Youjiang Medical College for Nationalities

Cadmium (Cd), a widespread environmental pollutant, has linked with various adverse health effects. However, the paternally inherited transgenerational effects of cadmium exposure on hepatotoxicity inoffspring and the underlying mechanism remained undefined. To address this issue, male mice (F0) were administrated with 100 mg/L cadmium chloride (CdCl₂) in drinking water for 3 months. Then, F0 males were mated with healthy female mice to produce F1 and F2 offspring.Liver function was assessed at age of 6 weeks and 6 months, respectively. Herein, we showed ancestral cadmium exposure led to liver injury in F1 male and F2 mice, characterized by hepatic steatosis and impaired glucose homeostasis. These results suggest that ancestral exposure to cadmium could induce the transgenerational inheritance of cadmium-induced liver injury, which was more profound in male offspring. Furthermore, methylated RNA immunoprecipitation (MeRIP) sequencing analysis identified 285 and 734 differentially methylation expressed genes in mice liver tissue treated with CdCl₂ for 3 months and 9 months, respectively. Among them, suppression of Irs1 and Il6st led to enhanced cytotoxicity induced by CdCl₂, indicating that Irs1 and Il6st might be involved in CdCl₂-induced liver injury. More importantly, the alteration of Irs1 and Il6st RNA methylation was also observed in F1 males and F2 mice, consistent with the phenotypes. Further analysis suggested the involvement of Irs1 methylation in the transgenerational inheritance of cadmium-induced hepatotoxicity, possibly mediated by METTL3. Collectively, these findings uncover the novel role of RNA methylation in the transgenerational inheritance of adverse effects and deepen the understanding of the etiology of disease.

Heavy metals could induce neurotoxicity, leading to cognitive function and motor deficiencies. Serum neurofilament light chain (sNfL) is a promising biomarker for neurological injury, and it may indicate nerve damage from heavy metals exposure. However, there's limited research exploring the associations among heavy metals, sNfL, and cognitive function in adults, and the existing findings are inconsistent.

959 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES) 2013-2014. This study was aimed to investigate the possible associations among heavy metals, sNfL, and cognitive function in adults.

We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, comprising 959 participants. Heavy metals were detected in blood samples including lead (Pb), cadmium (Cd), mercury (Hg), manganese (Mn), and selenium (Se), with measurements taken using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) technology. The level of sNfL was quantified via an innovative high-throughput immunoassay technology developed by Siemens Healthineers. Cognitive function were assessed using the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), and the Digit Number Symbol Substitution Test (DSST). Additionally, generalized linear models (GLMs), weighted quantile sum regression (WQS), Bayesian kernel machine regression (BKMR), quantile-based g computation (qgcomp), and restricted cubic splines (RCS) analyses were employed to examine the associations between heavy metals exposure and sNfL level. Finally, a mediation analysis to explore the interaction among heavy metals, sNfL, and cognitive function in adults aged 60 and above.

The generalized linear models exhibited a positive correlation between blood Pb or Cd levels and sNfL (β = 0.14, 95 % CI: 0.08-0.20; β = 0.14, 95 % CI: 0.07-0.20), in total population. Both WQS and BKMR analysis consistently showed a strong correlation between higher levels of the blood heavy metals mixture and increased sNfL (OR=0.051, 95 %CI: 0.025-0.090). The qgcomp model indicated that Cd had a significant positive correlation with sNfL, while Mn and Se showed a significant negative correlation with sNfL. Moreover, we have identified a significant relationship between sNfL or Cd and cognitive function scores (AFT, DSST) in adults aged 60 and above. The mediation analysis further revealed that sNfL partially mediated the relationship between Cd and AFT or DSST scores, with interpretive efficiencies of 23.35 % and 32.7 %, respectively.

This study is the first to utilize sNfL data to establish a link between heavy metals exposure and cognitive function. The finding highlight the the positive correlation between Pb or Cd and sNfL, the negative correlation between Se and sNfL. The impact of Cd exposure on cognitive function in individuals older than 60 was partially explained by sNfL. Further investigations are required to validate these findings, considering the constraints of the NHANES study.

Photodynamic therapy (PDT) can induce tumor cell death. Ru3, a metal-based photosensitizer, features a high positive charge, a long triplet excited-state lifetime, and an excellent PDT activity. The aptamer AS1411, known for its ability to selectively bind to nucleolin (which is overexpressed in tumor cells), self-assembled with Ru3 into nanoparticles termed Ru3ApNPs. These nanoparticles specifically target SiHa tumor cells. Upon light irradiation, Ru3ApNPs increase intracellular ROS levels, catalyze NADH redox reactions, and induce lysosomal disruption, ultimately triggering pyroptosis in tumor cells. Notably, Ru3ApNPs demonstrate excellent tumor penetration in 3D multicellular spheroids (MCSs) of SiHa cells and effectively inhibit their growth under light exposure. Ru3ApNPs exhibit a mechanism of action distinct from that of traditional PDT. Furthermore, under light irradiation, Ru3ApNPs can effectively inhibit the growth of distant tumors and induce systemic immune responses in mice. Our data suggest that Ru3ApNPs can be developed as promising targeted therapeutic agents in the future.