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1.
Mol Cell ; 82(21): 4080-4098.e12, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36272410

RESUMO

Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.


Assuntos
Neoplasias , Corpos Nucleares , Humanos , Domínios Proteicos , Cromatina/genética , Mutação , Neoplasias/genética
2.
Nano Lett ; 24(17): 5342-5350, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630899

RESUMO

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs. The suppression of both electron-phonon interaction and Auger recombination by the rigid ZnS shell results in CIS/ZnS core/shell QDs that exhibit a wide near-infrared (NIR) emission coverage and a remarkable PL quantum yield of 92.1%. This effect boosts the fabrication of high-performance, QD-based NIR light-emitting diodes with the best stability of such materials so far.

3.
Opt Lett ; 49(7): 1749-1752, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560853

RESUMO

Non-contact optical temperature measurement can effectively avoid the disadvantages of traditional contact thermometry and thus, become a hot research topic. Herein, a fluorescence intensity ratio (FIR) thermometry using a time-resolved technique based on La2CaZrO6:Cr3+ (LCZO) is proposed, with a maximum relative sensitivity (Sr - FIR) of 2.56% K-1 at 473 K and a minimum temperature resolution of 0.099 K. Moreover, the relative sensitivity and temperature resolution can be effectively controlled by adjusting the width of the time gate based on the time-resolved technique. Our work provides, to our knowledge, new viewpoints into the development of novel optical thermometers with adjustable relative sensitivity and temperature resolution on an as-needed basis.

4.
Opt Express ; 31(16): 25978-25992, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710470

RESUMO

Although Cr3+ as activator for Near infrared (NIR) phosphors has been widely studied, the peaks of Cr3+ emission spectra in most hosts are less than 1000 nm. Nd3+ as an activator in many hosts has a wide distribution of absorption peaks in the Ultraviolet-visible-Near infrared (UV-vis-NIR) band, especially in the 650-900 nm band for effective NIR to NIR Stokes luminescence (4F3/2→4I9/2, 4F3/2→4I11/2 transitions). Therefore, Cr3+, Nd3+ co-doping to achieve the emission in the NIR II region (1000-1700nm) is very meaningful. Here, we report La2CaZrO6(LCZO): Cr3+, Nd3+ NIR phosphors with emission spectra covering an ultra-wide range of 700-1400 nm and reveal their luminescence mechanism. The energy transfer efficiency of Cr3+ for Nd3+ can be as high as 88.4% under 471 nm blue light excitation. In the same case, the integrated intensity of the emission spectra of Cr3+, Nd3+ co-doped can reach 847% of that of Nd3+ alone and 204% of that of Cr3+ alone. Finally, the combination of commercial blue light chips and Cr3+, Nd3+ co-doped NIR phosphors shows great potential for applications in face recognition, night lighting, and angiography.

5.
Eur J Nutr ; 62(3): 1427-1439, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36631706

RESUMO

PURPOSE: The possible impact of preload food on insulin sensitivity has yet been reported. This study aimed to investigate the glycemic and insulinemic effect of an apple preload before breakfast, lunch and early supper, based on high glycemic index (GI) rice meals. METHODS: Twenty-three healthy participants in Group 1 and 14 participants in Group 2 were served with the reference meal (white rice containing 50 g of available carbohydrate) or experimental meals (apple preload and rice, each containing 15 and 35 g of available carbohydrate). The meals were either served at 8:00 for breakfast, 12:30 for lunch or 17:00 for early supper to explore the possible effect of time factor. The group 1 assessed the postprandial and subsequent-meal glycemic effect of the test meals by continuous glucose monitoring (CGM), along with subjective appetite; The group 2 further investigated the glycemic and insulin effect by blood collection. RESULTS: The apple preload lowered the blood glucose peak value by 33.5%, 31.4% and 31.0% in breakfast, lunch and supper, respectively, while increased insulin sensitivity by 40.5% only at breakfast, compared with the rice reference. The early supper resulted significantly milder glycemic response than its breakfast and lunch counterparts did. The result of CGM tests was consistent with that of the fingertip blood tests. CONCLUSION: Apple preload performed the best at breakfast in terms of enhancing the insulin sensitivity. The preload treatment could effectively attenuate postprandial GR without increasing the area under insulin response curve in any of the three meals.


