Knowledge, attitude, and practice towards bacterial multidrug-resistance and structural equation modeling analysis among intensive care unit nurses and physicians.

BACKGROUND: The intensive care unit (ICU) is a department with a high risk of MDR bacteria, and ICU nurses and physicians play critical roles in bacterial multidrug resistance (MDR) prevention. OBJECTIVES: To explore the knowledge, attitudes, and practice (KAP) towards bacterial MDR among ICU nurses and physicians. METHODS: A self-designed questionnaire was administered to collect data. Structural equation modeling (SEM) was applied to assess the associations among study variables. RESULTS: A total of 369 questionnaires were collected; 43 questionnaires were excluded due to self-contradictory on the trap question or the obviously repeated pattern. Finally, 326 (88.35%) valid questionnaires were included in the analysis. The knowledge, attitudes, and practice were 13.57 ± 1.69 (90.47%, possible range: 0-15), 38.75 ± 2.23 (96.88%, possible range: 8-40), and 47.40 ± 3.59 (94.80%, possible range: 10-50). The SEM showed that knowledge had a direct effect on attitude with a direct effect value of 0.61 (P < 0.001) and a direct negative effect on practice with a direct effect value of -0.30 (P = 0.009). The direct effect of attitude on practice was 0.89 (P < 0.001); the indirect effect of knowledge through attitude on practice was 0.52 (P < 0.001). Job satisfaction had a direct effect on attitude and practice, with an effect value of 0.52 (P = 0.030) and 0.75 (P = 0.040). Being a physician (OR = 0.354, 95%CI: 0.159-0.790, P = 0.011), 5-9.9 years of practice (OR = 4.534, 95%CI: 1.878-8.721, P < 0.001), and ≥ 10 years of practice (OR = 3.369, 95%CI: 1.301-8.721, P = 0.012) were independently associated with good knowledge. The attitude scores (OR = 1.499, 95%CI: 1.227-1.830, P < 0.001), male gender (OR = 0.390, 95%CI: 0.175-0.870, P = 0.022), and 5-9.9 years of experience (OR = 0.373, 95%CI: 0.177-0.787, P = 0.010) were independently associated with proactive practice. CONCLUSION: Nurses and physicians in the ICU showed good knowledge, positive attitudes, and proactive practice toward bacterial MDR. Nurses and physicians' knowledge had a direct effect on their attitude, while attitude might directly influence the practice and also play a mediating role between knowledge and practice. Job satisfaction might directly support the positive attitude and practice toward bacterial MDR.

The functional role of cellular senescence during vascular calcification in chronic kidney disease.

Vascular calcification (VC) has emerged as a key predictor of cardiovascular events in patients with chronic kidney disease (CKD). In recent years, an expanding body of research has put forth the concept of accelerated vascular aging among CKD patients, highlighting the significance of vascular cells senescence in the process of VC. Within the milieu of uremia, senescent vascular endothelial cells (VECs) release extracellular microvesicles (MV) that promote vascular smooth muscle cells (VSMCs) senescence, thereby triggering the subsequent osteogenic phenotypic switch and ultimately contributing to the VC process. In addition, senescent vascular progenitor or stem cells with diminished ability to differentiate into VECs and VSMCS, compromise the repair of vascular integrity, on the other hand, release a cascade of molecules associated with senescence, collectively known as the senescence-associated secretory phenotype (SASP), perpetuating the senescence phenomenon. Furthermore, SASP triggers the recruitment of monocytes and macrophages, as well as adjacent VECs and VSMCs into a pro-adhesive and pro-inflammatory senescent state. This pro-inflammatory microenvironment niche not only impacts the functionality of immune cells but also influences the differentiation of myeloid immune cells, thereby amplifying the reduced ability to effectively clear senescent cells of senescent macrophages, promoted calcification of VSMCs. The objective of this paper is to provide a comprehensive review of the contribution of vascular cell senescence to the emergence and advancement of VC. Gaining a comprehensive understanding of the involvement of cellular senescence within the vessel wall is pivotal, especially when it comes to its intersection with VC. This knowledge is essential for advancing groundbreaking anti-aging therapies, aiming to effectively mitigate cardiovascular diseases.

AraENCODE: A comprehensive epigenomic database of Arabidopsis thaliana.

