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We report a novel self-patterning method for solution-processed indium zinc oxide (IZO) thin films based on photosensitive precursors. This approach is an alternative and evolutionary approach to the traditional photoresist patterning techniques. Chelate bonds between metal ions and β-diketone compounds in ultraviolet light-exposed IZO solutions provided intrinsic photosensitivity, which resulted in a solubility difference between exposed and non-exposed regions. This difference enabled self-patterning of the IZO for thin-film transistor (TFT) fabrication. Compared with previously reported self-patterning methods based on photosensitive activators, our self-patterned IZO TFTs based on photosensitive precursors displayed excellent electrical characteristics and stability. The field-effect mobility increased from 0.27 to 0.99 cm2/Vs, the subthreshold swing decreased from 0.54 to 0.46 V/dec, and the threshold voltage shift under a positive bias stress test (1,000 s) improved from 9.32 to 1.68 V. The photosensitive precursor played a key role in these improvements permitting fewer organic species which act as defect sites after metal oxide formation. Consequently, our approach compares favorably with that of conventional fabrication process using photoresist in terms of its simplicity, cost efficiency, and electrical performance.The importance of dynamic factors in enzyme evolution is gaining recognition. Here we study how the evolution of a new enzymatic activity exploits conformational tinkering and demonstrate that conversion of a dimeric phosphotriesterase to an arylesterase in Pseudomonas diminuta is accompanied by structural divergence between the two subunits. Deviations in loop conformations increase with promiscuity, leading to functionally distinct states, while they decrease during specialisation for the new function. We show that opposite loop movements in the two subunits are due to a dynamic coupling with the dimer interface, the importance of which is also corroborated by the co-evolution of the loop and interface residues. These results illuminate how protein dynamics promotes conformational heterogeneity in a dimeric enzyme, leading to alternative evolutionary pathways for the emergence of a new function.A reliable diagnosis of adult Attention Deficit/Hyperactivity Disorder (ADHD) is challenging as many of the symptoms of ADHD resemble symptoms of other disorders. ADHD is associated with gambling disorder and obesity, showing overlaps of about 20% with each diagnosis. It is important for clinical practice to differentiate between conditions displaying similar symptoms via established diagnostic instruments. Applying the LightGBM algorithm in machine learning, we were able to differentiate subjects with ADHD, obesity, problematic gambling, and a control group using all 26 items of the Conners' Adult ADHD Rating Scales (CAARS-S S) with a global accuracy of .80; precision (positive predictive value) ranged between .78 (gambling) and .92 (obesity), recall (sensitivity) between .58 for obesity and .87 for ADHD. Models with the best 5 and best 10 items resulted in less satisfactory fits. The CAARS-S seems to be a promising instrument to be applied in clinical practice also for multiclassifying disorders displaying symptoms resembling ADHD.The recent implication of circular economy in Australia spurred the demand for waste material utilization for value-added product generations on a commercial scale. Therefore, this experimental study emphasized on agricultural waste biomass, rice husk (RH) as potential feedstock to produce valuable products. Rice husk biochar (RB) was obtained at temperature 180 °C, pressure 70 bar, reaction time 20 min with water via hydrothermal carbonization (HTC), and the obtained biochar yield was 57.9%. Enhancement of zeta potential value from - 30.1 to - 10.6 mV in RB presented the higher suspension stability, and improvement of surface area and porosity in RB demonstrated the wastewater adsorption capacity. Along with that, an increase of crystallinity in RB, 60.5%, also indicates the enhancement of the catalytic performance of the material significantly more favorable to improve the adsorption efficiency of transitional compounds. https://www.selleckchem.com/products/pimicotinib.html In contrast, an increase of the atomic O/C ratio in RB, 0.51 delineated high breakdown of the cellulosic component, which is favorable for biofuel purpose. 13.98% SiO2 reduction in RB confirmed ash content minimization and better quality of fuel properties. Therefore, the rice husk biochar through HTC can be considered a suitable material for further application to treat wastewater and generate bioenergy.The present paper studies the locations and linear stability of the triangular equilibrium points when both primaries are radiating and considered as heterogeneous spheroid with three layers of different densities. Additionally, we include the effects of small perturbations in the Coriolis and centrifugal forces and potential from a belt (circumbinary disc). It is observed that the positions of the triangular equilibrium points are substantially affected by all parameters (except a perturbation in Coriolis force) involved in the system.The stabilty of motion is found only when [Formula see text], where [Formula see text] is the critical mass value which depends on the combined effect of radiation pressures and heterogeneity of the primaries, small perturbations and the potential from a belt.It is also seen that the Coriolis force and the belt have stabilizing effect,while the centrifugal force, radiation and heterogeineity of the primaries have destabilizing behaviour.The net effect is that the size of the region of stability decreases when the value of these parameters increases where [Formula see text] is the mass ratio and [Formula see text] characterize heterogeneity of both primaries. A practical application of this model could be the study of motion of a dust grain near the heterogeneous and luminous binary stars surrounded by a belt.Finally, we carried out and discuss numerical experiments aiming at computing the positions of triangular points and critical masses of three binary systems Archid, Xi Booties and Kruger 60.
We report a novel self-patterning method for solution-processed indium zinc oxide (IZO) thin films based on photosensitive precursors. This approach is an alternative and evolutionary approach to the traditional photoresist patterning techniques. Chelate bonds between metal ions and β-diketone compounds in ultraviolet light-exposed IZO solutions provided intrinsic photosensitivity, which resulted in a solubility difference between exposed and non-exposed regions. This difference enabled self-patterning of the IZO for thin-film transistor (TFT) fabrication. Compared with previously reported self-patterning methods based on photosensitive activators, our self-patterned IZO TFTs based on photosensitive precursors displayed excellent electrical characteristics and stability. The field-effect mobility increased from 0.27 to 0.99 cm2/Vs, the subthreshold swing decreased from 0.54 to 0.46 V/dec, and the threshold voltage shift under a positive bias stress test (1,000 s) improved from 9.32 to 1.68 V. The photosensitive precursor played a key role in these improvements permitting fewer organic species which act as defect sites after metal oxide formation. Consequently, our approach compares favorably with that of conventional fabrication process using photoresist in terms of its simplicity, cost efficiency, and electrical performance.The importance of dynamic factors in enzyme evolution is gaining recognition. Here we study how the evolution of a new enzymatic activity exploits conformational tinkering and demonstrate that conversion of a dimeric phosphotriesterase to an arylesterase in Pseudomonas diminuta is accompanied by structural divergence between the two subunits. Deviations in loop conformations increase with promiscuity, leading to functionally distinct states, while they decrease during specialisation for the new function. We show that opposite loop movements in the two subunits are due to a dynamic coupling with the dimer interface, the importance of which is also corroborated by the co-evolution of the loop and interface residues. These results illuminate how protein dynamics promotes conformational heterogeneity in a dimeric enzyme, leading to alternative evolutionary pathways for the emergence of a new function.A reliable diagnosis of adult Attention Deficit/Hyperactivity Disorder (ADHD) is challenging as many of the symptoms of ADHD resemble symptoms of other disorders. ADHD is associated with gambling disorder and obesity, showing overlaps of about 20% with each diagnosis. It is important for clinical practice to differentiate between conditions displaying similar symptoms via established diagnostic instruments. Applying the LightGBM algorithm in machine learning, we were able to differentiate subjects with ADHD, obesity, problematic gambling, and a control group using all 26 items of the Conners' Adult ADHD Rating Scales (CAARS-S S) with a global accuracy of .80; precision (positive predictive value) ranged between .78 (gambling) and .92 (obesity), recall (sensitivity) between .58 for obesity and .87 for ADHD. Models with the best 5 and best 10 items resulted in less satisfactory fits. The CAARS-S seems to be a promising instrument to be applied in clinical practice also for multiclassifying disorders displaying symptoms resembling ADHD.The recent implication of circular economy in Australia spurred the demand for waste material utilization for value-added product generations on a commercial scale. Therefore, this experimental study emphasized on agricultural waste biomass, rice husk (RH) as potential feedstock to produce valuable products. Rice husk biochar (RB) was obtained at temperature 180 °C, pressure 70 bar, reaction time 20 min with water via hydrothermal carbonization (HTC), and the obtained biochar yield was 57.9%. Enhancement of zeta potential value from - 30.1 to - 10.6 mV in RB presented the higher suspension stability, and improvement of surface area and porosity in RB demonstrated the wastewater adsorption capacity. Along with that, an increase of crystallinity in RB, 60.5%, also indicates the enhancement of the catalytic performance of the material significantly more favorable to improve the adsorption efficiency of transitional compounds. https://www.selleckchem.com/products/pimicotinib.html In contrast, an increase of the atomic O/C ratio in RB, 0.51 delineated high breakdown of the cellulosic component, which is favorable for biofuel purpose. 13.98% SiO2 reduction in RB confirmed ash content minimization and better quality of fuel properties. Therefore, the rice husk biochar through HTC can be considered a suitable material for further application to treat wastewater and generate bioenergy.The present paper studies the locations and linear stability of the triangular equilibrium points when both primaries are radiating and considered as heterogeneous spheroid with three layers of different densities. Additionally, we include the effects of small perturbations in the Coriolis and centrifugal forces and potential from a belt (circumbinary disc). It is observed that the positions of the triangular equilibrium points are substantially affected by all parameters (except a perturbation in Coriolis force) involved in the system.The stabilty of motion is found only when [Formula see text], where [Formula see text] is the critical mass value which depends on the combined effect of radiation pressures and heterogeneity of the primaries, small perturbations and the potential from a belt.It is also seen that the Coriolis force and the belt have stabilizing effect,while the centrifugal force, radiation and heterogeineity of the primaries have destabilizing behaviour.The net effect is that the size of the region of stability decreases when the value of these parameters increases where [Formula see text] is the mass ratio and [Formula see text] characterize heterogeneity of both primaries. A practical application of this model could be the study of motion of a dust grain near the heterogeneous and luminous binary stars surrounded by a belt.Finally, we carried out and discuss numerical experiments aiming at computing the positions of triangular points and critical masses of three binary systems Archid, Xi Booties and Kruger 60.0 Commenti 0 condivisioni 261 Views 0 AnteprimaEffettua l'accesso per mettere mi piace, condividere e commentare! -
microRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3' non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3' NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified hundreds of miRNAs with 3' uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3' uridylation (adenylation) level of at least 10% in a specific biofluid. Strikingly, we found that 3' uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3' NTA levels possess fluid-specific information relatively robust to batch effects. In addition, we observed that extracellular miRNAs with 3' uridylations are enriched in processes related to angiogenesis, apoptosis, and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic, and translational discoveries.
In this study, we aimed to evaluate the efficiency of rotational thrombectomy device in pharmaco-mechanical thrombolysis for symptomatic acute ilio-femoral deep vein thrombosis.
Between August 2013 and May 2018,82 patients with acute deep vein thrombosis comprising the iliofemoral segment whom underwent Pharmaco-mechanical thrombolysis were evaluated retrospectively. The Cleaner thrombectomy device was used. The resolution of thrombi was examined and graded. Development of post-thrombotic syndrome was assessed with Villalta scores.
75 patients (91.4%) had complete thrombus resolution. Between 50-99% resolution was noted in 6 patients (7.4%) and in one (1.2%) case less than %50 thrombus resolution was obtained. Seventy-five patients (91%) of the cohort could be treated in a single session; 7 patients (8.6%) required reintervention(s). Although improved post-thrombotic syndrome rates were lower at the short term, Villalta scores gradually increased during follow up.
In conclusion, Pharmaco-mechanical thrombolysis with Cleaner thrombectomy device is a safe and beneficial method for the treatment of acute iliofemoral deep vein thrombosis. Long term follow up data of large volume multicenter studies are warranted.
