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Tissue-engineered models continue to experience challenges in delivering structural specificity, nutrient delivery, and heterogenous cellular components, especially for organ-systems that require functional inputs/outputs and have high metabolic requirements, such as the heart. While soft lithography has provided a means to recapitulate complex architectures in the dish, it is plagued with a number of prohibitive shortcomings. Here, concepts from microfluidics, tissue engineering, and layer-by-layer fabrication are applied to develop reconfigurable, inexpensive microphysiological systems that facilitate discrete, 3D cell compartmentalization, and improved nutrient transport. This fabrication technique includes the use of the meniscus pinning effect, photocrosslinkable hydrogels, and a commercially available laser engraver to cut flow paths. The approach is low cost and robust in capabilities to design complex, multilayered systems with the inclusion of instrumentation for real-time manipulation or measures of cell function. In a demonstration of the technology, the hierarchal 3D microenvironment of the cardiac sympathetic nervous system is replicated. Beat rate and neurite ingrowth are assessed on-chip and quantification demonstrates that sympathetic-cardiac coculture increases spontaneous beat rate, while drug-induced increases in beating lead to greater sympathetic innervation. Importantly, these methods may be applied to other organ-systems and have promise for future applications in drug screening, discovery, and personal medicine.The purpose of the current study was to investigate the impact of job demands on health and work outcomes among Malaysian workers. We hypothesized that job demands (i.e., emotional demands and physical demands) would predict future work-related burnout and work engagement, in turn affecting sleep problems and job performance (in-role, extra-role). A longitudinal two-wave survey was conducted among Malaysian workers and valid data from 345 participants were analyzed using structural equation modeling. The results revealed that work-related burnout predicts sleep problems while work engagement increased employees' job performance over time. Overall, the current study highlights the importance of specific job demands (i.e., emotional demands and physical demands) that specifically affect health-related behavior and work-related behavior among workers.In recent years, several tetracyanobuta-1,3-diene (TCBD) conjugates have been prepared by linking the tetracyano unit to various electroactive moieties. These push-pull conjugates, besides showing interesting physicochemical properties, are axially chiral, a feature arising from the restricted rotation around the central bond of the butadiene. Yet, only in a few cases, separation and isolation of the enantiomers have been successfully achieved, owing to the configurational lability of the corresponding enantiopure species. Herein, we report the first example of photo- and electroactive TCBD-based derivatives showing unprecedented configurational stability and a peculiar light-triggered enantiomer conversion mechanism enabled by triple-state photogeneration. These systems represent a nice addition to the fast-increasing arsenal of artificial, light-controllable molecular switches.
Most studies on tobacco and alcohol consumption empirically model the two behaviours separately. The primary aim of this study was to investigate the patterns of tobacco and alcohol co-consumption in Thailand, modelling the two behaviours jointly and identifying whether they complemented or substituted each other.
Data were extracted from the 2007, 2011, 2014 and 2017 waves of the nationally representative Tobacco and Alcohol Consumption Survey in Thailand. A bivariate ordered probit model, under which the frequencies of tobacco and alcohol consumption were jointly estimated, was performed on the repeated cross-sectional sample as well as each of the cross-sectional samples.
Based on the repeated cross-sectional sample (n = 411 981), the analyses suggested that tobacco and alcohol consumption were complementary behaviours. The predicted conditional probabilities revealed that the more frequently one drank, the higher the likelihood that he/she also smoked at a higher frequency, and vice versa.
Given the complementary nature of tobacco and alcohol consumption in Thailand, tobacco- and alcohol-prevention strategies should be realigned and better co-ordinated for greater efficiency. The net impacts of a given tobacco or alcohol policy should be incorporated into the optimal policy design to avoid duplication of efforts. Also, future studies of tobacco and alcohol consumption should consider modelling the two behaviours together using a joint estimation approach.
