Migration Pathways Research Articles

The influence of post-glacial migration and hybridization on the gene pool of marginal Quercus pubescens populations in Central Europe.

In Central Europe, the drought-tolerant downy oak (Quercus pubescens) is at the northern edge of its natural distribution range, often growing in small and spatially isolated populations. Here, we elucidate how the population genetic structure of Central European Q. pubescens was shaped by geographic barriers, genetic drift and introgression with the closely related sessile oak (Q. petraea). 27 Q. pubescens populations from the northern margin of Q. pubescens' natural distribution range were sampled. Based on 16 nuclear microsatellite markers (nSSRs), Bayesian clustering and distance-based analyses were performed to determine the intraspecific genetic structure and to identify genetic barriers. To identify drivers of introgression with Q. petraea, generalised linear models were applied to link levels of introgression with environmental conditions. To track post-glacial migration routes, the spatial distribution of haplotypes based on 8 chloroplast microsatellite markers (cpSSRs) was investigated. Based on nSSRs, the study populations of Q. pubescens were divided into a western and an eastern genetic cluster. Within these clusters, more pronounced genetic substructure was observed in the west, probably due to a rugged topography and limited gene flow. Introgression from Q. petraea was more prevalent at wetter and north-exposed sites and in the west. The identified cpSSR haplotypes followed known migration pathways. Our results suggest two late-glacial refugia in or near the southwestern Alps and the southeastern Alps as potential sources for post-glacial migration. Although some genetic exchange is evident in Northern Italy, south of the Alps, the two clusters remain distinct at a large scale. Landscape features and introgression with Q. petraea shaped the genetic substructure at a smaller scale. Our study provides a comprehensive overview of the genetic structure of Q. pubescens in Central Europe, relevant for conservation.

Temporal Trajectories: A Comparative Analysis of Mexican and Vietnamese Students’ Strategies in the Canadian Edugration System

This paper compares Mexican and Vietnamese international students’ and graduates’ migration decision-making while navigating Canadian policies merging international higher education and migration or the “edugration system.” While this system offers a delimited temporal framework and a linear pathway to permanent residency (PR) for international students; we argue that it does not align with the temporality of international students’ and graduates’ plans and aspirations. We draw from interviews conducted with 15 Mexican students and six graduates as well as 10 Vietnamese students and 11 graduates. Our findings highlight participants’ migration strategies for transnational social mobility, from childhood to postgraduation. These strategies unfold distinctively in time, depending on the region of origin. Rather than embracing the homogenizing edugration time frame, there is a need to emphasize international students’ and graduates’ own temporality to foster a nuanced and critical understanding of their migration pathways.

Investigation of HOTAIR rs12826786, rs920778 and rs4759314 variants with breast cancer susceptibility and clinicopathological characteristics in a Mexican population

BackgroundBreast cancer (BC) is a multifactorial disease of unknown etiology whose major risk factors are genetic alterations of cell proliferation and migration pathways. HOX transcript antisense RNA gene (HOTAIR) is a long non-coding RNA (lncRNA) related to cell proliferation, progression, invasion, metastasis, and poor survival of multiple cancers, including BC. Controversial results have emerged on the association between breast cancer risk in multiple ethnicities. This study explores the association of rs12826786, rs920778, and rs4759314 variants in the HOTAIR gene in BC patients. MethodsDNA of peripheral blood samples was obtained from 588 women (289 patients and 299 control females). Genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The association was calculated using the odds ratio (OR) test. P-values were adjusted by the Bonferroni test (0.016). ResultsThe rs12826786 (C>T), rs920778 (T>C), and rs4759314 (A>G) variants were associated with BC and with TNM stage, histologic type, and histologic molecular subtype (P=0.001). Likewise, the haplotype C-T-G in the HOTAIR gene (rs12826786-rs920778-rs4759314) was significantly related to BC (OR= 5.44, 95%, CI= 2.22-13.32, P= 0.001). ConclusionThe results suggest that rs12826786, rs920778, and rs4759314 variants in HOTAIR significantly influence breast cancer risk. Micro-abstractHOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA strongly correlated with the tumor grade and prognosis of various carcinomas, including breast cancer (BC). In this study, we analyzed the association of the rs12826786, rs920778, and rs4759314 variants in the HOTAIR gene and observed an increased susceptibility to BC and clinicopathological characteristics in a Mexican population.

