Freshwater crustacean exposed to active pharmaceutical ingredients: ecotoxicological effects and mechanisms.

Concerns over the ecotoxicological effects of active pharmaceutical ingredients (APIs) on aquatic invertebrates have been raised in the last decade. While numerous studies have reported the toxicity of APIs in invertebrates, no attempt has been made to synthesize and interpret this dataset in terms of different exposure scenarios (acute, chronic, multigenerational), multiple crustacean species, and the toxic mechanisms. In this study, a thorough literature review was performed to summarize the ecotoxicological data of APIs tested on a range of invertebrates. Therapeutic classes including antidepressants, anti-infectives, antineoplastic agents, hormonal contraceptives, immunosuppressants, and neuro-active drugs exhibited higher toxicity to crustaceans than other API groups. The species sensitivity towards APIs exposure is compared in D. magna and other crustacean species. In the case of acute and chronic bioassays, ecotoxicological studies mainly focus on the apical endpoints including growth and reproduction, whereas sex ratio and molting frequency are commonly used for evaluating the substances with endocrine-disrupting properties. The multigenerational and "Omics" studies, primarily transcriptomics and metabolomics, were confined to a few API groups including beta-blocking agents, blood lipid-lowing agents, neuroactive agents, anticancer drugs, and synthetic hormones. We emphasize that in-depth studies on the multigenerational effects and the toxic mechanisms of APIs on the endocrine systems of freshwater crustacean are warranted.

Metabolomic profiles in a green alga (Raphidocelis subcapitata) following erythromycin treatment: ABC transporters and energy metabolism.

A recent study showed that erythromycin (ERY) exposure caused hormesis in a model alga (Raphidocelis subcapitata) where the growth was promoted at an environmentally realistic concentration (4 µg/L) but inhibited at two higher concentrations (80 and 120 µg/L), associated with opposite actions of certain signaling pathways (e.g., xenobiotic metabolism, DNA replication). However, these transcriptional alterations remain to be investigated and verified at the metabolomic level. This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R. subcapitata using untargeted metabolomics. The metabolomic analysis showed that metabolomic pathways including ABC transporters, fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4 µg/L ERY. An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments, ultimately leading to the outperformance of growth. By contrast, algal growth inhibition in the 80 and 120 µg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to ABC transporters, energy metabolism and metabolism of nucleosides. Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria, the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis. This study provides novel insights into the dose-dependent toxicity of ERY on R. subcapitata.

Transcriptomic responses to cytotoxic drug cisplatin in water flea Daphnia magna.

Cytotoxic drugs have been recognized by the European Union as the potential threat in the aquatic environment. As a typical cytotoxic drug, effects of long-term exposure to cisplatin at the environmentally relevant concentrations on the crustacean health and its molecular mechanism remain undetermined. In this study, the growth and reproduction of Daphnia magna resulting from cisplatin exposure were initially assessed. While the phenotypes were not altered in 2 µg L-1, 20 µg L-1, and 200 µg L-1 treatment groups, cisplatin at 500 µg L-1 significantly reduced the offspring number to 8-13 neonates in each brood, which was lower than 13-27 neonates in the control group. In addition to the delay in the time of first pregnancy, the body length was decreased by approximate 12.13% at day 7. Meanwhile, all daphnids died after exposure to 500 µg L-1 cisplatin for 17 days. Transcriptome profiling bioassays were performed for 10 days to explore the alternation at the molecular level. Briefly, 980 (257 up- and 723 down-regulated), 429 (182 up- and 247 down-regulated) and 1984 (616 up-regulated and 1368 down-regulated) genes were differentially expressed (adj p < 0.05) in low (2 µg L-1), medium (200 µg L-1) and high (500 µg L-1) cisplatin treatment groups, respectively. Differentially expressed genes were primarily enriched in the digestion and absorption, nerve conduction, endocrine interference, and circulatory related pathways. Specifically, the down-regulated digestive secretion and nutrient absorption and neuronal conduction pathways may lead to insufficient energy supply involved in growth and reproduction, and hinder ovarian development and cell growth. Down-regulation of ovarian steroids and relaxin signaling pathways may be related to the reduction of offspring number and delayed pregnancy, and reduced body length of D. magna may attribute to the enrichment of insulin secretion pathway. In addition, the death of D. magna may result from the reduced expression of genes in cardiomyocyte contraction and apoptosome processes. Taken together, this study revealed the potential toxic mechanism of cisplatin in a model water flea.

Transcriptomic analysis of Raphidocelis subcapitata exposed to erythromycin: The role of DNA replication in hormesis and growth inhibition.

The occurrence of hormesis in the algal growth inhibition test is a major challenge in the dose-response characterization, whereas the molecular mechanism remains unraveled. The aim of this study is therefore to investigate the changes in the molecular pathways in a model green alga Raphidocelis subcapitata treated with erythromycin (ERY; 4, 80, 120 µg L-1) by transcriptomic analysis. After 7 day exposure, ERY at 4 µg L-1 caused hormetic effects (21.9 %) on cell density, whereas 52.0 % and 65.4 % were inhibited in two higher exposures. By using adj p < 0.05 and absolute log2 fold change> 1 as a cutoff, we identified 218, 950, and 2896 differentially expressed genes in 4, 80, 120 µg L-1 treatment groups, respectively. In two higher ERY treated groups, genes involved in phases I, II & III metabolism processes and porphyrin and chlorophyll metabolism pathway were consistently suppressed. Interestingly, genes (e.g., pri2, mcm2, and mcm6) enriched in DNA replication process were up-regulated in 4 µg L-1 group, whereas these genes were all repressed in 120 µg L-1 group. Alteration trend in gene expression was consistent with algal growth. Taken together, our results unveiled the molecular mechanism of action in ERY- stimulated/ inhibited growth in green alga.

Spatiotemporal impacts of climate change on food production: case study of Shaanxi Province, China.

The climate change on the impact of grain production potential has significant regional differences. Researchers have studied the grain production potential of various crop combinations or focused on single crop types in a typical area; however, the regional differences of the climate change on the impact of grain production potential were neglected. This paper used the Global Agro-Ecological Zone (GAEZ 3.0) model to focus on the analysis what is the climate change on the impact of grain production potential in different geographic units (Northern Shaanxi Plateau, Guanzhong Basin, Qinba Mountain) in Shaanxi Province of China. The case showed that the precipitation (Pre) what made changes of grain production potential was the most important factor in different geographic units. The increase of Pre had a positive impact on the grain production potential in Northern Shaanxi Plateau and Guanzhong Basin. However, in Qinba Mountain, due to excessive Pre in the Qinba Mountains, the decrease of Pre had a certain positive impact on the grain production potential. The precipitation was less in the Northern Shaanxi Plateau; therefore, its major factors leading to changes of crop production were precipitation and rainfall days. The increase of the mean maximum temperature (Tmx) and the mean minimum temperature (Tmn) had a positive impact of the grain production potential in the Northern Shaanxi Plateau and Guanzhong Basin. The higher temperature had a negative impact on the grain production potential. In Qinba Mountain, the increase of the temperature has a certain negative impact on the grain production potential. It has more influence of Tmx in the Guanzhong Basin and Qinba Mountain rather than that in the Northern Shaanxi Plateau. Generally speaking, the major climatic factors leading grain production potential were Pre and Tmx in Guanzhong Basin and Qinba Mountain.