Arabidopsis is an important model organism in plant biology and genetics, and a large number of a chromatin conformation and epigenomic datasets have been generated to study the biology in Arabidopsis. To make it easier to access the accumulated epigenomic data, a user-friendly and reproducible epigenomic database, AraENCODE was developed. It contains various datasets and resources, including chromatin conformation, epigenomic, and transcriptome data, allowing researchers to investigate the regulation of epigenetic and chromatin interactions in Arabidopsis.

The role of HBV cccDNA in occult hepatitis B virus infection.

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of replication-competent HBV DNA in the liver, with or without HBV DNA in the blood, in individuals who tested negative for HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Several advances have been made toward clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. Although the underlying mechanisms describing the genesis of OBI are not completely known, the presence of viral cccDNA, which remains in a low state of replication due to the host's strong immune suppression of HBV replication and gene expression, appears to be the causative factor. Through this review, we have provided an updated account on the role of HBV cccDNA in regulating OBI. We have comprehensively described the HBV cell cycle, cccDNA kinetics, current regulatory mechanisms, and the therapeutic methods of cccDNA in OBI-related diseases.

Improving the Transduction Efficiency and Antitumor Effect of Conditionally Replicative Adenovirus by Application of 6-cyclohexyl Methyl-ß-D-maltoside.

As a tumor-targeting oncolytic adenovirus (Ad), conditionally replicating adenovirus (CRAd) can access the cell interior by binding to coxsackievirus-Ad receptors (CARs) and specifically replicate and destroy cancer cells without lethal effects on normal cells. The transduction efficiency of CRAd is highly dependent on the number of CARs on the cell membrane. However, not all tumor cells highly express CARs; therefore, improving the transduction efficiency of CRAd is beneficial for improving its antitumor effect. In this study, 6-cyclohexyl methyl-ß-D-maltoside (6-ß-D), as maltoside transfection agent, showed several advantages, including high transfection efficiency, low toxicity, and potential for intensive use and easy operation. With pretreatment of cancer cells with low concentration of 6-ß-D (≤5 µg/mL), the transduction efficiency of "model" Ad (eGFP-Ad) was improved 18-fold compared to eGFP-Ad alone. 6-ß-D improved the antitumor effect of CRAd while being safe for normal cells, in which treatment with 6-ß-D helped the lethal effects of CRAd at a multiplicity-of-infection ratio of 10 (MOI 10) achieve the oncolytic outcomes of MOI 50. This means that if CRAd is combined with 6-ß-D, the amount of CRAd used in clinical practice could be greatly reduced without diminishing its curative effect or exposing patients to the potential side effects of high-titer CRAd. Finally, the underlying mechanism of antitumor effect of CRAd + 6-ß-D was primarily investigated, and we found that 6-ß-D increased the virus's replication in cancer cells at the early stage of infection and activated the apoptosis signaling pathway at the late stage of the cell cycle. This research will provide an effective technical reference for further improving Ad-mediated cancer gene therapy in clinical practice.

Durability of Antibody Response Against Hepatitis B Virus for a Decreased Crowd: A Retrospective Polycentric Cohort Study from a 10-Year Follow-Up Clinical Study.

Aim: Hepatitis B surface antibody (HBsAb) plays an important role in the prevention of hepatitis B virus (HBV) infection, especially in immunocompromised individuals and in those infected with HBV.HBsAb levels often fluctuate and decrease.This study aimed to determine the regularity of HBsAb persistence among different populations. Moreover, the risk factors and the optimal cutoff value were determined to predict a decreasing population in HBsAb level. Methods: The study involved 182 participants, including 76 patients with a 25% decrease in HBsAb levels and 106 patients with an HBsAb decrease rate of >50%. Both hepatitis B core antibody negative and positive patients were included.These patients were followed up for 10 years. The follow-up demographic and laboratory data were recorded and compared among the groups. Fluctuations in HBsAb data and HBsAb persistent immunity were evaluated. The independent factors and the optimal cutoff value were recorded. Results: The first HBsAb median of Group 4 was lower than that of the other groups, and its median was 50.8 mlU/mL. In addition, the persistent immunity of the case groups was shorter than that of the control groups (p < 0.05). Furthermore, previous HBV history, use of antiviral drugs, and low levels of first HBsAb were independent risk factors in people with obviously decreased antibody levels. Also, when the optimum cutoff value on the receiver operating characteristic curve of the HBsAb difference value was taken as 8.53 mIU/mL, its sensitivity and specificity were 94% and 70% between the control and case groups, respectively. Conclusion: To maintain optimal immunity against HBV infection, patients with a previous HBV history, those taking antiviral drugs, and/or those with low levels of HBsAb should be reimmunized with the hepatitis B vaccine in a timely manner.

