•DFT and molecular docking studies were realized on synthesized novel Chalcone-DIM hybrids and Pirazoline-DIM hybrids compounds.•The title compounds were fully characterized by spectroscopy and ...spectrometric techniques (FT-IR 1H NMR, 13C NMR and HRMS-DART).•Some compounds showed antibacterial activity against Staphilococcus aureus ATCC6538 strain.•Theoretical studies revealed good π-cation, π-π and hydrogen bonding interactions with both catalytic and allosteric sites with PBP2 enzyme of S. aureus strain.
In this research we present the synthesis of a novel series of Pyrazoline-DIM hybrids compounds using microwave irradiation as activation energy, derived from their corresponding parent Chalcone-DIM hybrid, both with potential biological activity and not related to β-lactam antibiotics. The antibacterial activity of these compounds, against Staphylococcus aureus, has been investigated by means of in-vitro radial growth inhibition technique and supported by in-silico DFT methods, as well as molecular docking studies on the allosteric and catalytic sites of Penicillin-Binding Protein 2a. Biological activity seems to be correlated with HOMO location in the molecular structure, the HOMO-LUMO gap, softness and electrophilicity index. Docking studies reveal π-cation interactions as well as hydrogen bonds. These interactions and their frequency suggest that the biological activity of the synthetized molecules can be attributed mainly to interactions with the allosteric site instead of the catalytic one.
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Recently, researchers in the artificial neural network field have focused their attention on connectionist models composed by several hidden layers. In fact, experimental results and heuristic ...considerations suggest that deep architectures are more suitable than shallow ones for modern applications, facing very complex problems, e.g., vision and human language understanding. However, the actual theoretical results supporting such a claim are still few and incomplete. In this paper, we propose a new approach to study how the depth of feedforward neural networks impacts on their ability in implementing high complexity functions. First, a new measure based on topological concepts is introduced, aimed at evaluating the complexity of the function implemented by a neural network, used for classification purposes. Then, deep and shallow neural architectures with common sigmoidal activation functions are compared, by deriving upper and lower bounds on their complexity, and studying how the complexity depends on the number of hidden units and the used activation function. The obtained results seem to support the idea that deep networks actually implements functions of higher complexity, so that they are able, with the same number of resources, to address more difficult problems.
In rheumatoid arthritis(RA) pathogenesis, activated RA fibroblast-like synoviocytes (RA-FLSs) exhibit similar proliferative features as tumor cells and subsequent erosion to cartilage will eventually ...lead to joint destruction. Therefore, it is imperative to search for compounds, which can effectively inhibit the abnormal activation of RA-FLSs, and retard RA progression.3'3-Diindolylmethane (DIM), the major product of the acid-catalyzed oligomerization of indole-3-carbinol from cruciferous vegetables, has been reported to be functionally relevant to inhibition of migration, invasion and carcinogenesis in some solid tumors. In this study, we explored the anti-proliferation, anti-metastasis and anti-inflammation effects of DIM on RA-FLSs as well as the underlying molecular mechanisms. To do this, primary RA-FLSs were isolated from RA patients and an animal model. Cell proliferation, migration and invasion were measured using CCK-8, scratch, and Transwell assays, respectively. The effects of DIM on Matrix metalloproteinases (MMPs) and some inflammatory factors mRNA and key molecules such as some inflammatory factors and those involved in aberrantly-activated signaling pathway in response to tumor necrosis factor α(TNF-α), a typical characteristic mediator in RA-FLS, were quantitatively measured by real-time PCR and western blotting. Moreover, the effect of DIM on adjuvant induced arthritis(AIA) models was evaluated with C57BL/6 mice
. The results showed that DIM inhibited proliferation, migration and invasion of RA-FLS
. Meanwhile, DIM dramatically suppressed TNF-α-induced increases in the mRNA levels of
, and
; as well as the proinflammatory factors
, and
β. Mechanistic studies revealed that DIM is able to suppress phosphorylated activation not only of p38, JNK in MAPK pathway but of AKT, mTOR and downstream molecules in the AKT/mTOR pathway. Moreover, DIM treatment decreased expression levels of proinflammatory cytokines in the serum and alleviated arthritis severity in the knee joints of AIA mice. Taken together, our findings demonstrate that DIM could inhibit proliferation, migration and invasion of RA-FLSs and reduce proinflammatory factors induced by TNF-α
by blocking MAPK and AKT/mTOR pathway and prevent inflammation and knee joint destruction
, which suggests that DIM might have therapeutic potential for RA.