Assuntos
Hiperglicemia , Resistência à Insulina , Malus , Humanos , Glicemia , Desjejum , Automonitorização da Glicemia , Farinha , Índice Glicêmico , Insulina , Refeições , Período Pós-Prandial , Estudos Cross-Over , Carboidratos da Dieta/farmacologia
6.
Phys Chem Chem Phys ; 25(8): 6214-6224, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36753232

RESUMO

Investigating the effect of different phases on the optical performance is crucial for thermal sensing phosphor materials. Ba(2-x)SrxMgWO6:Er3+, Yb3+, K+ double perovskite phosphors were successfully prepared using a high-temperature solid-phase method. The dominant up-conversion luminescent (UCL) mechanism was deduced by analyzing the power-dependence spectra and energy level diagrams. By X-ray diffraction tests and tolerance factor calculations, it was demonstrated that the substitution of Sr2+ ions for Ba2+ ions led to the phase changing from cubic to tetragonal. The phase transition led to a decrease in the crystallographic symmetry of the compounds and changes in the optical thermometric properties. The optical temperature sensing properties were investigated using the fluorescence intensity ratio of thermally coupled energy levels (2H11/2 and 4S3/2 to the ground state energy level 4I15/2) of Er3+ ions in Ba2MgWO6, BaSrMgWO6 and Sr2MgWO6. The maximum absolute sensitivities obtained for Ba2MgWO6, BaSrMgWO6 and Sr2MgWO6 doped with 7% Er3+, 2% Yb3+ and 9% K+ were 6.77 × 10-4 K-1, 10.09 × 10-4 K-1 and 23.4 × 10-4 K-1, respectively. The comparison revealed that the phase transition caused an increase in the luminescence intensity and absolute sensitivity. This provides a useful pathway for modulating the subsequent thermometric performance.

7.
Asia Pac J Clin Nutr ; 31(1): 57-65, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35357104

RESUMO

BACKGROUND AND OBJECTIVES: The variation in glycemic responses to white rice caused by the circadian rhythm has been widely investigated but remain controversial. This study investigated diurnal differences in the effect of rice meals on glycemic responses, insulin responses, satiety, and acute cognitive function. METHODS AND STUDY DESIGN: A total of 20 healthy participants in Group 1 and 14 in Group 2 were served identical servings of cooked white rice containing 50 g of available carbohydrates at 8:00 a.m. (rice at breakfast), 12:30 p.m. (rice at lunch), and 5:00 p.m. (rice at early supper) in a randomized order. Postprandial blood glucose, insulin, satiety, and cognitive performance tests were conducted for each test meal. RESULTS: The rice at an early supper elicited significantly milder glycemic responses than did the rice at lunch and resulted in a lower insulin sensitivity than did rice at breakfast. No difference was observed among the test meals in terms of hunger and prospective food intake. Diurnal acute cognitive performance did not differ considerably among the meals. A correlation analysis indicated that low variability in glycemic responses was positively associated with superior cognitive performance. CONCLUSIONS: A high-glycemic index white rice supper at 5:00 p.m. may facilitate daily glycemic management.


Assuntos
Oryza , Glicemia , Cognição , Humanos , Insulina , Refeições
8.
Nano Lett ; 21(4): 1620-1627, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33570415

RESUMO

Morphology control represents an important strategy for the development of functional nanomaterials and has yet to be achieved in the case of promising lead-free double perovskite materials so far. In this work, high-quality Cs2AgBiX6 (X = Cl, Br, I) two-dimensional nanoplatelets were synthesized through a newly developed synthetic procedure. By analyzing the optical, morphological, and structural evolutions of the samples during synthesis, we elucidated that the growth mechanism of lead-free double perovskite nanoplatelets followed a lateral growth process from mono-octahedral-layer (half-unit-cell in thickness) cluster-based nanosheets to multilayer (three to four unit cells in thickness) nanoplatelets. Furthermore, we demonstrated that Cs2AgBiBr6 nanoplatelets possess a better performance in photocatalytic CO2 reduction compared with their nanocube counterpart. Our work demonstrates the first example with two-dimensional morphology of this important class of lead-free perovskite materials, shedding light on the synthetic manipulation and the application integration of such promising materials.

