Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis
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- Biomolecules & Therapeutics
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- v.32 no.2
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- pp.214-223
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- 2024
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
Fast restoration time and service guarantee are the important goals to achieve the network reliability. In the protection switching scheme, one way to guarantee service fro an application session if a network happens to fail is to establish the restoration path that amounts to the same bandwidth of the working path of the session at the same time. When we setup the restoration path, we can reduce the bandwidth consumption by the restoration path if the path can share the bandwidth required by the other paths. This paper explains the methods how to determine the shared bandwidth of the restoration path in the protection switching scheme, given the maximum bandwidth assigned to a link along the working path. We point out that such sharing algorithm can not reduce the bandwidth consumption by the restoration paths in some cases, which contradict the general conception. We explain why this can happen, and show the simulation results in real network topologies to prove our arguments. We explain the reason of the failure of the sharing effect by the simple sharing algorithm. Finally we propose the way of how we can overcome the failure of the sharing effect, using the complete sharing algorithm based on the link database and showing the results.
One of the main challenges in personal communication services(PCS ) Is to locate many mobile terminals that nay move from place to place frequently. This kind of system operation is called location management. This task entails sophisticated signaling traffic and database queries. Several strategies have been proposed to improve the efficiency of location management. These strategies use location register databases to store the current locations of mobile terminals, and are vulnerable to failure of the location register databases. In this paper, we propose a fault-tolerant pointer forwarding scheme with distributed home location register in order to tolerate the failure of location registers. The performance of the proposed scheme is evaluated analytically by simulation, and Is compared with Biaz's bypass forwarding strategy and two-path forwarding strategy.
A finite element model development of a 50th percentile male cervical spine is presented in this paper. The model consists of rigid, geometrically accurate vertebrae held together with deformable intervertibral disks, facet joints, and ligaments modeled as a series of nonlinear springs. These deformable structures were rigorously tuned, through failure, to mimic existing experimental data; first as functional unit characterizations at three cervical levels and then as a fully assembled c-spine using the experimental data from Duke University and other data in the NHTSA database. After obtaining satisfactory validation of the performance of the assembled ligamentous cervical spine against available experimental data, 22 cervical muscle pairs, representing the majority of the neck's musculature, were added to the model. Hill's muscle model was utilized to generate muscle forces within the assembled cervical model. The muscle activation level was assumed to be the same for all modeled muscles and the degree of activation was set to correctly predict available human volunteer experimental data from NBDL. The validated model is intended for use as a post processor of dummy measurement within the simulated injury monitor (SIMon) concept being developed by NHTSA where measured kinematics and kinetic data obtained from a dummy during a crash test will serve as the boundary conditions to "drive" the finite element model of the neck. The post-processor will then interrogate the model to determine whether any ligament have exceeded its known failure limit. The model will allow a direct assessment of potential injury, its degree and location thus eliminating the need for global correlates such as Nij.
In this paper, we propose a scheduling strategy for grid environment that reduces resource cost. This strategy considers resource cost and job failure rate to efficiently allocate local computing resources. The key idea of our strategy is that we use two-level scheduling using remote and local scheduler. The remote scheduler determines the expected total execution times of jobs using the current network and local system status maintained in its resource database and allocates jobs with minimum total execution time to local systems. The local scheduler recalculates the waiting time and execution time of allocated job and uses it to determine whether the job can be processed within the specified deadline. If it cannot finish in time, the job is migrated other local systems, through simulation, we show that it is more effective to reduce the resource cost than the previous Greedy strategy. We also show that the proposed strategy improves the performance compared to previous Greedy strategy.
Pounding of structures may result in considerable damages, to the extent of total failure during severe lateral loading events (e.g., earthquakes and wind). With the new generation of tall buildings in densely occupied locations, wind-induced pounding becomes of higher risk due to such structures' large deflections. This paper aims to develop mathematical formulations to determine the maximum pounding force when two adjacent structures come into contact. The study will first investigate wind-induced pounding forces of two equal-height structures with similar dynamic properties. The wind loads will be extracted from the Large Eddy Simulation models and applied to a Finite Element Method model to determine deflections and pounding forces. A Genetic Algorithm is lastly utilized to optimize fitting parameters used to correlate the maximum pounding force to the governing structural parameters. The results of the wind-induced pounding show that structures with a higher natural frequency will produce lower maximum pounding forces than those of the same structure with a lower natural frequency. In addition, taller structures are more susceptible to stronger pounding forces at closer separation distances. It was also found that the complexity of the mathematical formula from optimization depends on achieving a more accurate mapping for the trained database.
In this study, a 2-D flood inundation model was developed to evaluate the impact of levee failure in a natural basin for flood analysis. The model was applied to analyze the inundation flow from the levee break of Gamcheon river during the typhoon Rusa on October 31 through September 1, 2002. To verify the simulated results, wide range field surveys have been performed including the collection of NGIS database, land use condition, flooded area, and flow depths. Velocity distributions and inundation depths were presented to demonstrate the robustness of the model. Model results have good agreements with the observed data in terms of flood level and flooded area. The model is able to compute maximum stage and peak discharge efficiently in channel and protected lowland. Methodology considering radar-rainfall estimation using cokriging scheme, flood-runoff and inundation analysis in this study will contribute to the establishment of the national integrated flood disaster prevention system and the river or protect lowland management system.
Kon - Ha Thanh River basin is the largest and the most important river basin in Binh Dinh, a province in the South Central Coast of Vietnam. In the lower rivers, frequent flooding and inundation caused by heavy rains, upstream flood and or uncontrolled flood released from upstream reservoirs, are very serious, causing damage to agriculture, socio-economic activity, human livelihood, property and lives. The damage is expected to increase in the future as a result of climate change. An advanced flood warning system could provide achievable non-structural measures for reducing such damages. In this study, we applied a modelling system which intergrates a 1-D river flow model and a 2-D surface flow model for simulating hydrodynamic flows in the river system and floodplain inundation. In the model, exchange of flows between the river and surface floodplain is calculated through established links, which determine the overflow from river nodes to surface grids or vice versa. These occur due to overtopping or failure of the levee when water height surpasses levee height. A GIS based comprehensive raster database of different spatial data layers was prepared and used in the model that incorporated detailed information about urban terrain features like embankments, roads, bridges, culverts, etc. in the simulation. The model calibration and validation were made using observed data in some gauging stations and flood extents in the floodplain. This research serves as an example how advanced modelling combined with GIS data can be used to support the development of efficient strategies for flood emergency and evacuation but also for designing flood mitigation measures.
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70