Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

[Altitudinal changes of soil organic carbon fractions of evergreen broadleaved forests in Guanshan Mountain, Jiangxi, China]. / 江西官山常绿阔叶林土壤有机碳组分沿海拔的变化.

We investigated soil total organic carbon (TOC), recalcitrant organic carbon (ROC), and labile organic carbon (LOC) of evergreen broadleaved forests at different altitudes (400, 600, 800, 1000 and 1200 m) in Guanshan National Nature Reserve, Jiangxi Province, with the aim to understand their altitudinal distribution. The results showed that soil TOC, ROC and LOC contents were the highest in the surface layer and decreased with soil depth. With the increases of altitude, contents of soil TOC, ROC, readily oxidizable organic carbon (ROOC), microbial biomass carbon (MBC), and particulate organic carbon (POC, 0-20 cm depth) increased with a peak at 1000 m and then decreased, whereas soil water-soluble organic carbon (WSOC) contents and POC contents in 20-40 cm layer did not change. In 0-10 cm soil layer, the proportions of ROC to TOC at 800 and 1200 m were significantly higher than those at 400 and 1000 m, while the proportions of LOC to TOC were the highest at 400 m. The proportions of ROC and LOC to TOC in 10-40 cm layer showed a low-high-low tendency along the altitude, with peaks at 1000 and 600 m, respectively. Soil organic carbon fractions were positively correlated with soil moisture, microbial biomass nitrogen, and soluble organic nitrogen. A positive correlation was observed between LOC and ammonium concentration. Our results suggested that altitude significantly affected the distribution of soil organic fractions, with soil ROC, ROOC and MBC being more sensitive to altitudinal changes. Soil ROC and LOC at high altitude were prone to decomposition and transformation under conditions with sufficient water and nitrogen, which reduced soil carbon stability. It was essential to study the dyna-mics of soil organic carbon in high altitude forests under global warming scenarios.

Exosomal MicroRNA-10a Is Associated with Liver Regeneration in Rats through Downregulation of EphA4.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration. METHODS: The Sprague-Dawley male rats were assigned to 70% partially hepatectomized group (n = 6) and sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA) staining was applied to study the effect of key miRNA overexpression on liver regeneration. Western blotting was used to validate the predicted target of the key miRNA. RESULTS: Exosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in the early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression of miR-10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein level of EphA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle. CONCLUSION: Exosomal miR-10a might accelerate liver regeneration through downregulation of EphA4.

ß-catenin deacetylation is essential for WNT-induced proliferation of breast cancer cells.

Deregulation of the WNT signaling pathway is associated with the development and progression of breast cancer. ß-catenin mutations have been found to constitutively activate ß-catenin-T-cell factor (TCF) signaling in other types of cancer. ß-catenin acetylation regulates ß-catenin-TCF4 interaction in WNT signaling, but it remains unknown whether the acetylation of ß-catenin is involved in WNT-induced proliferation of breast cancer cells. In this study, a lower level of acetylated ß-catenin (K345) was observed in breast cancer tissues. WNT3A stimulated the downregulation of ß-catenin acetylation and promoted the proliferation of MCF7 cells. The K345Q mutation in ß-catenin inhibited WNT-induced cell growth and axin2/TCF7 upregulation in breast cancer cells. By contrast, K345R mutants could mimic deacetylated ß-catenin to generate the WNT-elicited phenotype. Additionally, the acetylation of ß-catenin may prime ß-catenin for phosphorylation. Further investigation revealed that the deacetylase HDAC6 was responsible for WNT-induced deacetylation of ß-catenin in breast cancer cells. In conclusion, the epigenetic modification of ß-catenin may be essential for WNT signaling in breast cancer progression, and blocking the occurrence of ß-catenin acetylation may provide a novel therapeutic approach for breast cancer.