Biology subjects

Xia, B.

Publications and source records attributed to Xia, B..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Antimicrobial mechanism of in-situ plasma activated water treatment of pathogenic Escherichia coli and Staphylococcus aureus biofilms

AimsThis study investigated the efficacy and mechanisms of inactivation of against Escherichia coli UTI89 and Staphylococcus aureus NCTC8325 through an in-situ plasma-activated water (PAW) treatment. Methods and ResultsPAW was prepared by discharging atmospheric pressure cold plasma beneath the surface of sterile distilled water. The study investigated the inactivation of biofilm cells and biofilm matrix. A complete killing of biofilm cells was achieved on both of E. coli (6.76 {+/-} 0.01 log CFU/mL) and S. aureus (6.82 {+/-} 0.02 log CFU/mL). This process happened earlier in S. aureus. Simultaneously, PAW treatment disrupted the biofilm structure, inducing a significant reduction in general biofilm biomass and extracellular polymer substances (EPS) matrix. With the disruption of EPS, PAW was enabled to further interact with the bacterial membrane, causing a significant increase in membrane permeability and disrupted membrane structure. Finally, PAW treatment led to a significant accumulation of intracellular reactive oxygen and nitrogen species within the biofilm cells. ConclusionsCollectively, these findings indicate that PAW effectively inactivates biofilms by mechanically targeting the biofilm EPS matrix and biofilm cells in both gram-negative and gram-positive bacteria. Impact statementThis study contributes novel insights into plasma-activated waters mechanisms of action, particularly its impact on the biofilm extracellular polymeric substances matrix (exopolysaccharides, extracellular DNA, and protein), cell membrane permeability, depolarization, and intracellular ROS and RNS accumulation in both of Gram-positive and Gram-negative species. These findings highlight PAW-based treatments against biofilm-related challenges in antimicrobial development and water system decontamination.

microbiology↗

bioRxiv2024

scRNA-seq reveals transcriptional dynamics of Encephalitozoon intestinalis parasites in human macrophages

Microsporidia are single-celled intracellular parasites that cause opportunistic diseases in humans. Encephalitozoon intestinalis is a prevalent human-infecting species that invades the small intestine. Dissemination to other organ systems is also observed, and is potentially facilitated by macrophages. The macrophage response to infection and the developmental trajectory of the parasite are not well studied. Here we use single cell RNA sequencing to investigate transcriptional changes in both the host and parasite during infection. While a small population of infected macrophages mount a response, most remain transcriptionally unchanged, suggesting that the majority of parasites may avoid host detection. The parasite transcriptome reveals large transcriptional changes throughout the life cycle, providing a blueprint for parasite development. The stealthy microsporidian lifestyle likely allows these parasites to harness macrophages for replication and dissemination. Together, our data provide insights into the host response in primary human macrophages and the E. intestinalis developmental program.

microbiology↗

bioRxiv2024

Transcriptional Signatures Associated with the Survival of Escherichia coli Biofilm During Treatment with Plasma-Activated Water

Biofilm formation on surfaces, tools and equipment can damage their quality and lead to high repair or replacement costs. Plasma-activated water (PAW), a new technology, has shown promise in killing biofilm and non-biofilm bacteria due to its mix of reactive oxygen and nitrogen species (RONS), and in particular superoxide. However, the specific genetic mechanisms behind PAWs effectiveness, especially against biofilms, are not yet fully understood. Here, we examined the stress responses of Escherichia coli biofilms when exposed to sub-lethal PAW treatment with and without superoxide (by adding the scavenger Tiron to remove it). A 40% variation in gene expression was observed for PAW treated biofilms when compared to PAW-Tiron and controls. Specifically, PAW treatment resulted in 478 upregulated genes (> 1.5 log2FC) and 186 downregulated genes (< -1.5 log2FC) compared to the control. Pathway enrichment and biological process enrichment analysis revealed significant upregulation of sulfur metabolism, ATP-binding cassette transporter genes, amino acid metabolic/biosynthesis pathways, hypochlorite response systems and oxidative phosphorylation for biofilms treated with PAW compared to control. Knockout mutants of significantly upregulated genes associated with these pathways trxC (4.23-fold), cysP (1.58-fold) and nuoM (1.74-fold) were compared to the wild-type (WT) for their biofilm viability and intracellular RONS accumulation. Relative to PAW-treated WT,{Delta} trxC and{Delta} nuoM knockout mutants displayed significantly reduced biofilm viability (P [≤] 0.05) confirming their role in PAW-mediated response. Interestingly,{Delta} trxC biofilms had the highest intracellular ROS accumulation, as revealed by DCFDA staining after PAW treatment. This study gives a detailed insight into how E. coli biofilms respond to oxidative stress induced by PAW. It highlights the significance of superoxide in PAWs bactericidal effects. Overall, our findings shed light on the specific genes and pathways that help E. coli biofilms survive and respond to PAW treatment, offering a new understanding of plasma technology and its anti-biofilm mechanisms.

