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The blood clam (Tegillarca granosa), a marine bivalve of ecological and economic significance, often encounters intermittent hypoxia in mudflats and aquatic environments. To study the response of blood clam foot to prolonged intermittent hypoxia, the clams were exposed to intermittent hypoxia conditions (0.5 mg/L dissolved oxygen, with a 12-h interval) for 31 days. Initially, transcriptomic analysis was performed, uncovering a total of 698 differentially expressed genes (DEGs), with 236 upregulated and 462 downregulated. These genes show enrichments in signaling pathways related to glucose metabolism, sugar synthesis and responses to oxidative stress. Furthermore, the activity of the enzyme glutathione peroxidase (GPx) and the levels of gpx1 mRNA showed gradual increases, reaching their peak on the 13th day of intermittent hypoxia exposure. This observation suggests an indirect protective role of GPx against oxidative stress. The results of this study make a significantly contribute to our broader comprehensive of the physiological, biochemical responses, and molecular reactions governing the organization of foot muscle tissue in marine bivalves exposed to prolonged intermittent hypoxic conditions. [Display omitted] • The first foot transcriptome of T. granosa in long-term intermittent hypoxia. • Glutathione peroxidase plays an indirect protective role during oxidative stress. • Calcium signaling pathway were significantly enriched under hypoxia challenge. [ABSTRACT FROM AUTHOR]

Nitrate is a major pollutant component in ambient PM 2.5. It is known that chronic exposure to PM 2.5 NO 3 − damages respiratory functions. We aim to explore the underlying toxicological mechanism at single cell resolution. We systematically conducted exposure experiments on forty C57BL/6 mice, assessed respiratory functions, and profiled lung transcriptome.. Afterward, we estimated the cell type compositions from RNA-seq data using deconvolution analysis. The genes and pathways associated with respiratory function and dysregulated by to PM 2.5 NO 3 − exposure were characterized at bulk-tissue and single-cell resolution. PM 2.5 NO 3 − exposure did not significantly modify the cell type composition in lung, but profoundly altered the gene expression within each cell type. At ambient concentration (22 μg/m3), exposure significantly (FDR<10%) altered 95 genes' expression. Among the genes associated with respiratory functions, a large fraction (74.6–91.7%) were significantly perturbed by PM 2.5 NO 3 − exposure. For example, among the 764 genes associated with peak expiratory flow (PEF), 608 (79.6%) were affected by exposure (p = 1.92e-345). Pathways known to play role in lung disease pathogenesis, including circadian rhythms, sphingolipid metabolism, immune response and lysosome, were found significantly associated with respiratory functions and disrupted by PM 2.5 NO 3 − exposure. This study extended our knowledge of PM 2.5 NO 3 − exposure's effect to the levels of lung gene expression, pathways, lung cell type composition and cell specific transcriptome. At single cell resolution, we provided insights in toxicological mechanism of PM 2.5 NO 3 − exposure and subsequent pulmonary disease risks. [Display omitted] • We conducted the first single cell RNA-sequencing study on PM 2.5 exposure's health effect. • PM 2.5 NO 3 − exposure did not modify the cell type composition in lung, but dysregulated within-cell gene expression. • Even at ambient concentration (22mg/m3), PM 2.5 NO 3 − exposure produced profound consequences. • Circadian rhythms, lysosome and response to stimulus were associated with respiratory functions and disrupted by exposure. [ABSTRACT FROM AUTHOR]

• Placenta RNA-seq deconvolution analyses showed heterogeneous cell-type composition. • Periconception alcohol exposure was associated with a higher proportion of Hofbauer cells. • Alcohol exposure around conception increased expression inflammatory genes. Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses. We leveraged an existent placenta single-cell RNA-seq dataset to perform cell-type deconvolution of bulk placental RNA-seq data from 35 heavy drinking pregnant women and 33 controls in a prospective birth cohort in Cape Town, South Africa. We used bivariate analyses and multivariable adjusted linear regression models to assess the relation of PAE on inferred placental cell-type proportions. We also examined differential expression of inflammatory response genes and PAE, using multivariable adjusted linear models. Deconvolution analyses showed heterogeneous placenta cell-type composition in which stromal (27 %), endothelial (26 %) and cytotrophoblasts (18 %) were the predominant cell-types. PAE around conception was associated with a higher proportion of Hofbauer cells (B = 0.51, p = 0.035) in linear models adjusted for maternal age, infant sex, and gestational age. Among the 652 inflammatory genes examined, 35 were differential expressed in alcohol exposed placentas (FDR p < 0.05). Our findings suggest that heavy alcohol exposure during pregnancy can influence the proportion of fetal placental villi macrophages (Hofbauer cells) and increased expression of inflammatory genes. Future studies are needed to further characterize these effects and to assess the potential functional roles of placental inflammation in FASD. [ABSTRACT FROM AUTHOR]