Fundamental Mechanisms Research Articles

Unraveling the Emerging Niche Role of Extracellular Vesicles (EVs) in Traumatic Brain Injury (TBI).

Extracellular vesicles or exosomes, often known as EVs, have acquired significant attention in the investigations of traumatic brain injury (TBI) and have a distinct advantage in actively researching the fundamental mechanisms underlying various clinical symptoms and diagnosing the wide range of traumatic brain injury cases. The mesenchymal stem cells (MSCs) can produce and release exosomes, which offer therapeutic benefits. Exosomes are tiny membranous vesicles produced by various cellular entities originating from endosomes. Several studies have reported that administering MSC-derived exosomes through intravenous infusions improves neurological recovery and promotes neuroplasticity in rats with traumatic brain damage. The therapeutic advantages of exosomes can be attributed to the microRNAs (miRNAs), which are small non-coding regulatory RNAs that significantly impact the regulation of posttranscriptional genes. Exosome-based therapies, which do not involve cells, have lately gained interest as a potential breakthrough in enhancing neuroplasticity and accelerating neurological recovery for various brain injuries and neurodegenerative diseases. This article explores the benefits and drawbacks of exosome treatment for traumatic brain injury while emphasizing the latest advancements in this field with clinical significance.

Redox imbalance and metabolic defects in the context of Alzheimer disease.

Redox reactions play a critical role for intracellular processes, including pathways involved in metabolism and signaling. Reactive oxygen species (ROS) act either as second messengers or generators of protein modifications, fundamental mechanisms for signal transduction. Disturbance of redox homeostasis is associated with many disorders. Among these, Alzheimer's disease is a neurodegenerative pathology that presents hallmarks of oxidative damage such as increased ROS production, decreased activity of antioxidant enzymes, oxidative modifications of macromolecules, and changes in mitochondrial homeostasis. Interestingly, alteration of redox homeostasis is closely associated with defects of energy metabolism, involving both carbohydrates and lipids, the major energy fuels for the cell. As the brain relies exclusively on glucose metabolism, defects of glucose utilization represent a harmful event for the brain. During aging, a progressive perturbation of energy metabolism occurs resulting in brain hypometabolism. This condition contributes to increase neuronal cell vulnerability ultimately resulting in cognitive impairment. The current review discusses the crosstalk between alteration of redox homeostasis and brain energy defects that seems to act in concert in promoting Alzheimer's neurodegeneration.

The Nanoplasmonic Purcell Effect in Ultrafast and High-Light-Yield Perovskite Scintillators.

The development of X-ray scintillators with ultrahigh light yields and ultrafast response times is a long sought-after goal. In this work, a fundamental mechanism that pushes the frontiers of ultrafast X-ray scintillator performance is theoretically predicted and experimentally demonstrated: the use of nanoscale-confined surface plasmon polariton modes to tailor the scintillator response time via the Purcell effect. By incorporating nanoplasmonic materials in scintillator devices, this work predicts over tenfold enhancement in decay rate and 38% reduction in time resolution even with only a simple planar design. The nanoplasmonic Purcell effect is experimentally demonstrated using perovskite scintillators, enhancing the light yield by over 120% to 88 ± 11 ph/keV, and the decay rate by over 60% to 2.0 ± 0.2 ns for the average decay time, and 0.7 ± 0.1 ns for the ultrafast decay component, in good agreement with the predictions of ourtheoretical framework. Proof-of-concept X-ray imaging experiments are performed using nanoplasmonic scintillators, demonstrating 182% enhancement in the modulation transfer function at four line pairs per millimeter spatial frequency. This work highlights the enormous potential of nanoplasmonics in optimizing ultrafast scintillator devices for applications including time-of-flight X-ray imaging and photon-counting computed tomography.

