Niclosamide is an oral anthelmintic drug, approved for use against tapeworm infections. Recent studies suggest however that niclosamide may have broader clinical applications in cancers, spurring increased interest in the functions and mechanisms of niclosamide. Previously, we reported that niclosamide targets a metabolic vulnerability in p53-deficient tumours, providing a basis for patient stratification and personalised treatment strategies. In the present study, we functionally characterised the contribution of the aniline 4′-NO2 group on niclosamide to its cellular activities. We demonstrated that niclosamide induces genome-wide DNA damage that is mechanistically uncoupled from its antitumour effects mediated through mitochondrial uncoupling. Elimination of the nitro group in ND-Nic analogue significantly reduced γH2AX signals and DNA breaks while preserving its antitumour mechanism mediated through a calcium signalling pathway and arachidonic acid metabolism. Lipidomics profiling further revealed that ND-Nic-treated cells retained a metabolite profile characteristic of niclosamide-treated cells. Notably, quantitative scoring of drug sensitivity suggests that elimination of its nitro group enhanced the target selectivity of niclosamide against p53 deficiency. Importantly, the results also raise concern that niclosamide may impose a pleiotropic genotoxic effect, which limits its clinical efficacy and warrants further investigation into alternative drug analogues that may ameliorate any potential unwanted side effects. 相似文献
Three dinuclear coordination complexes generated from 1-n-butyl-2-((5-methyl-1H-pyrazole-3-yl)methyl)-1H-benzimidazole ( L ), have been synthesized and characterized spectroscopically and structurally by single crystal X-ray diffraction analysis. Reaction with iron(II) chloride and then copper(II) nitrate led to a co-crystal containing 78 % of [Cu(NO3)(μ-Cl)( L’ )]2 ( C1 ) and 22 % of [Cu(NO3)(μ-NO3)( L’ )]2 ( C2 ), where L was oxidized to a new ligand L’ . A mechanism is provided. Reaction with copper chloride led to the dinuclear complex [Cu(Cl)(μ-Cl)( L) ]2 ( C3 ). The presence of N−H⋅⋅⋅O and C−H⋅⋅⋅O intermolecular interactions in the crystal structure of C1 and C2 , and C−H⋅⋅⋅N and C−H⋅⋅⋅Cl hydrogen bonding in the crystal structure of C3 led to supramolecular structures that were confirmed by Hirshfeld surface analysis. The ligands and their complexes were tested for free radical scavenging activity and ferric reducing antioxidant power. The complex C1 / C2 shows remarkable antioxidant activities as compared to the ligand L and reference compounds. 相似文献
The thermal decomposition up to 400 °C of ammonium ferric citrate hydrate, of unknown structure and formula weight, was studied by thermogravimetry, differential thermal analysis, infrared (IR) spectroscopy and X-ray diffractometry. The possible identities of the formula weight and the intermediate products of calcination are discussed. The results revealed that the parent material is amorphous and contains two moles of water and two moles of ammonia. Decomposition takes place via six weight-loss processes, three endothermic (90–230 °C) and three exothermic (240–298 °C), leading eventually to the formation of Fe2O3. The intermediate solid products are mainly unstable amorphous oxycarbonates, as indicated by X-ray and IR spectroscopies. The gas-phase decomposition products identified by IR spectroscopy are NH3, CO2, CO, CH3COCH3, CH4 and NH4OH. Surface area measurement and scanning electron microscopy showed that Fe2O3, the final product at 400 °C, hada surface area of 40 m2/g and good crystalline and porous character. 相似文献
