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1.
Proc Natl Acad Sci U S A ; 121(10): e2319136121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38408257

RESUMO

Single-atom catalysts (SACs) with maximized metal atom utilization and intriguing properties are of utmost importance for energy conversion and catalysis science. However, the lack of a straightforward and scalable synthesis strategy of SACs on diverse support materials remains the bottleneck for their large-scale industrial applications. Herein, we report a general approach to directly transform bulk metals into single atoms through the precise control of the electrodissolution-electrodeposition kinetics in ionic liquids and demonstrate the successful applicability of up to twenty different monometallic SACs and one multimetallic SAC with five distinct elements. As a case study, the atomically dispersed Pt was electrodeposited onto Ni3N/Ni-Co-graphene oxide heterostructures in varied scales (up to 5 cm × 5 cm) as bifunctional catalysts with the electronic metal-support interaction, which exhibits low overpotentials at 10 mA cm-2 for hydrogen evolution reaction (HER, 30 mV) and oxygen evolution reaction (OER, 263 mV) with a relatively low Pt loading (0.98 wt%). This work provides a simple and practical route for large-scale synthesis of various SACs with favorable catalytic properties on diversified supports using alternative ionic liquids and inspires the methodology on precise synthesis of multimetallic single-atom materials with tunable compositions.

2.
Chem Soc Rev ; 53(13): 6860-6916, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38833171

RESUMO

Photoelectrochemical (PEC) water splitting provides a scalable and integrated platform to harness renewable solar energy for green hydrogen production. The practical implementation of PEC systems hinges on addressing three critical challenges: enhancing energy conversion efficiency, ensuring long-term stability, and achieving economic viability. Metal-insulator-semiconductor (MIS) heterojunction photoelectrodes have gained significant attention over the last decade for their ability to efficiently segregate photogenerated carriers and mitigate corrosion-induced semiconductor degradation. This review discusses the structural composition and interfacial intricacies of MIS photoelectrodes tailored for PEC water splitting. The application of MIS heterostructures across various semiconductor light-absorbing layers, including traditional photovoltaic-grade semiconductors, metal oxides, and emerging materials, is presented first. Subsequently, this review elucidates the reaction mechanisms and respective merits of vacuum and non-vacuum deposition techniques in the fabrication of the insulator layers. In the context of the metal layers, this review extends beyond the conventional scope, not only by introducing metal-based cocatalysts, but also by exploring the latest advancements in molecular and single-atom catalysts integrated within MIS photoelectrodes. Furthermore, a systematic summary of carrier transfer mechanisms and interface design principles of MIS photoelectrodes is presented, which are pivotal for optimizing energy band alignment and enhancing solar-to-chemical conversion efficiency within the PEC system. Finally, this review explores innovative derivative configurations of MIS photoelectrodes, including back-illuminated MIS photoelectrodes, inverted MIS photoelectrodes, tandem MIS photoelectrodes, and monolithically integrated wireless MIS photoelectrodes. These novel architectures address the limitations of traditional MIS structures by effectively coupling different functional modules, minimizing optical and ohmic losses, and mitigating recombination losses.

3.
Dig Dis Sci ; 69(4): 1263-1273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451429

RESUMO

BACKGROUND: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Estudos Retrospectivos , Estudos de Coortes , Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Pancreáticas/patologia
4.
J Chem Phys ; 160(4)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38270240

RESUMO

Due to the limitation of inherent ultra-high electron concentration, the electrical properties of In2O3 resemble those of conductors rather than semiconductors prior to special treatment. In this study, the effect of various annealing treatments on the microstructure, optical properties, and oxygen vacancies of the films and transistors is systematically investigated. Our finding reveals a progressive crystallization trend in the films with increasing annealing temperature. In addition, a higher annealing temperature is also associated with the reduction in the concentration of oxygen vacancies, as well as an elevation in both optical transmittance and optical bandgap. Furthermore, with the implementation of annealing process, the devices gradually transform from no pronounced gate control to exhibit with excellent gate control and electrical performances. The atomic layer deposited Hf-doped In2O3 thin film transistor annealed at 250 °C exhibits optimal electrical properties, with a field-effect mobility of 18.65 cm2 V-1 s-1, a subthreshold swing of 0.18 V/dec, and an Ion/Ioff ratio of 2.76 × 106. The results indicate that the impact of varying annealing temperatures can be attributed to the modulation of oxygen vacancies within the films. This work serves as a complementary study for the existing post-treatment of oxide films and provides a reliable reference for utilization of the annealing process in practical applications.

