Multiple physiology-pertinent transmembrane proteins reach the cell surface via the Golgi-bypassing unconventional protein secretion (UcPS) pathway. By employing C. elegans–polarized intestine epithelia, we recently have revealed that the small GTPase RAB-8/Rab8 serves as an important player in the process. Nonetheless, its function and the relevant UcPS itinerary remain poorly understood. Here, we show that deregulated RAB-8 activity resulted in impaired apical UcPS, which increased sensitivity to infection and environmental stress. We also identified the SNARE VTI-1/Vti1a/b as a new RAB-8–interacting factor involved in the apical UcPS. Besides, RAB-11/Rab11 was capable of recruiting RABI-8/Rabin8 to reduce the guanine nucleotide exchange activity of SMGL-1/GEF toward RAB-8, indicating the necessity of a finely tuned RAB-8/RAB-11 network. Populations of RAB-8– and RAB-11–positive endosomal structures containing the apical UcPS cargo moved toward the apical side. In the absence of RAB-11 or its effectors, the cargo was retained in RAB-8– and RAB-11–positive endosomes, respectively, suggesting that these endosomes are utilized as intermediate carriers for the UcPS.
Objective: To investigate the relationship between urinary polycyclic aromatic hydrocarbons(PAHs) metabolites and pulmonary function in community population. Methods: A total of 4 812 participants were recruited from two communities in Wuhan city from April to May 2011 and two communities in Zhuhai city in May 2012. Information of demographic characteristics and life style was collected by semi-structural questionnaire. Physical examination was performed and pulmonary function was measured. Morning urine was also collected. The concentration of 12 urinary PAHs metabolites was tested and classified into four types by chemical structure, including hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene and hydroxypyrene. The level of pulmonary function in different group of urinary PAHs metabolites was compared by using covariance analysis. The association of the urinary PAHs metabolites and pulmonary function was analyzed by using generalized linear model, and the interaction of different population characteristics and life style on the association was analyzed. Results: The age of participants was(51.99±13.64) years old, and 67.66% (n=2 565) of the population were women. The M (P(25), P(75)) of concentration of total urinary PAHs metabolites was 5.72 (3.91,8.72) μg/mmol Cr. After controlling for variables including age, gender, city, Waist-to-Hip Ratio, smoking status, drinking situation, physical activity, cooking meals at home or not, kitchen ventilation and exposure to dust as confounding factors, generalized linear model showed that each 1-unit increase in log-transformed levels of hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene, hydroxypyrene and total PAHs was associated with 26.83 (95%CI: -48.18, -5.48) , 21.86 (95%CI: -40.49, -3.23), 26.18(95%CI: -48.27, -4.09), 34.95 (95%CI: -55.95, -13.94), and 35.23 (95%CI: -58.93, -11.54) ml reduction of FVC and 29.36 (95%CI: -47.23, -11.48), 20.79 (95%CI: -36.39, -5.19), 22.65 (95%CI: -41.15, -4.15), 31.44(95%CI: -49.03, -13.85), and 33.20 (95%CI: -53.04, -13.36) ml reduction of FEV(1) respectively (all P values<0.05). Compared to non-alcohol users and participants with home cooking, the association was more evident in alcohol users and participants without home cooking(P for interaction<0.05). Conclusion: The exposure to PAHs was associated with decreased pulmonary function, and the association was more evident in alcohol users and participants without home cooking.目的： 分析社区人群尿中多环芳烃（PAHs）代谢产物水平与肺功能的关联。 方法： 分别于2011年4-5月及2012年5月在武汉市及珠海市各选取两个社区，招募到4 812名符合标准的居民。采用半结构式问卷收集人口学特征、生活方式等信息；进行体格检查，测定肺功能情况；收集晨尿样本，检测尿样中12种PAHs羟基化代谢产物，按其化学结构分为羟基萘、羟基芴、羟基菲、羟基芘4类。采用协方差分析比较不同PAHs代谢产物水平组的肺功能指标，采用广义线性模型分析各类PAHs代谢产物与肺功能之间的关联性，并分析不同人群特征及生活方式与尿中总PAHs代谢产物的交互作用。 结果： 研究对象年龄为（51.99±13.64）岁，女性2 565名（67.66%）。尿中总PAHs代谢产物M（P(25)，P(75)）值为5.72（3.91，8.72）μg/mmol Cr。广义线性模型分析结果显示，调整年龄、性别、城市、腰臀比、吸烟情况、饮酒情况、锻炼情况、是否做饭、厨房通风情况、是否接尘等因素后，尿羟基萘、羟基芴、羟基菲、羟基芘及总羟基化代谢产物每增加一个自然对数转换单位，用力肺活量分别下降26.83（95%CI：-48.18，-5.48）、21.86（95%CI：-40.49，-3.23）、26.18（95%CI：-48.27，-4.09）、34.95（95%CI：-55.95，-13.94）、35.23 （95%CI：-58.93，-11.54）ml，第一秒用力呼气容积分别下降29.36（95%CI：-47.23，-11.48）、20.79 （95%CI：-36.39，-5.19）、22.65（95%CI：-41.15，-4.15）、31.44（95%CI：-49.03，-13.85）、33.20（95%CI：-53.04，-13.36）ml（P值均<0.05）；与从不饮酒及做饭人群相比，饮酒及不做饭人群尿PAHs代谢产物水平与肺功能下降的关联更强（P(交互)值均<0.05）。 结论： 社区人群尿PAHs代谢产物水平与肺功能下降相关，在饮酒人群及不做饭人群中关联更强。.
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