Epigenomic modifications are instrumental for transcriptional regulation, but comprehensive reference epigenomes remain unexplored in rice. Here, we develop an enhanced chromatin immunoprecipitation (eChIP) approach for plants, and generate genome-wide profiling of five histone modifications and RNA polymerase II occupancy with it. By integrating chromatin accessibility, DNA methylation, and transcriptome datasets, we construct comprehensive epigenome landscapes across various tissues in 20 representative rice varieties. Approximately 81.8% of rice genomes are annotated with different epigenomic properties. Refinement of promoter regions using open chromatin and H3K4me3-marked regions provides insight into transcriptional regulation. We identify extensive enhancer-like promoters with potential enhancer function on transcriptional regulation through chromatin interactions. Active and repressive histone modifications and the predicted enhancers vary largely across tissues, whereas inactive chromatin states are relatively stable. Together, these datasets constitute a valuable resource for functional element annotation in rice and indicate the central role of epigenomic information in understanding transcriptional regulation.
Objective To analyze the clinical manifestations, diagnosis and treatment outcomes in a series of patients with epididymal tuberculosis. Methods This study is a retrospective data analysis of 47 cases of histologically-confirmed epididymal tuberculosis in patients treated at our hospital from November 2012 to December 2018. Results The average age of the patients was approximately 42 years. The epididymal lesion location was left-sided in 15 patients (31.9%), right-sided in 22 patients (46.8%) and bilateral in 10 patients (21.3%). The main symptoms were painless swelling of the scrotum in 21 cases (44.7%) and scrotal drop pain in 21 cases (44.7%). Scrotal physical examination revealed epididymal beaded enlargement in 12 patients (25.5%), testicular mass in one patient (2.1%), scrotal tenderness alone in seven patients (14.9%), ill-defined epididymal-testicular border in 21 patients (44.7%) and sinus formation in six patients (12.8%). After 2–4 weeks of anti-tuberculosis chemotherapy, the patients underwent a surgical procedure. We found that 10 (83.3%) of the 12 patients whose main symptom was epididymal beaded enlargement underwent simple epididymal surgery. Of the 21 patients whose main clinical manifestation was ill-defined testis-epididymis demarcation, 16 (72.2%) underwent epididymis-testicular surgery. All patients underwent postoperative chemotherapy for 3–6 months. Postoperative follow-up showed good response to treatment. Conclusion It is difficult to diagnose early-stage epididymal tuberculosis. Epididymal tuberculosis is likely to have invaded surrounding tissues when signs such as epididymal beaded changes and ill-defined epididymis-testis border are present. Surgical treatment combined with preoperative and postoperative chemotherapy is an effective approach to treating this condition.
Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose “degree of disorder” to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.
NHSBT Tissue Services issues bone to surgeons in the UK in two formats, fresh-frozen unprocessed bone from living donors and processed bone from deceased donors. Processed bone may be frozen or freeze dried and all processed bone is currently subjected to a washing protocol to remove blood and bone marrow. In this study we have improved the current bone washing protocol for cancellous bone and assessed the success of the protocol by measuring the removal of the bone marrow components: soluble protein, DNA and haemoglobin at each step in the process, and residual components in the bone at the end of the process. The bone washing protocol is a combination of sonication, warm water washes, centrifugation and chemical (ethanol and hydrogen peroxide) treatments. We report that the bone washing protocol is capable of removing up to 99.85 % soluble protein, 99.95 % DNA and 100 % of haemoglobin from bone. The new bone washing protocol does not render any bone cytotoxic as shown by contact cytotoxicity assays. No microbiological cell growth was detected in any of the wash steps. This process is now in use for processed cancellous bone issued by NHSBT.
Background Immunotherapeutic approaches have recently emerged as effective treatment regimens against various types of cancer. However, the immune‐mediated mechanisms surrounding papillary renal cell carcinoma (pRCC) remain unclear. This study aimed to investigate the tumor microenvironment (TME) and identify the potential immune‐related biomarkers for pRCC. Methods The CIBERSORT algorithm was used to calculate the abundance ratio of immune cells in each pRCC samples. Univariate Cox analysis was used to select the prognostic‐related tumor‐infiltrating immune cells (TIICs). Multivariate Cox regression analysis was performed to develop a signature based on the selected prognostic‐related TIICs. Then, these pRCC samples were divided into low‐ and high‐risk groups according to the obtained signature. Analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the biological function of the DEGs (differentially expressed genes) between the high‐ and low‐risk groups. The hub genes were identified using a weighted gene co‐expression network analysis (WGCNA) and a protein‐protein interaction (PPI) analysis. The hub genes were subsequently validated by multiple clinical traits and databases. Results According to our analyses, nine immune cells play a vital role in the TME of pRCC. Our analyses also obtained nine potential immune‐related biomarkers for pRCC, including TOP2A, BUB1B, BUB1, TPX2, PBK, CEP55, ASPM, RRM2, and CENPF. Conclusion In this study, our data revealed the crucial TIICs and potential immune‐related biomarkers for pRCC and provided compelling insights into the pathogenesis and potential therapeutic targets for pRCC.