microbiology↗

bioRxiv2023

Discrimination of Isomeric Glycans via High-sensitive Engineered Nanopore

Glycan isomers are the basis for forming the spatial structure of glycans, which poses great challenges to glycan structural analysis and hinders the study of the relationship between structure and function. An economical and convenient analytical method with high resolution is still in demand. Here, we designed an engineered -hemolysin nanopore with double-mutants (-HL M113R/T115A) to achieve sensing of glycans with different glycosidic linkages. By extracting three parameters to depict a 3D scatter plot, four glycans with different degrees of polymerization and glycosidic bonds could be distinguished. Through molecular dynamics (MD), we further elucidated the motion trajectories of two different glycosidic bonds in the pore region. In addition, the sensing ability was also applied in the direct identification of glycans in mixture systems. The obtained nanopore data permitted us to achieve a separation accuracy of over 90% independent of the assistance of machine learning algorithms. Designing biological nanopores with high discrimination and sensitivity for glycans with different lineages paves the way for nanopore glycan profiling and potentially sequencing.

bioengineering↗

bioRxiv2023

Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations

SARS-CoV-2 mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape, are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we show that the human microbiota may contribute to mutations in variants of concern (VOCs). We identified a mutation and adjacent 6 amino acids (aa) in a viral mutation fragment (VMF) and searched for homologous fragments (HFs) in the National Center for Biotechnology Information (NCBI) database. Among the approximate 8000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is a 12-fold higher than the natural variable proportion. Approximately 70% of these bacterial species belong to the human microbiota, are primarily distributed in the gut or lung and exhibit a composition pattern similar to that of COVID-19 patients. Importantly, SARS- CoV-2 RNA-dependent RNA polymerase (RdRp) replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. Collectively, SARS-CoV-2 may acquire mutations from the human microbiota, resulting in alterations in the binding sites or antigenic determinants of the original virus. Our study sheds light on the evolving mutational mechanisms of SARS-CoV-2.

microbiology↗

bioRxiv2023

Distinct functions of EHMT1 and EHMT2 in cancer chemotherapy and immunotherapy

EHTM1 (GLP) and EHMT2 (G9a) are closely related protein lysine methyltransferases often thought to function together as a heterodimer to methylate histone H3 and non-histone substrates in diverse cellular processes including transcriptional regulation, genome methylation, and DNA repair. Here we show that EHMT1/2 inhibitors cause ATM-mediated slowdown of replication fork progression, accumulation of single-stranded replication gaps, emergence of cytosolic DNA, and increased expression of STING. EHMT1/2 inhibition strongly potentiates the efficacy of alkylating chemotherapy and anti-PD-1 immunotherapy in mouse models of tripe negative breast cancer. The effects on DNA replication and alkylating agent sensitivity are largely caused by the loss of EHMT1-mediated methylation of LIG1, whereas the elevated STING expression and remarkable response to immunotherapy appear mainly elicited by the loss of EHMT2 activity. Depletion of UHRF1, a protein known to be associated with EHMT1/2 and LIG1, also induces STING expression, and depletion of either EHMT2 or UHRF1 leads to demethylation of specific CpG sites in the STING1 promoter, suggestive of a distinct EHMT2-UHRF1 axis that regulates DNA methylation and gene transcription. These results highlight distinct functions of the two EHMT paralogs and provide enlightening paradigms and corresponding molecular basis for combination therapies involving alkylating agents and immune checkpoint inhibitors.