Synergizing internal electric field and quantum-confined stark effect for customized carrier dynamics in two-dimensional heterostructures

The customized transport of carriers within two-dimensional (2D) heterostructures (HSs) is instrumental in enhancing the electronic and optoelectronic functionalities. Internal electric field (IEF) has opened potential pathways for manipulating carrier migration behaviors, unlocking diverse applications such as photocatalysts, solar cells, photodetectors, and other photoelectrochemical (PEC) devices. While it is intuitively understood that the orientation of IEF governs the direction of carrier transport, there are notable discrepancies between theoretical predictions and experimental results concerning the dynamics of photogenerated carriers. In this work, based on several polar HSs with tunable IEF, we unveiled the role of IEF in the carrier dynamics within these HSs. Our findings show that IEF not only regulates the band alignment of the HSs but also manipulates the electron–phonon (e-ph) coupling. The synergistic interplay of IEF and the quantum-confined Stark effect determines the dynamics of photoexcited carriers, facilitating the transition between type-Ⅱ and Z-scheme. These insights offer prospective strategies for tailoring interlayer charge carrier migration pathways and the photocatalytic activity of HSs.

Post-nesting migrations of green turtles from Aldabra Atoll, Seychelles: satellite tracking, flipper tag returns and marine protected areas

To effectively implement protective measures for migratory species such as marine turtles, knowledge of their breeding grounds, foraging areas, migratory pathways and possible threats encountered is required. Aldabra Atoll, a UNESCO World Heritage site in Seychelles, hosts and protects one of the largest nesting populations of green turtles Chelonia mydas in the Western Indian Ocean. We satellite tracked 21 post-nesting green turtles during 2011-2014 (n = 8) and in 2022 (n = 13). Nineteen turtles were tracked beyond Aldabra and took 8-49 d to reach their final recorded locations, travelling 743-2552 km along distinct routes, each taking a unique path to widely dispersed coastal sites in Tanzania, Madagascar, Somalia, Kenya, Mozambique and Seychelles, highlighting the connectivity of the region through one large rookery. When compared to the locations of 54 international flipper tag returns from Aldabra females recorded since the 1980s, there was consistency in the use of Tanzania, Kenya, Mozambique, Somalia and Madagascar as foraging destination countries for Aldabra turtles. However, satellite tracking expanded the countries used as foraging sites to include Seychelles and elevated the relative importance of remote sites for which fishermen were unlikely to report intercepted flipper tags—especially Somalia, northern Madagascar and distant offshore foraging habitat within Seychelles. The end points for >40% of the turtles were within or nearby marine protected areas (MPAs) in Madagascar, Mozambique, Tanzania and Seychelles, 5 (26.3%) within MPAs and 3 (15.8%) <25 km away from MPAs. Eleven (57.9%) turtles travelled through MPAs after leaving the Aldabra protected zone. There is further opportunity to increase the protection and connectivity of foraging areas by expanding existing MPAs. Identifying foraging hot spots within the region by pooling data from other important breeding grounds should be a priority to focus conservation efforts on migratory corridors and the status and state of those foraging areas.

Solar System Migration Points to a Renewed Concept: Galactic Habitable Orbits

Abstract Astrophysical evidence suggests that the Sun was born near 5 kpc from the Galactic center, within the corotation radius of the Galactic bar, around 6–7 kpc. This presents challenges for outward migration due to the Jacobi energy constraint, preventing stars from easily overcoming the corotation barrier. In this study, we use test particle simulations to explore two possible migration pathways for the Sun: a “trapped” scenario, where the Sun's orbit was influenced by a slowing Galactic bar, and an “untrapped” scenario driven by dynamic spiral arms. Our results demonstrate that both mechanisms can explain how the Sun migrated from its birth radius (≈5 kpc) to its current orbital radius around 8.5–9 kpc. Furthermore, we investigate the environmental changes experienced by the Sun along these migration pathways, focusing on variations in radiation hazards and comet fluxes, which may have impacted planetary habitability. These findings highlight the dynamic nature of galactic habitability, emphasizing that the path a star takes within the Milky Way can significantly affect its surrounding environment and the potential for life. We propose a new concept of “Galactic habitable orbits,” which accounts for evolving galactic structures and their effects on stellar and planetary systems. This work contributes to a deeper understanding of the solar system's migration and its implications for habitability within the Milky Way.

