Distinct Functions Research Articles

China's National Education Conference Matters: Major Education Discursive Blueprinting in 2024

Purpose This study aims to analyze the blueprint for China's future education development outlined in China's National Education Conference of September 2024, and to examine the role of conference speeches in shaping China's education policymaking. Design/Approach/Methods This study thematically analyzed both the conference speech and the related press releases. Findings Regarding the speech content, five key tasks outlined in the conference speeches for building a strong education system by 2035 were identified. These tasks address the public's demand for high-quality education and the needs of national development. Regarding the speech structure, the conference speeches were structured into four main parts, each serving a distinct function in shaping education policy. Originality/Value This study contributes to a deeper understanding of China's recent policy directions for education development. It also sheds light on the discursive blueprinting function of conference speeches in China's education policymaking process.

Extracellular vimentin is a damage-associated molecular pattern protein serving as an agonist of TLR4 in human neutrophils

BackgroundVimentin is a type III intermediate filament protein that plays an important role in cytoskeletal mechanics. It is now known that vimentin also has distinct functions outside the cell. Recent studies show the controlled release of vimentin into the extracellular environment, where it functions as a signaling molecule. Such observations are expanding our current knowledge of vimentin as a structural cellular component towards additional roles as an active participant in cell signaling.MethodsOur study investigates the immunological roles of extracellular vimentin (eVim) and its citrullinated form (CitVim) as a damage-associated molecular pattern (DAMP) engaging the Toll-like receptor 4 (TLR4) of human neutrophils. We used in vitro assays to study neutrophil migration through endothelial cell monolayers and activation markers such as NADPH oxidase subunit 2 (NOX2/gp91phox). The comparison of eVim with CitVim and its effect on human neutrophils was extended to the induction of extracellular traps (NETs) and phagocytosis of pathogens.ResultsBoth eVim and CitVim interact with and trigger TLR4, leading to increased neutrophil migration and adhesion. CitVim stimulated the enhanced migratory ability of neutrophils, activation of NF-κB, and induction of NET formation mainly mediated through reactive oxygen species (ROS)-dependent and TLR4-dependent pathways. In contrast, neutrophils exposed to non-citrullinated vimentin exhibited higher efficiency in favoring pathogen phagocytosis, such as Escherichia coli and Candida albicans, compared to CitVim.ConclusionsOur study identifies new functions of eVim in its native and modified forms as an extracellular matrix DAMP and highlights its importance in the modulation of immune system functions. The differential effects of eVim and CitVim on neutrophil functions highlight their potential as new molecular targets for therapeutic strategies aimed at regulation of neutrophil activity in different pathological conditions. This, in turn, opens new windows of therapeutic intervention in inflammatory and immunological diseases characterized by immune system dysfunction, in which eVim and CitVim play a key role.

Role of metabolism, resistance, and/or antagonism as drivers of endomicrobiomes assemblage in Origanum heracleoticum L

The understanding of selective forces driving the compartmentalization of microbiota in plants remains limited. In this study, we performed a phenotypic characterization of bacterial endophytes isolated from the medicinal plant Origanum heracleoticum, together with the determination of the antibiotic resistance profiles and the antagonistic interactions of communities within and across different plant organs. Results revealed organ-related differences in the metabolic capabilities of bacteria, with those associated with stems displaying the highest metabolic activity for carbon sources. Contrarily, the patterns of antibiotic resistance appeared closely aligned with the taxonomical classification of the endophytes. The presence of antagonistic interactions, likely spurred by resource limitations, favor bacteria exhibiting greater metabolic plasticity. In conclusion, this research advances our comprehension of the intricate dynamics between plants and their associated microbiota, indicating that its composition is mainly influenced by forces contributing to the selection of distinct functions and phenotypic traits.

Improving the Reliability of, and Confidence in, DFT Functional Benchmarking through Active Learning.

