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1.
BMC Med ; 22(1): 325, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113079

RESUMO

BACKGROUND: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study. METHODS: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort. RESULTS: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20). CONCLUSIONS: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status.


Assuntos
Índice de Massa Corporal , Análise da Randomização Mendeliana , Obesidade Abdominal , Obesidade , Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Obesidade/epidemiologia , Obesidade/fisiopatologia , Adulto , Circunferência da Cintura , Idoso , Reino Unido/epidemiologia , Análise de Onda de Pulso , Estudos de Coortes
2.
Clin Exp Hypertens ; 46(1): 2383232, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39045803

RESUMO

BACKGROUND: Studies have shown an association between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP). However, the relationship between the TyG index and plaque burden in individuals with primary hypertension remains uncertain. Our study specifically aimed to explore this relationship among primary hypertension patients. METHODS: This study involved 5,153 hospitalized patients diagnosed with primary hypertension who were undergoing treatment at the Affiliated Hospital of Jiangxi University of Chinese Medicine. We utilized multivariate logistic regression, penalized spline regression, and generalized additive models to assess the association between the TyG index and CAP burden. RESULTS: There were 2,400 patients with primary hypertension in all. The multivariate study, which took into account all covariables, showed a positive correlation between the TyG index and CAP (OR: 1.25, 95% CI: 1.04-1.5). When the TyG index was evaluated as quartiles, the risk of CAP in the Q3 and Q4 levels of the TyG index were 1.4 (95% CI: 1.03-1.91) and 1.54 (95% CI: 1.11-2.14) times greater than in the Q1 level after adjusting for all covariables (P for trend < .05). Regardless of whether the TyG index was used as a continuous variable or a categorical variable, it has no significant association with the risk of single plaque after adjusting for all confounders (p ≥ .05). The TyG index was found to be substantially correlated with the presence of multiple plaques when analyzed as a continuous variable (OR: 1.32, 95% CI: 1.09-1.59, p = .004). When the TyG index was evaluated as quartiles, the adjusted OR in Q3 and Q4 were 1.49 (95% CI: 1.06-2.1) and 1.67 (95% CI: 1.16-2.41), respectively, with Q1 as reference (P for trend = .005). The relationship between the TyG index and the presence of multiple plaques is also consistent in all subgroups. CONCLUSION: The TyG index is positively associated with the presence of multiple plaques in patients with primary hypertension, whereas no association is found between the TyG index and the presence of a single carotid plaque.


Assuntos
Glicemia , Hipertensão , Placa Aterosclerótica , Triglicerídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Triglicerídeos/sangue , Placa Aterosclerótica/sangue , Hipertensão/sangue , Glicemia/metabolismo , Glicemia/análise , Idoso , Fatores de Risco , Doenças das Artérias Carótidas/sangue , China/epidemiologia , Adulto
3.
J Ovarian Res ; 16(1): 160, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563658

RESUMO

Fanconi anemia (FA) gene mutations are critical components in the genetic etiology of premature ovarian insufficiency (POI). Fance-/- mice detected meiotic arrest of primordial germ cells (PGCs) as early as embryonic day (E) 13.5 and exhibited decreased ovarian reserve after birth. However, the mechanism of Fance defect leading to dysgenesis of PGCs is unclear. We aimed to explore the effect of Fance defects on mitotic proliferation of PGCs. Combined with transcriptomic sequencing and validation, we examined the effect of Fance defects on cell cycle, transcription-replication conflicts (TRCs), and multiple DNA repair pathways in PGCs during active DNA replication at E11.5 and E12.5. Results showed Fance defects cause decreased numbers of PGCs during rapid mitosis at E11.5 and E12.5. Mitotic cell cycle progression of Fance-/- PGCs was blocked at E11.5 and E12.5, shown by decreased cell proportions in S and G2 phases and increased cell proportions in M phase. RNA-seq suggested the mechanisms involved in DNA replication and repair. We found Fance-/- PGCs accumulate TRCs during active DNA replication at E11.5 and E12.5. Fance-/- PGCs down-regulate multiple DNA repair pathways at E11.5 and E12.5 including the FA pathway, homologous recombination (HR) pathway, and base excision repair (BER) pathway. In conclusion, Fance defect impaired the mitotic proliferation of PGCs leading to rapidly decreased numbers and abnormal cell cycle distribution. Proliferation inhibition of Fance-/- PGCs was associated with accumulated TRCs and down-regulation of FA, HR, BER pathways. These provided a theoretical basis for identifying the inherited etiology and guiding potential fertility management for POI.


