3D Landscape Research Articles

Diurnal Variation Reveals the Characteristics and Influencing Factors of Cool Island Effects in Urban Blue-Green Spaces

Urban blue-green space cooling island effect (BGCI) is effective in improving the thermal comfort of residents. However, there is little knowledge regarding the diurnal variation of BGCIs and the influencing factors. Therefore, we selected Beijing as the study area and used ECOSTRESS LST data and the inflection–maximum perspective method to explore the diurnal variation of BGCIs. Additionally, we investigated diurnal variations in the relative influence of the characteristics of the blue-green space itself, as well as the surrounding 2D and 3D landscape metrics using boosted regression tree model. The results indicated that BGCIs displayed distinct diurnal patterns. BGCIs progressively increased from sunrise to midday, decreased thereafter to sunset, reached its peak around midday, and diminished to a relatively low level and constant intensity at night. BGCIs of water bodies exhibited a significantly higher intensity compared to vegetation during the day, particularly around midday, with a difference in mean cooling intensity (CI) of 1.06 °C and mean cooling distance (CD) of 63.27 m, while the differences were minimal at night with a difference in mean CI of 0.02 °C and mean CD of 9.64 m. The features of vegetation had a more significant impact on BGCIs during the day, particularly around midday (CI: 32.30% around midday and 13.86% at night), while the 3D metrics influenced BGCIs more at night (CI: 26.40% around midday and 35.81% at night). The features of water bodies had a greater impact during the midday (52.87% around midday and 10.46% at night), with the landscape metrics of surrounding water bodies playing a more important role at night (15.56% around midday and 38.28% at night). The effect of tree height, shape index of vegetation, and surrounding building coverage ratio of water bodies on BGCIs exhibited opposite trends around midday and at night. Optimizing the landscape surrounding blue-green spaces is more cost-effective than the blue-green spaces themselves for nighttime thermal comfort, especially in 3D urban landscapes. These findings emphasize the imperative and essentiality of exploring diurnal variations in BGCIs, providing valuable information for mitigating UHI effects.

Unveiling Urban River Visual Features Through Immersive Virtual Reality: Analyzing Youth Perceptions with UAV Panoramic Imagery

The visual evaluation and characteristic analysis of urban rivers are pivotal for advancing our understanding of urban waterscapes and their surrounding environments. Unmanned aerial vehicles (UAVs) offer significant advantages over traditional satellite remote sensing, including flexible aerial surveying, diverse perspectives, and high-resolution imagery. This study centers on the Haihe River, South Canal, and North Canal in Tianjin China, employing UAVs to capture continuous panoramic image data. Through immersive virtual reality (VR) technology, visual evaluations of these panoramic images were obtained from a cohort of young participants. These evaluations encompassed assessments of scenic beauty, color richness, vitality, and historical sense. Subsequently, computer vision techniques were utilized to quantitatively analyze the proportions of various landscape elements (e.g., trees, grass, buildings) within the images. Clustering analysis of visual evaluation results and semantic segmentation outcomes from different study points facilitated the effective identification and grouping of river visual features. The findings reveal significant differences in scenic beauty, color richness, and vitality among the Haihe River, South Canal, and North Canal, whereas the South and North Canals exhibited a limited sense of history. Six landscape elements—water bodies, buildings, trees, etc.—comprised over 90% of the images, forming the primary visual characteristics of the three rivers. Nonetheless, the uneven spatial distribution of these elements resulted in notable variations in the visual features of the rivers. This study demonstrates that the visual feature analysis method based on UAV panoramic images can achieve a quantitative evaluation of multi-scene urban 3D landscapes, thereby providing a robust scientific foundation for the optimization of urban river environments.

Mediator Subunit Med4 Enforces Metastatic Dormancy in Breast Cancer.

