Self-organized bistability on globally coupled higher-order networks.

Self-organized bistability (SOB) stands as a critical behavior for the systems delicately adjusting themselves to the brink of bistability, characterized by a first-order transition. Its essence lies in the inherent ability of the system to undergo enduring shifts between the coexisting states, achieved through the self-regulation of a controlling parameter. Recently, SOB has been established in a scale-free network as a recurrent transition to a short-living state of global synchronization. Here, we embark on a theoretical exploration that extends the boundaries of the SOB concept on a higher-order network (implicitly embedded microscopically within a simplicial complex) while considering the limitations imposed by coupling constraints. By applying Ott-Antonsen dimensionality reduction in the thermodynamic limit to the higher-order network, we derive SOB requirements under coupling limits that are in good agreement with numerical simulations on systems of finite size. We use continuous synchronization diagrams and statistical data from spontaneous synchronized events to demonstrate the crucial role SOB plays in initiating and terminating temporary synchronized events. We show that under weak-coupling consumption, these spontaneous occurrences closely resemble the statistical traits of the epileptic brain functioning.

Specific Proton-Donor Properties of Glycine Betaine. Metric Parameters and Enthalpy of Noncovalent Interactions in its Dimer, Water Complexes and Crystalline Hydrate.

Trimethylglycine (glycine betaine, GB) is an important organic osmolyte that accumulates in various plant species in response to environmental stresses and has significant potential as a bioactive agent with low environmental impact. It is assumed that the hydration of GB is playing an important role in the protective mechanism. The hydration and aggregation properties of GB have not yet been studied in detail at the atomistic level. In this work, noncovalent interactions in the GB dimer and its complexes with water and crystalline monohydrate are studied. Depending on the object, periodic and non-periodic DFT calculations are used. Particular attention is paid to the metric parameters and enthalpies of intermolecular hydrogen bonds. The identification of noncovalent interactions is carried out by means of the Bader analysis of periodic or non-periodic electron density. The enthalpy of hydrogen bonds is estimated using the Rosenberg formula (PCCP 2 (2000) 2699). The specific proton donor properties of glycine betaine are due to its ability to form intermolecular C-H∙∙∙O bonds with the oxygen atom of a water molecule or the carboxylate group of a neighboring GB. The enthalpy of these bonds can be significantly greater than 10 kJ/mol. The water molecule that forms a hydrogen bond with the carboxylate group of GB also interacts with its CH groups through lone pairs of electrons. The C-H∙∙∙O bonds contribute up to 40% of the total entropy of the GB-water interaction, which is about 45 kJ/mol. The possibility of identifying C-H∙∙∙O bonds by the proton nuclear magnetic resonance method is discussed.

Perceptual Integration Compensates for Attention Deficit in Elderly during Repetitive Auditory-Based Sensorimotor Task.

Sensorimotor integration (SI) brain functions that are vital for everyday life tend to decline in advanced age. At the same time, elderly people preserve a moderate level of neuroplasticity, which allows the brain's functionality to be maintained and slows down the process of neuronal degradation. Hence, it is important to understand which aspects of SI are modifiable in healthy old age. The current study focuses on an auditory-based SI task and explores: (i) if the repetition of such a task can modify neural activity associated with SI, and (ii) if this effect is different in young and healthy old age. A group of healthy older subjects and young controls underwent an assessment of the whole-brain electroencephalography (EEG) while repetitively executing a motor task cued by the auditory signal. Using EEG spectral power and functional connectivity analyses, we observed a differential age-related modulation of theta activity throughout the repetition of the SI task. Growth of the anterior stimulus-related theta oscillations accompanied by enhanced right-lateralized frontotemporal phase-locking was found in elderly adults. Their young counterparts demonstrated a progressive increase in prestimulus occipital theta power. Our results suggest that the short-term repetition of the auditory-based SI task modulates sensory processing in the elderly. Older participants most likely progressively improve perceptual integration rather than attention-driven processing compared to their younger counterparts.

The Antimicrobial and Antibiofilm Potential of New Water-Soluble Tris-Quaternary Ammonium Compounds.