ObjectivesTo investigate the utility of spectral computed tomography (CT) parameters for the prediction of the preoperative Masaoka-Koga stage of thymic epithelial tumors (TETs).Materials and MethodsFifty-four patients with TETs, aged from 37 to 73 years old, an average age of 55.56 ± 9.79 years, were included in the study.According to the Masaoka-Koga staging method, there were 19 cases of stage I, 15 cases of stage II, 8 cases of stage III, and 12 cases of stage IV disease. All patients underwent dual-phase enhanced energy spectral CT scans. Regions of interest (ROIs) were defined in sections of the lesion with homogeneous density, the thoracic aorta at the same level as the lesion, the outer fat layer of the lesion, and the anterior chest wall fat layer. The single-energy CT value at 40-140 keV, iodine concentration, and energy spectrum curve of all lesion and thoracic aorta were obtained. The energy spectrum CT parameters of the lesions, extracapsular fat of the lesions, and anterior chest wall fat in stage I and stage II were obtained. The energy spectrum CT parameters of the lesions, enlarged lymph nodes and intravascular emboli in the 3 groups were obtained. The slope of the energy spectrum curve and the normalized iodine concentration were calculated.ResultsIn stage I lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the lesion and those of the fat outside the lesion and the anterior chest wall in the arteriovenous phase (P<0.001, P<0.001). The energy spectrum curve of the tumor parenchyma was the opposite of that of the extracapsular fat. In stage II lesions, there was a statistically significant difference between the slope of the energy spectrum curve for the anterior chest wall and those of the lesion and the fat outside the lesion in the arteriovenous phase(P<0.001, P<0.001). The energy spectrum curve of the tumor parenchyma was consistent with that of the extracapsular fat. Distinction between stage I and II tumors be evaluated by comparing the energy spectrum curves of the mass and the extracapsular fat of the mass. The accuracy rate of is 79.4%. For stages III and IV, there was no significant difference in the slope of the energy spectrum curve of the tumor parenchyma, metastatic lymph node, and intravascular embolism (P>0.05). The energy spectrum curve of the tumor parenchyma was consistent with that of the enlarged lymph nodes and intravascular emboli. The two radiologists have strong consistency in evaluating TETs Masaoka-Koga staging, The Kappa coefficient is 0.873,(95%CI:0.768-0.978).ConclusionSpectral CT parameters, especially the energy spectrum curve and slope, are valuable for preoperative TET and can be used in preoperative staging prediction.
Background: Immunotherapeutic approaches have recently emerged as effective treatment regimens against various types of cancer. However, the immune-mediated mechanisms surrounding papillary renal cell carcinoma (pRCC) remain unclear. This study aimed to investigate the tumor microenvironment (TME) and identify the potential immune-related biomarkers for pRCC.Methods: The CIBERSORT algorithm was used to calculate the abundance ratio of immune cells in each pRCC sample downloaded from the database UCSC Xena. Univariate Cox analysis was used to select the prognostic-related tumor-infiltrating immune cells (TIICs). Multivariate Cox regression analysis was performed to develop a signature based on the selected prognostic-related TIICs. Then, these pRCC samples were divided into low- and high-risk groups according to the obtained signature. Analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the biological function of the DEGs (differentially expressed genes) between the high- and low-risk groups. The hub genes were identified using a Weighted Gene Co-Expression Network Analysis (WGCNA) and a Protein-Protein Interaction (PPI) analysis. The hub genes were subsequently validated using Kaplan-Meier survival analysis, Receiver Operating Characteristic (ROC) analysis, a nomogram prediction model, and via the Gene Expression Omnibus (GEO) database, and the Human Protein Atlas (HPA) database. Finally, we validated the correlation between the nine hub genes and immune cells using the XCELL algorithm.Results: According to our analyses, nine immune cells play a vital role in the TME of pRCC. Our analyses also obtained nine potential immune-related biomarkers for pRCC, including TOP2A, BUB1B, BUB1, TPX2, PBK, CEP55, ASPM, RRM2, and CENPF.Conclusion: In this study, our data revealed the crucial TIICs and potential immune-related biomarkers for pRCC and provided compelling insights into the pathogenesis and potential therapeutic targets for pRCC.
Background Hypoxia-reperfusion (HR) and inflammation are causes of renal allograft injury. Pathological evidence has indicated that ischemia followed by reperfusion leads to the proteolysis and destruction of the extracellular matrix (ECM) in renal tubular epithelial cells. Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, play roles in cleaving and reshaping the ECM. Acute accumulation of MMP-9 secreted from neutrophils promotes the incidence of inflammation and exacerbates graft trauma. Our goal was to investigate the activities of MMP-9/MMP-2 and their correlation with HR injury and neutrophil-related inflammation in renal proximal tubular cells. Methods This model was established by placing HK-2 cells under hypoxic conditions (5% CO 2 , 1% O 2 ) for 6 h and then exposing them to reperfusion (5% CO 2 , 21% O 2 ) for 12 h in a tri-gas incubator. The cell culture medium was collected for culturing polymorphonuclear leukocytes (PMNs). BB-94 (MMP-9 inhibitor) was added to the culture medium in the inhibitor group. Results Flow cytometry showed a significant increase in reactive oxygen species (ROS) levels in HK-2 cells from the HR injury group. MMP-9 expression was significantly increased and MMP-2 expression was significantly decreased in HK-2 cells from the HR group. MMP-9 and MPO expression were significantly increased in the HR group, while MPO expression was significantly decreased in the PMN inhibitor group. Conclusions The outcomes indicated that MMP-9 and MMP-2 are important components of an underlying pathophysiological mechanism of injury following HR. MMP-9 inhibition may be a potential approach to mitigateHR injury.
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