5.
Drug Dev Ind Pharm ; : 1-13, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39259031

RESUMO

OBJECTIVE: This research aims to improve the bioavailability and anti-hepatocellular carcinoma (HCC) efficacy of Ginsenoside Rg3 by modification with poly (lactic acid hydroxyacetic acid)-poly(ethylene glycol) (PLGA-PEG). METHODS: PLGA-PEG-Rg3 was obtained by emulsification and evaluated it physiochemical characterization by FTIR, SEM, laser particle-size analyzer and HPLC. The effect of the PLGA-PEG-Rg3 and Rg3 on HepG2 cells was compared in vitro studies, including cell proliferation, transwell and a series of apoptosis detection, and in-situ HCC model. RESULTS: The PLGA-PEG-Rg3 were 122 nm in size and 0.112 in polydispersity index with sustained release profile in vitro. Compared to Rg3, PLGA-PEG-Rg3 was more effective in suppressing HepG2 growth and inducing apoptosis by the mitochondrial apoptosis pathway in vitro. And PLGA-PEG modification enhanced the liver-targeting ability and drug circulation time of Rg3 in vivo, resulting in PLGA-PEG-Rg3 possessing superior performance in inhibiting tumor growth and prolonging the survival time of tumor-bearing mice than Rg3. CONCLUSIONS: Overall, these results showed PLGA-PEG-Rg3 enhanced the anti-tumor effect of Rg3 in HCC.

6.
Angew Chem Int Ed Engl ; 63(36): e202408996, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38873975

RESUMO

Two-dimensional Ti3C2Tx MXene materials, with metal-like conductivities and versatile terminals, have been considered to be promising surface modification materials for Zn-metal-based aqueous batteries (ZABs). However, the oxygen-rich and hybridized terminations caused by conventional methods limit their advantages in inhibiting zinc dendrite growth and reducing corrosion-related side reactions. Herein, -O-depleted, -Cl-terminated Ti3C2Tx was precisely fabricated by the molten salt electrochemical etching of Ti3AlC2, and controlled in situ terminal replacement from -Cl to unitary -S or -Se was achieved. The as-prepared -O-depleted and unitary-terminal Ti3C2Tx as Zn anode coatings provided excellent hydrophobicity and enriched zinc-ionophilic sites, facilitating Zn2+ horizontal transport for homogeneous deposition and effectively suppressing water-induced side reactions. The as-assembled Ti3C2Sx@Zn symmetric cell achieved a cycle life of up to 4200 h at a current density and areal capacity of 2 mA cm-2 and 1 mAh cm-2, respectively, with an impressive cumulative capacity of up to 7.25 Ah cm-2 at 5 mA cm-2//2 mAh cm-2. These findings provide an effective electrochemical strategy for tailoring -O-depleted and unitary Ti3C2Tx surface terminals and advancing the understanding of the role of specific Ti3C2Tx surface chemistry in regulating the plating/stripping behaviors of metal ions.

7.
Angew Chem Int Ed Engl ; 63(23): e202405315, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38588049

RESUMO

The surface and interface chemistry are critical for controlling the properties of two-dimensional transition metal carbides and nitrides (MXenes). Numerous efforts have been devoted to the functionalization of MXenes with small inorganic ligands; however, few etching methods have been reported on the direct bonding of organic groups to MXene surfaces. In this work, we demonstrated an efficient and rapid strategy for the direct synthesis of 2D Ti3C2Tx MXene nanosheets with organic terminal groups in an organic Lewis acid (trifluoromethanesulfonic acid) solvent, without introducing additional intercalations. The dissolution of aluminum and the subsequent in situ introduction of trifluoromethanesulfonic acid resulted in the extraction of Ti3C2Tx MXene (T=CF3SO3 -) (denoted as CF3SO3H-Ti3C2Tx) flakes with sizes reaching 15 µm and high productivity (over 70 %) of monolayers or few layers. More importantly, the large CF3SO3H-Ti3C2Tx MXene nanosheets had high colloidal stability, making them promising as efficient electrocatalysts for the hydrogen evolution reaction.