Dim and small target detection in complex background is considered a difficult and challenging problem. Conventional algorithms using the local difference/mutation possibly produce high missed or ...mistaken detection rates. In this paper, we propose an effective algorithm for detecting dim and small infrared targets. In order to synchronously enhance targets and suppress complex background clutters, we adopt an adaptive entropy-based window selection technique to construct a novel local difference measure (LDM) map of an input image, which measures the dissimilarity between the current region and its neighboring ones. In this way, the window size can be adaptively regulated according to local statistical properties. Compared with the original image, the LDM map has less background clutters and noise residual. This guarantees the lower false alarm rates under the same probability of detection. Subsequently, a simple threshold is used to segment the target. More than 600 dim and small infrared target images against different complex and noisy backgrounds were utilized to validate the detection performance of the proposed approach. Extensive experimental results demonstrate that the proposed method not only works more stably for different target movements and signal-to-clutter ratio values, but also has a better performance compared with classical baseline methods. The evaluation results suggest that the proposed method is simple and effective with regard to detection accuracy.
•We present an adaptive entropy-based window selection scheme.•The novel local difference measure map can keep low false alarm rates under the same probability of detection.•The proposed method is simple and effective with regard to detection accuracy.
Robust detection of infrared dim and small target contributes significantly to the infrared systems in many applications. Due to the diversity of background scene and unique characteristic of target, ...the detection of infrared targets remains a challenging problem. In this paper, a novel approach based on total variation regularization and principal component pursuit (TV-PCP) is presented to deal with this problem. The principal component pursuit model only considers the low-rank feature of background images, which will result in poor detection ability in non-uniform and non-smooth scenes. We take into account the total variation regularization term to thoroughly describe background feature, which can achieve good detection result as well as good background estimation result. Firstly, the input infrared image is transformed to a patch image model. Secondly, the TV-PCP model is presented on the patch image. An effective optimization algorithm is proposed to solve this model. Experiments on six real datasets show that the proposed method has superior detection ability under various backgrounds, especially with good background suppression performance and low false alarm rate.
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•An infrared dim target detection method based on total variation regularization and principal component pursuit is proposed.•An optimization solver based on alternating direction method is proposed to solve the TV-PCP model.•By utilizing the total variation regularization, the TV-PCP performs well in target detection and background estimation.
Skin cancer has high incidence in the United States and is mainly caused by ultraviolet B (UVB) radiation. In this study, we demonstrated the role of 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane ...(DIM-D) in the prevention of skin photocarcinogenesis using an in vivo UVB-induced skin cancer model. We also evaluated the efficiency of oleic acid-modified nanostructured lipid carriers to deliver DIM-D across the skin barrier into the epidermis for chemopreventive activity. Nanocarriers were 203.00 ± 21.21 nm in diameter with polydispersity, zeta potential and entrapment efficiency of 0.33 ± 0.01, 37.17 ± 0.90 mV and 93.64 ± 0.65%, respectively. Oleic acid-modified nanocarriers were incorporated into Hydroxypropyl methylcellulose to form DIM-D-Nanogel (DIM-D-N). DIM-D-N pretreatment prior to UVB exposure delayed tumor initiation and reduced tumor multiplicity (p < 0.05) at the end of the study compared to Epigallocatechin gallate (EGCG) gel pretreatment. DIM-D-N pretreatment decreased UVB-induced damage to skin lipids and proteins (p < 0.05), respectively by 7.63 and 2.56-fold less than EGCG gel pretreatment and by 17.86 and 11.92-fold less than UVB-only treatment. Histology showed rete-ridge extension, epidermal thickening and hyperkeratosis for UVB-only treatment and EGCG gel pretreatment; DIM-D-N pretreatment showed similar features as the negative control. Western blot analysis showed increased Nurr1 expression (p < 0.05) for DIM-D-N pretreated group compared to EGCG gel (4.68-fold). DIM-D-N pretreatment reduced BCI-2 expression (p < 0.05) but increased Bax and cPARP. Knock down studies with Nurr1 siRNA reduced the expressions of Nurr1 and cPARP by 8.18 and 1.45-fold, respectively (p < 0.05). Our results suggest the role of DIM-D in skin cancer chemoprevention mediated by possible molecular therapeutic targets such as Nurr1.
