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1.
Nanoscale ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625417

RESUMO

Li-rich high-Mn oxides, xLi2MnO3·(1 - x)LiMO2 (x ≥ 0.5, M = Co, Ni, Mn…), have attracted extensive research interest due to their high specific capacity and low cost. However, slow Li2MnO3 activation and poor cycling stability have affected their electrochemical performance. Herein, to solve these problems, morphology regulation and LiAlF4 coating strategies have been synergistically applied to a Li-rich high-Mn material Li1.7Mn0.8Co0.1Ni0.1O2.7 (HM-811). This dual-strategy successfully promotes the activation process of the Li2MnO3 phase and thus improves the electrochemical performance of HM-811. Theoretical computation indicates that the LiAlF4 layer has a lower Li+ migration barrier than the HM-811 matrix, so it could boost the diffusion of Li+ ions and promote the activation of the Li2MnO3 phase. Benefiting from the morphology regulation and LiAlF4 coating, the HM-811 cathode shows a high initial charge capacity of >300 mA h g-1. In addition, the modified HM-811 could deliver superior electrochemical performance even at a low temperature of -20 °C. This work provides a new approach for developing high performance cathode materials for next-generation Li-ion batteries.

2.
Exp Cell Res ; 400(1): 112493, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33485843

RESUMO

Most cancer deaths are due to the colonization of tumor cells in distant organs. More evidence indicates that overexpression of RACGAP1 plays a critical role in cancer metastasis. However, the underlying mechanism still remains poorly understood. Here we found that RACGAP1 promoted breast cancer metastasis through regulating mitochondrial quality control. Overexpression of RACGAP1 in breast cancer cells led to the fragmentation of mitochondria, increased mitophagy intensity, mitochondrial turnover, and aerobic glycolysis ATP production. We showed that RACGAP1 promoted mitochondrial fission through recruiting ECT2 during anaphase and subsequently had activated ERK-DRP1 pathway. We further demonstrated the phosphorylation of RACGAP1 is essential for its ability of binding with ECT2 and its downstream effects. RACGAP1 overexpression also increased the expression of PGC-1a, a key mitochondrial biogenesis regulator, presumably by the increased mitophagy intensity induced by RACGAP1. PGC-1a increased the enrichment of DNMT1 in mitochondria, mitochondrial DNMT1 augmented mitochondrial DNA methylation and upregulated mitochondrial genome transcription. Our data indicated that RACGAP1 simultaneously facilitated mitophagy and mitochondrial biogenesis through regulating DRP1 phosphorylation and PGC-1a expression, eventually improved mitochondrial quality control in breast cancer cells. Our study provided a new angle in understanding the RACGAP1-overexpression related malignancy in breast cancer patients.

3.
Mol Cell ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33434504

RESUMO

STING-dependent cytosolic DNA sensing in dendritic cells (DCs) initiates antitumor immune responses, but how STING signaling is metabolically regulated in the tumor microenvironment remains unknown. Here, we show that oxidative stress is required for STING-induced DC antitumor function through a process that directs SUMO-specific protease 3 (SENP3) activity. DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon (IFN) signaling in DCs and dampening antitumor immune responses. DC-derived reactive oxygen species (ROS) trigger SENP3 accumulation and the SENP3-IFI204 interaction, thereby catalyzing IFI204 deSUMOylation and boosting STING signaling activation in mice. Consistently, SENP3 senses ROS to facilitate STING-dependent DC activity in tissue samples from colorectal cancer patients. Our results reveal that oxidative stress as a metabolic regulator promotes STING-mediated DC antitumor immune responses and highlights SENP3 as an overflow valve for STING signaling induction in the metabolically abnormal tumor microenvironment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33399262

