Core Mechanism Research Articles

Unifying Fourteen Post-Hoc Attribution Methods With Taylor Interactions.

Various attribution methods have been developed to explain deep neural networks (DNNs) by inferring the attribution/importance/contribution score of each input variable to the final output. However, existing attribution methods are often built upon different heuristics. There remains a lack of a unified theoretical understanding of why these methods are effective and how they are related. Furthermore, there is still no universally accepted criterion to compare whether one attribution method is preferable over another. In this paper, we resort to Taylor interactions and for the first time, we discover that fourteen existing attribution methods, which define attributions based on fully different heuristics, actually share the same core mechanism. Specifically, we prove that attribution scores of input variables estimated by the fourteen attribution methods can all be mathematically reformulated as a weighted allocation of two typical types of effects, i.e., independent effects of each input variable and interaction effects between input variables. The essential difference among these attribution methods lies in the weights of allocating different effects. Inspired by these insights, we propose three principles for fairly allocating the effects, which serve as new criteria to evaluate the faithfulness of attribution methods. In summary, this study can be considered as a new unified perspective to revisit fourteen attribution methods, which theoretically clarifies essential similarities and differences among these methods. Besides, the proposed new principles enable people to make a direct and fair comparison among different methods under the unified perspective.

Novel candidate metastasis-associated genes for synovial sarcoma.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

Protocol for a telephonic mixed methods study to understand needs and find solutions for bereaved dementia caregivers

IntroductionMost caregivers of people living with dementia will experience bereavement within 10 years, but study of and support for their needs rarely persists following the death of their care recipients....

A novel Transformer-based model with large kernel temporal convolution for chemical process fault detection

Fault detection and diagnosis (FDD) is an essential tool to ensure safety in chemical industries, and nowadays, many reconstruction-based deep learning methods are active in fault detection. However, many algorithms still suffer from not ideal actual performance. Inspired by the core mechanism of Transformer and large kernel convolution, this paper proposes a novel model combining variate-centric Transformer with large kernel temporal convolution. Variate-centric Transformer depends on self-attention to capture the multivariate correlations of input data, and large kernel temporal convolution collects period information to summarize temporal features. A benchmark dataset Tennessee Eastman process (TEP) and experiment data from the microreactor process are used to test the performance of fault detection. Compared with other reconstruction-based methods, results demonstrate that our model achieves a higher fault detection rate and a lower detection latency, and shows a significant potential for process safety.

Exploring the action mechanism of Gegensan in the treatment of alcoholic liver disease based on network pharmacology and bioinformatics.

Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the therapeutic mechanism and targets of action of GGS on alcoholic liver disease utilizing network pharmacology and bioinformatics. The active ingredients in GGS were screened in the literature and databases, and common targets of ALD were then obtained from public databases to construct the network diagram of traditional Chinese medicine-active ingredient targets. Based on the common targets, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to find target enrichment pathways, and the core targets were screened out by combining differential analysis and protein-protein interaction network analysis. Molecular docking was performed to verify the binding effect between the core targets and the corresponding active ingredients. ALD and GGS have 84 common targets, corresponding to 91 active ingredients. After subsequent differential analysis and protein-protein interaction network analysis, 10 core targets were identified. Gene Ontology and KEGG enrichment analyses showed that the main BPs corresponding to the common targets included the response to lipopolysaccharide, inflammatory response, etc. The KEGG pathways involved in the regulation of the common targets included the lipid-atherosclerosis pathway and the alcoholic liver disease pathway, etc. Further molecular docking showed that the core targets CYP1A1, CYP1A2, CXCL8, ADH1C, MMP1, SERPINE1, COL1A1, APOB, MMP1, and their corresponding 4 active ingredients, Naringenin, Kaempferol, Quercetin, and Stigmasterol, have a greater docking potential. The above results suggest that GGS can regulate lipid metabolism and inflammatory response in the ALD process, and alleviate the lipid accumulation and oxidative stress caused by ethanol. This study analyzed the core targets and mechanisms of action of GGS on ALD, which provides certain theoretical support for the further development of GGS in the treatment of ALD, and provides a reference for the subsequent research on the treatment of ALD.