8.
J Chem Phys ; 159(17)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37916595

RESUMO

The relocation of peripheral transistors from the front-end-of-line (FEOL) to the back-end-of-line (BEOL) in fabrication processes is of significant interest, as it allows for the introduction of novel functionality in the BEOL while providing additional die area in the FEOL. Oxide semiconductor-based transistors serve as attractive candidates for BEOL. Within these categories, In2O3 material is particularly notable; nonetheless, the excessive intrinsic carrier concentration poses a limitation on its broader applicability. Herein, the deposition of Hf-doped In2O3 (IHO) films via atomic layer deposition for the first time demonstrates an effective method for tuning the intrinsic carrier concentration, where the doping concentration plays a critical role in determine the properties of IHO films and all-oxide structure transistors with Au-free process. The all-oxide transistors with In2O3: HfO2 ratio of 10:1 exhibited optimal electrical properties, including high on-current with 249 µA, field-effect mobility of 13.4 cm2 V-1 s-1, and on/off ratio exceeding 106, and also achieved excellent stability under long time positive bias stress and negative bias stress. These findings suggest that this study not only introduces a straightforward and efficient approach to improve the properties of In2O3 material and transistors, but as well paves the way for development of all-oxide transistors and their integration into BEOL technology.

9.
Angew Chem Int Ed Engl ; 62(43): e202311336, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37670537

RESUMO

Rational design and engineering of high-performance molecular sieve membranes towards C2 H4 /C2 H6 and flue gas separations remain a grand challenge to date. In this study, through combining pore micro-environment engineering with meso-structure manipulation, highly c-oriented sub-100 nm-thick Cu@NH2 -MIL-125 membrane was successfully prepared. Coordinatively unsaturated Cu ions immobilized in the NH2 -MIL-125 framework enabled high-affinity π-complexation interactions with C2 H4 , resulting in an C2 H4 /C2 H6 selectivity approaching 13.6, which was 9.4 times higher than that of pristine NH2 -MIL-125 membrane; moreover, benefiting from π-complexation interactions between CO2 and Cu(I) sites, our membrane displayed superior CO2 /N2 selectivity of 43.2 with CO2 permeance of 696 GPU, which far surpassed the benchmark of other pure MOF membranes. The above multi-scale structure optimization strategy is anticipated to present opportunities for significantly enhancing the separation performance of diverse molecular sieve membranes.

10.
BMC Neurol ; 22(1): 130, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35382802

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) affects the occurrence and prognosis of acute ischemic stroke (AIS). However, the impact of diabetes on thrombus characteristics is unclear. The relationship between the composition and ultrastructure of clots and DM with admission hyperglycemia was investigated. METHODS: Consecutive patients with AIS who underwent endovascular thrombus retrieval between June 2017 and May 2021 were recruited. The thrombus composition and ultrastructure were evaluated using Martius scarlet blue stain and scanning electron microscopy. Clot perviousness was evaluated via thrombus attenuation increase on computed tomography angiography (CTA) versus non-contrast CT. Patients with admission hyperglycemia DM (ahDM) and those without DM (nonDM) were compared in terms of thrombus composition, ultrastructure, and perviousness. RESULTS: On admission, higher NIHSS scores (17 vs. 12, respectively, p = 0.015) was evident in ahDM patients. After the 90-day follow-up, the rates of excellent outcomes (mRS 0-1) were lower in patients with ahDM (16.6%, p = 0.038), but functional independence (mRS 0-2) and handicapped (mRS 3-5) were comparable between patients with ahDM and nonDM. The outcome of mortality was higher in patients with ahDM (33.3%, p = 0.046) than in nonDM patients. Clots in patients with ahDM had more fibrin (39.4% vs. 25.0%, respectively, p = 0.007), fewer erythrocyte components (21.2% vs. 41.5%, respectively, p = 0.043), equivalent platelet fraction (27.7% vs. 24.6%, respectively, p = 0.587), and higher WBC counts (4.6% vs. 3.3%, respectively, p = 0.004) than in nonDM patients. The percentage of polyhedral erythrocytes in thrombi was significantly higher in ahDM patients than in nonDM patients (68.9% vs. 45.6%, respectively, p = 0.007). The proportion of pervious clots was higher in patients nonDM than in patients with ahDM (82.61% vs. 40%, respectively, p = 0.026). CONCLUSION: Patients with ahDM presented with greater stroke severity on admission and poorer functional outcomes after 3 months. Clots in patients with ahDM had more fibrin, leucocytes, and fewer erythrocyte components than in patients nonDM. The content of polyhedral erythrocytes and impervious clots proportion were significantly higher in thrombi of patients with AIS and ahDM. Further research is required to validate these findings.


