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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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针对热液白云岩展布非均质性强的问题,开展基底断裂与茅三段沉积演化关系研究,分析断裂样式与白云岩分布关系,建立沉积演化模式,预测白云岩的分布。研究结果表明:茅三段可划分为5个小层,1~3小层为白云岩发育主要时期,4~5小层为台地均一化时期,不发育白云岩;15-1、15-2和16号基底断裂控制了早期“台-洼”相间的沉积地貌,断裂附近的地貌高部位为生屑滩发育有利部位,为白云岩的发育提供物质基础;15-1、15-2号基底断裂样式为花状,周边生屑滩白云石化程度高,为白云岩发育最有利区;16号基底断裂为直立状,附近白云石化发育程度较低,为白云岩发育较有利区。研究成果可为热液白云岩领域的进一步勘探提供指导依据。  相似文献   
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宰前倒挂因能有效提高屠宰效率成为肉鸭宰杀前必经的一个工艺过程,但倒挂往往会加剧肉鸭的应激程度,影响其血液品质,已成为工厂生产中亟待解决的问题。因此,本实验旨在借助血液学与凝血相关指标探究宰前倒挂应激对鸭血凝胶特性的影响。在屠宰前,将40 只樱桃谷鸭随机分为2 个处理组:对照组和宰前倒挂组(宰前倒挂2.5 min),屠宰后采集血样并制备血凝块,随后分析血液指标(应激指标、血液学指标、凝血指标)以及鸭血凝胶特性。结果表明,宰前倒挂组鸭血中皮质酮激素及促肾上腺皮质激素的水平均高于对照组,说明实验所建立宰前倒挂模型成立。倒挂应激后,红细胞计数、血小板计数、血红蛋白质量浓度增加,红细胞比容、平均红细胞体积及平均血小板体积增大;凝血酶原的水平极显著上升(P<0.01),组织因子的水平显著上升(P<0.05)。宰前倒挂最终导致鸭血凝胶化加快,鸭血凝胶体系中水分迁移速率增大,结合水与自由水比例减少,不易流动水比例增大,质构特性和保水性变差。研究揭示了宰前倒挂应激通过影响鸭血的血液学指标和凝血系统从而改变其凝胶行为及凝胶特性,可为工厂改善应激对鸭血凝胶品质的影响提供理论依据。  相似文献   
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Household fine particulate matter (PM2.5) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 μg/m3. HPL in the rural area (164.3 ± 104.5 μg/m3) was higher than that in the urban area (123.9 ± 122.3 μg/m3). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 μg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.  相似文献   
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To evaluate the separate impacts on human health and establish effective control strategies, it is crucial to estimate the contribution of outdoor infiltration and indoor emission to indoor PM2.5 in buildings. This study used an algorithm to automatically estimate the long-term time-resolved indoor PM2.5 of outdoor and indoor origin in real apartments with natural ventilation. The inputs for the algorithm were only the time-resolved indoor/outdoor PM2.5 concentrations and occupants’ window actions, which were easily obtained from the low-cost sensors. This study first applied the algorithm in an apartment in Tianjin, China. The indoor/outdoor contribution to the gross indoor exposure and time-resolved infiltration factor were automatically estimated using the algorithm. The influence of outdoor PM2.5 data source and algorithm parameters on the estimated results was analyzed. The algorithm was then applied in four other apartments located in Chongqing, Shenyang, Xi'an, and Urumqi to further demonstrate its feasibility. The results provided indirect evidence, such as the plausible explanations for seasonal and spatial variation, to partially support the success of the algorithm used in real apartments. Through the analysis, this study also identified several further development directions to facilitate the practical applications of the algorithm, such as robust long-term outdoor PM2.5 monitoring using low-cost light-scattering sensors.  相似文献   
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