Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

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.     

通信工程网络安全与对策探讨

分析研究目前通信工程网络安全问题,提出几点解决问题的对策,旨在为提升通信工程网络安全性提供一定的帮助,以此来促使通信工程网络系统安全性的提升。     

宰前倒挂应激对鸭血凝胶特性的影响

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。     

Cross-sector collaboration within Dutch flood risk governance: historical analysis of external triggers

ABSTRACT

This article synthesizes the literature on Dutch flood risk governance to analyze how external conditions shaped past and present dynamics of cross-sector collaboration for integrated flood risk management in the Netherlands. It traces the extent to which policy and legal frameworks, socio-economic circumstances, political realities, power relations and conflict situations have influenced attempts at collaboration between flood safety, spatial planning, environmental protection and other sectors. Despite the growing interdependences, existing power relations between the sectors are characterized by the dominance of the water sector. Hence, cross-sector collaboration can develop as long as it does not compromise flood safety.     

Occupational exposure and health risks of volatile organic compounds of hotel housekeepers: Field measurements of exposure and health risks

Hotel housekeepers represent a large, low-income, predominantly minority, and high-risk workforce. Little is known about their exposure to chemicals, including volatile organic compounds (VOCs). This study evaluates VOC exposures of housekeepers, sources and factors affecting VOC levels, and provides preliminary estimates of VOC-related health risks. We utilized indoor and personal sampling at two hotels, assessed ventilation, and characterized the VOC composition of cleaning agents. Personal sampling of hotel staff showed a total target VOC concentration of 57 ± 36 µg/m³ (mean ± SD), about twice that of indoor samples. VOCs of greatest health significance included chloroform and formaldehyde. Several workers had exposure to alkanes that could cause non-cancer effects. VOC levels were negatively correlated with estimated air change rates. The composition and concentrations of the tested products and air samples helped identify possible emission sources, which included building sources (for formaldehyde), disinfection by-products in the laundry room, and cleaning products. VOC levels and the derived health risks in this study were at the lower range found in the US buildings. The excess lifetime cancer risk (average of 4.1 × 10⁻⁵) still indicates a need to lower exposure by reducing or removing toxic constituents, especially formaldehyde, or by increasing ventilation rates.     

Characterization and exposure assessment of household fine particulate matter pollution in China

Household fine particulate matter (PM_2.5) pollution greatly impacts residents' health. To explore the current national situation of household PM_2.5 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 PM_2.5 (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 PM_2.5 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.     

消防监督检查中对火灾隐患的认定探析

文章将重点阐述消防监督检查中对火灾隐患的认定,并从实际角度出发,充分的考虑可能存在的问题,具体问题具体分析,制定相应的解决对策,以保证消防监督检查工作能够顺利的开展.