In conclusion, Pharmaco-mechanical thrombolysis with Cleaner thrombectomy device is a safe and beneficial method for the treatment of acute iliofemoral deep vein thrombosis. Long term follow up data of large volume multicenter studies are warranted.The pipeline length exerts great influence on flame propagation characteristics, Realizable k - ε model and Premixed combustion model were used to study the influence of pipe length on propane-air explosion flame in open-ended and close-ended pipes. Using the numerical model verified by experiments, the changes of flame structure and flame propagation speed are studied. The result showed that the Realizable model was in good agreement with the experimental results. It also proved that the reflected wave produced a strong interference on the flame front, which promoted the formation of tulip flame. Besides, some obvious vortices were usually generated in the burned gas after the tulip flame formed, which will affect the flow field around the flame front and thus exert influence on the flame structure. The formation mechanism of tulip flame as well as the flame self-acceleration is different in open-ended and close-ended pipes. In close-ended pipes, the reflection wave at the pipe end and the reflection-induced countercurrent both promote the formation of tulip flame. As the flame propagates to the pipe end, the flame propagation is inhibited by the compression wave formed by the rapid expansion of combustion products under high temperature. While, in open-ended pipes, the turbulence induced by the opening at the pipe end is the main cause of tulip flame formation. The flame acceleration depends on the combustion reaction of unburned gas, so the velocity of flame propagation continues to increase. Generally, the maximum flame propagation velocity in the open-ended pipe is larger than that in the close-ended pipe.Previous studies have found inconsistent results regarding the personality predictors of scholastic cheating. This study investigated whether personality was a predictor of scholastic cheating using the HEXACO-60 personality inventory and the Dark Triad (DT). A sample of 252 students completed the online questionnaire. Results from a one-way ANOVA showed that scholastic cheating was more common in associate degree/diploma/foundation students and undergraduate students than postgraduate students. Year of study or student status (local or international students) had no effect on scholastic cheating. https://www.selleckchem.com/products/troglitazone-cs-045.html MANOVA showed that academic qualification, year of study, and student status had no effect on reasons for cheating. A structural equation model (SEM) found that scholastic cheating was positively predicted by unmitigated achievement and psychopathy. Psychopathy emerged as the strongest significant predictor of scholastic cheating. These results supported the view that dark personality is relevant for understanding scholastic cheating.As a universal workplace phenomenon, the impact of work-related rumination on job performance is attracting scholars' attention. In the current study, the relationship between two types of work-related rumination, counterproductive behavior, and creativity at work were examined, as well as the mechanism of this association. Participants were 1109 employees from a variety of jobs in mainland China. The results showed that affective rumination was negatively associated with employees' work creativity and positively associated with counterproductive behavior. On the contrary, problem-solving pondering was positively related to creativity and negatively related to counterproductive behavior. The loss of self-control resource partially mediated the link between affective rumination and counterproductive behavior. Problem-solving pondering had no significant impact on self-control resource. Results suggest the significant effects of problem-solving pondering may be positive in the workplace and clarify the self-control resource is the internal mechanism linking rumination and job performance.
microRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3' non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3' NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified hundreds of miRNAs with 3' uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3' uridylation (adenylation) level of at least 10% in a specific biofluid. Strikingly, we found that 3' uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3' NTA levels possess fluid-specific information relatively robust to batch effects. In addition, we observed that extracellular miRNAs with 3' uridylations are enriched in processes related to angiogenesis, apoptosis, and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic, and translational discoveries. In this study, we aimed to evaluate the efficiency of rotational thrombectomy device in pharmaco-mechanical thrombolysis for symptomatic acute ilio-femoral deep vein thrombosis. Between August 2013 and May 2018,82 patients with acute deep vein thrombosis comprising the iliofemoral segment whom underwent Pharmaco-mechanical thrombolysis were evaluated retrospectively. The Cleaner thrombectomy device was used. The resolution of thrombi was examined and graded. Development of post-thrombotic syndrome was assessed with Villalta scores. 75 patients (91.4%) had complete thrombus resolution. Between 50-99% resolution was noted in 6 patients (7.4%) and in one (1.2%) case less than %50 thrombus resolution was obtained. Seventy-five patients (91%) of the cohort could be treated in a single session; 7 patients (8.6%) required reintervention(s). Although improved post-thrombotic syndrome rates were lower at the short term, Villalta scores gradually increased during follow up. In conclusion, Pharmaco-mechanical thrombolysis with Cleaner thrombectomy device is a safe and beneficial method for the treatment of acute iliofemoral deep vein thrombosis. Long term follow up data of large volume multicenter studies are warranted. In conclusion, Pharmaco-mechanical thrombolysis with Cleaner thrombectomy device is a safe and beneficial method for the treatment of acute iliofemoral deep vein thrombosis. Long term follow up data of large volume multicenter studies are warranted.The pipeline length exerts great influence on flame propagation characteristics, Realizable k - ε model and Premixed combustion model were used to study the influence of pipe length on propane-air explosion flame in open-ended and close-ended pipes. Using the numerical model verified by experiments, the changes of flame structure and flame propagation speed are studied. The result showed that the Realizable model was in good agreement with the experimental results. It also proved that the reflected wave produced a strong interference on the flame front, which promoted the formation of tulip flame. Besides, some obvious vortices were usually generated in the burned gas after the tulip flame formed, which will affect the flow field around the flame front and thus exert influence on the flame structure. The formation mechanism of tulip flame as well as the flame self-acceleration is different in open-ended and close-ended pipes. In close-ended pipes, the reflection wave at the pipe end and the reflection-induced countercurrent both promote the formation of tulip flame. As the flame propagates to the pipe end, the flame propagation is inhibited by the compression wave formed by the rapid expansion of combustion products under high temperature. While, in open-ended pipes, the turbulence induced by the opening at the pipe end is the main cause of tulip flame formation. The flame acceleration depends on the combustion reaction of unburned gas, so the velocity of flame propagation continues to increase. Generally, the maximum flame propagation velocity in the open-ended pipe is larger than that in the close-ended pipe.Previous studies have found inconsistent results regarding the personality predictors of scholastic cheating. This study investigated whether personality was a predictor of scholastic cheating using the HEXACO-60 personality inventory and the Dark Triad (DT). A sample of 252 students completed the online questionnaire. Results from a one-way ANOVA showed that scholastic cheating was more common in associate degree/diploma/foundation students and undergraduate students than postgraduate students. Year of study or student status (local or international students) had no effect on scholastic cheating. https://www.selleckchem.com/products/troglitazone-cs-045.html MANOVA showed that academic qualification, year of study, and student status had no effect on reasons for cheating. A structural equation model (SEM) found that scholastic cheating was positively predicted by unmitigated achievement and psychopathy. Psychopathy emerged as the strongest significant predictor of scholastic cheating. These results supported the view that dark personality is relevant for understanding scholastic cheating.As a universal workplace phenomenon, the impact of work-related rumination on job performance is attracting scholars' attention. In the current study, the relationship between two types of work-related rumination, counterproductive behavior, and creativity at work were examined, as well as the mechanism of this association. Participants were 1109 employees from a variety of jobs in mainland China. The results showed that affective rumination was negatively associated with employees' work creativity and positively associated with counterproductive behavior. On the contrary, problem-solving pondering was positively related to creativity and negatively related to counterproductive behavior. The loss of self-control resource partially mediated the link between affective rumination and counterproductive behavior. Problem-solving pondering had no significant impact on self-control resource. Results suggest the significant effects of problem-solving pondering may be positive in the workplace and clarify the self-control resource is the internal mechanism linking rumination and job performance.0 Commenti 0 condivisioni 78 Views 0 Anteprima -
The present paper shows that the amplitudes of oscillators in delay-coupled oscillator networks can be suppressed by switching the network topology at a rate **** lower than the oscillator frequencies. The mechanism of suppression was clarified numerically, and a procedure for determining the connection parameters to induce suppression is presented. The analytical and numerical results were obtained with Stuart-Landau oscillators and were experimentally validated using double-scroll chaotic circuits.Deriving evolution equations accounting for both anomalous diffusion and reactions is notoriously difficult, even in the simplest cases. In contrast to normal diffusion, reaction kinetics cannot be incorporated into evolution equations modeling subdiffusion by merely adding reaction terms to the equations describing spatial movement. A series of previous works derived fractional reaction-diffusion equations for the spatiotemporal evolution of particles undergoing subdiffusion in one space dimension with linear reactions between a finite number of discrete states. In this paper, we first give a short and elementary proof of these previous results. We then show how this argument gives the evolution equations for more general cases, including subdiffusion following any fractional Fokker-Planck equation in an arbitrary d-dimensional spatial domain with time-dependent reactions between infinitely many discrete states. In contrast to previous works which employed a variety of technical mathematical methods, our analysis reveals that the evolution equations follow from (1) the probabilistic independence of the stochastic spatial and discrete processes describing a single particle and (2) the linearity of the integro-differential operators describing spatial movement. We also apply our results to systems combining reactions with superdiffusion.We analyze the stochastic thermodynamics of systems with a continuous space of states. The evolution equation, the rate of entropy production, and other results are obtained by a continuous time limit of a discrete time formulation. We point out the role of time reversal and of the dissipation part of the probability current on the production of entropy. We show that the rate of entropy production is a bilinear form in the components of the dissipation probability current with coefficients being the components of the precision matrix related to the Gaussian noise. We have also analyzed a type of noise that makes the energy function to be strictly constant along the stochastic trajectory, being appropriate to describe an isolated system. This type of noise leads to nonzero entropy production and thus to an increase of entropy in the system. This result contrasts with the invariance of the entropy predicted by the Liouville equation, which also describes an isolated system.We present a new study on the interaction of the DNA molecule with the surfactant dodecyltrimethylammonium bromide (DTAB), performed mainly with optical tweezers. Single-molecule force spectroscopy experiments performed in the low-force entropic regime allowed a robust characterization of the DNA-DTAB interaction, unveiling how the surfactant changes the mechanical properties of the biopolymer, the binding parameters, and the competition of the two mechanisms involved in the interaction electrostatic attraction between the cationic surfactant heads and the negative phosphate backbone of the DNA and hydrophobic interactions between the tails of the bound DTAB molecules, which can result in DNA compaction in solution depending on the quantity of bound surfactant. Finally, force clamp experiments with magnetic tweezers and gel electrophoresis assays confirm that DTAB compacts DNA depending not only on the surfactant concentration but also on the conformation of the biopolymer in solution. The present study provides new insights on general aspects of the DNA-surfactant complexes formation, contributing to the fundamental knowledge of the physics of such interactions.Single-particle tracking (SPT) has become a popular tool to study the intracellular transport of molecules in living cells. Inferring the character of their dynamics is important, because it determines the organization and functions of the cells. For this reason, one of the first steps in the analysis of SPT data is the identification of the diffusion type of the observed particles. The most popular method to identify the class of a trajectory is based on the mean-square displacement (MSD). However, due to its known limitations, several other approaches have been already proposed. With the recent advances in algorithms and the developments of modern hardware, the classification attempts rooted in machine learning (ML) are of particular interest. In this work, we adopt two ML ensemble algorithms, i.e., random forest and gradient boosting, to the problem of trajectory classification. We present a new set of features used to transform the raw trajectories data into input vectors required by the classifiers. The resulting models are then applied to real data for G protein-coupled receptors and G proteins. The classification results are compared to recent statistical methods going beyond MSD.We describe the critical behavior of weak multiplex percolation, a generalization of percolation to multiplex or interdependent networks. A node can determine its active or inactive status simply by referencing neighboring nodes. This is not the case for the more commonly studied generalization of percolation to multiplex networks, the mutually connected clusters, which requires an interconnecting path within each layer between any two vertices in the giant mutually connected component. We study the emergence of a giant connected component of active nodes under the weak percolation rule, finding several nontypical phenomena. In two layers, the giant component emerges with a continuous phase transition, but with quadratic growth above the critical threshold. In three or more layers, a discontinuous hybrid transition occurs, similar to that found in the giant mutually connected component. https://www.selleckchem.com/products/kn-93.html In networks with asymptotically powerlaw degree distributions, defined by the decay exponent γ, the discontinuity vanishes but at γ=1.