RESUMO

Immediate reutilization of discarded blood from surgery has not received much attention, leading to the waste of a large amount of autologous blood. We used a concentration gradient and high-voltage electrospinning technology to immediately prepare a scaffold material with high biological activity but without immunogenicity from autologous waste blood collected during surgery. Here, we fabricated and characterized a 90 mg/mL group, 110 mg/mL group, and 130 mg/mL group of fibrinogen (FBG) scaffolds. Analyses revealed that the FBG scaffolds had good film-forming properties and a clear fiber structure. in vitro cell viability experiments confirmed that the cells showed an increasing trend with increasing FBG concentrations. The cells grew well in the scaffold material and secreted more cell matrix. When human bone mesenchymal stem cells (hBMSCs) were cocultured with the scaffold material, the hBMSCs expressed osteogenic and chondrogenic biomarkers. The cellular scaffold complexes from the 3 groups were implanted in four full-thickness round wounds (Φ12 mm) on the dorsal back of each rat, the 130 mg/mL group showed a 90% reduction in wound size and the data compared to other groups were better at 14 day. These results suggest that electrospinning technology-based FBG scaffold materials derived from autologous waste blood may become an ideal tissue engineering scaffold and can be immediately used for autologous hemostasis, anti-adhesion films, and wound dressing in surgery.

5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(1): 33-38, 2021 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-33448196

RESUMO

Objective: To compare the predictive abilities of O-C2 angle (O-C2a), O-EA angle (O-EAa), and Oc-Ax angle (Oc-Axa) for development of dysphagia in patients after occipitocervical fusion (OCF). Methods: Between April 2010 and May 2019, 114 patients who underwent OCF and met the selection criteria were selected as the research objects. Among them, 54 were males and 60 were females; they were 14-76 years old, with an average of 50.6 years old. The follow-up time was 13-122 months (median, 60.5 months). The O-C2a, O-EAa, Oc-Axa, and the narrowest oropharyngeal airway space (nPAS) were measured by the lateral X-ray films before operation and at last follow-up, and the differences before and after operation (dO-C2a, dO-EAa, dOc-Axa, and dnPAS) were calculated. Patients were divided into two groups according to whether they had developed postoperative dysphagia. The general data including age, gender, fixed segment, proportion of patients with rheumatoid arthritis (RA), atlantoaxial subluxation (AS), and combined with anterior release surgery (ARS), and imaging indicators were compared between the two groups. The correlations between dO-C2a, dO-EAa, and dOc-Axa and dnPAS in 114 patients were analyzed to further compare the predictive value of three imaging indicators for occurrence of dysphagia after OCF. Results: Dysphagia occurred after OCF in 31 cases with the incidence of 27.2%. There was significant difference in gender between the dysphagia group and the non-dysphagia group ( χ 2=7.940, P=0.005). There was no significant difference between the two groups in age, fixed segment, the proportion of patients with RA, the proportion of patients with AS, and the proportion of patients combined with ARS ( P>0.05). There was no significant difference in O-C2a and Oc-Axa of 114 patients before operation and at last follow-up ( P>0.05). The differences in O-EAa and nPAS were significant ( P<0.05). There was no significant difference in preoperative O-EAa, Oc-Axa, and nPAS between the dysphagia group and the non-dysphagia group ( P>0.05); the difference in the O-C2a was significant ( t=2.470, P=0.016). At last follow-up, the differences in the above imaging indicators were significant ( P<0.05). There were significant differences in the dO-C2a, dO-EAa, dOc-Axa, and dnPAS between the two groups ( P<0.05). Correlation analysis showed that the dO-C2a, dO-EAa, dOc-Axa were all positively correlated with dnPAS ( P<0.05). The dO-C2a≤-5°, postoperative O-EAa≤100°, postoperative Oc-Axa≤65° were all related to postoperative dysphagia ( P<0.05), and the highest risk factor suffering postoperative dysphagia was dO-C2a ≤-5° with a significant OR of 14.4. Conclusion: The dO-C2a, postoperative O-EAa, and postoperative Oc-Axa can be used as the predictive indexes of dysphagia after OCF, among which dO-C2a has the highest predictive value.


Assuntos
Transtornos de Deglutição , Luxações Articulares , Fusão Vertebral , Adolescente , Adulto , Idoso , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Transtornos de Deglutição/etiologia , Feminino , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Adulto Jovem
6.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355624

RESUMO

Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell-specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell-derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1-PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function.

