The growth of wafer-scale single-crystal two-dimensional transition metal dichalcogenides (TMDs) on insulating substrates is critically important for a variety of high-end applications1–4. Although ...the epitaxial growth of wafer-scale graphene and hexagonal boron nitride on metal surfaces has been reported5–8, these techniques are not applicable for growing TMDs on insulating substrates because of substantial differences in growth kinetics. Thus, despite great efforts9–20, the direct growth of wafer-scale single-crystal TMDs on insulating substrates is yet to be realized. Here we report the successful epitaxial growth of two-inch single-crystal WS2 monolayer films on vicinal a-plane sapphire surfaces. In-depth characterizations and theoretical calculations reveal that the epitaxy is driven by a dual-coupling-guided mechanism, where the sapphire plane–WS2 interaction leads to two preferred antiparallel orientations of the WS2 crystal, and sapphire step edge–WS2 interaction breaks the symmetry of the antiparallel orientations. These two interactions result in the unidirectional alignment of nearly all the WS2 islands. The unidirectional alignment and seamless stitching of WS2 islands are illustrated via multiscale characterization techniques; the high quality of WS2 monolayers is further evidenced by a photoluminescent circular helicity of ~55%, comparable to that of exfoliated WS2 flakes. Our findings offer the opportunity to boost the production of wafer-scale single crystals of a broad range of two-dimensional materials on insulators, paving the way to applications in integrated devices.A dual-coupling-guided growth mechanism enables the realization of wafer-scale single-crystal WS2 on vicinal a-plane sapphire.
Background
Four RNA adenosine modifications, including m6A, m1A, alternative polyadenylation, and adenosine-to-inosine RNA editing, have been identified as potentially valuable in influencing ...colorectal carcinogenesis, immune infiltration, and response to drug therapy. However, the regulatory mechanisms and clinical significance of these four RNA modifications in ovarian cancer (OC) remain unknown.
Methods
We comprehensively described the transcriptional and genetic modifications of 26 RNA modification “writers” in OC and assessed the expression patterns. We identified two RNA modification subtypes using an unsupervised clustering approach. Subsequently, using differentially expressed genes (DEGs) in both subtypes, we calculated RNA modification “writer” scores (RMW scores) to characterize the RNA modifications of single OC patients. RMW score-related gene expression was investigated by qRT-PCR. We explored the correlation between RMW score and clinical features, immune infiltration, and drug sensitivity. We drew a nomogram to more intuitively and accurately describe the application value of the RMW score.
Results
We found that molecular alterations in “writers” are strongly related to prognostic and immune-infiltrating features in OC patients. We identified two different clusters of RNA modifications. According to the immune infiltration characteristics in the two RNA modification isoforms, cluster A and cluster B can correspond to “hot” and “cold” tumors, respectively. With the median RMW score, we classified the patients into high- and low-score subgroups. A low RMW score was associated with good patient prognosis and lower immune infiltration. In addition, a low RMW score equated with a higher cancer stem cell index and a lower tumor mutation burden, which to some extent affected the sensitivity of patients to therapeutic drugs. Seven RMW score-related gene expressions were investigated by qRT-PCR in three OC cell lines. Compared to previously known models, our established RMW score has higher accuracy in predicting patient survival.
Conclusion
A comprehensive analysis of four RNA modification patterns in OC reveals their potential value in OC prognosis, immune microenvironment, and drug sensitivity. These results could deepen our knowledge of RNA modification and yield fresh insights for new personalized therapeutic strategies.
Berberine, an alkaloid derivative from Berberis vulgaris L., has been used extensively in traditional Chinese medicine to treat diarrhea and diabetes, but the underlying mechanisms for treating ...diabetes are not fully understood. Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation. Because type 1 diabetes is caused by T cell-mediated destruction of β cells and severe islet inflammation, we hypothesized that berberine could ameliorate type 1 diabetes through its immune regulation properties. Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion. Berberine suppressed Th17 and Th1 differentiation by reducing the expression of lineage markers. We found that berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation. Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation, and it controlled the stability of STAT4 through the ubiquitin-proteasome pathway. Our findings indicate that berberine targets MAPK to suppress Th17 and Th1 differentiation in type 1 diabetic NOD mice. This study revealed a novel role of ERK in Th17 differentiation through down-regulation of STAT3 phosphorylation and RORγt expression.
