**5. Conclusions**

In conclusion, the results from this study indicate that combined mixtures of BDE-47 and nickel pollutants were more toxic to *P. tricornutum* cells than either of the chemicals individually. Modeling analysis indicated a synergistic interaction between the pollutants, resulting in increased toxicity to *P. tricornutum*. Specifically, mixtures of BDE-47 and nickel decreased cell abundances, inhibited photosynthetic efficiency, and induced ROS production. Transcriptomic analysis further revealed that the mixtures affected photosynthesis, nitrogen metabolism, primary metabolism, and secondary metabolism processes, ultimately leading to cell growth inhibition in the diatom *P. tricornutum*.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/toxics10050211/s1, Figure S1: Volcano plot of differentially expressed genes under 2.5 mg/L mixture treatment for 48 h; Figure S2: Volcano plot of differentially expressed genes under 2.5 mg/L mixture treatment for 72 h; Figure S3: Venn diagram of differentially expressed genes under 2.5 mg/L mixture treatment for 48 and 72 h; Table S1: Chemical concentrations tested in this study; Table S2: Results of Levene statistic test to determine homoscedasticity in data and statistic method used in ANOVA; Table S3: The P-value of comparisons with Games–Howell of cell abundance; Table S4: The P-value of comparisons with Games–Howell of photosynthesis; Table S5: The P-value of comparisons with Games–Howell of ROS; Table S6: DEGs related to photosynthesis; Table S7: DEGs involved in nitrogen metabolism; Table S8: DEGs involved in oxidation-reduction process; Table S9: DEGs involved in biosynthesis of secondary metabolites.

**Author Contributions:** X.S. and X.D. designed the research; R.G. performed the experiments; X.S. and R.G. wrote the manuscript; D.L., P.W. and X.D. reviewed and revised all manuscript versions. All authors have read and agreed to the published version of the manuscript.

**Funding:** Please add: This work is supported by the following Projects: The National Key Research and Development Program of China (2016YFF0201104); The Zhejiang Provincial Natural Science Foundation of China (LY19D060007); Scientific Research Fund of the Second Institute of Oceanography, MNR (JG2108).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

#### **References**

