Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It ...regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut⁻liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The ongoing novel coronavirus disease (COVID-19) pandemic has already infected millions worldwide and, with no vaccine available, interventions to mitigate transmission are urgently needed. While ...there is broad agreement that travel restrictions and social distancing are beneficial in limiting spread, recommendations around face mask use are inconsistent. Here, we use mathematical modeling to examine the epidemiological impact of face masks, considering resource limitations and a range of supply and demand dynamics. Even with a limited protective effect, face masks can reduce total infections and deaths, and can delay the peak time of the epidemic. However, random distribution of masks is generally suboptimal; prioritized coverage of the elderly improves outcomes, while retaining resources for detected cases provides further mitigation under a range of scenarios. Face mask use, particularly for a pathogen with relatively common asymptomatic carriage, is an effective intervention strategy, while optimized distribution is important when resources are limited.
CONSTANS is an evolutionarily-conserved central component of the genetic pathway that controls the onset of flowering in response to daylength. However, the specific biochemical mechanism by which ...the CONSTANS protein regulates the expression of its target genes remains largely unknown. By using a combination of cell-based expression analysis and in vitro DNA binding studies, we have demonstrated that CONSTANS possesses transcriptional activation potential and is capable of directly binding to DNA. CONSTANS was found to bind DNA via a unique sequence element containing a consensus TGTG(N2-3)ATG motif. This element is present in tandem within the FLOWERING LOCUS T promoter and is sufficient for CO binding and activity. The conserved CCT (CONSTANS, CONSTANS-like and TOC1) domain of CONSTANS was shown to be required for its recruitment to the DNA motif and other CCT-containing proteins were also found to have the ability to regulate gene expression via this element. The CCAAT box, which has been previously hypothesized as a recruitment site for complexes containing the CONSTANS protein, potentiated CONSTANS-mediated activation but was not essential for CONSTANS recruitment to a target promoter or for its activity as a transcriptional factor.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Due to technological limitations and budget constraints, spatiotemporal fusion is considered a promising way to deal with the tradeoff between the temporal and spatial resolutions of remote sensing ...images. Furthermore, the generative adversarial network (GAN) has shown its capability in a variety of applications. This article presents a remote sensing image spatiotemporal fusion method using a GAN (STFGAN), which adopts a two-stage framework with an end-to-end image fusion GAN (IFGAN) for each stage. The IFGAN contains a generator and a discriminator in competition with each other under the guidance of the optimization function. Considering the huge spatial resolution gap between the high-spatial, low-temporal (HSLT) resolution Landsat imagery and the corresponding low-spatial, high-temporal (LSHT) resolution MODIS imagery, a feature-level fusion strategy is adopted. Specifically, for the generator, we first super-resolve the MODIS images while also extracting the high-frequency features of the Landsat images. Finally, we integrate the features from the MODIS and Landsat images. STFGAN is able to learn an end-to-end mapping between the Landsat-MODIS image pairs and predicts the Landsat-like image for a prediction date by considering all the bands. STFGAN significantly improves the accuracy of phenological change and land-cover-type change prediction with the help of residual blocks and two prior Landsat-MODIS image pairs. To examine the performance of the proposed STFGAN method, experiments were conducted on three representative Landsat-MODIS data sets. The results clearly illustrate the effectiveness of the proposed method.
This study proposes a framework based on the concept of fuzzy sets theory and the VIKOR method to provide a rational, scientific and systematic process for evaluating the hospital service quality ...under a fuzzy environment where the uncertainty, subjectivity and vagueness are addressed with linguistic variables parameterized by triangular fuzzy numbers. This study applies the fuzzy multi-criteria decision making approach to determine the importance weights of evaluation criteria and the VIKOR method is taken to consolidate the service quality performance ratings of the feasible alternatives. An empirical case involving 33 evaluation criteria, 2 public and 3 private medical centres in Taiwan assessed by 18 evaluators from various fields of medical industry is solicited to demonstrate the proposed approach. The analysis result reveals that the service quality of private hospitals is better than public hospitals because the private hospitals are rarely subsidized by governmental agencies. These private hospitals have to fend themselves to retain existing patients or attract new patients to ensue sustainable survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The human cutaneous sensory organ is a highly evolved biosensor that is efficient, sensitive, selective, and adaptable. Recently, with the development of various materials and structures inspired by ...sensory organs, artificial cutaneous sensors have been widely studied. In this study, the acquisition of biophysical signals is demonstrated at one point on the body using a wearable all‐gel‐integrated multimodal sensor composed of four element sensors, inspired by the slow/rapid adapting functions of the skin sensory receptors. The gel‐type sensors ensure flexibility, compactness, portability, adherence, and integrity. The wearable all‐gel multimodal sensor is easily attached to the wrist and simultaneously gathers blood pressure (BP), electrocardiogram (ECG), electromyogram (EMG), and mechanomyogram (MMG) signals related to cardiac and muscle health. Human activity causes muscle contraction, which affects blood flow; therefore, the relationship between the muscle and heart is crucial for screening and predicting heart health. Cardiac health is monitored by obtaining the two types of phase time differences (i.e., Δtbe: BP and ECG, Δtem: ECG and MMG) generated during muscle movement. The suggested multimodal sensor has potential applicability in monitoring biophysical conditions and diagnosing cardiac‐related health problems.