9.
Pharm Biol ; 60(1): 1449-1457, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938505

RESUMO

CONTEXT: A novobiocin derivative, XN4, has been shown to promote cell apoptosis in chronic myeloid leukaemia. OBJECTIVE: This study explores the mechanism by which XN4 promotes ferroptosis of gastric cancer (GC) cells. MATERIALS AND METHODS: Human GC SGC-7901 and BGC-823 cells were treated with different XN4 concentrations (0, 0.1, 0.5, 1.0, 5.0, and 10.0 µmol/L) to evaluate effects of XN4. Additionally, cells were pre-treated for 24 h with si-NOX4, for 1 h with the iron chelator deferoxamine mesylate (DFO) or for 1 h with the lipid peroxidation inhibitor liproxstatin-1 before being treated with XN4 to analyse the mechanism of XN4. RESULTS: XN4 increased cell death (IC50 values of XN4 on SGC-7901 and BGC-823 cells: 1.592 ± 0.14 µmol/L and 2.022 ± 0.19 µmol/L) and Fe2+ levels in SGC-7901 and BGC-823 cells. These effects of 2.0 µmol/L XN4 were abolished by 100 µmol/L DFO treatment. XN4 enhanced transferrin and transferrin receptor expression to induce Fe2+ accumulation. XN4 decreased mitochondrial membrane potentials in GC cells, similar to erastin. Additionally, XN4 increased MDA, hydrogen peroxide, and ROS levels, but diminished total glutathione levels. Liproxstatin-1 (200 nmol/L) nullified the effects of XN4 (2.0 µmol/L) on MDA levels and cell death. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. DISCUSSION AND CONCLUSIONS: The pro-ferroptotic role of XN4 in GC might enable it to become a promising drug for GC treatment in the future despite the need for extensive research.


Assuntos
Ferroptose , Neoplasias Gástricas , Apoptose , Morte Celular , Humanos , Peroxidação de Lipídeos , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/farmacologia , Novobiocina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico
10.
J Transl Med ; 18(1): 255, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580742

RESUMO

BACKGROUND: Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice. METHODS: We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10-20 mm in diameter, we performed survival surgery on each mouse to harvest 90-95% of subcutaneous PDX (incomplete resection), allowing the remaining 5-10% of PDX to continue growing in the same mouse. RESULTS: We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors. CONCLUSIONS: Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Análise Custo-Benefício , Xenoenxertos , Humanos , Camundongos , Camundongos SCID , Recidiva Local de Neoplasia , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Neurochem Res ; 45(7): 1614-1625, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279214

RESUMO

Glioma is a common invasive cancer with unfavorable prognosis in patients. Long non-coding RNAs (lncRNAs) exert significant functions in carcinogenesis of various cancers including glioma. Among them, long intergenic non-coding RNA 668 (LINC00668) was reported to function as oncogene in various cancers, but its molecular mechanism in glioma has not been thoroughly researched. Our current study aimed to investigate the role and molecular mechanism of LINC00668 in glioma cells. We initially found out that LINC00668 was up-regulated in glioma cells. Through a series of function assays, LINC00668 was verified to facilitate cell proliferation and inhibit apoptosis in glioma. Then, by means of online databases, RNA pull down assay and RIP assay, we verified the binding relation between LINC00668 and miR-518c-3p. Also, the next function assays exposed that miR-518c-3p was the tumor suppressor in glioma cells. Similarly, SOCS5 (suppressor of cytokine signaling 5) was found to bind with miR-518c-3p, which repressed glioma tumorigenesis by targeting SOCS5. Moreover, rescue assays manifested that LINC00668 modulated expression of SOCS5 in a miR-518c-3p-dependent way and further regulated glioma tumorigenesis. Overall, LINC00668 modulates SOCS5 expression through competitively sponging miR-518c-3p to facilitate glioma cell proliferation.


Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células/fisiologia , Glioma/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas Supressoras da Sinalização de Citocina/genética
12.
Sensors (Basel) ; 20(7)2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32235456

RESUMO

Aiming at addressing the issues related to the tuning of loop closure detection parameters for indoor 2D graph-based simultaneous localization and mapping (SLAM), this article proposes a multi-objective optimization method for these parameters. The proposed method unifies the Karto SLAM algorithm, an efficient evaluation approach for map quality with three quantitative metrics, and a multi-objective optimization algorithm. More particularly, the evaluation metrics, i.e., the proportion of occupied grids, the number of corners and the amount of enclosed areas, can reflect the errors such as overlaps, blurring and misalignment when mapping nested loops, even in the absence of ground truth. The proposed method has been implemented and validated by testing on four datasets and two real-world environments. For all these tests, the map quality can be improved using the proposed method. Only loop closure detection parameters have been considered in this article, but the proposed evaluation metrics and optimization method have potential applications in the automatic tuning of other SLAM parameters to improve the map quality.

13.
Antimicrob Agents Chemother ; 63(12)2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31527024

RESUMO

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.