Long term survival of breast cancer patients is limited due to recurrence from metastatic dormant cancer cells. However, the mechanisms by which these dormant breast cancer cells survive and awaken remain poorly understood. Our unbiased genome-scale genetic screen in mice identified Med4 as a novel cancer-cell intrinsic gatekeeper in metastatic reactivation. MED4 haploinsufficiency is prevalent in metastatic breast cancer patients and correlates with poorer prognosis. Syngeneic xenograft models revealed that Med4 enforces breast cancer dormancy. Contrary to the canonical function of the Mediator complex in activating gene expression, Med4 maintains 3D chromatin compaction and enhancer landscape, by preventing enhancer priming or activation through the suppression of H3K4me1 deposition. Med4 haploinsufficiency disrupts enhancer poise and reprograms the enhancer dynamics to facilitate extracellular matrix (ECM) gene expression and integrin-mediated mechano-transduction, driving metastatic growth. Our findings establish Med4 as a key regulator of cellular dormancy and a potential biomarker for high-risk metastatic relapse.

Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.

Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods. The aim of this study was to accurately detect novel RP17-SVs by establishing a systematic and efficient workflow. Genetically unexplained probands diagnosed with adRP (n = 509) from an international cohort were screened using a smMIPs or genomic qPCR-based approach tailored for the RP17 locus. Suspected copy number changes were validated using high-density SNP-array genotyping, and SV breakpoint characterization was performed by mutation-specific breakpoint PCR, genome sequencing and, if required, optical genome mapping. In silico modeling of novel SVs was performed to predict the formation of neo-TADs and whether ectopic contacts between the retinal enhancers and the GDPD1-promoter could be formed. Using this workflow, potential RP17-SVs were detected in eight probands of which seven were confirmed. Two novel SVs were identified that are predicted to cause TAD rearrangement and retinal enhancer-GDPD1 contact, one from Germany (DE-SV9) and three with the same SV from the United States (US-SV10). Previously reported RP17-SVs were also identified in three Australian probands, one with UK-SV2 and two with SA-SV3. In summary, we describe a validated multi-step pipeline for reliable and efficient RP17-SV discovery and expand the range of disease-associated SVs. Based on these data, RP17-SVs can be considered a frequent cause of adRP which warrants the inclusion of RP17-screening as a standard diagnostic test for this disease.

A Spatiotemporal Empowerment Framework for China’s National 3D Mapping Program 3dRGLM

Abstract. China has launched a national 3D mapping program to build 3D Realistic geospatial Landscape Model (3dRGLm) over the whole country, covering both cities and countryside. The 3dRGLM is a digital description and representation of the real 3D geospatial spaces, and is defined as a new generation geospatial data product with 3D structures, realistic scenes, and geospatial entities. Such a national or local 3dRGLm will set up a digital 3D realistic geospatial space which can facilitate the vital connection with the real geospatial space, and will serve as a new generation of geospatial information infrastructure for our society. With the acquisition of complex 3D spatial data continues to advance, managing and utilizing the massive volumes of 3D data to provide spatiotemporal empowerment applications has become a significant technological challenge. This paper analyzes the technical characteristics of 3d realistic geospatial landscape model, and then proposes the main content and basic structure of a 3d realistic geospatial landscape model database, as well as the spatiotemporal service empowerment methods based on the database. Finally, a case analysis is provided to serve as a reference for the construction and application of 3d realistic geospatial landscape.

A 3D Spatial Model to integrate Stormwater Drainage Design into Public Space

Abstract. This paper explores the integration of water sensitive urban design within public space planning using integrated 3D digital technologies. In traditional design processes, drainage and public space design often utilise distinct software and are led by different professionals, which creates significant communication barriers.Although civil and hydraulic engineers have made significant strides in integrating hydrology analysis with multi-objective space design, the collaboration of conventional 2D hydrology with 3D landscape design still presents challenges. To address these challenges, this study proposes a novel approach that integrates drainage analysis and design within a 3D design model. This methodology is specifically designed to aid landscape and urban designers in incorporating stormwater management and drainage systems early in the design process. The approach involves three key steps: (1) identifying critical factors that impact, or are impacted by, drainage design; (2) translating these factors into specific spatial parameters; and (3) developing a workflow to integrate these parameters. This integration not only streamlines the design process, making it more cohesive and efficient but also mitigates potential conflicts between drainage requirements and spatial design, thereby reducing unnecessary revisions. Ultimately, this approach enhances the incorporation of essential drainage considerations into urban and landscape planning, leading to more sustainable and functional public spaces.

