Early environmental exposure to oxytetracycline in Danio rerio may contribute to neurobehavioral abnormalities in adult zebrafish.

The common antibiotic oxytetracycline (OTC) is nowadays commonly found in natural aquatic environments. However, the underlying mechanisms of low-dose OTC exposure and its neurotoxic effects on aquatic animals remain unknown. In this study, we exposed zebrafish larvae to environmental concentrations of OTC in early life and performed neurobehavioral, 16S rRNA gene sequencing, and transcriptomic analyses. OTC exposure resulted in hyperactivity of larvae and a significant reduction in the number of neurons in the midbrain. The expression levels of 15 genes related to neural function changed. Additionally, the composition of 65 genera of the gut microbiota of larvae was altered, which may be one of the reasons for the abnormal neural development. We further studied the long-term outcomes among adult fish long after cessation of OTC exposure. OTC treatment caused adult fish to be depressive and impulsive, symbolizing bipolar disorder. Adult fish exposed to OTC had significantly fewer neurons and their gut bacteria composition did not recover 104 days after terminating OTC exposure. Finally, we analyzed the correlation between the gut microbiota of larvae, genes related to neural function, and metabolites of adult fish brain tissue. The results showed that the abundance of several members of the biome in larvae was related to the transcription levels of genes related to neural function, which were related to the metabolic levels in the adult brain. In conclusion, our study showed that early-life exposure to environmental concentrations of OTC can lead to persistent neurobehavioral abnormalities until adulthood through dysbiosis in the gut microbiota.

[Effect and Persistent Effect of Thiolated Montmorillonite on Safe Production in Cadmium-contaminated Cropland].

To explore the effect and persistent effect of thiolated montmorillonite (TM) on safe production in cadmium (Cd) contaminated cropland, a two-year field experiment was conducted with different application amounts of TM. By adding to highly contaminated soils containing 2.46-3.81 mg·kg-1 Cd with no replenishment, the impacts of TM on concentrations of Cd in different parts of rice and available Cd in soils were investigated. The results showed that TM could significantly reduce the contents of Cd in brown rice as well as the contents and proportions of available Cd in soils, and its persistent effects on the passivation of Cd were obvious. After applying 0.5% or 1% TM to soils, the contents of Cd in different parts of the rice decreased significantly in the first season compared with that in the control. The contents of Cd in brown rice in the first season decreased to 0.16 mg·kg-1 and 0.08 mg·kg-1, respectively, by 84.0% and 91.9% compared with that of the control (0.98 mg·kg-1). Contents of Cd in brown rice were significantly lower than the maximum allowable amount (0.2 mg·kg-1) set by China (GB 2762-2017). Under the 0.5% and 1% treatments, the contents of Cd in brown rice of the subsequent three seasons under successive planting decreased by 50.2%-67.8% and 56.0%-81.6%, respectively, which were within the allowable amount. The proportions of available Cd in soils in the first season decreased from 48.4% under the control to 27.9% and 18.4%, respectively, which decreased by 20.5% and 29.9% under the 0.5% and 1% treatments. Compared with that in the control, proportions of available Cd in soils of the following three seasons decreased by 10.0%-17.1% and 12.4%-20.8%. There was a significant positive correlation between available Cd contents in soils and Cd contents in various parts of the rice. TM mainly reduced available Cd contents in soils, then reduced the absorption and accumulation of Cd in rice. The results of the two-year field experiment showed significant and continuous effects of TM on inhibiting Cd uptake by rice, which could be applied to the safe production in heavily Cd contaminated cropland.

Disease Modification in Alzheimer's Disease: Current Thinking.

Alzheimer's disease (AD) has increasingly been recognized as a huge unmet medical need. Currently, there is no approved drug to cure, prevent, or even slow down the disease. It is imperative to develop disease-modifying treatments for AD to alter the underlying disease progression. This paper reviews the most up-to-date regulatory guidance on how to demonstrate disease modification and provides an overview of available methodologies and applications to clinical trials. The intent is to assist the field with future clinical trials designed to demonstrate disease-modifying effect in AD. The methodologies may be generalizable to broader neurodegenerative diseases.

The late and persistent pathogenic effects of cadmium at very low levels on the kidney of rats.

Cadmium (Cd) is an important nephrotoxic pollutant. To examine late effects on the kidney of individuals previously exposed to chronic Cd at very low levels, male Wistar rats were given 20 nmol/kg i.p. injections of Cd every other day for 4 weeks. At the 20(th), 28(th), 36(th), 44(th) and 52(nd) week of the study, renal metal accumulation, morphology and function were examined. Immunochemical staining was performed to detect renal 3-nitrotyrosine (3-NT) accumulation, metallothionein (MT) expression, cell proliferation and global DNA methylation. Results showed that renal Cd concentration and MT expression along with 3-NT accumulation were significantly higher in the Cd group than that in the control. Histopathologically renal tubule damage at the early stage and hyperplasia at the late stage were observed in the Cd group. Renal fibrosis in glomeruli was evident in the Cd group, particularly at the late stage of the study. Immunoreactivity of global DNA methylation was markedly diminished in the Cd group at both 20(th) and 52(nd) weeks. These results suggest that previous exposure to chronic Cd at very low level induced persistent damaging effects on the kidney along with increases in cell proliferation and global DNA hypomethylation.