The acquisition of biophysical signals is demonstrated at one point on the body using a wearable all‐gel‐integrated multimodal sensor. The wearable all‐gel multimodal sensor is easily attached to the wrist and simultaneously gathers blood pressure, electrocardiogram, electromyogram, and mechanomyogram signals related to cardiac and muscle health.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Three-dimensional genome structures play a key role in gene regulation and cell functions. Characterization of genome structures necessitates single-cell measurements. This has been achieved for ...haploid cells but has remained a challenge for diploid cells. We developed a single-cell chromatin conformation capture method, termed Dip-C, that combines a transposon-based whole-genome amplification method to detect many chromatin contacts, called META (multiplex end-tagging amplification), and an algorithm to impute the two chromosome haplotypes linked by each contact. We reconstructed the genome structures of single diploid human cells from a lymphoblastoid cell line and from primary blood cells with high spatial resolution, locating specific single-nucleotide and copy number variations in the nucleus. The two alleles of imprinted loci and the two X chromosomes were structurally different. Cells of different types displayed statistically distinct genome structures. Such structural cell typing is crucial for understanding cell functions.
Abstract
Photocatalytic formation of hydrocarbons using solar energy via artificial photosynthesis is a highly desirable renewable-energy source for replacing conventional fossil fuels. Using an
l
...-cysteine-based hydrothermal process, here we synthesize a carbon-doped SnS
2
(SnS
2
-C) metal dichalcogenide nanostructure, which exhibits a highly active and selective photocatalytic conversion of CO
2
to hydrocarbons under visible-light. The interstitial carbon doping induced microstrain in the SnS
2
lattice, resulting in different photophysical properties as compared with undoped SnS
2
. This SnS
2
-C photocatalyst significantly enhances the CO
2
reduction activity under visible light, attaining a photochemical quantum efficiency of above 0.7%. The SnS
2
-C photocatalyst represents an important contribution towards high quantum efficiency artificial photosynthesis based on gas phase photocatalytic CO
2
reduction under visible light, where the in situ carbon-doped SnS
2
nanostructure improves the stability and the light harvesting and charge separation efficiency, and significantly enhances the photocatalytic activity.
Although air transport has a good safety record, public perception often focuses excessively on accidents. Safety is affected by many factors such as management, operations, maintenance, environment, ...aircraft design, and air traffic control. Quantitative measurement of the airline safety index is the goal of this paper. Some previous efforts to measure aviation safety have assumed the criteria to be independent, but this is not the case in the real world. Here a hybrid multiple criteria decision-making model to address dependent relationships among criteria, using a decision-making trial and evaluation laboratory along with an analytical network process, to decide the relative weights of criteria, showing inter-dependence and feedback.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Single-atom catalysts provide an effective approach to reduce the amount of precious metals meanwhile maintain their catalytic activity. However, the sluggish activity of the catalysts for alkaline ...water dissociation has hampered advances in highly efficient hydrogen production. Herein, we develop a single-atom platinum immobilized NiO/Ni heterostructure (Pt
-NiO/Ni) as an alkaline hydrogen evolution catalyst. It is found that Pt single atom coupled with NiO/Ni heterostructure enables the tunable binding abilities of hydroxyl ions (OH*) and hydrogen (H*), which efficiently tailors the water dissociation energy and promotes the H* conversion for accelerating alkaline hydrogen evolution reaction. A further enhancement is achieved by constructing Pt
-NiO/Ni nanosheets on Ag nanowires to form a hierarchical three-dimensional morphology. Consequently, the fabricated Pt
-NiO/Ni catalyst displays high alkaline hydrogen evolution performances with a quite high mass activity of 20.6 A mg
for Pt at the overpotential of 100 mV, significantly outperforming the reported catalysts.
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