For decades, hydrogen (H2) gas has been recognized as an excellent antioxidant molecule that holds promise in treating many diseases like Alzheimer's, stroke, cancer, and so on. For the first time, active hydrogen is demonstrated to be highly efficient in antibacterial, antibiofilm, and wound‐healing applications, in particular when used in combination with the photothermal effect. As a proof of concept, a biocompatible hydrogen‐releasing PdH nanohydride, displaying on‐demand controlled active hydrogen release property under near‐infrared laser irradiation, is fabricated by incorporating H2 into Pd nanocubes. The obtained PdH nanohydride combines both merits of bioactive hydrogen and photothermal effect of Pd, exhibiting excellent in vitro and in vivo antibacterial activities due to its synergistic hydrogen‐photothermal therapeutic effect. Interestingly, combinational hydrogen‐photothermal treatment is also proved to be an excellent therapeutic methodology in healing rats' wound with serious bacterial infection. Moreover, an in‐depth antibacterial mechanism study reveals that two potential pathways are involved in the synergistic hydrogen‐photothermal antibacterial effect. One is to upregulate bacterial metabolism relevant genes like dmpI, narJ, and nark, which subsequently encode more expression of oxidative metabolic enzymes to generate substantial reactive oxygen species to induce DNA damage and another is to cause severe bacterial membrane damage to release intracellular compounds like DNA.
Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatformHPDA@MnO2@Ce6/DOX@PEG-RGD (HPMRCD)by means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO2), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and H2O2-rich TME. The dual-responsive release of Mn2+ ions and oxygen (O2) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.
Molecular selection, ion exclusion, and water permeation are well known regulatory mechanisms in aquaporin. Water permeability was found to be diverse in different subgroups of plasma membrane intrinsic proteins (PIPs), even though the residues surrounding the water holes remained the same across the subgroups. Upon homology modeling and structural comparison, a conserved Ala/Ile(Val) residue difference was identified in helix 2 that affected the conformation of the NPA region and consequently influenced the water permeability. The residue difference was found to be conservative within the two subgroups of PIPs in rice as well as in other plants. Func 52% reduction of water transportation. Based on structural analyses and molecular dynamics simulations, we proposed that the difference in water permeability was attributed to the orientation variations of helix 2 that modified waterwater and water-protein interactions. Aquaporins (AQPs)7 are small integral membrane proteins that facilitate water transport across the membranes and are widely distributed in animals, plants, and microbes. It is unique in plants that AQPs form a large family with 35 and 33 members in Arabidopsis and rice, respectively. According to the amino acid sequence, the AQPs could be classified into four subgroups, i.e. the plasma membrane intrinsic proteins (PIPs), the tonoplast intrinsic proteins, the NOD26-like intrinsic protein, and the small basic intrinsic proteins (reviewed in Maurel et al.(1) and references cited therein). Plant PIPs are divided into two phylogenic subgroups, PIP1 and PIP2 (2). The AQP monomer consists of six transmembrane ␣-helices tilted along the plane of the membrane and connected by five loops (A-E). Loop B and D as well as the N and C termini are cytoplasmic (3). Two highly conserved constrictions within the pore of AQPs were proposed by structural analysis of AQP proteins. One is the central constriction formed by two Asn-Pro-Ala (NPA) motifs located on two short ␣-helices and the other is the outer constriction or aromatic/arginine (ar/R) constriction formed by spatial arrangement of four aromatic amino acids. Recently it was found that in addition to facilitating the transport of water, AQPs also can transport other small solutes. Size exclusion at the two main constrictions is one of the mechanisms for water transport and substrate selectivity by AQPs (3, 4). Extensive investigation of the plant PIPs revealed that PIP2 paralogues induced water permeation when expressing on Xenopus oocyte or yeast membranes, whereas PIP1 paralogues were almost inactive (5-10). The sequence difference between the two subgroups, however, is quite subtle, as they share the same residues in main pore constrictions and almost the same hydrophobic residues around the aqueous pathway (6, 11).The first attempt to elucidate the mechanism of distinct water transport activities between the two subgroups was performed in radish PIPs (12). Based on the sequence difference, the authors identified a residue that discriminates PIP1s and PIP2s....
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