Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

High-precision detection and navigation surgery of colorectal cancer micrometastases.

Surgical resection is an effective treatment for colorectal cancer (CRC) patients, whereas occult metastases hinder the curative effect. Currently, there is no effective method to achieve intraoperatively diagnosis of tumor-positive lymph nodes (LNs). Herein, we adopt a near-infrared-II (NIR-II) organic donor-pi-acceptor-pi-donor probe FE-2PEG, which exhibits bright fluorescence over 1100 nm, excellent photostability, blood circulation time, and biocompatibility, to achieve high-performance bioimaging with improved temporal and spatial resolution. Importantly, the FE-2PEG shows efficient passive enrichment in orthotopic CRC, metastatic mesenteric LNs, and peritoneal metastases by enhanced permeability and retention effect. Under NIR-II fluorescence-guided surgery (FGS), the peritoneal micrometastases were resected with a sensitivity of 94.51%, specificity of 86.59%, positive predictive value (PPV) of 96.57%, and negative predictive value of 79.78%. The PPV still achieves 96.07% even for micrometastases less than 3 mm. Pathological staining and NIR-II microscopy imaging proved that FE-2PEG could successfully delineate the boundary between the tumor and normal tissues. Dual-color NIR-II imaging strategy with FE-2PEG (1100 ~ 1300 nm) and PbS@CdS quantum dots (> 1500 nm) successfully protects both blood supply and normal tissues during surgery. The NIR-II-based FGS provides a promising prospect for precise intraoperative diagnosis and minimally invasive surgery of CRC.

Surfactant-chaperoned donor-acceptor-donor NIR-II dye strategy efficiently circumvents intermolecular aggregation to afford enhanced bioimaging contrast.

Fluorescence emission in the near-infrared-II (NIR-II) optical window affords reduced autofluorescence and light scattering, enabling deep-tissue visualization for both disease detection and surgical navigation. Small-molecule NIR-II dyes are preferable for clinical bioimaging applications, as the flexibility in their molecular synthesis allows for precise control of their optical and pharmacokinetic properties. Among the various types of dye, donor-acceptor-donor-based (D-A-D) dyes demonstrate exceptional photostability, whereas the frequently used PEGylation approach does not keep their intrinsic brightness enough in water environments due to their inherent effect of self-assembly. Here, we demonstrate that the commercially-available surfactants can serve as a dispersant to prevent molecular aggregation of PEGylated D-A-D dyes. Due to the favorable energetics for co-assembly between D-A-D dyes and surfactants, the formed surfactant-chaperoned dye strategy dramatically increases dye brightness. Accordingly, this effect provides remarkably improved performance for in vivo bioimaging applications. In parallel, we also investigate the D-A-D dye uptake and signal enhancement properties in the liver of murine models and demonstrate that the lumen-lining Kupffer cells can potentially disassemble PEGylated D-A-D aggregates such that their inherent brightness is restored. This phenomenon is similar to the surfactant-chaperoned dye strategy and our investigations provide a positive addition to better use of the current NIR-II fluorophores, especially for visualizing high-brightness required events.

Shape control from thermodynamic growth conditions: the case of hcp ruthenium hourglass nanocrystals.

Recent successes in forming different shaped face centered cubic (fcc) metal nanostructures has enabled a greater understanding of nanocrystal growth mechanisms. Here we extend this understanding to the synthesis of hexagonally close packed (hcp) metal nanostructures, to form uniquely faceted ruthenium nanocrystals with a well-defined hourglass shape. The hourglass nanocrystals are formed in a three-step thermodynamic growth process with dodecylamine as the organic stabilizer. The hourglass nanocrystals are then shown to readily self-assemble to form a new type of nanocrystal superlattice.