Convergent evolution of desiccation tolerance in grasses.

Desiccation tolerance has evolved repeatedly in plants as an adaptation to survive extreme environments. Plants use similar biophysical and cellular mechanisms to survive life without water, but convergence at the molecular, gene and regulatory levels remains to be tested. Here we explore the evolutionary mechanisms underlying the recurrent evolution of desiccation tolerance across grasses. We observed substantial convergence in gene duplication and expression patterns associated with desiccation. Syntenic genes of shared origin are activated across species, indicative of parallel evolution. In other cases, similar metabolic pathways are induced but using different gene sets, pointing towards phenotypic convergence. Species-specific mechanisms supplement these shared core mechanisms, underlining the complexity and diversity of evolutionary adaptations to drought. Our findings provide insight into the evolutionary processes driving desiccation tolerance and highlight the roles of parallel and convergent evolution in response to environmental challenges.

Effect of interface properties between functionalized cellulose nanocrystals and tricalcium silicate on the early hydration mechanism of cement

The hydration process is a critical stage in the development of the properties of cement-based materials，however, the influence of cellulose nanocrystals (CNC) on cement during the early hydration is controversial. This study uses pure tricalcium silicate (C3S) as the object to analyze the influence of carboxyl CNC (CCNC) and sulfonic CNC (SCNC) on hydration parameters such as hydration rate, types, quality, and pore structure of hydration products during the early hydration period. The dissolution of C3S and the interaction between fluids and minerals at the C3S/CNC interface is the core mechanism of the early hydration. Ultraviolet and energy spectrum analyzed adsorption between CNC and C3S from a physical perspective, and molecular dynamics simulations deeply discussed the adsorption behavior between C3S/Water/CNC at nano-scale. The results show that CNC prolongs the hydration induction and acceleration period, delays the early hydration of C3S; CCNC exhibits a more significant effect than SCNC. Under the action of Ca-O and hydrogen bonds, CNC will adsorb on the surface of C3S and cover its surface, reducing the number of waters on the surface of C3S. Hydrophilic CNC molecules attract water molecules close to the CNC chain, and solidifying water molecules prevents it from entering the hydration surface. CNC also restricts the diffusion of Ca2+ on the surface of C3S to outside, improving the stability of Ca-O coordination, promoting the accumulation of hydration products at the C3S surface, and inhibiting the dissolution of C3S. Understanding the effect of functionalized CNCs on the diffusion and sedimentation mechanism of water molecules and Ca2+ during hydration can provide insights for guiding the design of nanomaterials with strong compatibility with cement systems and enlarging the application of functionalized nanomaterials in cement-based materials engineering fields.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo

BackgroundMost tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown.ResultsHere, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition.ConclusionsOur study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom’s cell membrane.

Self-construal modulates default mode network connectivity in refugees with PTSD

BackgroundWhile self-construal and posttraumatic stress disorder (PTSD) are independently associated with altered self-referential processes and underlying default mode network (DMN) functioning, no study has examined how self-construal affects DMN connectivity in PTSD. MethodsA final sample of 93 refugee participants (48 with DSM-5 PTSD or sub-syndromal PTSD and 45 matched trauma-exposed controls) completed a 5-minute resting state fMRI scan to enable the observation of connectivity in the DMN and other core networks. A self-construal index was calculated by substracting scores on the collectivistic and individualistic sub-scales of the Self Construal Scale. ResultsIndependent components analysis identified 9 active networks-of-interest, and functional network connectivity was determined. A significant interaction effect between PTSD and self-construal index was observed in the anterior ventromedial DMN, with spatial maps localizing this to the left ventromedial prefrontal cortex (vmPFC), extending to the ventral anterior cingulate cortex. This effect revealed that connectivity in the vMPFC showed greater reductions in those with PTSD with higher levels of collectivistic self-construal. LimitationsThis is an observational study and causality cannot be assumed. The specialized sample of refugees means that the findings may not generalize to other trauma-exposed populations. ConclusionsSuch a finding indicates that self-construal may shape the core neural architecture of PTSD, given that functional disruptions to the vmPFC underpin the core mechanisms of extinction learning, emotion dysregulation and self-referential processing in PTSD. Results have important implications for understanding the universality of neural disturbances in PTSD, and suggest that self-construal could be an important consideration in the assessment and treatment of post-traumatic stress reactions.