Evaluation of the urban heat island effect based on 3D modeling and planning indicators for urban planning proposals

ABSTRACT Urban planning plays an important role in the formation of urban space and microclimate. As a middle-level planning in the Chinese urban planning system, regulatory planning has a direct impact on the shaping of 3D urban space and can maximize the operability of urban planning. However, 3D space formation is not considered in the present preparation of regulatory plans, which leads to a misunderstanding of possibly formed 3D landscapes and microclimatic effects after the plan implementation. To support 3D visualization and quantitative analysis of the urban heat island effect (UHI) for regulatory planning, this study proposes a rule-based 3D modeling method to efficiently generate 3D models. The main elements of 3D models (terrain, building, road, vegetation, and land parcel) and their content were determined after analyzing the characteristics of 3D models in the regulatory plan. The 3D modeling process was constructed and combined with an UHI evaluation model through CGA programming. An index called heat island potential (HIP) was used as the UHI evaluation index and can be quantified using the correlation equations between planning indicators and HIP. The proposed method can support the planners to generate 3D models for a planning proposal, and simultaneously analyze 3D spatial effect and UHI.

Reshaping landscape factorization through 3D landscape clustering for urban temperature studies

As urban populations grow and cities expand, the challenge of managing urban heat and its environmental impacts becomes increasingly critical. Traditional methods for analyzing urban temperature dynamics often fall short in precisely capturing the complexity of urban landscapes. This paper introduces the 3D Landscape Clustering (3LC) framework, a new tool designed to analyze urban temperature dynamics by factoring in landscape variables. It clusters landscapes into homogeneous groups using high-resolution 3D land cover maps. The 3LC adopts a clustering mechanism to enhance flexibility and objectivity in landscape categorization, thereby enhancing the depth and accuracy of urban climate studies and moving beyond traditional classification frameworks such as the Local Climate Zone (LCZ). Case studies demonstrate its capability to provide detailed insights into the relationships between urban landscape features and temperature variations. Additionally, the paper details how the framework can excel in multi-city analyses and outlines advanced analytical techniques. Promising research opportunities and limitations are identified. This research reshapes our approach to landscape categorization, advancing our understanding of the interactions between landscape and climate dynamics, and contributing to more sustainable, climate-resilient cities.

Retraction Note: Application of dynamic simulation technology based on image detail enhancement algorithm in urban 3D landscape

Retraction Note: Application of dynamic simulation technology based on image detail enhancement algorithm in urban 3D landscape

Resolving 3-Dimensional Genomic Landscape of CD4+ T Cells in the Peripheral Blood of Patients with Psoriasis

A precise regulation of gene expression depends on the accuracy of the 3-dimensional (3D) structure of chromatin; however, the effects of the 3D genome on gene expression in psoriasis remain unknown. In this study, we conducted Hi-C and RNA sequencing on CD4+ T cells collected from 5 patients with psoriasis and 3 healthy controls and constructed a comprehensive 3D chromatin interaction map to delineate the genomic hierarchies, including A/B compartments, topologically associated domains, and chromatin loops. Then, the specific superenhancers related to psoriasis were identified by Hi-C and H3K27ac chromatin immunoprecipitation sequencing data. Subsequently, comprehensive analyses were carried out on the differentially expressed genes that are associated with altered topologically associated domains, loops, and superenhancers in psoriasis. Finally, we screened the candidate target genes and examined the potential functional SNP in psoriasis affected by disruptions of the spatial organization. This study provides a comprehensive reference for examining the 3D genome interactions in psoriasis and elucidating the interplay between spatial organization disruption and gene regulation. We hope that our findings can help clarify the mechanisms underlying the pathogenesis of psoriasis and shed light on the role of 3D genomic structure, therefore informing potential therapeutic approaches.

Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia

Relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains one of the leading causes of cancer mortality in children. We performed Hi-C, ATAC-seq, and RNA-seq on 12 matched diagnosis/relapse pediatric leukemia specimens to uncover dynamic structural variants (SVs) and 3D chromatin rewiring that may contribute to relapse. While translocations are assumed to occur early in leukemogenesis and be maintained throughout progression, we discovered novel, dynamic translocations and confirmed several fusion transcripts, suggesting functional and therapeutic relevance. Genome-wide chromatin remodeling was observed at all organizational levels: A/B compartments, TAD interactivity, and chromatin loops, including some loci shared by 25% of patients. Shared changes were found to drive the expression of genes/pathways previously implicated in resistance as well as novel therapeutic candidates, two of which (ATXN1 and MN1) we functionally validated. Overall, these results demonstrate chromatin reorganization under the selective pressure of therapy and offer the potential for discovery of novel therapeutic interventions.

