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1.
Angew Chem Int Ed Engl ; : e202410417, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38924241

RESUMO

The electrochemical production of hydrogen peroxide (H2O2) using metal-free catalysts has emerged as a viable and sustainable alternative to the conventional anthraquinone process. However, the precise architectural design of these electrocatalysts poses a significant challenge, requiring intricate structural engineering to optimize electron transfer during the oxygen reduction reaction (ORR). Herein, we introduce a novel design of covalent organic frameworks (COFs) that effectively shift the ORR from a four-electron to a more advantageous two-electron pathway. Notably, the JUC-660 COF, with strategically charge-modified benzyl moieties, achieved a continuous high H2O2 yield of over 1200 mmol g-1 h-1 for an impressive duration of over 85 hours in a flow cell setting, marking it as one of the most efficient metal-free and non-pyrolyzed H2O2 electrocatalysts reported to date. Theoretical computations alongside in-situ infrared spectroscopy indicate that JUC-660 markedly diminishes the adsorption of the OOH* intermediate, thereby steering the ORR towards the desired pathway. Furthermore, the versatility of JUC-660 was demonstrated through its application in the electro-Fenton reaction, where it efficiently and rapidly removed aqueous contaminants. This work delineates a pioneering approach to altering the ORR pathway, ultimately paving the way for the development of highly effective metal-free H2O2 electrocatalysts.

2.
Org Biomol Chem ; 22(26): 5401-5405, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38874577

RESUMO

A stable and practical electrochemical method was developed to promote the thio-Michael addition of N-substituted maleimides to various thiols in an aqueous medium. This protocol was found to be excellent in terms of facile scale-up, oxidant- and catalyst-free conditions, broad substrate scopes, good functional group tolerance, and easily available substrates. Notably, a plausible reaction mechanism was derived from the results of a series of control experiments and CV studies, which indicated that a radical pathway might speed up the thio-Michael addition under constant current.

3.
ACS Appl Mater Interfaces ; 16(27): 35390-35399, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38922684

RESUMO

The all-fused-ring acceptor (AFRA) is a success for nonfullerene materials and has attracted considerable attention as its high optical and chemical stability expected to reduce energy loss, and power conversion efficiency (PCE) approaching 15% in constructed all-small-molecule organic solar cells (OSCs). Herein, the intrinsic role of the structure of AFRA F13 and the reason for its high PCE were revealed by comparison with those of typical fused acceptors IDT-IC and Y6. An increased degree of conjugation in F13 leads to broader and red-shifted absorption peaks, facilitating enhancement of the short-circuit current. Multiple charge-transfer mechanisms are mainly attributed to the higher Frenkel exciton (FE) state due to the multiple transition ways for acceptors in the C1-CN:F13 system. The increased number of atoms contributing to the charge-transfer (CT) state facilitated the existence of more superior stacking patterns with easy formation of CT and FE/CT states and a high charge separation rate. It was found using the AFRA is an effective strategy to enhance end-group stacking, enhancing the borrowing of oscillator strength to promote multiple CT mechanisms in the complexes, explaining the high performance of this OSC device. This work is promising to guide designing an efficient AFRA in the future.

4.
J Colloid Interface Sci ; 656: 116-124, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37984167

RESUMO

In this work, we developed Manganese and Titanium based oxide composites with oxygen defects (MnOx@aTiOy) via plasma processing as anodes of lithium ion batteries. By appropriately adjusting the defect concentration, the ion transport kinetics and electrical conductivity of the electrodes are significantly improved, showing stable capacity retention. Furthermore, the incremental capacity is further activated and long-term stable cycling performance is achieved, with a specific capacity of 829.5 mAh/g at 1 A/g after 2000 cycles. To scrutinize the lithium migration paths and energy barriers in MnO2 and Mn2O3, the density functional theory (DFT) calculations is performed to explore the lithium migration paths and energy barriers. Although the transformation of MnO2 into Mn2O3 through oxygen defects was initially surmised to inhibit Li ions along their standard routes, our results indicate quite the contrary. In fact, the composite's lithium diffusion rate saw a substantial increase. This can be accredited to the pronounced enhancement of conductivity and ion transport efficiency in the amorphous and porous TiOy.

