Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

Stable and Label-Free Fluorescent Probe Based on G-triplex DNA and Thioflavin T.

G-triplexes have recently been identified as a new kind of DNA structures. They perhaps possess specific biological and chemical functions similar as identified G-quadruplex but can be formed by shorter G-rich sequences with only three G-tracts. However, until now, limited G-triplexes sequences have been reported, which might be due to the fact that their stability is one of the biggest concerns during their functional studies and application research. Herein, we found a G-rich sequence (5'-TGGGTAGGGCGGG-3') which can form a stable G-triplex (Tm ∼ 60 °C) at room temperature. The stable G-triplex can combine with thioflavin T and function as an efficient fluorescence light-up probe. Comparing with the traditional G-quadruplex based probe, this triplex based probe was easy to be controlled and excited. Finally, the probe was successfully applied into constructing a label-free molecular beacon for miRNA detection. Taking advantage of these abilities of the G-triplex based fluorescent probe, the challenges faced during designing G-rich sequences based fluorescent biosensors can be efficiently solved. These findings provide important information for the future application of G-triplex.

Methylation changes of liver DNA during the formation of gallstones.

Aim: To explore the overall methylation changes in liver tissues during the formation of gallstones, as well as the key pathways and genes involved in the process. Methods: Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. Results: A total of 8705 differentially methylated regions in CpG and 1410 differentially expressed genes were identified. The joint analysis indicated that aberrant DNA methylation may be associated with dysregulated gene expression in key pathways such as cholesterol metabolism and bile secretion. Conclusion: We propose for the first time that methylation changes in some key pathway genes in liver tissue may be involved in the formation of gallstones.

ß-Ni(OH)2 nanosheets: an effective sensing platform for constructing nucleic acid-based optical sensors.

In this study, beta nickel hydroxide (ß-Ni(OH)2) nanosheets, one of the transition metal oxyhydroxides with two dimensional (2D) structures, were explored as a new fluorescent biosensor platform and applied in constructing optical sensors for bioanalysis. It was found that ß-Ni(OH)2 nanosheets displayed a high fluorescence quenching ability and different affinity toward single- versus double-stranded DNA. Moreover, the absorption properties of ß-Ni(OH)2 nanosheets can be well controlled by changing cations, solution pH and the length of DNA. In comparison with some reported 2D nanosheet platforms (e.g. graphene, metal chalcogenides), the absorbed DNA can also be desorbed by degrading the ß-Ni(OH)2 nanosheets, which is a simple but effective DNA desorption method. Based on these findings, a sensitive and selective optical miRNA sensor with a detection limit of 1 pM was demonstrated by combining the fluorescence quenching ability of ß-Ni(OH)2 nanosheets and duplex-specific nuclease signal amplification. The presented sensor has been successfully used for miRNA analysis in samples containing cancer cells and shown great potential in multiplexed miRNA analysis for clinical diagnosis.