Validating the performance of exchange-correlation functionals is vital to ensure the reliability of density functional theory (DFT) calculations. Typically, these validations involve benchmarking data sets. Currently, such data sets are usually assembled in an unprincipled manner, suffering from uncontrolled chemical bias, and limiting the transferability of benchmarking results to a broader chemical space. In this work, a data-efficient solution based on active learning is explored to address this issue. Focusing─as a proof of principle─on pericyclic reactions, we start from the BH9 benchmarking data set and design a chemical reaction space around this initial data set by combinatorially combining reaction templates and substituents. Next, a surrogate model is trained to predict the standard deviation of the activation energies computed across a selection of 20 distinct DFT functionals. With this model, the designed chemical reaction space is explored, enabling the identification of challenging regions, i.e., regions with large DFT functional divergence, for which representative reactions are subsequently acquired as additional training points. Remarkably, it turns out that the function mapping the molecular structure to functional divergence is readily learnable; convergence is reached upon the acquisition of fewer than 100 reactions. With our final updated model, a more challenging─and arguably more representative─pericyclic benchmarking data set is curated, and we demonstrate that the functional performance has changed significantly compared to the original BH9 subset.

The multifaceted role of XCL1 in health and disease.

The chemokine XC motif chemokine ligand 1 (XCL1) is an unusually specialized member of a conserved family of around 50 small, secreted proteins that are best known for their ability to stimulate the directional migration of cells. All chemokines adopt a very similar folded structure that binds a specific G protein-coupled receptor (GPCR), and most chemokines bind extracellular matrix glycosaminoglycans, often in a dimeric or oligomeric form. Owing in part to the lack of a disulfide bond that is conserved in all other chemokines, XCL1 interconverts between two distinct structures with distinct functions. One XCL1 fold resembles the structure of all other chemokines (chemokine fold), while the other does not (alternate fold). The chemokine fold of XCL1 displays high affinity for the GPCR XCR1, while the alternative fold binds GAGs and exhibits antimicrobial activity. Although the canonical role of XCL1 as a CD8+ dendritic cell chemoattractant was defined more than a decade ago, the misconception that XCL1 is a lymphocyte-specific chemoattractant still prevails in the recent literature. This review aims to highlight the structure-guided functions of XCL1 and reclarify its immunological role. In addition, the implications of this metamorphic chemokine in vaccine development and emerging functions in the nervous system will be explored.

Augmenting flexibility: mutual inhibition between inhibitory neurons expands functional diversity.

Recent advances in microcircuit analysis of nervous systems have revealed a plethora of mutual connections between inhibitory interneurons across many different species and brain regions. The abundance of these mutual connections has not been fully explained. Strikingly, we show that neural circuits with mutually inhibitory connections are able to rapidly and flexibly switch between distinct functions. That is, multiple functions coexist for a single set of synaptic weights. Here, we develop a theoretical framework to explain how inhibitory recurrent circuits give rise to this flexibility and show that mutual inhibition doubles the number of cusp bifurcations in small neural circuits. As a concrete example, we study a class of functional motifs we call coupled recurrent inhibitory and recurrent excitatory loops (CRIRELs). These CRIRELs have the advantage of being both multi-functional and controllable, performing a plethora of functions, including decisions, memory, toggle, and so forth. Finally, we demonstrate how mutual inhibition maximizes storage capacity for larger networks.

Lineage-specific duplication and functional diversification of DOPA-decarboxylase genes in the Gryllidae family, as revealed in Gryllus bimaculatus.

