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1.
Adv Mater ; : e2105029, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34624162

RESUMO

Lithium metal is one of the most promising anode candidates for next-generation high-energy batteries. Nevertheless, lithium pulverization and associated loss of electrical contact remain significant challenges. Here, an antipulverization and high-continuity lithium metal anode comprising a small number of solid-state electrolyte (SSE) nanoparticles as conformal/sacrificial fillers and a copper (Cu) foil as the supporting current collector is reported. Guiding by the SSE, this new anode facilitates lithium nucleation, contributing to form a roundly shaped, micro-sized, and dendrite-free electrode during cycling, which effectively mitigates the lithium dendrite growth. The embedded Cu current collector in the hybrid anode not only reinforces the mechanical strength but also improves the efficient charge transfer among active lithium filaments, affording good electrode structural integrity and electrical continuity. As a result, this antipulverization and high-continuity lithium anode delivers a high average Coulombic efficiency of ≈99.6% for 300 cycles under a current density of 1 mA cm-2 . Lithium-sulfur batteries (elemental sulfur or sulfurized polyacrylonitrile cathodes) equipped with this anode show high-capacity retentions in their corresponding ether-based or carbonate-based electrolytes, respectively. This new electrode provides important insight into the design of electrodes that may experience large volume variation during operations.

2.
Front Aging Neurosci ; 13: 731180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616287

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.

3.
Chem Commun (Camb) ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647938

RESUMO

A series of macrocyclic compounds, including crown ether, cyclodextrin, cucurbituril and pillararene, bound to various specific organic/inorganic/biological guest molecules and ions through various non-covalent interactions, can not only make a single system multifunctional but also endow the system with intelligence, especially for luminescent materials. Due to their excellent luminescence properties, such as long-lived excited states, sharp linear emission bands and large Stokes shift, lanthanides have shown great advantages in luminescence, and have been more and more applied in the design of advanced functional luminescent materials. Based on reported research, we summarize the progress of lanthanide luminescent materials based on different macrocyclic compounds from ion or molecule recognition to functional nano-supramolecular assembly of the lanthanide-macrocycle supramolecular system including photo-reaction mediated switch of lanthanide luminescent molecules, multicolor luminescence, ion detection and cell imaging of rare-earth up-conversion of macrocyclic supramolecular assembly. Finally, we put forward the prospects of future development of lanthanide luminescent macrocyclic supramolecular materials.

4.
Nat Nanotechnol ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34594005

RESUMO

Nutritional metal ions play critical roles in many important immune processes. Hence, the effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonists and Mn2+. We screened various metal ions and discovered specific metal ions augmented STING agonist activity, wherein Mn2+ promoted a 12- to 77-fold potentiation effect across the prevalent human STING haplotypes. Notably, Mn2+ coordinated with CDN STING agonists to self-assemble into a nanoparticle (CDN-Mn2+ particle, CMP) that effectively delivered STING agonists to immune cells. The CMP, administered either by local intratumoural or systemic intravenous injection, initiated robust anti-tumour immunity, achieving remarkable therapeutic efficacy with minute doses of STING agonists in multiple murine tumour models. Overall, the CMP offers a new platform for local and systemic cancer treatments, and this work underscores the great potential of coordination nanomedicine for metalloimmunotherapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34606979

RESUMO

Isogenic cells growing in identical environments show cell-to-cell variations because of the stochasticity in gene expression. High levels of variation or noise can disrupt robust gene expression and result in tremendous consequences for cell behaviors. In this work, we showed evidence from single-cell RNA-sequencing data analysis that microRNAs (miRNAs) can reduce gene expression noise at the mRNA level in mouse cells. We identified that the miRNA expression level, number of targets, target pool abundance, and strength of miRNA interactions with its targets are the key features contributing to noise repression. miRNAs tend to work together in cooperative subnetworks to repress target noise synergistically in a cell-type-specific manner. By building a physical model of posttranscriptional regulation and observing in synthetic gene circuits, we demonstrated that accelerated degradation with elevated transcriptional activation of the miRNA target provides resistance to extrinsic fluctuations. Together, through the integrated analysis of single-cell RNA and miRNA expression profiles, we demonstrated that miRNAs are important posttranscriptional regulators for reducing gene expression noise and conferring robustness to biological processes.