5.
Arch Biochem Biophys ; 745: 109713, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37543352

RESUMO

Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.


Assuntos
Metaloproteinase 9 da Matriz , Tireoidite , Humanos , Biomarcadores , Biologia Computacional , Perfilação da Expressão Gênica
6.
Res Theory Nurs Pract ; 37(3): 386-400, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37591529

RESUMO

Background and Purpose: The main goal of hospice care is to improve the quality of life for people who are at the end-of-life phase. However, investigations on the awareness of hospice care among community-dwelling elderly participants are limited. This work aimed to reveal the awareness status of hospice care and explore the factors influencing the awareness rate among elderly participants. Methods: A questionnaire survey was conducted among individuals aged 60 years and above. Results: A total of 4,969 individuals aged 60 years and above were randomly selected from 48 primary medical institutions in Handan. The awareness rate of hospice care in the baseline survey was 19.3% (n = 959). All included individuals were divided into two groups in accordance with their awareness of hospice care. The awareness of hospice care among participants with low educational level, living alone, and afraid of talking about death was low (p < .05). Implications for Practice: The level of awareness of hospice care among community-dwelling elderly participants is low. The influencing factors included educational level, living status, and fear of talking about death. The community-dwelling elderly participants' awareness of hospice care must be improved. It is recommended that public medical education and training should be enhanced to improve knowledge and awareness of hospice care among community-dwelling elderly residents with low educational level, living alone, and afraid of talking about death.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Idoso , Humanos , Escolaridade , Medo , Vida Independente , Qualidade de Vida , Pessoa de Meia-Idade
7.
Histol Histopathol ; 38(12): 1381-1390, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36537752

RESUMO

Cervical cancer (CC) is one of the most common gynecological malignancies worldwide. Zinc Finger Protein 488 (ZNF488) has been identified as an oncogene in nasopharyngeal carcinoma. However, its biological role and potential mechanism in CC remain to be elucidated. In the present study, upregulation of ZNF488 expression in human CC tissues was found in clinical samples and analyzed in The Cancer Genome Atlas (TCGA) dataset, which was associated with clinical staging and lymph node metastasis. Quantitative real time polymerase chain reaction (PCR) and western blot assays indicated that the expression of ZNF488 was up-regulated in CC cells. Cell colony formation and cell cycle analysis assays suggested that ZNF488 promoted CC cell proliferation and cycle progression. Knockdown of ZNF488 inhibited tumor growth of xenograft tumor mice in vivo, in agreement with the levels of ZNF488 and Ki-67. Moreover, transwell and western assays demonstrated that ZNF488 enhanced CC cell migration and invasion. Additionally, knockdown of ZNF488 also inhibited lung metastasis of CC cells in vivo. Further mechanism analysis implied that ZNF488 promoted the MEK/ERK signaling pathway. ERK inhibitor PD98059 significantly weakened the proliferation and epithelial-mesenchymal transformation (EMT) promotion effect of ZNF488. Collectively, ZNF488 exerts its oncogene function partially through modulating MEK/ERK signaling pathway in CC, indicating that ZNF488 may provide a promising therapeutic target for the treatment of CC.


