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New Bedford, MA, United States

Vera D.M.A.,University of the Sea | Haynes M.H.,University of New Mexico | Ball A.R.,Toxikon Corporation | Dai T.,Massachusetts General Hospital | And 9 more authors.
Photochemistry and Photobiology | Year: 2012

Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy (PDT) was originally established as an anticancer modality and is currently used in the treatment of age-related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species (ROS). ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches. In just 20 years antimicrobial photodynamic therapy (PDT) has emerged as a discovery and development platform inspiring a proliferation of light-based antimicrobial explorations worldwide. However, the potential for microbial resistance development using PDT remains under-investigated. Studies of resistance have been sporadic but they are rapidly increasing, with recent reports examining key elements of the microbial phenotype. These include multidrug efflux systems, biofilm, spore formation, virulence and pathogenicity determinants. The emerging consensus is that the effectiveness of PDT may be profoundly impacted by all these systems, but the exact mechanisms of these effects remain elusive. For example, an array of studies suggests that antimicrobial photosensitizers are substrates of multidrug efflux systems. An evolving antimicrobial discovery concept is based on the exploration of synergies between photosensitizers and small molecules efflux pump inhibitors. PS photosensitizer (red), EPI efflux pump inhibitor (green). © 2012 The American Society of Photobiology. Source


Zhong L.,Toxikon Corporation
Frontiers of Medicine in China | Year: 2013

This study aimed to modify a chronic ocular hypertension (OHT) rat model to screen for potential compounds to protect retinal ganglion cells (RGCs) from responding to increased intraocular pressure (IOP). A total of 266 rats were prepared and randomly grouped according to different time-points, namely, weeks 3, 8, 16, and 24. Rats were sedated and eye examination was performed to score as the corneal damage on a scale of 1 to 4. The OHT rat model was created via the injection of a hypertonic saline solution into the episcleral veins once weekly for two weeks. OHT was identified when the IOP at week 0 was ≥ 6 mmHg than that at week -2 for the same eye. Viable RGCs were labeled by injecting 4% FluoroGold. Rats were sacrificed, and the eyes were enucleated and fixed. The fixed retinas were dissected to prepare flat whole-mounts. The viable RGCs were visualized and imaged. The IOP (mean ± SD) was calculated, and data were analyzed by the paired t-test and one-way ANOVA. The OHT model was created in 234 of 266 rats (87.97%), whereas 32 rats (12.03%) were removed from the study because of the absence of IOP elevation (11.28%) and/or corneal damage scores over 4 (0.75%). IOP was elevated by as much as 81.35% for 24 weeks. The average IOP was (16.68 ± 0.98) mmHg in non-OHT eyes (n = 234), but was (27.95 ± 0.97) mmHg in OHTeyes (n = 234). Viable RGCs in the OHT eyes were significantly decreased in a time-dependent manner by 29.41%, 38.24%, 55.32%, and 59.30% at weeks 3, 8, 16, and 24, respectively, as compared to viable RGCs in the non-OHT eyes (P < 0.05). The OHT model was successfully created in 88% of the rats. The IOP in the OHT eyes was elevated by approximately 81% for 24 weeks. The number of viable RGCs was decreased by 59% of the rats in a time-dependent manner. The modified OHT model may provide an effective and reliable method for screening drugs to protect RGCs from glaucoma. © 2013 Higher Education Press and Springer-Verlag Berlin Heidelberg. Source


Xia S.,Zhejiang University of Technology | Zhang L.,Zhejiang University of Technology | Zhou X.,Toxikon Corporation | Pan G.,Huzhou Teachers College | Ni Z.,Zhejiang University of Technology
Applied Clay Science | Year: 2015