7.
J Mater Sci Mater Med ; 31(12): 125, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33247818

RESUMO

This study aimed to investigate the effect of graphene oxide (GO)-hydroxyapatite (HA)-sodium alginate (SA) composite application in the field of bone tissue engineering. Four scaffold groups were established (SA-HA, SA-HA-0.8%GO, SA-HA-1.0%GO and SA-HA-1.2%GO) and mixed with bone marrow mesenchymal stem cells (BMSCs). Hydrogel viscosity was measured at room temperature, and after freeze-drying and Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) to detect substance crystallinity, the printability of each hydrogel type was measured with a printing grid. Scanning electron microscopy (SEM) was used to observe the internal microstructure of the scaffolds and to evaluate the growth and proliferation of cells on the scaffold. A hollow cylinder was printed to compare the forming effect of the hydrogel bioinks, and cell-hydrogel composites were implanted under the skin of nude mice to observe the effect of the hydrogels on osteogenesis in vivo. Increased GO concentrations led to reduced scaffold degradation rates, increased viscosity, increased printability, increased mechanical properties, increased scaffold porosity and increased cell proliferation rates. In vivo experiments showed that hematoxylin and eosin (HE) staining, Alizarin red staining, alkaline phosphatase staining and collagen type I immunohistochemical staining increased as the implantation time increased. These results demonstrate that GO composites have high printability as bioinks and can be used for bioprinting of bone by altering the ratio of the different components.

8.
Mol Oncol ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252198

RESUMO

Long non-coding RNAs (lncRNAs) are emerging as key molecules in various cancers, yet their potential roles in the pathogenesis of breast cancer are not fully understood. Herein, using microarray analysis, we revealed that the lncRNA RACGAP1P, corresponding to the pseudogene of Rac GTPase Activating Protein 1 (RACGAP1), is up-regulated in breast cancer tissues. Its high expression was confirmed in 25 pairs of breast cancer tissues and 8 breast cell lines by qRT-PCR. Subsequently, we found that RACGAP1P expression was positively correlated with lymph node metastasis, distant metastasis, TNM stage, and shorter survival time in 102 breast cancer patients. Then, in vitro and in vivo experiments were designed to investigate the biological function and regulatory mechanism of RACGAP1P in breast cancer cell lines. Overexpression of RACGAP1P in MDA-MB-231 and MCF7 breast cell lines increased their invasive ability and enhanced their mitochondrial fission. Conversely, inhibition of mitochondrial fission by Mdivi-1 could reduce the invasive ability of RACGAP1P-overexpressing cell lines. Furthermore, the promotion of mitochondrial fission by RACGAP1P depended on its competitive binding with miR-345-5p against its parental gene RACGAP1, leading to the activation of Drp1. In conclusion, lncRNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1 pathway-mediated mitochondrial fission.

9.
Sci Total Environ ; 741: 140262, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32886996

RESUMO

The river-blocking effects of debris flows have become common in numerous catchments in response to climate and environmental changes, and these effects have caused multiple, overlapping, and interconnected chain reactions that have led to huge losses in alpine regions. Considering this issue, this article developed a quantitative method for the regional river-blocking hazard assessment of debris flows by analyzing the in-depth relations among river-blocking hazard formation processes, factors and evolution mechanisms. Taking the debris flows in the Parlung Zangbo Basin in China as a case study, a multidimensional analysis was performed to analyze the characteristics of the hazard sequence and its relationship with climate change, including changes in temperature and precipitation. Accordingly, a new step toward a more comprehensive hazard assessment is proposed by establishing both a model and a system for regional river-blocking hazard assessment to analyze the debris flow evolution processes and environmental dynamics. Specifically, the sources of loose material were quantitatively estimated by establishing mathematical models based on the geometrical characteristics of diverse moraines, and the debris flow runoff was scientifically determined by focusing on the analysis of moraine sources, the brittleness index of the sediment mass and the geomorphological connectivity. Next, through coupling with the hydrodynamic conditions of debris flows and river flows, methods were established to determine the blocking degree of debris flow hazards at the regional scale. Validated by a field study and a remote-sensing interpretation of actual debris flows, a debris-flow-induced river-blocking hazard map was obtained, and the assessment results were in accordance with the actual disaster situation. The analysis shows that the distribution of zones with high to very high levels of river blocking is closely correlated with the topographic characteristics and actual disaster sequences of debris flows. These findings suggest that the assessment results provide scientific support for engineering planning and hazard prevention in climate-sensitive areas; thus, the presented method may serve as pertinent guidance for regional river-blocking hazard assessments of debris flows in the Parlung Zangbo Basin and beyond.