Assuntos
Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Hiperglicemia , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Hiperglicemia/complicações , Acidente Vascular Cerebral/etiologia , Trombectomia/métodos , Trombose/complicações , Trombose/patologia
11.
J Pineal Res ; 71(4): e12767, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34533844

RESUMO

Metabolic remodeling is now widely recognized as a hallmark of cancer, yet its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. In this study, metabolomic analysis of melatonin-treated HNSCC cell lines revealed that exogenous melatonin inhibited many important metabolic pathways including folate cycle in HNSCC cells. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), a metabolic enzyme of the folate cycle regulating the production of formate, was identified as a downstream target of melatonin. MTHFD1L was found to be markedly upregulated in HNSCC, and MTHFD1L overexpression was significantly associated with unfavorable clinical outcome of HNSCC patients. In addition, MTHFD1L promoted HNSCC progression in vitro and in vivo and reversed the oncostatic effects of exogenous melatonin. More importantly, the malignant phenotypes suppressed by knockdown of MTHFD1L or exogenous melatonin could be partially rescued by formate. Furthermore, we found that melatonin inhibited the expression of MTHFD1L in HNSCC cells through the downregulation of cyclic AMP-responsive element-binding protein 1 (CREB1) phosphorylation. Lastly, this novel regulatory axis of melatonin-p-CREB1-MTHFD1L-formate was also verified in HNSCC tissues. Collectively, our findings have demonstrated that MTHFD1L-formate axis promotes HNSCC progression and melatonin inhibits HNSCC progression through CREB1-mediated downregulation of MTHFD1L and formate. These findings have revealed new metabolic mechanisms in HNSCC and may provide novel insights on the therapeutic intervention of HNSCC.


Assuntos
Formiato-Tetra-Hidrofolato Ligase , Neoplasias de Cabeça e Pescoço , Melatonina , Aminoidrolases/genética , Aminoidrolases/metabolismo , Linhagem Celular Tumoral , Formiato-Tetra-Hidrofolato Ligase/genética , Formiato-Tetra-Hidrofolato Ligase/metabolismo , Formiatos , Regulação Neoplásica da Expressão Gênica , Humanos , Melatonina/farmacologia , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
12.
BMC Neurol ; 21(1): 398, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645398

RESUMO

BACKGROUND: The significance of carotid webs (CaWs) in ischemic stroke is becoming acknowledged. Histological features of clot composition in situ and secondary cerebrovascular embolized thrombi caused by CaW have not been described concurrently. Understanding clots' histological composition is essential for understanding the pathophysiology of clot formation in CaW. CASE PRESENTATION: A 50-year-old male patient with acute ischemic stroke, which was believed to be caused by ipsilateral CaW, was admitted to the hospital. Mechanical thrombectomy was used to retrieve thromboemboli from the middle cerebral artery. One month thereafter, the patient underwent carotid endarterectomy, and in situ CaW thrombi were retrieved. Histological analysis by hematoxylin and eosin staining revealed that histopathologic embolized thrombi appeared as typical mixed thrombi, 46.03% fibrin/platelet ratio, 48.12% RBCs, and 5.85% white blood cells. In situ thrombi had a higher fibrin/platelet ratio (68.0%), fewer RBCs (17.2%), and 14.8% white blood cells. CONCLUSION: The histopathology of large vessel occlusion stroke embolized thrombi by CaW is similar to that of other stroke etiologies. However, the clot composition of embolized thrombi significantly differs from that of in situ thrombi. CaW's in situ thrombi showed predominantly fibrin, and embolized thrombi had equivalent contents of red blood cells and fibrin/platelets. Histopathological differences between in situ and embolized thrombi suggest new research directions for the etiology of embolization. Further studies are required to confirm these results.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Trombose , Fibrina , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/terapia , Trombectomia , Trombose/etiologia
13.
Adv Exp Med Biol ; 1280: 149-159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791980

