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We examine the effect of screen-based activities on obesity and mental well-being for children, using a large survey dataset representative of the UK population and an event study model that exploits exogenous variation in the entry date of the digital television transition in the UK. The digital transition increased the number of available free television channels from 5 to 40, leading to a rise in television viewing time. Our results show that receiving access to digital television signal considerably increases the mental health total difficulties score among children, and that this impact grows over time. We also find suggestive evidence that the digital transition could have increased BMI for children. Underlying the net effects appear to be decreases in participation in social and physical activities.Here, we present a portable, selective and cost-effective fiber-optic surface plasmon resonance (SPR) based platform for early detection of Dengue virus. NS1 protein was targeted as the biomarker of dengue. Antibody-antigen specific binding was exploited for NS1 antigen detection. The binding of antibody was assisted by a self-assembled monolayer of alkanethiols on the surface of silver-coated unclad fiber. A wavelength interrogation mode of SPR was utilized to detect NS1 antigen in the dynamic range of 0.2-2.0 μg/ml. The 40 nm thick silver coated optical fiber exhibited resonance wavelength around 500 nm and change in resonance wavelength was monitored for each attachment step on the fiber. The sensitivity at the lowest concentration of NS1 antigen was found to be 54.7 nm/(μg/ml). The limit of detection of the sensor was found to be 0.06 μg/ml, which lies in the physiological range of NS1 protein present in the infected blood, hence the present technique may provide a very early detection advantage. Real blood serum samples were also successfully tested on the set-up, confirming compatibility with the conventional methods. The presented field-deployable platform has wide applications in mass monitoring of dengue, such as during outbreaks and epidemics.Human dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Although studies have reported the fact that genetic mutations in DHFR leads to a rare autosomal recessive inborn error of folate metabolism and drug resistance, there is a lack of an extensive study on how the deleterious non-synonymous SNPs (nsSNPs) disrupt its phenotypic effects. In this study, we aim at discovering the structural and functional consequences of nsSNPs in DHFR by employing a combined computational approach consisting of ten recently developed in silico tools for identification of damaging nsSNPs and molecular dynamics (MD) simulation for getting deeper insights into the magnitudes of damaging effects. Our study revealed the presence of 12 most deleterious nsSNPs affecting the native phenotypic effects, with three (R71T, G118D, Y122D) identified in the co-factor and ligand binding active sites. MD simulations also suggested that these three SNPs particularly Y122D, alter the overall structural flexibility and dynamics of the native DHFR protein which can provide more understandings into the crucial roles of these mutants in influencing the loss of DHFR function.Cross-target effect has been one of the major mechanisms of drug toxicity, this has necessitated the design of inhibitors that are specifically tailored to target particular biomolecules. 6-(2,4-difluorophenoxy)-5-((ethylmethyl)pyridine-3-yl)-8-methylpyrrolo[1,2-a] pyrazin-1(2H)-one (Cpd38) is an inhibitor possessing high inhibition rate and tailored specificity towards bromodomain-containing protein 4 (BRD4). In this research, we used an array of computational techniques to provide insight at the atomistic level the specific targeting of BRD4 by Cpd38 relative to the binding of Cpd38 with E1A binding protein P300 (EP300); another bromodomain-containing protein (BCP). Comparatively, binding of Cpd38 improved the conformational stability and compactness of BRD4 protein when compared to the Cpd38 bound EP300. Also, Cpd38 induced a conformational change in the active site of BRD4 that facilitated a complementary pose between Cpd38 and BRD4 suitable for effective atomistic interactions. Expectedly, thermodynamic calculations revealed that the Cpd38-BRD4 system had higher binding energy (-36.11 Kcal/mol) than the Cpd38-EP300 system with a free binding energy of -15.86 Kcal/mol. Noteworthy is the opposing role Trp81 (acting as hydrogen bond acceptor) and Pro1074 (acting as hydrogen bond donor) found on the WPF and LPF loops respectively play in maintaining Cpd38 stability. Furthermore, the hydrogen bond acceptor/donator ratio was approximately 41 in Cpd38-BRD4 system compared with 21 in Cpd38-EP300 system. Taken together, atomistic insights and structural perspectives detailed in this report supplements the experimental report supporting the improved selectivity of Cpd38 for BRD4 ahead of other BCPs while providing leeway for the future design of BET selective agents with better pharmacological profile.The high prevalence of Salmonella enterica in milk poses a risk of considerable concern in the preservation of certain dairy products, mainly those elaborated from raw milk. Essential oils (EOs) have been proposed as a promising food preservative for such products due to their strong antimicrobial properties. Additionally, these natural antimicrobials have been shown to be effective against multi-drug resistant strains. They can thus also be utilized to prevent the dissemination of antimicrobial resistances (AMR). However, recent evidence of the development of bacterial resistance under EO treatments may call their use into question. This study sought to assess the emergence of antimicrobial resistant genetic variants of S. enterica serovar Typhimurium from survivors after cyclic exposure to lethal doses (>5 log10 cycles of inactivation) of Thymbra capitata EO (TCO), in order to evaluate the impact that it could have on milk preservation, to ascertain whether cross-resistance to antibiotics occurs, and to idected SeWT strain with mutant soxRSeTCO demonstrated that the mutation of soxR was the main cause of the increased resistance and tolerance observed in SeTCO against TCO and antibiotics. The emergence of resistant strains against EOs might jeopardize their use as food preservatives. Further studies will thus be required to determine under which conditions such resistant strains might occur, and to assess the food risk they may pose, as well as to ascertain their impact on the spread of AMR.