Fairness-Aware Graph Neural Networks: A Survey

Graph Neural Networks (GNNs) have become increasingly important due to their representational power and state-of-the-art predictive performance on many fundamental learning tasks. Despite this success, GNNs suffer from fairness issues that arise as a result of the underlying graph data and the fundamental aggregation mechanism that lies at the heart of the large class of GNN models. In this article, we examine and categorize fairness techniques for improving the fairness of GNNs. We categorize these techniques by whether they focus on improving fairness in the pre-processing, in-processing (during training), or post-processing phases. We discuss how such techniques can be used together whenever appropriate and highlight the advantages and intuition as well. We also introduce an intuitive taxonomy for fairness evaluation metrics, including graph-level fairness, neighborhood-level fairness, embedding-level fairness, and prediction-level fairness metrics. In addition, graph datasets that are useful for benchmarking the fairness of GNN models are summarized succinctly. Finally, we highlight key open problems and challenges that remain to be addressed.

Processing speed and executive attention as causes of intelligence.

Individual differences in processing speed and executive attention have both been proposed as explanations for individual differences in cognitive ability, particularly general and fluid intelligence (Engle et al., 1999; Kail & Salthouse, 1994). Both constructs have long intellectual histories in scientific psychology. This article attempts to describe the historical development of these constructs, particularly as they pertain to intelligence. It also aims to determine the degree to which speed and executive attention are theoretical competitors in explaining individual differences in intelligence. We suggest that attention is the more fundamental mechanism in explaining variation in human intelligence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individual Alpha Frequency Contributes to the Precision of Human Visual Processing.

Brain oscillatory activity within the alpha band has been associated with a wide range of processes encompassing perception, memory, decision-making, and overall cognitive functioning. Individual alpha frequency (IAF) is a specific parameter accounting for the mean velocity of the alpha cycling activity, conventionally ranging between ∼7 and ∼13 Hz. One influential hypothesis has proposed a fundamental role of this cycling activity in the segmentation of sensory input and in the regulation of the speed of sensory processing, with faster alpha oscillations resulting in greater temporal resolution and more refined perceptual experience. However, although several recent theoretical and empirical studies would support this account, contradictory evidence suggests caution and more systematic approaches in the assessment and interpretation of this hypothesis. For example, it remains to be explored to what degree IAF shapes perceptual outcomes. In the present study, we investigated whether inter-individual differences in bias-free visual contrast detection threshold in a large sample of individuals in the general population (n = 122) could be explained by inter-individual differences in alpha pace. Our results show that the contrast needed to correctly identify target stimuli (individual perceptual threshold) is associated with alpha peak frequency (not amplitude). Specifically, individuals who require reduced contrast show higher IAF than individuals requiring higher contrasts. This suggests that inter-individual differences in alpha frequency contribute to performance variability in low-level perceptual tasks, supporting the hypothesis that IAF underlies a fundamental temporal sampling mechanism that shapes visual objective performance, with higher frequencies promoting enhanced sensory evidence per time unit.

Novel insights into phage biology of the pathogen Clostridioides difficile based on the active virome.

The global pathogen Clostridioides difficile is a well-studied organism, and researchers work on unraveling its fundamental virulence mechanisms and biology. Prophages have been demonstrated to influence C. difficile toxin expression and contribute to the distribution of advantageous genes. All these underline the importance of prophages in C. difficile virulence. Although several C. difficile prophages were sequenced and characterized, investigations on the entire active virome of a strain are still missing. Phages were mainly isolated after mitomycin C-induction, which does not resemble a natural stressor for C. difficile. We examined active prophages from different C. difficile strains after cultivation in the absence of mitomycin C by sequencing and characterization of particle-protected DNA. Phage particles were collected after standard cultivation, or after cultivation in the presence of the secondary bile salt deoxycholate (DCA). DCA is a natural stressor for C. difficile and a potential prophage-inducing agent. We also investigated differences in prophage activity between clinical and non-clinical C. difficile strains. Our experiments demonstrated that spontaneous prophage release is common in C. difficile and that DCA presence induces prophages. Fourteen different, active phages were identified by this experimental procedure. We could not identify a definitive connection between clinical background and phage activity. However, one phage exhibited distinctively higher activity upon DCA induction in the clinical strain than in the corresponding non-clinical strain, although the phage is identical in both strains. We recorded that enveloped DNA mapped to genome regions with characteristics of mobile genetic elements other than prophages. This pointed to mechanisms of DNA mobility that are not well-studied in C. difficile so far. We also detected phage-mediated lateral transduction of bacterial DNA, which is the first described case in C. difficile. This study significantly contributes to our knowledge of prophage activity in C. difficile and reveals novel aspects of C. difficile (phage) biology.

