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Toward a modeling and analysis method of cyber-physical systems architecture evolution based on bigraph
Loss of ARID1A leads to a cold tumor phenotype via suppression of IFNγ signaling
Abstract The collapse of inflammatory signaling that recruits cytotoxic immune cells to the tumor microenvironment contributes to the immunologically cold tumor phenotype in neuroblastoma (NB) and is a barrier to NB immunotherapy. Multiple studies have reported that MYCN amplification, a trait of high-risk NB, correlates with a loss of inflammatory signaling; but MYCN also correlates with 1p36 deletions in NB where the SWI/SNF chromatin remodeling complex subunit ARID1A (1p36.11) is located. ARID1A is known to support inflammatory signaling in adult cancers but its role in NB inflammatory signaling is unexplored. We find MYCN overexpression causes a stronger inflammatory response to interferon-gamma (IFNγ). ARID1A knockdown causes a weaker inflammatory response and reduces IFNγ induced gene signatures for the transcription factor interferon response factor 1 ( IRF1 ). We found ARID1A is a functional interactor of IRF1 by co-immunoprecipitation studies, and ARID1A silencing causes loss of activating chromatin marks at the IRF1 target gene CXCL10 . We model that IRF1 uses ARID1A containing SWI/SNF to promote CXCL10 in response to IFNγ. Our work clarifies that the loss of ARID1A, which tightly associates with MYCN amplification, causes reduced inflammatory signaling. This work finds that ARID1A is a critical regulator of inflammatory signaling in NB and provides rationale for testing immune therapies in MYCN amplified NB that are effective in adult ARID1A mutated cancers.
Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design
Abstract Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.
Preclinical evaluation of a novel antibody–drug conjugate OBI-992 for Cancer therapy
Aluminum doped zinc oxide nanoplatelets based sensor with enhanced hydrogen sulfide detection
Zein–sodium caseinate–diosmin nanoparticles as a promising anti-cancer agent with targeted efficacy against A2780 cell line
Machine learning reveals glycolytic key gene in gastric cancer prognosis
Psychopathic personality traits are associated with experimentally induced approach and appraisal of fear-evoking stimuli indicating fear enjoyment
Abstract The extent to which deficits in the perception and experience of fear contribute to psychopathic symptoms is an ongoing matter of debate. Traditional theories emphasize diminished threat processing as the core fear deficit in psychopathic individuals, whereas recent approaches, such as the fear enjoyment hypothesis (FEH), propose that anomalies in the subjective experience of fear are related to interpersonal-affective psychopathic traits. In order to test predictions of the FEH, we conducted an online experimental study to examine whether approach and avoidance tendencies in response to fear-eliciting stimuli are related to specific psychopathic traits (interpersonal-affective symptoms and boldness). We expected these traits to be associated with faster approach towards and slower avoidance of fear-evoking images in an approach-avoidance task (AAT). In a community-based sample of 211 individuals (69% female), self-reported interpersonal-affective traits predicted more positive appraisal ratings of and a faster approach towards fear-evoking stimuli in the AAT paradigm. The link between psychopathic traits and faster approach towards fear images could not be explained by traits related to impulsiveness or impaired inhibitory control. The present findings shed light on the subjective appraisal of fear-evoking situations by individuals with elevated psychopathic traits. Implications on etiological models of psychopathy are discussed.
Early-life gut microbiome is associated with behavioral disorders in the Rio birth cohort
Insight into the inhibitory activity of mangiferin and Silybin against HER2 and EGFR using theoretical and experimental approaches
Abstract Despite the advances made in diagnosing and treating breast cancer, it continues to pose a significant threat to women’s health. High-risk mutations can lead to high resistance to current treatments and poor prognosis. Therefore, new treatment strategies are needed. Mangiferin and silybin, two natural substances obtained from plants, have demonstrated encouraging results as anticancer drugs. This study investigated the activity of these compounds against two therapeutic targets, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR). We assessed the binding affinity and stability of these compounds with the active sites of wild-type and mutated HER2 and EGFR by using computational screening techniques, namely molecular docking, density functional theory, and molecular dynamics (MD) simulations with the MMGBSA method. We used molecular docking, triplicate MD simulations summing 300 ns each, and density functional theory analysis to estimate the binding mechanism of mangiferin and silybin inside the wild-type and mutated EGFR and HER2 active regions. Moreover, an in vitro experiment showed that mangiferin and silybin inhibited the growth of two HER2-positive breast cancer cell lines, BT-474 and SK-BR-3, at micromolar concentrations. These findings suggest the potential for developing novel anticancer therapies that specifically target EGFR and HER2.