10.
Materials (Basel) ; 13(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992831

RESUMO

Rolling contact fatigue (RCF) damages often occur, sometimes even leading to shelling on locomotive wheel treads. In this work, the RCF damage behaviors of two locomotive wheel materials with different molybdenum (Mo) contents were studied, and the influence of depth of wheel material was explored as well. The result indicates that with the increase in the Mo content from 0.01 wt.% (wheel 1, i.e., a standard wheel) to 0.04 wt.% (wheel 2, i.e., an improved wheel), the proeutectoid ferrite content and the interlamellar spacing of pearlite decreased, the depth and length of the RCF cracks increased and the average RCF live of locomotive wheel steel improved by 34.06%. With the increase in the depth of material, the proeutectoid ferrite content and the interlamellar spacing of pearlite increased, the depth of RCF cracks increased, the length of RCF cracks of wheel 1 increased and then decreased whereas that of wheel 2 decreased, the RCF live showed a decrease trend for wheel 1, while the RCF life increased and then decreased for wheel 2. The processes of shelling can be divided into three patterns: cracks propagating back to the surface, crack connection and fragments of surface materials.

11.
BMC Surg ; 20(1): 195, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883265

RESUMO

BACKGROUND: The windswept lower limb deformity describes valgus deformity in one leg with varus deformity in the other. It is mostly seen in young children with metabolic bone diseases (such as rickets) and may lead to leg length discrepancy (LLD) and Degenerative scoliosis (DS) in older age. To the best of our knowledge, there was no report of the spinal surgery in patient with severe DS associated with windswept deformity. The objective of this study is to report the unique case of a 60-year-old woman with severe degenerative scoliosis (DS) associated with windswept deformity caused by rickets who underwent a posterior correction and fusion surgery in spine. CASE PRESENTATION: The patient was diagnosed as rickets windswept lower limb deformity for 50 years but never went through routine treatment. Then, she performed lumbar scoliosis for more than 20 years and suffered from severe back pain for 4 years. After overall clinical evaluation and radiographic measures, we performed a posterior surgical correction and fusion from T9-L5. With this surgery, the main thoracolumbar curve Cobb angle corrected from 72.5° to 21.0°, the coronal balance from 0 cm to 2.0 cm while the sagittal vertical axis (SVA) from 1.5 cm to - 1.0 cm. At 2 years postoperative follow-up, her back pain has almost completely relieved with a satisfied fixation and bone fusion showed on CT scans. However, a coronal imbalance was found with C7-CSVLdistance equal to 4.0 cm. This coronal imbalance was highly correlated to the untreated LLD and pelvic obliquity, and should be improved by standing posture or shoe lifts. CONCLUSIONS: For such patient, the pure spinal correction and fusion surgery, in spite of lower limbs deformity, can achieve good relieve of back pain symptom, however may accompany by the complication of coronal imbalance due to the unimproved pelvic obliquity and LLD. However, longer follow-up is necessary to observe the long-term outcome of this patient's postoperative coronal imbalance.