6.
Cancer Cell Int ; 21(1): 509, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556138

RESUMO

BACKGROUND: Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive. METHODS: A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2'-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins. RESULTS: Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway. CONCLUSIONS: Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

8.
J Phys Chem B ; 125(38): 10796-10804, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34524821

RESUMO

Understanding how the conformational change of conjugated molecules with acceptor-donor-acceptor (A-D-A) architecture affects their physical and optoelectronic properties is critical for determining their ultimate performance in organic electronic devices. Here, we utilized femtosecond transient absorption, time-resolved upconversion photoluminescence spectroscopy, and tunable femtosecond-stimulated Raman spectroscopy, aided by quantum chemical calculations, to systematically investigate the excited state structural dynamics of the intramolecular charge transfer of the tetramethoxy anthracene-based fluorophore 2,3,6,7-tetramethoxy 9,10-dibenzaldehydeanthracene (AnDA) and its derivative 2,3,6,7-tetramethoxy 9,10-diphenylanthracene (TMDPAn) in chloroform. In the AnDA molecule, the tetramethoxy anthracene and benzaldehyde moieties exhibit a strong ability to donate and withdraw electrons. Upon photoexcitation, AnDA shows intriguing ultrafast fluorescence switch-on and red shift dynamics on charge transfer states, and the temporal evolution of AnDA recorded by ultrafast spectroscopy reveals a dynamic picture of two-step intramolecular charge transfer assisted by ultrafast conformational changes and solvation processes. Removing the aldehyde group from TMDPAn significantly decreases the electron pulling capacity of the phenyl unit and disables charge transfer characteristics.

9.
Neuroscience ; 475: 93-102, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487819

RESUMO

Two different but interacting neural systems exist in the human brain: the task positive networks and task negative networks. One of the most important task positive networks is the central executive network (CEN), while the task negative network generally refers to the default mode network (DMN), which usually demonstrates task-induced deactivation. Although previous studies have clearly shown the association of both the CEN and DMN with major depressive disorder (MDD), how the causal interactions between these two networks change in depressed patients remains unclear. In the current study, 99 subjects (43 patients with MDD and 56 healthy controls) were recruited with their resting-state fMRI data collected. After data preprocessing, spectral dynamic causal modeling (spDCM) was used to investigate the causal interactions within and between the DMN and CEN. Group commonalities and differences in causal interaction patterns within and between the CEN and DMN in patients and controls were assessed by a parametric empirical Bayes (PEB) model. Both subject groups demonstrated significant effective connectivity between regions of the CEN and DMN. In particular, we detected inhibitory influences from the CEN to the DMN with node-level PEB analyses, which may help to explain the anticorrelations between these two networks consistently reported in previous studies. Compared with healthy controls, patients with MDD showed increased effective connectivity within the CEN and decreased connectivity from regions of the CEN to DMN, suggesting impaired control of the DMN by the CEN in these patients. These findings might provide new insights into the neural substrates of MDD.

10.
Brief Bioinform ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472588

RESUMO

Quantifying cell proportions, especially for rare cell types in some scenarios, is of great value in tracking signals associated with certain phenotypes or diseases. Although some methods have been proposed to infer cell proportions from multicomponent bulk data, they are substantially less effective for estimating the proportions of rare cell types which are highly sensitive to feature outliers and collinearity. Here we proposed a new deconvolution algorithm named ARIC to estimate cell type proportions from gene expression or DNA methylation data. ARIC employs a novel two-step marker selection strategy, including collinear feature elimination based on the component-wise condition number and adaptive removal of outlier markers. This strategy can systematically obtain effective markers for weighted $\upsilon$-support vector regression to ensure a robust and precise rare proportion prediction. We showed that ARIC can accurately estimate fractions in both DNA methylation and gene expression data from different experiments. We further applied ARIC to the survival prediction of ovarian cancer and the condition monitoring of chronic kidney disease, and the results demonstrate the high accuracy and robustness as well as clinical potentials of ARIC. Taken together, ARIC is a promising tool to solve the deconvolution problem of bulk data where rare components are of vital importance.

11.
Sci Rep ; 11(1): 17113, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429442

RESUMO

The existence of toxic and carcinogenic pentavalent antimony in water is a great safety problem. In order to remove antimony(V) from water, the purpose of this study was to prepare a novel graphene nano iron zinc (rGO/NZV-FeZn) photocatalyst via hydrothermal method followed by ultrasonication. Herein, weakly magnetic nano-Fe-Zn materials (NZV-FeZn, GACSP/NZV-FeZn, and rGO/NZV-FeZn) capable of rapid and efficient Sb(V) adsorption from water were prepared and characterised. In particular, rGO/NZV-FeZn was shown to comprise franklinite, Fe0, and graphite. Adsorption data were fitted by a quasi-second-order kinetic equation and Langmuir model, revealing that among these materials, NZV-FeZn exhibited the best Sb removal performance (543.9 mgSb gNZV-FeZn-1, R2 = 0.951). In a practical decontamination test, Sb removal efficiency of 99.38% was obtained for a reaction column filled with 3.5 g of rGO/NZV-FeZn. Column regenerability was tested at an initial concentration of 0.8111 mgSb L-1, and the treated water obtained after five consecutive runs complied with the GB5749-2006 requirement for Sb. rGO/NZV-FeZn was suggested to remove Sb(V) through adsorption-photocatalytic reduction and flocculation sedimentation mechanisms and, in view of its high cost performance, stability, and upscalable synthesis, was concluded to hold great promise for source water and wastewater treatment.