Retinomorphic X-ray detection using perovskite with hydrion-conductive organic cations

X-ray detection is crucial across various sectors, but traditional techniques face challenges such as inefficient data transmission, redundant sensing, high power consumption, and complexity. The innovative idea of a retinomorphic X-ray detector shows great potential. However, its implementation has been hindered by the absence of active layers capable of both detecting X-rays and serving as memory storage. In response to this critical gap, our study integrates hybrid perovskite with hydrion-conductive organic cations to develop a groundbreaking retinomorphic X-ray detector. This novel device stands at the nexus of technological innovation, utilising X-ray detection, memory, and preprocessing capabilities within a single hardware platform. The core mechanism underlying this innovation lies in the transport of electrons and holes within the metal halide octahedral frameworks, enabling precise X-ray detection. Concurrently, the hydrion movement through organic cations endows the device with short-term resistive memory, facilitating rapid data processing and retrieval. Notably, our retinomorphic X-ray detector boasts an array of formidable features, including reconfigurable short-term memory, a linear response curve, and an extended retention time. In practical terms, this translates into the efficient capture of motion projections with minimal redundant data, achieving a compression ratio of 18.06% and an impressive recognition accuracy of up to 98.6%. In essence, our prototype represents a paradigm shift in X-ray detection technology. With its transformative capabilities, this retinomorphic hardware is poised to revolutionize the existing X-ray detection landscape.

Hepatocyte-specific Selenoi deficiency predisposes mice to hepatic steatosis and obesity.

Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.

Auditory Processing of Intonational Rises and Falls in German: Rises Are Special in Attention Orienting.

This article investigates the processing of intonational rises and falls when presented unexpectedly in a stream of repetitive auditory stimuli. It examines the neurophysiological correlates (ERPs) of attention to these unexpected stimuli through the use of an oddball paradigm where sequences of repetitive stimuli are occasionally interspersed with a deviant stimulus, allowing for elicitation of an MMN. Whereas previous oddball studies on attention toward unexpected sounds involving pitch rises were conducted on nonlinguistic stimuli, the present study uses as stimuli lexical items in German with naturalistic intonation contours. Results indicate that rising intonation plays a special role in attention orienting at a pre-attentive processing stage, whereas contextual meaning (here a list of items) is essential for activating attentional resources at a conscious processing stage. This is reflected in the activation of distinct brain responses: Rising intonation evokes the largest MMN, whereas falling intonation elicits a less pronounced MMN followed by a P3 (reflecting a conscious processing stage). Subsequently, we also find a complex interplay between the phonological status (i.e., accent/head marking vs. boundary/edge marking) and the direction of pitch change in their contribution to attention orienting: Attention is not oriented necessarily toward a specific position in prosodic structure (head or edge). Rather, we find that the intonation contour itself and the appropriateness of the contour in the linguistic context are the primary cues to two core mechanisms of attention orienting, pre-attentive and conscious orientation respectively, whereas the phonological status of the pitch event plays only a supplementary role.

