The first regioselective, parallel methodologies for N‐1 and C‐3 heteroarylation of indoles via radical–radical cross‐coupling by visible light irradiation have been developed with the aid of organocatalysis. Mechanism studies revealed that the reaction pathway switches from energy‐transfer to proton‐coupled electron‐transfer by consecutive hydrogen‐bonding association between the organic base and its conjugate acid, with the radical species of the indole and heteroarylnitrile.
Polylactic acid (PLA) microfibrous membranes, having high comfort and wearability features, have attracted considerable research interest for applications involving skin contactors. However, the poor ...softness and low strength of these membranes are the major challenges that prevent their large-scale fabrication and application. Herein, an advanced strategy for preparing a soft, strong, and breathable polylactic acid/polyethylene glycol (PLA/PEG) microfibrous membrane using an in situ drafting-assisted melt-blowing process has been developed. The introduction of PEG significantly improved the crystallization and plasticization of the PLA chain molecules, thus promoting the perfect crystallinity of the PLA phase. Benefiting from the synergy of the PEG and the drafting process, the prepared PLA/PEG microfibrous membranes exhibited a fluffy structure wherein the air permeability increased to 142.5 mm/s with the increase in DCD to 37 cm. Meanwhile, the PLA/PEG microfibrous membranes exhibit optimized anisotropic softness performance: a smaller maximum resistance of 0.13 N in the machine direction and a larger maximum resistance of 1.8 N in the cross direction were obtained in comparison with conventional membranes. This suggests the tremendous potential for using the fabricated membranes in flexible, breathable, and wearable skin contactors.
Neutrino physics with JUNO An, Guangpeng; Antonelli, Vito; Baussan, Eric ...
Journal of physics. G, Nuclear and particle physics,
02/2016, Letnik:
43, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy (MH) as a ...primary physics goal. The excellent energy resolution and the large fiducial volume anticipated for the JUNO detector offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. In this document, we present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. Following an introduction summarizing the current status and open issues in neutrino physics, we discuss how the detection of antineutrinos generated by a cluster of nuclear power plants allows the determination of the neutrino MH at a 3-4 significance with six years of running of JUNO. The measurement of antineutrino spectrum with excellent energy resolution will also lead to the precise determination of the neutrino oscillation parameters , , and to an accuracy of better than 1%, which will play a crucial role in the future unitarity test of the MNSP matrix. The JUNO detector is capable of observing not only antineutrinos from the power plants, but also neutrinos/antineutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, and solar neutrinos. As a result of JUNO's large size, excellent energy resolution, and vertex reconstruction capability, interesting new data on these topics can be collected. For example, a neutrino burst from a typical core-collapse supernova at a distance of 10 kpc would lead to ∼5000 inverse-beta-decay events and ∼2000 all-flavor neutrino-proton ES events in JUNO, which are of crucial importance for understanding the mechanism of supernova explosion and for exploring novel phenomena such as collective neutrino oscillations. Detection of neutrinos from all past core-collapse supernova explosions in the visible universe with JUNO would further provide valuable information on the cosmic star-formation rate and the average core-collapse neutrino energy spectrum. Antineutrinos originating from the radioactive decay of uranium and thorium in the Earth can be detected in JUNO with a rate of ∼400 events per year, significantly improving the statistics of existing geoneutrino event samples. Atmospheric neutrino events collected in JUNO can provide independent inputs for determining the MH and the octant of the mixing angle. Detection of the 7Be and 8B solar neutrino events at JUNO would shed new light on the solar metallicity problem and examine the transition region between the vacuum and matter dominated neutrino oscillations. Regarding light sterile neutrino topics, sterile neutrinos with and a sufficiently large mixing angle could be identified through a precise measurement of the reactor antineutrino energy spectrum. Meanwhile, JUNO can also provide us excellent opportunities to test the eV-scale sterile neutrino hypothesis, using either the radioactive neutrino sources or a cyclotron-produced neutrino beam. The JUNO detector is also sensitive to several other beyondthe-standard-model physics. Examples include the search for proton decay via the decay channel, search for neutrinos resulting from dark-matter annihilation in the Sun, search for violation of Lorentz invariance via the sidereal modulation of the reactor neutrino event rate, and search for the effects of non-standard interactions. The proposed construction of the JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics in a timely and cost-effective fashion. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.
Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight ...O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The relationship between insomnia and hypertension remains inconclusive. Thus, we conducted a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of ...hypertension. Relevant prospective cohort studies were searched from PubMed, Embase, and Web of Science from their inception to October 2019. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). A total of fourteen prospective cohort studies involving 395,641 participants were included in this study. The pooled RR of insomnia on hypertension was 1.21 (95%CI: 1.10–1.33). An increased risk of hypertension was observed in participants with difficulty maintaining sleep (RR = 1.27; 95%CI: 1.04–1.55) and early morning awakening (RR = 1.14; 95%CI: 1.08–1.20), but was not statistically significant in participants with difficulty falling asleep (RR = 1.14; 95%CI: 0.95–1.37). In addition, the results were statistically significant in the European population (RR = 1.08, 95%CI: 1.02–1.14), but not significant in Asian and American populations (RR = 1.54, 95%CI: 0.98–2.40; RR = 1.21, 95%CI: 0.89–1.65). The study findings indicate that insomnia is associated with a significantly increased risk of hypertension. This may have substantial implications for the prevention of hypertension in individuals with insomnia symptoms.
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