The DOPA-decarboxylase (DDC) gene is crucial for dopamine synthesis and influences various biological functions in insects, including body coloration, behavior, learning, and sleep. However, its evolutionary impact remains largely unexplored. This study reports on the tandem duplication of two bona fide ddc genes (ddc1 and ddc2) in the Gryllidae cricket family. We herein investigated the function of ddc1 and ddc2 using Gryllus bimaculatus (Gb) as a model. Our results revealed that Gb'ddc1 was expressed systemically, with its expression being higher immediately after molting compared to the stage following melanin pigmentation. In homozygous knockout mutants of Gb'ddc1, generated via CRISPR/Cas9, reduced body color pigmentation and had translucent cuticles, decreased dopamine levels, and over-accumulated DOPA. These mutants died shortly after hatching, likely due to cuticle defects, underscoring the essential role of dopamine, produced by Gb'ddc1, in melanin synthesis. Conversely, Gb'ddc2 expression was confined to the ovary and was not up-regulated after molting. Homozygous knockout mutants of Gb'ddc2 exhibited no body color defects, whereas hatchability and embryonic development rates were significantly reduced. Interestingly, dopamine levels in the ovaries were significantly elevated in Gb'ddc2 mutants. This suggests that normal ovarian dopamine levels, modulated by Gb'ddc2, are vital for fertility maintenance. The function of Gb'ddc2 differs from that of typical ddc, indicating neofunctionalization through evolutionary duplication. Overall, Gb'ddc1 and Gb'ddc2 have distinct functions, and precise regulation of ovarian dopamine levels using these two ddc genes may have enhanced cricket fertility.

The losses of Lem2 and Bqt4 exhibit similar impacts on intracellular movement dynamics in fission yeast.

Quantifying movement dynamics inside a cell provides a deeper understanding of cellular functions. The 3-dimensional live observation has been widely applied to movement dynamics research. Fission yeast is an ideal model organism for studying cellular movement dynamics. In this study, we developed a novel method to quantify intracellular movement in wild-type cells, using a vector originating from the cell center as the movement reference. This method obtained more movement information, including movement direction, compared to the previously reported method, which used a single point as the movement reference. Using this new method, we quantified intracellular movement in wild type, bqt4Δ, and lem2Δ cells across various parameters. We characterized the nature of intracellular movement in wild-type cells and revealed that the losses of Bqt4 and Lem2, two inner membrane proteins, impact intracellular movement in a similar pattern, although distinct differences were also observed. These findings offer new insights into the study of the overlapping and distinct functions of Bqt4 and Lem2. This study provides a novel method for evaluating the intracellular movement dynamics, contributing to the understanding of intracellular movement nature, biophysical properties, and the evaluation of genes or proteins from an intracellular movement perspective.

Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review.

Tumor-associated macrophages (TAMs) are present in and are important components of the tumor microenvironment (TME). TAMs differentiate into 2 functionally distinct morphologies, classically activated (M1)-type TAMs and alternatively activated (M2)-type TAMs, when stimulated by different cytokines. The 2 types of TAMs exhibit distinct properties and functions. M1 TAMs secrete high levels of pro-inflammatory and chemotactic factors, exerting proinflammatory, antitumor effects. Conversely, M2 TAMs alter the extracellular matrix, facilitate cellular immune escape, and stimulate tumor angiogenesis, thereby promoting anti-inflammatory responses and tumor growth. The ratio of M1 TAMs to M2 TAMs in the TME is closely related to the prognosis of the tumor. Tumor cells and other cells in the TME can regulate the polarization of TAMs and thus promote tumor progression through the secretion of various substances; however, polarized TAMs can also act on various cells in the TME through the secretion of exosomes, thus forming a positive feedback loop. Therefore, modulating the phenotype of TAMs in the TME or blocking the polarization of M2 TAMs might be a new approach for cancer treatment. However, the intracellular signaling pathways involved in the polarization of TAMs are poorly understood. The AKT signaling pathway is an important signaling pathway involved in the polarization, growth, proliferation, recruitment, and apoptosis of TAMs, as well as the action of TAMs on other cells within the TME. This paper reviews the AKT signaling pathway in the polarization of TAMs and the regulation of the TME and provides new ideas for tumor immunotherapy.

