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Green energy technology is generally becoming one of hot issues that need to be solved due to the adverse effects on the environment of fossil fuels. One of the strategies being studied and developed by theorists and experimentalists is the use of photoelectrochemical (PEC) cells, which are emerging as a candidate to produce hydrogen from water splitting. However, creating photoelectrodes that meet the requirements for PEC water splitting has emerged as the primary obstacle in bringing this technology to commercial fruition. Here, we construct a heterostructure, which consists of MoS2/TiO2/Au nanoparticles (NPs) to overcome the drawbacks of the photoanode. Owing to the dependence on charge transfer, the bandgap of MoS2/TiO2and the utilization the Au NPs as a stimulant for charges separation of TiO2by localized surface plasmon resonances effect as well as the increase of hot electron injection to cathode, leading to photocatalytic activities are improved. The results have recorded a significant increase in the photocurrent density from 2.3µAcm-2of TiO2to approximately 16.3µAcm-2of MoS2/TiO2/Au NPs. This work unveils a promising route to enhance the visible light adsorption and charge transfer in photo-electrode of the PEC cells by combining two-dimensional materials with metal NPs.
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Gastrointestinal (GI) perforation is common in the emergency department and has a high mortality rate. The present study aimed to identify risk factors for mortality in patients with GI perforation. The objective was to assess and prognosticate the surgical outcomes of patients, aiming to ascertain the efficacy of the procedure for individual patients. A retrospective cohort study of patients with GI perforation who underwent surgery in a public tertiary hospital in China from January 2012 to June 2022 was performed. Demographics, clinical characteristics, laboratory and imaging results, and outcomes were collected from electronic medical records. The primary outcome measure was in-hospital mortality, and patients were divided into survivor and non-survivor groups based on this measure. Univariate and multivariable logistic regression analyses were performed to obtain independent factors associated with mortality. A total of 529 patients with GI perforation were eligible for inclusion. The in-hospital mortality rate after emergency surgery was 10.59%. The median age of the patients was 60 years (interquartile range, 44-72 years). Multivariable logistic regression analysis indicated that age, shock on admission, elevated serum creatinine (sCr) and white blood cell (WBC) count <3.5x109 or >20x109 cells/l were predictors of in-hospital mortality. In conclusion, advanced age, shock on admission, elevated sCr levels and significantly abnormal WBC count are associated with higher in-hospital mortality following emergency laparotomy.
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Addressing the high false-positive rate of conventional low-dose computed tomography (LDCT) for lung cancer diagnosis, the efficacy of incorporating blood-based noninvasive testing for assisting practicing clinician's decision making in diagnosis of pulmonary nodules (PNs) is investigated. In this prospective observative study, next generation sequencing- (NGS-) based cell-free DNA (cfDNA) mutation profiling, NGS-based cfDNA methylation profiling, and blood-based protein cancer biomarker testing are performed for patients with PNs, who are diagnosed as high-risk patients through LDCT and subsequently undergo surgical resections, with tissue sections pathologically examined and classified. Using pathological classification as the gold standard, statistical and machine learning methods are used to select molecular markers associated with tissue's malignant classification based on a 98-patient discovery cohort (28 benign and 70 malignant), and to construct an integrative multianalytical model for tissue malignancy prediction. Predictive models based on individual testing platforms have shown varying levels of performance, while their final integrative model produces an area under the receiver operating characteristic curve (AUC) of 0.85. The model's performance is further confirmed on a 29-patient independent validation cohort (14 benign and 15 malignant, with power > 0.90), reproducing AUC of 0.86, which translates to an overall sensitivity of 80% and specificity of 85.7%.
Assuntos
Metilação de DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Nódulos Pulmonares Múltiplos/sangue , Nódulos Pulmonares Múltiplos/diagnóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/genética , Aprendizado de Máquina , Masculino , Nódulos Pulmonares Múltiplos/genética , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The vacuole/lysosome is the final destination of autophagic pathways, but can also itself be degraded in whole or in part by selective macroautophagic or microautophagic processes. Diverse molecular mechanisms are involved in these processes, the characterization of which has lagged behind those of ATG-dependent macroautophagy and ESCRT-dependent endosomal multivesicular body pathways. RESULTS: Here we show that as yeast cells gradually exhaust available nutrients and approach stationary phase, multiple vacuolar integral membrane proteins with unrelated functions are degraded in the vacuolar lumen. This degradation depends on the ESCRT machinery, but does not strictly require ubiquitination of cargos or trafficking of cargos out of the vacuole. It is also temporally and mechanistically distinct from NPC-dependent microlipophagy. The turnover is facilitated by Atg8, an exception among autophagy proteins, and an Atg8-interacting vacuolar membrane protein, Hfl1. Lack of Atg8 or Hfl1 led to the accumulation of enlarged lumenal membrane structures in the vacuole. We further show that a key function of Hfl1 is the membrane recruitment of Atg8. In the presence of Hfl1, lipidation of Atg8 is not required for efficient cargo turnover. The need for Hfl1 can be partially bypassed by blocking Atg8 delipidation. CONCLUSIONS: Our data reveal a vacuolar membrane protein degradation process with a unique dependence on vacuole-associated Atg8 downstream of ESCRTs, and we identify a specific role of Hfl1, a protein conserved from yeast to plants and animals, in membrane targeting of Atg8.
