Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (•OH). To overcome the current limitations of the insufficient endogenous H2O2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC‐DOX) that possesses both H2O2 self‐supply and GSH‐elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one‐step biomineralization method using poly(ethylene glycol)‐modified glucose oxidase (GOx) as a template to form biodegradable copper‐doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H2O2, which not only starves the tumor cells, but also supplies H2O2 for subsequent Fenton‐like reaction. Meanwhile, the redox reaction between the released Cu2+ ions and intracellular GSH will induce GSH depletion and reduce Cu2+ to Fenton agent Cu+ ions, and then trigger the H2O2 to generate •OH by a Cu+‐mediated Fenton‐like reaction, resulting in enhanced CDT efficacy. The integration of GOx‐mediated starvation therapy, H2O2 self‐supply and GSH‐elimination enhanced CDT, and DOX‐induced chemotherapy, endow the PGC‐DOX with effective tumor growth inhibition with minimal side effects in vivo.

Microbial biofilms are communities of aggregated microbial cells embedded in a self-produced matrix of extracellular polymeric substances (EPS). Biofilms are recalcitrant to extreme environments, and can protect microorganisms from ultraviolet (UV) radiation, extreme temperature, extreme pH, high salinity, high pressure, poor nutrients, antibiotics, etc., by acting as “protective clothing”. In recent years, research works on biofilms have been mainly focused on biofilm-associated infections and strategies for combating microbial biofilms. In this review, we focus instead on the contemporary perspectives of biofilm formation in extreme environments, and describe the fundamental roles of biofilm in protecting microbial exposure to extreme environmental stresses and the regulatory factors involved in biofilm formation. Understanding the mechanisms of biofilm formation in extreme environments is essential for the employment of beneficial microorganisms and prevention of harmful microorganisms.

Hydroxyurea therapy has proven laboratory and clinical efficacies for children with sickle cell anemia (SCA

Glucose oxidase (GOx) has been recognized as a “star” enzyme catalyst involved in cancer treatment in the past few years. Herein, GOx is mineralized with manganese-doped calcium phosphate (MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an in situ biomimetic mineralization method, followed by the loading of doxorubicin (DOX) to construct a biodegradable, biocompatible, and tumor acidity-responsive nanotheranostics for magnetic resonance imaging (MRI) and cascade reaction-enhanced cooperative cancer treatment. The GOx-driven oxidation reaction can effectively eliminate intratumoral glucose for starvation therapy, and the elevated H2O2 is then converted into highly toxic hydroxyl radicals via a Mn2+-mediated Fenton-like reaction for chemodynamic therapy (CDT). Moreover, the acidity amplification due to the gluconic acid generation will in turn accelerate the degradation of the nanoplatform and promote the Mn2+–H2O2 reaction for enhanced CDT. Meanwhile, the released Mn2+ ions can be used for MRI to monitor the treatment process. After carrying the anticancer drug, the DOX-loaded GOx-MnCaP can integrate starvation therapy, Mn2+-mediated CDT, and DOX-induced chemotherapy together, which showed greatly improved therapeutic efficacy than each monotherapy. Such an orchestrated cooperative cancer therapy demonstrated high-efficiency tumor suppression on 4T1 tumor-bearing mice with minimal side effects. Our findings suggested that the DOX-loaded GOx-MnCaP nanotheranostics with excellent biodegradability and biocompatibility hold clinical translation potential for cancer management.

and background absorption than that done in the first near-infrared window (NIR-I, 650-950 nm). [1] Therefore, the development of theranostic agents in NIR-II region has become something of a research hotspot. [1a,2] Recently, there is an ever-increasing number of papers describing the modification of gold nanomaterials for NIR-II photoacoustic imaging (PAI) and photothermal therapy (PTT) owing to its unique plasmonic, acoustic, and electric properties, as well as multifunctionality endowed by its various dimensions and morphologies. [1c,e,3] Furthermore, its excellent biosafety surpasses the limits of most inorganic nanomaterials. [4] Currently, there are few methods that shift the localized surface plasmon resonance (LSPR) peak of gold nanomaterials from NIR-I to NIR-II region. [2a,5] For instance, some gold nanorods (GNRs) with superhigh aspect ratios or GNRs with extremely thin shells have been reported. [6] However, most of them still bear poor photostability. In fact, tailoring the morphology is not the only method to obtain a redshift in the absorbance of gold nanomaterials. Substances coated to the surface of GNRs can also cause absorbance red or blueshifts. For example, Wu et al. found that a layer of Cu 2 O could cause absorbance redshift of GNRs from 600 to 800 nm. [7] Yeh et al. developed a rattle-like structure with a GNR encapsulated in a cavity of AuAg nanoshell to achieve a broad absorbance band span 300-1350 nm. [2a] However, most metal oxides suffer from biotoxicity and not responsive to tumor microenvironment. Therefore, the development of biocompatible and stimuli-responsive coatings for plasmonic modulation of GNRs remains a big challenge. Manganese is one of the most commonly used metal element in cancer theranostics on account of its good biosafety and rich quantity of valence states, which allows for the design and synthesis of intelligent theranostic agents. [8] For example, manganese dioxide (MnO 2) is widely used as a catalase to decompose hydrogen peroxide (H 2 O 2) in tumor microenvironment and produce oxygen and hence relieves the tumor hypoxia and reduces tumor resistance to radio-or chemotherapy. [9] Recently, it was reported that MnO 2 could decrease glutathione level in Nanotheranostic agents of gold nanomaterials in the second near-infrared (NIR-II) window have attracted significant attention in cancer management, owing to the reduced background signal and deeper penetration depth in tissues. However, it is still challenging to modulate the localized surface plasmon resonance (LSPR) of gold nanomaterials from the first near-infrared (NIR-I) to NIR-II region. Herein, a plasmonic modulation strategy of gold nanorods (GNRs) through manganese dioxide coating is developed for NIR-II photoacoustic/magnetic resonance (MR) duplex-imaging-guided NIR-II photothermal chemodynamic therapy. GNRs are coated with silica dioxide (SiO 2) and then covered with magnesium dioxide (MnO 2) to obtain the final product of GNR@SiO 2 @MnO 2 (denoted as GSM). The LSPR peak of GNRs could be tuned by adjust...

C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date.

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