Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Polymer-like Inorganic Double Helical van der Waals Semiconductor.

In high-performance flexible and stretchable electronic devices, conventional inorganic semiconductors made of rigid and brittle materials typically need to be configured into geometrically deformable formats and integrated with elastomeric substrates, which leads to challenges in scaling down device dimensions and complexities in device fabrication and integration. Here we report the extraordinary mechanical properties of the newly discovered inorganic double helical semiconductor tin indium phosphate. This spiral-shape double helical crystal shows the lowest Young's modulus (13.6 GPa) among all known stable inorganic materials. The large elastic (>27%) and plastic (>60%) bending strains are also observed and attributed to the easy slippage between neighboring double helices that are coupled through van der Waals interactions, leading to the high flexibility and deformability among known semiconducting materials. The results advance the fundamental understanding of the unique polymer-like mechanical properties and lay the foundation for their potential applications in flexible electronics and nanomechanics disciplines.

The invisible Threat: Assessing the reproductive and transgenerational impacts of micro- and nanoplastics on fish.

Micro- and nanoplastics (MNPs), emerging as pervasive environmental pollutants, present multifaceted threats to diverse ecosystems. This review critically examines the ability of MNPs to traverse biological barriers in fish, leading to their accumulation in gonadal tissues and subsequent reproductive toxicity. A focal concern is the potential transgenerational harm, where offspring not directly exposed to MNPs exhibit toxic effects. Characterized by extensive specific surface areas and marked surface hydrophobicity, MNPs readily adsorb and concentrate other environmental contaminants, potentially intensifying reproductive and transgenerational toxicity. This comprehensive analysis aims to provide profound insights into the repercussions of MNPs on fish reproductive health and progeny, highlighting the intricate interplay between MNPs and other pollutants. We delve into the mechanisms of MNPs-induced reproductive toxicity, including gonadal histopathologic alterations, oxidative stress, and disruptions in the hypothalamic-pituitary-gonadal axis. The review also underscores the urgency for future research to explore the size-specific toxic dynamics of MNPs and the long-term implications of chronic exposure. Understanding these aspects is crucial for assessing the ecological risks posed by MNPs and formulating strategies to safeguard aquatic life.

Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo.

We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to cells. After transfection, WSLP/NR2B-siRNA complexes reduced the NR2B transcriptional level by 50% and protein level by 55% compared to control siRNA. Moreover, 3 days after intrathecal injection of WSLP/NR2B-siRNA complexes into rats, the NR2B protein expression decreased significantly to 58%, compared to control treatment (p < 0.01). Injection of WSLP with scrambled siRNA or of polyethylenimine (PEI) with NR2B-siRNA did not show this inhibitory effect. Additionally, injection of WSLP/NR2B-siRNA complexes significantly relieved inflammatory pain in rats at 3, 4, and 5 days with reduced MWT and decreased TWL scores, while injection of WSLP with scrambled siRNA or of PEI with NR2B-siRNA did not. These results demonstrated that WSLP can efficiently deliver siRNA targeting NR2B to PC12 cells and relieve pain in rats with chronic inflammatory pain.