Assuntos
Proteína do Grupo de Complementação E da Anemia de Fanconi , Anemia de Fanconi , Animais , Camundongos , Ciclo Celular/genética , Divisão Celular , Reparo do DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Células Germinativas , Camundongos Knockout , Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
4.
Int J Endocrinol ; 2023: 5582306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37360061

RESUMO

Objective: The aim of this study was to investigate the association between the triglyceride glucose (TyG) index and hyperuricemia (HUA) in patients with grades 1-3 hypertension. Study Design. This is a cross-sectional study. A total of 1,707 patients from the cardiovascular department of Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were studied. In this study, 899 patients with grades 1-2 hypertension were included, of which 151 had HUA; additionally, 808 patients with grade 3 hypertension were included, of which 162 patients had HUA. This study obtained all patient data from the electronic medical record system of the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine. The TyG index was calculated as Ln (triglycerides × fasting glucose/2). Hyperuricemia was defined as uric acid ≥420 µmol/L (7 mg/dL). Multivariate logistic regression, penalized spline regression, and generalized additive models were used to evaluate the association between the TyG index and HUA. Stratified analyses were performed to assess the association in populations with different grades of hypertension. Results: The average TyG index was 8.71 ± 0.58. After adjusting for correlated variables, the logistic regression analysis revealed a positive correlation between the TyG index and HUA (OR = 1.83; 95% CI: 1.40-2.39). Smooth curve fitting showed that this correlation was linear in the whole range of the TyG index. In the subgroup analysis, the TyG index more strongly associated with HUA in the grades 1-2 hypertension group (OR = 2.22; 95% CI: 1.44-3.42) compared to that in the grade 3 hypertension group (OR = 1.58; 95% CI: 1.11-2.24; P for interaction = 0.03). In addition, this association was consistent in all models. Conclusion: The TyG index was positively associated with HUA in patients with hypertension, and the association was more strongly confirmed in those with grades 1-2 hypertension rather than in those with grade 3 hypertension.

5.
Front Immunol ; 14: 1114870, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283758

RESUMO

Background: Although more recent evidence has indicated COVID-19 is prone to azoospermia, the common molecular mechanism of its occurrence remains to be elucidated. The aim of the present study is to further investigate the mechanism of this complication. Methods: To discover the common differentially expressed genes (DEGs) and pathways of azoospermia and COVID-19, integrated weighted co-expression network (WGCNA), multiple machine learning analyses, and single-cell RNA-sequencing (scRNA-seq) were performed. Results: Therefore, we screened two key network modules in the obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) samples. The differentially expressed genes were mainly related to the immune system and infectious virus diseases. We then used multiple machine learning methods to detect biomarkers that differentiated OA from NOA. Enrichment analysis showed that azoospermia patients and COVID-19 patients shared a common IL-17 signaling pathway. In addition, GLO1, GPR135, DYNLL2, and EPB41L3 were identified as significant hub genes in these two diseases. Screening of two different molecular subtypes revealed that azoospermia-related genes were associated with clinicopathological characteristics of age, hospital-free-days, ventilator-free-days, charlson score, and d-dimer of patients with COVID-19 (P < 0.05). Finally, we used the Xsum method to predict potential drugs and single-cell sequencing data to further characterize whether azoospermia-related genes could validate the biological patterns of impaired spermatogenesis in cryptozoospermia patients. Conclusion: Our study performs a comprehensive and integrated bioinformatics analysis of azoospermia and COVID-19. These hub genes and common pathways may provide new insights for further mechanism research.