Selfless Minds, Unlimited Bodies?: Homeostatic Bodily Self-Regulation in Meditative Experiences

In this paper I focus on somatosensory attenuation of bodily signals as a core mechanism underlying the phenomenon of 'losing' one's sense of self in meditation. Specifically, I argue that somatosensory attenuation of bodily signals does not make the bodily self 'disappear' experientially. Rather, during the subjectively reported phenomena of 'self-loss', bodily sensory signals are self-attenuated, physiologically, and experientially processed in the background. Hence the term 'losing' the self or 'selfless' states may be misleading in describing these peculiar types of experiences reported during deep meditative states. What is 'lost', I claim, is a particular, ordinary way to explicitly, mentally model oneself in relation to the body and the world. Yet, the experience of being a living body, i.e.a self-organizing organism, is never 'lost' in this process. The proposal is that the explicit feeling of selfless minds may be tacitly accompanied by the implicit feeling of unlimited body, as two sides of the same coin.

Different systems, similar experiences: felt accountability in labor platforms and traditional organizations

Accountability systems are the core mechanisms by which workers are motivated and controlled. Sourced from customer ratings and powered by algorithmic control, the accountability systems of labor platforms are a substantial departure from those designed by human resources departments for use in traditional organizations. While considerable attention has been paid to the impacts of algorithmic control, it is ultimately a worker’s felt accountability that influences their behaviors and attitudes in the workplace. However, to date, there has been an absence of theory that explains how labor platforms’ accountability systems result in felt accountability. As such, our paper starts with an examination of the underexplored link between accountability systems and workers’ felt accountability. We next argue that features of the accountability environment (source, intensity, salience, and focus) can be described both objectively and phenomenologically. We then make use of this distinction to detail the differences between the accountability systems of labor platforms and traditional organizations and theorize about resultant differences in workers’ felt accountability. Finally, we discuss implications for the accountability and human resource management literatures, including the importance of the unexpected similarity between traditional workers’ and platform workers’ felt accountability.

Leveraging the Dominant Pole: How Champions of an Industry-Wide Environmental Alliance Navigate Coopetition Paradoxes

Companies increasingly collaborate with competitors to innovate, minimize risks, and address sustainability crises. However, these alliances often falter or fail due to challenges arising from coopetition paradoxes—contradictory yet interdependent tensions between competition and cooperation. Extant research predominantly focuses on addressing these paradoxes through seeking a stable balance between competition and cooperation; however, we lack in-depth processual understandings of how to navigate these paradoxes as they shift over time. To address this gap in the literature, we analyze longitudinal data over the 3 years it took to establish Canada’s Oil Sands Innovation Alliance (COSIA), the unlikely alliance across 13 competitive Canadian oil sands companies to improve their industry’s environmental performance. We noted the role of competition, which we label as the dominant pole—the more powerful of two paradoxical poles—and identify leveraging the dominant pole as a core mechanism for navigating intensifying coopetition paradoxes. Rather than diminishing the dominant competition pole, alliance champions leveraged competition to enable cooperation aided by a paradox mindset. These findings reorient coopetition scholarship away from seeking stability between the two forces, toward a processual understanding of how to navigate the shifting coopetition paradoxes in alliances over time.

Invariant representations in abstract concept grounding - the physical world in grounded cognition.

Grounded cognition states that mental representations of concepts consist of experiential aspects. For example, the concept "cup" consists of the sensorimotor experiences from interactions with cups. Typical modalities in which concepts are grounded are: The sensorimotor system (including interoception), emotion, action, language, and social aspects. Here, we argue that this list should be expanded to include physical invariants (unchanging features of physical motion; e.g., gravity, momentum, friction). Research on physical reasoning consistently demonstrates that physical invariants are represented as fundamentally as other grounding substrates, and therefore should qualify. We assess several theories of concept representation (simulation, conceptual metaphor, conceptual spaces, predictive processing) and their positions on physical invariants. We find that the classic grounded cognition theories, simulation and conceptual metaphor theory, have not considered physical invariants, while conceptual spaces and predictive processing have. We conclude that physical invariants should be included into grounded cognition theories, and that the core mechanisms of simulation and conceptual metaphor theory are well suited to do this. Furthermore, conceptual spaces and predictive processing are very promising and should also be integrated with grounded cognition in the future.