12.
Front Psychiatry ; 12: 694051, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421678

RESUMO

Objective: The 2019 novel coronavirus disease (COVID-19) broke out in Hubei Province and spread rapidly to the whole country, causing huge public health problems. College students are a special group, and there is no survey on insomnia among college students. The purpose of this study was to investigate the incidence and related factors of insomnia in college students during the period of COVID-19. Method: A total of 1,086 college students conducted a cross-sectional study through the questionnaire star platform. The survey time was from February 15 to February 22, 2020. The collected information included demographic informatics and mental health scale, Athens Insomnia Scale (AIS) to assess sleep quality, Self-Reporting Questionnaire-20 (SRQ-20) to assess general psychological symptoms, Chinese perceived stress scale (CPSS) to assess stress. We used logistic regression to analyze the correlation between related factors and insomnia symptoms. Results: The prevalence of insomnia, general psychological symptoms and stress were 16.67, 5.8, and 40.70%, respectively. Multivariate logistic regression analysis showed that gender (OR = 1.55, p = 0.044, 95% CI = 1.00-2.41), general psychological symptoms (OR = 1.49, p < 0.01, 95% CI = 1.40-1.60) and living in an isolation unit (OR = 2.21, p = 0.014, 95% CI = 1.17-4.16) were risk factors for insomnia of college students. Conclusion: Our results show that the insomnia is very common among college students during the outbreak of covid-19, and the related factors include gender, general psychological symptoms and isolation environment. It is necessary to intervene the insomnia of college students and warrants attention for mental well-being of college students.

13.
Cell Rep ; 36(8): 109573, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433047

RESUMO

MicroRNAs (miRNAs) have been shown to modulate gene expression noise, but less is known about how miRNAs with different properties may regulate noise differently. Here, we investigate the role of competing RNAs and the composition of miRNA response elements (MREs) in modulating noise. We find that weak competing RNAs could introduce lower noise than strong competing RNAs. In comparison with a single MRE, both repetitive and composite MREs can reduce the noise at low expression, but repetitive MREs can elevate the noise remarkably at high expression. We further observed the behavior of a synthetic cell-type classifier with miRNAs as inputs and find that miRNAs and MREs that could introduce higher noise tend to enhance cell state transition. These results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and the utilization of miRNAs to modulate the behavior of synthetic gene circuits.

14.
Front Oncol ; 11: 629633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367945

RESUMO

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.

15.
Viruses ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452329

RESUMO

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.

16.
Gastroenterology ; 161(4): 1288-1302.e13, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34224739

RESUMO

BACKGROUND & AIMS: DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated. METHODS: A genome-wide database of 488,235 mouse coding mononucleotide repeats was established, from which a set of candidates was selected based on repeat length, gene expression, and mutation frequency. In silico prediction, in vivo immunogenicity testing, and epitope mapping was used to identify candidates for FSP vaccination. RESULTS: We identified 4 shared FSP neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) that induced CD4/CD8 T cell responses in naïve C57BL/6 mice. Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival. Combination of FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival even more effectively than FSP vaccination alone. CONCLUSIONS: Our preclinical findings support a clinical strategy of recurrent FSP neoantigen vaccination for LS cancer immunoprevention.