RESUMO

Ion chromatography (IC) represents an important technique for separation of charged and polar compounds. Traditionally, IC is often used for the analysis of small inorganic ions. Due to the development of eluent suppression technology that allows continuous online desalting and conversion of high-salt eluents into pure water, IC has been coupled with mass spectrometry (MS) for the analysis of more diverse range of anionic and cationic analytes. Recent studies have demonstrated that IC-MS is a powerful technique with exquisite detection sensitivity, high reproducibility, and quantitative capability for metabolomic analysis. In this chapter, we provide a brief overview of IC principles and IC-MS for metabolomic analysis.


Assuntos
Cromatografia , Metabolômica , Íons , Espectrometria de Massas , Reprodutibilidade dos Testes
14.
Adv Exp Med Biol ; 1280: 231-241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791986

RESUMO

Although normal cells depend on exogenous lipids to function and survive, excessive amount of body fat has been associated with increased risk for certain human cancers. Cancer cells can redirect metabolic pathways to meet energy demands through the regulation of fatty acid metabolism. The importance of de novo fatty acid synthesis and fatty acid oxidation in cancer cells suggests fatty acid metabolism may be targeted for anticancer treatment through the use of pharmacological blockade to limit cell proliferation, growth, and transformation. However, our current knowledge about fatty acid metabolism in cancer cells remains limited, and the investigations of such processes and related pathways are certainly warranted to reveal the clinical relevance of fatty acid metabolism in cancer diagnosis and therapy.


Assuntos
Ácidos Graxos , Neoplasias , Proliferação de Células , Metabolismo Energético , Humanos , Metabolismo dos Lipídeos , Lipídeos
15.
Angew Chem Int Ed Engl ; 60(26): 14394-14398, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33856709

RESUMO

We have developed a generalizable strategy to quantify the effect of surface barriers on zeolite catalysis. Isomerization of n-pentane, catalyzed by Pt/Beta, is taken as a model reaction system. Firstly, the surface modification by chemical liquid deposition of SiO2 was carried out to control the surface barriers on zeolite Beta crystals. The deposition of SiO2 leads to a very slight change in the physical properties of Beta crystals, but an obvious reduction in Brønsted acid sites. Diffusion measurements by the zero-length column (ZLC) method show that the apparent diffusivity of n-pentane can be more than doubled after SiO2 deposition, indicating that the surface barriers have been weakened. Catalytic performance was tested in a fixed-bed reactor, showing that the apparent catalytic activity improved by 51-131 % after SiO2 deposition. These results provide direct proof that reducing surface barriers can be an effective route to improve zeolite catalyst performance deteriorated by transport limitations.

16.
J Cell Mol Med ; 24(16): 8998-9011, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32579303

RESUMO

Farnesyltransferase (FTase) is an important enzyme that catalyses the modification of protein isoprene downstream of the mevalonate pathway. Previous studies have shown that the tissue of the heart in the suprarenal abdominal aortic coarctation (AAC) group showed overexpression of FTaseß (FNTB) and the activation of the downstream protein Ras was enhanced. FTase inhibitor (FTI) can alleviate myocardial fibrosis and partly improve cardiac remodelling in spontaneously hypertensive rats. However, the exact role and mechanism of FTase in myocardial hypertrophy and remodelling are not fully understood. Here, we used recombinant adenovirus to transfect neonatal rat ventricular cardiomyocytes to study the effect of FNTB overexpression on myocardial remodelling and explore potential mechanisms. The results showed that overexpression of FNTB induces neonatal rat ventricular myocyte hypertrophy and reduces the survival rate of cardiomyocytes. FNTB overexpression induced a decrease in mitochondrial membrane potential and increased apoptosis in cardiomyocytes. FNTB overexpression also promotes autophagosome formation and the accumulation of autophagy substrate protein, LC3II. Transmission electron microscopy (TEM) and mCherry-GFP tandem fluorescent-tagged LC3 (tfLC3) showed that FNTB overexpression can activate autophagy flux by enhancing autophagosome conversion to autophagolysosome. Overactivated autophagy flux can be blocked by bafilomycin A1. In addition, salirasib (a Ras farnesylcysteine mimetic) can alleviate the hypertrophic phenotype of cardiomyocytes and inhibit the up-regulation of apoptosis and autophagy flux induced by FNTB overexpression. These results suggest that FTase may have a potential role in future treatment strategies to limit the adverse consequences of cardiac hypertrophy, cardiac dysfunction and heart failure.