Given the complementary nature of tobacco and alcohol consumption in Thailand, tobacco- and alcohol-prevention strategies should be realigned and better co-ordinated for greater efficiency. The net impacts of a given tobacco or alcohol policy should be incorporated into the optimal policy design to avoid duplication of efforts. Also, future studies of tobacco and alcohol consumption should consider modelling the two behaviours together using a joint estimation approach.In the field of nucleic acid therapy there is major interest in the development of libraries of DNA-reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs and CRISPR-Cas, but overcomes the limitations imposed by the delivery of a large protein endonuclease which is required for DNA cleavage. Dehydrogenase inhibitor Here, we introduce a chemistry-based DNA-cleavage system comprising an artificial metallo-nuclease (AMN) that oxidatively cuts DNA, and a triplex-forming oligonucleotide (TFO) that sequence-specifically recognises duplex DNA. The AMN-TFO hybrids coordinate CuII ions to form chimeric catalytic complexes that are programmable - based on the TFO sequence employed - to bind and cut specific DNA sequences. Use of the alkyne-azide cycloaddition click reaction allows scalable and high-throughput generation of hybrid libraries that can be tuned for specific reactivity and gene-of-interest knockout. As a first approach, we demonstrate targeted cleavage of purine-rich sequences, optimisation of the hybrid system to enhance stability, and discrimination between target and off-target sequences. Our results highlight the potential of this approach where the cutting unit, which mimics the endonuclease cleavage machinery, is directly bound to a TFO guide by click chemistry.Biosecurity risks are a major threat to the profitability of the industry as well as impacting human and animal health. Livestock producers play a crucial role in biosecurity as the first to notice changes in the health or productivity of their stock and are generally responsible for implementing protective measures. However, uptake of biosecurity measures by producers is variable. We critically appraised the current literature regarding biosecurity practices in Australian livestock industries and highlight aspects that are well understood as well as those where further research or information is needed. Findings from 12 cross-sectional studies suggest that Australian producers' knowledge of biosecurity methods and importance might have a positive influence on their willingness to implement or incorporate biosecurity practices. There is moderate evidence supportive of biosecurity being well understood by livestock producers across Australia. Barriers to producers using biosecurity practices included lack of information or communication from agricultural, veterinary or government organisations. It was found that larger stock numbers were positively correlated with biosecurity implementation and that producers used veterinarians, government and industry agencies as resources for trusted information.The role of breast magnetic resonance imaging (MRI) in the screening of breast cancer survivors with remaining breast tissue is not well studied. We sought to evaluate the outcomes of screening breast MRI in a cohort of breast cancer survivors. A population of patients with history of stage I-IIIa breast cancer and ≥1 MRI a year or later from diagnosis between 2006-2008 were identified using the National Comprehensive Cancer Network data base from two large Boston-area cancer centers. Patient and disease characteristics were obtained from the data base, and medical records were reviewed to identify the index MRI (first eligible), indications, and two-year outcomes. Overall, 647 patients had breast MRI scans during the study period including 342 eligible patients whose index MRIs were done for breast screening purposes. 47/342 (13.7%) were abnormal, and 3.8% (13/342) underwent biopsy, resulting in the detection of 3 cases of locoregional recurrence or new primary breast cancer (0.9%, 95% CI = 0.2%-2.5%). Of 295 patients with a normal index screening MRI, 12 had a breast cancer recurrence diagnosed within 2 years (4.1% 95%CI = 2.1%-7.0%), and 5 of these recurrences were limited to MRI-screened breast tissue. No statistically significant difference in the rate of 2-year locoregional or distant recurrence was observed between patients with an abnormal screening MRI and those with a normal scan. Adjunct single breast MRI surveillance in a general population of breast cancer survivors one year after diagnosis detected few recurrences, and its effect on short-term outcomes was unclear.
Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases (CVD). However, consumption of beverages containing fructose is allowed during gestation. Homocysteine (Hcy) is a well-known risk factor for CVD while hydrogen sulfide (H
S), a product of its metabolism, has been proved to exert opposite effects to Hcy.
First, it is investigated whether maternal fructose intake produces subsequent changes in Hcy metabolism and H
S synthesis of the progeny. Carbohydrates are supplied to pregnant rats in drinking water (10% wt/vol) throughout gestation. Adult female descendants from fructose-fed, control or glucose-fed mothers are studied. Females from fructose-fed mothers have elevated homocysteinemia, hepatic H
S production, cystathionine γ-lyase (CSE) (the key enzyme in H
S synthesis) expression and plasma H
S, versus the other two groups. Second, it is studied how adult female progeny from control (C/F), fructose- (F/F), and glucose-fed (G/F) mothers responded to liquid fructose and compared them to the control group (C/C). Interestingly, hepatic CSE expression and H
S synthesis are diminished by fructose intake, this effect being more pronounced in F/F females.
Maternal fructose intake produces a fetal programming that increases hepatic H
S production and, in contrast, exacerbates its fructose-induced drop in female progeny.
Maternal fructose intake produces a fetal programming that increases hepatic H2 S production and, in contrast, exacerbates its fructose-induced drop in female progeny.Freshwater ecosystems face many simultaneous pressures due to human activities. Consequently, there has been a rapid loss of freshwater biodiversity and an increase in biomonitoring programs. Our study assessed the potential of benthic stream bacterial communities as indicators of multiple-stressor impacts associated with urbanization and agricultural intensification. We conducted a fully crossed four-factor experiment in 64 flow-through mesocosms fed by a pristine montane stream (21 d of colonization, 21 d of manipulations) and investigated the effects of nutrient enrichment, flow-velocity reduction and added fine sediment after 2 and 3 weeks of stressor exposure. We used high-throughput sequencing and metabarcoding techniques (16S rRNA genes), as well as curated biological databases (METAGENassit, MetaCyc), to identify changes in bacterial relative abundances and predicted metabolic functional profile. Sediment addition and flow-velocity reduction were the most pervasive stressors. They both increased α-diversity and had strong taxon-specific effects on community composition and predicted functions.
Website: https://www.selleckchem.com/products/cpi-613.html
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