The invention and innovation of highly effective antimicrobials are always crucial tasks for medical and organic chemistry, especially at the current time, when there is a serious threat of shortages of effective antimicrobials following the pandemic. In the study presented in this article, we established a new approach to synthesizing three novel series of bioactive water-soluble tris-quaternary ammonium compounds using an optimized one-pot method, and we assessed their antimicrobial and antibiofilm potential. Five pathogenic microorganisms of the ESKAPE group, including highly resistant clinical isolates, were used as the test samples. Moreover, we highlighted the dependence of antibacterial activity from the hydrophilic-hydrophobic balance of the QACs and noted the significant performance of the desired products on biofilms with MBEC as low as 16 mg/L against bacteria and 8 mg/L against fungi. Particularly notable was the high activity against Pseudomonas aeruginosa and Acinetobacter baumannii, which are among the most resilient bacteria known. The presented work will provide useful insights for future research on the topic.

Multicationic Quaternary Ammonium Compounds: A Framework for Combating Bacterial Resistance.

During previous stages of research, high biocidal activity toward microorganism archival strains has been used as the main indicator in the development of new antiseptic formulations. Although this factor remains one of the most important characteristics of biocide efficiency, the scale of antimicrobial resistance spread causes serious concern. Therefore, focus shifts toward the development of formulations with a stable effect even in the case of prolonged contact with pathogens. Here, we introduce an original isocyanuric acid alkylation method with the use of available alkyl dichlorides, which opened access to a wide panel of multi-QACs with alkyl chains of various lengths between the nitrogen atoms of triazine and pyridine cycles. We used a complex approach for the resulting series of 17 compounds, including their antibiofilm properties, bacterial tolerance development, and antimicrobial activity toward multiresistant pathogenic strains. As a result of these efforts, available compounds have shown higher levels of antibacterial activity against ESKAPE pathogens than widely used commercial QACs. Hit compounds possessed high activity toward clinical bacterial strains and have also demonstrated a long-term biocidal effect without significant development of microorganism tolerance. The overall results indicated a high level of antibacterial activity and the broad application prospects of multi-QACs based on isocyanuric acid against multiresistant bacterial strains.

From Antibacterial to Antibiofilm Targeting: An Emerging Paradigm Shift in the Development of Quaternary Ammonium Compounds (QACs).

In a previous development stage, mostly individual antibacterial activity was a target in the optimization of biologically active compounds and antiseptic agents. Although this targeting is still valuable, a new trend has appeared since the discovery of superhigh resistance of bacterial cells upon their aggregation into groups. Indeed, it is now well established that the great majority of pathogenic germs are found in the environment as surface-associated microbial communities called biofilms. The protective properties of biofilms and microbial resistance, even to high concentrations of biocides, cause many chronic infections in medical settings and lead to serious economic losses in various areas. A paradigm shift from individual bacterial targeting to also affecting more complex cellular frameworks is taking place and involves multiple strategies for combating biofilms with compounds that are effective at different stages of microbiome formation. Quaternary ammonium compounds (QACs) play a key role in many of these treatments and prophylactic techniques on the basis of both the use of individual antibacterial agents and combination technologies. In this review, we summarize the literature data on the effectiveness of using commercially available and newly synthesized QACs, as well as synergistic treatment techniques based on them. As an important focus, techniques for developing and applying antimicrobial coatings that prevent the formation of biofilms on various surfaces over time are discussed. The information analyzed in this review will be useful to researchers and engineers working in many fields, including the development of a new generation of applied materials; understanding biofilm surface growth; and conducting research in medical, pharmaceutical, and materials sciences. Although regular studies of antibacterial activity are still widely conducted, a promising new trend is also to evaluate antibiofilm activity in a comprehensive study in order to meet the current requirements for the development of highly needed practical applications.

Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications.