DNA methylation in transposable elements buffers the connection between three-dimensional chromatin organization and gene transcription upon rice genome duplication.

INTRODUCTION: Polyploidy is a major force in plant evolution and the domestication of cultivated crops. OBJECTIVES: The study aimed to explore the relationship and underlying mechanism between three-dimensional (3D) chromatin organization and gene transcription upon rice genome duplication. METHODS: The 3D chromatin structures between diploid (2C) and autotetraploid (4C) rice were compared using high-throughput chromosome conformation capture (Hi-C) analysis. The study combined genetics, transcriptomics, whole-genome bisulfite sequencing (WGBS-seq) and 3D genomics approaches to uncover the mechanism for DNA methylation in modulating gene transcription through 3D chromatin architectures upon rice genome duplication. RESULTS: We found that 4C rice presents weakened intra-chromosomal interactions compared to its 2C progenitor in some chromosomes. In addition, we found that changes of 3D chromatin organizations including chromatin compartments, topologically associating domains (TADs), and loops, are uncorrelated with gene transcription. Moreover, DNA methylations in the regulatory sequences of genes in compartment A/B switched regions and TAD boundaries are unrelated to their expression. Importantly, although there was no significant difference in the methylation levels in transposable elements (TEs) in differentially expressed gene (DEG) and non-DEG promoters between 2C and 4C rice, we found that the hypermethylated TEs across genes in compartment A/B switched regions and TAD boundaries may suppress the expression of these genes. CONCLUSION: The study proposed that the rice genome doubling might modulate TE methylation to buffer the effects of chromatin architecture on gene transcription in compartment A/B switched regions and TAD boundaries, resulting in the disconnection between 3D chromatin structure alteration and gene transcription upon rice genome duplication.

Using Pandemic Data to Examine the Government's Pandemic Prevention Measures and Its Support Policies for Vulnerable Groups.

The outbreak of COVID-19 and the uncertainty it brings have created enormous pressure on governments to control the global pandemic and restore economic growth. It is an inevitable choice for governments of various countries to seek to control the pandemic and to provide support such as subsidies to people who lose their jobs or cannot work. However, governments should evaluate their pandemic policies to determine their effectiveness. To maintain social stability and help vulnerable groups, governments also must determine when subsidies are needed and when these support policies should be withdrawn. This research demonstrates that the administration of vaccines and the wearing of masks have a relatively limited impact on preventing the spread of the COVID-19 virus. By contrast, strict school closure policies combined with personal movement restrictions are more helpful in mitigating the spread of the virus. Compared with vaccine policies and wearing masks, controlling internal movement is the most effective way to manage the pandemic in schools. Additionally, economic support such as subsidies for the unemployed and underemployed is not only conducive to prevention of the virus' spread but also to economic recovery and social stability. When the pandemic is brought under control, economic support for vulnerable groups can be gradually reduced or even withdrawn.

Dynamic insights into increasing antibiotic resistance in Staphylococcus aureus by label-free SERS using a portable Raman spectrometer.

Rapid and quantitative detection of bacterial antibiotic resistance is of great significance for the prevention and treatment of infections and understanding drug-resistant mechanism. In this study, label-free surface-enhanced Raman spectroscopy (SERS) technology was applied to dynamically explore oxacillin/cefazolin-derived resistance in Staphylococcus aureus using a portable Raman spectrometer. The results showed that S. aureus rapidly responded to oxacillin/cefazolin stimulation and gradually developed different degrees of drug resistance during the 21 days of exposure. The molecular changes that accumulated in the drug-resistant strains were sensitively recorded by SERS in a whole-cell manner. Principal components-linear discriminant analysis correctly distinguished various degrees of drug-resistant strains. The typical Raman peak intensities of I734/I867 showed a negative and non-linear correlation with the minimum inhibitory concentration (MIC). The correlation coefficient reached above 0.9. The target sites of oxacillin/cefazolin on S. aureus clearly reflected on SERS profiles. The results collected by SERS were further verified by other biological methods including the antibiotic susceptibility test, MIC determination, and PCR results. This study indicates that SERS technology provides a rapid and flexible alternative to current drug susceptibility testing, laying a foundation for qualitative and quantitative evaluation of drug resistance in clinical detection.