The cooling capacity of urban vegetation and its driving force under extreme hot weather: A comparative study between dry-hot and humid-hot cities

Extreme heat events in cities necessitate closer examination of urban vegetation’ capacity to mitigate extreme hot weather. However, the cooling capacity of vegetation (CCV) and its driving forces of 2D and 3D landscape metrics under extreme hot weather conditions in dry-hot and humid-hot cities, particularly within different functional zones is still not well understood. The results indicate that the CCV is more pronounced in humid-hot cities than in dry-hot cities, particularly during periods of extreme hot weather. This CCV varied significantly across different functional zones, being the lowest in commercial zones and the highest in green space zones. Moreover, residential zones in humid-hot cities have higher CCV when the weather is more extreme. In dry-hot and humid-hot cities, urban vegetation landscape configuration metrics (such as patch and edge densities) contribute significantly to the CCV, and landscape composition (vegetation coverage) also contributes, with a significant increase during periods of extreme hot weather, particularly in humid-hot cities. Additionally, the 3D building morphology plays a crucial role in moderating the CCV; however, its impact diminishes during extreme heat. We also found that the CCV does not increase further after vegetation coverage is greater than 30–40 % in dry-hot cities, compared to approximately 60–80 % in humid-hot cities. The CCV increased nonlinearly with increasing urban vegetation largest patch index and decreasing urban vegetation patch density in dry-hot and humid-hot cities, with different thresholds of vegetation coverage and largest patch index under normal and extreme hot weather. A higher building height increased the CCV in humid-hot cities and reduced the CCV in dry-hot cities, particularly under extreme hot weather, and sparse high-rise buildings were better suited to humid-hot cities for increasing urban CCV. These findings provide valuable insights for urban planners to enhance the urban CCV, contributing to long-term urban resilience and public health protection during extreme heat events.

Stiff extracellular matrix drives the differentiation of mesenchymal stem cells toward osteogenesis by the multiscale 3D genome reorganization

Extracellular matrix (ECM) stiffness is a major driver of stem cell fate. However, the involvement of the three-dimensional (3D) genomic reorganization in response to ECM stiffness remains unclear. Here, we generated comprehensive 3D chromatin landscapes of mesenchymal stem cells (MSCs) exposed to various ECM stiffness. We found that there were more long-range chromatin interactions, but less compartment A in MSCs cultured on stiff ECM than those cultured on soft ECM. However, the switch from compartment B in MSCs cultured on soft ECM to compartment A in MSCs cultured on stiff ECM included genes encoding proteins primarily enriched in cytoskeleton organization. At the topologically associating domains (TADs) level, stiff ECM tends to have merged TADs on soft ECM. These merged TADs on stiff ECM include upregulated genes encoding proteins enriched in osteogenesis, such as SP1, ETS1, and DCHS1, which were validated by quantitative real-time polymerase chain reaction and found to be consistent with the increase of alkaline phosphatase staining. Knockdown of SP1 or ETS1 led to the downregulation of osteogenic marker genes, including COL1A1, RUNX2, ALP, and OCN in MSCs cultured on stiff ECM. Our study provides an important insight into the stiff ECM-mediated promotion of MSC differentiation towards osteogenesis, emphasizing the influence of mechanical cues on the reorganization of 3D genome architecture and stem cell fate.

3D dynamic landscape simulation of artificial intelligence in environmental landscape design