Assuntos
Azoospermia , COVID-19 , Masculino , Humanos , COVID-19/complicações , Azoospermia/genética , Azoospermia/diagnóstico , Azoospermia/patologia , Biomarcadores , Transdução de Sinais , Proteínas dos Microfilamentos
6.
Reproduction ; 166(1): 65-75, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184052

RESUMO

In brief: Fanconi anemia results in subfertility and germ cell deficiency in women. We present histological and RNA-seq analysis of Fance-deficient primordial germ cells to explore the possible mechanisms of their progressive depletion. Abstract: Primordial germ cells (PGCs) development is a subtle and complex regulatory process. Fance is an important substrate molecule necessary for the activation of the Fanconi anemia pathway, and its homozygous mutant causes massive oogonia loss as early as embryonic day 13.5 (E13.5). Here, we present histological and RNA-seq analysis of Fance-deficient PGCs to explore the possible mechanisms responsible for its progressive depletion of germ cells. In Fance-/- embryos, the reduction of PGCs was already evident at E9.5 and the progressive loss of PGCs led to the PGCs being almost exhausted at E12.5. An increase of apoptotic cells was detected among Fance-/- PGCs, which may intuitively explain their reduced number in embryos. Moreover, abnormal cell proliferation and accumulating DNA damage were detected in E12.5 Fance-/- PGCs. We identified 3026 differentially expressed genes in E12.5 Fance-/- PGCs compared to Fance+/+. KEGG pathway analysis revealed that the upregulated genes were highly associated with 'lysosome', and various metabolism pathways, whereas the downregulated genes were mainly enriched in 'cell cycle', 'oocyte meiosis', 'ribosome', and various DNA repair pathways. In addition, multiple genes of various cell death pathways were found to be differentially expressed in E12.5 Fance-/- PGCs, indicating that PGCs death in Fance-/- embryos might diverge from canonical apoptosis. These findings indicate that Fance is essential for PGCs survival and the potential mechanisms involve cell cycle regulation, DNA damage repair, cell death prevention, and by regulating lysosome and ribosome function. Our results provide an important reference for further studies.


Assuntos
Anemia de Fanconi , Feminino , Humanos , Diferenciação Celular , Reparo do DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Células Germinativas , Transcriptoma
7.
J Low Genit Tract Dis ; 27(4): 324-330, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37163703

RESUMO

OBJECTIVE: This study aimed to evaluate the feasibility of combined human papillomavirus (HPV) and optical coherence tomography (OCT) cervical cancer screening strategies. MATERIALS AND METHODS: The OCT and cytology results were compared with the pathological results to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and immediate cervical intraepithelial neoplasia grade 3 or worse (CIN3+) risk. The authors compared the efficiency of colposcopy by using different triage strategies. They discussed differentiation in OCT screening in different age groups. RESULTS: Eight hundred thirteen participants with high-risk HPV-positive and cervical cytology results underwent OCT before colposcopy between March 1 and October 1, 2021. The HPV16/18 genotyping with OCT triage has a specificity of CIN3+ lesions (61.1%; 95% CI = 57.6%-64.6%), intraepithelial neoplasia grade 2 or worse (CIN2+) (66.0%; 95% CI = 62.4%-69.6%). The HPV16/18 genotyping with cytology triage has a specificity of CIN3+ (44.0%; 95% CI = 40.4%-47.6%), CIN2+ (47.0%; 95% CI = 43.2%-50.8%). The OCT triage has a higher positive predictive value compared with the cytology, with a significant difference in CIN2+ lesions (45.0%; 95% CI = 38.8%-51.3% vs 29.2%; 95% CI = 24.7%-33.7%). CONCLUSIONS: The combination of OCT and high-risk HPV triage (both genotyping and nongenotyping) had a similar immediate CIN3+ risk stratification and reduced the number of colposcopies compared with the cytological triage strategy.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Gravidez , Humanos , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Detecção Precoce de Câncer/métodos , Tomografia de Coerência Óptica , Papillomavirus Humano 18 , Displasia do Colo do Útero/patologia , Colposcopia , Encaminhamento e Consulta , Papillomaviridae/genética
8.
Cancer Epidemiol Biomarkers Prev ; 32(7): 936-946, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37104672

RESUMO

BACKGROUND: Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. METHODS: We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models. RESULTS: Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women. CONCLUSIONS: Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer. IMPACT: Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.