Assuntos
Neoplasias Nasofaríngeas , Neoplasias do Colo do Útero , Feminino , Humanos , Animais , Camundongos , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Transdução de Sinais , Proliferação de Células/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica
8.
Phys Chem Chem Phys ; 24(43): 26853-26862, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36317503

RESUMO

The emergence and development of radical luminescent materials is a huge breakthrough toward high-performance organic light-emitting diodes (OLEDs) without spin-statistical limits. Herein, we design a series of radicals based on tris(2,4,6-trichlorophenyl)methyl (TTM) by combining skeleton-engineering and periphery-engineering strategies, and present some insights into how different chemical modifications can modulate the chemical stability and luminescence properties of radicals by quantum chemistry methods. Firstly, through the analysis of the geometric structure changes from the lowest doublet excited state (D1) to the doublet ground state (D0) states, the emission energy differences between the BN orientation isomers are explained, and it is revealed that the radical with a smaller dihedral angle difference can more effectively suppress the geometric relaxation of the excited states and bring a higher emission energy. Meanwhile, a comparison of the excited state properties in different radicals can help us to disclose the luminescence behavior, that is, the enhanced luminescent intensity of the radical is caused by the intensity borrowing between the charge transfer (CT) state and the dark locally excited (LE) state. In addition, an efficient algorithm for calculating the internal conversion rate (kIC) is introduced and implemented, and the differences in kIC values between designed radicals are explained. More specifically, the delocalization of hole and electron wave functions can reduce nonadiabatic coupling matrix elements (NACMEs), thus hindering the non-radiative decay process. Finally, the double-regulation of chemical stability and luminescence properties was realized through the synergistic effect of skeleton-engineering and periphery-engineering, and to screen the excellent doublet emitter (BN-41-MPTTM) theoretically.

9.
RSC Adv ; 12(29): 18466-18474, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35799939

RESUMO

Organic and inorganic materials have their own advantages and limitations, and new properties can be displayed in organic-inorganic hybrid materials by uniformly combining the two categories of materials at small scale. The objective of this study is to hybridize activated carbon (AC) with ferrocene to obtain a new material, ferrocene/AC, as the cathode for Zn-ion hybrid supercapacitors (ZHSCs). The optimized ferrocene/AC material owns fast charge transfer kinetics and can obtain pseudo-capacitance through redox reaction. Due to the introduction of ferrocene/AC, the ZHSCs exhibit remarkable electrochemical performances relative to that using ferrocene cathode, including high discharge specific capacity of 125.1 F g-1, high energy density (up to 44.8 Wh kg-1 at 0.1 A g-1) and large power density (up to 1839 W kg-1 at 5 A g-1). Meanwhile, the capacity retention rate remains 73.8% after 10 000 charge and discharge cycles. In particular, this cathode material can be used at low temperatures (up to -30 °C) with 60% capacity remained, which enlarges the application temperature range of ZHSCs. These results of this study can help understand new properties of organic-inorganic hybrid materials.

10.
J Colloid Interface Sci ; 619: 198-206, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35395538

RESUMO

For the high theoretical specific capacity and low redox potential, lithium (Li) metal is considered as one of the most promising anode materials for the next generation of rechargeable batteries. In this work, we have developed an effective and accurate plasma strategy to regulate the surface morphology and functional groups of three-dimensional nitrogen-containing carbon foam (CF) to control the Li nucleation and growth. Besides the rougher surface induced by oxygen (O2) plasma, the conversion of carbon-nitrogen chemical bond (CN), namely, change from the quaternary N to pyrrolic/pyridinic N was realized by the nitrogen (N2) plasma. This chemical regulation of nitrogen boosts the lithiophilicity of carbon foam, which is evidenced by lower overpotential obtained from the experiment and higher binding energy for Li ions (Li+) calculated by density functional theory (-1.43, -1.85, -2.41 and -2.45 eV for the amorphous C-, C-quaternary N-, C-pyrrolic N- and C-pyridinic N-, respectively). The electrochemical performance of the half cells and full cells based on this plasma regulated carbon foam collectors also proved the prominent effectiveness of this plasma strategy on guiding the uniform dispersion of Li+ and thus inducing the homogeneous Li nucleation, as well as suppressing the growth of Li dendrites.