Three-dimensional (3D) simulations and precise landscape visualizations are crucial for various applications, like landscape management and planning, computer and connection of the landscape, evaluation, and tracking of land use. The consequences of several plans and a large scene cannot be communicated using older methods of comprehensive environmental planning and development in a timely, rational, and coordinated manner. Architects have trouble incorporating ideas into other comprehensive planning implementation processes. Architects did not thoroughly investigate the neighbourhood's demographics and matching behavioural needs and lacked critical thinking. The 3D dynamic landscape simulation is a detailed computerized three-dimensional simulation of the environment that can be dynamically presented. With the aid of Artificial Intelligence (AI) technology, the system possesses a strong sense of reality, a user-friendly interface, and interactive features that can be tailored to the requirements of the contemporary urban environmental landscape. Regarding exterior publicity, domestic assistance, environmental land use planning, and information systems. The novelty of the proposed Interactive Design System based on AI (IDS-AI) is to create a 3D dynamic landscape model based on a real-life environmental scene, utilizing a Geographic Information System (GIS) to optimize landscape vision. Secondly, 3D environmental landscape design simulation was implemented using GIS spatial analysis in conjunction with the Fuzzy Analytical Hierarchical Process (FAHP) to reduce the data overlap rate and help make an accurate decision. Finally, the design incorporates the development of the interactive interface system application of landscape design and environmental resources for viewing the landscape, the factors that affect them, and the area coverage ratio of various land cover types. The experimental outcomes show that the suggested IDS model increases the gradient sensitivity level of 98.3 % and area coverage ratio of 93.4 % compared to other existing models.

Recent Progress in the Physical Principles of Dynamic Ground Self-Righting.

Animals and robots must self-right on the ground after overturning. Biology research has described various strategies and motor patterns in many species. Robotics research has devised many strategies. However, we do not well understand the physical principles of how the need to generate mechanical energy to overcome the potential energy barrier governs behavioral strategies and 3D body rotations given the morphology. Here, I review progress on this which I led studying cockroaches self-righting on level, flat, solid, low-friction ground, by integrating biology experiments, robotic modeling, and physics modeling. Animal experiments using three species (Madagascar hissing, American, and discoid cockroaches) found that ground self-righting is strenuous and often requires multiple attempts to succeed. Two species (American and discoid cockroaches) often self-right dynamically, using kinetic energy to overcome the barrier. All three species use and often stochastically transition across diverse strategies. In these strategies, propelling motions are often accompanied by perturbing motions. All three species often display complex yet stereotyped body rotation. They all roll more in successful attempts than in failed ones, which lowers the barrier, as revealed by a simplistic 3D potential energy landscape of a rigid body self-righting. Experiments of an initial robot self-righting via rotation about a fixed axis revealed that the longer and faster appendages push, the more mechanical energy can be gained to overcome the barrier. However, the cockroaches rarely achieve this. To further understand the physical principles of strenuous ground self-righting, we focused on the discoid cockroach's leg-assisted winged self-righting. In this strategy, wings propel against the ground to pitch the body up but are unable to overcome the highest pitch barrier. Meanwhile, legs flail in the air to perturb the body sideways to self-right via rolling. Experiments using a refined robot and an evolving 3D potential energy landscape revealed that, although wing propelling cannot generate sufficient kinetic energy to overcome the highest pitch barrier, it reduces the barrier to allow small kinetic energy from the perturbing legs to probabilistically overcome the barrier to self-right via rolling. Thus, only by combining propelling and perturbing can self-righting be achieved when it is so strenuous; this physical constraint leads to the stereotyped body rotation. Finally, multi-body dynamics simulation and template modeling revealed that the animal's substantial randomness in wing and leg motions helps it, by chance, to find good coordination, which accumulates more mechanical energy to overcome the barrier, thus increasing the likelihood of self-righting.

Tree selection for a virtual urban park: Comparing aided and unaided decision-making to support public engagement in greenspace design

To meet urban resilience goals and the needs of growing populations, cities aim to develop multifunctional greenspaces and urban forests. Urban greening is seen to improve the quality of life for residents, contribute significantly to biodiversity conservation and socio-ecological resilience, and meet climate mitigation and adaptation goals. There is also a growing recognition of the importance of involving individuals and communities in the design and planning of greenspace in cities, particularly in the configuration of parks and in identifying the types of vegetation found there. In these contexts, it is increasingly common to engage the public with virtual 3D landscapes, with the ultimate goals of crowdsourcing preferences, knowledge, and patterns of use. There have been few studies to systematically examine how the public interacts with these virtual spaces, and their decision-making needs. Experts have a fluency with a broad range of ecosystem services that flow from urban greenspaces, as well as a familiarity with trees and other landscape elements. This is not the case for the public, who may instead rely on familiar and visually salient landscape attributes. This is in keeping with the concept of constructed preferences, where judgements are formed as they are elicited and are heavily influenced by available information. This study thus compares aided and unaided decision-making by the public in a virtual 3D urban park. Participants were invited to plant trees in park; some participants were provided with a brief description of a key ecosystem function of each tree (along with an illustration of that tree), other participants were only provided the illustration. Three key insights emerge from this research: (i) public tree preferences are sensitive to whether information is provided or withheld, (ii) in the absence of information, easy to evaluate characteristics (i.e., visually salient characteristics) played a large role in tree selection within the virtual urban parks, and (iii) for most participants, and consistent with other studies, aesthetics was the most important attribute guiding tree choice. These insights can support improved public engagement in landscape design and planning, particularly in crowdsourced and virtual settings.