A Review Study of Srotas CoArrelation between Modern Science

Srotas are terms in Ayurveda that refer to tiny channels within the body that carry out various functions such as the circulation of micronutrients, detoxification, and supply of nutrition. Each specific Srotas carries out distinct functions based on its location and distribution throughout different body regions. The anatomical and physiological aspects of Srotas are crucial for maintaining an individual's overall health, as any disruption in their anatomical alignment or improper physiological functions can result in various health problems. Conditions related to Srotas, known as Srotas vyadhi, can arise, therefore. infrequent respiration, excessive thirst, anorexia, Adhimamsa, Asthisula and accumulation of toxins, etc. Considering the physiological and pathological importance of Srotas present article described Ayurveda and modern perspective on Srotas and diseases related to malfunctioning of Srotas.

Platelet membrane-cloaked biomimetic nanoparticles for targeted acute lung injury therapy.

Acute lung injury (ALI) is a medical condition characterized by significant morbidity and elevated mortality rates; however, to date, there are no clinically approved pharmacological interventions that are both safe and effective for its treatment. In the pathophysiology of ALI, a robust inflammatory response is a critical factor. Dexamethasone (Dex), a potent glucocorticoid, is commonly employed in clinical settings to manage inflammatory conditions. However, the frequent or high-dose administration of corticosteroids can result in significant adverse effects and long-term complications. In this study, we have developed a biomimetic anti-inflammatory nanosystem, designated PM-LPs@Dex, aimed at treating ALI. This system leverages the inherent affinity of platelets for sites of inflammation, alongside the advantageous drug encapsulation properties of liposomes (LPs). By harnessing the suitable physicochemical characteristics of LPs and the distinctive biological functions of platelet membranes (PM), PM-LPs@Dex is capable of stable and sustained drug release in vitro. Experimental results regarding cellular uptake and biodistribution reveal that PM-LPs@Dex is preferentially internalized by inflammatory cells and exhibits enhanced accumulation in inflamed lung tissue compared to LPs@Dex. Pharmacokinetic studies displayed that PM-LPs@Dex showed prolonged circulation time in blood. Additionally, pharmacodynamic assessments demonstrate that PM-LPs@Dex significantly mitigates the severity of ALI, as evidenced by reductions in pulmonary edema, tissue pathology, bronchoalveolar lavage cell counts, protein concentration, and levels of inflammatory cytokines. Notably, PM-LPs@Dex also exhibits favorable biocompatibility. This research is anticipated to contribute novel strategies for the safe and effective targeted management of inflammatory diseases.

Is this scenery worth exploring? Insight into the visual encoding of navigating ants.

Solitary foraging insects like desert ants rely heavily on vision for navigation. While ants can learn visual scenes, it is unclear what cues they use to decide if a scene is worth exploring at the first place. To investigate this, we recorded the motor behavior of Cataglyphis velox ants navigating in a virtual reality set-up (VR) and measured their lateral oscillations in response to various unfamiliar visual scenes under both closed-loop and open-loop conditions. In naturalistic-looking panorama, ants display regular oscillations as observed outdoors, allowing them to efficiently scan the scenery. Manipulations of the virtual environment revealed distinct functions served by dynamic and static cues. Dynamic cues, mainly rotational optic flow, regulated the amplitude of oscillations but not their regularity. Conversely, static cues had little impact on the amplitude but were essential for producing regular oscillations. Regularity of oscillations decreased in scenes with only horizontal, only vertical or no edges but was restored in scenes with both edge types together. The actual number of edges, the visual pattern heterogeneity across azimuths, the light intensity or the relative elevation of brighter regions did not affect oscillations. We conclude that ants use a simple but functional heuristic to determine if the visual world is worth exploring, relying on the presence of at least two different edge orientations in the scene.

Identification of intestinal mediators of Caenorhabditis elegans DBL-1/BMP immune signaling shaping gut microbiome composition.