Comprehensive Analysis of RNA Methylation Regulated gene signature and Immune Infiltration in Ischemia/Reperfusion-Induced Acute Kidney Injury.

The morbidity and mortality of acute kidney injury (AKI) are increasing. Epigenetic regulation and immune cell infiltration are thought to be involved in the AKI. However, the relationship between epigenetic regulation and immune cell infiltration in AKI has not been elucidated. This study was conducted to identify the differentially expressed genes (DEGs), differentially expressed RNA methylation genes (DEMGs), and infiltrated immune cells in the kidneys of ischemia reperfusion induced- acute kidney injury (IRI-AKI) models and further explore their relationships in IRI-AKI. This is a bioinformatic analysis using R programming language in 3 selected IRI-AKI datasets from the Gene Expression Omnibus (GEO) database, including 16 IRI-AKI kidney tissues and 10 normal kidney tissues. The DEGs were screened, and enrichment pathways were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The DEMGs and core DEMGs were identified using the R package. The ROC curve was plotted to predict disease occurrence of 7 core DEMGs. The correlation of 7 core DEMGs and other genes was analyzed using Pearson's correlation test. The gene set enrichment analysis (GSEA) of each DEMG was conducted using the R package. The upstream miRNAs and transcript factors of 7 core DEMGs were predicted based on the RegNetwork database and Cytoscape software. The STITCH database was used to predict the possible binding compounds of the 7 core DEMGs. Immune cell infiltration in kidney tissues between the IRI-AKI group and control group was evaluated using the R package. A total of 2367 DEGs were obtained, including 1180 upregulated and 1187 downregulated genes in IRI-AKI kidney associated with the cell structure, proliferation, molecule binding/interaction, and signaling pathways such as the leucocyte migration and chemokine signaling pathways. Ten DEMGs were identified, with Ythdf1, Rbm15, Trmt6, Hnrnpc, and Dnmt1 being significantly upregulated, while Lrpprc, Cyfip2, Mettl3, Ncbp2, and Nudt7 were significantly downregulated in IRI-AKI tissues. The molecules interacting with 7 core DEMGs were identified. Significant changes in the infiltration of 8 types of immune cells were observed in IRI-AKI kidneys compared to normal controls. The significant correlation between 6 core DEMGs and the infiltration of immune cells was observed. IRI may induce AKI through RNA methylation to regulate the expression of genes involved in immune cell infiltration.

Methane sealed due to the formation of gas hydrate system in the South China Sea

Although the release of methane into oceans and potentially the atmosphere could accelerate climate change, detailed investigations on the gas source from deep-buried strata and its migration through the gas hydrate stability zone (GHSZ) to the seafloor are limited. These studies are often hindered by the presence of diffracted waves and inaccuracies in seismic velocity models, leading to poor seismic imaging that hampers the understanding of gas sources, migration pathways, and gas hydrate accumulation. In the study, we utilize the technique of common scatter point (CSP) gathers to build an accurate velocity model and obtain high-quality images for a complex gas-hydrate and natural-gas petroleum system. The CSP processing enables the accurate migration of reflected and diffracted waves, resulting in improvements in signal-to-noise ratio and lateral resolution. The improved seismic images offer clearer visualization of various petroleum elements. Specifically, we can identify the top of the hydrate zone and base of the free gas zone within a shallow-buried hydrate system, fault geometries within the free gas zone, a middle-buried natural gas reservoir, gas chimneys as migration pathways, and the deep-buried source rock strata beneath the intrusive volcanic rocks. As a result, we reveal a joint prospect of natural-gas reservoir and gas-hydrate system in the deep-water region of the South China Sea. Our results suggest that methane in the natural gas reservoir has migrated upwardly into the hydrate system, and it is unlikely to leak into the water column.