11.
J Colloid Interface Sci ; 616: 246-252, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35203037

RESUMO

To tackle the intrinsic inferior conductivity of the sodium ion batteries (SIBs) cathode Na3V2(PO4)3, transitional metal cation doping, and carbon frame design are employed for NASICON structural modification. Herein, a hard carbon skeleton Na3+xV2-xZnx(PO4)3 NASICON structure is proposed resorting to the combination of flimsy hard carbon slices coating and Zn2+ doping along with the introduction of spare Na+. The structural distortion caused by the insertion of Zn2+ and Na+ broadens the transfer channels and increases diffusion routes for Na+. At the same time, the anchoring effect for Na3+xV2-xZnx(PO4)3 nanoparticles brought by external hard carbon layers and pillar effect aroused by Zn2+ provide a stable and firm skeleton, which is conducive to structural stability and reversibility at high current density. Among various doping concentrations, Na3.03V1.97Zn0.03(PO4)3 performs a significantly enhanced rate performance with a reversible capacity up to 60 mAh·g-1 (40C) and ultra-long cycle life of 1000 cycles with a capacity retention of 92.6% at 5C.

12.
ACS Appl Mater Interfaces ; 13(45): 53996-54004, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34732046

RESUMO

By compensating the irreversible loss of lithium ions during the first cycle, prelithiations can solve the issue of insufficient initial Coulombic efficiency for various anodes. Recently, the chemical prelithiation using organolithium compounds has attracted increasing attention because of its uniform and fast reaction, safety, and easily adjustable degree of prelithiation. However, the nature and activity of organolithium involved in chemical prelithiations have not been deeply explored yet. Here, by monitoring the electrical conductivity change in the lithiation solution in the duration of its formation, we have demonstrated the essential role of lithium radical anions for chemical prelithiation and compared the prelithiation activity of dissociated species and aggregates of lithium radical anions. The mechanistic understanding of the nature of the lithiation solution leads to controllable chemical prelithiation, as demonstrated in full cells of prelithiated hard carbon and LiFePO4.

13.
J Colloid Interface Sci ; 599: 819-827, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33989934

RESUMO

Lithium metal is the most promising anode materials for the next generation lithium ion battery. However, the electrode polarization leads to the formation of dendrites and "dead lithium", which degrades the performance of lithium metal batteries and induce a variety of security risk. The electrode polarization and lithium dendrites can be suppressed by lithium metal composite electrode. Herein, a simple and effective strategy is adopted to construct nickel and lithium bimetallic composite (NiLi-BC) electrode by a double roll process. The Ni framework inside the electrode can optimize the electric field and Li+ distribution at the electrode/electrolyte interface and induce the uniform lithium deposition. As a result, the NiLi-BC exhibits a lithium dendrite-free feature and stable cycling performance under a low overpotential (<15 mV throughout 2180 h at 1 mA cm-2 with a deposition capacity of 1 mAh cm-2). Moreover, the assembled NiLi-BC||LiFePO4 coin cell and pouch cell exhibit improved capability and stable cycling performance. Finally, the in-situ optical microscopy and in-situ Raman spectroscopy are employed to obtain a better understanding of the interfacial structure and chemical component during the Li plating and striping processes. The scheme of this study of the NiLi electrode has great practical application value.