The present paper shows that the amplitudes of oscillators in delay-coupled oscillator networks can be suppressed by switching the network topology at a rate much lower than the oscillator frequencies. The mechanism of suppression was clarified numerically, and a procedure for determining the connection parameters to induce suppression is presented. The analytical and numerical results were obtained with Stuart-Landau oscillators and were experimentally validated using double-scroll chaotic circuits.Deriving evolution equations accounting for both anomalous diffusion and reactions is notoriously difficult, even in the simplest cases. In contrast to normal diffusion, reaction kinetics cannot be incorporated into evolution equations modeling subdiffusion by merely adding reaction terms to the equations describing spatial movement. A series of previous works derived fractional reaction-diffusion equations for the spatiotemporal evolution of particles undergoing subdiffusion in one space dimension with linear reactions between a finite number of discrete states. In this paper, we first give a short and elementary proof of these previous results. We then show how this argument gives the evolution equations for more general cases, including subdiffusion following any fractional Fokker-Planck equation in an arbitrary d-dimensional spatial domain with time-dependent reactions between infinitely many discrete states. In contrast to previous works which employed a variety of technical mathematical methods, our analysis reveals that the evolution equations follow from (1) the probabilistic independence of the stochastic spatial and discrete processes describing a single particle and (2) the linearity of the integro-differential operators describing spatial movement. We also apply our results to systems combining reactions with superdiffusion.We analyze the stochastic thermodynamics of systems with a continuous space of states. The evolution equation, the rate of entropy production, and other results are obtained by a continuous time limit of a discrete time formulation. We point out the role of time reversal and of the dissipation part of the probability current on the production of entropy. We show that the rate of entropy production is a bilinear form in the components of the dissipation probability current with coefficients being the components of the precision matrix related to the Gaussian noise. We have also analyzed a type of noise that makes the energy function to be strictly constant along the stochastic trajectory, being appropriate to describe an isolated system. This type of noise leads to nonzero entropy production and thus to an increase of entropy in the system. This result contrasts with the invariance of the entropy predicted by the Liouville equation, which also describes an isolated system.We present a new study on the interaction of the DNA molecule with the surfactant dodecyltrimethylammonium bromide (DTAB), performed mainly with optical tweezers. Single-molecule force spectroscopy experiments performed in the low-force entropic regime allowed a robust characterization of the DNA-DTAB interaction, unveiling how the surfactant changes the mechanical properties of the biopolymer, the binding parameters, and the competition of the two mechanisms involved in the interaction electrostatic attraction between the cationic surfactant heads and the negative phosphate backbone of the DNA and hydrophobic interactions between the tails of the bound DTAB molecules, which can result in DNA compaction in solution depending on the quantity of bound surfactant. Finally, force clamp experiments with magnetic tweezers and gel electrophoresis assays confirm that DTAB compacts DNA depending not only on the surfactant concentration but also on the conformation of the biopolymer in solution. The present study provides new insights on general aspects of the DNA-surfactant complexes formation, contributing to the fundamental knowledge of the physics of such interactions.Single-particle tracking (SPT) has become a popular tool to study the intracellular transport of molecules in living cells. Inferring the character of their dynamics is important, because it determines the organization and functions of the cells. For this reason, one of the first steps in the analysis of SPT data is the identification of the diffusion type of the observed particles. The most popular method to identify the class of a trajectory is based on the mean-square displacement (MSD). However, due to its known limitations, several other approaches have been already proposed. With the recent advances in algorithms and the developments of modern hardware, the classification attempts rooted in machine learning (ML) are of particular interest. In this work, we adopt two ML ensemble algorithms, i.e., random forest and gradient boosting, to the problem of trajectory classification. We present a new set of features used to transform the raw trajectories data into input vectors required by the classifiers. The resulting models are then applied to real data for G protein-coupled receptors and G proteins. The classification results are compared to recent statistical methods going beyond MSD.We describe the critical behavior of weak multiplex percolation, a generalization of percolation to multiplex or interdependent networks. A node can determine its active or inactive status simply by referencing neighboring nodes. This is not the case for the more commonly studied generalization of percolation to multiplex networks, the mutually connected clusters, which requires an interconnecting path within each layer between any two vertices in the giant mutually connected component. We study the emergence of a giant connected component of active nodes under the weak percolation rule, finding several nontypical phenomena. In two layers, the giant component emerges with a continuous phase transition, but with quadratic growth above the critical threshold. In three or more layers, a discontinuous hybrid transition occurs, similar to that found in the giant mutually connected component. https://www.selleckchem.com/products/kn-93.html In networks with asymptotically powerlaw degree distributions, defined by the decay exponent γ, the discontinuity vanishes but at γ=1.0 Commenti 0 condivisioni 83 Views 0 Anteprima -
AMT-101 administered to healthy **** by oral gavage or to cynomolgus monkeys (nonhuman primates) by colonic spray increased circulating levels of IL-1R antagonist (IL-1Ra). Oral gavage of AMT-101 in two mouse models of induced colitis prevented associated pathological events and plasma cytokine changes. Overall, these studies suggest that AMT-101 can efficiently overcome the epithelial barrier to focus biologically active IL-10 to the intestinal lamina propria.Iron is an essential element for Mycobacterium tuberculosis; it has at least 40 enzymes that require iron as a cofactor. Accessibility of iron at the phagosomal surface inside macrophage is crucial for survival and virulence of M. tuberculosis ESAT-6, a 6-kDa-secreted protein of region of difference 1, is known to play a crucial role in virulence and pathogenesis of M. tuberculosis In our earlier study, we demonstrated that ESAT-6 protein interacts with β-2-microglobulin (β2M) and affects class I Ag presentation through sequestration of β2M inside endoplasmic reticulum, which contributes toward inhibition of ****class Iβ2Mpeptide complex formation. https://www.selleckchem.com/products/jke-1674.html The 6 aa at C-terminal region of ESAT-6 are essential for ESAT6β2M interaction. β2M is essential for proper folding of HFE, CD1, and ****class I and their surface expression. It is known that M. tuberculosis recruit holotransferrin at the surface of the phagosome. But the upstream mechanism by which it modulates holotransferrin-mediated iron uptake at the surface of macrophage is not well understood. In the current study, we report that interaction of the ESAT-6 protein with β2M causes downregulation of surface HFE, a protein regulating iron homeostasis via interacting with transferrin receptor 1 (TFR1). We found that ESAT-6β2M interaction leads to sequestration of HFE in endoplasmic reticulum, causing poorer surface expression of HFE and HFETFR1 complex (nonfunctional TFR1) in peritoneal macrophages from C57BL/6 ****, resulting in increased holotransferrin-mediated iron uptake in these macrophages. These studies suggest that M. tuberculosis probably targets the ESAT-6 protein to increase iron uptake.Malaria is associated with complicated immunopathogenesis. In this study, we provide evidence for an unexpected role of TLR3 in promoting the establishment of Plasmodium yoelii infection through delayed clearance of parasitemia in wild type C57BL/6jRj (B6) compared with TLR3 knockout ****. In this study, we confirmed an increased expression of Tlr3, Trif, Tbk1, and Irf7/Irf3 in the liver 42 h postinfection and the initiation of an early burst of proinflammatory response such as Ifng, NF-kB, and Tnfa in B6 **** that may promote parasite fitness. Interestingly, in the absence of TLR3, we showed the involvement of high IFN-γ and lower type I IFN response in the early clearance of parasitemia. In parallel, we observed an increase in splenic NK and NKT cells expressing TLR3 in infected B6 ****, suggesting a role for TLR sensing in the innate immune response. Finally, we find evidence that the increase in the frequency of CD19+TLR3+ B cells along with reduced levels of total IgG in B6 **** possibly suggests the initiation of TLR3-dependent pathway early during P. yoelii infection. Our results thus reveal a new mechanism in which a parasite-activated TLR3 pathway promotes blood stage infection along with quantitative and qualitative differences in Ab responses.Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2-specific Abs are based on serum detection of Abs to either the viral spike glycoprotein (the major target for neutralizing Abs) or the viral nucleocapsid protein that is known to be highly immunogenic in other coronaviruses. Conceivably, exposure of Ags released from infected cells could stimulate Ab responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other nonstructural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titer IgG, IgM, and IgA Ab responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher Ab titers in these assays associated with more-severe disease, and no cross-reactive Abs against prior betacoronavirus were found. Remarkably, IgG Abs specific for Mpro and other SARS-CoV-2 Ags can also be detected in saliva. In conclusion, Mpro is a potent Ag in infected patients that can be used in serological tests, and its detection in saliva could be the basis for a rapid, noninvasive test for COVID-19 seropositivity.The chronic inflammatory autoimmune disease rheumatoid arthritis (RA) is characterized by an infiltration of activated proinflammatory immune cells into the joint that is accompanied by an overproduction of various mediators, leading to destruction of cartilage and bone erosion. Angiotensin II type 2 receptor (AT2R) is involved in antioxidative, anti-inflammatory, and antifibrotic responses. Synovial macrophages (SMs) are a type of tissue macrophages that are derived from bone marrow cells. SMs plays a central role in synovial regional immunization, which is significantly increased in both collagen-induced **** with arthritis **** and RA patients. AT2R activation caused a reversal of the polarization of SMs in the joint from the proinflammatory M1 SM to the tolerogenic, benign M2 SM. In consequence, this switch resulted in an attenuated form of the joint pathology in a rat model of collagen-induced arthritis. These results were mechanistically linked to the observation that GRK2 was translocated into cytoplasm, and ERK1/2 and NF-κB activation were inhibited. These findings open the way to a new therapeutic approach using an activation of AT2R to subvert joint inflammation in RA.
