Physiological and genetic responses of Chlorella sp. to nitrite accumulation in microalgal-bacterial consortium with partial nitrification treating municipal wastewater

Article

Author: Li, Mengting ; Chen, Zhipeng ; Yu, Sheng ; Ge, Shijian ; Li, Xiang ; Qiu, Shuang ; Xu, Shiling

The integration of microalgal-bacterial consortium (MBC) with partial nitrification (PN-MBC) offers a promising strategy for low-carbon wastewater treatment. However, the gradually accumulated nitrite levels challenge microalgal activities and system stability. This study demonstrated the nitrite tolerance (10-300 mg/L) of Chlorella sp., isolated from the PN-MBC system, and the underlying mechanism. Physiological assays, transcriptomic analysis, and bioinformatics revealed that nitrite significantly affected photosynthesis, DNA processing, carbon metabolism, signal transduction, and protein processing. Specifically, nitrite inhibited photosystem II by targeting the PsbO subunit, disrupting electron transport and the proton gradient, hindering carbon fixation in the Calvin cycle. It also caused DNA damage, including strand breaks, base modifications and mismatches, with upregulated DNA repair pathways and biomass growth stagnation between Days 5-7. In response, Chlorella sp. upregulated carbon metabolism and oxidative phosphorylation to enhance ATP synthesis, while exopolysaccharides were secreted for energy storage, and protein processing was downregulated to mitigate proteotoxic stress. Evolution analysis suggested that active site variations in carbon metabolism enzymes contributed to Chlorella sp.'s enhanced nitrite resilience. These findings advance current understandings of nitrite's effects on microalgae and offer insights for optimizing PN-MBC performance under high-nitrite conditions.

01 Mar 2025·Cell Reports

Translesion-synthesis-mediated bypass of DNA lesions occurs predominantly behind replication forks restarted by PrimPol

Article

Author: Spratt, Thomas E ; Nicolae, Claudia M ; Dhoonmoon, Ashna ; Rebok, Abbey ; Lascarez-Espana, Cynthia ; Moldovan, George-Lucian ; Ambrose, Julia R ; Garg, Sonal

The bypass of DNA lesions by translesion synthesis (TLS) polymerases is a critical step for DNA damage tolerance, allowing the completion of DNA synthesis. It has been under debate whether TLS-mediated bypass restarts stalled forks or occurs post-replicationally. We developed cell imaging techniques based on proximity ligation to monitor the recruitment of TLS polymerases Polκ and Polη to DNA adducts. We show that this recruitment is adduct specific, with Polκ being preferentially recruited to benzo[a]pyrene diol epoxide (BPDE) lesions and Polη to cisplatin lesions. The recruitment depends on the primase-polymerase PrimPol, which reprimes downstream of stalled forks to restart DNA synthesis. TLS polymerase deficiency results in the accumulation of single-stranded DNA (ssDNA) gaps in an adduct-specific manner, which are processed into double-strand breaks (DSBs). Our findings argue that TLS occurs mainly behind the restarted replication fork in order to fill PrimPol-derived gaps and is essential to suppress the nucleolytic conversion of ssDNA gaps into cytotoxic DSBs in a lesion-specific manner.

01 Jan 2025·International Journal of Pharmaceutics

Intracellular mechanistic insights into cRGD-modified Bi2Se3 nanofoams for enhanced photothermal therapy via exocytosis inhibition

Article

Author: Li, Jieyun ; Meng, Wenjing ; Liu, Jiahan ; Zhang, Xuejuan ; Wu, Chuanbin ; Cai, Shihao ; Ding, Li ; Liu, Xiaotong ; Mahmood, Azhar ; Yu, Xinghua

The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of Bi₂Se₃ nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking. Our findings reveal that the cRGD-coated Bi₂Se₃ nanofoams are internalized through three distinct endocytosis pathways: Rab34-mediated macropinocytosis, caveolae-dependent, and clathrin-dependent endocytosis. These nanofoams then accumulate in lysosomes via autophagy. Furthermore, inhibiting exocytosis reduces the loss of these nanofoams from cancer cells, enhancing photothermal and chemotherapy effects. This exocytosis-inhibiting strategy demonstrates significant potential for cancer therapy, validated by successful in vitro and in vivo results.

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Indication	Highest Phase	Country/Location	Organization	Date
Metabolic Diseases	Preclinical	United States	National Center for Biotechnology Information	02 Sep 2010

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