The concentration of nitrogen (N) in vegetative tissues is largely dependent on the balance among growth, root N uptake, and N assimilation. Elevated CO2 (eCO2) plus warming is likely to affect the vegetative-tissue N and protein concentration of wheat by altering N metabolism, but this is poorly understood. To investigate this, spring wheat (Triticum aestivum) was grown for three weeks at two levels of CO2 (400 or 700 ppm) and two temperature regimes (26/21 or 31/26 °C, day/night). Plant dry mass, plant %N, protein concentrations, NO3- and NH4+ root uptake rates (using 15NO3 or 15NH4), and whole-plant N- and NO3–assimilation were measured. Plant growth, %N, protein concentration, and root N-uptake rate were each significantly affected only by CO2, while N- and NO3–assimilation were significantly affected only by temperature. However, plants grown at eCO2 plus warming had the lowest concentrations of N and protein. These results suggest that one strategy breeding programs can implement to minimize the negative effects of eCO2 and warming on wheat tissue N would be to target the maintenance of root N uptake rate at eCO2 and N assimilation at higher growth temperatures.Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees’ health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted.Drug nanoformulations hold remarkable promise for the efficient delivery of therapeutics to a disease site. Unfortunately, artificial nanocarriers, mostly liposomes and polymeric nanoparticles, show limited applications due to the unfavorable pharmacokinetics and rapid clearance from the blood circulation by the reticuloendothelial system (RES). Besides, many of them have high cytotoxicity, low biodegradability, and the inability to cross biological barriers, including the blood brain barrier. Extracellular vesicles (EVs) are novel candidates for drug delivery systems with high bioavailability, exceptional biocompatibility, and low immunogenicity. They provide a means for intercellular communication and the transmission of bioactive compounds to targeted tissues, cells, and organs. These features have made them increasingly attractive as a therapeutic platform in recent years. However, there are many obstacles to designing EV-based therapeutics. In this review, we will outline the main hurdles and limitations for therapeutic and clinical applications of drug loaded EV formulations and describe various attempts to solve these problems.Psychological anxiety and physiological stress hormone management is closely related to an athlete’s performance, especially in shooting competitions. Thus, we aimed to investigate the changes in saliva stress hormones according to anxiety scores of Korean elite shooters immediately before a shooting competition. Seventy-two Korean national shooting athletes (Rifle = 62, Pistol = 8, Shotgun = 2) were recruited for the present study. The physiological stress hormones were assessed based on cortisol and immunoglobulin A level in saliva. The psychological stress was assessed based on Beck Anxiety Inventory (BAI) questionnaire. Cortisol concentration and cortisol secretion rate were significant higher in severe anxiety group. Secretory immunoglobulin A (SIgA) concentration and SIgA secretion rate did not significant different in among the groups. A positive correlation was found between BAI score and cortisol concentration. These findings provide preliminary evidence indicating that psychological anxiety affects physiological stress and therefore may have a negative effect on athletes’ performance. Thus, research is needed to develop a strategy to reduce physiological stress in these athletes.For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins, and carbohydrates in their seeds, distinctly dominate modern agriculture, thus play an essential role in food industry and fuel production. Therefore, seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, seed development and germination as well as age- and stress-related alterations in seed vigor, longevity, nutritional value, and safety can be addressed by a broad panel of analytical, biochemical, and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes accompanying plant development, senescence, and response to biotic or abiotic stress. Among individual post-genomic methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. During the recent decades, multiple methodological advances were introduced in different branches of life science, although only some of them were established in seed proteomics so far. Therefore, here we discuss main methodological approaches already employed in seed proteomics, as well as those still waiting for implementation in this field of plant research, with a special emphasis on sample preparation, data acquisition, processing, and