Assuntos
Neoplasias Colorretais , Neoplasias Gastrointestinais , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Estudos Prospectivos , Fatores de Risco , Hormônios Esteroides Gonadais , Testosterona , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Globulina de Ligação a Hormônio Sexual/análise , Estradiol
9.
Exp Cell Res ; 421(2): 113388, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36257352

RESUMO

Defective DNA damage repair is a key mechanism affecting tumor susceptibility, treatment response, and survival outcome of endometrial cancer (EC). Fanconi anemia complementation group D2 (FANCD2) is the core component of the Fanconi anemia repair pathway. To explore the function of FANCD2 in EC, we examined the expression of FANCD2 in human specimens and databases, and discussed the possible mechanism of carcinogenesis by in vitro assays. Immunohistochemistry results showed overexpression of FANCD2 was detected in EC tissues compared to normal and atypical hyperplasia endometrium. Higher FANCD2 expression was correlated with deeper myometrial invasion (MI) and proficient mismatch repair status. The Cancer Genome Atlas (TCGA) database analysis showed FANCD2 was upregulated in EC compared with normal tissue. The high expression of FANCD2 was associated with poor overall survival in EC. Knockdown of FANCD2 expression in EC cell lines inhibited malignant proliferation and migration ability. We demonstrated that decreased FANCD2 expression results in increased DNA damage and decreased S-phase cells, leading to a decrease in proliferative capacity in EC cells. Down-regulated FANCD2 confers sensitivity of EC cells to interstrand crosslinking agents. This study provides evidence for the malignant progression and prognostic value of FANCD2 in EC.


Assuntos
Neoplasias do Endométrio , Anemia de Fanconi , Feminino , Humanos , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Prognóstico , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Dano ao DNA/genética , Neoplasias do Endométrio/genética , Endométrio/metabolismo , Reparo do DNA/genética
10.
Reproduction ; 164(3): 71-82, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671285

RESUMO

In brief: Fanconi anemia results in subfertility and primary ovarian deficiency in females. This study reveals that disrupted meiosis in oocytes is one of the mechanisms involved. Abstract: Fance is an important factor participating in the repair of DNA interstrand cross-links and its defect causes severe follicle depletion in female mice. To explore the underlying mechanisms, we investigated the effects of Fance on ovarian development in embryonic and newborn mice. We found that the number of oocytes was significantly decreased in Fance-/- mice as early as 13.5 days post coitum (dpc). The continuous decrease of oocytes in Fance-/- mice compared with the Fance+/+ mice led to the primordial follicles being almost exhausted at 2 days postpartum (dpp). The mitotic-meiotic transition occurred normally, but the meiotic progression was arrested in pachytene in Fance-/- oocytes. We detected the expressions of RAD51 (homologous recombination repair factor), 53BP1 (non-homologous end-joining repair factor), and γH2AX by immunostaining analysis and chromosome spreads. The expressions of 53BP1 were increased and RAD51 decreased significantly in Fance-/- oocytes compared with Fance+/+ oocytes. Also, the meiotic crossover indicated by MLH1 foci was significantly increased in Fance-/- oocytes. Oocyte proliferation and apoptosis were comparable between Fance-/- and Fance+/+ mice (P > 0.05). The aberrant high expression at 17.5 dpc and low expressions at 1 and 2 dpp indicated that the expression pattern of pluripotent marker OCT4 (POU5F1) was disordered in Fance-/- oocytes. These findings elucidate that Fance mutation leads to a progressive reduction of oocytes and disrupts the progression of meiotic prophase I but not the initiation. And, our study reveals that the potential mechanisms involve DNA damage repair, meiotic crossover, and pluripotency of oocytes.