cancer biology↗

bioRxiv2023

Tick hemocytes have pleiotropic roles in microbial infection and arthropod fitness

Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here, we describe immune cells or hemocytes from the clinically relevant tick Ixodes scapularis using bulk and single cell RNA sequencing combined with depletion via clodronate liposomes, RNA interference, Clustered Regularly Interspaced Short Palindromic Repeats activation (CRISPRa) and RNA-fluorescence in situ hybridization (FISH). We observe molecular alterations in hemocytes upon tick infestation of mammals and infection with either the Lyme disease spirochete Borrelia burgdorferi or the rickettsial agent Anaplasma phagocytophilum. We predict distinct hemocyte lineages and reveal clusters exhibiting defined signatures for immunity, metabolism, and proliferation during hematophagy. Furthermore, we perform a mechanistic characterization of two I. scapularis hemocyte markers: hemocytin and astakine. Depletion of phagocytic hemocytes affects hemocytin and astakine levels, which impacts blood feeding and molting behavior of ticks. Hemocytin specifically affects the c-Jun N-terminal kinase (JNK) signaling pathway, whereas astakine alters hemocyte proliferation in I. scapularis. Altogether, we uncover the heterogeneity and pleiotropic roles of hemocytes in ticks and provide a valuable resource for comparative biology in arthropods.

immunology↗

bioRxiv2023

Plasma Activated Water as a Pre-Treatment Strategy in the Context of Biofilm-Infected Chronic Wounds

Healing and treatment of chronic wounds are often complicated due to biofilm formation by pathogens. Here, the efficacy of Plasma Activated Water (PAW) as a pre-treatment strategy has been investigated prior to the application of topical antiseptics polyhexamethylene biguanide, povidone iodine, and MediHoney, which are routinely used to treat chronic wounds. The efficacy of this treatment strategy was determined against biofilms of Escherichia coli formed on a plastic substratum and on a human keratinocyte monolayer substratum used as an in vitro biofilm-skin epithelial cell model. PAW pre-treatment greatly increased the killing efficacy of all the three antiseptics to eradicate the E. coli biofilms formed on the plastic and keratinocyte substrates. However, the efficacy of the combined PAW-antiseptic treatment and single treatments using PAW or antiseptic alone was lower for biofilms formed in the in vitro biofilm-skin epithelial cell model compared to the plastic substratum. Scavenging assays demonstrated that reactive species present within the PAW were largely responsible for its anti-biofilm activity. PAW treatment resulted in significant intracellular RONS accumulation within the E. coli biofilms, while also rapidly acting on the microbial membrane leading to outer membrane permeabilisation and depolarisation. Together, these factors contribute to significant cell death, potentiating the antibacterial effect of the assessed antiseptics.

microbiology↗

bioRxiv2023

Bestrophin-4 relays Hes4 and interacts with Twist1 to suppress epithelial-to-mesenchymal transition in colorectal cancer cells

AbstractBestrophin isoform 4 (BEST4) is a newly identified subtype of the calcium-activated chloride channel family. Analysis of colonic epithelial cell diversity by single cell RNA-sequencing has revealed the existence of a cluster of BEST4+ mature colonocytes in humans. However, if the role of BEST4 is involved in regulating tumour progression remains largely unknown. In this study, we demonstrate that BEST4 overexpression attenuates cell proliferation, colony formation, and mobility in colorectal cancer (CRC) in vitro, and impedes the tumor growth and the liver metastasis in vivo. BEST4 is coexpressed with hairy/enhancer of split 4 (Hes4) in the nucleus of cells, and Hes4 signals BEST4 by interacting with the upstream region of the BEST4 promoter. BEST4 is epistatic to Hes4 and downregulates Twist1, thereby inhibiting epithelial-to-mesenchymal transition (EMT) in CRC. Conversely, knockout of BEST4 using CRISPR/Cas9 in CRC cells revitalises tumor growth and induces EMT. Furthermore, the low level of the BEST4 mRNA is correlated with advanced and the worse prognosis, suggesting its potential role in regulating CRC progression.

cancer biology↗

bioRxiv2023

Integrative Multi-omic Profiling of Two Human Decedents Receiving Pig Heart Xenografts Reveals Strong Perturbations in Early Immune-Cell and Cellular Metabolism Responses.