Piperidines are among the most important synthetic fragments for designing drugs and play a significant role in the pharmaceutical industry. Their derivatives are present in more than twenty classes of pharmaceuticals, as well as alkaloids. The current review summarizes recent scientific literature on intra- and intermolecular reactions leading to the formation of various piperidine derivatives: substituted piperidines, spiropiperidines, condensed piperidines, and piperidinones. Moreover, the pharmaceutical applications of synthetic and natural piperidines were covered, as well as the latest scientific advances in the discovery and biological evaluation of potential drugs containing piperidine moiety. This review is designed to help both novice researchers taking their first steps in this field and experienced scientists looking for suitable substrates for the synthesis of biologically active piperidines.

Self-organized bistability on scale-free networks.

A dynamical system approaching the first-order transition can exhibit a specific type of critical behavior known as self-organized bistability (SOB). It lies in the fact that the system can permanently switch between the coexisting states under the self-tuning of a control parameter. Many of these systems have a network organization that should be taken into account to understand the underlying processes in detail. In the present paper, we theoretically explore an extension of the SOB concept on the scale-free network under coupling constraints. As provided by the numerical simulations and mean-field approximation in the thermodynamic limit, SOB on scale-free networks originates from facilitated criticality reflected on both macro- and mesoscopic network scales. We establish that the appearance of switches is rooted in spatial self-organization and temporal self-similarity of the network's critical dynamics and replicates extreme properties of epileptic seizure recurrences. Our results, thus, indicate that the proposed conceptual model is suitable to deepen the understanding of emergent collective behavior behind neurological diseases.

Microbiological Evaluation of Novel Bis-Quaternary Ammonium Compounds: Clinical Strains, Biofilms, and Resistance Study.

This work is devoted to the investigation of biocidal properties of quaternary ammonium compounds (QACs) based on pyridine structures with aromatic spacers, and their widely known analogs, against clinically significant microorganisms. This study is focused on investigating their antimicrobial activity (minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs)), antibiofilm properties (minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs)), synergetic effect with different alcohols in antiseptic formulations, and bacterial resistance development. It was shown that all combined analogue preparations had a higher level of antibacterial activity against the tested bacterial strains, with a 16- to 32-fold reduction in MICs and MBCs compared to previously used antiseptic preparations. Moreover, hit-QACs demonstrated a stable effect against Gram-negative E. coli, K. pneumoniae, and A. baumannii within a month of incubation. Overall results indicated a high level of antibacterial activity of pyridine-based QACs.

Age-Related Changes in Functional Connectivity during the Sensorimotor Integration Detected by Artificial Neural Network.

Large-scale functional connectivity is an important indicator of the brain's normal functioning. The abnormalities in the connectivity pattern can be used as a diagnostic tool to detect various neurological disorders. The present paper describes the functional connectivity assessment based on artificial intelligence to reveal age-related changes in neural response in a simple motor execution task. Twenty subjects of two age groups performed repetitive motor tasks on command, while the whole-scalp EEG was recorded. We applied the model based on the feed-forward multilayer perceptron to detect functional relationships between five groups of sensors located over the frontal, parietal, left, right, and middle motor cortex. Functional dependence was evaluated with the predicted and original time series coefficient of determination. Then, we applied statistical analysis to highlight the significant features of the functional connectivity network assessed by our model. Our findings revealed the connectivity pattern is consistent with modern ideas of the healthy aging effect on neural activation. Elderly adults demonstrate a pronounced activation of the whole-brain theta-band network and decreased activation of frontal-parietal and motor areas of the mu-band. Between-subject analysis revealed a strengthening of inter-areal task-relevant links in elderly adults. These findings can be interpreted as an increased cognitive demand in elderly adults to perform simple motor tasks with the dominant hand, induced by age-related working memory decline.

Machine learning evaluates changes in functional connectivity under a prolonged cognitive load.

One must be aware of the black-box problem by applying machine learning models to analyze high-dimensional neuroimaging data. It is due to a lack of understanding of the internal algorithms or the input features upon which most models make decisions despite outstanding performance in classification, pattern recognition, and prediction. Here, we approach the fundamentally high-dimensional problem of classifying cognitive brain states based on functional connectivity by selecting and interpreting the most relevant input features. Specifically, we consider the alterations in the cortical synchrony under a prolonged cognitive load. Our study highlights the advances of this machine learning method in building a robust classification model and percept-related prestimulus connectivity changes over the conventional trial-averaged statistical analysis.