AMT-101 administered to healthy mice by oral gavage or to cynomolgus monkeys (nonhuman primates) by colonic spray increased circulating levels of IL-1R antagonist (IL-1Ra). Oral gavage of AMT-101 in two mouse models of induced colitis prevented associated pathological events and plasma cytokine changes. Overall, these studies suggest that AMT-101 can efficiently overcome the epithelial barrier to focus biologically active IL-10 to the intestinal lamina propria.Iron is an essential element for Mycobacterium tuberculosis; it has at least 40 enzymes that require iron as a cofactor. Accessibility of iron at the phagosomal surface inside macrophage is crucial for survival and virulence of M. tuberculosis ESAT-6, a 6-kDa-secreted protein of region of difference 1, is known to play a crucial role in virulence and pathogenesis of M. tuberculosis In our earlier study, we demonstrated that ESAT-6 protein interacts with β-2-microglobulin (β2M) and affects class I Ag presentation through sequestration of β2M inside endoplasmic reticulum, which contributes toward inhibition of MHC class Iβ2Mpeptide complex formation. https://www.selleckchem.com/products/jke-1674.html The 6 aa at C-terminal region of ESAT-6 are essential for ESAT6β2M interaction. β2M is essential for proper folding of HFE, CD1, and MHC class I and their surface expression. It is known that M. tuberculosis recruit holotransferrin at the surface of the phagosome. But the upstream mechanism by which it modulates holotransferrin-mediated iron uptake at the surface of macrophage is not well understood. In the current study, we report that interaction of the ESAT-6 protein with β2M causes downregulation of surface HFE, a protein regulating iron homeostasis via interacting with transferrin receptor 1 (TFR1). We found that ESAT-6β2M interaction leads to sequestration of HFE in endoplasmic reticulum, causing poorer surface expression of HFE and HFETFR1 complex (nonfunctional TFR1) in peritoneal macrophages from C57BL/6 mice, resulting in increased holotransferrin-mediated iron uptake in these macrophages. These studies suggest that M. tuberculosis probably targets the ESAT-6 protein to increase iron uptake.Malaria is associated with complicated immunopathogenesis. In this study, we provide evidence for an unexpected role of TLR3 in promoting the establishment of Plasmodium yoelii infection through delayed clearance of parasitemia in wild type C57BL/6jRj (B6) compared with TLR3 knockout mice. In this study, we confirmed an increased expression of Tlr3, Trif, Tbk1, and Irf7/Irf3 in the liver 42 h postinfection and the initiation of an early burst of proinflammatory response such as Ifng, NF-kB, and Tnfa in B6 mice that may promote parasite fitness. Interestingly, in the absence of TLR3, we showed the involvement of high IFN-γ and lower type I IFN response in the early clearance of parasitemia. In parallel, we observed an increase in splenic NK and NKT cells expressing TLR3 in infected B6 mice, suggesting a role for TLR sensing in the innate immune response. Finally, we find evidence that the increase in the frequency of CD19+TLR3+ B cells along with reduced levels of total IgG in B6 mice possibly suggests the initiation of TLR3-dependent pathway early during P. yoelii infection. Our results thus reveal a new mechanism in which a parasite-activated TLR3 pathway promotes blood stage infection along with quantitative and qualitative differences in Ab responses.Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2-specific Abs are based on serum detection of Abs to either the viral spike glycoprotein (the major target for neutralizing Abs) or the viral nucleocapsid protein that is known to be highly immunogenic in other coronaviruses. Conceivably, exposure of Ags released from infected cells could stimulate Ab responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other nonstructural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titer IgG, IgM, and IgA Ab responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher Ab titers in these assays associated with more-severe disease, and no cross-reactive Abs against prior betacoronavirus were found. Remarkably, IgG Abs specific for Mpro and other SARS-CoV-2 Ags can also be detected in saliva. In conclusion, Mpro is a potent Ag in infected patients that can be used in serological tests, and its detection in saliva could be the basis for a rapid, noninvasive test for COVID-19 seropositivity.The chronic inflammatory autoimmune disease rheumatoid arthritis (RA) is characterized by an infiltration of activated proinflammatory immune cells into the joint that is accompanied by an overproduction of various mediators, leading to destruction of cartilage and bone erosion. Angiotensin II type 2 receptor (AT2R) is involved in antioxidative, anti-inflammatory, and antifibrotic responses. Synovial macrophages (SMs) are a type of tissue macrophages that are derived from bone marrow cells. SMs plays a central role in synovial regional immunization, which is significantly increased in both collagen-induced mice with arthritis mice and RA patients. AT2R activation caused a reversal of the polarization of SMs in the joint from the proinflammatory M1 SM to the tolerogenic, benign M2 SM. In consequence, this switch resulted in an attenuated form of the joint pathology in a rat model of collagen-induced arthritis. These results were mechanistically linked to the observation that GRK2 was translocated into cytoplasm, and ERK1/2 and NF-κB activation were inhibited. These findings open the way to a new therapeutic approach using an activation of AT2R to subvert joint inflammation in RA.0 Commenti 0 condivisioni 70 Views 0 Anteprima -
Carotid artery stenosis causes significant morbidity and mortality accounting for approximately 8% of all ischaemic strokes. Carotid artery stenting (CAS) offers an endovascular alternative to carotid endarterectomy (CEA), suggested as a viable option in those deemed high-risk for open CEA due to comorbidities or operative technical considerations. A number of large randomised-controlled trials (RCTs) and meta-analysis comparing CAS vs. CEA in unselected patient populations support the conclusion that CAS is associated with a higher risk of stroke and CEA is associated with a higher risk of myocardial infraction. Initial promise for CAS in high-risk patients was demonstrated by The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial that reported CAS was non-inferior to CEA. However, there is evidence to suggest age-related adverse outcome in patients undergoing CAS. There is limited evidence to suggest that CEA could be suitable even in patients deemed high-risk for medical or technical reasons. Further contemporary research on the use of CAS and CEA in high-risk patients is required to re-evaluate current guidelines and high-risk criterion. It is common for a composite outcome of death, ipsilateral stroke and MI which should be questioned as subsequent quality of life is likely to differ after suffering a stroke in comparison to MI. This literature review will discuss the current evidence for CAS and CEA interventions in unselected populations and high-risk patients with carotid disease requiring intervention.Acute occlusion of the internal carotid artery is the underlying etiology in 4 to 15% of all ischemic strokes. The clinical presentation varies considerably ranging from asymptomatic occlusion to severe ischemic strokes. Substantial differences in the acute management of acute symptomatic internal carotid artery occlusions (ICAO) exists between centers. Thusly, we comprised a narrative review of the natural course of acute ICAO and of available treatment options [i.v. thrombolysis, endovascular thrombectomy and stenting, bypass between the superficial temporal and the middle cerebral arteries (MCA) and carotid endarterectomy (CEA)]. We found that very few randomized treatment trials have been performed in patients acute symptomatic ICAO. Most evidence stems from case series and observational studies. Especially in older studies the intracranial vessel status has rarely been considered. After revision of these studies we concluded that the mainstay of the acute management of acute symptomatic ICAO is i.v. thrombolysis when applied within the label and in combination with mechanical thrombectomy in case of intracranial large vessel occlusion. In cases without intracranial large vessel occlusion mechanical thrombectomy of acute ICAO is associated with a risk of distal embolization. More research on prognostic parameters is needed to better characterize the risk of decompensation of collateral flow and to better define the time-window of intervention. https://www.selleckchem.com/products/gw9662.html When mechanical thrombectomy fails or is not available, surgical approaches are an alternative in selected patients.The timing of carotid endarterectomy (CEA) for symptomatic ipsilateral carotid artery stenosis has evolved in practice over time. Key landmark trials outlined the benefit of performing CEA in the recently symptomatic carotid artery stenosis, defined as revascularisation within 6 months of the index neurological event. Further evidence and sub-analysis demonstrate that performing CEA within 2 weeks of symptoms has the maximal benefit in reducing stroke free survival and is associated with a safe perioperative complication profile. This has translated into guideline recommendations and widespread clinical practice. The case for performing urgent CEA (within 48 hours of index neurological event) over early CEA (within 2 weeks) has been put forward and studied. Data examining perioperative complications for urgent CEA are mostly derived from retrospective single series studies. A moderate balance exists in the literature for the safety and risk of urgent CEA. Although many studies present acceptable perioperative stroke and mortality rates associated with urgent CEA, evidence still exists that the perioperative complications may not be insignificant. This is particularly the case if the presenting neurology is a stroke, rather than a transient ischaemic attack (TIA) or amaurosis fugax. This should be contextualised in the practice of modern aggressive medical therapy with dual antiplatelets and statins, with evidence suggesting a reduction in recurrent ischaemic events prior to surgical intervention. Careful patient selection, presenting neurology and medical therapy is likely to be a key feature in considering urgent CEA versus early CEA.Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T1-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.
Carotid artery stenosis causes significant morbidity and mortality accounting for approximately 8% of all ischaemic strokes. Carotid artery stenting (CAS) offers an endovascular alternative to carotid endarterectomy (CEA), suggested as a viable option in those deemed high-risk for open CEA due to comorbidities or operative technical considerations. A number of large randomised-controlled trials (RCTs) and meta-analysis comparing CAS vs. CEA in unselected patient populations support the conclusion that CAS is associated with a higher risk of stroke and CEA is associated with a higher risk of myocardial infraction. Initial promise for CAS in high-risk patients was demonstrated by The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial that reported CAS was non-inferior to CEA. However, there is evidence to suggest age-related adverse outcome in patients undergoing CAS. There is limited evidence to suggest that CEA could be suitable even in patients deemed high-risk for medical or technical reasons. Further contemporary research on the use of CAS and CEA in high-risk patients is required to re-evaluate current guidelines and high-risk criterion. It is common for a composite outcome of death, ipsilateral stroke and MI which should be questioned as subsequent quality of life is likely to differ after suffering a stroke in comparison to MI. This literature review will discuss the current evidence for CAS and CEA interventions in unselected populations and high-risk patients with carotid disease requiring intervention.Acute occlusion of the internal carotid artery is the underlying etiology in 4 to 15% of all ischemic strokes. The clinical presentation varies considerably ranging from asymptomatic occlusion to severe ischemic strokes. Substantial differences in the acute management of acute symptomatic internal carotid artery occlusions (ICAO) exists between centers. Thusly, we comprised a narrative review of the natural course of acute ICAO and of available treatment options [i.v. thrombolysis, endovascular thrombectomy and stenting, bypass between the superficial temporal and the middle cerebral arteries (MCA) and carotid endarterectomy (CEA)]. We found that very few randomized treatment trials have been performed in patients acute symptomatic ICAO. Most evidence stems from case series and observational studies. Especially in older studies the intracranial vessel status has rarely been considered. After revision of these studies we concluded that the mainstay of the acute management of acute symptomatic ICAO is i.v. thrombolysis when applied within the label and in combination with mechanical thrombectomy in case of intracranial large vessel occlusion. In cases without intracranial large vessel occlusion mechanical thrombectomy of acute ICAO is associated with a risk of distal embolization. More research on prognostic parameters is needed to better characterize the risk of decompensation of collateral flow and to better define the time-window of intervention. https://www.selleckchem.com/products/gw9662.html When mechanical thrombectomy fails or is not available, surgical approaches are an alternative in selected patients.The timing of carotid endarterectomy (CEA) for symptomatic ipsilateral carotid artery stenosis has evolved in practice over time. Key landmark trials outlined the benefit of performing CEA in the recently symptomatic carotid artery stenosis, defined as revascularisation within 6 months of the index neurological event. Further evidence and sub-analysis demonstrate that performing CEA within 2 weeks of symptoms has the maximal benefit in reducing stroke free survival and is associated with a safe perioperative complication profile. This has translated into guideline recommendations and widespread clinical practice. The case for performing urgent CEA (within 48 hours of index neurological event) over early CEA (within 2 weeks) has been put forward and studied. Data examining perioperative complications for urgent CEA are mostly derived from retrospective single series studies. A moderate balance exists in the literature for the safety and risk of urgent CEA. Although many studies present acceptable perioperative stroke and mortality rates associated with urgent CEA, evidence still exists that the perioperative complications may not be insignificant. This is particularly the case if the presenting neurology is a stroke, rather than a transient ischaemic attack (TIA) or amaurosis fugax. This should be contextualised in the practice of modern aggressive medical therapy with dual antiplatelets and statins, with evidence suggesting a reduction in recurrent ischaemic events prior to surgical intervention. Careful patient selection, presenting neurology and medical therapy is likely to be a key feature in considering urgent CEA versus early CEA.Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T1-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.0 Commenti 0 condivisioni 84 Views 0 Anteprima -
21 ± 0.44D. Although there was a marginal increase in the blur thresholds postoperatively, the difference was not statistically significant (DB P = 0.320; BB P = 0.229; NB P = 0.054).
All three blur thresholds showed an insignificant minimal increase at 1 month post-operatively suggesting that patients adapt to the induced blur following refractive surgery. A longer follow up would reveal how the adaptation to blur would change with time.
All three blur thresholds showed an insignificant minimal increase at 1 month post-operatively suggesting that patients adapt to the induced blur following refractive surgery. A longer follow up would reveal how the adaptation to blur would change with time.
To calculate a modified percentage tissue altered (mPTA) in post laser-assisted in-situ keratomileusis (LASIK) eyes and to validate its role as an independent factor to evaluate ectasia in the Indian population.
A total of 333 consecutive eyes with normal preoperative corneal topography by combined placido and scheimpflug imaging-based topography system (SIRIUS) who underwent LASIK using a microkeratome between 2011 and 2014 at a tertiary level teaching hospital in south India, were retrospectively analyzed. Preoperatively patient's refraction, flap thickness (FT), ablation depth (AD), residual stromal bed (RSB), and thinnest corneal thickness (TCT) were recorded. The formula used was mPTA = (FT + AD)/TCT. https://www.selleckchem.com/products/pimicotinib.html mPTA was grouped into <0.4 (low risk), 0.40 - 0.45 (moderate risk), and >0.45 (high risk). All patients were called for follow-up and underwent a topography to look for ectasia.
In total 60.1%, 29.1%, and 10.8% patients had mPTA of <0.4, 0.40 - 0.45 and >0.45, respectively. However, after a minimum follow-up of 2 years, none of the patients had any sign of ectasia.