14.
J Colloid Interface Sci ; 570: 11-19, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32135264

RESUMO

Amine-functionalized graphitic carbon nitride (g-C3N4) decorated with Au nanoparticles (CN/Au) was prepared by N2 plasma treatment of g-C3N4 powders impregnated with HAuCl4·3H2O. Well-dispersed Au nanoparticles with a small particle size were deposited on g-C3N4 nanosheets. In addition, the amino group was introduced into the CN/Au system. Without the addition of cocatalyst and sacrificial agent, CN/Au exhibited enhanced photocatalytic activity for CO2 reduction under visible-light irradiation. CO and CH4 evolution rates of CN/Au reached 28.3 and 1.3 µmol·h-1·g-1, which were 7.6 and 2.6 times higher than those of pristine g-C3N4 (CN-0), respectively. The enhanced activity can be explained by these factors. (1) The introduced amino group improved the adsorption capacity of CN/Au for CO2; (2) the hot electrons generated by Au nanoparticles activated the surrounding electrons through energy transfer and caused local temperature to rise, increasing the efficiency of the photoreduction reaction of CO2; (3) the Schottky junction between Au and g-C3N4 promoted the migration of electrons from g-C3N4 to Au nanoparticles, suppressing the recombination of the carriers. Time-of-flight secondary ion mass spectrometry confirmed the introduction of amino groups, and solid-state 13C nuclear magnetic resonance spectra provided a support for inferring the position of the amino group.

15.
J Colloid Interface Sci ; 556: 376-385, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470352

RESUMO

Strong demand for affordable clean energy to support applications ranging from conventional energy supply to space propulsion places spotlight on advanced energy generation using photovoltaic and wind power. Yet, the intermittent nature of solar and wind sources drives the search for energy storage solutions that would permit the needed level of resilience and support further growth in the use of renewable sources of power. Hydrogen generation using sunlight is a promising pathway to decouple demand from supply. Herein, we show how exposure to reactive Ar-H2, Ar-H2-N2, and Ar-O2 plasma environments can notably enhance surface properties of photocatalytic TiO2 nanosheets used in advanced energy generation systems. Treatment using Ar-H2 plasmas produced highly hydrogenated, surface-disordered TiO2 nanosheets with oxygen vacancies, whereas exposure to Ar-H2-N2 plasmas resulted in N doping. Surprisingly, Ar-O2 plasma treatment did not change surface properties of TiO2. Optical emission spectroscopy was used to monitor transient species to further understand surface modification in plasma. Direct measurements demonstrated that among thus-produced samples, hydrogenated TiO2 nanosheets exhibit the highest photocatalytic H2-generation activity under visible-light irradiation, which is also greater than the activity of pure, untreated nanosheets. The mechanism of enhancing the visible-light photocatalytic H2-generation activity on hydrogenated TiO2 nanosheets is also proposed. The level of surface disorder and oxygen vacancies plays an important role in enhancing visible-light absorption and reducing the recombination of photogenerated electrons and holes.

16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(6): 678-684, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29968244