In this paper, four types of CuMgM layered double hydroxides (LDHs, M=Al, Cr, Fe, Ce) with good crystal structures were successfully synthesized. The activity of those LDH materials for photocatalytic reduction of water splitting under visible light was investigated. The experimental results showed that CuMgCr-LDHs with the narrowest band gap and the largest surface areas behave with the highest efficiency for hydrogen production under visible light than the other CuMgM-LDHs. The yield for hydrogen production catalyzed by CuMgCr-LDHs was 452.9μmol/gh, which was very highly efficient. Furthermore, the electronic band structure of CuMgM-LDHs was analyzed by periodic density functional theory (DFT) calculation, which is in good agreement with the experimental result from UV-vis. In addition, the influence of the different M3+ on the structures and stability of the CuMgM-LDHs was also investigated by analyzing the geometric parameters, electronic arrangement, charge populations, and hydrogen-bonding and binding energies by density functional theory (DFT) analysis. The theoretical calculation results showed that the structural stability of LDH materials followed the order of CuMgAl>CuMgCe>CuMgFe>CuMgCr, while the experimental results indicated that the photocatalytic activity of the four materials followed the order of CuMgCr>CuMgFe>CuMgCe>CuMgAl. © 2015 Elsevier B.V.. Source


Xia S.,Zhejiang University of Technology | Shao M.,Zhejiang University of Technology | Zhou X.,Toxikon Corporation | Pan G.,Huzhou Teachers College | Ni Z.,Zhejiang University of Technology
Journal of Molecular Catalysis A: Chemical | Year: 2015

Abstract In this paper, we synthesized ZnFeTi layered double hydroxides (LDHs) by hydrothermal synthetic method at high temperature. The LDHs was further calcined by microwave to make ZnFeTi mixed metal oxides (MMO) with special particle size. In addition, the band gap of ZnFeTi-LDHs and MMO were calculated by DFT for the first time, which was in good agreement with the experimental result from UV-vis. MMO was finally dye sensitized and used as thin film electrode to test the photoelectrocatalytic performance for both p-chlorophenol oxidation degradation and CO2 reduction under visible light. The results showed that without the applied voltage, the p-chlorophenol degradation and CO2 reduction rates were not high; after the electric filed was introduced into the reaction, not only the degradation efficiency of p-chlorophenol was increased to 99.1% within 210 min, but also the reactivity of CO2 reduction reaction was enhanced a lot. Furthermore, from the results of HPLC and UV-vis, we could conclude that p-chlorophenol was finally decomposed into small inorganic molecules going through 4-chloropyrocatechol and hydrochinone under the co-effect of hydroxide radicals and the photoelectrons. This result could be proved by frontier electron densities on atoms of p-chlorophenol calculated by DFT. © 2015. Elsevier B.V. Source


Xia S.,Zhejiang University of Technology | Meng Y.,Zhejiang University of Technology | Meng Y.,Huzhou Teachers College | Zhou X.,Toxikon Corporation | And 3 more authors.
Applied Catalysis B: Environmental | Year: 2016

In this paper, Ti/ZnO-Fe2O3 composite derived from Ti/Schiff base intercalated ZnFe layered double hydroxides was used as thin film electrode in CO2 photoelectroreduction. The influence of molar ratio of Ti/Fe and calcination temperature, which would affect the composites' physicochemical property and the photoelectrocatalytic performance for CO2 reduction, were investigated in detail. The characterization results from XRD, SEM, TEM, UV-vis and BET showed that Ti/ZnO-Fe2O3 composite with flower-like crystal from had small particle sizes, narrow band gap and excellent textural properties. The final product of CO2 photoelectroreduction was methanol and the intermediates were formic acid and formaldehyde. The methanol field reached at 0.773 mmol/cm2 after 3 h reaction with 0.5 V voltage by Ti/ZnO-Fe2O3 composite with Ti/Fe=1, calcined at 800°C. In addition, the CO2 photoelectroreduction pathway and the reason for highly efficient photoelectrocatalytic activity of the composite were also discussed. © 2016 Elsevier B.V. Source

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