post-processing. Thereby, the overall goal of this review is to bring new methodologies emerging in different areas of proteomics research (clinical, food, ecological, microbial, and plant proteomics) to the broad society of seed biologists.Fruits are a valuable source of phytochemicals. However, there is little detailed information about the compounds contained in fruit wines. Zilurgisertib fumarate manufacturer In this study, wines from six different berries were analyzed using HPLC-DAD-ESI-MSn. link2 About 150 compounds were identified, including anthocyanins (34), hydroxycinnamic acids (12) and flavonols (36). Some of the compounds were identified for the first time in berry wines. The blackberry wines were found to contain the largest number of bioactive compounds (59). Elderberry wines where the richest source of polyphenols (over 1000 mg/L) and contained the largest amounts of all of the analyzed groups of compounds (hydroxycinnamic acids, anthocyanins and flavonols). The lowest concentration of polyphenols was observed in the wines made from cranberries and bilberries (less than 500 mg/L). The antioxidant activity was determined in relation to ABTS+, DPPH, and FRAP. The highest values were observed in the blackberry wines, and the lowest for the cranberry wines. The wines were analyzed to test their antimicrobial activity. link3 Five of the six wines (with the exception of elderberry wine) inhibited Bacillus cereus growth and two (blackberry and cranberry wines) were active against Listeria monocytogenes.The AUC (area under the concentration time curve) is considered the pharmacokinetic exposure parameter best associated with clinical effects. Unfortunately, no prospective studies of clinical outcomes have been conducted in adult transplant recipients to investigate properly the potential benefits of AUC(0-12) monitoring compared to the C0-guided therapy. The aim of the present study was to compare two methods, C0 (through level) and AUC(0-12) (area under the concentration time curve), for assessing cyclosporine and tacrolimus concentrations. The study included 340 kidney recipients. The AUC(0-12) was estimated using a Bayesian estimator and a three-point limited sampling strategy. Therapeutic drug monitoring of tacrolimus performed by using AUC(0-12) and C0 showed that tacrolimus in most cases is overdosed when considering C0, while determination of the AUC(0-12) showed that tacrolimus is effectively dosed for 27.8-40.0% of patients receiving only tacrolimus and for 25.0-31.9% of patients receiving tacrolimus with MMF (mycophenolate mofetil). In the 1-5 years post-transplantation group, 10% higher CsA (cyclosporine) dose was observed, which was proportionate with a 10% higher AUC(0-12) exposure value. This indicates good compatibility of the dosage and the AUC(0-12) method. The Bland-Altman plot demonstrated that C0 and AUC(0-12) might be interchangeable methods, while the ROC (receiver operating characteristic) curve analysis of the C0/AUC(0-12) ratio in the tacrolimus-receiving patient group demonstrated reliable performance to predict IFTA (interstitial fibrosis and tubular atrophy) after kidney transplantation, with an ROC curve of 0.660 (95% confidence interval (CI) 0.576-0.736), p less then 0.01. Moreover, AUC(0-12) and C0 of tacrolimus depend on concomitant medication and adjustment of the therapeutic range for AUC(0-12) might influence the results.Non-alcoholic fatty liver disease (NAFLD), which affects both adults and children, is the most common liver disorder worldwide. NAFLD is characterized by excess fat accumulation in the liver in the absence of significant alcohol use. NAFLD is strongly associated with obesity, insulin resistance, metabolic syndrome, as well as specific genetic polymorphisms. Severe NAFLD cases can further progress to cirrhosis, hepatocellular carcinoma (HCC), or cardiovascular complications. Here, we describe the pathophysiological features and critical genetic variants associated with NAFLD. Recent advances in genome-engineering technology have provided a new opportunity to generate in vitro and in vivo models that reflect the genetic abnormalities of NAFLD. We review the currently developed NAFLD models generated using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) genome editing. We further discuss unique features of CRISPR/Cas9 and Cas9 variants, including base editors and prime editor, that are useful for replicating genetic features specific to NAFLD. We also compare advantages and limitations of currently available methods for delivering genome-editing tools necessary for optimal genome editing. This review should provide helpful guidance for selecting “good fit” genome-editing tools and appropriate gene-delivery methods for the successful development of NAFLD models and clinical therapeutics.