A comprehensive metric scheme for characterizing the heterogeneity of urban thermal landscapes: A case study of 14-year evaluation in Beijing

Urbanization has affected land surface temperature (LST) significantly. The spatial average of LST is widely applied to evaluate urban heat islands (UHI), but a simple comparison of mean temperature is insufficient to evaluate the heterogeneity of LST and the effectiveness of urban heat mitigation strategies. This study took the spatial distribution of LST as the thermal landscape and firstly employed 3D landscape metrics to analyze its spatial heterogeneity. To perform collaborative analysis with UHI, the urban–rural differences of landscape metrics were defined as thermal metric islands (TMI). Significant UHI and TMI were revealed by temperature amplitude, aggregation, and complexity parameters, indicating higher temperature fluctuation and fragmentation in urban regions. Before 2007, the standard deviation of thermal surface, landscape fragmentation, and shape irregularity increased significantly, particularly in the suburbs. Later, benefiting from the Summer Olympic Games, the temperature fluctuation, fragmentation, and shape complexity decreased obviously, and UHI intensity hit the lowest. Both UHI intensities and TMI increased after 2010, and various metrics suggest that maximum temperatures, landscape fragmentation, and shape complexity declined over most of the district, even as the mean temperatures increased. This study concludes that urban temperatures have risen at a higher rate than suburban areas, but the thermal landscape composition and configuration have changed more dramatically in rural areas.

MDB-19. THE 3D CHROMATIN LANDSCAPE OF MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is a highly malignant childhood cerebellar tumor comprised of four molecularly and clinically distinct subgroups. Sporadic yet subgroup-specific genetic and epigenetic landscapes suggest that higher-order chromatin topology may contribute to distinct subgroup identities and disease biology. Herein, we investigated the 3D chromatin landscape of MB by performing genome-wide chromosome conformation capture (Hi-C) across molecular subgroups using a cohort of n=24 patient-derived xenografts and primary tumor specimens, aiming to elucidate regulatory mechanisms facilitated by genome organization. METHODS Integrative analyses were adapted to incorporate a wide variety of sample-paired datasets. Chromatin contact matrices generated from Hi-C allowed for the mapping of active/inactive compartments (A/B compartments), topologically associated domains (TADs), and distal pairwise chromatin contacts (loops). Topological insights of chromatin architecture were complemented with whole-genome sequencing, RNA-seq, ATAC-seq, DNA methylation, CTCF and histone modification (H3K27ac/H3K27me3) ChIP-seq datasets to dissect mechanisms of gene regulation. RESULTS Unsupervised analysis revealed that chromatin compartmentalization is subgroup stratified. Gene loci contained in subgroup-unique active compartments correspondingly exhibited subgroup-specific chromatin contact patterns, adopted open chromatin conformations, and remained transcriptionally active. As an example, LIN28B resides within a Group 3-specific ‘A’ compartment where its local topology displays higher complexity compared to that of other subgroups. This consequentially facilitates a Group 3-unique loop connecting the LIN28B promoter with a distal enhancer, resulting in subgroup-specific transcriptional upregulation. Targeted displacement of CTCF that anchors and stabilizes chromatin looping at the LIN28B locus was sufficient to alter its transcriptional activity. Using similar lines of investigation, mechanistic insights into the topological determinants of known enhancer-hijacking events, including GFI1, GFI1B and PRDM6, were resolved. CONCLUSIONS Pioneering this integrative approach centered on comprehensive Hi-C maps, our study provides a high-resolution blueprint of the 3D chromatin landscape defining MB subgroups, informing the mechanistic basis of recurrent driver gene activation, and disclosing putative subgroup-specific vulnerabilities.