: As is well understood, peroxisome proliferator-activated receptor gamma cofactor-related 1 (
) plays a central role in the transcriptional control of the mitochondrial biogenesis and oxidative ...phosphorylation (OXPHOS) process, yet its critical role in pan-cancer remains unclear.
: In this paper, the expression levels of PPRC1 in different tumor tissues and corresponding adjacent normal tissues were analyzed based on four databases: The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Tumor Immune Estimation Resource (TIMER). Meanwhile, the prognostic value of
was inferred using Kaplan-Meier plotter and forest-plot studies. In addition, the correlation between
expression and tumor immune cell infiltration, immune checkpoints, and the tumor-stemness index was analyzed using TCGA and TIMER databases.
: According to our findings, the expression level of
was found to be different in different cancer types and there was a positive correlation between
expression and prognosis in several tumor types. In addition,
expression was found to be significantly correlated with immune cell infiltration, immune checkpoints, and the tumor-stemness index in both ovarian and hepatocellular carcinoma.
:
demonstrated promising potential as a novel biomarker in pan-cancer due to its potential association with immune cell infiltration, expression of immune checkpoints, and the tumor-stemness index.
Th17 cells are a subset of CD4+ T cells with an important role in clearing certain bacterial and fungal pathogens. However, they have also been implicated in autoimmune diseases such as multiple ...sclerosis. Exposure of naive CD4+ T cells to IL-6 and TGF-β leads to Th17 cell differentiation through a process in which many proteins have been implicated. We report here that ectopic expression of liver X receptor (LXR) inhibits Th17 polarization of mouse CD4+ T cells, while LXR deficiency promotes Th17 differentiation in vitro. LXR activation in mice ameliorated disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, whereas LXR deficiency exacerbated disease. Further analysis revealed that Srebp-1, which is encoded by an LXR target gene, mediated the suppression of Th17 differentiation by binding to the E-box element on the Il17 promoter, physically interacting with aryl hydrocarbon receptor (Ahr) and inhibiting Ahr-controlled Il17 transcription. The putative active site (PAS) domain of Ahr and the N-terminal acidic region of Srebp-1 were essential for this interaction. Additional analyses suggested that similar LXR-dependent mechanisms were operational during human Th17 differentiation in vitro. This study reports what we believe to be a novel signaling pathway underlying LXR-mediated regulation of Th17 cell differentiation and autoimmunity.
Epithelial-mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including ...initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).
EMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.
A total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher
-methyladenosine (m
A) RNA expression, microsatellite instability level, and stemness indices.
We constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.
Colorectal adenocarcinoma (COAD) is one of the most common malignancies and angiogenesis is vital to the development of cancer. Here, we explored the roles of angiogenesis-related genes (ARGs) that ...affect the prognosis of COAD and constructed risk models to assess patient prognosis, immune characteristics, and treatment outcomes.
We comprehensively characterized the transcriptional and genetic modifications of 48 ARGs in COAD and evaluated the expression patterns. We identified two ARG subgroups using the consensus clustering algorithm. Based on the differentially expressed genes (DEGs) of two ARG subtypes, we calculated risk score, namely ARG_scores, and calssified COAD patients into different risk groups. To investigate the expression of ARG_score-related genes, qRT-PCR was performed. Subsequently, we mapped the nomogram to visually and accurately describe the value of the application of ARG_score. Finally, the correlation between ARG_score and clinical features, immune infiltration along with drug sensitivity were explored.
We identified two ARG related subgroups and there were great differences in overall survival (OS) and tumor microenvironment. Then, we created an ARG_score for predicting overall survival based on eight DEGs and confirmed its reliable predictive power in COAD patients, with higher ARG_score associated with worse prognosis. Furthermore, eight ARG_score-related genes expression was investigated by qRT-PCR. To make the ARG_score clinically feasible, we created a highly reliable nomogram. We also found a higher proportion of microsatellite instability-high (MSI-H) and higher tumor mutational burden (TMB) in the high-risk group. In addition, ARG_score was notably correlated with cancer stem cell indices and drug sensitivity.