Exploiting the Fracture in Metal-Organic Frameworks: A General Strategy for Bifunctional Atom-Precise Nanocluster/ZIF-8(300 °C) Composites.

Atom-precise nanoclusters-metal-organic framework (APNC/MOF) composites, as bifunctional material with well-defined structures, have attracted considerable attention in recent years. Despite the progress made to date, there is an urgent need to develop a generic and scalable approach for all APNCs. Herein, the authors present the Exploiting Fracture Strategy (EFS) and successfully construct a super-stable bifunctional APNC/ZIF-8(300 °C) composite overcoming the limitations of previous strategies in selecting APNCs. The EFS utilizes the fracture of ZnN in ZIF-8 after annealing at 300 °C. This method is suitable for all kinds of S/P protected APNCs with different sizes, including uncharged clusters Au1 Ag39 , Ag40 , negatively charged Au12 Ag32 , positively charged Ag46 Au24 , Au4 Cu4 and P-ligand-protected Pd3 Cl. Importantly, the generated APNC/MOF show significantly improved performances, for example, the activities of Au12 Ag32 /ZIF-8(300°C), Au4 Cu4 /ZIF-8(300°C), and Au1 Ag39 /ZIF-8(300°C) in the corresponding reactions are higher than those of Au12 Ag32 , Au4 Cu4 , and Au1 Ag39 , respectively. In particular, Au12 Ag32 /ZIF-8(300 °C) shows higher activity than Au12 Ag32 @ZIF-8. Therefore, this work offers guidance for the design of bifunctional APNC/MOF composites with excellent optimization of properties and opens up new horizons for future related nanomaterial studies and nanocatalyst designs.

Rapid, Label-Free Prediction of Antibiotic Resistance in Salmonella typhimurium by Surface-Enhanced Raman Spectroscopy.

The rapid identification of bacterial antibiotic susceptibility is pivotal to the rational administration of antibacterial drugs. In this study, cefotaxime (CTX)-derived resistance in Salmonella typhimurium (abbr. CTXr-S. typhimurium) during 3 months of exposure was rapidly recorded using a portable Raman spectrometer. The molecular changes that occurred in the drug-resistant strains were sensitively monitored in whole cells by label-free surface-enhanced Raman scattering (SERS). Various degrees of resistant strains could be accurately discriminated by applying multivariate statistical analyses to bacterial SERS profiles. Minimum inhibitory concentration (MIC) values showed a positive linear correlation with the relative Raman intensities of I990/I1348, and the R2 reached 0.9962. The SERS results were consistent with the data obtained by MIC assays, mutant prevention concentration (MPC) determinations, and Kirby-Bauer antibiotic susceptibility tests (K-B tests). This preliminary proof-of-concept study indicates the high potential of the SERS method to supplement the time-consuming conventional method and help alleviate the challenges of antibiotic resistance in clinical therapy.

TAD boundary and strength prediction by integrating sequence and epigenetic profile information.

Topologically associated domains (TADs) are one of the important higher order chromatin structures with various sizes in the eukaryotic genomes. TAD boundaries, as the flanking regions between adjacent domains, can restrict the interactions of regulatory elements, including enhancers and promoters, and are generally dynamic and variable in different cells. However, the influence of sequence and epigenetic profile-based features in the identification of TAD boundaries is largely unknown. In this work, we proposed a method called pTADS (prediction of TAD boundary and strength), to predict TAD boundaries and boundary strength across multiple cell lines with DNA sequence and epigenetic profile information. The performance was assessed in seven cell lines and three TAD calling methods. The results demonstrate that the TAD boundary can be well predicted by the selected shared features across multiple cell lines. Especially, the model can be transferable to predict the TAD boundary from one cell line to other cell lines. The boundary strength can be characterized by boundary score with good performance. The predicted TAD boundary and TAD boundary strength are further confirmed by three Hi-C contact matrix-based methods across multiple cell lines. The codes and datasets are available at https://github.com/chrom3DEpi/pTADS.