Assuntos
Anemia de Fanconi , Prófase Meiótica I , Animais , Anemia de Fanconi/metabolismo , Feminino , Meiose , Camundongos , Oócitos/metabolismo , Folículo Ovariano
11.
Reprod Biol ; 22(1): 100603, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35026551

RESUMO

DNA double-strand break (DSB) repair is crucial to maintain genomic stability for sufficient ovarian reserve. It remains unknown the changes of DSBs formation and DNA repair in germ cells during ovarian reserve formation in FVB/N mice. We demonstrated germ cell numbers increased significantly (all P < 0.05) from E11.5 to E13.5 and decreased significantly (all P> 0.05) until P2. OCT4 and SOX2 analyses indicated pluripotency peaks at E13.5 then decreases significantly (all P 0.05) until P2. γH2AX analyses revealed DSB formation significantly (P < 0.05) increased from E13.5 until P2. RAD51 and DMC1 data revealed homologous recombination (HR) pathway repair of DSBs is persistent active during meiosis (E13.5- P2) (all P> 0.05). 53BP1 and KU70 data indicate the non-homologous end-joining pathway (NHEJ) remains active during meiosis. 53BP1 expression was highest at E13.5 (P < 0.05). KU70 expression was higher in germ cells from E15.5 to P2 (all < P 0.05). PH3 and KI67 analyses revealed germ cell proliferation was not significantly different (all P> 0.05) from E13.5 to P2. Caspase-3 and TUNEL analyses showed germ cells apoptosis was not significantly different (all P > 0.05) from E13.5 to P2. In conclusion, we found both germ cell number and pluripotency peak at E13.5 and decline during meiosis. We demonstrated HR and NHEJ continually repair DSBs during meiosis. RAD51 and DMC1 are continuously expressed during meiosis. 53BP1 is mainly expressed at E13.5. KU70 continually functions from E15.5 to P2. Proliferating and apoptotic cells were rarely detected during meiosis. Results provide a basis for further study of how DSBs and DNA repair affect germ cell development.


Assuntos
Quebras de DNA de Cadeia Dupla , Reserva Ovariana , Animais , DNA/metabolismo , Reparo do DNA , Meiose , Camundongos
12.
Front Genet ; 13: 1024989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685883

RESUMO

Fanconi anemia (FA) genes contribute to tumorigenesis by regulating DNA repair. Despite its importance for assembly and functionality of the FA core complex, no pan-cancer analysis of FANCE was performed. We aimed to provide a comprehensive understanding of the role of FANCE in cancers. Based on The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype Tissue-Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), and Cancer Single-cell Atlas (CancerSEA) databases, we investigated the carcinogenicity of FANCE using various bioinformatics methods, including FANCE expression and prognosis, immune invasion, tumor mutation burden, microsatellite instability, and neoantigens. We monitored Fance mutations in mice that caused tumorigenesis. FANCE expression and activity scores were upregulated in 15 and 21 cancers. High expression of FANCE affected shorter overall survival (OS) in seven cancers and longer overall survival in three cancers. It was correlated with shorter overall survival and progression-free interval (PFI) in endometrial cancer and longer overall survival and PFI in cervical cancer. FANCE expression negatively correlated with stromal/immune scores in 21 cancers including cervical cancer, endometrial cancer, and ovarian cancer. FANCE expression negatively correlated with CD8 T cells in endometrial cancer and positively correlated with M1 macrophages in cervical cancer, possibly related to cancer prognosis. FANCE positively correlated with immune checkpoint inhibitors PD-1, PD-L1, and CTLA4 in endometrial cancer and ovarian cancer. FANCE expression positively correlated with microsatellite instability, tumor mutational burden, and neoantigens in 7, 22, and five cancers, especially in endometrial cancer, potentially increasing the effectiveness of immunotherapy. Single-cell sequencing data showed FANCE was primarily expressed in cancer cells in cervical and ovarian cancer, and in fibroblasts in endometrial cancer. Fance heterozygous mutant mice had increased tumor incidences and shorter overall survival and tumor-free survival (TFS) than Fance homozygous mutant mice and wild-type mice. Conclusively, FANCE potential to serve as a biomarker for cancer prognosis and may predict cancer immunotherapy responses. Fance heterozygous mutant resulted in increased tumorigenesis and poor prognosis in mice.