12.
Br J Cancer ; 123(7): 1154-1163, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32632148

RESUMO

BACKGROUND: Hepatitis B virus (HBV) has a crucial role in the progression of hepatocellular carcinoma (HCC). Tumour cells must develop anoikis resistance in order to survive before metastasis. This study aimed to investigate the mechanism of IQGAP1 in HBV-mediated anoikis evasion and metastasis in HCC cells. METHODS: IQGAP1 expression was detected by immunohistochemistry, real-time PCR and immunoblot analysis. Lentiviral-mediated stable upregulation or knockdown of IGAQP1, immunoprecipitation, etc. were used in function and mechanism study. RESULTS: IQGAP1 was markedly upregulated in HBV-positive compared with HBV-negative HCC cells and tissues. IQGAP1 was positively correlated to poor prognosis of HBV-associated HCC patients. IQGAP1 overexpression significantly enhanced the anchorage-independent growth and metastasis, whereas IQGAP1-deficient HCC cells are more sensitive to anoikis. Mechanistically, we found that HBV-induced ROS enhanced the association of IQGAP1 and Rac1 that activated Rac1, leading to phosphorylation of Src/FAK pathway. Antioxidants efficiently inhibited IQGAP1-mediated anoikis resistance and metastasis. CONCLUSIONS: Our study indicated an important mechanism by which upregulated IQGAP1 by HBV promoted anoikis resistance, migration and invasion of HCC cells through Rac1-dependent ROS accumulation and activation of Src/FAK signalling, suggesting IQGAP1 as a prognostic indicator and a novel therapeutic target in HCC patients with HBV infection.

13.
Huan Jing Ke Xue ; 41(7): 3102-3111, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608882

RESUMO

To explore the variation of mercury in the atmosphere in Suzhou, continuous monitoring of gaseous element mercury (GEM), gaseous oxidized mercury (GOM), and particulate bound mercury (PBM) was conducted from January 1 to December 31, 2018, in Suzhou. The weights trajectory analysis method (CWT) and concentration rose were used to analyze the atmospheric mercury sources and concentration variation. The results showed that during the monitoring period, the concentration ranges of GEM, GOM, and PBM in Suzhou were 0-53.3 ng·m-3, 0-256 pg·m-3, and 0-5208 pg·m-3, respectively. The corresponding annual average concentrations of the three mercury species were (2.57±2.09) ng·m-3, (5.27±15.7) pg·m-3, and (16.0±157) pg·m-3, respectively. GEM was the main component of atmospheric mercury in Suzhou. During the monitoring period, the average concentration of GEM in Suzhou was highest in winter, higher in spring than in autumn, and lowest in summer. According to the CWT, the mercury-containing air mass in spring and winter predominantly originated from inland; in summer, it mainly originated from the local area, the Yellow Sea, and the East China Sea, and in autumn from inland, the Yellow Sea, and the Bohai Sea. The wind and mercury rose charts showed that atmospheric mercury concentrations were higher from inland and lower from the ocean. During the monitoring period, the average concentrations of GEM and PBM in Suzhou were lower during the day than the night. The diurnal variation of GEM and PBM was significantly and strongly correlated with solar radiation, humidity, and air temperature. The average concentration of GOM showed multiple peaks and valleys in one day. Some peaks were caused by fuel oil combustion emissions, and some by O3 oxidation with GEM.

14.
Int J Genomics ; 2020: 3750673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509843

RESUMO

Heterogeneous nuclear ribonucleoproteins (HNRNPs) are crucial members in the pathogenesis and progression of numerous cancers. However, the expression pattern and clinical significance of HNRNPs in breast carcinoma (BC) remain to be investigated. In the present study, bioinformatic analysis identified HNRNPAB as the only commonly upregulated HNRNP in BC. Elevated expression of HNRNPAB was positively associated with more aggressive diseases and poorer survival rates in BC. Pathway analysis revealed that HNRNPAB coexpressed genes were enriched in the pathway of G2/M phase transition, and the expression level of HNRNPAB was strongly correlated with those of CCNB1, CDK1, CDC25A, and CDC25C. Experiments in vitro demonstrated that HNRNPAB knockdown suppressed cell proliferation and blocked the G2/M phase transition in BC. Taken together, this study provides the initial evidence that HNRNPAB may be employed as an innovative therapeutic target as well as a prognostic biomarker in BC patients.

