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High-quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi-C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein-coding genes and 1265 non-coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole-genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi-omics (integrated transcriptome and metabolome) analysis showed the tissue-specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up-regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments.
Assuntos
Cromossomos de Plantas , Genoma de Planta , Genoma de Planta/genética , Cromossomos de Plantas/genética , Adaptação Fisiológica/genética , Salvia/genética , Salvia/metabolismo , Antioxidantes/metabolismo , Rosmarinus/genética , Rosmarinus/metabolismo , Transcriptoma/genética , Regulação da Expressão Gênica de Plantas , Depsídeos/metabolismo , MultiômicaRESUMO
A.D. is a common disease among other neurodegenerative disorders primarily developing due to amyloid-ß (Aß) neurotoxicity derived from the amyloid-ß protein precursor (AßPP). The amyloid precursor-like proteins 1 and 2 (APP1 and APLP2) biochemically behave similarly in many aspects to AßPP. We, therefore, proposed to test WGX-50 and Alpha-M for their interaction mechanism with APLP1 and APLP2 because both these drug candidate compounds previously showed inhibition of Aß aggregation. We employed a comparative atomic investigation on Alpha-M and WGX-50 in complex with novel targets, i.e., APLP1 and APLP2, using biophysical and molecular simulation methods. The docking score was -6.83 kcal mol-1 for Alpha-M-APLP1, -8.41 kcal mol-1 for WGX-50-APLP1, -7.02 kcal mol-1 for Alpha-M-APLP2 and -8.25 kcal mol-1 for the WGX-50-APLP2 complex. Our results also elaborate that in the case of their interaction with both APLP1 and APLP2, the WGX-50 complex exhibits better stability than the APLP1/2-Alpha-M complexes during simulation. Furthermore, WGX50 in both APLP1 and APLP2 stabilized the internal flexibility upon binding in contrast to the Alpha-M complexes. The data showed that the BFE for Alpha-M-APLP1 was calculated to be -27.38 ± 0.93 kcal mol-1, for WGX-50-APLP1 -39.65 ± 0.95 kcal mol-1, for Alpha-M-APLP2 -24.80 ± 0.63 kcal mol-1 while for WGX-50-APLP2 the BFE was -57.16 ± 1.03 kcal mol-1 respectively. These results highlight that APLP2-WGX50 has greater binding energies in all four systems. PCA and FEL analysis further revealed variations in the dynamic behavior of these complexes. Overall, our findings demonstrate that WGX50 potentially acts as a more potent inhibitor for APLP1 and APLP2 than Alpha-M and thus shows the diverse pharmacological potential of WGX50. Due to its stable binding interaction, WGX50 might be a suitable candidate drug compound for targeting these precursors under pathological conditions.
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Acrilamidas , Proteínas do Tecido Nervoso , Proteínas do Tecido Nervoso/metabolismoRESUMO
Cancer is one of the leading causes of death across the world, and the prevalence and mortality rates of cancer will continue to grow. Chemotherapeutics play a critical role in cancer therapy, but drug resistance and side effects are major hurdles to effective treatment, evoking an immediate need for the discovery of new anticancer agents. Triazines including 1,2,3-, 1,2,4-, and 1,3,5-triazine have occupied a propitious place in drug design and development due to their excellent pharmacological profiles. Mechanistically, triazine derivatives could interfere with various signaling pathways to induce cancer cell death. Hence, triazine derivatives possess potential in vitro and in vivo efficacy against diverse cancers. In particular, triazine hybrids are able to overcome drug resistance and reduce side effects. Moreover, several triazine hybrids such as brivanib (indole-containing pyrrolo[2,1-f][1,2,4]triazine), gedatolisib (1,3,5-triazine-urea hybrid), and enasidenib (1,3,5-triazine-pyridine hybrid) have already been available in the market. Accordingly, triazine hybrids are useful scaffolds for the discovery of novel anticancer chemotherapeutics. This review focuses on the anticancer activity of 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids, together with the structure-activity relationships and mechanisms of action developed from 2017 to the present. The enriched structure-activity relationships may be useful for further rational drug development of triazine hybrids as potential clinical candidates.