BackgroundRecent advances in xenotransplantation in living and decedent humans using pig xenografts have laid promising groundwork towards future emergency use and first in human trials. Major obstacles remain though, including a lack of knowledge of the genetic incompatibilities between pig donors and human recipients which may led to harmful immune responses against the xenograft or dysregulation of normal physiology. In 2022 two pig heart xenografts were transplanted into two brain-dead human decedents with a minimized immunosuppression regime, primarily to evaluate onset of hyper-acute antibody mediated rejection and sustained xenograft function over 3 days. MethodsWe performed multi-omic profiling to assess the dynamic interactions between the pig and human genomes in the first two pig heart-xenografts transplants into human decedents. To assess global and specific biological changes that may correlate with immune-related outcomes and xenograft function, we generated transcriptomic, lipidomic, proteomic and metabolomics datasets, across blood and tissue samples collected every 6 hours over the 3-day procedures. ResultsSingle-cell datasets in the 3-day pig xenograft-decedent models show dynamic immune activation processes. We observe specific scRNA-seq, snRNA-seq and geospatial transcriptomic changes of early immune-activation leading to pronounced downstream T-cell activity and hallmarks of early antibody mediated rejection (AbMR) and/or ischemia reperfusion injury (IRI) in the first xenograft recipient. Using longitudinal multiomic integrative analyses from blood in addition to antigen presentation pathway enrichment, we also observe in the first xeno-heart recipient significant cellular metabolism and liver damage pathway changes that correlate with profound physiological dysfunction whereas, these signals are not present in the other xenograft recipient. ConclusionsSingle-cell and multiomics approaches reveal fundamental insights into early molecular immune responses indicative of IRI and/or early AbMR in the first human decedent, which was not evident in the conventional histological evaluations.

systems biology↗

bioRxiv2023

Determinants of Disordered Protein Co-Assembly Into Discrete Condensed Phases

Cells harbor numerous mesoscale membraneless compartments that house specific biochemical processes and perform distinct cellular functions. These protein and RNA-rich bodies are thought to form through multivalent interactions among proteins and nucleic acids resulting in demixing via liquid-liquid phase separation (LLPS). Proteins harboring intrinsically disordered regions (IDRs) predominate in membraneless organelles. However, it is not known whether IDR sequence alone can dictate the formation of distinct condensed phases. We identified a pair of IDRs capable of forming spatially distinct condensates when expressed in cells. When reconstituted in vitro, these model proteins do not co-partition, suggesting condensation specificity is encoded directly in the polypeptide sequences. Through computational modeling and mutagenesis, we identified the amino acids and chain properties governing homotypic and heterotypic interactions that direct selective condensation. These results form the basis of physicochemical principles that may direct subcellular organization of IDRs into specific condensates and reveal an IDR code that can guide construction of orthogonal membraneless compartments.

biophysics↗

bioRxiv2023

Inspiration of SARS-CoV-2 envelope protein mutations on pathogenicity of Omicron XBB