Camera-Based Safety System for Optical Wireless Power Transmission Using Dynamic Safety-Distance

This paper introduces a new safety approach for Optical Wireless Power Transmission (OWPT), a technology that is integral to the new kinds of Wireless Power Transmission technology (WPT). It starts from the fundamental configuration of the current OWPT system, addressing the safety concerns related to lasers by involving laser irradiation hazards, laser exposure regulation and guidelines, and a comparison with other safety methods. A camera-based OWPT safety system focused on the emission control of the light source is proposed, and it utilizes a depth camera and finely tuned computer vision-based control program. Through meticulous system design and experiments, the proposed system can detect moving objects in a limited indoor environment and control the laser/LED light transmission according to the object’s velocity dynamically. Various functions and exclusive improvements towards OWPT operation are mentioned, and Dynamic Safety-Distance is proposed as the core mechanism of the safety system. Through on-site experiments, indoor safety control and system operation’s evaluation are discussed, acknowledging both the advantages and limitations of the proposed safety system. This paper concludes with suggestions for further developments in camera-based OWPT safety incorporating the concept of Automatic Emission Control.

Inducing ferroptosis by traditional medicines: a novel approach to reverse chemoresistance in lung cancer

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy is the first-line treatment for the most common type of lung cancer, i.e., non-small-cell lung cancer (NSCLC), but its therapeutic efficiency is limited by chemotherapeutic resistance. Therefore, it is vital to develop effective therapeutic modalities that bypass the common molecular mechanisms associated with chemotherapeutic resistance. Ferroptosis is a form of non-apoptotic regulated cell death characterized by iron-dependent lipid peroxidation (LPO). Ferroptosis is crucial for the proper therapeutic efficacy of lung cancer-associated chemotherapies. If targeted as a novel therapeutic mechanism, ferroptosis modulators present new opportunities for increasing the therapeutic efficacy of lung cancer chemotherapy. Emerging studies have revealed that the pharmacological induction of ferroptosis using natural compounds boosts the efficacy of chemotherapy in lung cancer or drug-resistant cancer. In this review, we first discuss chemotherapeutic resistance (or chemoresistance) in lung cancer and introduce the core mechanisms behind ferroptosis. Then, we comprehensively summarize the small-molecule compounds sourced from traditional medicines that may boost the anti-tumor activity of current chemotherapeutic agents and overcome chemotherapeutic resistance in NSCLC. Cumulatively, we suggest that traditional medicines with ferroptosis-related anticancer activity could serve as a starting point to overcome chemotherapeutic resistance in NSCLC by inducing ferroptosis, highlighting new potential therapeutic regimens used to overcome chemoresistance in NSCLC.

Ultrafast fabrication of W/Cu composites using flash sintering

When the proportion of reinforcing phases is high and the wettability between the secondary phase and the metal is poor, preparing fully dense particle-reinforced metal matrix composites becomes challenging. This study employs the flash sintering method to prepare fully dense WCu20 composite materials within a few tens of seconds. It is found that during the “thermal runaway' process of flash sintering, the Cu phase undergoes rapid melting and solidification, and the core mechanism of material densification is that pressure causes Cu liquid to quickly fill the gaps between tungsten particles. Pressure not only promotes the contraction of the framework formed by tungsten particles but also facilitates the complete filling of gaps within the tungsten frameworks by the Cu liquid and promotes the rapid expulsion of bubbles from the Cu liquid, thereby achieving rapid densification of WCu20 composite materials. Moreover, an increase in the temperature enhances the fluidity of the Cu liquid, which aids in filling the gaps between tungsten particles and promotes the discharge of bubbles from the Cu liquid. Flash sintering is a common technique for the sintering and densification of metal powders, suitable for the rapid preparation of various metal matrix composites.

Immunotherapy in the context of sepsis-induced immunological dysregulation.

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.