Careful selection of patients is mandatory before proceeding for LASIK. Factors like corneal thickness, RSB, degree of myopia, and AD are more important. The role of mPTA >0.4 as an independent risk factor for post LASIK ectasia is questionable in Indian eyes. Other factors or a modified formula suitable for Indian eyes needs to be investigated. A larger follow-up period is also required as ectasia has been known to develop even after 2 years.
0.4 as an independent risk factor for post LASIK ectasia is questionable in Indian eyes. Other factors or a modified formula suitable for Indian eyes needs to be investigated. A larger follow-up period is also required as ectasia has been known to develop even after 2 years.
The aim of this study was to analyze the effect of timolol maleate (0.5%) eye drops in the treatment of myopic regression after laser-assisted in-situ keratomileusis (LASIK).
The study was conducted at a tertiary care eye hospital in north India between April 2017 & March 2018 as a prospective interventional study. Patients who underwent uneventful myopic LASIK with hansatome mechanical keratome and presented with regression were included in the study. Baseline demographic characteristics, time to presentation with regression best-corrected visual acuity (BCVA), refraction, intraocular pressure, central corneal thickness and keratometry were recorded at baseline and at each follow-up visit. The enrolled patients were prescribed timolol maleate (0.5%) eyedrops twice daily. They were followed up every month till 3 months on timolol maleate (0.5%) eyedrops and at 6 months post stopping the treatment.
Twenty-nine eyes of 15 patients were enrolled in the study. Mean pre LASIK spherical equivalent (SE) wa post LASIK circumventing the need for laser re-treatment in such patients. The most probable mechanism is reversal of the anterior bowing of the cornea in response to intraocular pressure changes.
The aim of this study was to compare the predictability and accuracy of the American Society of Cataract and Refractive Surgery (ASCRS) online calculator with the Haigis-L formula for intraocular lens (IOL) power calculation in post myopic laser-assisted in-situ keratomileuses (LASIK) eyes undergoing cataract surgery and also to analyze the postoperative refractive outcome among the ASCRS average, maximum and minimum values.
A retrospective study was conducted on post myopic LASIK eyes which underwent cataract surgery between June 2017 and December 2019. IOL power was calculated using both Haigis-L & ASCRS methods. Implanted IOL power was based on the ASCRS method. The expected postoperative refraction for IOL power based on the Haigis-L formula was calculated and compared with the Spherical Equivalent (SE) obtained from the patient's actual refraction. Prediction error (PE) & Mean Absolute Error (MAE) was calculated. Intragroup analysis of ASCRS values was done.
Among the 41 eyes analyzed, pre-operative and post-operative mean best-corrected visual acuity was 0.58 ± 0.21 and 0.15 ± 0.26 logMAR, respectively. In the ASCRS method, 36 (87.8%) and 40 (97.6%) eyes had PE within ± 0.5D and ± 1.0 D, respectively, whereas, in the Haigis-L method, 29 (70.7%) eyes, and 38 (92.7%) eyes had PE within ± 0.5D and ± 1.0 D, respectively. Among the ASCRS subgroups, ASCRS average, maximum and minimum values had 83%, 80.6%, and 48.8% eyes with SE within ± 0.5D, respectively.
ASCRS method can be considered as an equally efficient method of IOL power calculation as the Haigis-L method in eyes which have undergone post myopic LASIK refractive surgery. ASCRS maximum & average values gave better emmetropic results.
ASCRS method can be considered as an equally efficient method of IOL power calculation as the Haigis-L method in eyes which have undergone post myopic LASIK refractive surgery. ASCRS maximum & average values gave better emmetropic results.
To evaluate the long-term contrast sensitivity (CS) after laser in-situ keratomileusis (LASIK) for myopia.
This retrospective, single-center, cohort study involved 190 eyes of 95 patients who underwent bilateral LASIK between January 2001 and October 2007. This study includes patients who underwent CS and higher-order aberration (HOA) measurements in a five-year postoperative period. For all enrolled patients, visual acuity, refractive error (RE) in diopters (D), CS at 3-, 6-, 12-, and 18-cycles per degree (cpd), and HOA in a 4 mm area of the dilated pupil were measured before surgery and 6 months, 1 year, and 5 years after it.
The mean RE measured before the surgery and after 6 months, 1 year, and 5 years after was -6.08 ± 2.50D, -0.26 ± 0.65D, -0.28 ± 0.65D, and -0.48 ± 0.80D, respectively. There were no clinically significant changes between preoperative results and the measures taken 6 months, 1 year, and 5 years after surgery. The slight increase in HOA had little effect on CS over the mid to long-term postoperative period.
21 ± 0.44D. Although there was a marginal increase in the blur thresholds postoperatively, the difference was not statistically significant (DB P = 0.320; BB P = 0.229; NB P = 0.054). All three blur thresholds showed an insignificant minimal increase at 1 month post-operatively suggesting that patients adapt to the induced blur following refractive surgery. A longer follow up would reveal how the adaptation to blur would change with time. All three blur thresholds showed an insignificant minimal increase at 1 month post-operatively suggesting that patients adapt to the induced blur following refractive surgery. A longer follow up would reveal how the adaptation to blur would change with time. To calculate a modified percentage tissue altered (mPTA) in post laser-assisted in-situ keratomileusis (LASIK) eyes and to validate its role as an independent factor to evaluate ectasia in the Indian population. A total of 333 consecutive eyes with normal preoperative corneal topography by combined placido and scheimpflug imaging-based topography system (SIRIUS) who underwent LASIK using a microkeratome between 2011 and 2014 at a tertiary level teaching hospital in south India, were retrospectively analyzed. Preoperatively patient's refraction, flap thickness (FT), ablation depth (AD), residual stromal bed (RSB), and thinnest corneal thickness (TCT) were recorded. The formula used was mPTA = (FT + AD)/TCT. https://www.selleckchem.com/products/pimicotinib.html mPTA was grouped into <0.4 (low risk), 0.40 - 0.45 (moderate risk), and >0.45 (high risk). All patients were called for follow-up and underwent a topography to look for ectasia. In total 60.1%, 29.1%, and 10.8% patients had mPTA of <0.4, 0.40 - 0.45 and >0.45, respectively. However, after a minimum follow-up of 2 years, none of the patients had any sign of ectasia. Careful selection of patients is mandatory before proceeding for LASIK. Factors like corneal thickness, RSB, degree of myopia, and AD are more important. The role of mPTA >0.4 as an independent risk factor for post LASIK ectasia is questionable in Indian eyes. Other factors or a modified formula suitable for Indian eyes needs to be investigated. A larger follow-up period is also required as ectasia has been known to develop even after 2 years. 0.4 as an independent risk factor for post LASIK ectasia is questionable in Indian eyes. Other factors or a modified formula suitable for Indian eyes needs to be investigated. A larger follow-up period is also required as ectasia has been known to develop even after 2 years. The aim of this study was to analyze the effect of timolol maleate (0.5%) eye drops in the treatment of myopic regression after laser-assisted in-situ keratomileusis (LASIK). The study was conducted at a tertiary care eye hospital in north India between April 2017 & March 2018 as a prospective interventional study. Patients who underwent uneventful myopic LASIK with hansatome mechanical keratome and presented with regression were included in the study. Baseline demographic characteristics, time to presentation with regression best-corrected visual acuity (BCVA), refraction, intraocular pressure, central corneal thickness and keratometry were recorded at baseline and at each follow-up visit. The enrolled patients were prescribed timolol maleate (0.5%) eyedrops twice daily. They were followed up every month till 3 months on timolol maleate (0.5%) eyedrops and at 6 months post stopping the treatment. Twenty-nine eyes of 15 patients were enrolled in the study. Mean pre LASIK spherical equivalent (SE) wa post LASIK circumventing the need for laser re-treatment in such patients. The most probable mechanism is reversal of the anterior bowing of the cornea in response to intraocular pressure changes. The aim of this study was to compare the predictability and accuracy of the American Society of Cataract and Refractive Surgery (ASCRS) online calculator with the Haigis-L formula for intraocular lens (IOL) power calculation in post myopic laser-assisted in-situ keratomileuses (LASIK) eyes undergoing cataract surgery and also to analyze the postoperative refractive outcome among the ASCRS average, maximum and minimum values. A retrospective study was conducted on post myopic LASIK eyes which underwent cataract surgery between June 2017 and December 2019. IOL power was calculated using both Haigis-L & ASCRS methods. Implanted IOL power was based on the ASCRS method. The expected postoperative refraction for IOL power based on the Haigis-L formula was calculated and compared with the Spherical Equivalent (SE) obtained from the patient's actual refraction. Prediction error (PE) & Mean Absolute Error (MAE) was calculated. Intragroup analysis of ASCRS values was done. Among the 41 eyes analyzed, pre-operative and post-operative mean best-corrected visual acuity was 0.58 ± 0.21 and 0.15 ± 0.26 logMAR, respectively. In the ASCRS method, 36 (87.8%) and 40 (97.6%) eyes had PE within ± 0.5D and ± 1.0 D, respectively, whereas, in the Haigis-L method, 29 (70.7%) eyes, and 38 (92.7%) eyes had PE within ± 0.5D and ± 1.0 D, respectively. Among the ASCRS subgroups, ASCRS average, maximum and minimum values had 83%, 80.6%, and 48.8% eyes with SE within ± 0.5D, respectively. ASCRS method can be considered as an equally efficient method of IOL power calculation as the Haigis-L method in eyes which have undergone post myopic LASIK refractive surgery. ASCRS maximum & average values gave better emmetropic results. ASCRS method can be considered as an equally efficient method of IOL power calculation as the Haigis-L method in eyes which have undergone post myopic LASIK refractive surgery. ASCRS maximum & average values gave better emmetropic results. To evaluate the long-term contrast sensitivity (CS) after laser in-situ keratomileusis (LASIK) for myopia. This retrospective, single-center, cohort study involved 190 eyes of 95 patients who underwent bilateral LASIK between January 2001 and October 2007. This study includes patients who underwent CS and higher-order aberration (HOA) measurements in a five-year postoperative period. For all enrolled patients, visual acuity, refractive error (RE) in diopters (D), CS at 3-, 6-, 12-, and 18-cycles per degree (cpd), and HOA in a 4 mm area of the dilated pupil were measured before surgery and 6 months, 1 year, and 5 years after it. The mean RE measured before the surgery and after 6 months, 1 year, and 5 years after was -6.08 ± 2.50D, -0.26 ± 0.65D, -0.28 ± 0.65D, and -0.48 ± 0.80D, respectively. There were no clinically significant changes between preoperative results and the measures taken 6 months, 1 year, and 5 years after surgery. The slight increase in HOA had little effect on CS over the mid to long-term postoperative period.0 Commenti 0 condivisioni 83 Views 0 Anteprima -
Resulting adaptations to the intervention consisted of two activities (school lesson and an extracurricular activity) that address knowledge gaps and myths. Conclusions This study demonstrates the importance of qualitative research in unpacking adolescent girls' experiences with menarche and menstruation. Study findings also show how formative research can contribute to the adaptation and development of a contextually and culturally-relevant water, sanitation, and hygiene intervention.Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as Porphyromonas gingivalis, through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostativarious effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.
ClinicalTrials.gov identifier NCT02087137.