All-Inorganic Perovskite Solar Cells: Defect Regulation and Emerging Applications in Extreme Environments.

All-inorganic perovskite solar cells (PSCs), such as CsPbX3, have garnered considerable attention recently, as they exhibit superior thermodynamic and optoelectronic stabilities compared to the organic-inorganic hybrid PSCs. However, the power conversion efficiency (PCE) of CsPbX3 PSCs is generally lower than that of organic-inorganic hybrid PSCs, as they contain higher defect densities at the interface and within the perovskite light-absorbing layers, resulting in higher non-radiative recombination and voltage loss. Consequently, defect regulation has been adopted as an important strategy to improve device performance and stability. This review aims to comprehensively summarize recent progresses on the defect regulation in CsPbX3 PSCs, as well as their cutting-edge applications in extreme scenarios. The underlying fundamental mechanisms leading to the defect formation in the crystal structure of CsPbX3 PSCs are firstly discussed, and an overview of literature-adopted defect regulation strategies in the context of interface, internal, and surface engineering is provided. Cutting-edge applications of CsPbX3 PSCs in extreme environments such as outer space and underwater situations are highlighted. Finally, a summary and outlook are presented on future directions for achieving higher efficiencies and superior stability in CsPbX3 PSCs.

From Stress to Screen: Understanding Cyberloafing through Cognitive and Affective Pathways.

This investigation delves into the pervasive yet insufficiently examined phenomenon of "cyberloafing", characterized by employees engaging in non-work-related internet activities during office hours. Despite its frequent occurrence in contemporary work environments, the fundamental mechanisms underpinning cyberloafing remain largely uncharted. This study uses the conservation of resources theory and the cognitive-affective personality system framework to demystify the relationship between role stress and cyberloafing. We developed a dual-path model to assess the mediating roles of perceived insider status and emotional exhaustion. Employing SPSS and Smart PLS for data analysis, our research sampled 210 corporate employees. The findings reveal that role stress predicts perceived insider status and emotional exhaustion significantly. Notably, while perceived insider status negatively correlates with cyberloafing, emotional exhaustion shows a positive correlation. These factors mediate the relationship between role stress and cyberloafing, underscoring a multifaceted dynamic. Our results provide new theoretical insights into the mechanisms of employee counterproductive behavior, specifically in the context of cyberloafing, and broaden our understanding of its determinants. This study illuminates theoretical nuances and offers practical implications for managerial strategies and future scholarly inquiries into organizational behavior.

Light Enables the Cathodic Interface Reaction Reversibility in Solid-State Lithium-Oxygen Batteries.

Limited triple-phase boundaries arising from the accumulation of solid discharge product(s) in solid-state cathodes (SSCs) pose a challenge to high-property solid-state lithium-oxygen batteries (SSLOBs). Light-assisted SSLOBs have been gradually explored as an ingenious system; however, the fundamental mechanisms of the SSCs interface behavior remain unclear. Here, we discovered that light assistance can enhance the fast inner-sphere charge transfer in SSCs and regulate the discharge products with spherical particles generated via the surface growth model. Moreover, the high photoelectron excitation and transportation capabilities of SSCs can retard cathodic catalytic decay by avoiding structural degradation of the cathode with a reduced charge voltage. The light-induced SSLOBs exhibited excellent stability (170 cycles) with a low discharge-charge polarization overpotential (0.27 V). Furthermore, transparent SSLOBs with exceptional flexibility, mechanical stability, and multiform shapes were fabricated for theory-to-practical applications in sunlight-induced batteries. Our study opens new opportunities for the introduction of solar energy into energy storage systems.