15.
ACS Nano ; 14(6): 6539-6547, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32363855

RESUMO

How superconductivity emerges from antiferromagnetic ordering is an essential question for Fe-based superconductors. Here, we explore the effect of dimensionality on the interplay between antiferromagnetic ordering and superconductivity by investigating nanoribbons of single-layer FeTe1-xSex films grown on SrTiO3(001) substrates by molecular beam epitaxy. Using scanning tunneling microscopy/spectroscopy, we find a one-dimensional (1D) superconducting channel 2 nm wide with a TC of 42 ± 4 K on the edge of FeTe1-xSex (x < 0.1) ribbons, coexisting with a non-superconducting ribbon interior that remains bicollinear antiferromagnetically ordered. Density functional theory calculations indicate that both Se and the presence of the edge destabilize the bicollinear antiferromagnetic magnetic order, resulting in a paramagnetic region near the edge with strong local checkerboard fluctuations that is conducive to superconductivity. Our results represent the highest TC achieved in 1D superconductors and demonstrate an effective route toward stabilizing superconductivity in Fe-based superconductors at reduced dimensions.

16.
Immunol Lett ; 224: 14-20, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32473185

RESUMO

Under lymphopenic conditions, the rapid spontaneous proliferation produces cells that robustly differentiate into effector memory T (TEM) cells, and the aberrant expansion is preferentially driven by self-antigens. The pool size of effector memory T-cell is governed by a complex homeostatic balance between proliferation and death. Perp is a critical effector involved in the p53-dependent apoptotic pathway and widely expressed in mammalian tissues. We have previously shown that Perp has a prominent role in activation-induced cell death of peripheral Th17 cells. Here, we show that Peripheral Perp-/-CD4+ TEM cells outcompete wild type TEM cells for access to splenic niches in vivo. The skewing of the Perp-/- TEM cells compartment was not the result of a difference in lymphopenia-induced proliferation, but the resistance to apoptosis, particularly after anti-Fas treatment. Data presented in this work indicate that Perp mediates the persistence of CD4+ TEM cells in irradiation-induced lymphopenic settings.

17.
Med Sci Monit ; 26: e923517, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381997

RESUMO

BACKGROUND Fibroblast growth factor receptors (FGFRs) play vital roles in the development and progression of human cancers. This study aimed to comprehensively understand the prognostic performances of FGFR1-4 expression in breast cancer (BC) by mining databases. MATERIAL AND METHODS The levels of FGFR1-4 expression in BC were analyzed by online databases, GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN. Survival analysis of FGFR1-4 was carried out by Kaplan-Meier plotter. GSE74146 was downloaded from Gene Expression Omnibus (GEO) and analyzed by GEO2R to screen the differentially expressed genes (DEGs) between FGFR2-silenced BC cells and control. Over-presentation for DEGs were done by Enrichr tool. Networks of DEGs were obtained by using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Hub genes were identified by cytoHubba Cytoscape plugin. RESULTS The online databases showed that FGFR1 was significantly downregulated whereas FGFR3 was upregulated in BC. Kaplan-Meier plotter demonstrated the upregulation of both FGFR1 and FGFR3 indicated favorable relapse free survival (RFS) whereas FGFR4 overexpression predicted unfavorable overall survival (OS) in BC patients. Importantly, our results showed FGFR2 overexpression robustly predicted favorable OS and RFS in BC. Further bioinformatics analysis of GSE74146 suggested FGFR2 mainly participated in regulating degradation and organization of the extracellular matrix and signaling of retinoic acid. Moreover, CXCL8, CD44, MMP9, and BMP7 were identified as crucial FGFR2-related hub genes. CONCLUSIONS Our study comprehensively analyzed the prognostic values of FGFR1-4 expression in BC and proposed FGFR2 might serve as a promising biomarker. However, the underlying mechanisms remain to be elucidated.

