The occurrence of mental fatigue during tasks like driving a vehicle increases risk of injury or death. Changes in electroencephalographic (EEG) activity associated with mental fatigue has been ...frequently studied and considered a promising biomarker of mental fatigue. This is despite differences in methodologies and outcomes in prior research. A systematic review with meta‐analyses was conducted to establish the influence of mental fatigue on EEG activity spectral bands, and to determine in which regions fatigue‐related EEG spectral changes are likely to occur. A high‐yield search strategy identified 21 studies meeting inclusion criteria for investigating the change in EEG spectral activity in non‐diseased adults engaged in mentally fatiguing tasks. A medium effect size (using Cohen's g) of 0.68 (95%CI: 0.24–1.13) was found for increase in overall EEG activity following mental fatigue. Further examination of individual EEG spectral bands and regions using network meta‐analyses indicated large increases in theta (g = 1.03; 95%CI: 0.79–1.60) and alpha bands (g = 0.85; 95%CI: 0.47–1.43), with small to moderate changes found in delta and beta bands. Central regions of the scalp showed largest change (g = 0.80; 95%CI: 0.46–1.21). Sub‐group analyses indicated large increases in theta activity in frontal, central and posterior sites (all g > 1), with moderate changes in alpha activity in central and posterior sites. Findings have implications for fatigue monitoring and countermeasures with support for change in theta activity in frontal, central and posterior sites as a robust biomarker of mental fatigue and change in alpha wave activity considered a second line biomarker to account for individual variability.
There is significant risk of injury during tasks such as driving or operating machinery when mentally fatigued. Reliable biomarkers are needed that warn a fatigued person so they can take preventive action. This review uses meta‐analytic methods to synthesise the results from 21 studies. Results highlight the spectral bands and regions most promising for an EEG biomarker.
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to ...become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties.
* Serves as an essential working handbook aimed at scientists and students in medicinal chemistry* Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies * Discusses improvements in pharmacokinetics from a practical chemist's standpoint
Monoterpenes, comprising hydrocarbons, are the largest class of plant secondary metabolites and are commonly found in essential oils. Monoterpenes and their derivatives are key ingredients in the ...design and production of new biologically active compounds. This review focuses on selected aliphatic, monocyclic, and bicyclic monoterpenes like geraniol, thymol, myrtenal, pinene, camphor, borneol, and their modified structures. The compounds in question play a pivotal role in biological and medical applications. The review also discusses anti-inflammatory, antimicrobial, anticonvulsant, analgesic, antiviral, anticancer, antituberculosis, and antioxidant biological activities exhibited by monoterpenes and their derivatives. Particular attention is paid to the link between biological activity and the effect of structural modification of monoterpenes and monoterpenoids, as well as the introduction of various functionalized moieties into the molecules in question.
A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow ...inference of a neuron’s activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations.
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•Distinct durations of neuronal activity induce different gene expression profiles•Neuronal activity history can be inferred from gene expression•Brief activity induces a gene set defined by sensitivity to MAPK/ERK signaling•H3K27ac and eRNA induction are two separable steps of enhancer activation
Tyssowski et al. report that different durations of neuronal activity induce different gene expression profiles, enabling inference of past neuronal activity from gene expression data. Furthermore, they show that MAPK/ERK signaling partially establishes this activity-pattern-to-gene-induction coupling.
The role played by cinnamic acid derivatives in treating cancer, bacterial infections, diabetes and neurological disorders, among many, has been reported. Cinnamic acid is obtained from cinnamon ...bark. Its structure is composed of a benzene ring, an alkene double bond and an acrylic acid functional group making it possible to modify the aforementioned functionalities with a variety of compounds resulting in bioactive agents with enhanced efficacy. The nature of the substituents incorporated into cinnamic acid has been found to play a huge role in either enhancing or decreasing the biological efficacy of the synthesized cinnamic acid derivatives. Some of the derivatives have been reported to be more effective when compared to the standard drugs used to treat chronic or infectious diseases in vitro, thus making them very promising therapeutic agents. Compound
displayed potent anti-TB activity, compound
exhibited significant antibacterial activity on
strain of bacteria and compounds with potent antimalarial activity are
,
,
,
, and
. Furthermore, compounds
,
,
,
,
displayed potent anticancer activity and compounds
were active against both hAChE and hBuChE. This review will expound on the recent advances on cinnamic acid derivatives and their biological efficacy.
