Artificial intelligence (AI), and, in particular, deep learning as a subcategory of AI, provides opportunities for the discovery and development of innovative drugs. Various machine learning ...approaches have recently (re)emerged, some of which may be considered instances of domain-specific AI which have been successfully employed for drug discovery and design. This review provides a comprehensive portrayal of these machine learning techniques and of their applications in medicinal chemistry. After introducing the basic principles, alongside some application notes, of the various machine learning algorithms, the current state-of-the art of AI-assisted pharmaceutical discovery is discussed, including applications in structure- and ligand-based virtual screening, de novo drug design, physicochemical and pharmacokinetic property prediction, drug repurposing, and related aspects. Finally, several challenges and limitations of the current methods are summarized, with a view to potential future directions for AI-assisted drug discovery and design.
Sandwich‐structured BaTiO3/poly(vinylidene fluoride) (PVDF) nanocomposites are successfully prepared by the solution‐casting method layer by layer. They possess both high breakdown strength and large ...dielectric polarization simultaneously. An ultra‐high energy‐storage density of 18.8 J cm−3 can be achieved by adjusting the volume fraction of ceramic fillers: this is almost three times larger than that of pure PVDF.
Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively ...relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery. However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates. In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy. We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair. We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death. Imbalanced cell proliferation is typically utilized by cancer cells to acquire resistance. Finally, we discuss the possibility of a potent anticancer therapeutic strategy that targets selective autophagy or autophagy and cell cycle together.
Abstract
Solar-driven electrochemical carbon dioxide (CO
2
) reduction is capable of producing value-added chemicals and represents a potential route to alleviate carbon footprint in the global ...environment. However, the ever-changing sunlight illumination presents a substantial impediment of maintaining high electrocatalytic efficiency and stability for practical applications. Inspired by green plant photosynthesis with separate light reaction and (dark) carbon fixation steps, herein, we developed a redox-medium-assisted system that proceeds water oxidation with a nickel-iron hydroxide electrode under light illumination and stores the reduction energy using a zinc/zincate redox, which can be controllably released to spontaneously reduce CO
2
into carbon monoxide (CO) with a gold nanocatalyst in dark condition. This redox-medium-assisted system enables a record-high solar-to-CO photoconversion efficiency of 15.6% under 1-sun intensity, and an outstanding electric energy efficiency of 63%. Furthermore, it allows a unique tuning capability of the solar-to-CO efficiency and selectivity by the current density applied during the carbon fixation.
There is an urgent need to develop advanced energy storage materials to meet the ever-increasing demands of modern electronics and electrical power systems. Polymer-based dielectric materials are one ...of the most promising energy materials due to their unique combination of high breakdown strength, low dielectric loss, light weight and ultrahigh power density. However, their energy densities are severely limited by their low dielectric constants (
K
) and thus fall short of the demands of compact and efficient energy storage devices. Remarkable efforts have been performed to improve
K
, and consequently, energy densities of polymers,
e.g.
introducing high-
K
inorganic fillers into the polymer matrix to form polymer composites. However, a general drawback is that the increased
K
is usually achieved at the cost of substantially decreased breakdown strength, thus leading to a moderate improvement of energy density. More recently, the polymer dielectrics with optimized hierarchically layered structures has become an emerging approach to resolve the existing paradox between high
K
and high breakdown strength in single-layered composite films, which resulted in substantial improvement in their capacitive energy storage performance. It is demonstrated that the electric field distribution, breakdown strength and capacitive performance can be readily adjusted by systematically varying the interfaces, chemical structures and ratios of the constituent layers. This review, for the first time, outlines the contemporary models and theories, and summarizes the research advances of multilayered hierarchical polymer composites (MHPCs), including inorganic particle/organic MHPCs and all-organic layered films in the field of high-energy-density capacitors. The efficient strategies for improving the energy storage performance of MHPCs have been highlighted. To conclude, the remaining challenges and the promising opportunities for the development of MHPCs for capacitive energy storage applications are presented.
Recent progress in multilayered hierarchical polymer composites for advanced dielectric energy storage are reviewed.