Light Enables the Cathodic Interface Reaction Reversibility in Solid‐State Lithium‐Oxygen Batteries

AbstractLimited triple‐phase boundaries arising from the accumulation of solid discharge product(s) in solid‐state cathodes (SSCs) pose a challenge to high‐property solid‐state lithium‐oxygen batteries (SSLOBs). Light‐assisted SSLOBs have been gradually explored as an ingenious system; however, the fundamental mechanisms of the SSCs interface behavior remain unclear. Here, we discovered that light assistance can enhance the fast inner‐sphere charge transfer in SSCs and regulate the discharge products with spherical particles generated via the surface growth model. Moreover, the high photoelectron excitation and transportation capabilities of SSCs can retard cathodic catalytic decay by avoiding structural degradation of the cathode with a reduced charge voltage. The light‐induced SSLOBs exhibited excellent stability (170 cycles) with a low discharge–charge polarization overpotential (0.27 V). Furthermore, transparent SSLOBs with exceptional flexibility, mechanical stability, and multiform shapes were fabricated for theory‐to‐practical applications in sunlight‐induced batteries. Our study opens new opportunities for the introduction of solar energy into energy storage systems.

Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.

Cognitive impairment is a common comorbidity of chronic pain, significantly disrupting patients' quality of life. Despite this comorbidity being clinically recognized, the underlying neuropathological mechanisms remain unclear. Recent preclinical studies have focused on the fundamental mechanisms underlying the coexistence of chronic pain and cognitive decline. Pain chronification is accompanied by structural and functional changes in the neural substrate of cognition. Based on the developments in electrophysiology and optogenetics/chemogenetics, we summarized the relevant neural circuits involved in pain-induced cognitive impairment, as well as changes in connectivity and function in brain regions. We then present the cellular and molecular alternations related to pain-induced cognitive impairment in preclinical studies, mainly including modifications in neuronal excitability and structure, synaptic plasticity, glial cells and cytokines, neurotransmitters and other neurochemicals, and the gut-brain axis. Finally, we also discussed the potential treatment strategies and future research directions.

Emergence, Pattern, and Frequency of Spontaneous Waves in Spreading Epithelial Monolayers.

A striking phenomenon of collective cell motion is that they can exhibit a spontaneously emerging wave during epithelia expansions. However, the fundamental mechanism, governing the emergence and its crucial characteristics (e.g., the eigenfrequency and the pattern), remains an enigma. By introducing a mechanochemical feedback loop, we develop a highly efficient discrete vertex model to investigate the spatiotemporal evolution of spreading epithelia. We find both numerically and analytically that expanding cell monolayers display a power-law dependence of wave frequency on the local heterogeneities (i.e., cell density) with a scaling exponent of -1/2. Moreover, our study demonstrates the quantitative capability of the proposed model in capturing distinct X-, W-, and V-mode wave patterns. We unveil that the phase transition between these modes is governed by the distribution of active self-propulsion forces. Our work provides an avenue for rigorous quantitative investigations into the collective motion and pattern formation of cell groups.

Acid-assisted subcritical blunt-tip crack propagation in carbonate rocks

AbstractSubcritical crack propagation in stressed carbonate rocks in a chemically reactive environment is a fundamental mechanism underlying many geomechanical processes frequently encountered in the engineering of geo-energy, including unconventional shale gas, geothermal energy, carbon sequestration and utilization. How a macroscopic Mode I crack propagates driven by a reactive fluid pressurizing on the crack surfaces with acidic agents diffusing into the rock matrix remains an open question. Here, the carbonate rock is modeled as an elasto-viscoplastic material with the mineral mass removal process affecting the rock properties in both elastic and plastic domains. A blunt-tip crack is considered to avoid any geometrically induced singularity problem and to allow a numerical analysis on the evolution of the chemical field being linked to the micro-cracking activities in front of the crack tip, affecting the delivery of acid. The model is capable of reproducing an archetypal three-region behavior of subcritical crack growth in a reactive environment. The crack propagation exhibits a prominent acceleration in Region III due to a two-way mutually enhancing feedback between mineral dissolution and the degradation process, which is most pronounced in front of the crack tip. With the consideration of initial imperfections in the rock, the macroscopic crack propagation is further accelerated with a secondary acceleration arising due to self-organization of micro-bands inside the chemically enabled plasticity zone.