17.
Bioengineered ; 12(1): 2511-2522, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251959

RESUMO

Cerebral infarction (CI) has become a leading cause of death in China. Long non-coding RNAs (lncRNAs) are intensively involved in the progression of CI. Here, we aimed to investigate the effects of lncRNA LOC366613 (LOC366613) on cerebral I/R injury, as well as its possible mechanism. Transient middle cerebral artery occlusion (MCAO) was used to establish a mouse model of cerebral I/R, and the PC12 cell line was used to establish an in vitro oxygen-glucose deprivation (OGD) injury model. The MTT assay was used to determine cell viability, and qRT-PCR was used to determine RNA levels. Western blotting was conducted to detect protein expression levels. The TUNEL assay and flow cytometry were used to measure cell apoptosis, and 2,3,5-triphenyltetrazolium chloride (TTC) was used to determine cerebral infarct volume. Finally, RNA pull-down and luciferase activity assays were used to examine interactions between miR-532-5p and LOC366613, as well as between miR-532-5p and phosphatase and tensin homolog (PTEN). LOC366613 was overexpressed in patients with cerebral I/R injury. In PC12 cells, knockdown of LOC366613 reduced the apoptosis rate and lactic acid dehydrogenase (LDH) expression, while increasing cell viability. Moreover, miR-532-5p was shown to be a target of LOC366613, as predicted. Downregulation of miR-532-5p reversed the effects of LOC366613 knockdown on PC12 cell apoptosis, LDH release, and cell viability. Finally, PTEN was verified as a target of miR-532-5p. LOC366613 participates in cerebral I/R injury by regulating the miR-532-5p/PTEN axis, potentially providing a new CI treatment target.

18.
Micromachines (Basel) ; 12(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205469

RESUMO

MEMS/NEMS resonators are widely studied in biological detection, physical sensing, and quantum coupling. This paper reviews the latest research progress of MEMS/NEMS resonators with different structures. The resonance performance, new test method, and manufacturing process of single or double-clamped resonators, and their applications in mass sensing, micromechanical thermal analysis, quantum detection, and oscillators are introduced in detail. The material properties, resonance mode, and application in different fields such as gyroscope of the hemispherical structure, microdisk structure, drum resonator are reviewed. Furthermore, the working principles and sensing methods of the surface acoustic wave and bulk acoustic wave resonators and their new applications such as humidity sensing and fast spin control are discussed. The structure and resonance performance of tuning forks are summarized. This article aims to classify resonators according to different structures and summarize the working principles, resonance performance, and applications.

19.
Front Cell Dev Biol ; 9: 673374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211974

RESUMO

Breast cancer stem cells (BCSCs) represent a subpopulation of tumor cells that can self-renew and generate tumor heterogeneity. Targeting BCSCs may ameliorate therapy resistance, tumor growth, and metastatic progression. However, the origin and molecular mechanisms underlying their cellular properties are poorly understood. The transcriptional coactivator with PDZ-binding motif (TAZ) promotes mammary stem/progenitor cell (MaSC) expansion and maintenance but also confers stem-like traits to differentiated tumor cells. Here, we describe the rapid generation of experimentally induced BCSCs by TAZ-mediated reprogramming of human mammary epithelial cells, hence allowing for the direct analysis of BCSC phenotypes. Specifically, we establish genetically well-defined TAZ-dependent (TAZDEP) and -independent (TAZIND) cell lines with cancer stem cell (CSC) traits, such as self-renewal, variable resistance to chemotherapeutic agents, and tumor seeding potential. TAZDEP cells were associated with the epithelial to mesenchymal transition, embryonic, and MaSC signature genes. In contrast, TAZIND cells were characterized by a neuroendocrine transdifferentiation transcriptional program associated with Polycomb repressive complex 2 (PRC2). Mechanistically, we identify Cyclin D1 (CCND1) as a critical downstream effector for TAZ-driven tumorigenesis. Overall, our results reveal a critical TAZ-CCND1-CDK4/CDK6 signaling axis, suggesting novel therapeutic approaches to eliminate both BCSCs and therapy-resistant cancer cells.

20.
Brief Bioinform ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245239

RESUMO

Detecting cancer signals in cell-free DNA (cfDNA) high-throughput sequencing data is emerging as a novel noninvasive cancer detection method. Due to the high cost of sequencing, it is crucial to make robust and precise predictions with low-depth cfDNA sequencing data. Here we propose a novel approach named DISMIR, which can provide ultrasensitive and robust cancer detection by integrating DNA sequence and methylation information in plasma cfDNA whole-genome bisulfite sequencing (WGBS) data. DISMIR introduces a new feature termed as 'switching region' to define cancer-specific differentially methylated regions, which can enrich the cancer-related signal at read-resolution. DISMIR applies a deep learning model to predict the source of every single read based on its DNA sequence and methylation state and then predicts the risk that the plasma donor is suffering from cancer. DISMIR exhibited high accuracy and robustness on hepatocellular carcinoma detection by plasma cfDNA WGBS data even at ultralow sequencing depths. Further analysis showed that DISMIR tends to be insensitive to alterations of single CpG sites' methylation states, which suggests DISMIR could resist to technical noise of WGBS. All these results showed DISMIR with the potential to be a precise and robust method for low-cost early cancer detection.

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