Combined effects of copper and cadmium exposure on ovarian function and structure in Nile Tilapia (Oreochromis niloticus).

With the rapid development of industrialization and urbanization, the issue of copper (Cu) and cadmium (Cd) pollution in aquatic ecosystems has become increasingly severe, posing threats to the ovarian tissue and reproductive capacity of aquatic organisms. However, the combined effects of Cu and Cd on the ovarian development of fish and other aquatic species remain unclear. In this study, female Nile tilapia (Oreochromis niloticus) were individually or co-exposed to Cu and/or Cd in water. Ovarian and serum samples were collected at 15, 30, 60, 90, and 120 days, and the bioaccumulation, ovarian development, and hormone secretion were analyzed. Results showed that both single and combined exposure significantly reduced the gonadosomatic index and serum hormone levels, upregulated estrogen receptor (er) and progesterone receptor (pr) gene transcription levels, and markedly affected ovarian metabolite levels. Combined exposure led to more adverse effects than single exposure. The data demonstrate that the Cu and Cd exposure can impair ovarian function and structure, with more pronounced adverse effects under Cu and Cd co-exposure. The Cu and Cd affect the metabolic pathways of nucleotides and amino acids, leading to ovarian damage. This study highlights the importance of considering combined toxicant exposure in aquatic toxicology research and provides insights into the potential mechanisms underlying heavy metal-induced reproductive toxicity in fish.

Bio-based epoxidized soybean oil branched cardanol ethers as compatibilizers of polybutylene succinate (PBS)/polyglycolic acid (PGA) blends.

Blending poly(butylene succinate) (PBS) with another biodegradable polymer, polyglycolic acid (PGA), has been demonstrated to improve the barrier performance of PBS. However, blending these two polymers poses a challenge because of their incompatibility and large difference of their melting temperatures. In this study, we synthesized epoxidized soybean oil branched cardanol ether (ESOn-ECD), a bio-based and environmentally friendly compatibilizer, and used it to enhance the compatibility of PBS/PGA blends. It was demonstrated that the terminal carboxyl/hydroxyl groups of PBS and PGA can react with ESOn-ECD in situ, leading to branching and chain extension of PBS and PGA. The addition of ESO3-ECD to the blend considerably diminished the dispersed phase of PGA. Specifically, in comparison to the PBS/PGA blend without a compatibilizer, the diameter of the PGA phase decreased from 2.04 µm to 0.45 µm after the addition of 0.7 phr of ESO3-ECD, and the boundary between the two phases became difficult to distinguish. Additionally, the mechanical properties of the blends were improved after addition of ESO3-ECD. This research expands the potential applications of these materials and promotes the use of bio-based components in blend formulations.

Effects of four hormones on the mitigation of ovarian damage in tilapia (Oreochromis niloticus) after copper and cadmium exposure.

Female tilapia of the Genetic Improvement of Farmed Tilapia (GIFT) strain were selected as an animal model to study the effects of four hormonal drugs in mitigating ovarian damage following exposure to copper and cadmium. After combined exposure to copper and cadmium in aqueous phase for 30 d, tilapia were randomly injected with oestradiol (E2), human chorionic gonadotropin (HCG), luteinizing hormone releasing hormone (LHRH), or coumestrol and raised in clear water for 7 d Ovarian samples were collected after combined exposure to heavy metals for 30 d and after recovery for 7 d Gonadosomatic index (GSI), copper and cadmium levels in the ovary, reproductive hormone levels in serum, and mRNA expression of key reproductive regulatory factors were determined. After 30 d of exposure to the combined copper and cadmium in aqueous phase, the Cd2+ content in tilapia ovarian tissue increased by 1,242.46% (p < 0.05), whereas the Cu2+ content, body weight, and GSI decreased by 68.48%, 34.46%, and 60.00% (p < 0.05), respectively. Additionally, E2 hormone levels in tilapia serum decreased by 17.55% (p < 0.05). After drug injection and recovery for 7 d, compared to the negative control group, the HCG group exhibited an increase of 39.57% (p < 0.05) in serum vitellogenin levels. Increases of 49.31%, 42.39%, and 45.91% (p < 0.05) in serum E2 levels were observed, and mRNA expression of 3ß-HSD increased by 100.64%, 113.16%, and 81.53% (p < 0.05) in the HCG, LHRH, and E2 groups, respectively. The mRNA expression of CYP11A1 in tilapia ovaries increased by 282.26% and 255.08% (p < 0.05) and mRNA expression of 17ß-HSD increased by 109.35% and 111.63% in the HCG and LHRH groups, respectively (p < 0.05). All four hormonal drugs, particularly HCG and LHRH, promoted the restoration of tilapia ovarian function to varying degrees after injury induced by combined exposure to copper and cadmium. This study presents the first hormonal treatment protocol for the mitigation of ovarian damage in fish exposed to combined aqueous phases of copper and cadmium as a strategy to prevent and treat fish ovarian damage induced by heavy metals.

Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for ß-Thalassemia.

Reactivation of γ-globin expression is a promising therapeutic approach for ß-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of ß-thalassemia: Natural HPFH mutations -113A > G, -114C > T, -117G>A, -175T > C, -195C > G, and -198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from ß-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for ß-thalassemia.