Assuntos
Apoptose/fisiologia , Morte Celular Autofágica/fisiologia , Cardiomegalia/metabolismo , Farnesiltranstransferase/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas ras/metabolismo , Animais , Autofagossomos/metabolismo , Autofagossomos/patologia , Autofagia/fisiologia , Cardiomegalia/patologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Potencial da Membrana Mitocondrial/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Miocárdio , Miócitos Cardíacos/patologia , Ratos , Ratos Endogâmicos SHR/metabolismo , Ratos Sprague-Dawley , Remodelação Ventricular/fisiologia
17.
Funct Integr Genomics ; 20(3): 409-419, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31745672

RESUMO

Emerging evidence suggests that long non-coding RNAs (lncRNAs) are critical regulators of diverse biological processes, including adipogenesis. Despite being considered an ideal animal model for studying adipogenesis, little is known about the roles of lncRNAs in the regulation of rabbit preadipocyte differentiation. In the present study, visceral preadipocytes isolated from newborn rabbits were cultured in vitro and induced for differentiation, and global lncRNA expression profiles of adipocytes collected at days 0, 3, and 9 of differentiation were analyzed by RNA-seq. A total of 2066 lncRNAs were identified from nine RNA-seq libraries. Compared to protein-coding transcripts, lncRNA transcripts exhibited characteristics of a longer length and lower expression level. Furthermore, 486 and 357 differentially expressed (DE) lncRNAs were identified when comparing day 3 vs. day 0 and day 9 vs. day 3, respectively. Target genes of DE lncRNAs were predicted by the cis-regulating approach. Prediction of functions revealed that DE lncRNAs when comparing day 3 vs. day 0 were involved in gene ontology (GO) terms of developmental growth, growth, developmental cell growth, and stem cell proliferation, and involved in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PI3K-Akt signaling pathway, fatty acid biosynthesis, and the insulin signaling pathway. The DE lncRNAs when comparing day 9 vs. day 3 were involved in GO terms that associated with epigenetic modification and were involved in the KEGG pathway of cAMP signaling pathway. This study provides further insight into the regulatory function of lncRNAs in rabbit visceral adipose and facilitates a better understanding of different stages of preadipocyte differentiation.


Assuntos
Adipócitos/metabolismo , Adipogenia , Gordura Intra-Abdominal/citologia , RNA Longo não Codificante/genética , Adipócitos/citologia , Animais , Células Cultivadas , Insulina/genética , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Coelhos , Transdução de Sinais , Transcriptoma
18.
Biochem Biophys Res Commun ; 523(2): 389-397, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31870550

RESUMO

The development of head and neck squamous cell carcinoma (HNSCC) is a complex pathological process and many cellular and molecular events may occur. The ubiquitin conjugating enzyme E2 (UBE2C) was found to play an oncogenic role in several human cancers. However, its functional role in HNSCC tumorigenesis remains unknown. In this study, UBE2C gene expression in HNSCC was first evaluated using the data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The connection between UBE2C gene expression and patients' survival rates of HNSCC and other human cancers was also investigated. Liquid chromatography with tandem mass spectrometry was used to identify differentially expressed proteins, including UBE2C, between UMSCC1 oral cancer cells and normal human oral keratinocytes (NHOKs). Immunohistochemistry (IHC) was used to verify the differential expression of UBE2C protein between HNSCC and adjacent control tissues. Cell cycle analysis, MTT, colony formation, Transwell migration, and Matrigel invasion assays were used to study the effect of UBE2C downregulation on the malignant phenotypes of HNSCC cells. The bioinformatic analysis of the proteins interacting with UBE2C in HNSCC cells was also performed. Based on the data obtained from the cancer databases and our in vitro studies, we found that UBE2C was overexpressed in HNSCC and patients with high UBE2C expression suffered a remarkably worse overall survival rate than those with low UBE2C expression, and a similar observation was found in a number of other human cancers. UBE2C was also found to be overexpressed in HNSCC cells versus normal human oral keratinocytes and inhibition of UBE2C expression significantly suppressed the malignant phenotypes of HNSCC cells in vitro. The bioinformatic analysis indicated that UBE2C may be involved in head and neck tumorigenesis through the mediation of important pathways such as ubiquitin mediated proteolysis, proteasome, and cell cycle. In conclusion, our results suggest that UBE2C is consistently upregulated in many human solid tumors. It promotes HNSCC progression and may serve as a potential prognostic biomarker in HNSCC. Future studies are warranted to unveil the underlying molecular pathways of UBE2C in HNSCC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Enzimas de Conjugação de Ubiquitina/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Prognóstico , Mapas de Interação de Proteínas , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/metabolismo , Regulação para Cima
19.
Electrophoresis ; 41(16-17): 1392-1399, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32506495

