COL8A1 is a potential prognostic biomarker associated with migration, proliferation, and tumor microenvironment in glioma.

Glioblastoma (GBM) is a common primary central nervous system tumor. The molecular mechanisms of glioma are unknown, and the prognosis is poor. Therefore, exploring the underlying mechanisms and screening for new prognostic markers and therapeutic targets is crucial. We utilized the weighted gene co-expression network analysis (WGCNA), Differentially Expressed Genes (DEGs), and LASSO-COX analysis to identify three target genes. Next, we constructed and evaluated a prognostic model, screening out COL8A1 as a risk gene. Through a sequence of cellular functional experiments, in vivo studies, and RNA sequencing, we delved into exploring the functional effects and molecular mechanisms of COL8A1 on GBM cells. Finally, the correlation between COL8A1 and tumor immune cells and different inflammatory responses was analyzed. Immunohistochemistry experiments revealed the influence of COL8A1 on macrophage polarization. The COL8A1 expression level was associated with the grade, prognosis, and tumor microenvironment (TME) of glioma. Functional experiments showed that COL8A1 inhibited GBM cell apoptosis and promoted migration, invasion, and proliferation in vitro and in vivo. We also found that COL8A1 promotes the epithelial-mesenchymal transition process and may mediate the activation of the ERK pathway through SHC1. In addition, immune infiltration analysis showed that COL8A1 was closely associated with macrophages in glioma tissues, significantly suppressing the signaling of M1-like -type macrophages and enhancing the signaling of M2-like -type macrophages. COL8A1 was first found to be associated with prognosis, progression, and immune microenvironment of glioma and may serve as a new marker of prognosis and a therapeutic target.

RBBP4 is an epigenetic barrier for the induced transition of pluripotent stem cells into totipotent 2C-like cells.

Cellular totipotency is critical for whole-organism generation, yet how totipotency is established remains poorly illustrated. Abundant transposable elements (TEs) are activated in totipotent cells, which is critical for embryonic totipotency. Here, we show that the histone chaperone RBBP4, but not its homolog RBBP7, is indispensable for maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms mESCs to the totipotent 2C-like cells. Also, loss of RBBP4 enhances transition from mESCs to trophoblast cells. Mechanistically, RBBP4 binds to the endogenous retroviruses (ERVs) and functions as an upstream regulator by recruiting G9a to deposit H3K9me2 on ERVL elements, and recruiting KAP1 to deposit H3K9me3 on ERV1/ERVK elements, respectively. Moreover, RBBP4 facilitates the maintenance of nucleosome occupancy at the ERVK and ERVL sites within heterochromatin regions through the chromatin remodeler CHD4. RBBP4 depletion leads to the loss of the heterochromatin marks and activation of TEs and 2C genes. Together, our findings illustrate that RBBP4 is required for heterochromatin assembly and is a critical barrier for inducing cell fate transition from pluripotency to totipotency.

Spinster homolog 2 reduces malignancies of glioblastoma via PTEN/PI3K/AKT pathway.

The molecular mechanisms of glioblastoma (GBM) are unclear, and the prognosis is poor. Spinster homolog 2 (SPNS2) is reportedly involved in pathological processes such as immune response, vascular development, and cancer. However, the biological function and molecular role of SPNS2 in GBM are unclear. SPNS2 is aberrantly low expressed in glioma. Survival curves, risk scores, prognostic nomograms, and univariate and multifactorial Cox regression analyses showed that SPNS2 is an independent prognostic indicator significantly associated with glioma progression and prognosis. Cell function assays and in vivo xenograft transplantation were performed that downregulation of SPNS2 promoted GBM cell growth, migration, invasion, epithelial-mesenchymal transition (EMT), anti-apoptosis, drug resistance, and stemness, while overexpression of SPNS2 had the opposite effect. Meanwhile, the functional enrichment and signaling pathways of SPNS2 in the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and RNA sequencing were analyzed by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA). The above results were related to the inhibition of the PTEN/PI3K/AKT pathway by SPNS2. In addition, we predicted that SPNS2 is closely associated with immune infiltration in the tumor microenvironment by four immune algorithms, ESTIMATE, TIMER, CIBERSORT, and QUANTISEQ. In particular, SPNS2 was negatively correlated with the infiltration of most immune cells, immunomodulators, and chemokines. Finally, single-cell sequencing analysis also revealed that SPNS2 was remarkably correlated with macrophages, and downregulation of SPNS2 promotes the expression of M2-like macrophages. This study provides new evidence that SPNS2 inhibits malignant progression, stemness, and immune infiltration of GBM cells through PTEN/PI3K/AKT pathway. SPNS2 may become a new diagnostic indicator and potential immunotherapeutic target for glioma.

YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency.

Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.

Surgical Resection of Primary Cardiac Cavernous Hemangioma: A Case Report.

Cardiac tumors are rare. They were found in only 0.001%-0.300% of cases in a relatively recently reported autopsy series. Among cardiac tumors, primary hemangioma accounted for approximately 2.8% of all primary resected tumors, indicating this is a particularly rare benign neoplasm. We present a patient with a 5×3×2 cm cavernous hemangioma, arising from the right atrial roof and occupying the atrial septum and inseparable from the aortic root. We successfully accomplished a complete surgical resection of a cardiac cavernous hemangioma and reconstructed the cardiac atrium by a bovine pericardial patch.

Quadruple valve replacement for patient with infective endocarditis 16 years after Fallot's Tetralogy Repair procedure: A case report.

A 33-year-old man, who had previously undergone repair for Tetralogy of Fallot, presented with extensive infective endocarditis. Following thorough preoperative preparation and evaluation, we performed a simultaneous quadruple valve replacement alongside the repatching of the remaining defect. We posit that this comprehensive one-stage surgical intervention not only enhanced the patient's quality of life but also reduced the necessity for future reoperations. Our approach offers valuable insights for managing adult patients with repaired congenital heart diseases and multiple valve pathologies.

CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.

Native bicuspid aortic valve thrombus in a patient with an ascending aorta aneurysm: A case report.

Thrombus formation on a well-conserved bicuspid aortic valve is rare. We encountered a patient with organized thrombus formation on a native bicuspid aortic valve without calcification or stenosis, which was found occasionally during an elective operation for ascending aorta replacement surgery. The location of the thrombus was just at the orifice of left coronary artery, which produced the atherosclerosis-like symptoms such like exertional chest tightness and dyspnea. And these are no apparent predisposing causes of thrombosis could be ascertained postoperatively. The patient is in excellent condition 6 months after the operation. The lesson we learned from our case is that when the patient's symptom can't correspond with his or her diagnosis, we should ask more questions, evaluate the patient thoroughly and make the differential diagnosis as possible as we can. And the surgery can be performed aggressively when patient's symptoms cannot be figured out by physical examination, not only for pathologic confirmation but also for the prevention of life-threatening complications that can caused by either condition.

Surgery for angiosarcoma and other cardiac sarcomas: A single-institution experience.

Background: Cardiac sarcomas are rare malignancies with a poor prognosis. Although angiosarcoma is the most common histological subtype, its features are poorly characterized. This study aimed to compare the clinical characteristics of the various cardiac sarcomas and the surgical techniques used and to identify factors influencing the prognosis. Methods: Forty patients who underwent surgery for cardiac sarcomas were included; 60% of them had angiosarcoma. Clinical characteristics, tumor location, surgical techniques used, and the prognosis were compared between patients with angiosarcoma and patients with other subtypes. Kaplan-Meier curves and multivariable Cox regression were used to identify predictors of postoperative survival. Results: Angiosarcomas were more likely than the other subtypes to present as pericardial effusion (85% vs 50%, P = .014). Early surgery was performed (median 24.0 days) regardless of histological subtype. The surgical technique varied according to histological subtype. Mean postoperative survival was 10 months. A positive margin (P = .13), high Ki-67 index (P = .19), younger age (P = .86), and angiosarcoma (P = .87) were identified to be potentially poor prognostic factors in univariate analyses. Cox regression identified R0 resection to be the only significant independent predictor of the prognosis after surgery (hazard ratio, 0.423, P = .039). Conclusions: Angiosarcoma differs from other subtypes of cardiac sarcoma in terms of clinical symptoms, tumor location, surgical techniques used, and prognosis. Early surgery is needed regardless of subtype. R0 resection is the only independent predictor of postoperative survival, and complete resection is usually achievable. The prognosis may be poorer in patients with a positive margin, high Ki-67 index, younger age, and angiosarcoma.

Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study.

Purpose: We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction. Methods: In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann-Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses. Results: Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = -0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = -0.379, P = 0.033). Conclusion: Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.