Aligned Hollow Silicon Nanorods Containing Ionic Liquid Enhanced Solid Polymer Electrolytes with Superior Cycling and Rate Performance.

The low lithium-ion conductivity of polyethylene oxide (PEO)-based polymer electrolytes limits their application in solid-state lithium batteries and related fields. Here, ionic liquids (ILs) are injected into hollow silicon nanorods (HSNRs) to prepare a composite solid polymer electrolyte (CSPE) with aligned HSNRs containing ILs (F-ILs@HSNRs). Applying a magnetic field promoted uniform dispersion and orientation of F-ILs@HSNRs in CSPE. The addition of F-ILs@HSNRs reduced PEO crystallinity and formed Li+ transport pathways at the F-ILs@HSNRs/PEO interface. Calculations and multi-physics simulations reveal that ILs within F-ILs@HSNRs contribute most to lithium-ion conduction, followed by the F-ILs@HSNRs/PEO interface. When F-ILs@HSNRs are arranged perpendicular to the electrodes, the CSPE exhibits the shortest Li+ migration pathways, resulting in stable and efficient lithium-ion conduction. The conductivity (2.14 × 10-4 S cm-1) and lithium-ion migration number tLi+ (0.307) are the highest, being 125 times and 184% higher, respectively, than those of PEO-LiTFSI, when compared to CSPEs with randomly arranged or parallel-aligned F-ILs@HSNRs. Furthermore, Li|CSPE|Li batteries and LiFePO4|CSPE|Li batteries display stable cycling for over 2000h, with coulombic efficiency approaching 100%. Excellent electrochemical reversibility is also confirmed in the rate performance test.

Design and Development of g-C3N4/ZnO/CdS Ternary Photocatalyst for the Removal of Environmentally Hazardous Organic Dyes under Visible Light

The processing of wastewater has emerged as a primary focus of research owing to the unavailability of clean water to satisfy the current population’s needs. In this work, a ternary nano-photocatalyst, g-C3N4/ZnO/CdS exhibiting visible light activity has been fabricated via a dual-step process that involved a pyrolytic transformation of urea to g-C3N4 subsequently followed by the solid state mechanochemical method to fabricate g-C3N4/ZnO/CdS. The synthesized nanomaterial underwent characterization using advanced techniques such as XRD, FTIR, FE-SEM/EDAX and UV-DRS techniques. The decomposition of Indigo Carmine dye was performed under the illumination of visible light, resulting in 99.6% degradation using a 50-mg photocatalytic dosage. Kinetic studies indicate that the photodegradation process followed pseudo-first-order where the phenomenon of adsorption adhered to the Langmuir–Hinshelwood model. This work attempted the generation of a multi pathway of electron migration by combining more than one Type-II heterojunction, which can effectively delay the electron-carrier recombination.

Global distribution prediction and ecological conservation of basking shark (Cetorhinus maximus) under integrated impacts

Global climate change presents substantial threats to marine ecosystems, with particularly profound impacts on widely distributed migratory species. The basking shark (Cetorhinus maximus), the second-largest fish species, faces significant conservation challenges due to overfishing, habitat degradation, and climate change, necessitating urgent research to address knowledge gaps in its spatial distribution and interactions with changing marine environments. This study employs various environmental variables and distribution data to construct a global species distribution model for basking sharks, predicting their distribution patterns under current and future climate scenarios. The results indicate that chlorophyll, sea surface temperature, silicate and mixed layer depth are the primary factors determining habitat suitability for basking sharks. Under high-emission scenarios (Shared Socioeconomic Pathway, SSP5–8.5), our model predicts a shift toward the higher latitudes of the northern hemisphere in basking shark habitats, including temperate and sub-Arctic waters. Ecological corridor analysis identifies critical migratory pathways and pinch points, emphasizing the importance of incorporating the effects of climate change and human activities in the formulation of conservation strategies. The finding underscores the importance of integrated conservation strategies, highlighting how positive human interventions can aid in accurately identifying critical ecological corridors to ensure the long-term survival of the basking shark. Adaptive, science-based conservation measures are crucial to mitigating the effects of climate change and human activities, supporting the resilience of marine ecosystems.