Exploring the relationships between 3D urban landscape patterns and PM2.5 pollution using the multiscale geographic weighted regression model

Fine particulate matter (PM2.5) is a major source of air pollution and exerts serious impacts on human health. The 3D urban landscape patterns can significantly affect the diffusion and emissions of PM2.5. However, studies on the relationships between 3D urban landscape patterns and PM2.5 pollution across different seasons remain understudied. With the ground-level air pollutants estimated by the remote sensing and fine-scale building information, this study applied the multiscale geographically weighted regression model to explore such relationships. Wuhan, the largest metropolis in Central China, was selected as the study area for the application of our methodology. The results showed that the direction, degree, and scale of the effect of 3D urban landscape patterns on PM2.5 pollution varied across seasons. For building height, the standard deviation of building height had a significant positive correlation with PM2.5 all year round. For building density, the building count density showed a significant positive correlation with PM2.5 in general, with the bandwidth in winter and autumn smaller than in spring and summer. The building plan area fraction exerted both positive and negative influences on PM2.5, dependent on season and location. The bandwidth of it gradually increased from spring to winter, with the effect changing from local to regional scale. For building volume, the floor area ratio showed a significant negative correlation with PM2.5 in winter and autumn, and a localized effect was found, especially in winter. The findings of this study provide practical implications for urban planning and policy making to mitigate PM2.5 pollution in the rapidly urbanizing regions.

Abstract 3771: 3D correlated multi-scale cellular and molecular architecture of solid tumors

Abstract A solid tumor presents heterogeneous 3D structures at tissue, cell, and molecule levels. To develop advanced cancer diagnostics and therapies, it is important to understand in-depth cellular and molecular architecture of a tumor at multiple scales. Here we introduce novel optical microscopy methodologies for in-depth 3D spatial analysis of tumor tissues: 1) LED photobleaching-mediated 3D multiplex immunofluorescence (IF) microscopy, 2) Correlated 3D multi-resolution optical microscopy, and 3) 3D tissue region-based cell type-selective multi-omics. We built a high-power LED light irradiator with a broad emission spectrum (490-700 nm) that bleaches a broad wavelength of fluorescence signals simultaneously throughout an optically cleared, 400 µm-thick tumor tissue. Cyclic workflow involving IF staining, optical tissue clearing, 3D confocal microscopy, and LED photobleaching enables visualization of multiple cell types in the same whole 400 µm-thick tumor tissue after computational 3D image registration. The constructed multiplex image offers comprehensive 3D cellular landscape of a tumor. We also developed a method for tracking regions of interest (ROIs) in the middle of a large tumor tissue using a UV-activated visible dye in light sheet microscopy. Light sheet microscopy allows imaging an optically cleared large-sized tumor tissue at a low spatial, tissue resolution. To mark the ROI positions on a tumor, the dye is infused into agarose gel surrounding the tumor tissue and be activated and present purple-colored lines where are exposed to UV light sheets in light sheet microscopy. The tumor tissue was physically sectioned at the marked ROI positions using a vibratome after reversing tissue clearing process. Sequential IF staining and high-resolution confocal microscopy permit for visualizing detailed cellular compositions of the ROIs in the tumor. The tissue and cellular-resolution 3D images from light sheet and confocal microscopy are correlatively integrated to display ‘Google Earth’-like multi-scale view of a tumor tissue. To further analyze the ROIs of a tumor at molecular level, we have developed optical microscope-mediated fluorescence lithography methods that allow fluorescently labeling of a selected cell type in ROIs of an optically cleared 3D tumor tissue. After wash free from clearing solution and dissociation of the tumor into cells, fluorescence-marked, intact cells from the ROIs are collected through flow cell sorting. Proteins and mRNAs are extracted from the collected cells and sent to LC-MS/MS analysis and RNA sequencing. The spatial multi-omics method provides in-depth molecular information of selected cells in the ROIs of a tumor. We believe all these 3D microscopy methods will provide powerful spatial analysis tools for better understanding cellular and molecular architecture of solid tumors. Citation Format: Steve Seung-Young Lee, Yi-Chien Wu, Jingtian Zheng, Elie Abi Khalil, Samuel Wang, Alexander Lippert, Joshua Plank. 3D correlated multi-scale cellular and molecular architecture of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3771.