13.
ACS Appl Mater Interfaces ; 13(8): 10594-10602, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33617715

RESUMO

We report the fabrication of hexagonal-boron-nitride (hBN) encapsulated multiterminal WSe2 Hall bars with 2D/2D low-temperature Ohmic contacts as a platform for investigating the two-dimensional (2D) metal-insulator transition. We demonstrate that the WSe2 devices exhibit Ohmic behavior down to 0.25 K and at low enough excitation voltages to avoid current-heating effects. Additionally, the high-quality hBN-encapsulated WSe2 devices in ideal Hall-bar geometry enable us to accurately determine the carrier density. Measurements of the temperature (T) and density (ns) dependence of the conductivity σ(T, ns) demonstrate scaling behavior consistent with a metal-insulator quantum phase transition driven by electron-electron interactions but where disorder-induced local magnetic moments are also present. Our findings pave the way for further studies of the fundamental quantum mechanical properties of 2D transition metal dichalcogenides using the same contact engineering.

14.
ACS Appl Mater Interfaces ; 12(41): 46476-46482, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32867473

RESUMO

Two-dimensional (2D) transition metal dichalcogenide (TMDC) materials have garnered great attention on account of their novel properties and potential to advance modern technology. Recent studies have demonstrated that TMDCs can be utilized to create high-performing heterostructures with combined functionality of the individual layers and new phenomena at these interfaces. Here, we report an ultrafast photoresponse within MoSe2-based heterostructures in which heavily p-doped WSe2 and MoS2 flakes share an undoped MoSe2 channel, allowing us to directly compare the optoelectronic properties of MoSe2-based heterojunctions with different 2D materials. Strong photocurrent signals have been observed in both MoSe2-WSe2 and MoSe2-MoS2 heterojunctions with a photoresponse time constant of ∼16 µs, surmounting previous MoSe2-based devices by three orders of magnitude. Further studies have shown that the fast response is independent of the integrated 2D materials (WSe2 or MoS2) but is likely attributed to the high carrier mobility of 260 cm2 V-1 s-1 in the undoped MoSe2 channel as well as the greatly reduced Schottky barriers and near absence of interface states at MoSe2-WSe2/MoS2 heterojunctions, which lead to reduced carrier transit time and thus short photocurrent response time. Lastly, a high detectivity on the order of ∼1014 Jones has been achieved in MoSe2-based heterojunctions, which supersedes current industry standards. These fundamental studies not only shed light on photocurrent generation mechanisms in MoSe2-based heterojunctions but also open up new avenues for engineering future high-performance 2D optoelectronic devices.

15.
ACS Nano ; 14(5): 6232-6241, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32320204

RESUMO

We report a contact engineering method to minimize the Schottky barrier height (SBH) and contact resistivity of MoS2 field-effect transistors (FETs) by using ultrathin 2D semiconductors as contact interlayers. We demonstrate that the addition of a few-layer MoSe2 between the MoS2 channel and Ti electrodes effectively reduces the SBH at the contacts from ∼100 to ∼25 meV, contact resistivity from ∼6 × 10-5 to ∼1 × 10-6 Ω cm2, and current transfer length from ∼425 to ∼60 nm. The drastic reduction of SBH can be attributed to the synergy of Fermi-level pinning close to the conduction band edge of the MoSe2 interlayer and favorable conduction-band offset between the MoSe2 interlayer and MoS2 channel. As a result of the improved contacts, MoS2 FETs with Ti/MoSe2 contacts also demonstrate higher two-terminal mobility.

16.
Nanoscale ; 11(30): 14410-14416, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334533

RESUMO

We investigate electronic and optoelectronic properties of few-layer palladium diselenide (PdSe2) phototransistors through spatially-resolved photocurrent measurements. A strong photocurrent resonance peak is observed at 1060 nm (1.17 eV), likely attributed to indirect optical transitions in few-layer PdSe2. More interestingly, when the thickness of PdSe2 flakes increases, more and more photocurrent resonance peaks appear in the near-infrared region, suggesting strong interlayer interactions in few-layer PdSe2 help open up more optical transitions between the conduction and valence bands of PdSe2. Moreover, gate-dependent measurements indicate that remarkable photocurrent responses at the junctions between PdSe2 and metal electrodes primarily result from the photovoltaic effect when a PdSe2 phototransistor is in the off-state and are partially attributed to the photothermoelectric effect when the device turns on. We also demonstrate PdSe2 devices with a Seebeck coefficient as high as 74 µV K-1 at room temperature, which is comparable with recent theoretical predications. Additionally, we find that the rise and decay time constants of PdSe2 phototransistors are ∼156 µs and ∼163 µs, respectively, which are more than three orders of magnitude faster than previous PdSe2 work and two orders of magnitude over other noble metal dichalcogenide phototransistors, offering new avenues for engineering future optoelectronics.