Enhancing object pose estimation for RGB images in cluttered scenes
High-throughput workflow for cultivation and characterization of gut microbiota strains with anti-inflammatory properties and metabolite signature associated with gut-brain communication
Soil characteristics and bacterial community characteristics of shelterbelts of different tree species in black soil region of China
Abstract To understand how surface soil characteristics and bacterial communities are affected by the establishment of farmland shelterbelts. Five types of shelterbelts in the mid-west of Heilongjiang Province China were selected for the study. The physicochemical characteristics and bacterial diversity of Populus×xiaohei monoculture (X), Larix gmelinii monoculture (L), Pinus sylvestris monoculture (Z), Pinus sylvestris and Larix gmelinii mixed forest (ZL), and Fraxinus mandshurica and Larix gmelinii mixed forest (SL), as well as in fallow land (CK), were measured and analyzed, respectively. Soil physicochemical characteristics and bacterial diversity (via high-throughput sequencing) were analyzed across 0–20 cm depths. Results showed that shelterbelts significantly altered soil characteristics: X increased moisture, ammonium nitrogen, and microbial biomass nitrogen but reduced aeration. ZL exhibited the highest bacterial richness and enhanced water-holding capacity, aeration, and nutrient retention (total organic carbon, nitrogen, phosphorus). ZL outperformed monocultures in promoting soil health, with available potassium (0–10 cm) and pH (10–20 cm) identified as key drivers of bacterial community variation. Unique genera like Krasilnikovia and Rubrobacter dominated shelterbelt soils, reflecting species-specific effects. Shelterbelts induced surface accumulation of nitrate-nitrogen, potassium, and microbial biomass carbon. Overall, Pinus sylvestris and Larix gmelinii mixed forests optimized soil structure, microbial diversity, and nutrient cycling, underscoring their ecological benefits for sustainable agroforestry. This study highlights the critical role of mixed forest shelterbelts in enhancing soil health and microbial biodiversity, which are essential for sustainable land management practices in the black soil region of China.
Study on the predictive value of preoperative CT features for the mitotic index of GIST based on the nomogram
Study on the law of stress distribution in the presence of remaining coal pillar in a close-distance coal seam and the reasonable location of the roadway
ELTIRADS framework for thyroid nodule classification integrating elastography, TIRADS, and radiomics with interpretable machine learning
Metabolomics insights into the protective molecular mechanism of Vaccinium myrtillus against oxidative stress in intestinal cells
Abstract Blueberry (Vaccinium myrtillus L.) is a rich source of secondary metabolites known for their potent antioxidant, anti-inflammatory, and cytoprotective properties. These compounds are essential in neutralizing reactive oxygen species (ROS), which are implicated in oxidative stress-related diseases. In this study, we induced oxidative stress in IEC-6 small intestine cells using hydrogen peroxide (H2O2), creating a cellular model to investigate the biochemical response. The obtained results showed that a blueberry extract (BLUBE) significantly exhibited strong antioxidant capacity, as evidenced by DPPH, FRAP and ABTS in vitro tests. Additionally, BLUBE effectively inhibited the release of reactive species in cells and enhanced cytoprotective response, as indicated by improved wound healing and clonogenic potential reduction of stress fibers rearrangement and apoptosis. Metabolomic analysis, specifically High-Resolution Mass Spectrometry (HR-MS), was employed to elucidate the metabolic alterations associated with the protective activity of BLUBE against oxidative stress in IEC-6 cells. Chemometric approaches were applied to preprocess the data, explore variability, and identify systematic biases, ensuring the removal of batch effects and other experimental artifacts. A Partial Least Squares Discriminant Analysis classification model confirmed clear group stratifications with high accuracy (98.75 ± 2.31%), sensitivity, and specificity, aiding in the identification of significant metabolites for pathway enrichment analysis. Key metabolic pathways, including sphingolipid metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism, were significantly modulated, supporting the biochemical basis of BLUBE’s protective effects. In fact, BLUBE was able to partially reverse the downregulation of these pathways, effectively reducing oxidative stress and promoting cell survival. This study highlights the power of HR-MS-based metabolomics in uncovering the mechanisms of nutraceuticals and emphasizes the potential of BLUBE as a protective agent for oxidative stress-related diseases. It also underscores the growing significance of metabolomics in the food and pharmaceutical industries.