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Saccharomyces cerevisiae , Vacúolos , Animais , Autofagia , Família da Proteína 8 Relacionada à Autofagia/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteínas de Membrana/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Growing data have recognized the significance of Response Gene to Complement (RGC)-32 in numerous tumour developments. Notwithstanding, the functional role and underlying mechanism of it in tongue squamous cell carcinoma (TSCC) remain enigmatic. Here, to identify the impact of RGC-32 in TSCC, its expression in multiple TSCC cells was measured and loss-of-function experiments in cell lines were performed to illuminate the function of it induced TSCC progression, via si-RNA knockdown, CCK-8, colony formation, wound-healing, transwell, flow cytometry and western blot assays. To clarify potential mechanism, expressions of hallmarks in epithelial-mesenchymal transition (EMT) process and PI3K/AKT signalling were assessed, and the upstream miR regulator of RGC-32 was predicted and verified by applying bioinformatic approaches and dual-luciferase reporter assay, respectively. Finally, the rescue experiments were applied to better elucidate the effect of miR-26b/RGC-32 axis in TSCC behaviours. As a result, RGC-32 was upregulated in TSCC cells and knocking down of it abrogated cell proliferation, trans-migration and invasion, whilst promoted apoptosis in TSCC, which was regulated through repressing EMT and inactivation of PI3K/AKT signalling. Subsequently, miR-26b was predicted and identified as an upstream regulator of RGC-32, and the pro-tumorigenic effect of RGC-32 was reversed by miR-26b overexpression. Collectively, our results demonstrated that RGC-32 facilitated TSCC progression, which was modulated by activations of PI3K/AKT pathway and EMT process, and reduction of its negative regulator of miR-26b. These findings highlight a novel role of miR-26b/RGC-32 axis in TSCC and underlying mechanism, encouraging a potent usage in TSCC treatment. SIGNIFICANCE OF THE STUDY: We first uncovered that Response Gene to Complement-32 played a significantly pro-tumorigenic role in tongue squamous cell carcinoma (TSCC), which was closely regulated by downregulation of miR-26b and activations of epithelial-mesenchymal transition process and PI3K/AKT signalling. These findings contribute to better understand the molecular mechanism in carcinogenesis of TSCC, and shed some light on promising strategy for TSCC therapeutics.
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Proteínas de Ciclo Celular/metabolismo , Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Antagomirs/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Regulação para CimaRESUMO
Polygalacturonase (PG) is crucial in plant organ abscission process. This paper investigated the cellular and subcellular localization of PG in ethylene-stimulated abscission of tomato pedicel explants. Confocal laser scanning microscopy of abscission zone sections with the fluorescent probe Cy3 revealed that PG was initially accumulated in parenchyma cells in cortical and vascular tissues after 8 h of ethylene treatment and then extended throughout the abscission zone when the abscission zone separated at 24 h after ethylene treatment. At the subcellular level, transmission electron microscopy with immunogold staining showed that PG showed abundant accumulation in the cortical and vascular tissues at 8 h after ethylene treatment, and the distribution area extended to the central parenchyma cells at 16 h after ethylene treatment. In addition, PGs were observed in the distal and proximal parts of the tomato pedicel explants throughout the abscission process. The results provided a visualized distribution of PG in the pedicel abscission zone and proved that PG was closely related to abscission.
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Poligalacturonase/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/ultraestrutura , Ativação Enzimática/efeitos dos fármacos , Etilenos/farmacologia , Espaço Intracelular , Solanum lycopersicum/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Transporte ProteicoRESUMO
This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30 mg/g, and an estimated glomerular filtration rate (eGFR) of >60 mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10 mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC = 0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC = 0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10 mg/g) and HbA1c < 8%. The adjusted hazard ratio for subjects with low-normal UACR/HbA1c > 8%, high-normal UACR/HbA1c < 8%, and high-normal UACR/HbA1c >8% were 2.59 (p = 0.107), 6.15 (p = 0.001), and 16.96 (p < 0.001), respectively. It was determined that an increase of HbA1c levels (<8, 8-9, 9-10, >10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.