MiR-101-3p Promotes Tumor Cell Proliferation and Migration via the Wnt Signal Pathway in MNNG-Induced Esophageal Squamous Cell Carcinoma.

N-methyl-n'-nitroso-n'-nitroso guanidine (MNNG) can induce esophageal squamous cell carcinoma (ESCC), and microRNAs are associated with the development of ESCC and may serve as potential tumor prognostic markers. Thus, the aim of this study was to evaluate the potential function of miR-101-3p in MNNG-induced ESCC. An investigation of risk factors in patients with ESCC was carried out and the concentration of nine nitrosamines in urine samples was detected by the SPE-GC-MS technique. Then, we performed cancer tissue gene sequencing analysis, and RT-qPCR verified the expression level of miR-101-3p. Subsequently, the relationship between miR-101-3p potential target genes and the ESCC patients' prognosis was predicted. Finally, we investigated the function of miR-101-3p in MNNG-induced ESCC pathogenesis and the regulatory mechanism of the signaling pathway by in vivo and in vitro experiments. The results revealed that high dietary nitrosamine levels are high-risk factors for ESCC. MiR-101-3p is down-regulated in ESCC tissues and cells, and its potential target genes are enriched in cell migration and cancer-related pathways. MiR-101-3p target genes include AXIN1, CK1, and GSK3, which are involved in the regulation of the Wnt signaling pathway. MiR-101-3p overexpression promotes apoptosis and inhibits the proliferation and migration of Eca109 cells. The Wnt pathway is activated after subchronic exposure to MNNG, and the Wnt pathway is inhibited by the overexpression of miR-101-3p in Eca109 cells. Down-regulated miR-101-3p may exert tumor suppressive effects by regulating the Wnt pathway and may be a useful biomarker for predicting ESCC progression.

Characterisation and Clinical Relevance of Tertiary Lymphoid Structures in Primary Biliary Cholangitis

ABSTRACTBackground and AimsThe pathological characteristics of lymphocyte infiltration in the hepatic portal tracts of patients with primary biliary cholangitis (PBC) remain unclear. Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues associated with the exacerbation of autoimmune reactions. Here, we evaluate the role of TLSs in PBC and investigate their potential therapeutic value.MethodsWe recruited 75 patients with PBC and 53 control patients with liver biopsies who were followed more than 2 years. TLSs and their maturity were identified by the amount and spatial distribution of immune cells. Bulk RNA sequencing of liver was performed in PBC patients with different TLS maturity. The sphingosine‐1‐phosphate receptor (S1PRs) modulator FTY720 was administered to dnTGFβRII mice to assess the role of TLSs on cholangitis.ResultsTLSs presented in 61.3% (46/75) of liver tissues from patients with PBC, including 26 patients with mature TLS (mTLS) and 20 patients with immature TLS (imTLS). The proportion of mTLS was higher in PBC compared with chronic hepatitis B and autoimmune hepatitis. PBC patients with mTLS exhibited the highest serum levels of biochemical indicators, immune globulin and proportions of liver cirrhosis. Gene sets for lymphocyte migration and chemokine signalling pathways were enriched in patients with PBC presenting with TLS. FTY720 inhibited TLS formation and relieved cholangitis and fibrosis in dnTGFβRII mice.ConclusionTLSs are characteristics of lymphocyte accumulation in the portal tracts of PBC, of which the maturity of TLSs correlates with the inflammation and fibrosis of PBC. Targeting TLSs formation is a potential treatment of PBC.

