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Gas‐mediated sonodynamic therapy (SDT) has the potential to become an effective strategy to improve the therapeutic outcome and survival rate of cancer patients. Herein, titanium sulfide nanosheets (TiSX NSs) are prepared as cascade bioreactors for sequential gas–sonodynamic cancer therapy. TiSX NSs themselves as hydrogen sulfide (H2S) donors can burst release H2S gas. Following H2S generation, TiSX NSs are gradually degraded to become S‐defective and partly oxidized into TiOX on their surface, which endows TiSX NSs with high sonodynamic properties under ultrasound (US) irradiation. In vitro and in vivo experiments show the excellent therapeutic effects of TiSX NSs. In detail, large amounts of H2S gas and reactive oxygen species (ROS) can simultaneously inhibit mitochondrial respiration and ATP synthesis, leading to cancer cell apoptosis. Of note, H2S gas also plays important roles in modulating and activating the immune system to effectively inhibit pulmonary metastasis. Finally, the metabolizable TiSX NSs are excreted out of the body without inducing any significant long‐term toxicity. Collectively, this work establishes a cascade bioreactor of TiSX NSs with satisfactory H2S release ability and excellent ROS generation properties under US irradiation for programmed gas–sonodynamic cancer therapy. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases. In this study, a new type of hydrogen peroxide (H2O 2) -activated photoacoustic nanoprobe [Mn-AH nanoscale coordination polymer nanodots (NCPs)] was successfully synthesized by a simple one-step method in water phase containing 2,2 ′ -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), horse radish peroxidase (HRP), and manganese ion (Mn 2 +). After modification by polyethylene glycol (PEG), Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H2O2-responsive chromogenic assay with great specificity and sensitivity. In the presence of H2O2, colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of endogenous H2O2. Using H2O2-activated Mn-AH NCPs, we have successfully performed PA imaging and H2O2 detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder tumor. Due to the inherent Mn element existence inside the Mn-AH, this nanoprobe also serves as a good T1-weighted magnetic resonance imaging (MRI) contrast agent simultaneously. Lastly, after accomplishing its imaging functions, the Mn-AH NCPs could be cleared out from the body without any long-term toxicity, providing a new opportunity for cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Cathepsin cysteine proteases play multiple roles in the life cycle of parasites such as food uptake, immune invasion and pathogenesis, making them valuable targets for diagnostic assays, vaccines and drugs. The purpose of this study was to identify a cathepsin B of Clonorchis sinensis (CsCB) and to investigate its diagnostic value for human helminthiases. Results The predicted amino acid sequence of the cathepsin B of C. sinensis shared 63%, 52%, 50% identity with that of Schistosoma japonicum, Homo sapiens and Fasciola hepatica, respectively. Sequence encoding proenzyme of CsCB was overexpressed in Escherichia coli. Reverse transcription PCR experiments revealed that CsCB transcribed in both adult worm and metacercaria of C. sinensis. CsCB was identified as a C. sinensis excretory/secretory product by immunoblot assay, which was consistent with immunohistochemical localization showing that CsCB was especially expressed in the intestine of C. sinensis adults. Both ELISA and western blotting analysis showed recombinant CsCB could react with human sera from clonorchiasis and other helminthiases. Conclusions Our findings revealed that secreted CsCB may play an important role in the biology of C. sinensis and could be a diagnostic candidate for helminthiases.

Magnetic hyperthermia therapy (MHT) is able to ablate tumors using an alternating magnetic field (AMF) to heat up magnetocaloric agents (e.g. magnetic nanoparticles) administered into the tumors. For clinical applications, there is still a demand to find new magnetocaloric agents with strong AMF-induced heating performance and excellent biocompatibility. As a kind of biocompatible and biodegradable material, magnesium (Mg) and its alloys have been extensively used in the clinic as an implant metal. Herein, we discovered that the eddy thermal effect of the magnesium alloy (MgA) could be employed for MHT to effectively ablate tumors. Under low-field-intensity AMFs, MgA rods could be rapidly heated, resulting in a temperature increase in nearby tissues. Such AMF-induced eddy thermal heating of MgA could not only be used to kill tumor cells in vitro , but also be employed for effective and accurate ablation of tumors in vivo. In addition to killing tumors in mice, we further demonstrated that VX2 tumors of much larger sizes growing in rabbits after implantation of MgA rods could also be eliminated after exposure to an AMF, illustrating the ability of MgA-based MHT to kill large-sized tumors. Moreover, the implanted MgA rods showed excellent biocompatibility and ∼20% of their mass was degraded within three months. Our work thus discovered for the first time that non-magnetic biodegradable MgA, an extensively used implant metal in clinic, could be used for effective magnetic thermal ablation of tumors under a low-field-intensity AMF. Such a strategy could be readily translated into clinical use. [ABSTRACT FROM AUTHOR]