Neuromorphic Nanoionics for Human-Machine Interaction: From Materials to Applications.

Human-machine interaction (HMI) technology has undergone significant advancements in recent years, enabling seamless communication between humans and machines. Its expansion has extended into various emerging domains, including human healthcare, machine perception, and biointerfaces, thereby magnifying the demand for advanced intelligent technologies. Neuromorphic computing, a paradigm rooted in nanoionic devices that emulate the operations and architecture of the human brain, has emerged as a powerful tool for highly efficient information processing. This paper delivers a comprehensive review of recent developments in nanoionic device-based neuromorphic computing technologies and their pivotal role in shaping the next-generation of HMI. Through a detailed examination of fundamental mechanisms and behaviors, the paper explores the ability of nanoionic memristors and ion-gated transistors to emulate the intricate functions of neurons and synapses. Crucial performance metrics, such as reliability, energy efficiency, flexibility, and biocompatibility, are rigorously evaluated. Potential applications, challenges, and opportunities of using the neuromorphic computing technologies in emerging HMI technologies, are discussed and outlooked, shedding light on the fusion of humans with machines.

Moving forward to understand the alteration of physiological mechanism by seed priming with different halo-agents under salt stress.

Soil salinity hampers the survival and productivity of crops. To minimize salt-associated damages in plant, better salt management practices in agriculture have become a prerequisite. Seed priming with different halo-agents is a technique, which improves the primed plant's endurance to tackle sodium. Salt tolerance is achieved in tolerant plants through fundamental physiological mechanisms- ion-exclusion and tissue tolerance, and salt-tolerant plants may (Na+ accumulators) or may not (Na+ excluders) allow sodium movement to leaves. While Na+ excluders depend on ion exclusion in roots, Na+ accumulators are proficient Na+ managers that can compartmentalize Na+ in leaves and use them beneficially as inexpensive osmoticum. Salt-sensitive plants are Na+ accumulators, but their inherent tissue tolerance ability and ion-exclusion process are insufficient for tolerance. Seed priming with different halo-agents aids in 'rewiring' of the salt tolerance mechanisms of plants. The resetting of the salt tolerance mechanism is not universal for every halo-agent and might vary with halo-agents. Here, we review the physiological mechanisms that different halo-agents target to confer enhanced salt tolerance in primed plants. Calcium and potassium-specific halo-agents trigger Na+ exclusion in roots, thus ensuring a low amount of Na+ in leaves. In contrast, Na+-specific priming agents favour processes for Na+ inclusion in leaves, improve plant tissue tolerance or vacuolar sequestration, and provide the greatest benefit to salt-sensitive and sodium accumulating plants. Overall, this review will help to understand the underlying mechanism behind plant's inherent nature towards salt management and its amelioration with different halo-agents, which helps to optimize crop stress performance.

Unraveling quantum coherences mediating primary charge transfer processes in photosystem II reaction center.

Photosystem II (PSII) reaction center (RC) is a unique complex that is capable of efficiently separating electronic charges across the membrane. The primary energy- and charge-transfer (CT) processes occur on comparable ultrafast timescales, which makes it extremely challenging to understand the fundamental mechanism responsible for the near-unity quantum efficiency of the transfer. Here, we elucidate the role of quantum coherences in the ultrafast energy and CT in the PSII RC by performing two-dimensional (2D) electronic spectroscopy at the cryogenic temperature of 20 kelvin, which captures the distinct underlying quantum coherences. Specifically, we uncover the electronic and vibrational coherences along with their lifetimes during the primary ultrafast processes of energy and CT. We construct an excitonic model that provides evidence for coherent energy and CT at low temperature in the 2D electronic spectra. The principles could provide valuable guidelines for creating artificial photosystems with exploitation of system-bath coupling and control of coherences to optimize the photon conversion efficiency to specific functions.