Predicting pathogenicity of Omicron sub-variants is critical for assessing disease dynamics and developing public health strategies. As an important virulence factor, SARS-CoV-2 envelope protein (2-E) causes cell death and acute respiratory distress syndrome (ARDS)-like pathological damages. Evaluation of 2-E mutations might offer clues to pathogenicity forecast. Here, the frequency and cell lethality of 92 mutations of 2-E in five early "variants of concern" (VOCs, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.3, BA.4, and BA.5) were analyzed, which could be divided into three classes. Most (87) mutations belong to Class I, no obvious frequency changes. Class II consists of 2 mutations, exhibiting enhanced cell lethality but decreased frequency. The rest 3 mutations in Class III were characterized by attenuated cell lethality and increased frequency. Remarkably, the Class II mutations are always observed in the VOCs with high disease severity while the Class III mutations are highly conserved in the VOCs with weakened pathogenicity. For example, P71L, the most lethal mutation, dropped to nearly 0.00% in the milder Omicrons from 99.12% in Beta, while the less lethal mutation T9I, sharply increased to 99.70% in BA.1 and is highly conserved in BA.1-5. Accordingly, we proposed that some key 2-E mutations are pathogenicity markers of the virus. Notably, the highly contagious Omicron XBB retained T9I also. In addition, XBB gained a new dominant-negative mutation T11A with frequency 90.52%, exhibiting reduced cell lethality, cytokine induction and viral production capabilities in vitro, and particularly weakened lung damages in mice. No mutations with enhanced cell lethality were observed in XBB. These clues imply a further weakened pathogenicity of XBB among Omicron sub-variants.

microbiology↗

bioRxiv2023

An effective sanitizer for fresh produce production: In situ plasma activated water treatment inactivates pathogenic bacteria and maintains the quality of cucurbit fruit

The effect of plasma activated water (PAW) generated with a dielectric barrier discharge diffusor (DBDD) system on microbial load and organoleptic quality of cucamelons was investigated and compared to the established sanitizer, sodium hypochlorite (NaOCl). Pathogenic serotypes of Escherichia coli, Salmonella enterica, and Listeria monocytogenes were inoculated onto the surface of cucamelons (6.5 log CFU g-1) and into the wash water (6 log CFU mL-1). PAW treatment involved 2 minutes in situ with water activated at 1500 Hz and 120 V, and air as the feed gas; NaOCl treatment was a wash with 100 ppm total chlorine; and the control treatment was a wash with tap water. PAW treatment produced a 3 log CFU g-1 reduction of pathogens on the cucamelon surface without negatively impacting quality or shelf life. NaOCl treatment reduced the pathogenic bacteria on the cucamelon surface by 3-4 log CFU g-1, however, this treatment also reduced fruit shelf life and quality. Both systems reduced 6 log CFU ml-1 pathogens in the wash water to below detectable limits. The critical role of superoxide anion radical ({middle dot}O2-) in the antimicrobial power of DBDD-PAW was demonstrated through a scavenger assay, and chemistry modelling confirmed that {middle dot}O2- generation readily occurs in DBDD-PAW generated with the employed settings. Modelling of the physical forces produced during plasma treatment showed that bacteria likely experience strong local electric fields and polarization. We hypothesize that these physical effects synergise with reactive chemical species to produce the acute antimicrobial activity seen with the in situ PAW system. ImportancePlasma activated water (PAW) is an emerging sanitizer in the fresh food industry, where food safety must be achieved without a thermal kill step. Here we demonstrate PAW generated in situ to be a competitive sanitizer technology, providing a significant reduction of pathogenic and spoilage micro-organisms while maintaining the quality and shelf life of the produce item. Our experimental results are supported by modelling of the plasma chemistry and applied physical forces, which show that the system can generate highly reactive superoxide radicals and strong electric fields that combine to produce potent antimicrobial power. In situ PAW has promise in industrial applications as it only requires low power (12 W), tap water and air. Moreover, it does not produce toxic by-products or hazardous effluent waste, making it a sustainable solution for fresh food safety.

microbiology↗

bioRxiv2022

Pooled genome-wide CRISPR activation screening for rapamycin resistance genes in Drosophila cells

Loss-of-function and gain-of-function genetic perturbations provide valuable insights into gene function. In Drosophila cells, while genome-wide loss-of-function screens have been extensively used to reveal mechanisms of a variety of biological processes, approaches for performing genome-wide gain-of-function screens are still lacking. Here, we describe a pooled CRISPR activation (CRISPRa) screening platform in Drosophila cells and apply this method to both focused and genome-wide screens to identify rapamycin resistance genes. The screens identified three genes as novel rapamycin resistance genes: a member of SLC16 family of monocarboxylate transporters (CG8468), a member of the lipocalin protein family (CG5399), and a zinc finger C2H2 transcription factor (CG9932). Mechanistically, we demonstrate that CG5399 overexpression activates the RTK-Akt-mTOR signaling pathway and that activation of InR by CG5399 requires cholesterol and clathrin-coated pits at the cell membrane. This study establishes a novel platform for functional genetic studies in Drosophila cells.

