Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this ...pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.
Background
The aim of this study was to apply texture analysis (TA) to cone‐beam computed tomography (CBCT) scans of patients with grade C periodontitis for detection of non‐visible changes in the ...image.
Methods
TA was performed on CBCT scans of 34 patients with grade C periodontitis. Axial sections of CBCT were divided into three groups as follows: Group L (lesion) in which there is a furcal lesion with periodontal bone loss; Group I (intermediate) in which the border of the furcal lesion has normal characteristics; and Group C (control) in which the area is healthy. Eleven texture parameters were extracted from the region of interest. Mann‐Whitney U test was used to assess the differences in the texture between the three groups as follows: L versus I; L versus C, and I versus C.
Results
Statistically significant differences (P <0.05) were observed in almost all parameters in the intergroup analyses (i.e., L versus I and L versus C). However, statistical differences were smaller in groups I versus C in which only entropy of sum, entropy of difference, mean of sum, and variance of difference were statistically different (P < 0.05).
Conclusion
TA can potentially provide prognostic information to improve the diagnostic accuracy in the grading of the tissue around the furcal lesion, thus potentially accelerating the treatment decision‐making process.
Fertilizers contain essential nutrients for agricultural growth and development. However, most nitrogen fertilizers are substances with high solubility of ions and are very susceptible to leaching ...and volatilization. To minimize these losses, an alternative is the creation of a physical barrier around granules. One way is to coat granules with polymers. In the present work urea granules were coated with polyhydroxybutyrate and ethyl cellulose in various conditions in the presence of emulsifiers. The original granules and the final products were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry, to evaluate the surface morphology, the interaction between the granules and the coating, and the rates of mass change. The rates of urea release in distilled water were measured with a commercial enzyme kit. It is shown that those polymers are effective for coating of granules, leading to reduction of rates of urea dissolution in water.
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the ...formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT
in vitro
. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).
Nanotechnology has the potential to overcome the challenges of sustainable agriculture, and nanopesticides can control agricultural pests and increase farm productivity with little environmental ...impact. However, it is important to evaluate their toxicity on non-target organisms, such as honeybees (Apis mellifera) that forage on crops. The aims of this study were to develop a nanopesticide that was based on solid lipid nanoparticles (SLNs) loaded with pyrethrum extract (PYR) and evaluate its physicochemical properties and short-term toxicity on a non-target organism (honeybee). SLN + PYR was physicochemically stable after 120 days. SLN + PYR had a final diameter of 260.8 ± 3.7 nm and a polydispersion index of 0.15 ± 0.02 nm, in comparison with SLN alone that had a diameter of 406.7 ± 6.7 nm and a polydispersion index of 0.39 ± 0.12 nm. SLN + PYR had an encapsulation efficiency of 99%. The survival analysis of honeybees indicated that PYR10ng presented shorter longevity than those in the control group (P ≤ 0.01). Empty nanoparticles and PYR10ng caused morphological alterations in the bees’ midguts, whereas pyrethrum-loaded nanoparticles had no significant effect on digestive cells, so are considered safer, at least in the short term, for honeybees. These results are important in understanding the effects of nanopesticides on beneficial insects and may decrease the environmental impacts of pesticides.
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•Nanoparticles showed good properties to be used as pyrethrum carrier system.•Pyrethrum extract in nanocarrier and sublethal concentrations is safer for honeybees.•Pyrethrum and nanotechnology showed promising results aiming agriculture applications.
Super-host plants are elegant models to evaluate the peculiarities of gall structural and nutritional profiles due to the stimuli of distinct gall inducers in temporal and spatial perspectives. Galls ...induced by congeneric insects,
Lopesia
spp. (Diptera, Cecidomyiidae) on the same host plant,
Mimosa gemmulata
Barneby (Fabaceae) were analyzed to estimate if variations of 1 or 2 months in gall lifespans may result in differences over the accumulation of nutritional resources, and their compartmentalization both in cell walls and protoplasm.
Mimosa gemmulata
hosts four
Lopesia
-induced galls: the lenticular bivalve-shaped gall (LG) with a 2-month life cycle, the brown lanceolate bivalve-shaped gall (BLG) and the green lanceolate bivalve-shaped gall (GLG) with 3 month-life cycles, and the globoid bivalve-shaped gall (GG) with a 4 month-life cycle. The comparisons among the four
Lopesia
galls, using anatomical, histometric, histochemical, and immunocytochemical tools, have demonstrated that the longest lifespan of the GG related to its highest increment in structural and nutritional traits compared with the LG, GLG, and BLG. The differences among the tissue stratification and cell wall thickness of the galls with the 2-month and the 3-month lifespans were subtle. However, the GG had thicker cell walls and higher stratification of the common storage tissue, schlerenchymatic layers and typical nutritive tissue than the other three gall morphospecies. The higher tissue thickness of the GG was followed by the formation of a bidirectional gradient of carbohydrates in the protoplasm, and the detection of xyloglucans in cell walls. Current data supported the presumption that the longest the lifespan, the highest the impact over the structural and nutritional metabolism of the
Lopesia
galls associated to
M. gemmulata
.