17.
ACS Nano ; 13(5): 5103-5111, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31038922

RESUMO

In search of an improved strategy to form low-resistance contacts to MoS2 and related semiconducting transition metal dichalcogenides, we use ab initio density functional electronic structure calculations in order to determine the equilibrium geometry and electronic structure of MoO3/MoS2 and MoO2/MoS2 bilayers. Our results indicate that, besides a rigid band shift associated with charge transfer, the presence of molybdenum oxide modifies the electronic structure of MoS2 very little. We find that the charge transfer in the bilayer provides a sufficient degree of hole doping to MoS2, resulting in a highly transparent contact region.

18.
Nanoscale ; 11(15): 7358-7363, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30938719

RESUMO

We report a reversible photo-induced doping effect in two-dimensional (2D) tungsten diselenide (WSe2) field effect transistors on hexagonal boron nitride (h-BN) substrates under low-intensity visible light illumination (∼10 nW µm-2). Our experimental results have shown that this reversible doping process is mainly attributed to two types of defects in h-BN substrates. Moreover, the photo-doped WSe2 transistors can be stable for more than one week in a dark environment and maintain the high on/off ratio (108) and carrier mobility, since there are no additional impurities involved during the photo-induced doping process to increase the columbic scattering in the conducting channel. These fundamental studies not only provide an accessible strategy to control the charge doping level and then to achieve a writing/erasing process in 2D transistors, but also shed light on the defect states and interfaces in 2D materials.

19.
Nano Lett ; 18(5): 2766-2771, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29614223

RESUMO

We report high-performance WSe2 phototransistors with two-dimensional (2D) contacts formed between degenerately p-doped WSe2 and undoped WSe2 channel. A photoresponsivity of ∼600 mA/W with a high external quantum efficiency up to 100% and a fast response time (both rise and decay times) shorter than 8 µs have been achieved concurrently. More importantly, our WSe2 phototransistor exhibits a high specific detectivity (∼1013 Jones) in vacuum, comparable or higher than commercial Si- and InGaAs-based photodetectors. Further studies have shown that the high photoresponsivity and short response time of our WSe2 phototransistor are mainly attributed to the lack of Schottky-barriers between degenerately p-doped WSe2 source/drain contacts and undoped WSe2 channel, which can reduce the RC time constant and carrier transit time of a photodetector. Our experimental results provide an accessible strategy to achieve high-performance WSe2 phototransistor architectures by improving their electrical transport and photocurrent generation simultaneously, opening up new avenues for engineering future 2D optoelectronic devices.

20.
ACS Nano ; 11(10): 10472-10479, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-28926227

RESUMO

van der Waals heterojunctions using 2D semiconducting materials could overcome the defect issues included by lattice mismatch in conventional epitaxially grown heterojunctions with bulk materials and could enable a much wider palette for choice of materials and more sophisticated device design. Such 2D heterojunction devices are of great interest for important functional devices such as diodes, bipolar junction transistors, light-emitting diodes, and photodetectors. In this paper, we demonstrate a truly vertical p-n heterojunction diode built from 2D semiconductors (MoS2 and BP) and compare its performance against conventional lateral 2D heterojunction devices (partially overlapped 2D heterostructures). Both vertical and lateral p-n heterostructure diodes exhibit a strong rectification ratio even with no gate voltage applied. More importantly, the results show that the vertical diode delivers 70 times higher current density under forward bias than a conventional lateral device design and the improved device performance can be attributed to the complete elimination of series resistance. Low-temperature measurements and TCAD simulations are used to determine the barrier height at the junctions. Moreover, the vertical device structure allows certain ambiently unstable 2D semiconductors to be fully encapsulated by the materials on top, preventing the material from degradation. This work demonstrates the potential of using the vertically stacked 2D semiconductors for future nanoelectronic and optoelectronic devices with optimal performance.

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