To describe the trajectory, number, and types of symptom clusters at three time points (i.e., day of admission [T1], 2-4 days postoperatively [T2], and 1 month postoperatively [T3]) using ratings of symptom occurrence and severity and to identify the changes in these symptom clusters over time in patients with lung cancer.
We analysed the data of 217 lung cancer patients who received surgical treatment at a tertiary hospital affiliated to Anhui Medical University, in Hefei City, China. The occurrence and severity of 19 symptoms at all points of measurement were measured using the general and lung cancer modules of the M.D. read more Anderson Symptom Inventory. Exploratory factor analysis was performed to extract the symptom clusters.
Seven symptom clusters were identified across symptom dimensions. However, only three of them (i.e., lung cancer specific, sleep disturbance, and nervous system) were relatively stable across dimensions and time. Two symptom clusters varied over time but not with dimensions (nutritional and gastrointestinal). The other two symptom clusters (psychological and respiratory) differed in terms of time and dimensions.
Findings may provide insights into the seven identified clusters and overall stability of three symptom clusters in lung cancer patients perioperatively.
Findings may provide insights into the seven identified clusters and overall stability of three symptom clusters in lung cancer patients perioperatively.For exploring the influence of ultrasound on the flavor characteristic of unsmoked bacon, sensory evaluation combined with E-nose and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were performed to analyze the overall flavor profile and specific volatile flavor compounds (VFCs), respectively. Furthermore, the metabolic pathway of VFCs affected by ultrasound was also investigated. Results demonstrated that ultrasound improved the flavor characteristic of unsmoked bacon by raising the levels of nonanal, heptanal, octanal, 3-methylbutanal n-hexyl acetate and n-propyl acetate. Enzymatic oxidation was found to be an important metabolic pathway responsible for the development of flavor characteristic after ultrasound treatment, which could be attributed to the increased activities of lipases and lipoxygenase and the higher concentration of polyunsaturated free fatty acids. The increased level of lipid oxidation after ultrasound treatment was also confirmed by thiobarbituric acid reactive substances. Consequently, ultrasound is an effective approach to enhance the flavor characteristic of unsmoked bacon.Mas-related G protein-coupled receptor X2 (MrgX2) has been identified to be critical in drug-induced pseudo-allergic reactions and allergic diseases. Herein, an affinity high-performance liquid chromatography was established for the specific detection and enrichment of MrgX2. Substance P was used as an affinity ligand and immobilized on a glutaraldehyde-modified amino silica gel. The successful grafting of substance P was characterized by infrared spectroscopy, elemental analysis, X-ray photoelectron spectroscopy, thermogravimetric analysis, and nitrogen adsorption and desorption analyzes. The prepared materials were then used as the stationary phase to investigate the retention behavior of MrgX2 recombinant protein on the affinity column. The results obtained with the analytical techniques show the specificity and selectivity of the MrgX2 recombinant protein on the affinity column. The repeatability and reproducibility for the analysis of MrgX2 on the NH2-Silico@GD@SP column show relative standard deviation (RSD) values lower than the acceptance criteria of 2 and 5% of retention time, and RSD of peak areas less then 7%. The RSD value of the results obtained for the control of the activity of the prepared columns respond to the acceptance criteria of 5% and proves that the NH2-Silico@GD@SP column are stable until 48 h. The suitability of the NH2-Silico@GD@SP column offline SEC system has been tested by using MrgX2 as positive control. The results of this experiment indicate that the offline system may be used to analyze the retention fraction. MrgX2 extracted from human mast cells LAD2 was also verified. An obvious retention can be observed and the natural MrgX2 was concentrated 114.6 times compared with the original complex components by using the affinity column. These results may provide a new approach for the specific detection and enrichment of G-protein-coupled receptors.A rapid and efficient QuEChERS-based preparation method was established for the simultaneous determination of 43 mycotoxins in chestnut and jujube (Chinese date). The contaminants were extracted using acetonitrile and subjected to dispersive solid-phase extraction for further clean-up. Central composite design was conducted to overcome the limitations of conventional optimization methods, and assess the interaction effects between variables and reach the true optimal conditions. Quantitative analysis was performed on UHPLC-MS/MS with the aid of stable isotope internal standards and matrix-matched curves, whereas qualitative identification was carried out by using high-resolution MS based on exact masses and fragmentation patterns. In addition to the mycotoxins that are routinely monitored (like aflatoxins, ochratoxin A, etc.), this study also revealed a non-negligible contamination of zearalenone (56/170), beauvericin (52/170), enniatin B (43/170), and alternariol monomethyl ether (42/170) in chestnut and jujube, especially the chestnut flour.
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