Multi-stage hydrothermal activity affecting the early Jurassic K7 coal seam from the Gaosheng coal Mine, Sichuan Basin, southwest China: Evidence from whole-rock geochemistry and C-O-Sr isotopes in authigenic carbonates

Hydrothermal fluid is one of the major sources of elevated concentrations of elements in coals from southwestern China. However, the sources, timing, migration pathways of hydrothermal fluids remain unclear. This study investigated the petrology, mineralogy, elemental geochemistry of whole rocks, and isotope geochemistry (δ13C, δ18O, and 87Sr/86Sr) of carbonate minerals, to reveal the sources and migration of fluids associated with hydrothermal mineralization within the K7 coal seam from northeastern Sichuan Basin, China. This seam was deposited in an intermontane basin under fresh-water conditions. It contains a complex epigenetic mineral assemblage including carbonates, quartz, pyrophyllite, clay, and minor sulfides and sulfates (gypsum, barite). Syngenetic siderite from the roof and floor mudstones with relatively high 87Sr/86Sr values (0.710993 and 0.710994) was deposited from fresh water. The δ18OVPDB and δ13CVPDB values (from −16.4 ‰ to −13.8 ‰ and from −11.7 ‰ to −8.1 ‰, respectively) of epigenetic calcite and ankerite in the coal indicate their formation from hydrothermal fluids originating from igneous, organic-sedimentary, and, less significantly, marine-carbonate sources. The low 87Sr/86Sr values (0.708556 to 0.708870) and positive Eu anomaly in coal further indicate the influence of hydrothermal fluids. Elevated Sr/Ba ratios (0.9–1.5) and enriched Ca, Fe, and Mg in the lowermost seam section are attributed to the exfiltration of fluids along coal seam boundaries. The fluids probably penetrated the Mesozoic strata of the northeastern Sichuan Basin through fractures connected with the deep-seated detachment faults. This faulting was associated with Palaeo Pacific-Plate subduction and the Yanshanian post-collisional strike-slip movements in the East China region.

Optimization method for predicting coal reservoir fractures in the Laochang area of Eastern Yunnan using paleotectonic stress inversion

IntroductionCoal reservoir fractures serve as critical storage spaces and migration pathways for coalbed methane (CBM), significantly influencing CBM enrichment. The characteristics of coal reservoir fracture development can be obtained using traditional simulation methods, but these still have shortcomings. This work presents an optimization approach for the traditional method.MethodsThis study introduces an optimization approach for traditional methods with two novel contributions. This study integrates the simulation of tectonic stress fields with fracture prediction, using surface sandstone fractures as constraints to reconstruct the paleostress field of the coal seam, while also accounting for the influence of coal thickness on fracture development to calculate fracture density.ResultsThe predicted fracture density results were validated against measured values from the Bailongshan mine and Xiongdong coal mine with a relative error of approximately 12%, suggesting a reasonable degree of reliability.DiscussionBased on the results of the fracture simulation predictions, it is believed that the coal seam fracture density in the study area is mostly 10–20 lines/m and that the sweet spot for CBM development is located in the Yuwang block.

Abstract 4122717: An Epigenetic Drug, GSK126 Mitigates Endothelial to Mesenchymal Transition Attenuating Atherosclerosis in Diabetes

