Core Mechanism Research Articles

Influence of Carboxylic Acid Structure on the Kinetics of Polyurethane Foam Acidolysis to Recycled Polyol.

Closed-loop recycling of plastics is needed to bridge the gap between the material demands imposed by a growing global population and the depletion of nonrenewable petroleum feedstocks. Here, we examine chemical recycling of polyurethane foams (PUFs), the sixth most produced polymer in the world, through PUF acidolysis via dicarboxylic acids (DCAs) to release recyclable polyols. Acidolysis enables recycling of the polyol component of PUFs to high-quality materials, and while the influence of DCA structure on recycled PUF quality has been reported, there are no reports that examine the influence of DCA structure on the kinetics of polyol release. Here, we develop quantitative relationships between DCA structure and PUF acidolysis function for ∼10 different DCA reagents. PUF acidolysis kinetics were quantified with ∼1 s time resolution using the rate of carbon dioxide (CO2) gas generation, which is shown to occur concomitantly with polyol release. Pseudo-zeroth-order rate constants were measured as a function of DCA composition, reaction temperature, and DCA concentration, and apparent activation barriers were extracted. Our findings demonstrate that DCA carboxyl group proximity and phase of transport are descriptors of PUF acidolysis rates, rather than expected descriptors like pK a. DCAs with closer proximity acid groups exhibited faster PUF acidolysis rate constants. Furthermore, a shrinking core mechanism effectively describes the kinetic functional form of the kinetics of PUF acidolysis by DCAs. Measurements of acidolysis kinetics for model PUF (M-PUF) and end-of-life PUF (EOL PUF) confirm the applicability of our analysis to postconsumer materials. This work provides insights into the physical and chemical mechanisms controlling acidolysis, which can facilitate the development of efficient closed-loop PUF chemical recycling schemes.

Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms.

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.

The Principle of Cortical Development and Evolution.

Human's robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes made to the cerebral cortex. This paper reviews the biology and evolution of mammalian cortical radial glial cells (primary neural stem cells) and introduces the concept that a genetically step wise process, based on a core molecular pathway already in use, is the evolutionary process that has molded cortical neurogenesis. The core mechanism, which has been identified in our recent studies, is the extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor, is an increase in SHH signaling in radial glia, that antagonizes ERK-BMP7 signaling. Finally, I propose that: (1) SHH signaling is not a key regulator of primate cortical expansion and folding; (2) human cortical radial glial cells do not generate neocortical interneurons; (3) human-specific genes may not be essential for most cortical expansion. I hope this review assists colleagues in the field, guiding research to address gaps in our understanding of cortical development and evolution.

CORE: Counteracting overwhelming requests effectively—A method for interest flooding attack mitigation in NDNoT

<p>The<strong> </strong>Named Data Network (NDN) is a promising architecture for the near future. NDN communicates by naming data, unlike IP-based Internet architecture. Architectural understandability, ease of use, security, content presentation, and simplicity of data exchange logic make this architecture preferable. The NDNoT approach, which recently combines IoT and NDN, enables Internet of Things applications using NDN naming conventions and basic data structure. However, increasing technological applications bring security vulnerabilities. In this study, we propose a new method called CORE that will secure the intended data transfer. The presented CORE mechanism was developed as a countermeasure against the Interest Flooding attack, one of the NDN security attacks. Tests were carried out in the Cooja simulation environment using three different topology scenarios. CORE’s performance metrics were evaluated based on success rate, average delay, and interest traffic. The results showed that when the CORE mechanism was active, there was an improvement in the success rate and average delay. In terms of interest traffic, at least a 70% success rate was achieved compared to scenarios in which the CORE mechanism was not operated.</p>

Bacteriocins in Cancer Treatment: Mechanisms and Clinical Potentials.

Cancer poses a severe threat to human health. Although conventional chemotherapy remains a cornerstone of cancer treatment, its significant side effects and the growing issue of drug resistance necessitate the urgent search for more efficient and less toxic anticancer drugs. In recent years, bacteriocins, antimicrobial peptides of microbial origin, have garnered significant attention due to their targeted antitumor activity. This unique activity is mainly attributed to their cationic and amphiphilic nature, which enables bacteriocins to specifically kill tumor cells without harming normal cells. When involving non-membrane-disrupting mechanisms, such as apoptosis induction, cell cycle blockade, and metastasis inhibition, the core mechanism of action is achieved by disrupting cell membranes, which endows bacteriocins with low drug resistance and high selectivity. However, the susceptibility of bacteriocins to hydrolysis and hemolysis in vivo limits their clinical application. To overcome these challenges, structural optimization of bacteriocins or their combination with nanotechnology is proposed for future development. This review aims to study the mechanism of action and current research status of bacteriocins as anticancer treatments, thus providing new insights for their clinical development and application.

Structural idiosyncrasies of glycyl T-box riboswitches among pathogenic bacteria.

T-box riboswitches are widespread bacterial regulatory noncoding RNAs that directly interact with tRNAs and switch conformations to regulate the transcription or translation of genes related to amino acid metabolism. Recent studies in Bacilli have revealed the core mechanisms of T-boxes that enable multivalent, specific recognition of both the identity and aminoacylation status of the tRNA substrates. However, in-depth knowledge on a vast number of T-boxes in other bacterial species remains scarce, although a remarkable structural diversity, particularly among pathogens, is apparent. In the present study, analysis of T-boxes that control the transcription of glycyl-tRNA synthetases from four prominent human pathogens revealed significant structural idiosyncrasies. Nonetheless, these diverse T-boxes maintain functional T-box:tRNAGly interactions both in vitro and in vivo. Probing analysis not only validated recent structural observations, but also expanded our knowledge on the substantial diversities among T-boxes and suggest interesting distinctions from the canonical Bacilli T-boxes. Surprisingly, some glycyl T-boxes seem to redirect the T-box trajectory in the absence of recognizable K-turns or contain Stem II modules that are generally absent in glycyl T-boxes. These results consolidate the notion of a lineage-specific diversification and elaboration of the T-box mechanism and corroborate the potential of T-boxes as promising species-specific RNA targets for next-generation antibacterial compounds.

The implementation of Public-Private Partnership in China: A sustainable pathway?

The organizational forms of infrastructure in China are divided into two categories, the traditional Public Procurement Model (PUB) model and Public-Private Partnership(PPP) model. The main difference is the separation or binding of the construction and operation phases. A systematic understanding is needed of how Chinese local governments choose between these two models. In this paper, we take public capital congestion and local government objectives as the entry point to study the effects of both on PPP choice. Firstly, by constructing an endogenous economic growth model under the PPP model, and comparing it with the model under the PUB model, this paper initially explains how the rise in public capital congestion affects the choice of the PPP by growth-oriented local governments. Then the data from prefecture-level cities from 2009-2018 are utilized to conduct empirical tests. We find that urban economic growth pressures have a positive effect on the choice of PPP when the congestion of public capital increases. Furthermore, the implementation of PPP is indeed conducive to economic performance, and its core mechanism is to provide more infrastructure (like roads) rather than tax competition. The PPP model is more sustainable. We are the first to employ both modeling approach and the empirical research to address the implementation of Public-Private Partnership in China. And we have systematically analyzed the conditions and results of PPP selection by local governments. It formulates the Chinese PPP theory.

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.