RESUMO

Caffeine (CA) is a common xanthine alkaloid found in tea leaves, coffee beans, and other natural plants, and is the most widely used psychotropic substance in the world. Accumulating evidence suggests that low plasma levels of CA and its metabolites may serve as reliable diagnostic markers for early Parkinson's disease (PD) patients. In this study, we demonstrated a new MEKC method for determining CA and its three main downstream metabolites, paraxanthine (PX), theobromine (TB), and theophylline (TP), in human plasma. Plasma samples were collected, and analyzed using MEKC, after SPE. The running buffer was composed of 35 mM phosphate, pH of 10.5, and 25 mM SDS. The separation voltage was 15 kV and the detection wavelength was at 210 nm. Under the optimum conditions, four distinct analytes were completely separated and detected in less than 12 min. Method limits of detection were as low as 7.5 ng/mL for CA, 5.0 ng/mL for TB, and 4.0 ng/mL for both PX and TP. The recoveries were between 88.0% and 105.9%. This method was successfully applied to 27 human plasma samples. The results indicate that the plasma concentrations of the four analytes are significantly lower in patients with early PD than in control subjects (p < 0.05). The area under curve was improved to 0.839 when CA and its three main metabolites were included, suggesting that MEKC testing of CA, TP, TB, and PX may serve as a potential method for early diagnosis of PD.


Assuntos
Cafeína/sangue , Cromatografia Capilar Eletrocinética Micelar/métodos , Doença de Parkinson/diagnóstico , Xantinas/sangue , Cafeína/metabolismo , Diagnóstico Precoce , Humanos , Limite de Detecção , Modelos Lineares , Doença de Parkinson/sangue , Reprodutibilidade dos Testes , Xantinas/metabolismo
20.
Cerebrovasc Dis ; 49(4): 382-387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756062

RESUMO

INTRODUCTION: Safety of carotid artery stenting (CAS) in patients having carotid stenosis with coexistent unruptured intracranial aneurysms (UIAs) is rarely reported. Thus, we studied the 3-month outcome of CAS in the presence of coexistent UIAs in our institution. METHODS: A retrospective analysis of patients receiving CAS at our institution from September 2011 to December 2019 was carried out. Patients were stratified into 2 groups: group of CAS with UIAs (CAS-UIA) and group of CAS without UIAs (CAS). The main complications within 3 months after stenting were TIA, ischemic stroke, symptomatic intracranial hemorrhage (sICH), rupture of UIAs, and death. The baseline characteristics and complications of the 2 groups were compared. RESULTS: Five hundred fifty-six patients (CAS, n = 468; CAS-UIA, n = 88) were included and 604 stenting procedures were performed. More patients had hypertension in the CAS-UIA group (87.5 vs. 73.7%, p = 0.006). There was no significant difference in TIAs, ischemic stroke, sICH, and death within 3 months after stenting between the CAS and CAS-UIA groups. None of the 113 coexistent UIAs detected in 88 patients had aneurysm rupture within 3 months after CAS. CONCLUSIONS: In our large cohort of CAS patients, coexistent UIAs are not uncommon. Stenting of a carotid artery in the presence of coexistent UIAs could be conducted safely. Together with 3-month dual antiplatelet therapy, CAS did not increase the rupture risk of the coexistent UIAs within 3 months.


Assuntos
Estenose das Carótidas/terapia , Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/complicações , Stents , Idoso , Aneurisma Roto/etiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Terapia Antiplaquetária Dupla , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/mortalidade , Hemorragias Intracranianas/etiologia , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
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