Recent Advancements in Subcellular Proteomics: Growing Impact of Organellar Protein Niches on the Understanding of Cell Biology.

The mammalian cell is a complex entity, with membrane-bound and membrane-less organelles playing vital roles in regulating cellular homeostasis. Organellar protein niches drive discrete biological processes and cell functions, thus maintaining cell equilibrium. Cellular processes such as signaling, growth, proliferation, motility, and programmed cell death require dynamic protein movements between cell compartments. Aberrant protein localization is associated with a wide range of diseases. Therefore, analyzing the subcellular proteome of the cell can provide a comprehensive overview of cellular biology. With recent advancements in mass spectrometry, imaging technology, computational tools, and deep machine learning algorithms, studies pertaining to subcellular protein localization and their dynamic distributions are gaining momentum. These studies reveal changing interaction networks because of "moonlighting proteins" and serve as a discovery tool for disease network mechanisms. Consequently, this review aims to provide a comprehensive repository for recent advancements in subcellular proteomics subcontexting methods, challenges, and future perspectives for method developers. In summary, subcellular proteomics is crucial to the understanding of the fundamental cellular mechanisms and the associated diseases.

Cryo-Electron Microscopy Reveals Na Infiltration into Separator Pore Free-Volume as a Degradation Mechanism in Na Anode:Liquid Electrolyte Electrochemical Cells.

Batteries utilizing a sodium (Na) metal anode with a liquid electrolyte are promising for affordable large-scale energy storage. However, a deep understanding of the intrinsic degradation mechanisms is limited by challenges in accessing the buried interfaces. Here, cryogenic electron microscopyof intact electrode:separator:electrode stacks is performed and degradation and failure of symmetric Na||Na coin cells occurs through the infiltration of Na metal through thepores of the separator rather than by mechanical puncturing by dendrites is revealed. It is shown the interior structure of the cell (electrode:separator:electrode) must be preserved anddeconstructing the cell into different layers for characterization results in artifacts. In intact cell stacks, minimal liquid is found between the electrodes and separator, leading to intimate electrode:separator interfaces. After electrochemical cycling, Na infiltrates into the pore free-volume, growing through the separator to create electrical shorts and degradation. The Na infiltration occurs at interfacial regions devoid of solid-electrolyte interphase (SEI), revealing SEI plays an important role in preventing Na from growing into the separator by being a physical barrier that the plated Na cannot penetrate. These results shed new light on the fundamental failure mechanisms in Na batteries and demonstrate the importance of preserving the cell structure and buried interfaces.

Microtubule length correlates with spindle length in C. elegans meiosis.

The accurate segregation of chromosomes during female meiosis relies on the precise assembly and function of the meiotic spindle, a dynamic structure primarily composed of microtubules. Despite the crucial role of microtubule dynamics in this process, the relationship between microtubule length and spindle size remains elusive. Leveraging Caenorhabditis elegans as a model system, we combined electron tomography and live imaging to investigate this correlation. Our analysis revealed significant changes in spindle length throughout meiosis, coupled with alterations in microtubule length. Surprisingly, while spindle size decreases during the initial stages of anaphase, the size of antiparallel microtubule overlap decreased as well. Detailed electron tomography shows a positive correlation between microtubule length and spindle size, indicating a role of microtubule length in determining spindle dimensions. Notably, microtubule numbers displayed no significant association with spindle length, highlighting the dominance of microtubule length regulation in spindle size determination. Depletion of the microtubule depolymerase KLP-7 led to elongated metaphase spindles with increased microtubule length, supporting the link between microtubule length and spindle size. These findings underscore the pivotal role of regulating microtubule dynamics, and thus microtubule length, in governing spindle rearrangements during meiotic division, shedding light on fundamental mechanisms dictating spindle architecture.