Copper matrix composites reinforced with graphene nanoplatelets (GNPs) were prepared via molecular-level mixing process and spark plasma sintering process. The impacts of graphene content on ...microstructure, mechanical performance, thermal diffusivity, electrical conductivity and tribological properties of the composites were investigated. For microstructure, GNPs distributed randomly in composites with low graphene concentration (no more than 0.8 vol.%), but aligned in the direction perpendicular to the consolidation force when graphene concentration was above 2.0 vol.%. The mechanical performance of copper was strengthened evidently by the graphene addition. However, the strengthen effects were firstly enhanced and then deteriorated by increasing graphene content. Thermal diffusivity showed a constant decrease with the increase of graphene content. Anisotropy thermal performance was obtained by composites with graphene alignment. Furthermore, graphene addition showed little negative impact on electrical conductivity but dramatically improved tribological performance.
Cinnamon essential oil (EO) exhibited effective antibacterial activity against foodborne spoilage and pathogenic bacteria in model systems using Escherichia coli and Staphylococcus. The minimum ...inhibition concentration (MIC) of cinnamon EO was similar for both bacteria (1.0 mg/ml) while the minimum bactericide concentration (MBC) were 4.0 mg/ml and 2.0 mg/ml for E. coli and Staphylococcus aureus. GC–MS analysis confirmed that cinnamaldehyde was the major constituent in cinnamon EO (92.40%). Much effort was focused on elucidating the mechanism of antibacterial action of cinnamon EO against E. coli and S. aureus by observing the changes of cell microstructure using scanning electron microscope, determination of cell permeability, membrane integrity and membrane potential. After adding cinnamon EO at MIC level, there were obvious changes in the morphology of bacteria cells indicating cell damage. When cinnamon EO were added at MBC levels, the cells were destroyed. Cinnamon EO led to leakage of small electrolytes, causing rapid increase in the electric conductivity of samples at the first few hours. The values for E. coli and S. aureus reached 60% and 79.4% respectively at 7 h. Moreover, the concentration of proteins and nucleic acids in cell suspension also rose with increased cinnamon EO. Bacterial metabolic activity was decreased 3–5 folds as reflected by the results of membrane potential. Overall, S. aureus was more susceptible to cinnamon EO than E. coli.
•We tested cinnamon EO exhibited effective antibacterial against Escherichia coli and Staphylococcus aureus.•The mechanism relies on cinnamon EO effects cell membrane structure.•Cinnamon EO results in irregular cell metabolic activity.•Cinnamon EO changes membrane permeability and membrane integrity.
Hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ether (PBDEs) are three legacy brominated flame retardants (BFRs); however, they are still produced and used ...in China. In this study, these three BFRs were measured in commonly consumed animal-based and plant-based foodstuffs from Beijing, China, and the dietary intakes of these BFRs by adults in Beijing were estimated to assess the related health concerns. The median levels of TBBPA in animal-based foodstuffs ranged from <LOD to 8.03 ng/g lipid weight (lw), whereas those in all the plant-based food groups were lower than the LOD. The median levels of total HBCD in animal-based foodstuffs were from 1.14 to 5.65 ng/g lw, and α-HBCD was the predominant isomer. The median HBCD level in vegetables was 0.266 ng/g wet weight (ww), whereas γ-HBCD was the most abundant isomer. The median levels of total PBDEs in animal-based foodstuffs were from 3.22 to 13.7 ng/g lw, and BDE-209 was the most abundant congener, comprising a proportion of at least 85% of total PBDEs. The daily dietary intakes of TBBPA, HBCD and PBDEs for adults in Beijing were 2.52, 2.74 and 9.77 ng/kg body weight/day, respectively. Meat consumption was found to be the primary source of BFR dietary intake. A comparison between the calculated estimated daily intakes (EDIs) and the corresponding threshold reference values (TRVs) indicated that daily intake of BFRs via food consumption is unable to cause significant health risks. Likewise, the margin of exposures (MOEs) calculated following the European Food Safety Authority (EFSA) approach were far higher than the threshold, which also proved that the EDIs of BFRs are unlikely to raise significant health concerns.
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•HBCD, TBBPA and PBDEs were measured in animal- and plant-based foods from Beijing.•Contamination levels and EDIs of PBDEs were higher than those of TBBPA and HBCD.•Meat consumption was the primary source of BFRs' dietary intake.•Daily dietary BFRs intake is still innocuous to adults in Beijing.
FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and ...tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein-protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising ...materials in the preparation of nanometeric carriers. This review relates to the newest developments in the preparation of polysaccharides-based nanoparticles. In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles, that is, covalent crosslinking, ionic crosslinking, polyelectrolyte complex, and the self-assembly of hydrophobically modified polysaccharides.
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