The composition of the gut microbiome is determined by a complex interplay of diet, host genetics, microbe-microbe interactions, abiotic factors, and stochasticity. Previous studies have demonstrated the importance of host genetics in community assembly of the Caenorhabditis elegans gut microbiome and identified a central role for DBL-1/BMP immune signaling in determining the abundance of gut Enterobacteriaceae. However, the effects of DBL-1 signaling on gut bacteria were found to depend on its activation in extra-intestinal tissues, highlighting a gap in our understanding of the proximal factors that determine microbiome composition. In the present study, we used RNA-seq gene expression analysis of wildtype, dbl-1 and sma-3 mutants, and dbl-1 over-expressors to identify candidate DBL-1/BMP targets that may mediate the pathway's effects on gut commensals. Bacterial colonization experiments in mutants, or following RNAi-mediated knock-down of candidate genes specifically in the intestine, demonstrated their local contribution to intestinal control of Enterobacteriaceae abundance. Furthermore, epistasis analysis suggested that these contributions were downstream of the DBL-1 pathway, together suggesting that examined candidates were intestinal effectors and mediators of DBL-1 signaling, contributing to the shaping of gut microbiome composition.IMPORTANCECompared to the roles of diet, environmental availability, or lifestyle in determining gut microbiome composition, that of genetic factors is the least understood and often underestimated. The identification of intestinal effectors of distinct molecular functions that control enteric bacteria offers a glimpse into the genetic logic of microbiome control as well as a list of targets for future exploration of this logic.

Doing ‘detective work’ to find a cancer: how are non-specific symptom pathways for cancer investigation organised, and what are the implications for safety and quality of care? A multisite qualitative approach

BackgroundOver the past two decades, the UK has actively developed policies to enhance early cancer diagnosis, particularly for individuals with non-specific cancer symptoms. Non-specific symptom (NSS) pathways were piloted and...

Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3

Apical and basal dendrites of pyramidal neurons receive anatomically and functionally distinct inputs, implying compartment-level functional diversity during behavior. To test this, we imaged in vivo calcium signals from soma, apical dendrites, and basal dendrites in mouse hippocampal CA3 pyramidal neurons during head-fixed navigation. To capture compartment-specific population dynamics, we developed computational tools to automatically segment dendrites and extract accurate fluorescence traces from densely labeled neurons. We validated the method on sparsely labeled preparations and synthetic data, predicting an optimal labeling density for high experimental throughput and analytical accuracy. Our method detected rapid, local dendritic activity. Dendrites showed robust spatial tuning, similar to soma but with higher activity rates. Across days, apical dendrites remained more stable and outperformed in decoding of the animal’s position. Thus, population-level apical and basal dendritic differences may reflect distinct compartment-specific input-output functions and computations in CA3. These tools will facilitate future studies mapping sub-cellular activity and their relation to behavior.

Recombinant SpTransformer proteins bind to specific sites on sea urchin phagocytes and modulate SpTransformer gene expression and immune responsiveness

IntroductionThe California purple sea urchin, Strongylocentrotus purpuratus, relies exclusively on an innate immune system to survive in its pathogen rich marine environment. Central to this defense is the SpTransformer (SpTrf) gene family that is unique to the euechinoid group of echinoderms. These genes were initially identified based on their striking upregulation in response to immune challenge. The SpTrf gene family encodes structurally similar proteins with a wide range of sequence diversity within and among individual sea urchins. A recombinant (r)SpTrf protein interacts specifically with a variety of non-self targets. Other rSpTrf proteins cross-linked to inert beads show distinct functions for cell binding and augmenting phagocytosis . However, whether the rSpTrf proteins bind to sea urchin phagocytes, and the cellular consequences of binding are largely unexplored. MethodsrSpTrf protein binding to, and responses by phagocytes was investigated by cytology, flow cytometry, binding competitions using In-cell ELISA, and gene expression analyses. ResultsSoluble rSpTrf proteins bind specifically and exclusively to both live and fixed polygonal and small phagocytes. The different rSpTrf proteins appear to bind shared receptor(s) or other form of cell surface binding site. The phagocyte response to bound rSpTrf proteins culminates in modulated expression of the SpTrf gene family as well as other immune-related genes. ConclusionsThese findings underscore the multifaceted and dynamic functions of SpTrf proteins within the innate immune system of the purple sea urchin. Their varied functions enable a robust immune response while also providing a unique modulatory mechanism by which response levels are controlled and adjusted to the level of the foreign threat.

