Constructing a self-healing injectable SABA/Borax/PDA@AgNPs hydrogel for synergistic low-temperature photothermal antibacterial therapy.

Infections caused by bacteria are one of the biggest challenges humans face around the world. Photothermal therapy (PTT) has been regarded as a promising strategy in combating pathogenic infection, however the high temperatures (55-65 °C) required during a single PTT process can induce injury to healthy tissues nearby. Combination therapy could overcome this problem by reducing the photothermal temperature. Here, we developed a self-healing and injectable hydrogel to realize low-temperature PTT (LT-PTT, ≤45 °C) for antisepsis with high-efficiency. The hybrid hydrogel is prepared by incorporating borax into a mixture of 3-aminophenylboronic acid grafted sodium alginate and nano-silver decorated polydopamine nanoparticles. Our results showed that the SABA/Borax/PDA@AgNPs hydrogel possesses satisfactory mechanical properties and self-healing capacity, and as a result, it can repair itself after being damaged mechanically, retaining its integrality and recovering its initial functionalities. Furthermore, through utilizing the photothermal property of polydopamine nanoparticles and broad-spectrum antibacterial activity of nano-silver, the hybrid hydrogel achieves excellent LT-PTT for sterilization both in vitro as well as in an in vivo mice skin wound model with no distinct injury to normal tissues. Overall, our prepared hydrogel is expected to be an excellent candidate for treating bacterial infections.

Intracellular and extracellular untargeted metabolomics reveal the effect of acute uranium exposure in HK-2 cells.

Uranium exposure poses a serious threat to the health of occupational populations and the public. Although metabolomics is a promising research approach to study the toxicological mechanisms of uranium exposure, in vitro studies using human cells are scarce. Applying cultured cell metabolomics, we exhaustively analyzed the intracellular and extracellular differential metabolites upon uranium exposure and characterized the possible biological effects of uranium exposure on human kidney cells. Uranium exposure significantly induced disturbance in the amino acid biosynthesis and linoleic acid metabolism of the cells. Cells exposed to uranium produce excessive amounts of arachidonic acid, which has the potential to cause oxidative stress and damage cells. The results provide new evidence for an oxidative stress mechanism of uranium-induced renal cell injury. Cell metabolomics has proven to be a useful diagnostic tool to study the molecular mechanisms of uranium poisoning.

Thorium inhibits human respiratory chain complex IV (cytochrome c oxidase).

Thorium is a radioactive heavy metal and an emerging environmental pollutant. Ecological and human health risks from thorium exposure are growing with the excavation of rare earth metals and implementation of thorium-based nuclear reactors. Thorium poisoning is associated with carcinogenesis, liver impairments, and congenital anomalies. To date, the biomolecular targets that underlie thorium-induced toxicity remain unknown. Here, we used in vitro enzymatic activity assays to comprehensively evaluate the effects of thorium on the mitochondrial respiration process. Thorium was found to inhibit respiratory chain complex IV (cytochrome c oxidase) at sub-micromolar concentrations (IC50 ~ 0.4 µM, 90 µg/L). This is lower than the thorium level limit (246 µg/L) in drinking water specified by the World Health Organization. The inhibitory effects were further verified in mitochondria from human bone and liver cells (thorium mainly deposits in these organs). The inhibition of cytochrome c oxidase can readily rationalize well-documented cellular toxicities of thorium, such as alteration of mitochondrial membrane potential and production of reactive oxygen species. Therefore, cytochrome c oxidase is potentially a key molecular target underlying thorium-induced toxicological effect.

Binding behaviors and kinetics studies on the interaction of silver nanoparticles with trypsin.

The interaction of nanoparticles (NPs) with proteins is a topic of high relevance for the medical application of nanomaterials. In this study, a comprehensive investigation was performed to clarify the binding mechanism, adsorption isotherms and kinetics of the interaction between silver nanoparticles (AgNPs) and trypsin. The experimental results indicate that the binding of AgNPs to trypsin seems to be a static quenching mechanism. Thermodynamic analysis reveals that AgNPs binding to trypsin is synergistically driven by enthalpy and entropy, and the major driving forces are hydrophobic and electrostatic interactions. The adsorption of trypsin on AgNPs was analyzed by Langmuir and Freundlich models, suggesting that the equilibrium adsorption data fit well with Freundlich model. The kinetics of adsorption data were modeled using the pseudo-first-order and pseudo-second-order kinetic equations. The results indicate that a pseudo-second-order kinetic equation describes better. The conformational change at the secondary structural level of trypsin induced by AgNPs was investigated with the circular dichroism (CD) measurements and no obvious changes in trypsin secondary structural elements are observed. These fundamental works will provide some new insights into the safe and effective application of AgNPs in biological and medical areas.