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1.
The influence of the microstructure on the corrosion rate of three monolithic SiC samples in FLiNaK salt at 900 °C for 250 h was studied. The SiC samples, labeled as SiC-1, SiC-2, and SiC-3, had corrosion rates of 0.137, 0.020, and 0.043 mg/cm2h, respectively. Compared with grain size and the presence of special grain boundaries (i.e., Σ3), the content of high-angle grain boundaries (HAGBs) appeared to have the strongest influence on the corrosion rate of SiC in FLiNaK salt, since the corrosion rate increased six times as the concentration of high-angle grain boundaries increased from 19 to 32% for SiC-2 and SiC-1, respectively. These results stress the importance of controlling the content of HAGBs during the production process of SiC.  相似文献   
2.
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.  相似文献   
3.
Spinal Cord Injury (SCI) is a debilitating condition characterized by damage to the spinal cord, resulting in loss of function, mobility, and sensation. Although increasingly prevalent in the US, no FDA-approved therapy exists due to the unfortunate complexity of the condition, and the difficulties of SCI may be furthered by the development of SCI-related complications, such as osteoporosis. SCI demonstrates two crucial stages for consideration: the primary stage and the secondary stage. While the primary stage is suggested to be immediate and irreversible, the secondary stage is proposed as a promising window of opportunity for therapeutic intervention. Enolase, a metabolic enzyme upregulated after SCI, performs non-glycolytic functions, promoting inflammatory events via extracellular degradative actions and increased production of inflammatory cytokines and chemokines. Neuron-specific enolase (NSE) serves as a biomarker of functional damage to neurons following SCI, and the inhibition of NSE has been demonstrated to reduce signs of secondary injury of SCI and to ameliorate dysfunction. This Viewpoint article involves enolase activation in the regulation of RANK-RANKL pathway and summarizes succinctly the mechanisms influencing osteoclast-mediated resorption of bone in SCI. Our laboratory proposes that inhibition of enolase activation may reduce SCI-induced inflammatory response and decrease osteoclast activity, limiting the chances of skeletal tissue loss in SCI.  相似文献   
4.
The calcium pump (sarco/endoplasmic reticulum Ca2+-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca2+ during muscle relaxation. Active Ca2+ transport by SERCA involves the structural transition from a low-Ca2+ affinity E2 state toward a high-Ca2+ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca2+ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump.  相似文献   
5.
吕阳  钱斌  胡蓉  张梓琪 《机械工程学报》2021,57(19):192-207
浇次不固定的炼钢连铸调度问题(Cast uncertain steelmaking continuous casting scheduling problem,CUSCCSP)广泛存在于钢铁生产行业中。该问题对应炼铁、精炼和连铸三个连续生产阶段,其中炼铁和精炼阶段为带运输时间的混合流水线调度子问题,连铸阶段为带独立设置时间的复杂并行机调度子问题,且两个子问题相互耦合。针对该问题,建立优化目标为最小化最大完工时间和平均等待时间加权和的排序模型,并提出一种协同进化交叉熵算法(Co-evolution cross-entropy optimization algorithm,CCOA)进行求解。设计前后子问题两段式编码和双向解码的策略,并采用启发式规则和随机方式初始化种群,以确保初始解的质量和分散性。在算法全局搜索阶段,采用分别对应前后子问题的双概率分布协同学习和积累优质解信息,并在采样概率分布生成新个体时引入考虑子问题耦合的模糊关系矩阵对概率分布取值进行适当调整,以增强算法较快到达优质解区域的能力,同时设计种群分裂机制来提高算法的引导性并扩大搜索范围。为提高算法的局部搜索能力,对分裂后的双种群中个体执行基于interchange和insert邻域操作的协同搜索,进而对当前历史最优解执行结合SWAP邻域快速评价的变邻域搜索,可增加算法在解空间中多个优质区域的搜索深度。仿真试验和算法比较验证了所提算法的有效性。  相似文献   
6.
7.
Glycine is an amino acid with unique properties because its side chain is composed of a single hydrogen atom. It confers conformational flexibility to proteins and conserved glycines are often indicative of protein domains involving tight turns or bends. All six beta-type connexins expressed in human epidermis (Cx26, Cx30, Cx30.3, Cx31, Cx31.1 and Cx32) contain a glycine at position 12 (G12). G12 is located about halfway through the cytoplasmic amino terminus and substitutions alter connexin function in a variety of ways, in some cases altering protein interactions and leading to cell death. There is also evidence that alteration of G12 changes the structure of the amino terminus in connexin- and amino acid- specific ways. This review integrates structural, functional and physiological information about the role of G12 in connexins, focusing on beta-connexins expressed in human epidermis. The importance of G12 substitutions in these beta-connexins is revealed in two hereditary skin disorders, keratitis ichthyosis and erythrokeratodermia variabilis, both of which result from missense mutations affecting G12.  相似文献   
8.
Artificial domestication and improvement of the majority of crops began approximately 10,000 years ago, in different parts of the world, to achieve high productivity, good quality, and widespread adaptability. It was initiated from a phenotype-based selection by local farmers and developed to current biotechnology-based breeding to feed over 7 billion people. For most cereal crops, yield relates to grain production, which could be enhanced by increasing grain number and weight. Grain number is typically determined during inflorescence development. Many mutants and genes for inflorescence development have already been characterized in cereal crops. Therefore, optimization of such genes could fine-tune yield-related traits, such as grain number. With the rapidly advancing genome-editing technologies and understanding of yield-related traits, knowledge-driven breeding by design is becoming a reality. This review introduces knowledge about inflorescence yield-related traits in cereal crops, focusing on rice, maize, and wheat. Next, emerging genome-editing technologies and recent studies that apply this technology to engineer crop yield improvement by targeting inflorescence development are reviewed. These approaches promise to usher in a new era of breeding practice.  相似文献   
9.
Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several AuI and AuIII complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds.  相似文献   
10.
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.  相似文献   
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