Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders. 相似文献
Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV-visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications. 相似文献
Neat poly (lactic acid) (PLA) and PLA/cassava bagasse (CB) composites were used to produce seedling tubes by extrusion and injection molding. The tubes were buried in simulated soil, and their biodegradation was investigated by weight loss, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). After 180 days, the composites' biodegradation was higher than neat PLA material, and the higher the CB content, the higher the biodegradation, which caused fissures and voids in the material. The biodegradation of PLA/CB composites increased the phosphorus content in the soil after 180 days. Composites of PLA with CB, an abundant agro-industrial residue in Brazil, are promising because they can reduce the environmental impact due to CB's proper destination, and the composites' costs and biodegradation are faster than pure PLA material. Both the faster biodegradation of the tube and the higher P content are advantageous for seedling tubes. 相似文献
The problem of classification is shared across various disciplines. Designing even less computationally demanding and more effective classifiers has been a key challenge for researchers for many years. No single classifier can be highly effective for all types of datasets and thus, depending on the data distribution, various classifiers have been proposed in the literature. To our knowledge, feature values have been vastly exploited as the base for discriminating classes, while feature sequence information has been somehow under-exploited so far. In the proposed approach normalised features are sorted and ranked, creating a sequence of finite numbers. The associated rank of the created sequence is used as an additional feature, which in a way defines the sample-specific intra-feature relationship. Three novel dictionary-based approaches such as Sequence Classifier (SC), Sequence-dictionary-based k-Nearest Neighbours Classifier (SDk-NN) and Combined-dictionary-based k-Nearest Neighbours Classifier (CDk-NN) are proposed in this paper.
In the case of remotely sensed data, and specifically in Hyper-Spectral Images (HSI), the spectral features (Spectral signatures) represent a strong, object-specific spectral relationship, which is a key point in our proposed approach. In this case, indeed, the proposed classifiers were tested over various (five) HS datasets and found to be effective. Based on the classifiers features, two derived distance measures are proposed and validated for the HS dataset, namely: the Normalised Sequence Distance (NSD) measure and Combined Distance (CD) measure. These measures appear to overperform the conventional Normalised Euclidean Distance (NED) in this context. Also, validation for both binary and multi-class datasets are experimented and their performances are evaluated in terms of accuracy and other standard measures. Experimental results over 21 datasets revealed that the proposed approaches perform comparably, and in some cases even better than other classifiers. Stack-operated, class-specific sparse dictionaries are also introduced in order to reduce the computational complexity, which can be used as an active learning-based approach for optimal training sample selection. Additional tests were performed with variable levels of dictionary sparsity for assessing its impact on accuracy. 相似文献
Boronic acids are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β-lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two-step synthesis that relies on the solid and versatile copper-catalyzed azide–alkyne cycloaddition (CuAAC) followed by boronate deprotection. All of the compounds show very good inhibition of the Klebsiella pneumoniae carbapenemase KPC-2, with Ki values ranging from 1 nM to 1 μM, and most of them are able to restore cefepime activity against K. pneumoniae harboring blaKPC-2. In particular, compound 1 e , bearing a sulfonamide substituted by a thiophene ring, proved to be an excellent KPC-2 inhibitor (Ki=30 nM); it restored cefepime susceptibility in KPC-Kpn cells (MIC=0.5 μg/mL) with values similar to that of vaborbactam (Ki=20 nM, MIC in KPC-Kpn 0.5 μg/mL). Our findings suggest that α-triazolylboronates might represent an effective scaffold for the treatment of KPC-mediated infections. 相似文献