关键词： Gene silencing   miRNAs  

摘要： Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. Macrophages exhibit different functional states and are classified as classically activated (M1) and alternatively activated (M2) macrophages. However, the mechanisms that govern M1/M2 polarization in chronic ALD remain to be elucidated. Prostacyclin (PGI(2)) synthase (PTGIS) is an enzyme of the prostaglandin pathway which catalyzes the conversion of Prostaglandin H-2 (PGH(2)) to PGI(2). PTGIS has anti-inflammatory properties. However, the function of PTGIS in ALD has not yet been determined. In this study, we demonstrated that PTGIS was downregulated in ALD and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed PTGIS overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice. Loss- and gain-of function-experiments demonstrated that forced PTGIS expression inhibited the macrophage switch to the M1 phenotype and promoted M2 polarization. Furthermore, we identified the genes regulated by PTGIS through RNA-sequencing (RNA-seq) analysis. Gene ontology and KEGG pathway analyses showed that PTGIS regulates many genes involved in the immune response and is enriched in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway, which plays an important role in regulating macrophage polarization. The proteins interacting with JAKs were predicted using the STRING database. The overlap between the RNA-seq and the STRING database was interleukin-6;this indicated that it was involved in macrophage polarization regulated by JAK/STAT signaling. We further explored the microRNAs that could regulate the expression of PTGIS through TargetScan. The results of luciferase assay illustrated that the expression of PTGIS was regulated by miR-140-3p.1. These results imply that PTGIS plays a pivotal role in ALD, partly by influencing macrophage polarization. Prostacycli

关键词： TREM2   Alzheimer's disease   alternative splicing   low-frequency variant   aggregation of low-frequency variants  

摘要： TREM2 is among the most well-known Alzheimer's disease (AD) risk genes;however, the functional roles of its AD-associated variants remain to be elucidated, and most known risk alleles are low-frequency variants whose investigation is challenging. Here, we utilized a splicing-guided aggregation method in which multiple low-frequency TREM2 variants were bundled together to investigate the functional impact of those variants on alternative splicing in AD. We analyzed whole genome sequencing (WGS) and RNA-seq data generated from cognitively normal elderly controls (CN) and AD patients in two independent cohorts, representing three regions in the frontal lobe of the human brain: the dorsolateral prefrontal cortex (CN = 213 and AD = 376), frontal pole (CN = 72 and AD = 175), and inferior frontal (CN = 63 and AD = 157). We observed an exon skipping event in the second exon of TREM2, with that exon tending to be more frequently skipped (p = 0.0012) in individuals having at least one low-frequency variant that caused loss-of-function for a splicing regulatory element. In addition, genes differentially expressed between AD patients with high vs. low skipping of the second exon (i.e., loss of a TREM2 functional domain) were significantly enriched in immune-related pathways. Our splicing-guided aggregation method thus provides new insight into the regulation of alternative splicing of the second exon of TREM2 by low-frequency variants and could be a useful tool for further exploring the potential molecular mechanisms of multiple, disease-associated, low-frequency variants.

关键词： Orthotropic elasticity   Analytical solution   Finite volume  

摘要： Anisotropic materials are those that the value of a property depends on the direction of analysis. This article addresses both analytical and numerical stress computation for orthotropic beams under normal and shear loads. The analytical solution is based on potential polynomial functions and the present work establishes general strategies which allow systematic evaluation of the polynomial coefficients. The numerical approximation uses an alternative formulation of finite volumes based on an area weighted average associated with parabolic interpolation functions. The numerical scheme is verified against results obtained for orthotropic beams using both the analytical method and a classical finite volume approximation. Assessment of the global error based on the L-2 norm indicates a high convergence rate and substantially smaller absolute differences when compared to the conventional finite volume approximation.

