Clotting and inflammation are effective danger response patterns positively selected by evolution to limit fatal bleeding and pathogen invasion upon traumatic injuries. As a trade-off, thrombotic, ...and thromboembolic events complicate severe forms of infectious and non-infectious states of acute and chronic inflammation, i.e., immunothrombosis. Factors linked to thrombosis and inflammation include mediators released by platelet granules, complement, and lipid mediators and certain integrins. Extracellular deoxyribonucleic acid (DNA) was a previously unrecognized cellular component in the blood, which elicits profound proinflammatory and prothrombotic effects. Pathogens trigger the release of extracellular DNA together with other pathogen-associated molecular patterns. Dying cells in the inflamed or infected tissue release extracellular DNA together with other danger associated molecular pattern (DAMPs). Neutrophils release DNA by forming neutrophil extracellular traps (NETs) during infection, trauma or other forms of vascular injury. Fluorescence tissue imaging localized extracellular DNA to sites of injury and to intravascular thrombi. Functional studies using deoxyribonuclease (DNase)-deficient mouse strains or recombinant DNase show that extracellular DNA contributes to the process of immunothrombosis. Here, we review rodent models of immunothrombosis and the evolving evidence for extracellular DNA as a driver of immunothrombosis and discuss challenges and prospects for extracellular DNA as a potential therapeutic target.
It is difficult to measure the surface temperature of continuous casting billet, which results in the lack of important feedback parameters for further scientific control of the billet quality. This ...paper proposes a sparrow search algorithm to optimize the Least Square Support Vector Machine (LSSVM) model for surface temperature prediction of the billet, which is further improved by Logistic Chaotic Mapping and Golden Sine Algorithm (Improve Logistic Golden Sine Sparrow Search Algorithm LSSVM, short name ILGSSA-LSSVM). Using the Improved Logistic Chaos Mapping and Golden Sine Algorithm to find the optimal initial sparrow population, the value of penalty factor Formula: see text and kernel parameter Formula: see text for LSSVM are calculated. Global optimization method is adopted to find the optimal parameter combination, so that the negative influence of randomly initializing parameters on the prediction accuracy would be reduced. Our proposed ILGSSA-LSSVM soft sensing model is compared respectively with traditional Least Square Support Vector Machine, BP neural network and Gray Wolf optimized Least Square Support Vector Machine, results show that proposed model outperformed the others. Experiments show that the maximum error of ILGSA-LSSVM soft sensing model is 3.85733 °C, minimum error is 0.0174 °C, average error is 0.05805 °C, and generally outperformed other comparison models.
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The enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) is a key enzyme in the methylerythritol 4-phosphate pathway and is a target for the development of antibiotics, herbicides, and antimalarial ...drugs. DXPS catalyzes the formation of 1-deoxy-D-xylulose 5-phosphate (DXP), a branch point metabolite in isoprenoid biosynthesis, and is also used in the biosynthesis of thiamin (vitamin B₁) and pyridoxal (vitamin B₆). Previously, we found that DXPS is unique among the superfamily of thiamin diphosphate (ThDP)-dependent enzymes in stabilizing the predecarboxylation intermediate, C2-alpha-lactylthiamin diphosphate (LThDP), which has subsequent decarboxylation that is triggered by D-glyceraldehyde 3-phosphate (GAP). Herein, we applied hydrogen–deuterium (H/D) exchange MS (HDX-MS) of full-length Escherichia coli DXPS to provide a snapshot of the conformational dynamics of this enzyme, leading to the following conclusions. (i) The high sequence coverage of DXPS allowed us to monitor structural changes throughout the entire enzyme, including two segments (spanning residues 183–238 and 292–317) not observed by X-ray crystallography. (ii) Three regions of DXPS (spanning residues 42–58, 183–199, and 278–298) near the active center displayed both EX1 (monomolecular) and EX2 (bimolecuar) H/D exchange (HDX) kinetic behavior in both ligand-free and ligand-bound states. All other peptides behaved according to the common EX2 kinetic mechanism. (iii) The observation of conformational changes on DXPS provides support for the role of conformational dynamics in the DXPS mechanism: The closed conformation of DXPS is critical for stabilization of LThDP, whereas addition of GAP converts DXPS to the open conformation that coincides with decarboxylation of LThDP and DXP release.
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RATIONALE:Cholesterol crystal embolism can be a life-threatening complication of advanced atherosclerosis. Pathophysiology and molecular targets for treatment are largely unknown.
OBJECTIVE:We aimed ...to develop a new animal model of cholesterol crystal embolism to dissect the molecular mechanisms of cholesterol crystal (CC)–driven arterial occlusion, tissue infarction, and organ failure.
METHODS AND RESULTS:C57BL/6J mice were injected with CC into the left kidney artery. Primary end point was glomerular filtration rate (GFR). CC caused crystal clots occluding intrarenal arteries and a dose-dependent drop in GFR, followed by GFR recovery within 4 weeks, that is, acute kidney disease. In contrast, the extent of kidney infarction was more variable. Blocking necroptosis using mixed lineage kinase domain–like deficient mice or necrostatin-1s treatment protected from kidney infarction but not from GFR loss because arterial obstructions persisted, identifying crystal clots as a primary target to prevent organ failure. CC involved platelets, neutrophils, fibrin, and extracellular DNA. Neutrophil depletion or inhibition of the release of neutrophil extracellular traps had little effects, but platelet P2Y12 receptor antagonism with clopidogrel, fibrinolysis with urokinase, or DNA digestion with recombinant DNase I all prevented arterial occlusions, GFR loss, and kidney infarction. The window-of-opportunity was <3 hours after CC injection. However, combining Nec-1s (necrostatin-1s) prophylaxis given 1 hour before and DNase I 3 hours after CC injection completely prevented kidney failure and infarcts. In vitro, CC did not directly induce plasmatic coagulation but induced neutrophil extracellular trap formation and DNA release mainly from kidney endothelial cells, neutrophils, and few from platelets. CC induced ATP release from aggregating platelets, which increased fibrin formation in a DNase-dependent manner.