Insight into the Mechanism of the CuAAC Reaction by Capturing the Crucial Au4Cu4-π-Alkyne Intermediate.

The classic Fokin mechanism of the CuAAC reaction of terminal alkynes using a variety of Cu(I) catalysts is well-known to include alkyne deprotonation involving a bimetallic σ,π-alkynyl intermediate. In this study, we have designed a CNT-supported atomically precise nanocluster Au4Cu4 (noted Au4Cu4/CNT) that heterogeneously catalyzes the CuAAC reaction of terminal alkynes without alkyne deprotonation to a σ,π-alkynyl intermediate. Therefore, three nanocluster-π-alkyne intermediates [Au4Cu4(π-CH≡C-p-C6H4R)], R = H, Cl, and CH3, have been captured and characterized by MALDI-MS. This Au4Cu4/CNT system efficiently catalyzed the CuAAC reaction of terminal alkynes, and internal alkynes also undergo this reaction. DFT results further confirmed that HC≡CPh was activated by π-complexation with Au4Cu4, unlike the classic dehydrogenation mechanism involving the bimetallic σ,π-alkynyl intermediate. On the other hand, a Cu11/CNT catalyst was shown to catalyze the reaction of terminal alkynes following the classic deprotonation mechanism, and both Au11/CNT and Cu11/CNT catalysts were inactive for the AAC reaction of internal alkynes under the same conditions, which shows the specificity of Au4Cu4 involving synergy between Cu and Au in this precise nanocluster. This will offer important guidance for subsequent catalyst design.

Rapid and label-free identification of different cancer types based on surface-enhanced Raman scattering profiles and multivariate statistical analysis.

Rapid detection and classification of cancer cells with label-free and non-destructive methods are helpful for rapid screening of cancer patients in clinical settings. Here, surface-enhanced Raman scattering (SERS) was used for rapid, unlabeled, and non-destructive detection of seven different cell types, including human cancer cells and non-tumorous cells. Au nanoparticles were used as enhanced substrates and directly added to cell surfaces. The single cellular SERS signals could be easily and stably collected in several minutes, and the cells maintained structural integrity over one hour. Different types of cells had unique Raman phenotypes. By applying multivariate statistical analysis to the Raman phenotypes, the cancer cells and non-tumorous cells were accurately identified. The high sensitivity enabled this method to discriminate subtle molecular changes in different cell types, and the accuracy reached 81.2% with principal components analysis and linear discriminant analysis. The technique provided a rapid, unlabeled, and non-destructive method for the detection and identification of various cancer types.

Copper stress induces zebrafish central neural system myelin defects via WNT/NOTCH-hoxb5b signaling and pou3f1/fam168a/fam168b DNA methylation.

Unbalanced copper (Cu) homeostasis is associated with neurological development defects and diseases. However, the molecular mechanisms remain elusive. Here, central neural system (CNS) myelin defects and the down-regulated expression of WNT/NOTCH signaling and its down-stream mediator hoxb5b were observed in Cu2+ stressed zebrafish larvae. The loss/knockdown-of-function of hoxb5b phenocopied the myelin and axon defects observed in Cu2+ stressed embryos. Meanwhile, the activation of WNT/NOTCH signaling and ectopic expression of hoxb5b could rescue Cu induced myelin defects. Additionally, fam168b, similar to pou3f1/2, exhibited significant promoter hypermethylation and reduced expression in Cu2+ stressed embryos. The hypermethylated locus in fam168b promoter acted pivotally in its transcription, and the loss/knockdown of fam168b/pou3f1 also induced myelin defects. This study also demonstrated that fam168b/pou3f1 and hoxb5b axis acted in a seesaw manner during fish embryogenesis: Cu induced the down-regulated expression of the WNT&NOTCH-hoxb5b axis through the function of copper transporter cox17, coupled with the promoter methylation of genes fam168b/pou3f1, and its subsequent down-regulated expression through the function of another transporter atp7b, making joint contributions to myelin defects in embryos.