18.
Med Sci Monit ; 26: e922982, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32305991

RESUMO

BACKGROUND SETDB1, an H3K9-specific histone methyltransferase, plays important roles in the progression of various human cancers. However, the expression patterns and its clinical roles of SETDB1 remain elusive in breast cancer (BC). MATERIAL AND METHODS The transcriptional level of SETDB1 and survival data in BC were analyzed through UALCAN, ONCOMINE, and Pan Cancer Prognostics Database. SETDB1 protein expression was assessed by immunohistochemistry (IHC) in 159 BC tissue samples. The associations between SETDB1 expression and clinical pathological characteristics of patients were analyzed. The GEO dataset GSE108656 was downloaded and analyzed to identify the differentially expressed genes (DEGs) between control and BC cells targeting interference with SETDB. The DEGs were further integrated by bioinformatics analysis to decipher the key signaling pathways and hub genes that are regulated by SETDB. RESULTS The public databases showed the level of SETDB1 mRNA was significantly upregulated in BC. Our IHC results demonstrated the level of SETDB1 protein was associated with tumor size (P=0.028), histopathological grading (P=0.012), lymph node metastasis (P<0.001), and TNM stage (P<0.001). High expression of SETDB1 indicated worse overall survival (P=0.015) and shorter relapse-free survival (P=0.027). The bioinformatic analysis of GSE108656 suggested that the SETDB1-related DEGs was mainly enriched in antigen processing and presentation, as well as immune networks in BC. The cytoHubba analysis suggested the top 10 hub genes were IL6, BMP4, CD74, PECAM1, HLA-DPA1, HLA-DRA, LAMC1, CTSB, SERPINA1, and CTSD. CONCLUSIONS The results suggest that SETDB1 is an oncogene and can serve as a prognostic biomarker for BC. However, the mechanisms of SETDB1 in BC remain to be explored.

19.
Nat Mater ; 19(6): 637-643, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32157191

RESUMO

Atomically thin two-dimensional (2D) metals may be key ingredients in next-generation quantum and optoelectronic devices. However, 2D metals must be stabilized against environmental degradation and integrated into heterostructure devices at the wafer scale. The high-energy interface between silicon carbide and epitaxial graphene provides an intriguing framework for stabilizing a diverse range of 2D metals. Here we demonstrate large-area, environmentally stable, single-crystal 2D gallium, indium and tin that are stabilized at the interface of epitaxial graphene and silicon carbide. The 2D metals are covalently bonded to SiC below but present a non-bonded interface to the graphene overlayer; that is, they are 'half van der Waals' metals with strong internal gradients in bonding character. These non-centrosymmetric 2D metals offer compelling opportunities for superconducting devices, topological phenomena and advanced optoelectronic properties. For example, the reported 2D Ga is a superconductor that combines six strongly coupled Ga-derived electron pockets with a large nearly free-electron Fermi surface that closely approaches the Dirac points of the graphene overlayer.

20.
Blood ; 136(1): 119-129, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32202634

RESUMO

Abnormal megakaryocyte development and platelet production lead to thrombocytopenia or thrombocythemia and increase the risk of hemorrhage or thrombosis. Acylglycerol kinase (AGK) is a mitochondrial membrane kinase that catalyzes the formation of phosphatidic acid and lysophosphatidic acid. Mutation of AGK has been described as the major cause of Sengers syndrome, and the patients with Sengers syndrome have been reported to exhibit thrombocytopenia. In this study, we found that megakaryocyte/platelet-specific AGK-deficient mice developed thrombocytopenia and splenomegaly, mainly caused by inefficient bone marrow thrombocytopoiesis and excessive extramedullary hematopoiesis, but not by apoptosis of circulating platelets. It has been reported that the G126E mutation arrests the kinase activity of AGK. The AGK G126E mutation did not affect peripheral platelet counts or megakaryocyte differentiation, suggesting that the involvement of AGK in megakaryocyte development and platelet biogenesis was not dependent on its kinase activity. The Mpl/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat3) pathway is the major signaling pathway regulating megakaryocyte development. Our study confirmed that AGK can bind to JAK2 in megakaryocytes/platelets. More interestingly, we found that the JAK2 V617F mutation dramatically enhanced the binding of AGK to JAK2 and greatly facilitated JAK2/Stat3 signaling in megakaryocytes/platelets in response to thrombopoietin. We also found that the JAK2 JAK homology 2 domain peptide YGVCF617CGDENI enhanced the binding of AGK to JAK2 and that cell-permeable peptides containing YGVCF617CGDENI sequences accelerated proplatelet formation. Therefore, our study reveals critical roles of AGK in megakaryocyte differentiation and platelet biogenesis and suggests that targeting the interaction between AGK and JAK2 may be a novel strategy for the treatment of thrombocytopenia or thrombocythemia.

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