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Albuminúria/urina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Hemoglobinas Glicadas/metabolismo , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To quantify the CD4+ CD25+ CD127(low) regulatory T cell (Treg), the expression levels of forkhead/winged helix transcription factor FOXP3 and Notch1 mRNA in aplastic anemia (AA) patients before and after treatment, and explore the significance of Treg in pathogenesis of AA. METHOD: CD4+ CD25+ and CD4+ CD25+ CD127(low) T cells in peripheral blood were examined with FACS in 29 AA patients at active phase, 14 at recovery phase, 11 at unrecovery phase, and 15 normal controls. The levels of FOXP3 mRNA and Notch1 mRNA expression were detected with RT-PCR, and the correlations between Treg, FOXP3 mRNA and Notchl mRNA were analyzed. RESULTS: The percentages of peripheral activated CD4+ CD25+ T cells in AA patients at active phase (4.3 +/- 0.7)% and unrecovery phase (4.2 +/- 0.6)% were significantly higher than those in normal controls (2.4 +/- 0.8)% (P < 0.05). The proportion of these cells in AA patients at recovery phase was reduced to (2.6 +/- 0.7)% (P < 0.05), being no difference from that in control group. The number of CD4+ CD25+ CD127(low) T cells in AA patients at active phase (2.4 +/- 1.2)% and unrecovery phase (2.5 +/- 1.1)% was decreased significantly compared with those in normal controls (7.1 +/- 2.7)% (P < 0.01) and in AA patients at recovery phase (5.3 +/- 1.0)% (P < 0.01), there was no difference between the latter two groups. In active phase AA patients, the levels of FOXP3 mRNA and Notchl mRNA (0.260 +/- 0.011 and 0.018 +/- 0.005, respectively) were lower than that in control group (1.307 +/- 0.011 and 0.308 +/- 0.028, respectively) (P < 0.01 and P < 0.01). After treatment, the levels significantly increased to 1.287 +/- 0.012 and 0.281 +/- 0.013 (P < 0.01 and P < 0.01), but there was no difference with that of normal controls (P > 0.05). CD4+ CD25+ CD2(low) T cells and FOXP3 were positively related with Notchl (P < 0.01) in AA patients. CONCLUSION: The decreased number and suppressive activity of CD4 CD25+ CD127(low) Treg cells in the peripheral blood of AA patients cause over-activation of autoreactive T cells and suppression of haematopoiesis. One of the mechanisms maybe the reduced expression of Notch1 in the target cells.
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Anemia Aplástica/imunologia , Fatores de Transcrição Forkhead/metabolismo , Receptor Notch1/metabolismo , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Anemia Aplástica/metabolismo , Antígenos CD4 , Estudos de Casos e Controles , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Subunidade alfa de Receptor de Interleucina-7 , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Receptor Notch1/genética , Adulto JovemRESUMO
OBJECTIVE: To investigate the highly specific proteasomal inhibitor MG132-induced apoptosis and its effect on nuclear factor (NF)-kappaB activation and survivin expression in leukemic K562 cell line. METHODS: leukemic cells of the line K562 were cultured and divided into 2 groups: treatment group, undergoing co-incubation with MG132 of the concentrations of 2, 4, 6, and 8 micromol/L respectively for 24 hours, and control group without treatment of MG132. Apoptosis was detected by examination of cell morphology and flow cytometry. Survivin expression and NF-kappaB activation were analyzed by immunocytochemistry and Western blotting. RESULTS: MG132 induced apoptosis of the K562 cells dose-dependently. Both survivin and NF-kappaB were highly expressed in the K562 cells. Compared with the control group, K562 cell treated with MG132 at the concentrations of 2, 4, 6, and 8 micromol/L for 24 hours showed the decrease of NF-kappaB activation to 75.0% +/- 3.7%, 59.9% +/- 5.3%, 45.4% +/- 5.7%, and 25.0% +/- 4.2% respectively, and decrease of survivin expression to 90.9% +/- 10.1%, 66.7% +/- 5.2%, 45.4% +/- 5.7%, and 30.3% +/- 6.6% respectively. Downregulation of survivin expression was closely correlated with the inhibition of NF-kappaB activation (Pearson correlation coefficient = 0.989, P < 0.01). CONCLUSION: MG132 induces apoptosis of leukemic cells, and effectively inhibits the NF-kappaB activation accompanied by the downregulation of survivin expression.