Monitoring the Cortical Activity of Children and Adults during Cognitive Task Completion.

In this paper, we used an EEG system to monitor and analyze the cortical activity of children and adults at a sensor level during cognitive tasks in the form of a Schulte table. This complex cognitive task simultaneously involves several cognitive processes and systems: visual search, working memory, and mental arithmetic. We revealed that adults found numbers on average two times faster than children in the beginning. However, this difference diminished at the end of table completion to 1.8 times. In children, the EEG analysis revealed high parietal alpha-band power at the end of the task. This indicates the shift from procedural strategy to less demanding fact-retrieval. In adults, the frontal beta-band power increased at the end of the task. It reflects enhanced reliance on the top-down mechanisms, cognitive control, or attentional modulation rather than a change in arithmetic strategy. Finally, the alpha-band power of adults exceeded one of the children in the left hemisphere, providing potential evidence for the fact-retrieval strategy. Since the completion of the Schulte table involves a whole set of elementary cognitive functions, the obtained results were essential for developing passive brain-computer interfaces for monitoring and adjusting a human state in the process of learning and solving cognitive tasks of various types.

Extreme synchronization events in a Kuramoto model: The interplay between resource constraints and explosive transitions.

Many living and artificial systems possess structural and dynamical properties of complex networks. One of the most exciting living networked systems is the brain, in which synchronization is an essential mechanism of its normal functioning. On the other hand, excessive synchronization in neural networks reflects undesired pathological activity, including various forms of epilepsy. In this context, network-theoretical approach and dynamical modeling may uncover deep insight into the origins of synchronization-related brain disorders. However, many models do not account for the resource consumption needed for the neural networks to synchronize. To fill this gap, we introduce a phenomenological Kuramoto model evolving under the excitability resource constraints. We demonstrate that the interplay between increased excitability and explosive synchronization induced by the hierarchical organization of the network forces the system to generate short-living extreme synchronization events, which are well-known signs of epileptic brain activity. Finally, we establish that the network units occupying the medium levels of hierarchy most strongly contribute to the birth of extreme events emphasizing the focal nature of their origin.

Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials.

Quaternary ammonium compounds (QACs) belong to a well-known class of cationic biocides with a broad spectrum of antimicrobial activity. They are used as essential components in surfactants, personal hygiene products, cosmetics, softeners, dyes, biological dyes, antiseptics, and disinfectants. Simple but varied in their structure, QACs are divided into several subclasses: Mono-, bis-, multi-, and poly-derivatives. Since the beginning of the 20th century, a significant amount of work has been dedicated to the advancement of this class of biocides. Thus, more than 700 articles on QACs were published only in 2020, according to the modern literature. The structural variability and diverse biological activity of ionic liquids (ILs) make them highly prospective for developing new types of biocides. QACs and ILs bear a common key element in the molecular structure-quaternary positively charged nitrogen atoms within a cyclic or acyclic structural framework. The state-of-the-art research level and paramount demand in modern society recall the rapid development of a new generation of tunable antimicrobials. This review focuses on the main QACs exhibiting antimicrobial and antifungal properties, commercial products based on QACs, and the latest discoveries in QACs and ILs connected with biocide development.

Novel Phenyl-Based Bis-quaternary Ammonium Compounds as Broad-Spectrum Biocides.

Herein we report the synthesis and microbiological evaluation of novel phenyl based bis-quaternary ammonium compounds (bis-QACs). Using a simple 2-step synthetic route from dibromo- and dihydroxybenzenes, we obtained a structurally diverse broad panel of bis-QACs with topologically distinct bridging connections between pyridinium heads. Selected analogs possessed potent broad-spectrum biocidal activity against both bacterial and fungal pathogens: methicillin-resistant Staphylococcus aureus (ATCC 43300); Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (ATCC 90028), Cryptococcus neoformans var. grubii (ATCC 208821). Promising compounds displayed minimum inhibitory concentrations (MIC) values ≤0.25 µg/mL alongside improved cytotoxicity and hemolytic profiles compared to modern antiseptics. Thus, synthesized bis-QACs represent a promising class of biocides with the potential to replace existing household sanitizers.