In December 2020,
emerged in Brazil in the city of Salvador. The first two
colonized patients were in the same COVID-19 intensive care unit. Antifungal susceptibility testing showed low minimal ...inhibitory concentrations of 1 µg/mL, 2 µg/mL, 0.03 µg/L, and 0.06 µg/mL for amphotericin B, fluconazole, voriconazole, and anidulafungin, respectively. Microsatellite typing revealed that the strains are clonal and belong to the South Asian clade
. The travel restrictions during the COVID-19 pandemic and the absence of travel history among the colonized patients lead to the hypothesis that this species was introduced several months before the recognition of the first case and/or emerged locally in the coastline Salvador area.
Gall anatomical and metabolic peculiarities are determined by the feeding habit of the gall inducer, but develop under the constraints of the host plants. The chewing habit of the Lepidoptera larvae ...imposes a high impact on the host plant cells, and supposedly drives peculiar structural and histochemical patterns. So, our starting point was the search of such patterns in literature, and the test of these traits on the Andescecidium parrai (Cecidosidae)-Schinus polygama (Anacardiaceae) system, as a case study in Chilean flora. The literature on the structure of lepidopteran galls in the temperate and tropical regions comprises 13 works, describing stems as the most frequent host organs, followed by leaves, buds, and flowers. As common structural traits of Lepidoptera galls, the literature converge in describing the processes of cell hypertrophy and hyperplasia, resulting in a variable number of common storage parenchyma layers, interspersed by the redifferentiated sclerenchyma, vascular, and typical nutritive cells around the larval chamber. These nutritive cells accumulate lipids and proteins, which support the lepidopteran larvae nutrition. As expected, the A. parrai galls follow the patterns herein described for the lepidoptera-induced galls, but with peculiarities associated with its host organ. Even though the Lepidoptera galls have destructive mouthparts and can induce large and complex galls, they cannot alter important conservative features of their hosts' organs.
Oil spill detection and mapping using deep learning (OSDMDL) is crucial for assessing its impact on coastal and marine ecosystems. A novel approach was employed in this study to evaluate the ...scientific literature in this field through bibliometric analysis and literature review. The Scopus database was used to evaluate the relevant scientific literature in this field, followed by a bibliometric analysis to extract additional information, such as architecture type, country collaboration, and most cited papers. The findings highlight significant advancements in oil detection at sea, with a strong correlation between technological evolution in detection methods and improved remote sensing data acquisition. Multilayer perceptrons (MLP) emerged as the most prominent neural network architecture in 11 studies, followed by a convolutional neural network (CNN) in 5 studies. U-Net, DeepLabv3+, and fully convolutional network (FCN) were each used in three studies, demonstrating their relative significance too. The analysis provides insights into collaboration, interdisciplinarity, and research methodology and contributes to the development of more effective policies, strategies, and technologies for mitigating the environmental impact of oil spills in OSDMDL.
Solitary bees present greater species diversity than social bees. However, they are less studied than managed bees, mainly regarding the harmful effects of pesticides present in agroecosystems ...commonly visited by them. This study aimed to evaluate the effect of residual doses of imidacloprid and pyraclostrobin, alone and in combination, on the fat body (a multifunctional organ) of the neotropical solitary bee Tetrapedia diversipes by means of morphological and histochemical evaluation of oenocytes and trophocytes. Males and females of newly-emerged adults were submitted to bioassays of acute topical exposure. Experimental groups were essayed: control (CTR), solvent control (ACT), imidacloprid (IMI, 0.0028 ng/μL), pyraclostrobin (PYR, 2.7 ng/μL) and imidacloprid + pyraclostrobin (I + P). The data demonstrated that the residual doses applied in T. diversipes adults are sublethal at 96 h. Both oenocytes and trophocytes cells responded to topical exposure to the pesticides, showing morphological changes. In the IMI group, the bee oenocytes showed the greatest proportion of vacuolization and altered nuclei. The pyraclostrobin exposure increased the intensity of PAS-positive labeling (glycogen) in trophocytes. This increase was also observed in the I + P group. Changes in energy reserve (glycogen) of trophocytes indicate a possible mobilization impairment of this neutral polysaccharide to the hemolymph, which can compromise the fitness of exposed individuals. Also, changes in oenocytes can compromise the detoxification function performed by the fat body. This is the first study to show sublethal effects in neotropical solitary bees and highlight the importance of studies with native bees.
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•Residual doses of imidacloprid and pyraclostrobin caused cellular changes on fat body.•Oenocytes and trophocytes are susceptible to the effects of both pesticides.•Imidacloprid caused the greatest number of morphological changes in oenocytes.•Pyraclostrobin increases the polysaccharides storage in the trophocytes cytoplasm.•Cell biomarkers are sensible tools to evaluate the fat body in pesticide-exposed bees.
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