Background: Endothelial to mesenchymal transition (EndMT) involves transformation of an endothelial to mesenchymal like cellular state. Recent studies implicate EndMT in atherosclerosis development. Diabetes is associated with both EndMT as well as accelerated atherosclerosis. Experimental evidence supports the use of epigenetic drugs that act on relevant epigenetic mechanisms to attenuate atherosclerosis. Recently, inhibition of a histone methyltransferase Enhancer of zest homolog 2 (EZH2) with GSK-126 attenuated atherosclerosis development. However, the role of EZH2 in induction of EndMT in diabetes induced atherosclerosis is not known. Methods: An in-vitro model of EndMT was generated using high glucose (HG) and TNF-α in human aortic endothelial cells (HAECs). EZH2 methyltransferase activity was inhibited using EZH2 specific inhibitor GSK-126. RNA sequencing was performed in this setting. EZH2 genetic knockdown (shRNA) in HAECs was also performed to validate role of EZH2 in EndMT. In addition, EZH2 mediated H3K27me3 and EndMT was assessed in atheroprone diabetic mouse model. Results: In HAECs, morphological changes as well as gene and protein expression confirmed TNF-α+HG induced EndMT, which was blunted by GSK-126. Elevated EZH2 mediated H3K27me3 activity by the TNF-α + HG stimulation was blunted with GSK-126 treatment. Furthermore, RNA sequencing identified several enriched pathways including AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and leukocyte trans-endothelial migration directly relevant to EndMT and commonly deregulated in diabetic complications, which were rescued by EZH2 inhibition. Transcriptomic analysis showed that 242 genes including MMP2, NOS3 linked to EndMT were dysregulated. Interestingly, expression of 76 dysregulated genes in EndMT were rescued by GSK-126. EZH2 knockdown studies in HAECs also validated the role of EZH2 in EndMT. Furthermore, immunofluorescence staining identified elevated levels of H3K27me3 in the aortic endothelial layer of diabetic Apoe -/- mice. Co-localization of EndMT markers was observed in the endothelial layer of aortic sinus of diabetic Apoe -/- mice which was blunted with GSK-126 treatment. Conclusion: The study identified EZH2 inhibition as a novel therapeutic target in diabetes induced EndMT in atherosclerosis. These findings highlighted ongoing efforts to develop targeted therapies for diabetic patients who are at risk to develop cardiovascular disease.

Calcium Alginate Fibers/Boron Nitride Composite Lithium-Ion Battery Separators with Excellent Thermal Stability and Cycling Performance.

As one of the most critical components in lithium-ion batteries (LIBs), commercial polyolefin separators suffer from drawbacks such as poor thermal stability and the inability to inhibit the growth of dendrites, which seriously threaten the safety of LIBs. In this study, we prepared calcium alginate fiber/boron nitride-compliant separators (CA@BN) through paper-making technology and the surface coating method using calcium alginate fiber and boron nitride. The CA@BN had favorable electrolyte wettability, flame retardancy, and thermal dimensional stability of the biomass fiber separator. Meanwhile, the boron nitride coating provided excellent thermal conductivity and mechanical strength for the composite separator, which inhibited the growth of lithium dendrites and enabled lithium-ion symmetric batteries to achieve more than 1000 stable and long cycles at a current density of 0.5 mA cm-2. The interwoven fiber mesh formed by the boron nitride coating and the calcium alginate provided multiple pathways for ion migration, which enhanced the storage capacity of the electrolyte, improved the interfacial compatibility between the separator and the electrode, widened the window of electrochemical stability, and enhanced ionic migration. This eco-friendly bio-based separator paves a new insight for the design of heat-resistance separators as well as the safe running of LIBs.

NIMG-50. MULTIPARAMETRIC MRI DISTINGUISHES NEURONAL AND IMMUNE SIGNATURES IN INVASIVE HIGH-GRADE GLIOMA RIM THROUGH GRAPH NETWORK ANALYSIS

Abstract BACKGROUND Standard of care surgery for high grade glioma (HGG) employs Magnetic Resonance Imaging to identify the contrast enhancing (CE) core for resection, leaving a non-enhancing (NE) invasive rim of tumor which contributes to recurrence. Multi-parametric MRI (mpMRI) has recently been used to map regional biological heterogeneity of neuronal and immune signatures in HGG, and continues to offer a promising strategy for non-invasive surveillance of tumor progression. Here, we present a graph network analysis relating mpMRI to biological signatures in the NE tumor rim and show the utility of communities of imaging features for discriminating tumor phenotypes. METHODS 53 mpMRI features across 101 spatially-localized RNA-sequenced biopsy samples from 64 patients with IDH-wt HGG were represented as nodes within a Neo4j graph network. Modularity optimization was used to identify communities of densely connected nodes. Communities of nodes representing high proportions of NE samples (one-tailed test) were kept for further analysis. Gene set enrichment analysis (GSEA) on samples within selected imaging communities was analyzed for biological process enrichment using clusterProfiler. Single sample GSEA (ssGSEA) using ssGSEA2 was used to annotate neuronal and immune cell states across samples within selected communities. mpMRI feature selection within each community identified the most relevant imaging features for isolating samples classified into neuronal and immune cell states. RESULTS 11 imaging communities gathered a high proportion of NE samples. Three NE communities showed significant enrichment of neuronal signatures, while one showed significant enrichment of immune pathways. One neuronal-predominant community showed unique upregulation of 14 pathways related to neuronal migration/astrocyte projection. CONCLUSION Network imaging communities can identify clusters of NE glioma samples showing contrasting neuronal and immune signatures, including distinct upregulation of migration and projection pathways. Mapping these imaging feature communities to specific biological processes implicated in glioma progression may aid treatment planning and prognostication for glioma patients.