CONCLUSIONS:CC embolism causes arterial obstructions and organ failure via the formation of crystal clots with fibrin, platelets, and extracellular DNA as critical components. Therefore, our model enables to unravel the pathogenesis of the CC embolism syndrome as a basis for both prophylaxis and targeted therapy.
For the problem of gas accumulation in the product bunker of a company’s coal processing plant, three different ventilation schemes are proposed. The first one opens rectangular air inlet louvers on ...the wall of the product bunker and adds fans on the top for exhaust; the second one sets six ventilation windows evenly on the top of the product bunker for natural ventilation; the third one sends air to the interior of the bunker through small holes evenly distributed on the ventilation pipes and opens six exhaust ports on the wall. Finally, the effect of gas accumulation management of the ventilation scheme is simulated and analyzed through numerical simulation. The ventilation scheme is applicable to the gas accumulation management of raw coal bunkers with different coal storage heights, and provides a technical reference for the gas accumulation management of product bunkers in coal processing plants.
Currently, undetectable damage to workers and factory products is caused by the large number of oily fine particles present in the industrial environment. Previous studies have shown that different ...intensities of sound waves can promote the coalescence of fine particles, and the combination of water vapor condensation can further enhance the effect of acoustic coalescence. However, the research on acoustic coalescence is not extensive enough at present, especially research on the mechanism of the coalescence and growth of oily fine particles under acoustic and water vapor complex fields, which is even less studied. This paper focused on summarizing domestic and foreign research results on the interaction mechanism of acoustic convergence on particles and the agglomeration and growth of particles under the action of acoustic convergence and combined water vapor condensation, so as to explore the technical path of using acoustic convergence and combined water vapor condensation to regulate the size of oily fine particles and improve the purification efficiency in industrial situations. This research has significant scientific significance and application value for industrial environmental control, pollutant emission control, and healthy environment construction.
An accurate understanding of the relationship between reservoir construction and the dynamic change of groundwater level in downstream areas is of great significance for rational development and ...utilization of water resources. At present, the research on the interaction between surface water (SW) and groundwater (GW) mainly focuses on the interaction between river and GW. There are few studies on the impact of the reservoir construction on GW level in downstream loess irrigation area. Rainfall, evaporation and climate temperature have a great impact on W level, but the impact of reservoir construction on the GW level should not be ignored in the utilization of water resources. In this paper, a GW flow model under a natural boundary was established by numerical simulation. Taking Heihe Jinpen Reservoir in Heihe River watershed as the research object, the influence of the construction of a mountain reservoir on the dynamic change of GW level in the downstream loess region is studied. By comparing the GW level under the natural state without reservoir construction and the measured GW level after the reservoir was built, the variation of the GW depth in the loess area of the lower reaches in the Heihe River watershed is obtained. The results show that simulation accuracy of the interaction between SW and GW was reasonable; after the Heihe Jinpen Reservoir construction, the mean GW level decrease was about 6.05 m in the downstream loess irrigation area in Guanzhong Basin. It provides a method for the simulation and prediction of SW–GW conversion laws. This study is also of great significance to explore the change law of the water cycle and improve the utilization rate of water resources.
The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the tricarboxylic acid (TCA) cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive ...oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging.
is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in
have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxoacid dehydrogenase complexes, their function and regulation.
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Abstract
Loess Plateau provides a broad growing environment for crops. However, due to the loose soil, soil erosion is serious. Gully Consolidation and Highland Protection is the key work in the ...construction of ecological civilization in Loess Plateau. Using the method of simulating the Gully Consolidation and Highland Protection, the terrain conditions are changed, and the hydrological model is used to simulate the change of erosion before and after ditch head landfill. In this paper, Yangjiagou, was chosen as the research area. The spatial analysis function of ArcGIS was used to process DEM, and GeoWEPP model was used to simulate soil erosion, the variation of runoff and sediment yield in gully head landfill before and after landfill was analyzed. Results show that gully head landfill has effective on soil erosion control and provides an effective verification method for the feasibility of soil erosion control scheme in the Loess Plateau.
The Gully Consolidation and Highland Protection (GCHP) project is an important governance measure for controlling source erosion and reducing soil erosion in the Loess Plateau, which has been ...explored and developed continuously in recent decades. However, there is no international precedent for research on the implementation effect of the GCHP project, and it is still relatively weak. In order to quantify the erosion of a small watershed under the construction of a gully head landfill, this study selected Yangjiagou (YJG) as the research area. The spatial analysis function of ArcGIS was used to process DEM and soil type data, the GeoWEPP model was used to simulate soil erosion, and the changes of runoff and sediment yield before and after gully head landfill were analyzed. The results showed that compared with the simulated original soil erosion amount, the annual runoff decreased by 13.13%, and the sediment yield decreased by 37.61% after gully head landfill, indicating that the GCHP project positively influenced soil erosion control. After the gully head landfill measures are taken, the flow path becomes shorter, so the flow scour capacity is weakened. Soil and water control is very effective in the short term, but if long-term maintenance is not carried out, the intensity of soil and water loss is likely to be aggravated. This study provides an effective verification method for the feasibility of a soil loss control scheme on the Loess Plateau and provides a reference for promoting ecological priority and efficient management in the Loess gully area. Ultimately, it will serve the ecological protection and high-quality development of the Yellow River Basin.
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