RESUMO

OBJECTIVE: To determine the detection rate and distribution characteristics of colorectal adenomas in Ningbo area of China, and to identify the risk factors for colorectal adenoma, in order to provide reference for colorectal cancer screening. METHODS: A cross-sectional study was performed among 8660 subjects undergoing colonoscopy in the Ningbo No.2 Hospital between January and December 2016, using a questionnaire, including demographic data (age, gender, height and weight), history of diseases (diabetes, hypertension, hyperlipidemia, and family history of malignant neoplasm), lifestyle (smoking, alcohol, dietary bias on red meat, dietary bias on fruit and vegetables, dietary frequency of pickled food and physical activities), and intestinal early warning symptoms. All colonoscopically detected polyps were removed for histological examination. Polyps were histologically divided into non-adenomatous (hyperplastic polyps and inflammatory polyps) and adenomatous polyps (tubular, villous, tubulovillous and serrated adenomas). Pathologic features were analyzed according to anatomical site. Multivariate logistic regression analysis was used to identify the risk factors for colorectal adenoma. RESULTS: A total of 7077 subjects who received colonoscopic examination and completed the questionnaire survey were enrolled in this study. There were 3633 males and 3444 females with a median age of 53 (ranged 17 to 83) years. Adenoma detection rate was 15.6% (1103/7077) in all cases, 21.0%(762/3633) for males, and 9.9%(341/3444) for females(P=0.000). Detection rate of 6.2%(29/469) was recorded in individuals aged less than 30 years, 8.0%(87/1086) in those from 30 to 39 years, 12.1%(148/1222) in those from 40 to 49 years, 16.8%(272/1623) in those from 50 to 59 years, 20.4%(326/1601) in those from 60 to 69 years, and 22.4%(241/1076) in those ≥70 years. The detection rate increased according to age(P=0.000). A total of 1521 adenomas were detected in 1103 cases, including 1455 tubular adenomas, 33 tubulovillous adenomas, 9 villous adenomas and 24 serrated adenomas. Among 1521 adenomas, 44.1%(n=671) located in the right hemicolon, 39.0%(n=593) in the left hemicolon, and 16.9%(n=257) in the rectum. Significantly larger number of serrated adenomas and advanced adenomas (advanced adenoma was defined as any adenoma with high-grade intraepithelial neoplasia, diameter ≥10 mm or with villous component) was observed in the right hemicolon compared to left hemicolon and rectum [serrated adenomas: 2.5%(17/671) vs. 0.8% (5/593) and 0.8% (2/257), P=0.029; advanced adenoma: 9.2% (62/671) vs. 5.2% (31/953) and 6.6% (17/257), P=0.021]. Multivariate analysis showed that malely (P=0.003), elderly (P=0.000), obesity (P=0.014), smoking (P=0.001), alcohol (P=0.032), and family history of malignancy (P=0.000) were independent risk factors of colorectal adenoma. CONCLUSIONS: In view of a higher detection rate of colorectal adenoma in population aged 40 to 49 years especially in male individuals, the starting age of colonoscopy screening may be advanced to 40 years old. People with family history of malignancy, obesity, and habit of smoking or drinking should be regarded as important subjects for colonoscopy screening. During colonoscopy screening, special emphasis should be given to right hemicolon.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Adenoma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Pólipos do Colo , Colonoscopia , Neoplasias Colorretais/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
17.
Sci Rep ; 6: 25596, 2016 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-27157475

RESUMO

Missense mutations of fibroblast growth factor receptor 3 (FGFR3) occur in up to 80% of low-grade papillary urothelial carcinoma of the bladder (LGP-UCB) suggesting that these mutations are tumor drivers, although direct experimental evidence is lacking. Here we show that forced expression of FGFR3b-S249C, the most prevalent FGFR3 mutation in human LGP-UCB, in cultured urothelial cells resulted in slightly reduced surface translocation than wild-type FGFR3b, but nearly twice as much proliferation. When we expressed a mouse equivalent of this mutant (FGFR3b-S243C) in urothelia of adult transgenic mice in a tissue-specific and inducible manner, we observed significant activation of AKT and MAPK pathways. This was, however, not accompanied by urothelial proliferation or tumorigenesis over 12 months, due to compensatory tumor barriers in p16-pRB and p19-p53-p21 axes. Indeed, expressing FGFR3b-S249C in cultured human urothelial cells expressing SV40T, which functionally inactivates pRB/p53, markedly accelerated proliferation and cell-cycle progression. Furthermore, expressing FGFR3b-S243C in transgenic mouse urothelium expressing SV40T converted carcinoma-in-situ to high-grade papillary urothelial carcinoma. Together, our study provides new experimental evidence indicating that the FGFR3 mutations have very limited urothelial tumorigenicity and that these mutations must collaborate with other genetic events to drive urothelial tumorigenesis.