Evaluation of the effects of sequence length and microsatellite instability on single-guide RNA activity and specificity.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology is effective for genome editing and now widely used in life science research. However, the key factors determining its editing efficiency and off-target cleavage activity for single-guide RNA (sgRNA) are poorly documented. Here, we systematically evaluated the effects of sgRNA length on genome editing efficiency and specificity. Results showed that sgRNA 5'-end lengths can alter genome editing activity. Although the number of predicted off-target sites significantly increased after sgRNA length truncation, sgRNAs with different lengths were highly specific. Because only a few predicted off-targets had detectable cleavage activity as determined by Target capture sequencing (TargetSeq). Interestingly, > 20% of the predicted off-targets contained microsatellites for selected sgRNAs targeting the dystrophin gene, which can produce genomic instability and interfere with accurate assessment of off-target cleavage activity. We found that sgRNA activity and specificity can be sensitively detected by TargetSeq in combination with in silico prediction. Checking whether the on- and off-targets contain microsatellites is necessary to improve the accuracy of analyzing the efficiency of genome editing. Our research provides new features and novel strategies for the accurate assessment of CRISPR sgRNA activity and specificity.

Label-Free Exosomal Detection and Classification in Rapid Discriminating Different Cancer Types Based on Specific Raman Phenotypes and Multivariate Statistical Analysis.

Exosomes contain different functional bimolecular characteristics related to physiological or pathological processes and are now recognized as new biomarkers in different human cancers. Rapid detection and classification of cancer-related exosomes might be helpful in the rapid screening of patients that may have cancer. Here, we report a surface enhanced Raman scattering technology for rapid and label-free exosomal detection (Exo-SERS) to aid in the discrimination of different cancer cells based on specific Raman phenotypes and multivariate statistical analysis. The results demonstrated that exosomes derived from both tumor cells and normal cells exhibit special, unique Raman phenotypes. Using the Exo-SERS method, the cancer cells were accurately discriminated from normal cells, and subtle molecular changes between the different cell types could be detected with high sensitive. This research provides a rapid, label-free and non-destructive manner for detecting and discriminating between cancer types.

The effects of Arabidopsis genome duplication on the chromatin organization and transcriptional regulation.

Autopolyploidy is widespread in higher plants and important for agricultural yield and quality. However, the effects of genome duplication on the chromatin organization and transcriptional regulation are largely unknown in plants. Using High-throughput Chromosome Conformation Capture (Hi-C), we showed that autotetraploid Arabidopsis presented more inter-chromosomal interactions and fewer short-range chromatin interactions compared with its diploid progenitor. In addition, genome duplication contributed to the switching of some loose and compact structure domains with altered H3K4me3 and H3K27me3 histone modification status. 539 genes were identified with altered transcriptions and chromatin interactions in autotetraploid Arabidopsis. Especially, we found that genome duplication changed chromatin looping and H3K27me3 histone modification in Flowering Locus C. We propose that genome doubling modulates the transcription genome-wide by changed chromatin interactions and at the specific locus by altered chromatin loops and histone modifications.

Hierarchical cooperation of transcription factors from integration analysis of DNA sequences, ChIP-Seq and ChIA-PET data.

BACKGROUND: Chromosomal architecture, which is constituted by chromatin loops, plays an important role in cellular functions. Gene expression and cell identity can be regulated by the chromatin loop, which is formed by proximal or distal enhancers and promoters in linear DNA (1D). Enhancers and promoters are fundamental non-coding elements enriched with transcription factors (TFs) to form chromatin loops. However, the specific cooperation of TFs involved in forming chromatin loops is not fully understood. RESULTS: Here, we proposed a method for investigating the cooperation of TFs in four cell lines by the integrative analysis of DNA sequences, ChIP-Seq and ChIA-PET data. Results demonstrate that the interaction of enhancers and promoters is a hierarchical and dynamic complex process with cooperative interactions of different TFs synergistically regulating gene expression and chromatin structure. The TF cooperation involved in maintaining and regulating the chromatin loop of cells can be regulated by epigenetic factors, such as other TFs and DNA methylation. CONCLUSIONS: Such cooperation among TFs provides the potential features that can affect chromatin's 3D architecture in cells. The regulation of chromatin 3D organization and gene expression is a complex process associated with the hierarchical and dynamic prosperities of TFs.