The Seneca Falls Convention is typically seen as the beginning of the first women's rights movement in the United States.Revolutionary Backlashargues otherwise. According to Rosemarie Zagarri, the ...debate over women's rights began not in the decades prior to 1848 but during the American Revolution itself. Integrating the approaches of women's historians and political historians, this book explores changes in women's status that occurred from the time of the American Revolution until the election of Andrew Jackson. Although the period after the Revolution produced no collective movement for women's rights, women built on precedents established during the Revolution and gained an informal foothold in party politics and male electoral activities. Federalists and Jeffersonians vied for women's allegiance and sought their support in times of national crisis. Women, in turn, attended rallies, organized political activities, and voiced their opinions on the issues of the day. After the publication of Mary Wollstonecraft'sA Vindication of the Rights of Woman, a widespread debate about the nature of women's rights ensued. The state of New Jersey attempted a bold experiment: for a brief time, women there voted on the same terms as men. Yet as Rosemarie Zagarri argues inRevolutionary Backlash, this opening for women soon closed. By 1828, women's politicization was seen more as a liability than as a strength, contributing to a divisive political climate that repeatedly brought the country to the brink of civil war. The increasing sophistication of party organizations and triumph of universal suffrage for white males marginalized those who could not vote, especially women. Yet all was not lost. Women had already begun to participate in charitable movements, benevolent societies, and social reform organizations. Through these organizations, women found another way to practice politics.
A rapid and ecofriendly fabrication of metal oxide nanoparticles using biogenic sources is the current trend being used to replace the toxic chemical method. The present study was carried out to ...synthesize magnesium oxide nanoparticles (MgONPs) using the marine brown algae Sargassum wighitii as the reducing and capping agent. The as-prepared MgONPs were characterized by spectroscopic and microscopic analyses. UV–visible spectrum of the MgONPs showed a sharp absorption peak at 322 nm. X- ray diffraction analysis illustrated that the MgONPs were crystalline in nature with a face-centered cubic structure. Presence of magnesium and oxygen were further confirmed by EDX profile. FTIR analysis showed the presence of functional groups specific for sulfated polysaccharides, which might be responsible for the synthesis of MgONPs. Zeta potential and dynamic light scattering analysis illustrated that the MgONPs were highly stable at 19.8 mV with an average size of 68.06 nm. MgONPs showed potent antibacterial activity and antifungal activities against human pathogens. Photocatalytic activity of MgONPs was witnessed by the quick degradation of the organic dye methylene blue on exposure to both sunlight and UV irradiation. MgONPs showed significant cytotoxicity against the lung cancer cell lines A549 in a dose dependent manner with the IC50 value of 37.5 ± 0.34 μg/ml. Safety evaluation using peripheral blood mononuclear cells (PBMCs) illustrated the MgONPs to be non-toxic in nature. Overall, the results concluded that the MgONPs generated using marine algae have exhibited scope for multifaceted biological applications.
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•Facile green synthesis of MgONPs using aqueous extract of Sargassum wightii.•MgONPs showed significant antibacterial and antifungal activity against human pathogens.•MgONPs displayed high photocatalytic activity for dye degradation of methylene blue.•MgONPs exhibited potent anticancer effect against lung cancer cell lines A549 cells.•MgONPs induced ROS mediated apoptosis in A549 cells.
Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such ...as insufficient endogenous hydrogen peroxide (H2O2) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation‐enhanced nanozyme‐based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF‐β inhibitor (TI)‐loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN‐PEG‐TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase‐like and catalase‐like activities under acidic TME, which can decompose H2O2 into hydroxyl radicals (•OH) and oxygen (O2), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2O2, which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN‐PEG‐TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26‐tumor‐bearing mice models. It is believed that the immunomodulation‐enhanced nanozyme‐based tumor treatment strategy is a promising tool to kill cancer cells.
An immunomodulation‐enhanced nanozyme‐based tumor catalytic treatment strategy is developed to fight against cancer. By regulating the tumor immune microenvironment, an increased generation level of hydrogen peroxide is demonstrated, thus effectively improving the catalytic activities of iron manganese silicate nanoparticle nanozymes. As a result, a high tumor therapeutic effect with a tumor inhibition rate of 87.5% is achieved.
For centuries, nature has been an inspirational source for the discovery of drugs used in modern medicine. Nowadays, natural-based treatments continue to be employed for primary health care, ...particularly playing a significant role in folk medicine. In addition, we are currently observing an increasing use of natural-products-based supplements from botanical and marine sources, making their standardization and scientific validation a priority to guarantee the safety of these products. Natural products and/or synthetic derivatives using their novel structures have also been of utmost importance in drug discovery and development in several clinical areas. After a period of discreditation and reduced investment, we are now witnessing a renewed interest from the pharmaceutical industry and scientific community due to the urgent need to develop new drugs. This reprint comprises 11 original and 6 review articles dedicated to plant and marine natural products research, contributing to the scientific validation of their use and opening new perspectives in drug discovery
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