Epigenetic modulation of social cognition: exploring the impact of methylation in brain-derived neurotrophic factor and oxytocin receptor genes across sex

Social cognition, which ranges from recognizing social cues to intricate inferential reasoning, is influenced by environmental factors and epigenetic mechanisms. Notably, methylation variations in stress-related genes like brain-derived neurotrophic factor (BDNF) and the oxytocin receptor (OXTR) are linked to distinct social cognitive functions and exhibit sex-specific differences. This study investigates how these methylation differences affect social cognition across sexes, focusing on both perceptual and inferential cognitive levels. Social cognitive abilities were assessed using the Korean version of the Reading the Mind in the Eyes Test (K-RMET) and Brune’s story-based Theory of Mind tasks (ToM-PST). DNA methylation levels in BDNF and OXTR were analyzed for correlations with performance on these cognitive tasks in a cohort of male and female participants. A moderation model was applied to determine if sex moderates the relationship between social cognition and DNA methylation. No significant overall correlation was found between social cognition and DNA methylation across participants. However, sex-specific correlations were identified, including a negative impact of BDNF methylation on K-RMET scores in males, and a similar effect of OXTR methylation on ToM-PST scores in females. The findings underscore the complex relationship between epigenetic modifications and social cognition, revealing sex-specific effects and highlighting the importance of considering sex in epigenetic studies of social cognition. This research contributes to understanding how epigenetic factors, influenced by sex, shape social cognitive processes and supports the need for sex-specific therapeutic approaches.

Distinct functions of CD4+ and CD8+ regulatory T cells in autoimmunity.

Distinct functions of CD4+ and CD8+ regulatory T cells in autoimmunity.

Warming-driven migration of enterotypes mediates host health and disease statuses in ectotherm Litopenaeus vannamei

Global warming has threatened all-rounded hierarchical biosphere by reconstructing eco-structure and bringing biodiversity variations. Pacific white shrimp, a successful model of worldwide utilizing marine ectothermic resources, is facing huge losses due to multiple diseases relevant to intestinal microbiota (IM) dysbiosis during temperature fluctuation. However, how warming mediates shrimp health remains poorly understood. Herein, a global shrimp IM catalogue was conducted via 1,369 shrimp IM data from nine countries, including 918 samples from previously published data and 451 generated in the study. Shrimp IMs were stratified into three enterotypes with distinctive compositions and functions, dominated by Vibrio, Shewanella and Candidatus Bacilloplasma, which showed an obvious distribution bias between enterotypes and diseases. The ratio of Vibrio and Candidatus Bacilloplasma was a crucial indicator for shrimp health. Moreover, temperature was the most driving factor for microbial composition, which potentially led to the migration of enterotypes, and high probability of white feces syndrome and low risk of hepatopancreas necrosis syndrome. Collectively, the warming-driven enterotypes mediated shrimp health, which exemplified the causal relationship between temperature rising and ectothermic animals’ health. These findings enlarged the cognition of shrimp health culture management from a microecological perspective, and alerted the inevitable challenge of global warming to ectothermic animals.

Exploring a Novel Approach to Deferred Nörlund Statistical Convergence

This study introduces novel concepts of convergence and summability for numerical sequences, grounded in the newly formulated deferred Nörlund density, and explores their intrinsic connections to symmetry in mathematical structures. By leveraging symmetry principles inherent in sequence behavior and employing two distinct modulus functions under varying conditions, profound links between sequence convergence and summability are established. The study further incorporates lacunary refinements, enhancing the understanding of Nörlund statistical convergence and its symmetric properties. Key theorems, properties, and illustrative examples validate the proposed concepts, providing fresh insights into the role of symmetry in shaping broader convergence theories and advancing the understanding of sequence behavior across diverse mathematical frameworks.