Effective detoxification of oil sands process-affected water (OSPW) is one issue associated with bitumen extraction in the Alberta oil sands. It has been suggested that reclamation ponds can be used to passively treat OSPW, potentially allowing for its safe return to the environment. In this study, OSPW was sampled in two batches (A and B) from the Syncrude Canada Ltd. West In-Pit (WIP) settling pond and from three experimental reclamation ponds - Big Pit, FE5, and TPW. Acute (10 d) and chronic (until adult emergence) exposures of Chironomus dilutus larvae to OSPW were conducted and survival, growth, development, and behavior were assessed. Masses of larvae exposed to WIP-OSPW were 64-77% less than the freshwater control (p < 0.001). Similarly, chronic exposure to WIP-OSPW resulted in significantly (p < 0.05) less pupation than in the freshwater control, with 31% (A) and 71% (B) less pupation of larvae exposed to WIP-OSPW. Rates of emergence were significantly less for larvae exposed to WIP-OSPW, with only 13% (A) and 8% (B) of larvae emerging as adults when exposed to WIP-OSPW, compared to 81% in the freshwater control (p < 0.0001). Pupation and emergence rates were significantly less in TPW than freshwater control (p < 0.05), but there were no differences observed in Big Pit or FE5. Lesser toxicity was observed in reclaimed OSPW compared to fresh OSPW and this coincided with lesser concentrations of NAs. The results presented are consistent with the hypothesis that an organic fraction is the cause of the toxicity of OSPW toward C. dilutus and that OSPW aged in reclamation ponds retains toxicity and therefore, more aggressive, targeted treatment of OSPW is required to accelerate decreases. 相似文献
Zinc oxide/polyvinylpyrrolidone (ZnO/PVP) nanocomposite fibers with enhanced structural, morphological and optical properties were purposefully tailored using electrospinning technique. Meanwhile, ZnO nanoparticles (NPs),with particle size of ~50 nm, were synthesized using a co-precipitation method. The nanocomposite fibers were prepared by an electrospun solution of PVP containing ZnO NPs of 2, 4, 6 and 8 wt%. Evidently, the morphological, thermal and optical properties of the ZnO/PVP nanocomposite fibers were enhanced by dispersing ZnO NPs into PVP fibers. Typically, controlling the ZnO NPs content and their dispersibility (0–8 wt%) into PVP fibers result in improved the thermal stability (an increase of onset decomposition temperature by ~120 °C above pure PVP fibers) as well as the UV–Vis protection (reduction in UV transmission by 70%) and the photoluminescence properties (a sharp UV emission around 380 nm) Overall, based on the enhanced properties, the PVP/ZnO nanocomposite fibers can be considered a promise material in optoelectronic sensors and UV photoconductor. 相似文献
A series of (50 ? x) P2O5–20B2O3–20CaO–10Na2O (x?=?0–15 mol% MoO3) glass composition was prepared. Glass structure was analyzed using infrared absorption, UV–visible spectroscopy, electron spin resonance, density, and molar volume calculations. FTIR confirmed that Mo ions are contributed as MoO6 octahedral units in the glassy matrix, resulting in an increase in the pyrophosphate and BO3 groups at the expense of metaphosphate and BO4 units. UV–visible and ESR spectra detected Mo3+ and Mo5+ ions as species in the host glass due to the increase in MoO3 content. Broadband dielectric spectroscopy investigation on a broad range of frequencies and at different temperatures indicated that the enhancement of electrical conductivity of the prepared glasses due to molybdenum doping was prevented using confinement effect at the wells, causing demobilization of the charge carriers. Hence the dielectric spectra were caused by the mobility of charge carriers rather than the dynamics at the molecular scale. There is a clear correlation between the transport mechanism and dynamics at the interface of the charge carriers. Presently, the challenge is to understand if optimizing the accumulation of charges at the interfaces and electrodes is the origin of electrical storage energy.