ClinicalTrials.gov identifier NCT02087137.In this review, we describe how technological advances in ultrasound imaging related to transducer construction and image processing fundamentally alter generation of ultrasound images to produce better quality images with higher resolution. However, carotid intima-media thickness (IMT) measurements made from images acquired on modern ultrasound systems are not comparable to historical population nomograms that were used to determine wall thickness thresholds that inform atherosclerotic cardiovascular disease risk. Because it is nearly impossible to replicate instrumentation settings that were used to create the reference carotid IMT nomograms and to place an individual's carotid IMT value in or above a clinically relevant percentile, carotid IMT measurements have a very limited role in clinical medicine, but remain a useful research tool when instrumentation, presets, image acquisition, and measurements can be standardized. In addition to new validation studies, it would be useful for the ultrasound imaging community to reach a consensus regarding technical aspects of ultrasound imaging acquisition, processing, and display for blood vessels so standard presets and imaging approaches could reliably yield the same measurements.Objectives A significant gap in our knowledge concerns sexual health among the older lesbian, gay, and bisexual (LGB) population. Methods We compared a community-based sample of self-identified LGB older adults (n = 128) with population-based samples of behaviorally-defined LGB older adults (i.e., reporting same-sex experiences) (n = 112) and behaviorally-defined older heterosexuals (i.e., reporting no same-sex experiences) (n = 2,893) from the National Social Life, Health and Aging Project (NSHAP). Differences in sexual activity and sexual problems were examined. Results Older LGB adults were as likely to remain sexually active as older heterosexuals. Gay and bisexual men were more likely than heterosexual men to report some sexual problems. Regardless of sexual orientation, older adults rarely had their sexual health needs addressed in healthcare settings. Conclusions Results highlight the need for more research on LGB older adult sexual health. Clinical Implications The lack of attention to LGB older adults' sexual health in healthcare settings may be exacerbated by ageism and heterosexism, leading these individuals to avoid disclosing their sexual orientations and avoid conversations about sexuality. https://www.selleckchem.com/products/cia1.html Mental health practitioners require education on associations between sexual health and mental health, and how sexual health problems may contribute to mental health concerns in vulnerable populations like older LGB adults.This longitudinal qualitative study examines staff experience of disinvestment from a service they are accustomed to providing to their patients. It took place alongside a disinvestment trial that measured the impact of the removal of weekend allied health services from acute wards at two hospitals. Data were gathered from repeated interviews and focus groups with 450 health care staff. We developed a grounded theory, which explains changes in staff perceptions over time and the key modifying factors. Staff appeared to experience disinvestment as loss; a key difference to other operational changes. Early staff experiences of disinvestment were primarily negative, but evolved with time and change-management strategies such as the provision of data, clear and persistent communication approaches, and forums where the big picture context of the disinvestment was robustly discussed. These allowed the disinvestment trial to be successfully implemented at two health services, with high compliance with the research protocol.
Lay attitudes are often seen as potential barriers to mental health recovery. But apart from perceiving them as potential barriers, they can also play an important role in stimulating individuals to consult (in)formal help sources, in particular through the process of help referral. Where existing research mainly focusses on actual help seeking behaviour, this study will focus on lay publics' referral behaviour.
This study analyses the relation between causal beliefs and stigmatising attitudes and social distance on the one hand, and (in)formal help seeking recommendations on the other.
Data from a survey carried out in 2019, assessing the attitudes of Public Health Insurance Provider (HIP) members towards mental health problems, was used. Part of the survey questions was based on a quantitative quasi-experimental design, using hypothetical written vignettes. The weighted data represent a sample of the adult Flemish population (22-94 years,
= 5675). Multiple linear regression analysis was used to examine the relation between causal beliefs and stigma, while binominal logistic regression analysis was used to investigate the relation between causal beliefs and help seeking recommendations.
Resulting adaptations to the intervention consisted of two activities (school lesson and an extracurricular activity) that address knowledge gaps and myths. Conclusions This study demonstrates the importance of qualitative research in unpacking adolescent girls' experiences with menarche and menstruation. Study findings also show how formative research can contribute to the adaptation and development of a contextually and culturally-relevant water, sanitation, and hygiene intervention.Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as Porphyromonas gingivalis, through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostativarious effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria. ClinicalTrials.gov identifier NCT02087137. ClinicalTrials.gov identifier NCT02087137.In this review, we describe how technological advances in ultrasound imaging related to transducer construction and image processing fundamentally alter generation of ultrasound images to produce better quality images with higher resolution. However, carotid intima-media thickness (IMT) measurements made from images acquired on modern ultrasound systems are not comparable to historical population nomograms that were used to determine wall thickness thresholds that inform atherosclerotic cardiovascular disease risk. Because it is nearly impossible to replicate instrumentation settings that were used to create the reference carotid IMT nomograms and to place an individual's carotid IMT value in or above a clinically relevant percentile, carotid IMT measurements have a very limited role in clinical medicine, but remain a useful research tool when instrumentation, presets, image acquisition, and measurements can be standardized. In addition to new validation studies, it would be useful for the ultrasound imaging community to reach a consensus regarding technical aspects of ultrasound imaging acquisition, processing, and display for blood vessels so standard presets and imaging approaches could reliably yield the same measurements.Objectives A significant gap in our knowledge concerns sexual health among the older lesbian, gay, and bisexual (LGB) population. Methods We compared a community-based sample of self-identified LGB older adults (n = 128) with population-based samples of behaviorally-defined LGB older adults (i.e., reporting same-sex experiences) (n = 112) and behaviorally-defined older heterosexuals (i.e., reporting no same-sex experiences) (n = 2,893) from the National Social Life, Health and Aging Project (NSHAP). Differences in sexual activity and sexual problems were examined. Results Older LGB adults were as likely to remain sexually active as older heterosexuals. Gay and bisexual men were more likely than heterosexual men to report some sexual problems. Regardless of sexual orientation, older adults rarely had their sexual health needs addressed in healthcare settings. Conclusions Results highlight the need for more research on LGB older adult sexual health. Clinical Implications The lack of attention to LGB older adults' sexual health in healthcare settings may be exacerbated by ageism and heterosexism, leading these individuals to avoid disclosing their sexual orientations and avoid conversations about sexuality. https://www.selleckchem.com/products/cia1.html Mental health practitioners require education on associations between sexual health and mental health, and how sexual health problems may contribute to mental health concerns in vulnerable populations like older LGB adults.This longitudinal qualitative study examines staff experience of disinvestment from a service they are accustomed to providing to their patients. It took place alongside a disinvestment trial that measured the impact of the removal of weekend allied health services from acute wards at two hospitals. Data were gathered from repeated interviews and focus groups with 450 health care staff. We developed a grounded theory, which explains changes in staff perceptions over time and the key modifying factors. Staff appeared to experience disinvestment as loss; a key difference to other operational changes. Early staff experiences of disinvestment were primarily negative, but evolved with time and change-management strategies such as the provision of data, clear and persistent communication approaches, and forums where the big picture context of the disinvestment was robustly discussed. These allowed the disinvestment trial to be successfully implemented at two health services, with high compliance with the research protocol. Lay attitudes are often seen as potential barriers to mental health recovery. But apart from perceiving them as potential barriers, they can also play an important role in stimulating individuals to consult (in)formal help sources, in particular through the process of help referral. Where existing research mainly focusses on actual help seeking behaviour, this study will focus on lay publics' referral behaviour. This study analyses the relation between causal beliefs and stigmatising attitudes and social distance on the one hand, and (in)formal help seeking recommendations on the other. Data from a survey carried out in 2019, assessing the attitudes of Public Health Insurance Provider (HIP) members towards mental health problems, was used. Part of the survey questions was based on a quantitative quasi-experimental design, using hypothetical written vignettes. The weighted data represent a sample of the adult Flemish population (22-94 years, = 5675). Multiple linear regression analysis was used to examine the relation between causal beliefs and stigma, while binominal logistic regression analysis was used to investigate the relation between causal beliefs and help seeking recommendations.0 Commenti 0 condivisioni 185 Views 0 Anteprima -
Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.CircRNAs are now under hot discussion as novel promising bio-markers for patients with clear cell renal cell carcinoma. The purpose of our study is to identify several circRNAs related to the metastasis and progression of clear cell renal cell carcinoma, and to further investigate the mechanism of their influence on tumor progression. The transcriptome data of ccRCC and clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus database. A total of 114 circRNAs were found to be related to tumor initiation, progression and metastasis after the intersection. In addition, 14 miRNAs and 201 eligible mRNAs were selected as targets gene, respectively. CeRNA network was constructed based on 8 circRNAs, 14 miRNAs, and 201 mRNAs. Besides, another 6 hub genes were identified via the PPI network. It should be noted that only TRIM2 was confirmed as an independent prognostic factor, which was simultaneously significantly related to both clinical stage and pathological grade in clinical cohorts. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated the possible function of TRIM2 in ccRCC progression, such as ubiquitin mediated protein hydrolysis, cell adhesion molecules, Th17 cell differentiation signaling pathway and so on. Gene set enrichment analysis analysis revealed that TRIM2 may be involved in ubiquitin mediated proteolysis, apoptosis, autophagy and citrate cycle TCA cycle. Hub circ_RNAs expressions were validated in ccRCC tissues and cell lines. Our study revealed that the hsa_circ_0002286 / has-mir-222-5p / TRIM2 axis played a critical role in the progression of ccRCC. Specifically, it may inhibit the metastasis and progression of ccRCC, which could serve as a potential therapeutic target.The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. Many identified that impaired DNA polymerase β (Pol β)-mediated DNA base-excision repair (BER) drives to mouse oocyte aging. With aging, DNA lesions accumulate in primordial follicles. However, the expression of most DNA BER genes, including APE1, OGG1, XRCC1, Ligase I, Ligase α, PCNA and FEN1, remains unchanged during aging in mouse oocytes. Also, the reproductive capacity of Pol β+/- heterozygote **** was impaired, and the primordial follicle counts were lower than that of wild type (wt) ****. The DNA lesions of heterozygous **** increased. Moreover, the Pol β knockdown leads to increased DNA damage in oocytes and decreased survival rate of oocytes. Oocytes over-expressing Pol β showed that the vitality of senescent cells enhances significantly. Furthermore, serum concentrations of anti-Müllerian hormone (AMH) indicated that the ovarian reserves of young **** with Pol β germline mutations were lower than those in wt. These data show that Pol β-related DNA BER efficiency is a major factor governing oocyte aging in ****.Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male **** as a T2DM model, and the gut microbiota of db/db and m/m **** were transplanted successfully into pseudo germ-free ****. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db ****. Interestingly, the host after gut microbiota transplantation from db/db **** showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m ****. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.The 5-year survival rate of ovarian cancer patients is only 47%, and developing novel drugs for ovarian cancer is needed. Herein, we evaluated if and how SRT2183, a sirtuin-1 activator, impairs the ovarian cancer cells. OVCAR-3 and A2780 cells were treated with SRT2183. https://www.selleckchem.com/products/brd7389.html Cell viability was measured by cell counting kit-8 assay and clonogenic assay. Apoptosis was determined by flow cytometry with Annexin V and propidium iodide. The level of autophagy was evaluated by western blot and immunofluorescence. The activities of AKT/mTOR/70s6k and MAPK signaling pathway were measured by immunoblot. SRT2183 inhibited the growth of ovarian cancer cells, increased the accumulation of BAX, cleaved-caspase 3 and cleaved-PARP, and decreased the level of anti-apoptotic Bcl-2 and Mcl-1. SRT2183 increased the LC3II level, and enhanced the degradation of p62/SQSTM1. SRT2183 increased the formation of GFP-LC3 puncta and induced the maturation of autophagosome. Interestingly, knockdown of autophagy related 5 and 7 significantly impaired the anti-carcinoma activity of SRT2183, implying that SRT2183 impaired the ovarian cancer cells by inducing autophagy.
Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.CircRNAs are now under hot discussion as novel promising bio-markers for patients with clear cell renal cell carcinoma. The purpose of our study is to identify several circRNAs related to the metastasis and progression of clear cell renal cell carcinoma, and to further investigate the mechanism of their influence on tumor progression. The transcriptome data of ccRCC and clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus database. A total of 114 circRNAs were found to be related to tumor initiation, progression and metastasis after the intersection. In addition, 14 miRNAs and 201 eligible mRNAs were selected as targets gene, respectively. CeRNA network was constructed based on 8 circRNAs, 14 miRNAs, and 201 mRNAs. Besides, another 6 hub genes were identified via the PPI network. It should be noted that only TRIM2 was confirmed as an independent prognostic factor, which was simultaneously significantly related to both clinical stage and pathological grade in clinical cohorts. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated the possible function of TRIM2 in ccRCC progression, such as ubiquitin mediated protein hydrolysis, cell adhesion molecules, Th17 cell differentiation signaling pathway and so on. Gene set enrichment analysis analysis revealed that TRIM2 may be involved in ubiquitin mediated proteolysis, apoptosis, autophagy and citrate cycle TCA cycle. Hub circ_RNAs expressions were validated in ccRCC tissues and cell lines. Our study revealed that the hsa_circ_0002286 / has-mir-222-5p / TRIM2 axis played a critical role in the progression of ccRCC. Specifically, it may inhibit the metastasis and progression of ccRCC, which could serve as a potential therapeutic target.The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. Many identified that impaired DNA polymerase β (Pol β)-mediated DNA base-excision repair (BER) drives to mouse oocyte aging. With aging, DNA lesions accumulate in primordial follicles. However, the expression of most DNA BER genes, including APE1, OGG1, XRCC1, Ligase I, Ligase α, PCNA and FEN1, remains unchanged during aging in mouse oocytes. Also, the reproductive capacity of Pol β+/- heterozygote mice was impaired, and the primordial follicle counts were lower than that of wild type (wt) mice. The DNA lesions of heterozygous mice increased. Moreover, the Pol β knockdown leads to increased DNA damage in oocytes and decreased survival rate of oocytes. Oocytes over-expressing Pol β showed that the vitality of senescent cells enhances significantly. Furthermore, serum concentrations of anti-Müllerian hormone (AMH) indicated that the ovarian reserves of young mice with Pol β germline mutations were lower than those in wt. These data show that Pol β-related DNA BER efficiency is a major factor governing oocyte aging in mice.Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male mice as a T2DM model, and the gut microbiota of db/db and m/m mice were transplanted successfully into pseudo germ-free mice. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db mice. Interestingly, the host after gut microbiota transplantation from db/db mice showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m mice. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.The 5-year survival rate of ovarian cancer patients is only 47%, and developing novel drugs for ovarian cancer is needed. Herein, we evaluated if and how SRT2183, a sirtuin-1 activator, impairs the ovarian cancer cells. OVCAR-3 and A2780 cells were treated with SRT2183. https://www.selleckchem.com/products/brd7389.html Cell viability was measured by cell counting kit-8 assay and clonogenic assay. Apoptosis was determined by flow cytometry with Annexin V and propidium iodide. The level of autophagy was evaluated by western blot and immunofluorescence. The activities of AKT/mTOR/70s6k and MAPK signaling pathway were measured by immunoblot. SRT2183 inhibited the growth of ovarian cancer cells, increased the accumulation of BAX, cleaved-caspase 3 and cleaved-PARP, and decreased the level of anti-apoptotic Bcl-2 and Mcl-1. SRT2183 increased the LC3II level, and enhanced the degradation of p62/SQSTM1. SRT2183 increased the formation of GFP-LC3 puncta and induced the maturation of autophagosome. Interestingly, knockdown of autophagy related 5 and 7 significantly impaired the anti-carcinoma activity of SRT2183, implying that SRT2183 impaired the ovarian cancer cells by inducing autophagy.0 Commenti 0 condivisioni 83 Views 0 Anteprima -
The United States (US) has been among those nations most severely affected by the first-and subsequent-phases of the pandemic of COVID-19, the disease caused by SARS-CoV-2. With only 4% of the worldwide population, the US has seen about 22% of COVID-19 deaths. Despite formidable advantages in resources and expertise, presently the per capita mortality rate is over 585/million, respectively 2.4 and 5 times higher compared to Canada and Germany. As we enter Fall 2020, the US is enduring ongoing outbreaks across large regions of the country. Moreover, within the US, an early and persistent feature of the pandemic has been the disproportionate impact on populations already made vulnerable by racism and dangerous jobs, inadequate wages, and unaffordable housing, and this is true for both the headline public health threat and the additional disastrous economic impacts. In this article we assess the impact of missteps by the Federal Government in three specific areas the introduction of the virus to the US and the establishment of community transmission; the lack of national COVID-19 workplace standards and enforcement, and lack of personal protective equipment (PPE) for workplaces as represented by complaints to the Occupational Safety and Health Administration (OSHA) which we find are correlated with deaths 16 days later (ρ = 0.83); and the total excess deaths in 2020 to date already total more than 230,000, while COVID-19 mortality rates exhibit severe-and rising-inequities in race/ethnicity, including among working age adults.
Although uncommon, breast cancer is the leading cause of cancer death in young women. There are limited studies on the presentation and characteristics of breast cancer in women under age 40.
This is a retrospective study investigating patient demographics, clinical presentations, imaging findings, and cancer characteristics of a cohort of 145 women under age 40 with breast cancer.
Our cohort had more aggressive cancer subtypes than reported in older women; 33.1% triple negative, 80% high Ki-67, and 21.3% with stage 3+ disease. Most were referred from primary care or obstetrician/gynecologist, though 5.5% initially presented from the emergency department and another 2.1% were incidental findings. 16.6% of patients presented while pregnant or breastfeeding. Most patients presented with breast related symptoms. Of the 9.1% of patients diagnosed through our high-risk screening program, 84.6% of the cancers were identified on mammography or simultaneously with mammography and MRI. Most breast cancers presennancy-related breast changes to minimize delays in diagnosis. Additionally, it is important to identify patients who qualify for high risk screening, since cancers in screening patients were found at a lower grade than those presenting with symptoms.Aspartic proteases (APs) are one of the four main protease super families. In plants, they are involved in many biological processes, such as biotic and abiotic stress resistance, protein processing and degradation, senescence, and programmed cell death. By performing a database (TGACv1) search and domain prediction, we identified 263 wheat AP (TaAP) proteins and observed 38 TaAP genes exhibiting alternative splicing. Moreover, by constructing a phylogenetic tree, we found that the TaAP proteins can be divided into three families and have a certain close evolutionary relationship to Arabidopsis thaliana and rice AP proteins. Transcriptome analysis showed that 29 genes in the TaAP family were up-regulated after being induced by powdery mildew. The expression of TaAP224 showed the most significant difference in transcriptome and qRT-PCR analyses. Subsequently, the promoters of these 29 genes were analysed, and we found that they contained multiple disease resistance and hormone elements, such as WRKY71OS, a common disease resistance element that is also involved in the GA signalling pathway and inhibits starch hydrolysis. The comprehensive annotation and expression profiling performed in this study increased our understanding of the TaAP family genes in wheat growth and development, and the results can be used as a basis for further study of candidate TaAP genes involved in powdery mildew resistance mechanisms.Cancer treatment is a complex process due to the several encountered obstacles during therapy, such as metastasis, angiogenesis, and drug resistance. The methylation status of elements that are thought to play crucial roles in these mechanisms is considered valuable targets. https://www.selleckchem.com/products/i-138.html Matrix metalloproteinase-3 (MMP-3), one of the possible targets, is a well-known endopeptidase and secreted by several types of cancer cells. Paclitaxel, cisplatin, and methotrexate are frequently used for several malignancies, individually or in combination. Therefore, the aims of this study is that demonstration of possible effects of different doses of single or jointly application of these agents with maintaining their antiproliferative activity in clinically relevant cell lines, as well as revealing epigenetic results of this pharmacological alteration with exploring promoter methylation status of the MMP-3 gene. Cell viability was determined with Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Further methylation-specific PCR (MSP) experiments for determining the promoter methylation status of MMP-3 were performed according to the obtained IC50 values of the drug treatments. The MMP-3 promoter methylation status was analayzed with MSP and determined with agarose gel electrophoresis. As a result, methotrexate and paclitaxel treatment significantly methylated the MMP-3 promoter; however, cisplatin caused MMP-3 promoter unmethylation in MCF-7 and SH-SY5Y cells. Our study indicates that decreasing the dose of clinically prevalent chemotherapeutic agents while maintaining the same tumor-killing potency might be a rational strategy for treatment. In addition to avoiding adverse effects of these compounds, decreasing treatment doses will bring substantial benefits for patient life-quality.Water pollution caused by heavy metal leaves human beings exposed to various health risks. Although many studies have focused on the efficiency of industrial water use (IWU) systems, few studies further address analysis for the harmful effect of heavy metal polluted water on human health. This paper first considers both IWU and healthcare (HC) systems as an integrated two-stage IWUHC system. Detailed efficiencies and its dynamic evolution are further revealed by integrating a dynamic two-stage DEA model within a slacks-based measure and Kernel density estimation. Results are as follows (1) During 2011-2017, the IWUHC systems for 30 provinces in China have low efficiencies, which may have been caused by the bad performance of HC sub-system. The rankings of the average IWU efficiencies in four regions are in agreement with that of HC sub-system northeastern, eastern, western, and central regions. (2) Provincial differences of IWU efficiencies are more significant than that of HC sub-system. The two-level distribution of IWUHC efficiencies is not helpful for improving IWUHC efficiencies in the eastern and western regions.
