Schroedermcclure1988

Although tremendous efforts have been made to construct gene vectors incorporating multiple functionalities and moieties, designing gene vectors integrating innovative features to successfully negotiate biological impediments which hamper efficacious responses in gene-based therapy is still very urgent. Herein, a light-induced virus-inspired mimic in which a modular envelope was utilized to mask PEI/DNA polyplexes, was developed based on two pH-responsive polymers. The virus-inspired envelope, which was capable of achieving multi-targeting and dual pH-responsiveness in endo/lysosomal compartments, was composed of an iRGD-modified module and a NLS(Cit)-functionalized module. The envelope conjugated with chlorin e6 was shielded on the surface of PEI/DNA polyplexes. Dual pH-responsive deshielding of the virus-inspired mimic in endo/lysosomes allowed generation of a non-fatal amount of ROS under short-time photoirradiation, leading to photochemical internalization and much more substantial enhancement in light-induced gene expression without DNA damage caused by ROS. Confocal images revealed the virus-inspired mimic achieved successful nuclear translocation of chlorin e6, resulting in nucleus-targeting photodynamic therapy. Furthermore, pTRAIL-mediated gene therapy, accompanied by a fatal amount of ROS under long-time photoirradiation, additionally consolidated in vitro anti-tumor outcomes. This study demonstrates a novel paradigm of "one arrow, two hawks", accomplishing a combination of enhanced gene therapy and photodynamic therapy.Lead oxide (PbO) nanosheets are of significance in the design of functional devices. However, facile, green, and fast fabrication of ultrathin and homogenous PbO nanosheets with a chemically clean surface is still desirable. Herein, a simple and chemically clean route is developed for fabricating such nanosheets via laser ablation of a lead target in water for a short time and then ambient aging. The obtained PbO nanosheets are (002)-oriented with microsize in planar dimension and ∼15 nm in thickness. They are mostly hexagonal in shape. Experimental observations of the morphological evolution have revealed that the formation of such PbO nanosheets can be attributed to two processes (i) laser ablation-induced formation of ultrafine Pb and PbO nanoparticles (NPs) and (ii) PbO NP aggregation and their oriented connection growth. Importantly, a composite surface-enhanced Raman spectroscopy (SERS) chip is designed and fabricated by covering a PbO nanosheet monolayer on a Au NP film. Such a composite SERS chip can be used for the fast and trace detection of gaseous H2S in which the PbO nanosheets can effectively chemically trap H2S molecules, demonstrating a new application of these PbO nanosheets. The response of this chip to H2S can be detected within 10 s, and the detection limit is below 1 ppb. Also, this PbO nanosheet-based chip is reusable by heating after use. This study not only deepens the understanding of the NP-based formation mechanism of nanosheets but also provides the renewable SERS chips for the highly efficient detection of trace gaseous H2S.The formation of biofilms provides a formidable defense for many bacteria against antibiotics and host immune responses. As a consequence, biofilms are thought to be the root cause of most chronic infections, including those occurring on medical indwelling devices, endocarditis, urinary tract infections, diabetic and burn wounds, and bone and joint infections. In cystic fibrosis (CF), chronic Pseudomonas aeruginosa (P. aeruginosa) respiratory infections are the leading cause of morbidity and mortality in adults. Previous studies have shown that many bacteria can undergo a coordinated dispersal event in the presence of low concentrations of nitric oxide (NO), suggesting that NO could be used to initiate biofilm dispersal in chronic infections, enabling clearance of the more vulnerable planktonic cells. In this study, we describe efforts to create "all-in-one" cephalosporin-based NO donor prodrugs (cephalosporin-3'-diazeniumdiolates, C3Ds) that show both direct β-lactam mediated antibacterial activity and antibiofilm effects. Twelve novel C3Ds were synthesized and screened against a panel of P. aeruginosa CF clinical isolates and other human pathogens. The most active compound, AMINOPIP2 ((Z)-1-(4-(2-aminoethyl)piperidin-1-yl)-2-(((6R,7R)-7-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methoxy)diazene 1-oxide)-ceftazidime 12, showed higher antibacterial potency than its parent cephalosporin and front-line antipseudomonal antibiotic ceftazidime, good stability against β-lactamases, activity against ceftazidime-resistant P. aeruginosa in vitro biofilms, and efficacy equivalent to ceftazidime in a murine P. aeruginosa respiratory infection model. buy Aminoguanidine hydrochloride The results support further evaluation of AMINOPIP2-ceftazidime 12 for P. aeruginosa lung infections in CF and a broader study of "all-in-one" C3Ds for other chronic infections.Efficient charge separation can promote photocatalysis of semiconductors. Herein, a hollowed TiO2 sphere decorated with spatially separated bi-functional cocatalysts was designed, which exhibited enhanced photocatalytic hydrogen generation. Ultrasmall sized MOx (M = Pd, Co, Ni or Cu) nanoparticles (NPs) were first introduced into zeolite via confinement synthesis, and then hollow TiO2 was fabricated by using zeolite as a sacrificial template forming MOx@TiO2. Finally, Pt NPs were decorated at the outer shell, giving rise to MOx@TiO2@Pt, in which the MOx NPs and Pt NPs acted as holes captures and electrons sinks, respectively. Thanks to the enhanced light harvesting of the hollow structure, improved charge separation induced by the smaller sized cocatalysts as well as spatially separated bi-functional cocatalysts, the as-prepared PdOx@TiO2@Pt catalyst exhibited superior photocatalytic hydrogen generation property (0.45 mmol h-1). This work demonstrates the advantage of the spatially separated bi-functional cocatalysts in enhancing the photocatalytic property of semiconductors.