In this study, we construct the new solitary wave solutions for two well known nonlinear wave equations whose describe the wave propagation in nonlinear media. We implemented a new technique which is ...extension of modified rational expansion method on nonlinear three-dim modified Kortewege–de Vries Zakharov–Kuznetsov and extended Zakharov–Kuznetsov equations. The new results are elliptic, hyperbolic, trigonometric, rational type which are representing to solitary waves, periodic waves, traveling waves, kink-antikink solitons, dark-bright solitons. The physical behavior of some calculated results represented graphical by using the software Mathematica. The determined results are new, more general and have numerous applications in the area of nonlinear sciences including nonlinear plasma, fiber optics, mechanics, quantum physics, laser physics, fluid physics, engineering and other types of physical sciences. The demonstrated results show that new technique is efficient, fruitful, powerful and reliable to study analytically different types of higher order complex NLPDEs arises in various types of applied sciences.
A biophysical model of the key aspects of melatonin synthesis and excretion has been developed, which is able to predict experimental dynamics of melatonin in plasma and saliva, and of its urinary ...metabolite 6‐sulfatoxymelatonin (aMT6s). This new model is coupled to an established model of arousal dynamics, which predicts sleep and circadian dynamics based on light exposure and times of wakefulness. The combined model thus predicts melatonin levels over the sleep‐wake/dark‐light cycle and enables prediction of melatonin‐based circadian phase markers, such as dim light melatonin onset (DLMO) and aMT6s acrophase under conditions of normal sleep and circadian misalignment. The model is calibrated and tested against group average data from 10 published experimental studies and is found to reproduce quantitatively the key dynamics of melatonin and aMT6s, including the timing of release and amplitude, as well as response to controlled lighting and shift work.
Dim light melatonin onset, or the rise in melatonin levels representing the beginning of the biological night, is the gold standard indicator of circadian phase. Considerably less is known about dim ...light melatonin offset, or the decrease in melatonin to low daytime levels representing the end of the biological night. In the context of insufficient sleep, morning circadian misalignment, or energy intake after waketime but before dim light melatonin offset, is linked to impaired insulin sensitivity, suggesting the need to characterize dim light melatonin offset and identify risk for morning circadian misalignment.
We examined the distributions of dim light melatonin offset clock hour and the phase relationship between dim light melatonin offset and waketime, and associations between dim light melatonin offset, phase relationship, and chronotype in healthy adults (N = 62) who completed baseline protocols measuring components of the circadian melatonin rhythm and chronotype.
74.4% demonstrated dim light melatonin offset after waketime, indicating most healthy adults wake up before the end of biological night. Later chronotype (morningness-eveningness, mid-sleep on free days corrected, and average mid-sleep) was associated with later dim light melatonin offset clock hour. Later chronotype was also associated with a larger, positive phase relationship between dim light melatonin offset and waketime, except for morningness-eveningness.
These findings suggest morning circadian misalignment risk among healthy adults, which would not be detected if only dim light melatonin onset were assessed. Chronotype measured by sleep timing may better predict this risk in healthy adults keeping a consistent sleep schedule than morningness-eveningness preferences. Additional research is needed to develop circadian biomarkers to predict dim light melatonin offset and evaluate appropriate dim light melatonin offset timing to promote health.
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