Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors.

A better understanding of the biological and environmental variables that contribute to exceptional longevity has the potential to inform the treatment of geriatric diseases and help achieve healthy aging. Here, we compared the gut microbiome and blood metabolome of extremely long-lived individuals (94-105 years old) to that of their children (50-79 years old) in 116 Han Chinese families. We found extensive metagenomic and metabolomic remodeling in advanced age and observed a generational divergence in the correlations with socioeconomic factors. An analysis of quantitative trait loci revealed that genetic associations with metagenomic and metabolomic features were largely generation-specific, but we also found 131 plasma metabolic quantitative trait loci associations that were cross-generational with the genetic variants concentrated in six loci. These included associations between FADS1/2 and arachidonate, PTPA and succinylcarnitine and FLVCR1 and choline. Our characterization of the extensive metagenomic and metabolomic remodeling that occurs in people reaching extreme ages may offer new targets for aging-related interventions.

Assessment of the Ecological Compensation Standards for Cross-Basin Water Diversion Projects from the Perspective of Main Headwater and Receiver Areas.

This paper aims to explore how to develop reasonable ecological compensation standards to improve the effectiveness of water diversion projects. Watershed ecological compensation is an important means to coordinate watershed protection and development and, additionally, compensation standard accounting is the core issue of ecological compensation. The previous literature has mainly calculated watershed ecological compensation standards from a single perspective, such as the main headwater or receiver areas, meaning the interests of another under-appreciated area would inevitably be ignored. The calculation results of different perspectives and methods vary greatly, directly affecting the implementation of watershed ecological compensation mechanisms. In this paper, the world's largest water diversion project, the Middle Route of the South-to-North Water Diversion Project, was selected as the study area. The total cost correction model was selected from the perspective of the main headwater areas. The water resources input-output model was selected from the perspective of the receiver areas to evaluate the ecological compensation criteria and compare the differences between the two models. The results show that the ecological compensation standards based on the perspective of water source areas are mainly influenced by the ecological construction expenditures and industrial opportunity cost losses in the watershed, with higher compensation costs in the early period but a more moderate growth trend in the later period. The ecological compensation standards based on the perspective of the receiver areas increase with the annual increase in project water diversion, with a low compensation cost in the early period, but a faster growth trend in the later period. The ecological compensation standards calculated by different perspectives and methods differ significantly; the main contribution of this paper is to enrich the ecological compensation research on cross-basin water diversion projects from multiple perspectives.

Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo.

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines. Superparamagnetic iron oxide nanoparticles (SPION) are effective carriers for targeted drug delivery. This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI) (SPION-PEI) designed for small interfering RNA (siRNA) delivery both in vitro and in vivo. SPION-PEI/siRNA complexes were prepared at different weight ratios. Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Rats were divided into three groups: a control group, a normal-saline group and a SPION-PEI/siRNA group. After a single intravenous injection, in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart, liver, spleen, lung and kidney 8 h, 24 h, and 7 days after the injection. Their distribution was histologically studied at the three time points by measuring ironpositive areas (µm2) in organ sections stained with Prussian blue. The same organs were analyzed by H&E staining for any possible histopathological changes. Furthermore, biochemical indexes such as alanine amino transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine (CREA) were also assessed at all experimental time points. Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4. MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity. In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition. The iron content was significantly increased in the liver and spleen, peaking 24 h after intravenous injection and then declining gradually. No evidence was found of irreversible histopathological damage to any of the organs tested. These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen, which might be the target organs of SPION-PEI/siRNA complexes. SPIONPEI/siRNA may serve as in vivo carrier for biomedical medicines.