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Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Humanos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Desenho de Fármacos , Triazinas/farmacologia , Estrutura MolecularRESUMO
Low-carbon steel pipelines are frequently used as transport pipelines for various media. As the pipeline transport industry continues to develop in extreme directions, such as high efficiency, long life, and large pipe diameters, the issue of pipeline reliability is becoming increasingly prominent. This study selected Q235 steel, a typical material for low-carbon steel pipelines, as the research object. In accordance with the pipeline service environment and the accelerated corrosion environment test spectrum, cyclic salt spray accelerated corrosion tests that simulated the effects of the marine atmosphere were designed and implemented. Corrosion properties, such as corrosion weight loss, morphology, and product composition of samples with different cycles, were characterized through appearance inspection, scanning electron microscopy analysis, and energy spectrum analysis. The corrosion behavior and mechanism of Q235 low-carbon steel in the enhanced corrosion environment were studied, and the corrosion weight loss kinetics of Q235 steel was verified to conform to the power function law. During the corrosion process, the passivation film on the surface of the low-carbon steel and the dense and stable α-FeOOH layer formed after the passivation film was peeled off played a role in corrosion resistance. The passivation effect, service life, and service limit of Q235 steel were studied and determined, and an evaluation model for quick evaluation of the corrosion life of Q235 low-carbon steel was established. This work provides technical support to improve the life and reliability of low-carbon steel pipelines. It also offers a theoretical basis for further research on the similitude and relevance of cyclic salt spray accelerated corrosion testing.
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Water environmental pollution caused by spent batteries is a nonignorable environmental issue. In this study, the early life stage of zebrafish was employed to assess the environmental risk of spent batteries after exposure to 0, 1%, 2%, 5% and 10% spent battery extract for 120 h. Our results clearly indicated that spent battery extract can significantly decrease the survival rate, hatching rate and body length and increase heart rate. Moreover, spent battery extract exposure-induced zebrafish larvae generate oxidative stress and inhibit the mRNA transcriptional levels of heat shock protein (HSP70) and metallothionein (MT) genes. These results showed that the spent batteries not only affected the survival and development performance of zebrafish at an early life stage but also caused oxidative stress and interfered with the detoxification of zebrafish. This study provided novel insight into spent battery induced toxicity in the early life stage of fish.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Biomarcadores/metabolismo , Embrião não Mamífero/metabolismo , Larva , Estresse Oxidativo , Extratos Vegetais , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Brief bursts of high-frequency spikes are a common firing pattern of neurons. The cellular mechanisms of bursting and its biological significance remain a matter of debate. Focusing on the energy aspect, this paper proposes a neural energy calculation method based on the Chay model of bursting. The flow of ions across the membrane of the bursting neuron with or without current stimulation and its power which contributes to the change of the transmembrane electrical potential energy are analyzed here in detail. We find that during the depolarization of spikes in bursting this power becomes negative, which was also discovered in previous research with another energy model. We also find that the neuron's energy consumption during bursting is minimal. Especially in the spontaneous state without stimulation, the total energy consumption (2.152 × 10-7 J) during 30 s of bursting is very similar to the biological energy consumption (2.468 × 10-7 J) during the generation of a single action potential, as shown in Wang et al. (Neural Plast 2017, 2017a). Our results suggest that this property of low energy consumption could simply be the consequence of the biophysics of generating bursts, which is consistent with the principle of energy minimization. Our results also imply that neural energy plays a critical role in neural coding, which opens a new avenue for research of a central challenge facing neuroscience today.
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Based on the Hodgkin-Huxley model, the present study established a fully connected structural neural network to simulate the neural activity and energy consumption of the network by neural energy coding theory. The numerical simulation result showed that the periodicity of the network energy distribution was positively correlated to the number of neurons and coupling strength, but negatively correlated to signal transmitting delay. Moreover, a relationship was established between the energy distribution feature and the synchronous oscillation of the neural network, which showed that when the proportion of negative energy in power consumption curve was high, the synchronous oscillation of the neural network was apparent. In addition, comparison with the simulation result of structural neural network based on the Wang-Zhang biophysical model of neurons showed that both models were essentially consistent.
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OBJECTIVE: To study the genuine of 32 samples of Niuxi from 14 provinces, and compare some samples stored for different time to check the change in the coures of store. METHOD: IR spectroscopy and Analyze Technology Auxiliary softeare. RESULT: The coefficient correlations had certain difference among these Niuxi from different places. They were divided into two parts if r = 0.9840 the standerd: trueborn crude drugs (r > 0.9840) and non-trueborn (r < 0.9840). And we can know the change in medicinal materials according r. CONCLUSION: The method is operated simple and determined fast; the result is reliable; repetitiveness is good.