Association of co-exposure to metal(loid)s during pregnancy with birth outcomes in the Tibetan plateau.

Maternal metal (loid)s exposure has been related to birth outcomes but the results are still inconclusive. Most previous studies have discussed the single metal (loid)s, neglecting the scene of co-exposure. We examined the associations of both single metal (loid)s and metal mixtures with birth outcomes in a birth cohort from the Tibetan Plateau, including body weight, body length, head circumference, small for gestational age (SGA), and Ponderal index (PI). In our analysis of 1069 women, we measured 29 metal (loid)s in urine samples in the third trimester. The associations of single metal (loid)s with categorical or continuous birth outcomes were evaluated using a generalized linear mixed-effects model or linear mixed-effects model, respectively. The least absolute shrinkage and selection operator, Bayesian kernel machine, and Quantile g-computation regression were used to explore the joint association. We also evaluated the interactive effects of ethnicity and altitude on the effect of metal (loid)s on birth outcomes. Copper (Cu) concentration in maternal urine was positively associated with SGA, birth weight, birth length, and head circumference in the single pollutant models. For instance, Cu was associated with an increased risk of SGA [OR (95% CI) = 1.56 (1.23, 1.97); P < 0.001]. We didn't find significant joint association of metal mixtures with birth outcomes except a positive association between the mixture of Cu, Magnesium (Mg), and Iron (Fe) with the risk of SGA when the exposure level was above its 80th percentile, and Cu dominated the adverse association in a non-linear manner. Living altitude modified the associations of Cu with SGA and the positive association was only found in participants living at high altitude. In conclusion, maternal urinary metal (loid)s, especially Cu, was the dominant harmful metal (loid)s when associated with SGA on the Tibetan Plateau.

Maternal urinary metal(loid)s and risk of preterm birth: A cohort study in the Tibetan Plateau.

Maternal metal(loid)s exposure has been related to preterm birth (PTB), but the results are still inconclusive. Previous studies have mainly discussed the harmful metal(loid)s, neglecting beneficial ones. We examined the association of maternal metal(loid)s with PTB and gestational age (GA) in a birth cohort from the Tibetan Plateau. We measured 29 metal(loid)s in urine samples from 1081 pregnant women in the third trimester. Information regarding demographics, socioeconomic status, diet, medication, and lifestyle was collected through standardized interviews. The associations of single metal(loid)s with PTB or GA were evaluated using a generalized linear mixed-effects model or linear mixed-effects model. Elastic net and Bayesian kernel machine regressions were used to explore the joint associations. Magnesium (Mg), Copper (Cu), and Tin (Sn) were the main "harmful" metal(loid)s positively and negatively associated with PTB or GA, respectively. Mg was the dominant "harmful" metal(loid)s associated with PTB in a J-shape. A one-fold increase in Mg was associated with a 38% increased risk of PTB [OR (95% CI) = 1.38 (1.15, 1.65), PFDR＜0.05] and 0.17 weeks shortening of GA [ß (95% CI) = -0.25 (-0.35, -0.14), PFDR＜0.05]. Cesium (Cs), rubidium (Rb), and Molybdenum (Mo) were the main "beneficial" metals. Cs dominated the "beneficial" associations and was negatively associated with PTB in a linear manner. A one-fold increase in Cs was associated with a 67% decreased risk of PTB [OR (95% CI) = 0.43 (0.27, 0.67), PFDR＜0.05] and 0.24 weeks of prolonged GA [ß (95% CI) = 0.35 (0.13, 0.56), PFDR＜0.05]. Ethnicity and living altitude modified the association of Mg and Cu with PTB or GA. In conclusion, Maternal urinary metal(loid)s were bi-directionally associated with PTB in a population in the Tibetan Plateau. Mg and Cs were the dominant "harmful" and "beneficial" metal(loid)s, respectively.

The Role of a Nascent Polypeptide-Associated Complex Subunit Alpha in Siderophore Biosynthesis, Oxidative Stress Response, and Virulence in Alternaria alternata.

The present study demonstrates that a nascent polypeptide-associated complex α subunit (Nac1) functions as a transcriptional regulator and plays both positive and negative roles in a vast array of functions in Alternaria alternata. Gain- and loss-of-function studies reveal that Nac1 is required for the formation and germination of conidia, likely via the regulation of Fus3 and Slt2 mitogen-activated protein kinase (MAPK)-coding genes, both implicated in conidiation. Nac1 negatively regulates hyphal branching and the production of cell wall-degrading enzymes. Importantly, Nac1 is required for the biosynthesis of siderophores, a novel phenotype that has not been reported to be associated with a Nac in fungi. The expression of Nac1 is positively regulated by iron, as well as by the Hog1 MAPK and the NADPH-dependent oxidase (Nox) complex. Nac1 confers cellular susceptibility to reactive oxygen species (ROS) likely via negatively regulating the expression of the genes encoding Yap1, Skn7, Hog1, and Nox, all involved in ROS resistance. The involvement of Nac1 in sensitivity to glucose-, mannitol-, or sorbitol-induced osmotic stress could be due to its ability to suppress the expression of Skn7. The requirement of Nac1 in resistance to salts is unlikely mediated through the transcriptional activation of Hog1. Although Nac1 plays no role in toxin production, Nac1 is required for fungal full virulence. All observed deficiencies can be restored by re-expressing a functional copy of Nac1, confirming that Nac1 contributes to the phenotypes. Thus, a dynamic regulation of gene expression via Nac1 is critical for developmental, physiological, and pathological processes of A. alternata.

Four Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting Cervical Cancer.

BACKGROUND/AIMS: Circulation long non-coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and might be applied for cancer diagnosis, prognosis, or potential therapeutic targets. In this study, we aimed to explore whether the circulation lncRNA could predict the tumorigenesis of surgical squamous cervical cancer (CC). METHODS: In this study, we applied the lncRNA microarray to screen the potential biomarker for CC. Real-time quantitate polymerase chain reaction was conducted for further validation in a larger sample size. The multi-stage validation and risk score formula analysis were used to examine the sensitivity and specificity. RESULTS: We discovered 4 lncRNAs including HOTAIR, PVT1, XLOC_000303, and AL592284.1, which were upregulated in CC comparing with the cancer-free controls. Further, the receiver operating characteristic curve (ROC) analysis by risk score formula revealed the combined 4 factors with a high diagnostic ability with the area under ROC curve value of 0.875 and 0.958 in training set and validation set respectively. We finally confirmed the stable detection of the 4 lncRNAs by 5 cycles of freezing and thawing. CONCLUSION: HOTAIR, PVT1, XLOC_000303, and AL592284.1 might be the potential biomarkers for predicting the tumorigenesis of CC in the future.