关键词： Prevalence   Complementary and alternative medicine   Diabetes   Systematic review  

摘要： Aim This study aimed to undertake a systematic review and meta-analysis of global prevalence and types of complementary and alternative medicine (CAM) use amongst adults with diabetes. Methods Nine databases, including MEDLINE and EMBASE, were searched for studies published between 2009 and 2019 which included extractable data for CAM use in adult patients with diabetes. Study characteristics, types of CAM, and overall and subgroup prevalence data in relation to CAM use were extracted. Meta-analysis of aggregate level data on prevalence and prevalence ratios (PRs) was performed using a random effects model. Results From the 38 studies included in the review, a total of 37 types of CAM and 223 types of herbs were identified. Pooled prevalence of CAM use was 51%. A wide variation in prevalence rates (predictive interval 8-93%) was observed. In the context of high heterogeneity, we found no evidence that CAM use was associated with gender, chronicity or type of diabetes. Approximately one third of patients did not disclose their use of CAM to healthcare professionals (95% PrI 25%, 97%). Herbal medicines, acupuncture, homoeopathy and spiritual healing were the common CAM types reported. Conclusions A wide variation in prevalence of CAM use by patients with diabetes was identified. Healthcare professionals should be aware of their patients' use of CAM to ensure treatment optimization, avoid herb-drug interactions and promote medication adherence in diabetes. Diabetic reviews and clinical guidelines should incorporate exploration of patient use of CAM as many patients do not proactively disclose the use of CAM to their healthcare professionals. Registration The protocol for this study was registered with the Centre for Review and Dissemination (CRD). Protocol registration number CRD42019125036.

摘要： The successful anesthesiologist anticipates and prepares for when things do not go as expected-the “routine” operation becomes more complicated, or the “healthy” patient develops myocardial ischemia midprocedure. The PSO who is successful is no different. They must anticipate and prepare for when things do not go as expected. Seemingly simple solutions to patient safety problems will turnout to be anything but straightforward. The sabotage of a safety culture may come from within, undermining the best-laid plans. Oftentimes the situations that we are confronted with are not unique to our practice, our hospital, or our patients. Much like the operating room anesthesiologist manages unanticipated events based on medical science, so must the PSO. Safety is more than a practice, it is a science, and we must study it with the same rigor as pharmacology and physiology. Standing on the shoulders of giants and sharing our own experiences and challenges are essential elements to ensuring that we continue anesthesiologists’ legacy as forerunners in patient safety. © 2021 Lippincott Williams and Wilkins. All rights reserved.

关键词： Normal cone   Supremum of convex functions   Subdifferentials   Convex optimization   Optimality conditions  

摘要： The first part of the paper provides new characterizations of the normal cone to the effective domain of the supremum of an arbitrary family of convex functions. These results are applied in the second part to give new formulas for the subdifferential of the supremum function, which use both the active and nonactive functions at the reference point. Only the data functions are involved in these characterizations, the active ones from one side, together with the nonactive functions multiplied by some appropriate parameters. In contrast with previous works in the literature, the main feature of our subdifferential characterization is that the normal cone to the effective domain of the supremum (or to finite-dimensional sections of this domain) does not appear. A new type of optimality conditions for convex optimization is established at the end of the paper.

关键词： Honey   Colour   Transmission spectra   Pfund   CIE L*a*b  

摘要： Honey is popular and versatile nutraceutical product, widely used as a sweetener. Its sensory properties, determined by the botanical origin, play a high role in consumers' decision. Among these, colour is an important, often price-defining property. Colour evaluation of honey can be done by different ways, the most commonly known being the Pfund scale, but Lovibond scale or spectral analysis are used as well. The Pfund method provides a specific evaluation scale for honeys, however, this method is not able to detect slight differences and it also has some deficiencies. Our aim was to provide some examples proving the shortages of the present methodology for determination of honey colour and suggest a solution that could qualify as a possible standardized method. A template providing all the calculations (Pfund value, L*a*b*, C*ab, h degrees ab, Delta E*ab, Delta C* ab, Delta h*ab, Delta H*ab, Delta L*, Delta a*, Delta b*) based on the UV-VIS transmission spectra, comparing the results of honey samples is attached. The experiment revealed the drawbacks of the Pfund scaling system. We provide an alternative analytical method that can deliver more details and information on honey colour and could overcome the deficiencies of the present protocols.