Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen‐vacancy molybdenum trioxide nanodots (MoO3−x NDs) are proposed as an efficient and safe bacteriostatic. The MoO3−x NDs alone possess triple‐therapy synergistic efficiency based on the single near‐infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase‐like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad‐spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO3−x NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H2O2 (100 µm). The MoO3−x NDs show excellent antibacterial efficiency against drug‐resistance extended spectrum β‐lactamases producing Escherichia coli and methicillin‐resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO3−x NDs can effectively treat wounds infected with MRSA in living systems.

The application of the antibiotic drug has dramatically decreased the infection and promoted the development of surgery, but drug-resistant bacteria appeared along with the abuse of antibiotics. Especially, wound in diabetic patients provides more glucose for bacteria resulting in poor wound healing. Therefore, it is imminent to explore advanced agents for combating multidrug-resistant bacteria and accelerating diabetic wound healing. Herein, metal-organic frameworks based nanoreactors loaded with glucose oxidase (GOx) and peroxidase-like bovine hemoglobin (BHb) are designed to construct an effective cascaded catalytic antibacterial system. Therein, GOx can cost the glucose, and release H 2 O 2 simultaneously, which can then be transformed into hydroxyl radicals by BHb. As a result, the as-prepared nanoreactors can play the roles of both starving and killing toward the multidrug-resistant bacteria. Furthermore, the produced gluconic acid can reduce the pH of working condition, which is beneficial for both the enhancement of peroxidase activity and the inhibition of the bacteria growth. More importantly, the constructed nanoreactors can be degraded and excreted from the body in the form of feces, which render the as-proposed nanoreactors qualified as effective and safe materials for both combating multidrug-resistant bacteria in vitro and accelerating the diabetic wound healing in vivo of the mouse model.

Many clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.

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The emergence of peroxidase (POD)-like nanozyme-derived catalytic therapy has provided a promising choice for reactive oxygen species (ROS)-mediated broad-spectrum antibacterials to replace antibiotics, but it still suffers from limitations of low therapeutic efficiency and unusual addition of unstable H2O2. Considering that the higher blood glucose in diabetic wounds provides much more numerous nutrients for bacterial growth, a cascade nanoenzymatic active material was developed by coating glucose oxidase (GOx) onto POD-like Fe2(MoO4)3 [Fe2(MoO4)3@GOx]. GOx could consume the nutrient of glucose to produce gluconic acid (weakly acidic) and H2O2, which could be subsequently converted into highly oxidative •OH via the catalysis of POD-like Fe2(MoO4)3. Accordingly, the synergistic effect of starvation and ROS-mediated therapy showed significantly efficient antibacterial effect while avoiding the external addition of H2O2 that affects the stability and efficacy of the therapy system. Compared with the bactericidal rates of 46.2–59.404% of GOx or Fe2(MoO4)3 alone on extended-spectrum β-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus, those of the Fe2(MoO4)3@GOx group are 98.396 and 98.776%, respectively. Animal experiments showed that the as-synthesized Fe2(MoO4)3@GOx could much efficiently promote the recovery of infected wounds in type 2 diabetic mice while showing low cytotoxicity in vivo.