TMIC-37. GEMISTOCYTIC TUMOR CELLS AND IMMUNE REACTIVE MICROGLIA PROGRAMMED FOR GLIAL SCARRING CHARACTERIZE T CELL CONTAINMENT IN IDH-MUTANT ASTROCYTOMA

Abstract Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotype that relates to T cell exclusion. To aid better understanding of this mechanism, we systematically characterized the IDHmt astrocytoma immune microenvironment in a large cohort by multiplex immunofluorescence (IF) (n=75), bulk RNA sequencing (n=158), single nucleus RNA sequencing (n=7) and spatial RNA and protein profiling (n=12). We integrated and analyzed all datasets to acquire a robust characterization of the microenvironment organization and validated our results using IF stainings. We demonstrated that in IDHmt astrocytomas, T cells were contained in the perivascular space (i.e., T cell cuffs). In the tumor stroma surrounding T cell cuffs, we found a dense accumulation of gemistocytic tumor cells (GTCs), a histologically distinct tumor cell subtype. GTC-high tumors demonstrated enhanced expression of immune cell migration and activation pathways that were reliably expressed by TAMs and T cells. Notably, we found that GTCs formed a unique transcriptional cell sub-cluster that expressed markers including CD44, TNC and CRYAB, which are specific for glial scarring, a central nervous system specific mechanism for immune exclusion. Surrounding T cell cuffs, GTCs co-localized with immune-reactive microglia that expressed the chemoattractants CCL3 and CCL4. Together, co-localizing GTCs and reactive microglia expressed receptor-ligand pairs that take part in reactive astrogliosis and glial scarring, including Osteopontin – CD44 and IL-1β – IL1R1. Validation whole-slide multiplex IF stainings for this spatial relationship showed specific local accumulation of CD44 positive GTCs and TAMs around T cell cuffs in GTC-high tumors, which was absent in GTC-low tumors. Together, we show that IDHmt astrocytomas organize a network of tumor cells and leukocytes that mimics glial scarring and can aid T cell exclusion. Elucidating such specific immune exclusion mechanisms is vital for more appropriate target selection in novel immune therapies.

Nuclear EGFR in breast cancer suppresses NK cell recruitment and cytotoxicity.

Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. The epidermal growth factor receptor (EGFR) is a potent oncogene that can activate survival, migration, and proliferation pathways, and clinical data suggests it may also play an immunomodulating role in cancers. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain. Using a novel peptide therapeutic (cSNX1.3) that inhibits retrograde trafficking of EGFR and an EGFR nuclear localization mutant, we discovered that nEGFR suppresses NK cell recruitment and cytotoxicity. RNA-Seq analysis of breast cancer cells treated with cSNX1.3 or modified to lack a nuclear localization sequence (EGFRΔNLS) revealed the EGF-dependent induction of NK activating receptor ligands, while kinase inhibition by erlotinib did not impact these genes. NanoString analysis of tumor-bearing WAP-TGFα transgenic mice treated with cSNX1.3 demonstrated an increase in immune cell populations and activating genes. Additionally, immunohistochemistry confirmed an increase in NK cells upon cSNX1.3 treatment. Finally, cSNX1.3 treatment was found to enhance NK cell recruitment and cytotoxicity in vitro. Together, the data demonstrate a unique immunomodulatory role for nEGFR.