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Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS. 相似文献
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Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films are attracting famous applications in antistatic coating, energy storage and conversion, printed electronics, and biomedical fields due to their conductivity, optical transparency and flexibility. However, PEDOT:PSS has poor dispersion stability during long-term storage and transport. Moreover, the dried PEDOT:PSS films are insoluble in any solvent and cannot be redispersed again. In comparison to bake drying, here, a feasible strategy to achieve mechanically redispersed PEDOT:PSS with the help of freeze-drying process was reported. The redispersed PEDOT:PSS can recover not only the initial characters such as pH, chemical composition, viscosity, and particle size under similar solid contents, but also conductivity and surface morphology of treated films. In addition, the treated film exhibits self-healing properties similar to pristine film in terms of mechanical and electrical properties. This technology enables reuse and overcomes the technical problems of PEDOT:PSS dispersion, realizing real-time processing to meet variable applications. 相似文献
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目的:研究抗坏血酸(ascorbic acid,AsA)-还原型谷胱甘肽(reduced glutathione,GSH)循环代谢在水杨酸处理采后甜瓜诱导的过量H2O2清除过程中的作用。方法:用4 mmol/L水杨酸浸泡‘玉金香’厚皮甜瓜10 min,测定处理后果实常温贮藏过程中丙二醛(malondialdehyde,MDA)含量,分析活性氧的积累水平、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)活力,以及AsA-GSH循环过程相关酶活力及产物和底物含量。结果:水杨酸处理降低了果实MDA含量,第10天处理组MDA含量较对照组降低14.6%;显著提高了果实O2-·的产生速率和H2O2含量(P<0.05),其中处理后第2天O2-·的产生速率高出同期对照组的1.9 倍,第6天H2O2含量高出对照组果实29.7%;提高了果实SOD活力,但抑制了CAT活力,说明H2O2的清除可能是依赖于除酶促系统外的其他系统。此外,水杨酸处理提高了果实抗坏血酸过氧化物酶、单脱氢抗坏血酸过氧化物酶、脱氢抗坏血酸还原酶和谷胱甘肽还原酶的活力,增加了AsA和氧化型谷胱甘肽的含量,降低了脱氢抗坏血酸和GSH的含量。结论:水杨酸处理诱导了厚皮甜瓜果实的氧爆,抑制了MDA产生,由水杨酸诱导产生的过量H2O2主要依靠AsA-GSH循环系统清除。 相似文献
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Fernanda Monedeiro Viorica Railean-Plugaru Maciej Monedeiro-Milanowski Pawe Pomastowski Bogusaw Buszewski 《International journal of molecular sciences》2021,22(9)
Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL−1. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled. 相似文献
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Chenglai Xin Rong Yuan Jiang Wu Qingyuan Wang Yanan Zhou 《Ceramics International》2021,47(3):3411-3420
A novel method for fabricating a nano-Cu/Si3N4 ceramic substrate is proposed. The nano-Cu/Si3N4 ceramic substrate is first fabricated using spark plasma sintering (SPS) with the addition of nanoscale multilayer films (Ti/TiN/Ti/TiN/Ti) as transition layers. The microstructures of the nano-Cu metal layer and the interface between Cu and Si3N4 are investigated. The results show that a higher SPS temperature increases the grain size of the nano-Cu metal layer and affects the hardness. The microstructure of the transition layer evolves significantly after SPS. Ti in the transition layer can react with Si3N4 and with nano-Cu to form interfacial reaction layers of TiN and Ti–Cu, respectively; these ensure stronger bonding between nano-Cu and Si3N4. Higher SPS temperatures improve the diffusion ability of Ti and Cu, inducing the formation of Ti3Cu3O compounds in the nano-Cu metal layer and Ti2Cu in the transition layer. This study provides an important strategy for designing and constructing a new type of ceramic substrate. 相似文献