This scoring model has potential clinical application value in the prognosis, immune microenvironment and therapeutic drug sensitivity of COAD, which provides new insights for personalized treatment.
T cell factor 1 (Tcf1) promotes the central memory CD8+ T (TCM) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the ...CD103high tissue-resident memory CD8+ T (TRM) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung TRM cell formation. Abrogation of transforming growth factor β (TGF-β) signaling is associated with a loss of CD103+ and reciprocal gain of Tcf1+ cells among TRM precursors in vivo. T-cell-specific ablation of Tcf7 enhances CD103 protein expression in TRM cells and precursors and increases TRM cell numbers after primary and secondary infections. Tcf1 directly binds to the Itgae (encoding CD103) locus and partly inhibits TGF-β-induced CD103 expression. Our study suggests that memory T cell tissue residency and homeostatic proliferation are reciprocally regulated by Tcf1. Tcf1 may play either immunosupportive or immunosuppressive roles in CD8+ T cells, depending on systemic or mucosal infections.
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•Tcf1 and CD103 are negatively correlated in lung TRM precursors•Tcf1 binds to the Itgae locus and inhibits CD103 expression•TGF-β reduces Tcf1 binding to the Itgae locus•Tcf1 suppresses CD103 protein expression in TRM cells and precursors
Tcf1 promotes circulating memory T cell development and maintenance after systemic infections. Wu et al. show that Tcf1 inhibits CD103+ resident memory T cell development in influenza-virus-infected mice. Tcf1 may either promote or suppress memory T cell development, depending on systemic or mucosal infections.
In this paper, the synthesis of the three-dimensional (3D) composite of spherical reduced graphene oxide (RGO) with uniformly distributed CeO₂ particles is reported. This synthesis is done via a ...facile and large-scalable spray-drying process, and the CeO₂/RGO materials are hydrothermally compounded with sulfur. The morphology, composition, structure, and electrochemical properties of the 3D S/CeO₂/RGO composite are studied using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), Raman spectra and X-ray photoelectron spectroscopy (XPS), etc. The electrochemical performance of the composites as electrodes for lithium⁻sulfur batteries is evaluated. The S/CeO₂/RGO composites deliver a high initial capacity of 1054 mAh g
, and retain a reversible capacity of 792 mAh g
after 200 cycles at 0.1 C. Profiting from the combined effect of CeO₂ and RGO, the CeO₂/RGO materials effectively inhibit the dissolution of polysulfides, and the coating of spherical RGO improves the structural stability as well as conductivity.
Background
Cuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated ...with epigenetic controllers and regulate histone protein modification or DNA methylation during gene transcription. The roles of cuproptosis-related lncRNAs (CRLs) in Colon adenocarcinoma (COAD), however, remain unknown.
Methods
COAD transcriptome data was obtained from the TCGA database. Thirteen genes associated to cuproptosis were identified in published papers. Following that, correlation analysis was used to identify CRLs. The cuproptosis associated prognostic signature was built and evaluated using Lasso regression and COX regression analysis. A prognostic signature comprising six CRLs was established and the expression patterns of these CRLs were analyzed by qRT-PCR. To assess the clinical utility of prognostic signature, we performed tumor microenvironment (TME) analysis, mutation analysis, nomogram generation, and medication sensitivity analysis.
Results
We identified 49 prognosis-related CRLs in COAD and constructed a prognostic signature consisting of six CRLs. Each patient can be calculated for a risk score and the calculation formula is: Risk score =TNFRSF10A-AS1 * (-0.2449) + AC006449.3 * 1.407 + AC093382.1 *1.812 + AC099850.3 * (-0.0899) + ZEB1-AS1 * 0.4332 + NIFK-AS1 * 0.3956. Six CRLs expressions were investigated by qRT-PCR in three colorectal cancer cell lines. In three cohorts, COAD patients were identified with different risk groups, with the high-risk group having a worse prognosis than the low-risk group. Furthermore, there were differences in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups. We also identified certain drugs that were more sensitive to the high-risk group: Paclitaxel, Vinblastine, Sunitinib and Elescloml.
Conclusions
Our findings may be used to further investigate RCD, comprehension of the prognosis and tumor microenvironment infiltration characteristics in COAD.
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