The BEIR VI Committee applied recent developments in the comparative dosimetry of radon exposures in mines and homes to evaluate the so-called K-factor used to extrapolate the excess relative risk of lung cancer determined for underground uranium miners to exposures in homes. This paper describes methodological aspects of these developments that were specified ambiguously in the BEIR VI report. Specifically, in the section dealing with dosimetry (Appendix B of the BEIR VI report), the K-factor was unusually defined in terms of exposure to radon gas (K(gas)), and not in terms of exposure to potential alpha energy (K). An incorrect value of unity was calculated for K(gas). This implies a value of 0.44 for K. In this paper, we describe how application of the ICRP Publication 66 lung and dosimetric models to evaluate the regional lung dose per unit exposure to potential alpha-energy in mines and homes yields the value of K = unity. This confirms the BEIR VI Committee's choice of K = 1 for application in their risk extrapolation model. The paper also reviews the use of doses to specific sub-cellular targets in the evaluation of K. This yields a somewhat greater divergence in the corresponding estimates of K, but again an overall average value of K = unity. The paper describes the methods used to calculate alpha particle hit probabilities for specific subcellular targets, and the resulting estimates of single- and multiple-hit probabilities obtained for exposures in mines and homes, as a function of the respective exposure rates. 相似文献
Grease lubrication is a complex mixture of science and engineering, requiring an interdisciplinary approach, and is applied to the majority of bearings worldwide. Grease can be more than a lubricant; it is often expected to perform as a seal, corrosion inhibitor in electrical joints, electrical insulator and electrical connection improver. This work is concerned, therefore, with the comparative study between prepared electrical grease and the imported one. Physicochemical and electrical properties for the prepared grease and the imported one were evaluated. The results of dropping point, penetration, dynamic viscosity, corrosion inhibition, evaporation loss, total acid number and oil separation for the prepared grease under investigation are mostly the same compared with the imported grease. In addition, the results interpreted in terms of the physical and chemical properties of both greases revealed that no remarkable differences. In this respect, calorimetric study shows that the prepared grease, like the imported one, is thermally stable up to about 200 °C then decomposition and degradation started slightly faster and higher than that of the imported one. The electrical and dielectric parameters are very close at and around room temperature then the increase of charge carriers' mobility at higher temperatures explains the deviation from stability in case of the prepared grease. One can conclude that the prepared electrical grease could replace efficiently the imported electrical grease especially in isothermal application at and around room temperature. 相似文献
In this paper, we present a visionary concept referred to as Collaborative and Cognitive Network Platforms (CCNPs) as a future-proof solution for creating a dependable, self-organizing and self-managing communication substrate for effective ICT solutions to societal problems. CCNP creates a cooperative communication platform to support critical services across a range of business sectors. CCNP is based on the personal network (PN) technology which is an inherently cooperative environment prototyped in the Dutch Freeband PNP2008 and the European Union IST MAGNET projects. In CCNP, the cognitive control plane strives to exploit the resources to better satisfy the requirements of networked applications. CCNP facilitates collaboration inherently. Through cognition in the cognitive control plane, CCNP becomes a self-managed substrate. The self-managed substrate, in this paper, is defined as cognitive and collaborative middleware on which future applications run without user intervention. Endemic sensor networks may be incorporated into the CCNP concept to feed its cognitive control plane. In this paper, we present the CCNP concept and discuss the research challenges related to collaboration and cognition. 相似文献
We consider receiver design for coded transmission over linear Gaussian channels. We restrict ourselves to the class of lattice codes and formulate the joint detection and decoding problem as a closest lattice point search (CLPS). Here, a tree search framework for solving the CLPS is adopted. In our framework, the CLPS algorithm is decomposed into the preprocessing and tree search stages. The role of the preprocessing stage is to expose the tree structure in a form matched to the search stage. We argue that the forward and feedback (matrix) filters of the minimum mean-square error decision feedback equalizer (MMSE-DFE) are instrumental for solving the joint detection and decoding problem in a single search stage. It is further shown that MMSE-DFE filtering allows for solving underdetermined linear systems and using lattice reduction methods to diminish complexity, at the expense of a marginal performance loss. For the search stage, we present a generic method, based on the branch and bound (BB) algorithm, and show that it encompasses all existing sphere decoders as special cases. The proposed generic algorithm further allows for an interesting classification of tree search decoders, sheds more light on the structural properties of all known sphere decoders, and inspires the design of more efficient decoders. In particular, an efficient decoding algorithm that resembles the well-known Fano sequential decoder is identified. The excellent performance-complexity tradeoff achieved by the proposed MMSE-DFE Fano decoder is established via simulation results and analytical arguments in several multiple-input multiple-output (MIMO) and intersymbol interference (ISI) scenarios. 相似文献