14.
J Neuropsychiatry Clin Neurosci ; 30(2): 122-129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29458280

RESUMO

Depressive symptoms and sensory dysfunction, such as reduction in visual and olfactory function, are common in Parkinson's disease (PD). Previous studies have suggested that depressive symptoms are associated with visual impairments and potentially with hyposmia in several types of mood disorders. However, the relationship between depressive symptoms and sensory dysfunction remains unclear in PD. To examine the association of depressive symptoms with color vision and olfactory function in PD, the authors conducted a cross-sectional study in 159 patients with PD. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI-II) and the 30-item Geriatric Depression Scale (GDS-30); color vision was tested with the Farnsworth-Munsell 100 Hue Test (FMT); and olfactory function was tested with the Sniffin' Sticks Screening 12 Test. Results showed that the total error score (TES) for the FMT was significantly and independently correlated with scores on both the BDI-II and GDS-30 in a positive manner, suggesting that more severe depressive symptoms are associated with poorer color vision in PD. In addition, both somatic and effective subscores for the BDI-II were correlated with the TES on the FMT, while no significant correlation was observed between total scores on the Sniffin' Sticks Screening 12 Test and BDI-II or GDS-30. The decrease in color vision but not olfactory function was found to be associated with the severity of depressive symptoms in PD patients, supporting the idea that the occurrence of depressive symptoms in PD is linked with disruption of the visual system.


Assuntos
Visão de Cores , Depressão/fisiopatologia , Doença de Parkinson/fisiopatologia , Olfato , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica
15.
Tumour Biol ; 39(2): 1010428317691429, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28218035

RESUMO

Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Glutaminase/metabolismo , Glutamina/metabolismo , MicroRNAs/metabolismo , Neoplasias Encefálicas/genética , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Glioblastoma/genética , Glutaminase/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , MicroRNAs/biossíntese , MicroRNAs/genética
17.
BMC Public Health ; 15: 474, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-25952360

RESUMO

BACKGROUND: Non-adherence to tuberculosis (TB) treatment threatens the success of treatment, increases the risk of TB spread, and leads to the development of drug resistance. The present study assessed non-adherence to anti-TB treatment among internal migrants with pulmonary TB living in Shenzhen, China, and examined risk factors for non-adherence in order to identify targets for intervention. METHODS: A total of 794 internal migrants with TB treated at Bao'an Hospital for Chronic Disease Prevention and Cure, Shenzhen, were recruited. Structured questionnaires were used to collect data on these patients' history and experiences with TB treatment. Ordinal logistic regression model were used to identify risk factors for non-adherence. RESULTS: The proportion of patients who had missed one dose of medication within two weeks was 93/794 (11.71%), and those who missed at least two doses of medication within two weeks was 167/794 (21.03%), with a total of 33.74% of patients not adhering to TB treatment. Lack of knowledge about TB treatment and longer travel time to the nearest community health centers are significant predictors for non-adherence. CONCLUSIONS: The present study shows that non-adherence is common among internal migrants with TB. Patients who lack knowledge about TB treatment or have to travel far to get treated are prone to miss one or more doses of medication. Interventions to improve health education and healthcare access are essential to reduce non-adherence to TB treatment among internal migrants.


Assuntos
Antituberculosos/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Migrantes/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Atitude Frente a Saúde , China/epidemiologia , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos em Cuidados de Saúde/métodos , Pesquisa Qualitativa , Fatores de Risco , Adulto Jovem
18.
Carcinogenesis ; 35(7): 1500-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24445145

RESUMO

The mouse double minute 4 (MDM4) oncoprotein may inhibit tumorigenesis by regulating the apoptotic mediator p53. Ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme that protects MDM4 against degradation, so USP2-MDM4 interaction may be a key determinant of the malignant potential of human cancers. MDM4 and USP2a, as well as the MDM4-USP2a complex, were more highly expressed in glioblastoma multiforme tissue samples from patients with good prognosis compared with patients with poor prognosis. Analysis of the prognostic parameters indicated that MDM4 expression was positively correlated with an increased likelihood for survival. Compared with the poor prognosis patients, mitochondria from good prognosis glioma patients contained higher levels of both MDM4 and the proapoptotic protein p53Ser46(P). In U87MG glioma cell line, the overexpression of MDM4 enhanced ultraviolet (UV)-induced cytochrome c release and apoptosis. In contrast, MDM4 knockdown decreased mitochondrial p53Ser46(P) levels and rescued cells from UV-induced apoptosis. The expression of MDM4 and USP2a were positively correlated with each other. MDM4-USP2a complexes were found only in the cytoplasmic fraction, whereas the mitochondrial fraction contained MDM4-p53Ser46(P) and MDM4-Bcl-2 complexes. Overexpression of USP2a increased p53 and p53Ser46(P) levels in the mitochondria, whereas simultaneous MDM4 knockdown completely reversed this effect. UV-induced apoptosis was reduced by USP2a knockdown but restored by the simultaneous overexpression of MDM4. This apoptotic response was reduced by knockdown of p53 but not p21. Our results suggest that USP2a binds to and stabilizes MDM4; thus in turn, it enhances the mitochondrial localization of p53 and promotes apoptosis in glioma cells.