Assuntos
Carcinogênese/genética , Carcinoma Papilar/genética , Mutação/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/química , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Proteína do Retinoblastoma/deficiência , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/genética , Animais , Carcinogênese/patologia , Carcinoma Papilar/patologia , Ciclo Celular , Proliferação de Células , Humanos , Camundongos , Camundongos Transgênicos , Gradação de Tumores , Especificidade de Órgãos , Fosforilação , Estrutura Secundária de Proteína , Transdução de Sinais , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
18.
Oncotarget ; 7(17): 23947-60, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-26992222

RESUMO

The conversion of precancerous lesions to full-fledged cancers requires the affected cells to surpass certain rate-limiting steps. We recently showed that activation of HRAS proto-oncogene in urothelial cells of transgenic mice causes simple urothelial hyperplasia (SUH) which is persistent and whose transition to low-grade papillary urothelial carcinoma (UC) must undergo nodular urothelial hyperplasia (NUH). We hypothesized that NUH, which has acquired fibrovascular cores, plays critical roles in mesenchymal-to-epithelial signaling, breaching the barriers of urothelial tumor initiation. Using proteomics involving two-dimensional gel electrophoresis, immunoblotting with pan-phosphotyrosine antibody and MALDI-mass spectrometry, we identified isoform 2 of pyruvate kinase (PKM2) as the major tyrosine-phosphorylated protein switched on during NUH. We extended this finding using specimens from transgenic mice, human UC and UC cell lines, establishing that PKM2, but not its spliced variant PKM1, was over-expressed in low-grade and, more prominently, high-grade UC. In muscle-invasive UC, PKM2 was co-localized with cytokeratins 5 and 14, UC progenitor markers. Specific inhibition of PKM2 by siRNA or shRNA suppressed UC cell proliferation via increased apoptosis, autophagy and unfolded protein response. These results strongly suggest that PKM2 plays an important role in the genesis of low-grade non-invasive and high-grade invasive urothelial carcinomas.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/patologia , Proteínas de Transporte/metabolismo , Transformação Celular Neoplásica/patologia , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Neoplasias da Bexiga Urinária/patologia , Uroplaquina II/fisiologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Proteínas de Transporte/genética , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Invasividade Neoplásica , Isoformas de Proteínas , Proto-Oncogene Mas , Hormônios Tireóideos/genética , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
19.
Dalton Trans ; 44(37): 16251-5, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26343777

RESUMO

The reaction pathway as well as the mechanism of the solid state reaction between MgH2 and AlCl3 has been a mystery so far. Based on SEM, TEM and NMR (Nuclear Magnetic Resonance) analyses, an amorphous intermediate (AlH6)n was preferentially formed and recrystallized as a γ phase at the final stage of the reaction. As a novel finding, this research provides a deep insight into the process and mechanism of this mechanically activated reaction.

20.
Oncol Lett ; 9(6): 2687-2693, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26137129

RESUMO

Breast cancer occurring following injection with polyacrylamide hydrogel (PAMG) for augmentation mammaplasty is rare. The present study reports the case of a 43-year-old female presenting with bilateral breast cancer 10 years after augmentation mammaplasty with PAMG injection and no family history of breast cancer. A 5.5×6.0-cm mass in the right breast with multiple intumescent axillary lymph nodes was revealed and a palpable mass of ~1.0 cm was identified in the outer upper quadrant of the left breast. Multiple smaller nodules were observed in the pulmonary field. Pathological examination revealed invasive lobular grade II carcinoma in both breasts with ER(+++), PR(+++), C-erbB2(-), Top-2(+), in the right breast and ER(++), PR(++), c-erb-B2(-), Top-2(+) in the left. Preoperative chemotherapy, modified radical bilateral mastectomy with axillary clearance, postoperative chemotherapy, and an oophorectomy were conducted, followed by treatment with Arimedex® until the present date A number of valuable insights can be garnered from this case. First, close follow-up is required for female patients who receive an injection of PAMG for augmentation mammaplasty in order to achieve an early diagnosis and to intervene in any incidences of breast cancer. Second, the differential diagnosis of dual primary carcinoma versus metastatic breast cancer is important and may be aided by the use of molecular technology. Third, it remains difficult to determine gene expression values for the prediction of chemotherapy sensitivity. Thus, discrimination between primary and secondary carcinomas is the principle barrier for identifying an appropriate treatment strategy when a patient is diagnosed with bilateral breast cancer.

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