Effect of repetition on the behavioral and neuronal responses to ambiguous Necker cube images.

A repeated presentation of an item facilitates its subsequent detection or identification, a phenomenon of priming. Priming may involve different types of memory and attention and affects neural activity in various brain regions. Here we instructed participants to report on the orientation of repeatedly presented Necker cubes with high (HA) and low (LA) ambiguity. Manipulating the contrast of internal edges, we varied the ambiguity and orientation of the cube. We tested how both the repeated orientation (referred to as a stimulus factor) and the repeated ambiguity (referred to as a top-down factor) modulated neuronal and behavioral response. On the behavioral level, we observed higher speed and correctness of the response to the HA stimulus following the HA stimulus and a faster response to the right-oriented LA stimulus following the right-oriented stimulus. On the neuronal level, the prestimulus theta-band power grew for the repeated HA stimulus, indicating activation of the neural networks related to attention and uncertainty processing. The repeated HA stimulus enhanced hippocampal activation after stimulus onset. The right-oriented LA stimulus following the right-oriented stimulus enhanced activity in the precuneus and the left frontal gyri before the behavioral response. During the repeated HA stimulus processing, enhanced hippocampal activation may evidence retrieving information to disambiguate the stimulus and define its orientation. Increased activation of the precuneus and the left prefrontal cortex before responding to the right-oriented LA stimulus following the right-oriented stimulus may indicate a match between their orientations. Finally, we observed increased hippocampal activation after responding to the stimuli, reflecting the encoding stimulus features in memory. In line with the large body of works relating the hippocampal activity with episodic memory, we suppose that this type of memory may subserve the priming effect during the repeated presentation of ambiguous images.

Investigations into the structure-activity relationship in gemini QACs based on biphenyl and oxydiphenyl linker.

Eighteen novel gemini quaternary ammonium compounds were synthesized to examine the effect of linker nature, aliphatic chain length and their relative position on antibacterial and antifungal activity. The synthesized compounds showed strong bacteriostatic activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and two fungi. Some of these compounds exhibited a wider and more potent antimicrobial spectrum than commonly-used antiseptics, such as benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHG) and octenidine dihydrochloride (OCT).

Revealing a multiplex brain network through the analysis of recurrences.

A multilayer approach has recently received particular attention in network neuroscience as a suitable model to describe brain dynamics by adjusting its activity in different frequency bands, time scales, modalities, or ages to different layers of a multiplex graph. In this paper, we demonstrate an approach to a frequency-based multilayer functional network constructed from nonstationary multivariate data by analyzing recurrences in application to electroencephalography. Using the recurrence-based index of synchronization, we construct intralayer (within-frequency) and interlayer (cross-frequency) graph edges to model the evolution of a whole-head functional connectivity network during a prolonged stimuli classification task. We demonstrate that the graph edges' weights increase during the experiment and negatively correlate with the response time. We also show that while high-frequency activity evolves toward synchronization of remote local areas, low-frequency connectivity tends to establish large-scale coupling between them.

Age-Related Distinctions in EEG Signals during Execution of Motor Tasks Characterized in Terms of Long-Range Correlations.

The problem of revealing age-related distinctions in multichannel electroencephalograms (EEGs) during the execution of motor tasks in young and elderly adults is addressed herein. Based on the detrended fluctuation analysis (DFA), differences in long-range correlations are considered, emphasizing changes in the scaling exponent α. Stronger responses in elderly subjects are confirmed, including the range and rate of increase in α. Unlike elderly subjects, young adults demonstrated about 2.5 times more pronounced differences between motor task responses with the dominant and non-dominant hand. Knowledge of age-related changes in brain electrical activity is important for understanding consequences of healthy aging and distinguishing them from pathological changes associated with brain diseases. Besides diagnosing age-related effects, the potential of DFA can also be used in the field of brain-computer interfaces.