The United States (US) has been among those nations most severely affected by the first-and subsequent-phases of the pandemic of COVID-19, the disease caused by SARS-CoV-2. With only 4% of the worldwide population, the US has seen about 22% of COVID-19 deaths. Despite formidable advantages in resources and expertise, presently the per capita mortality rate is over 585/million, respectively 2.4 and 5 times higher compared to Canada and Germany. As we enter Fall 2020, the US is enduring ongoing outbreaks across large regions of the country. Moreover, within the US, an early and persistent feature of the pandemic has been the disproportionate impact on populations already made vulnerable by racism and dangerous jobs, inadequate wages, and unaffordable housing, and this is true for both the headline public health threat and the additional disastrous economic impacts. In this article we assess the impact of missteps by the Federal Government in three specific areas the introduction of the virus to the US and the establishment of community transmission; the lack of national COVID-19 workplace standards and enforcement, and lack of personal protective equipment (PPE) for workplaces as represented by complaints to the Occupational Safety and Health Administration (OSHA) which we find are correlated with deaths 16 days later (ρ = 0.83); and the total excess deaths in 2020 to date already total more than 230,000, while COVID-19 mortality rates exhibit severe-and rising-inequities in race/ethnicity, including among working age adults. Although uncommon, breast cancer is the leading cause of cancer death in young women. There are limited studies on the presentation and characteristics of breast cancer in women under age 40. This is a retrospective study investigating patient demographics, clinical presentations, imaging findings, and cancer characteristics of a cohort of 145 women under age 40 with breast cancer. Our cohort had more aggressive cancer subtypes than reported in older women; 33.1% triple negative, 80% high Ki-67, and 21.3% with stage 3+ disease. Most were referred from primary care or obstetrician/gynecologist, though 5.5% initially presented from the emergency department and another 2.1% were incidental findings. 16.6% of patients presented while pregnant or breastfeeding. Most patients presented with breast related symptoms. Of the 9.1% of patients diagnosed through our high-risk screening program, 84.6% of the cancers were identified on mammography or simultaneously with mammography and MRI. Most breast cancers presennancy-related breast changes to minimize delays in diagnosis. Additionally, it is important to identify patients who qualify for high risk screening, since cancers in screening patients were found at a lower grade than those presenting with symptoms.Aspartic proteases (APs) are one of the four main protease super families. In plants, they are involved in many biological processes, such as biotic and abiotic stress resistance, protein processing and degradation, senescence, and programmed cell death. By performing a database (TGACv1) search and domain prediction, we identified 263 wheat AP (TaAP) proteins and observed 38 TaAP genes exhibiting alternative splicing. Moreover, by constructing a phylogenetic tree, we found that the TaAP proteins can be divided into three families and have a certain close evolutionary relationship to Arabidopsis thaliana and rice AP proteins. Transcriptome analysis showed that 29 genes in the TaAP family were up-regulated after being induced by powdery mildew. The expression of TaAP224 showed the most significant difference in transcriptome and qRT-PCR analyses. Subsequently, the promoters of these 29 genes were analysed, and we found that they contained multiple disease resistance and hormone elements, such as WRKY71OS, a common disease resistance element that is also involved in the GA signalling pathway and inhibits starch hydrolysis. The comprehensive annotation and expression profiling performed in this study increased our understanding of the TaAP family genes in wheat growth and development, and the results can be used as a basis for further study of candidate TaAP genes involved in powdery mildew resistance mechanisms.Cancer treatment is a complex process due to the several encountered obstacles during therapy, such as metastasis, angiogenesis, and drug resistance. The methylation status of elements that are thought to play crucial roles in these mechanisms is considered valuable targets. https://www.selleckchem.com/products/i-138.html Matrix metalloproteinase-3 (MMP-3), one of the possible targets, is a well-known endopeptidase and secreted by several types of cancer cells. Paclitaxel, cisplatin, and methotrexate are frequently used for several malignancies, individually or in combination. Therefore, the aims of this study is that demonstration of possible effects of different doses of single or jointly application of these agents with maintaining their antiproliferative activity in clinically relevant cell lines, as well as revealing epigenetic results of this pharmacological alteration with exploring promoter methylation status of the MMP-3 gene. Cell viability was determined with Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Further methylation-specific PCR (MSP) experiments for determining the promoter methylation status of MMP-3 were performed according to the obtained IC50 values of the drug treatments. The MMP-3 promoter methylation status was analayzed with MSP and determined with agarose gel electrophoresis. As a result, methotrexate and paclitaxel treatment significantly methylated the MMP-3 promoter; however, cisplatin caused MMP-3 promoter unmethylation in MCF-7 and SH-SY5Y cells. Our study indicates that decreasing the dose of clinically prevalent chemotherapeutic agents while maintaining the same tumor-killing potency might be a rational strategy for treatment. In addition to avoiding adverse effects of these compounds, decreasing treatment doses will bring substantial benefits for patient life-quality.Water pollution caused by heavy metal leaves human beings exposed to various health risks. Although many studies have focused on the efficiency of industrial water use (IWU) systems, few studies further address analysis for the harmful effect of heavy metal polluted water on human health. This paper first considers both IWU and healthcare (HC) systems as an integrated two-stage IWUHC system. Detailed efficiencies and its dynamic evolution are further revealed by integrating a dynamic two-stage DEA model within a slacks-based measure and Kernel density estimation. Results are as follows (1) During 2011-2017, the IWUHC systems for 30 provinces in China have low efficiencies, which may have been caused by the bad performance of HC sub-system. The rankings of the average IWU efficiencies in four regions are in agreement with that of HC sub-system northeastern, eastern, western, and central regions. (2) Provincial differences of IWU efficiencies are more significant than that of HC sub-system. The two-level distribution of IWUHC efficiencies is not helpful for improving IWUHC efficiencies in the eastern and western regions.0 Commenti 0 condivisioni 4 Views 0 Anteprima -
Sensitive and rapid detection of pathogenic bacteria remains important and challenging for food safety and preventing outbreaks of foodborne disease. The major limitations of standard analytical methods for detecting vibrio parahaemolyticus (V.P) lie in their bulky equipment and tedious and long-time operation. This study presents an electrochemical aptasensor for the rapid on-site quantification of V.P in seafood. Magnetic nanoscale metal-organic frameworks (Fe3O4@NMOF) labeled with an aptamer against V.P served as capture probes, while gold nanoparticles combined with phenylboronic acid and ferrocene acted as the nanolabels. When detecting V.P, the sandwich-type complex of capture probe-V.P-nanolabel was formed and magnetically attached to a screen-printed electrode (SPE) for signal measurement. Under optimal conditions, the increase in the ferrocene electrochemical signals could assess the V.P amount; the quantified concentration range was 10-109 cfu/mL. Then, the developed signal-on sensor successfully detected V.P in real seafood samples, exhibiting many advantages. It could not only specifically enrich and rapidly separate the V.P in complex samples but also largely amplify the signal. Moreover, using compact SPE with a detection time of maximum 20 min as the measurement platform allows rapid on-site assays. Thus, the proposed method is a feasible strategy for screening V.P in seafood.Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab2) conjugation which was denoted as Au NR@SBA-15/Ab2-HRP. https://www.selleckchem.com/products/hs-10296.html The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1-5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers.Phosphate (Pi) not only plays a significant role in physiological processes, but also is an important indicator for aquatic ecosystems. The dual-functional lanthanide metal organic frameworks (MOFs) were synthesized for visual and ultrasensitive ratiometric fluorescent detection of Pi based on aggregation-induced energy transfer. In the MOFs material, ciprofloxacin (CIP) functions as an energy donor and results in the fluorescence enhancement of Eu3+; the introduction of pyromellitic acid can cause the aggregation of the CIP-Eu3+ complex, and red characteristic fluorescence of Eu3+ at 614 nm is further enhanced (about 40 times). When Pi is added to the MOFs solution, CIP is released from the MOFs, red fluorescence of Eu3+ is quenched and blue fluorescence of CIP is simultaneously recovered, thereby a ratiometric fluorescent probe for the detection of Pi was fabricated. The fluorescent response based on intermolecular energy transfer of the CIP-Eu3+ complex is very sensitive to Pi. The limit of detection (3σ/K) of the probe is ultrasensitive and attains 4.4 nM. The possible interferential substances such as 17 common metal ions and 14 anions investigated do not interfere with the Pi detection. The ratiometric fluorescent probe has been successfully used in the determination of Pi in real human urine and lake water samples. This work may supply a new strategy for fabricating ratiometric fluorescent probe and a prospective application in biological and environmental samples.Alzheimer's disease (AD) is a chronic neurodegenerative disease. Better imaging and early diagnosis of biomarkers of AD is extremely important for therapeutic interventions. The amyloid cascade hypothesis and its revised version identify insoluble β-amyloid deposition as a good diagnostic biomarker for AD. Moreover, lipid droplets may also act as an auxiliary biomarker related to AD pathology based on recent studies. Herein, two quinoline-based AIE probes were designed and synthesized for the imaging of Aβ plaques and lipid droplets. The probes exhibited remarkable turn-on fluorescence enhancements with the Aβ aggregates. The lipid droplets-targeting probe FB exhibited high selectivity and binding affinity towards the Aβ aggregates with a detection limit as low as 26.9 nM. Furthermore, FB was capable of readily imaging Aβ plaques and lipid droplets at the cellular level and in brain sections of transgenic AD ****. The probe FB can serve as a promising tool for developing early diagnosis and innovative therapeutics of AD.Triphenyl phosphate (TPhP), a typical model of organophosphorus flame retardants (OPFRs), has been regarded as emerging environmental contaminants of health concern. In this study, TPhP molecularly imprinted polymers immobilized on graphene oxide (GO) film (TPhP-MIPs/GO) monolithic fiber for direct immersion solid phase microextraction (DI-SPME) was fabricated and evaluated. Compared with TPhP molecularly imprinted polymers (TPhP-MIPs) monolithic fiber, TPhP-MIPs/GO fiber had bigger extraction capacity, stronger hydrophilicity and faster mass transfer rate. Furthermore, TPhP-MIPs/GO fiber displayed excellent selectivity for TPhP among its structure analogues. It was thermally stable up to 320 °C so that it can withstand the high temperature of gas chromatography (GC) injection port for desorption and detection by flame photometric detector (FPD). Under optimal conditions, TPhP-MIPs/GO-SPME-GC/FPD method was developed by yielding satisfactory ultralow limit of quantification (0.4 ng L-1); linearity (≥0.99), good intra- and inter-day precision for a single fiber and fiber-to-fiber reproducibility.
Sensitive and rapid detection of pathogenic bacteria remains important and challenging for food safety and preventing outbreaks of foodborne disease. The major limitations of standard analytical methods for detecting vibrio parahaemolyticus (V.P) lie in their bulky equipment and tedious and long-time operation. This study presents an electrochemical aptasensor for the rapid on-site quantification of V.P in seafood. Magnetic nanoscale metal-organic frameworks (Fe3O4@NMOF) labeled with an aptamer against V.P served as capture probes, while gold nanoparticles combined with phenylboronic acid and ferrocene acted as the nanolabels. When detecting V.P, the sandwich-type complex of capture probe-V.P-nanolabel was formed and magnetically attached to a screen-printed electrode (SPE) for signal measurement. Under optimal conditions, the increase in the ferrocene electrochemical signals could assess the V.P amount; the quantified concentration range was 10-109 cfu/mL. Then, the developed signal-on sensor successfully detected V.P in real seafood samples, exhibiting many advantages. It could not only specifically enrich and rapidly separate the V.P in complex samples but also largely amplify the signal. Moreover, using compact SPE with a detection time of maximum 20 min as the measurement platform allows rapid on-site assays. Thus, the proposed method is a feasible strategy for screening V.P in seafood.Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab2) conjugation which was denoted as Au NR@SBA-15/Ab2-HRP. https://www.selleckchem.com/products/hs-10296.html The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1-5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers.Phosphate (Pi) not only plays a significant role in physiological processes, but also is an important indicator for aquatic ecosystems. The dual-functional lanthanide metal organic frameworks (MOFs) were synthesized for visual and ultrasensitive ratiometric fluorescent detection of Pi based on aggregation-induced energy transfer. In the MOFs material, ciprofloxacin (CIP) functions as an energy donor and results in the fluorescence enhancement of Eu3+; the introduction of pyromellitic acid can cause the aggregation of the CIP-Eu3+ complex, and red characteristic fluorescence of Eu3+ at 614 nm is further enhanced (about 40 times). When Pi is added to the MOFs solution, CIP is released from the MOFs, red fluorescence of Eu3+ is quenched and blue fluorescence of CIP is simultaneously recovered, thereby a ratiometric fluorescent probe for the detection of Pi was fabricated. The fluorescent response based on intermolecular energy transfer of the CIP-Eu3+ complex is very sensitive to Pi. The limit of detection (3σ/K) of the probe is ultrasensitive and attains 4.4 nM. The possible interferential substances such as 17 common metal ions and 14 anions investigated do not interfere with the Pi detection. The ratiometric fluorescent probe has been successfully used in the determination of Pi in real human urine and lake water samples. This work may supply a new strategy for fabricating ratiometric fluorescent probe and a prospective application in biological and environmental samples.Alzheimer's disease (AD) is a chronic neurodegenerative disease. Better imaging and early diagnosis of biomarkers of AD is extremely important for therapeutic interventions. The amyloid cascade hypothesis and its revised version identify insoluble β-amyloid deposition as a good diagnostic biomarker for AD. Moreover, lipid droplets may also act as an auxiliary biomarker related to AD pathology based on recent studies. Herein, two quinoline-based AIE probes were designed and synthesized for the imaging of Aβ plaques and lipid droplets. The probes exhibited remarkable turn-on fluorescence enhancements with the Aβ aggregates. The lipid droplets-targeting probe FB exhibited high selectivity and binding affinity towards the Aβ aggregates with a detection limit as low as 26.9 nM. Furthermore, FB was capable of readily imaging Aβ plaques and lipid droplets at the cellular level and in brain sections of transgenic AD mice. The probe FB can serve as a promising tool for developing early diagnosis and innovative therapeutics of AD.Triphenyl phosphate (TPhP), a typical model of organophosphorus flame retardants (OPFRs), has been regarded as emerging environmental contaminants of health concern. In this study, TPhP molecularly imprinted polymers immobilized on graphene oxide (GO) film (TPhP-MIPs/GO) monolithic fiber for direct immersion solid phase microextraction (DI-SPME) was fabricated and evaluated. Compared with TPhP molecularly imprinted polymers (TPhP-MIPs) monolithic fiber, TPhP-MIPs/GO fiber had bigger extraction capacity, stronger hydrophilicity and faster mass transfer rate. Furthermore, TPhP-MIPs/GO fiber displayed excellent selectivity for TPhP among its structure analogues. It was thermally stable up to 320 °C so that it can withstand the high temperature of gas chromatography (GC) injection port for desorption and detection by flame photometric detector (FPD). Under optimal conditions, TPhP-MIPs/GO-SPME-GC/FPD method was developed by yielding satisfactory ultralow limit of quantification (0.4 ng L-1); linearity (≥0.99), good intra- and inter-day precision for a single fiber and fiber-to-fiber reproducibility.0 Commenti 0 condivisioni 6 Views 0 Anteprima
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