Assuntos
Apoptose , Endopeptidases/metabolismo , Glioblastoma/patologia , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Animais , Western Blotting , Proteínas de Ciclo Celular , Núcleo Celular/metabolismo , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citoplasma/metabolismo , Endopeptidases/genética , Imunofluorescência , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ubiquitina Tiolesterase
19.
Comput Med Imaging Graph ; 111: 102316, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039866

RESUMO

Cylindrical organs, e.g., blood vessels, airways, and intestines, are ubiquitous structures in biomedical optical imaging analysis. Image segmentation of these structures serves as a vital step in tissue physiology analysis. Traditional model-driven segmentation methods seek to fit the structure by constructing a corresponding topological geometry based on domain knowledge. Classification-based deep learning methods neglect the geometric features of the cylindrical structure and therefore cannot ensure the continuity of the segmentation surface. In this paper, by treating the cylindrical structures as a 3D graph, we introduce a novel contour-based graph neural network for 3D cylindrical structure segmentation in biomedical optical imaging. Our proposed method, which we named CylinGCN, adopts a novel learnable framework that extracts semantic features and complex topological relationships in the 3D volumetric data to achieve continuous and effective 3D segmentation. Our CylinGCN consists of a multiscale 3D semantic feature extractor for extracting inter-frame multiscale semantic features, and a residual graph convolutional network (GCN) contour generator that combines the semantic features and cylindrical topological priors to generate segmentation contours. We tested the CylinGCN framework on two types of optical tomographic imaging data, small animal whole body photoacoustic tomography (PAT) and endoscopic airway optical coherence tomography (OCT), and the results show that CylinGCN achieves state-of-the-art performance. Code will be released at https://github.com/lzc-smu/CylinGCN.git.


Assuntos
Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Tomografia de Coerência Óptica/métodos , Processamento de Imagem Assistida por Computador/métodos
20.
Sci Total Environ ; 946: 174162, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909807

RESUMO

Organophosphate esters (OPEs), increasingly used as alternatives to brominated flame retardants, are ubiquitous in the global aquatic environment. Despite their potential toxicological impact on ecosystems, community-level risk assessments for OPEs in sediments remain scarce. This study investigated OPE occurrences and composition characteristics in the Bohai Sea's sediments and appraised both individual and joint ecological risks posed by characteristic OPE homologs using ten commonly used species sensitivity distribution (SSD) models, integrating acute-to-chronic conversion and phase equilibrium partitioning. OPEs were detected across all sediment samples, with total concentrations ranging from 0.213 ng/g dry weight (dw) to 91.1 ng/g dw. The predominant congeners included tri-n-butyl phosphate (TnBP), triisobutyl phosphate (TiBP), tri(2-ethylhexyl) phosphate, tri(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP), and triphenylphosphine oxide. Best-fit SSD models varied among TnBP, TiBP, TCEP, TCPP, and TDCIPP, demonstrating Sigmoid, Burr III, Sigmoid, Burr III, and Burr III, respectively. The same parametric model demonstrated variability in the fitting process for different OPE congeners, which also happened to the fitting results of ten parametric models for the same specific characteristic congener, underscoring the necessity of employing multiple models for precise community-level risk assessments. Hazard concentrations for a 5% cumulative probability were 0.116 mg/L, 2.88 mg/L, 1.30 mg/L, 1.44 mg/L, and 1.85 mg/L for each respective congener. The resulting risk quotients (RQ) and overall hazard index (HI) were selected as criteria to assess the individual and joint ecological risks of OPEs in sediments from the Bohai Sea, respectively. RQ and HI were both below 0.1, indicating a low risk to the local ecosystems. Multi-model SSD analysis could provide refined data for community-level risk evaluation, offering valuable insights for the development of evidence-based environmental standards and pollution control strategies.

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