genetics↗

bioRxiv2022

Cell type-specific prediction of 3D chromatin architecture

The mammalian genome is spatially organized in the nucleus to enable cell type-specific gene expression. Investigating how chromatin organization determines this specificity remains a challenge. Methods for measuring the 3D chromatin organization, such as Hi-C, are costly and bear strong technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. In this study, we present C.Origami, a deep neural network model that performs de novo prediction of cell type-specific chromatin organization. The C.Origami model enables in silico experiments to examine the impact of genetic perturbations on chromatin interactions in cancer genomes and beyond. In addition, we propose an in silico genetic screening framework that enables high-throughput identification of impactful genomic regions on 3D chromatin organization. We demonstrate that cell type-specific in silico genetic perturbation and screening, enabled by C.Origami, can be used to systematically discover novel chromatin regulatory mechanisms in both normal and disease-related biological systems.

genomics↗

bioRxiv2022

Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters.

SARS-CoV-2 Omicron variant is highly transmissible and extensive morbidity, which has raised concerns for antiviral therapy. In addition, the molecular basis for the attenuated pathogenicity and replication capacity of Omicron remains elusive. Here, we report for the first time that a high-frequency mutation T9I on 2-E of SARS-CoV-2 variant Omicron forms a non-selective ion channel with abolished calcium permeability and reduced acid sensitivity compared to the WT channel. In addition, T9I caused less cell death and a weaker cytokine production. The channel property changes might be responsible for the Omicron variant releases less efficiently and induces a comparatively lower level of cell damage in the infected cells. Our study gives valuable insights into key features of the Omicron variant, further supporting 2-E is a promising drug target against SARS-CoV-2 and providing critical information for the COVID-19 treatment.

microbiology↗

bioRxiv2021

Recurrence of cancer cell states across diverse tumors and their interactions with the microenvironment

While genetic tumor heterogeneity has long been recognized, recent work has revealed significant variation among cancer cells at the epigenetic and transcriptional levels. Profiling tumors at the single-cell level in individual cancer types has shown that transcriptional heterogeneity is organized into cancer cell states, implying that diverse cell states may represent stable and functional units with complementary roles in tumor maintenance and progression. However, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Furthermore, the role of cancer cell states in tumor progression and their specific interactions with cells of the tumor microenvironment remain to be elucidated. Here, we perform a pan-cancer single-cell RNA-Seq analysis across 15 cancer types and identify a catalog of 16 gene modules whose expression defines recurrent cancer cell states, including stress, interferon response, epithelial-mesenchymal transition, metal response, basal and ciliated. Using mouse models, we find that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Moreover, spatial transcriptomic analysis further links the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance, and metastasis.

cancer biology↗

bioRxiv2021

LungCancer3D: A Comprehensive Database for Integrating Lung Cancer Chromatin Architecture with Other Multi-omics

With the breakthrough of chromatin conformation capture technologies in recent years, the importance of three-dimensional (3D) genome structure in gene expression, cell function regulation, disease occurrence, and development has been gradually recognized. To provide a comprehensive visualization of chromatin architecture and other multi-omics data for lung cancer research, we have constructed a comprehensive database, LungCancer3D (http://www.lungcancer3d.net). This web-based tool focuses on displaying human lung cancer-related HiC data along with a variety of other publicly available data, such as RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, DNA methylation, DNA mutation, and copy number variations. Researchers can visualize these diverse multi-omics data directly through the genome browser and discover how the genes expression is regulated at diverse levels. For example, we have demonstrated that the high expression level of C-MYC in lung cancer may be caused by the distant enhancer introduced by the de novo chromatin loops in lung cancer cells to bind the C-MYC promoter. The integrated multi-omics analyses through the LungCancer3D website can reveal the mechanisms underlying lung cancer development and provide potential targets for lung cancer therapy.

bioinformatics↗